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Biomedical subjects

J Goldman

Publications and source records attributed to J Goldman.

At least 181 records · Page 10Linked to original sources

Spectrum of endocrine abnormalities associated with acanthosis nigricans.

Acanthosis nigricans is a marker for disorders of insulin action, endocrine abnormalities, and cancer of internal organs. To evaluate the clinical significance of this marker the systemic alterations and clinical features of 26 patients with acanthosis nigricans seen at two institutions were reviewed. Most subjects affected by acanthosis nigricans were female (20 patients), Caucasian (22 patients), in the third decade of life (13 patients), and overweight (24 patients greater than 120 percent ideal body weight). Gonadal disease, present in 17 patients, was expressed as polycystic ovary syndrome (11 cases), disorders of prolactin secretion (two cases, one with polycystic ovary syndrome), streak gonads (one case), and hypogonadism of the male (four cases). Thyroid disease and tinea versicolor were present in four patients each. Three patients were receiving insulin therapy for diabetes mellitus, and in two additional patients diabetes mellitus was detected during the diagnostic workup. All patients had elevated fasting insulin levels; most of them also had an exaggerated insulin response to a glucose load. Two of 18 patients tested had antibodies against the insulin receptor in the circulation. Skin biopsy of acanthosis nigricans lesions from all 26 patients showed a typical pattern of hyperkeratosis, acanthosis, and epidermal papillomatosis. Colloidal iron staining showed glycosaminoglycan infiltration of the papillary dermis (21 of 21 cases), consisting mainly of hyaluronic acid. It is concluded that: (1) hyperinsulinenemia and local dermal glycosaminoglycan deposition are regular features in acanthosis nigricans and (2) patients with acanthosis nigricans should be screened for diabetes mellitus, gonadal disease, and hypothyroidism.

Acanthosis Nigricans↗

Potentiation of insulin stimulation of hexose transport by kallikrein and bradykinin in isolated rat adipocytes.

Kallikrein and bradykinin additively increased adipocyte hexose transport under conditions of maximal intrinsic insulin stimulation, while no such effect occurred in the absence of insulin. The potentiation of insulin action follows a dose-response relationship with kallikrein and bradykinin concentrations consistent with a physiological role for the latter in the modulation of insulin action. Insulin degradation by isolated adipocytes and insulin binding to its receptors on adipocyte plasma membranes were not affected by either kallikrein or bradykinin. Thus, the kallikrein and bradykinin potentiation of insulin action occur at post-insulin binding sites. In conclusion, the kallikrein-bradykinin system increases the supply of substrates to target tissues through vasodilation and augmented blood perfusion, and it also stimulates glucose uptake and metabolism via its potentiation of insulin action. These actions suggest that the kallikrein-bradykinin system regulate both the availability and utilization of metabolic substrates, in target tissues.

Adipose Tissue↗

Relationship between renal function and metabolic alterations in early streptozocin-induced diabetes in rats.

To investigate the temporal relationship of diabetes-induced renal growth and its associated metabolic alterations to the early development of renal hyperfunction, parallel functional and metabolic studies were performed shortly after the onset of diabetes in rats. Hyperglycemia and hypoinsulinemia were evident 18 h after streptozocin injection, and significant hyperglucagonemia and acidosis were present at 36-48 h. Glomerular filtration rate (GFR), expressed per unit of body weight, first increased at 3 days of diabetes [1.35 +/- 0.07 (SE) (N = 14)] and was 18% greater than in controls [1.14 +/- 0.03 ml X min-1 X 100 g-1 (SE) (N = 38)] (P less than .005). Renal enlargement preceded GFR changes, so that GFR per unit of kidney weight was lower at 48 h in diabetics [1.31 +/- 0.06 (SE) (N = 16)] than in controls [1.54 +/- 0.04 ml X min-1 X g-1 (SE) (N = 38)] (P less than .01). Nucleotide and RNA metabolism was studied in the renal cortex after infusion of radio-labeled orotate or adenine. Rate of RNA synthesis, total cellular RNA, and the pools of ATP, UTP, and uridine 5'-diphospho-N-acetyl glucosamine were significantly increased 13-51% in 48-h diabetics. Nucleotide precursor incorporation was significantly increased only in uracil ribonucleotides. The increase in uracil ribonucleotide pool exceeded the degree of cell hypertrophy. Our studies indicate that renal hypertrophy and specific increases in uracil ribonucleotide synthesis precede functional changes in early diabetes. Renal metabolic changes may be the critical primary factors in diabetic nephropathy.

Animals↗

Primary choriocarcinoma of the fallopian tube. Report of a case with survival and postoperative delivery. Review of the literature.

