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Biomedical subjects

F T Murray

Publications and source records attributed to F T Murray.

49 records · Page 3Linked to original sources
PubMed1977

The metabolic response to moderate exercise in diabetic man receiving intravenous and subcutaneous insulin.

The responses to moderate exercise of circulating energy fuels and endocrine pancreatic hormones were examined in insulin-dependent diabetics receiving insulin either sc or by continuous iv infusion. Eight subjects received one-third of their usual daily insulin doses sc in the thigh 1 h prior to exercise. Seven subjects exercised during infusion (iv) of insulin at 8-20 mU"min, started 12-14 h earlier. Exercise was on a bicycle ergometer for 45 min at 50% maximum oxygen consumption. The diabetics receiving sc insulin showed a sharp decline in glycemia from elevated resting levels (227 +/- 16 mg/dl), in contrast to the control subjects whose glycemia did not change. The control subjects insulin (IRI) fell, and glucagon (IRG) remained unchanged. In the sc-insulin diabetics, exercise induced a further rise in IRG from elevated levels (296 +/- 76 pg/ml). Resting lactate, pyruvate and alanine were normal and increased as in controls. Though FFA, glycerol and ketone body levels were normal at rest, FFA failed to rise with exercise as in the controls and glycerol and ketone body increments were smaller. RQ increased and remained elevated in contrast to the later fall in controls during exercise. These results are consistent with selective insulin deficiency at rest, and increased insulin effect during exercise. This resulted in greater carbohydrate utilization during exercise, but without the normal shift back toward utilization of fat-derived fuels with continuation of exercise. Diabetics receiving insulin by infusion showed no glycemic change with exercise. Exercise caused greater increases in lactate and pyruvate levels (4-fold), although alanine levels increased only during recovery. The significantly elevated resting FFA levels showed a rise which was sustained at higher than control values during recovery; glycerol and ketone body increments also tended to be greater than in controls. Intravenous insulin sustained euglycemia in exercise, obviating the fall in glycemia with sc insulin. The responses of other metabolite levels were abnormal, and consistent with a subtle degree of underinsulinization.

Adult↗
PubMed1977

The spontaneously diabetic Wistar rat. Metabolic and morphologic studies.

A new, spontaneously diabetic syndrome has been recognized in nonobese outbred Wistar rats of both sexes. The age at detection of first glycosuria has varied from 48 to 120 days, with a mean of 67 days. Eighteen rats have been studied, 14 untreated and four during and after cessation of insulin treatment. The affected animals have demonstrated a spectrum of severity, with hyperglycemia (252-732 mg./dl.), hypoinsulinemia (0-1 ng./ml.), and hyperketonemia. The severely ketotic rats, with total blood ketone body levels between 6 and 13 mM, showed rapid loss in weight and dehydration over one to six days. The moderately ketotic (1-5 mM) declined gradually in weight over 15 days, with marked polyuria and glycosuria. The stable rats, with ketonemia less than 1 mM, sustained their weights, polyuria, and glycosuria for longer than 40 days. A relative or absolute increase in plasma immunoreactive glucagon and elevated levels of free fatty acids and branched-chain amino acids were observed in relation to the severity of the syndrome. Intraperitoneal arginine or tolbutamide elicited no insulin response, but the glucagon response to arginine was exaggerated. Pancreatic insulin content was normal or moderately decreased. Light-microscopic examination of pancreases of ketotic animals at the end stage of the disease showed islets to be very small and rare, consisting virtually of non-beta cells. In stable and earlier ketotic rats, the islets were small, with reduction in beta-cell number and a striking inflammatory cell infiltration. Surviving beta cells showed variable degranulation. This model of spontaneous diabetes in nonobese rats displays insulin deficiency, glucagon excess, and ketosis, with a dramatic inflammatory lesion during active beta-cell destruction.

Aging↗
PubMed1977

Normalization of glycemia in diabetics during meals with insulin and glucagon delivery by the artificial pancreas.

An extracorporeal "closed-loop" system has been employed to maintain glycemia in the normal range during consumption of meals in nine insulin-treated diabetics. This artificial pancreas system incorporated continuous blood glucose monitoring (0.05 ml. per minute, delay time 90 seconds), a computer programed to respond to glycemia, and a hormone delivery system. Intravenous insulin delivery rates were determined by control parameters responsive to both glucose concentration and its rate of change. Because insulin-dependent diabetics often defend themselves poorly against hypoglycemia (in some cases due to inadequate glucagon responses), the instrument was also programed for exogenous glucagon delivery. A priori selection of ideal parameters for insulin and glucagon delivery for each individual is not yet possible. Consequently, when the parameters were used for the first time on each subject, they were varied over a reasonable range. This approach resulted in a corresponding variety of glycemic responses, the average of which characterized a set of initial parameters that is generally applicable. Appropriate control parameters are presented that successfully prevented hypoglycemia. Glucagon delivery directly related to glycemia appeared sufficient for this purpose, thus obviating the need for dextrose administration. This system provides a technique for complete normalization of blood glucose concentration in the types of diabetics tested, during both fed and interprandial periods. It has yielded insights essential to the development of more sophisticated future devices.

