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Biomedical subjects

B Richard

Publications and source records attributed to B Richard.

At least 73 records · Page 4Linked to original sources
PubMed1990

Structure of an exocellular beta-D-glucan from Pediococcus sp., a wine lactic bacteria.

Pediococcus sp. produces an exocellular slime containing exclusively D-glucose. The structure of the polysaccharide was determined by methylation analysis, Smith degradation, enzymic hydrolysis, and 13C-n.m.r. spectroscopy as having a trisaccharide repeating unit, ----3)-beta-D-Glcp-(1---- 3)-[beta-D-Glcp-(1----2)]-beta-D-Glcp-(1----.

Carbohydrate Sequence↗
PubMed1990

High-dose cytosine arabinoside and mitoxantrone in previously-treated acute leukemia patients.

35 patients with refractory or relapsed acute leukemia received salvage chemotherapy using high-dose cytosine arabinoside 2 g/m2 intravenously for 3 hours every 12 h, in 8 doses, followed by continuous infusion of mitoxantrone 12 mg/m2/day for 2 d. 9 patients had acute myeloblastic leukemia (AML), (4 relapsed, 5 refractory), 20 had acute lymphoblastic leukemia (ALL) (11 relapsed, 9 refractory) and 6 had chronic myelogenous leukemia (CML) in the blastic phase (BP). 4 out of 9 AML and 16 out of 20 ALL achieved complete remission. Median survival was 6 months for all patients and 10 months for responders. A short (1.5 months) chronic phase was achieved in 3 patients with CML. The main toxic effect was hematologic. A pharmacokinetic study was performed on mitoxantrone. No correlation was found with clinical response. The combination of mitoxantrone and ara-C is an effective antileukemic regimen, especially in ALL.

Adolescent↗
PubMed1990

Energy expenditure and subsequent nutrient intakes in overfed young men.

We investigated the mechanisms of body weight regulation in young men of normal body weight leading unrestricted lives. Changes in total and resting energy expenditure, body composition, and subsequent voluntary nutrient intakes in response to overeating by 4,230 +/- 115 (SE) kJ/day (1,011 +/- 27 kcal/day) for 21 days were measured in seven subjects consuming a typical diet. On average, 85-90% of the excess energy intake was deposited (with 87% of this amount in fat and 13% in protein on average). There was no detectable difference between individuals in susceptibility to energy deposition. The resting metabolic rate, averaged for fasting and fed states, increased during overfeeding (mean +/- SE, 628 +/- 197 kJ/day, P less than 0.01), but at least some of this amount was obligatory expenditure associated with nutrient assimilation. No significant increase in energy expenditure for physical activity or thermoregulation resulted from overfeeding. Thus energy expenditure did not substantially adapt to increased energy intake. However, significant decreases in voluntary energy intake (1,991 +/- 824 kJ/day, P less than 0.05) and fat intake (48 +/- 11 g/day, P less than 0.01) followed overeating, indicating that adaptive changes in nutrient intakes can contribute significantly to body weight regulation after overeating.

Adult↗
PubMed1989

Excretion and metabolism of mitoxantrone in rabbits.

The hepatic clearance of mitoxantrone was evaluated in rabbits using both bile-duct cannulated animals and freshly isolated hepatocytes in suspension or in primary culture. Mitoxantrone metabolic behavior was assessed by high-performance liquid chromatography using a method which specifically resolved mitoxantrone from its mono- and dicarboxylic acid derivatives. Excretion of mitoxantrone in bile and urine was studied over a 6-h period of observation following i.v. bolus injection of 0.04, 0.20, and 1.0 mg [14C]mitoxantrone/kg. Bile route represented the main excretion pathway for mitoxantrone and its metabolites--mainly the monocarboxylic acid derivative. Biliary excretion was very rapid (maximum biliary concentration achieved 9 to 18 min following drug administration) and amounted to 29.5 +/- 9.3%, 27.6 +/- 7.9%, and 28.3 +/- 3.8% of administered drug, respectively. Urinary excretion amounted to 7.3 +/- 0.2%, 7.1 +/- 4.6%, and 6.0 +/- 1.5%, respectively. Both biliary and urinary excretions of mitoxantrone and its metabolites remained linear over the range of concentrations routinely used in clinic. Metabolism of mitoxantrone was first studied using rabbit hepatocytes in suspension. Since metabolic rate was slow under these incubation conditions (observation period, 1 h), mitoxantrone metabolism was investigated in primary cultures of rabbit hepatocytes. Mitoxantrone was rapidly accumulated within the cells and metabolized to its various metabolites which rapidly effluxed in the extracellular medium. After a 48-h exposure of hepatocytes to a broad range of mitoxantrone concentrations (1 to 20 microM), it could be seen that (a) drug accumulation and metabolism did not exhibit saturation processes, (b) mitoxantrone was the main intracellular form, while (c) metabolites rapidly effluxed in the extracellular compartment and (d) the monocarboxylic acid derivative represented the main extracellular metabolite. This data demonstrates the important role played by the liver in the pharmacokinetic behavior of mitoxantrone and suggests a careful drug monitoring in patients with severe liver dysfunction.

