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Biomedical subjects

S E Kahn

Publications and source records attributed to S E Kahn.

At least 127 records · Page 7Linked to original sources

Rhabdomyolysis in a case of free-base cocaine ("crack") overdose.

This is the case of a 27-year-old black man who was admitted to Loyola University Medical Center after a one-time experience of smoking free-base ("crack") cocaine. Clinical manifestations of the resulting cocaine intoxication were rhabdomyolysis, acute renal failure, and transient liver failure. This patient came to our attention because of the striking alterations in his blood-chemistry values, which indicated acute tissue damage, and his remarkable recovery within 96 h. We discuss the dramatic changes in the laboratory findings and the clinical course of this patient.

Acute Kidney Injury↗

Testicular dysfunction in experimental chronic renal insufficiency: a deficiency of nocturnal pineal N-acetyltransferase activity.

Biochemical correlates of neuroendocrine/gonadal function and nocturnal levels of serotonin N-acetyltransferase (NAT) activity were determined in partially nephrectomized (PNx), male, Long Evans rats following a 5-week period of chronic renal insufficiency (CRI). PNx animals demonstrated two to four-fold elevations in urea nitrogen and three to four-fold reductions (P less than 0.02) in plasma total testosterone concentrations as compared to sham-operated controls. The pituitary LH contents of PNx rats were decreased to approximately 60% of the control value (P less than 0.05). There were no differences in plasma prolactin levels between the control and PNx groups either at mid-day or in the middle of the night. Nocturnal pineal NAT activity in PNx rats was markedly reduced to approximately 20% of the control value (P less than 0.001). Similar evidence of gonadal dysfunction (reduced plasma total testosterone and testes testosterone content) and a significant decrease in night-time levels of pineal NAT activity were also observed after 13 weeks of CRI in PNx rats of the Sprague-Dawley strain that were housed under a different photoperiod. These results suggest that pineal gland dysfunction is a feature of CRI in the PNx model. Such an abnormality might contribute to the pathogenesis of gonadal dysfunction in CRI.

Animals↗

Islet dysfunction in non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus is characterized by fasting hyperglycemia associated with defects in the pancreatic islet, the liver, and the peripheral tissues, which together comprise a feedback loop responsible for maintenance of glucose homeostasis. This review focuses on the key role of the endocrine pancreas A and B cells to coordinate glucose output from the liver with glucose utilization. The basal rate of hepatic glucose production is elevated in subjects with non-insulin-dependent diabetes mellitus and this is positively correlated with the degree of fasting hyperglycemia. This increased rate of glucose release by the liver results from impaired hepatic sensitivity to insulin and reduced insulin secretion. Though basal insulin levels in patients with non-insulin-dependent diabetes mellitus may appear normal when compared with those of healthy persons, islet function testing at matched glucose levels reveals impairments of basal and stimulated insulin secretion due to a reduction in B cell secretory capacity. The degree of impaired beta-cell responsiveness to glucose is closely related to the degree of fasting hyperglycemia but in a curvilinear fashion. The efficiency of glucose uptake by the peripheral tissues is also impaired due to a combination of decreased insulin secretion and defective cellular insulin action. This impairment becomes more important to the hyperglycemia as the islet dysfunction declines. Therapeutic interventions either improve islet dysfunction and raise plasma insulin levels, reduce hepatic glucose production, or improve the efficiency of tissue glucose uptake. All result in a decline in the fasting glucose level regardless of the cause of hyperglycemia. It is concluded that non-insulin-dependent diabetes mellitus is characterized by a steady-state re-regulation of plasma glucose concentration at an elevated level in which islet dysfunction plays a necessary role.

Blood Glucose↗

Defects in beta-cell function and insulin sensitivity in normoglycemic streptozocin-treated baboons: a model of preclinical insulin-dependent diabetes.