Adult↗
PubMed1977

Studies with an artificial endocrine pancreas.

Short-term studies with an artificial endocrine pancreas have provided insights into the pathophysiology of diabetes and demonstrated the ability of such a system to restore and maintain glucose homeostasis in human subjects given either their usual diet, a 50 gm oral glucose tolerance test, or a moderate level of physical exercise. Animals were used to demonstrate that a peripheral route of insulin delivery by the artificial pancreas is equivalent to the portal route.

Animals↗
PubMed1976

Effect of ketosis on respiratory sensitivity to carbon dioxide in obesity.

We investigated whether the respiratory defect in the obesity-hypoventilation syndrome might respond to dietary manipulation. The effects of hypocaloric ketogenic regimens on the ventilatory response to carbon dioxide were studied in a manner excluding changes in weight or thoracic mechanics as factors. Six obese subjects with hyporesponse (less than 1.1 1/min/mm Hg) and 12 with normal response were fasted or given a diet containing 400 kcal per day of protein. During ketosis carbon dioxide response more than doubled in those with hyporesponse (0.8 +/- 0.1 to 1.8 +/- 1/min/mm Hg, P less than 0.05) but was unchanged in those with normal response. This improvement could not be accounted for by changes in weight, pulmonary function, pH or degree of ketosis between the two groups. However, a significant positive (r = 0.70; P less than 0.001) correlation between ketone-body concentrations and carbon dioxide response was observed in subjects with hyporesponse. These results indicate that depressed sensitivity to carbon dioxide in obese patients can be increased by dietary manipulation.

Acidosis↗
PubMed1975

Acute mitral regurgitation from ruptured chordae tendineae in systemic lupus erythematosus.

A patient with systemic lupus erythematosus developed acute mitral regurgitation due to ruptured chordae tendineae, requiring mitral valve replacement. Typical changes of Libman-Sacks endocarditis were observed in the excised mitral valve. Immunofluorescent studies revealed antinuclear antibody and deposits of immunoglobulins and complement within small vessels.

Adult↗
PubMedDate not supplied

Serum aminoglutethimide levels: studies of serum half-life, clearance, and patient compliance.

Serum aminoglutethimide was measured in 13 women with mastastatic breast carcinoma who were treated with 1.0 Gm aminoglutethimide and 40 mg hydrocortisone daily over a period of one year. Serum concentrations of aminoglutethimide were used to evaluate drug half-life, clearance, and patient compliance. Mean half-life and clearance rates were determined in six patients. The mean half-life of aminoglutethimide prior to therapy was 13.3 +/- 2.65 (S.D.) hours and fell significantly (P less than 0.01) to 7.3 +/- 2.14 hours after six to 32 weeks of therapy. The mean clearance rate prior to therapy was 2.58 +/- 0.33 (S.D.) 1./hour and increased significantly (P less than 0.01) to 5.29 +/- 1.4 1./hour after therapy. The mean serum concentration was 11.5 +/- 3.6 microgram/ml in seven patients. No significant variation of mean aminoglutethimide concentration from the overall mean was noted during the course of therapy. We conclude that serum aminoglutethimide concentrations are useful in evaluating patient compliance. Our data also suggest that aminoglutethimide increases its own metabolism, which may explain the absence of toxicity symptoms seen late in the treatment period.

Aminoglutethimide↗
PubMedDate not supplied

Ultrastructural lesions in testes from hyperprolactinemic men.

Testicular tissue from eight men with prolactinomas and elevated serum prolactin were evaluated by light (LM) and transmission electron microscopy (TEM). A semiquantitative assessment of testicular morphology was employed to provide a morphology index for each tissue specimen. Although in each biopsy specimen germ cell exfoliation was evident, as was abnormal structural change in the seminiferous epithelium, there was no apparent correlation with the overall degree of tissue pathology (morphology index) and the serum level of prolactin. All of the tissue displayed variably thickened seminiferous tubule walls which, when viewed by TEM, were composed of thickened laminae propriae and redundant and involuted basal laminae. Likewise, all tubules contained Sertoli cells with overt cytoplasmic degeneration, principally in the apical (adluminal) region of the cell. This was visualized, in part, as a retraction of the apical cytoplasm from periluminal spermatids and degeneration or absence of Sertoli-germ cell junctional specializations. Sertoli-Sertoli cell junctional complexes appeared structurally intact. Leydig cell ultrastructure was typical of normal cells and contained a variable amount of lipid and smooth endoplasmic reticulum. This also was without positive correlation with the overall degree of tissue pathology or level of serum prolactin. Our results demonstrate the variable degree of testicular pathology associated with hyperprolactinemia in man, and suggest that abnormal tubule walls and altered Sertoli cell ultrastructure are consistent findings in this abnormal endocrine condition.

