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Biomedical subjects
Publications and source records attributed to A Dupuy.
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OBJECTIVE: To assess risk factors for erysipelas of the leg (cellulitis). DESIGN: Case-control study. SETTING: 7 hospital centres in France. SUBJECTS: 167 patients admitted to hospital for erysipelas of the leg and 294 controls. RESULTS: In multivariate analysis, a disruption of the cutaneous barrier (leg ulcer, wound, fissurated toe-web intertrigo, pressure ulcer, or leg dermatosis) (odds ratio 23.8, 95% confidence interval 10.7 to 52.5), lymphoedema (71.2, 5.6 to 908), venous insufficiency (2.9, 1.0 to 8.7), leg oedema (2.5, 1.2 to 5.1) and being overweight (2.0, 1.1 to 3.7) were independently associated with erysipelas of the leg. No association was observed with diabetes, alcohol, or smoking. Population attributable risk for toe-web intertrigo was 61%. CONCLUSION: This first case-control study highlights the major role of local risk factors (mainly lymphoedema and site of entry) in erysipelas of the leg. From a public health perspective, detecting and treating toe-web intertrigo should be evaluated in the secondary prevention of erysipelas of the leg.
BACKGROUND: Oral localization of Crohn disease is uncommon and must be differentiated from nonspecific lesions. Its natural course and its long-term prognosis are unknown. OBSERVATIONS: We studied 9 patients (8 male, 1 female; age range, 7-52 years; median age, 16 years) with Crohn disease and specific oral lesions, including deep linear ulcers, pseudopolyps, and/or labial or buccal swelling and induration. The prevalence of such lesions was 0.5%. The median follow-up was 11 years. Oral localization developed before (n = 2), at the same time as (n = 2), or after (n = 5) the onset of the digestive disease. Noticeable associated localizations were observed in the anoperineum (n = 8) and the esophagus (n = 3). The median duration of the oral lesions was 4 years (range, 1-13 years), without necessary parallelism with the digestive localization. Five patients had complete healing after a median delay of 2 years. CONCLUSIONS: Oral localization of Crohn disease is characterized by a marked male predominance, a young age at onset of Crohn disease, and a very protracted course. The high prevalence of associated anal and esophageal involvement suggests that Crohn lesions have a particular trophicity for squamous cell epithelium.
OBJECTIVES: Skin reactions to drugs affect about 2.2 percent of inpatients. More often, they are described as morbilliform or maculopapular. The objectives of this study were to characterize these skin reactions and to look for severity markers. METHODS: We retrospectively analyzed 133 cases of drug reactions collected in a Dermatology unit from 1973 to 1995 for whom, photographs and blood cell count were available. Well recognized disorders were excluded (Stevens-Johnson syndrome, Lyell syndrome, TEN, AGEP, vasculitis, phototoxicity, fixed drug eruption). Severity was defined on 3 criteria: hospitalization, skin reaction prolonged more than 21 days and visceral involvement. For each criteria, we studied the association with clinical and laboratory findings, first with univariate analysis, then with multivariate analysis for significant associations. RESULTS: Characteristics of the 133 included cases were: women: 58 p. 100, mean age: 52 years, inpatients: 80 p. 100, mean interval from beginning of drug therapy to reaction: 12 days, mean duration: 26 days, responsible drugs: antibiotics: 41 p. 100, nonsteroidal antiinflammatory drugs: 11 p. 100, anticonvulsants: 10 p. 100. A few reactions showed a monomorphous pattern fitting a single denomination in a classic dermatological nomenclature: maculopapular: 10 p. 100, morbilliform: 6 p. 100, scarlatiniform: 5 p. 100, small papules: 5 p. 100. Polymorphous reactions were observed in 73 p. 100 of cases with 3 different patterns on the average. Nearly half of the cases exhibited maculopapular and scarlatiniform lesions simultaneously. We observed fever (61 p. 100), mucosal lesions (26 p. 100), lymphadenopathy (30 p. 100), eosinophilia (count > 500/mm3: 44 p. 100, > 1500/mm3: 17 p. 100), and visceral involvement (22 p. 100), including hepatitis (18 p. 100). Four severity markers were identified: fever, lymphadenopathy, erythema involving more than 60 p. 100 of the body surface area, eosinophilia. CONCLUSION: This study underlines the polymorphous clinical presentation of skin reactions to drugs and the minority of maculopapular or morbilliform patterns leading us to propose the term of "erythematous drug reactions". Despite several biases (hospital recruitment of more severe reactions, retrospective analysis) this study is the first to show some severity markers. Close to the criteria used to define the "hypersensitivity syndrome" these simple clinical markers may have important practical implications.