Animals↗
PubMed1989

Population pharmacokinetics of mitoxantrone performed by a NONMEM method.

To date, the pharmacokinetics of mitoxantrone (1,4-dihydroxy-5,8-bis[[2-[(2- hydroxyethyl)amino]ethyl]amino]anthraquinone) has been described either by an open two- or three-compartment model, showing high interindividual variability. In order to evaluate this variability, residual intraindividual variability, and measurement error, we carried out a population study. A sensitive HPLC method allowed analysis of blood samples drawn from 21 patients with breast cancer or acute nonlymphocytic leukemia. Individual data treatment (22 kinetics) using weighted nonlinear least squares regression confirmed the huge interindividual variability whatever the administration protocol of mitoxantrone: bi- or tri-exponential models fitted the data. The NONMEM population method used herein describes all concentration-time curves by a single three-compartment model, considering biphasic kinetics as fragmentary data. Residual intraindividual variability was 21.4%. Population mean values (+/- interindividual SD) of clearance, terminal half-life, and total volume of distribution were, respectively, 23.40 (+/- 10.76) L/h, 46.87 (+/- 12.18) h, and 385.49 (+/- 196.60) L. These results are of particular interest in clinical routines to calculate dosage regimens by Bayesian estimation methods.

Chromatography, High Pressure Liquid↗
PubMed1989

The interaction between cyclosporin A and erythromycin studied by means of an isolated perfused rat liver model.

The isolated perfused rat liver model was successfully used to study the clinical interaction observed between cyclosporin A (CsA) and erythromycin (ER). Three experimental studies were performed. In a "Control group", isolated rat livers were perfused with 60 micrograms 3H-CsA for 20 min. In an "ER group", isolated rat livers were simultaneously perfused with 60 micrograms 3H-CsA and 6.0 mg ER. In an "ER ind group", rats were treated with ER for 5 days, conditions under which the P450IIIA gene subfamily, principally involved in CsA metabolism, was specifically induced, and isolated rat livers were perfused with 60 micrograms 3H-CsA for 20 min. Biological parameters of the liver model such as biliary flow, oxygen consumption and pH were similar whatever group of animals. Biliary excretion of total radiolabel (sum of CsA and all the metabolites = CsAT) was similar in both the "Control" and "ER" groups but significantly higher in the "ER ind" group with respectively 8.05 +/- 0.81%, 8.45 +/- 1.93% and 14.54 +/- 2.12% of the entire amount of infused drug excreted during 2 hr. Using a high performance liquid chromatography method which specifically resolves unchanged CsA from its metabolites, we demonstrated that, although similar amounts of radiolabelled material were excreted in both the "Control" and "ER" groups, the CsA/metabolite ratio was lower than 1.0 in the "Control group" and higher than 1.0 in the "ER group", suggesting an inhibition of CsA metabolism by ER in the "ER group". These data could explain the increase in CsA blood levels observed in the clinic following administration of high ER doses and the reversing effect when ER administration is stopped.

Animals↗
PubMed1988

Extrapolation of preclinical pharmacokinetic data to therapeutic drug use.

1. Preclinical in vivo and in vitro studies are fundamental to the safe and effective development of new drugs. 2. Pharmacokinetic and metabolic research is essential to a better understanding of the pharmacological and toxicological activities of drugs and their metabolites. 3. Data generated by such a strategy can be used to improve Phase I trials, particularly those for anticancer drugs. 4. Human and animal in vitro models are potentially powerful preclinical tools in: (i) The prediction of the pharmacological behaviour of analogues belonging to the same family, e.g. vinca alkaloids; (ii) The selection of the animal species most closely related to humans on the basis of metabolic pattern; (iii) The assessment of the duration of drug action--particularly those drugs exhibiting different metabolic clearances (e.g. benzodiazepines); (iv) The understanding and prediction of drug interactions, i.e. those described for cyclosporin A and macrolide antibiotics; and (v) The explanation of the metabolic origins of interindividual variabilities in pharmacological activity.

