Search PubMed⌕ Search

Biomedical subjects

M J Horwitz

Publications and source records attributed to M J Horwitz.

10 recordsLinked to original sources
PubMed1995

Comparison of the minimal model and the hyperglycemic clamp for measuring insulin sensitivity and acute insulin response to glucose.

Glucose clamp techniques are established methods for assessment of insulin sensitivity and secretion. The minimal model technique (MMT) has been proposed as an alternative approach to the hyperinsulinemic-euglycemic clamp technique for determination of an insulin sensitivity index (ISI), but has not been directly compared with the hyperglycemic clamp for measurement of ISI or insulin secretion. To address this issue, the present study was undertaken to compare determinations of ISI and the acute insulin response to glucose (AIRg) obtained using the MMT with similar measures obtained from a hyperglycemic clamp. Measures for ISI and AIRg obtained from MMT analysis of a tolbutamide-modified frequently sampled intravenous glucose tolerance test (FSIGT) were compared with similar measures obtained from a 3-hour hyperglycemic clamp performed at a plasma glucose level of 10 mmol/L (180 mg/dL). Paired comparisons were performed in 14 women with normal glucose tolerance. Significant positive correlation coefficients were obtained for both ISI (r = .88, P < .001) and AIRg (r = .75, P < .005) between the MMT and clamp studies. We conclude that indices for ISI and AIRg obtained with the MMT are highly correlated with those obtained using the hyperglycemic clamp. The MMT is a valid alternative to the hyperglycemic clamp for assessing insulin sensitivity and AIRg.

Female↗
PubMed1995

Metabolic effects of oral contraceptives in women with polycystic ovary syndrome.

Insulin resistance and dyslipidemia have been described in women with polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism and oligomenorrhea. Although oral contraceptives (OC) are often instituted to regulate menses and suppress HA in women with PCOS, their use has been postulated to cause a deterioration in insulin sensitivity and to adversely affect circulating lipids. To investigate these effects, 9 women with PCOS and 10 age- and weight-matched control women were studied before and during the third month of therapy with a low-dose norethindrone-containing triphasic combination OC using the hyperglycemic clamp technique. At baseline, the PCOS group had higher androgen, triglyceride, and glycosylated hemoglobin concentrations, with a greater insulin response to oral glucose and a lower insulin sensitivity index (ISI) than controls. During OC therapy, a reduction in ISI was observed in both groups, whereas an increase in triglycerides was observed only in controls, removing any observed difference between the two groups in ISI or lipids. In women with PCOS, an increase in insulin concentrations during hyperglycemia accounted for the decline in ISI (P = 0.026), whereas in control women the decrease in ISI was attributable to a decrease in glucose disposal (P = 0.004). In conclusion, PCOS is characterized by insulin resistance in the untreated state. Short-term therapy with a triphasic OC results in a further decline in ISI in women with PCOS, without inducing additional adverse effects on lipids. A more pronounced decline in ISI together with an elevation in triglyceride levels occurs in normal women with OCs. The mechanisms leading to this decrease in ISI are different for each group.

Adult↗
PubMed1995

Developmental expression and anatomical localization of endothelin-1 messenger ribonucleic acid and immunoreactivity in the rat placenta: a northern analysis and immunohistochemistry study.

Endothelin-1 (ET-1) immunoreactivity and messenger ribonucleic acid (mRNA) have previously been identified in the mammalian placenta. In the present study we examined the developmental expression of ET-1 mRNA and the localization of ET-1 mRNA and immunoreactivity within the rat placenta. Placental tissues were removed from primiparous Sprague-Dawley rats on gestational days 14, 18, and 21 and processed for blot hybridization of ET-1 mRNA and immunohistochemistry of ET-1 immunoreactive peptide. Placental tissue contained a 2.3 kb size ET-1 mRNA transcript. Placental ET-1 mRNA abundance increased approximately five-fold from day 14 to 21 of gestation (p = 0.02). To localize ET-1 mRNA within the rat placenta, day 18 placentas were dissected into the basal and labyrinth layers and processed separately for blot hybridization of ET-1 mRNA. ET-1 mRNA localized to the labyrinth zone. This was confirmed by immunohistochemical staining of day 18, 20, and 21 placental tissues with an antiserum specific to ET-1. The presence of ET-1 immunoreactivity and the stage-specific increase in ET-1 mRNA in the rat placenta suggest that ET-1 may exert paracrine effects on the placenta or uterus of the pregnant rat.

Animals↗
PubMed1994

Expression of the endothelin-1 and oxytocin genes in the hypothalamus of the pregnant rat.

