DNA-based HLA class II postmortem typing: evaluation of different techniques for prospective corneal allografting

BACKGROUND: Two new types of lasers, the pulsed dye laser and the Q-switched ruby laser, have shown good to excellent results in the treatment of vascular malformations and benign pigmented lesions of the skin. A new and very effective alternative to pulsed dye laser is the recently introduced Photoderm VL. This device is based on the use of a wide-band non-coherent intense pulsed light source which emits a continuous spectrum in the range of 515 nm to 1200 nm. PATIENTS AND METHODS: More than a 1000 patients with a variety of lesions of the skin were treated by these new laser systems and the Photoderm VL. The Q-switched ruby laser (wavelength 694 nm, pulse duration 25 ns) is suitable for the treatment of benign lentigines, café-au-lait macules, seborrhoic ceratosis, tattoos, and traumatic tattoos. The pulsed dye laser (585 nm, 0,3-0,45 ms) treats nevi flammei, capillary hemangiomas, telangiectasias, xanthelasma, hypertrophic scarring, and adenoma sebaceum. In addition we present the facilities of the new Photoderm VL (515 nm-1200 nm, 0,5-20 ms) for the treatment of nevi flammei, benign hemangiomatous malformations, telangiectasias, erythrosis interfollicularis colli, hypertrophic scarring, and hypertrichosis. RESULTS AND CONCLUSIONS: the Q-switched ruby laser, the pulsed dye laser, and the Photoderm VL show excellent results in the treatment of lesions of the skin, which otherwise would have been difficult to treat of untreatable. The efficiency of the laser types presented is based on the theory of selective photothermolysis. Scarring is almost never seen and hypo- or hyperpigmentation is in most cases transient.     

Q-switched ruby laser treatment of mucocutaneous melanosis associated with Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is an eponym for circumscribed mucocutaneous melanosis in association with gastrointestinal polyposis. Irregular pigmented macules of varying size and color can be found on the perioral skin, lip vermillion border, buccal mucosa, palate, and tongue. Previous treatments, such as surgical excision, cryosurgery, electrodesiccation, dermabrasion, and carbon dioxide or argon laser ablation commonly result in incomplete removal, scarring, or changes in normal pigmentation. The Q-switched ruby laser used at 694 nm, a wavelength well absorbed by melanin relative to other optically absorbing structures in skin, causes highly selective destruction of pigment-laden cells. In addition, the 20-nanosecond pulse duration produced by this laser approximates the thermal relaxation time for melanosomes, thereby confining the energy to the target. The Q-switched ruby laser produces clinically significant fading of mucocutaneous melanosis in association with Peutz-Jeghers syndrome without complications often seen with other therapeutic modalities.     

Complications of laser surgery

Medical lasers have advanced so rapidly over the past 10 years that a thorough review of the complications of laser surgery must be based on fundamental laser physics in order to provide a general working framework of knowledge. New laser systems are being introduced and older systems have been improved, often making modern laser technology appear intimidating. In order to understand and even predict the side-effect profile of a specific laser, one must comprehend the principles on which the laser operates. The first medical lasers to be designed, continuous wave lasers, are effective but are extremely operator-dependent and can potentially result in a great deal of scarring. In 1983, the theory of selective photothermolysis was introduced that enabled physician-scientists to design lasers that were highly selective and safer to operate. Lasers designed on the theory of selective photothermolysis are capable of affecting a specific target tissue without a high risk of scarring and pigmentary changes. They accomplish this task by producing a wavelength and pulse duration that are best absorbed by a specific target. Not all modern lasers use selective photothermolysis and therefore may operate in either a continuous wave, quasi-continuous wave, pulsed, or Q quality-switched mode. Continuous wave lasers are least selective and tend to produce unwanted tissue damage and scarring through heat dissipation. Quasi-continuous wave lasers attempt to limit unwanted thermal damage by producing a series of brief laser pulses or by chopping a continuous wave beam; however, they still have a relatively high risk of causing nonspecific tissue damage and thermal injury. The pulsed and Q-switched systems adhere most closely to the laws of selective photothermolysis and result in the most selective destruction with the lowest risk of scarring and unwanted thermal diffusion. Of course, any laser system can potentially result in scarring and tissue damage; therefore, adequate operator education and skill are essential when using any medical laser.     

