[Problems posed by the therapeutic use of photosensitizers in dermatology]. / Problèmes posés par l'utilisation thérapeutique des photosensibilisateurs en dermatologie.

Three phototherapeutic regimens with photosensitization are now used in dermatology: PUVA (psoralen + UVA), TUV (crude coaltar + UV), PRT (phototherapy with hematoporphyrin derivative). The efficiency of PUVA and TUV is well known in several dermatoses. PRT is now being tested experimentally. For TUV, the lack of a standardized regimen does not allow a clear-cut evaluation of the therapy. For PUVA, late side-effects, particularly carcinogenicity have to be considered. To improve efficiency and minimize the side-effects of PUVA some procedures, such as association with retinoïds, pharmaco-kinetic studies for individual adaptation of the therapeutic regimen and the use of new less mutagenic psoralens are helpful. The persistent phototoxicity following treatments with hematoporphyrin derivative constitutes the major side-effect observed, for this phototherapy.

Does manganese protect cultured human skin fibroblasts against oxidative injury by UVA, dithranol and hydrogen peroxide?

Reactive oxygen species (ROS) are involved in the mechanism of photoaging and carcinogenesis. Skin is endowed with antioxidant enzymes including superoxide dismutases (SOD): cytosolic copper zinc SOD and mitochondrial manganese SOD. The aim of our study was to estimate the protective effect of manganese against oxidative injury on cultured human skin fibroblasts. Dithranol, hydrogen peroxide and UV-A radiation (375 nm) were employed as oxidative stressors. The supply of manganese chloride produced an increase in cellular content of this element up to 24 fold without concomitant elevation of MnSOD activity. Nevertheless, manganese protects cells against two of the three ROS generating systems assessed, namely hydrogen peroxyde and UV-A. This protective effect depends on the concentration of manganese in the medium, 0.1 mM and 0.2 mM protect against UVA cytotoxicity, only 0.2 mM protects against H2O2 cytotoxicity.

Protective effect of selenium and zinc on UV-A damage in human skin fibroblasts.

Ultraviolet A radiation participates in cytotoxicity and carcinogenesis of the skin by a mechanism involving the generation of reactive oxygen species. Endogenous antiradical defense systems utilize metalloenzymes including Se-dependent glutathione peroxidase and Cu and Zn superoxide dismutase. The aim of the present work was to determine the protective effect of two trace elements, Se and Zn, on cultured human diploid fibroblasts exposed to UV-A radiation (broad-spectrum source with a maximum intensity at 375 nm). Selenium in the culture medium (0.1 mg/L) in the form of sodium selenite increased the synthesis and activity of glutathione peroxidase by 60.5% in the absence of exposure to UV-A radiation and by 35% after irradiation with 5 J/cm2 (P = 0.043). The presence of this element significantly increased the survival of UV-A-irradiated fibroblasts (P < 0.0001). This confirms the essential role of Se in the detoxifying activity of the enzyme. In addition, thiobarbituric acid-reacting substances (TBAR), which are lipid peroxidation markers, decreased in the presence of exogenous Se: -19% and -22% without irradiation and after irradiation with 5 J/cm2 (P = 0.056). When Zn was added at the dose of 6.5 mg/L as ZnCl2, fibroblasts subjected to oxidizing stress induced by UV-A were protected from cytotoxicity (P < 0.0001). The TBAR production decreased significantly: -33% without irradiation and -34% after irradiation with 5 J/cm2 (P = 0.008). Superoxide dismutase activity, however, decreased after supplementing with Zn: -26% without irradiation and -20% after UV-A irradiation (P = 0.017). The antioxidant properties of Zn are thus apparently independent of superoxide dismutase activity.

Statistical study of individual variations in sunburn sensitivity in 303 volunteers without photodermatosis.

