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Biomedical subjects

M P Diamond

Publications and source records attributed to M P Diamond.

At least 19 recordsLinked to original sources
PubMed1992

HLA-DQ beta 57 in Hispanic patients with insulin-dependent diabetes mellitus.

OBJECTIVE: The purpose of our study was to investigate the distribution of HLA-DQ beta-chain amino acid residue 57 (HLA-DQ beta 57) as a genetic marker of susceptibility for insulin-dependent diabetes mellitus in the Hispanic population. STUDY DESIGN: Fifteen patients of Puerto Rican descent with juvenile-onset insulin-dependent diabetes mellitus underwent human leukocyte antigen typing for HLA-DQ beta 57 by polymerase chain reaction amplification of the target genomic DQ sequence followed by hybridization of the polymerase chain reaction product to phosphorus 32-labeled allele-specific oligonucleotide probes. A control group of 44 Hispanic adults without diabetes who were undergoing human leukocyte antigen typing for tissue donation were concurrently typed for comparison. RESULTS: The Hispanic insulin-dependent diabetes mellitus group showed a significant increase in homozygosity for a non-aspartate amino acid (p = 0.023) over a control group of Hispanic subjects without diabetes. A high rate of heterozygosity for aspartate (53.3%) is found in Hispanic subjects with insulin-dependent diabetes mellitus as well. CONCLUSIONS: HLA-DQ beta 57 in the Hispanic population has a distribution distinct from HLA-DQ beta 57 in the Caucasian population. A single aspartate is not protective against insulin-dependent diabetes mellitus in Hispanic subjects.

Amino Acid Sequence↗
PubMed1992

Aldose reductase inhibition prevents galactose-induced ovarian dysfunction in the Sprague-Dawley rat.

OBJECTIVE: Our objective was to determine whether impaired ovarian function induced by short-term creation of a galactosemic state in the rat might be prevented by the coadministration of an aldose reductase inhibitor. STUDY DESIGN: Prepubertal Sprague-Dawley rats were fed four different diets including (1) control, (2) 40% galactose, (3) 40% galactose and an aldose reductase inhibitor, and (4) an aldose reductase inhibitor with the control diet. Percentage germinal vesicle breakdown, postovulatory oocyte quantities, hormonal parameters, ovarian histologic evaluation, and ovarian galactitol concentrations were determined. RESULTS: The galactose-fed animals (group 2) had decreased germinal vesicle breakdown (47%) versus control (69%, p < 0.05). Galactose-exposed animals had significantly decreased quantities of postovulatory eggs (6.4 per animal) after menotropin ovarian stimulation in comparison with controls (14.1, p < 0.01). In rats exposed to high dietary levels of galactose (group 2) ovarian galactitol concentrations were significantly higher (protein 42.12 mumol/gm versus 0.0 for controls, p < 0.005). When galactose-fed animals received the aldose reductase inhibitor, ovarian accumulation of galactitol was significantly reduced and the observed detrimental effects on the oocyte were prevented. CONCLUSION: Galactitol accumulation or metabolic flux through aldose reductase in galactosemic rodents may be involved in the demonstrated ovarian dysfunction.

Aldehyde Reductase↗
PubMed1992

Impairment of counterregulatory hormone responses to hypoglycemia in pregnant women with insulin-dependent diabetes mellitus.

Intensive insulin therapy directed at elimination of hyperglycemia is advocated during pregnancy in women with insulin-dependent diabetes mellitus. Because such treatment is complicated by frequent hypoglycemic episodes, we evaluated maternal and fetal responses in nine intensively treated pregnant women with insulin-dependent diabetes mellitus during an insulin-induced, gradual, controlled fall in plasma glucose levels. In contrast to values in nonpregnant control women, reductions in glucose to 44 +/- 2 mg/dl in pregnant diabetic patients failed to elicit an increase in glucagon levels. Epinephrine release during hypoglycemia was also markedly suppressed in the pregnant diabetic subjects (106 +/- 32 vs 327 +/- 52 pg/ml in controls, p less than 0.001). Furthermore, the plasma glucose level at which epinephrine and growth hormone were released was 5 to 10 mg/dl lower in the pregnant women with insulin-dependent diabetes mellitus (p less than 0.05). The basal fetal heart rate remained unchanged and continued to manifest accelerations during the hypoglycemic state. We conclude that the high frequency of hypoglycemia in intensively treated pregnant women with insulin-dependent diabetes mellitus may be due in part to impaired counterregulatory hormonal responses.

