The authors have selected 15 randomised double blind studies where musculoskeletal
disorders have been treated by laser therapy. No evaluation about the methodological quality has been made, focus has been on the dose. It was clearly found that in the 8 studies with no effect, the dose was considerably lower than in the 7 studies with higher doses. This confirms the observations in the literature analyses by Bjordal et al, indicating a dose-response pattern, which has been vastly overlooked in many studies. The Italian evaluators also state that lasers working in the pulsed mode are more efficient. However, since GaAs and GaAlAs lasers have been included in the evaluation, this general conclusion must be questioned. The “true” pulsing of a GaAs laser is not similar to the mechanical on-off pulsing of a continuos laser like GaAlAs.

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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.

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Effects of near-infra-red laser irradiation on adenosine triphosphate and adenosine diphosphate contents of rat brain tissue. Neuroscience letters. 2002; 323 (3): 207-210.
Mochizuki O N, Kataoka Y, Cui Y et al.

Low-power, near-infra-red laser irradiation has been used to relieve patients from various kinds of pain, though the precise mechanisms of such biological actions of the laser have not yet been resolved. To investigate the cellular mechanisms by near-infra-red laser on the nervous system, we examined the effect of 830-nm laser irradiation on
the energy metabolism of the rat brain. The diode laser was applied for 15 min with an irradiance of 4.8 W/cm(2). Tissue adenosine triphosphate (ATP) content of the irradiated area in the cerebral cortex was 19% higher than that of the non-treated area, whereas the adenosine diphosphate (ADP) content showed no significant difference.
Laser irradiation at another wavelength (652 nm) had no effect on either ATP or ADP contents. The temperature of the tissue was increased by 4.4-4.7 degrees C during the irradiation of both wavelengths. These results suggest that the increase in tissue ATP content did not result from the thermal effect, but from a specific effect of the laser operated at the 830-nm wavelength.

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Double-blind, randomised,placebo controlled low level laser therapy study in patients with primary Raynaud's phenomenon. Journal of Vascular Diseases. 2002;31(2): 91-94.
Hirschl M, Katzenschlager R, Ammer K et al.

No causal treatment of primary Raynaud's phenomenon is available due to its unclear aetiology. Low level laser therapy (LLLT) is applied in a multitude of medical conditions often without sufficient evidence of efficacy and established mechanisms. To asses the effect of this therapy in patients with primary Raynaud's phenomenon a randomised, double blind, placebo controlled cross over study was designed. Absolute and relative frequency and intensity of vasospastic attacks during three weeks of either LLLT or placebo therapy and results of infrared thermography before onset and at the end of both therapy sequences were evaluated in 15 patients with primary Raynaud's phenomenon. Frequency of Raynaud's attacks was not significantly affected by low level laser therapy. Compared to placebo a significantly lower intensity of attacks during laser irradiation was observed, but no transfer effect occurred. Additionally the mean temperature gradient after cold exposure was reduced after laser irradiation, while the number of fingers showing prolonged rewarming was unaffected.

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Transmeatal low-power laser irradiation for tinnitus. Otology & neurotology 2002; 23 (3): 296-300.
Nakashima T, Ueda H, Misawa H et al.

To evaluate effectiveness of 60mW laser irradiation in the treatment of tinnitus. Prospective, randomised double-blind study. This investigation included 68 ears in 45 patients with disabling unilateral or bilateral tinnitus. The active or placebo laser treatment was administered trans-meatally once a week for 6 minutes. Laser irradiation was performed four times during a 4-week period. A questionnaire was administered to evaluate the loudness, duration, quality, and annoyance of tinnitus before and after irradiation. The loudness and pitch match for tinnitus were obtained, and distortion product otoacoustic emissions were also examined.: No significant difference was observed between the active and placebo laser groups with regard to outcome of loudness, duration, quality, and annoyance of tinnitus. In one patient who received active laser treatment, acute hearing deterioration occurred after the third irradiation. Transmeatal low-power laser irradiation with 60 mW is not effective for the treatment of tinnitus.

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Computerized morphometric assessment of the effect of low-level laser therapy on bone repair: an experimental animal study. Journal of clinical laser medicine & surgery. 2002; 20 (2): 83-87.
Silva Junior A, Pinheiro A, Oliveira M et al.

The aim of this study was to evaluate morphometrically the amount of newly formed bone after GaAlAs laser irradiation of surgical wounds created in the femur of rats. Low- level laser therapy (LLLT) has been used in several medical specialties because of its biomodulatory effects on different biological tissues. However, LLLT is still controversial because of contradictory reports. This is a direct result of the different methodologies used in these works. In this study, 40 Wistar rats were divided into four groups of 10 animals each: group A (12 sessions, 4.8 J/cm2 per session, observation time of 28 days); group C (three sessions, 4.8 J/cm2 per session, observation time of 7 days). Groups B and D acted as non-irradiated controls. The specimens were routinely processed to wax and cut at 6- micron thickness and stained with HE. For computerised morphometry, Computerised morphometry showed a significant difference between the areas of mineralised bone in groups C and D There was no difference between groups A and B .It is concluded that, under this experimental condition, LLLT increased bone repair at early bone healing.