Variations in individual sunburn sensitivity have been studied using erythema as the photobiologic criterion. The minimal erythema dose (MED), the minimal dose necessary to elicit an intense erythema (MED++), and an edema (MOD), were determined by Saidman's method. The irradiation was performed with a 2,500-W xenon arc solar simulator fitted with a water filter and WG 305 Schott filter. The high correlation between MED, MED++, and MOD and the existence of saturation phenomenon confirm that determination of MED is the best photobiologic criterion. The average MED and the pathologic threshold for total light spectrum irradiation are, respectively, 889 mJ/cm2 and 347 mJ/cm2. A statistically significant variation in MED as a function of age, sex, complexion, eye color, hair color, and Fitzpatrick skin type has been established. Finally, complexion has been shown to be the best clinical criterion for the characterization of sunburn sensitivity and a new classification of the epidermis for UV therapy and artificial photoprotection is proposed.

Intra-uterine device failure: relation with drug use.

A case-control study was undertaken in order to test the relationship between commonly used anti-inflammatory agents and the efficacy of intra-uterine devices (IUDs). Women who had become pregnant while wearing an IUD were compared with non-pregnant IUD users. 717 cases and 717 controls were recruited from the same medical practices. The case-women (IUD failure) used anti-inflammatory drugs, particularly aspirin, more frequently than the controls (p less than 0.001). In contrast, oral progestins, taken in the second part of the cycle (16th to 25th day) were more frequently used by the control-women group (p less than 0.001). Although cases and controls differed in age and gravidity (younger and higher, respectively) standardization for these items did not change the findings for drug use.

PIP: A retrospective case-control study examining medication incidence in women with failure of IUDs was conducted by questionnaires mailed to French physicians. Doctors who entered their patients in the study were self-selected in response to extensive advertising, and knew the nature of the hypothesis being tested. 228 physicians and 35 hospital obstetrics and gynecology departments provided 717 cases and 717 controls. The cases differed from controls in age, mean 31.1 vs 34.2 yrs, gravidity, 2.9 vs 2.4, and births, 2.1 vs. 2.0, respectively. Also, Multiload Cu 250 was used more often by failures and ML Cu 375 more often by controls. Cases took medication more often than controls, 46.5% vs 40.8%. Anti-inflammatory drugs, antibiotics and hormones, particularly progestins, were the individual drugs that differed significantly (p0.001). Aspirin remained significant for the failure group even after dissociation. Potential bias due to lack of blinding and selective recall was discussed.

[Systemic mastocytosis: incidence and risks of vasomotor seizures]. / Mastocytose systémique: fréquence et risques des crises vasomotrices.

We report on 9 cases of systemic mastocytosis which underline the frequency and the potential severity of this disease. All patients had intercritical signs (usually urticaria). Seven patients had also typical crises with flush and vascular collapses are observed together, doctors should measure histamine blood level and perform correct biopsy.

[Cutaneous argyria: an electron microscopic study of four eases with microanalysis X study of one case (author's transl)]. / Etude en microscopie électronique et en microanalyse X de 4 cas.

This study was done in order to follow the fate of silver in the dermis of chronic argyria. Silver was easily recognizable in the tissue as irregular aggregates of elementary granules round or ovoid in shape, ranging from 30 to 40 mm in size. The microanalysis X showed that the metal was bound with sulfur. In the cases of recent intoxication, the main location of silver was intracellular: the granules were found in the lysosomes as elementary particle or as dense heterogen bodies. In the cases where intoxication had been stopped a long time ago, silver was found either on fibrillar component of the connective tissue or in the basal material of sweat glands. The results show that silver is at first phagocytized by macrophages but this cell is unable to perform complete degradation of the silver salt or metal. Then silver is found on connective fibers where it remains on sulfated glycoproteins.

[Cutaneous symptoms of carcinoid tumours of the small bowel (author's transl)]. / Les manifestations cutanées des carcinoïdes du grêle.

Cutaneous symptoms of carcinoid tumours are classified in 4 groups: --Acute type: flusch and vasomotor signs (the caracters of which are described). --Chronic type: telangiectasia, hyperpigmentation, sclerodermia-like, cutaneous maetastasis. --Rare type with non-diagnostic sign. --Types in association with other dermatological conditions either unrelated disease or with a likely related disease such as phacomatosis. Dermatological diagnosis is generally easy as cutaneous symptoms is concomitant with metastatic tumours and increased levels of serotonin and 5-H.I.A. The carcinoid syndrom may take place in the concept of the tumours of the A.P.U.D. system on clinical, embryological, histological and biochemical basis.