Adult↗
PubMed1992

Influence of basal androgen levels in euandrogenic women on glucose homeostasis.

OBJECTIVE: To evaluate possible relationships between insulin action and the normal variations of serum androgens in euandrogenic women. DESIGN: Prospective evaluation of insulin action in normal nonobese women using hyperglycemic and euglycemic hyperinsulinemic clamp techniques, correlating insulin action to serum testosterone (T), free T, androstenedione (A), and dehydroepiandrosterone sulfate (DHEAS). Statistical analysis used Spearman's rank correlation. SETTING: Yale University Clinical Research Center. PARTICIPANTS: Nonobese females with normal oral glucose tolerance tests, on no medications known to affect glucose metabolism, having the following range of serum androgen levels: T, 0.69 to 3.12 nmol/L; free T, 0.17 to 1.25 nmol/L; A, 2.48 to 11.31 nmol/L; DHEAS, 0.68 to 10.61 mumol/L. Total number of patients studied: hyperglycemic clamps, n = 58; euglycemic hyperinsulinemic clamps, n = 43. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Pancreatic insulin secretion in response to hyperglycemia and insulin action as assessed by insulin-mediated glucose utilization using the euglycemic, hyperinsulinemic clamp technique. RESULTS: We identified no significant correlation between serum androgens and either glucose uptake or insulin-mediated glucose utilization. Glucose-stimulated insulin release was negatively correlated with serum T and free T throughout the normal range of these hormones. CONCLUSION: We conclude that, within the normal range, variations of serum androgens are not correlated with changes in the response to insulin. It seems unlikely, therefore, that modest increases of serum androgens within the normal range are responsible for inducing insulin resistance.

Androgens↗
PubMed1992

Alterations in glucose metabolism during menstrual cycle in women with IDDM.

OBJECTIVE: To examine the hormonal mechanisms underlying the variability in glycemic control during the different phases of the menstrual cycle in women with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Hyperglycemic (11.7 +/- 0.1 mM), hyperinsulinemic (24 +/- 3 mU/L) clamp studies were performed in 16 women with IDDM during the follicular (day 8 +/- 1) and luteal (day 23 +/- 1) phases of the menstrual cycle. Seven of the patients (group 1) experienced worsening glucose control during the luteal phase, whereas nine patients (group 2) did not. RESULTS: In group 1, glucose metabolism fell from 30.2 +/- 3.8 mumol.kg-1.min-1 during the follicular phase to 24.5 +/- 2.0 mumol.kg-1.min-1 during the luteal phase (P = 0.09), whereas in group 2 it increased from 18.5 +/- 1.2 to 23.2 +/- 2.3 mumol.kg-1.min-1 (P = 0.03). The decrease in glucose metabolism during the luteal phase in patients in group 1 was associated with a significant rise in the serum estradiol levels from the follicular to luteal phase (164 +/- 39 vs. 352 +/- 59 pM, P = 0.006), whereas this rise was not observed in group 2 (334 +/- 156 vs. 423 +/- 74 pM, NS). Changes in other reproductive hormones (progesterone, testosterone, dihydrotestosterone, androstenedione, luteinizing hormone, follicular-stimulating hormone, or prolactin) were not related to the differences in glucose uptake in the two groups. CONCLUSIONS: 1) Marked heterogeneity in glucose metabolism is seen throughout the menstrual cycle in women with IDDM, 2) a subgroup of patients exhibits worsening premenstrual hyperglycemia and a decline in insulin sensitivity during the luteal phase, and 3) the deterioration in glucose uptake in this subgroup was associated with a greater increment in estradiol levels from the follicular to the luteal phase.

