Infrared-monitored cold response in the assessment of Raynaud's phenomenon.

BACKGROUND: Evaluation of treatments for Raynaud's phenomenon (RP) requires objective response parameters in addition to clinical activity scores. Thermographic monitoring of fingertip re-warming after cold challenge has been widely used but usually requires sophisticated equipment. We have previously shown that fingertip re-warming after cold challenge follows a first-order transient response curve that can be described by a single variable, designated tau. OBJECTIVES: Here, we describe a novel device termed a duosensor, which records the tau value upon cold challenge in an automated manner. METHODS: We determined tau values in healthy probands, patients with primary or secondary RP associated with autoimmune disease and patients with scleroderma-associated RP following cold challenge, to determine assay variability, sensitivity and specificity. RESULTS: Duosensor-based thermography exhibited low intraindividual variability in healthy probands. As expected, tau values in RP patients were significantly increased compared with controls (8.08 +/- 3.65 min vs. 3.23 +/- 1.65 min). The duosensor-determined tau value yielded a specificity of 94.6% and predictive value of 95.3% for the presence of RP in a retrospective analysis of 139 patients. Furthermore, in a cohort of scleroderma patients with RP, patient self-assessment of RP severity correlated with tau values. CONCLUSIONS: Taken together, the present data suggest that tau value determination provides a suitable outcome measure for clinical studies of novel RP treatments. As the duosensor is a simple stand-alone device requiring no supporting equipment and minimal personnel attention, it should allow RP activity monitoring even in clinical settings with minimal technical infrastructure.

Dermatomyositis: comparative studies of cutaneous photosensitivity in lupus erythematosus and normal subjects.

PURPOSE: Cutaneous features of dermatomyositis (DM) strongly suggest that ultraviolet (UV) radiation plays an important role in the pathogenesis of the disease. However, the incidence and the nature of photosensitivity in this disorder have not been established. The aim of this study was to investigate the UVB (290-320 nm) minimal erythema dose (MED) in DM patients in comparison with those in lupus erythematosus (LE) and healthy controls. METHODS: Non-irradiated back skin of 75 Caucasians with skin types II and III according to the Fitzpatrick classification were present in three different subject groups and tested for photomanifestation on non-irradiated suprascapular back skin with an ETG-1 Erythemtester. The first group included 19 DM patients, the second 30 patients with LE, and the third 26 healthy control volunteers. The MEDs were determined 24 h after irradiation adjusted according to skin type. RESULTS: Nine of the 19 DM patients (47.4%) demonstrated reduced MEDs to UVB radiation. Seven DM patients (36.8%) had a history of increased cutaneous photosensitivity and four of these (21.1%) reported diseased aggravation after sun exposure. Both the DM and LE patient groups showed reduced MED to UVB radiation (P<0.05) compared with the control group (19.2%). Increased erythemal sensitivity to UVB irradiation was found more frequently in patients with systemic LE and cutaneous discoid LE, than in those with subacute cutaneous LE. CONCLUSION: DM patients, similar to those with LE, showed a significantly reduced MED to UVB irradiation compared with healthy persons.

Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study.

BACKGROUND: Actinic keratoses (AKs) are the most common premalignant tumors. Without treatment, a significant number of patients with AK will experience squamous cell carcinoma. Photodynamic therapy (PDT) using the new highly selective photosensitizer methyl 5-aminolevulinate is a promising new treatment modality for AK. OBJECTIVE: We investigated the complete response rates, cosmetic outcome, and patient satisfaction after photodynamic therapy (PDT) using methyl 5-aminolevulinate (Metvix) versus cryotherapy in the treatment of AKs. METHODS: Patients were randomized to receive either cryotherapy with liquid nitrogen spray or PDT using methyl 5-aminolevulinate cream 160 mg/g, 3 hours application time, and red light (75 J/cm(2)). RESULTS: Efficacy results from 193 patients with 699 lesions (92% face/scalp and 93% thin/moderately thick) were analyzed. Overall complete response rates after 3 months were 69% for PDT and 75% for cryotherapy. Both treatments gave higher response rates in thin lesions (PDT 75%, cryotherapy 80%). PDT gave better cosmetic results and higher patient satisfaction than cryotherapy. CONCLUSION: PDT using methyl 5-aminolevulinate is an attractive treatment option for patients with AK, with a response rate similar to that of cryotherapy, but with superior cosmetic results and high patient satisfaction.