A patient is presented with primary choriocarcinoma of the fallopian tube arising from a tubal pregnancy. Treatment consisted of an initial operation including adnexectomy and resection of bilateral ovarian thecalutein cysts, followed by chemotherapy. The patient delivered a healthy infant 2 years later, and is alive and well 5 years after the event.

Adult↗

Fluorescent anti-immunoglobulin G assay of circulating immune complexes extracted with polyethylene glycol.

After a polyethylene glycol extraction which removes monomeric immunoglobulin G (IgG), circulating immune complexes were assayed by the FIAX fluorescence assay (Whittaker M. A. Bioproducts, Walkersville, Md.). The extraction portion of the procedure can be completed within a few hours after an overnight precipitation step, and the fluorescence assay takes about 0.5 h. The fluorescence assay is similar to the routine FIAX method for measuring IgG in cerebrospinal fluid except that a 10-microliter sample from sera is substituted for a 50-microliter sample. Good parallelism between endogenous immune complexes, monomeric IgG, and aggregated human globulin, along with good between-run precision (coefficients of variation, less than 10%), indicates that monomeric IgG calibrators from the kit could be used to standardize the assay. This standardization eliminates the need for aggregated human globulin, which is unstable and difficult to prepare. A reference range of 9 to 63 mg/liter followed a gaussian distribution. Correlation data indicate that the test provides information similar to the C1q-binding test (rho = 0.87; n = 30) but has better diagnostic sensitivity and better discrimination in the high range. Because of its simplicity, good reproducibility, and accessibility to equipment available in many laboratories, the method described here may be a preferred technique for measuring circulating immune complexes.

Antigen-Antibody Complex↗

Regulation of growth hormone and somatomedin-C secretion in postmenopausal women: effect of physiological estrogen replacement.

To determine the effects of estrogen deficiency and replacement on GH secretion, we measured the 22-h GH secretory pattern and response to 1 h of light exercise in 16 normal postmenopausal women before and after treatment replacement with ethinyl estradiol (20 micrograms/day for 15 days). To determine whether the changes found were due to pituitary sensitization by estrogen, the response to synthetic GH-releasing hormone (GHRH; 1.0 microgram/kg, iv) was measured. To assess the biological effectiveness of GH in estrogen-treated women, somatomedin-C (Sm-C) responses to GHRH were measured. Pre- and postestrogen GH secretion rates, expressed as mean areas circumscribed by plasma GH values, were as follows: 22-h study, 1.4 +/- 0.1 (+/- SEM) vs. 2.0 +/- 0.3 ng/ml X h (P = 0.04; n = 5); during 1 h of exercise, 2.3 +/- 0.4 vs. 3.2 +/- 0.4 ng/ml X h (P = 0.03; n = 16); after GHRH-(1-40), 6.7 +/- 1.7 vs. 8.5 +/- 1.5 ng/ml X h (P = 0.12; n = 16). There also was a modest but significant increase in resting plasma GH (1.5 +/- 0.2 vs. 2.3 +/- 0.5 ng/ml (P = 0.039). Pre- and postestrogen plasma Sm-C concentrations were 0.56 +/- 0.08 and 0.32 +/- 0.03 U/ml, respectively (P = 0.006; n = 16). Thus, estrogen therapy increased spontaneous and exercise-induced GH secretion in postmenopausal women and reduced Sm-C levels. The mechanisms of GH elevation by estrogen may include both central effects and a negative feedback linkage to reduced plasma Sm activity.

Aged↗

Determination of the source(s) of androgen overproduction in hirsutism associated with polycystic ovary syndrome by simultaneous adrenal and ovarian venous catheterization. Comparison with the dexamethasone suppression test.

To determine the source(s) of the excessive androgen production in patients with the polycystic ovary syndrome (PCOS), 12 hirsute women with PCOS underwent selective left adrenal and left ovarian venous catheterization. Blood samples were collected simultaneously for determination of cortisol, 17-hydroxy-progesterone, androstenedione (delta), testosterone (T), dehydroepiandrosterone, and dehydroepiandrosterone sulfate. The relative contributions of adrenal secretion rates of T and delta in each patient were estimated by relating their adrenal gradients to those of cortisol. From such calculations we found that in all patients the major source of androgens was the ovary (direct ovarian secretion and/or ovarian secretion of prehormones which then were converted to androgen in the peripheral circulation). After catheterization, 11 of the 12 patients underwent a 5-day dexamethasone suppression test (2 mg/day). In 7 patients studied, plasma delta and/or T levels decreased significantly. Our results indicate that in hirsutism associated with the PCOS, the predominant source of androgens is the ovaries and that glucocorticoid suppression cannot assign adrenal origin as the site of excessive androgens.

