[Livedoid vasculopathy secondary to coeliac disease]. / Vasculopathie livédoïde secondaire à une maladie cœliaque.

BACKGROUND: Livedoid vasculopathy (LV) is a painful ulcerative condition involving white atrophy and livedo; a histopathologic feature seen is occlusive dermal vasculopathy. This may be associated with coagulation disorders such as hyperhomocysteinaemia (HHC). PATIENTS AND METHODS: We report the case of a 52-year-old woman presenting LV in which an abnormal scan image led us to diagnose coeliac disease. This enteropathy had caused vitamin B12 and folic acid deficiency, as well as HHC. Vitamin supplementation and a gluten-free diet resulted in complete healing of the lesions. DISCUSSION: This case underlines the importance of screening for and correction of coagulation disorders in patients with LV. It also suggests that in the event of HHC, coeliac disease should be sought, even in the absence of gastrointestinal symptoms.

Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.

Immunogenicity of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria, tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study.

This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap-IPV, Repevax(®); Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis(®); Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap-IPV, Tetravac(®); Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection. All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap-IPV, Tdap+OPV and DTap-IPV, respectively, had protective antitoxin levels greater than 0.1IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV. Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination.

3-amino-3,4-dihydro-2H-1-benzopyran derivatives as 5-HT1A receptor ligands and potential anxiolytic agents. 2. Synthesis and quantitative structure-activity relationship studies of spiro[pyrrolidine- and piperidine-2,3'(2'H)-benzopyrans].

In continuation of our work on 3-amino-3,4-dihydro-2H-1-benzopyran derivatives with high affinity for 5-HT1A receptors, we have prepared rigid spirobenzopyran analogues designed from the pharmacophore models of Mellin and selected via a quantitative structure-activity relationship approach mainly based on similarity indices. A series of spiro[pyrrolidine- and piperidine-2,3'(2'H)-benzopyrans] with various substitutions on the aromatic ring as well as on the extracyclic spiranic nitrogen atom were then synthesized and evaluated for their serotonergic and dopaminergic activities. Good correlation between the predicted and the experimental binding values was observed with an average difference of 0.2 unit on log(IC50). Affinities for the 5-HT1A receptors were in the nanomolar range for the best compounds ((+)-11a,23) with a high selectivity versus other 5-HT (5-HT1B, 5-HT2, 5-HT3) or dopamine (D1, D2) receptor subtypes. As for the 3-amino-3,4-dihydro-2H-1-benzopyran series, the dextrorotatory enantiomer (+)-11a showed better affinity and selectivity for 5-HT1A receptors than its levorotatory analogue (-)-11a. Compound (+)-11a proved in vitro to be a full agonist and in vivo to be active in various comportmental tests predictive of psychotropic activity, such as the forced swim test and the tail suspension test, and is currently under complementary investigations.

Uniqueness of the gaussian kernel for scale-space filtering.

Scale-space filtering constructs hierarchic symbolic signal descriptions by transforming the signal into a continuum of versions of the original signal convolved with a kernal containing a scale or bandwidth parameter. It is shown that the Gaussian probability density function is the only kernel in a broad class for which first-order maxima and minima, respectively, increase and decrease when the bandwidth of the filter is increased. The consequences of this result are explored when the signal¿or its image by a linear differential operator¿is analyzed in terms of zero-crossing contours of the transform in scale-space.

[Idiopathic and secondary Raynaud's phenomenon. A comparative psychosomatic approach]. / Phénomène de raynaud idiopathique et secondaire. Approche psychosomatique comparative.

Thirty subjects with Raynaud's phenomenon admitted for determination of its cause underwent psychological examination. Raynaud's phenomenon was regarded as primary in 14 cases, secondary (usually to scleroderma) in 13 cases and eluding classification in 3 cases. The mean age of patients with primary Raynaud's phenomenon was higher than in the other groups. Interviews and psychological tests were carried out with all but 2 patients and all investigators being totally unaware of the aetiological category. Patients with secondary Raynaud's phenomenon significantly differed from those with primary Raynaud's phenomenon in their personality patterns, attitudes towards interlocutors and way of coping with conflicts. Patients with primary Raynaud's phenomenon were characterized by a relatively frequent hysterical personality and by their dodging behaviour when faced with their own aggressiveness. Patients with secondary Raynaud's phenomenon were found to be more distant, more conformist, more able to control their emotions and seemed to be less inclined to seek help when in trouble. Such findings suggest that Raynaud's phenomenon has a "psychosomatic" component: a psychic vulnerability which might contribute to the progress of the disease, and more clearly so in patients with secondary Raynaud's phenomenon than in patients with primary Raynaud's phenomenon, as confirmed by the so-called psychic fragility" score used to quantify the efficiency of mental functioning. These psychological features were unrelated to age. The profile of patients with secondary Raynaud's phenomenon is close to pattern C described as possibly having a prognostic value in proliferative or autoimmune diseases.

[Psychological consequences in organ transplantations]. / Conséquences psychologiques des transplantations d'organes.

Organ transplantations constitute therapeutic advances for some fatal diseases. Their specificity are: severe prognosis, waiting for an alive donor (kidney or marrow transplantations) or a dead one, uncertainty of results or side effects. Identity troubles, debt towards the donor characterize also transplantations. They realize a traumatic situation difficult to communicate and demand a long working through psychic procedure. We shall describe these patients' defense mechanisms and those of their family and care takers--the psychologist's role in transplantation units.