Endothelin (ET)-1, a neuropeptide and possible neuromodulator, has been found in the hypothalamic supraoptic and paraventricular nuclei (SON and PVN) of the rat in the distribution of oxytocin (OT) neurons. Within the hypothalamus of the pregnant rat, we investigated the developmental expression of the ET-1 gene and the possibility of coordinate expression of the ET-1 and OT genes. Blots containing hypothalamic mRNAs from 4-, 14-, 18-, and 21-day-old pregnant rats were hybridized to a 32P-labeled probe specific to the rat ET-1 gene. Hypothalamic tissue contained an ET-1 transcript of approximately 2.3 kb size. ET-1 mRNA abundance increased significantly in the SON and PVN from early to late gestation (P = 0.005 and 0.05, respectively). Blots containing hypothalamic mRNA were rehybridized to a 32P-labeled probe specific to exon C of the rat OT gene. OT gene expression increased significantly within both the hypothalamic SON (p = 0.0009) and PVN (P = 0.003) as gestation advanced. The sizes of the hypothalamic ET-1 and OT transcript sizes remained unchanged throughout gestation. Hypothalamic ET-1 and OT transcripts display stage-specific increases during gestation. ET-1 may be a neuroendocrine regulator of pregnancy-related events in the rat, and may act alone or in concert with OT.

Animals↗
PubMed1994

Primary hyperparathyroidism and parathyroid hormone-related protein.

Hypercalcemia is most commonly associated with primary hyperparathyroidism and malignancy due to parathyroid hormone-related protein (PTHrP). Primary hyperparathyroidism is characterized by excessive secretion of parathyroid hormone in association with hypercalcemia. The modern presentation of primary hyperparathyroidism is as an asymptomatic disorder. Diagnostic tools such as bone mineral densitometry, bone histomorphometry, and the measurement of markers of bone turnover, as well as other clinical assessments, have all led to the development of guidelines to help direct decisions for parathyroid surgery or for medical management. Hypercalcemia of malignancy is often distinguishable from primary hyperparathyroidism by the presence of an obvious tumor. Primary hyperparathyroidism is excluded by the immunoradiometric assay for parathyroid hormone, which is suppressed. A number of clinical characteristics of hypercalcemia of malignancy can be explained on the basis of the tumor product, PTHrP, which directly causes hypercalcemia in many cases. Assays for PTHrP show elevated levels in patients in whom hypercalcemia is associated with the classic syndrome. Recent recognition that PTHrP is found ubiquitously in virtually all normal tissues and that it is possibly involved in a number of normal physiologic processes, apart from its pathologic role, provides an exciting basis for future research.

Animals↗
PubMed1993

Endothelin-1 gene expression in human pheochromocytoma.

We examined expression of human endothelin-1 (ET-1) in adrenal tissues removed from five patients with pheochromocytomas and two patients with aldosterone-producing adenomas. The pheochromocytomas contained a 2.3 kilobase ET-1 transcript, which was not found int he aldosteronomas. Constitutive expression of ET-1 varied in magnitude among the pheochromocytomas but was generally at a low level. Immunohistochemical staining of the pheochromocytomas with an antiserum to human ET-1 showed the presence of immunoreactive ET-1 as well. The presence of ET-1 messenger ribonucleic acid and ET-1 immunoreactivity in human pheochromocytomas suggests a possible paracrine role for this peptide in human chromaffin cells.

Adenoma↗
PubMed1977

Progressive necrotizing external otitis: treatment with ticarcillin and tobramycin.

The history of necrotizing external otitis, its diagnosis and management are reviewed. A case history is presented of a patient who was diagnosed as having progressive necrotizing external otitis with facial paralysis. In spite of standard medical treatment and aggressive surgical management, the disease process continued with progressive involvement of Cranial nerves IX and X. The Pseudomonas aeruginosa bacteria developed an increased minimal inhibitory concentration (MIC) to carbenicillin and gentamicin by requiring near toxic blood levels to be effective. Investigational ticarcillin (alpha-carboxy-3-thienylmethylpenicillin) and tobramycin were used successfully in resolving the infection.

Anti-Bacterial Agents↗
PubMedDate not supplied

The Leyla retractor: use in acoustic neuroma and neurotologic surgery.

The Leyla retractor is a self-retaining retractor used in the translabyrinthine removal of acoustic neuroma and middle fossa surgery. It is used to maintain constant, even pressure on a decompressed sigmoid sinus and cerebellum in translabyrinthine surgery and the temporal lobe in middle fossa surgery. The Leyla retractor provides excellent exposure and greater freedom and dexterity for the neurotologist.

Brain↗