Adolescent↗

Lymphoid hypophysitis associated with sudden maternal death: report of a case review of the literature.

A case of lymphoid hypophysitis in a woman who died during labor is presented. From a review of the 14 previously reported cases it is apparent that this is a specific disease entity, that it involves only woman, especially in association with pregnancy, and that it may have a fatal outcome. The clinical manifestations are either related to hypopituitarism, or those of a space occupying lesion. Attention drawn to the possible occurrence of the disease may result in earlier recognition of the disease and a better outcome of this potentially fatal disease.

Adult↗

Hematoma of the umbilical cord with acute antepartum fetal distress. A case report.

In a case of spontaneous hematoma of the umbilical cord, no pathologic lesion was found in the umbilical blood vessels. However, an extremely short cord (14 cm) may have contributed to the vessel rupture. A prolonged deceleration discovered during a routine nonstress test led to emergency cesarean section, with delivery of a healthy neonate.

Cesarean Section↗

Effect of splenectomy before bone-marrow transplantation on survival in chronic granulocytic leukaemia.

Splenectomy is commonly carried out before bone-marrow transplantation in chronic granulocytic leukaemia to reduce tumour burden and prevent relapse and blastic transformation. In a retrospective analysis of 210 European patients transplanted between 1980 and 1984, 105 splenectomised and 105 not, neither splenectomy nor splenic irradiation was found to alter survival and relapse. Debulking in this disease is of no value, and routine splenectomy before transplantation should be abandoned.

Adolescent↗

Reduction in the stearic to oleic acid ratio in leukaemic cells--a possible chemical marker of malignancy.

Total lipid extracts of peripheral blood cells from patients with chronic leukaemias were analysed for relative values of saturation of the eighteen carbon chain length fatty acids (C 18 FA). The results are expressed as saturation index (C 18 S:C 18 U) of the saturated C 18 FA (stearic acid) over the unsaturated C 18 FA (oleic, linoleic and linolenic acids). The saturation indices of the white blood cells (WBC) and the red blood cells (RBC) in specimens from 14 patients with chronic granulocytic leukaemia (CGL) and 17 patients with chronic lymphocytic leukaemias (CLL) were significantly and consistently lower than control specimens. It is proposed that the relative increase in the unsaturated oleic acid could prove to be a chemical marker of malignancy reflecting a deficient cellular control of the process of stearic acid desaturation. The theoretical implications of the implied increase in membrane fluidity for the cells are discussed.

Chromatography, Gas↗

Insulin and glucose levels during CPR in the canine model.

Cardiopulmonary arrest and resuscitation produces tremendous physiological stress with resultant biochemical derangements. We undertook this study to determine insulin and glucose levels during cardiopulmonary arrest in the canine model. Baseline insulin and glucose levels were obtained from an ascending aortic arch catheter in six mongrel dogs. Ventricular fibrillation was induced by an electrical stimulus and ventilation was terminated. After five minutes of fibrillation, cardiopulmonary resuscitation (CPR) was initiated using external, mechanical CPR and a continuous epinephrine infusion at 5 micrograms/kg/min. Serum insulin and glucose levels were repeated 15 minutes after beginning CPR. Mean blood glucose 15 minutes after initiation of resuscitation (379 +/- 114 mg/dL) was significantly increased from prearrest levels (124 +/- 29 mg/dL, P less than .01). Mean serum insulin 15 minutes after initiation of resuscitation (11.3 +/- 3.3 microU/mL) was significantly decreased compared to prearrest levels (16.2 +/- 6.0 microU/mL, P less than .05). During ischemia, the myocardium becomes dependent primarily on glucose as a source of energy. Inappropriately low insulin levels during CPR may adversely affect an already compromised myocardial glucose metabolism. Further investigation is needed to determine the utility of insulin infusion during CPR.

Animals↗

Evaluation of the sterility and stability of insulin from multidose vials used for prolonged periods.

Diabetic patients frequently use their insulin vials for prolonged periods, even though antibacterial preservatives used in multidose insulin vials are not required to be effective beyond 28 days. For this reason, we evaluated the antibacterial activity present in multidose insulin vials for up to 50 days. Multidose lente insulin vials were inoculated with S. aureus and P. aeruginosa. Vials incubated at room temperature (21 degrees C) were sterile by 48 hours, whereas when they were incubated at refrigerator temperatures (4 degrees C), S. aureus contamination persisted up to the 17th day and P. aeruginosa were killed after 10 days. The same vials were serially contaminated on days 17, 30, and 50, and a similar antibacterial effect was maintained. Sixty-nine multidose insulin vials used for an average of 53 days were cultured. Eight vials demonstrated bacterial contamination with 1 cfu/ml of S. epidermidis or Propionibacterium acnes. No endotoxin was detected in the multidose vials used for more than 28 days. Insulin assays on 40 multidose insulin vials used for more than 28 days showed an average insulin content of 101.6 +/- 1.9 units/ml. This study did not demonstrate significant bacterial contamination, endotoxin activity, or insulin degradation of multidose insulin in vials used for periods longer than 28 days. In addition, antibacterial preservatives were more effective at room temperature than at refrigerator temperature; thus, the practice of patients not refrigerating insulin vials is sensible.