Animals↗
PubMed1987

Analysis of phospholipid transfer during HDL binding to platelets using a fluorescent analog of phosphatidylcholine.

Electron microscopic examination of the interaction of gold labelled HDL with platelets indicates that the internalized lipoprotein becomes closely associated with surface connected canaliculae and endocytic vacuoles. At the same time granule centralization occurs. Using fluorescent derivatives of naturally occurring lipids we have further investigated lipid exchange between HDL and platelets. Analogs of phosphatidylcholine containing fluorescent fatty acids are rapidly transferred from the lipoproteins to the cells and remain at the plasma membrane as long as they are kept at 4 degrees C. However when the platelets are warmed to 37 degrees C, a rapid degradation of the fluorescent lipids occurs, generating fluorescent diacylglycerol as a consequence of the activation of platelet enzymes.

Blood Platelets↗
PubMed1977

[The Holoscan: a great improvement for diagnosis by ultrasonics].

We present a new B-scan device, the Holoscan, which combines real time imaging and high resolution capabilities. These capabilities are given by electronic scanning of a linear array and by a holographic focusing technique. This instrument is easy to use and allows high quality pictures to be obtained. Some results are presented.

Aorta, Abdominal↗
PubMed1975

Calcium-binding protein: its cellular localization in jejunum, kidney and pancreas.

Calcium-binding protein (CaBP) was localized with peroxidase-labeled antibody in human jejunum and kidney, and in kidney and pacreas of several animal species. The protein was associated with plasma membrane and intercellular space of jejunal absorptive cells. It was present in a specific population of renal tubule cells and in pancreatic islet cells. Immunohistochemical staining of intestinal CaBP with antibody to renal CaBP indicates structural similarity between the two proteins despite their different molecular weight.

Animals↗
PubMedDate not supplied

Parathyroid adenomectomy under local anesthesia with intra-operative monitoring of UcAMP and/or 1-84 PTH.

Because 80% of patients with primary hyperparathyroidism have a single adenoma and because most adenomas are now visualized by ultrasonography, we have attempted to remove these suspected single adenomas under local anesthesia with intra-operative monitoring of urinary cAMP (UcAMP) and 1-84 parathyroid hormone (PTH) serum levels. In the last 2 years, 45 patients (mean age 65 years) with primary hyperparathyroidism underwent surgery with local anesthesia when a single adenoma was strongly suspected by ultrasonography. Patients with equivocal or misleading ultrasonography, e.g., those with associated thyroid or multiglandular pathology and those who were non-cooperative, were excluded from this procedure. UcAMP and 1-84 PTH were determined prior to the incision, at the time of removal of the adenoma, and at regular intervals until 120 minutes after the operation. Results were available 45 min to 60 min after sampling for PTH and 60 min to 80 min for UcAMP. Forty-two adenomas were removed through a 2 cm to 3 cm skin incision in a mean time of 25 minutes, with no adverse effect, no morbidity, and minimal discomfort. The 42 patients were normocalcaemic on follow-up. The monitorings always predicted the success of the operation. In the 3 remaining patients, because the monitorings remained elevated at the end of the procedure, the patients underwent classical bilateral neck dissection under general anesthesia. This new approach can be safely accomplished with short operative time and hospital stay. The absence of general anesthesia is reassuring for the patients who are reluctant to undergo general anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMedDate not supplied

[Iodine 131 uptake by a bronchogenic cyst in a patient with differentiated carcinoma of the thyroid gland].

BACKGROUND: After thyroidectomy for differentiated thyroid carcinoma, extracervical uptake of iodine 131 is suggestive of metastasic dissemination. False positives can however occur. CASE REPORT: Differentiated thyroid carcinoma was found in a female patient with a non-functional nodule. Two years after subtotal thyroidectomy and an ablative dose of iodine 131, the whole body scan showed abdominal mediastinal uptake with low serum thyroglobulin level. Considering the possibility of tumor recurrence or lymph node metastasis, the mass was excised. The histology diagnosis was mediastinal bronchogenic cyst. DISCUSSION: To date, iodine uptake in a bronchogenic cyst has not been reported among other false-positives previously described. The pathophysiology of this iodine 131 uptake in a bronchogenic cyst is still unknown: the presence of NIS symporter or a protein which can organify iodine in the mucus cells of the cyst remains to be proven.

Adenocarcinoma↗