Adult↗
PubMed1992

The in vitro perifused rat ovary: I. Steroid secretion in response to ramp and pulsatile stimulation with luteinizing hormone and follicle stimulating hormone.

A computer-controlled perifusion apparatus has been used to investigate the effects of different patterns of hormonal stimulation on secretion of steroids by ovaries from untreated, or pregnant mare serum gonadotropin (PMSG)-pretreated, immature rats. With ovaries from untreated rats, a low rate of increasing concentration of gonadotropins (luteinizing hormone (LH) plus follicle stimulating hormone (FSH)) induced a maximum secretion of estradiol within 60 min (22.6 +/- 1.4 pg/mg/30 min). An intermediate and a high rate of increasing gonadotropin concentration stimulated maximum secretion (26.0 +/- 1.2 pg/mg/30 min) and 28.1 +/- 2.8 pg/mg/30 min), respectively) within 30 min. Peak secretion, however, was not maintained and was reduced despite continued LH/FSH pulses. Progesterone secretion increased during, and subsequent to, the decreasing estradiol output. Increasing amplitudes of LH/FSH or constant perifusion with LH/FSH did not change the profile, or the concentration of estradiol, but these measures increased progesterone release. An occasional transient increase in estradiol secretion was observed when ovaries from unstimulated rats were perifused with low LH/FSH pulse frequency. Thus, these studies support the hypothesis that in the prepubertal rat ovary, elements of pulse characteristics, such as rate of increasing LH/FSH concentration, and amplitude are important in differentially regulating steroid output. The steroid secretory pattern of ovaries from PMSG-treated prepubertal rats was different from that of untreated rats. With ovaries from PMSG-treated rats, an acute increase in secretion of progesterone, testosterone or estradiol was not observed, whether low or high rates of increasing gonadotropin concentration were used. Rather, the concentration of these steroids continued to rise following LH/FSH pulses. Thus, in contrast to the untreated ovary, the PMSG-treated ovary did not show differential regulation of steroid secretion in response to LH/FSH. In conclusion, we have shown the in vitro perifusion model to be a useful tool for studying the effects of different patterns of hormonal stimulation on ovarian steroidogenesis. In addition, differential effects of gonadotropins on steroid output were shown, depending upon prior maturation of the ovary.

Animals↗
PubMed1992

The in vitro perifused rat ovary: II. Role of oxygen tension in the whole and quartered ovary.

In vitro perifusion of whole ovaries raises questions about tissue viability and its effects on the observed ovarian steroid secretion. To assess effects of tissue degeneration, whole and quartered ovaries from pregnant mare serum gonadotropin (PMSG-) treated immature rats were perifused for 8 h, employing various levels of pO2. Histological examination of both the whole and quartered ovary showed signs of degeneration in centrally located follicles but not in follicles located near the surface. However, basal and gonadotropin-stimulated (luteinizing hormone plus follicle stimulating hormone) secretion of estradiol, testosterone and progesterone were not significantly different in the whole ovary whether in the presence of high or low pO2 (n = 8; p > 0.05). Similarly, although the quartered ovary secreted greater amounts of steroids than did the whole ovaries (p < 0.05, n = 8), pO2 levels did not affect the steroid output. We conclude that during in vitro perifusion, minimal oxygen supply is sufficient for ovarian steroidogenesis to proceed. In addition, although quartered ovaries displayed some evidence of tissue degeneration, they were more responsive in terms of steroid output per mg ovary than were whole ovaries.

Animals↗
PubMed1992

Comparison of ovarian response in the same women with the same or different lots of human menopausal gonadotropin.

