[A case of Orf disease complicated by erythema multiforme]. / Echtyma contagiosum compliqué d'érythème polymorphe : à propos d'un cas.

Ecthyma contagiosum, or Orf, is a specific infection of small ruminants accidentally reaching humans. Few cases have been reported in the literature to date. We report here a case of ecthyma contagiosum occurred in a 9-year-old girl after contact with a flock of ecthyma sheep. This Orf was then complicated by superinfection and then by erythema multiforme. Orf is often underdiagnosed, probably because of small ruminant breeders' knowledge of this disease and its benignity in humans. It is caused by a very resistant Parapoxvirus in the environment. The diagnosis is clinical and anamnestic. Orf is therefore a benign pathology, the course of which is spontaneously favorable outside any specific treatment. However, it is important to prevent certain complications such as superinfections with appropriate local care. Other complications cannot be prevented and require appropriate care.

Ethical Issues in the Development of Readiness Cohorts in Alzheimer's Disease Research.

There is growing interest in the development of novel approaches to secondary prevention trials in Alzheimer's disease to facilitate screening and recruitment of research participants and to reduce the time and costs associated with clinical trials. Several international research collaborations are setting up research infrastructures that link existing research cohorts, studies or patient registries to establish 'trial-ready' or 'readiness' cohorts. From these cohorts, individuals are recruited into clinical trial platforms. In setting up such research infrastructures, researchers must make ethically challenging design decisions in at least three areas: re-contacting participants in existing research studies, obtaining informed consent for participation in a readiness cohort, and disclosure of Alzheimer's disease-related biomarkers. These ethical considerations have been examined by a dedicated workgroup within the European Prevention of Alzheimer's Dementia (EPAD) project, a trans-European longitudinal cohort and adaptive proof-of-concept clinical trial platform. This paper offers recommendations for the ethical management of re-contact, informed consent and risk disclosure which may be of value to other research collaborations in the process of developing readiness cohorts for prevention trials in Alzheimer's disease and other disease areas.

Guidance synthesis. Medical research for and with older people in Europe: proposed ethical guidance for good clinical practice: ethical considerations.

INTRODUCTION: In Europe the population is ageing rapidly. Older people are taking many medicinal products daily and these may not necessarily be suitable for them. Publications show that older patients are underrepresented in clinical trials, especially those over 75 years, with multiple co-morbidities, concomitant treatments and/or frailty. This document provides a summary of recommendations on ethical aspects of clinical trials with older people, who may in some cases be considered a vulnerable patient population. The EFGCP's Geriatric Medicine Working Party (GMWP) has developed this guidance to promote such research and to support health care professionals in their efforts. ETHICAL, SCOPE AND CONTEXT: The definition of a geriatric patient is reviewed. Frail and vulnerable patients, who are a minority of geriatric patients, should be included whenever it is relevant. The legal context is described. THE PROCESS OF INFORMED CONSENT: All adults should be presumed capable of consent, unless proven otherwise; informed consent must be sought for all older people who are able to consent. A simple, short and easy-to-understand information sheet and consent form will contribute to improving the readability and understanding of the older participant. A participant guide and the use of a simple tool to ensure decision making capacity, are recommended. Whenever older people are unable to consent, their assent should be sought systematically using adequate information, in addition to seeking the consent of their legal or authorised representative as appropriate. ETHICS COMMITTEES: Research ethics committees need internal and/or external geriatric expertise to balance the benefits and risks of research in older people and to appreciate and recognise their autonomy. DESIGN AND ANALYSES: Design and Analyses should be adapted to the objectives with appropriate outcomes and are not different from other clinical trials. CONCLUSIONS: The absence of proper recruitment or insufficient presence of older patients in clinical development plans for new medicinal products is detrimental; there is a need to improve evidence-based knowledge, understanding and management of their conditions and treatment. The aim of this guidance is to facilitate clinical research for and with the older patient population. The long version of the guidance will be available on the EFGCP's website: www.efgcp.be/.

Effect of niprisan on single oral dose pharmacokinetics of paracetamol in rats.

The single oral dose pharmacokinetics of paracetamol was studied alone and after coadministration with NIPRISAN In rats. Paracetamol concentrations were measured in rat plasma using UV-spectrophotometer and the data were fitted into an open two-compartment pharmacokinetic model using the computer program (STATIS Version 3.0). Results indicated no significant difference in the absorption of paracetamol between study and control groups but a significant reduction (p < 0.05) at some sampling time as the dose of NIPRISAN was increased double-fold. The pharmacokinetic parameters showed only 1.51 and 7.19% reduction in AUC(0-infinity) and Cmax respectively for paracetamol (20 mg/kg) + NIPRISAN (500 mg/kg). It was thus concluded that the gastric presence of NIPRISAN did not significantly reduce the absorption of paracetamol in rats.

