Recipes for creating animal models of diabetic cardiovascular disease.

For more than 50 years, investigators have unsuccessfully tried to recreate in experimental animals the cardiovascular complications of diabetes seen in humans. In particular, accelerated atherosclerosis and dilated cardiomyopathy, the major causes of mortality in patients with diabetes, have been conspicuously absent in many mouse models of the disease. Under the auspices of the NIH, the Animal Models of Diabetic Complications Consortium has worked to address this issue. This effort has focused on the development of mouse models because of the high level of genomic information available and the many well-developed genetic manipulations that may be performed in mice. Importantly, the consortium has also worked to standardize many methods to assess metabolic and cardiovascular end points for measurement of the diabetic state and its macrovascular complications. Finally, for maximum benefits from these animal models in the study of atherosclerosis and of other diabetic complications, the consortium has created a system for sharing both the animal models and the accumulated phenotypic data with the greater scientific community.

The benefits and risks of long-term PUVA photochemotherapy.

In 1974 a new photobiologic principle i.e. light + drug, called photochemotherapy was discovered in Boston and immediately confirmed in Vienna. Psoralen + UVA (PUVA) photochemotherapy has now been applied to the treatment of more than 24 heterogeneous groups of diseases, especially psoriasis and mycosis fungoides. After 24 years of experience in thousands of patients with psoriasis and 23 other skin disorders, virtually the only risk is the development of squamous-cell carcinomas. This risk is low with two exceptions: previous history of treatment with ionizing radiation or inorganic trivalent arsenic, and patients with recalcitrant psoriasis who require continuous treatment for many years. In a recent report from a large USA clinical trial, melanoma developed in a few patients with psoriasis treated with PUVA. This prospective clinical trial did not have a control population, and therefore, the conclusion that PUVA can cause melanoma is tentative.

Treatment of pyogenic granulomas with the 585 nm pulsed dye laser.

BACKGROUND: Current therapeutic alternatives for pyogenic granulomas include surgical excision, electrodesiccation and curettage, cryotherapy, and ablation with CO2 or continuous-wave vascular lasers. OBJECTIVE: Our purpose was to investigate the use of the 585 nm flashlamp-pumped pulsed dye laser (585 nm PDL) for the treatment of pyogenic granulomas in terms of efficacy, advantages in technique, and side effects. METHODS: Eighteen patients with symptomatic pyogenic granulomas in a variety of locations were treated with the 585 nm PDL and examined. RESULTS: Sixteen of 18 treated patients demonstrated both symptomatic and clinical clearing of the lesions with excellent cosmetic results after treatment. The two patients who dropped out after one to two 585 nm PDL treatments were eventually treated successfully with electrodesiccation and curettage. No postoperative complications and no persistent pigmentary changes or scarring were observed. The procedure required no anesthesia, and postoperative care was limited to the application of a topical antibiotic ointment. CONCLUSION: Our experience suggests that treatment of pyogenic granulomas with the 585 nm PDL is a safe, effective, and reasonable alternative to conventional therapy.

Induction of Darier-White disease with UVB radiation in a clinically photo-insensitive patient.

Combination UVA/UVB radiation and UVB radiation alone have been shown to induce the lesions of Darier-White disease. However, 6% of patients with Darier-White disease claim that sunlight ameliorates their condition. We performed an unblinded, side-by-side controlled trial of UVB, UVA, and combination UVB/UVA phototherapy in a patient with historically photoameliorated Darier-White disease to determine whether phototherapy was beneficial, to determine whether phototherapy-related heat was detrimental, and to confirm, with appropriate controls, the action spectrum of the disease. Phototherapy with radiation in the UVB but not UVA spectrum evoked Darier-White disease in this patient, both clinically and histologically. UVB radiation was capable of inducing Darier-White disease in vivo in spite of a history of photoamelioration, whereas UVA radiation alone and the heat associated with phototherapy in our protocol had no effect on the disease.

Treatment of telangiectases and other benign vascular lesions with the 577 nm pulsed dye laser.

BACKGROUND: This study was undertaken to evaluate the effectiveness and safety of the 577 nm pulsed dye laser in the treatment of various vascular lesions of the face. OBJECTIVE: Our purpose was to make observations on the effects of different variables that could affect response. METHODS: Ninety-two adults with telangiectases of the face were sequentially selected for treatment according to a protocol previously established. Evaluation consisted of visual inspection by two investigators, and before and after photographs at 2-months intervals. A few patients with other vascular lesions were also treated and reported. RESULTS: Ninety-one percent of the patients (84 of 92) showed good to excellent response after a single treatment. Recurrence occurred in 2%. Atrophy of the skin occurred in 2%. Venous lakes, pyogenic granulomas, and mucosal vascular malformations showed significant improvement. CONCLUSION: The 577 nm pulsed dye laser is effective and safe for vascular lesions of the face.

Role of ultraviolet A in phototherapy for psoriasis.