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Evaluation of quantum therapy for the treatment of stable angina
[Otsinka efektyvnosti vplyvu kvantovoi terapii na perebig stabil'noi stenokardii].
Likars'ka sprava. 2001; (5-6): 111-114.

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 pain-free episodes of myocardial ischemia, this being regarded as a prognostically favourable fact.

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Effect of low-power laser irradiation on cell growth and procollagen synthesis of cultured fibroblasts. Lasers Surg Med. 2002; 31: 263-267.
Pereira A, de Paula Eduardo C, Matson E et al

The cell growth and procollagen synthesis of cultured fibroblasts were studies by irradiation at energy densitites ranging from 3-5 J/cm2 over a period of 6 days. To simulate a situation of stress the cells were grown in a 2.5% FBS solution (10% being optimal). The laser was a 120 mW GaAs laser. Irradiation at 3 to 4 J/cm2 increased the cell numbers about threefold to sixfold, compared to control cultures. However, the effect was restricted to a small range of densities, since 5 J/cm2 had no effect on cell growth. The energy density of 3 J/cm2 remarkably increased cell growth, with no effect on procollagen synthesis, as demonstrated by immunoprecipitation analysis.

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Selected abstracts from May 2002
Changes in absorbance of monolayer of living cells induced by laser radiation at 633, 670 and 820 nm. IEEE J Selected Topics in Quantum Electronics. 2001; 7 (6): 982-988.
Karu T, Afanaseyeva N, Kolyakov S et al.
Abstract-Redox absorbance changes in living cells (monolayer of HeLa cells) under laser irradiation at 633, 670, and 820 nm have been studied by the method of multichannel recording in spectral range 530-890 nm. It has been found that the irradiation causes changes in the absorption spectrum of the cells in two regions, near 754-795 nm (maxima at 757, 775, and 795 nm) and near 812-873 nm (maxima at 819, 837, 858, and 873 nm). Changes occur in band
parameters (peak positions, width, and integral intensity). Virtually no changes occur in the red spectral region and a few changes are recorded in the green region near 556-565 nm. The results obtained evidence that cytochrome c oxidase becomes more oxidized (which means that the oxidative metabolism is increased) due to irradiation at all wavelengths used. The results of present experiment support the suggestion (Karu, Lasers Life Sci., 2:53, 1988) that the mechanism of low-power laser therapy at the cellular level is based on the electronic excitation of chromophores in cytochrome c oxidase which modulates a redox status of the molecule and enhances its functional activity.
Index Terms-Cytochrome c oxidase, low power laser therapy, redox-absorbance changes in living cells.

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Irradiation with diode at 820 nm induces changes in circular dichronism spectra (250-780 nm) of living cells. IEEE J Selected Topics in Quantum Electronics. 2001; 7 (6): 976-981.
Karu T, Kolyakov S, Pyatibrat L et al.
Abstract-A sensitive method for measuring the circular dichroism (CD) of living HeLa cells in the visible-near infrared
(IR) region is developed. The changes in CD spectra from 250 to 780 nm of HeLa cell suspension after the first and second irradiation at 820 nm in dose 9 J/cm2 are investigated. The CD spectrum of the intact cells is well structured and characterized by a positive signal in the UV (250-290 nm) and visible-near IR (500-780 nm) regions as well as by a negative signal in 300-450 nm region. Distinct maxima in the visible-near IR region are recorded at 566, 634, 680, 712, and 741 nm. As a rule, the peak circular dichroism signals decrease in the irradiated cells except of the
area 750-770 nm. Peak positions (except the peak at 680 nm) shift as a rule to the long-wavelength direction. The most remarkable changes in peak positions as well as in CD signals are recorded in the region 750-770 nm: an appearance of the new peak at 767 nm after the first irradiation and its shift to 752 nm after the
second irradiation. The peaks at 712 and 741 nm disappear after the irradiation. A new peak appears at 601 nm. It is assumed that the changes in the degree of oxidation of the chromophores of cytochrome c oxidase caused by the irradiation are accompanied by conformational changes in their vicinity. It can be suggested that these changes are occurring in CuB environment. Index Terms-Circular dichroism of cells, cytochrome c oxidase, low power laser therapy.

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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 nm; 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 non-irradiated 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.

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[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.