As part of the U.S. EPA Dioxin Reassessment Program, the 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and furans were measured at part per trillion (ppt) levels in beef fat collected from slaughter facilities in the United States. This is the first statistically designed national survey of these compounds in the U.S. beef supply. Analyte concentrations were determined by high-resolution gas chromatography/high-resolution mass spectrometry, using isotope dilution methodology. Method limits of detection on a whole weight basis were 0.05 ppt for TCDD and 0.10 ppt for TCDF, 0.50 ppt for the pentas (PeCDDs/PeCDFs)/hexas (HxCDDs/HxCDFs)/heptas (HpCDDs/HpCDFs), and 3.00 ppt for the octas (OCDD/OCDF). Method detection and quantitation limits were established on the basis of demonstrated performance criteria utilizing fortified samples rather than by conventional signal-to-noise or variability of response methods. The background subtraction procedures developed for this study minimized the likelihood of false positives and increased the confidence associated with reported values near the detection limits. Mean and median values for each of the 2,3,7,8-Cl-substituted dioxins and furans are reported, along with the supporting information required for their interpretation. The mean toxic equivalence values for the samples are 0.35 ppt (nondetects = 0) and 0.89 ppt (nondetects = 1/2 LOD).
The USEPA and the USDA have completed the first statistically designed survey of the occurrence and concentration of CDDs and CDFs in the fat of beef animals raised for human consumption in the United States. Back fat was sampled from 63 carcasses at federally inspected slaughter establishments nationwide. The sample design called for sampling beef animal classes in proportion to national annual slaughter statistics. All samples were analyzed using a modification of EPA method 1613, using isotope dilution, High Resolution GC/MS to determine the rate of occurrence of 2,3,7,8-substituted CDDs/CDFS. The whole weight method detection limits ranged from 0.05 ng kg-1 for TCDD to 3 ng kg-1 for OCDD. The results of this survey showed a mean concentration (reported as I-TEQ, lipid adjusted) in U.S. beef animals of 0.35 ng kg-1 and 0.89 ng kg-1 when either non-detects are treated as 0 value or assigned a value of 1/2 the detection limit, respectively.
Processing of rat prodynorphin (proDyn) by the mouse prohormone convertase PC1 was investigated. Recombinant vaccinia virus vectors were used to coexpress proDyn and PC1 in rat PC12 pheochromocytoma and mouse AtT-20 corticotroph cells. In vitro experiments were also conducted by co-incubating purified proDyn and PC1. The results demonstrate that PC1 cleaves proDyn at pairs of basic residues to yield 10 and 16 kDa high molecular weight (HMW) intermediates. Additionally, PC1 cleaves proDyn at a single arginine residue to yield an 8 kDa product and the C-peptide. This demonstrates that PC1 cleaves proDyn at single and pairs of basic residues.