Multiple studies have demonstrated that the doses of ultraviolet A (UVA) (320-400 nm) achieved with ultraviolet sources presently used for phototherapy for psoriasis are inadequate to induce coal tar phototoxicity (as manifested by delayed erythema). Some centers still use a phototherapy protocol that combines UVA, ultraviolet B (UVB), and tar for the treatment of generalized psoriasis. We designed a bilateral comparison study to determine whether the addition of UVA to one side, in doses sufficient to induce an immediate burning or smarting sensation in tar-treated skin, would add to the beneficial effects of UVB. The psoriasis of ten of thirteen ambulatory patients cleared in a mean of 26.1 treatments. Despite a mean cumulative UVA dose of 130.8 joules/cm2, none of the thirteen patients showed a better response on the side that received additional UVA. A "nonaggressive" inpatient protocol was designed to maximize the chances of demonstrating a beneficial effect of UVA. The psoriasis of eight of twelve patients cleared in a mean of 21.0 treatments. Despite a mean cumulative UVA dose of 40.3 joules/cm2, the twelve patients showed no difference in clearing between sides. The threshold for smarting increased throughout the treatment and provided a convenient guide to the delivery of increasing doses of UVA. In doses sufficient to induce coal tar phototoxicity manifested by the smarting reaction, UVA does not add to the known benefits of UVB phototherapy.

Skin typing for assessment of skin cancer risk and acute response to UV-B and oral methoxsalen photochemotherapy.

Skin typing is a clinical classification system based on a patient's historical reporting of the acute skin response to sunlight. It is advocated as a means of determining an individual's relative risk of skin tumors and has been used to determine the initial therapeutic dose of UV radiation for UV-B phototherapy or oral methoxsalen photochemotherapy (PUVA) for psoriasis. Among PUVA-treated patients, the relative risk of cutaneous carcinoma was significantly higher among patients with skin types I and II compared with patients with skin type IV (3.2 and 2.3, respectively). Skin type was a better predictor of this risk than eye or hair color. The minimal erythemal dose ( MErD ) and minimal phototoxic dose (MPD) increased with increasing skin type number, but within a given skin type each varied as much as sixfold. Skin type was a good clinical predictor of skin cancer risk, but lacked specificity as a predictor of an individual's MErD or MPD.

Combined methotrexate--ultraviolet B therapy in the treatment of psoriasis.

Twenty-six patients with extensive psoriasis were treated with a 3-week course of methotrexate followed by a combination of ultraviolet B (UVB) therapy and methotrexate. A plaque of psoriasis was shielded during UV therapy to serve as a control. When lesions cleared to less than 5% of body involvement, the methotrexate was stopped and UVB therapy alone was used as maintenance therapy. This protocol achieved clearance of disease in all twenty-six patients in a mean of 7 (+/- 1.5) weeks, with twelve (+/- 4.0) exposures to UVB therapy and a final UVB radiation dose at clearance of 320 (+/- 157) mjoules/cm2. The mean total dose of methotrexate was 112 mg (range, 75 mg-165 mg). At the time of clearing, the shielded area had a decrease in sealing and thickness in twenty-two patients but was free of psoriasis in only four patients. In a preliminary study we were unable to reproduce a methotrexate recall of UV-induced erythema. The combination therapy of methotrexate and UVB allows for clearing of psoriasis at relatively low doses of UVB and methotrexate, and thus may reduce the long-term cumulative toxicity of both agents.

Solar urticaria: treatment with PUVA and mediator inhibitors.

Several therapeutic regimes for solar urticaria were evaluated. A short course of PUVA therapy produced a marked increase in the minimal dose of radiation required to produce urticaria in the six patients treated. This objective evidence of improvement was supported by the patients' reports of greatly increased tolerance to sun-exposure. Chlorpheniramine, an antihistamine, produced a slight increase in the minimal dose of radiation necessary to produce urticaria but its effectiveness was limited by side-effects. Indomethacin, an inhibitor of prostaglandin synthetase, produced no beneficial effect.

Combined methotrexate-PUVA therapy in the treatment of psoriasis.

Thirty patients with psoriasis were treated with a 3-week course of methotrexate followed by a combination of PUVA therapy and methotrexate. When lesions cleared to less than 1% UVA-exposed body involvement, the methotrexate was stopped and PUVA therapy alone was used as maintenance therapy. This protocol achieved clearance of disease in twenty-eight of the thirty patients in a mean of 5.7 (+/- 1.0) weeks, with 9.3 (+/- 3.0) exposures to PUVA therapy and a final UVA radiation dose at clearance of 6.2 (+/- 2.5) J/cm2. The mean total dose of methotrexate was 93.0 mg (range, 67.5-127.5 mg). The only significant adverse effect seen was prolonged phototoxicity in eight patients. By reducing the total cumulative exposure dose of PUVA therapy, this treatment may reduce long-term side effects.