Adult↗
PubMedDate not supplied

Alterations of testicular function induced by hyperprolactinemia in the rat.

The effects of hyperprolactinemia on testicular structure and pituitary-gonadal function were investigated in male rats. Hyperprolactinemia was induced in the Wistar-Furth rat by implantation of tissue fragments of a prolactin-secreting MtTW15 pituitary adenoma. The MtTW15 tissue was maintained in one animal group for 27 days (group A) and in another group for 37 days (group B). Appropriate age-matched controls were utilized in each study. Serum prolactin was significantly elevated (P less than 0.001) in both groups of MtTW15-bearing rats compared with their controls. The degree of hyperprolactinemia was more severe in rats of group B (2842 +/- 546 ng/ml) than in rats of group A (367 +/- 38 ng/ml). Accessory sex organ weights in group B rats were significantly lower than in controls, but were apparently unaffected in group A rats. Hyperprolactinemia induced definite but variable testicular alterations in both animal groups that presented as seminiferous epithelial disorganization, germ cell exfoliation, increased tubule wall thickness, and abnormal Leydig cell lipid content. Electron microscopy revealed structural disruption of Sertoli-germ cell junctional complexes and apical Sertoli cell cytoplasmic degeneration. The hyperprolactinemic rat exhibited significant reductions in serum luteinizing hormone (LH), testosterone (T), and androgen binding protein (ABP) when compared with controls. Eighty-six days following surgical removal of the MtTW15 tissue in a subgroup of group B rats, serum levels of prolactin and LH returned to normal, as did weights of accessory sex organs and testicular morphology. These results indicate that exposure to the MtTW15 adenoma and its later removal in the rat provides a workable model for studying the effects of hyperprolactinemia on testicular structure and function, and for identifying events involved in the subsequent recovery of spermatogenic disruption.

Adenoma↗
PubMedDate not supplied

The pituitary-testicular axis at rest and during moderate exercise in males with diabetes mellitus and normal sexual function.

Hormonal studies of pituitary-testicular function in insulin-dependent diabetes mellitus were examined at rest and during moderate exercise to assess whether diabetes per se caused abnormalities of nocturnal penile tumescence and androgen function in men with normal sexual function. The present study compared 10 healthy men and eight men with Type I diabetes mellitus in whom normal sexual function was determined by clinical history. Urinary gonadotropin excretion, semen analysis and diurnal variation of serum glucose, prolactin, testosterone and free testosterone were determined in both groups. In addition, the serum levels of testosterone, free testosterone, prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured at rest, during 45 minutes of exercise on a bicycle ergometer at 50% of the subjects previously determined maximal oxygen uptake (VO2 max) and during a 30-minute recovery period. Nocturnal penile tumescence and parameters of semen analysis were similar in both groups. Urinary FSH excretion and serum FSH were higher (P less than or equal to 0.01) in the diabetic subjects while urinary LH excretion was similar. Diurnal variation of serum prolactin, testosterone and free testosterone were similar in both groups. Exercise produced a significant (P less than or equal to 0.01) increase in maximal free and total testosterone in both groups without changes in serum FSH or LH. Prolactin increased significantly (P less than or equal to 0.01) during exercise in the diabetic group only. We conclude that, for the most part, the pituitary-testicular axis and nocturnal penile tumescence under basal conditions and the pituitary-testicular axis during moderate exercise are similar in healthy males and insulin-dependent diabetic males with normal sexual function.

Adolescent↗
PubMedDate not supplied

Use of the Florida Sexual History Questionnaire to differentiate primary organic from primary psychogenic impotence.

A recent study demonstrated the Florida Sexual History Questionnaire (FSHQ) is reliable and valid when used to discriminate impotent from nonimpotent men. This study examined the ability of the FSHQ to discriminate between men with primary psychogenic and primary organic impotence in a sample of impotent diabetics and a larger group of impotent men. The hit rate in the diabetic sample was 81% using an eight-item discriminant function, and 70% using the total score. Hit rates in the larger sample were significant but lower (73% and 66%). The results suggest that the FSHQ has concurrent validity in terms of discriminating primary organic from primary psychogenic impotence.

Diabetes Mellitus, Type 2↗