Biomedical subjects
Publications and source records attributed to F Piette.
Blau syndrome (MK186580) comprises granulomatous arthritis, iritis, and skin rash, and is an autosomal-dominant trait with variable expressivity. So far it was described in 5 families. We report on a sixth family with severe progression of eye involvement and discuss the nosology with similar diseases, such as early-infantile sarcoidosis.
Senile plaques and neurofibrillary tangles are the markers of Alzheimer's disease. They are also found in old patients who have been considered to be intellectually normal throughout their life, a situation referred to as "physiological aging". The neurofibrillary tangles are made of abnormally phosphorylated tau. The anti-tau antibody labels not only the neurofibrillary tangles, but also the crown of the senile plaques and the neuropil threads interspersed between the cell bodies and the plaques. The senile plaque comprises a core made of A beta peptide surrounded by a neuritic crown. The anti-A beta antibody also labels "diffuse deposits", i.e. ill limited areas of immunoreactivity which lacks the characteristics of the amyloid substance. The intellectual deficit appears to be statistically linked with the density of the tau-positive alterations-tangles, threads and plaque crowns--which usually appear simultaneously in a given cortical area. In the entorhinal area, their density increases proportionally to the intellectual deficit without threshold, suggesting that ageing and disease are a continuum. In the isocortex, the progression of the tau positive alterations is, on the contrary, stepwise--in a "all or none" fashion--from the hippocampus to the primary cortices, through the associative multimodal areas. The tau positive lesions probably progress through connections: they indeed disappear from areas, that have been disconnected by additional lesions (such as infarcts).
OBJECTIVE: Amisulpride is a substituted benzamide neuroleptic, which binds selectively to dopamine D2 and D3 receptors, mainly in the limbic structures. States of delusion and agitation occur frequently in the population aged more than 65 years, especially in demented patients and this sometimes requires the use of neuroleptics. The objectives of this study were to determine the safety and the pharmacokinetic profile of 50 mg of amisulpride administered orally as a single dose to elderly volunteers. METHODS: Twenty healthy volunteers (10 men and 10 women) aged 65 79 years were included in this open trial. Frequent measurements of blood pressure and heart rate were made and ECG and blood samples were performed up to 72 h after drug intake. RESULTS: The overall clinical and cardiovascular safety was satisfactory. The mean Cmax of the racemate amisulpride in elderly people was 64.1+/-6.7 ng ml(-1), and was not different from the value of 56+/-4.1 ng ml(-1) in young subjects. As with the Cmax, the mean values of t1/2 and AUC in elderly people (15.6+/-1.3 h and 667+/-51 ng. ml(-1).h, respectively) were not different to values observed in young subject (respectively 11.7+/-0.5 h and 603+/-25 ng m1(-1) h). CONCLUSION: A single oral dose of amisulpride was well tolerated and showed a similar pharmacokinetic profile in healthy elderly and young subjects. However, these findings should be confirmed after multiple dosing in a larger population in order to establish the lack of need of dosage adjustment in this elderly population.
The clinical-pathological correlations that were prospectively obtained in a cohort of old patients (> 75 years of age) are reviewed. The pathological data were obtained in 31 cases, either normal or affected by Alzheimer disease of various degrees of severity. The density of the A beta peptide deposits was poorly linked with the intellectual status. One patient had a very high density of deposits, although she was considered intellectually normal. When present in a patient, the A beta deposits usually involved all the cortical samples; the samples devoid of deposits most often belonged to the limbic system. The distribution of the neurofibrillary tangles was highly selective: the primary areas (such as the visual cortex) were lesioned only in a few cases, invariably the most severely affected ones. Neurofibrillary tangles involved the associative cortices (sparing the primary areas) in the cases of intermediate severity. The hippocampal-parahippocampal areas contained at least a few neurofibrillary tangles in all the cases. The prevalence of the neurofibrillary lesions in that cohort of cases probably indicated the chronological (and hierarchical) order of involvement: from limbic to associative, from associative to primary areas. There was a linear relationship between the density of the neurofibrillary tangles and the intellectual deficit in the hippocampal-parahippocampal gyrus. The relationship was stepwise rather than linear in the isocortical samples, suggesting that the neurofibrillary tangles were a late phenomenon in those types of cortices. An accumulation of SNAP 25 immunoreactivity was found in some of the most severely affected cases, pointing to a deficit in axonal transport. The density and the total number of neurons were evaluated in a sample of the supramarginal gyrus. The neuronal loss was found to be severe, but only in the most affected cases, when the density of neurofibrillary tangles was higher than 5/mm2.