Evaporative cooling of ventral regions of the skin in heat-stressed laying hens.

Laying hens held in battery cages in naturally ventilated poultry houses in hot countries usually develop hyperthermia, which adversely affects their performance. The present means of cooling alleviate to some degree, but cannot eliminate, the stress imposed by heat. A new approach to cooling of laying hens was developed, based on wetting the skin and promoting evaporation of water from the ventral regions of the bird. The type of plumage in the ventral regions and the exposed skin of the apteria enable more efficient wetting than is possible with dorsal cooling. A ventral cooling regime, comprising an initial period of frequent wettings followed by intermittent wetting for 10 s every 30 min was able to maintain normothermia of laying hens subjected to a 10-h period of heat exposure. Dorsal cooling was less efficient; body temperature and respiration rate were higher and skin temperatures were lower than in ventrally cooled hens. During 10 d of heat exposure, ventrally cooled hens maintained egg weight and shell index (mg/cm2), whereas their food intake decreased moderately. In contrast, egg weight, shell index, and food intake all decreased markedly in uncooled or dorsally cooled hens. Transient alterations in plasma concentrations of corticosterone, progesterone, and estradiol were noted in uncooled and dorsally cooled hens but not in ventrally cooled hens. Results indicate that ventral cooling is an efficient method to alleviate heat stress in laying hens during summer. Successful implementation of ventral cooling in poultry houses will depend on optimal installation of sprinklers and on minimal wetting of manure.

"Primary" versus "secondary" vulvar vestibulitis: one disease, two variants.

OBJECTIVE: Our aim was to determine whether women with primary vestibulitis-since the first episode of sexual intercourse-differ in disease characteristics and outcome of operative treatment from women with secondary vestibulitis. STUDY DESIGN: A total of 111 patients with severe vulvar vestibulitis underwent perineoplasty from 1991 to 1995. Thirty-nine (35%) of them had primary vestibulitis (ie, dyspareunia from the first attempt at sexual intercourse). They were compared with 72 (65%) who had secondary vestibulitis with regard to demographic, social, and medical variables, the presence of human papillomavirus deoxyribonucleic acid, physical and histopathologic findings in the vestibule, and surgical outcome. RESULTS: Women with primary vestibulitis were 5 years younger than those who had secondary vestibulitis (22.9 +/- 2.9 years vs 27.7 +/- 8.6 years, respectively; P <.0001) and differed in their marital status (unmarried, 84% vs 56%, respectively; P <.008), parity (nulliparous, 97% vs 67%, respectively; P <.0002), and involvement of the whole vestibule (74% vs 93%, respectively; P <.006). The 2 groups were similar in all other variables, including use of oral contraception, smoking, presence of human papillomavirus, dysuria, success of perineoplasty (average, 83%), and histopathologic findings. CONCLUSIONS: Women with primary vestibulitis were younger than women with secondary vestibulitis. Most other differences were dependent on the different ages of the 2 groups. Primary and secondary vestibulitis may therefore be two presentations of the same disease.

[The aging face in Black Africans]. / Senescence faciale chez le Negro-Africain.

The face is the part of the human body that most reflects external marks of time. The change of this region concerns the body support as well as the musculo-cutaneous surface. In this survey, we have described its evolution during the life, in the Black African, particularly on the esthetical plane.

Entry and distribution of fluorescent antiproliferative heparin derivatives into rat vascular smooth muscle cells: comparison between heparin-sensitive and heparin-resistant cultures.

