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Biomedical subjects

D M Brown

Publications and source records attributed to D M Brown.

At least 289 records · Page 16Linked to original sources

Alteration in the balance of prostaglandin and thromboxane synthesis in diabetic rats.

An evaluation of platelet and vascular (aortic) arachidonic acid metabolism was performed in Lewis male rats rendered diabetic by injection of streptozotocin, and the results were compared to those in matched controls. Parameters evaluated included the release of this fatty acid from prelabeled platelets and aortas and conversion of labeled fatty acid to thromboxane B2 and 6-keto-PGF1 alpha in platelets and aortas, respectively. Diabetic rat platelets showed markedly increased release of arachidonic acid with thrombin used as the aggregating stimulus. Conversion of arachidonic acid to thromboxane B2 was slightly, but not significantly, higher in the diabetic rats. In the vessel, thrombin-stimulated release of arachidonic acid was slightly, but not significantly, increased in the diabetic animals when compared to controls. This finding was associated with a decrease in vascular production of 6-keto-PGF1 alpha both in vascular tissues incubated with arachidonic acid alone and in vascular tissues incubated with thrombin. The changes observed both in platelet and vascular metabolism of arachidonic acid were corrected by islet issue transplantation, suggesting a disease-specific effect. The changes observed in arachidonic acid metabolism suggest a significant imbalance in thromboxane A2 and PGI2 production in diabetic rats. Such changes might promote the development of the microvascular changes seen in diabetes mellitus.

Animals↗

Studies of the glomerular mesangium and the juxtaglomerular apparatus in the genetically diabetic mouse.

Intact and uninephrectomized genetically diabetic (db/db) mice (C57BL/KsJ) and their nondiabetic littermates (dm/m) had renal biopsies performed at 6 months of age. Renal tissues were studied by regular light microscopy and by a variety of immunohistochemical techniques. Intact db/db mice had peripheral mesangial thickening as compared to db/m mice. This thickening, predominantly due to increased mesangial matrix material, extended to the glomerular hilum and the extraglomerular mesangium of the juxtaglomerular apparatus. This abnormality was markedly increased an uninephrectomized db/db mice (db/db-UN) compared to intact db/db mice. Db/m-UN animals had slightly greater mesangial thickness than intact db/mice but less than that of db/db mice. Intact db/db mice had increased mesangial IgM staining compared to db/m mice and these differences were magnified by uninephrectomy. The IgM staining, especially in the diabetic mice, involved the peripheral mesangium and the glomerular hilum extending into extraglomerular mesangium and the distal tubule at the level of the macula densa. The tubular staining in the region of the juxtaglomerular apparatus was between the tubular basement membrane and the epithelial cells and between epithelial cells. The distal tubular epithelial cell cytoplasm also showed increased staining for IgM as the tubule coursed away from the glomerulus. These studies amplify the argument that alterations in glomerular hemodynamics influence the rate of development of diabetic glomerular lesions. Further, these diabetic mice appear to represent an important model for the study of mesangial macromolecular processing mechanisms.

Animals↗

The development, enhancement, and reversal of the secondary complications of diabetes mellitus.

Diabetic glomerulopathy continues as a major problem in the management of the patient with diabetes mellitus; however, evidence in man and in animals underlines the fact that good control of diabetes favorably alters the course of this complication. Islet transplantation in the diabetic rat returns plasma glucose and insulin levels to normal. In parallel mesangial matrix thickening, mesangial deposition of immunoglobulin and urinary excretion of albumin markedly improve following islet transplantation. Although amelioration of diabetes affects the course of glomerulopathy, other factors (most notably measures that increase glomerular capillary pressure) enhance the development of the diabetic renal lesions. Following uninephrectomy or clipping of a renal artery, the remaining (in the case of uninephrectomy) or unclipped diabetic kidney develops the morphologic and functional changes of diabetic nephropathy at a rate greater than in kidneys in an intact diabetic rat. The clipped kidney demonstrates diminished diabetic changes, suggesting a protective effect with decreased glomerular capillary pressures. In addition to measures improving the control of diabetes, procedures reducing factors accelerating diabetic complications may improve the prognosis in diabetic glomerulopathy.

