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Biomedical subjects

P Humbert

Publications and source records attributed to P Humbert.

At least 19 recordsLinked to original sources
PubMed1992

Role and environment of the conserved Lys27 of snake curaremimetic toxins as probed by chemical modifications, site-directed mutagenesis and photolabelling experiments.

The positive charge of Lys27 was suppressed by chemical means in two short-chain curaremimetic toxins, namely erabutoxin a (Ea) from Laticauda semifasciata and toxin alpha from Naja nigricollis. This modification leads to a decrease in the binding affinity of the toxins for the nicotinic acetylcholine receptor, which range 6-15-fold, as judged from both the data reported here and those previously described in the literature. A negatively charged glutamate residue has been introduced at position 27 of erabutoxin a by site-directed mutagenesis. This change provokes a 120-fold decrease in the affinity, which reflects a major alteration of toxin-receptor cognate events. Using toxin-alpha derivative harbouring a photoactive group at Lys27, we probed the toxin local environment in a receptor-bound state by photocoupling experiments. The delta chain was the predominant coupling target, in contrast to previous observations indicating that a photoactive probe on Lys47 predominantly labelled the alpha chain. The toxin derivative weakly labelled the alpha and gamma chains but not the beta chain. The toxin may therefore interact with subunits other than the alpha chain, at least in the vicinity of Lys27.

Amino Acid Sequence↗
PubMed1992

Plasma polyunsaturated fatty acid pattern in active inflammatory bowel disease.

Plasma fatty acid patterns were assessed by gas liquid chromatography in 73 patients with active inflammatory bowel disease and 107 healthy controls. The influence of the disease activity on fatty acid profile was also investigated. Plasma fatty acid patterns in patients with ulcerative colitis and Crohn's disease were similar. Plasma C18:3n3 and C22:6n3 were significantly higher in active ulcerative colitis (p = 0.0143 and p < 0.00001 respectively) and in Crohn's disease (p < 0.00001 for both) than in controls, whereas C20:3n6 was significantly lower in patients than in controls, both in ulcerative colitis (p = 0.0001) and in Crohn's disease (p = 0.0041). In more severe disease, plasma polyunsaturated fatty acid concentrations fell with a significant stepwise decrease in the desaturation index (p = 0.0031 in ulcerative colitis and p = 0.0355 in Crohn's disease). Even in patients with severe disease, however, plasma n3 fatty acids (C18:3n3 and C22:6n3) never fell below those of healthy controls. These findings suggest that in active inflammatory bowel disease, an increased biosynthesis might coexist with an increased consumption of polyunsaturated fatty acids. These observations may be of relevance in the pathogenesis of the disease as polyunsaturated fatty acids are involved in tissue eicosanoid synthesis and cellular membrane function, including that of immunocompetent cells. These results also question the rationale of using n3 polyunsaturated fatty acids in the treatment of inflammatory bowel disease.

Adolescent↗
PubMed1992

A new micronized 5-methoxypsoralen preparation. Higher bioavailability and lower UVA dose requirement.

A new tablet of micronized 5-methoxypsoralen (5-MOP) and a commonly used tablet in therapy (Psoraderm 5) were compared in 12 healthy subjects. Each subject ingested 1.2 mg/kg body weight of each formulation on different days. Bioavailability and phototoxicity of 5-MOP were compared. The results showed that serum and suction blister concentrations were significantly higher and occurred earlier after the oral intake of the micronized preparation. A series of graduated UVA doses were administered, one dose each time the concentration serum peaked, in order to determine the minimum phototoxic dose for each formulation. The micronized preparation induced greater photosensitivity than the unmicronized one. The micronized 5-MOP tablet may thus allow lower doses of UVA to achieve therapeutic results in photochemotherapy and a shortened waiting period following ingestion of drug.

5-Methoxypsoralen↗
PubMed1992

[Calcifying panniculitis].