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[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 low-intensity laser radiation in the treatment of other complications that are common in pediatric oncological care is briefly described.

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[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.

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[Effects of low-intensity infrared laser irradiation on the eye An experimental study]. Vestn-Oftalmol. 1996; 112 (1): 31-32
Prokofeva G L, Kravchenko E V, Mozherenkov-V P.

Prokofeva evaluated the doses of infrared laser exposure for the structures of the eye in rabbit experiments, and the potentials of such lasers in ophthalmology were assessed. Wavelength was 890 nm and doses varied from 0.0001 to 1.0 J/cm2, corresponding to exposure duration of 0.3 to 45 min. Experiments were carried out on 20 animals. The right eyes were exposed, and the left ones were control. An increase of intraocular pressure was recorded at a dose of 0.1 J /cm2 (4.5 min) and higher. Morphological examination showed dilated, well filled and newly formed vessels in the ciliary body and iris, as well as oedema and destruction of the external layers of the retina. Exposure to a dose of 0.05 J/cm2 and lower did not lead to destruction of any ocular structures or increase of intraocular pressure. The maximal dose causing no side effects for the organ of vision was established at 0.05 J/cm2.

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Effects of visible NIR low intensity laser on implant osseointegration in vivo. Laser Med Surg Abstract issue, 2002: 11.
Blay A, Blay C C, Groth E B et al.

The effects of 680 and 830 nm lasers on osseointegration was studied by Blay. 30 adult rats were divided into three groups; two laser groups and one control. The rats in the two laser groups had pure titanium Frialit-2 implants implanted into each proximal metaphysis of their respective tibias, inserted with a 40 Ncm torque. The initial stability was monitored by means of a resonance frequency analyser. Ten irradiations were performed, 48 hours apart, 4 J/cm2 on two points, starting immediately after surgery. Resonance frequency analysis indicated a significant difference between frequency values at 3 and 6 weeks, as compared to control. At 6 weeks the removal torque in the laser groups was much higher than in the control group.

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Cellular invasion following spinal cord lesion and low power laser irradiation. Laser Med Surg Abstract issue, 2002: 11.
Byrnes K R, Waynant R W, Ilev I K et al.
In a rat experiment by Byrnes the spinal cord was hemisected at vertebral level T9. 810 nm laser was applied immediately after hemisection and daily for 14 days, 1589 J/cm2. Control rats received identical treatment, but without laser. The results indicate that laser therapy initially blocks cell invasion and activation of the injured spinal cord. Once laser therapy ceases at 14 days post-injury (the time point at which lesioned axons are reported to begin to sprout) there is a rebound increase in non-inflammatory cell invasion and activation that is visible 16 days post-injury. These alterations in the spinal cord environment may contribute to the ability of lesioned axons to regenerate following injury.

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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.

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Gingival healing after gingivectomy procedure and low intensity laser irradiation. A clinical and biometrical study in anima nobile. Laser Med Surg Abstract issue, 2002: 20.
Amorim J C F, Ribeiro M S, Groth E B.

Amorim selected seven patients who were to undergo gingivectomy on both sides of the jaw. In these patients laser therapy (685 nm, 50 mW, 4 J/cm2) was applied on one side only, the other side serving as control. The healing process was monitored clinically and biometrically, using photographs for a period of 35 days. The analysis was performed by three specialists in periodontology. Biometrical evaluation showed improvement of the healing for the period of 21 and 28 days in the laser group. Clinical evaluation showed better reparation mainly after the third day.

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Low-energy laser irradiation promotes the survival and cell cycle entry of skeletal muscle satellite cells. J Cell Science. 2002; 115: 1461-1469.
Shefer G, Partridge T A, Heslop L et al.

Shefer has demonstrated that HeNe laser can stimulate cell cycle entry and the accumulation of satellite cells around isolated single fibres, grown under serum-free conditions. It is demonstrated that laser therapy promotes the survival of muscle fibres and their adjacent cells, as well as cultured myogenic cells, inder serum-free conditions that normally lead to apoptosis.

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Transplantation of embryonal spinal cord nerve cells cultured in biodegradable microcarriers followed by low power laser irradiation for the treatment of traumatic paraplegia in rats. Neur Res. 2002; 24.
Rochkind S, Shahar A, Alon M, Nevo Z.

In the study by Rochkind embryonal spinal cord nerve cells dissociated from rat fetuses, cultured in biodegradable microcarriers and embedded in hyaluronic acid, were implanted in the completely transsected spinal cords in 24 adult rats. 15 rats underwent 14 days of consecutive laser irradiation (780 nm, 250 mW, 30 minutes daily). 7 rats received the same treatment but without laser. Eleven of the 15 laser treated rats showed different degrees of active leg movements and gait performance compared to 4 of the 9 rats with implantation alone. In a control group of 7 rats with no therapy after the transsection of the spinal cord, six remained completely paralysed. Intensive axonal sprouting occurred in the laser group. In the control group the transsected area contained proliferating fibroblasts and blood capillaries only.