Albuminuria↗

Effect of nitrous oxide on the cardiovascular system and coronary circulation of the dog.

A comparison was made in seven dogs anaesthetized with pentobarbitone of cardiovascular measurements during ventilation with 65-70% nitrous oxide in oxygen and ventilation with 65-70% nitrogen in oxygen. The substitution of nitrous oxide for nitrogen was found to be associated, after 15 min, with a significant decrease in cardiac output and significant increases in right atrial and left ventricular end-diastolic pressure and systemic vascular resistance. There was no significant change in mean coronary artery flow, coronary vascular resistance or myocardial oxygen consumption.

Animals↗

Canine coronary blood flow responses to hypoxaemia: the influence of halothane.

Electromagnetic flow meters were used to measure blood flow in the coronary and pulmonary arteries of six anaesthetized dogs following thoracotomy. Halothane 1% (v/v) caused a reduction in arterial pressure, coronary artery flow, cardiac output and myocardial and total body oxygen consumption and an increase in coronary vascular resistance. Hypoxaemia caused large increases in coronary artery flow during both cardiac systole and diastole, but not until PaO2 was less than 5.3 kPa. This response was not influenced by the presence of halothane. Although myocardial oxygen availability and consumption were maintained during hypoxaemia, total body oxygen availability and consumption were markedly reduced.

Animals↗

Effect of hypotension induced with sodium nitroprusside on canine coronary arterial flow.

In seven dogs anaesthetized with pentobarbitone, coronary and pulmonary artery blood flows were measured using electromagnetic flow meters. The infusion of a 0.01% solution of sodium nitroprusside caused an initial small increase in mean coronary artery flow which returned to control as the arterial pressure decreased. No changes were noted in cardiac output nor were further changes observed in coronary flow. Heart rate was increased consistently during the hypotension and left ventricular dp/dt max was reduced as were coronary and total peripheral resistances. There were no significant changes in myocardial or total body oxygen extraction or consumption.

Animals↗

Response of mean and phasic coronary arterial blood flow to graded hypercapnia in dogs.

An electromagnetic flow meter was used to assess the changes in coronary blood flow in response to four levels of increased PaCO2 in six dogs. Mean, diastolic and systolic flow all increased during hypercapnia, the increase being maximal at mean PaCO2 11.3 KPa. Mean and diastolic coronary vascular resistances decreased progressively as PaCO2 increased, but systolic resistance, although decreasing with the lower levels of hypercapnia, returned to control at the greatest PaCO2. Although the oxygen available to the myocardium was increased markedly during hypercapnia, coronary sinus PO2 increased also, reflecting a reduction in myocardial oxygen extraction; thus myocardial oxygen consumption was unchanged. Cardiac output was increased significantly only at the greatest PaCO2. Total body oxygen handling was not altered significantly.

Animals↗

The effects of ketamine on the canine coronary circulation.

Systemic and coronary haemodynamic measurements have been made in six healthy greyhounds anaesthetized with trichloroethylene. The administration of ketamine in bolus doses of 5 mg/kg, 10 mg/kg and 5 mg/kg followed by an infusion 0.1 mg/kg/min was found to be accompanied by a decrease in arterial pressure and an increase in cardiac output produced by an increase (84%) in stroke volume. Coronary blood flow increased greatly as did myocardial oxygen consumption and there was no change in myocardial oxygen extraction.

Animals↗

The supply of physicians' services.

This paper presents a model of the supply of physicians' services based upon the assumption that physicians are price-taking utility maximizers. Assuming physicians' services are produced using physicians' labor and purchased inputs, the paper shows that the impact of changes in final product or input prices on the supply of physicians' services depends on the physicians' labor-leisure choice and on the degree of substitutability between physicians' labor and purchased inputs. The empirical results presented indicate that the physicians' labor supply curve is backward-bending, but that the supply curve of physicians' services is positively sloped.

Economics, Medical↗