IgA class serum antibodies against three different Klebsiella serotypes in ankylosing spondylitis

BACKGROUND: Over the past decade, the 585-nm pulsed dye laser (PDL) has been used successfully to treat a variety of cutaneous vascular lesions as well as hypertrophic scars. Laser scar revision has been revolutionized by the recent development of high-energy, pulsed carbon dioxide (CO2) laser systems. These new CO2 lasers allow controlled vaporization of thin layers of skin while minimizing damage to surrounding dermal structures. OBJECTIVE: To determine the effect of a high-energy, pulsed CO2 laser alone and in combination with a 585-nm PDL on nonerythematous hypertrophic scars. METHODS: Twenty patients with nonerythematous hypertrophic scars were treated with a high-energy, pulsed CO2 laser. One-half of each scar was additionally treated with the 585-nm PDL laser. Sequential clinical and photographic analyses were performed independently by two blinded assessors. In addition, erythema reflectance spectrometry measurements were obtained from the scars before and at regular postoperative intervals. RESULTS: Global assessment scores and erythema spectrometry measurements were significantly improved after laser treatment. Combination CO2 and PDL laser treatment resulted in more significant improvement than CO2 laser irradiation alone. CONCLUSION: Concomitant use of the high-energy, pulsed CO2 and PDL laser systems was superior to CO2 laser vaporization alone for revision of nonerythematous hypertrophic scars. Once again, the vascular specificity of the 585-nm PDL has been linked to improvement in hypertrophic scar tissue.     

Laser treatment of pigmented lesions

Several pigment-specific lasers can effectively treat epidermal and dermal pigmented lesions without complications using the basic principles of selective photothermolysis. Although such pigmented lesions as solar lentigines and nevi of Ota are relatively easy to treat using pigment-specific laser technology, café-au-lait macules and melasma show variable responses to treatment. New, long-pulsed pigment-specific lasers may prove to further enhance the clinical results obtained in resistant pigmented lesions and other conditions.     

Successful treatment of dark-colored epidermal nevus with ruby laser

The pulsed ruby laser has a selective thermolytic effect. Recently, it has been available for the treatment of superficial pigmented disorders. We studied 5 cases of epidermal nevus treated with the pulsed ruby laser. In comparison with the usual methods including electrocautery, cryotherapy and skin abrasion, ruby laser therapy is an excellent tool due to technological ease and rapid improvement. Depigmentation after treatment in 2 cases was the only side effect of this therapy. Bose cases had a dark pigmentation of the skin. Despite of the risk of discoloration, the ruby laser is one of the most effective tools for therapy of pigmented epidermal nevus.     

510-nm pigmented lesion dye laser. Its characteristics and clinical uses

BACKGROUND: Benign pigmented lesions are of a cosmetic concern to many individuals. Numerous treatments exist, including several types of lasers. The Candela 510 nm pigmented lesion dye laser has recently been added to this armamentarium. It is designed specifically for the treatment of superficial pigmented lesions while significantly decreasing the risk of scarring and prolonged hypopigmentation. OBJECTIVES: To describe the characteristics of the Candela pigmented lesion dye laser and report on the therapeutic outcome of patients treated for actinic lentigines, café-au-lait macules, melasma and red tattoos by one of the authors (RCG). METHODS: The Candela 510 nm pigmented lesion dye laser was used to treat solar lentigines, café-au-lait macules, melasma and red tattoo. RESULTS: Excellent outcomes resulted on facial and hand lentigines (89% and 88% of patients had greater than 75% clearing, respectively), but often required more than one treatment. Lentigines located on the upper extremities and trunk improved less dramatically. Immediate greying occurred universally. Bruising was often noted. Treatment failures have been observed especially in treating lentigines located on the lower extremities. Café-au-lait macules responded inconsistently, with facial lesions giving the best results. Melasma responded poorly, often with hyperpigmentation. Three red tattoos cleared. Treatment failure may be related to inaccurate clinical assessment of pigment depth or regrowth of the lesion. Several cases are presented to demonstrate clinical and histologic effects of the laser. CONCLUSION: The Candela 510-nm pigmented lesion dye laser is an effective treatment for superficial pigmented lesions. Its associated morbidity is minimal.     

