Laser Therapy

25 downloads 0 Views 6MB Size Report
based devices, to review the clinical experience and results, and to outline ..... Group A was treated with low level laser, using two GaAlAs diode lasers (670 nm .... Low-level laser therapy (LLLT) is a new therapy for the treatment of hair loss.
Laser Therapy Research

Contents ACNE ........................................................................................................................................................... 10 Alcoholism................................................................................................................................................... 12 Allergic Purpura........................................................................................................................................... 13 Alopecia – Hair Regrowth ........................................................................................................................... 23 Case Study – Alopecia Areata ..................................................................................................................... 27 Alzheimer’s Disease .................................................................................................................................... 28 Amyotrophic Lateral Sclerosis..................................................................................................................... 32 Analgesic Effects ......................................................................................................................................... 33 Angina – Ischemic Heart Disease ................................................................................................................ 41 Angiogenesis ............................................................................................................................................... 51 Ankle Sprains............................................................................................................................................... 52 Antiinflammatory Effect and CRP Levels .................................................................................................... 54 Antimicrobial Effects ................................................................................................................................... 59 Arteriosclerosis - Atherosclerosis ............................................................................................................... 62 Arthritis - Shoulder...................................................................................................................................... 69 Arthritis – Cervical....................................................................................................................................... 72 Arthritis – Elbow.......................................................................................................................................... 74 Arthritis - General ....................................................................................................................................... 83 Arthritis – Knee ........................................................................................................................................... 91 Arthritis – Osteoarthritis ........................................................................................................................... 100 Arthritis – Rheumatoid.............................................................................................................................. 105 Arthritis - Positive Double Blind Studies ................................................................................................... 115 Asthma ...................................................................................................................................................... 116 Atheroembolism ....................................................................................................................................... 123 Back Pain ................................................................................................................................................... 123 Benign Fibrotic Breast Lumps ................................................................................................................... 130 Blepharoptosis .......................................................................................................................................... 130 Blinding Techniques For Laser Therapy .................................................................................................... 131 Blood - Effects of Laser Therapy ............................................................................................................... 135

Blue 405 Nm Laser Light Mediates Heart Rate – ...................................................................................... 145 Blue Light and MRSA ................................................................................................................................. 155 Bone – How Laser Therapy & Ultrasound Promote Repair ...................................................................... 158 Bone Healing – Formation - Resorption.................................................................................................... 158 Bone-Implant Interaction.......................................................................................................................... 183 Brain Injury – Cerebral Circulation ............................................................................................................ 187 Breast Reduction ....................................................................................................................................... 189 Breast Tenderness..................................................................................................................................... 190 Bronchitis .................................................................................................................................................. 191 Burger’s Disease ........................................................................................................................................ 196 Burn Scars ................................................................................................................................................. 197 Burns ......................................................................................................................................................... 198 Burns and Carbon Monoxide Poisoning.................................................................................................... 199 C Reactive Protein Levels .......................................................................................................................... 199 Cancer ....................................................................................................................................................... 200 Candidiasis ................................................................................................................................................ 211 Cardiovascular........................................................................................................................................... 211 Carpal Tunnel Syndrome ........................................................................................................................... 231 Cartilage Regeneration ............................................................................................................................. 239 Cataract Extraction – Lens Implantation................................................................................................... 242 Cerebral Effects ......................................................................................................................................... 243 Cerebral Palsy ........................................................................................................................................... 244 Cerebrovascular Insufficiency ................................................................................................................... 250 Cervical Pain .............................................................................................................................................. 252 Chemotherapy & Radiation, Treating Side Effects ................................................................................... 257 Chlamydia ................................................................................................................................................. 263 Cholecystitis .............................................................................................................................................. 264 Chronic Placental Insufficiency ................................................................................................................. 265 Circulation ................................................................................................................................................. 266 Cleft Palate ................................................................................................................................................ 270 Collagen and Elastic Fiber Effects ............................................................................................................. 270 Combining Nanotechnology with LLLT ..................................................................................................... 271

Contraindications of Low Level Laser Therapy ......................................................................................... 273 Coronary Stent Implantation .................................................................................................................... 274 Dental ........................................................................................................................................................ 275 Dental Caries ............................................................................................................................................. 297 Depression ................................................................................................................................................ 297 Depth of Penetration ................................................................................................................................ 298 Dermatological – Aesthetics, Burns, Scars ................................................................................................ 302 Diabetes .................................................................................................................................................... 322 Diabetic Retinopathy ................................................................................................................................ 336 Dosage: Effects On Fibroblasts In Wounds ............................................................................................... 336 Dosage - Irradiance ................................................................................................................................... 337 Ear – Hearing Loss, Tinnitus, Meniere’s Disease ....................................................................................... 338 Effects on Blood ........................................................................................................................................ 357 Effects on brain in alcoholic coma ............................................................................................................ 369 Effects on DNA .......................................................................................................................................... 369 Effects on Erythrocytes ............................................................................................................................. 372 Effects on Hemostasis ............................................................................................................................... 378 Effects on Stored Blood ............................................................................................................................ 378 Elbow Pain................................................................................................................................................. 379 Endobronchial ........................................................................................................................................... 389 Endothelial Effects and Angiogenesis ....................................................................................................... 391 ENT (Ear, Nose, Throat)............................................................................................................................. 392 Epididymitis............................................................................................................................................... 401 Episiotomy ................................................................................................................................................ 401 Equipment For Laser And Other Light Therapy ........................................................................................ 402 Erectile Dysfunction .................................................................................................................................. 403 Eye ............................................................................................................................................................. 404 Facial Nerve Neuropathy .......................................................................................................................... 412 Facial Pain ................................................................................................................................................. 413 Facial Thermographic Changes ................................................................................................................. 414 Fertility ...................................................................................................................................................... 415 Eye ............................................................................................................................................................. 416

Facial Nerve Neuropathy .......................................................................................................................... 424 Facial Pain ................................................................................................................................................. 425 Facial Thermographic Changes ................................................................................................................. 427 Fertility ...................................................................................................................................................... 427 Fibromyalgia.............................................................................................................................................. 429 Gallbladder ................................................................................................................................................ 432 Gallbladder Inflammation / Gallstones ..................................................................................................... 434 Gallstones.................................................................................................................................................. 435 Gallbladder Inflamation - Gallstones ........................................................................................................ 436 Glaucoma .................................................................................................................................................. 436 Glossodynia ............................................................................................................................................... 438 Guiding Neuronal Growth with Light ........................................................................................................ 438 Gynecology................................................................................................................................................ 439 Hair Regrowth - Alopecia .......................................................................................................................... 442 Headache – Migraine ................................................................................................................................ 446 Headache – Migraine ................................................................................................................................ 448 Headache – Tension .................................................................................................................................. 449 Heart Disease ............................................................................................................................................ 451 Hepatitis .................................................................................................................................................... 461 Herpes ....................................................................................................................................................... 462 Hyperlipidemia .......................................................................................................................................... 468 Hypertension............................................................................................................................................. 480 Hypertension – Vascular Disease .............................................................................................................. 487 Immune Response .................................................................................................................................... 498 Improvement In Quality Of Life Of An Oncological Patient By Laser Phototherapy ................................ 505 In Vitro Effects........................................................................................................................................... 516 In Vivo Effects............................................................................................................................................ 523 Increased Antioxidant Activity .................................................................................................................. 527 Insomnia - Auriculotherapy ...................................................................................................................... 527 Interstitial Cystitis ..................................................................................................................................... 529 Irradiance vs. Dosage ................................................................................................................................ 529 Kidney ....................................................................................................................................................... 530

Kidney Stones............................................................................................................................................ 533 Knee Pain – Osteoarthritis ........................................................................................................................ 533 Lacrimal Duct Diseases.............................................................................................................................. 543 Laser Acupuncture .................................................................................................................................... 543 Laser Acupuncture – Gerhard Litscher ..................................................................................................... 559 Laser Acupuncture in Equ ......................................................................................................................... 566 Laser Acupuncture in Post Operative Fields in Veterinary Medicine ....................................................... 571 Laser Acupuncture on Horses with COPD ................................................................................................. 578 Laser Blood Irradiation and Surgical Stress............................................................................................... 588 Laser Elicited Nerve Action Potentials ...................................................................................................... 588 Laser Speckles ........................................................................................................................................... 589 Laser Therapie in Veterinary Medicine ..................................................................................................... 591 Laser Therapy – Effects on DNA ................................................................................................................ 597 Laser Therapy and Exercise ....................................................................................................................... 598 Laser Therapy on Darker Ethnic Skin ........................................................................................................ 600 Laser Therapy vs. Ultrasound.................................................................................................................... 601 Laser vs. Polarized Light ............................................................................................................................ 603 Laser, Needle and Electroacupuncture ..................................................................................................... 605 Lichen Planus ............................................................................................................................................ 609 Liver........................................................................................................................................................... 610 Lung Abscess ............................................................................................................................................. 629 Lupus Erythematosus ................................................................................................................................ 629 Lymphadenitis ........................................................................................................................................... 630 Lymphedema ............................................................................................................................................ 631 Macular Degeneration – Macular Edema – Retinal Disease..................................................................... 635 Manual needle acupuncture vs. laser needle acupuncture...................................................................... 639 Maxillofacial .............................................................................................................................................. 641 Meniere’s Disease – Tinnitus – Case Studies ............................................................................................ 645 Menopause ............................................................................................................................................... 646 Migraine .................................................................................................................................................... 646 Morphine withdrawal sign attenuation .................................................................................................... 648 MRSA and Blue Laser Light ....................................................................................................................... 648

Mucositis ................................................................................................................................................... 651 Muscle Regeneration ................................................................................................................................ 660 Musculoskeletal – Myofascial Pain ........................................................................................................... 668 Myocardial Infarction................................................................................................................................ 670 Myocardial Protective Effect..................................................................................................................... 672 Myocarditis ............................................................................................................................................... 672 Myopia ...................................................................................................................................................... 673 Neck Pain – Cervical Osteoarthritis – Myofascial Pain.............................................................................. 673 Nerve Regeneration .................................................................................................................................. 678 Nerve Regeneration in Children................................................................................................................ 690 Neurogenic Pruritus .................................................................................................................................. 695 Neuropathy ............................................................................................................................................... 695 Neurosensory Recovery after Surgery ...................................................................................................... 699 Nocturnal Enuresis .................................................................................................................................... 700 Osteomylelitis ........................................................................................................................................... 702 Osteonecrosis of the jaw and laser therapy ............................................................................................. 702 Osteoporosis - Bone Healing ..................................................................................................................... 704 Otitis .......................................................................................................................................................... 728 Pain ........................................................................................................................................................... 729 Pancreatitis ............................................................................................................................................... 736 Pancreatobiliary Disease ........................................................................................................................... 737 Parkinson’s Disease ................................................................................................................................... 738 Pediatrics................................................................................................................................................... 740 Pelvic Inflammatory Disease ..................................................................................................................... 740 Perineal Healing in Maternity Patients ..................................................................................................... 741 Peyronie’s Disease .................................................................................................................................... 742 Plantar Fasciitis ......................................................................................................................................... 743 Platelet Aggregation in Chronic Obstructive Bronchitis ........................................................................... 744 Platelet Effects .......................................................................................................................................... 744 Pleurisy ...................................................................................................................................................... 749 Pneumonia ................................................................................................................................................ 750 Pneumothorax .......................................................................................................................................... 753

Polarization ............................................................................................................................................... 754 Positive Double Blind Studies ................................................................................................................... 754 Postherpetic Neuralgia ............................................................................................................................. 759 Post-Herpetic Neuralgia - Shingles............................................................................................................ 761 Post-Operative Nausea and Vomiting....................................................................................................... 765 Pregnancy.................................................................................................................................................. 765 Prostate – Male Genital ............................................................................................................................ 767 Protection of Skeletal Muscles from Ischemic Injury ............................................................................... 773 Psoriasis .................................................................................................................................................... 774 Radiation – Chemotherapy, Treating Side Effects .................................................................................... 775 Radioprotective Effect .............................................................................................................................. 780 Raynaud’s Phenomenon ........................................................................................................................... 781 Reflex Sympathetic Dystrophy / Complex Regional Pain Syndrome ........................................................ 782 Respiratory ................................................................................................................................................ 783 Rheumatoid Arthritis ................................................................................................................................ 797 Rosacea ..................................................................................................................................................... 808 Scars .......................................................................................................................................................... 809 Scleroderma .............................................................................................................................................. 810 Schizophrenia ............................................................................................................................................ 811 Sciatic Nerve Regeneration ....................................................................................................................... 811 Scleroderma .............................................................................................................................................. 812 Shingles - Post-Herpetic Neuralgia............................................................................................................ 812 Shoulder Pain ............................................................................................................................................ 816 Sinusitis ..................................................................................................................................................... 819 Sinusitis ..................................................................................................................................................... 828 Snakebite .................................................................................................................................................. 829 Specific Effects of Laserpuncture on Cerebral Circulation ........................................................................ 830 Spinal Cord – Cerebral Injury .................................................................................................................... 831 Sports Injuries ........................................................................................................................................... 834 Laser Stellate Ganglion Block .................................................................................................................... 841 Stem Cells .................................................................................................................................................. 843 Stem Cells and Transplantation ................................................................................................................ 845

Stomatitis .................................................................................................................................................. 847 Strangulated Intestinal Obstruction ......................................................................................................... 849 Stroke ........................................................................................................................................................ 849 Temporomandibular Joint Disorder .......................................................................................................... 862 Tendon and Ligament Healing .................................................................................................................. 869 Tendonitis ................................................................................................................................................. 872 Tenosynovitis – Trigger Finger .................................................................................................................. 877 Thyroid ...................................................................................................................................................... 878 Tinnitus ..................................................................................................................................................... 879 Trauma ...................................................................................................................................................... 894 Trauma – Blood Loss ................................................................................................................................. 895 Treating Side Effects of Radiation & Chemotherapy ................................................................................ 895 Trigeminal Neuralgia ................................................................................................................................. 900 Trigger Points ............................................................................................................................................ 901 Tuberculosis .............................................................................................................................................. 903 Ulcer .......................................................................................................................................................... 909 Ulcerative Colitis ....................................................................................................................................... 912 Urinary Inflammation – Trauma ............................................................................................................... 913 Uveitis ....................................................................................................................................................... 913 Vaginitis ..................................................................................................................................................... 913 Vasomotor Rhinitis.................................................................................................................................... 914 Veterinary ................................................................................................................................................. 914 Vitiligo ....................................................................................................................................................... 921 Wavelength - 685 nm vs 830 nm in Tendon Repair .................................................................................. 922 Wound – Caesarean Incision Healing........................................................................................................ 923 Wound Dressing Transillumination........................................................................................................... 923 Wounds ..................................................................................................................................................... 924

ACNE Light Therapy In The Treatment Of Acne Vulgaris Elman M, Lebzelter J. Surg. 2004 Feb;30(2 Pt 1):139-46. Dermatology and Lasers Clinic, Tel Aviv Msq, Caesarea, Israel. BACKGROUND

Over the past decade, lasers and light-based systems have become a common modality to treat a wide variety of skin-related conditions, including acne vulgaris. In spite of the various oral and topical treatments available for the treatment of acne, many patients fail to respond adequately or may develop side effects. Therefore, there is a growing demand by patients for a fast, safe, and side-effect-free novel therapy. OBJECTIVES

To address the role of light therapy in the armamentarium of treatments for acne vulgaris, to discuss photobiology aspects and biomedical optics, to review current technologies of laser/lightbased devices, to review the clinical experience and results, and to outline clinical guidelines and treatment considerations. RESULTS

Clinical trials show that 85% of the patients demonstrate a significant quantitative reduction in at least 50% of the lesions after four biweekly treatments. In approximately 20% of the cases, acne eradication may reach 90%. At 3 months after the last treatment, clearance is approximately 70% to 80%. The nonrespondent rate is 15% to 20%. CONCLUSIONS

Laser and light-based therapy is a safe and effective modality for the treatment of mild to moderate inflammatory acne vulgaris. Amelioration of acne by light therapy, although comparable to the effects of oral antibiotics, offers faster resolution and fewer side effects and leads to patient satisfaction.

Optical Treatments For Acne Author: Ross EV. Source: Dermatol Ther. 2005 May-Jun;18(3):253-66. Location: Dermatology Department, Naval Medical Center San Diego, 34800 Bob Wilson Drive, San Diego, CA 92134, USA. [email protected]

Light-based treatments for acne are becoming increasingly commonplace in dermatology. This article reviews various light approaches in acne therapy. Methods are discussed from an anatomical and a functional perspective. The emphasis is on the practicality of treatment as well as the pros and cons of various devices. Also, a review of the recent literature is presented. The article is intended to give the reader a panoramic view of this still-young and developing area. Most likely, light-based acne treatment will receive more popularity as dermatologists learn how to integrate this type of therapy within the context of more established drug agents.

Light, Laser And PDT Therapy For Acne 1: Hautarzt. 2005 Nov;56(11):1027-32. [Article in German] Borelli C, Merk K, Plewig G, Degitz K. Klinik für Dermatologie und Allergologie der Ludwig-Maximilians-Universität München. [email protected]

In recent years, a number of studies have evaluated the treatment of acne using electromagnetic waves, such as lasers, photodynamic therapy, visible light or radio waves. While the efficacy of laser treatment is still uncertain, photodynamic therapy shows promising results, but with marked side-effects, as destruction of sebaceous glands. Treatment with blue light (405-420 nm wavelength) also appears effective and can be regarded as an treatment option for inflammatory acne.

Lasers And Light Therapy For Acne Vulgaris Semin Cutan Med Surg. 2005 Jun;24(2):107-12. Bhardwaj SS, Rohrer TE, Arndt K. Department of Dermatology, University of Minnesota, USA.

Acne vulgaris remains an emotionally and debilitating dermatologic disease, and is conventionally treated with a variety of oral and topical therapies with a number of significant side effects. An evolving understanding of laser-tissue interactions involving Propionibacterium acnes-produced porphyrins, and the development of infrared nonablative lasers to target sebaceous glands, has lead to the development of an escalating number of laser, light and radiofrequency devices for acne. Used as monotherapy or in combination, these devices are showing promise as a method to clear acne in a convenient, non-invasive manner, though there remains a clear need for longterm data and randomized, blinded studies.

Light/Laser Therapy In The Treatment Of Acne Vulgaris J Cosmet Dermatol. 2005 Dec;4(4):318-20 Nouri K, Villafradez-Diaz LM. Department of Dermatology, University of Miami School of Medicine, Miami, FL.

Acne vulgaris is one of the most prevalent skin diseases known. As common as this condition is, the social and psychological consequences are limitless. Although current treatments are available and include topical or oral antibiotics, it is crucial to develop a less risky and more effective therapy such as light/laser therapy. This article focuses specifically on the benefits of the light/laser treatment on acne vulgaris. Porphyrins accumulated in the bacteria, Propionibacterium acnes, one of the etiologic factors involved in the pathogenesis, allows phototherapy to be a successful modality. They have specific absorption peaks at which lasers have optimal effects. The longer the wavelength of the light is, the deeper its penetration and thus the greater its damage to the sebaceous glands. Although blue light is best for the activation of porphyrins, red light is best for deeper penetration and an anti-inflammatory effect. Ultraviolet (UV) light, although it may have initial an anti-inflammatory effects, has been proven to be potentially carcinogenic and have adverse effects such as aging (by UV-A) and burning (by UVB). Previous studies indicate successful long-term intervention and selective damage of the sebaceous glands by using a diode laser with indocyanine green (ICG) dye. Mid-infrared lasers have been found to decrease lesion counts while also reducing the oiliness of skin and the

scarring process. Nonablative laser treatment of acne scars using the Er:YAG laser with a shortpulsed mode has been successful in reducing the appearance of scars by stimulating neocollagenesis. The light/laser therapy has started to be explored with promising results in highly selected patients that require further investigation in greater populations and welldesigned protocols.

The New Age Of Acne Therapy: Light, Lasers, And Radiofrequency. J Cosmet Laser Ther. 2004 Dec;6(4):191-200. Rotunda AM, Bhupathy AR, Rohrer TE. Division of Dermatology, David Geffen School of Medicine, UCLA Medical Center, Los Angeles, CA, USA. BACKGROUND

Current treatments for acne vulgaris include topical and oral medications that counteract microcomedone formation, sebum production, Propionibacterium acnes, and inflammation. Concerns about the short- and long-term consequences of these medications, along with technological advancements, have to significant progress in the management of acne. These developments include light, laser, and radio frequency, which may offer faster onset of action, equal or greater efficacy, and greater convenience than traditional approaches. CONCLUSION

Research emphasizing long-term follow-up and comparative, randomized trials is necessary to determine whether these emerging technologies will become a viable alternative to standard therapies such as antibiotics.

Lasers, Light, And Acne. Cutis. 2003 May;71(5):353-4. Hirsch RJ, Shalita AR. Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Boston 02114, USA. [email protected]

Acne vulgaris is a highly prevalent disease with significant potential for physical and emotional scarring. Acne lesions have long been noted to improve after exposure to sunlight. This improvement may be secondary to activation of endogenous porphyrins produced by Propionibacterium acnes. Recently, several investigators have presented studies in which light of particular wavelengths has been used to treat acne vulgaris. In this article, we review the results of these studies as we look to the future of light-based acne treatment.

Alcoholism Use Of Low-Energy Laser As Adjunct Treatment Of Alcohol Addiction. Lasers Med Sci. 2004;19(2):100-4. Zalewska-Kaszubska J, Obzejta D. Department of Pharmacodynamics, Medical University, Muszynskiego 1, 90-151 Lodz, Poland. [email protected]

Auricular acupuncture is a medical method that has been used in the treatment of alcohol addiction. In our study we decided to intensify this method by additional biostimulation of the whole organism. The aim of this study was the therapy of patients with alcohol dependence syndrome. Fifty-three alcoholics were treated with two types of laser stimulation in four sessions. Each session consisted of 20 consecutive daily helium-neon laser neck biostimulations and 10 auricular acupuncture treatments with argon laser (every 2nd day). The Beck Depression Inventory-Fast Screen (BDI-FS) was used to assess their frame of mind before the session and after 2 months of treatment. Moreover, beta-endorphin plasma concentration was estimated five times using the radioimmunoassay (RIA) method. Improvement in BDI-FS and increase in, betaendorphin level were observed. These results suggest that laser therapy can be useful as an adjunct treatment for alcoholism.

Allergic Purpura Low Level Laser Therapy in Children’s Allergic Purpura Used by the kind permission of the Czech Society for the Use of Laser in Medicine, www.laserpartner.org Laser Partner, 1.2.2002 C. Ailioaie, Laura Ailioaie, Iassy, Romania. E-mail: [email protected] ABSTRACT

Patients with allergic purpura have characteristic purpuric skin rash and some of the following clinical manifestations may be present: migratory polyarthralgias or polyarthritis, colicky abdominal pain, nephritis. Because until now there is no satisfactory treatment, we applied low level laser therapy (LLLT) in order to compare it with the classical therapy. Thirty-one children (2-16 years of age) have been included in the study and treated at debut of the disease. They were randomly divided: group A - (15 children) received LLLT; group B (16 children) was administrated classical therapy. Two GaAlAs diode lasers in red and infrared region (670 nm and 830 nm) were used. The density of energy (4 - 10 J/cm2), irradiating frequency (2.4 Hz) - was applied one session daily, using scanning technique under a special treatment protocol on cutaneous purpuric areas (21 sessions). Very good results were obtained in laser group. In the control group, after an apparent improvement, subsequent exacerbations and remissions were present, and three children developed chronic renal disease. The results prove that LLLT is acting as a triggering factor, which induces systemic effects through the circulation, followed by a response of the children‘s entire immune system. That is why LLLT is a very promising modality of treatment for the allergic diseases in children. INTRODUCTION

Allergic purpura or anaphylactoid purpura is characterized by vasculitis of the small vessels, particularly those of the skin, gastrointestinal tract and kidney, which is most often manifested as a nonthrombocytopenic purpura, arthritis, nephritis, and abdominal pain. Heberden described for the first time this syndrome before 1800. In the 1830s, Schönlein described the typical rash and joint manifestations, and in 1870s Henoch recognized the gastrointestinal and renal manifestations. Osler pointed out the similarity between this disease and the hypersensitivity reactions, erythema multiforme and serum sickness. 1

The skin rash is often urticarial initially and then progresses to a macular-papular appearance that transforms into a diagnostic symmetric purpuric skin rash distributed on the ankles, buttocks, and elbows. The visceral lesions are less easily recognized but are more serious. The primary manifestations are due to vasculitis of the small blood vessels. Immune complexes (IgA with complement, IgG, or IgM) have been found in the serum and associated with blood vessel walls of the kidney, intestine, and skin. The etiology is unknown. Suspected though not proved inciting antigens include group A hemolytic streptococci and other bacteria, viruses, drugs, foods, and insect bites. The syndrome may occur at any age; it is more common in children than in adults, with most cases occurring in early childhood (2-8 yr. of age). Approximately two-thirds of patients develop migratory polyarthralgias or polyarthritis, primarily of the ankles and knees. Abdominal colic – due to hemorrhage and edema primarily of the small intestine - occurs in about half of those affected. Twenty-five to fifty percent of those affected develop renal involvement. Hematuria alone is never the presenting complaint for purpura but usually manifests in the second to third week of illness.2 CONVENTIONAL TREATMENT

There is no specific and no satisfactory treatment. Therapeutic management is primarily supportive with close observation for signs of renal or gastrointestinal manifestations. In the rare instance in which a specific allergen can be proved the patient should avoid the antigen. When the disease follows a bacterial infection, particularly streptococcal illness, the organism should be eliminated and, if the disease recurs, prophylaxis considered. If culture for group A _hemolytic streptococcus is positive or if the ASLO titer is elevated, penicillin should be given in full therapeutic doses for 10 days. Symptomatic treatment is indicated for arthritis, rash, edema, fever, and malaise. Nonsteroidal anti-inflammatory drugs usually alleviate these self-limited discomforts. Intestinal hemorrhage, obstruction, intussusception, or perforation may be life threatening in the acute phase; these complications may be managed by the early use of corticosteroids. Therapy with prednisone, 1-2 mg/kg/24 hr, is often associated with dramatic improvement. Corticosteroid therapy is also indicated for the rare patient with central nervous system manifestations. Corticosteroid therapy may provide symptomatic relief for severe gastrointestinal or joint manifestations but does not alter skin or renal manifestations. Acute renal failure should be managed in the same way as acute glomerulonephritis. Therapy for severe nephritis with corticosteroids, azathioprine and cyclophosphamide remains experimental, rarely justified. 3 PROGNOSIS

The prognosis for recovery is generally good, though symptoms frequently (25-50%) recur over a period of several months. In-patients who develop renal manifestations, microscopic hematuria may persist for years, and progression to renal failure occasionally occurs. Rarely death occurs from severe gastrointestinal complications, acute renal failure, or central nervous system involvement.4 LOW LEVEL LASER THERAPY - A NEW MODALITY OF TREATMENT

Although it has been employed in the medical purposes from early sixties of the 20th Century, LLLT is still undergoing thorough scientific and clinical investigations. Three basic effects of

LLLT (e.g., biostimulative-regenerative, analgesic and anti-inflammatory effect) haven‘t been challenged but fulfilled with effects of laser irradiation on the immune circulatory and hematological system, as well as promising effect of laser light on the oncological patients. Additionally, LLLT appear to have a virustatic and bacteriostatic effect. 5 The first application of LLLT was completed on dermatological disorders like skin ulcers in early sixties. In the meantime, the range of dermatological indications for LLLT has increased. 6 In order to reduce the suffering of children with allergic purpura we applied low level laser therapy for its biomodulation action on the entire immune system. This therapeutic modality was previously proven to have a benefic effect on blood circulation. That is why we thought that LLL could regenerate the microcirculation in the skin, affected by this disease. In the end, analyzing the obtained results for the LLL-treated patients, our presumption proved to be true. METHODS

Patients and Study Design. Thirty-one children (2-16 years of age) were suffering from allergic purpura at debut of the disease. They were included in a two-year long study and randomly divided as follows: Group A - 15 children (5 girls and 10 boys, mean age 7.13 yr.) were applied LLLT. Group B - including 16 children (5 girls and 11 boys, mean age 7.0 yr.), was administrated classical therapy. Exclusion criterion for the both groups was the presence of any renal involvement. Also, patients were excluded if they had a history of chronic allergic purpura. They have been checked for an eventual previous upper respiratory infection, even streptococcal; allergy or drug sensitivity, as triggering factors for allergic purpura. The accurate diagnosis of allergic purpura was confirmed by the clinical manifestations of the disease and laboratory tests results. Basic demographic information and clinical characteristics before initializing the treatment are presented in Table 1. Table 1. Demographic information and initial clinical characteristics.

Characteristics Sex: Boys Girls: Average Age at Onset Purpuric Rash Fever Angioedema Arthritis Abdominal Pain Nephritis Laboratory Findings (%) Hb ( 400 x 109 / L) Leukocyte count (> 15.5 x 109 / L) Neutrophils-―segs‖ (> 62%) ESR (>15 mm/h) C Reactive Protein (> 0,75 mg/dl) Serum IgA (>160 ui/l) CH50 (> 125 CH50 u.)

Group A - LLLT (n=15) 66.7% (10) 33.3% (5) 7.13 15 (100%) 13 (86.7%) 8 (53.3%) 15 (100%) 12 (80%) 0

Group B (n=16) 68.8% (11) 31.2% (5) 7.0 16 (100%) 14 (87.5%) 6 (37.5%) 12 (75%) 11 (68.7%) 0

9 (60%) 4 (26.7%) 11 (73.3%) 11 (73.3%) 12 (80%) 14 (93.3%) 5 (33.3%) 6 (40%)

10 (62.5%) 5 (31.3%) 11 (68.7%) 11 (68.7%) 12 (75%) 14 (87.5%) 4 (25%) 7 (43.8%)

CIC (> 20 mgeq/ml.) c-ANCA (> 10 ui/ml) p-ANCA (> 6 ui/ml) Urinary Sediment - Hematuria

5 (33.3%) 3 (20%) 3 (20%) -

6 (37.5%) 3 (18.8%) 3 (18.8%) -

PLAUSIBLE TRIGGERING FACTORS FOR ALLERGIC PURPURA

Because the etiology of allergic purpura remains uncertain and some specialists tend to think that the disease often follows an upper respiratory infection, sometimes streptococcal, we checked each patient for an eventual upper respiratory infection. We also looked for allergy or drug sensitivity as triggering factors for allergic purpura and for the critical role played by immunoglobuline A in the immunopathogenesis of this disease (see Table 1), trying to place a particular emphasis on new information about the etiology, immunopathogenesis, and treatment of allergic purpura. Our patients‘ clinical data concerning the association of group A _-hemolytic streptococcal infection, bacterial infection, allergy or drug sensitivity, and allergic purpura are presented in Table 2. Table 2. Plausible Triggering Factors for allergic purpura.

Plausible Triggering Factors Group A - b - hemolytic Streptococci Group B - b - hemolytic Streptococci Respiratory infection (bacteria, viruses) Drugs (Aspirin, Biseptol) Foods

GROUP A (N=15) 4 (26.7 %) 2 (13.3 %) 3 (20 %) 3 (20 %) 2 (13.3 %)

GROUP B (N=16) 3 (18.8 %) 2 (12.5 %) 4 (25 %) 2 (12.5 %) 2 (12.5 %)

DISEASE EVALUATION SCORES

In order to evaluate the clinical severity at presentation and status at follow-up, each patient was categorized according to the original criteria defined in Table 3. As such, each patient was assigned a total score that was calculated summing the separate scores assessed for each clinical manifestation (see Table 3). Table 3. Clinical severity scoring system.

Clinical Manifestations Purpuric Rash

Areas Affected by Purpuric Rash

Angioedema

Status Absent Urticaria Erythema Maculopapular Lesions and Petechial Lesions Larger Hemorrhages ('Palpable Purpura") Absent Lower Extremities Lower Extremities + Buttocks + Elbows Extended to Upper Extremities Extended to Upper Trunk and Face Absent Dorsal Surfaces of Feet

Score 0 1 2 3 4 0 1 2 3 4 0 1

Fever

Arthritis

Abdominal Manifestations

Renal Involvement

Dorsal Surfaces of Feet and Hands Extended to Scalp Scalp + Eyelids + Lips + Ears 36,5 °C 36,5 - 38,0 °C 38,0 - 39,0 °C 39,0 - 40,0 °C > 40 °C Absent Polyarthralgias Single Joint Several Joints Absent Nausea Vomiting Recurrent Colicky Midabdominal Pain Blood and Mucus in Stool because of Hemorrhage and Edema of the Small Intestine Absent Hematuria Proteinuria Chronic Renal Disease

2 3 4 0 1 2 3 4 0 1 2 3 0 1 2 3 4

0 1 2 3

SKIN AND RENAL BIOPSIES

For skin biopsy a fresh but well-developed lesion from skin should be selected for removal. The selection of primary lesions is extremely important to obtain an accurate diagnosis. The site of the biopsy should have relatively low risk for damage to underlying dermal structures. Lidocaine (Xylocaine) 1 or 2 %, with or without epinephrine, should be injected intradermally after cleansing of the site. The biopsy should be made at the proper depth in order that all three layers (epidermis, dermis, and subcutis) can be examined. 7 The biopsy specimen should be placed in 10 % formaldehyde solution (Formalin) for appropriate processing. Biopsy of skin by excision is rarely required for diagnosis in children. More recommended is the punch biopsy, which is a relatively painless procedure and usually provides adequate tissue for examination. TREATMENT PROTOCOL

Group A was treated with low level laser, using two GaAlAs diode lasers (670 nm and 830 nm, maximum output power 50 mW, respectively 300 mW). The density of energy was 4 - 10 J/cm2. Irradiation (2.4 Hz frequency) at both wavelengths combined with the same dosages - was applied one session daily, using scanning technique on cutaneous purpuric areas (21 sessions). These patients had an unrestricted regime of life concerning the sleep and resting period. Group B was administrated a complex medication: the classical therapy (antihistamines, capillaro-trophics, steroidal anti-inflammatory drugs) and all patients had an obligatory period of rest. Both groups were prescribed a non-allergic diet. Corticosteroid therapy was initiated in group B whenever it was necessary to relieve severe gastrointestinal or joint manifestations; in

group A only two patients were administrated this kind of therapy. But this did not alter skin manifestations (or renal involvement). Diclofenac was administrated in cases of manifested arthritis, only in group B. Sedatives represented a benefit for patients with gastrointestinal pain. If culture for group A and B _-hemolytic streptococci was positive or if the ASLO titer was elevated, penicillin had been given in full therapeutic doses for 10 days, in both groups. Patients have been monitored also after the end of treatment protocol for 2 years, and some are still under observation. DATA ANALYSIS

The evolution of the total acuity score of allergic purpura manifestations was the main objective of the present study. A step by step approach was used for the statistical evaluation. Initially, score data were transformed by square rooting. On this transformed data, a paired two-way t test was performed within each group, evaluating the clinical symptoms and parameters, from the beginning of the treatment until the end. Any difference was considered to be significant for p values less than 0.05. Data were analyzed using appropriate software. RESULTS

Even if the distribution of patients was randomly designed, both groups resembled each other concerning the initial clinical manifestations and laboratory findings (two relatively homogeneous groups of patients) (see Tables 1 and 2). The onset of the disease was abrupt with simultaneous appearance of several manifestations in 71% of patients, and gradual with sequential appearance of different manifestations for the rest. The dominant clinical feature of allergic purpura, cutaneous purpura was present in 100% of the children, with a symmetrical anatomic distribution (mostly on the buttocks and lower extremities) and the same patterns of skin involvement. The rash was associated with maculopapular lesions and variable elements of urticaria and erythema. Most patients had arthritis, which frequently affected the knees and ankles (100% - group A and 75% - group B), abdominal pain (80% - group A and 68.7% - group B), angioedema (53.3% group A and 37.5% - group B), and none of the patients manifested nephritis at onset. Laboratory findings revealed anemia in both groups (60% - Group A and 62.5% - Group B), an increased number of leukocytes (73.3% - Group A and 73.3% - Group B) and platelets (26.7% Group A and 31.3% - Group B), while platelet function tests, and bleeding time were normal. One can also notice the elevation of serum C-reactive protein and increased serum immunoglobuline A (IgA) concentrations, IgA-containing circulating immune complexes (see Table 1). The associations of group A beta-hemolytic streptococcal infections and allergic purpura was identified in both groups A and B (26.7% and 18.8%, respectively). A potential eliciting factor mostly infectious could be respiratory infections (20% - group A and 25% - group B) (see Table 2). Biopsy data from the patients who underwent skin biopsies revealed vasculitis and inflammatory perivascular infiltrate with mononuclears in derma, useful for the differential allergic purpura diagnosis (Photos 1 and 2).

Photo 1: Perivascular mononuclear infiltrate (0,05 ); 2) a reduction in a number of FBS sessions from 5-7 conducted during the con vcntional treatment down to 3-4 ones carried out with LL- cured AL suspension. 3) a reduction in the quantity of anti-biotics administered: while carrying out transplantation of autoleukosuspension cured with HNlascr light we could completely reject antibiotics administration and only 1 pt had to be subjected to a second course of administering antibactcria] preparations, whereas during .the conventional treatment antibiotics were administered to all the pts, and 47,1% of them had to be subjected to a double course of antibiotics therapy; 4) a reduction in an average hospital stay period from 30,2 down to 23,8 days. Thus, an in-troduction of transplantation of HNLL-curcd AL-suspcnsion into the CPB pts therapy causes an increase in the organism's non-specific resistant-resistance, minimises a mcdicamcntous load upon a pt and cuts down a duration of a hosoital stay period.

[The Efficacy Of Membrane-Stabilizing Therapy In Patients With Chronic Obstructive Bronchitis] Ter Arkh. 1997;69(10):34-6. [Article in Russian] Prozorova GG, Sil'vestrov VP, Simvolokov SI, Nikitin AV.

A membrane stabilizing effect of endobronchial laser therapy and antioxidative drugs piracetam and solcoseril was studied in 83 patients with chronic bronchitis. Malonic dialdehyde was measured to evaluate effects of this treatment on cellular and humoral immunity, blood coagulation and lipid peroxidation. It was found that the addition of membrane stabilizers to standard therapy of chronic bronchitis lowered malonic dialdehyde concentrations while the addition of the stabilizers and endobronchial laser therapy relieved clinical symptoms earlier, improved parameters of immunity, hemostasis and lipid peroxidation.

[The Treatment Of Patients With Chronic Obstructive Bronchitis By Using A Low-Power Laser At A General Rehabilitation Center] Ter Arkh. 1997;69(3):17-9. [Article in Russian] Vorotnev AI, Deriabin NM, Romanov AI, Sil'vestrov VP, Titov VI.

100 patients with chronic obstructive bronchitis were examined and treated in the therapeutic department of rehabilitation center. Combined treatment including lowenergy laser radiation produced good results. Laser therapy has improved bronchial permeability, sensitivity of bronchial beta 2-receptors to sympathomimetics. As a result, their intake was reduced or discontinued. Laser radiation combined well with other nonpharmacological modalities.

[Morphologic Studies Of Bronchial Biopsies In Chronic Bronchitis Before And After Treatment] Arkh Patol. 1995 Nov-Dec;57(6):21-5. [Article in Russian] Chumakov AA, Boikova SP, Popkova AM, Igonina NP, Boikov KA. N. A. Semashko Moscow Medical Institute, Russia.

Bronchial biopsies in patients with chronic bronchitis were studied histochemically, light and electron microscopically before and after conventional treatment and combined therapy (standard regimen plus He-Ne laser puncture). The conclusion is made that the combined therapy is more effective especially at early stages of the disease when irreversible sclerotic changes in the submucosa and microcirculatory bed are absent. This therapy at early stages of the disease stimulates regeneration of the surface bronchial epithelium and facilitates reversibility of initial metaplasia.

[Clinico-Morphological Comparisons In The Laser Therapy Of Chronic Bronchitis Patients] Lik Sprava. 1993 Oct-Dec;(10-12):75-9. [Article in Russian] Feshenko IuI, Dziublik AIa, Gomoliako IV, Chechel' LV, Kulik IV.

The article presents results of endobronchial treatment with low-intensity laser in 56 patients with chronic non-obstructive bronchitis (CNOB). Irradiation was carried out in 5-7 positions. Course of the treatment consisted of 4-6 seances. 14 days after the start of the treatment patients showed improvement of general condition, normalization of body temperature, reduction of cough, disappearance of endoscopic inflammatory changes in bronchial mucosa. Morphometrical data evidenced activation of proliferative processes and normalization of bronchial secretion which indicated increase of tissue metabolism. Cytological study revealed qualitative improvement of epithelial cover. Low-intensity laser is noted to be highly effective in the treatment of patients with CNOB, especially in the early stage of pathological process.

[Effect Of Low-Energy Laser Irradiation Of Bronchial Mucosa On Systemic And Local Immunity In Patients With Chronic Bronchitis] Probl Tuberk. 1991;(6):26-9. [Article in Russian] Ivaniuta OM, Chernushenko EF, Dzublik AIa, Tyshko NA, Naida IV, Kulik IV.

The effectiveness of endobronchial low-energy laser therapy was studied in 28 patients with chronic nonobstructive bronchitis concurrent with thinning of bronchial mucosa. The course of treatment made it possible to obtain positive dynamics of most parameters of immunologic reactivity in CNB patients. Systemic immunity parameters, except for the NST and concentration of circulating immune complexes, underwent essential normalization. Marked positive changes were found in the parameters characterizing functional activity of alveolar macrophages: there was a 2.5-fold increase in adhesive properties and over 1.3-fold increase in the percentage of phagocytes. The level of secretory IgA rose significantly (by 3.5 times). Hence, a manifested therapeutic effect of this therapeutic method is mainly associated with its immune-stimulating action.

[Treatment Of Nonspecific Endobronchitis With Low-Intensity Laser Irradiation (Experimental Study)] Probl Tuberk. 1989;(4):50-3. [Article in Russian] Maliev BM, Shesterina MV, Solov'eva IP, Boikov AK.

Results of endobronchial treatment of experimental purulent endobronchitis (PE) in dogs with low intensity He-Ne laser are presented. The endobronchial use of the laser energy in treatment of PE was shown expedient and valid. Comparison of the visual endoscopic picture with the findings of the histochemical and electron microscopic examination of the bronchial mucosa bioptates in the time course of the treatment provided establishment of the optimal regimen for the treatment of nonspecific PE with He-Ne laser.

[Optimal Effectiveness Of Complex Treatment Of Patients With Chronic Obstructive Bronchitis By Intravascular Laser Irradiation Of Blood] Probl Tuberk. 1992;(5-6):21-4. [Article in Russian]

Ivaniuta OM, Dziublik AIa, Skopichenko VN.

Results of combined treatment of 100 patients with chronic obstructive bronchitis are presented in the paper. Intravascular laser irradiation of blood had a favourable effect on the clinical disease course, normalized parameters of lipid peroxidation, produced a marked immune stimulating and anti-inflammatory action, controlled the blood coagulation system and improved rheological blood properties. Intravascular laser irradiation of blood included in the complex of therapeutic measures increased the efficiency of therapy in patients with chronic obstructive bronchitis by 12.0 +/- 2.6%.

[Dynamics Of The Indices Of The Immune System As Affected By Endobronchial Laser Therapy In Patients With Complicated Tuberculosis Of The Lungs] Probl Tuberk. 1991;(9):64-7. [Article in Russian] Maliev BM, Selitskaia RP, Kupavtseva EA.

The results of study of the local and humoral immune defense during endobronchial laser therapy of nonspecific endobronchitis in patients with newly diagnosed pulmonary tuberculosis are presented. Laser therapy proved to have no negative action on the humoral immunity in pulmonary tuberculosis patients during treatment of catarrhal and purulent endobronchitis, while a marked increase in IgM levels, thus rapidly reacting and well opsonizing antibodies can be regarded as a positive or stimulating the impact on the whole immune system. Endobronchial laser therapy for catarrhal and especially purulent inflammatory bronchial process in the multimodality treatment of patients with newly diagnosed pulmonary tuberculosis normalized parameters of the local immune system, especially that of locally secreted immunoglobulins, i.e. helium-neon laser radiation has a favourable influence on local immune defense, which is essential in increasing the efficacy of therapy of this category of patients.

Burger’s Disease Low Level Laser Therapy (LLLT) For Thrombonagitis Obliterans. Sasaki K et al. Proc. 2nd Congress World Association for Laser Therapy, Kansas City, USA, September 2-5 1998; p 95-96 .

In this case report a patient with thrombonagitis obliterans (Bürgers disease) was treated with a 60 mW 830 nm laser and a defocused 20 W Nd:YAG laser. Ulcers were remarkably improved. Agonizing pain and ischemia were relieved. In the MRA findings, sudden arterial obliteration disappeared. In the thermographical findings, skin temperature increased to normal level.

Low Level Laser Therapy (LLLT) For Thrombonagitis Obliterans. Sasaki K et al. Vopr Kurortol Fizioter Lech Fiz Kult. 2001 May-Jun;(3):5-7. Proc. 2nd Congress World Association for Laser Therapy, Kansas City, USA, September 2-5 1998; p 95-96 .

In this case report a patient with thrombonagitis obliterans (Bürgers disease) was treated with a 60 mW 830 nm laser and a defocused 20 W Nd:YAG laser. Ulcers were remarkably improved. Agonizing pain and ischemia were relieved. In the MRA findings, sudden arterial obliteration disappeared. In the thermographical findings, skin temperature increased to normal level.

[Supravascular Laser Exposure In Combined Modality Treatment Of Patients With Arteriosclerosis Obliterans Of Blood Vessels Of Lower Extremities] [Article in Russian] Leont'eva NV, Evdokimova TA, Sedletskaia EIu, Dmitrieva IaV, Zolotnitskaia VP.

The efficiency of supravascular laser exposure in multiple-modality treatment of patients with atherosclerosis obliterans with distal vascular lesions is demonstrated and the method of noninvasive laser exposure of the lower limbs is validated. Difficulties in the treatment of this category of patients prompted supplementing traditional therapy by supravascular laser exposure in 32 patients. No laser therapy was used in the controls.

Burn Scars Low Level Laser Therapy--A Conservative Approach To The Burn Scar? Burns. 2004 Jun;30(4):362-7. Gaida K, Koller R, Isler C, Aytekin O, Al-Awami M, Meissl G, Frey M. Department of Reconstructive and Plastic Surgery, Burn Unit, Division of Surgery, University of Vienna, Austria.

Burn scars are known to be difficult to treat because of their tendency to worsen with hypertrophy and contracture. Various experimental and clinical efforts have been made to alleviate their effects but the problem has not been solved. Since patients keep asking for Low Level Laser Therapy (LLLT) and believe in its effectiveness on burn scars, and since former studies show contradictory results of the influence of LLLT on wound healing, this prospective study was designed to objectify the effects of LLLT on burn scars. Nineteen patients with 19 burn scars were treated with a 400 mW 670 nm Softlaser twice a week over 8 weeks. In each patient a control area was defined, that was not irradiated. Parameters assessed were the Vancouver Scar Scale (VSS) for macroscopic evaluation and the Visual Analogue Scale (VAS) for pruritus and pain. Photographical and clinical assessments were recorded in all the patients. Seventeen out of 19 scars exhibited an improvement after treatment. The average rating on the VSS decreased from 7.10+/-2.13 to 4.68+/-2.05 points in the treated areas, whereas the VSS in the control areas decreased from 6.10+/-2.86 to 5.88+/-2.72. A correlation between scar duration and improvement through LLLT could be found. No negative effects of LLLT were reported. The present study shows that the 400 mW 670 nm softlaser has a positive, yet sometimes limited effect on burn scars concerning macroscopic appearance, pruritus, and pain.

Burns Effect Of Low-Level Laser Therapy On The Healing Of Second-Degree Burns In Rats: A Histological And Microbiological Study. J Photochem Photobiol B. 2005 Feb 1;78(2):171-7. Bayat M, Vasheghani MM, Razavi N, Taheri S, Rakhshan M. Anatomy Department, Medical Faculty, Cell and Molecular Biology Research Center, Shaheed Beheshti University of Medical Sciences, P.O. Box 19395/4719, Tehran, Iran. [email protected]

This paper presents the results of a study on the effects of two different doses of lowlevel laser therapy on healing of deep second-degree burns. Sixty rats were randomly allocated to one of four groups. A deep second-degree burn was inflicted in each rat. In the control group burns remained untreated; in two laser treated groups the burns were irradiated daily with low-level helium-neon laser with energy densities of 1.2 and 2.4 J/cm2, respectively. In the fourth group the burns were treated topically with 0.2% nitrofurazone cream every day. The response to treatments was assessed histologically at 7, 16 and 30 days after burning, and microbiologically at Day 15. The number of macrophages at day 16, and the depth of new epidermis at day 30, was significantly less in the laser treated groups in comparison with control and nitrofurazone treated groups (P=0.000). Staphylococcus epidermidis was found in the 70% of rat wounds in the laser treated groups in comparison with 100% of rats in the control group. S. aureus was found in the 40% rat wounds in the nitrofurazone treated group, but there was not found in the wounds of laser treated, and control groups. It is concluded that low-level laser therapy of deep seconddegree burn caused significant decrease in the number of macrophage and depth of new epidermis. In addition, it decreased incidence of S. epidermidis and S. aureus.