[Persistent light reaction due to phenothiazines in atopic disease (author's transl)]. / Photo-allergie rémanente aux phénothiazines chez l'atopique.

Phototesting has been performed in 6 atopic patients who had been suffering of eczematous lesions on sun exposed areas. MED was always of normal value. Phototest was positive in 2 patients. Above all photopatch-test with chlorpromazine was positive in 5 out of 6 patients, allowing the diagnostic of persistent light reaction. The cause of photosensitivity may be the use of phenothiazin derivatives anti-histaminic drugs. The use of phenothiazin derivatives has to be avoided in the treatment of atopic condition for this reason and because of the potential risk of actinic reticuloid in the course of persistent light reaction.

[Cutaneous symptoms of thrombocytemia (author's transl)]. / Manifestations cutanées des thrombocytémies

By the study of 4 personal cases and a review of the literature, the authors describe the symptoms which may complicate and even reveal an essential thrombocythemia. They are: painful symptoms which indicate a permanent or paroxystic vasculomotor syndrome by their localization and their course: -erythematous lesions of an inflammatory livedo type located on the legs and blue-red reticular spots on the sole of the foot: --occurrence of gangrene on finger ends or of necrotic ulcerations of the legs. Etiological conditions, exploration of primary hemostasis, physiopathology of the troubles are described. As for therapeutics the antiaggregants have a suspensive effect on the symptoms but only the control of the hematological status may allow recovery.

[Influence of retinoids on the bioavailability of methoxy-8-psoralen]. / Influence des rétinoïdes sur la biodisponibilité du méthoxy-8-psoralène.

The retinoid-PUVA combination has been recognized as a satisfactory treatment of psoriasis. The absorption of 8-methoxypsoralen (8-MOP) is subject to wide interindividual variations under the influence of factors that are not yet known with certainty but are independent of age, sex and food taken at the same time as the psoralen. Whether concomitant retinoid administration influences the bioavailability of 8-MOP was considered an interesting question. The pharmacokinetics of 8-MOP were studied and compared in two populations of psoriatic patients: 119 patients treated with PUVA alone (psoralen-ultraviolet A) and 40 patients treated with the etretinate-PUVA combination (RePUVA). 8-MOP was assayed by the modified Ljunggren method 1 h, 1 h 30, 2 h, 2 h 30, 3 h and 4 h after ingestion of 8-MOP. The pharmacokinetic values recorded were: time and peak value of maximum plasma 8-MOP concentration (Tmax, Cmax) and area under the curve of time-related 8-MOP concentrations (AUC). The results obtained were as follows: Tmax PUVA 2 h 02 +/- 53 min RePUVA 1 h 56 +/- 50 min Cmax PUVA 159.12 +/- 88.85 ng/ml RePUVA 163.63 +/- 92.85 ng/ml AUC PUVA 343.33 +/- 211.06 ng*h/ml RePUVA 388.12 +/- 251.03 ng*h/ml Statistical analysis showed no significant difference in pharmacokinetic values between patients on PUVA alone and patients on RePUVA. Taking etretinate therefore does not alter the pharmacokinetics of 8-MOP and should not require any change in PUVA treatment.

[Plasma levels of psoralens after celery ingestion]. / Etude des taux plasmatiques de psoralènes après ingestion de céleri.

Psoralens are photosensitizing substances present in many vegetables, some of which are routinely consumed. These vegetables are responsible for contact phytophotodermatitis, but it was agreed that they did not produce photodermatitis when taken orally. Ljunggren has recently questioned this concept by reporting a case of phototoxic accident which occurred after ingestion of 450 grams of celery roots (Apium graveolens). In a study in healthy volunteers we looked for psoralens in blood and analyzed the cutaneous photosensitivity by the minimal phototoxic doses (MPD) method, after ingestion of celery in large amounts (500 grams and more). Plasma concentrations of psoralens were inexistant in all subjects and at all sampling times, and no phototoxic reaction was detected by MPD. Celery roots, therefore, do not seem to be photosensitizing, even after ingestion in large amounts, but they might increase the risk of phototoxicity in PUVA-therapy. The same applies to fennel and parsnip.