Cyclosporine in severe psoriasis. Results of a meta-analysis in 579 patients.

OBJECTIVE: A meta-analysis of 3 major German studies conducted between 1989 and 1994 with cyclosporine in severe psoriasis was performed to allow an integrated evaluation of the efficacy and tolerability of cyclosporine in this indication. DESIGN AND SETTING: All 3 studies were prospective, randomized, parallel group studies. The studies were conducted in 61 dermatologic centers in Germany. PATIENTS AND INTERVENTIONS: The studies involved 597 patients with severe plaque type psoriasis. Treatment consisted of cyclosporine (at a dosage of 1.25, 2.5 or 5 mg/kg/day), etretinate (at a mean daily dose of 0.53 mg/kg/day) or placebo in a total of 756 treatment cycles with a maximum duration of 12 weeks. MAIN OUTCOME MEASURES: The main outcome measures were the psoriasis area and severity index (PASI) and serum creatinine level. RESULTS: The meta-analysis revealed that cyclosporine given in a dosage of 2.5 and 5 mg/kg/day was significantly superior to etretinate. In addition cyclosporine 1.25 mg/kg/day proved to be significantly more effective than placebo. An increase in serum creatinine level that required intervention occurred in 3.4% of cyclosporine treatment cycles. CONCLUSION: Cyclosporine is highly effective and well tolerated in the short term treatment of severe psoriasis.

Synthesis and biological activities of an alpha-methyl and a beta-methyl carbapenem and the corresponding unsubstituted compound.

The carbapenem potassium salts 4, 7 and 8 were prepared. Their rates of beta-lactam hydrolysis and their biological activities, particularly their beta-lactamase inhibiting properties, were examined and explained on the basis of their different substitution and pyramidality.

[Optical radiation and its effect on the skin]. / Optische Strahlung und ihre Wirkungen auf die Haut.

Optical radiation ranges from short wave ultraviolet via visible light to the far infra-red. Both natural and artificial light sources may cause desired and undesired effects, both on the skin and on the organism as a whole. The nature and extent of such effects depend primarily on the energy of the photons, the absorption capacity of the chromophores, the mean depth of penetration, and on the density and dose of the radiation. The present paper discusses the mechanisms of action and desired and undesired effects in the organism, including therapeutic applications, separately for ultraviolet radiation, visible light and infrared radiation.

Determination of the horny layer profile by tape stripping in combination with optical spectroscopy in the visible range as a prerequisite to quantify percutaneous absorption.

A new method was developed to determine the horny layer profile of volunteers using tape stripping in combination with UV/visible spectroscopy. The optical absorbance and the weight of corneocyte aggregates were compared as parameters for the determination of the mass of the horny layer particles fixed to the individual tapes. It was shown that the potential disturbances influencing both parameters must be considered critically before calculating the correlation factor, found as R2mean = 0.93 +/- 0.05. It was proven that the absorbance in the visible range is better suited than the weight to quantify the amount of corneocyte aggregates removed by a single strip. The new method allows an exact anatomical localization of the individual tapes and all data obtained within the depth profile of the stratum corneum. This was exemplified by the determination of the penetration of chemical and physical UV filters into the horny layer.

High-dose UVA1 therapy for atopic dermatitis: results of a multicenter trial.

BACKGROUND: The results of an open, single-center study suggested that phototherapy with high doses of UVA1 radiation (UVA1R; 340-400 nm) is effective for acute, severe exacerbations of atopic dermatitis (AD). OBJECTIVE: The purpose of this study was to assess the effectiveness of high-dose UVA1 phototherapy for acute, severe AD in a randomized multicenter trial in direct comparison with topical glucocorticoid therapy. METHODS: Patients were treated with high-dose UVA1R (10 days, 130 J/cm2/day; n = 20), topically with fluocortolone (10 days, 1 x daily; n = 17), or with UVA-UVB therapy (10 days, 1 x daily, minimal erythema dose-dependent; n = 16). RESULTS: With a clinical scoring system, significant differences in favor of high-dose UVA1R and fluocortolone therapy were observed (p < 0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was superior to fluocortolone (p < 0.002) therapy. Serum levels of eosinophil cationic protein and the blood eosinophil count were significantly reduced after high-dose UVA1 or fluocortolone, but not UVA-UVB therapy. CONCLUSION: This study confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for treatment of severe exacerbations of AD.