Effects Of Low-Intensity Polarized Visible Laser Radiation On Skin Burns: A Light Microscopy Study. J Clin Laser Med Surg. 2004 Feb;22(1):59-66. Ribeiro MS, Da Silva Dde F, De Araujo CE, De Oliveira SF, Pelegrini CM, Zorn TM, Zezell DM. Center for Lasers and Applications, IPEN-CNEN/SP, Cidade Universitaria, Sao Paulo, Brazil. [email protected]

OBJECTIVE: This study was carried out to investigate the influence of low-intensity polarized visible laser radiation on the acceleration of skin wound healing. Background Data: Low-level laser therapy (LLLT) at adequate wavelength, intensity, and dose can accelerate tissue repair. However, there is still unclear information about light characteristics, such as coherence and polarization. Some studies indicate that linearly polarized light can survive through long propagation distance in biological tissue. MATERIALS AND METHODS: Three burns about 6 mm in diameter were created on the back of rats with liquid N(2). Lesion "L(//)" was irradiated by He-Ne laser (lambda = 632.8 nm), D= 1.0 J/cm(2), with linear polarization parallel to the spinal column of the rat. Lesion "L(inverted v)" was irradiated using the same laser and dose, but the light polarization was aligned perpendicularly to the relative orientation. Lesion "C" was not irradiated in order to be considered as control. The animals were sacrificed at day 3-17 after lesion creation. Samples were collected and prepared for histological analysis. RESULTS: Histological analysis showed that the healing of irradiated wounds was faster than that of nonirradiated wounds. Moreover, it was observed that skin wound repair is dependent on

polarization orientation with respect to a referential axis as the animal's spinal column. Consequently, "L(//)" was completely healed after 17 days, whereas "L (perpendicular) " showed a moderate degree of healing after the same period. CONCLUSIONS: These results indicate that the relative direction of the laser polarization plays an important role in the wound healing process when highly coherent He-Ne laser is used.

Burns and Carbon Monoxide Poisoning [Intensive Therapy In Burns And Carbon Monoxide Poisoning] Klin Khir. 1998;(11):21-3. [Article in Russian] Grigor'eva TG, Balenko AA.

While treatment conduction of 38 patients with severe burns and poisoning with carbonic oxide in complex of antishock measures there was applied a nondirect electrochemical oxidation of blood and internal laser irradiation of blood. There was used He-Nd laser. The mortality lowering by 3.3 times in comparison with 40 patients, in whom the traditional intensive therapy was applied, was noted.

C Reactive Protein Levels Assessment Of Anti-Inflammatory Effect Of 830nm Laser Light Using Creactive Protein Levels. Braz Dent J. 2001;12(3):187-90 Freitas AC, Pinheiro AL, Miranda P, Thiers FA, Vieira AL. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, PUC-RS, Porto Alegre, RS, Brazil.

The anti-inflammatory effect of non-surgical lasers has been proposed previously, however it was not scientifically proven. One method to assess levels of inflammation is the measurement of C-reactive protein (CRP), which is increased with the course of inflammation. The aim of this study was to assess the effect of 830 nm laser irradiation after the removal of impacted third molars using the CRP as the marker of inflammation. Twelve patients were irradiated with 4.8 J of laser light per session 24 and 48 h after surgery. A control group (N = 12) was treated with a sham laser. Blood samples were taken prior to, and 48 and 72 h after surgery. CRP values were more symmetric and better distributed for the irradiated group (0.320 mg/dl) than for the control (0.862.mg/dl) 48 h after surgery, however there was no statistically significant difference. After 72 h, both groups had statistically similar CRP levels (0.272 and 0.608 mg/dl), because of the normal tendency of decreasing CRP levels.

Cancer Improvement In Quality Of Life Of An Oncological Patient By Laser Phototherapy. Photomed Laser Surg. 2009 Apr;27(2):371-4 Campos L, Simões A, Sá PH, Eduardo Cde P. Oral Biology Research Center, Department of Biomaterials and Oral Biochemistry, School of Dentistry, University of São Paulo, São Paulo, Brazil.

OBJECTIVE AND BACKGROUND DATA: Common side effects of radiotherapy (RT) to the head and neck include oral mucositis, xerostomia, and severe pain. The aim of this study is to report improvement in the quality of life of an oncological patient by laser phototherapy (LPT). CLINICAL CASE AND LASER PHOTOTHERAPY PROTOCOL: The patient, a 15-year-old girl diagnosed with mucoepidermoid carcinoma, underwent surgical excision of a tumor of the left palatomaxilla. After that, she was subjected to 35 sessions of RT (2 Gy/d). Clinical examination revealed the spread of severe ulcerations to the jugal mucosa, gums, lips, hard palate, and tongue (WHO mucositis score 3). She had difficulty in moving her tongue and she was unable to eat any solid food. Oral hygiene orientation and LPT were performed throughout all RT sessions. A continuous diode laser, 660 nm, 40 mW, 6 J/cm(2), 0.24 J per point in contact mode, with spot size of 0.04 cm(2) was used in the entire oral cavity. A high-power diode laser at 1 W, 10 sec per cm of mucositis, approximately 10 J/cm(2), was used in defocused mode only on ulcerative lesions. After the first laser irradiation session, decreases in pain and xerostomia were reported; however, a more significant improvement was seenafter five sessions. At that point although the mucositis score was still 2, the patient reported that she was free of pain, and consequently a palatine plate could be made to rehabilitate the entire surgical area. Seventeen laser irradiation sessions were necessary to eliminate all oral mucositis lesions. CONCLUSION: Normal oral function and consequent improvements in the quality of life of this oncologic patient were observed with LPT.

Effects Of Diode 808 Nm Gaalas Low-Power Laser Irradiation On Inhibition Of The Proliferation Of Human Hepatoma Cells In Vitro And Their Possible Mechanism. Res Commun Mol Pathol Pharmacol. 2004;115-116:185-201. Liu YH, Cheng CC, Ho CC, Pei RJ, Lee KY, Yeh KT, Chan Y, Lai YS. Center for Research and Development, Chung-tai Institute of Health Sciences and Technology, Taichung, Taiwan.

Low-power laser irradiation (LPLI) has come into a wide range of use in medical field. Considering basic research, LPLI can enhance DNA synthesis and increases proliferation rate of human cells. But only a few data about the effects of LPLI on human liver or hepatoma cells are available. The cytoskeleton plays important roles in cell function and therefore is implicated in the pathogenesis of many human liver diseases, including malignant tumors. In our previous study, we found the stability of cytokeratin molecules in human hepatocytes was related to the intact microtubule network that was influenced by colchicine. In this study, we are going to search the effect of LPLI on proliferation of human hepatoma cell line HepG2 and J-5 cells. In

addition, the stability of cytokeratin and synemin (one of the intermediate filament-associated proteins) were analyzed under the action of LPLI to evaluate the possible mechanism of LPLI effects on proliferation of human hepatoma cells. In experiment, HepG2 and J-5 cells were cultured in 24-well plate for 24 hours. After irradiation by 130 mW diode 808 nm GaAlAs continue wave laser in different time intervals, the cell numbers were counted. Western blot and immunofluorescent staining examined the expression and distribution of PCNA, cytokeratin and synemin. The cell number counting and PCNA expression were evaluated to determine the proliferation. The organization and expression of cytokeratin and synemin were studied to identify the stability of cytoskeleton affected by LPLI. The results revealed that proliferation of HepG2 and J-5 cells was inhibited by LPLI since the cell number and PCNA expression was reduced. Maximal effect was achieved with 90 and 120 seconds of exposure time (of energy density 5.85 J/cm2 and 7.8 J/cm2, respectively) for HepG2 and J-5, respectively. The decreased ratio of cell number by this dose of irradiation was 72% and 66% in HepG2 and J-5 cells, respectively. Besides that, the architecture of intermediate filaments in these cells was disorganized by laser irradiation. The expression of intermediate filament-associated protein, synemin, was also reduced. Two significant findings are raised in this study: (1) Diode 808 nm GaAlAs continuous wave laser has an inhibitory effect on the proliferation of human hepatoma cells line HepG2 and J-5. (2) The mechanism of inhibition might be due to downregulation of synemin expression and alteration of cytokeratin organization that was caused by laser irradiation.

Effects Of Low-Level Laser Therapy On Malignant Cells: In Vitro Study. J Clin Med Surg. 2002; 20 (1): 23-26. Pinheiro A L, Carneiro Nascimento S, De Barros Vieira A L et al.

The aim of a study by Pinheiro was to assess the effect of 635- and 670-nm laser irradiation on H.Ep.2 cells in vitro using MTT. It was decided to evaluate the effect of increased doses of laser light on these cells. The cells, obtained from SCC of the larynx. The cultures were kept either at 5% or 10% of FBS. Twenty-four hours after transplantation, the cells were irradiated with laser light (5 mW diode lasers; 635 and 670 m; beam cross section 1 mm at local light doses between 0.04 and 4.8.10(4) J cm2. For 670 nm, significant differences in the proliferation were observed between the two concentrations of FBS and between irradiated cultures and controls. Although the results were not significant, 635-nm irradiated cells also proliferated more than nonirradiated ones. This occurred under both conditions of nutrition. It was concluded, that irradiation with 670 nm laser light applied at doses between 0.04 and 4.8104 J/cm2 could significantly increase proliferation of laryngeal cancer cells.

[Validation And Approaches To Correction Of Hemorheologic Disorders In Patients With Gastrointestinal Cancer] Anesteziol Reanimatol. 2001 Sep-Oct;(5):47-50. [Article in Russian] Karabanov GN, Karimov AI, Ogii II, Gantsev KSh, Khalikov RA, Ishmuratova RSh.

A total of 237 patients were examined: 127 with gastric cancer and 110 with colonic cancer, 99 women and 138 men, mean age 57.5 years. Erythrocyte deformability and aggregation were

studied by original methods. Red blood, protein metabolism, and endogenous intoxication parameters were evaluated by routine laboratory tests. Increased aggregation and volume of erythrocytes and decrease of their deformability and hemoglobin content in parallel with hypoand dysproteinemia and increased level of endogenous intoxication were observed in all patients with gastrointestinal cancer. Correction of these disorders by intravenous laser exposure of the blood essentially improved the erythron status and protein metabolism and decreased endotoxicosis. Infusion/transfusion therapy also notably improved the erythron function and decreased endogenous intoxication. Analysis of the results of surgery showed decreased incidence of complications and lethal outcomes, which was due to methods of corrective therapy.

[Intravascular Laser Irradiation Of The Blood In Complex Treatment Of The Patient With Esophageal Cancer] Klin Khir. 1999;(5):27-9. [Article in Ukrainian] Hanul VL, Zaitsev SL, Kirkilevs'kyi SI, Fil'chakov FV.

Complex treatment of 41 patients with intrathoracic esophageal cancer using intravascular laser irradiation of the blood was done. The immunorehabilitating method application had promoted the postoperative complications rate lowering, the mortality reduction, the three-year survival rate indexes improvement.

[Microcirculation In Gastrointestinal Cancer And Some Possibilities Of Its Correction] Vopr Onkol. 1998;44(6):672-5. [Article in Russian] Karabanov GN, Ogiij II, Reshetova LA. Bashkir Republican Oncological Dispensary, Ufa.

Microcirculation and blood rheology were studied in 348 patients with tumors of the gastrointestinal tract. Such disorders as increased blood and plasma viscosity, aggregates of erythrocytes and their increased stability of shape were recorded in conjunction with hypo- and dysproteinemia, endogenous intoxication syndrome and microvascular disturbances. Microcirculation significantly improved and endoxemia was alleviated following photomodification of the blood by use of helium-neon laser radiation and application of an original procedure of infusion.

[Results Of The Clinical Use Of Laser Therapy In Malignant Tumors] Klin Khir. 1998;(3):40-1. [Article in Ukrainian] Dryzhak VI, Halaichuk II, Dombrovich MI, Oleksii OP, Zahurs'ka NO.

The raise of natural antitumoral resistance level, the reduction of intoxication severity, the raise of an organism tolerance to irradiation and polychemotherapy were permitted by adjuvant lowenergy laser therapy absorption in the complex of treatment of 27 patients with colonic cancer in early postoperative period, 16--cervix uteri cancer while irradiation therapy conduction, and 14-with cutaneous melanoma during polychemotherapy.

Biomodulation Of Normal And Tumor Cells J Photochem Photobiol B: Biology. 1997; (40): 253-257

In a study by Schaffer et al. various cells were irradiated by 805 nm laser light. The cells were (1) murine skeletal myotubes, (2) normal urothelial cells, (3) human squamous carcinoma cells of the gingival mucosa and (4) urothelial carcinoma cells. Mitotic index for 1, 2 and 4 increased at fluences of 4 J/cm2 while irradiation at 20 J/cm2 resulted in a slight decrease. The no 3 cells showed a decrease of the mitotic index with both fluences. The most interesting observation is the different reaction of the two carcinoma cells.

Biological Effect Of Helium-Neon (He-Ne) Laser Irradiation On Mouse Myeloma (Sp2-Ag14) Cell Line In Vitro Abstract Volume 13 Issue 3 (1998) pp 214-218 J.M. Ocaña-Quero (1), J. Perez de la Lastra (1), R. Gomez-Villamandos (2), M. Moreno- Millán (1)(1) Departamento de Genética(2) Departamento de Patología Animal, Facultad de Veterinaria de Córdoba, Spain Received for publication 22 July 1997; accepted following revision 6 February 1998.

We examined the effect of helium-neon (He-Ne) laser irradiation with a wavelength of 632.8 nm on cell cycle synchronisation of monolayer growing mouse myeloma (Sp2-Ag14) cell line. The monolayer cultures were exposed to repeated doses of different energy densities (4-64 J/cm2). The nuclear DNA content has been studied by flow cytometry to obtain the cell percentage in each cell cycle phase. Results showed that the He-Ne laser irradiation at energy densities of 8-64 J/cm2 produced a significative and different effect on the G0-G1 and S phases of cell cycle over control. In contrast, no significant effect in G2-M phase was produced by He-Ne laser irradiation at any energy density compared with non-treated control. These results support previous observations suggesting that He-Ne laser irradiation of low energy density interferes with cell cycling and may inhibit cell proliferation when irradiation is performed at doses of 8 J/cm2 or more.

[Nizkointensivnaia Lazernaia Terapiia V Detskoi Onkologii] Voprosy Onkologii. 2000; 46 (4): 459-461. Balakirev S A, Gusev L I, Kazanova M B et al.

The study by Balakirev suggests that the application of laser therapy makes it possible to reduce the time needed for the management of radiation injury and chemotherapy complications in pediatric patients 1.5-2- fold. It was shown that exposure to laser caused mononuclear levels of donors' blood to rise, which in turn led to release, in higher concentrations, of IL-1 and FNO cytokins, major factors of immune response development.

[Low-Intensity Lasers In Pediatric Oncology].Vestn Ross Akad Med Nauk. 2000; (6): 24-27. Durnov L A, Gusev L I, Balakirev S A et al

The study by Durnov outlines the outcomes of treatment for complications associated with chemo- and radiation therapy in children with malignant neoplasms by using low-intensity laser radiation. The use of this therapy may reduce the duration of treatment of these complications by 1.5-2 times. The use of lowintensity laser radiation in the treatment of other complications that are common in pediatric oncological care is briefly described.. [The

Correction Of The Subcellular Postradiation Changes In The Hypothalamus And Parathyroid Gland By Using Low-Intensity Laser Radiation. An Experimental Study]. Vopr Kurortol Fizioter Lech Fiz Kult. 2000; (3): 3-4.

Korolev Iu N, Panova L N, Geniatulina M S The study by Korolev showed that exposure of the rat adrenals 30 days after radiation (1 Gy) to infrared laser radiation arrested the development of ultrastructural disorders in the cells of the hypothalamus and the parathyroid gland and enhanced subcellular manifestations of adaptation and rehabilitation processes.

Use Of Low-Level Laser Therapy (Lllt) For Treatment Of The Patients With A Cancer Of A Esophagus T3n0mx V.A.Mikhailov,* I.B.Sudakov,** I.N.Denisov,*** V.L.Osin Moscow scientific-practical center on laser therapy,*Oncologic hospital, Rjasan, **Moscow medical academy named after Setchenov,***Medical Center at business management of the President of Russian Federation

In this part of work at 20 patients received the laser therapy (LLLT) in a combination with external radial therapy under the radical program (1group), 15 patients (2 groups) received only one laser therapy , the control group consist of 18 men receiving only external radial therapy on the radical program (3 groups), 10 patients received only symptomatic therapy (4 groups). The stage of disease T3N0MX and spent treatment in skilled and control groups was identical. Radial therapy carried out on kettles "Lutch-1" and "Agat- ?" on a procedure from three fields (1 parasternal, 2 and 3 - juxtaspinal under an angle of 40 degrees to a backbone) with a single dose till 90 % on doses by a curve 1,8 Gr and cooperative dose 64-66 Gr. The irradiation was carried out 5 days per one week with a break 2 days. A GaAs semiconductor laser (wavelength 890 nm., pulsed mode, pulse power 5-10 W.) was used for laser therapy. Laser therapy carried out after leading to a tumor of a dose 15-20 Gr. The sessions LLLT carried out 3 times per one week in day. A cooperative dose - 5,8 J/cm2 The analysis of lifespan of the patients in group receiving LLLT with radial therapy and in control group has shown, that use of laser therapy increases lifespan of the patients: 1 group - up to 10,28 ±2,03 months, in 2 groups up to 11,4 ±3,02 months, in 3 groups it makes 7,35 ±2,4 months, in 4 groups - 6,3 ± 1,94 months. Use LLLT allows to reduce quantity of occurrence of complications after radiation therapy in 2,9 times.

Hene Laser Reduces Mucositis a) Barasch B et al. Helium-neon laser effects on conditioning-induced mucositis in bone marrow transplantation patients. Cancer. 1995; 76 (12): 2550-2556.

Oral mucositis is a common complication of bone marrow transplantation conditioning therapy. Different drugs are given in order to reduce rejection of the implant. These drugs induce an oral mucosits. The mucositis is painful and complicates nutrition. Sometimes the intake of the drug has to be stopped due to complications. In the study above 20 patients received HeNe to their oral mucosa, either right or left of midline. One side was sham irradiated. Laser treatment was well-tolerated and reduced the severity of oral mucositis. b) Cowen D et al. Low energy helium-neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial. Int J Radiat Oncol Biol Phys. 1997; 38

(4): 697-707. Significant reduction of oral mucositis using a 60 mW HeNe laser

Chemo-And Radiation-Induced Mucositis : Results Of Multicenter Phase Iii Studies. Rene Jean Bensadoun Centre Antoine-Lacassagne, Nice, France

Considerable buccal toxicity of radiotherapy and/or chemotherapy in patients with cancer can cause patients to become discouraged and can alter their quality of life. In addition, such toxicity often necessitates alterations of treatment planning, with grave consequences in term of tumor response and even survival (concept of dose-intensity). With 5-fluorouracil and head and neck radiotherapy for example, acute mucosal toxic effect is the main limiting factor for which no clinically appropriate prophylaxis or efficacious antidote has been found to date. Management of oral mucositis is currently primarily directed at palliation of the symptoms, and prevention of infections. Low Level Laser Therapy (LLLT) has been reported effective in reducing the severity of oral mucositis lesions in a non-randomized trial, initiated in Nice (France) by Ciais et al. (1). The efficacy of this method in the prevention of chemotherapy induced oral mucositis has been subsequently confirmed in two prospective, double-blind randomized trials, in patients undergoing bone marrow transplant (2 ; 3). These initial findings and the high incidence of radiation-induced mucositis prompted a randomized multicenter trial to evaluate LLLT for the prevention of acute radiation-induced oropharyngeal mucosal lesions. The trial was open to patients with carcinoma of the oropharynx, hypopharynx and oral cavity being treated by external radiotherapy, with a total dose of 65 Gy at a rate of 1 fraction of 2 Gy/day, 5 days a week, from cobalt-60 or linear accelerator photons, without prior surgery or concomitant chemotherapy. Between September 1994 and March 1998, thirty patients entered this doubleblind randomized study conforming to the Huriet law. The goal was to determine whether preventive HeNe laser beam applications could reduce or prevent oropharyngeal mucositis caused by radiotherapy. Patients characteristics: There were 26 men and 4 women. Mean age was 60.4 years (range 36 78). Oral examination and preventive dental management were performed prior to radiotherapy. Daily oral hygiene (cleaning of the teeth and dental prosthesis) during treatment was recommended. Patients were assigned to either laser treatment (L+) or sham-treatment (L-) by computer blocked randomization. The protocol called for the inclusion of 30 patients, 15 in each arm. No associated anti-inflammatory or other treatment was authorized. Analgesics could be prescribed, but not during the 2 days preceding each week evaluation. Patients received HeNe laser applications daily for five consecutive days (Monday to Friday) each week, during the seven weeks of radiotherapy. The malignant tumor had to be located outside the areas selected for randomized preventive LLL application. Laser was delivered to the tissues by a straight

optical fiber with a 1.2 mm spot size. The 9 treatment areas included : posterior third of buccal mucosa, soft palate and anterior tonsillar pillars. Laser illumination consisted of a continuous beam (wavelength: 632.8 nm; power: 60 mW), calibrated at the end of the optical fiber every day. The treatment time (t) for each application point was given by the equation : t (sec) = energy (J/cm2) x surface (cm2)/ Power (W). The average energy density delivered to the treatment areas was 2 J/cm2, and was applied on these nine points, equally distributed on the treated surfaces, for 33 s per point (each specific LLL session lasted approximately 5 minutes). The 60 mW lasers were designed and produced by Fradama S.A. (Geneva, Switzerland). All laser illuminations were performed by the same individual in each center. This operator was the only person to know whether or not the patient was sham-treated, and did not participate in the evaluation and scoring mucositis. During the sessions, patients wore wavelength-specific dark glasses and were instructed to keep their eyes closed, to assure that they did not know whether they were shamtreated or whether they received laser applications. The laser made the same noises, and the probe was held in the mouth exactly the same way, when treating control subjects and when treating laser patients. The whole irradiation field, the oral cavity and the visible oropharynx were inspected weekly during seven weeks by the same physician (head and neck surgeon, or radiation oncologist), blinded to the result of randomization. The evaluation of mucositis and pain was performed on the oropharyngeal areas (9 points). Criteria for evaluation were the standard WHO scale for mucositis in the oropharynx; and a segmented visual analogic scale for pain (patient self evaluation). In this phase III study, no adverse effect was noted with the use of a 60-mW HeNe laser, though it is important to emphasize the importance of preventing retinal damage by the use of wavelength-specific goggles. This is consistent with previous reports. Laser applications delayed time of onset, attenuated the peak severity and shortened the duration of oral mucositis. The difference between L+ and L- patients was statistically significant from week 4 to week 7. With the total delivered dose of 65Gy, conventionally fractionated, all Lpatients developed mucositis at week 2, with a peak at week 5 (13 with grade 3 mucositis, and 2 with grade 2 mucositis). All L+ patients also had mucositis at week 2, with a peak at week 5 (5 with grade 3 mucositis, 9 with grade 2, 1 with grade 1). During the 7 weeks of treatment, the mean grade of mucositis in L+ patients was significantly lower (p=0.01) than the mean grade in L- patients .Results on decrease in pain intensity were also quite convincing. Laser applications reduced the incidence and duration of morphine administration. Ability to swallow was also improved. These results confirm previous data collected with this method, especially for patients undergoing bone marrow transplant (BMT). In a prospective study, Barasch et al. (2) used a 25mW laser on one side of the mouth only and reported a statistically significant reduction in oral mucositis on that side, according to the scoring system they used. In the Barasch study, each patient was his or her own control, which could be of importance, since mucosal damage on the sham-treated side could have benefited also from a distant systemic laser effect. Cowen et al. (3), using a 60 mW HeNe laser, performed a double-blind randomized phase III trial, in which laser was administered to the treatment group during conditioning, prior to the day of transplant. This study showed a 33% reduction of grades 3 and 4 mucositis in L+ patients. In this trial, mucositis was scored according to an oral examination guide, with a 16 items scale, of which 4 were assessed by the patients themselves. Daily mucositis index was significantly lower in L+ patients (p < 0.05) from d+2 to d+7 after BMT. The duration of grade 3 stomatitis was also reduced in L+ patients (p = 0.01). Oral pain was lower (p = 0.05), and L+ patients required less morphinomimetics (p = 0.05). Finally, xerostomia and ability to swallow were improved among L+ patients (p = 0.05, and p = 0.01, respectively). All these results were in keeping with previous

observations, suggesting the efficacy of the method (1, 4). Schubert et al. for example (4), identified a trend towards lower oral mucositis scores, on all examination days, in an interim results report of a phase I/II study, in which laser application was performed prophylactically during conditioning before BMT. In conclusion, LLLT seems to be a safe and efficient method for the prevention of chemo- and radiationinduced mucositis, with a tremendous potential interest for combined modality treatment. The concomitant use of chemo- and radiotherapy is becoming the new standard of care in advanced head and neck cancer, with very encouraging results, even in nonresectable cases. Since the main limiting factor of these combined protocols is the acute mucositis, this complementary treatment option with low level HeNe laser could be important in enhancing the feasibility of such regimens, and especially in the conservation of dose-intensity effect. At Nice, where the method is now used routinely during head and neck radiation, we project a new study testing LLL in patients being treated with concomitant chemo- and radiotherapy for advanced head and neck cancer. Even more than the improvement of patient comfort, the therapeutic index of combined specific treatment should be increased by the use of LLLT, besides standard supportive care, oral care and enteral nutrition (5). During this study, other laser wavelengths and powers could be tested, and compared to 60-mW HeNe laser. Ref :

1. CIAIS G., NAMER M., SCHNEIDER M., DEMARD F., POURREAU-SCHNEIDER N., MARTIN P.M., SOUDRY M., FRANQUIN J.C., ZATTARA H. La laserthérapie dans la prévention et le traitement des mucites liées à la chimiothérapie anticancéreuse. Bull. Cancer 79 : 183-191, 1992. 2. BARASCH A., PETERSON D., TANZER J.M., D'AMBROSIO J.A., NUKI K., SCHUBERT M., FRANQUIN J.C., CLIVE J., TUTSCHKA P. Helium-Neon laser effects on conditioninginduced oral mucositis in bone marrow transplantation patients. Cancer 76:2550-2556, 1995. 3. COWEN D., TARDIEU C., SCHUBERT M., PETERSON D., RESBEUT M., FAUCHER C., FRANQUIN J.C. Low energy helium-neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant : results of a double blind randomized trial. Int. J. Radiat Oncology Biol. Phys. 38 (4):697-703, 1997. 4. SCHUBERT M.M., FRANQUIN J.C., NICCOLI-FILHO F., MARCIAL F., LLOID M., KELLY J. Effects of low-energy laser on oral mucositis : a phase I/II pilot study. Cancer Researcher Weekly 7:14, 1997. 5. R. J. BENSADOUN, J. C. FRANQUIN, G. CIAIS, V. DARCOURT, M. M. SCHUBERT, M. VIOT, J. DEJOU, C. TARDIEU, K. BENEZERY, T. D. NGUYEN, Y. LAUDOYER, O. DASSONVILLE, G. POISSONNET, J. VALLICIONI, A. THYSS, M. HAMDI, P. CHAUVEL, F. DEMARD. Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer. Support Care Cancer 7(4):244-252, 1999.

Effects Of Low-Level Laser Therapy On Malignant Cells: In Vitro Study. J Clin Laser Med Surg. 2002 Feb;20(1):23-6 Barbosa P, Carneiro NS, de B, Brugnera A Jr, Zanin FA, Barros RA, Soriano D. School of Dentistry, Universidade Federal da Bahia, Salvador, BA, Brazil. [email protected]

The aim of this study was to assess the effect of 635- and 670-nm laser irradiation on H.Ep.2 cells in vitro using MTT. In addition to our previous report on the effects of LLLT on the

proliferation of laryngeal carcinoma cells in which it was found that irradiaton H.Ep.2 cells with 670-nm laser results in increased cell proliferation, it was decided to evaluate the effect of increased doses of laser light on these cells. The cells, obtained from SCC of the larynx, were routinely processed from defrost to the experimental condition. The cultures were kept either at 5% or 10% of FBS. Twenty-four hours after transplantation, the cells were irradiated with laser light (5-mW diode lasers; 635 and 670-nm; beam cross section approximately 1 mm) at local light doses between 0.04 and 4.8.10(4) Jm(-2). For 670 nm, significant differences in the proliferation were observed between the two concentrations of FBS (p = 0.002) and between irradiated cultures and controls (p = 0.000). Although the results were not significant, 635-nm irradiated cells also proliferated more than nonirradiated ones. This occurred under both conditions of nutrition. It is concluded, that irradiation with 670-nm laser light applied at doses between 0.04 and 4.810(4) Jm(-2) could significantly increase proliferation of laryngeal cancer cells.

Magnetic Resonance Imaging (MRI) Controlled Outcome Of Side Effects Caused By Ionizing Radiation, Treated With 780 Nm-Diode Laser -- Preliminary Results. J Photochem Photobiol B. 2000 Dec;59(1-3):1-8. Schaffer M, Bonel H, Sroka R, Schaffer PM, Busch M, Sittek H, Reiser M, Duhmke E. Department of Radiation Therapy, University of Munich, Germany. [email protected]. de

BACKGROUND and OBJECTIVE: Ionizing radiation therapy by way of various beams such as electron, photon and neutron is an established method in tumor treatment. The side effects caused by this treatment such as ulcer, painful mastitis and delay of wound healing are well known, too. Biomodulation by low level laser therapy (LLLT) has become popular as a therapeutic modality for the acceleration of wound healing and the treatment of inflammation. Evidence for this kind of application, however, is not fully understood yet. This study intends to demonstrate the response of biomodulative laser treatment on the side effects caused by ionizing radiation by means of magnetic resonance imaging (MRI). STUDY DESIGN/PATIENTS and METHODS: Six female patients suffering from painful mastitis after breast ionizing irradiation and one man suffering from radiogenic ulcer were treated with lambda=780 nm diode laser irradiation at a fluence rate of 5 J/cm2. LLLT was performed for a period of 4-6 weeks (mean sessions: 25 per patient, range 19-35). The tissue response was determined by means of MRI after laser treatment in comparison to MRI prior to the beginning of the LLLT. RESULTS: All patients showed complete clinical remission. The time-dependent contrast enhancement curve obtained by the evaluation of MR images demonstrated a significant decrease of enhancement features typical for inflammation in the affected area. CONCLUSION: Biomodulation by LLLT seems to be a promising treatment modality for side effects induced by ionizing radiation.

Low-Level 809 Nm Gaalas Laser Irradiation Increases The Proliferation Rate Of Human Laryngeal Carcinoma Cells In Vitro. Lasers Med Sci. 2003;18(2):100-3. Kreisler M, Christoffers AB, Willershausen B, d'Hoedt B. Poliklinik fur Zahnarztliche Chirurgie, Johannes Gutenberg-University, Mainz, Germany. [email protected]

The aim of the study was to investigate the effect of low-level 809 nm laser irradiation on the proliferation rate of human larynx carcinoma cells in vitro. Epithelial tumor cells were obtained from a laryngeal carcinoma and cultured under standard conditions. For laser treatment the cells were spread on 96-well tissue culture plates. Sixty-six cell cultures were irradiated with an 809 nm GaAlAs laser. Another 66 served as controls. Power output was 10 mW(cw) and the time of exposure 75-300 s per well, corresponding to an energy fluence of 1.96-7.84 J/cm2. Subsequent to laser treatment, the cultures were incubated for 72 h. The proliferation rate was determined by means of fluorescence activity of a redox indicator (Alamar Blue Assay) added to the cultures immediately after the respective treatment. The indicator is reduced by metabolic activity related to cellular growth. Proliferation was determined up to 72 h after laser application. The irradiated cells revealed a considerably higher proliferation activity. The differences were highly significant up to 72 h after irradiation (Mann-Whitney U test, p < 0.001). A cellular responsiveness of human laryngeal carcinoma cells to low-level laser irradiation is obvious. The cell line is therefore suitable for basic research investigations concerning the biological mechanisms of LLLT on cells.

Does LLLT Stimulate Laryngeal Carcinoma Cells? An In Vitro Study. Braz Dent J. 2002;13(2):109-12. Pinheiro AL, do Nascliento SC, de Vieira AL, Rolim AB, da Silva PS, Brugnera A Jr. Faculty of Dentistry, Federal University of Bahia, Salvador, BA, Brazil. [email protected]

Low level laser therapy (LLLT) has been used successfully in biomedicine and some of the results are thought to be related to cell proliferation. The effects of LLLT on cell proliferation is debatable because studies have found both an increase and a decrease in proliferation of cell cultures. Cell culture is an excellent method to assess both effects and dose of treatment. The aim of this study was to assess the effect of 635nm and 670 nm laser irradiation of H.Ep.2 cells in vitro using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide). The cells were obtained from squamous cell carcinoma (SCC) of the larynx and were routinely processed from defrost to the experimental condition. Twenty-four hours after transplantation the cells were irradiated with doses ranging from 0.04 to 0.48J/cm2 for seven consecutive days (5 mW diode lasers: 635nm or 670 nm, beam cross-section approximately 1 mm) at local light doses between 0.04 and 0.48 J/cm2. The results showed that 635nm laser light did not significantly stimulate the proliferation of H.Ep.2 cells at doses of 0.04 J/cm2 to 0.48 J/cm2, However, 670nm laser irradiation led to an increased cell proliferation when compared to both control and 635nm irradiated cells. The best cell proliferation was found with 670nm laser irradiated cultures exposed to doses of doses of 0.04 to 0.48 J/cm2. We conclude that both dose and wavelength are factors that may affect cell proliferation of H.Ep.2 cells.

Combined Endoscopic Laser And Radiotherapy Palliation Of Advanced Rectal Cancer. ANZ J Surg. 2002 Feb;72(2):95-9. Chapuis PH, Yuile P, Dent OF, Sinclair G, Low L, Aggarwal G. Department of Colon and Rectal Surgery, The University of Sydney at Concord Hospital, New South Wales, Australia. [email protected]

BACKGROUND: In the palliative treatment of patients with advanced, inoperable rectal cancer, combined endoscopic laser and radiotherapy have been claimed to be more effective than laser

therapy alone. The number of laser treatments, laser energy used, relapse rate, treatment of relapse, morbidity and survival in consecutive patients who were treated either by laser therapy alone or laser plus radiotherapy was compared. METHODS: Prospective data were analysed with regard to number of treatments, laser energy used, relapse rate, morbidity and survival for 56 consecutive patients. RESULTS: The crude relapse rate was significantly higher in the laser only group than in the laser plus radiotherapy group (58 and 15%, respectively; P = 0.002). There was no difference between the groups in the median total number of laser treatments or the mean total laser energy used. In patients experiencing a relapse, there was no difference in the median number of relapses, the number of laser treatments post-relapse or the total energy used post-relapse. Survival did not differ between the groups and there were no treatmentrelated deaths. CONCLUSIONS: These findings demonstrate a clear reduction in relapse after using combined laser and radiotherapy to palliate patients with advanced rectal cancer with no appreciable additional morbidity and have encouraged continuing use of this treatment.

Laser Therapy In Clinical Oncology R. Kabisov, V. Chissov, V. Sokolov Moscow Gertsen Cancer Research Institute, Moscow, Russia

The methodological basis for the treatment of malignant tumors will remain multivariant combinations of surgical, radiation and medicinal methods in the next century just like in this century. Such approach undoubtedly provides some results although the effectiveness of the treatment, rehabilitation indices and the existing standards of oncological patients do not meet requirements of society, physicians and patients. It is for the first time that system of Low Intensity Laser Therapy (LILT) has been used. From the position of the system approach LILT technologies with oncological patients represent complicated biotechnical processes and at its application specific features of the system, i.e. "tumororganism", technology of the irradiation as well as professional experience of the operator (i.e. physician) play a very important role and should be taken into account. LILT has been applied for 1000 patients with oncologic pathology of major localizations, different clinical states and morphological forms, independent of sex, age, psychosomatic features and other standard factors. The main trends of LILT in the treatment of oncological patient were: protective action during the antitumorogenic and radiation therapy (hemo-clinical correction); stimulation of growth-inhibiting factors and increase of the tumor sensivity to special and other additional means of treatment; preventive measures and treatment of complications after surgical operations; improvement of the results and quality of rehabilitation therapy and palliative treatment; treatment of opportunist pathologies with oncological patients; provides elimination of reaction for radiation therapy in 93,6% of cases; elimination of surgical complications in 89,4%. Effectiveness of the palliative LILT is 68,4%. Absolute contraindications of LILT have not been revealed. The analysis of immediate and longterm results reveals a complete absence of oncostimulating influence of LILT. Thus, it is possible to say that LILT is a new mean, improving the quality and results of a combined treatment of patients with malignant tumors.

Candidiasis [The Efficacy Of High-Intensity Laser Irradiation In The Combined Treatment Of Patients With Esophageal Candidiasis] Ter Arkh. 1996;68(2):23-4. [Article in Russian] Preobrazhenskii VN, Kasatkin NN.

High-intensity impulse laser radiation proved effective in 23 patients with esophageal candidiasis. The highest effect was achieved in its use with nistatin. In low laser efficacy radiation should be combined with transendoscopic administration of granulocytes concentrate. This produced clinico-endoscopic remission in 98.3% of the cases.

Effect Of Low-Level Laser Therapy On Candida Albicans Growth In Patients With Denture Stomatitis. Photomed Laser Surg. 2005 Jun;23(3):328-32. Maver-Biscanin M, Mravak-Stipetic M, Jerolimov V. Department of Prosthodontics, Clinical Hospital Centre, Zagreb, Croatia.

Objective: The purpose of our report is to present the effect of low-level laser therapy on Candida albicans growth and palatal inflammation in two patients with denture stomatitis. Background Data: The most common oral mucosal disorder in denture wearers is denture stomatitis, a condition that is usually associated with the presence of the yeast Candida albicans. Different treatment methods have been suggested to treat this symptom, none of which is proven to be absolutely effective. Methods: Two denture-wearing patients, both with palatal inflammation diagnosed as Newton type II denture stomatitis were treated with low-power semiconductor diode laser (BTL-2000, Prague, Czech Republic) at different wavelengths (685 and 830 nm) for 5 d consecutively. In both patients, palatal mucosa and acrylic denture base were irradiated in noncontact mode (probe distance of 0.5 cm from irradiated area) with different exposure times-5 min (830 nm, 3.0 J/cm(2), 60 mW) and 10 min (685 nm, 3.0 J/cm(2), 30 mW). The effect of laser light on fungal growth in vivo was evaluated after the final treatment using the swab method and semiquantitative estimation of Candida albicans colonies growth on agar plates. The severity of inflammation was evaluated using clinical criteria. Results: After lowlevel laser treatment, the reduction of yeast colonies on the agar plates was observed and palatal inflammation was diminished. Conclusion: LLLT is effective in the treatment of denture stomatitis. Further placebo controlled studies are in progress.

Cardiovascular Low-Level Laser Irradiation Inhibits Abdominal Aortic Aneurysm Progression In Apolipoprotein E-Deficient Mice. Cardiovasc Res. 2009 Jun 8. [Epub ahead of print] Gavish L, Rubinstein C, Bulut A, Berlatzky Y, Beeri R, Gilon D, Gavish L, Harlev M, Reissman P, Gertz SD.

Department of Anatomy and Cell Biology, The Hebrew University-Hadassah Medical School, PO Box 12272, Jerusalem 91120, Israel.

AIMS: Increased early detection of abdominal aortic aneurysm (AAA) and the severe complications of its current treatment have emphasized the need for alternative therapeutic strategies that target pathogenetic mechanisms of progression and rupture. Recent in vitro studies from our laboratory have shown that low-level laser irradiation (LLLI) (780 nm) modifies cellular processes fundamental to aneurysm progression. The present study was designed to determine whether LLLI retards the progression of suprarenal AAA in vivo. METHODS AND RESULTS: High-frequency ultrasonography (0.01 mm resolution) was used to quantify the effect of LLLI on aneurysmatic aortic dilatation from baseline to 4 weeks after subcutaneous infusion of angiotensin II by osmotic minipumps in the apolipoprotein E-deficient mouse. At 4 weeks, seven of 15 non-irradiated, but none of the 13 LLLI, mice had aneurysmal dilatation in the suprarenal aneurysm-prone segments that had progressed to >/=50% increase in maximal crosssectional diameter (CSD) over baseline (P = 0.005 by Fisher's exact test). The mean CSD of the suprarenal segments (normalized individually to inter-renal control segments) was also significantly lower in irradiated animals (LLLI vs. non-irradiated: 1.32 +/- 0.14 vs. 1.82 +/- 0.39, P = 0.0002 by unpaired, two-tailed t-test) with a 94% reduction in CSD at 4 weeks compared with baseline. M-mode ultrasound data showed that reduced radial wall velocity seen in nontreated was significantly attenuated in the LLLI mice, suggesting a substantial effect on arterial wall elasticity. CONCLUSION: These in vivo studies, together with previous in vitro studies from this laboratory, appear to provide strong evidence in support of a role for LLLI in the attenuation of aneurysm progression. Further studies in large animals would appear to be the next step towards testing the applicability of this technology to the human interventional setting.

[Platelet Aggregatory Properties In Patients With Chronic Pancreatitis And Possibilities Of Correcting Their Impairments] Klin Lab Diagn. 2009 Apr;(4):19-21. [Article in Russian] Burduli NM, Gutnova SK.

The purpose of the investigation was to study the impact of low-intensity laser therapy (LILT) on platelet aggregatory properties in patients with chronic pancreatitis (CP) on an exacerbation. A total of 105 patients aged 36 to 77 years who were divided into a study group (n = 60) and a control one (n = 45) were examined. Thirty persons who formed a healthy group were additionally examined. In the study group patients, drug therapy was supplemented by LILT via various methods. The control group received only drug therapy. The investigation revealed that patients with CP on an exacerbation showed diverse changes in platelet aggregatory properties towards hyperaggregation. LILT was ascertained to have a normalizing effect on platelet aggregatory properties in the study group patients.

Laser Biostimulation In End-Stage Multivessel Coronary Artery Disease--A Preliminary Observational Study. Kardiol Pol. 2007 Jan;65(1):13-21; discussion 22-3. \[Article in English, Polish]

Zycinski P, Krzeminska-Pakuła M, Peszynski-Drews C, Kierus A, Trzos E, Rechcinski T, Figiel L, Kurpesa M, Plewka M, Chrzanowski L, Drozdz J. II Katedra i Klinika Kardiologii Uniwersytetu Medycznego, ul. Kniaziewicza 1/5, Łódz.

BACKGROUND: Low-energy laser radiation through its direct influence on tissue repair processes without heating effect may have vital importance in the therapy of patients with advanced coronary artery disease (CAD). AIM: The introductory assessment of the effects of laser biostimulation applied to patients with advanced multivessel CAD. METHODS: 39 patients with advanced CAD were assigned (mean age 64.8+/-9.6, male gender 64%, CCS class 2.5+/0.5, EF=46+/-11%, 69% with a history of acute myocardial infarction), to undergo two sessions of irradiation of low-energy laser light on skin in the chest area from helium-neon B1 lasers. The time of irradiation was 15 minutes while operations were performed 6 days a week for one month. Before including the patients in the experimental group a full clinical evaluation, basic biochemical tests, ECG, 24h Holter recordings, 6-minute walk test, treadmill test using Bruce protocol and full echocardiographic examination were performed. After the first and second period of laser therapy with a one-month break between them analogical parameters with the initial examination were measured. RESULTS: No side effects associated with the laser biostimulation or performed clinical tests were noted. Lower CCS class (2.5+/-0.5 --> 2.2+/-0.4 -> 2.0+/-0.4, p 5.8+/-2.2 --> 6.6+/-2.5 [METS], p=0.023), longer exercise time (257+/-126 --> 286+/-127 --> 325+/- 156 [s], p=0.06), less frequent angina symptoms during the treadmill test (65% --> 44% - -> 38%, p=0.02), longer distance of 6-minute walk test (341+/-93 --> 405+/-113 --> 450+/-109 [m], p 125+/- 12 --> 124+/-14 [mmHg], p=0.05) and trend towards less frequent 1 mm ST depression lasting 1 min during Holter recordings were noted. CONCLUSIONS: An improvement of functional capacity and less frequent angina symptoms during exercise tests without a significant change in the left ventricular function were observed. Laser biostimulation in short-term observation was a very safe method. These encouraging results should be confirmed in a larger, placebo-controlled study

Successful Treatment Of Finger Atheroembolism With Low-Level Laser Irradiation (LLLI): Report Of A Case. EMLA Laser Health J 2007;2:46-67 10th International Congress of the European Medical Laser Association (EMLA) Laser Prague 2005 Kazemikhou N. 1, Mokmeli S. 1, Gousheh S.J. 2, Mir-Abdul-Hagh M. 3 1. Laser clinic, Milad hospital, Tehran, Iran. 2. Division of Reconstructive and Microsurgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Bagiyatollah hospital, Molla-Sadra St., Bagiyatollah University of Medical Sciences, Tehran

Atheroembolism constitutes a subset of acute arterial occlusion, in which, multiple small deposits of fibrin, platelet, and cholesterol debris embolize from proximal atherosclerotic lesions or aneurysmal sites. Ischemia resulting from atheroemboli in extremities is notoriously difficult to treat and circulatory disturbance in these regions usually results in amputation. During past 30 years, low-level lasers have been widely used in medical fields. Low-level laser irradiation in red and near infrared region, locally or intravenously may result in vasodilatation, increased tissue perfusion and neovascularization.

A 64 years-old Iranian man referred to our clinic with acute atheroembolism of right index finger distal phalanx. There was no predisposing cardiovascular factor except for a mild hypercholesterolemia, and physical examination was generally normal. During 12 sessions (about 30 days) of low-level laser therapy with infrared light, 980 nm/ 100 mW and red light, 650 nm/ 30 mW, associated with 3 sessions of intravenous red light laser, 2 mW, ischemia disappeared and the finger was quite normal. On 12 months of follow-up, the patient was uneventful. Our observations during treatment process confirmed the results of previous experimental and clinical observations about LLLI effects on tissue healing of ischemic areas demonstrating that delivery of laser energy to the ischemia-induced necrotic area may have an important beneficial effect on patients with acute thromboembolism of fingers, preventing them from amputation or other invasive surgical interventions. However, additional studies and more clinical evidences are to be needed to demonstrate the various aspects of this application of lasers in medical practice.

Photoengineering Of Tissue Repair In Skeletal And Cardiac Muscles. Photomed Laser Surg. 2006 Apr;24(2):111-20. Oron U. Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Israel. [email protected]

This review discusses the application of He-Ne laser irradiation to injured muscles at optimal power densities and optimal timing, which was found to significantly enhance (twofold) muscle regeneration in rats and, even more, in the cold-blooded toads. Multiple and frequent (daily) application of the laser in the toad model was found to be less effective than irradiation on alternate days. It was found that in the ischemia/reperfusion type of injury in the skeletal leg muscles (3 h of ischemia), infrared Ga-Al-As laser irradiation reduced muscle degeneration, increased the cytoprotective heat shock proteins (HSP-70i) content, and produced a twofold increase in total antioxidants. In vitro studies on myogenic satellite cells (SC) revealed that phototherapy restored their proliferation. Phototherapy induced mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) phosphorylation in these cells, probably by specific receptor phosphorylation. Cell cycle entry and the accumulation of satellite cells around isolated single myofibers cultured in vitro was also stimulated by phototherapy. Phototherapy also had beneficial effects on mouse, rat, dog and pig ischemic heart models. In these models, it was found that phototherapy markedly and significantly reduced (50-70%) the scar tissue formed after induction of myocardial infarction (MI). The phototherapeutic effect was associated with reduction of ventricular dilatation, preservation of mitochondria and elevation of HSP- 70i and ATP in the infarcted zone. It is concluded that phototherapy using the correct parameters and timing has a markedly beneficial effect on repair processes after injury or ischemia in skeletal and heart muscles. This phenomenon may have clinical applications.

Progress in Low-level Laser Therapy Jackson Streeter PhotoThera, Carlsbad, CA; This paper appears in: Lasers and Electro-Optics Society, 2006. LEOS 2006. 19th Annual Meeting of the IEEE

Publication Date: Oct. 2006 On page(s): 665-666 ISBN: 0-7803-9555-7 INSPEC Accession Number: 9364378 Digital Object Identifier: 10.1109/LEOS.2006.278888 Current Version Published: 2007-01-15 ABSTRACT

The presentation covers fundamental operating principles of some of the most widely used methods of low-level laser therapy (LLLT). It includes also recently developed LLLT technologies and medical devices such as LLLT cardiovascular and brain therapy, tissue regeneration and pain relive. The mechanism of LLLT involving interaction with mitochondria. The effects of LLLT are wavelength specific upon a known mitochondrial receptor (cytochrome C oxidase). Targeting of this receptor results in formation of adenosine triphosphate (ATP), enhanced mitochondrial survival and maintenance of cytochrome C oxidase activity

Evaluation Of Quantum Therapy For The Treatment Of Stable Angina Likars'ka sprava. 2001; (5-6): 111-114.