A variation in the bioactivity of different production lots of human menopausal gonadotropin (hMG) has been suggested. Therefore, we evaluated ovarian response to hMG in 14 women during three separate IVF cycles. The first two cycles were performed with the same lot (#03310027; Cycles A1 and A2); the third cycle utilized different lots of hMG (Cycle B). In all cycles, hMG was administered 3 ampules/day beginning cycle Day 3 and continued for at least 6 days. Estradiol and ultrasound evaluations were performed on Day 3, and then daily, beginning on cycle Day 8. Fourteen women completed all three cycles. There were no significant differences in baseline estradiol and ultrasound. Estradiol levels on Day 8 (A1, 754 +/- 130; A2, 700 +/- 107; B, 520 +/- 80 pg/ml, analysis of variance p greater than 0.5) and on Day 9 (A1, 1051 +/- 144; A2, 1140 +/- 155; B, 840 +/- 124 pg/ml, p greater than 0.05) were similar as well. The number of small (1.0-1.4 cm) follicles, large (greater than or equal to 1.5 cm) follicles, and total follicles (Day 8: total A1, 5.5 +/- 0.9; A2, 4.0 +/- 0.7; B, 4.5 +/- 0.9, p greater than 0.05; Day 9: total A1, 6.7 +/- 0.9; A2, 6.9 +/- 0.8; B, 6.9 +/- 0.9, p greater than 0.05) in all three cycles were also similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗
PubMed1992

Effect of thrombin-induced hemostasis on the efficacy of an absorbable adhesion barrier.

Serosal injury, bleeding and fibrin deposition are major factors in the development of surgical adhesions; meticulous hemostasis is desirable but not always achievable. The effects of thrombin on adhesion formation and the performance of Interceed Barrier were tested in separate series using a standard model and two levels of bleeding: an "oozing" model in which rabbit uterine horns were scraped to produce uncontrolled punctate bleeding and a "bleeding" model, in which four small blood vessels nicked on the ligament to each horn produced heavier bleeding. Substantial clots in the bleeding model were not removed. Adhesions, assessed after two weeks, were not worsened by the use of thrombin to control bleeding. While Interceed Barrier alone did not reduce adhesions at sites of bleeding, achieving hemostasis with thrombin and then applying Interceed Barrier significantly reduced adhesions. The effect was not achieved by applying thrombin to previously blood-soaked Interceed Barrier. The efficacy of Interceed Barrier applied after achieving hemostasis was further improved by moistening it with heparin. Achieving hemostasis at a bleeding site with thrombin facilitates the efficacy of Interceed Barrier.

Animals↗
PubMed1991

The effect of interleukin-1 on adhesion formation in the rat.

The potential role of interleukin-1 in postoperative adhesion formation was examined. Cecal abrasion gave a consistently higher adhesion score when compared with sham laparotomy, on the basis of adhesion number, density, and vascularity, and so was chosen for use in further studies. The extent of serosal bleeding during cecal abrasion did not affect adhesion scores. Intraperitoneal injection of 10 micrograms murine recombinant interleukin-1 alpha in cecally abraded animals on the day of surgery and on the following 4 days resulted in a significant increase in adhesion scores when compared with those of cecally abraded animals injected with vehicle alone. Adhesions enhanced with murine recombinant interleukin-1 alpha, which were thicker and more vascular, were equivalently enhanced at doses from 10 to 10,000 ng, implying maximal response over that range. Rats not operated on and receiving recombinant interleukin-1 alpha 2 weeks after injury had increased adhesion formation. These results demonstrate that interleukin-1 alpha may be an important short-term mediator of postsurgical adhesion formation.

Animals↗
PubMed1991

Dose-response effects of glucose, insulin, and glucagon on mouse pre-embryo development.