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The effects of adding low energy laser irradiation after skin resurfacing in lowering complication. Laser Surg Med. Abstract issue, 2002, abstract 242.
Fereydson E, Samieh M.

Laser therapy is a valuable supportive therapy after skin resurfacing with CO2 laser. In a study by Fereydson. twenty patients had full face skin resurfacing with superpulse CO2 laser, 500 mJ/cm2. Ten patients had additional 780 nm laser therapy. This additional therapy lowered complications such as pain, erythema, infection rate and itching.

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Bone repair of the periapical lesions treated or not with low intensity laser (wavelenght=904 nm). Laser Surg Med. Abstract Issue 2002. abstract 303.
Sousa G R, Ribeiro M S, Groth E B.

.The effect of bone repair in periapical lesions has been studied by Sousa []. 15 patients with a total of 18 periapical lesions were divided into two groups. One group received endodontic treatment and/or periapical surgery. The patients in the other group were submitted to the same procedure and in addition the lesions were irradiated by GaAs laser, 11 mW, 9 J/cm2. This therapy was performed during 10 sessions with an interval of 72 hours. Bone regeneration was evaluated through X-ray examination. The results showed a significant difference between the laser and the control group in favour of the laser group.

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In vivo study on mast cells behaviour following low-intensity visible and near infrared laser radiation. Laser Surg Med. Abstract issue 2002, abstract 304.
Silveira L B, Ribeiro M S, Garrocho A A et al.

The effect of laser therapy in periodontal surgery has been reported by Silveira. 20 patients with periodontal disease were subjected to gingivectomies. Gingival biopsies were taken from a non-mineralised wall of a suprabony periodontal pocket. The first sample was taken before laser irradiation, the second after 785 nm laser irradiation and the third after 688 nm laser irradiation (50 mW, 8 J/cm2). After biopsy the samples were fixed, cut and stained. Both laser wavelengths promoted mast cell degranulation as compared to control and there was no statistical difference between the two wavelengths.

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A comparative study of the effects of low laser radiation on mast cells in inflammatory fibrous hyperplasia coloured or not coloured by the toluidine blue. Laser Surg Med. Abstract issue 2002, abstract 301
Sawazaki I, Ribeiro M S, Mizuno L T et al. A

The effect of toluidine blue and laser in combination has been studied by Sawazaki. Eight patients with inflammatory fibrous hyperplasias caused by ill-fitting dentures were selected for the study. Each hyperplasia was randomly divided into three areas. One was surgically removed without any treatment; one was treated by a 670 nm laser, 15 mW, 8 J/cm2 and then removed. The third part was dyed with TBO, and laser treated in the same way as part two. Mast cell degranulation in the control specimens was average 49´%, in the laser specimens 87% and in the combined TBO/laser specimens 88%. With these parameters the TBO did not have any additional effect.

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Low level laser treatment of primary and secondary Raynaud's phenomenon. Vasa - Journal of Vascular Diseases. 2001; 30 (4): 281-284.
Al Awami M, Schillinger M, Gschwandtner M E et al.

The pilot study by Al Awami was performed to evaluate the efficacy of LLLT as a new non-drug non-invasive treatment for patients with primary and secondary Raynaud's phenomenon. Forty patients ( 29 female, 11 male, mean age 51 years) with active primary (28%) and secondary (72%) Raynaud's phenomenon received 10 sessions of LLLT distant irradiation during winter months. Assessment of subjective and objective parameters was performed at baseline, one week after the last session and three months later. Variations of subjective parameters as number of daily acute episodes and severity of discomfort were assessed by a coloured visual analogue scale. A standardised cold challenge test using computed thermography of continuous temperature recordings by means of infrared telethermography was used to assess the digital blood flow. A significant improvement was noticed clinically and thermographically after 6 weeks and 3 months, respectively

Selected abstracts from December 2001
Low level laser therapy for tendinopathy. Evidence of a dose-response pattern.
Physical Therapy Reviews. 2001; 6: 91-99.
Bjordal J M, Couppé C, Ljunggren E.