[Otsinka efektyvnosti vplyvu kvantovoi terapii na perebig stabil'noi stenokardii]. A total of 68 patients were examined. Of these, 21 had functional class (FC) I stabile angina, 23 presented with FC II angina, 24 had FC III angina. Instituted in the control group patients (n = 30) was standard antianginal therapy (SAT). Laser therapy against the background of SAT employed has been found to improve the functional state of the myocardium, enhance tolerance to physical loads, improve indices for intracardiac hemodynamics. HeNe laser irradiation has an analgecizing effect. Patients with FC I-III exertional angina can derive benefit from laser therapy due to its cardioprotective effect. Positive hemodynamic shifts were accompanied by improvement in general health of patients manifested by lower frequency of angina attacks and episodes of pain-free ischemia of the myocardium. Laser therapy had an effect on relation between painful and painless ischemia of the myocardium as evidenced by a predominant decrease in painfree episodes of myocardial ischemia, this being regarded as a prognostically favourable fact.

[Clinico-Functional Efficacy Of Medicinal And Photon Stabilization Of Cell Membrane In Patients With Angina Pectoris] Klin Med (Mosk). 2003;81(1):24-7. [Article in Russian] Vasil'ev AP, Senatorov IuN, Strel'tsova NN, Gorbunova TIu.

Modification of erythrocytic membrane and the trend in clinicofunctional indices were studied in 90 patients with angina of effort (FC I-IV) in the course of treatment with a combination of membranoprotective drugs (group 1), magneto-laser radiation (group 2) and imitation of laser radiation (group 3). In patients of groups 1 and 2 the treatment resulted in stabilization of cell membrane accompanied with a hypotensive effect and increased exercise tolerance due to more effective cardiac performance.

Low-Power Helium-Neon Laser Irradiation Enhances The Expression Of VEGF In Murine Myocardium. Chin Med J (Engl). 2004 Oct;117(10):1476-80 Zhang WG, Wu CY, Pan WX, Tian L, Xia JL. Department of Anatomy and Histoembryology, Peking University Health Science Center, Beijing 100083, China. [email protected]

BACKGROUND: Low-power helium-neon (He-Ne) lasers have been increasingly widely applied in the treatment of cardiovascular diseases, and its vasodilation effect has been proven. The aim of this study was to determine the effects of low-power He-Ne laser irradiation directed at the precardial region of Wistar rats on capillary permeability in the myocardium and the expression of myocardial vascular endothelial growth factor (VEGF). METHODS: Sixteen rats were divided randomly into control and irradiated groups (n = 8, each). A He-Ne laser (632.8 nm) was applied to the irradiated group with a dose of 60.5 J/cm(2). Ferritin was perfused into the left femoral vein and capillary permeability was examined under an electron microscope. VEGF expression in the myocardium was investigated by immunohistochemical methods, RTPCR, and image analysis. RESULTS: The ultrastructures of the myocardial capillaries were examined. Compared to the control group, more high-density granules (ferritin), which were present within the capillary endothelium and the mitochondrions of myocardial cells in the internal layer of the myocardium, were observed in the irradiated group. VEGF staining of the myocardium was stronger in the irradiated group than that in the control group. The optic density of the irradiated group (0.246 +/- 0.015) was significantly higher than that of the control group (0.218 +/- 0.012, P < 0.05). Finally, the levels of RT-PCR products of VEGF165 mRNA were 2.79 times higher in irradiated rats than in the control rats. CONCLUSIONS: Our study demonstrates that He-Ne laser irradiation (in doses of 60.5 J/cm(2)) increases myocardial capillary permeability and the production of VEGF in myocardial microvessels and in myocardium. Our study provides experimental morphological evidence that myocardial microcirculation can be improved using He-Ne laser irradiation.

Fifteen-Year Experience With Low-Energy Laser Applications For Patient Treatment In Emergency-Care Clinics Nemtsev, Igor Z.; Lapshin, V. P. Proc. SPIE Vol. 2100, p. 284-291, Cell and Biotissue Optics: Applications in Laser Diagnostics and Therapy, Valery V. Tuchin; Ed.

Low energy lasers have been successfully applied for the treatment of more than 10 thousand patients in the Sklifosovsky Scientific Research Institute for Emergency Medicine. We have reviewed and generalized the results of clinical investigations of 34 patients with trauma of motor-locomotive system, 15 patients with muscular atrophy occurred as a result of lower extremity fracture immobilization, 124 patients with burns and of 88 post-infarction patients with ischemic heart disease, who underwent laser therapy with He-Ne laser, N2 Ultra-Violet and GaAs Infra-Red lasers.

Influence Of Low Dose Laser Herapy On Endothelial Function In Patients With Cad S. Belousov, E. Galperin, E. Smetova

The purpose of this study was the evaluation of arterial relaxation ability in 15 patients with CAD before and after the course of infrared laser therapy. 18 controls (healthy men). With highresolution ultrasound and impulse wave doppler we measured the increasing of volumic velocity flow (%) of the arteria poplitea at rest and during reactive hiperaemia (with increased flow causing endothelium-dependent dilatation). In controls flowmediated mean dilatation was normal. Endothelial dysfunction is present in majority of patients with CAD, flow-mediated dilatation was much reduced of absent. Course of infrared laser therapy was benefit to restore endothelial function in patients with CAD.

[Efficacy Of Laser Therapy In Patients With Ischemic Heart Disease] Vopr Kurortol Fizioter Lech Fiz Kult. 2003 Jul-Aug;(4):10-3. [Article in Russian] Vasil'ev AP, Strel'tsova NN, Senatorov IuN.

Modification of erythrocytic membrane and the trend in clinicofunctional indices were studied in 93 patients with angina of effort (FC i-IV) in the course of treatment with laser radiation (group 1) and imitation of laser radiation (group 2). In patients of group 1 the treatment resulted in stabilization of cell membrane accompanied with positive cardiodynamic changes.

[Diagnostic Implications Of Changed Red Cell Count In Low-Intensity Laser Radiation Of Blood In Elderly Patients With Coronary Heart Disease] Klin Med (Mosk). 2002;80(4):31-3. [Article in Russian] Simonenko VB, Siuch NI, Vokuev IA.

Intravenous laser therapy in combination with medication was conducted in 41 elderly patients with coronary heart disease (633 nm, 1 mW, 124 mW/cm2). The study of qualitative and quantitative (osmotic resistance) erythrocyte indices of blood demonstrated the change of erythrocyte number in circulating blood by the third laser procedure. Frequency of these changes correlated with duration of the treatment course. Intravenous laser therapy had a wider spectrum of effects on erythrocyte number than medication. Changes in erythrocyte number in the peripheral blood upon intravenous laser radiation reflects efficiency of treatment of coronary heart disease patients.

[The Efficiency Of Low-Intensity Laser Radiation In The Treatment Of Arterial Hypertension Complicated By Ischemic Heart Disease] Vopr Kurortol Fizioter Lech Fiz Kult. 2001 Jul-Aug;(4):3-6. [Article in Russian] Shuvalova IN, Klimenko IT, Svinina NG, Tsereteli MV, Zankina VG, Miasoed FR.

The efficiency of low-intensity laser radiation (LILR) was studied in the treatment of 291 patients with arterial hypertension and ischemic heart disease. Clinical grounds are given for use of LILR red and infrared rays in rehabilitation of hypertensive patients with ischemia. The rehabilitation regimens can be differentiated according to the disease severity, type of hemodynamics, state of cerebral circulation.

[Laser Irradiation In The Treatment Of Ischemic Heart Disease] Vopr Kurortol Fizioter Lech Fiz Kult. 2001 Nov-Dec;(6):10-3. [Article in Russian] Vasil'ev AP, Strel'tsova NN, Senatorov IuN.

Cardiodynamic changes due to beta-blocker carvedilol and low-intensity infrared laser radiation were compared in 115 patients with ischemic heart disease (IHD). The comparison has shown a similar positive effect on heart contractility and diastolic function. This gave arguments for feasibility of laser beam usage as a neurohormonal modulator in IHD patients to reduce cardiac remodulation and prevent cardiac failure.

[Antioxidant Action And Therapeutic Efficacy Of Laser Irradiation Of Blood In Patients With Ischemic Heart Disease] Vopr Kurortol Fizioter Lech Fiz Kult. 2003 May-Jun;(3):22-5. [Article in Russian] Volotovskaia AV, Ulashchik VS, Filipovich VN.

Laser irradiation in therapeutic doses (gamma = 632.8 nm, 14 mW) has an antioxidant effect in blood irradiation in vitro as shown by activation of superoxide dismutase (SOD) which is a key enzyme of the antioxidant system (AOS) and suppression of lipid peroxidation. Adjuvant supravascular He-Ne laser irradiation of blood in combined therapy of 82 patients with ischemic heart disease (IHD) produces a positive trend in the clinical picture, hemostasis, lipid metabolism, blood SOD activity. Thereby, this method of laser hemotherapy is recommended for use in IHD patients. The dependence of the treatment results on the initial blood AOS necessitates consideration of AOS state in deciding on laser therapy in this group of patients.

[Use Of Infrared Laser Therapy In Patients With Ischemic Heart Disease Associated With Diabetes Mellitus Type 2 In Health Resort] Vopr Kurortol Fizioter Lech Fiz Kult. 2002 Jul-Aug;(4):9-11. [Article in Russian] Zin'kovskaia TM, Zavrazhnykh LA, Golubev AD.

Infrared laser therapy (300 Hz) combined with balneotherapy and patients' education is more effective than standard sanatorium rehabilitation in patients with ischemic heart disease associated with diabetes mellitus type 2. 81.8% patients showed good response manifesting in less frequent anginal attacks, episodes of pain and painless ischemia and lower doses of antianginal drugs. Systolic and diastolic arterial pressure lowered by 18 and 10 mm Hg on the average, respectively. Multimodality rehabilitation of IHD patients with type 2 diabetes mellitus improves hemostasis, carbohydrate and lipid metabolism. Coronary circulation response lasted for 24 weeks.

Effects Of Laser Therapy On Ventricular And Supraventricular Extrasystoles In Patients With Angina Pectoris Of 1-3 Functional Classes V.A. Lyusov, K.G. Khutchumova, Y.N. Fedullaev The Russian Medical State University, Moscow, Russia

The aim of the present investigation is to study the effect of low level laser on extrasystoles. The amount of citrasystoles is registered before treatment and on the 10th day after the therapy. 64 patients with angina pectoris underwent laser therapy. We registered patients with more than 200 supraventricular extrasystoles and with more than 100 ventricular extrasystoles before our therapy. The treatment was carried out the keep of GaAs laser - "Elat" (890 nm) with pulse regime. The region of projection of carotid sinuses and heart were irradiated with pulse repetition rate 150 - 300 Hz with expositions 20 min. The amount of extrasystoles was counted by Holter monitor device. Laser therapy lessened supraventricular citrasystoles from 308,4±29,6 to 134,6±21,8 (p 0.05). The VAS scores were significantly lower in the laser group than the placebo group after treatment and at follow-up (p < 0.05). After 2 wk of treatment, no significant differences were found in grip strengths or for symptoms and functional assessments (p > 0.05). However, there were statistically significant differences in these variables at 2-wk follow-up (p < 0.05). Regarding the findings of NCS, there was no statistically significant difference between groups after treatment and at 2-wk follow-up. Conclusions: LLLT was

effective in alleviating pain and symptoms, and in improving functional ability and finger and hand strength for mild and moderate CTS patients with no side effects.

The Effects Of Low Level Laser In Clinical Outcome And Neurophysiological Results Of Carpal Tunnel Syndrome. Electromyogr Clin Neurophysiol. 2008 Jun-Jul;48(5):229-31. Shooshtari SM, Badiee V, Taghizadeh SH, Nematollahi AH, Amanollahi AH, Grami MT. Shiraz University of medical science, Shiraz, Iran. [email protected]

OBJECTIVES: Carpal tunnel syndrome (CTS) is the most common neuropathy that can be diagnosed with confidence by the nerve conduction study (NCS). One of the recent treatments of CTS is the application of low power laser (LPL) therapy. The present study evaluates the effects of LPL irradiation through NCS and clinical signs and symptoms. METHODS: A total of 80 patients were included in this study. Diagnosis of CTS was based on both clinical examination and electromyographic (EMG) findings. Patients were randomly assigned into two groups. Test group (group A) underwent laser therapy (9-11 joules/cm2) over the carpal tunnel area. Control group (group B) received sham laser therapy. Pain, hand grip strength, median proximal sensory and motor latencies, transcarpal median sensory nerve conduction (SNCV) were recorded. After fifteen sessions of irradiation (five times per week), parameters were recorded again and clinical symptoms were measured in both groups. Pain was evaluated by Visual Analog Scale (VAS; day-night). Hand grip was measured by Jamar dynometer. Paired t-test and independent sample t-test were used for statistical analysis. RESULTS: There was a significant improvement in clinical symptoms and hand grip in group A (p < 0.001). Proximal median sensory latency, distal median motor latency and median sensory latencies were significantly decreased (p < 0.001). Transcarpal median SNCV increased significantly after laser irradiation (p < 0.001). There were no significant changes in group B except changes in clinical symptoms (p < 0.001). CONCLUSIONS: Laser therapy as a new conservative treatment is effective in treating CTS paresthesia and numbness and improves the subjects' power of hand grip and electrophysiological parameters.

Effect Of Low Level Laser Therapy In Rheumatoid Arthritis Patients With Carpal Tunnel Syndrome. Swiss Med Wkly. 2007 Jun 16;137(23-24):347-52 Ekim A, Armagan O, Tascioglu F, Oner C, Colak M. Osmangazi University, Department of Physical Therapy and Rehabilitation, Eskisehir, Turkey.

OBJECTIVE: the aim of the present study was to evaluate the efficacy of low level laser therapy (LLLT) in patients with rheumatoid arthritis (RA) with carpal tunnel syndrome (CTS). MATERIAL AND METHODS: a total of 19 patients with the diagnosis of CTS in 19 hands were included and randomly assigned to two treatment groups; LLLT (Group 1) (10 hands) with dosage 1.5 J/ per point and placebo laser therapy group (Group 2) (9 hands). A GaliumAluminum-Arsenide diode laser device was used as a source of low power laser with a power output of 50 mW and wavelength of 780 nm. All treatments were applied once a day on week days for a total period of 10 days. Clinical assessments were performed at baseline, at the end of the treatment and at month 3. Tinel and Phalen signs were tested in all patients. Patients were evaluated for such clinical parameters as functional status scale (FSS), visual analogue scale

(VAS), symptom severity scale (SSS) and grip-strength. However, electrophysiological examination was performed on all hands. Results were given with descriptive statistics and confidence intervals between group means at 3 months adjusted for outcome at baseline and for the difference between unadjusted group proportions. RESULTS: clinical and electrophysiological parameters were similar at baseline in both groups. Improvements were significantly more pronounced in the LLLT group than placebo group. A comparison between groups showed significant improvements in pain score and functional status scale score. Group mean differences at 3 months adjusted at baseline were found to be statistically significant for pain score and functional status scale score. The 95% significant confidence intervals were [-15 (-5)] and [-5 - (-2)] respectively. There were no statistically significant differences in other clinical and electrophysiological parameters between groups at 3 months. CONCLUSIONS: our study results indicate that LLLT and placebo laser therapy seems to be effective for pain and hand function in CTS. We, therefore, suggest that LLLT may be used as a good alternative treatment method in CTS patients with RA.

Treatment Of Carpal Tunnel Syndrome By Low-Level Laser Versus Open Carpal Tunnel Release. Lasers Med Sci. 2007 Mar 3; [Epub ahead of print] • Elwakil TF, • Elazzazi A, • Shokeir H. Unit of General Surgery, National Institute of Laser Enhanced Sciences (NILES), Cairo University, Cairo, Egypt, [email protected].

Carpal tunnel syndrome (CTS) is an entrapment neuropathy of the median nerve at the wrist. It is one of the most common peripheral nerve disorders. The cause of idiopathic CTS remains unclear. The diagnosis of CTS is still mainly clinical. Open carpal tunnel release is the standard treatment. The present study was conducted to evaluate the effectiveness of low level laser treatment (LLLT) for CTS in comparison to the standard open carpal tunnel release surgery. Out of 54 patients, 60 symptomatic hands complaining of CTS were divided into two equal groups. Group A, was subjected to LLLT by Helium Neon (He-Ne) laser (632.8 nm), whereas group B was treated by the open approach for carpal tunnel release. The patients were evaluated clinically and by nerve conduction studies (NCSs) about 6 months after the treatment. LLLT showed overall significant results but at a lower level in relation to surgery. LLLT showed significant outcomes in all parameters of subjective complaints (p 0.05). Treatment with a dosage of 4 J/cm(2) exhibited more expressive results than that with 8 J/cm(2). In this study, the authors concluded that low-level laser therapy contributed to a larger expression of collagen and elastic fibers during the early phases of the wound healing process.

Combining Nanotechnology with LLLT Combining Nanotechnology With LLLT: Visions For The Next Ten Years Used by the kind permission of the Czech Society for the Use of Laser in Medicine, www.laserpartner.org Laser Partner, 3.6.2002 Andrei P. Sommer, Department of Biomaterials, ENSOMA-Lab, Central Institute of Biomedical Engineering, University of Ulm, Germany [email protected] ABSTRACT

Theoretical paper on the importance of direct research of molecular mechanisms in individual cells induced by irradiation with laser beam. New possibilities of cells imaging through Nearfield optical analysis contribute to a detailed understanding of phenomenons in laser stimulated cells. Wound healing via laser light goes back to Prof. Endre Mester. First reports on his pioneering work started in 1967. For biostimulation he used the coherent light of powerful 50mW He/Nelasers (632.8nm). The Mester group has been continuously successful from the beginning. But only a minority of researchers could reproduce the success of the biostimulation experiments. 33 years after introducing the paradigm of photobiostimulation, the LILAB-equation has been anchored into LLLT [1] – establishing the biological limits of the dose (energy density) and the light intensity. Recent laboratory experiments, demonstrating that various individually administered wavelengths of laser light applied at energy densities of the same order induced comparable biological effects in rats, could be interpreted as additional evidence in support of the LILAB-equation [2]. During the 1st NOA Conference [3] a multidisciplinary group of ten scientists from Brazil, Denmark, Finland, France, Germany, Hungary, Israel, Saudi Arabia and U.S.A. evaluated possibilities of validating LLLT. One of the discussed visions has been to directly investigate the molecular mechanisms of light-induced wound healing processes occurring in LLLT via Nearfield Optical Analysis (NOA). The vision has been so promising that Attila Pavláth – President ACS – became eventually interested in supporting the group, and the ACS officially cosponsored the 1st NOA Conference for "evaluating the molecular mechanism of accelerated and normal wound healing processes", thus ignoring the insurmountable gap which persisted

between the vision and the experimental possibilities: Nearfield Optical Analysis (NOA) via Nearfield Scanning Optical Microscopy (NSOM) existed since 10 years, however, nobody has so far succeeded to image a living cell under physiological conditions with this method. Two particular reasons seemed to oppose any substantial progress: the problem of operations in aqueous environments, and the "low optical contrast", characteristic of optically investigated unlabeled living cells. The first problem has been solved at the European Nearfield Scanning Optical Microscopy (ENSOMA) Laboratory by the use of hydrophobically coated biosensors, and the milestone could be presented during the 1st NOA Conference in November 2000 [4]. NSOM [5] has produced highest optical resolution that has ever been achieved, a method exploiting the energy transfer from the tip of an optical element (tip diameter > 20nm) oscillating within the characteristic range of the energy transfer (~ 10nm) in the nearfield of the surface to be analyzed. Irradiation-induced energy transfer between excited molecules (emitter) and receptor molecules (acceptor) positioned in the proximity of the emitter molecules via spacer molecules, has been confirmed experimentally (Kuhn, 1970). During the 2nd NOA Conference, held in May 2001, and cosponsored by NASA and DARPA: 2nd International NASA/DARPA Photobiology Conference on Nearfield Optical Analysis (NOA), at the National Aeronautics and Space Administration – Johnson Space Flight Center (NASA-JSC), Houston, TX, U.S.A., we went, en route to solve the "low optical contrast" problem, one step further and demonstrated that clear NOA images could be obtained from nanobacteria in an aqueous environment – an encouraging advance [6]. The 2nd NOA – with more than 40 international photobiology peers – promoted both LLLT and NOA, with the special result that LLLT/LILAB could advance in less than six month to scientific acceptance in three fields: civil, military and space relevant. The scientific breakthrough came just before the 3rd NOA (Brazil, June, 2002) in form of the publication of clear nanoscale images of human dentin in an aqueous environment [7], and the very first images of living endothelial cells in liquid cell culture medium [8], thus opening an optimistic perspective to a direct analysis of LLLT mechanisms. The cells were attached to polished titanium discs and analysed with hydrophobically coated optical biosensors mounted to a conventional NSOM microscope. We are presently in an era where cellular imaging and photobiology is becoming important to wide ranging disciplines. The recent advances in NOA have provided us with the technology necessary for identifying relationships between cellular activities and various photonic stimuli – on Earth and in space. Cellular imaging of living cells via NOA has been recognized as extremely beneficial, in particular for biomedical applications [3] and in tissue bioengineering [9]. Our vision, presumably realizable via NOA, could be generalized as: Time resolved analysis of the LLLT induced molecular mechanisms in living cells, with the light energy densities and intensities conform to the LILAB-equation, and with different wavelengths of coherent and non-coherent light, allowing to systematically understand and optimise the LLLT parameters. REFERENCES 1. Sommer, A.P, Pinheiro, A.L.B., Mester, A.R., Franke, R.P., Whelan, H.T. Biostimulatory, Windows in Low Intensity Laser Activation: Lasers, Scanners and NASA‘s Light Emitting Diode Array System. J. Clin. Laser Med. & Surg., 19, 29-33, 2001. (Medline) 2. Al-Watban, F. Comparison between Laser Therapy and Pharmacological Treatments in Accelerating Wound Healing - an extended study in: Proc. 2nd International conference on

nearfield optical analysis: photodynamic therapy & photobiology effects. Johnson Space Flight Center, May 2001, Houston, TX, NASA Conference Publication, in press. 3. Preface, Proc. 1st International Workshop on Nearfield Optical Analysis, Reisensburg, Germany, November 2000, (ed. A.P. Sommer) J. Clin. Laser Med. & Surg., 19, 109-112, 2001. 4. Sommer, A.P. Components for NOA of Biosystems and Nanoscale Resolution, in: Proc. 1st International Workshop on Nearfield Optical Analysis, Reisensburg, Germany, November 2000, (ed. A.P. Sommer), J. Clin. Laser Med. & Surg., 19, 112, 2001. 5. For a schematic of NSOM and a short principle explanation see: http://www.ensoma.net (click on the Greek letters l and n in the middle). 6. Sommer, A.P. Nearfield Optical Analysis (NOA) via Hydrophobic Optical Elements & Low Intensity Light Activated Biostimulation (LILAB) Effect of NOA. Proc. 2nd International conference on near-field optical analysis: photodynamic therapy & photobiology effects. Johnson Space Flight Center, May 2001, Houston, TX, NASA Conference Publication, in press. 7. Sommer, A.P., Franke, R.P. Hydrophobic optical elements for near-field optical analysis (NOA) in liquid environment – a preliminary study. Micron, 33, 227-231, 2002. (Medline) 8. Sommer, A.P., Franke R.P. Near-Field Optical Analysis of Living Cells in Vitro. Journal of Proteome Research, 1, 111-114, 2002. (ACS/ASAP-article) 9. A.P. Sommer, Novel Low Intensity Light Activated Biostimulation Paradigm, in: Abstracts of the Second Congress of the North American Association for Laser Therapy & First Consensus Conference on Laser Medicine, Photobiology and Bioengineering of Tissue Repair, Atlanta, GA, March 2002.

Contraindications of Low Level Laser Therapy Contraindications In Noninvasive Laser Therapy: Truth And Fiction. J Clin Laser Med Surg. 2002 Dec;20(6):341-3. Navratil L, Kymplova J. University of South Bohemia, Faculty of Social and Health Studies, Section of Radiobiology and Toxicology, Department of Radiology, Ceske Budejovice, Prague, Czech Republic. [email protected]

OBJECTIVE: Noninvasive laser therapy is a treatment method employed in many disciplines. This review article points out instances when it appears to be effective to administer such therapy. MATERIALS AND METHODS: Noninvasive laser therapy has a number of suitable applications that cause minimal damage to the patient. Many patients are not sent to institutions equipped with relevant instruments, since physicians are burdened by a number of contraindications, many of which are incorrect. The purpose of this article was to divide these contraindications into the following three groups: correct indications, indications doubtful under certain conditions, and incorrect indications. DISCUSSION: We consider the following contraindications as correct: history of a histologically demonstrated malignant carcinoma; irradiation of the neck region in hyperthyreosis; epilepsy; exposure of the retina; and exposure of the abdomen during pregnancy. The contraindications that are doubtful under certain conditions are as follows: fever and infectious diseases; certain blood diseases; heavy blood losses;

neuropathies; and irradiation in the region of gonads. The other contraindications reported in the literature are considered to be incorrect.

Coronary Stent Implantation Optimal Dosing Of Intravascular Low-Power Red Laser Light As An Adjunct To Coronary Stent Implantation: Insights From A Porcine Coronary Stent Model. J Clin Laser Med Surg. 2001 Oct;19(5):261-5. De Scheerder IK, Wang K, Zhou XR, Szilard M, Verbeken E, Ping QB, Yanming H, Jianhua H, Nikolaychik V, Moses JW, Kipshidze N, Van de Werf F. University Hospitals, Leuven, Belgium.

BACKGROUND: It is believed that restenosis following coronary interventions is the result of endothelial denudation that leads to thrombus formation, vascular remodeling, and smooth muscle cell proliferation. Low-power red laser light (LPRLL) irradiation enhances endothelial cell growth in vitro and in vivo, and reduces restenosis in animal models. The present study investigated the optimal dose of intravascular LPRLL therapy in the prevention of in-stent stenosis in a porcine coronary stent model. METHODS AND RESULTS: Selected right coronary artery segments were pretreated with a LPRLL balloon, delivering a dose of 0 mW during 1 min (group 1, n = 10), 50 mW during 1 min (group II, n = 10), or 100 mW during 1 min (group III, n = 10) before stenting. Quantitative coronary analysis of the stented vessel was performed before stenting, immediately after stenting, and at 6 weeks follow-up. The pigs were sacrificed, and histologic and morphometric analyses were conducted. At 6 weeks, minimal luminal stent diameter was significantly narrower in the control group compared to the 50-mW dose group (p < 0.05). These results were confirmed by morphometric analysis. Neointimal area was also significantly decreased in the 50-mW dose group. CONCLUSIONS: Intravascular LPRLL contributes to reduction of angiographic in-stent restenosis and neointimal hyperplasia in this animal model. The optimal dose using the LPRLL balloon system seems to be approximately 5 mW delivered during 1 min.

Intravascular Red Light Therapy After Coronary Stenting N Angiographic And Clinical Follow-Up Study In Humans. J Invasive Cardiol. 1998 Nov;10(9):534-538. Kaul U, Singh B, Sudan D, Ghose T, Kipshidze N. Director, Interventional Cardiology, Batra Hospital and Medical Research Centre 1, Tughlakabad Institutional Area, Mehrauli Badarpur Road, New Delhi-110 062, India.

In animal models of coronary restenosis, intravascular red light therapy (IRLT) using a diode laser source has been shown to reduce neointimal hyperplasia following ballooninduced injury and coronary stenting. We studied the safety and efficacy of catheterbased IRLT for preventing restenosis after coronary stenting in 22 patients with angina pectoris. IRLT was performed using a diode laser (650 nm) at an energy level of 10 megawatts delivered through a rapid exchange balloon system containing the fiberoptics. The procedure was successful in all patients, with no procedural or in-hospital complications. Two patients with recurrence of symptoms had

angiography at 3 and 4.1 months respectively. Angiographic follow-up was also done after 6 months in the 20 remaining asymptomatic patients. The mean minimal lumen diameter (MLD) for the whole group at 6 months follow-up was 2.57 +/- 0.62 mm. The calculated late lumen loss was 0.49 +/- 1.12 mm with a late loss index of 0.21 +/- 0.54. Four patients (2 symptomatic and 2 asymptomatic) in the series developed angiographic restenosis. Clinical events at follow-up of 10.9 +/- 3.5 months were repeat angioplasty in 2 patients for symptomatic restenosis with a 91% event free survival. These preliminary results demonstrate that IRLT after coronary artery stenting is safe and feasible; it is associated with low rates of angiographic indices of restenosis

Dental Effect Of Soft Laser And Bioactive Glass On Bone Regeneration In The Treatment Of Infra-Bony Defects (A Clinical Study). Lasers Med Sci. 2009 May;24(3):387-95. Epub 2008 Jun 26. AboElsaad NS, Soory M, Gadalla LM, Ragab LI, Dunne S, Zalata KR, Louca C. Department of Oral Medicine and Periodontology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt.

This study aimed to investigate the influence of low-power 830 nm gallium-aluminiumarsenide (GaAlAs) laser [continuous wave (CW) 40 mW and fluence 4 J/cm(2), with total energy density of 16 J/cm(2)] on the healing of human infra-bony defects treated with bioactive glass graft material. Twenty patients with chronic periodontitis and bilateral infrabony defects were included. Using a split mouth design, we treated 20 defects with bioactive glass plus laser irradiation during surgical procedures and on days 3, 5, 7 postoperatively; 20 contra-lateral defects were treated with bioactive glass only. Clinical probing pocket depths, clinical attachment levels and standardized periapical radiographs were recorded at baseline and at 3 months and 6 months postoperatively. At 3 months there was a statistically significant difference between the laser and non-laser sites in the parameters investigated. However, at 6 months, no difference was observed. Our results have confirmed the positive effect of soft laser in accelerating periodontal wound healing.

Low Level Laser Treatment (LLLT) During & After Multiple Teeth Extirpations- Randomised Clinical Study With Control Group EMLA Laser Health J 2007;2:46-67 European Medical Laser Association (EMLA) Z. Simunovic 1, K. Simunovic 2 1. Pain Clinic - Laser Center, Switzerland 2. Private Dental Practice, Switzerland

Multiple teeth extraction is a dental surgical procedure, which is sometimes followed by complications like haemorrhage, oedema, pain and inflammation, leading to intake of related drugs, usually analgesics. The current clinical study was conducted in order to observe the efficacy of LLLT applied during and immediately after multiple teeth extractions. Study Design - Irradiation Parameters: Total number of patients: 40, randomly allocated to two groups (20 p. - irradiated, Energy density applied: 4J/cm 2 HeNe laser & IR Laser; 20 p.- control

group, no laser irradiation). The following parameters were observed: haemorrhage, oedema, redness and pain. The presence of each parameter was scored as follows: absent (0 point), mild (5 points), moderate (10 points), severe (15 points), worst (20 points). The difference was calculated for each evaluated parameter, and demonstrated significance in favour of LLLT (p 0.9). Thus, ILIB not only increases tolerance to exercise in patients with severe stable effort angina, but also it is not decreases the antianginal effect of nitroglycerin.

[Use Of Infrared Laser Therapy In Patients With Ischemic Heart Disease Associated With Diabetes Mellitus Type 2 In Health Resort] Vopr Kurortol Fizioter Lech Fiz Kult. 2002 Jul-Aug;(4):9-11. [Article in Russian] Zin'kovskaia TM, Zavrazhnykh LA, Golubev AD.

Infrared laser therapy (300 Hz) combined with balneotherapy and patients' education is more effective than standard sanatorium rehabilitation in patients with ischemic heart disease associated with diabetes mellitus type 2. 81.8% patients showed good response manifesting in less frequent anginal attacks, episodes of pain and painless ischemia and lower doses of antianginal drugs. Systolic and diastolic arterial pressure lowered by 18 and 10 mm Hg on the average, respectively. Multimodality rehabilitation of IHD patients with type 2 diabetes mellitus improves hemostasis, carbohydrate and lipid metabolism. Coronary circulation response lasted for 24 weeks.

[Helium-Neon Laser Therapy In The Combined Treatment Of Unstable Stenocardia] Sov Med. 1990;(3):12-5. [Article in Russian] Korochkin IM, Kapustina GM, Babenko EV, Zhuravleva NIu.

He-Ne laser therapy included in complex of therapeutic methods for patients with unstable angina pectoris is a highly effective treatment modality; it helps essentially reduce the risk of acute myocardial infarction in these patients. Clinical efficacy of laser therapy is confirmed by its favorable action on hemostasis plasma factors, consisting in reduction of fibrinogen level, normalization of antithrombin-III (AT-III), decrease of the level of soluble fibrinomonomer complexes, this indicating a lowering of the blood coagulation potential. Absence of significant changes in plasminogen level may be an indicator of the nonenzymic route of fibrinogen system activation. Sessions of intravenous laser therapy should be administered 2-3 times a week to unstable angina pectoris patients with low AT-III levels, whereas for patients with initially high or normal AT-III levels combined laser therapy is advisable (4-5 daily invasive procedures and 6-8 skin surface ones on the Zakharyin-Head's zones). Measurements of endogenic anticoagulants is an effective means for monitoring laser therapy in this patient population.

[The Effect Of Different Methods Of Photohemotherapy On The Rheological Properties Of The Blood In Patients With Ischemic Heart Disease] Vestn Khir Im I I Grek. 2000;159(2):60-4. [Article in Russian] Gavrisheva IA, Dutkevich IG, Pleshakov VT, Kolesnik VS.

The authors made an analysis of results of examination of 41 patients with ischemic heart disease treated by the standard medicamentous therapy and when using different methods of photohemotherapy against its background. It was established that medicamentous therapy during 2 weeks failed to result in a substantial improvement of rheological properties of blood, while its combination with photohemotherapy could give a considerable positive effect coinciding with clinical improvement of the patient's state. Shorter terms are required to correct hemorheological indices when autotransfusions of photomodified blood are used.

[The Effect Of Different Types Of Laser Therapy On The Reactivity Of The Peripheral Blood Neutrophils In Patients With Ischemic Heart Disease] Vopr Kurortol Fizioter Lech Fiz Kult. 1995 Jan-Feb;(1):5-7. [Article in Russian] Siuch NI, Illarionov VE.

The responses to laser therapy (intravenous, continuous skin exposure without a magnet, magnetic laser therapy) of 83 patients with coronary heart disease aged 50-80 demonstrated the advantages of noninvasive laser irradiation of blood. Myeloperoxidase activity may serve a criterion for estimating the number of irradiation procedures needed.

[Changes In Central Hemodynamics And Microcirculation During Laser Therapy In Patients With Coronary Insufficiency] Kardiologiia. 1993;33(2):22-3. [Article in Russian] Gel'fgat EB, Samedov RI, Kurbanova ZN, Gadzhiev GG.

The study was undertaken to examine 45 patients with Stages IIB-III heart failure (HF) by the classification developed by V. Kh. Vasilenko and N. D. Strazhesko. Thirty patients had laser therapy in addition to the routine treatment, 15 patients served as a control group. The combined drug treatment along with laser therapy in patients substantially improved peripheral circulatory parameters than in the controls. There was a positive dynamics of central hemodynamic parameters as shown by lower left ventricular volumes and higher myocardial contractile and pump functions. Improvement of microcirculatory and central hemodynamic parameters in patients treated with laser occurred in earlier periods of hospital stay than in the controls.

[The Laser Therapy Of Patients With Hypertension In Combination With Coronary Insufficiency] Vopr Kurortol Fizioter Lech Fiz Kult. 1996 Mar-Apr;(2):3-5. \ [Article in Russian] Kniazeva TA, Badtieva VA, Zubkova SM.

Hypertensive patients with coronary insufficiency have received infrared (lambda = 0.85 microns) laser radiation to the skin. The treatment is shown to have antianginal, antihypertensive effects, to improve cardiac performance, myocardial contractility, to increase myocardial, coronary and aerobic reserves. This clinicofunctional efficacy is accompanied by positive shifts in lipid metabolism, lipid peroxidation activity, antioxidant defense, hemocoagulation and microcirculation.

Hepatitis [Comparative efficacy of various methods of laser therapy in patients with acute viral hepatitis B] Ter Arkh. 2001;73(11):26-30. [Article in Russian] Makashova VV, Poliakova AM, Maleev VV, Astrina OS, Shatrun TM.

AIM: To study response to laser therapy in different modes and effects on hemocoagulation in patients with acute viral hepatitis B (AVHB). MATERIAL AND METHODS: Of 173 patients with AVHB, 87 received only basic therapy, 28 patients received placebo (no laser radiation, only signal of the timer) and 58 patients were exposed to laser radiation (32 of them intravenously and 26 supravenously). A course consisted of 10-12 sessions, laser radiation per 1 procedure 300 and 30 mJ, respectively. In addition to routine examinations, hemocoagulation was studied (platelet aggregation and desaggregation, electrocogulogram). RESULTS: Intoxication, hemorrhagic phenomena, jaundice, infusion therapy, hospital stay were shorter in AVHB patients exposed to laser therapy. Mode of action (intra- or supravenous) was

insignificant. CONCLUSION: Laser therapy normalizes hemostasis and platelet function. Clinical effectiveness of laser was the same in both modes.

Herpes Laser Therapy Of Human Herpes Simplex Lesions Used by the kind permission of the Czech Society for the Use of Laser in Medicine, http://www.laserpartner.org/ Arturo Guerra Alfonso, Pedro José MuZoz Clinic “Leonardo Fernández Sánchez“, Cienfuengos, Cuba ABSTRACT

Herpes Simplex is rather a widespread illness caused by human herpes virus generally combining primary lesions with periods of latency. The authors evaluate results of treatment with a low power laser and with classical antivirals. Obtained results are demonstrated in attached tables. By way of illustration the editor also attached a series of images showing typical history of a herpes lesion treated with a laser. INTRODUCTION

Herpes Simplex is an illness caused by the human herpes virus types 1 and 2 that generally present a primary lesion, with periods of latency and a tendency to relapse. It is also known as Button of fever or Bladder of fever. According to the World Health Organisation (WHO) an international prevalence of about 60 % is observed (1, 2). An experimental study was carried out, where 232 patients affected by the Herpes Simplex type 1 virus were treated. All patients attended the clinic „Leonardo Fernández― in Cienfuengos during the period of January 2001 to January 2003, with the objective of determining the time of recurrence of labial herpes in the groups, studied before and after treatment, and to evaluate the effectiveness of low power laser in the treatment of the infection of the virus. MATERIALS AND METHODS

Two groups were selected (study and control) with 116 patients in each group, distributed and classified according to the clinical stage in which they went to consultation. In the study group the patients were offered treatment with a GaAlAs diode laser (670 nm / 30 mW - 40 sec) in the prodromal stage and the stage of vesicles; or (670 nm /20 mW - 2 min) in the crust stage and in infections infected secondarily. To all these patients radiation among vertebras C2 - C3, where the resident ganglion of the virus is located during the latent periods (670 nm / 30 mW - 30 sec), was also applied. Control group was offered indicated treatment with antivirals (Aciclovir in cream and in pills) and other paliative therapies. After having carried out the analysis of the data obtained, the following results were obtained:

Table 1: Patients of the study group, distribution according to the frequency of annual recurrence of the labial herpes before and after laser therapy.

When analysing Table 1 it is observed that the groups of patients suffering from herpes with high frequencies of recurrence (after being treated with laser an waiting one year prior to evaluation of the effectiveness) reported recurrence for more elongated periods of time and 32 patients did not even have any more recurrence.

Table 2: Patients of the control group, distribution according to the annual recurrence frequency of labial herpes before and after treatment.

In Table 2 the same previous aspects are reflected but in the control group. As it can be observed the cases diminished in number, although discreetely; those that presented more recurrence and of equal number of recurrencies increased in number of patients in the periods of more lingering recurrence. In this group 2 patients reported not having had any more lesions during the analyzed year.

Table 3: Patients of both groups, distribution according to annual recurrence frequency of labial herpes after receiving treatment.

Table 3 compares both groups as for annual frequency of recurrence after having received corresponding treatment. When analyzing this, superiority of the group treated with laser becomes evident.

Table 4: Patients of both groups, distribution with relation to the clinical stage in which we intervened and the time of cure of the same ones.

As it can be observed in Table 4, in the study group 100 % of the prodromal stages, 95 % of the vesicular ones, and 91 % of the crust stages were able to cure during the first 48 hours. Patients with lesions infected secondarily needed more than 48 hours to cure, although they never surpassed 5 days. These results, although astonishing, are corroborated by authors like Tunér and Schindl, where they highlight that treatment with a laser in the initial stages of Herpes Labialis has a percentage of superior success compared to conventional treatment, besides achieving an almost immediate relief of the symptoms (3, 4). In the control group remarkable differencies are appreciated when comparing them with that of the study group. Therapy with Aciclovir in early stages (first 72 hours) has b een broadly suitable for many professionals and their use against Herpes Labialis has been studied by some authors (5).

CONCLUSIONS

Periods of annual recurrence in the study group were prolonged considerably after having received treatment, whilst in the control group such evident changes were not shown. In the prodromal period the patients treated with laser all healed up in the first 48 hours, whilst those treated conventionally needed from 3 to 4 days to cure. In the vesicular period and the period of crust, those of the study group cured in majority in the first 48 hours, whilst those of the control group needed more than 5 days. In infected lesions those treated with laser cured mainly in 3 to 4 days, whilst those treated with medication needed more than 7 days to cure. REFERENCES 1. Santana, J. C.: Altas of pathology of the buccal complex, Havana: Editorial scientifictechnique, 1985:30-34 2. Eversole, L. R.: Buccal pathology, Diagnosis and Treatment, Havana: Editorial scientifictechnique, 1985:82-87 3. Tunér, J., Hode, L.: Low Level Laser Therapy - clinical practice and scientific background, 1999, ISBN 91-630-7616-0 4. Parker, J. et al.: The effects of laser therapy on tissue repair and pain control: a metaanalysis of literature, Proc. Third Congress WALT, Athens, Greece, May 10-13, 2000, p. 77 5. Vélez-González, M. et al.: Treatment of relapse in herpes simplex on labial and facial areas and of primary herpes simplex on genital areas and area pudenda with low power He-Ne laser or Acyclovir administered orally, SPIE Proc. 1995, Vol. 2630:43-50 6. Garrigó M. I., Valiant C.: Biological effects of radiation of low power laser in the repair histica, Rev. Cub. Estomat, 1996:33 (2) 7. Simunovic, Z.: Lasers in Medicine and Dentistry, Vitagraf, Croatia, 2000. ILLUSTRATIONAL IMAGES Fig. 1: Herpes Day 1 (occurrence)

Fig. 2: Herpes Day 1+ (first laser treatment)

Fig. 3: Herpes Day 2 (morning, condition after 2 treatments)

Fig. 4: Herpes Day 2+ (afternoon, condition after 3 treatments)

Fig. 5: Herpes Day 3 (afternoon, cured after 4 treatments)

Low-Intensity Laser Therapy Is An Effective Treatment For Recurrent Herpes Simplex Infection. Results From A Randomized Double-Blind Placebo Controlled Study. Schindl A, Neuman R.

J Investigative Dermatology. 1999; 113 (2): 221-223. 50 patients with recurrent perioral herpes simplex infections (at least once a month for more than 6 months) were treated with 690 nm, 80 mW laser, 48 J/cm2, in a double blind study. Patients received daily irradiations for two weeks, 10 treatments. The treatment was given in a recurrence-free period and the irradiation was given at the site of the original herpes simplex infection. If both lips were involved, both upper and lower lips were treated. Patients were monitored for 52 weeks. The mean recurrence-free interval in the laser group was 37.5 weeks (range; 2-52 weeks) and in the placebo group 3 weeks (range 1-20 weeks). No side effects were noted.

Double Blind Crossover Trial Of Low Level Laser Therapy In The Treatment Of Post Herpetic Neuralgia Kevin C Moore Naru Hira. Parswanath S. Kramer, Copparam S. Jayakumar and Toshio Oshiro

Post herpetic. neuralgia can he an extremely painful condition which in many cases proves resistant lo all the accepted forms of treatment. II is frequently most severe in the elderly and may persist for years with no predictable course. This trial was designed as a double blind assessment of the efficacy of low level laser therapy in the relief of the pain of post herpetic neuralgia with patients acting as their own controls. Admission to the trial was limited to patients with . established post herpetic neuralgia of at least six months duration and who had shown little or no response to conventional methods of treatment. Measurements of pain intensity and distribution were noted over a period of eight treatments in two groups of patients each of which received tour consecutive laser treatments. The results ides demonstrate a significant reduction in both pain intensity and distribution following a course of low level laser therapy.

Efficacy Of Laser Irradiation On The Area Near The Stellate Ganglion Is Dose-Dependent: Double-Blind Crossover Placebo-Controlled Study Toshikazu Hashimoto, Osamu Kemmotsu, Hiroshi Otsuka, Rie Numazawa, and Yoshihiro Ohta, Department of Anaesthesia, Hokkaido University Hospital, Sapporo, Japan

In the present study we evaluate the effects of laser irradiation on the area near the stellate ganglion on regional skin temperature and pain intensity in patients with postherpetic neuralgia. A double blind, crossover and placebo-controlled study was designed to deny the placebo effect of laser irradiation. Eight inpatients (male 6, female 2) receiving laser therapy for pain attenuation were enrolled in the study after institutional approval and informed consent. Each patient received three session s of treatment on a separate day in a randomised fashion. Three minutes irradiation with a 150 mW laser (session 1), 3 minutes irradiation with a 60 mW laser (session 2), and 3 minutes placebo treatment without laser irradiation Neither the patient nor the therapist was aware which session type was being applied until the end of the study. Regional skin temperature was evaluated by thermography of the forehead, and pain intensity was recorded using a visual analogue scale(VAS). Measurement were performed before treatment,

immediately after (0 minutes) then 5, 10, 15, and 30 min after treatment. Regional skin temperature increased following both 150 mW and 60mW laser irradiation, whereas no changes were obtained by placebo treatment. VAS decreased following both 150 mW and 60 mW laser treatments, but no changes in VAS were obtained by placebo treatment. These changes in the temperature and VAS were further dependent on the energy density, i.e the dose. Results demonstrate that laser irradiation near the stellate ganglion produces effects similar to stellate ganglion block. Our results clearly indicate that they are not placebo effects but true effects of laser irradiation.

Efficacy Of Low Reactive-Level Laser Therapy For Pain Attenuation Of Postherpetic Neuralgia Addressee for Correspondance: Toshikazu Hashimoto MD, Department of Anesthesia, I Hokkaido University I Hospital N15, W7, Kita-ku Sapporo, Japan 060. 3/97 Rep US $ 8-10 12 ©1997 by LT Publishers l. .K., Ltd. LASER THERAPY 1997:9:7-- 12 Osamu Kemmotsu, Kenichi Sato,Hitoshi Furumido, Koji Harada, Chizuko Takigawa, Shigeo Kaseno, Sho Yokota, Yukari Hanaoka and Takeyasu Yamamura Department of Anaesthesiology, Hokkaido University School of Medicine, N-15. W-7, Kita-ku. Sapporo 060, Japan.

The efficacy of low reactive-level laser therapy (LLLT) for pain attenuation in patients with postherpetic neuralgia (PHN) was evaluated in 63 patients (25 males. 38 females with an average age of 69 years) managed at our pain clinic over the past four years. A double blind assessment of LLLT was also performed in 12 PHN patients. The LLLT system is a gallium aluminum arsenide (GaAlAs) diode laser (830 nm, 60 mW continuous wave). Pain scores (PS) were obtained using a linear analog scale (i) to 10))) before and after LLLT. The immediate effect after the initial LLLT was very good (PS: (}3) in 26, and good (PS: 7-4) in 30 patients. The longterm effect at the end of LLLT (the average number of treatments 36 + 12) resulted in no pain (PS: 0) in 12patients and slight pain (PS: 1-4) in 46 patients. No complications attributable to LLLT occurred. Although a placebo effect was observed, decreases in pain scores and increases of the body surface temperature by LLLT were significantly greater than those that occurred with the placebo treatment. Our results indicate that LLLT is a useful modality for pain attenuation in PHN patients and because LLLT is a noninvasive, painless and safe method of therapy, it is well acceptable by patients. Addressee for correspondence: Osamu Kemmotsu, Department of Anaesthesiology,Hokkaido University School of Medicine, N-15, W-7, Kita-ku, Sapporo 060,Japan. 0898-5901/91/020071-05$05.00 Ì 1991 by John Wiley & Sons, Ltd.

Hyperlipidemia Effect Of Low-Intensity Laser Radiation On Lipid Metabolism And Hemostasis In Patients With Myocardial Infarction Vopr Kurortol Fizioter Lech Fiz Kult. 2006 Mar-Apr;(2):6-8. [Article in Russian] Kemalov RF.

Progression of coronary atherosclerosis often causes complications resulting in myocardial infarction, early disability and death of patients with coronary heart disease. Low efficacy of medicines against coronary atherosclerosis progression after myocardial infarction gave rise to investigations of nonpharmacological methods, laser radiation, in particular. Our study shows a noticeable positive effect of low-intensity laser radiation on blood lipid spectrum and hemostasis. This makes laser therapy promising in combined rehabilitation of postmyocardial infarction patients.