5. Update on lasers in dermatology

A range of lasers with acceptably low rates of side effects is now available. Improved laser therapy has been made possible by combining wavelengths that are selectively absorbed by the target and pulses short enough to prevent heat transfer to surrounding tissue. Carbon dioxide (CO2) lasers are useful for treating disorders of skin surface texture and topography (wrinkles, scars, sun damage, benign skin appendages and rhinophyma). Vascular lasers, such as the flashlamp-pumped dye laser, are particularly effective for treating port-wine stains, haemangiomas, telangiectasia, rosacea and spider naevi. Q-switched lasers, which allow ultrashort high intensity pulses, are effective for treating most tattoos and some benign pigmented lesions.     

Autoreactive B cell regulation: peripheral induction of developmental arrest by lupus-associated autoantigens

Continuous wave (CW) lasers, the first medical lasers to be used, continue to be effective, but are extremely operator dependent and can potentially result in significant risks, including scarring. In 1983, the theory of selective photothermolysis was introduced, which enabled physician-scientists to design lasers that were highly selective and safer to operate. These newer lasers are capable of affecting a specific target tissue without a high risk of scarring and pigmentary changes. They accomplish this task by producing a wavelength and pulse duration that is best absorbed by a specific target. However, not all modern lasers employ this theory and, therefore, may operate in either a CW, quasi-CW, pulsed, or Q-switched mode. CW lasers are least selective and tend to produce unwanted tissue damage and scarring through heat dissipation. Quasi-CW lasers attempt to limit unwanted thermal damage by producing a series of brief laser pulses or by the chopping of a CW beam; however, they still have a relatively high risk of causing nonspecific tissue damage and thermal injury. The pulsed and Q-switched systems adhere most closely to the principles of selective photothermolysis and result in the most selective destruction with the lowest risk of scarring and unwanted thermal diffusion. Of course, any laser system can potentially result in scarring and tissue damage; therefore, adequate operator education and skill are essential when utilizing medical lasers.     

Electron paramagnetic resonance studies of cobalt-substituted angiotensin I-converting enzyme

The traditional treatment of high-flow vascular malformations consists of selective embolization, surgical removal, or a combination of both. Recurrence of the lesion and bleeding control are still the main problems, and the result of treatment is sometimes disappointing. We suggest treatment of these lesions with surgical ligation of the distal major feeding arteries followed by intravascular injection of a sclerosing agent (3% tetradecyl sulfate), and surgical excision and reconstruction when indicated. We have found this to be an effective treatment regimen. We present 14 cases of high-flow vascular malformations of the head and neck area treated with this approach, of which 4 cases developed skin necrosis. Three of these 4 cases of skin necrosis were later treated with skin grafting and, in 1 case, an upper arm skin tube flap was used for nasal tip reconstruction. Three cases underwent delayed reconstruction using tissue expanders. From a symptomatic and aesthetic point of view, preliminary satisfactory results were obtained. We feel that this approach is a good option for treating difficult, high-flow vascular malformations.     

Current status of laser therapy in dermatology]

Indications for dermatological laser therapy have been enlarged during the last few years. In this article the physics and biophysics of laser therapy and the common laser systems in dermatology are described. Modern pulsed laser systems are combined with little side effects. Nevertheless, successfully used alternative methods should not be neglected.     