To investigate whether low-level laser therapy can reduce pain from tendinopathy, the authors performed a review of randomised placebo-controlled trials with laser therapy for tendinopathy. Validity assessment of each trial was done acc. to predefined criteria for location-specific dosage and irradiation of the skin directly overlying the affected tendon. The literature search identified 78 randomised control trials of which 20 included tendinopathy. Seven trails were excluded for not meeting the validity criteria on treatment procedure and trial design. 12 of the remaining 13 trials investigated the effect of laser therapy for patients with subacute and chronic tendinopathy and provided a pooled mean effect of 21%. If results from only the nine trials adhering to assumed optimal treatment parameters were included, the mean effect over placebo increased to 32%. Laser therapy can reduce pain in subacute and chronic tendinopathy if a valid treatment procedure and location-specific dose is used.
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Chemotherapy- and radiotherapy-induced mucositis in head and neck cancer patients: New trends in pathophysiology, prevention and treatment.
European Archives of Oto-Rhino-Laryngology. 2001; 258 (9): 481-487
Bensadoun R J, Magne N, Marcy P Y, Demard F

Mucositis is the intensity-limiting toxicity in the management of locally advanced non-resectable head and neck cancer with radiotherapy and chemotherapy. The addition of chemotherapy introduces systemic toxicity and can exacerbate local tissue reactions when used concurrently with radiotherapy. Mucositis is recognized as the principal limiting factor to further treatment intensification. As local regional control and overall survival are related to dose-intensity in this case, further research into the assessment, analysis, prevention an treatment of mucosal toxicity is not only crucial to improvement in quality of life, but certainly also to improved rates of disease control. Several topical and systemic treatments are directed to the decrease and the acceptance of this acute toxicity, but few have shown a significant preventive effect. The efficacy of low-level laser therapy in the management of such toxicity could hence yield important developments with this method in the field of oncology

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Amelioration of oral mucosal lesions of acute graft-versus-host disease by low-level laser therapy.
Haematologica; 2001 Dec;86(12):1321.
Ana Chor, Alexandre Barbosa Sotero Caio, Alexandre Mello de Azevedo

A 42-year old male allogeneic bone marrow transplant recipient was diagnosed as having grade III acute graft-versus-host disease (GVHD). On day +50, he had severe oral GVHD, with xerostomia, cheilitis, and lesions on the oropharynx and tongue. Low-level laser therapy (LLLT) was applied on the palate and inferior labial mucosa. In 24 hours, xerostomia had improved, and LLLT was continued, including the tongue. Four days later, cheilitis disappeared, salivation improved, the papillae recovered and oropharyngeal lesions improved, with relief of pain. Unfortunately, systemic GVHD persisted, and the patient died of disseminated aspergillosis. Prophylactic LLLT can reduce the severity of mucositis in autologous bone marrow transplantation. According to our observation, it may also be useful for treatment of oral lesions in GVHD.

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Low level laser treatment of primary and secondary Raynaud's phenomenon.
Vasa - Journal of Vascular Diseases. 2001; 30 (4): 281-284.
Al Awami M, Schillinger M, Gschwandtner M E et al.

This pilot study was performed to evaluate the efficacy of LLLT as a new non-drug non-invasive treatment for patients with primary and secondary Raynaud's
phenomenon Forty patients ( 29 female, 11 male, mean age 51 years) with active primary (28%) and secondary(72%)Raynaud's phenomenon received 10 sessions of LLLT distant irradiation during winter months. Assessment of subjective and objective parameters was performed at baseline, one week after the last session and three months later. Variations of subjective parameters as number of daily acute episodes and severity of discomfort were assessed by a coloured visual analogue scale. A standardised cold challenge test using computed thermography of continuous temperature recordings by means of infrared telethermography was used to assess the digital blood flow. A significant improvement was noticed clinically and thermographically after 6 weeks and 3 months, respectively

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Low-power diode laser stimulation of surgical osteochondral defects:results after 24 weeks.
Artificial cells, blood substitutes, amd immobilization biotechnology. 2001.29 (3): 235-44.
Guzzardella G A, Tigani D, Torricelli P, Fini M, Martini L, Morrone G, Giardino R.

The purpose of this study was to evaluate osteochondral lesions of the knee, treated intraoperatively with low-power laser stimulation, and assess results at 24 weeks. Surgery was performed under general anesthesia on six rabbits; a bilateral osteochondral lesion was created in the femoral medial condyles with a drill. All of the left lesions underwent immediate stimulation using the diode Ga-Al-As laser (780nm), whereas the right knees were left untreated as control group. After 24 weeks, the explants from the femoral condyles, either treated employing laser energy or left untreated, were examined histomorphometrically. Results obtained on the lased condyles showed good cell morphology and a regular aspect of the repaired osteocartilaginous tissue.

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Optimal dosing of intravascular low-power red laser light as an adjunct to coronary stent implantation: Insights from a porcine coronary stent model.
Journal of Clinical Laser Medicine and Surgery. 2001; 19 (5): 261-265.
De Scheerder I K, Wang K, Zhou XR et al.

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. Selected right coronary artery segments were pretreated with a LPRLL balloon, delivering a dose of 0 mW during 1 min (group I, 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. 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.

