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Biomedical subjects

G Reach

Publications and source records attributed to G Reach.

At least 145 records · Page 8Linked to original sources

[Application of the saralasin test to the treatment of malignant or accelerated arterial hypertension (author's transl)].

A test using saralasin, an antagonist of angiotensin II, was carried out in 9 patients with malignant or accelerated arterial hypertension, and the initial treatment was modified according to the results: if the fall in mean arterial blood pressure was greater than 10 p. cent, beta-blockers or alpha-beta blockers were prescribed alone; if not, diuretics were used concomitantly. Blood pressure response correlated with plasma renin activity and aldosterone, and the reduction in mean arterial blood pressure after 24 hours' treatment correlated with that observed with saralasin. In longer term saralasin has no predictive value with regard to the course of the hypertensive disease or the results of future treatments.

Adult↗

[Phaeochromocytoma: localisation by computerised scanner tomography. 5 cases (author's transl)].

In five patients with a phaeochromocytoma, axial computerised scanner tomography made it possible to localise the tumour without ambiguity, even when intravenous urography had been interpreted as normal. Although all the tumours diagnosed were relatively large (between 3 and 9 cm), this is nevertheless a non-invasive examination, free of danger and worthy of consideration in the preoperative assessment of a case of phaeochromocytoma.

Adrenal Gland Neoplasms↗

Glucagon and diabetes mellitus.

The present status of knowledge about glucagon pathophysiology in diabetes is reviewed. 1) A-cells behave abnormally in all varieties of diabetes mellitus, spontaneous and experimental, except perhaps in case of pancreatectomized humans. These abnormalities are : hyperreactivity of A-cells to arginine, non suppressibility by glucose, and absence of stimulation following hypoglycemia. 2) These abnormalities appear as secondary in most instances : a) A-cells behave in a normal way in most studies with prediabetics ; b) plasma glucagon concentration is normalized by excellent control of diabetes or following prolonged insulin infusion. High doses of insulin are required most of the times to obtain a normalization of A-cell function : in insulin-dependent diabetics, the physiological portoperipheral insulin gradient no longer exists, and the high doses of insulin which are necessary may be the only mean to reconstitute the high insulin concentrations supposed to be present at the A-cell level. 3) Conflicting results have been collected about the role of this glucagon excess in aggravating the diabetic metabolic syndrome. Evanescent effects follow sustained glucagon infusions: but in diabetics, glucagon bursts rather than permanent hyperglucagonemia are observed and these appear deleterious to glucose tolerance. It seems clear however that insulin deprivation is required for the full expression of the consequences of glucagon excess.

Animals↗

Aldosterone metabolism in isolated perfused rat kidney.

The renal metabolism and handling of [1,2-3H]aldosterone ([3H]A) was studied using isolated perfused rat kidney under different perfusion conditions. The metabolite production rate (MPR) and the urinary excretion of [3H]A together with its radiometabolites (UV/P3H) were studied. Among the formed metabolites, no acid-labile conjugate of aldosterone (ALC) was detected. The MPR was not altered in studies using nonfiltering kidney, a result that suggests that the majority of metabolites were formed without requirement of the process of glomerular filtration and tubular uptake of the hormone. High perfusion pressure (high PP) resulted in a striking increase in whole metabolic clearance rate of aldosterone (MCR[3H]A) due mostly to an enhanced urinary excretion of intact aldosterone and, to a lesser degree, to a significant increase in MPR. Factors determining the excretion rate of [3H]A and its metabolites were than investigated under administration of diuretics. Mannitol (44 mM) induced a marked increase in urine volume (UV) accompanied by a significant UV/P3H increase. Meanwhile, 0.1 mM furosemide resulted in an increase only in UV, but not in UV/P3H. These results revealed the UV dependence of aldosterone excretion in certain diuretic conditions.

Aldosterone↗

Cortisol metabolism and excretion in the isolated perfused rat kidney.

The isolated perfused rat kidney allows a simultaneous kinetic study of both the renal metabolism and the urinary excretion of cortisol and its metabolites in the rat. In this system, cortisol was completely metabolized within 120 minutes. The main renal metabolites of cortisol (cortisone, 20 reduced cortisol and 20 reduced cortisone) were found in the recirculating perfusate and in urine. The formation of these metabolites was quantitatively evaluated and compared to a theoretical model.

Animals↗

Kinetic modelling as a tool for the design of a vascular bioartificial pancreas: feedback between modelling and experimental validation.