[Laser Correction Of Microcirculation Disorders In Patients Having CHD With Hypercholesterinemia] Klin Med (Mosk). 2005;83(2):33-7. [Article in Russian] Vasil'ev AP, Sekisova MA, Strel'tsova NN, Senatorov IuN.

The study demonstrates that hypercholesterinemia in patients with coronary heart disease (CHD) is associated with functional depression of microcirculation, increase in total peripheral vascular resistance, reduction in the functional efficiency of heart and decrease in activity tolerance. After receiving a course of low-intensity infrared laser radiation treatment the patients displayed positive changes in blood lipid spectrum, which was associated with improvement in microcirculation, decrease in afterload, increase in economization of heart functioning and activity tolerance. The obtained results demonstrate that the hypolipidemic effect of laser radiation is a substantial factor in the regression of CHD manifestations.

Dynamics Of Hyperlipidemia And Peripheral Blood Flow In Patients With Diabetes Mellitus After The Course Of Combined Laser Therapy In Ambulatorypolyclinic Conditions T.V. Kovalyova, A.V. Farvayeva, L.T. Pimenov, S.M. Denisov Medical Academy, 2nd Municipal Out-Patient Department, Izhevsk, RF Russian Medical University, 13th State Clinic Hospital, Moscow, RF

The problem of metabolic-vascular disturbances in patients with diabetes mellitus still is one of the most important in clinic of inner diseases. In the course ofLT 218 patients, between 19-67 years of age, with diabetes mellitus (the period of observation is 7 years) have been investigated. Among them 93 had the 1st type of DM, 125 - the lind type. The absolute majority of the patients had a compensation or subcompensation of diabetes. To estimate peripheral blood flow we used doppler-and/or rheovasography. 57 patients underwent a conjuctival biomicroscopy, In all patients we examined total blood cholesterol (TC), in a part of the patients • triglycerides, LDL and HDL cholesterol level. We also controlled glycemia and peripheral blood flow. For the treatment we used intravenous laser blood irradiation (ILBI) by continuous He- Ne irradiation (wavelength - 0,63 mm, power at the light-guide end - 2 mW). Simultaneously we performed percutaneous procedure by low-energy laser irradiation (apparatus 'MUSTANG') with the wavelength - 0,89 mm, power - from 5 to 20 mW on shin muscles (dose 4,5 J, frequency 80 Hz), liver, pancreas, spleen projections (frequency 150 Hz), 4 min on each zone, 8-10 procedures, daily. Repeated courses were given in 3 and 6 months. Sugarcorrecting medications were decreased 2 times in combination with antioxidant AEVIT. From the first days of treatment the patients' extremeties grew warmer, decreased the pain syndrome, disappeared the symptoms of encephalopathy. Together with the subjective rehabilitation of the patients, figures of TC, LDL

cholesterol and triglycerides decreased to their norm or its upper limits with simultaneous increase of alpha-LP. Sugar concentration in blood also decreased. It is known that diabetic angiopathy is a result of generalised pathological metabolic disorder, lipid metabolism disorder in particular, when the rates of LDL cholesterol and VLDL cholesterol in blood increase and damage the endothelium. Thus, the application of combined laser therapy in complex treatment of patients with diabetes mellitus we regard as an important and necessary component of angiopathies prevention or their regress in cases of DM of any type and as a basis for prolonged compensation of DM.

Ambulatory Application Of Combined Laser Therapy In Patients With Diabetes Mellitus And Dyslipidemia Used by permission of the Czech Society for the Use of Laser in Medicine, www.laserpartner.org Laser Partner, 17.5.2002 T.V. Kovalyova, Out-Patient Department of the 2-nd Municipal Clinical Hospital, Izhevsk, Russia e-mail: [email protected] ABSTRACT

This study sought to evaluate the dynamics of lipid metabolism in blood plasma and clinical efficiency of combined laser therapy (CLT) in patients with diabetes mellitus. INTRODUCTION

Atherosclerosis in patients with diabetes mellitus (DM) is characterized by early development and spreading, that enables to speak about DM as a natural model of atherosclerosis [5]. DM and atherosclerosis are diseases with similar lipid disorders accompanied by hypercholesterolemia, hypertriglyceridemia and hypo-alphacholesterolemia [5]. It is established that under insulindependent DM (IDDM) hyperlipoproteinemia is secondary. It results from absolute insulin insufficiency and reduction of lipoprotein lipase activity. Hyperlipoproteinemia may be reversible provided that it is effectively treated. Besides, any dyslipoproteinemia under DM is not only a strong risk factor for the development of atherosclerosis, but also is one of the leading factors in a specific microangiopathy pathogenesis [1,2]. ―Usual‖ for DM patients hypoxia is considerably intensified under dys- and hyperlipoproteinemia, simultaneously increasing insulin defficiency and decreasing receptor sensitivity of cells. It hampers the treatment of patients and promotes the progression of diabetic microangiopathies. Patients with NIDDM are not protected from CHD caused by qualitative and quantitative changes of blood lipoproteins (LP) [3]. Out of quantitative LP changes characteristic of NIDDM are hypertriglyceridemia and high-density lipoprotein cholesterol reduction [6,15,16,20,25,27] on early stages of the disease [9], which are registered in 20% patients [17,22,26]. According to some investigations [4,7,14] the most common lipid disorder under NIDDM is combined hyperlipidemia, revealed in the high levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and the reduced level of high-density lipoprotein cholesterol (HDL-c). The most usual lipid disorder under NIDDM is hypertriglyceridemia, in most cases type IV, generally stipulated by the intensified very low-density lipoproteins cholesterol (VLDL-c) synthesis [5]. The HDL-c reduction is revealed both under newly established NIDDM and in patients with a prolonged diabetic record corrected by hypoglycemic preparations and insulin. Some investigations established a connection between insulin resistance and the low level of HDL-c [18]. The HDL-c concentration increases under insulin therapy [21] and weight reduction [3,13]. According to M.

Laakso et al. (1988), the HDL-c reduction is of great importance for CHD morbidity and mortality prognosis in patients with NIDDM. The HDL-c reduction down to 0,9 mmol/l and less was accompanied by the fourfold risk of CHD death. A number of investigations [10,17,22] showed that hypercholesterolemia, stipulated by the increased level of LDL-c, is revealed in 5477% of patients. Correction of glycemia is accompanied by the reduction of TC and LDL-c level [27]. Multiple Risk Factor Intervention Trial (MRFIT) [24] established the interconnection between TC and heart mortality of patients with DM. The obtained results showed that the higher cholesterol level in diabetic patients caused the higher risk of heart death. However, the same cholesterol level caused the higher (3-4 times) CHD mortality in patients with DM as compared to patients without it. The analysis of not numerous literature showed that there are still no any optimum approaches to lipid disorders treatment under DM. Moreover, dyslipidemia in diabetic patients are not practically corrected at present, that is mainly stipulated by high prices for known drugs. Objective: This study sought to evaluate the dynamics of lipid metabolism in blood plasma and clinical efficiency of combined laser therapy (CLT) in patients with IDDM and NIDDM. MATERIALS AND METHODS

Within the last 2 years in conditions of out-patient department we observed 205 patients with NIDDM and 54 – with IDDM. The lipidnormalizing effect of CLT in combination with antioxidant therapy (aevit 600 mg a day) we have studied in 60 individuals with NIDDM (8 men and 52 women), mean age - 57,3± 3,2 years, with the level of fasting glycemia no more than 9,0 mmol/l, HbA1c – 7,3± 0,19 and 7,27± 0,23%. The other 29 patients (with NIDDM) constituted the control group and have been treated only by sugar-reducing medications. In all patients we conducted lipid profile investigation. We also controlled glycemia, enzymatic blood activity (ALT, AST), clinical manifestations of angiopathy and performed the conjunctival biomicroscopy. All examinations have been done prior to treatment, in 2 weeks (i.e. immediately after the treatment), in 8 days, 1, 4 and 9 months after the treatment. Hypolipidemic action of CLT has been evaluated by the dynamics of TC, TG, LDL-C, HDL-C and atherogenity rate (AR). Lipid profile has been investigated in venous blood serum taken in the morning hours after 12-14 hours fasting. For trials we used biochemical analyser. TC - by Enzyme methods (CHOD-PAP), TG - UV enzyme method, HDL-c – after VLDL-c and LDL-c sedimentation by heparin in magnesium ions presence. VLDL-c and LDL-c we determined by W. Friedwald: VLDL-c = TG/5, LDL-c = TC - (HDL-c – VLDL-c). AR has been calculated by A.N. Klimov: AR = TC – HDLc/ HDL-c. The conjunctival biomicroscopy has been conducted with the help of photoobservation slot lamp. Different parameters of microcirculation (vascular convolution, blood flow speed, arteriovenular interrelations, red blood cell aggregation, etc.) have been assessed. We performed a staged course treatment within 9 months. Repeated courses were given in 3 and 6 months. Each course consisted of 8-10 sessions of intravenous laser blood irradiation (ILBI) by red spectrum laser, l =0,63 mm, capacity at the light-guide end – 2 mW, exposure - 15-30 min. Simultaneously we conducted a percutaneous procedure by low intensive laser irradiation (LILI) in the near infrared spectrum, l =0,89 mm, capacity at the light-guide end - 5 - 20 mW in combination with magnetic nozzles on gastrocnemius muscle, liver, pancreas, spleen projections - frequency 150 Hz, exposure 4 min. on each zone.

RESULTS

29 patients of the control group showed no obvious deviations of blood plasma lipids after 10days intake of aevit (table 1). This conformity has been also registered under the subsequent courses of antioxidant therapy by aevit in 3 and 6 months. In the main group of patients (table 2) TC level prior to treatment averaged to 8,2± 0,31 mmol/l, TG - 2,14± 0,08 mmol/l, LDL-c - 7,87± 0,30 mmol/l, HDL-c - 0,99± 0,04 mmol/l. AR made up 7,28± 0,28, LDL/HDL-c ratio - 7,94± 0,30 (with current standard being < 5,0). Immediately after the conducted therapy no significant deviations of lipid profile have been seen. The level of TC slightly decreased to 7,98± 0,31 (p 0.05). However, although the number of degranulated mast cells was higher in all laser-treated wounds, in comparison with the sham-irradiated group, only the 20 Hz (pulse duration 45 ms) and 292 Hz (pulse duration 3 ms) frequencies were significantly effective (P < 0.05). CONCLUSION: Increase in mast cell number is not pulsing frequency dependent, whereas degranulation is.

Ultrastructure Of The Blood And Lymphatic Capillaries Of The Respiratory Tissue During Inflammation And Endobronchial Laser Therapy. Ultrastruct Pathol. 2000 May-Jun;24(3):183-9. Polosukhin VV. Laboratory of Ultrastructural Research, Russian Academy of Medical Sciences, Novosibirsk, Russia. [email protected]

For wide application of low-energy laser irradiation in the pulmonary clinic, study of the structural basis of the therapeutic effect is necessary. The aim of this research is to describe the structural changes of the blood and lymphatic capillaries in the respiratory tissues during inflammation and following laser biostimulation. Comparative ultrastructural study was carried out on 127 open respiratory biopsy specimens from 45 patients with infectious-destructive lung diseases. These patients were divided into two groups, depending on tactic of pre-operative therapy: patients treated by only traditional anti-inflammatory measures and patients receiving additional laser therapy. Heightened permeability of the blood capillary endotheliocytes was noted as the initial stage in the development of the inflammatory reaction. Intensification of the process of permeability is accompanied by interstitial edema, deformation of the interalveolar septa, and structural disorganization of alveolar epithelium cells. Local lesions of microcirculation result in tissue hypoxia and induce processes of fibrosis. Laser biostimulation promotes reversion of the inflammatory process and stabilizes fibroplastic processes. Basic

principles of pathogenetic therapy were stated. It was shown that low-energy laser irradiation satisfies these requirements as an additional method in the therapy of destructive lung diseases.

Increased Antioxidant Activity Protection Of Skeletal Muscles From Ischemic Injury: Low-Level Laser Therapy Increases Antioxidant Activity. Photomed Laser Surg. 2005 Jun;23(3):273-7. Avni D, Levkovitz S, Maltz L, Oron U. Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.

Objective: The aim of this study was to investigate the effect of low-level laser therapy (LLLT) on ischemic-reperfusion (I-R) injury in the gastrocnemius muscle of the rat. Background Data: Ischemic injury in skeletal muscle is initiated during hypoxia and is aggravated by reoxygenation during blood reperfusion and accumulation of cytotoxic reactive oxygen superoxides. LLLT has been found to biostimulate various biological processes, such as attenuation of ischemic injury in the heart. Materials and Methods: The injury was induced in the gastrocnemius muscles of 106 rats by complete occlusion of the blood supply for 3 h, followed by reperfusion. Another group of intact rats served to investigate the effect of LLLT on intact nonischemic muscles. Creatine phosphokinase, acid phosphatase, and heat shock protein were determined 7 days after I-R injury and antioxidant levels 2 h after reperfusion. Results: Laser irradiation (Ga-As, 810 nm) was applied to the muscles immediately and 1 h following blood supply occlusion. It was found that laser irradiation markedly protects skeletal muscles from degeneration following acute I-R injury. This was evident by significantly (p < 0.05) higher content of creatine phosphokinase activity and lower (p < 0.05) activity of acid phosphatase in the LLT-treated muscles relative to the injured non-irradiated ones. The content of antioxidants and heat shock proteins was also higher (p < 0.05) in the LLLT-treated muscles relative to that of injured non-irradiated muscles. Conclusion: The present study describes for the first time the ability of LLLT to significantly prevent degeneration following ischemia/reperfusion injury in skeletal muscles, probably by induction of synthesis of antioxidants and other cytoprotective proteins, such as hsp-70i. The elevation of antioxidants was also evident in intact muscle following LLLT. The above phenomenon may also be of clinical relevance in scheduled surgery or microsurgery requiring extended tourniquet applications to skeletal muscle followed by reperfusion.

Insomnia - Auriculotherapy 46 Cases of Insomnia Treated with Semiconductor Laser Irridiation on Auricular Points by Yao Shuying (Institute of Acupuncture and Moxbustion, China Academy of Traditional Chinese Medicine, Beijing 100700)

Insomnia is a commonly encountered symptom in clinical practice. The author has treated it with semiconductor laser irradiation on auricular points with satisfactory therapeutic results. A report is presented as follows. GENERAL DATA

In this series, there were 46 cases of insomnia. l9 cases were male and 27 female, ranging in age of 23-55 years, averaging 38 years. The course of disease ranged from over l month to l2 years. l5 cases were differentiated as disharmony between the heat and kidney,l8 cases deficiency of both the heart and spleen, and l3 cases liver-fire upward invasion. METHOD OF TREATMENT

Bilateral auricular points of Shenmen, Endocrine, Subcortex, and Brain were selected. Add Heart and Kidney for disharmony between the heart and kidney; Spleen and Stomach for deficiency of both the heart and spleen, and Liver and Kidney for liver-fire upward invasion. PU-l semiconductor laser apparatus developed by the Physics Department of Qinghua University was used to irradiate on the above-mentioned auricular points, with a wave length of 820 nm, output power 3 mw and facula 2 mm in diameter. Each point was irradiated for l minute till a local warm sensation was felt. The treatment was given once daily, 12 treatments constituting one therapeutic course with a 5-7 day interval between courses. The clinical results were evaluated after 1-3 courses of treatment. THERAPEUTIC CRITERIA

Cured: Able to sleep for more than 7 hours. Improved: Able to sleep for 5-6 hours. Ineffective: Able to sleep for less than 3 hours. THERAPEUTIC RESULTS

Of the 46 cases treated, 32 cases (69.5%)were cured, l3 cases (28.3%) were improved, and l case (2.2%) failed. The total effective rate was 97.8%. TYPICAL CASE

Ms. Zhao, 52 years old, presented herself on Oct. 5, l998, with a chief complaint of insomnia for 9 years. She often couldn't fall asleep or had dream-disturbed sleep because of heavy mental stress. She could hardy fall asleep for the whole night if the condition worsened. The accompanying symptoms included palpitation, shortness of breath, dizziness, tinnitus, general lassitude, and poor appetite. The tongue was pale with white coating, and the pulse thready and weak. It was diagnosed as deficiency of both the heart and spleen. The treatment was aimed at tonifying the heart, reinforcing the spleen, nourishing blood and tranquilizing the mind.The points selected were Heart, Spleen, Kidney, Endocrine Shenmen, Brain, and Subcortex, on which semiconductor laser irradiation was applied. After 3 sessions of treatment, the patient was able to sleep intermittently, and palpitation and shortness of breath were relieved. After 1 course of treatment, the patient could sleep quietly for 4 hours or more, and general lassitude was improved. After 2 courses of treatment, the patient could sleep quietly for about 6 hours, and all the other accompanying symptoms were relieved. After 3 courses of treatment, she could sleep for 7 hours every night, and all the other symptoms disappeared.

COMMENT

The photochemical, magnetic and warming effects of semiconductor laser on the ear points may promote the circulation of Qi and blood in the meridians, regulate the functions of the Zang-Fu organs, thus obviously improving the physiological functions. In view of modern science, semiconductor laser irradiation on the auricular points is able to regulate the nervous system and tranqualize the mind, suitable for treatment of insomnia. This therapy is well accepted by the patients for the satisfactory results with no pain and no side effects.

Interstitial Cystitis [Combined Therapy Of Interstitial Cystitis Using The "Aeltis-Synchro02- Iarilo" Device] Urologiia. 2004 Mar-Apr;(2):20-2. [Article in Russian] Kalinina SN, Molchanov AV, Rutskaia NS.

Multiple modality therapy of interstitial cystitis (IC)--the disease characterized by nicturia, pelvic pains, imperative pollakiuria--is considered. As IC nature is not well known, its treatment remains empiric. Among the underlying causes, most probable are autoimmune, allergic, infectious, neurological, vascular. Therefore, the treatment should be multi-modality. Most usable now is combined chemotherapy. Perspective is also IC treatment with medicines in combination with physiotherapy (electromagnetolaser AELTIS-SYNCHRO-02-YARILO"). Endovesical electrophoresis can be also applied.

Irradiance vs. Dosage Relevance Of Laser Irradiance Threshold In The Induction Of Alkaline Phosphatase In Human Osteoblast Cultures. Lasers Med Sci. 2007 Oct 31; [Epub ahead of print] Haxsen V, Schikora D, Sommer U, Remppis A, Greten J, Kasperk C. Faculty of Science, Biophotonics Group, University of Paderborn, Paderborn, Germany, [email protected].

Induction of matrix synthesis by low-level laser has been demonstrated extensively.However, the question of dose- or power intensity-dependency is under-investigated. To address this issue we chose human osteoblast cell cultures and measured their alkaline phosphatase (ALP) activity after laser irradiation. The cell cultures were irradiated periodically by 690 nm radiation via optical transmission fiber-based laser needles, reaching into the culture dishes. The osteoblasts showed no induction of ALP activity when we used a single laser needle stimulation with a laser irradiance of 51 mW/cm(2), an increase of approximately 43% at 102 mW/cm(2) irradiance (two needles per well) and a ninefold increase at 204 mW/cm(2) irradiance (four needles per well), leaving the temperature of the culture medium unaffected. We concluded that the osteoblastic response in ALP activity to a laser stimulus shows a logarithmic relationship, with a distinct

threshold, rather than a linear dose-dependency. Secondly, the laser irradiance, rather than the dose, is relevant for the impact of the laser.

Kidney [The Magneto-Laser Effect On Liver Functions In The Complex Treatment Of Hepatorenal Failure] Anesteziol Reanimatol. 1993 Sep-Oct;(5):49-51. [Article in Russian] Shimanko II, Limarev VM.

Complex therapy of acute hepatorenal failure included magnetic field and laser applied to hepatic area and blood extracorporeally. In 26 patients magnetic field and laser were applied to the hepatic area. When compared to a control group of 30 patients a more prompt decrease in blood bilirubin was noted, alongside with a drop in blood fibrinogen, which enhanced a threat of profuse bleeding. There was no decrease in blood fibrinogen or an accelerated drop in bilirubin during extracorporeal application of the technique in 23 patients, as compared to a control group of 20 patients. As the technique has different effects on the liver it should be used with care and only when clinically indicated in patients with acute hepatorenal failure.

[Effect Of Low-Intensity Laser Therapy On Urinary Tract Function] Urol Nefrol (Mosk). 1999 Mar-Apr;(2):28-9. [Article in Russian] Kul'chavenia EV.

The paper reports the results of the study of low-intensity infrared laser radiation effects on partial kidney functions. The course of the laser radiation resulted in improved blood supply to the kidney in 57.9% of the cases. Stimulation of the secretion and urodynamics was registered in 63.1 and 79% of the cases, respectively. Positive changes were also noted in diuresis, nitrogenexcretory and concentration functions of the kidneys.

Estimation Of Efficiency Of Magnetolaserotherapy In Metaphilactik Of Stone Disease Avdoshin V.P.,Andruchin M.I., Lahlou H.F. Russia peoples friendship university. Moscow

The cause of stones formation in kidneys are rather various, one of which is membranes distabilisation of renal tubuls and infringement of colloid system. For an estimation ofefficacity of influence magneto-laser therapy on frequency of a stones relapse we studed 68 patients from 18 to 70 years old, after natural stone elimination within one to three months. The estimation of activity stone formation was made on the basis of a phenomenon "Shatochina-Shabolma". 33 patients were treated with medicines and medical plants. The therapy was given according to the nature of the stone. 35 patients besides common therapy got magneto-laser therapy on a kidneys area, the number of sessions was 8-12 during course of treatment. The results of research have shown, that in group of the patients who have received magnetolaser therapy only in 2 (5.7 %) patients in a month have come active stone formation , m 9 (25.7

%) - in 2 months, in 17 (48,6 %) - in 3 months, and in 18 (51.4 %) - active stone formation 3 months later was not revealed. At the same time in the group of control receiving common therapy, active stone formation was revealed in a month in 13 (39.4 %) patients, in 2 months - in 21 (63.6 %), and in three months - in 29 (87.9 %) and only in 4 (12.1 %) patients active stone formation was not revealed. Thus, magneto-laserotherapy in patients with stone disease is pathogenicaly reasonable with laser radiation stabilizing influence on biomembranes, that brings about colloid systems normalization and decreasing the risk of stone formation.

Quantum Therapy Of Diabetic Nephropathy V.Soklakov, S.Bouglova, V.Finin, Ye.Belskaya Belarusian Science Research Institute of Cardiology of Mmisfay of Health, Belarusian State University, Minsk, Republic of Belarus

The influence of low energy helium-neon (HN) and infrared (IR) laser irradiation on the clinical laboratory indications of 33 patients with insulin dependent diabetes mellitus was studied. It was shown that laser therapy must be prescribed strictly individually for each case taking into account the immune status of the organism. Laser therapy is effective only at the early stages of renal disorder. HN laser irradiation of kidneys is accompanied by activation indications of primarily humoral immunity while in case of IR laser irradiation these are activation indications of cell-bound immunity. Considering the partially auto-immune nature of kidney affection this phenomenon can be regarded as a positive factor which liquidates immunity deficit on the one hand and as a dangerous tendency of the activation of some nephron alteration mechanisms on the other. The difference in the therapeutic effectiveness of the two kinds of lasers is connected with the different penetrating power of the rays and changes in the organism's photochemical processes which depend on the wavelength and irradiation power.

Dynamics Of Renal Function In Patients With Acute Pyelonephritis And Diabetes Treated With Magnitolaserotherapy Peoples friendship University of Russia. Moscow Avdoshin V.P. Andrukhin M.I. Makarov O.V.

We studed 98 patients with acute pyelonephritis and diabetes, 62 (63,3 %) patients out of them with not complicated forms , with complicated 36 (36,7 %). The renal function was controled on the base of clinical sings, biochemical and radioimmunological data. Renal disfunction was revealed in all patients. Reani disfiinrion of the first degree in patients with not complicated pyelonephritis was diagnosed in 36 (58%), the second degree – in 21 (34%), the third degree - in 5 (8%) patients. Rean] disfiinrion of the first degree in patients with complicated pyelonephritis was diagnosed in 11 (30.6%),the second - in 17 (47.2 %), the third degree in 8 (22.2 %). Patients with complicated pyelonephritis were treated after restoration of urine outflow by upper unnary tract. Kidney catheterisation was performed in 32 (88.9%) patients, trancutaneal kidney puncture - in 4 (11.1%) patients. Besides antibiotics, detoxical therepy all patients were threated with magnitolaserotherapy useing "MILTA" apparatus. bi patients with not complicated pyelonephritis the renal function has normalized in 21 patients (33,9 %), first degree renal disfunction was found in 26 (41,9 %), second - in 15 (24. %). The improvement of renal disfunction by one degree was revealed in 29 (46,7 %) patients, in 8 (12,9 %) by two degrees. In patients with the complicated pyelonephritis the renal function has normalized in 7 (19 %), the first degree renal disfunction – inIO patients (27,7 %), the second - in 13 (36 %),the third -in 6

(16,6 %), improvement of renal disfunction by one degree was revealed in 11 (30.6%), by two degrees – in 2 (5.6%) patients. The results received are explained by positive medical effect of magnetolaserotherapy on inflammatory process in kidneys and renal function. Such effect is caused by improvement of microcirculation and reduction of kidneys tissue edema.

Dynamics Of Lipid Metabolism And Peripheral Blood Flow Rates In Patients With Atherosclerosis In Conjunction With Renal Dysfunction After The Course Of Combined Laser Therapy. Kovalyova T V et al.

During an 8 year period patients with atherosclerosis and renal dysfunction have been treated with intravenous laser blood irradiation (ILBI). The study has demonstrated a decreased level of total cholesterol, LDL cholesterol and triglycerides with an simultaneous increase of HDL cholesterol levels. No pharmaceuticals were given during the treatment period. The authors state that ILBI results in a stable hypolipidemic situation which prevents atherogenesis in patients with metabolic disorders, particularly in patients with renal pathologies.

[Changes In The Oxygen Tension Of The Kidney Cortex In Exposure To Laser Irradiation At Different Wavelengths (An Experimental Study)] Urol Nefrol (Mosk). 1997 Mar-Apr;(2):12-3. [Article in Russian] Safarov RM, Ianenko EK, Kazachenko AV.

Experiments with exposure of the renal cortex to different kinds of laser radiation with measurement of pO2 demonstrated that intravenous UV laser radiation inhibits tissue oxygenation. Subvascular blood exposure to infrared and intravenous one to He-Ne laser are beneficial as such radiations improve oxygenation of the renal cortex.

Application Of A Helium-Neon Laser (Hnl) For The Correctioh Of Renal Function In Patients With Chronic Glomerulonephritis (Cgn) M.B. Lutoshkin, M.W. Tsypilev, M.A. Lutoshkina Town Hospital #1, JSC "E.T.L.", Vologda, Russia

The non-immune mechanisms of progressing renal failure are hemodynamic disorders and breaking of coagulation processes. The increase of spontaneous and induced hypercoagulation and depression of enzymatic link of blood fibrinolytic activity are present in the active stage of CGN. The prolonged antitrombotic treatment by anticoagulants and desagregants renders favourable stabilizing effect on preservation of residual renal function in patients with CGN. According to the results of many studies (non-nephrology) it is considered proved that the use HNL real improvement of microcirculation and decrease systematic hypertension and correction of hemocoagulation changes. 45 patients with CGN: 30 men and 15 women at the age 23-45 were examined. All the patients got the intravenous blood irradiation by the light of HNL (632,8 nm, with 2.5-3,0 mW capacity on its end, during 25-30 min). The three-year observation the patients got 4-6 courses of 12-15 procedures in laser therapy (LT). The condition of

microcirculation, intraglomerular hypertension and hyperfiltration was estimated by renal functional reserve (RFR). The condition of hemocoagulation processes was estimated by coagulation parameters. Before the course of treatment RFR was retained - 22,2% pts, reduced 31,2% pts, absent - 46,6% pts. After the course of treatment RFR was retained - 56,3% pts, reduced - 25,9% pts, absent - 17,8% pts. The use of LT given authentic (p 0.05) between subjects given active LLLT and those given placebo LLLT. For volleyball athletes, the change in CK levels from before to after the exercise test was significantly lower (P = 0.0133) for those given active LLLT (2.52 U l(-1) +/- 7.04 U l(-1)) than for those given placebo LLLT (28.49 U l(-1) +/- 22.62 U l(-1)). For the soccer athletes, the change in blood lactate levels from before exercise to 15 min after exercise was significantly lower (P < 0.01) in the group subjected to active LLLT (8.55 mmol l(-1) +/- 2.14 mmol l(-1)) than in the group subjected to placebo LLLT (10.52 mmol l(-1) +/- 1.82 mmol l(-1)). LLLT irradiation before the Wingate test seemed to inhibit an expected post-exercise increase in CK level and to accelerate post-exercise lactate removal without affecting test performance. These findings suggest that LLLT may be of benefit in accelerating post-exercise recovery.

Laser Therapy on Darker Ethnic Skin Laser therapy on darker ethnic skin. Dermatol Clin. 2003 Oct;21(4):713-23. Battle EF Jr, Hobbs LM. Department of Dermatology, Howard University College of Medicine, 2041 Georgia Avenue, NW, Washington, DC 20060, USA. [email protected]

Like all medical procedures laser therapy comes with inherent risks and complications. Because of the increased risk in epidermal side effects when performing laser therapy on patients with darker skin, a higher level of laser expertise and clinical experience in treating darker ethnic skin is recommended to ensure that patients are treated safely. Test spots should always be done as an aid to selecting safe and efficacious treatment parameters. Because of the limited experience in treating patients with darker skin a conservative approach should always be used. Unfortunately, there are no national policies establishing credentialing requirements for those planning to practice laser surgery. The US Food and Drug Administration are responsible for granting individual laser manufacturers' permission to market their lasers for specific indications. The Food and Drug Administration also recommends operator training to use these lasers, but credentialing is a state function and consequently standards for laser therapy vary greatly from state to state. Until the bar is raised and national credentialing polices on laser therapy are established clinicians must police themselves and fully be aware of their capabilities and

limitations to ensure that all patients regardless of skin color or ethnicity receive safe and effective treatments.

Laser Therapy vs. Ultrasound Comparison Between The Effect Of Low-Level Laser Therapy And LowIntensity Pulsed Ultrasonic Irradiation In Vitro. Photomed Laser Surg. 2008 Feb;26(1):6-9. Oliveira RF, Oliveira DA, Monteiro W, Zangaro RA, Magini M, Soares CP. Laboratório de Dinâmica de Compartimento Celular, Instituto de Pesquisa e Desenvolvimento (IP&D), UNIVAP, São José dos Campos, São Paulo, Brazil.

ABSTRACT Objective: The objective of this study was to compare the effect of lowlevel laser therapy (LLLT) and low-intensity pulsed ultrasound (LIPUS) on fibroblast cell culture. Several methods, including ultrasound treatment and LLLT, are being used to facilitate tissue repair and healing processes. Materials and Methods: L929 fibroblast cell cultures were irradiated with lowlevel laser energy and LIPUS. Cultures irradiated with ultrasound were divided into five groups: group 1: control (did not receive irradiation); group 2: 0.2 W/cm(2) in pulsed mode at 10% (1:9 duty cycle); group 3: 0.6 W/cm(2) in pulsed mode at 10% (1:9 duty cycle); group 4: 0.2 W/cm(2) in pulsed mode at 20% (2:8 duty cycle); and group 5: 0.6 W/cm(2) in pulsed mode at 20% (2:8 duty cycle). Cultures irradiated with laser energy were divided into three groups: group 1: control (did not receive irradiation); group 2: 6 J/cm(2); and group 3: 50 mJ/cm(2). Each group was irradiated at 24-h intervals, with the following incubation periods post-irradiation: 24, 48, and 72 h; after each irradiation cycle the cultures were analyzed using MTT [3-(4.5dimethylthiazol-2-yl)-2.5 diphenyltetrazolium bromide]. Results: Analysis of results after LLLT and LIPUS demonstrated that the effect of laser therapy on fibroblast cell culture was greater than that of LIPUS (p < 0.05). Conclusion: Results demonstrated that LLLT significantly increased fibroblastic activity more than LIPUS. Therefore, in the first and second phases of tissue repair, laser treatment may be more effective than ultrasound treatment.

The Short-Term Efficacy Of Laser, Brace, And Ultrasound Treatment In Lateral Epicondylitis: A Prospective, Randomized, Controlled Trial. J Hand Ther. 2008 Jan-Mar;21(1):63-8. Oken O, Kahraman Y, Ayhan F, Canpolat S, Yorgancioglu ZR, Oken OF. Ankara Education and Research Hospital, Department of Physical Medicine and Rehabilitation, Division of Hand Rehabilitation, Ankara, Turkey.

The aims of this study were to evaluate the effects of low-level laser therapy (LLLT) and to compare these with the effects of brace or ultrasound (US) treatment in tennis elbow. The study design used was a prospective and randomized, controlled, single-blind trial. Fifty-eight outpatients with lateral epicondylitis (9 men, 49 women) were included in the trial. The patients were divided into three groups: 1) brace group-brace plus exercise, 2) ultrasound group-US plus exercise, and 3) laser group-LLLT plus exercise. Patients in the brace group used a lateral counterforce brace for three weeks, US plus hot pack in the ultrasound group, and laser plus hot pack in the LLLT group. In addition, all patients were given progressive stretching and

strengthening exercise programs. Grip strength and pain severity were evaluated with visual analog scale (VAS) at baseline, at the second week of treatment, and at the sixth week of treatment. VAS improved significantly in all groups after the treatment and in the ultrasound and laser groups at the sixth week (p or =2 lines of VA gain) at the 12- and 24-month examinations, and timing of macular edema resolution. RESULTS: Changes in mean FT and TMV from the initial values were statistically significant for TGLT from the 6-month examination (P 0.05) between subjects given active LLLT and those given placebo LLLT. For volleyball athletes, the change in CK levels from before to after the exercise test was significantly lower (P = 0.0133) for those given active LLLT (2.52 U l(-1) +/- 7.04 U l(-1)) than for those given placebo LLLT (28.49 U l(-1) +/- 22.62 U l(-1)). For the soccer athletes, the change in blood lactate levels from before exercise to 15 min after exercise was significantly lower (P < 0.01) in the group subjected to active LLLT (8.55 mmol l(-1) +/- 2.14 mmol l(-1)) than in the group subjected to placebo LLLT (10.52 mmol l(-1) +/- 1.82 mmol l(-1)). LLLT irradiation before the Wingate test seemed to inhibit an expected post-exercise increase in CK level and to accelerate post-exercise lactate removal without affecting test performance. These findings suggest that LLLT may be of benefit in accelerating post-exercise recovery.

Photoengineering Of Tissue Repair In Skeletal And Cardiac Muscles. Photomed Laser Surg. 2006 Apr;24(2):111-20. Oron U. Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Israel. [email protected]

This review discusses the application of He-Ne laser irradiation to injured muscles at optimal power densities and optimal timing, which was found to significantly enhance (twofold) muscle regeneration in rats and, even more, in the cold-blooded toads. Multiple and frequent (daily) application of the laser in the toad model was found to be less effective than irradiation on alternate days. It was found that in the ischemia/reperfusion type of injury in the skeletal leg muscles (3 h of ischemia), infrared Ga-Al-As laser irradiation reduced muscle degeneration, increased the cytoprotective heat shock proteins (HSP-70i) content, and produced a twofold increase in total antioxidants. In vitro studies on myogenic satellite cells (SC) revealed that phototherapy restored their proliferation. Phototherapy induced mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) phosphorylation in these cells, probably by specific receptor phosphorylation. Cell cycle entry and the accumulation of satellite cells around isolated single myofibers cultured in vitro was also stimulated by phototherapy. Phototherapy also had beneficial effects on mouse, rat, dog and pig ischemic heart models. In these models, it was found that phototherapy markedly and significantly reduced (50-70%) the scar tissue formed after induction of myocardial infarction (MI). The phototherapeutic effect was associated with reduction of ventricular dilatation, preservation of mitochondria and elevation of HSP- 70i and ATP in the infarcted zone. It is concluded that phototherapy using the correct parameters and timing has a markedly beneficial effect on repair processes after injury or ischemia in skeletal and heart muscles. This phenomenon may have clinical applications.

Effect Of Low-Level Laser (Ga-Al-As 655 Nm) On Skeletal Muscle Fatigue Induced By Electrical Stimulation In Rats. J Appl Physiol. 2006 Jul;101(1):283-8. Epub 2006 Apr 20. Lopes-Martins RA, Marcos RL, Leonardo PS, Prianti AC Jr, Muscará MN, Aimbire F, Frigo L, Iversen VV, Bjordal JM.

Department of Pharmacology, Laboratory of Biochemical Pharmacology of Free Radicals, Institute of Biomedical Sciences, University of São Paulo, Brazil. [email protected]

We investigated whether low-level laser therapy (LLLT) can reduce muscular fatigue during tetanic contractions in rats. Thirty-two male Wistar rats were divided into four groups receiving either one of three different LLLT doses (0.5, 1.0, and 2.5 J/cm2) or a no-treatment control group. Electrical stimulation was used to induce six tetanic muscle contractions in the tibial anterior muscle. Contractions were stopped when the muscle force fell to 50% of the initial value for each contraction (T50%). There was no significant difference between the 2.5 J/cm2 laserirradiated group and the control group in mean T50% values. Laser-irradiated groups (0.5 and 1.0 J/cm2) had significantly longer T50% values than the control group. The relative peak force for the sixth contraction in the laser-irradiated groups were significantly higher at 92.2% (SD 12.6) for 0.5 J/cm2, 83.2% (SD 20.5) for 1.0 J/cm2, and 82.9% (SD 18.3) for 2.5 J/cm2 than for the control group [50% (SD 15)]. Laser groups receiving 0.5 and 1.0 J/cm2 showed significant increases in mean performed work compared with both the control group and their first contraction values. Muscle damage was indirectly measured by creatine kinase levels in plasma. A distinct dose-response pattern was found in which 1.0 and 2.5 J/cm2 LLLT groups had significantly lower creatine kinase levels than the 0.5 J/cm2 LLLT group and the control group. We conclude that LLLT doses of 0.5 and 1.0 J/cm2 can prevent development of muscular fatigue in rats during repeated tetanic contractions.

Protection Of Skeletal Muscles From Ischemic Injury: Low-Level Laser Therapy Increases Antioxidant Activity. Photomed Laser Surg. 2005 Jun;23(3):273-7 Avni D, Levkovitz S, Maltz L, Oron U. Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.

OBJECTIVE: The aim of this study was to investigate the effect of low-level laser therapy (LLLT) on ischemic-reperfusion (I-R) injury in the gastrocnemius muscle of the rat. BACKGROUND DATA: Ischemic injury in skeletal muscle is initiated during hypoxia and is aggravated by reoxygenation during blood reperfusion and accumulation of cytotoxic reactive oxygen superoxides. LLLT has been found to biostimulate various biological processes, such as attenuation of ischemic injury in the heart. MATERIALS AND METHODS: The injury was induced in the gastrocnemius muscles of 106 rats by complete occlusion of the blood supply for 3 h, followed by reperfusion. Another group of intact rats served to investigate the effect of LLLT on intact nonischemic muscles. Creatine phosphokinase, acid phosphatase, and heat shock protein were determined 7 days after I-R injury and antioxidant levels 2 h after reperfusion. RESULTS: Laser irradiation (Ga-As, 810 nm) was applied to the muscles immediately and 1 h following blood supply occlusion. It was found that laser irradiation markedly protects skeletal muscles from degeneration following acute I-R injury. This was evident by significantly (p < 0.05) higher content of creatine phosphokinase activity and lower (p < 0.05) activity of acid phosphatase in the LLLT-treated muscles relative to the injured non-irradiated ones. The content of antioxidants and heat shock proteins was also higher (p < 0.05) in the LLLT-treated muscles relative to that of injured non-irradiated muscles. CONCLUSION: The present study describes for the first time the ability of LLLT to significantly prevent degeneration following ischemia/reperfusion injury in skeletal muscles, probably by induction of synthesis of antioxidants and other cytoprotective proteins, such as hsp-70i. The elevation of antioxidants was

also evident in intact muscle following LLLT. The above phenomenon may also be of clinical relevance in scheduled surgery or microsurgery requiring extended tourniquet applications to skeletal muscle followed by reperfusion.

Low-Level Laser Therapy Can Reduce Lipopolysaccharideinduced Contractile Force Dysfunction And TNF-Alpha Levels In Rat Diaphragm Muscle. Lasers Med Sci. 2006 Dec;21(4):238-44. Epub 2006 Oct 11 Aimbire F, Lopes-Martins RA, Castro-Faria-Neto HC, Albertini R, Chavantes MC, Pacheco MT, Leonardo PS, Iversen VV, Bjordal JM. Research Group of Animal Experimental, IP & D UNIVAP R. Shishima Hifumi, 2911, 12240-000, São José dos Campos, SP, Brazil.

Our objective was to investigate if low-level laser therapy (LLLT) could improve respiratory function and inhibit tumor necrosis factor (TNF-alpha) release into the diaphragm muscle of rats after an intravenous injection of lipopolysaccharide (LPS) (5 mg/kg). We randomly divided Wistar rats in a control group without LPS injection, and LPS groups receiving either (a) no therapy, (b) four sessions in 24 h with diode Ga-AsIAl laser of 650 nm and a total dose of 5.2 J/cm2, or (c) an intravenous injection (1.25 mg/kg) of the TNF-alpha inhibitor chlorpromazine (CPZ). LPS injection reduced maximal force by electrical stimulation of diaphragm muscle from 24.15+/-0.87 N in controls, but the addition of LLLT partly inhibited this reduction (LPS only: 15.01+/-1.1 N vs LPS+LLLT: 18.84+/-0.73 N, P increased pain, etc.). Results measured according to VAS/VRS/PTM: in acute pain, diminished more than 70%; in chronic pain more than 60%. Clinical effectiveness (success or failure) depends on the correctly applied energy dose--over/underdosage produces opposite, negative effects on cellular metabolism. We did not observe any negative effects on the human body and the use of analgesic drugs could be reduced or completely excluded. LLLT suggests that the laser beam can be used as monotherapy or as a supplementary treatment to other therapeutic procedures for pain treatment.

Low Level Laser Therapy For Myofascial Pain In The Neck And Shoulder Girdle. A Double-Blind, Cross-Over Study. Scand J Rheumatol. 1992;21(3):139-41. Thorsen H, Gam AN, Svensson BH, Jess M, Jensen MK, Piculell I, Schack LK, Skjott K. Department of General Practice, University of Copenhagen, Denmark.

In a controlled, cross-over study the effect of low level laser therapy (LLLT) was evaluated. During a five weeks period forty-seven female laboratory technicians received six laser and six placebo treatments to tender points in the neck and shoulder girdle. Subjects rated the placebo treatment significantly more beneficial than LLLT (p = .04). There was no reduction in

consumption of analgesics associated with either laser or placebo treatment. The results indicate no beneficial effect of LLLT for myofascial pain.

Myocardial Infarction [Therapeutic Effects Of Laser Therapy In Patients With Silent Myocardial Ischemia] Vopr Kurortol Fizioter Lech Fiz Kult. 2007 Jul-Aug;(4):12-5. [Article in Russian] Krysiuk OB, Ponomarenko GN, Obrezan AG.

The technique of registration of pain and vibration sensitivity providing early diagnosis of painless ischemic heart disease is described. Basing on evident pathogenetic direction of a therapeutic action of laser therapy to different links of pathogenesis of arterial hypertension and ischemic heart disease, therapeutic effects of laser therapy in patients with painless myocardial ischemia in combination with essential hypertension were studied.

Effect Of Low-Intensity Laser Radiation On Lipid Metabolism And Hemostasis In Patients With Myocardial Infarction Vopr Kurortol Fizioter Lech Fiz Kult. 2006 Mar-Apr;(2):6-8. [Article in Russian] Kemalov RF.

Progression of coronary atherosclerosis often causes complications resulting in myocardial infarction, early disability and death of patients with coronary heart disease. Low efficacy of medicines against coronary atherosclerosis progression after myocardial infarction gave rise to investigations of nonpharmacological methods, laser radiation, in particular. Our study shows a noticeable positive effect of low-intensity laser radiation on blood lipid spectrum and hemostasis. This makes laser therapy promising in combined rehabilitation of postmyocardial infarction patients.

[Effect Of The He-Ne Laser Irradiation On Resistance Of The Isolated Heart To The Ischemic And Reperfusion Injury] Ross Fiziol Zh Im I M Sechenova. 2003 Dec;89(12):1496-502. [Article in Russian] Kolpakova ME, Vlasov TD, Petrishchev NN, Vislobokov AI. St.-Petersburg Acad. I. P. Pavlov State Medical University, 197089, Russia, St.-Petersburg, L. Tolstoy st., 6/8.

The aim of this work was to investigate the myocardial protection against ischemia/reperfusion using low level laser irradiation (LLLI). It has been shown that pulse pressure was higher in the period of post-ischemic reperfusion as compared with the control group. It provided a better restoration of myocardial contractility as well as increasing of coronary flow in the reperfusion period. The amount of ventricular rhythm disorder episodes decreased. These effects of laser

application were registered in conditions of coronary flow reduction less than 50%. One of the suggested mechanisms of laser effect is an ATP-sensitive channel activation.

[The Use Of Laser Therapy And Physical Exercises In Myocardial Infarct Patients At The Hospital Stage] Vopr Kurortol Fizioter Lech Fiz Kult. 1995 Nov-Dec;(6):14-6. [Article in Russian] Kuimov AD, Beliavskaia NV, Barbarich VB, Potanina LM, Metelkina NV.

89 postmyocardial infarction patients were exposed to low-intensity laser radiation combined with muscular training. The treatment improved clinical condition of the patients, myocardial contractility, exercise tolerance.

The Deviation Of Some Hemorheological Indicators Among The Patients With Acute Myocardial Infarction After Infrared Laser Therapy K.G.Khutchumova, V.A.Lyusov Moscow State University, Russia

The article deals with hemorheological and clinical aspects of therapeutic effects of lowlaser therapy in patients with acute myocardial infarction. 20 patients were investigated by laser therapy together with traditional treatment (1), and 20 patients - only by traditional treatment (2). The treatment was carried out by means of infrared laser 'Vector' in persistent regime. The region of projection of carotid sinuses and heart, expositions 3 min. The levels of fibrinogen, platelet aggregation, blood viscosity, antithrombin III, fibrinogen fragments were investigated before applying laser light and on the 5th and the 10th day after the treatment. Laser therapy lessened cardiac pain and arrhythmias. The improvement of the clinical state of the patients was accompanied with improvement of hemorheological properties. The impact of laser therapy on fibronectin level which rose from 245±19,4 to 310±21,2 on the 10th day and on antithrombin III level wich changed from 56,3±3,5 to 75,8±6,2 was statistically significant. The amount of fibrinogen fragments decreased on 16% (p 0.05) was found regarding the amplitude, area, duration and conduction velocity of CMAP for each applied dose (0.31, 2.48 and 19 J/cm2) on the irradiated (right) side and the control (left) side, or between irradiated groups. Twenty-one days after injury there were no qualitative differences in the morphological pattern of the regenerated nerve fibres in either irradiated (0.31, 2.48 and 19 J/cm2) or control nerves when evaluated by light microscopy. This study showed that low-energy GaAs irradiation did not have any effect on the injured rat sciatic nerve.

An Innovative Approach To Induce Regeneration And The Repair Of Spinal Cord Injury. Laser Therapy.1997; 9 (4): 151.

Rochkind S, Shahar A. Nevo Z.

An Israeli research group has investigated an innovative method of repairing injured spinal cords. In a rat model the spinal cords were transected in 31 animals (between T7/T8). In vitro constructed composite implants were used in the transected area. These implants contained embryonal spinal cord neuronal cells dissociated from rat fetuses, cultured on biodegradable microcarriers. After being embedded in hyaluronic acid the implants were ready to be placed into the injured area. The whole lesion area was covered with a thin coagulated fibrin-based membrane. Control animals underwent the same laminectomy but did not receive any implant. In all animals the wound was closed normally. Laser therapy was started immediately after surgery. It was continued daily for two weeks using 780 nm, 200 mW, 30 minutes daily. One group received the implant but no laser. During the 3-6 months follow up, 14 of the 15 animals that received laser (A) showed different degrees of active movements in one or both legs, compared to 4 of 9 animals in the group who had received implants but no laser (B). In the group receiving no implant and no laser (C), 1 out of 7 showed some motor movements in one leg. Somatosensory evoked potentials were elicited in 10 of the 15 rats in group A at three months, and on one side in one animal in group B. Axon sprouting was observed as soon as three days post surgery, in group A only.

New Hope For Patients With Spinal Cord Injuries. Laser Therapy.1997; 9 (4): 151 Rochkind S, Shahar A. Nevo Z. An innovative approach to induce regeneration and the repair of spinal cord injury.

