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Biomedical subjects

A Genton

Publications and source records attributed to A Genton.

At least 37 records · Page 2Linked to original sources

[Value of simultaneous determination of cyclosporin blood levels using specific and nonspecific methods in liver transplantation].

Cyclosporine's narrow therapeutic window and the large inter- and intra-individual variation of its pharmacokinetics require therapeutic monitoring. Cyclosporine is metabolized in the liver and excreted with its metabolite into the bile. An accumulation of metabolites occurs in liver dysfunction, leading to a high cyclosporine blood concentration when measured by a non-specific method (polyclonal antibodies). Specific methods (HPCL, monoclonal antibody) are therefore recommended by some authors. We evaluated the potential usefulness of simultaneous cyclosporine determination by a non-specific (fluorescent polarisation TDx, polyclonal antibodies) and a specific method (I125-RIA, monoclonal antibody). 10 patients were followed from 51 days to 32 months after hepatic transplantation. 2 patients who showed no graft rejection presented a polyclonal antibodies/monoclonal antibody ratio below or equal to 4 throughout their evolution. Other patients presented a rise of this ratio during periods of liver dysfunction, particularly in acute graft rejection. When bilirubin concentrations are plotted versus this ratio, an hysteresis is present during periods of acute rejection, but not during an episode of histological hepatitis. The same holds true for alkaline phosphatase and gamma-GT. These data suggest that this ratio could be a sensitive test for early detection of rejection. Simultaneous cyclosporine blood determination with specific and nonspecific methods may be useful in the follow-up of liver-transplanted patients.

Adult↗

[Splenic abscess: therapeutic options].

Pyogenic splenic abscess is a rare condition that tends to occur in patients with underlying often infectious diseases. The sensitivity of ultrasonography and computerized tomography has improve early diagnosis and follow-up. In our hands, splenectomy remains the therapy of choice, but we report the resolution of two uncomplicated splenic abscesses with antibiotics alone.

Abscess↗

Assay of tyrosine protein kinase activity from HL-60 by high-performance liquid chromatography for specificity studies.

Using a partially purified HL-60 tyrosine protein kinase, we designed a new HPLC method for the measurement of tyrosylphosphorylation of angiotensin II. The present method uses reversed-phase chromatography and elution involving an acetonitrile gradient containing the counterion tetrabutylammonium phosphate. The peptide substrate, [gamma-32P]ATP, the cosubstrate, and 32P-labeled phosphorylated peptides were quantified online by measuring the Cerenkov effect. Injections, separation, and analysis were performed automatically. Furthermore, the method permits a direct visualization of peptide substrate phosphorylation and has a potentially universal application; i.e., it is usable with any kind of peptide in a given range of hydrophobicity. This assay was designed for specificity studies, which are of major importance at the molecular level, in order to understand active site topology and the biophysical requirements of tyrosine protein kinases. As examples, data on chromatography separations of angiotensin II analogs (five to ten amino acids in length) are presented, as well as for other peptide substrates such as RR-src, the pp60src autophosphorylation site-derived peptide, and minigastrin. We adapted our experimental conditions to accommodate crude extracts from HL-60 cells. Preliminary experiments clearly indicated that other biological sources can be used. Despite the existence of numerous methods published in the literature for the measurement of kinase activities, the method presented herein is the only one to the authors' knowledge that can be used in and has been assessed for specificity studies. Peptides do not require particular features such as charged residues (i.e., arginine) to be analyzed.

Adenosine Triphosphate↗

[Cure of recurrent ascites in alcoholic hepatitis following transient placement of a LeVeen shunt].

Three cases of severe alcoholic hepatitis associated with refractory ascites are reported. A LeVeen shunt was inserted which was effective and well tolerated. However, the shunt was removed in all 3 patients 8 months, 12 months and 9 years after insertion because of spontaneous migration (n = 2) or superior vena cava thrombosis (n = 1). At time of shunt removal all 3 patients had micronodular cirrhosis, but none had recurrent ascites during the 1-3 years of observation and despite the absence of diuretics. The eventual transient aspect of refractory ascites associated with alcoholic hepatitis is discussed, together with the potential beneficial and temporary role of LeVeen shunts in this condition.

Adult↗

Partial purification and characterization of a new p36/40 tyrosine protein kinase from HL-60.

A major peak of tyrosine protein kinase activity was partially purified from a Triton X100 extract of HL-60. This preparation submitted to high pressure gel filtration was eluted at a volume corresponding to a mass of 35/40 kD. This activity was insensitive to EGF and insulin. Autoradiographs of the preparations incubated with [gamma P32]-ATP and separated by electrophoresis do not give any evidence that autophosphorylation occurs for that particular tyrosine protein kinase. Furthermore, we failed to immunoprecipitate the enzyme with a specific antiphosphotyrosine antibody and anti v-src antibody. All the data presented herein suggest that this enzyme has not been previously purified.

Adenosine Triphosphate↗

Effects of the new nitrosourea derivative, fotemustine, on the glutathione reductase activity in rat tissues in vivo and in isolated rat hepatocytes.

Fotemustine, a new clinically active nitrosourea, is demonstrated herein to be a poor inhibitor of glutathione reductase activity from rat liver, lung and kidney cytosols. In order to show that an intracellular step of activation does not lead to a toxic intermediary metabolite, rat hepatocytes were incubated with fotemustine. Their glutathione-related pathways were checked and shown not to be altered, while under similar experimental conditions BCNU was shown to be dramatically harmful. Furthermore, association of fotemustine with a H2O2 production leading drug, diquat, was shown to be inefficient--while BCNU is efficient--in potentiating the diquat toxicity. Considering the role of glutathione level in the detoxification of mutagens and carcinogens, the advantage of fotemustine over BCNU in therapeutic use seems substantiated.

Animals↗

[Epidermoid carcinoma of the esophagus: preliminary results of combined treatment].

In 1986, a prospective study was started in CHUV on the squamous-cell carcinoma of the esophagus treated with a multimodality protocol associating preoperative chemotherapy and surgery. Nineteen patients are currently followed-up. Dysphagia is the main symptom and was found in 16 patients (84%). After chemotherapy, dysphagia disappeared completely in 7 cases (44%), regressed in 7 other cases and worsened in 1 case. Twelve patients were operated on, without operative mortality. Histologically, no tumor was found in one case (5%) after the preoperative treatment. Follow-up is currently too short to draw statistical conclusions. The rationale, advantages and perspectives of the multimodality treatment are presented and compared with different recent series.

Antineoplastic Combined Chemotherapy Protocols↗

[Totally implantable catheters. Experience at the University Hospital Center Vaudois from March 1984 to December 1987].

With cancer patients, the venous access remains a major problem. It causes phlebitis, venous sclerosis, skin necrosis and sepsis. Its maintenance implies careful nursing and a great dependence for the patient. Arterio-venous fistulas have been abandoned and replaced by Hickman-type subcutaneous indwelling catheters. These have a complication rate, mainly infectious, of about 0.4/100 days. The development of totally implanted catheters diminishes even more this rate and improves the patient's comfort. In this article we report the experience gained from 100 cancer patients equipped with 107 catheters. 31 complications occurred over a total time of 15,421 days, this averages a rate of 0.2 complications/100 days. The respectively rate of thrombosis and infections are of 0.02/100 days each. In 61% of the cases the whole system was functional after management of the complication. This results confirm the excellent tolerance of the system, its minimal rate of complication and its great possibility of reutilization.

Antineoplastic Agents↗