Low-dose (1.25 mg/kg) cyclosporin A: treatment of psoriasis and investigation of the influence on lipid profile.

This study was designed to investigate the therapeutical efficacy of a comparatively low dose cyclosporin A (1.25 mg/kg/day) in the treatment of psoriasis and to assess the influence of cyclosporin A on lipid profiles. In the first, double-blind part of the study, 133 patients with moderate to severe psoriasis were randomized to receive a daily dose of 1.25 or 2.5 mg cyclosporin A/kg or placebo for a period of 10 weeks (period I). Subsequently, the patients entered a second open-label 12-week study (period II), in which the dosage could be increased up to 5.0 mg/kg/day. This was followed by a period of 4 weeks without treatment. After 10 weeks the percentage improvement from baseline in the Psoriasis Area and Severity Index (PASI) was 5.9% on placebo, 27.2% on 1.25 mg/kg/day and 51.0% on 2.5 mg/kg/day cyclosporin A. The final average dose at the end of study period II was 2.99 mg cyclosporin A/kg/day. At this time the PASI was reduced by at least 75% in 63.0% of the patients. From this group of good responders no patient relapsed (PASI > 50% of baseline) during the four weeks after termination of active treatment. No significant effects of the drug on the lipid profiles were detected. We conclude that 1.25 mg cyclosporin A/kg/day is superior to placebo in the treatment of psoriasis vulgaris and that a dose reduction to 1.25 mg/kg/day should be considered in patients responding well to a conventional dose between 2.5 and 5.0 cyclosporin A/kg/day.

Efficacy and tolerability of multiple-dose SDZ IMM 125 in patients with severe psoriasis.

Although cyclosporin is effective in immunosuppression following organ transplantation and in the treatment of psoriasis, its use is limited by its side-effects, notably impaired renal function and hypertension. As SDZ IMM 125, a new derivative of the cyclosporin family, showed considerable immunosuppressive activity in experimental studies, with less effect on renal function, it was considered a potential successor to cyclosporin for both indications. In this multicentre, double-blind, placebo-controlled study, the efficacy and tolerability of 40, 100, 200 and 400 mg SDZ IMM 125 daily were studied in 59 patients with psoriasis. Patients were followed for a period of 5 weeks (4 weeks treatment, and 1 week post-treatment observation). A dose-dependent effect of SDZ IMM 125 was observed. A significant correlation was found between the dose of SDZ IMM 125 and changes in the sum of severity scores of three indicator plaques. There was a significant decrease in the body surface area affected by psoriasis in the 400-mg group (P < or = 0.01), whereas a decrease of the global psoriasis severity was observed in the 200-mg (P < or = 0.01) and the 400-mg groups (P < or = 0.001). No serious adverse events occurred during the 4 weeks of treatment. Three patients discontinued treatment because of adverse events (one sore throat, two influenza). Clinical adverse events were similar to those reported with cyclosporin, the most frequent being gastrointestinal disturbances. Estimation of renal function indices showed that increases from baseline values were dose-dependent, and appeared to be similar to those seen with cyclosporin.(ABSTRACT TRUNCATED AT 250 WORDS)

[UV-A-1 therapy of subacute cutaneous lupus erythematosus]. / UV-A-1-Therapie bei subakut-kutanem Lupus erythematodes.

Because of relative contraindications to corticosteroid or immunosuppressive treatment, a 71-year-old female patient with subacute cutaneous lupus erythematosus underwent serial whole-body irradiation with extremely long-wave ultraviolet light (UVA-1). The cumulative dosage was 186.1 J/cm2 within 9 weeks. Impressive improvement was achieved with some delay.

Studies on the effects of a high dose UVA-1 radiation therapy on surface markers and function of epidermal Langerhans cells.