An Israeli research group has investigated an innovative method of repairing injured spinal cords. In a rat model the spinal cords were transected in 31 animals (between T7/T8). In vitro constructed composite implants were used in the transected area. These implants contained embryonal spinal cord neuronal cells dissociated from rat fetuses, cultured on biodegradable microcarriers. After being embedded in hyaluronic acid the implants were ready to be placed into the injured area. The whole lesion area was covered with a thin coagulated fibrin-based membrane. Control animals underwent the same laminectomy but did not receive any implant. In all animals the wound was closed normally. Laser therapy was started immediately after surgery. It was continued daily for two weeks using 780 nm, 200 mW, 30 minutes daily. One group received the implant but no laser. During the 3-6 months follow up, 14 of the 15 animals that received laser (A) showed different degrees of active movements in one or both legs, compared to 4 of 9 animals in the group who had received implants but no laser (B). In the group receiving no implant and no laser (C), 1 out of 7 showed some motor movements in one leg. Somatosensory evoked potentials were elicited in 10 of the 15 rats in group A at three months, and on one side in one animal in group B. Axon sprouting was observed as soon as three days post surgery, in group A only.

Guiding Neuronal Growth With Light J. Käs . PNAS. 2002; 99: 16024-16028 A. Ehrlicher, T. Betz, B. Stuhrmann, D. Koch, V. Milner, M. G. Raizen,

We have shown experimentally that we can use weak optical forces to guide the direction taken by the leading edge, or growth cone, of a nerve cell. In actively extending growth cones, we place a laser spot in front of a chosen area of the nerve‘s leading edge, promoting growth into the

beam focus. This allows us to guide neuronal turns as well as enhance growth. The power of our laser has been selected so that the resulting gradient forces are sufficiently powerful to bias the actin polymerization-driven lamellipodia extension, but too weak to hold and move the growth cone. We are therefore using light to control a natural biological process, in sharp contrast to the established technique of optical tweezers, which uses large optical forces to manipulate entire structures. Our results therefore open a new avenue to controlling neuronal growth in vitro and in vivo with a simple, non-contact technique. Currently we have been using 800nm with continuous application of powers ranging from 20 to 130 mW over a circular area of 1 to 4 um in radius. Recently we've developed and active feedback mechanism to trace the contour of the growth cone and subsequently raster the beam image upon that, instead of the pure beam profile we had used previously.

Transplantation Of Embryonal Spinal Cord Nerve Cells Cultured On Biodegradable Microcarriers Followed By Low Power Laser Irradiation For The Treatment Of Traumatic Paraplegia In Rats. (Abstract supplied by Allen Ehrlicher, main author) Neurol Res. 2002 Jun;24(4):355-60. Rochkind S, Shahar A, Amon M, Nevo Z. Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Israel. [email protected]

This pilot study examined the effects of composite implants of cultured embryonal nerve cells and laser irradiation on the regeneration and repair of the completely transected spinal cord. Embryonal spinal cord nerve cells dissociated from rat fetuses and cultured on biodegradable microcarriers and embedded in hyaluronic acid were implanted in the completely transected spinal cords of 24 adult rats. For 14 consecutive post-operative days, 15 rats underwent low power laser irradiation (780 nm, 250 mW), 30 min daily. Eleven of the 15 (73%) showed different degrees of active leg movements and gait performance, compared to 4 (44%) of the 9 rats with implantation alone. In a controlgroup of seven rats with spinal cord transection and no transplantation or laser, six (86%) remained completely paralyzed. Three months after transection, implantation and laser irradiation, SSEPs were elicited in 69% of rats (p = 0.0237) compared to 37.5% in the nonirradiated group. The control group had no SSEPs response. Intensive axonal sprouting occurred in the group with implantation and laser. In the control group, the transected area contained proliferating fibroblasts and blood capillaries only. This suggests: 1. These in vitro composite implants are a regenerative and reparative source for reconstructing the transected spinal cord. 2. Post-operative low power laser irradiation enhances axonal sprouting and spinal cord repair.

Growth-Associated Protein-43 Is Elevated In The Injured Rat Sciatic Nerve After Low Power Laser Irradiation. Neurosci Lett. 2003 Jun 26;344(2):71-4. Shin DH, Lee E, Hyun JK, Lee SJ, Chang YP, Kim JW, Choi YS, Kwon BS. Department of Anatomy, Seoul National University College of Medicine, Seoul, South Korea.

Low power laser irradiation (LPLI) has been used in the treatment of peripheral nerve injury. In this study, we verified its therapeutic effect on neuronal regeneration by finding elevated immunoreactivities (IRs) of growth-associated protein-43 (GAP-43), which is up-regulated

during neuronal regeneration. Twenty Sprague-Dawley rats received a standardized crush injury of the sciatic nerve, mimicking the clinical situations accompanying partial axonotmesis. The injured nerve received calculated LPLI therapy immediately after injury and for 4 consecutive days thereafter. The walking movements of the animals were scored using the sciatic functional index (SFI). In the laser treated rats, the SFI level was higher in the laser treated animals at 3-4 weeks while the SFIs of the laser treated and untreated rats reached normal levels at 5 weeks after surgery. In immunocytochemical study, although GAP-43 IRs increased both in the untreated control and the LPLI treated groups after injury, the number of GAP-43 IR nerve fibers was much more increased in the LPLI group than those in the control group. The elevated numbers of GAP-43 IR nerve fibers reached a peak 3 weeks after injury, and then declined in both the untreated control and the LPLI groups at 5 weeks, with no differences in the numbers of GAP-43 IR nerve fibers of the two groups at this stage. This immunocytochemical study using GAP-43 antibody study shows for the first time that LPLI has an effect on the early stages of the nerve recovery process following sciatic nerve injury.

Low-Level Laser Effect On Neural Regeneration In Gore-Tex Tubes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002 Jan;93(1):27-34. Miloro M, Halkias LE, Mallery S, Travers S, Rashid RG. Department of Surgery, Division of Oral and Maxillofacial Surgery, University of Nebraska Medical Center, Omaha 68198-5180, USA.

PURPOSE: The purpose of this investigation was to determine the effects of low-level laser (LLL) irradiation on neural regeneration in surgically created defects in the rabbit inferior alveolar nerve. STUDY DESIGN: Five adult female New Zealand White rabbits underwent bilateral exposure of the inferior alveolar nerve. A 6-mm segment of nerve was resected, and the nerve gap was repaired via entubulation by using a Gore-Tex conduit. The experimental side received 10 postoperative LLL treatments with a 70-mW gallium-aluminum-arsenide diode at 4 sites per treatment. At 15 weeks after surgery, the nerve segments were harvested bilaterally and prepared for light microscopy. Basic fuchsin and toluidine blue were used to highlight myelinated axons. The segments were examined histomorphometrically by using computer analysis to determine mean axonal diameter, total fascicular surface area, and axonal density along the repair sites. RESULTS: Gross examination of all nerves showed intact neural bundles with variable degrees of osseous remodeling. Light microscopic evaluation revealed organized regenerated neural tissue in both groups with more intrafascicular perineural tissue in the control group. Histomorphometric evaluation revealed increased axonal density in the laser treated group as compared with the control. CONCLUSIONS: LLL irradiation may be a useful noninvasive adjunct to promote neuronal wound healing in surgically created defects repaired with expanded polytetrafluoroethylene entubulation.

Effect Of Low-Level Laser Treatment On Neurosensory Deficits Subsequent To Sagittal Split Ramus Osteotomy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996 Aug;82(2):132-8. Khullar SM, Emami B, Westermark A, Haanaes HR. Department of Oral Surgery and Oral Medicine, University of Oslo, Norway.

OBJECTIVES: Low-level laser treatment has been advocated as a possible treatment for patients with paresthesia. An objectively verified improvement in sensory function is relevant if, at the

same time, it is perceived as a subjective improvement by the patient. The aim of this double blind clinical study was to see if low-level laser treatment with a GaAlAs laser (820 nm, Rønvig, Denmark) resulted in objectively verified improvement in sensory function and whether this correlated with the patient's subjective evaluation subsequent to treatment. STUDY DESIGN: The 13 patients in this study had all undergone saggittal split ramus osteotomy resulting in either compression or traction of the inferior alveolar nerve as reported by the surgery notes. The material was collected from a consecutive series of patients at the Karolinska Hospital, all of whom had shown reduced sensibility at their final 2-year postoperative checkup. The patients were randomly divided into two groups; one (eight subjects) group received real low-level laser treatment (4 x 6 J per treatment along the distribution of the inferior alveolar nerve, at the following points extraoral: lateral third of lower lip, intraoral; buccally to the apex of the second premolar tooth and the apex of the second molar tooth; lingually in the region of the mandibular foramen; for a total of 20 treatments). The other group received an equivalent placebo treatment. The study was conducted in a double blind fashion for both patient and doctor as the low-level laser equipment had two settings, A and B, one of which was an unknown void setting. The degree of mechanoceptor neurosensory deficit was assessed by Semmes Weinstein monofilaments (North Coast Medical, USA) and the degree of thermoceptor neurosensory deficit was assessed by a Thermotester (Somedic, Sweden). The degree of subjective neurosensory deficit was assessed by means of a visual analogue scale. Both variables and the degree of subjective injury were comparable between the two groups before starting treatment. RESULTS: The patients in the real low-level laser treatment group experienced a subjective improvement in both lip (p = 0.01) and chin (p = 0.02) after completion of the course of treatment. In addition, this group showed a significant decrease in the area of mechanoperception neurosensory deficit (p = 0.01) compared with no difference in the placebo group. The real low-level laser treatment group exhibited a strong tendency toward improvement in mechanoreceptor neurosensory deficit in the areas of most damage for both lip and chin. This improvement was especially pronounced in the lip region (p = 0.06). No similar tendency was demonstrated in the placebo group. Neither group showed any significant change or tendency to improvement in thermoception on completion of the course of treatment. CONCLUSION: In conclusion GaAlAs low-level laser treatment results in both a subjective and objective improvement in mechanical sensory perception in longstanding neurosensory deficit in the inferior alveolar nerve.

Nerve Regeneration in Children Laser Regeneration of Nerve Injuries in Children Used by the kind permission of the Czech Society for the Use of Laser in Medicine, www.laserpartner.org Laser Regeneration of Nerve Injuries in Children C. AILIOAIE*, L.M. AILIOAIE**, D.A. CHIRAN *** * Faculty of Medicine, "Gr.T. Popa" University of Medicine & Pharmacy, Iasi, Romania ** Department of Medical Physics, "Al.I. Cuza" University, Iasi, Romania *** Laser Clinic, Iasi, Romania

SUMMARY

The current research makes a systematic examination of the influence of Low Level Laser Therapy (LLLT) in the regeneration of nerves in children, diagnosed with facial asymmetry, brachial plexus, or radial nerve injuries. Thirty-one patients (no case of central paralysis) were randomly separated into two groups. Group 1 (16 patients) was treated using low-level laser radiation and group 2 (15 patients – the control group) was applied classical methods of treatment. Two diode lasers were used (670 and 830 nm wavelengths & 100 mW respectively 300 mW max. output power). All the children were followed closely with active and passive corrective exercises. The final analysis clearly indicates the validity of this new treatment technique, as 87.5% of the patients treated with laser displayed a complete recovery, reported to only 60.0% of the patients in the control group. INTRODUCTION

Peripheral nerve palsies in newborns and infants are known to occur with a frequency between 26% of cases [1]. The causes of palsies are very diverse; those of central nervous system are rare. The most frequently observed nerve injuries are those involving the facial nerve and the brachial plexus. Usually, facial palsy is a peripheral paralysis that results from pressure over the facial nerve in utero, from efforts during labor, or from forceps during delivery. Facial asymmetry may be present at birth or may develop later, suddenly or gradually, unilaterally or bilaterally [2, 3]. LLL radiation actions on electrophysiological parameters of nerves [4], and represents a hope in treating these problems [5, 6, 7]. MATERIALS AND METHODS

Thirty-one patients were randomly separated into two groups: group 1 (16 patients) was treated using low-level laser radiation, and group 2 (15 patients) was applied classical methods of treatment. In the present research both groups did not present any case of central paralysis, but the local traumatic etiology was the most frequently observed. At the newborns treated for facial asymmetry, the paralysis did not disappear spontaneously in a few days after delivery. See Table 1 for patient data.

Group 1 received LLL therapy every other day, three times a week, 12 days per month, during a 3-month period. The clinical work has been performed with Med 700 (670nm, Lasotronic – Switzerland) and Maestro (830nm, Medicom – Czech Republic). The treatment parameters were: density of energy in range of 2.0 – 8.0 J/cm2; pulsed wave – 8.2 Hz, in IR domain. Every paralysis was treated following the trajectory of the nerve from its origins, applying the treatment in 10 - 20 irradiation points by contact mode. In the case of the facial nerve there was applied a density of energy of 8.0 J/cm2 on its intaosseus trajectory. Group 2 was applied classical treatment. All the children were closely followed with active & passive corrective exercises. The integrity of the facial nerve was evaluated testing 10 muscular groups belonging to medial and lateral half of the face (See Figure 1). In this clinical test, points have been given for each muscular group, and then added, as follows: absence of contraction = 0 p, normal contraction = 3p.

RESULTS AND DISCUSSIONS

The efficiency of LLLT was very good. The improvement began after 12 sessions and the total recovery of function was observed at the end of treatment. Figure 2 displays the evolution of the motricity score in the tested patients, diagnosed with facial asymmetry.

The recorded results showed that the response after the first stage of treatment was positive in 43.7% of the children in LLLT group, comparatively with only 13.3% of the patients in the control group. The final analysis proved that 87.5% of the patients treated with laser displayed a complete recovery, reported to only 60.0% of the patients in the control group (Table 2).

The final outcome of the therapy related to the clinical forms of paralyses showed that all patients suffering of radial nerve palsy and Erb-Duchenne paralysis from the laser group were totally recovered and those with facial asymmetry cured in a proportion of 80.0%. In the control group 50% of the patients with radial paralysis were healed completely, while 44.4% of the facial asymmetry and 25% of the Erb-Duchenne paralysis subjects did not experience a complete recovery (Table 3).

The positive evolution of two patients: one diagnosed with Radial Palsy and treated with LLL is displayed in Figure 3: a – before treatment, b – after treatment, c – after 10 months from the therapeutic trial; and the other one diagnosed with Facial Asymmetry is shown in Figure 4: a – before treatment, b – after treatment.

CONCLUSIONS

The high efficacy rate in the regeneration of peripheral nerve injuries triggered by LLLT, especially in newborns and infants, clearly indicates the validity of this new treatment technique. More considerations could be offered regarding the future of nerve regeneration to help move this method into broader clinical applications. 12. References

1. Nelson Textbook of Pediatrics (2000). (Philadelphia, W.B. Saunders Comp). 2. Whaley, L.F., and wong, D.L. (1987). Nursing Care of Infants and Children, (St. Louis – Missouri, The C.V. Mosby Company). 3. Singhi, S. (1980). Congenital Asymmetrical Crying Faces. Clin Pediatr. 19, 673 – 678. 4. Karu, T. (1998). The Science of Low-Power Laser Therapy. (Amsterdam: Gordon and Breach Science Publishers). 5. Lasers in Medicine and Dentistry: Basic science and up-to-date clinical application of Low Energy-Level Laser Therapy – LLLT, (2000). (Rijeka – Croatia, Vitagraf). 6. Ailioaie, L.M., Ailioaie C. and Topoliceanu F. (2001). Laser Action in Nerve Injuries in Children. Book of Abstracts, 8-th International Congress of EMLA, Moscow, 42. 7. Ailioaie C, Ailioaie LM. (2002). Low Level Laser Therapy as a Medical Treatment Modality in Pediatrics – Invited Educational Lecture. International Proceedings Division – Monduzzi Editore, Proceedings of the 4th Congress of the World Association for Laser

Therapy ***book***, Editor(s): Hanaoka K., Kubota J., Arita H., p. 1-6, Tokyo, Japan, ISBN: 88-323-2627-2.

Neurogenic Pruritus The Use Of Laser Acupuncture For The Treatment Of Neurogenic Pruritus In A Child--A Case History. Acupunct Med. 2005 Mar;23(1):31-3. Stellon A. [email protected]

This report describes the successful treatment using laser acupuncture of a six year old girl with neurogenic pruritus of the abdomen. It is the first case report of neurogenic pruritus treated by laser acupuncture. The main advantage of using low energy laser, as opposed to acupuncture needles, to stimulate points, is that low energy laser causes little or no sensation, which is particularly useful when treating children.

Neuropathy [Influence Of Low-Intensity Laser Therapy On Spatial Perception Threshold And Electroneurographic Finding In Patients With Diabetic Polyneuropathy] Srp Arh Celok Lek. 2007 May-Jun;135(5-6):257-63 [Article in Serbian] Peric Z.

INTRODUCTION: Low-intensity laser therapy (LILT) can be applied in cases when patients with diabetic polyneuropathy (DPN) suffer from chronic severe neuropathic pain. OBJECTIVE: We wanted to analyse influence of LILT on spatial perception threshold (SPT) and electroneurographic (ENG) parameters in patients with painful DPN. METHOD: We analysed 45 patients (25 males), average age 54.3 years (54.3 +/- 10.9), with clinical and ENG signs of painful DPN. The patients were divided into two groups: A and B. Group A consisted of 30 patients with DPN who had 30 LILT treatments over the period of 12 weeks and group B consisted of 15 patients with DPN who received only vitamin therapy per os within the same period. Prior to and after 12 weeks of treatment, the following ENG parameters were determined using surface electrodes: motor (MCV) and sensory conduction velocities (SCV) values (in m/s) of nervus (n.) peroneus (NP), n. tibialis (NT) and n. medianus (NM) and their motor distal latency (MDL) values (in ms). SPT value (score as number from 1 to 8) was determined with Tactile Circumferential Discriminator on dorsal part of foot's big toe skin. For statistical analysis, we used Student's t-test and Pearson correlation (sig. 2 tailed) study. RESULTS; We registered statistically significant difference between SPT (p < 0.01) values prior to (5.25 +/- 1.11) and after (4.87 +/- 0.90) LILT, as well as NMMCV (p < 0.05) values prior to (47.18 +/-

5.08) and after (49.12 +/- 3.72) LILT. Besides, we registered, only after LILT, statistically significant correlation beetwen SPT and NMDML (p < 0.01) values and also beetwen SPT and NMSCV (p < 0.05) values. The differences and correlations beetwen other analysed parameters before and after treatments were not significant (p > 0.05). CONCLUSION: In this study we registered significant decrease of SPT and increase of NMMCV after LILT and that indicated a favourable effect of this treatment in analysed patients with painful DPN. In our opinion these results need further investigation.

Improved Sensitivity In Patients With Peripheral Neuropathy: Effects Of Monochromatic Infrared Photo Energy. J Am Podiatr Med Assoc. 2005 Mar-Apr;95(2):143-7. DeLellis SL, Carnegie DH, Burke TJ. Gulf Coast Foot, Ankle and Wound Center, Tarpon Springs, FL, USA.

The medical records of 1,047 patients (mean age, 73 years) with established peripheral neuropathy were examined to determine whether treatment with monochromatic infrared photo energy was associated with increased foot sensitivity to the 5.07 Semmes- Weinstein monofilament. The peripheral neuropathy in 790 of these patients (75%) was due to diabetes mellitus. Before treatment with monochromatic infrared photo energy, of the ten tested sites (five on each foot), a mean +/- SD of 7.9 +/- 2.4 sites were insensitive to the 5.07 Semmes-Weinstein monofilament, and 1,033 patients exhibited loss of protective sensation. After treatment, the mean +/- SD number of insensate sites on both feet was 2.3 +/- 2.4, an improvement of 71%. Only 453 of 1,033 patients (43.9%) continued to have loss of protective sensation after treatment. Therefore, monochromatic infrared photo energy treatment seems to be associated with significant clinical improvement in foot sensation in patients, primarily Medicare aged, with peripheral neuropathy. Because insensitivity to the 5.07 Semmes-Weinstein monofilament has been reported to be a major risk factor for diabetic foot wounds, the use of monochromatic infrared photo energy may be associated with a reduced incidence of diabetic foot wounds and amputations.

Reversal of diabetic peripheral neuropathy and new wound incidence: the role of MIRE. Adv Skin Wound Care. 2004 Jul-Aug;17(6):295-300. Powell MW, Carnegie DE, Burke TJ. Northwest Orthopedic Center, Springdale, AR, USA.

OBJECTIVE: To determine if improved foot sensitivity to the Semmes-Weinstein 10-g (5.07) monofilament, originally impaired because of diabetic peripheral neuropathy, might be associated with a reduced incidence of new diabetic foot wounds. DESIGN: Retrospective cohort study using a health status questionnaire. SUBJECTS: Sixty-eight individuals over age 64 with diabetes, diabetic peripheral neuropathy, and loss of protective sensation who had clinically demonstrable increases in foot sensation to the Semmes-Weinstein monofilament after treatment with monochromatic near infrared photo energy. MAIN RESULTS: After reversal of diabetic peripheral neuropathy following treatment with monochromatic near infrared photo energy, only 1 of 68 patients developed a new diabetic foot

wound, for an incidence of 1.5%. Comparatively, the incidence previously reported in the Medicare-aged population with diabetes was 7.3%. CONCLUSIONS: Improved foot sensitivity to the Semmes-Weinstein monofilament in patients previously suffering from loss of protective sensation due to diabetic neuropathy appears to be associated with a lower incidence of new diabetic foot ulcers when compared with the expected incidence in the Medicare-aged population with diabetes. CLINICAL RELEVANCE: Therapeutic interventions that effectively improve foot sensitivity that has been previously diminished due to diabetic peripheral neuropathy may substantially reduce the incidence of new foot wounds in the Medicare-aged population with diabetes.

[Laser Therapy And Electric Stimulation In Rehabilitation Treatment Of Peripheral Neuropathy] Vopr Kurortol Fizioter Lech Fiz Kult. 2002 Jul-Aug;(4):25-7. [Article in Russian] Miriutova NF, Abdulkina NG, Luksha LV, Levitskii EF.

73 patients with compression-ischemic myeloradiculopathy received treatment including infrared laser radiation on the paravertebral fields, motor points of the affected nerves and biologically active points Y63, Y67, YB34, YB42, YB43, E34, E42 (1.0-5.0 mW/cm2; 5 and 5000 Hz), electrostimulation of motor nerve points and innervated by them muscles by double square impulses with a fixed gap 5 ms. Impulse infrared laser therapy relieves pain syndrome, stimulates repair processes in the affected nerve structures. Further modified electric stimulation activates a regenerative growth of the nerve fibers, reinnervation of the limb muscles.

[Use Of Physical Factors In The Complex Therapy Of Patients With Diabetic Angio- And Polyneuropathies Of The Lower Extremities] Lik Sprava. 2002 Jul-Sep;(5-6):62-5. [Article in Ukrainian] Shablinskaia NB.

Results are submitted of treatment of 110 patients with diabetes mellitus (61 male and 49 female subjects) presenting with angio- and polyneuropathies of the lower extremities. 70 patients, in addition to a drug therapy, were administered physiotherapeutic treatments, such as amplipulsetherapy, darsonvalization, and laserotherapy. Forty patients received medicamentous therapy only. Based on clinical findings and laboratory methods of investigation expediency has been shown of employment of physiotherapeutic methods in the treatment of the above pathology.

Symptomatic Reversal Of Peripheral Neuropathy In Patients With Diabetes. J Am Podiatr Med Assoc. 2002 Mar;92(3):125-30. Kochman AB, Carnegie DH, Burke TJ. The Medical Center of Aurora, Aurora, CO, USA.

Forty-nine consecutive subjects with established diabetic peripheral neuropathy were treated with monochromatic near-infrared photo energy (MIRE) to determine if there was an improvement of sensation. Loss of protective sensation characterized by Semmes- Weinstein monofilament values of 4.56 and above was present in 100% of subjects (range, 4.56 to 6.45), and 42 subjects (86%) had Semmes-Weinstein values of 5.07 or higher. The ability to discriminate between hot and cold sensation was absent (54%) or impaired (46%) in both groups prior to the initiation of MIRE treatment. On the basis of Semmes-Weinstein monofilament values, 48 subjects (98%) exhibited improved sensation after 6 treatments, and all subjects had improved sensation after 12 treatments. Therefore, MIRE may be a safe, drug-free, noninvasive treatment for the consistent and predictable improvement of sensation in diabetic patients with peripheral neuropathy of the feet.

[Laser therapy and cryomassage in rehabilitation of patients with facial nerve neuropathy] [Article in Russian] Maslovskaia SG, Gusarova SA, Gorbunov FE, Strel'tsova EN.

Cryomassage and its combination with low-intensity infra-red laser radiation have been introduced as a novel treatment of facial nerve neuropathy (FNN) in 32 patients. Electrophysiological investigations (facial thermography, classical electrodiagnosis, electromyography of the mimic muscles) and clinical data including those of long-term followup show that neither cryomassage nor infra-red laser radiation studied promote transformation of facial tissues in FNN patients. Use of the above factors is effective in a preclinical stage of forming contracture of the mimic muscles. Special techniques of application of local hypothermia and laser radiation can be used in multimodality treatment of both the established contracture and sluggish paresis of the facial muscles.

HELIUM-NEON LASERTHERAPY IN TREATMENT OF FACIAL NERVE NEUROPATHY A. Scherbonosova, V.V. Skupchenko Medical university, Far Eastern Medical Center, Khabarovsk, Russia

Facial nerve damage is the result of different factors influence and it appears at the background of ischemia anoxia. Elimination of a local pathologically fixed ergothroimages ischemia condition with the help of helium-neon laser therapy (FTNLT) has been conducted taking into consideration initial vegetative pattern of patients. It allowed to adjust treatment methods based on laser effect individually for every patient. Mimic muscles function restoration in the course of treatment had begun after 5 treatment sessions with HNLT and matched vegetative status normalization as well as reofaciogram, ultrasound Dopplerography of temporal and ophthalmic arteries and general conjunctive index. Thus, HNLT is a gentle corrector of vegetative homeostasis and sanogenic mechanisms. It allows to synchronize local and cerebral hemodynamics rhythms and trigger reparative regeneration of the facial nerve.

[Infrared Laser Therapy In Distal Diabetic Polyneuropathy] Zh Nevrol Psikhiatr Im S S Korsakova. 1998;98(6):23-5. [Article in Russian]

Kalinina OV, Alekseeva NV, Burtsev EM.

A course of laser therapy was applied to 50 patients with diabetic polyneuropathy by laser irradiation of low intensiveness in the nearest infrared spectrum. 20 patients from the group were treated by monotherapy only by laser exposure. Control group consisted of 24 patients treated by conventional therapy without laser exposure. According to the changes of vibratory and algesic sensitivity and electromyographic data the efficiency of therapy was estimated. It was found that laser exposure resulted in more pronounced restoration of functional state of nervous fibers than conventional therapy. Application of laser irradiation of low intensiveness was effective while in combined therapy of distal diabetic polyneuropathy as well as monotherapy.

Infrared laser therapy influence on blood circulation in patients with diabet distal polyneuropathy. Protasyeva L.G., Burtsev E.M., Alekseyeva N.V., Osnovina I.P., Cheida A.A., Nazarov S.B. I.S.M.A. Ivanovo. Russia.

96 patients with DDPNP received infrared lasertherapy. Their bloodflow including parameters of microcirculation issas carefeully exarnined. Laser therapy stimulated microcirculation in both groups of patients with microcirculation disorders alone and with the combination of marked micro –and makrocirculation therapy disturbances. High effectiveness of Laser in DDPNP was proved. Authors conclude that laser therapy is a pathogenic method of DDPNP treatment.

Laser irradiation suppresses hyperalgesia in neuropathic rats. Proc. 2nd Congress World Assn for Laser Therapy, Kansas City, September 1998; p. 28 Katsuyama I et al.

Katsuyama studied the effect of 830 nm laser in a neuropathic pain model of rat. The left side sciatic nerves of two groups of rats were ligated loosely to produce a neuropathic pain. The latency of the foot withdrawal reflex to noxious heat stimuli was measured before the ligation, immediately after laser/placebo radiation and at 14 days after ligation. The laser group received 72 J through the dermis. This group showed a significant reduction in left foot withdrawal immediately after irradiation and at 14 days, the right foot being unchanged. Placebo irradiation did not change the latency in the ligated in the ligated group, nor in non-ligated rats.

Neurosensory Recovery after Surgery Low-Level Laser Effect On Neurosensory Recovery After Sagittal Ramus Osteotomy. Oral surgery, oral medicine, oral pathology, oral radiology,and endodontics. 2000; 89(1):12-18 Miloro-M, Repasky-M.

This study examined the potential benefit of perioperative and short-term postoperative low-level laser (LLL) therapy on objective and subjective neurosensory recovery after bilateral sagittal split osteotomy surgery. Six consecutive patients undergoing bilateral sagittal split osteotomy

procedures were enrolled in this prospective study. A complete preoperative clinical neurosensory test, consisting of brush stroke directional discrimination, 2-point discrimination, contact detection, pin prick nociception, and thermal discrimination, was performed on each patient; and a subjective assessment of neurosensory function was made by using a visual analog scale (VAS). The protocol for LLL treatments consisted of real LLL (4 x 6 J per treatment) along the distribution of the inferior alveolar nerve at 4 sites, for a total of 7 treatments, delivered immediately before surgery; at 6 and 24 hours after surgery; and on postoperative days 2, 3, 4, and 7. The clinical neurosensory test and VAS were completed just before each of the treatment sessions and on days 14 and 28, by one examiner. When the results of the patients treated with LLL were compared with published values for neurosensory recovery after orthognathic surgery, there was a significant acceleration in the time course, as well as in the magnitude, of neurosensory return. Brush stroke directional discrimination approached normal values by 14 days, whereas 2-point discrimination and contact detection showed significant improvement at 14 days and returned to near-normal values by 2 months. The results of thermal discrimination and pin prick nociception revealed few neurosensory deficits; however, those patients who were affected showed a slower recovery trend ann remained neurosensory-deficient for up to 2 months. The VAS analysis revealed a rapidly progressive improvement in subjective assessment,showing a 50% deficit at 2 days and only a 15% subjective deficit at 2 months. This study demonstrates that neurosensory recovery after bilateral sagittal split osteotomy procedures can be significantly improved, both in terms of time course and magnitude of return of function.

Nocturnal Enuresis [Laser Acupuncture As Third-Line Therapy For Primary Nocturnal Enuresis. First Results Of A Prospective Study] Urologe A. 2004 Jul;43(7):803-6 [Article in German] Heller G, Langen PH, Steffens J. Klinik für Urologie und Kinderurologie, St.-Antonius-Hospital [email protected]

Laser acupuncture is a painless, non-invasive, and cost effective treatment for children with therapy resistant monosymptomatic nocturnal enuresis. This kind of acupuncture is an alternative treatment with positive results. Currently, we are treating 24 children (22 males, 2 females) out of a planned 200 children aged between 5 and 12 years. These patients have had a classic monosymptomatic nocturnal enuresis. Up to now, school medicine therapy has been unsuccessful. Over 3 months, we treated the children once a week with acupuncture, inserting at the following points: medial Ren 3, bilateral Ma 36, bilateral Mi 6, bilateral Bl 33, medial Ren 6, medial Ex B5.A better enuresis frequency was achieved in 21 out of the 24 children (87.5%). Before the end of the 12th treatment, six of the 24 children (25%) were completely dry and 16 (66.6%) had an enuresis frequency reduced by more than half after the 12th treatment.

Nocturnal Enuresis. Curr Opin Urol. 2002 Jul;12(4):317-20

Djurhuus JC, Rittig S. Institute of Experimental Clinical Research, Aarhus University Hospital, Skejby Section, Denmark. [email protected]

PURPOSE OF REVIEW: The purpose of this review is to highlight and comment upon important areas of enuresis research. RECENT FINDINGS: Current areas of pathophysiological focus are nocturnal urine production, in which alternative mechanisms other than deficient vasopressin secretion has been implicated in some patients. Bladder reservoir function has gained renewed interest, and has proved to be one of the best predictors of treatment response to desmopressin. Various aspects of central nervous system function, including arousability and pontine reflexes, are in focus, and molecular genetics has provided firm evidence of a link between enuresis and different chromosomal markers. The therapeutic focus is directed towards a differential approach based upon the underlying mechanism and towards combination therapies such as alarm devices and desmopressin as well as anticholinergic agents and desmopressin. Furthermore, new exciting treatment concepts such as laser acupuncture have shown promising results in initial studies. SUMMARY: Despite recent advances in our understanding of nocturnal enuresis, we are still far from understanding in detail this socially discomfiting and scientifically intriguing condition, and many controversies remain. However, the substantiation that enuresis is a heterogeneous condition that requires a differential approach has provided the basis for further progress.

Prospective Randomized Trial Using Laser Acupuncture Versus Desmopressin In The Treatment Of Nocturnal Enuresis. Eur Urol. 2001 Aug;40(2):201-5 Radmayr C, Schlager A, Studen M, Bartsch G. Department of Urology, University of Innsbruck, Austria. [email protected]

OBJECTIVES: Several treatment modalities for children suffering from monosymptomatic nocturnal enuresis are available, but desmopressin is a wellestablished option. On the other hand, alternative nonpharmacological therapies such as laser acupuncture are more frequently requested by the parents. To our knowledge, there is no prospective randomized trial which evaluated the efficacy of such an alternative approach in comparison with the widespread use of desmopressin. METHODS: Forty children aged over 5 years presenting with primary nocturnal enuresis underwent a previous evaluation of their voiding function to assure normal voiding patterns and a high nighttime urine production. Then the children were randomized into two groups: group A children were treated with desmopressin alone, and group B children underwent laser acupuncture. All children were investigated after a minimum follow-up period of 6 month to evaluate the duration of the response. RESULTS: The children of both groups had an initial mean frequency of 5.5 wet nights per week. After a minimum follow-up period of 6 months reevaluation revealed a complete success rate of 75% in the desmopressin-treated group. Additional 10% of the children had a reduction of their wet nights of more than 50%. On the other hand, 6 months after laser acupuncture, 65% of the randomized children were completely dry. Another 10% had a reduction of the enuresis frequency of more than 50% per week. 20% of the children in the desmopressintreated group did not respond at all as compared with 15% in the acupuncture-treated group. Statistical evaluation revealed no significant differences among the response rates in both groups. CONCLUSION: Im comparison with pharmacological therapy using desmopressin, our study shows that laser acupuncture should be taken into account as an

alternative, noninvasive, painless, cost-effective, and short-term therapy for children with primary nocturnal enuresis in case of a normal bladder function and high nighttime urine production. Success rates indicated no statistically significant differences between the wellestablished desmopressin therapy and the alternative laser acupuncture.

Osteomylelitis The effect of low level laser therapy on chronic osteomyelitis: a case report EMLA Laser Health J 2007;2:46-67 European Medical Laser Association (EMLA) Kazemi-Khoo N. Iran University of Medical Science, Head Office of Laser Center of Milad Hospital prof Ismailov

Low level laser therapy (LLLT) could increase tissue perfusion, reinforcement of immune system and may have antibacterial effect. In this article we report the successful treatment of chronic osteomyelitis by LLLT. Patient was a 16-year-old girl who had been severely injured in a truck accident. Her right metatarsal bones were crushed and resistant osteomyelitis complicated the patient, but she rejected amputation. She referred to our laser center due to chronic osteomyelitis with a discharging fistula. Antibiotics (ceftrixone and cloxacillin prescribed according to the culture showed Staphylococcus aureus). We also applied laser with a dose of 10-12 J/cm 2, using continuous infrared light (wavelength 980 nm, power 100 mW) and continuous red light (wavelength 650 nm, power 30 mW), 3 times a week for 4 weeks and then 2 times a week until discharge was disappeared (totally 28 sessions). After a month fistula discharged again and the same laser protocol along with laser acupuncture was applied for 23 sessions. This treatment was successful and after 3 months Elizarov's surgery was done. At this time (10 month after the last session of laser therapy) she can stand straight and walk.

Osteonecrosis of the jaw and laser therapy Nd:YAG Laser Biostimulation In The Treatment Of BisphosphonateAssociated Osteonecrosis Of The Jaw: Clinical Experience In 28 Cases. Photomed Laser Surg. 2008 Feb;26(1):37-46 Vescovi P, Merigo E, Manfredi M, Meleti M, Fornaini C, Bonanini M, Rocca JP, Nammour S. Unit of Oral Pathology and Medicine, Section of Dentistry, Department of ENT/Dental/Ophthalmological and Cervico-Facial Sciences, University of Parma, Parma, Italy. [email protected]

OBJECTIVE: To research an efficient treatment for the management of bisphosphonate associated osteonecrosis. BACKGROUND DATA: Necrosis of the jawbone has recently been described in association with systemic bisphosphonate therapy with drugs including

zoledronic acid, pamidronate, and alendronate. The extent and clinical characteristics of bisphosphonate-associated osteonecrosis (BON) of the jaw are extremely variable, and range from the presence of fistulae in the oral mucosa or orofacial tissues, to large exposed areas of necrotic bone within the oral cavity. Clinical signs and symptoms commonly reported include pain, swelling, the presence of pus, loose teeth, ill-fitting dentures, and paresthesias of the inferior alveolar nerve when the necrosis affects the mandible. Fractures have also been reported. The treatment of BON of the jaw is still controversial since no therapy has proven to be efficacious as shown by the literature on the subject. MATERIALS AND METHODS: In this study we report results achieved with 28 patients affected by BON of the jaw, who received treatment with the Nd:YAG laser alone or in combination with conventional medical or surgical treatment. Clinical variables such as severity of symptoms, presence of pus, and closure of mucosal flaps before and after therapy were evaluated to establish the effectiveness of laser irradiation. The 28 patients with BON were subdivided into four groups: eight patients were treated with medical therapy only (antibiotics with or without antimycotics and/or antiseptic rinses), six patients were treated with medical and surgical therapy (necrotic bone removal and bone curettage), six patients were treated with medical therapy associated with laser biostimulation, and eight patients were treated with medical therapy associated with both surgical therapy and laser biostimulation. RESULTS: Of the 14 patients who underwent laser biostimulation, nine reported complete clinical success (no pain, symptoms of infection, or exposed bone or draining fistulas), and three improved their symptomatology only, with a follow-up of between 4 and 7 mo. CONCLUSIONS: While the results reported in this study are not conclusive, they indicate that laser therapy has potential to improve management of BON.

Bone Necrosis Of The Jaws Associated With Bisphosphonate Treatment: A Report Of Twenty-Nine Cases. Acta Biomed. 2006 Aug;77(2):109-17. Merigo E, Manfredi M, Meleti M, Guidotti R, Ripasarti A, Zanzucchi E, D'Aleo P, Corradi D, Corcione L, Sesenna E, Ferrari S, Poli T, Bonaninil M, Vescovi P. Unit of Oral Pathology and Medicine, Section of Odontostomatology, Department of ENT/Dental/Ophthalmological and Cervico-Facial Sciences, University of Parma, Parma, Italy. [email protected]

Bone necrosis of the jaws is often related to head and neck radiotherapy, to surgical procedures at maxillary or mandibular level but also to various local and systemic factors such as haematological diseases, haemoglobinopathies and systemic lupus eritematosus; its pathogenesis maybe associated with defects of vascularization. Bisphosphonate are synthetic analogues of pyrophosphate used for the treatment of hypercalcemia in patients with malignancies and bone metastasis and for the treatment of many other disorders such as metabolic bone diseases, Paget's disease, and osteoporosis; their pharmacological activity is related to the inhibition of the osteoclastic function which leads to resorption and reduction of bone vascularization. Since the end of 2003 Bisphosphonate-associated Osteonecrosis (BON) has become an increasing problem and the test of that is the increase of the relative published case report and case series. Here we report 29 cases of bone necrosis of the jaws in patients treated with pamidronate (Aredia), zoledronate

(Zometa) and alendronate: 15 underwent surgical procedures and 14 occurred spontaneously. Among these patients (21 females, 8 males; mean age between 45 and 83 years); 14 were treated for bone metastasis, 12 for multiple myeloma and 3 for osteoporosis. Bone necrosis involved only maxilla in 7 patients, only mandible in 20 patients and both in 2 patients. Six patients had multiple osteonecrotic lesions, 3 contemporary lesions and 3 non contemporary. In these patients we performed 3 kinds of therapy, associated or not: medical therapy (with antibiotic drugs, antimycotics and antiseptic mouthwashes), surgical therapy with curettage or sequestrectomy and Nd:YAG laser biostimulation.

Osteoporosis - Bone Healing Effects Of Low-Level Laser Therapy On Bone Formed After Distraction Osteogenesis. Lasers Med Sci. 2009 Jun 23. [Epub ahead of print Hübler R, Blando E, Gaião L, Kreisner PE, Post LK, Xavier CB, de Oliveira MG. School of Physics, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681, Prédio 10, sala 222, Caixa Postal 1429, 90619-900, Porto Alegre, RS, Brazil.

This study evaluated the effect of low-level laser therapy (LLLT) on the chemical composition, crystallinity and crystalline structure of bone at the site of distraction osteogenesis. Five rabbits were subjected to distraction osteogenesis (latency = 3 days; rate and frequency = 0.7 mm/day for 7 days; consolidation = 10 days), and three were given LLLT with arsenidegallium- aluminum (AsGaAl; 830 nm, 40 mW): 10 J/cm(2) dose per spot, applied directly to the distraction osteogenesis site during the consolidation stage at 48 h intervals. Samples were harvested at the end of the consolidation stage. X-ray fluorescence and X-ray diffraction were used to analyze chemical composition, crystallinity and crystalline structure of bone at the distraction osteogenesis site. The analysis of chemical composition and calcium (Ca) and phosphorus (P) ratios revealed greater mineralization in the LLLT group. Diffractograms showed that the crystalline structure of the samples was similar to that of hydroxyapatites. Crystallinity percentages were greater in rabbits that were given LLLT. Crystallinity (41.14% to 54.57%) and the chemical composition of the bone at the distraction osteogenesis site were similar to the that of the control group (42.37% to 49.29%). The results showed that LLLT had a positive effect on the biomodulation of newly formed bone.

Superpulsed Laser Irradiation Increases Osteoblast Activity Via Modulation Of Bone Morphogenetic Factors. Lasers Surg Med. 2009 Apr;41(4):298-304 Saracino S, Mozzati M, Martinasso G, Pol R, Canuto RA, Muzio G. Department of Experimental Medicine and Oncology, University of Turin, Corso Raffaello 30, 10125 Turin, Italy.

BACKGROUND AND OBJECTIVE: Laser therapy is a new approach applicable in different medical fields when bone loss occurs, including orthopedics and dentistry. It has also been used to induce soft-tissue healing, for pain relief, bone, and nerve regeneration. With regard

to bone synthesis, laser exposure has been shown to increase osteoblast activity and decrease osteoclast number, by inducing alkaline phosphatase (ALP), osteopontin, and bone sialoprotein expression. Studies have investigated the effects of continuous or pulsed laser irradiation, but no data are yet available on the properties of superpulsed laser irradiation. This study thus aimed to investigate the effect of superpulsed laser irradiation on osteogenic activity of human osteoblast-like cells, paying particular attention to investigating the molecular mechanisms underlying the effects of this type of laser radiation. STUDY DESIGN/MATERIALS AND METHODS: Human osteoblast-like MG-63 cells were exposed to 3, 7, or 10 superpulsed laser irradiation (pulse width 200 nanoseconds, minimum peak power 45 W, frequency 30 kHz, total energy 60 J, exposure time 5 minutes). The following parameters were evaluated: cell growth and viability (light microscopy, lactate dehydrogenase release), calcium deposits (Alizarin Red S staining), expression of bone morphogenetic factors (real-time PCR). RESULTS: Superpulsed laser irradiation decreases cell growth, induces expression of TGF-beta2, BMP-4, and BMP-7, type I collagen, ALP, and osteocalcin, and increases the size and the number of calcium deposits. The stimulatory effect is maximum on day 10, that is, after seven applications. CONCLUSIONS: Reported results show that superpulsed laser irradiation, like the continuous and pulsed counterparts, possesses osteogenic properties, inducing the expression of molecules known to be important mediators of bone formation and, as a consequence, increasing calcium deposits in human MG-63 cells. Moreover, the data suggest a new potential role for PPARgamma as a regulator of osteoblast proliferation.

Nd:YAG Laser Biostimulation In The Treatment Of BisphosphonateAssociated Osteonecrosis Of The Jaw: Clinical Experience In 28 Cases. Vescovi P, Merigo E, Manfredi M, Meleti M, Fornaini C, Bonanini M, Rocca JP, Nammour S. Unit of Oral Pathology and Medicine, Section of Dentistry, Department of ENT/Dental/Ophthalmological and Cervico-Facial Sciences, University of Parma, Parma, Italy. [email protected]

OBJECTIVE: To research an efficient treatment for the management of bisphosphonate associated osteonecrosis. BACKGROUND DATA: Necrosis of the jawbone has recently been described in association with systemic bisphosphonate therapy with drugs including zoledronic acid, pamidronate, and alendronate. The extent and clinical characteristics of bisphosphonate-associated osteonecrosis (BON) of the jaw are extremely variable, and range from the presence of fistulae in the oral mucosa or orofacial tissues, to large exposed areas of necrotic bone within the oral cavity. Clinical signs and symptoms commonly reported include pain, swelling, the presence of pus, loose teeth, ill-fitting dentures, and paresthesias of the inferior alveolar nerve when the necrosis affects the mandible. Fractures have also been reported. The treatment of BON of the jaw is still controversial since no therapy has proven to be efficacious as shown by the literature on the subject. MATERIALS AND METHODS: In this study we report results achieved with 28 patients affected by BON of the jaw, who received treatment with the Nd:YAG laser alone or in combination with conventional medical or surgical treatment. Clinical variables such as severity of symptoms, presence of pus, and closure of mucosal flaps before and after therapy were evaluated to establish the effectiveness of laser irradiation. The 28 patients with BON were subdivided into four groups: eight patients were treated with medical therapy only (antibiotics with or without antimycotics and/or antiseptic rinses), six patients were treated with medical and surgical therapy (necrotic bone

removal and bone curettage), six patients were treated with medical therapy associated with laser biostimulation, and eight patients were treated with medical therapy associated with both surgical therapy and laser biostimulation. RESULTS: Of the 14 patients who underwent laser biostimulation, nine reported complete clinical success (no pain, symptoms of infection, or exposed bone or draining fistulas), and three improved their symptomatology only, with a follow-up of between 4 and 7 mo. CONCLUSIONS: While the results reported in this study are not conclusive, they indicate that laser therapy has potential to improve management of BON.

Bone Necrosis Of The Jaws Associated With Bisphosphonate Treatment: A Report Of Twenty-Nine Cases. Acta Biomed. 2006 Aug;77(2):109-17. Merigo E, Manfredi M, Meleti M, Guidotti R, Ripasarti A, Zanzucchi E, D'Aleo P, Corradi D, Corcione L, Sesenna E, Ferrari S, Poli T, Bonaninil M, Vescovi P. Unit of Oral Pathology and Medicine, Section of Odontostomatology, Department of ENT/Dental/Ophthalmological and Cervico-Facial Sciences, University of Parma, Parma, Italy. [email protected]

Bone necrosis of the jaws is often related to head and neck radiotherapy, to surgical procedures at maxillary or mandibular level but also to various local and systemic factors such as haematological diseases, haemoglobinopathies and systemic lupus eritematosus; its pathogenesis maybe associated with defects of vascularization. Bisphosphonate are synthetic analogues of pyrophosphate used for the treatment of hypercalcemia in patients with malignancies and bone metastasis and for the treatment of many other disorders such as metabolic bone diseases, Paget's disease, and osteoporosis; their pharmacological activity is related to the inhibition of the osteoclastic function which leads to resorption and reduction of bone vascularization. Since the end of 2003 Bisphosphonate-associated Osteonecrosis (BON) has become an increasing problem and the test of that is the increase of the relative published case report and case series. Here we report 29 cases of bone necrosis of the jaws in patients treated with pamidronate (Aredia), zoledronate (Zometa) and alendronate: 15 underwent surgical procedures and 14 occurred spontaneously. Among these patients (21 females, 8 males; mean age between 45 and 83 years); 14 were treated for bone metastasis, 12 for multiple myeloma and 3 for osteoporosis. Bone necrosis involved only maxilla in 7 patients, only mandible in 20 patients and both in 2 patients. Six patients had multiple osteonecrotic lesions, 3 contemporary lesions and 3 non contemporary. In these patients we performed 3 kinds of therapy, associated or not: medical therapy (with antibiotic drugs, antimycotics and antiseptic mouthwashes), surgical therapy with curettage or sequestrectomy and Nd:YAG laser biostimulation.

Effect Of IR Laser Photobiomodulation On The Repair Of Bone Defects Grafted With Organic Bovine Bone. Lasers Med Sci. 2008 Jul;23(3):313-7. Epub 2007 Sep 20. Márquez Martínez ME, Pinheiro AL, Ramalho LM. School of Dentistry, Pernambuco University, Camaragibe, Pernambuco, Brazil.