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Painful piezogenic pedal papules-successful low level laser therapy.
Acta Dermatovenerologica Alpina, Panonica et Adriatica
Mijailovic B, Karadaglic D, Mladenovic T, Popovic L et al.

Painful piezogenic pedal papules may be very difficult to treat. The authors describe two patients with this condition successfully treated with a low-level laser. A two-week treatment protocol induced a relatively long-lasting pain relief without any side effects.

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The use of lasers for endodontic applications in dentistry.
Medical Laser Application. 2001; 16 (3): 231-243.
De Paula Eduardo C, Gouw Soares S

Several applications of lasers in clinical procedures for dental hard tissues are either currently in practice or being developed since newer wavelengths as well as different methods and delivery systems are being applied in the field of dentistry. In endodontic therapy lasers have been used as treatment coadjuvant with reference to both, low intensity laser therapy (LILT) and high intensity laser treatment (HILT) to increase the success rate of the clinical procedures. The purpose of this article is to review in vitro studies and clinical procedures for the use of lasers in endodontics. Low intensity laser therapy has the ability to produce analgesic, anti-inflammatory and biomodulation effects on the irradiated soft tissue thereby improving the wound healing process and giving the patient a better condition of the postoperative experience.

Selected abstracts from December 2001

Laser photostimulation accelerates wound healing in diabetic rats. Wound Repair and Regeneration. 2001; 9 (3): 248-255.
Reddy G K, Stehno-Bittel L, Enwemeka C S.

In this study the hypothesis that laser photostimulation can facilitate healing of impaired wounds in experimental diabetes using a rat model was studied. Diabetes was induced in male rats by streptozotocin injection and two 6 mm diameter circular wounds were created on either side of the spine. The left wound of each animal was treated with a 632.8 nm He:Ne laser at a dose of 1.0 J/cm2 for five days a week until the wounds closed (three weeks). Measurements of the biomechanical properties of the laser-treated wounds indicated there was a marginal increase in maximum load (16%), stress (16%), strain (27%), energy absorption (47%) and toughness (84%) compared to control wounds of diabetic rats. Biochemical assays revealed that the amount of total collagen was significantly increased in laser treated wounds (274 +/- 8.7 microg) over the control wounds
(230 +/- 8.4 microg). Sequential extractions of collagen from healing wounds showed that laser treated wounds had significantly greater concentrations of neutral salt soluble (15%) and insoluble collagen (16%) than control wounds, suggesting accelerated collagen production in laser treated wounds. There was an appreciable decrease in pepsin soluble collagen (19%) in laser treated wounds over control wounds, indicating higher resistance to proteolytic digestion. In conclusion, the biomechanical and biochemical results collectively suggest that
laser photostimulation promotes the tissue repair process by accelerating collagen production and promoting overall connective tissue stability in healing wounds of diabetic rats.

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Comparison of the low level laser therapy effects on cultured human gingival fibroblasts proliferation using different irradiance and same fluence. Lasers in Surgery and Medicine. 2001; 29(2): 179-184.
Almeida-Lopes L, Rigau J, Zangaro R A et al.
Low level laser therapy (LLLT)has been used in Dentistry to improve wound healing. In order to analyse the effect of LLLT on the in vitro proliferation of gingival fibroblasts we developed a primary culture of human gingival fibroblasts. The cell line named LMF was grown in Dulbecco's Modified Eagle's medium (DME) with either 5% (nutritional deficit) or 10% fetal bovine serum fibs). Laser irradiation was carried out with diode lasers with the following wavelengths: 670 n (L1), 780 nm (L2), 692 nm (L3), and 786 nm (L4). The fluence was fixed in 2 J/cm2. For growth analysis, control (not irradiated) and treated cultures (irradiated) were plated in 60 mm diameter culture dishes for 12 h before the irradiation. Results: We found that cells cultured in nutritional deficit condition grown in medium supplemented by only 5% fbs presented a cell proliferation rate significantly smaller that cell grown in ideal culture conditions 10% fbs). However, when irradiated, cells in nutritional deficit presented cell growth similar or higher than that of control cells grown in ideal culture conditions. Using the same fluence, the infrared laser induced a higher cell proliferation than visible laser when the power outputs were different. However, lasers of equal power output presented similar effect on cell growth independently of their wavelengths. Conclusions: The LLLT acts by improving the in vitro fibroblast proliferation and a smaller laser exposure time results in higher proliferation

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Conservative closure of antro-oral communication stimulated with laser light. Journal of Clinical Laser Medicine and Surgery. 2001; 19 (4):181-184.
Grzesiak-Janas G, Janas A.