We report a case of calcifying panniculitis which occurred in a 67-year old woman suffering from chronic renal failure and primarily involved anticoagulant injection sites. Calcifying panniculitis is a rare condition belonging to the spectrum of calciphylaxis first described by Selye in 1962. This disease seems to imply necessarily a specific morbid background including renal failure together with calcium-phosphate metabolism impairment. Following the action of a so-called "challenger" (in the present case calcium heparinate [Calciparine], a subcutaneously administered anticoagulant drug), the lesions start as painful subcutaneous nodules soon turning into plaques of necrosis. The area involved mainly includes the abdomen and thighs, due to the preferential distribution of fat and the classical use of such regions for subcutaneous injections. In our patients, histological examination disclosed an initial involvement of subcutaneous fat vessels mimicking mediacalcosis, soon followed by calcium-phosphate deposits within interadipocyte spaces. An electron microscopy study confirmed the presence of calcium crystals within the cytoplasms of some connective tissue cells and the extracellular matrix. From a review of the literature, it seems reasonable to normalize the calcium-phosphate product by reducing hyperparathyroidism as a first therapeutic step. Then, wide surgical excision of the necrotic areas should be performed to rule out any possibility of self worsening of the lesions and provide the best chance of healing without superinfection. The use of diphosphonates on pathophysiological grounds is discussed.

Aged↗
PubMed1992

[Cutaneous pigmentation induced by minocycline: ultrastructural analysis and X-ray microanalysis].

The authors report a case of cutaneous pigmentation induced by minocycline. The patient (aged 59) presented with a bluish-grey pigmentation on her face, legs and nails. She had been receiving minocycline for 8 years for asthma. The cumulative dose was 400 g. Skin biopsy specimens from the pigmented areas were examined by light and electron microscopy. Light microscopy displayed hyperpigmentation with Fontana's stain in the dermis, macrophages and basal layer of the epidermis. Electron microscopy showed an increase in melanosomes within the basal keratinocytes, and dense granules in macrophages of the dermis. An X-ray microanalysis of the electron-dense granules showed the presence of larger quantities of iron and smaller quantities of sulphur and calcium. The different types of pigmentation are reviewed. Several pigments are thought to be responsible for the pigmentation but the underlying mechanism remains unclear.

Female↗
PubMed1992

Health services at the Kennedy Space Center.

Comprehensive occupational health services are provided to approximately 17,000 workers at the Kennedy Space Center and an additional 6000 on Cape Canaveral Air Force Station. These areas cover about 120,000 acres encompassing part of the Merritt Island Wild Life Refuge and wetlands which are the habitat of numerous endangered and protected species of wildlife. The services provided at the Kennedy Space Center optimally assure a safe and healthy working environment for the employees engaged in the preparation and launching of this country's Space Shuttle and other important space exploration programs.

Aerospace Medicine↗
PubMed1991

[Prophylactic sclerosis of esophageal varices. Results of a controlled prospective study].

BACKGROUND: Endoscopic sclerosis of esophageal varices is effective both to treat active hemorrhage and to prevent recurrences. By contrast, its usefulness for the prophylaxis of the first episode of hemorrhage is not well established, the available data being contradictory. METHODS: Overall 46 patients with cirrhosis and esophageal varices of type B or higher, without previous upper gastrointestinal hemorrhage, were randomized to be treated with prophylactic sclerosis or not (n = 22 and 24, respectively). Both groups were comparable in age, sex, etiology of cirrhosis (mainly alcoholic), Child's degree of hepatic failure, coagulation studies, laboratory data and endoscopic findings. RESULTS: In a mean follow up of 16 months, the patients treated with sclerosis had a higher frequency of hemorrhage from gastroesophageal varices (27%) than those in the control group (8%) (n.s.). However, this difference reached significance (p = 0.02) when only patients from Child's classes A and B were considered (31% in the sclerosis group vs 5% in the control group). The mortality rate was similar in both groups, with a probability of one year survival of 80 and 76% in the sclerosis and control groups, respectively. CONCLUSIONS: The results indicate that prophylactic sclerotherapy does not improve short-term survival or reduce the risk of a first hemorrhage due to gastroesophageal varices of type B or higher in hepatic cirrhosis. It may even facilitate the development of this severe complication in Child's A and B class patients.

Endoscopy, Digestive System↗
PubMed1991

High-performance liquid chromatographic determination of citropten and bergapten in suction blister fluid after solar product application in humans.