A major problem on modern dentistry is the recovery of bone defects of different etiologies. Biomaterials are used to improve the repair of these defects. Previous studies have shown

positive effects of Laser Photobiomodulation (LPBM) on the repair of both soft and bone tissues. This study assessed histologically the effect of LPBM on the repair of surgical defects on the femur of rats filled with lyophilized bovine bone. The animals were divided into three groups: group I (control); group II (graft); group III (graft + LPBM). The animals on the irradiated groups received 16 J/cm(2) per session divided into four points around the defect being the first irradiation immediately after surgery and repeated at every 48 h during 2 weeks. Animal death occurred 15, 21, and 30 days after surgery. The specimens were routinely processed and stained with H/E and Sirius red and analyzed by light microscopy. There was histological evidence of improved collagen fiber deposition at early stages of the healing; increased amount of well-organized bone trabeculae at the end of the experimental period on irradiated animals. It is concluded that LPBM has positive biomodulative effect on the healing process bone defects.

Assessment Of Bone Repair Associated With The Use Of Organic Bovine Bone And Membrane Irradiated At 830 Nm. Photomed Laser Surg. 2005 Aug;23(4):382-8 Gerbi ME, Pinheiro AL, Marzola C, Limeira Júnior Fde A, Ramalho LM, Ponzi EA, Soares AO, Carvalho LC, Lima HV, Gonçalves TO. School of Dentistry, Federal University of Bahia, Salvador, Brazil.

OBJECTIVE: The aim of the present investigation was to assess histologically the effect of LLLT (GaAIAs, 830 nm, 40 mW, CW, (Phi) approximately 0.6 mm, 16 J/cm(2) per session) on the repair of surgical defects created in the femur of the Wistar Albinus rat. The defects were filled to lyophilized bovine bone (Gen-ox), organic matrix) associated or not to GTR (Genderm). BACKGROUND DATA: A major problem on modern Dentistry is the recovery of bone defects caused by trauma, surgical procedures or pathologies. Several types of biomaterials have been used in order to improve the repair of these defects. These materials are often associated to procedures of GTR. Previous studies have shown positive effects of LLLT on the repair of soft tissue wounds, but there are a few on its effects on bone healing. METHODS: Surgical bone defects were created in 42 animals divided into five groups: Group I (control, 6 animals); Group II (Gen-ox, 9 animals); Group III (Gen-ox + Laser, 9 animals); Group IV (Gen-ox + Gen-derm, 9 animals); Group V (Gen-ox + Gen-derm + Laser, 9 animals). The animals on the irradiated group received 16 J/cm(2) per session divided into four points around the defect (4 J/cm(2)) being the first irradiation immediately after surgery and repeated seven times at every 48 h. The animals were humanly killed after 15, 21, and 30 days. RESULTS: The results of the present investigation showed histological evidence of improved amount of collagen fibers at early stages of the bone healing (15 days) and increased amount of well organized bone trabeculae at the end of the experimental period (30 days) on irradiated animals compared to non irradiated ones. CONCLUSIONS: It is concluded that a positive biomodulative effect on the healing process of one defect associated or not to the use of organic lyophilized bone and biological bovine lyophilized membrane on the femur of the rat.

Evaluation Of Low-Level Laser Therapy Of Osteoblastic Cells. Photomed Laser Surg. 2008 Aug;26(4):401-4 Pires Oliveira DA, de Oliveira RF, Zangaro RA, Soares CP. Laboratório de Dinâmica de Compartimentos Celulares, Instituto de Pesquisa e

Desenvolvimento (UNIVAP), São José dos Campos, São Paulo, Brazil.

Abstract Objective: The purpose of the present study was to evaluate the effect of biomodulation on osteoblastic cells using a gallium-aluminium-arsenide diode laser. Background Data: Lowlevel laser therapy (LLLT) is a non-pharmacological therapeutic resource to which biological tissues respond well, producing such effects as the acceleration of bone formation and bone repair. Materials and Methods: Osteoblastic cell cultures (OFCOL II) were irradiated with a gallium-aluminium-arsenide diode laser (GaAlAs lambda = 830 nm; 50 mW; 3 J/cm(2); 600mum-diameter optical fiber) and divided into two groups: group 1-irradiated cells, and group 2non-irradiated cells. Irradiation occurred at 24-h intervals for a total of 3 d. After each interval, the cells were marked with Mito Tracker Orange dye to assess the biostimulatory effect on mitochondrial activity and cell proliferation using an MTT assay. Results: Intense grouping of mitochondria in the perinuclear region was observed at 24 h and 48 h following irradiation. Changes from a filamentous to a granular appearance in mitochondrial morphology and mitochondria distributed throughout the cytoplasm were observed 72 h following proliferation. Such changes led to an in vitro proliferation process, as confirmed by the MTT assay. Conclusion: LLLT has shown itself capable of altering mitochondrial activity and the population of OFCOL II cells.

Initial Effects Of Low-Level Laser Therapy On Growth And Differentiation Of Human Osteoblast-Like Cells. Wien Klin Wochenschr. 2008 Feb;120(3-4):112-117 Stein E, Koehn J, Sutter W, Wendtlandt G, Wanschitz F, Thurnher D, Baghestanian M, Turhani D. Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Austria.

Low-level laser therapy is a clinically well established tool for enhancement of wound healing. In vitro studies have also shown that low level laser therapy has a biostimulatory effect on cells of different origin. The aim of this in vitro study was to investigate the initial effect of low-level laser therapy on growth and differentiation of human osteoblastlike cells. SaOS-2 cells were irradiated with laser doses of 1 J/cm(2) and 2 J/cm(2) using a diode laser with 670 nm wave length and an output power of 400 mW. Untreated cells were used as controls. At 24 h, 48 h and 72 h post irradiation, cells were collected and assayed for viability of attached cells and alkaline phosphatase specific activity. In addition, mRNA expression levels of osteopontin and collagen type I were assessed using semi-quantitative RT-PCR. Over the observation period, cell viability, alkaline phosphatase activity and the expression of osteopontin and collagen type I mRNA were slightly enhanced in cells irradiated with 1 J/cm(2) compared with untreated control cells. Increasing the laser dose to 2 J/cm(2) reduced cell viability during the first 48 h and resulted in persistently lower alkaline phosphatase activity compared with the other two groups. The expression of osteopontin and collagen type I mRNA slightly decreased with time in untreated controls and cells irradiated with 1 J/cm(2), but their expression was increased by treatment with 2 J/cm(2) after 72 h. These results indicate that low-level laser therapy has a biostimulatory effect on human osteoblast-like cells during the first 72 h after irradiation. Further studies are needed to determine the potential of low-level laser therapy as new treatment concept in bone regeneration.

Low-Level Laser Therapy Modulates Cyclooxygenase- 2 Expression During Bone Repair In Rats. Lasers Med Sci. 2008 Feb 29 [Epub ahead of print] Matsumoto MA, Ferino RV, Monteleone GF, Ribeiro DA. Department of Oral Maxillofacial Surgery, School of Dentistry, University of the Sacred Heart (USC), Bauru, SP, Brazil.

The goal of this study was to analyze the role of cyclo-oxygenase-2 following bone repair in rats submitted to low-level laser therapy. A total of 48 rats underwent surgery to inflict bone defects in their tibias having been randomly distributed into two groups: negative control and laser exposed group, i.e., the animals were treated with low-level laser therapy by means of gallium arsenide laser at 16 J/cm(2). The animals were killed after 48 h, 7 days, 14 days, or 21 days. The tibias were removed for morphological, morphometric, and immunohistochemistry analysis for cyclo-oxygenase-2. Statistical significant differences (P < 0.05) were observed in the quality of bone repair and quantity of formed bone between groups 14 days after surgery in the laser exposed group. In the same way, cyclo-oxygenase-2 immunoreactivity was more intense in bone cells for intermediate periods evaluated in this group. Taken together, such results suggest that low-level laser therapy is able to improve bone repair in the tibia of rats after 14 days of surgery as a result of an up-regulation for cyclo-oxygenase-2 expression in bone cells.

Effect Of Lower-Level Laser Therapy On Rabbit Tibial Fracture. Photomed Laser Surg. 2007 Dec;25(6):487-94 Liu X, Lyon R, Meier HT, Thometz J, Haworth ST. Musculoskeletal Functional Assessment Center, Medical College of Wisconsin, Milwaukee, Wisconsin.

Objective: The purpose of the study was to demonstrate the biological effects of lowlevel laser therapy (LLLT) on tibial fractures using radiographic, histological, and bone density examinations. Methods: Fourteen New Zealand white rabbits with surgically induced mid-tibial osteotomies were included in the study. Seven were assigned to a group receiving LLLT (LLLT-A) and the remaining seven served as a sham-treated control group (LLLT-C). A low-energy laser apparatus with a wavelength of 830 nm, and a sham laser (a similar design without laser diodes) were used for the study. Continuous outflow irradiation with a total energy density of 40 J/cm(2) and a power level of 200 mW/cm(2) was directly delivered to the skin for 50 seconds at four points along the tibial fracture site. Treatment commenced immediately postsurgery and continued once daily for 4 weeks. Results: Radiographic findings revealed no statistically significant fracture callus thickness difference between the LLLT-A and LLLT-C groups (p > 0.05). However, the fractures in the LLLT-A group showed less callus thickness than those in LLLT-C group 3 weeks after treatment. The average tibial volume was 14.5 mL in the LLLT-A group, and 11.25 mL in the LLLT-C group. The average contralateral normal tibial volume was 7.1 mL. Microscopic changes at 4 weeks revealed an average grade of 5.5 and 5.0 for the LLLT-A group and the LLLT-C group, respectively. The bone mineral density (BMD) as ascertained using a grey scale (graded from 0 to 256) showed darker coloration in the LLLT-A group (138) than in the LLLT-C group (125). Conclusion: The study suggests that LLLT may accelerate the process of fracture repair or cause increases in callus volume and BMD, especially in the early stages of absorbing the hematoma and

bone remodeling. Further study is necessary to quantify these findings.

The effects of laser irradiation on osteoblast and osteosarcoma cell proliferation and differentiation in vitro. Photomed Laser Surg. 2007 Aug;25(4):275-80. Renno AC, McDonnell PA, Parizotto NA, Laakso EL. Physical Therapy Department, Federal University of Sao Carlos, Sao Carlos, Brazil. [email protected]

OBJECTIVE: The aim of this study was to investigate the effects of 670-nm, 780-nm, and 830nm laser irradiation on cell proliferation of normal primary osteoblast (MC3T3) and malignant osteosarcoma (MG63) cell lines in vitro. BACKGROUND: Some studies have shown that laser phototherapy is able to stimulate the osteogenesis of bone tissue, increasing osteoblast proliferation and accelerating fracture consolidation. It has been suggested that laser light may have a biostimulatory effect on tumor cells. However, the mechanism by which the laser acts on cells is not fully understood. MATERIALS AND METHODS: Neonatal, murine, calvarial, osteoblastic, and human osteosarcoma cell lines were studied. A single laser irradiation was performed at three different wavelengths, at the energies of 0.5, 1, 5, and 10 J/cm(2). Twentyfour hours after laser irradiation, cell proliferation and alkaline phosphatase assays were assessed. RESULTS: Osteoblast proliferation increased significantly after 830-nm laser irradiation (at 10 J/cm(2)) but decreased after 780-nm laser irradiation (at 1, 5, and 10 J/cm(2)). Osteosarcoma cell proliferation increased significantly after 670-nm (at 5 J/cm(2)) and 780-nm laser irradiation (at 1, 5, and 10 J/cm(2)), but not after 830-nm laser irradiation. Alkaline phosphatase (ALP) activity in the osteoblast line was increased after 830-nm laser irradiation at 10 J/cm(2), whereas ALP activity in the osteosarcoma line was not altered, regardless of laser wavelength or intensity. CONCLUSION: Based on the conditions of this study, we conclude that each cell line responds differently to specific wavelength and dose combinations. Further investigations are required to investigate the physiological mechanisms responsible for the contrasting outcomes obtained when using laser irradiation on cultured normal and malignant bone cells.

Comparative study of how low-level laser therapy and lowintensity pulsed ultrasound affect bone repair in rats. Photomed Laser Surg. 2006 Dec;24(6):735-40. Lirani-Galvao AP, Jorgetti V, Da Silva OL. Bioengineering Department, University of Sao Paulo, Sao Paulo, Brazil.

Objective: This study aimed to compare the consequences of low-level laser therapy (LLLT) and low-intensity pulsed ultrasound (LIPUS) on bone repair. Background Data: Many studies have assessed the effects of LLLT and LIPUS on bone repair, but a comparison of them is rare. Methods: Male Wistar rats (n = 48) with tibial bone osteotomy were used. One group had the osteotomized limb treated with LLLT (GaAlAs laser, 780 nm, 30 mW, 112.5 J/cm(2)) and the second group with LIPUS (1.5 MHz, 30 mW/cm(2)), both for 12 sessions (five times per week); a third group was the control. After 20 days, rats were sacrificed and had their tibias submitted to a bending test or histomorphometric analysis. Results: In the bending test, maximum load at failure of LLLT group was significantly higher (p < 0.05). Bone histomorphometry revealed a significant increase in osteoblast number and surface, and osteoid volume in the LLLT group,

and a significant increase in eroded and osteoclast surfaces in the LIPUS group. Conclusion: LIPUS enhanced bone repair by promoting bone resorption in the osteotomy area, while LLLT accelerated this process through bone formation.

Effects of 830-nm Laser Light on Preventing Bone Loss after Ovariectomy. Photomed Laser Surg. 2006 Oct;24(5):642-5 Renno AC, Moura FM, Santos NS, Tirico RP, Bossini PS, Parizotto NA. Department of Physiotherapy, Federal University of Sao Carlos, Sao Carlos, Brazil.

Objective: The aim of this study was to investigate the effects of low-level laser therapy (LLLT; infrared, 830 nm) on the bone properties and bone strength of rat femora after ovariectomy (OVX). Background Data: Osteoporosis affects 30% of postmenopausal women, and it has been recognized as a major public health problem. Based on the stimulatory effects of LLLT on proliferation of bone cells, we hypothesized that LLLT would be efficient in preventing bone mass loss in OVX rats. Methods: Forty female rats were divided into four groups: sham-operated control (SC), OVX control (OC), shamoperated irradiated at a dose of 120 J/cm(2) (I120), and O X irradiated at a dose of 120 J/cm(2) (O120). Animals were operated at the age of 90 days. Laser irradiation was initiated 1 day after the operation and was performed three times a week, for 2 months. Femora were submitted to a biomechanical test and a physical properties evaluation. Results: Maximal load of O120 was higher than in control groups. Wet weight, dry weight, and bone volume of O120 did not show any difference when compared with SC. Conclusion: The results of the present study indicate that LLLT was able to prevent bone loss after OVX in rats. However, further studies are needed to investigate the effects of different parameters, wavelengths, and sessions of applications on OVX rats.

Laser Therapy Improves Healing Of Bone Defects Submitted To Autologous Bone Graft. Photomed Laser Surg. 2006 Feb;24(1):38-44. Weber JB, Pinheiro AL, de Oliveira MG, Oliveira FA, Ramalho LM. School of Dentistry, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.

OBJECTIVE: The aim of the present study was to assess histologically the effect of lowlevel laser thrapy (LLLT) (lambda 830 nm) on the healing of bone defects associated with autologous bone graft. BACKGROUND DATA: LLLT has been used on the modulation of bone healing because of the photo-physical and photochemical properties of some wavelengths. The use of correct and appropriate parameters has been shown to be effective in the promotion of a positive biomodulative effect on the healing bone. METHODS: Sixty male Wistar rats were divided into four groups: G1 (control), G2 (LLLT on the surgical bed), G3 (LLLT on the graft), and G4 (LLLT on both the graft and the surgical bed). The dose per session was 10 J/cm(2), and it was applied to the surgical bed (G2/G4) and on the bone graft (G3/G4). LLLT was carried out every other day for 15 days (lambda 830 nm, phi = 0.5 cm(2), 50 Mw, 10 J/cm(2)). The dose was fractioned in four points. The animals were sacrificed 15, 21, and 30 days after surgery; specimens were taken and routinely processed (wax, cut, and stain with H&E and Sirius red stains). Light microscopic analysis was performed by a pathologist. RESULTS: In the groups in

which the LLLT was used trans-operatively on the surgical bed (G2/G4), bone remodeling was both quantitatively and qualitatively more evident when compared to subjects of groups G1 and G3. CONCLUSION: The present study indicates that the use of LLLT trans-operatively resulted in a positive biomodulative effect on the healing of bone defects associated with autologous bone grafts.

Repair Of Bone Defects Treated With Autogenous Bone Graft And Low-Power Laser. J Craniofac Surg. 2006 Mar;17(2):297-301 da Silva RV, Camilli JA. Department of Anatomy, Institute of Biology, State University of Campinas, UNICAMP, Sao Paulo, Brazil.

Because bone healing at the graft site is similar to a fracture repair, the purpose of the present study was to evaluate the effects of low-power laser irradiation on the repair of rat skull defects treated with autogenous bone graft. A defect measuring 3 mm in diameter was produced in the left parietal bone and filled with an autogenous bone graft obtained from the right parietal bone. The animals were divided into 3 groups of 20 rats each: nonirradiated control, irradiated with 5.1 J/cm, and irradiated with 10.2 J/cm. The laser (2.4 mW, 735 nm, 3.4 x 10 W/cm, 3-mm spot size) was applied three times per week for 4 weeks. Greater volume of newly formed bone was observed in the irradiated group with 10.2 J/cm. In both irradiated groups, a greater volume of newly formed bone occurred only in the first 2 weeks. The results demonstrated that laser irradiation at the grafted site stimulated osteogenesis during the initial stages of the healing process in a skull defect of the rat and that this effect was dose dependent.

Photoengineering Of Bone Repair Processes. Photomed Laser Surg. 2006 Apr;24(2):169-78 Pinheiro AL, Gerbi ME. Laser Center, School of Dentistry, Department of Propedêutica and Clínica Integrada, Universidade Federal da Bahia, Canela Salvador, BA, Salvador, Brazil. [email protected]

OBJECTIVE: This paper aims to report the state of the art with respect to photoengineering of bone repair using laser therapy. BACKGROUND DATA: Laser therapy has been reported as an important tool to positively stimulate bone both in vivo and in vitro. These results indicate that photophysical and photochemical properties of some wavelengths are primarily responsible for the tissue responses. The use of correct and appropriate parameters has been shown to be effective in the promotion of a positive biomodulative effect in healing bone. METHODS: A series of papers reporting the effects of laser therapy on bone cells and tissue are presented, and new and promising protocols developed by our group are presented. RESULTS: The results of our studies and others indicate that bone irradiated mostly with infrared (IR) wavelengths shows increased osteoblastic proliferation, collagen deposition, and bone neorformation when compared to nonirradiated bone. Further, the effect of laser therapy is more effective if the treatment is carried out at early stages when high cellular proliferation occurs. Vascular responses to laser therapy were also suggested as one of the possible mechanisms responsible for the positive clinical results observed following laser therapy. It still remains uncertain if bone stimulation by laser light is a general effect or if the isolate stimulation of osteoblasts is possible. CONCLUSION: It is possible that the laser therapy effect

on bone regeneration depends not only on the total dose of irradiation, but also on the irradiation time and the irradiation mode. The threshold parameter energy density and intensity are biologically independent of one another. This independence accounts for the success and the failure of laser therapy achieved at low-energy density levels.

[Evidences Of Physical Agents Action On Bone Metabolism And Their Potential Clinical Use] Arq Bras Endocrinol Metabol. 2005 Dec;49(6):891-6. Epub 2006 Mar 16. [Article in Portuguese] Lirani AP, Lazaretti-Castro M. Departamento de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP. [email protected]

The action of physical agents such as low level laser therapy, low-intensity pulsed ultrasound and electrical and electromagnetic fields on bone have been often studied, showing that they are able to promote osteogenesis, accelerate fracture consolidation and augment bone mass. The use of these therapeutic modalities was first based on the finding that bone is a piezoelectric material, that means it can generate polarization when deformed, transforming mechanical energy into electric energy, and this has widen therapeutic possibilities to bony tissue. The present work aims to present evidences of physiologic effects and mechanisms of action of these physical agents on bone metabolism, based on articles published in international scientific literature.

The effect of low level laser irradiation on implant-tissue interaction. In vivo and in vitro studies. Swed Dent J Suppl. 2005;(172):1-63. Khadra M. Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Norway.

Low-level laser therapy (LLLT) is increasingly used in medicine and dentistry. It has been suggested that LLLT may be beneficial in the management of many different medical conditions, including pain, wound healing and nerve injury. The present thesis is based on a series of in vivo and in vitro experimental studies investigating whether LLLT has the potential to enhance titanium-implant interaction. Information about LLLT effect on bone healing is fundamental to understand whether LLLT may improve implant-tissue interaction. Thus in the initial study (I), the effect of LLLT on bone healing and growth in rat calvarial bone defects was investigated. It was found that LLLT may accelerate metabolism and/or mineralization during early bone healing. Based on these findings, study II explored the hypothesis that LLLT can enhance implant integration in the rabbit tibial bone. It was shown that LLLT stimulated the mechanical strength of the interface between the implant and bone after a healing period of 8 weeks. Histomorphometrical and mineral analyses showed that the irradiated implants had greater bone-to-implant contact than the controls. In the in vitro experiments, cellular responses to LLLT were studied in two cell types: primary cultures of human gingival fibroblasts and human osteoblast-like cells, with special reference to attachment, proliferation, differentiation and production of transforming growth factor beta1 (TGF-beta1). The objectives of studies III & IV were to develop a standardized, reproducible in vitro model for testing a GaAlAs diode laser device and to document the influence of single or multiple doses of

LLLT, as a guide to defining the optimal laser dose for enhancing cell activity. A further objective was to investigate the effect of LLLT on initial attachment and subsequent behaviour of human gingival fibroblasts cultured on titanium. While both multiple doses (1.5 and 3 J/cm2) and a single dose (3 J/cm2) enhanced cellular attachment, proliferation increased only after multiple doses (1.5 and 3 J/cm2). Study V concerned the response to LLLT of osteoblast-like cells, derived from human alveolar bone cultured on titanium implant material. In this study LLLT significantly enhanced cellular attachment. Greater cell proliferation in the irradiated groups was observed first after 96 h indicating that the cellular response is dose dependent. Osteocalcin synthesis and TGF-beta1 production were significantly stimulated on the samples exposed to 3 J/cm2. The following conclusions are drawn from the results of these five studies: LLLT can promote bone healing and bone mineralization and thus may be clinically beneficial in promoting bone formation in skeletal defects. It may be also used as additional treatment for accelerating implant healing in bone. LLLT can modulate the primary steps in cellular attachment and growth on titanium surfaces. Multiple doses of LLLT can improve LLLT efficacy, accelerate the initial attachment and alter the behaviour of human gingival fibroblasts cultured on titanium surfaces. The use of LLLT at the range of doses between 1.5 and 3 J/cm2 may modulate the activity of cells interacting with an implant, thereby enhancing tissue healing and ultimate implant success.

Molecular structure of the bony tissue after experimental trauma to the mandibular region followed by laser therapy. Photomed Laser Surg. 2004 Jun;22(3):249-53 Rochkind S, Kogan G, Luger EG, Salame K, Karp E, Graif M, Weiss J. Department of Neurosurgery, Division of Peripheral Nerve Reconstruction, Tel Aviv Sourasky Medical Center, Tel Aviv University, Israel. [email protected]

OBJECTIVE: We investigated the therapeutic efficiency of laser irradiation and Bio-Oss, both and separately, on the post-traumatic regeneration of bone tissue in rats using infrared spectroscopy as an informative and accurate measuring method. BACKGROUND DATA: The therapeutic effect of low-power laser irradiation on bone tissue regeneration processes in animal models has been studied using morphogenic, biochemical, roentgenographic and electron microscopic measurements. Natural bone minerals, such as Bio-Oss collagen, were recommended for the reconstruction of bone defects in the alveolar process. MATERIALS AND METHODS: 29 male Wistar rats, divided into four random groups in a blinded manner were operated on the right alveolar process. A bone defect was made by penetrating the right alveolar process of the mandible bone using a 3-mm drill. The rats were divided into four groups as follows: Group I, left side served as intact bone and right injured side as the control; Group II, right injured side was treated by organic bovine bone (Bio-Oss); Group III, right side bone defect was treated by HeNe laser (632.8 nm, 35 mW) applied transcutaneously for 20 min to the injured area daily for the following 14 consecutive days; and Group IV, Bio-Oss was placed loosely in the right side defect followed by laser treatment. After 2 weeks, the intact bone and bone replicas of the trauma area were removed and analyzed by infra-red spectroscopy technique. The composition and the structure of the bone tissue mineral substances were determined and compared among the four groups. For quantitative analysis of the regenerative bone process, the Mineralization index was used. An increase in this index indicates regenerative bone processes.

RESULTS: The normal state analysis of the IR spectra of the normal alveolar bone tissue within the intervals of 400 to 4000 cm(-1) revealed characteristic absorption bands for the inorganic bone component in spectrum regions 450-1480 cm(-1), and the organic component at 1540- 3340 cm(-1). In the case of trauma, the intensity of absorption of the inorganic component was decreased by 54%, and the absorption band became narrow, which can be interpreted as quantitative changes of the bone tissue mineral content. The wavelength characteristics of the inorganic component remained unchanged; that is, the induced trauma under these experimental conditions did not provoke alterations in the structure of the phosphate framework. The organic component showed decreased absorption by 10- 15%, compared to the normal bone, and slight displacement of the wavelength, which can be interpreted as changes occurring in the quality of the organic content of the bone tissue. In the Bio-Oss-treated group, the intensity of absorption of the inorganic component increased by 43%, compared to the control injured area; however, there was a decrease of 22.6% in the normal bone. The wavelength characteristics of the inorganic component remained unchanged. The organic component showed similar absorption results in the injured non-treated group and absorption was 10-15% less than in the normal bone. Mineralization Index in the Bio-Oss-treated group was 0.93, compared to 0.63 in the control group and 2.04 in the normal bone. In the laser-treated group, the intensity of absorption of the inorganic component increased by 62, compared to the control injured area, and decreased only 11.4% in the normal bone. The wavelength characteristics of the organic component remained unchanged; that is, the organic component was similar to that of normal bone. Mineralization Index in the laser-treated group increased significantly to 1.86, compared to 0.63 in the control group and 2.04 in the normal bone. In the combined laser and Bio-Oss-treated groups, the intensity of absorption of the inorganic component and organic component was similar to that of normal bone. Mineralization Index in this group increased significantly to 1.98, compared to 0.63 in the control group and 2.04 in the normal bone. CONCLUSION: The results suggest that low-power laser irradiatults suggest that low-power laser irradiation alone and in combination with Bio-Oss enhances bone healing and increases bone repair.

Bone Stimulation by Low Level Laser - A Theoretical Model for the Effects Used by the kind permission of the Czech Society for the Use of Laser in Medicine, www.laserpartner.org Philip Gable, B App Sc P.T. G Dip Sc Res (LLLT) MSc, Australia Jan Tunér, D.D.S., Sweden ABSTRACT

The anecdotal and researched evidence for the effects of Low Level Laser Therapy (LLLT) on the stimulation of bone have been reported for over 20 years. This has been in the form of local as well as systematic effects - including contra-lateral effects. Reports of stimulation of rabbit radii fractures and mice femurs were made as early as 1986 and 1987 with irradiated bones healing faster than controls and contra-lateral non-treated fractures similarly demonstrating faster healing times. Over the following decade and a half, further studies have also investigated and demonstrated that LLLT is effective for the stimulation of bone tissue. The reasons for this have been attributed to the general effects of LLLT and its ability to increase the rates of healing through mitochondrial ATP production and alteration in the cellular lipid bilayer. Additional hypothesis include the subsequent capacity of irradiated cells to alter their ion

exchange rate and thus influence the catalytic effects of the specific enzymes and substrates. These in turn initiate and promote the healing process completing the cascading cycle of events. In the area of bone specific research, Dr. Tony Pohl of the Royal Adelaide Hospital in South Australia, has provided a new theory that postulates that the majority of fluid transfer and exchange within living bone is predominantly influenced by the lymphatic circulation. LLLT is well documented and known as having effects that influence the lymphatic circulation and wound healing process. A coupling of these two areas of theory can demonstrate a positive description and explanation of the predominant effects of LLLT in bone stimulation. In reality, LLLT's effects on bone may well be a further consequence of its actions on the lymphatic circulation. Reports of stimulation of Rabbit radii fractures were made by Tang in 1986 and similar reports by Trelles in 1987 on mice femurs. In both situations the irradiated bones healed faster than the controls. In another study by Hernandez-Ros, in 1987, LLLT demonstrated stimulation of fresh fractures on Sprague-Dawley rats that were fractured bilaterally. The unexpected results of this study were that the contra-lateral fractured non-treated limb also healed faster than the control group. Over the following decade and a half further studies (Yamada 1991; Pyczek, Sopala et al. 1994; Ozawa 1995; Horowitz 1996; Yaakobi 1996; Saito and Shimizu 1997) have also investigated and demonstrated that LLLT is effective for promoting the stimulation of bone healing. Recently Nicolau and colleagues (2002) from Brazil demonstrated the positive effect of LLLT on the stimulation of bone in mice with latent promotion of bone remodulation at injury sites without changes in bone architecture, increased bone volume and increased osteoblast surface through increased resorption and formation of bone with higher apposition rates. A positive effect on bony implants has been demonstrated by Dörtbudak (2002) and Guzzardella (2003). The effect of laser irradiation on osteoblastic cells has been reported by Yamamoto (2001) and Guzzardella (2002). The reasoning for this amelioration in all experimental circumstances, based on electron microscopy as well as macroscopic histological evidence, was concluded to be due to i.a. improved vascularisation as a consequence of blood vessel formation, absorption of the haematoma, macrophage action, fibroblast proliferation, chondrocyte activity, bone remodeling from increased osteoblastic activity and deposition of calcium salts. These changes and evidence based studies attribute the macro- and microscopic effects to the known and accepted general actions of LLLT and its ability to increase rates of healing through stimulation of ATP production, (Karu 1989; Smith 1990) promoting repair and polarization of the cellular lipid bilayer (Fenyo 1990) as well as LLLT's capacity to affect cells through alterations in their exchange rate of ions (Robinson and Walters 1991) and influences the catalytic effects of the specific enzymes and substrates (Pouyssegur 1985; Karu 1988) which in turn initiate and promote the healing process. More recent work by Dr. Tony Pohl, an internationally renowned Orthopaedic Surgeon from the Royal Adelaide Hospital in South Australia and lecturer at the Adelaide and South Australian Universities, has given rise to a new theory on bone circulation through reconsideration of fluid and protein transfer within bone (Pohl 1999). This theory suggests that the general understanding of the circulatory action within bone has been incorrect. Pohl postulates that the majority of fluid transfer and exchange within the living bone is predominantly influenced by the lymphatic rather than the vascular circulation. This is justified through studies on bone fluid input and output levels that have demonstrated that the venous and arterial aspect of circulation alone cannot account for the demonstrated levels of output nor the

presence of free radical molecules which exceed those of the vascular input. Furthermore, the diameter of large protein cells within the bone exceed the diameter of the vessels that form the terminal aspects of the circulatory system making it impossible for them to have been delivered via this system. Consequently, an additional circulatory system must be present that will account for both the increased output and the presence of the large diameter protein cells as well as the free radicals. If LLLT is then considered within the context of this new theory on bone circulation and the contribution of the lymphatic circulation then a further logical reasoned deduction for the action of LLLT on bone stimulation can be made. LLLT has a well documented and known effect influencing the lymphatic circulation. This has been demonstrated from the early works of Lievens, (1985) that demonstrated the influence of "Laser Irradiation" on the motricity of the lymphatic system and on the wound healing process. This is supported by several wound studies that demonstrate that the levels of protein rich exudates in non-healing wounds increase markedly from exposure to LLLT. This demonstrated action is determined to be as a result of the increase in lymphatic circulation (Robinson and Walters 1991; Gabel 1995). More recent work at the Flinders Medical Center in Adelaide South Australia has been completed and presented at the World Association of Laser Therapy conference in Tokyo Japan (Anderson, Carati et al. 2002). This study has demonstrated the positive effects of LLLT on the lymphatic circulation and its consequential benefits to the post mastectomy patient. An understanding of the existing knowledge of the effects of LLLT on the lymphatic system combined with the hypothesis of bone fluid transport provides a coupled theory that would demonstrate a positive description and explain of the predominant effects of LLLT in bone stimulation. In the trauma situation of direct or indirect damage to the bone, including fractures and periosteal induced damage such as stress fractures, the tissue damage leads to compromises that include but are not limited to, physical blockage from the trauma and waste / debris, increased fluid and circulatory viscosity from added cellular content within the lymphatics, lower speed motility and energy deficit in the tissue and cells from the loss of ATP production as a general effect from the trauma, cell changes and inability of mitochondria to function at the normal higher level to promote self repair and regeneration. LLLT with its known general effects and specific direct effects on the lymphatic system would act to stimulate mitochondria ATP that increases cellular and circulatory motility as well as directly influencing lymphatic flow. LLLT also promotes increased permeability in interstitial tissue and facial layers (Gabel 1995) reducing stagnation and blockage. These actions would assist the increase in lymphatic flow and consequently the circulation within the affected bone. There is also a hypothetical potential that the presence of LLLT by increasing lymphatic circulation does so by virtue of an increase in the diameter of the lymphatic vessels, not just by increased flow rates within the vessel at an unchanged diameter. This diameter increase, if definitively present, would also explain the presence of large diameter protein cells within the normal bone circulation that cannot be attributed to the vascular circulation and would additionally explain a facilitated process for removal of debris and larger protein cells passing out of traumatized areas that is additionally stimulated by the use of LLLT. Stimulation of bone healing by LLLT has till now has been generally classified as a consequence of the general healing effects of LLLT. In reality LLLT's effect on bone may well be a further consequence of its actions on the lymphatic circulation.

REFERENCES • • • • • • • •

• • • •

• • • •

• • •



Anderson, S, Carati, C et al. (2002). Low Level Laser Therapy (LLLT) as a Treatment for Postmatestectomy Lymhoedema. WALT 2002, Tokyo Japan. Coombe, A R et al (2001). The effect of low level laser irradiation on osteoblastic cells. Clin Ort Res. 4: 3-14. Dörtbudak, O et al (2002). Effect of low-power laser irradiation on bony implant sites. Clin Oral Implants Res 13(3):288-292. Fenyo, M. (1990). Theoretical and Experimental Basis of Biostimulation by Bioptron, Bioptron AG, Monchaltorf, Switzerland. Gabel, C. P. (1995). ―Does Laser enhance bruising in acute sporting injuries.‖ Aust. J. Physio. 41(4): 267-269. Gabel, C. P. (1995). The effect of LLLT on slow healing wounds and ulcers. Health Sciences. Darwin, Northern Territory. Guzzardella, G A et al (2002). Laser stimulation on bone defect healing: An in vitro study. Lasers Med Sci. 17(3): 216-220. Guzzardella, G A et al (2003). Osseointegration of endosseous ceramic implants after postoperative low-power laser stimulation: an in vivo comparative study. Clin Oral Implants Res. 14: 226-232. Horowitz, I. et al. (1996). ―Infrared spectroscopy analysis of the effect of low power laser irradiation on calvarial bone defect healing in the rat (abstract).‖ Laser Therapy 8: 29. Karu, T. I. (1988). ―Molecular mechanism of the therapeutic effects of low intensity laser radiation.‖ Lasers in Life Science 2: 53-74. Karu, T. I. (1989). Photobiology of low-power laser therapy. London, Harwood Academic Publishers. Lievens, P. (1985). The influence of "Laser Irradiation" on the motricity of the lymphatical system and on the wound healing process. International Congress on Laser in Medicine and Surgery., Bologna. Nicolau, R A., Jorgetti, V, Rigau, J et al. "Effect of low power laser Ga-Al-As (660nm) in the bone tissue remodulation in mice‖ Ozawa, Y. et al (1995). ―Stimulatory effects of low-power laser irradiation on bone formation in vitro.‖ SPIE Proc. 1995 Vol. 1984: 281-288. Pohl, T. (1999). Bone circulation, the lymphatic system contribution. Personal Communication to C. P. Gabel. Adelaide Oct 1999. Pouyssegur, J. (1985). ―The growth factor-activatable Na+/H+ exchange system: a genetic approach. In Karu, T.I. 1988, 'Molecular mechanism of the therapeutic effects of low intensity laser radiation', Lasers in Life Science, vol.2, p.53-74.‖ Trends in Biochemical Science 10: 453-455. Pycek, M., Sopala, M et al. (1994). ―Effect of low-energy laser power on the bone marrow of the rat.‖. Folia Biol (Krakow) 42(3-4): 151-156. Robinson, B. and Walters, J (1991). ―The use of low level laser therapy in diabetic and other ulcerations.‖ Journal of British Podiatric Medicine 46(10): 186-189. Saito, S. and. Shimizu, N. (1997). ―Stimulatory effects of low-power laser irradiation on bone regeneration in midpalatal suture during expansion in the rat.‖ Am J Ortod Dentofac Orthop 11(5): 525-. Smith, K. C. (1990). Light and life: The photobiological basis of the therapeutic use of radiation from lasers. International Laser Therapy Association Conference, Osaka.

• • •

Yaakobi, T. et. al. (1996). ―Promotion of bone repair in the cortical bone of the tibia in rats by low energy laser (He-Ne) irradiation.‖ Calcif Tissue Int. 59(4): 297-300. Yamada, K. (1991). ―Biological effects of low power laser irradiation on clonal osteoblastic cells (MC3T3-E1).‖ Nippon Seikeigeka Gakkai Zasshi 65(9): 787- 799. Yamamoto, M et al (2001). Stimulation of MCM3 gene expression in osteoblast by low level laser irradiation. Laser in Med Sci. Abstract issue. 16(3): 213-217.

Assessment Of Bone Repair Associated With The Use Of Organic Bovine Bone And Membrane Irradiated At 830 Nm. Photomed Laser Surg. 2005 Aug;23(4):382-8 Gerbi ME, Pinheiro AL, Marzola C, Limeira Júnior Fde A, Ramalho LM, Ponzi EA, Soares AO, Carvalho LC, Lima HV, Gonçalves TO. School of Dentistry, Federal University of Bahia, Salvador, Brazil.

OBJECTIVE: The aim of the present investigation was to assess histologically the effect of LLLT (GaAIAs, 830 nm, 40 mW, CW, (Phi) approximately 0.6 mm, 16 J/cm(2) per session) on the repair of surgical defects created in the femur of the Wistar Albinus rat. The defects were filled to lyophilized bovine bone (Gen-ox), organic matrix) associated or not to GTR (Genderm). BACKGROUND DATA: A major problem on modern Dentistry is the recovery of bone defects caused by trauma, surgical procedures or pathologies. Several types of biomaterials have been used in order to improve the repair of these defects. These materials are often associated to procedures of GTR. Previous studies have shown positive effects of LLLT on the repair of soft tissue wounds, but there are a few on its effects on bone healing. METHODS: Surgical bone defects were created in 42 animals divided into five groups: Group I (control, 6 animals); Group II (Gen-ox, 9 animals); Group III (Gen-ox + Laser, 9 animals); Group IV (Gen-ox + Gen-derm, 9 animals); Group V (Gen-ox + Gen-derm + Laser, 9 animals). The animals on the irradiated group received 16 J/cm(2) per session divided into four points around the defect (4 J/cm(2)) being the first irradiation immediately after surgery and repeated seven times at every 48 h. The animals were humanly killed after 15, 21, and 30 days. RESULTS: The results of the present investigation showed histological evidence of improved amount of collagen fibers at early stages of the bone healing (15 days) and increased amount of well organized bone trabeculae at the end of the experimental period (30 days) on irradiated animals compared to non irradiated ones. CONCLUSIONS: It is concluded that a positive biomodulative effect on the healing process of one defect associated or not to the use of organic lyophilized bone and biological bovine lyophilized membrane on the femur of the rat.

Effect of 830-nm laser light on the repair of bone defects grafted with inorganic bovine bone and decalcified cortical osseous membrane. J Clin Laser Med Surg. 2003 Dec;21(6):383-8. Barbos Pinheiro AL, Limeira Junior Fde A, Marquez Gerbi ME, Pedreira Ramalho LM, Marzola C, Carneiro Ponzi EA, Oliveira Soares A, Bandeira De Carvalho LC, Vieira Lima HC, Oliveira Goncalves T. Laser Center, School of Dentistry, Federal University of Bahia, Salvador, Brazil. [email protected]

OBJECTIVE: The aim of this study was to assess histologically the effect of LLLT (lambda830 nm) on the repair of standardized bone defects on the femur of Wistar albinus rats grafted with inorganic bovine bone and associated or not to decalcified bovine cortical bone membrane.

BACKGROUND DATA: Bone loss may be a result of several pathologies, trauma or a consequence of surgical procedures. This led to extensive studies on the process of bone repair and development of techniques for the correction of bone defects, including the use of several types of grafts, membranes and the association of both techniques. There is evidence in the literature of the positive effect of LLLT on the healing of soft tissue wounds. However, its effect on bone is not completely understood. MATERIALS AND METHODS: Five randomized groups were studied: Group I (Control); Group IIA (Gen-ox); Group IIB (Gen-ox + LLLT); Group IIIA (Gen-ox + Gen-derm) and Group IIIB (Gen-ox + Gen-derm + LLLT). Bone defects were created at the femur of the animals and were treated according to the group. The animals of the irradiated groups were irradiated every 48 h during 15 days; the first irradiation was performed immediately after the surgical procedure. The animals were irradiated transcutaneously in four points around the defect. At each point a dose of 4 J/cm2 was given (phi approximately 0.6 mm, 40 mW) and the total dose per session was 16 J/cm2. The animals were humanely killed 15, 21, and 30 days after surgery. The specimens were routinely processed to wax, serially cut, and stained with H&E and Picrosirius stains and analyzed under light microscopy. RESULTS: The results showed evidence of a more advanced repair on the irradiated groups when compared to nonirradiated ones. The repair of irradiated groups was characterized by both increased bone formation and amount of collagen fibers around the graft within the cavity since the 15th day after surgery, through analysis of the osteoconductive capacity of the Gen-ox and the increment of the cortical repair in specimens with Gen-derm membrane. CONCLUSION: It is concluded that LLLT had a positive effect on the repair of bone defect submitted the implantation of graft.

Effect Of Low-Power Gaalas Laser (660 Nm) On Bone Structure And Cell Activity: An Experimental Animal Study. Lasers Med Sci. 2003;18(2):89-94. Nicola RA, Jorgetti V, Rigau J, Pacheco MT, dos Reis LM, Zangaro RA. Vale of Paraiba University, Sao Jose dos Campos, SP, Brazil. [email protected]

Low-level laser therapy (LLLT) is increasingly being used in the regeneration of soft tissue. In the regeneration of hard tissue, it has already been shown that the biomodulation effect of lasers repairs bones more quickly. We studied the activity in bone cells after LLLT close to the site of the bone injury. The femurs of 48 rats were perforated (24 in the irradiated group and 24 in the control group) and the irradiated group was treated with a GaAlAs laser of 660 nm, 10 J/cm2 of radiant exposure on the 2nd, 4th, 6th and 8th days after surgery (DAS). We carried out histomorphometry analysis of the bone. We found that activity was higher in the irradiated group than in the control group: (a) bone volume at 5 DAS (p=0.035); (b) osteoblast surface at 15 DAS (p=0.0002); (c) mineral apposition rate at 15 and 25 DAS (p=0.0008 and 0.006); (d) osteoclast surface at 5 DAS and 25 DAS (p=0.049 and p=0.0028); and (e) eroded surface ( p=0.0032). We concluded that LLLT increases the activity in bone cells (resorption and formation) around the site of the repair without changing the bone structure.

Effects Of Pulse Frequency Of Low-Level Laser Therapy (LLLT) On Bone Nodule Formation In Rat Calvarial Cells. J Clin Laser Med Surg. 2003 Oct;21(5):271-7. Links Ueda Y, Shimizu N. Department of Orthodontics, Nihon University School of Dentistry at Matsudo Chiba, Japan.

OBJECTIVE: The purpose of this study was to determine the effect of pulse frequencies of low-level laser therapy (LLLT) on bone nodule formation in rat calvarial cells in vitro. BACKGROUND DATA: Various photo-biostimulatory effects of LLLT, including bone formation, were affected by some irradiation factors such as total energy dose, irradiation phase, laser spectrum, and power density. However, the effects of pulse frequencies used during laser irradiation on bone formation have not been elucidated. MATERIALS AND METHODS: Osteoblast-like cells isolated from fetal rat calvariae were irradiated once with a low-energy Ga-Al-As laser (830 nm, 500 mW, 0.48-3.84 J/cm2) in four different irradiation modes: continuous irradiation (CI), and 1-, 2-, and 8-Hz pulsed irradiation (PI1, PI-2, PI-8). We then investigated the effects on cellular proliferation, bone nodule formation, alkaline phosphatase (ALP) activity, and ALP gene expression. RESULTS: Laser irradiation in all four groups significantly stimulated cellular proliferation, bone nodule formation, ALP activity, and ALP gene expression, as compared with the nonirradiation group. Notably, PI-1 and -2 irradiation markedly stimulated these factors, when compared with the CI and PI-8 groups, and PI-2 irradiation was the best approach for bone nodule formation in the present experimental conditions. CONCLUSION: Since low-frequency pulsed laser irradiation significantly stimulates bone formation in vitro, it is most likely that the pulse frequency of LLLT an important factor affecting biological responses in bone formation.

The Effects Of Low Level Laser Irradiation On Osteoblastic Cells. Clin Orthod Res. 2001 Feb;4(1):3-14 Coombe AR, Ho CT, Darendeliler MA, Hunter N, Philips JR, Chapple CC, Yum LW. Discipline of Orthodontics, Faculty of Dentistry, University of Sydney, New South Wales, Australia; Institute of Dental Research, United Dental Hospital, New South Wales, Australia.

Low level laser therapy has been used in treating many conditions with reports of multiple clinical effects including promotion of healing of both hard and soft tissue lesions. Low level laser therapy as a treatment modality remains controversial, however. The effects of wavelength, beam type, energy output, energy level, energy intensity, and exposure regime of low level laser therapy remain unexplained. Moreover, no specific therapeutic window for dosimetry and mechanism of action has been determined at the level of individual cell types. The aim of this study was to investigate the effects of low level laser irradiation on the human osteosarcoma cell line, SAOS-2. The cells were irradiated as a single or daily dose for up to 10 days with a GaAlAs continuous wave diode laser (830 nm, net output of 90 mW, energy levels of 0.3, 0.5, 1, 2, and 4 Joules). Cell viability was not affected by laser irradiation, with the viability being greater than 90% for all experimental groups. Cellular proliferation or activation was not found to be significantly affected by any of the energy levels and varying exposure regimes investigated. Low level laser irradiation did result in a heat shock response at an energy level of 2 J. No significant early or late effects of laser irradiation on protein expression and alkaline phosphatase activity were found. Investigation of intracellular calcium concentration revealed a tendency of a transient positive change after irradiation. Low level laser irradiation was unable to stimulate the

osteosarcoma cells utilised for this research at a gross cell population level. The heat shock response and increased intracellular calcium indicate that the cells do respond to low level laser irradiation. Further research is required, utilising different cell and animal models, to more specifically determine the effects of low level laser irradiation at a cellular level. These effects should be more thoroughly investigated before low level laser therapy can be considered as a potential accelerator stimulus for orthodontic tooth movement.

Osseointegration Of Endosseous Ceramic Implants After Postoperative Lowpower Laser Stimulation: An In Vivo Comparative Study. Clin Oral Implants Res. 2003 Apr;14(2):226-32. Guzzardella GA, Torricelli P, Nicoli-Aldini N, Giardino R. Department of Experimental Surgery/Codivilla-Putti Research Institute, Rizzoli Orthopaedic Institute, Bologna, Italy. [email protected]

Stimulation with low-power laser (LPL) can enhance bone repair as reported in experimental studies on bone defects and fracture healing. Little data exist concerning the use of LPL postoperative stimulation to improve osseointegration of endosseous implants in orthopaedic and dental surgery. An in vivo model was used for the present study to evaluate whether Ga-Al-As (780 nm) LPL stimulation can improve biomaterial osseointegration. After drilling holes, cylindrical implants of hydroxyapatite (HA) were placed into both distal femurs of 12 rabbits. From postoperative day 1 and for 5 consecutive days, the left femurs of all rabbits were submitted to LPL treatment (LPL group) with the following parameters: 300 J/cm2, 1 W, 300 Hz, pulsating emission, 10 min. The right femurs were sham-treated (control group). Three and 6 weeks after implantation, histomorphometric and microhardness measurements were taken. A higher affinity index was observed at the HA-bone interface in the LPL group at 3 (P16 hours (median time to treatment 18 hours for active and 17 hours for control). Time to treatment ranged from 2 to 24 hours. More patients (70%) in the active treatment group had successful outcomes than did controls (51%), as measured prospectively on the bNIH (P=0.035 stratified by severity and time to treatment; P=0.048 stratified only by severity). Similarly, more patients (59%) had successful outcomes than did controls (44%) as measured at 90 days as a binary mRS score of 0 to 2 (P=0.034 stratified by severity and time to treatment; P=0.043 stratified only by severity). Also, more patients in the active treatment group had successful outcomes than controls as measured by the change in mean NIHSS score from baseline to 90 days (P=0.021 stratified by time to treatment) and the full mRS ("shift in Rankin") score (P=0.020 stratified by severity and time to treatment; P=0.026 stratified only by severity). The prevalence odds ratio for bNIH was 1.40 (95% CI, 1.01 to 1.93) and for binary mRS was 1.38 (95% CI, 1.03 to 1.83), controlling for baseline severity. Similar results held for the Barthel Index and Glasgow Outcome Scale. Mortality rates and serious adverse events (SAEs) did not differ significantly (8.9% and 25.3% for active 9.8% and 36.6% for control, respectively, for mortality and SAEs). CONCLUSIONS: The NEST-1 study indicates that infrared laser therapy has shown initial safety and effectiveness for the treatment of ischemic stroke in humans when initiated within 24 hours of stroke onset. A larger confirmatory trial to demonstrate safety and effectiveness is warranted.