BACKGROUND: Pyostomatitis-pyodermatitis vegetans is an uncommon condition associated with chronic inflammatory bowel disease in 75% of the cases, usually hemorrhagic rectocolitis. CASE REPORT: A 48-year-old man was referred for recent development of pustulous lesions of the lips and buccal mucosa and weight loss. He complained of abdominal pain and intermittent diarrhea which had persisted for more than one year. During the last three months, a pseudotumoral plaque with a pustulous rim had developed over the two distal phalanxes of the right middle finger in association with ungueal lysis and nodular, vegetating and crusted lesions on the lateral aspect of the left arm. Small pustules covered the entire buccal mucosa excepting the tongue and the glans forming a typical snail trace aspect. Bacterial and mycological samples were negative. The histology reports for skin and mucosa were similar: epithelial hyperplasia, intra- and subepithelial granulocyte micro-abscesses and polymorphous infiltration of the superficial derma with numerous neutrophils and eosinophils. There was a discrete interkeratinocytic fluorescence at direct immunofluorescence but indirect immunofluorescence was negative. Anti-desmogleine 1 immunolabeling showed typical normal skin uptake and immunotransfer was negative. Digestive tract endoscopy and histopathology examination of the bowel specimens confirmed the diagnosis of Crohn's disease. Clinical manifestations improved dramatically with prednisone. DISCUSSION: This case of pyostomatitis-pyodermatitis vegetans involved several aspects rarely reported in the literature: a) the cutaneomucosal signs were inaugural; b) the association with Crohn's disease; c) the presence of lesions to the genital mucosa; d) the unusual localization of the inaugural skin manifestations. This clinical entity has now been clearly distinguished from pemphigus vegetans. There was however a long debate on the similar clinical, histological and even immunological expressions. We suggest that pyostomatitis-pyodermatitis vegetans belongs to the spectrum of neutrophilic dermatoses and other authors even propose it is a clinical form of pyoderma gangrenosum.
BACKGROUND: Tufted angioma belongs to the family of vascular skin proliferations. Clustered capillaries is the characteristic histological feature. Classically, tufted angioma is an acquired disease observed in children or young adults with lesions predominating on the neck, the shoulders and the upper trunk. CASE REPORTS: Four children were seen for flat skin lesions which were either initially or secondarily erythematous. The lesions were observed at birth or within the first weeks of life. In all 4 cases, the lesions progressed by infiltration, leading to sclerous plaques within a few weeks. The hip area was involved in case n(o) 2 and the thigh in the other cases. Pathology reported tufted angioma. A repeated biopsy 4 years after the first biopsy demonstrated the progressive nature of the fibrosis in case n(o) 2. Magnetic resonance imaging, performed in 3 of the 4 cases, demonstrated deep penetration of the vascular proliferation. The lesions were in contact with bony structures in case n(o) 2, reached the hypodermis in case n(o) 3 and infiltrated between the adducter muscles in case n(o) 4. DISCUSSION: Among tufted angiomas, there is a clinical variant characterized by very early discovery (congenital or within the first months of life), preferential localization on the lower limbs and progression to sclerosis. Although non-specific, hypersudation and lanuginous hypertrichosis are also highly suggestive signs. The main clinical and histological differential diagnosis is angio-eccrine hamartoma and, to a lesser degree, Kaposi hemangioendothelioma which does not predominate on the lower limbs. This particular clinical presentation of tufted angioma should lead to wide and sufficiently deep biopsy to allow precise diagnosis prior to initiating therapy. The possibility of spontaneous involution would allow abstention with regular surveillance to detect reactivation and progression or functional impairment. Such unfavorable progression has lead certain authors to propose high-dose systemic corticosteroid therapy or alpha-interferon.