Expression of hindlimb abnormalities under rearing temperature effects during the larval development of the salamander Pleurodeles waltl (urodele amphibian)

The Q-switched ruby laser (694 nm, 25-40 nsec) is an effective and safe therapeutic device for the treatment of tattoos and well-defined, benign, pigmented epidermal and dermal lesions. Because of its selective mode of action, dermal pigments of natural and artificial origin are destroyed photothermically and removed without scar. This method is exceptionally suited for the elimination of lay and professional tattoos, traumatic tattoos, and permanent makeup. Other frequent indications include benign pigmented lesions such as lentigines, freckles, café-au-lait spots, seborrheic keratosis, and Becker nevi. As a dermal pigmented lesion, the nevus of Ota is perfectly treatable. However, chloasma can no longer be considered an indication for ruby laser treatment due to unsatisfactory results. Melanocytic nevi and congenital nevi should be treated only in clinical studies. The effectiveness of the long-term epilation of dark hair with this laser device has to be verified in future investigations. Particularly attractive is the nonproblematic and straightforward removal of pigmented lesions in precarious anatomic regions like the lips, eyelids, and genitals (e.g., benign melanosis of the lips or of the penis, seborrheic keratosis of the lid angle).     

Tissue effects of subclinical diode laser treatment of the retina

OBJECTIVE: To determine whether consistent tissue effects are obtained when laser lesions are produced with a commercially available diode laser that are near the limit of clinical detection at the time of treatment. METHODS: Continuous-wave or micropulse diode laser was used to produce clinically undetectable (subthreshold) or barely detectable (threshold) retinal lesions in pigmented rabbits. Tissue effects at intervals after treatment were determined in retinal pigment epithelial (RPE) whole mounts by fluorescence microscopy, and in sections of retina and RPE by light and electron microscopy. RESULTS: Continuous-wave and micropulse laser lesions that were originally clinically undetectable were detectable as zones of pigment mottling after 5 days. By microscopy, compaction and/or swelling was seen in the outer retina, and cells in the RPE monolayer became heterogeneous in size, shape, and pigmentation, but the tissue responses in the outer retina and RPE were variable even within and among lesions in the same eye. CONCLUSIONS: Subthreshold energies used to create both continuous-wave and micropulse laser lesions produced variable effects on the RPE and the overlying neurosensory retina. It appears that, near the minimum effective dose of laser irradiation, individual RPE cell heterogeneity becomes detectable as variability in sensitivity to laser injury. CLINICAL RELEVANCE: As laser energy is reduced to limit collateral tissue damage in clinical applications, it may be difficult to generate reproducible lesions because of heterogeneity among individual cells.     

Effects of various laser types and beam transmission methods on female organ tissue in the pig: an in vitro study

The purpose of this in vitro study was to investigate and compare effects of various laser types (CO2, Argon, Erbium:YAG, Erbium:YSGG, and Holmium:YAG) and laser beam transmission methods (optical lens and flexible fiber) on ovarian and uterine tissue of the pig. The Erbium laser radiation was transmitted through Zirconium fluoride fibers (ZrF4). To circumvent the low mechanical stability of these fibers, we developed a special microlens system, which refocuses the radiation and protects the distal end from damage. Tissue lesions were performed with 1 and 5 joule. Histologic analysis of acute Er:YAG laser lesions reveal precise cutting effects with a minimal thermal damage zone of 40 microns and a high damage resistance of the fiber microlens systems. The extent of thermal damage caused by the Erbium:YSGG and CO2 laser is about two times larger, whereas the Argon and Holmium laser tissue lesions show a damage of the surrounding tissue of 200-300 microns. This study suggests that for precise cutting and coagulation, Erbium and Holmium lasers transmitted via our modified fiber tip may render the use of these lasers possible in a wide range of laparoscopic surgery applications.     