We studied the binding and entry of fluorescein (FITC)-labeled heparin derivatives into rat aortic smooth muscle cells (SMC) by confocal microscopy. FITC-labeled heparin fractions or FITC-labeled SR 80037A, a potent antiproliferative heparin derivative (Bârzu et al., Eur. J. Pharmacol., 219:225-233 1992), were prepared and their antiproliferative activity was confirmed. By incubating SMC with FITC-labeled heparins, a specific cell-associated fluorescence was found. Cellular fluorescence was mostly located around the nucleus and at the level of cell contacts or cell adhesion. The fluorescence was displaced neither by chasing with excess of unlabeled heparins nor by washing with 1 M NaCl, which proved that labeled heparins had been internalized by SMC. Kinetics of internalization of FITC-heparins suggested receptor-mediated endocytosis of heparins by SMC. Double labeling of SMC with biotinylated Concanavalin A and FITC-SR 80037A also indicated that heparin derivative enters the endocytic pathway. The process was accelerated when serum was present in the incubation medium. Treatment of cells with chloroquine (50 microM) induced accumulation of FITC-SR 80037A in the late endosomes, around the nucleus. No fluorescence labeling could be evidenced inside the nucleus. Neither electron microscopy nor cell fractionation experiments performed with SMC previously incubated with [3H]-heparin were able to ascertain nuclear uptake of heparin, as proposed by other workers (Busch et al., Cell Biol., 116:31-42; 1992; Sing et al., Drug Dev. Res., 29:129-136 1993). The cell-associated fluorescence was very weak in SMC resistant to the antiproliferative activity of heparin, selected by long-term heparin treatment (HT-SMC) as previously shown [Bârzu et al., J. Cell. Physiol., 160:239-248, 1994]. The HT-SMC differed from control SMC with regard to expression of extracellular matrix proteins. These cells exhibited very low expression of fibronectin and prevalent expression of laminin and synthesized less cell-associated glycosaminoglycans. From our results, the following conclusions can be drawn: (1) the antiproliferative heparins are bound and internalized by SMC without being taken up into the nucleus; (2) there is a correlation between the binding and/or the internalization process and the sensitivity of SMC to the antiproliferative activity of heparins; and (3) selection of heparin-resistant SMC by long treatment with heparin results in particular growth pattern of SMC (absence of focal overgrowth), associated with changes in the expression of the extracellular matrix components (fibronectin, laminin, and cell-bound glycosaminoglycans).

Interactions between body condition at calving and cooling of dairy cows during lactation in summer.

This study examined the interactions between dietary manipulation for increased body condition during the last trimester of pregnancy (spring) and postpartum cooling (summer lactation). Effects of diet on milk production of Holstein cows were examined to determine whether body stores could compensate for reduced DMI during heat stress. Cows calving between May and July with high (3.8 on a six-point scale) or low (2.7) body condition scores were assigned postpartum to be cooled by sprinkling and ventilation or to serve as uncooled controls. Cooled cows ate 1.6 kg more DM/d and consumed 9 L less of water/d than uncooled cows. Cooled cows maintained body temperatures below 38.9 degrees C during day hours; peak body temperature for uncooled cows was 39.7 degrees C. For 8 wk postpartum, glucose and insulin concentrations in plasma were unaltered by cooling or body condition. The NEFA were lower, and urea was slightly higher, for cows with low body condition. Milk production increased 1.9 kg/d with cooling, fat production increased with both body condition and cooling, and protein production increased with cooling but not with body condition. Performance was lowest for the uncooled subgroup with low body condition. Among cooled cows, no advantage was attributable to high body condition. An additive effect of high body condition and cooling on milk production in summer was not evident.

The complete amino acid sequence of bovine antithrombin (ATIII).

Bovine antithrombin (ATIII) is a glycoprotein of Mr 56,600. Its primary structure was established using peptide sequences from five different digests. Bovine ATIII exhibits four glcosylation sites as well as human ATIII. The primary structures of bovine and human ATIII were compared: all the residues required for the integrity of the heparin-binding domain are strictly conserved. However, there are differences in the secondary structures of both proteins, bovine and human ATIII.

Studies on a highly active anticoagulant fraction of high molecular weight isolated from porcine sodium heparin.

We have studied heparin fractionation using gel filtration and ion-exchange chromatographic methods. The starting material was commercial grade porcine mucosal sodium heparin (PSH). The fractionation was monitored employing synthetic substrates for assaying both antithrombin (with H-D-Phe-Pip-Arg-pNA ; S-2238) and anti-FXa (with Bz-Ileu-Glu-Gly-Arg-pNA ; S-2222) activities. The resulting fractions were evaluated in different amidolytic and coagulation methods used to determine heparin potency by comparison with PSH. By gel filtration of PSH on Ultrogel Aca 54, both strong anti-FXa and antithrombin activities were associated with the fractions eluted in the high molecular weight range (MW congruent to 20 x 10(3)). These fractions also had potent anticoagulant action when assayed by conventional clotting methods. PSH was also subjected to fractionation by an ion-exchange technique (DEAE-Sephacel) with increasing salt molarity. The patterns for antithrombin and anti-FXa activities were again closely related, if not identical. Four fractions were usually distinguished, with respectively negligible, intermediate, high and very high activities when compared to PSH. The very highly active fraction (HAF), approximately 15% by weight, was eluted at high salt molarity (greater than 0.8 M NaCl). On a weight basis its anticoagulant activity was congruent to 2-3 times that of PSH as determined by amidolytic as well as clotting methods. Intravenous injection of HAF to rabbits and dogs (1.0 and 2.5 mg/kg) produced a much stronger anticoagulant response than PSH, also showing an effect which persisted for a longer duration.