The diabetic state, as well as elevated culture media glucose level (950 mg D-glucose/dL) per se, significantly retards in vitro development of mouse pre-implantation embryos from a two-cell stage to blastocyst stage; maternal insulin therapy to diabetic mice reverses this impairment. This study was undertaken to assess (1) whether less extreme elevation of the media glucose concentration would also impair development, and (2) whether elevated culture media insulin or glucagon levels would alter development. Two-cell pre-embryos were recovered from B6C3F1 mice that had been stimulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hGG), mated, and killed 48 hours later. Pre-embryos were observed in culture at 24-hour intervals for a total of 72 hours at four glucose levels: 110 (n = 108), 220 (n = 101), 440 (n = 65), and 950 (n = 106) mg D-glucose/dL. Impairment in progression of development was noted at each time period; compared with development in 110 mg glucose/dL, the distribution of development was significantly different at 24 hours (chi 2 = 60.1, P less than .001), at 48 hours (chi 2 = 36.7, P less than .001), and at 72 hours (chi 2 = 45.1, P less than .001). Rate of development as assessed by ANOVA was also significantly reduced at increasing glucose levels (P less than .0001), with Duncan Multiple Range test demonstrating differences between development at higher glucose levels in the comparison of development in 110 mg/dL versus 440 mg/dL and 950 mg/dL, and at 220 mg/dL versus 950 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Effects of small changes in glucagon on glucose production during a euglycemic, hyperinsulinemic clamp.

The aim of this study was to examine the influence of small changes in glucagon on hepatic glucose production during a euglycemic, hyperinsulinemic clamp. During 1.0 mU/kg.min insulin infusion, euglycemia was maintained by glucose infusion and glucagon was infused at various rates so as to cause plasma glucagon levels to increase, decrease, or remain unchanged. Changes in glucagon were found to be positively associated with changes in glucose production and inversely related to the degree of suppression of tracer or arteriovenous difference determined endogenous glucose production. Thus, animals in which the glucagon levels increased, appeared to have decreased hepatic insulin sensitivity, while animals in which glucagon levels decreased, appeared to have increased insulin sensitivity. In conclusion, since glucagon often declines during a euglycemic hyperinsulinemic clamp, and since small changes in glucagon can have marked effects on the suppression of hepatic glucose output even in the presence of high insulin levels, changes in glucagon should be considered when conclusions regarding hepatic insulin sensitivity are being drawn.

Animals↗
PubMed1991

Adhesiolysis.

Lysis of adhesions improves pregnancy rates. Results of laparoscopic lysis are not different from those of laparotomy. Since laparoscopy is more convenient to the patient, less expensive, saves hospital beds, and involves low morbidity, it should be the preferred surgical approach to the diagnosis and treatment of pelvic adhesions whenever possible. The use of a sharp dissection combined with electrocautery seems, at this time, to be equally effective to the use of lasers of different kinds. Adjuvants presently available, especially Hyskon or INTERCEED, have an added benefit to surgery alone. Even with the best surgical technique, adhesions tend to re-form. Although SLL will identify the extent of adhesion re-formation, the therapeutic advantage of lysing re-formed adhesions is yet to be proved.

Animals↗
PubMed1991

Effect of acute physiological elevations of insulin on circulating androgen levels in nonobese women.