Phacomatosis pigmentovascularis (PPV) is described as the association of cutaneous vascular malformations and different pigmentary disorders. The different associations are classified into four types, with localized and systemic forms. The constant alteration in each type is a nevus flammeus. Associated pigmented abnormalities are nevus pigmentosus and verrucosus in type I, blue spots in type II, nevus spilus in type III, blue spots and nevus spilus in type IV. Type II is the most frequently reported. In this type, half of the patients have visceral involvement, more often Klippel-Trenaunay or/and Sturge-Weber syndrome. We report two cases of phacomatosis pigmentovascularis type II. The particularity of the first case is the association with a cranio-cervical junction malformation (Arnold-Chiari type I), which to our knowledge, has never been described with PPV. The second case presents with a bilateral scleral melanosis without visceral involvement. Definition of visceral involvement and ophthalmologic manifestations are discussed.
Conservative management is usually proposed for common childhood hemangiomas because most lesions resolve spontaneously. The authors report 29 cases of children with hemangiomas treated surgically. Surgical indications were defined at various stages. The study concerned 29 children operated in our pediatric surgery and plastic surgery departments between 1989 and 1995. The average postoperative follow-up was 3 years and 8 months. The average age of the patients was 5 years; two-thirds of children were girls. The hemangioma was a very large lesion, subcutaneous and cutaneous (mixed) in 23 cases, only subcutaneous in 2 cases, only cutaneous in 4 cases, and was located on the face in 19 cases. Six complications (5 ulcerations, 1 Kassabach-Merritt syndrome) were observed.
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BACKGROUND: Surgical treatment of cystic lymphangioma (CL) is so often followed by local and general complications that non invasive treatment must be considered. POPULATION AND METHODS: Between 1987 and 1993, 20 patients with a superficial macrocystic lymphangioma were treated by percutaneous injection of Ethibloc in order to reduce the volume of the CL, with a minimum follow-up of 1 year. Fourteen CL were cervico-facial and six were located in the upper half of the body. The size of the lesion was determined by echography: three CL were less than 5 cm in diameter, 12 between 5 and 10 cm, five more than 10 cm. Two to 5 mL of Ethibloc were injected during one (15 cases) or several sessions (five cases). RESULTS: Reduction in volume was excellent in 12 patients after one session and in four patients after several sessions. Four patients had a poor result. All the patients suffered from an important inflammatory reaction for 2 or 3 days followed by exteriorisation of the Ethibloc in seven patients, with a discrete final scar. CONCLUSION: These fair results suggest that intracystic injection of Ethibloc represents an effective alternative to surgery.
Sulfasalazine is an effective agent for chronic discoid lupus erythematosus (CDLE) but the response to treatment is considerably variable between patients and is also unpredictable. The reason for this might relate to differences in metabolism of the drug which is extensively acetylated by the polymorphic enzyme N-acetyltransferase 2 (NAT2). To test this possibility, the N-acetylation phenotype of eleven patients with CDLE and treated by standard doses of sulfasalazine was retrospectively determined by genotyping. A clear-cut difference in the outcome of treatment was observed according to whether the patients were slow acetylators (SA) or rapid acetylators (RA). Eight out of 11 patients responded to treatment with a complete or marked remission of the disease. Seven of them were RA. The three other patients who did not respond at all to the drug were SA. In addition, SA seem to be more prone to toxic events. These findings strongly suggest that the genetic polymorphism of NAT2 is responsible for differences in the response to sulfasalazine in patients with CDLE. Therefore, candidates for sulfasalazine therapy should be genotyped to identify those patients who might benefit from the drug.
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Advanced age is an established risk factor for gastrointestinal toxicity of nonsteroidal antiinflammatory drugs, and the duration of use of these agents in elderly patients should be kept as short as possible. A multicenter, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of misoprostol in preventing gastrointestinal toxicity in elderly patients (> or = 65 years) given nonsteroidal antiinflammatory agents for no more than ten days. Patients who were to receive a nonsteroidal antiinflammatory agent for ten days to treat an acute rheumatic condition were randomly allocated to treatment with either a placebo or misoprostol in a dose of 200 micrograms bid. The primary efficacy criterion was the result of a gastroduodenal endoscopic evaluation done on day 10. The outcome of the rheumatic condition, changes in serum creatinine levels, and clinical safety were also evaluated. The study population included 208 subjects with a mean age of 81.4 +/- 6.4 years, of whom 81.3% were women. The misoprostol group (n = 104) and the placebo group (n = 104) were comparable at baseline. The incidence of endoscopically visible gastric lesions after ten days of nonsteroidal antiinflammatory drug therapy was significantly lower in the misoprostol group (25%) than in the placebo group (43%) (P = 0.001). In contrast, no statistically significant difference was found for the incidence of duodenal lesions between the two groups. The incidence of gastroduodenal ulcers was significantly lower (P < 0.021) in the misoprostol group (4.1%) than in the placebo group (13.5%). Changes in serum creatinine levels on day 10 versus baseline were similar in the two groups. The nonsteroidal antiinflammatory drug was well tolerated clinically when given alone or in combination with misoprostol.