Comparative bioavailability of two immediate release tablets of cisapride in healthy volunteers

Irradiation of B16 pigmented melanoma subcutaneously transplanted in C57 mice with a single 650 mJ pulse (10 ns) of 1064 nm light from a Q-switched Nd: YAG laser caused instantaneous bleaching of the pigmented tissue. Visual and histological examination of the resulting gray-colored tumor revealed the breakdown of melanosomes with no detectable alteration of the normal and tumor-overlying skin. Histological examination of the irradiated tumor showed some degree of vascular damage; the depth of the photodamage was not affected by the successive delivery of three consecutive light pulses. The bleached tumor grew at a modestly slower rate but the high-peak-power (HPP) laser treatment did not affect the tumor concentration of a photodynamic sensitizer Si(i.v.)-naphthalocyanine (isoBO-SiNc) intravenously injected 24 h before Nd:YAG irradiation. Treatment of the B16 pigmented melanoma by photodynamic therapy (PDT: 1 mg/kg isoBO-SiNc, 300 mW/cm2, 520 J/cm2) from a 774 nm diode laser immediately after the 1064 nm irradiation resulted in a 16 day delay of tumor regrowth, which was markedly longer than the delay (ca 6 days) obtained after PDT under identical conditions without the preirradiation. Thus, pretreatment of pigmented tumors with HPP 1064 nm light appears to enhance their susceptibility to conventional PDT. The tumor response was further enhanced by repeating the combined HPP/PDT treatment at an interval of 10 days (regrowth delay: 27 days), as well as by applying hyperthermia immediately after HPP/PDT (regrowth delay: ca 34 days).     

Evaluation of the effect of Q-switched ruby and Q-switched Nd-YAG laser irradiation on melanosomes in dermal melanocytosis

Q-switched ruby laser (QSRL) and Q-switched Nd-YAG laser (QSNYL) treatment of dermal melanocytosis, especially nevus of Ota, has produced favorable results that are mediated by selective photothermolysis. However, the precise effects of irradiation on melanosomes and cells containing melanosomes remain unclear, and an optimal method of irradiation has not been found. In this study synthetic melanin powder and pigmented dermal tissue obtained from five blue nevus lesions, also classified as dermal melanocytosis, were used as targets to identify the specific effects of these forms of irradiation in vitro. Morphological changes were assessed by microscopy after irradiation with QSRL and QSNYL at a fluence of 5 J/cm2, the fluence ordinarily utilized in clinical applications. Light microscopy revealed that most of the synthetic melanin powder retained in 1% agar was no longer visible after QSRL irradiation. In contrast, melanin powder particles were partly crushed by QSNYL irradiation. Electron microscopic examination of melanosomes in the blue nevus tissue after irradiation showed expansion and various other forms of disruption. Statistical analysis by 2-way analysis of variance (ANOVA) of the length of the major axis of the melanosomes indicated that QSRL irradiation caused significantly greater melanosome expansion than QSNYL irradiation. These findings indicate that QSRL irradiation had a greater photothermal effect on dermal melanosomes than QSNYL irradiation. This suggests that QSRL is more efficacious in the treatment of dermal melanocytosis than QSNYL.     

Laser-activated solid protein bands for peripheral nerve repair: an in vivo study

As clinical dermatologists, we are all striving to achieve the highest possible accuracy in our clinical acumen and diagnostic skills. Over the past decade, one relatively simple advance, epiluminescence microscopy with the use of the dermatoscope, has significantly contributed to our diagnostic skills in the detection of benign versus pigmented lesions. In the paper by Kawabata and Tamaki, these authors delineate distinctive dermatoscopic features of acral lentiginous melanoma in situ, and contrast this with melanocytic nevi. The restructuring of healthcare delivery systems by third party payers and governmental programs is impacting on the pattern of our medical practices. In Canada, this has limited access to widespread use of techniques such as Mohs' micrographic surgery. The article by Arlette and colleagues has further supported the well-established studies indicating that Mohs' micrographic surgery for high-risk skin cancers has a dramatic benefit. Healthcare restructuring has also led to a decreased number of trainees in a number of subspecialties, including dermatology. This decrease in manpower has been an impetus to look at alternative forms of care for underserviced areas. Telemedicine, the use of telecommunications technology to provide healthcare services over a distance, has been examined as one attempt at solving this problem. In the Point-Counterpoint articles, we have two distinct views on the future of telemedicine as it applies to dermatology. Over the past decade, there have been dramatic advances in our understanding at a molecular nature of various disease processes. This rapid development has translated into a large number of therapies. Regulatory agencies such as the Food and Drug Administration in the United States, or the Health Protection Branch in Canada, are caught between demands to bring effective therapies to the market in an expedited fashion, and yet establish efficacy and maintain safety of new therapeutic entities. This occurs by a multistaged approval process. During the early phases, exposure is limited in order to accumulate preliminary data on pharmacology and toxicity. In the Critical Appraisal CME series, Muglia and DiGiovanna describe early testing processes in Phase 1 clinical trials. Calciphylaxis is a severe disease associated with calcification of the skin, subcutaneous tissue and potentially, internal organs. While the disease itself is relatively uncommon, the manifestations are quite distinctive. In this issue of the Journal, we have a review of calciphylaxis from Richard Worth, as well as a preamble by Dr. Goodall and a case report by Kalaaji et al. illustrating the consequences of this rare but distinctive entity.     