Extreme pharmacological elevation of the circulating insulin level acutely lowers dehydroepiandrosterone sulfate (DHEAS) levels. To assess whether more physiological elevations in plasma insulin (due to exogenous infusion or endogenous secretion) would have similar effects, we examined the levels of DHEAS, androstenedione, testosterone, and free testosterone before and after euglycemic hyperinsulinemic and hyperglycemic hyperinsulinemic clamp studies. Studies were performed in women within 20% of ideal body weight after an overnight fast. Androgen levels were measured before and at the conclusion of studies in which either insulin was infused exogenously at 1 mU/kg.min or endogenous insulin secretion was stimulated for 2 h by elevation of the plasma glucose concentration by 125 mg/dL above basal levels by an exogenous glucose infusion. Basal plasma DHEAS (6.2 +/- 0.5 mumol/L) declined to 5.2 +/- 0.4 mumol/L (P less than 0.001) during the euglycemic insulin clamp, without any significant change in testosterone, free testosterone, or androstenedione. During the hyperglycemic clamp, DHEAS fell from 6.7 +/- 0.5 to 5.1 +/- 0.4 mumol/L (P less than 0.001) in response to endogenous hyperinsulinemia; plasma testosterone, free testosterone, and androstenedione did not change significantly. There was no correlation between the elevation in plasma insulin concentration and the fall in DHEAS during either the euglycemic or hyperglycemic clamps. However, the magnitude of fall of DHEAS was directly correlated with the initial DHEAS level in both the euglycemic (r = 0.51; P less than 0.05) and hyperglycemic (r = 0.75; P less than 0.01) studies. This association of hyperinsulinemia with a reduction of circulating levels of DHEAS, but not other C-19 steroids (e.g. testosterone and androstenedione) may reflect differential mechanisms by which DHEAS levels are regulated and suggests that insulin either inhibits its biosynthesis and/or secretion, or enhances its MCR.

Androgens↗
PubMed1991

Suppression of counterregulatory hormone response to hypoglycemia by insulin per se.

Although assessment of counterregulatory hormone responses to hypoglycemia relies upon insulin to lower the glucose level, it is not known if the exogenous insulin does used itself influences the magnitude of the hormone response. To assess this, 12 normal subjects randomly received 2 hypoglycemic clamp studies in which the only variable was the insulin dose (0.6 or 5.0 mU/kg-min). Despite 10-fold differences in circulating insulin (265 +/- 29 vs 2576 +/- 222 pmol/L respectively), the hypoglycemic stimulus did not vary. Glucose levels fell over one hour, and then were maintained for two hours at the same hypoglycemic plateau (approximately 3.1 mmol/L for each study) by a variable glucose infusion. Although basal counterregulatory hormone levels in low and high dose studies were indistinguishable, during hypoglycemia the response of epinephrine, growth hormone, and glucagon was significantly suppressed when the degree of hyperinsulinemia was increased. We conclude that raising the magnitude of hyperinsulinemia suppresses the magnitude of the counterregulatory hormone response to hypoglycemia in normal subjects. This modulating effect of insulin per se is yet another variable in the interpretation of hypoglycemic counterregulation.

Adult↗
PubMed1991

Effect of diabetes mellitus on mouse pre-implantation embryo development.

Fifteen spontaneously diabetic, non-obese mice (NOD strain), 17 non-diabetic NOD mice (in which diabetes had not yet developed) and 9 diabetic NOD mice were treated with insulin. All animals were superovulated with 5 iu of pregnant mares' serum gonadotrophin followed 48 h later by 5 iu human chorionic gonadotrophin (hCG) and mated overnight with NOD males of proven fertility. To assess in-vitro and early in-vivo development, 23 NOD mice were killed 72 h after hCG treatment. Embryos were recovered from oviduct flushings and cultured in Ham's F-10 medium with 0.1% bovine serum albumin at 37 degrees C in an atmosphere of 5% O2, 5% CO2, and 90% N2. Development was assessed at intervals of 24 h for 72 h. Compared with embryos from non-diabetic NOD mice (n = 81), embryos from diabetic NOD mice (n = 68) demonstrated marked impairment in growth assessed by distribution of developmental stages at each observation period (24, 48, 72 h, all P less than 0.001) and by overall rates of progression of developmental stages (P less than 0.01). In diabetic NOD mice treated with insulin, embryo development (n = 7) was not significantly different from that of embryos from non-diabetic NOD mice (n = 81), but was significantly faster than in embryos from diabetic NOD mice not treated with insulin (n = 68) (P less than 0.001, for all periods, overall rate P less than 0.01). To assess late in-vivo growth, 18 NOD mice were killed 120 h after hCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