Low-Level Laser Therapy Applied Transcranially To Rats After Induction Of Stroke Significantly Reduces Long-Term Neurological Deficits. Stroke. 2006 Oct;37(10):2620-4. Epub 2006 Aug 31 Oron A, Oron U, Chen J, Eilam A, Zhang C, Sadeh M, Lampl Y, Streeter J, DeTaboada L, Chopp M. Department of Orthopedics, Assaf Harofeh Medical Center, Zerifin 70300, Israel. [email protected]

BACKGROUND AND PURPOSE: Low-level laser therapy (LLLT) modulates various biological processes. In the present study, we assessed the hypothesis that LLLT after induction of stroke may have a beneficial effect on ischemic brain tissue. METHODS: Two sets of experiments were performed. Stroke was induced in rats by (1) permanent occlusion of the middle cerebral artery through a craniotomy or (2) insertion of a filament. After induction of stroke, a battery of neurological and functional tests (neurological score, adhesive removal) was performed. Four and 24 hours poststroke, a Ga-As diode laser was used transcranially to illuminate the hemisphere contralateral to the stroke at a power density of 7.5 mW/cm2. RESULTS: In both models of stroke, LLLT significantly reduced neurological deficits when applied 24 hours poststroke. Application of the laser at 4 hours poststroke did not affect the neurological outcome of the stroke-induced rats as compared with controls. There was no statistically significant difference in the stroke lesion area between control and laser-irradiated rats. The number of newly formed neuronal cells, assessed by double immunoreactivity to bromodeoxyuridine and tubulin isotype III as well as migrating cells (doublecortin immunoactivity), was significantly elevated in the subventricular zone of the hemisphere ipsilateral to the induction of stroke when treated by LLLT. CONCLUSIONS: Our data suggest that a noninvasive intervention of LLLT issued 24 hours after acute stroke may provide a significant functional benefit with an underlying mechanism possibly being induction of neurogenesis.

Effects of power densities, continuous and pulse frequencies, and number of sessions of low-level laser therapy on intact rat brain. Photomed Laser Surg. 2006 Aug;24(4):458-66 Ilic S, Leichliter S, Streeter J, Oron A, DeTaboada L, Oron U. Photothera Inc., Carlsbad, California, USA.

OBJECTIVE: The aim of the present study was to investigate the possible short- and long-term adverse neurological effects of low-level laser therapy (LLLT) given at different power densities, frequencies, and modalities on the intact rat brain. BACKGROUND DATA: LLLT has been shown to modulate biological processes depending on power density, wavelength, and frequency. To date, few well-controlled safety studies on LLLT are available. METHODS: One hundred and eighteen rats were used in the study. Diode laser (808 nm, wavelength) was used to deliver power densities of 7.5, 75, and 750 mW/cm2 transcranially to the brain cortex of mature rats, in either continuous wave (CW) or pulse (Pu) modes. Multiple doses of 7.5 mW/cm2 were also applied. Standard neurological examination of the rats was performed during the followup

periods after laser irradiation. Histology was performed at light and electron microscopy levels. RESULTS: Both the scores from standard neurological tests and the histopathological examination indicated that there was no long-term difference between laser-treated and control groups up to 70 days post-treatment. The only rats showing an adverse neurological effect were those in the 750 mW/cm2 (about 100-fold optimal dose), CW mode group. In Pu mode, there was much less heating, and no tissue damage was noted. CONCLUSION: Long-term safety tests lasting 30 and 70 days at optimal 10x and 100x doses, as well as at multiple doses at the same power densities, indicate that the tested laser energy doses are safe under this treatment regime. Neurological deficits and histopathological damage to 750 mW/cm2 CW laser irradiation are attributed to thermal damage and not due to tissue-photon interactions.

Transcranial Application Of Low-Energy Laser Irradiation Improves Neurological Deficits In Rats Following Acute Stroke. Lasers Surg Med. 2006 Jan;38(1):70-3 Detaboada L, Ilic S, Leichliter-Martha S, Oron U, Oron A, Streeter J. Photothera, Inc., 2260 Rutherford Road, Carlsbad, California 92008, USA.

BACKGROUND AND OBJECTIVES: Low-level laser therapy (LLLT) has been shown to have beneficial effects on ischemic skeletal and heart muscles tissues. The aim of the present study was to approve the effectiveness of LLLT treatment at different locations on the brain in acute stroked rats. STUDY DESIGN/MATERIALS AND METHODS: Stroke was induced in 169 rats that were divided into four groups: control non-laser and three laser-treated groups where laser was employed ipsilateral, contralateral, and both to the side of the induced stroke. Rats were tested for neurological function. RESULTS: In all three laser-treated groups, a marked and significant improvement in neurological deficits was evident at 14, 21, and 28 days post stroke relative to the non-treated group. CONCLUSIONS: These observations suggest that LLLT applied at different locations in the skull and in a rather delayed-phase post stroke effectively improves neurological function after acute stroke in rats.

Progress In Low-Level Laser Therapy Jackson Streeter PhotoThera, Carlsbad, CA; This paper appears in: Lasers and Electro-Optics Society, 2006. LEOS 2006. 19th Annual Meeting of the IEEE Publication Date: Oct. 2006 On page(s): 665-666 ISBN: 0-7803-9555-7 INSPEC Accession Number: 9364378 Digital Object Identifier: 10.1109/LEOS.2006.278888 Current Version Published: 2007-01-15

Abstract The presentation covers fundamental operating principles of some of the most widely used methods of low-level laser therapy (LLLT). It includes also recently developed LLLT technologies and medical devices such as LLLT cardiovascular and brain therapy, tissue regeneration and pain relive. The mechanism of LLLT involving interaction with mitochondria. The effects of LLLT are wavelength specific upon a known mitochondrial receptor (cytochrome C oxidase). Targeting of this receptor results in formation of adenosine triphosphate (ATP), enhanced mitochondrial survival and maintenance of cytochrome C oxidase activity

Transcranial Infrared Laser Therapy Improves Clinical Rating Scores After Embolic Strokes In Rabbits. Stroke. 2004 Aug;35(8):1985-8. Epub 2004 May 20 Lapchak PA, Wei J, Zivin JA. Department of Neuroscience, University of California San Diego, MTF 316, 9500 Gilman Drive, La Jolla, CA 92093-0624, USA. [email protected]

BACKGROUND AND PURPOSE: Because photon energy delivered using a low-energy infrared laser may be useful to treat stroke, we determined whether transcranial laser therapy would improve behavioral deficits in a rabbit small clot embolic stroke model (RSCEM). METHODS: In this study, the behavioral and physiological effects of laser treatment were measured. The RSCEM was used to assess whether low-energy laser treatment (7.5 or 25 mW/cm2) altered clinical rating scores (behavior) when given to rabbits beginning 1 to 24 hours postembolization. Behavioral analysis was conducted from 24 hours to 21 days after embolization, allowing for the determination of the effective stroke dose (P50) or clot amount (mg) that produces neurological deficits in 50% of the rabbits. Using the RSCEM, a treatment is considered beneficial if it significantly increases the P50 compared with the control group. RESULTS: In the present study, the P50 value for controls were 0.97+/-0.19 mg to 1.10+/-0.17 mg; this was increased by 100% to 195% (P50=2.02+/-0.46 to 2.98+/-0.65 mg) if laser treatment was initiated up to 6 hours, but not 24 hours, postembolization (P50=1.23+/-0.15 mg). Laser treatment also produced a durable effect that was measurable 21 days after embolization. Laser treatment (25 mW/cm2) did not affect the physiological variables that were measured. CONCLUSIONS: This study shows that laser treatment improved behavioral performance if initiated within 6 hours of an embolic stroke and the effect of laser treatment is durable. Therefore, transcranial laser treatment may be useful to treat human stroke patients and should be further developed.

[Magnetic and laser therapy of acute ischemic stroke] Vopr Kurortol Fizioter Lech Fiz Kult. 2003 Mar-Apr;(2):19-20. [Article in Russian] Samosiuk NI.

The paper presents the technique of frequency-modulated magnetolaser therapy (FMMLT) used in combined treatment of 121 patients with ischemic stroke in acute period. The results were compared with those in the control group of 30 patients who received conventional drug treatment. The results of the comparison allowed the author to recommend FMMLT in ischemic stroke especially in the period of "therapeutic window".

Treatment of experimentally induced transient cerebral ischemia with low energy laser inhibits nitric oxide synthase activity and upregulates the expression of transforming growth factor-beta 1. Lasers Surg Med 2002 31:283-8 Leung MC, Lo SC, Siu FK, So KF

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) has been shown to be neurotoxic while transforming growth factor-beta 1 (TGF-beta1) is neuroprotective in the stroke model. The present study investigates the effects of low energy laser on nitric oxide synthase (NOS) and TGF-beta1 activities after cerebral ischemia and reperfusion injury. STUDY DESIGN/MATERIALS AND METHODS: Cerebral ischemia was induced for 1 hour in male adult Sprague-Dawley (S.D.) rats with unilateral occlusion of middle cerebral artery (MCAO). Low energy laser irradiation was then applied to the cerebrum at different durations (1, 5, or 10 minutes). The activity of NOS and the expression of TGF-beta1 were evaluated in groups with different durations of laser irradiation. RESULTS: After ischemia, the activity of NOS was gradually increased from day 3, became significantly higher from day 4 to 6 (P < 0.001), but returned to the normal level after day 7. The activity and expression of the three isoforms of NOS were significantly suppressed (P < 0.001) to different extents after laser irradiation. In addition, laser irradiation was shown to trigger the expression of TGF-beta1 (P < 0.001). CONCLUSIONS: Low energy laser could suppress the activity of NOS and up-regulate the expression of TGF-beta1 after stroke in rats.

[The Optimization Of An Early Rehabilitation Program For Cerebral Stroke Patients: The Use Of Different Methods Of Magneto- And Laser Therapy] Vopr Kurortol Fizioter Lech Fiz Kult. 2000 May-Jun;(3):17-21. [Article in Russian] Kochetkov AV, Gorbunov FE, Minenkov AA, Strel'tsova EN, Filina TF, Krupennikov AI.

Magnetotherapy and laser therapy were used in complex and complex-combined regimens in 75 patients after cerebral ischemic or hemorrhagic stroke starting on the poststroke week 4-5. Clinico-neurologic, neurophysiological and cerebrohemodynamic findings evidence for the highest effectiveness of neurorehabilitation including complex magneto-laser therapy in hemispheric ischemic and hemorrhagic stroke of subcortical location in the absence of marked clinico-tomographic signs of dyscirculatory encephalopathy. Complex-combined magneto-laser therapy is more effective for correction of spastic dystonia. Mutual potentiation of magnetotherapy and laser therapy results in maximal development of collateral circulation and cerebral hemodynamic reserve (84% of the patients). Complex effects manifest in arteriodilating and venotonic effects. Complex magneto-laser therapy is accompanied by reduction of hyperthrombocythemia and hyperfibrinogenemia.

[The treatment of patients with chronic cerebral circulatory failure by using laser puncture and the microclimate of the biotron] Lik Sprava. 1996 Jul-Sep;(7-9):142-5.

[Article in Ukrainian] Macheret IeL, D'iachenko OIe, Korkushko OO.

A mode is proposed of treatment of chronic cerebrovascular disorders, such as initial manifestations of cerebral blood supply insufficiency (IMBSI) and dyscirculatory encephalopathy (DE) stage I-II in hypertensive disease, involving the use of laser puncture and microclimate of biotron. All patients (n = 162) were exposed to laser puncture (10-12 procedures). Laser puncture treatments were devised according to classical approaches of reflexotherapy, using determinants of electropuncture diagnostic method by Riodoraku. The treatments were carried out with the aid of infrared portable laser "Biomed-001". IMBSI patients presenting with vegetovascular dystonia and about 70% of IMBSI patients presenting with hypertensive disease derived benefit from a course of laser puncture, as evidenced by REG, EEG, acupuncture diagnosis, iridodiagnosis according. In DE stage I-II patients and about 30% IMBSI patients presenting with hypertensive disease good therapeutic effect occurred after treatment in a ward with a stable microclimate of biotron. The proposed method can be used for treating chronic cerebrovascular disorders and administering stroke prophylaxis. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2000 Apr;20(4):264-6.

[Effect Of Intravascular Laser Irradiation Of Blood And Traditional Chinese Medical Therapy On Immune Function In Senile Cerebral Infarction Patients Of Kidney Deficiency Type] [Article in Chinese] Xiao X, Chu X, Ni J. Shenzhen Municipal People's Hospital, Guangdong (518020).

OBJECTIVE: To observe the effect of intravascular laser irradiation of blood (ILIB) therapy on cellular immunity, change of T-lymphocyte subsets and humoral immunity in senile cerebral infarction patients of Kidney deficiency type. METHODS: Seventy-five patients were divided randomly into the ILIB group and the control group treated by conventional medicine (CM). Serum CD3, CD4, CD8, IgG, IgA, IgM, C3 and C4 levels of patients were determined before and after treatment for self-control and comparing between various groups and that of normal control. RESULTS: Before treatment, in patients of both groups, the levels of CD3, CD4, CD4/CD8, C3 were all lower than normal levels significantly, C4 and IgM higher than normal (P < 0.05, P < 0.01), the level of IgG lowered in patients inclined to Kidney-Yang deficiency and raised in those inclined to Kidney-Yin deficiency (P < 0.01). After treatment, in the ILIB group, CD3, CD4 and CD4/CD8 raised significantly (P < 0.05, P < 0.01), IgG and C3 varied towards normal control (P < 0.01, P < 0.05), and C4 lowered but without significance. In the control group, the indexes changed also toward normal but without significance except the change of IgG (P < 0.05). As for IgA and IgM, marked changes were not found in both groups in comparison between before and after treatment. CONCLUSION: ILIB therapy could bi-directionally regulate cellular and humoral immunity in senile cerebral infarction patients of Kidney deficiency type, which was similar to the function in supplementing Qi and invigorating Kidney of Chinese herbal medicine.

Intravascular Laser Therapy On The Cerebral Circulation Ischemic Disturbances T.O. Makhovskaya, V.V. Skupchenko Far Eastern State Medical University (Khabarovsk), State Medical University (Samara), Russia

The dynamics of clinical and pathophysiological alterations on the various forms of cerebral circulation ischemic disturbances (CCID) was investigated in the course of helium-neon laser therapy (HNL). There were treated 600 patients. Clinical, vegetative, and neurophysiological pattern indices were examined. Results of the complex investigation reliably testified that vegetative indices play the important role in CCID pathogenesis, accompanied by pathologic neuro-dynamic disbalance formation. Patients with phase somatovegetative hyperactivity prevailed. Clinical effect of HNL correlated with system vegetative dynamic, its effectiveness was higher in the patients with initial sympathicotonia. HNL was not effective on cholinergic influences. After HNL positive neuro-physiological changes were registered in patients with initial adrenergic activity, there were no changes at cholinergic intensity or slight modulate effect was observed. HNL improved blood circulation, blood filling was increased in the affected vascular basin, the increased cerebral arteries tone decreased, pulse blood filling increased, venous circulation was improved. Therefore, HNL has neurodynamic effect, relaxes sympathicotonic influences and has vagotrope regulatory effect. Photoneurodynamic HNL influence renders trophotroimages action, preventing or reducing cerebral tissue ischemization at all stages of cerebro-vascular diseases with sympatic pattern and is not expedient on neurodynamic disbalance in the form of parasympathicotonia. HNL allows to receive stable therapeutic effect in patients with initial cerebral blood supply insufficiency, transient disturbances of cerebral blood circulation, slight insult, ischemic insult in the acute phase, discirculatory encephalopathy at the first stage.

Laser Acupuncture To Treat Paralysis In Stroke Patients, CT Scan Lesion Site Study Margaret Naeser, Ph.D., Lic.Ac., Dipl.Ac. (NCCAOM) Department of Neurology, Boston University School of Medicine and Neuroimaging/Aphasia Research, V.A. Boston Healthcare System, Boston, MA. [email protected] PURPOSE:

1) To study the effectiveness of low-level laser stimulation of acupuncture points to treat paralysis in stroke patients; 2) To examine the relationship between neuroanatomical lesion sites on CT scan and potential for improvement following laser acupuncture treatments. We have conducted previous research with needle stimulation of acupuncture points in the treatment of paralysis in stroke patients (1-3). SUBJECTS:

Seven stroke patients participated (ages 48-71 years when entering the study; 5 men, 2 women). Five cases had single left hemisphere stroke; two cases, single right hemisphere stroke. Five patients were treated for residual arm/leg paralysis; they had greatly reduced arm and leg power (and severely reduced or no voluntary isolated finger

movement). Two cases were treated only for hand paresis; they had good arm and leg power, but they had mildly reduced isolated finger movement. CT scans were obtained on all patients after at least 3 months poststroke. Six patients began receiving the laser acupuncture treatments during the chronic phase poststroke (10 months to 6.5 years). These times are beyond the spontaneous recovery period of up to 6 months poststroke (4, 5). One hand paresis case began receiving treatments during the acute phase poststroke (1 month poststroke). Because all patients were beyond the spontaneous recovery period except for one, each patient served as his/her own control. No sham laser treatments were administered. None of the stroke patients was receiving physical therapy or occupational therapy treatments during the course of the laser acupuncture treatments. METHOD:

A 20 mW Gallium Aluminum Arsenide (780 nm) near-infrared, diode laser (Unilaser, Denmark) with 1 mm diameter aperture, was used for 20-40 seconds (51-103 J/cm2) on each acupuncture point. The laser was used for 20 seconds on shallow points (hands and face), and 40 seconds on deeper acupuncture points (arms and legs). The points used on the paralyzed arm included: LI 4 (Hegu), LI 11 (Quchi), LI 15 (Jianyu), TW 5 (Waiguan), TW 9 (Sidu), and three distal Baxie points in the web-spaces between the fingers. The points used on the paralyzed leg included: ST 31 (Biguan), ST 36 (Zusanli), GB 34 (Yanglingquan), GB 39 (Xuanzhong), and LIV 3 (Taichong). Points used on the non-paralyzed side included LI 4 (Hegu) and ST 36 (Zusanli). These points include some of those used in our previous research where needle acupuncture was used to treat paralysis in stroke patients (1-3). If facial paralysis was present, the following points on the paralyzed side were used: ST 4 (Dicang), ST 6 (Jiache), ST 7 (Xiaguan), LI 20 (Yingxiang), and SI 18 Quanliao). The patients were tested a few days prior to the first laser acupuncture treatment, and within a few days after completing the 20th, 40th and/or 60th laser acupuncture treatment. P.T. and O.T. testers were blinded; testers were part of a needle acupuncture study with real or sham or no acupuncture. Some patients received only 20 or 40 treatments. The number of treatments a patient received (20, 40 or 60) was based solely on patient availability and transportation issues. All patients were offered a maximum of 60 laser treatments. The patients were treated 2 - 3 times per week, for 3 - 4 months. For patients with arm/leg paralysis, improvement was defined as a minimum increase of at least 10% isolated active range of motion, on at least one arm/leg test, following 20, 40 or 60 laser acupuncture treatments. For the patients treated for hand paresis, improvement was defined as an increase of at least 1 lb., on at least one hand strength test, following 20, 40 or 60 laser acupuncture treatments. RESULTS:

Overall, 5/7 patients (71.4%) treated with laser acupuncture showed improvement. Four of the six chronic stroke patients (66%) showed improvement. The single acute stroke patient (hand paresis case) also showed improvement. Three of the five arm/leg cases showed a minimum of at least 10% improvement in isolated active range of motion on knee flexion; knee extension and/or shoulder abduction (range, +11 to +28%; mean, +15.8%, S.D., 7.08).

The two cases with hand paresis each showed improvement in hand strength. For the chronic hand paresis case (33 months poststroke), grip strength, pre- treatment, 62.7 lbs., post- 20 treatments, 68.4 lbs; strength in first 2 fingers opposing thumb (3-Jaw Chuck), pre- 12, post- 18 lbs.; strength in index finger opposing thumb (Tip Pinch), pre8, post- 11 lbs; and strength in thumb opposing the lateral surface of index finger (Lateral Pinch) pre- 12, post- 14 lbs. For the acute hand paresis case (starting at 1 month poststroke), grip strength, pre- 32.2, post- 20 Tx.'s, 47.7 lbs.; 3-Jaw Chuck, pre- 0, post11.3 lbs.; Tip Pinch, pre- 0, post- 10.7 lbs; Lateral Pinch, pre- 3.7, post- 14.7 lbs. The five cases who showed improvement following the laser acupuncture Treatments had either no lesion in, or lesion in less than half of the motor pathway areas, including the periventricular white matter (PVWM) area on CT scan. The PVWM area is located adjacent to the body of the lateral ventricle, superior to the posterior limb, internal capsule. The two arm/leg cases who showed no improvement following the laser acupuncture treatments had lesion in more than half of the motor pathway areas, including the PVWM area. These behavioral and neuroanatomical findings are similar to our previous research using needle acupuncture to treat paralysis in stroke patients. The PVWM area appears to be the most important area to examine on CT scan or MRI scan, in understanding whether a stroke patient is likely to benefit from needle or laser acupuncture to help reduce the severity of paralysis. This area contains many important intra- and inter-hemispheric pathways including, in part: 1) The descending pyramidal fibers from motor cortex, where the pathways for the leg are more medial. 2) The body of the caudate nucleus. 3) The mid-callosal pathways. 4) The medial subcallosal fasciculus containing connections to caudate from supplementary motor area and cingulate gyrus. 5) The occipito-frontal fasciculus. 6) The superior lateral thalamic peduncle which includes projections from dorsomedial nucleus and anterior nucleus to cingulate and projections from the ventrolateral nucleus to motor cortex. Thus, even within this small PVWM region there are numerous motor systems that might, if incompletely damaged, respond to needle or laser acupuncture. These systems include dorsal striatum, supplementary motor area, or the frontal-striatalventrolateral thalamic-frontal loop, as well as the descending pyramidal system. One patient with severe arm/leg paralysis did have improvement in her facial paralysis with good control of food and liquids in the left side of her mouth for the first time poststroke (4 years poststroke). She also improved in walking, with a ―loosening‖ of the left Achilles tendon. The author has observed that red-beam laser stimulation (4.59 J/cm2) on the JingWell points on the fingers (LU 11, Shaoshang; LI 1, Shangyang; PC 9, Zhongchong; TW 1, Guanchong; HRT 9, Shaochong; SI 1, Shaoze), in combination with the use of a microamps TENS device (MicroStim 100 TENS, Tamarac, FL) placed on the hand (HRT 8, Shaofu; and TW 5; Waiguan), is helpful in treating hand paresis and reducing hand spasticity in stroke patients (6, p. 40, Naeser Laser HAND Treatment Program). This method is also helpful in the prevention/ reduction of contractures of the hand, in patients with severe hand paralysis (personal observation). DISCUSSION:

The use of low-level laser for long-term treatment is especially desirable for chronic stroke patients with hand paresis. The patient can be trained to treat him/herself

at home, using an inexpensive 5mW red-beam diode, laser pointer and a microamps TENS device (MicroStim 100, Tamarac, FL). See Websites listed below. Acupuncture studies using needle acupuncture have observed the best outcome levels when acupuncture treatments were initiated at less than 3 months poststroke (7, 8), and especially when the acupuncture treatments were initiated at less than 24 hours and 36 hours poststroke (9, 10). This is the first study to examine the effect of low-level laser therapy on acupuncture points to treat paralysis in stroke patients where lesion location was known for each patient. Results suggest that low-level laser therapy on acupuncture points is effective to help reduce the severity of paralysis in stroke patients, especially those with mild-moderate paralysis. The treatments should be initiated as soon as possible poststroke, even within 24 hours poststroke. A comprehensive rehabilitation program of P.T., O.T. plus needle and/or laser acupuncture is recommended. REFERENCES

1. Naeser MA, Alexander MP, Stiassny-Eder D, Galler V, Hobbs J, Bachman D: Real versus sham acupuncture in the treatment of paralysis in acute stroke patients: A CT scan lesion site study. Journal of Neurologic Rehabilitation 1992;6:163-173. 2. Naeser MA, Alexander MP, Stiassny-Eder D, Lannin LN, Bachman D: Acupuncture in the treatment of hand paresis in chronic and acute stroke patients - Improvement observed in all cases. Clinical Rehabilitation 1994; 8:127-141. 3. Naeser MA, Alexander MP, Stiassny-Eder D, Galler V, Hobbs J, Bachman D: Acupuncture in the treatment of paralysis in chronic and acute stroke patients Improvement correlated with specific CT scan lesion sites. Acupuncture & Electrotherapeutics 4. Bard G, Hirschberg GG: Recovery of voluntary motion in upper extremity following hemiplegia. Arch Phys Med Rehabil 1965; 46:567-572. 5. Sunderland A, Tinson D, Bradley L, Hewer R: Arm function after stroke: An evaluation of grip strength as a measure of recovery and a prognostic indicator. J Neurol, Neurosurg, and Psych 1989; 52:1267-1272. 6. Naeser MA, Wei XB: Laser Acupuncture, An Introductory Textbook for Treatment of Pain, Paralysis, Spasticity and Other Disorders. Boston, Boston Chinese Medicine, 1994, p. 40. 7. Zhang WX, Li SC, Chen GB, Zhang QM, Wang YX, Fang YA. Acupuncture treatment of apoplectic hemiplegia. Journal of Traditional Chinese Medicine 1987;7:157-160. 8. Johansson K, Lindgren I, Widner H, Wiklung I, Johansson BB: Can sensory stimulation improve the functional outcome in stroke patients? Neurol 1993; 43:2189-2192. 9. Li DM, Li WD, Wei LH, Zhao YL, Lu HZ. Clinical observation on acupuncture therapy for cerebral hemorrhage. J. of Traditional Chinese Medicine 1989;9(1):9-13. 10. Hu HH, Chung C, Liu TJ, Chen RC, Chen CH, Chou P, Huang WS, Lin JCT, Tsuei JJ. A randomized controlled trial on the treatment for acute partial ischemic stroke with acupuncture. Neuroepidemiology 1993;12:106-113. ADDITIONAL INFORMATION: www.Acupuncture.com/Acup/Naeser.htm and www.Acupuncture.com/Acup/laser.htm

See also: Naeser MA: Neurological Rehabilitation: Acupuncture and Laser Acupuncture to Treat Paralysis in Stroke and Other Paralytic Conditions and Pain in Carpal Tunnel Syndrome. Chapter in National Institutes of Health Consensus Development Conference on Acupuncture sponsored by the Office of Alternative Medicine and the Office of Medical Applications of Research. Bethesda, MD, November 3-5, 1997. pp. 93-109 Abstract based on: Naeser MA, Alexander MP, Stiassny-Eder D, Galler V, Hobbs J, Bachman D, Lannin L: Laser Acupuncture in the Treatment of Paralysis in Stroke Patients: A CT Scan Lesion Site Study. Am J of Acupuncture, 23(1):13-28, 1995: Zhong Xi Yi Jie He Xue Bao. 2005 Mar;3(2):128-31.

[Protective effect of low-level laser irradiation on acupuncture points combined with iontophoresis against focal cerebral ischemiareperfusion injury in rats] [Article in Chinese] Dai JY, Ge LB, Zhou YL, Wang L. Acupuncture Clinic, Institute of Qigong, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China. [email protected]

OBJECTIVE: To investigate the effects of low-level laser irradiation on acupuncture points combined with iontophoresis against brain damage after middle cerebral artery occlusion (MCAO) in rats. METHODS: Sixty-nine SD rats were randomly divided into five groups, including normal group, sham operation group, model group, electro-acupuncture group and lowlevel laser irradiation on acupuncture points combined with iontophoresis group (LLLI group). The cerebral ischemia-reperfusion (I/R) model was established by thread embolism of middle cerebral artery. The rats in the LLLI group, as well as the electroacupuncture group were given treatment as soon as the occlusion finished (0 hour) and 12, 24 hours after the occlusion. We observed the changes of neurological deficit scores and the body weight of the rats at different time. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the ratos brain tissue were tested. RESULTS: The neurological deficit score of the LLLI group was significantly lower than that of the model group. The body weight and the activity of SOD of the rats decreased slightly, and the content of MDA decreased significantly after the treatment. CONCLUSION: The low-level laser irradiation on acupuncture points combined with iontophoresis can prevent focal cerebral ischemia-reperfusion injury. One of its mechanisms may be increasing the activity of SOD and decreasing the damage of the oxidation products to the body.

Temporomandibular Joint Disorder Low Intensity Laser Application In Temporomandibular Disorders: A Phase I Double-Blind Study. Cranio. 2007 Jul;25(3):186-92.

Mazzetto MO, Carrasco TG, Bidinelo EF, de Andrade Pizzo RC, Mazzetto RG. Department of Restorative Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo (FORP-USP), Brazil. [email protected]

The purpose of this study was to evaluate the effectiveness of low intensity laser therapy (LILT) for the control of pain from temporomandibular disorder (TMD) in a random and double-blind research design. Forty-eight (48) patients presenting temporomandibular joint (TMJ) pain were divided into an experimental group (GI) and a placebo group (GII). The sample was submitted to the treatment with infrared laser (780 nm, 70 mW, 10 s, 89.7 J/cm2) applied in continuous mode on the affected temporomandibular region, at one point: inside the external auditive duct toward the retrodiskal region, twice a week, for four weeks. For the control group, two identical probes (one active and one that does not emit radiation) were used unknown by the clinician and the subjects. A tip planned for laser acupuncture was used and connected to the active point of the probe. The parameter evaluated was the intensity of pain after palpation of the condylar lateral pole, pre-auricular region and external auditive duct, according to the Visual Analogue Scale (VAS). Four evaluations were performed: Ev1 (before laser application), Ev2 (after 4th application), Ev3 (after 8th application) and Ev4 (30 days after the last application). Data were submitted to statistical analysis. The results showed a decrease in the pain level mainly for the active probe. Among the evaluations, the Ev3 exhibited lower sensitivity to palpation. In conclusion, the results show that low intensity laser is an effective therapy for the pain control of subjects with TMD.

Effectiveness of low-level laser therapy in temporomandibular joint disorders: a placebo-controlled study. Photomed Laser Surg. 2007 Aug;25(4):297-303. Fikácková H, Dostálová T, Navrátil L, Klaschka J. Institute of Biophysics and Informatics, 1st Medical Faculty., Department of Anatomy and Biomechanics, Faculties of Physical Education and Sports, Czech Republic.

Objective: Low-level laser therapy (LLLT) treatment for pain caused by temporomandibular joint disorders (TMD) was investigated in a controlled study comparing applied energy density, subgroups of TMD, and duration of disorders. Background Data: Although LLLT is a physical therapy used in the treatment of musculoskeletal disorders, there is little evidence for its effectiveness in the treatment of TMD. Methods: The study group of 61 patients was treated with 10 J/cm(2) or 15 J/cm(2), and the control group of 19 patients was treated with 0.1 J/cm(2). LLLT was performed by a GaAlAs diode laser with output of 400 mW emitting radiation wavelength of 830 nm in 10 sessions. The probe with aperture 0.2 cm(2) was placed over the painful muscle spots in the patients with myofascial pain. In patients with TMD arthralgia the probe was placed behind, in front of, and above the mandibular condyle, and into the meatus acusticus externus. Changes in pain were evaluated by selfadministered questionnaire. Results: Application of 10 J/cm(2) or 15 J/cm(2) was significantly more effective in reducing pain compared to placebo, but there were no significant differences between the energy densities used in the study group and between patients with myofascial pain and temporomandibular joint arthralgia. Results were marked in those with chronic pain. Conclusion: The results suggest that LLLT (application of 10 J/cm(2) and 15 J/cm(2)) can be considered as a useful method for the

treatment of TMD-related pain, especially long lasting pain.

Low intensity laser application in temporomandibular disorders: a phase I double-blind study. Cranio. 2007 Jul;25(3):186-92. Mazzetto MO, Carrasco TG, Bidinelo EF, de Andrade Pizzo RC, Mazzetto RG. Department of Restorative Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo (FORP-USP), Brazil. [email protected]

The purpose of this study was to evaluate the effectiveness of low intensity laser therapy (LILT) for the control of pain from temporomandibular disorder (TMD) in a random and double-blind research design. Forty-eight (48) patients presenting temporomandibular joint (TMJ) pain were divided into an experimental group (GI) and a placebo group (GII). The sample was submitted to the treatment with infrared laser (780 nm, 70 mW, 10 s, 89.7 J/cm2) applied in continuous mode on the affected temporomandibular region, at one point: inside the external auditive duct toward the retrodiskal region, twice a week, for four weeks. For the control group, two identical probes (one active and one that does not emit radiation) were used unknown by the clinician and the subjects. A tip planned for laser acupuncture was used and connected to the active point of the probe. The parameter evaluated was the intensity of pain after palpation of the condylar lateral pole, pre-auricular region and external auditive duct, according to the Visual Analogue Scale (VAS). Four evaluations were performed: Ev1 (before laser application), Ev2 (after 4th application), Ev3 (after 8th application) and Ev4 (30 days after the last application). Data were submitted to statistical analysis. The results showed a decrease in the pain level mainly for the active probe. Among the evaluations, the Ev3 exhibited lower sensitivity to palpation. In conclusion, the results show that low intensity laser is an effective therapy for the pain control of subjects with TMD.

Arthralgia of the temporomandibular joint and low-level laser therapy. Photomed Laser Surg. 2006 Aug;24(4):522-7 Fikácková H, Dostálová T, Vosická R, Peterová V, Navrátil L, Lesák J. Institute of Biophysics and Informatics, 1st Medical Faculty, Charles University, Prague, Czech Republic. [email protected]

OBJECTIVE: This case report describes the treatment of a patient with arthralgia of the temporomandibular joint (TMJ) caused by disc displacement. BACKGROUND DATA: The goal of the treatment of TMJ arthralgia is to decrease pain by promotion of the musculoskeletal system's natural healing ability. METHODS: This report describes the complex treatment of TMJ arthralgia. Low-level laser therapy (LLLT) was chosen for its antiinflammatory and analgesic effects. Laser therapy was carried out using the GaAlAs diode laser with an output power of 400 mW, emitting radiation with a wavelength of 830 nm, and having energy density of 15 J/cm2; the laser radiation was applied by contact mode on four targeted spots in 10 sessions. Physiotherapy was recommended to this patient to prevent the injury of intraarticular tissue caused by incorrect movement during opening of the mouth. Splint stabilization and prosthetic treatment were used to reduce overloading of the TMJ, resulting from unstable occlusion and to help repositioning of the dislocated disc. RESULTS: Five applications of LLLT led to decrease of pain in the area of the TMJ on the Visual Analog Scale, from 20 to 5 mm. The anti-inflammatory

effect of the laser was confirmed by thermographic examination. Before treatment, the temperature differences between the areas of the normal TMJ and TMJ with arthralgia was higher than 0.5 degrees C. However, at the conclusion of LLLT, temperatures in the areas surrounding the TMJ were equalized. CONCLUSION: This study showed the effectiveness of complex non-invasive treatment in patients with arthralgia of the TMJ. The analgesic and anti-inflammatory effects of LLLT were confirmed by infrared thermography.

Evaluation of low-level laser therapy in the treatment of temporomandibular disorders. Photomed Laser Surg. 2006 Oct;24(5):637-41 Cetiner S, Kahraman SA, Yucetas S. Department of Oral and Maxillofacial Surgery, School of Dentistry, Gazi University, Ankara, Turkey.

Objective: The purpose of this study was to assess the effectiveness of low-level laser therapy (LLLT) in the treatment of myogenic originated temporomandibular disorders (TMD). Background Data: Limited studies have demonstrated that LLLT may have a therapeutic effect on the treatment of TMD. Methods: Thirty-nine patients with myogenic TMD-associated orofacial pain, limited mandibular movements, chewing difficulties, and tender points were included in this study. Twenty-four of them were treated with LLLT for 10 sessions per day excluding weekends as test group, and 15 patients with the same protocol received placebo laser treatment as a control group. These parameters were assessed just before, just after, and 1 month after the treatment. Results: Maximal mouthopening improvement, and reductions in pain and chewing difficulty were statistically significant in the test group when compared with the control group. Statistically significant improvements were also detected between two groups regarding reduction in the number of tender points. Conclusion: Based on the results of this placebo-controlled report, LLLT is an appropriate treatment for TMD and should be considered as an alternative to other methods.

Effectiveness of low-level laser therapy in temporomandibular disorder. Scand J Rheumatol. 2003;32(2):114-8. Kulekcioglu S, Sivrioglu K, Ozcan O, Parlak M. Department of Physical Medicine and Rehabilitation, Uludag University School of Medicine, Bursa, Turkey.

OBJECTIVE: To investigate the effectiveness of low-level laser therapy in the treatment of temporomandibular disorder and to compare treatment effects in myogenic and arthrogenic cases. METHODS: Thirty-five patients were evaluated by magnetic resonance imaging and randomly allocated to active treatment (n=20) and placebo treatment (n= 15) groups. In addition to a daily exercise program, all patients were treated with fifteen sessions of low-level laser therapy. Pain, joint motion, number of joint sounds and tender points were assessed. RESULTS: Significant reduction in pain was observed in both active and placebo treatment groups. Active and passive maximum

mouth opening, lateral motion, number of tender points were significantly improved only in the active treatment group. Treatment effects in myogenic and arthrogenic cases were similar. CONCLUSION: Low-level laser therapy can be considered as an alternative physical modality in the management of temporomandibular disorder.

Clinical evaluation of the low intensity laser antialgic action of GaAlAs (wavelenght=785 nm) in the treatment of the temporomandibular disorders. Laser Med Surg Abstract issue, 2002: 18. Sanseverino N T M, Sanseverino C A M, Ribeiro M S et al.

The improved outcome of laser therapy, if higher doses are given, is documented in the study by Sanseverino 10 patients with pain and limitation of movements of the jaw were treated by 785 nm GaAlAs laser, dose 45 J/cm2. The joint and tender points in the masticatory and otherwise involved muscles was applied three times per week during three weeks. A control group of 10 patients was given sham laser therapy. The evaluation was performed through subjective pain assessment and measurement of the movements of the jaw. There was a significant improvement in the laser group only.

Clinical evaluation of the low intensity laser antialgic action of GaAlAs in the treatment of the temporomandibular disorders. 2001. SANSEVERINO, N. T. M. Dissertation (Professional Master's Degree "Lasers in Dentistry") - Nuclear and Energy Research Institute / School of Dentistry, University of São Paulo, São Paulo. Advisor: Eduardo De Bortoli Groth, DDS, PhD, Martha Simões Ribeiro, DDS, PhD

The therapy with laser emitting low intensity has been currently used in the most diverse fields of medicine as therapeutic conduct for pain. lt is a non-invasive, painless, nonthermal and aseptic type therapy, without any collateral effects, having a good cost/benefit relationship. However, for the therapy with low-intensity laser to result in positive effects, a correct diagnosis is fundamental, as well as a protocol of adequate application. In odontology, the majority of patients diagnosed with temporomandibular disorders (TMD), present pain and limitations in the movements of the jaw. In this work, a GaAlAs laser emitting low intensity, was used, ?=785nm, in patients having a dysfunction of the temporomandibular joint with a complaint of pain. Twenty patients were divided into two groups. The group treated received laser treatment in the temporomandibular articulations and in the muscles affected. The dose applied was 45J/cm2, while the ten patients in the control group received 0J/cm2, in a total of nine applications, carried out three times a week, during three weeks. The evaluation of the patients was made through clinical examinations of manual palpation of the masseter, temporal, cervical, posterior neck and sternocleidomastoid muscles, and measurements of opening and laterality of the mouth. The results obtained showed a diminishing of the pain and an increase of the mandibular mobility in the patients treated, when compared to the control group. These results point to this therapy as being an important tool in the treatment of pain in patients with a dysfunction in the TMJ, indicating this therapeutic modality as a co-adjuvant in these treatments.

Low Intensity Laser Therapy (Lilt) In The Maxillofacial Region Paul Bradley The Royal London School of Medicine and Dentistry, London, England

The region of the face and mouth is well suited to Low Intensity Laser Therapy (LILT) in view of ease of access. It is also an area associated with a variety of painful conditions and intractable ulcers which have proved amenable to LILT in a total of around 500 cases. Our practice is based on several postgraduate research projects: 1. Studies of depth penetration of 820nm. These have been undertaken using a CCD camera to demonstrate penetration depths in non vital tissue specimens augmented by observations in the living subject with isotropic detectors. 2. Investigation of vascular response. A thermographic camera has been used for local heating effects while laser doppler has been employed to measure microcirculatory flux. Ultrasound doppler allowed monitoring of arterial status. A variety of wavelengths and fluxes have been investigated. 3. Double blind clinical trial in temporomandibular joint disorder pain. Methods have included algometry for pressure point thresholds, electromyography for muscular activity and sensor tracking for mandibular movement. 4. Study of effect on osseointegration of implants in jaw and femur. Research methods have involved mechanical push out testing, radiovisiography, x-ray microtomography and histomorphometry in the rabbit experimental model. On the basis of the data acquired clinical practice has been undertaken particularly in the following conditions: 1. Post Herpetic Neuralgia, 2. Temporomandibular Joint Disorder Pain 3. Trigeminal Neuralgia 4. Atypical Facial Pain, 5. Pain from Acute Maxillofacial Trauma 6. Palliation of Pain from Unresectable Orofacial Cancer, 7. Intractable Oral Ulcerations, 8. Nerve Lesions, 8. Cavernous Haemangiomas Of the Facial Region in Infants The results of this clinical practice are described and analyzed.

Low-level laser therapy is an important tool to treat disorders in the maxillofacial region. J Clinical Laser Med & Surg. 1998; 16 (4): 223-226. Pinheiro A et al.

241 patients with different disorders in the maxillofacial region were treated with LLLT. Indications were temporomandibular disorders, trigeminal neuralgia, muscular pain, aphtae etc. Lasers of 633, 670 and 830 nm were used. Most treatments consisted of a series of 12 applications (twice a week). Average dose was 1.8 J/cm2. At the end of treatment 154 patients were asymptomatic, 50 improved considerably and 37 were symptomatic. PHD DISSERTATION ON TMD PROBLEMS

Dr Sajee Sattayut of The Department of Oral & Maxillofacial Surgery, St Bartholomew's and the Royal London School of Medicine and Dentistry (professor Paul Bradley) has put forward his PhD thesis on the effect of 820 nm low level laser on patients with TMD

(temporo-mandibular-joint-disorders). In a double blind study on 30 female TMD patients one group was given placebo laser, one a low dose from a 60 mW laser and the third a high dose from a 300 mW GaAlAs laser. Three treatments were given during one week. The patients in the high energy density group had significantly increases in Pressure Pain Threshould and EMG amplitude, recorded from voluntary clenching. A significantly greater number of patients recovered from myofacial pain and TMJ arthralgia as assessed clinically in the higher energy group. At a period of 2 to 4 weeks review after LLLT, there was an average 52% reduction of pain as assessed by Symptom Severity Index pain questionnaire. In an in vitro study laser was observed to reduce IL-1 stimulated PGE2 production.

A systematic review of low level laser therapy with location-specific doses for pain from chronic joint disorders. Australian J Physiother. 2003; 49: 107-116. Bjordal J M, Couppè, C, Chow R, Tunér J, Ljunggren A E.

The authors investigated if low level laser therapy of the joint capsule can reduce pain in chronic joint disorders (CJD). A literature search identified 88 randomised-controlled trials, of which 20 trials included patients with CJD. Six trials had to be excluded for not irradiating the joint capsule. Three trials used doses lower than a denominated a priori dose range for reducing inflammation in the joint capsule. These trials found no significant difference between active and placebo treatments. The remaining 11 trials, including 565 patients, were of acceptable methodological quality with an average PEDro score of 6.9 (range 5-9). In these trials, LLLT within the suggested dose-range was administered to the knee, temporomandibular and zygapophyseal joints. The results showed a mean weighted difference in change of pain on VAS by 45.6 % (95 % CI 35.0 to 56.2) in favour of LLLT. Global status was improved for 33.4 % (95% CI 20.9 to 45.9) more patients in the LLLT group. LLLT with the suggested dose range significantly reduces pain in CJD, but the heterogeneity in patient samples, treatment procedures and trial design calls for cautious interpretation of the results.

Low level laser therapy in the treatment of temporomandibular disorders (TMD): a double-blind pilot study. Cranio. 1997 Apr;15(2):144-9. Conti PC. Bauru School of Dentistry, University of Sao Paulo, Brazil.

The aim of this paper was to evaluate the efficacy of a Low-Level Laser therapy in patients with Temporomandibular Disorders (TMD) using a double-blind design. A sample of 20 patients with a chief complaint of pain was divided into myogenous and arthrogenous groups. The sample was also divided on the basis of the treatment rendered: real versus placebo treatment. An 830 nm Ga-Al-As Laser device with a energy power of 4 joules was used (OMNILASE, LASERDYNE PTY LTD.) in three treatment sessions. To evaluate the effectiveness of laser treatment, a Visual Analogue Scale (VAS) was used for pain and active range of motion (AROM) was used to measure changes in mandibular function. Using real laser treatment, the author found that there was a

reported improvement in pain only for the myogenous pain patients (p < or = 0.02). For the arthrogenous pain patients, real laser treatment resulted in an improvement in Total Vertical Opening (TVO) (p < 0.05), Protrusive excursion (PROT) (p < 0.02) and Left lateral excursion (LATLEF) (p < 0.02). The placebo control group showed improvement in TVO and PROT for those patients having myogenous pain and LATLEF for those patients having arthrogenous pain. A repeated measurement one-way ANOVA demonstrated no significant differences between real and placebo groups. Considering the non-invasive and harmless characteristics of this modality, more research is recommended, using higher power and increased frequency of laser applications.

Tendon and Ligament Healing Combined treatment of therapeutic laser and herbal application improves the strength of repairing ligament. Connect Tissue Res. 2005;46(3):125-30 Fung DT, Ng GY, Leung MC. Orthopaedic Rehabilitation Research and Microscopy Laboratory, Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong, China.

The present study investigated the effects of combined therapeutic laser and herbal medication protocols on injured medial collateral ligaments (MCLs) of rat knees. Fully 36 rats were evenly divided into 9 groups. Right MCLs of groups 1 to 6 and 8 were transected, while that of groups 7 and 9 remained intact. After surgery, group 1 was treated with 1 session of high-dosed laser; group 2 with 9 sessions of low-dosed laser; group 3 with an herbal plaster; groups 4 and 5 received combined treatments of groups 1 and ss and 2, and 3 respectively; groups 6 and 7 received only bandaging; groups 8 and 9 received placebo laser and no treatment, respectively. All MCLs were subjected to biomechanical testing at 3 weeks postsurgery. Results revealed significant differences among groups in ultimate tensile strength (UTS) and stiffness (p < 0.01). Combination of multiple low-dosed laser treatment with herbal treatment (group 5) resulted in higher UTS than either no treatment (groups 6 and 8), single high-dosed laser treatment (group 1), multiple low-dosed laser treatment (group 2), or herbal treatment (group 2) alone. We concluded that combined applications of laser and herb can enhance further biomechanical properties of repairing rat MCLs than separate applications at 3 weeks postinjury.

Low-level laser therapy (LLLT) prevents oxidative stress and reduces fibrosis in rat traumatized Achilles tendon. Lasers Surg Med. 2005 Oct;37(4):293-300 Fillipin LI, Mauriz JL, Vedovelli K, Moreira AJ, Zettler CG, Lech O, Marroni NP, González-Gallego J. Department of Physiology, Universidade Federal de Rio Grande do Sul, Brazil.

BACKGROUND AND OBJECTIVES: The present study investigated the effects of lowlevel laser therapy (LLLT) on oxidative stress and fibrosis in an experimental model of Achilles tendon injury induced by a single impact trauma. STUDY DESIGN/MATERIALS AND

METHODS: Male Wistar rats were randomly divided into four groups (n = 8): control, trauma, trauma+LLLT for 14 days, and trauma+LLLT for 21 days. Achilles tendon traumatism was produced by dropping down a load with an impact kinetic energy of 0.544 J. A low level Ga-As laser was applied with a 904 nm wavelength, 45 mW average power, 5 J/cm(2) dosage, for 35 seconds duration, continuously. Studies were carried out at day 21. RESULTS: Histology showed a loss of normal architecture, with inflammatory reaction, angiogenesis, vasodilatation, and extracellular matrix formation after trauma. This was accompanied by a significant increase in collagen concentration when compared the control group. Oxidative stress, measured by the concentration of thiobarbituric acid reactive substances and hydroperoxyde-initiated chemiluminiscence, was also significantly increased in the trauma group. Administration of LLLT for 14 or 21 days markedly alleviated histological abnormalities reduced collagen concentration and prevented oxidative stress. Superoxide dismutase activity was significantly increased by LLLT treatment over control values. CONCLUSION: LLLT by Ga-As laser reduces histological abnormalities, collagen concentration, and oxidative stress in an experimental model of Achilles tendon injury. Reduction of fibrosis could be mediated by the beneficial effects on the oxidant/antioxidant balance.