During the preclinical period of human insulin-dependent diabetes, both impaired pancreatic beta-cell function and increased insulin resistance are found, although normoglycemia is preserved. To better understand the changes in beta-cell function and insulin sensitivity that occur in preclinical insulin-dependent diabetes, we performed a panel of in vivo beta-cell function tests and measured insulin sensitivity in adolescent male baboons both in normal health and after a small dose of streptozocin which did not induce hyperglycemia. Nine animals were studied before (stage 1) and 1 week after receiving a low dose of streptozocin (stage 2). There was no change in fasting plasma glucose or insulin. The mean glucose disposal rate (Kg) remained within the normal range, but dropped from 2.0 +/- 0.2% +/- SE) to 1.2 +/- 0.1%/min (P less than 0.01), the acute insulin response to arginine (AIR(arg)) fell from 67.7 +/- 19.4 microU/mL (485.8 +/- 139.2 pmol/L) to 32.8 +/- 7.2 microU/mL (235.3 +/- 51.7 pmol/L; P less than 0.05), and the acute insulin response to glucose (AIR(gluc)) fell from 881 +/- 243 microU/mL.10 min (6321 +/- 1744 pmol/L.10 min) to 334 +/- 82 microU/mL.10 min (2396 +/- 588 pmol/L.10 min; P less than 0.01). The most dramatic change, however, was in the ability of hyperglycemia to potentiate AIR(arg) (expressed as the slope of potentiation). This was reduced by 94% from 1.8 +/- 0.5 to 0.1 +/- 0.1 (P less than 0.01), with almost no overlap in values between stages 1 and 2. Insulin sensitivity was also lower 1 week after streptozocin treatment. When the animals were restudied 8 weeks after streptozocin treatment (stage 3) most measures of beta-cell function were not significantly different from those in stage 1. The fasting plasma glucose level was 85.4 +/- 4.3 mg/dL (4.7 +/- 0.2 mmol/L), Kg was 1.8 +/- 0.3%/min, fasting plasma insulin was 35.9 +/- 8.5 microU/mL (257.6 +/- 61.0 pmol/L), AIR(arg) was 67.0 +/- 15.4 microU/mL (480.7 +/- 110.5 pmol/L), and AIR(gluc) was 615.3 +/- 265.3 microU/mL.10 min (4413 +/- 1901 pmol/L.10 min), and tissue insulin sensitivity was 2.7 +/- 0.4 x 10(4) min/microU.mL. These values show extensive overlap with those of stage 1, from which they are not significantly different. The slope of glucose potentiation, however, remained low in all animals at stage 3.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Tryptophan distribution and metabolism in experimental chronic renal insufficiency.

Several aspects of tryptophan distribution and metabolism in chronic renal insufficiency (CRI) were investigated in a rat model prepared by partial nephrectomy. Partially nephrectomized (pNx) rats with a moderate degree of CRI demonstrated a 40% decrease in plasma total tryptophan concentration between 5 and 11 weeks after the acute reduction of renal functional mass. This decrease was accompanied by hypoalbuminemia, polyuria, albuminuria, and tryptophanuria. After 5 weeks of sustained plasma total tryptophan deficiency (from Week 6 to Week 11), the plasma free tryptophan concentration, the plasma concentrations of large neutral amino acids, and the tryptophan levels in red cells, liver, and kidney of the pNx rats were similar to those of the controls. However, evidence for abnormal brain tryptophan metabolism in pNx rats after 11 weeks of CRI included 16% reductions of tryptophan levels in the midbrain and pons and 65% increases in the serotonin contents of the hypothalamus and medulla. Monoamine oxidase activities in hypothalamus and cerebellum of pNx rats were the same as those of the controls. These studies indicate that tryptophanuria is an important factor in the development of the plasma tryptophan deficiency in the pNx model. In addition, the results support the hypothesis that regional abnormalities in tryptophan metabolism contribute to the neurological and neuroendocrine dysfunction of CRI.

Albumins↗

The Stratus immunofluorometric assay system evaluated for quantifying human choriogonadotropin in serum.

We evaluated the Stratus (American Dade, Miami, FL), an automated immunofluorometric assay system, for the quantification of human choriogonadotropin (hCG) in serum or plasma. The assay is based on the "sandwich" (two-site) immunoassay methodology: use of two monoclonal antibodies, one specific for the alpha subunit and the other for the beta subunit, results in an assay that is specific for the intact hCG molecule. Results for the first sample are obtained in 7 min; subsequent additional values are produced at 1-min intervals. Inter-run precision (CV), estimated from replicate determinations of sera, was 4.5% at an hCG concentration of 38 int. units/L, 4.9% at 114, and 6.1% at 194. Intrarun CV was less than 2% at all three concentrations. Correlations of results for 127 specimens analyzed in duplicate with the Stratus (y) and by a radioimmunoassay (x) for beta hCG (Gamma Dab M [cf931125I] beta-hCG, Travenol-Genentech Diagnostics, Cambridge, MA) yielded the following regression equation: y = 0.969x - 6.0 (r = 0.995). The Stratus immunofluorometric system provides a rapid and convenient assay of hCG in serum or plasma.