Bacteria↗

Sialic acid in newborn and maternal lymphocytes: preterm deliveries.

Sialic acid was determined in newborn and maternal lymphocytes immediately after preterm deliveries of 34 and 35 weeks of gestation. The results were compared with those found in full-term deliveries. In contrast with full-term deliveries, in preterm deliveries a significant increase in sialic acid in maternal as compared to newborn lymphocytes was found. However, the mean cumulative value of sialic acid for maternal and newborn lymphocytes was similar in both groups. In addition to this, sialic acid concentrations seem to be sex-dependent and higher mean cumulative values for maternal and newborn lymphocytes could be found for male as compared to female newborns after full- as well as after preterm deliveries.

Female↗

Contrast analysis for the evaluation of the circadian rhythms of plasma cortisol, androstenedione, and testosterone in normal men and the possible influence of meals.

To evaluate the circadian rhythms of plasma androstenedione (delta) and testosterone (T), we used continuous blood withdrawal at 30-min intervals for 24 h to obtain integrated concentrations in six normal men. The data were submitted to contrast analysis as well as to a graphical method with smoothing of the variations between samples. As reference, cortisol (F) levels also were measured, since they have a well defined circadian rhythm. Integrated F concentrations had a circadian rhythm, with the highest levels between 0500 and 0900 h, nadir values between 2000 and 300 h, and secretory peaks coincident with lunch and dinner hours, suggesting the influence of food ingestion on secretion. Integrated androstenedione concentrations also had a circadian rhythm, with the highest levels between 0530 and 0930 h and the lowest between 1900 and 0230 h. There also were peaks with lunch and dinner, however, occurring some minutes before the corresponding ones for F. Integrated T concentrations had a circadian rhythm, with the peak values between 0100 and 1130 h and the lowest levels between 0700 and 2100 h. There were no peaks of the T integrated concentrations during the meal periods as found with F and delta. Furthermore, no correlation was found between the integrated concentrations of T and F or delta.

Adult↗

Components of the total serum thyroid hormone concentrations during pregnancy: high free thyroxine and blunted thyrotropin (TSH) response to TSH-releasing hormone in the first trimester.

The distribution of thyroid hormones between free solution and their several protein-binding sites during pregnancy was studied under physiological conditions of temperature and pH. Single serum specimens were obtained from individual women at different stages of pregnancy. During the first 5 weeks of pregnancy, mean serum free T4 and free T3 concentrations were 50% higher than in nonpregnant women or women during the third trimester. Free T4 was increased significantly throughout the first trimester, but because of wide variance, free T3 was significantly above control values only during the first 5 weeks. Free T4 and free T3 concentrations decreased to control levels in the third trimester. These changes in free T4 concentrations are consistent with a weak thyrotropic action of hCG, which attained maximal concentrations early in the first trimester and then decreased markedly in the second and third trimesters. TRH testing of women scheduled for abortion in the first and second trimesters revealed marked inhibition of TSH response to TRH in those first trimester women who had elevated free T4 concentrations. The percent free T4 did not decrease during the first 5 weeks, but then declined progressively to term as T4-binding globulin (TBG) affinity, defined as the product of the capacity and affinity constant, progressively increased. T4 bound to TBG (T4-TBG) increased from early in the first trimester to term, and then decreased in postterm pregnancy and postpartum. T4 bound to prealbumin (T4-PA) and to albumin (T4-Alb) decreased significantly in the third trimester compared with either control or first trimester concentrations. The concentration of free T3 was positively correlated with T4-PA (r = 0.25) and T4-Alb (r = 0.31), but not with free T4 (r = 0.18) or T4-TBG (r = -0.30) concentrations. These results suggest that 1) only the high concentrations of hCG present in the first trimester of pregnancy have a thyrotropic effect in excess of normal levels of TSH, and this can be sufficient to suppress the TSH response to TRH; 2) hepatic TBG secretion continues to respond to the continuously rising estrogen levels throughout pregnancy; and 3) T4-PA and T4-Alb, but not free T4 or T4-TBG, are possible precursors for the extrathyroidal generation of T3.

Chorionic Gonadotropin↗