[Value of rheoplethysmographic methods in the etiological diagnosis of leg ulcers]. / Apport des méthodes rhéopléthysmographiques au diagnostic étiologique des ulcères de jambe.

Two recently introduced impedance plethysmographic methods have been used in the etiologic diagnosis of 100 leg ulcers: the occlusive rheoplethysmography (RPO) and the irrigraphy. RPO investigates the venous part of the lower limb circulation and irrigraphy the arterial blood flow. These two quantitative methods associated with Doppler examination of venous system allow to point out the type and the topography of the vascular alterations. The value of rheoplethysmographic methods in etiological leg ulcers investigation is reported.

[Immuno-allergological study on 30 atopic patients (author's transl)]. / Exploration immuno-allergologique de 30 sujets atopiques.

An immuno-allergological study was performed on 30 atopic patients and the data were compared to those of 30 healthy controls. The findings were: --increased level of IgE class immunoglobulins in the atopic patients; --increased frequency of the presence of specific reagin to numerous allergens in the sera of atopics (RAST). The total amount of IgE was related to the presence of numerous and/or strongly positive RAST; --immediate hypersensitivity reaction (IHR) to various allergens and specially house-dust. No well-definite correlation was found between IHR and RAST for the same allergens and between the in vitro determination of allergens and a known history of clinical provocation by these allergens. The frequency of positive IHR was related with high level of total IgE; --decreased frequency of delayed cutaneous hypersensitivity tests and specially of those with candidin extracts. Cutaneous hyporeactivity to natural antigens was in relation with high level of total IgE; --no significant statistical difference was found between the amount of T and B lymphocytes; --increased frequency of HLA-A2 group and decreased frequency of HLA-B7 group.

[Salmonella enteritidis septicemia manifesting as a suppurated thrombophlebitis]. / Thrombophlébite suppurée révélatrice d'une septicémie à Salmonella enteritidis.

BACKGROUND: Non-typloid salmonella can cause septicemia and extradigestive disorders in immunodepressed adults. These frequent diseases can be life-threatening. CASE REPORT: A 76-year-old woman was treated with corticosteroid therapy for 1 year for suppurated thrombophlebitis of the right greater saphenous vein. Weight loss, fever at 41 degrees C and Salmonella enterididis isolated from blood cultures and skin samples led to the diagnosis of septicemia with multiple septic foyers including the venous endothelium and surrounding soft tissue. DISCUSSION: In Western countries, there has been an uprise in the frequency of low-grade salmonella infections by food poisoning usually causing acute diarrhea. S. enterididis can also cause severe infectious syndromes with multiple septic localizations, main in patients with a compromised immune reaction. In our cases, Salmonella enteritidis septecemia was revealed by an unusual situation. In the literature, inaugural signs usually involve the heart or arteries, but our patient had isolated foyers involving the superficial venous network. This is exceptional especially since there was no iatrogenic venous catheter insult. For our patient, favoring factors were the long-term corticosteroid therapy and altered venous network. The portal of entry could not be clearly identified but the discovery of a sigmoid diverticulosis would be an argument favoring a digestive origin. Medical and surgical management with resection of the necrosed tissues and two adapted antibiotics in a long-term regimen led to a successful outcome.

[Candida vasculitis]. / Vascularite à Candida.