Pigmented lesion pathology: the specimen and its report. A personal and probably biased approach

The author outlines general principles and pitfalls in the pathologic interpretation of pigmented skin lesions, then focuses on issues related specifically to gross tissue specimens and to the histologic report. He concludes that definitive therapy for melanoma should not be based on partial biopsies, that frozen sections are not indicated, and that the pathologist should report all of the relevant histologic attributes whenever possible.     

Cutaneous resurfacing with CO2 and erbium: YAG lasers: preoperative, intraoperative, and postoperative considerations

The development and integration of pulsed and scanned CO2 and erbium:YAG laser systems into mainstream surgical practice over the past years has revolutionized cutaneous resurfacing. These lasers are capable of delivering to skin high peak fluences to effect controlled tissue vaporization, while leaving an acceptably narrow zone of residual thermal damage. The inherent technological differences that exist between the two distant laser systems in terms of ablation depths, degree of thermal coagulation, and postoperative side-effects and complications guide patient selection and management. This article reviews the basic principles of CO2 and erbium:YAG laser resurfacing, including preoperative, intraoperative, and postoperative patient considerations. Side-effects and complications encountered after laser resurfacing are discussed with specific guidelines provided on their appropriate management. Anticipated future developments and cutting-edge research endeavors in cutaneous laser resurfacing are also briefly outlined.     

Diagnosis of acute localized irradiation lesions: review of the French experimental experience

In the last 50 years several radiation accidents occurred in which industrial radiographers and others suffered severe radiation injuries from inadvertent contact with radiation sources. Such accidents involving acute localized injuries are characterized by a severe initial reaction progressing through erythema to skin necrosis with a spontaneous resolution of the lesion over a 2-mo period for the lower doses. However, the early symptoms observed on the skin give no indication as to the in-depth pathology, and cutaneous and muscular radionecrosis started generally from early epithelial, microvascular, and vascular lesions and from delayed muscular and connective tissue lesions. In a case of acute localized irradiation, different biophysical techniques are able to give real responses in biological dosimetry. More numerous are the methods, especially imaging methods, that make it possible for the clinician to evaluate the extent of the early injuries and to manage the medical intervention. We have developed animal experimental models of acute localized irradiation: overexposure to the gamma rays of a 192Ir industrial radiographic collimated source (in the pig and the rabbit) and overexposure to the beta rays of a 90Sr-90Y collimated source (in the pig). In these experimental models, most of the imaging techniques used in clinical practice, as infra-red thermography, microwave thermography, cutaneous and tissular vascular scintigraphy (beta or gamma emitters), cutaneous blood flow measurements by cutaneous laser Doppler, x ray computed tomography, nuclear magnetic resonance imaging, and skin topography, were correlated with clinical evaluation and histopathological observations, after high doses of gamma or beta irradiations ranging from 4 to 340 Gy at the skin surface. All these techniques are not for isolated use and the present review indicates that their combination is necessary to give an improved diagnostic and prognostic picture of early and late delayed radiation damage to the skin and subcutaneous tissues.