INTRODUCTION: Low-molecular weight heparin-induced cutaneous necrosis is exceptional. Pathogenesis remains unclear. We report an exceptional case with elective localization of the necrotic areas in insulin lipodystrophic tissue. CASE REPORT: A 69-year old patient developed areas of skin necrosis after starting enoxaparin therapy. These areas were located far from the points of injection and focalized on skin areas where the patient had been injecting insulin daily for the last four years. These areas had an aspect of insulin lipodystrophy. Biopsy specimens showed leukocytoclastic vasculitis. There were no associated biological anomalies. One month later, prick-tests were made with different low-molecular weight heparins and calcium heparinate in a lipodystrophic area together with an enoxaparin control test in healthy skin. The only positive test was for enoxaparin in an insulin lipodystrophic area (hard erythema at 24 hours). Histology at 72 hours demonstrated leukocytoclastic vasculitis. DISCUSSION: Six cases of cutaneous necrosis induced by low-molecular weight heparin have been reported, including three cases with enoxaparin. Two pathophysiological mechanisms could be involved: (i) localized heparin-dependent platelet aggregation, or (ii) vasculitis induced by type III hypersensitivity reaction. In our case, the leukocytoclastic aspect of the vasculitis was compatible with an immune complex hypersensitivity reaction. The localization of the necrotic areas would be explained by enoxaparin-induced preferential deposit of immune complexes in the vascular turbulences present in lipodystrophic areas.
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INTRODUCTION: Antimalaria agents and thalidomide are two reference drugs for discoid lupus erythematosus. In non-responders or after secondary resistance or contraindications, there are a number of alternative therapeutics which are less effective and more toxic. We therefore conducted an open study in patients with discoid lupus erythematosus treated with sulfasalazine. PATIENTS AND METHODS: Seven men and four women (mean age 40 years) with severe discoid lupus erythematosus (mean duration of disease 14 years) were treated with sulfasalazine (2 g/d). This treatment was initiated after a previous failure or contraindication of antimalarial drugs or thalidomide. The acetylation phenotype was predicted in all patients with N-acetyltransferase 2 genotyping. Genome DNA was tested for mutations causing an N-acetyltransferase deficiency. Homozygous individuals or those with heterozygous composites for the tested mutations were predicted slow acetylators and those with a homozygous or heterozygous genotype for an allele carrying a normal sequence at the mutation sites were predicted rapid acetylators. RESULTS: We had 7 complete responses, 1 partial response and 3 failures. Mean delay to efficacy was 7 weeks, longer for lesions involving the scalp (4 to 5 months). Six of the 8 responders were given sulfasalazine exclusively. The effect was suspensive and dose-dependent; the minimal effective dose was 1.5 g/d. Excepting light sensitization requiring discontinuation, there were no clinically significant side effects. Neutropenia occurred in one patient and moderate and transient live enzyme movements did not require treatment withdrawal. The only immunoallergic side effect (light sensitization) observed occurred in a slow acetylator. All responders except one were rapid acetylators. DISCUSSION: Salazosulfapyridine, or sulfasalazine, is composed of a derivative of 5-aminosalicylic acid and a sulfamide fraction, sulfapyridine. It is only marginally used in dermatology except for psoriasis. Its efficacy in chronic lupus erythematosus has been reported in one case. We confirmed the role of this compound in the treatment of chronic lupus erythematosus. The rare observations of induced lupus and development of antinuclear antibodies are not a contraindication, but require close regular clinical and biological surveillance. The potential risk is that possible hypersensitivity could lead to reserving sulfasalazine for severe resistant chronic lupus erythematosus after failure with antimalarials and thalidomide. Nevertheless, our study demonstrates that the slow acetylator phenotype predicts immunoallergic events, as observed by other authors, and would be a factor predicting nonresponse. If these results are confirmed by other studies, it would be possible to propose sulfasalazine as a treatment for discoid lupus erythematosus in rapid acetylators.