Apart from direct skin attacks, yeasts of the Candida group hold a place that is much discussed in the occurrence of immuno-allergic reactions of the skin, because of their usual saprophytic characteristics. We report here on observation of a patient of 62 years who presented with a secondary purpuric maculo-papular eruption making a tri-symptom of Gougerot, for which we have incriminated the role of the immunogenicity of Candida. Skin histology confirmed the presence of an angiitis and necrotising capillarity. An intradermal test with candidine reproduced the skin symptoms and histology, whilst other microbial and fungal tests remained within normal limits. Other examinations showed the transitory presence of circulating immune complexes, although the remainder of the immunity factors were negative. A digestive focus of Candida was present. Recovery occurred after systemic mycological treatment was started, though there was a return of symptoms after a temporary initial check.

[True and false acrocyanoses]. / Vraies et fausses acrocyanoses.

Acrocyanosis is an acrosyndrome frequently found among adolescent or young women. Four clinical symptoms are necessary and sufficient to establish the diagnosis: permanent and painless cyanosis of extremities, local hypothermia, permanent sweatiness, and elastic infiltration of the integument. In practice, only one investigation is useful but not indispensable: capillaroscopy which visualizes capillarovenular stasis. Numerous clinical forms have been described, but they are exceptions, but for supramalleolar erythrocyanosis. Treatment is mainly preventive: protection against cold. Two conditions can be regarded as false acrocyanosis: acrorhigosis and acroiodesis.

[Skin diseases with photosensitivity]. / Dermatoses avec photosensibilité.

Skin diseases associated with photosensitivity are numerous and may be divided into three main groups: photo-aggravated dermatoses, genophotodermatoses and metabolic photodermatoses. Photo-aggravated dermatoses are autonomous skin diseases in which exposure to sunlight may make the disease worse or precipitate its onset and/or its progressiveness; this group includes lupus erythematosus, autoimmune bullous diseases, acantolytic dyskeratoses, acne vulgaris, rosacea and cutaneous lymphoid infiltrates. To these must be added photosensitive forms of autonomous dermatoses such as atopic dermatitis, psoriasis, herpes labialis, erythema multiforme, granuloma and disseminated superficial actinic porokeratosis. Genophotodermatoses are genodermatoses which are made photosensitive by a recognized or as yet unidentified deficiency of the natural photoprotection system. In this group are albinism, vitiligo, xeroderma pigmentosum and poikiloderma. Metabolic photodermatoses are diseases in which photosensitization reactions, often revealing, are due to the accumulation in the skin of an endogenous chromophore as a result of a congenital (porphyria) or acquired (pellagra) enzymatic disorder.

Water recovery in space.

In the absence of recycling, water represents over 90% of the life-support consumables for a manned spacecraft. In addition, over 90% of the waste water generated can be classified as moderately or slightly contaminated (e.g. shower water, condensate from the air-conditioning system, etc.). The ability to recover potable water from moderately contaminated waste water hence enables significant savings to be made in resupply costs. A development model of such a water-recovery system, based on membrane technology has been produced and tested using "real waste water" based on used shower water Results indicate some 95% recovery of potable water meeting ESA standards, with total elimination of microbial contaminants such as bacteria, spores and viruses.

Optimal sensor selection for noisy binary detection in stochastic pooling networks.

Stochastic Pooling Networks (SPNs) are a useful model for understanding and explaining how naturally occurring encoding of stochastic processes can occur in sensor systems ranging from macroscopic social networks to neuron populations and nanoscale electronics. Due to the interaction of nonlinearity, random noise, and redundancy, SPNs support various unexpected emergent features, such as suprathreshold stochastic resonance, but most existing mathematical results are restricted to the simplest case where all sensors in a network are identical. Nevertheless, numerical results on information transmission have shown that in the presence of independent noise, the optimal configuration of a SPN is such that there should be partial heterogeneity in sensor parameters, such that the optimal solution includes clusters of identical sensors, where each cluster has different parameter values. In this paper, we consider a SPN model of a binary hypothesis detection task and show mathematically that the optimal solution for a specific bound on detection performance is also given by clustered heterogeneity, such that measurements made by sensors with identical parameters either should all be excluded from the detection decision or all included. We also derive an algorithm for numerically finding the optimal solution and illustrate its utility with several examples, including a model of parallel sensory neurons with Poisson firing characteristics.