Teratogenic risk with etretinate and acitretin treatment.

Etretinate (Tigason, Tegison) and its active metabolite acitretin (Neotigason, Soriatane) are known teratogens. Pregnancy should be avoided during treatment and until 2 years after treatment discontinuation. The question is discussed whether a dose or a blood concentration of the drug below which there is no teratogenic risk can be determined. Animal experimental and human pharmacokinetic data are reviewed. An evaluation of the outcomes of pregnancies which occurred in mothers exposed to etretinate or acitretin was performed. A threshold dose in human therapy below which there is no risk of congenital malformation cannot be determined based on animal experimental data. With regard to pharmacokinetics, there are currently no data suggesting that blood levels of the drug below the detection limit of 2 ng/ml are associated with a teratogenic risk. The most useful information is given by reports in women who were exposed to either retinoid before or during pregnancy. The data indicate that the risk of spontaneous abortion or congenital malformation is high when the drug is administered during the first trimester of pregnancy. After treatment discontinuation, the risk is low since the number of abnormalities seems not to exceed those observed in a general population. There are currently no available data which suggest that the pregnancy warnings are inappropriate in terms of duration of contraception.

Inhibitor of the release of mast cell mediators does not improve the psoriatic plaque.

The number of mast cells is increased in psoriatic lesions and this is particularly prominent in their early phase. Mediators released by mast cells may interfere with various aspects of cutaneous inflammation and epidermal proliferation. Therefore, the aim of the present investigation was to find out whether a 4-week treatment period with Tiacrilast, a highly potent inhibitor of mast cell degranulation, might have antipsoriatic potential. A total of 31 patients with plaque-type psoriasis were evaluated after treatment with a 3% Tiacrilast hydrogel and hydrogel alone, in a double-blind, placebo-controlled, within-patient comparative study. No statistically significant improvement of the Tiacrilast-treated plaques compared to the hydrogel-treated sites could be demonstrated. Therefore, the present study does not provide evidence of a potential role of mast cell degranulation in the treatment of psoriasis.

Acitretin in the treatment of severe lichen sclerosus et atrophicus of the vulva: a double-blind, placebo-controlled study.

BACKGROUND: Promising results have been reported from treatment with oral retinoids in patients with severe lichen sclerosus et atrophicus (LSA) of the vulva. OBJECTIVE: The aim of our study was to determine the efficacy of acitretin (20 to 30 mg/day) for 16 weeks in LSA. METHODS: Seventy-eight patients were enrolled into a multicenter, randomized, placebo-controlled, double-blind trial. The primary measure of efficacy was the "responder" rate based on the assessment of characteristic clinical features of LSA of the vulva (pruritus, burning, atrophy, hyperkeratosis, and secondary features such as erosions, ulcers, edema, or lichenification) and on the extent of the lesions. RESULTS: From the 46 patients eligible for efficacy analysis, a significantly higher number of responders was observed in the acitretin-treatment group (14 of 22 patients) as compared with the placebo-treatment group (6 of 24 patients). Typical retinoid adverse reactions were observed in all patients receiving active drug. CONCLUSION: Acitretin is effective in treating women with severe LSA of the vulva.

Topical tiacrilast, a potent mast cell degranulation inhibitor, does not improve adult atopic eczema.

Tiacrilast is a potent mast cell degranulation inhibitor in vitro and in animal studies. Since mast cells and their mediators are possibly involved in atopic eczema, we have studied a topically applied 3% hydrogel formulation of tiacrilast against vehicle in a multicenter, double-blind, placebo-controlled trial. Drug or vehicle were applied on involved skin for 28 days. Efficacy was assessed weekly using a 4-point scale for erythema, scaling, induration, exudation and pruritus. An overall assessment of the sites for efficacy and site preference was performed at the end of treatment. In the 32 patients evaluable for efficacy, > 33% improvement was noted on 78% of the drug- and 75% of the vehicle-treated sites, with no statistically significant differences for any of the parameters tested. Treatment was generally well tolerated by all patients. These data suggest that mast cells may not play a major role in the maintenance of atopic eczema lesions.

Central nervous system involvement in Sjögren's syndrome: evidence from neuropsychological testing and HMPAO-SPECT.

OBJECTIVE: To investigate the clinical, neuropsychological and imaging manifestations of Sjögren's syndrome (SS), a chronic auto-immune disease with peripheral and central nervous system (CNS) involvement. DESIGN/METHODS: Fourteen female patients suffering from confirmed SS underwent within 2 weeks: neurological examination, immunological staging, brain MRI, brain 99m Tc-HMPAO SPECT, psychological evaluation and in-depth neuropsychological testing. RESULTS: All patients showed neuropsychological abnormalities. The cognitive symptoms were of the same type in all patients, mostly frontal lobe syndrome and memory problems. The neuropsychological involvement was not associated with other kinds of CNS involvement or MRI abnormalities, but accurately reflected HMPAO imaging results. CONCLUSIONS: The results of this study indicate that cognitive evaluation is the most sensitive clinical test to diagnose CNS involvement in patients with SS, and that CNS involvement in SS seems to be more frequent when systematically assessed by neuropsychological tests.