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Biomedical subjects

A Hassoun

Publications and source records attributed to A Hassoun.

85 records · Page 5Linked to original sources
PubMedDate not supplied

Excretion of tacrolimus glucuronides in human bile.

Tacrolimus is extensively metabolized by the cytochrome P-450 system. Hepatic metabolic phase I reactions of tacrolimus include mainly demethylation and/or hydroxylation. No valid data have been published on phase II pathways (glucuronide- or sulfo-conjugation). In order to investigate these pathways, different beta-glucuronidase/sulfatase enzyme preparations were used to hydrolyse the conjugates potentially present in human bile extracts. Two analytical methods were used: a non-specific method, MEIA, and a specific combined HPLC/MEIA method. The influence of the extraction pH was investigated. After beta-glucuronidase hydrolysis and extraction at pH 5, tacrolimus concentrations, obtained either from HPLC-MEIA or MEIA, always appeared significantly higher, suggesting the presence of glucuronides in the bile. When the extraction was performed at pH 1.5, only the HPLC-MEIA concentrations appeared higher after hydrolysis. MEIA concentrations obtained before and after hydrolysis were similar. These data are consistent with the fact that glucuronides are extracted at pH 1.5 but not at pH 5 and suggest first that, without hydrolysis, the extracted glucuronides are separated from the tacrolimus fraction in the HPLC-MEIA procedure, and second, that the glucuronides are cross-detected by the monoclonal antibody in the immunoassay. From these data, it is concluded that clues have been found, suggesting the presence in human bile of tacrolimus glucuronides, which cross-react with the monoclonal antibody, provided they are extracted in the sample tested.

Adult↗
PubMedDate not supplied

The use of radioreceptor assays for the determination of benzodiazepines in biological samples: a review.

Benzodiazepines are the most widely prescribed class of psychotropes. The demonstration of specific, high affinity binding sites for benzodiazepines in mammalian brain has provided a basis for a radioreceptor assay (RRA) of these compounds in biological samples (fluids or tissues). The RRA permits the simultaneous measurement of the benzodiazepine molecules that bind to the receptor, providing a total estimate of all pharmacologically active forms of the drug, which is useful in drug monitoring and in the intensive care of patients. After a complete description of the methodological aspects of this technique, the results obtained in therapeutic monitoring and in toxicological analysis are reviewed, and the advantages and disadvantages of this method are examined.

Animals↗
PubMedDate not supplied

Potential use of a radioreceptor assay for the determination of benzodiazepine compounds in serum.

The clinical monitoring and intensive care of patients who have taken an overdose of a benzodiazepine require rapid and quantitative methods to assess benzodiazepine concentrations in biological fluids. A radioreceptor assay (RRA) permits the simultaneous measurement of the benzodiazepine molecules that bind to the receptor, providing a total estimate of all pharmacologically active forms of the drug(s) (parent drug and active metabolites). This study describes the development of an RRA for the determination of benzodiazepine compounds in serum using a lyophilized bovine brain cerebral cortex receptor preparation. The standard curves and the sensitivity of this RRA are determined for 20 different benzodiazepines and the specific antagonist flumazenil. The sensitivity ranges from 5 ng/mL for clonazepam to 3500 ng/mL for chlordiazepoxide. The IC50 values are significantly correlated (r = 0.81) with the lowest recommended therapeutic concentrations. The advantages and disadvantages of this RRA are discussed and compared with those of other chromatographic and immunological methods.

Animals↗
PubMedDate not supplied

[Myasthenia gravis and thymectomy. Report of forty cases (author's transl)].

Forty operated cases of myasthenia gravis correspond to 14 thymomas, 18 hyperplasias and 8 vestigial thymus : 3 stages, I, 28 stages, II, 6 stages III, 3 stages IV. For vestigial thymus and moderate hyperplasias, cervicotomy was used in 11 cases. Surgery allowed 15 remissions, 12 ameliorations, 11 failures, aggravations and late deaths, and 2 post-operative deaths (one of them avoidable). Apart from its oncologic interest in thymomas (1/3 of the patients), thymectomy is beneficial in 2/3 of the cases of myasthenia gravis in general.

Adult↗
PubMedDate not supplied

Use of octreotide in the treatment of digestive neuroendocrine tumours. Seven year experience in 20 cases including 9 cases of metastatic midgut carcinoid and 5 cases of metastatic gastrinoma.

The authors report their experience with octreotide in 20 patients (median age 57 years, 10 M, 10 F) from 1984 to 1991; 16 had metastatic APUDoma: 1 PPoma with VIPoma, 1 glucagonoma, 5 gastrinoma including 1 associated to PP-oma, 9 mid-gut carcinoid; 3 patients had multiple-endocrine neoplasia type I (MEN-I) with Zollinger-Ellison syndrome (ZES) and 1 patient a non-metastatic VIPoma. Octreotide (200-750 micrograms/day) was administered bid or tid with regular laboratory controls and morphological assessment. There was a striking improvement of symptoms, particularly in the carcinoid group (reduction of flushing in all patients and of diarrhoea in 3/5), in the patient with gastrinoma + acromegaly (regression of congestive heart failure) and in the patient with non-metastatic VIPoma. The hormonal markers were markedly reduced, particularly gastrin, PP (except in the patient with PPoma + VIPoma), VIP, GH and Somatomedin-C and urinary 5HIAA in 4/9 patients with carcinoid. There was only one partial regression of metastases (gastrinoma) and 4 apparent stabilizations of tumour growth, in the 16 metastatic cases. Among them, 4 patients died: 1 glucagonoma, 1 PPoma + VIPoma, 2 mid-gut carcinoids after a treatment of 5, 16, 30, 36 months, respectively. The patient with acromegaly + ZES died after 6 years of treatment at age 81. A patient with prolactinoma, resected insulinoma, hyperparathyroidism and ZES was not improved by a short course of octreotide (hypoglycemia); he died later of recurrent insulinoma. In conclusion, octreotide is a useful drug to control most of the symptoms related to gut endocrine tumours; it may inhibit tumour growth.

Adolescent↗
PubMedDate not supplied

[Drug-induced syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Review of literature].

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is caused by an incapacity of plasmatic hypotonia to inhibit antidiuretic hormone (ADH) secretion. This phenomenon leads to a water retention and an expanded extracellular fluid volume, and secondary to a dilution of plasmatic sodium and also to a renal loss of sodium. The SIADH is a relatively rare syndrome, which may occur in various circumstances: central nervous system diseases, cancers, infections... Sometimes, it may be observed as a drug-related side effect: carbamazepine, chlorpropamide, antidepressors, anticancer drugs are particularly involved.

Humans↗