Recently, high-dose UVA-1 therapy (340-400 nm) was introduced as an effective treatment of severe exacerbated atopic dermatitis. Since the target of this type of radiation in the skin is not known we investigated using the mouse model whether surface markers of the antigen-presenting function of epidermal Langerhans cells are affected by UVA-1 radiation. Even repeated high doses of UVA-1 radiation (up to 50 J/cm2) had no detectable effect on surface ATPase activity and Ia antigen expression on Langerhans cells. Also, the contact allergen oxazolone was presented normally in skin treated with UVA-1 radiation. In contrast, if the mice were injected 1 h before irradiation with 8-methoxypsoralen a dramatic reduction in ATPase activity and Ia antigen expression on Langerhans cells was observed and the induction of contact sensitivity was suppressed (PUVA effect). These results show that epidermal Langerhans cells are not impaired either in structure or function and that these cells probably do not represent the primary target of UVA-1 radiation in the skin. No side effects resulting from a diminished Langerhans cell function should result from high-dose UVA-1 therapy.

Effects of a multiple mild infra-red-A induced hyperthermia on central and peripheral pulse waves in hypertensive patients.

The paper reports on the effects of multiple whole-body infra-red-A irradiational (IRA) on 13 male patients known to have stage I or stage II essential arterial hypertension (WHO definition). The peripheral blood pressure was decreased significantly by IRA exposures. The lowered diastolic blood pressure lasted into posttreatment time. This effect is regarded as a consequence of an improvement in peripheral haemodynamics. A measure of this improvement is the different shape of the blood pressure pulse waves. Calculation and comparison of the spectral components of the recorded pulse signals show that these components are useful for a prediction of the blood pressure lowering effect.

[The cytotoxic effect of anti-Ro- (SS-A) antibodies and UVA light on human endothelial cells in vitro]. / Zytotoxische Wirkung von Anti-Ro- (SS-A-) Antikörpern und UVA-Licht auf menschliche Endothelzellen in vitro.

There is in photosensitive lupus erythematosus a strong association of high titers of anti-Ro(SS-A) antibodies in the serum of the patient with the development of special skin reactions depending on UV-light. The aim of our experiments was to detect a cytotoxic effect of anti-Ro(SS-A) antibodies and UVA-light on human endothelial cells in vitro (standard trypan blue exclusion test, SEM). After UVA-doses of 1 to 100 J/cm2, which were tested, and influence of serum containing anti-Ro(SS-A) antibodies (62 E, ELISA) membrane destructions of endothelial cells depending on the UVA-dose can be seen, irrespective of the fact whether the antibodies are present throughout the irradiation or added afterwards. This cytotoxic reaction depends on complement. A UVA-dose of 100 J/cm2 causes lethal damage of 40% of the cells. These results were confirmed by scanning electron microscopy.

[Systemic effects of ultraviolet, visible and infrared radiation in serial whole body irradiation. II. Effect on the immune cells of the skin]. / Systemische Effekte der Ultraviolett-, sichtbaren bzw. Infrarot-Strahlung bei seriellen Ganzkörperbestrahlungen. II. Der Einfluss auf die Immunzellen der Haut.

Before and after skin treatment by ultraviolet radiation, infrared radiation or visible light the ability of polymorphonuclear leukocytes (PMN) to form oxygen intermediates was investigated in 31 healthy volunteers. Superoxide production was evaluated photometrically as the reduction of Iodonitrotetrazoliumchloride (INT). After whole body treatment by 4 UV exposures all persons exhibited significantly enhanced rates of INT-reduction for 26-62 days. The in vivo half-time of PMN is 5-7 hours. Therefore a direct effect of irradiation over that long period is rather unlikely, suggesting that mediators should play a crucial role in signal transduction from the skin to the peripheral blood cells. Most likely candidates for connective links are interferon-gamma (IFN-gamma), granulocyte-monocyte colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF).

Hydroxyl radical scavenging and antipsoriatic activity of benzoic acid derivatives.

The hydroxyl radical scavenging and antipsoriatic activity of a number of lipophilic and hydrophilic benzoic acid derivatives was investigated. To quantify antioxidative effects, a newly introduced test system based on the diminution of the ESR signal of DMPO-OH (generated by Fenton's reagent) by the tested compounds was applied. It was found that the in vitro antioxidative (toward hydroxyl radical) activity of benzoic acid esters decreases with increasing chain length whereas the antipsoriatic activity increases. This effect is discussed in terms of a larger lipophilicity of long-chain esters. Propyl gallate was found to be the most active OH scavenger since it is some orders of magnitude more efficient than "model" antioxidants like alpha-tocopherol or mannitol. The highest antipsoriatic activity was exhibited by hydroxy benzoic acid decyl ester.