Sixty-one patients between the ages of 14 and 58 were subjected to biostimulation with laser light. Therapy was performed with a 830 nm laser of 30 mW power. Three cycles of laser irradiation were performed in a continuous mode. During one cycle, 3.5 min of extraoral irradiation of 4J with the contact "sweeping" method or the woodpecker technique" was made through the facial skin to the suborbital region, 3.5 min of intraoral irradiation of 4J with the contact "point" method to the region of maxillary sinus floor, and 3.5 min of intraoral one of 4J with the contact "point" method to the alveolar process at the site of the antro-oral communication. The above cycle of irradiation was repeated for 4 days. After 4 days of laser therapy, a complete closure of antro-oral communication occurred.

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Pulse irradiation of low-power laser stimulates bone nodule formation.Journal of oral science:2001; 43 (1): 55-60.
Ueda Y, Shimizu N.
Although low-power laser irradiation provides many anabolic effects such as acceleration of bone formation, the effects of different pulse frequencies used during laser irradiation on bone formation have not been elucidated. Osteoblastic cells isolated from fetal rat calvariae were irradiated once with a low-power Ga-Al-As laser (830 nm, 500 mW) in two different irradiation modes; continuous irradiation (CI), and 1 Hz pulsed irradiation (PI). We then investigated the effects on cellular proliferation, bone nodule formation, alkaline phosphatase (ALP) activity, and ALP gene expression. Laser irradiation in both groups significantly stimulated cellular proliferation, bone nodule formation, ALP activity, and ALP gene expression, as compared with the nonirradiation group. Notably, PI markedly stimulated these factors, when compared with the CI group. Since 1 Hz pulsed laser irradiation significantly stimulates bone formation in vitro, it is most likely that pulse frequency is an important factor affecting biological responses in bone formation.
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Double-blind randomized study evaluating regeneration of the rat transected sciatic nerve after suturing and postoperative low-power laser treatment. Journal of reconstructive microsurgery. 2001; 17 (2): 133-137.
Shamir M H, Rochkind S, Sandbank J, Alon M.

This double-blind randomized study evaluated the therapeutic effect of low-power laser irradiation (LPLI) on peripheral nerve regeneration, after complete transection and direct anastomosis of the rat sciatic nerve. After this procedure, 13 of 24 rats received postoperative LPLI, with a wavelength of 780 nm laser, applied transcutaneously, 30 min daily for 21 consecutive days, to corresponding segments of the spinal cord and to the injured sciatic nerve. Positive somatosensory evoked responses were found in 69.2 percent of the irradiated rats compared to 18.2 percent of the non-irradiated rats. Immunohistochemical staining in the laser-treated group showed an increased total number of axons and better quality of the regeneration process, due to an increased number of large-diameter axons compared to the non-irradiated control group. The study suggests that postoperative LPLI enhances the regenerative processes of peripheral nerves after complete transection and anastomosis.

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Low intensity laser therapy in wound healing - A review with special respect to diabetic angiopathies. Acta Chirurgica Austriaca. 2001, 33(3):132-137.
Schindl A, Schindl M, Pernerstorfer-Schoen H, Schindl L.

Low intensity laser radiation is characterized by its ability to induce athermic, non-destructive photobiological processes. Albeit in use for about thirty years, this phototherapy is still not an established therapeutic modality in wound healing.We have reviewed the literature addressing both in vitro and in vivo effects of low intensity laser therapy on constituents of the wound healing process. Results: A large number of in vivo studies on the effects of low intensity laser irradiation on wound healing show a lack of accuracy on dosimetric data and appropriate controls. Despite this fact, data from appropriately designed studies seem to indicate that this type of phototherapy should be considered avaluable (adjuvant) therapy for otherwise therapy-refractory wound-healing disorders including such in diabetic patients.

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Low intensity laser therapy (830nm) in the management of minor postsurgical wounds: a controlled clinical study. Lasers in surgery and medicine. 2001; 28 (1) : 27-32.
Lagan K M, Clements B A, McDonough S, Baxter G D.

The stimulatory effects of low intensity laser therapy (LILT) have been widely published for the treatment of chronic ulceration. In contrast to this previous work, the currentstudy investigated its potential efficacy (by using a dosage of 9 J/cm2) in the management of acute wounds. For this purpose,uncomplicated postoperative wounds after minor podiatric surgery were examined. The study was designed as a controlled group study. Patients (n = 9)presenting with a total of 12 wounds after minor surgical procedures (partial/total nail avulsions/electrosurgery) were recruited. Patients attended the clinic once per week for assessment and treatment. Weekly irradiation was performed. The physical parameters of the output of the laser were as follows: wavelength, 830 nm; average power output, 30 mW; spot size, 0.1 cm2; irradiance, 300 mW/cm2; continuous wave output. Wound assessment and recording of pain levels were conducted weekly. Wound measurement was completed by using planimetry and digitising methods. Current findings indicated no statistically significant differences between Laser and Control groups for wound closure digitising; nor for pain levels reported. It would seem that LILT provides no advantages in the management of minor postoperative wounds over current practice.