A bioartificial pancreas is a system which contains isolated islets of Langerhans protected against immune rejection by an artificial membrane, permeable to glucose and insulin, but not to lymphocytes and immunoglobulins. However, it is necessary to design a device which performs as a closed-loop insulin delivery system, more specifically which rapidly responds to a change in the recipient's blood glucose concentration by an appropriate change in insulin release. We have designed a system intended to be connected as an arteriovenous shunt of the recipient; islets are placed between two flat ultrafiltration membranes, and blood circulates successively above the upper, and below the lower, membrane, in reverse direction. A complete kinetic model of glucose transfer from blood to the islet compartment, of insulin generation by the islets displaying a biphasic insulin pattern, and of insulin transfer into the bloodstream was described, and parameters were calculated on the basis of experimental data obtained when islets of Langerhans were perfused in vitro with a synthetic buffer. The resulting calculations indicated that both diffusional and convective transfers were involved in glucose and insulin mass transfer across the membrane, the contribution of diffusion being the most important. The geometry of the system was therefore modified in order to decrease the resistance to flow inside the blood channel. This should increase, at a given hydrostatic pressure, the blood flow rate, and thereby improve the diffusional transfer of insulin. This should also decrease the thrombogenicity of the device.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Use of polyethyleneglycol for porcine islet cryopreservation.

The aim of this work was to determine whether polyethylene glycol 20000 Da (PEG) could be used as protective agent in porcine islet cryopreservation. Cryopreservation was performed on 1-wk cultured pig islets and consisted in an overnight storage in liquid nitrogen. In a first set of experiments, we compared the in vitro function of PEG-cryopreserved islets to that of porcine islets cryopreserved under the standard procedure using dimethylsulfoxide (DMSO), by incubating the islets over 45 min in Krebs buffer containing either 2.8 or 10 mmol/L glucose. Insulin secretion of both types of islets reached a maximum at day 10 postthawing and had stimulation indices above 2 up to 3 wk after thawing. PEG-cryopreserved islets secreted more insulin than DMSO-treated islets and showed glucose-dependency insulin secretion in a 0-16.6 mmol/L glucose range. We also established that PEG-cryopreserved islets were as functional in vitro as nonfrozen tissue and that they could reverse experimental diabetes of the mouse for longer periods of time than noncryopreserved islets (p < 0.005 3 wk after transplantation) when implanted in the peritoneal cavity, being immunoprotected in a semipermeable hollow fiber. PEG can, therefore, be considered as a suitable cryoprotective compound for porcine islet storage.

Animals↗

In vitro and in vivo evaluation in dogs of a miniaturized glucose sensor.

A miniaturized glucose sensor was developed, consisting of a platinum wire entirely coated with teflon, except for a 1 mm section near its extremity where glucose oxidase is immobilized. The in vitro sensitivity to glucose of the sensors was 2.3 +/- 0.4 nA/mM, mean +/- SEM (n = 23). These sensors were implanted in the subcutaneous tissue of normal beagles. Two consecutive glucose infusions (15-30 mg/kg/min) were performed. The current generated by the sensor was used for calculation of the sensitivity coefficient (SC) (nA/mM), and the background current in the absence of glucose (lo) (nA). These parameters were used for determination of the apparent subcutaneous glucose concentration. The in vivo sensitivity was less than the in vitro sensitivity (0.5 +/- 0.1 vs. 2.2 +/- 0.2; n = 12 comparisons; p less than 0.01). Stability of sensor function was demonstrated by the absence in variation of SC and lo, calculated from the different plateaus obtained during the glucose infusions. This study provides a simple method for evaluating in vivo the function of a miniaturized sensor implanted in subcutaneous tissue.

Animals↗

Effect of insulin immunization on glucose tolerance in normal rats.

Normal rats were immunized with insulin and Freund's adjuvant and submitted to an intravenous glucose tolerance test. Plasma glucose and free and total IRI levels were determined and compared to those observed in untreated rats, and in animals injected with the Freund's adjuvant used for the immunization procedure. In six of the 15 insulin injected animals, a significant amount of IRI (more than 100 mU/l) was found to circulate in bound form. In these animals, the fasting plasma glucose concentrations, and glucose disappearance rates were not different from those observed in all the other groups. However, the rise in their free IRI level was delayed, as was the return to basal level: 45 min after glucose injection, the free IRI concentration was still 98 +/- 29 mU/l in the six immunized rats vs 14 +/- 6 mU/l in those treated with Freund's adjuvant (p less than 0.01). Furthermore, the secondary nadir in the plasma glucose concentration observed at 60 min after glucose injection, was lower in the immunized rats (5.4 +/- 0.5 vs 6.8 +/- 0.3 mmol/l, p less than 0.05). It is concluded that in normal animals, IRI binding in proportions similar to those commonly observed in insulin-treated diabetic patients does not alter glucose tolerance but might lead to abnormal insulin kinetics and secondary hypoglycemia. These results might have implications for the use of closed-loop insulin delivery systems in type 1 (insulin-dependent) diabetic patients with insulin antibodies.

Animals↗