Citropten (5,7-dimethoxycoumarin) and bergapten (5-methoxypsoralen) are present in bergamot oil which is used as a tanning cosmetic product. The aim of this study was to quantify, using high-performance liquid chromatography, the amount of citropten and bergapten in the skin after suntan products application (an emulsion and an oil formulation). A suction blister technique performed of the anterior aspect of the forearm permitted the collection of these two accumulated molecules. Fluorometric and ultraviolet detections were used for citropten and bergapten determinations, respectively.

5-Methoxypsoralen↗
PubMed1991

Peak blistering point: influence on fluid levels of 5-MOP in human skin in vivo after systemic administration.

The concentration of 5-methoxypsoralen (5-MOP) in suction blister fluid (SBF) after oral intake was determined in relation to the peak blistering point. Interstitial fluid was obtained from nine healthy male volunteers by applying mild suction (300-350 mmHg) to the skin of the volar aspect of the forearm. Blisters were raised at three different times: 18 h prior to drug administration (group I); 2 h prior to drug administration (group II); and during drug ingestion (group III). SBF levels of 5-MOP were determined in each group of blisters 2 h after oral administration of 1.2 mg/kg micronized 5-MOP. The results showed a statistically significant difference in the concentrations of 5-MOP between each group of blisters. The highest concentration of 5-MOP in the SBF was found in group III and the lowest in group II blisters. These findings suggest that the point of peak blistering in relation to drug administration needs to be known in each pharmacological study using suction blisters.

5-Methoxypsoralen↗
PubMed1991

Effect of obesity on gastroesophageal resistance to flow in man.

Chronic (obesity) and acute intraabdominal pressure increases appear to favor gastroesophageal reflux, but the mechanism is not completely understood. We hypothesized that it could be due to an alteration in the resistance gradient between the stomach and the gastroesophageal junction, even increasing intragastric resistance above resistance at the gastroesophageal junction. Hence, we used a pneumatic resistometer to measure gastric and gastroesophageal resistance to flow in 11 lean healthy controls and eight morbidly obese individuals without gastroesophageal reflux disease. Resistance was quantified at rest and during acute intraabdominal pressure increases, both in the recumbent and sitting positions. We found that gastroesophageal junction resistance was higher than gastric resistance in lean as well as in obese subjects (P less than 0.001). In obese individuals both gastric and gastroesophageal junction resistance were increased (P less than 0.001), thus a normal gastric-gastroesophageal junction resistance gradient was maintained. Body position did not modify resistance. Acute increases in intraabdominal pressure decreased the gastric-gastroesophageal junction resistance gradient similarly in obese and lean subjects. We conclude that obesity by itself does not appear to predispose to gastroesophageal reflux, but it creates intraabdominal conditions that may favor reflux whenever the gastroesophageal barrier becomes weakened.

Adult↗
PubMed1991

Portacaval shunt versus endoscopic sclerotherapy in the elective treatment of variceal hemorrhage.

Eighty-two consecutive Child-Campbell class A and B cirrhotic patients were included in a prospective controlled trial to assess the efficacy and safety of portacaval anastomosis vs. endoscopic sclerotherapy as elective treatment of variceal hemorrhage. Forty-one patients were randomized to portacaval anastomosis and 41 to sclerotherapy. After excluding dropouts, 34 patients were treated with portacaval anastomosis and 35 with sclerotherapy. The incidence of variceal rebleeding during follow-up (mean +/- SD, 20.6 +/- 14.2 months) was significantly higher in the sclerotherapy than in the portacaval groups, either considering the overall treated group or only patients completing sclerotherapy (40% and 25% vs. 2.9%; P = 0.0002 and P = 0.01, respectively). The 2-year probability of suffering from at least one episode of hepatic encephalopathy was significantly higher in patients submitted to portacaval anastomosis than in those treated with endoscopic sclerotherapy (40% vs. 12%; P = 0.04). However, disabling encephalopathy only appeared in 3 of 34 patients who underwent surgery (8.8%). Early and long-term mortality did not differ between the therapeutic groups; 2-year survival rates were 83% for portacaval anastomosis and 79% for sclerotherapy. It is concluded that portacaval anastomosis is more effective than endoscopic sclerotherapy in preventing variceal rebleeding in spite of the greater incidence of hepatic encephalopathy. The role of portacaval anastomosis in the elective treatment of variceal rebleeding should be reassessed.

Adult↗