Antibodies, Monoclonal↗

Hypothalamic-pituitary sarcoidosis. A case report.

A 42-year-old woman suffered from sarcoidosis and hypothalamic-pituitary involvement. When she presented initially, an abnormal chest radiograph and abnormal features on histological examination of the lymph nodes, which showed caseating granulomas, suggested a diagnosis of tuberculosis. Failure to respond to antituberculosis therapy and the progressive development of symptoms of both posterior and anterior pituitary deficiency prompted a review of the initial diagnosis. Subsequent dynamic tests of hypothalamic and pituitary function indicated lesions at both the hypothalamic and pituitary levels. Further tests, including the Kveim reaction, favoured a diagnosis of sarcoidosis. This case illustrates the uncommon association of caseating granulomas with sarcoidosis and documents hypopituitarism due to combined hypothalamic and pituitary disease caused by sarcoid infiltration.

Adult↗

Comparison of the use of reserpine versus alpha-methyldopa for second step treatment of hypertension in the elderly.

A retrospective chart analysis was conducted on all new elderly hypertensive patients referred to a community hypertension clinic who were being treated with either reserpine or alpha-methyldopa plus a diuretic. There were no significant differences between the two groups on entry in age, gender, co-morbid diagnoses, or systolic or diastolic blood pressure. There were no significant differences between the two groups in terms of side effects over three years, but the proportion of persons having compliance problems was significantly lower in the reserpine group. Mean diastolic pressures were significantly lower after one, two, and three years, and systolic pressures were lower after one and two years in the reserpine group. Reserpine is at least as effective as alpha-methyldopa in treating hypertension in the elderly and is associated with fewer problems in compliance.

Aged↗

Salivary cortisol assessment in the evaluation of hypothalamic-pituitary-adrenal function.

A simple, short and sensitive direct radio-immunoassay technique for the determination of salivary cortisol concentration was employed to assess saliva as a medium for evaluating cortisol response during endocrine testing in 9 controls and 40 patients. Results in controls suggested that an adequate salivary cortisol response to insulin hypoglycaemia was an increase of 150% above the basal value with a minimum peak of 15 nmol/l. Thirty-three patients were classified as being either good or poor responders to insulin hypoglycemia on the basis of criteria for plasma cortisol levels. When the defined salivary cortisol response was used for assessment, all 33 patients were correctly categorized into the same response groups. The salivary cortisol response to intramuscular tetracosactrin in 3 patients and an intravenous dexamethasone infusion in 4 patients confirmed the value of saliva as an assay medium. These studies show that the salivary cortisol response parallels that of total plasma cortisol in all cases. However, with sampling at short intervals a lag in secretion of the free fraction from the plasma into the saliva becomes apparent. The relative change in cortisol levels from the basal value is greater in saliva than in plasma.

Adult↗

Rapid resolution of visual field defects and reduction in macroprolactinoma size with bromocriptine therapy. A case report.

Therapy for large prolactinomas depends very much on the treatment modalities available at a particular institution. Surgery is often unsuccessful in restoring endocrine function to normal. Previous reports have demonstrated evidence of tumour regression after 3 or more months' therapy with bromocriptine (Parlodel; Sandoz). More recently, objective evidence of rapid reduction in the size of large prolactin-secreting pituitary tumours, in patients who have had no prior therapy, has been reported. We describe a patient presenting with a chiasmal syndrome and amenorrhoea due to a pituitary macro-adenoma with suprasellar extension i whom rapid tumour regrowth to its pre-operative size occurred 3 months after surgery and irradiation. Administration of bromocriptine (up to 7.5 mg/d) resulted in complete resolution of the visual field defects, radiographic evidence of tumour regression and normoprolactinaemia within 12 days of commencing bromocriptine. Further significant tumour size reduction and improved anterior pituitary function were found after another 5 weeks of therapy.

Adenoma, Chromophobe↗