1. RP 62203 (2-[3-(4-(4-fluorophenyl)-piperazinyl)propyl]naphto[1,8- ca]isothiazole-1,1-dioxide) is a novel naphtosultam derivative which shows very high affinity for 5-HT2 receptors in the rat cerebral cortex (Ki = 50.0 pM). 2. RP 62203 is relatively selective for this sub-type of 5-hydroxytryptamine (5-HT) receptor, having lower affinity for the 5-HT1A receptor and very low affinity for the 5-HT, receptor. RP 62203 displayed low to moderate affinity for alpha 1-adrenoceptors, dopamine D2 receptors and histamine H1 receptors. 3. In vivo binding experiments demonstrated that oral administration of low doses of RP 62203 led to a long-lasting (greater than 6 h) occupation of cortical 5-HT2 receptors (ID50 = 0.39 mgkg-1). 4. In cortical slices from the neonatal rat, RP 62203 potently inhibited inositol phosphate formation evoked by 5-HT, with an IC50 of 7.76 nM. 5. The activity of neurones in the raphé and their responses to microiontophoretically applied 5-HT were studied with extracellular recording electrodes in the anaesthetized rat. RP 62203 potently and dose-dependently blocked excitations evoked by 5-HT when administered at doses of 0.5-4.0 mg kg-1, i.p. In contrast, neither 5-HT-evoked depressions nor glutamate-evoked excitations of raphé neuronal firing were blocked by RP 62203 at doses as high as 8.0 mg kg-1, i.p. 6. Head twitches induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) could be abolished by low doses of RP 62203 in mice (ED50 = 0.44 mg kg-1, p.o.) and in rats (ED50 = 1.54 p.o.). Similar results were obtained with mescaline and 5-hydroxytryptophan (5-HTP). 7. The potency of RP 62203 was compared with that of three other 5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ICI 170,809. In all models, RP 62203 showed similar activity to ritanserin, whilst either ICI 169,369 or ICI 170,809 was several fold less active. 8. It is concluded that RP 62203 is a potent and selective antagonist at 5-HT2 receptors in the rodent central nervous system.
Certain 99mTc-labeled derivatives of ethylene diamine substituted in NN', when labeled with 99mTc, have been proposed for studying renal excretion, and others for brain imaging. Ethambutol, a well known antituberculosis drug, possesses a structure very similar to these derivatives. We prepared a complex of [99mTc]ethambutol using hypophosphorus acid as the reducing agent. The complex was then analyzed by paper and cellulose F chromatography and by FAB mass spectrometry. A pharmacokinetic study in the mouse and rat indicated that the complex is eliminated by the kidney faster than DTPA, slower than [131I]hippuran and without significant renal retention. The [99mTc]ethambutol complex is easy to prepare and shows good stability in water at physiological pH, making it potentially useful in renal excretion studies.
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The genome of the Pasteur 17D-204 vaccine strain of yellow fever virus has been cloned into pBR327. The inserts of recombinant plasmids were analysed by restriction cleavage pattern and compared with that of the genome of another substrain previously cloned and sequenced. Ten of the overlapping inserts were found to contain the sequence of the complete genome. We have sequenced approximately 3680 bases of the 5' region which codes for the C, M and E structural proteins and the NS1 non-structural protein. This sequence is the same as that reported previously, indicating a remarkable stability of these two vaccine substrains.
The authors report a case of haemorrhage due to cephalexin therapy. The bleeding started after an orthopedic operation in a patient without renal failure, receiving 3 g/day of cephalexin. Platelet function was very abnormal at the time of the haemorrhage with a bleeding time of over 20 minutes, which returned to normal when treatment was stopped. This case seems to be similar to other reports of haemorrhages during treatment with other beta-lactams.
Following orthopedic surgery of the lower limb, ten patients were given fentanyl 5 micrograms . kg-1 in a single epidural injection. Almost complete analgesia (P less than 0.001) was rapidly obtained. The total period of analgesia was rather short (182.3 +/- 32.1 min). The maximal analgesia period was 87 +/- 8.34 minutes. Despite this high dose of fentanyl (245 to 450 micrograms), in five patients the passive mobilization of the knee following surgery was extremely painful and, for that matter, impossible in three of them. Such high doses of fentanyl entail the risk of respiratory depression as respiratory rate is decreased (P less than 0.01) and the Pco2 is increased (P less than 0.01). Fentanyl should not be used at such high dosage and should probably not be preferred to morphine, considering that the duration of analgesia is short, that the analgesic score is identical to that obtained with lower doses or with longer lasting narcotics, that it does not prevent passive mobilization pains and that it entails a definite risk of respiratory depression.
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