Low-level laser therapy improves early healing of medial collateral ligament injuries in rats. Photomed Laser Surg. 2005 Dec;23(6):556-60 Bayat M, Delbari A, Almaseyeh MA, Sadeghi Y, Bayat M, Reziae F. Cell and Molecular Biology Research Center, Medical School, Shaheed Beheshti University of Medical Sciences, Tehran, Iran. [email protected]

OBJECTIVE: This study sought to investigate whether or not low-level laser therapy (LLLT) with a helium-neon laser increased biomechanical parameters of transected medial collateral ligament (MCL) in rats. BACKGROUND DATA: It has been reported that LLLT can enhance tendon healing. METHODS: Thirty rats received surgical transection to their right MCL, and five were assigned as the control group. After surgery, the rats were divided into three groups: group 1 (n = 10) received LLLT with 0.01 J/cm(2) energy density per day, group 2 (n = 10) received LLLT with 1.2 J/cm(2) energy density per day, and group 3 (sham = exposed group; n = 10) received daily placebo laser with shut-down laser equipment, while the control group received neither surgery nor LLLT. Biomechanical tests were performed at 12 and 21 days after surgery. The data were analyzed by one-way analysis of variance. RESULTS: The ultimate tensile strength (UTS) of group 2 on day 12 was significantly higher than that of groups 1 and 3. Furthermore, the UTS and energy absorption of the control (uninjured) group were significantly higher than those of the other groups. CONCLUSIONS: LLLT with a helium-neon laser is effective for the early improvement of the ultimate tensile strength of medial collateral ligament injuries.

Comparison of the effects of laser, ultrasound, and combined laser + ultrasound treatments in experimental tendon healing. Lasers Surg Med. 2004;35(1):84-9

Demir H, Menku P, Kirnap M, Calis M, Ikizceli I. Erciyes University Medical Faculty, Department of Physical Medicine & Rehabilitation, Kayseri, Turkey. [email protected]

BACKGROUND AND OBJECTIVE: Therapeutic ultrasound (US) and laser (L) treatments accelerate and facilitate wound healing, and also have beneficial effects on tendon healing. This randomized control study was designed to evaluate the effects of low-intensity US and low-level laser therapy (LLLT) on tendon healing in rats. STUDY DESIGN/MATERIALS AND METHODS: Eighty-four healthy male Swiss-Albino rats were divided into three groups consisting of 28 rats, the left Achilles tendons were used as treatment and the right Achilles tendons as controls. The right and left Achilles tendons of rats were traumatized longitudinally. The treatment was started on postinjury day one. We applied the treatment protocols including low-intensity US treatment in Group I (US Group), Sham US in Group II (SUS Group), LLLT in Group III (L Group), Sham L in Group IV (SL Group), US and LLLT in Group V (US + L Group), and Sham US and Sham L in Group VI (SUS + SL Group). The US treatment was applied with a power of 0.5 W/cm2, a frequency of 1 MHz, continuously, 5 minutes daily. A low-level Ga-As laser was applied with a 904 nm wavelength, 6 mW average power, 1 J/ cm2 dosage, 16 Hz frequency, for 1 minute duration, continuously. In the control groups, the similar procedures as in the corresponding treatment groups were applied with no current (Sham method). The treatment duration was planned for 9 days (sessions) in all groups, except the rats used for biochemical evaluation on the 4th day of treatment, which were treated for 4 days. We measured the levels of the tissue hydroxyproline for biochemical evaluation on the 4th, 10th, and 21st days following the beginning of treatment and the tendon breaking strength on the 21st day following the beginning of treatment for biomechanical evaluation. Seven rats in each group were killed on the 4th, 10th, and 21st days for biochemical evaluation and on the 21st day for biomechanical evaluation. RESULTS: The hydroxyproline levels were found to be significantly increased in the treatment groups on the 10th and 21st days compared to their control groups (P < 0.05). In comparison of the treatment groups on the 4th, 10th, and 21st days of the treatment, the levels of tissue hydroxyproline were found to be more increased in combined US+L Group compared with US Group and L Group, but the difference was not significant (P > 0.05). In comparison of the tendon breaking strengths, it was found as significantly increased in the treatment groups compared with their control groups (P < 0.05), although there was no significant difference between the treatment groups. CONCLUSIONS: Although US, L, and combined US + L treatments increased tendon healing biochemically and biomechanically more than the control groups, no statistically significant difference was found between them. Also we did not find significantly more cumulative positive effects of combined treatment. As a result, both of these physical modalities can be used successfully in the treatment of tendon healing.

Effect of low-level laser therapy on healing of medial collateral ligament injuries in rats: an ultrastructural study. Photomed Laser Surg. 2007 Jun;25(3):191-6 Delbari A, Bayat M, Bayat M. Avicenna Hospital, Tehran, Iran.

OBJECTIVE: This study sought to investigate whether low-level laser therapy (LLLT) with a helium-neon (He-Ne) laser would increase fibril diameter of transected medial collateral ligament (MCL) in rats. BACKGROUND DATA: It has been shown that LLLT can increase ultimate tensile strength MCL healing. METHODS: Thirty rats received surgical transect to their right MCL, and five were assigned as the control group. After surgery, the rats were divided into three groups: group 1 (n = 10) received LLLT with He-Ne laser and 0.01 J/cm(2) energy fluency per day, group 2 (n = 10) received LLLT with 1.2 J/cm(2) energy fluency (density) per day and group 3 (sham-exposed group; n = 10) received daily placebo laser with shut-down laser equipment, while control group received neither surgery nor LLLT. Transmission electron microscope (TEM) examination was performed on days 12 and 21 after surgery and dimension and density of ligament fibrils were measured. The data were analyzed by Student t-test and Mann-Whitney tests, respectively. RESULTS: On day 12, the fibril dimension of group 2 and their density were higher than of groups 1 and 3. CONCLUSION: LLLT with He-Ne laser on incised MCL in rats could not significantly increase fibril diameter and their density in comparison with sham-exposed group.

Tendonitis Comparison of the effects of laser, ultrasound, and combined laser + ultrasound treatments in experimental tendon healing. Lasers Surg Med. 2004;35(1):84-9. Demir H, Menku P, Kirnap M, Calis M, Ikizceli I. Erciyes University Medical Faculty, Department of Physical Medicine & Rehabilitation, Kayseri, Turkey. [email protected]

BACKGROUND AND OBJECTIVE: Therapeutic ultrasound (US) and laser (L) treatments accelerate and facilitate wound healing, and also have beneficial effects on tendon healing. This randomized control study was designed to evaluate the effects of low-intensity US and low-level laser therapy (LLLT) on tendon healing in rats. STUDY DESIGN/MATERIALS AND METHODS: Eighty-four healthy male Swiss-Albino rats were divided into three groups consisting of 28 rats, the left Achilles tendons were used as treatment and the right Achilles tendons as controls. The right and left Achilles tendons of rats were traumatized longitudinally. The treatment was started on postinjury day one. We applied the treatment protocols including low-intensity US treatment in Group I (US Group), Sham US in Group II (SUS Group), LLLT in Group III (L Group), Sham L in Group IV (SL Group), US and LLLT in Group V (US + L Group), and Sham US and Sham L in Group VI (SUS + SL Group). The US treatment was applied with a power of 0.5 W/cm2, a frequency of 1 MHz, continuously, 5 minutes daily. A low-level Ga-As laser was applied with a 904 nm wavelength, 6 mW average power, 1 J/ cm2 dosage, 16 Hz frequency, for 1 minute duration, continuously. In the control groups, the similar procedures as in the corresponding treatment groups were applied with no current (Sham method). The treatment duration was planned for 9 days (sessions) in all groups, except the rats used for biochemical evaluation on the 4th day of treatment, which were treated for 4 days. We measured the levels of the tissue hydroxyproline for biochemical evaluation on the 4th, 10th, and 21st days following the beginning of treatment and the tendon breaking strength on the 21st day

following the beginning of treatment for biomechanical evaluation. Seven rats in each group were killed on the 4th, 10th, and 21st days for biochemical evaluation and on the 21st day for biomechanical evaluation. RESULTS: The hydroxyproline levels were found to be significantly increased in the treatment groups on the 10th and 21st days compared to their control groups (P < 0.05). In comparison of the treatment groups on the 4th, 10th, and 21st days of the treatment, the levels of tissue hydroxyproline were found to be more increased in combined US+L Group compared with US Group and L Group, but the difference was not significant (P > 0.05). In comparison of the tendon breaking strengths, it was found as significantly increased in the treatment groups compared with their control groups (P < 0.05), although there was no significant difference between the treatment groups. CONCLUSIONS: Although US, L, and combined US + L treatments increased tendon healing biochemically and biomechanically more than the control groups, no statistically significant difference was found between them. Also we did not find significantly more cumulative positive effects of combined treatment. As a result, both of these physical modalities can be used successfully in the treatment of tendon healing.

LLLT Is As Well Documented As Nsaids And Steroid Injections For Shoulder Tendinitis/Bursitis And Epicondylaglia. The Norwegian physiotherapist Jan M Bjordal published his thesis “Low level laser therapy in shoulder tendinitis/bursitis, epicondylalgia and ankle sprain” in 1997, at the Division of Physiotherapy Science, University of Bergen. It has also been published in Physical Therapy Reviews. 1998; 3: 121-132.

Here is the Conclusion of the thesis: ―A systematic review has been performed on the effect of LLLT for three diagnoses. LLLT was evaluated on similar criteria for methodological assessments of trials as previously established for medical interventions. No evidence was found to indicate that randomized controlled trials on LLLT for tendinitis/bursitis of the shoulder, lateral epicondylalgia and ankle sprains were methodologically inferior to RCTs on medical interventions. The clinical effects of LLLT were found to be supported by scientific evidence regarding short (0-4 weeks) and medium term (3 months) for subacute or chronic lateral epicondylitis, and short term efficacy (> 3 months) for subacute or chronic shoulder tendinitis/bursitis. The evidence of effect from LLLT for acute ankle sprain is inconclusive, although there seems to be a slight tendency in favour of LLLT. Adverse effects of LLLT are rarely seen and only in minor forms (nausea, headache) compared to medication, where more serious gastrointestinal discomfort or ulcers are not uncommon. It has also been shown that trials in favour of active treatment had more treatments per week than the trials showing no difference in effect. In short one could say that LLLT should be used much in the same way as NSAID are used for short periods of time. Most trials showing significant effects used an IR 904 nm laser, but some results in favour of IR lasers with wavelengths of 780, 820 and 830 nm were also observed. Clinical effects of LLLT were best in subacute conditions. In chronic conditions a higher dosage and more treatments seem to be needed. The results of the high quality LLLT trials were all in favour of treatment with confidence intervals not including zero, and the trials came from several different research groups. Evidence was found to be at the highest or the second highest level depending on what level of clinical significance is decided according to the classification of Oxman (1994) and McQuay (1997). The review found little support for the alleged large placebo effects of LLLT. In chronic cases the placebo effect is probably less that

10%, after the natural history of the complaints is taken into account.‖ In the ―Summary of discussion on clinical effect estimates for LLLT‖ the author writes: ―The majority of the included LLLT-trials found significant clinical effect from LLLT. Seven of the eleven LLLTtrials with acceptable methods included calculations of 95% confidence limits above zero, and one LLLT-trial on anke sprain included zero (Axelsen & Bjerno 1993). The clincal effect estimates from LLLT-trials for shoulder tendinitis/bursitis are similar or higher than for NSAID or steroid injections. For lateral epicondylalgia estimates for short term clinical effects are similar or lower for LLLT than for steroid injections, but medium clinical effect estimates are similar or higher for LLLT. Recurrence of symptoms in lateral epicondylalgia is less likely after LLLT than after steroid inje ctions. Evidence of clinical effects from ankle sprain is inconclusive. Adverse effects from LLLT are seldom seen and they appear less serious than for patients treated with NSAID and steroid injections.‖

The Biological Effects of Laser Therapy and Other physical Modalities on Connective Tissue Repair Processes Chukuka S. Enwemeka, P.T., Ph.D., FACSM, G. Kesava Reddy, Ph.D., Department of Physical Therapy and Rehabilitation Sciences, University of Kansas Medical Center, Kansas City, KS 66160-7601, USA Connective tissue injuries, such as tendon rupture and ligamentous strains, are common. Unlike most soft tissues that require 7-10 days to heal, primary healing of tendons and other dense connective tissues take as much as 6 - 8 weeks during which they are inevitably protected in immobilization casts to avoid re-injury. Such long periods of immobilization impair functional rehabilitation and predispose a multitude of complications that could be minimized if healing is quickened and the duration of cast immobilization reduced. In separate studies, we tested the hypothesis that early function, ultrasound, 632.8 nm He-Ne laser, and 904 nm Ga-As laser, when used singly or in combination, promote healing of experimentally severed and repaired rabbit Achilles tendons as evidenced by biochemical, biomechanical, and morphological indices of healing. Our results demonstrate that: (1) appropriate doses of each modality, i.e., early functional activities, ultrasound, He-Ne and Ga-As laser therapy augment collagen synthesis, modulate maturation of newly synthesized collagen, and overall, enhance the biomechanical characteristics of the repaired tendons. (2) Combinations of either of the two lasers with early function and either ultrasound or electrical stimulation further promote collagen synthesis when compared to functional activities alone. However, the biomechanical effects measured in tendons receiving the multi-therapy were similar, i.e., not better than the earlier single modality trials. Although tissue repair processes in humans may differ from that of rabbits, these findings suggest that human cases of connective tissue injuries, e.g., Achilles tendon rupture, may benefit from appropriate doses of He-Ne laser, Ga-As laser, and other therapeutic modalities, when used singly or in combination. Our recent meta-analysis of the laser therapy literature further corroborate these findings.

Laser Treatment for Tendinitis Jan M. Bjordal, PT-MSc, Faculty of Medicine, University of Bergen, Norway Christian Couppe, PT, Copenhagen, Denmark Tendinitis is a common disorder of the musculoskeletal system. Cardinal symptoms from the tendon are pain from increased tension like muscle contraction or stretching and pain on pressure. In an acute stage inflammation is the most common pathophysiological manifestation, while degeneration of the collagen structure is observed in subacute and chronic cases. However, the episodic nature of chronic tendinitis with increased pain after strenous use of the affected tendon, may indicate that inflammation also play a

part at this stage. A successful strategy of treatment should include reduction of inflammation and regeneration of collagen. In the laboratory several experiments have shown that laser treatment may have the potential to achieve both these goals. The findings of the laboratory also shows that these effects are highly dependent on dose.

1. A synthesis of dose from 4 laboratory trials on inflamed collagen producing cell cultures gives the following dose for optimal reduction of tendon tissue inflammation: Dose : 3 - 8 J/cm2 Intensity : 5 - 21 mW/cm2 2. A synthesis from 10 laboratory trials investigating collagen proliferation gives the following optimal dose for stimulation of tendon regeneration : Dose : 0.2 - 4 J/cm2 Intensity : 2 - 10 mW/ cm2 3. For the treatment of tendinitis an optimal suggested dosage at target location will be : Dose : 0.2 - 4 J/cm2 Intensity : 2 - 10 mW/ cm2 Treatment should be applied daily for at least five days to reduce inflammation, and for at least 10 days to increase collagen production. DETERMINATION OF CLINICAL DOSE

The clinical dose depends on several factors such as laser type, depth to target from skin surface, the type of tissue between skinsurface and target location and the volume of injured tissue. Characteristics for common tendon disorders The various tendon locations have different characteristics that affects determination of dose. Tendon Depth to target tendon (mm) Tendon thickness (mm) Typical area of tendon defect (cm2) Values for different conditions are as follows: Plantar fasciitis 10.0 - 12.0 3.0 - 4.0 0.1 - 0.8 Achilles 1.5 - 3.0 4.5 - 6.0 0.5 - 2.0 Patellar 2.5 - 4.0 5.5 - 8.0 1.0 - 4.0 Epicondylitis 1.5 - 2.5 2.0 - 4.0 0.09 - 0.3 Rotatorcuff 5.0 - 10.0 5.5 - 8.0 0.5 - 1.5 Recommendations for optimal laser therapy for common tendon disorders: Infrared lasers (GaAlAs 820/830 nm) are recommended when : * Power density on skin does not exceed 30 mW/cm2, when treating superficial disorders

* Spot size should not be smaller than 0.5 cm2 Dose on skin: Number of points: Lateral epicondylitis : 2 J/cm2 1-2 Rotatorcuff : 2.5 J/cm2 2-4 Patellar : 8 J/cm2 : 3-5 Achilles : 6 J/cm2 2-3 It must be added that there are only two clinical trials showing effect on tendinitis (rotatorcuff) with these lasers and that the dose recommendations for other locations are extrapolations and have not yet been tested clinically. Infrared pulse lasers (GaAs 904 nm) are recommended when : * Power density on skin does not exceed 20 mW/cm2, when treating superficial disorders * Spot size should not be smaller than 0.5 cm2 Dose on skin: Number of points: Lateral epicondylitis : 0.5 - 2 J/cm2 1-2 Rotatorcuff : 0.8 - 6 J/cm2 2-4 Patellar : 0.8 - 6 J/cm2 : 3-5 Achilles : 0.5 - 4 J/cm2 2-3 Clinical results from seven trials suggests that pulse lasers overcome the skin barrier with less need for variation of dose for the different tendon locations. Red HeNe lasers (632 nm) are only recommended for superficially situated tendon disorders like epicondyitis and paratendonitis of the achilles or patellar tendon. Use of HeNe laser on rotatorcuff, deeply situated patellar tendinitis (jumpers' knee), plantar fascitis or carpal tunnel is not recommended, due to the poor penetration of visible red light. Editors note: The master thesis in Physiotherapy Science of Jan Bjordal is called "Low Level Laser therapy in shoulder tendinitis/bursitis, epicondylalgia and ankle sprain. A critical review on clinical effects". Division of Physiotherapy Science, University of Bergen. 1997. Part of this thesis can be found in Physical Therapy Reviews. 1998; 3: 121-132. "What may alter the conclusions of reviews?".

Low Level Laser Therapy Can Be Effective For Tendinitis: A MetaAnalysis Jan M. Bjordal, PT-MSc, Faculty of Medicine, University of Bergen, Norway Christian Couppe, PT, Copenhagen, Denmark Email: bjordal J.M. Bjordal, C. Couppe University of Bergen, Dept. Physiotherapy Science, Bergen, Norway

Purpose: To investigate if low level laser therapy (LLLT) with previously defined optimal treatment parametres can be effective for tendinitis. Material : Randomized controlled trials with LLLT for tendinitis. Method : Literature search for trials published after 1980 using LLLT on Medline, Embase, Cochrane Library and handsearch of physiotherapy journals in English and Scandinavian languages. Only trials that compared laser exposure of the skin directly over the injured tendon with optimal treatment parametres with identical placebo treatment were included. Results: The literature search identified 77 randomized controlled trials with LLLT, of which 18 included tendinitis. Three trials were excluded for lack of placebo control, of which one trial was comparative, another lacked patients with tendinitis in the treatment group, while the last unwittingly gave the placebo group active treatment. Four trials used

too high power density or dose, and three trials did not expose the skin directly overlying the injured tendon. The remaining eight trials were included in a statistical pooling, where the mean effect of LLLT over placebo in tendinitis was calculated to 32% [25.039.0, 95% CI]. Conclusion: Low level laser therapy with optimal treatment procedure/parametres can be effective in the treatment of tendinitis.

The Use Of Low Level Laser Therapy (Lllt) In The Treatment Of Trigger Points That Are Associated With Rotator Cuff Tendonitis. Al-Shenqiti, J Oldham

60 patients were randomly allocated to either sham or laser therapy. The active laser parameters included a wavelength 820 nm, power output 100 mW, frequency 5000 Hz (modulated) and energy density 32 J/cm2. 12 treatments were given over four weeks. The blinded outcome measures were pain, range of motion (ROM), functional activities and pressure pain threshold (PPT). Outcome measures were carried out pre and post treatment, then 3 months later. Considerable improvement in pain (p < 0.001) was seen for the laser compared to sham group post treatment, and at follow-up (6 points on a 10 VAS compared to 2 points respectively). Similarly, significant differences in favour of laser were seen for ROM (p < 0.01), functional activities (p < 0.001) and PPT (p < 0.05).

Tenosynovitis – Trigger Finger Low level laser therapy with trigger points technique: a clinical study on 243 patients. J Clin Laser Med Surg. 1996 Aug;14(4):163-7. Simunovic Z. Laser Center, Locarno, Switzerland.

Among the various methods of application techniques in low level laser therapy (LLLT) (HeNe 632.8 nm visible red or infrared 820-830 nm continuous wave and 904 nm pulsed emission) there are very promising "trigger points" (TPs), i.e., myofascial zones of particular sensibility and of highest projection of focal pain points, due to ischemic conditions. The effect of LLLT and the results obtained after clinical treatment of more than 200 patients (headaches and facial pain, skeletomuscular ailments, myogenic neck pain, shoulder and arm pain, epicondylitis humery, tenosynovitis, low back and radicular pain, Achilles tendinitis) to whom the "trigger points" were applied were better than we had ever expected. According to clinical parameters, it has been observed that the rigidity decreases, the mobility is restored (functional recovery), and the spontaneous or induced pain decreases or even disappears, by movement, too. LLLT improves local microcirculation and it can also improve oxygen supply to hypoxic cells in the TP areas and at the same time it can remove the collected waste products. The normalization of the microcirculation, obtained due to laser applications, interrupts the "circulus vitiosus" of the origin of the pain and its development (Melzak: muscular tension > pain > increased tension > increased pain, etc.). Results measured according to VAS/VRS/PTM: in acute pain, diminished more than 70%; in chronic pain more than 60%.

Clinical effectiveness (success or failure) depends on the correctly applied energy dose-over/underdosage produces opposite, negative effects on cellular metabolism. We did not observe any negative effects on the human body and the use of analgesic drugs could be reduced or completely excluded. LLLT suggests that the laser beam can be used as monotherapy or as a supplementary treatment to other therapeutic procedures for pain treatment.

Thyroid Effectiveness Of Using Laserotherapy In The Treatment Of AutoImmune Thyreoiditis J. Karachentsev Ukrainian Scientific-Research Institute for Pharmakotherapy of Endocryne Diseases, Kharkov, Ukraine

During last 10 years quantity of chronic auto-immune thyreoiditis (AIT) patients increased more than 10 times. This causes the search of new alternative methods of treatment. New pathogenic method of treatment AIT, which includes low-energetic laser radiation of thyroid gland (TG), was developed in Surgical Department. Transcuta-neous radiation ofTG proection was done on 21 patients with the help of semiconductor apparatus "Mustang-BlO" (Russia), wavelength 0,89 [im, pulse regime. Energetically control was provided by automated system of integral and differential electropuncture diagnostics "Lotos". Dynamic investigations, conducted during 7 months after laserotherapy, showed decreasing sizes of TG and lymphoid infiltration centres with almost all patients, normalisation of thyroid hormones level against decreasing of substitutive therapy doses. When studying cellular and humoral immunity was found normalisation of T-suppressors and T-active lymphocytes against authentic decreasing of antythyroid anti-bodies (anti-bodies index to thyreoglobulin lowered from 1,25±0,11 to 0,45±0,05, P 0.05). CONCLUSIONS: In our study, immediate and cumulative effects of a GaAlAs laser applied on MTrS were demonstrated on the basis of the assessment of EPN prevalence. It seems that laser irradiation may inhibit the irritability of an MTrS in rabbit skeletal muscle. This effect may be a possible mechanism for myofascial pain relief with laser therapy.

Low level laser therapy with trigger points technique: a clinical study on 243 patients. Clin Laser Med Surg. 1996 Aug;14(4):163-7. Simunovic Z. Laser Center, Locarno, Switzerland.

Among the various methods of application techniques in low level laser therapy (LLLT) (HeNe 632.8 nm visible red or infrared 820-830 nm continuous wave and 904 nm pulsed emission) there are very promising "trigger points" (TPs), i.e., myofascial zones of particular sensibility and of highest projection of focal pain points, due to ischemic conditions. The effect of LLLT and the results obtained after clinical treatment of more than 200 patients (headaches and facial pain, skeletomuscular ailments, myogenic neck pain, shoulder and arm pain, epicondylitis humery, tenosynovitis, low back and radicular pain, Achilles tendinitis) to whom the "trigger points" were applied were better than we had ever expected. According to clinical parameters, it has been observed that the rigidity decreases, the mobility is restored (functional recovery), and the spontaneous or induced pain decreases or even disappears, by movement, too. LLLT improves local microcirculation and it can also improve oxygen supply to hypoxic cells in the TP areas and at the same time it can remove the collected waste products. The normalization of the microcirculation, obtained due to laser applications, interrupts the "circulus vitiosus" of the origin of the pain and its development (Melzak: muscular tension > pain > increased tension > increased pain, etc.). Results measured according to VAS/VRS/PTM: in acute pain, diminished more than 70%; in chronic pain more than 60%. Clinical effectiveness (success or failure) depends on the correctly applied energy dose-- over/underdosage produces opposite, negative effects on cellular metabolism. We did not observe any negative effects on the human body and the use of analgesic drugs could be reduced or completely excluded. LLLT suggests that the laser beam can be used as monotherapy or as a supplementary treatment to other therapeutic procedures for pain treatment.

Comparison of laser, dry needling, and placebo laser treatments in myofascial pain syndrome. Photomed Laser Surg. 2004 Aug;22(4):306-11

Ilbuldu E, Cakmak A, Disci R, Aydin R. Department of Physical Medicine and Rehabilitation, Istanbul Medical Faculty, Istanbul University, 34390 Sehremini, Istanbul, Turkey.

OBJECTIVE: We aimed to evaluate the effectiveness of laser therapy in myofascial pain syndrome treatment. BACKGROUND DATA: Myofascial pain syndrome is a disease that is characterized by hypersensitive points called trigger points found in one or more muscles and/or connective tissues. It can cause pain, muscle spasm, sensitivity, stiffness, weakness, limitation of r ange of motion and rarely autonomic dysfunction. Physical therapy modalities and exercise are used in the treatment of this frequently encountered disease. METHODS: The placebo controlled, prospective, long-term follow up study was planned with 60 patients who had trigger points in their upper trapezius muscles. The patients were divided into three groups randomly. Stretching exercises were taught to each group and they were asked to exercise at home. Treatment duration was 4 weeks. Placebo laser was applied to group 1, dry needling to group 2 and laser to group 3. He-Ne laser was applied to three trigger points in the upper trapezius muscles on both sides with 632.8 nm. The patients were assessed at before, post-treatment, and 6 months after-treatment for pain, cervical range of motion and functional status. RESULTS: We observed a significant decrease in pain at rest, at activity, and increase in pain threshold in the laser group compared to other groups. Improvement according to Nottingham Health Profile gave the superiority of the laser treatment. However, those differences among the groups were not observed at 6-month follow up. CONCLUSIONS: Laser therapy could be useful as a treatment modality in myofascial pain syndrome because of its noninvasiveness, ease, and shortterm application.

Tuberculosis [Laser therapy in the complex treatment of prostatic tuberculosis at the sanatorium stage of rehabilitation] Probl Tuberk Bolezn Legk. 2008;(4):35-8. [Article in Russian] Shakirov RG, Pavlov VN, Iagafarova RK.

Seventy nine patients with prostatic tuberculosis were examined and treated at the specialized "Glukhovskaya" sanatorium. All the patients were divided into 2 groups: a study group and a control one. In the study group patients, low-intensity laser radiotherapy was additionally performed in combination with etiological and pathogenetical treatments. The performed studies demonstrated that in the patients exposed to low-intensity laser radiation, there was a rapid relief of dysuric symptoms, cessation or diminishment of the signs of copulative dysfunction; positive changes in life quality indices and laboratory parameters were statistically significantly more frequently and more rapidly recorded. Laser therapy simultaneously was found to affect a few links of the pathogenesis of genitourinary tuberculosis, to have limited number of contraindications, to be well tolerated, and to be an effective method of the complex treatment of patients with prostatic tuberculosis during sanatorium rehabilitation.

[Patients With Tuberculosis Associated With Chronic Nonspecific Lung Diseases]

Lik Sprava. 2007 Apr-May;(3):42-6. [Article in Ukrainian] Nikolaieva OD.

159 patients have been observed to assess the efficiency of laseropuncture use in a complex treatment of patients with lung tuberculosis and chronic bronchitis. Disbalance in renal meridian (R), urinary bladder (V) and insufficiency of the energy in colon meridian (60.3%) were observed in patients with tuberculosis associated with chronic bronchitis. Medium deviations of electro-skin conductivity from the physiological gape in meridians of GI, IG, F, V, R in patients with tuberculosis associated with chronic bronchitis considerably differ from those data obtained from patients with only tuberculosis. Obtained data testify more severe disorders of energy balance in meridians of patients having except tuberculosis other associated diseases. Medium parameters of deviations from the physiological gape considerably decrease after the course of laseropuncture compared with those patients treated traditionally. Improve of the course of the chronic bronchitis was noted in patients who underwent laseropuncture.

Role Of Gallium Arsenide Laser Irradiation At 890 Nm As An Adjunctive To Anti-Tuberculosis Drugs In The Treatment Of Pulmonary Tuberculosis. Indian J Chest Dis Allied Sci. 2003 Jan-Mar;45(1):19-23. Puri MM, Arora VK. Department of Tuberculosis and Chest Diseases, LRS Institute of Tuberculosis and Allied Diseases, Sri Aurobindo Marg, New Delhi, India.

BACKGROUND: Tuberculosis is a global emergency with about nine million people developing disease every year. The long duration of treatment has emerged as a major obstacle in the control of tuberculosis. There is a need for development of new drugs and or shortened therapy. METHODS: The present study was carried out to explore whether any benefit could be achieved by the addition of low level energy laser therapy (LLLT) to the conventional anti-tubercular chemotherapy. One-hundred-thirty new sputum smear positive patients of pulmonary tuberculosis were enrolled to evaluate the bio-stimulatory effects of Gallium Arsenide laser irradiation at 890 nm, as an adjuvant therapy. These patients were randomly divided into two groups to receive either LLLT or sham irradiation (control) concomitantly with anti-tuberculosis chemotherpy. RESULTS: The patients treated with semiconductor laser as an adjuvant therapy along with antituberculosis drugs had a faster clearance of tubercle bacilli from the sputum as compared to the control group (P value at :45 days=0.1392, 60 days=0.0117, 75 days=0.00805, 90 days=0.00739). CONCLUSIONS: These findings provide preliminary evidence that low level laser therapy with Gallium Arsenide laser may be a promising adjunctive therapy for patients with tuberculosis. Faster conversion of sputum should prevent the development of resistant mutants.

Low level laser therapy for treating tuberculosis. The Cochrane Database of Systemic Reviews. 2002. Vlassov V V, Pechatnikov L M, MacLehose H G.

The authors have made a thorough literature search for studies using laser therapy as an adjunct therapeutic modality in the treatment of tuberculosis. These studies come from the former Soviet

states and India. The studies in Russian language have generally only been available as Medline abstract and they have been vague on the details. Now, for the first time, Russian researchers have evaluated the original texts. Laser therapy has been used in many ways. Acupuncture points, irradiation over the organ, blood irradiation, puncture into the lungs, irradiation into the trachea and into the urinary bladder. Laser types used have also differed a lot; HeNe, nitrogen, GaAs, Nd:YVO4 and at powers ranging from 2 to 200 mW. The weak spot in previous Cochrane reviews on laser therapy has been the lack of dosage analyses. No such analysis has been made in the current study, but with the different therapeutic approaches used, such an analysis is not possible in this case. The reviewers have not found any randomised or quasi-randomised studies, but an evaluation of the quality of the studies has been performed. There is a lack of relevant information on procedures in many studies and some contradictory statements. All in all, the reviewers come to the conclusion that laser therapy is currently being used to treat tuberculosis without evidence of its benefits and harms.

[Efficiency of supra-venous blood laser radiation used in the treatment of disseminated pulmonary tuberculosis in adolescents] Probl Tuberk. 2002;(8):16-8. [Article in Russian] Rusakova LI, Dobkin VG, Ovsiankina ES.

In 19 of 40 adolescent patients with disseminated pulmonary tuberculosis, supravenous blood laser radiation was used in the complex treatment 2-3 weeks after the initiation of chemotherapy. The use of this type of laser therapy enhanced the efficiency of the treatment, accelerated positive changes of tuberculosis by 2.5-3.5 months, as evidenced by clinical and laboratory parameters, led to a smooth course of tuberculosis to develop less pronounced residual changes in the lung.

Low level laser therapy for treating tuberculosis. Cochrane Database Syst Rev. 2002;(3):CD003490. Vlassov VV, Pechatnikov LM, MacLehose HG. Russian Branch, The Cochrane Collaboration, PO Box 54, Moscow, Russia, 127238. [email protected]

BACKGROUND: The main treatment for tuberculosis is antituberculous drugs. Low energy laser therapy is used as an adjunct to antituberculous drugs, predominantly in the former Soviet Union and India. OBJECTIVES: To assess the benefits and harms of low level laser therapy for treating tuberculosis in randomized and quasi-randomized controlled trials. To seek information about potential benefits or harms from observational studies. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (up to June 2001), the Cochrane Controlled Trials Register (Issue 1, 2001), MEDLINE (1966 to December 2001), EMBASE (1988 to December 2001), CINAHL (up to November 2001), PEDro (up to November 2001), the Science Citation Index (up to December 2001), National Centre for Science Information at the Indian Institute of Science (15 April 2002), electronic catalogue of the Central Medical Library (Moscow; 1988 to January 2002), the internet using 'Google' (21 January 2002), and reference lists of articles. We contacted relevant organizations and researchers. SELECTION CRITERIA: (1) Randomized and quasi-randomized controlled trials comparing low level laser therapy with no low level laser therapy in people with tuberculosis. We also conducted a

subsidiary analysis of of the potential benefits and harms from observational studies. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. We contacted study authors for additional information. Adverse event information was collected from the studies. MAIN RESULTS: No randomized or quasirandomized controlled trials met the inclusion criteria for the review. The potential benefits and harms from 29 observational studies involving over 3500 people are described. REVIEWER'S CONCLUSIONS: We have not identified any well designed trials using low level laser therapy (LLLT) to treat tuberculosis. Therefore, the use of LLLT to treat tuberculosis is not supported by reliable evidence.

[Intravenous laser radiation treatment of acute and progressive forms of tuberculosis in teenagers] Probl Tuberk. 2000;(1):14-7. [Article in Russian] Ovsiankina ES, Firsova VA, Dobkin VG, Rusakova LI.

In 25 of 44 teenagers suffering from acute and progressive tuberculosis, intravenous blood laser radiation was included into its multimodality treatment following 2-4 weeks of the initiation of chemotherapy. The use of laser enhanced the efficiency of treatment, accelerated positive changes by 1.5-2 months by major clinical and laboratory indices, made the disease run smoothly and caused less pronounced residual changes in the lung.

[Magnetic laser therapy in combination with lymphotropic drugs administration in treating teenagers with common forms of tuberculosis] Probl Tuberk. 2000;(2):18-21. [Article in Russian] Ovsiankina ES, Dobkin VG, Kobulashvili MG, Rusakova LI, Gubkina MF.

The paper shows the efficiency of combined use of magnetic laser therapy (MLT) and lymphotropic drug therapy in 40 teenagers with common forms of tuberculosis. The use of laser makes it possible to modify methods of regional lymphotropic therapy, to prolong its use and increase indications for it. MLT in combination with lymphotropic drug therapy accelerates positive changes and hence enhances the efficiency of tuberculosis treatment.

[Combined low-intensity laser radiation in renal tuberculosis] Probl Tuberk. 2003;(6):28-33. [Article in Russian] Parmon EM, Borshchevskii VV, Kamyshnikov VS, Bortkevich LG.

Combined external radiation in the projection of the kidneys and intravascular laser blood radiation by applying an AZOR-2K apparatus were used in the combined treatment of 54 patients with tuberculosis of the urinary system. Analysis of the biochemical and immunological parameters of the patients' peripheral blood before and 3 weeks and 3 months after the combined treatment provided evidence suggesting a decrease in the magnitude of lipid peroxidation, an increase in the antioxidative status, and a reduction in the level of metabolites that affect on the

development of the intoxication syndrome. The clinical findings suggest that the combined treatment has a beneficial impact on the course of renal tuberculosis, as appeared as better functional indices of urinary organs.

[Low-intensity laser irradiation in patients with urinary tuberculosis] Urologiia. 2001 Nov-Dec;(6):13-7. [Article in Russian] Parmon EM, Borshchevskii VV, Bortkevich LG.

Combined surface radiation of renal projection area and intravascular laser radiation of blood (AZOR-2K unit) were used in combined treatment of 54 patients with urinary tuberculosis. Analysis of immunological and hematological indices of peripheral blood of patients before and after the combined treatment showed that low-intensity laser radiation activates local system of T-helpers which after specific antigenic impact differentiate into T-helpers-1. The latter synthesize in loco gamma-interferon, TNF-alpha and beta and IL- 2 stimulating bactericidal mechanisms directed at destruction of M. tuberculosis and resolution of the infection focus.

[Efficiency of supra-venous blood laser radiation used in the treatment of disseminated pulmonary tuberculosis in adolescents] Probl Tuberk. 2002;(8):16-8. [Article in Russian] Rusakova LI, Dobkin VG, Ovsiankina ES.

In 19 of 40 adolescent patients with disseminated pulmonary tuberculosis, supravenous blood laser radiation was used in the complex treatment 2-3 weeks after the initiation of chemotherapy. The use of this type of laser therapy enhanced the efficiency of the treatment, accelerated positive changes of tuberculosis by 2.5-3.5 months, as evidenced by clinical and laboratory parameters, led to a smooth course of tuberculosis to develop less pronounced residual changes in the lung.

[Role of external laser radiation in the multimodality treatment of patients with destructive pulmonary tuberculosis] Probl Tuberk. 1997;(3):23-4. [Article in Russian] Abashev IM, Kozlova AI. Chuvash State University, Cheboksary.

Patients with destructive pulmonary tuberculosis were examined. Comparing those receiving chemopathogenetic, epicutaneous laser and ultrasound therapies showed an increase in the incidence of cavitary scarring in those taking successive epicutaneous laser and ultrasound therapies and exposed to biologically active points. Epicutaneous laser therapy promoted cicatrization of large cavities.

[Use of external laser radiation in patients with infiltrative pulmonary tuberculosis] Probl Tuberk. 1997;(2):21-2.

[Article in Russian] Vinokurova MK, Gavril'ev SS, Petukhova NI, Baisheva NN. NPO "Phthisiology", Iakutia.

A procedure has been developed for the use of semiconductor laser radiation in the combined drug therapy of patients with disseminated infiltrative pulmonary tuberculosis with multiple destructions and massive bacterial excretion, by increasing the number of sessions, which reduces the time of bacterial excretion cessation by 2-4 weeks, decay cavity closure by a months, and hospital treatment by 1.5 months and promotes minimal residual changes in most of them.

[Lasers in combined modality treatment of patients with pulmonary tuberculosis] Probl Tuberk. 1996;(6):54-7. [Article in Russian] Dobkin VG, Bagirov MA, Bondarev GB, Sadovnikova SS. Central NII of Tuberculosis RAMN, Moscow.

Low-energy lasers were used in the combined preoperative treatment and therapy of 548 patients with chronic fibrocavernous tuberculosis. Indications for some types of exposure were defined, namely, transcutaneous exposure of the tuberculous involvement zone, combination of transcutaneous laser exposure and laser puncture, intravenous and endocavitary laser exposure. Low-energy lasers, as a many-factor pathogenetic exposure, are conducive to a more rapid and effective stabilization of tuberculosis progress, which helps sooner prepare the patients to surgical interventions and in some patients even do without them, reduce the number of postoperative complications, and improve the efficacy of surgical treatment of grave patients

Comparative Effectiveness Detoxication Transfusion Of Therapy (Tt) And Intravenous Of A Laser Irradiation Blood (Ilib) In Complex Treatment Of Patients By A Pulmonary Tuberculosis P.I.Pitcyco, E.I.Krivoshapova Kharkov Institute of Physicians Advanced Training, Kharkov. Ukraine

Two groups of the patients infiltrotivc by a pulmonary tuberculosis in a phase of de-cay, MBT+, (discovered Koch's bacillus), comparable on a floor, age, pronounced intoxication and syndrome, extent of process in lungs and regime of chemotherapy. I groups 45 patients receiving TT (albumen 5%- 100 ml alternated with hacmodesum 200 ml, daily ?10), II groups - 68 patients, which was carried out ILIB(wavclcngth 0,63 urn, capacity of radiation on an output flexible monofibcr conductor of light 2 mW, duration of a procedure 15 minutes, course 10 sessions). The efficiency of ther-apy was estimated on a reduction intoxication, which degree was defined on a level and structure middle molecules (MM) ( presence of pathological fractions and dispolypcptidcmy) in whey of blood. MM were studied prior to the beginning and after realisation of rates TT and ILIB by a method hclium-chromatography on hcle "Toyop-carl HW-40F" (Japan). A normal level and structure MM (361 ± 14 cond I. unit) was established with inspection 40 healthy donors. Is established, that at the patients from I groups after realisation of a course TT the general level MM on the average has de-creased from 858 ± 29 unit till 769 ± 31 unit (p 0.05). However, although the number of degranulated mast cells was higher in all laser-treated wounds, in comparison with the sham-irradiated group, only the 20 Hz (pulse duration 45 ms) and 292 Hz (pulse duration 3 ms) frequencies were significantly effective (P < 0.05). CONCLUSION: Increase in mast cell number is not pulsing frequency dependent, whereas degranulation is.

[Low Level Laser Irradiation And Its Effect On Repair Processes In The Skin] Med Pregl. 2003 Mar-Apr;56(3-4):137-41. [Article in Croatian] Matic M, Lazetic B, Poljacki M, Duran V, Ivkov-Simic M. Klinika za kozno-venericne bolesti, Medicinski fakultet Novi Sad, Klinicki centar Novi Sad. [email protected]

INTRODUCTION: Application of laser beams for therapeutic purposes is of relatively recent date, but today there is no field of medicine where lasers cannot be used. PHYSICAL

CHARACTERISTICS OF LASER RADIATION: Laser radiation is a type of electromagnetic radiation with some specific characteristics such as coherence, monochromaticity and parallelity. TYPES OF LASER DEVICES: Nowadays, there are many laser devices on the market used in medicine and dentistry. According to the type of their active medium, lasers can be classified as solid, gas, semiconductor and liquid. EFFECTS OF LOW LEVEL LASER THERAPY ON BIOLOGICAL SYSTEMS: The exact mechanism of action of low level laser therapy is still not completely understood. Its basic feature is to modulate cell behaviour, without causing significant temperature increase. During irradiation of a tissue with a laser beam, an interaction between cells and photons takes place--photochemical reaction. After a cell absorbs the photon, the photon stops existing, and its energy is incorporated into the molecule which has absorbed it. Once this energy is transferred to different biomolecules, it can be transferred to other molecules as well. The energy transferred to the molecule can increase its kinetic energy, and activate or deactivate enzymes or alter physical or chemical properties of main macromolecules. EFFECTS OF LOW LEVEL LASER THERAPY ON WOUND HEALING: Effects of low level laser therapy on wound healing process is one of the most fully studied aspects of this type of therapy. It affects all phases of this very complex process. This paper offers a more detailed analysis of these aspects.

Effect Of NASA Light-Emitting Diode Irradiation On Wound Healing. J Clin Laser Med Surg. 2001 Dec;19(6):305-14. Whelan HT, Smits RL Jr, Buchman EV, Whelan NT, Turner SG, Margolis DA, Cevenini V, Stinson H, Ignatius R, Martin T, Cwiklinski J, Philippi AF, Graf WR, Hodgson B, Gould L, Kane M, Chen G, Caviness J. Department of Neurology, Medical College of Wisconsin, Milwaukee 53226, USA.

OBJECTIVE: The purpose of this study was to assess the effects of hyperbaric oxygen (HBO) and near-infrared light therapy on wound healing. BACKGROUND DATA: Light-emitting diodes (LED), originally developed for NASA plant growth experiments in space show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper, we review and present our new data of LED treatment on cells grown in culture, on ischemic and diabetic wounds in rat models, and on acute and chronic wounds in humans. MATERIALS AND METHODS: In vitro and in vivo (animal and human) studies utilized a variety of LED wavelength, power intensity, and energy density parameters to begin to identify conditions for each biological tissue that are optimal for biostimulation. Results: LED produced in vitro increases of cell growth of 140-200% in mouse-derived fibroblasts, rat-derived osteoblasts, and rat-derived skeletal muscle cells, and increases in growth of 155-171% of normal human epithelial cells. Wound size decreased up to 36% in conjunction with HBO in ischemic rat models. LED produced improvement of greater than 40% in musculoskeletal training injuries in Navy SEAL team members, and decreased wound healing time in crew members aboard a U.S. Naval submarine. LED produced a 47% reduction in pain of children suffering from oral mucositis. CONCLUSION: We believe that the use of NASA LED for light therapy alone, and in conjunction with hyperbaric oxygen, will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/illness level of activity. This work is supported and managed through the NASA Marshall Space Flight Center-SBIR Program.

Wound healing of animal and human body sport and traffic accident injuries using low-level laser therapy treatment: a randomized clinical study of seventy-four patients with control group. J Clin Laser Med Surg. 2000 Apr;18(2):67-73. Simunovic Z, Ivankovich AD, Depolo A. Department of Anesthesiology, La Carita Medical Center, Laser Center, Locarno, Switzerland. [email protected]

BACKGROUND AND OBJECTIVE: The main objective of current animal and clinical studies was to assess the efficacy of low level laser therapy (LLLT) on wound healing in rabbits and humans. STUDY DESIGN/MATERIALS AND METHODS: In the initial part of our research we conducted a randomized controlled animal study, where we evaluated the effects of laser irradiation on the healing of surgical wounds on rabbits. The manner of the application of LLLT on the human body are analogous to those of similar physiologic structure in animal tissue, therefore, this study was continued on humans. Clinical study was performed on 74 patients with injuries to the following anatomic locations: ankle and knee, bilaterally, Achilles tendon; epicondylus; shoulder; wrist; interphalangeal joints of hands, unilaterally. All patients had had surgical procedure prior to LLLT. Two types of laser devices were used: infrared diode laser (GaAlAs) 830 nm continuous wave for treatment of trigger points (TPs) and HeNe 632.8 nm combined with diode laser 904-nm pulsed wave for scanning procedure. Both were applied as monotherapy during current clinical study. The results were observed and measured according to the following clinical parameters: redness, heat, pain, swelling and loss of function, and finally postponed to statistical analysis via chi2 test. RESULTS: After comparing the healing process between two groups of patients, we obtained the following results: wound healing was significantly accelerated (25%-35%) in the group of patients treated with LLLT. Pain relief and functional recovery of patients treated with LLLT were significantly improved comparing to untreated patients. CONCLUSION: In addition to accelerated wound healing, the main advantages of LLLT for postoperative sport- and traffic-related injuries include prevention of side effects of drugs, significantly accelerated functional recovery, earlier return to work, training and sport competition compared to the control group of patients, and cost benefit.

Low-level laser irradiation attenuates production of reactive oxygen species by human neutrophils. Fujimaki Y, Shimoyama T, Liu Q, Umeda T, Nakaji S, Sugawara K. Department of Hygiene, Hirosaki University School of Medicine, Japan.

OBJECTIVE: The aim of this study was to examine the effects of low-level laser therapy (LLLT) on production of reactive oxygen (ROS) species by human neutrophils. BACKGROUND DATA: LLLT is an effective therapeutic modality for inflammatory conditions. MATERIALS AND METHODS: The laser device used was the infrared diode laser (GaAlAs), 830-nm continuous wave (150 mW/cm(2)). After irradiation, ROS production by neutrophils was measured using luminol-dependent chemiluminescence (LmCL) and expression of CD11b and CD16 on neutrophil surface was measured by flow cytometry. RESULTS: The LmCL response of neutrophils was reduced by laser irradiation at 60 min prior to the stimulation with opsonized zymosan and calcium ionophore. The attenuating effect of LLLT was larger in neutrophils of smokers than nonsmokers, while the amount of produced ROS was larger in

neutrophils of smokers. Expression of CD11b and CD16 on neutrophil surface was not affected by LLLT. CONCLUSION: Attenuation of ROS production by neutrophils may play a role in the effects of LLLT in the treatment of inflammatory tissues. There is a possible usage of LLLT to improve wound healing in smokers.