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Laser enhancement in hepatic regeneration for partially hepatectomized rats.. Lasers in Surgery and Medicine. 2001; 29(1): 73-77.
De Castro e Silva O Jr, Zucoloto S, Menegazzo L A G, Granato R G et al.

The bio-stimulation effect of laser has been observed in many areas of Medicine. However, there are a few works which investigate its use for liver regeneration. Most of their results were inconclusive due to the use of high power lasers. This work was carried out to investigate the bio-stimulation effect of laser in liver regeneration using low power lasers. We used Wistar male rats, which were irradiated with laser light (wavelength 590 nm and intensity of 50 mW/cm2 for 5 minutes after 70% hepatectomy. The respiratory mitochondrial activity, the serum level of aminotransferase and the PCNA were measured. Results: Our results show a dramatic increase in the mitochondrialactivity for the laser treated group at 24 hours after the hepatectomy. Conclusion: We conclude that the laser promotes a bio-stimulation effect on the early stages of liver regeneration without any detectable damage of the cells.

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Lightdosimetric quantitative analysis of the human petrous bone: experimental study for laser irradiation of the cochlea. Lasers in surgery and medicine. 2001; 28 (1) : 18-26.
Tauber S, Baumgartner R, Schorn K, Beyer W.

Application of laser irradiation targeting the inner ear has to be investigated for therapeutic effectiveness in cochlear injury and dysfunction. In vitro data demonstrate low-level laser-induced photochemical and photobiologic cell response,depending on cell type and irradiation parameters such as light dose.The aim of the presented study was to determine the light dose received by the cochlear hair cells by using different irradiation modalities for the human petrous bone. Lightdosimetric assessment was performed in human cadaver temporal bones (n = 13) after removing the cochlear membranous labyrinth. The external auditory meatus, the tympanic membrane (quadrants), and the mastoid bone were illuminated by a helium-neon laser (lambda = 593 nm) and diode lasers of different wavelengths (lambda = 635, 690, 780, and 830 nm). The spatial distribution of transmitted light in the cochlear windings was measured by means of a retrocochlearly positioned endoscopic CCD camera for image processing and was assigned to acoustic frequencies according to the tonotopic organization of the cochlea. For an estimation of the corresponding space irradiance in an intact cochlea, correction factors have been calculated by a Monte Carlo procedure on the basis of experimentally determined optical properties of skull bone. The transmission of light across the tympanic cavity and the promontory depends strongly on wave-length of the laser and the position of the radiator. Transtympanal irradiation results in spatial intensity variations of a factor 4 to 10 within the cochlear windings. The space irradiance in an intact cochlea is 10 to 20 times the measured irradiance. For an irradiation of the mastoid, the light transmission within the cochlea is 10(3) to 10(5) times smaller compared with an irradiation of the tympanic membrane and is extremely variable for different specimens. The strong dependence of the cochlear light distribution on various irradiation parameters demonstrates the impact of preclinical lightdosimetric investigations for effective individual laser irradiation of the human cochlea. Because of the observed spatial intensity variations, the optimal external light dose has to be chosen with regard to the tonotopy of the human cochlea. The obtained results are enabling us to apply defined laser light doses to different cochlear winding areas. Mastoidal irradiation leads to therapeutically insufficient light doses within reasonable treatment times, whereas transmeatal irradiation is recommendable. Further studies are mandatory for development of clinical devices for transmeatal irradiation of the cochlea.

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The clinical efficacy of low-power laser therapy on pain and function in cervical osteoarthritis. Clinical Rheumatology. 2001; 20(3): 181-184.
Oezdemir F, Birtane M, Kokino S

Pain is a major symptom in cervical osteoarthritis (COA). Low-powerlaser (LPL) therapy has been claimed to reduce pain inmusculoskeletal pathologies, but there have been concerns about thispoint. The aim of this study was to evaluate the analgesic efficacy of LPL therapy and related functional changes in COA. Sixty patients between 20 and 65 years of age with clinically and radiologically diagnosed COA were included in the study. They were randomised into two equal groups according to the therapies applied, either with LPL or placebo laser. Patients in each group were investigated blindly in terms of pain and pain-related physical findings, such as increased paravertebral muscle spasm, loss of lordosis and range of neck motion restrictio n before and after therapy. Functional improvements were also evaluated. Pain, paravertebral muscle spasm, lordosis angle, the range of neck motion and function were observed to improve significantly in the LPL group, but no improvement was found in the placebo group. LPL seems to be successful in relieving pain and improving function in osteoarthritic diseases.