Search PubMed⌕ Search

Biomedical subjects

D H Lockwood

Publications and source records attributed to D H Lockwood.

At least 55 records · Page 3Linked to original sources
PubMed1982

Hypothalamic and pituitary dysfunction in obese males.

Previous studies have indicated dysfunction of the hypothalamic-hypophyseal axis in obesity. We have studied 12 obese males to further characterize the extent of this dysfunction. The hypothalamic-hypophyseal-gonadal axis is normal as determined by the testicular response to human chorionic gonadotropin (hCG), the pituitary response to 200 micrograms gonadotropin-releasing hormone (GnRH), and the hypothalamic-pituitary-testicular response to clomiphene. Although L-dopa suppresses prolactin normally, the ability of thyrotropin releasing hormone (TRH) to stimulate the release of prolactin and thyroid stimulating hormone (TSH) is blunted. These latter responses are inversely related to the degree of obesity. The response to chlorpromazine, a hypothalamic stimulus for prolactin secretion, is also blunted, and to a greater extent than the prolactin response to TRH. These data indicate that exogenous obesity in males is associated with more extensive hypothalamic and pituitary dysfunction than previously realized. The abnormalities with regard to prolactin and TSH release become progressively worse when body weight exceeds 200 percent of ideal. In addition, when evaluating pituitary function with regard to gonadotropin release, obese males may have an abnormal response to 100 micrograms GnRH but respond normally to 200 micrograms.

Adult↗
PubMed1981

Determinants of response to anorexiants.

We analyzed data from an 81-patient clinical trial of anorexiant medication, searching for the predictors of response. In the trial we assigned treatments to participants by minimization, a process that decreases differences between treatment groups. Based on the literature, the investigators' experience, and the pharmacologic properties of the medications, we selected 25 factors for use in the minimization process. Retrospective examination by contingency-table analysis indicated that the most important predictors of weight loss in this study were weight loss during the 3-wk diet-only run-in period (chi 2, p less than 0.001), physician estimation of patients motivation (chi 2, P less than 0.003), participant eating habits (nighttime "binge" eaters responded best; chi 2, P less than 0.003), adherence to treatment (chi 2, P less than 0.01), and type of treatment (chi 2, P = 0.05). When multiple regression analysis was applied, several other factors aided in explaining the variance in the weight loss results. For example, duration of obesity was inversely related to weight loss and weight loss during the study increased with family income. Depending on the treatment used, anxiety and depression visual analogue scores also explained some of the variance. Failure to account for factors such as these in treatment assignment may account for the low discriminant power of clinical trials of anorexiants.

Anxiety↗
PubMed1981

Abnormal regulation of monocyte insulin-binding affinity after glucose ingestion in patients with myotonic dystrophy.

Insulin insensitivity of uncertain etiology often exists in myotonic muscular dystrophy, a multitissue, autosomal dominant disorder hypothesized to be a hereditary membrane disease. The present studies show that monocytes from patients with myotonic dystrophy fail to demonstrate the normally observed qualitative increase in insulin-binding affinity after oral glucose loading. Monocytes from 10 normal volunteers developed a significantly increased insulin-binding affinity by 2 hr after glucose ingestion (mean +/- SEM, 11.7 +/- 2.7 ng/ml compared to basal 50% insulin displacement value of 23.3 +/- 2.2 ng/ml, P less than 0.005). This increase was maintained at 5 hr (13.5 +/- 2.7 ng/ml, P less than 0.05). In contrast, no significant increase in monocyte insulin-binding affinity occurred in cells from nine myotonic dystrophy patients at 2 and 5 hr after glucose loading (50% insulin displacement values: basal, 14.2 +/- 2.8 ng/ml; 2 hr, 16.7 +/- 1.7 ng/ml; 5 hr, 10.8 +/- 2.1 ng/ml). These alterations document the presence of abnormalities in the insulin receptor or receptor-associated processes that modulate insulin binding. A hereditary plasma membrane defect may underlie these findings. This abnormality may have an etiologic role in the decreased insulin sensitivity that frequently afflicts patients with myotonic dystrophy.

Glucose↗
PubMed1981

Errors in potassium balance.

Six overweight adult subjects given a low calorie diet containing adequate amounts of nitrogen but subnormal amounts of potassium (K) were observed on the Clinical Research Center for periods of 29 to 40 days. Metabolic balance of potassium was measured together with frequent assays of total body K by 40K counting. Metabolic K balance underestimated body K loses by 11 to 87% (average 43%); the intersubject variability is such as to preclude the use of a single correction value for unmeasured losses in K balance studies.

Adult↗
PubMed1981

In vitro effects of a sulfonylurea on insulin action in adipocytes. Potentiation of insulin-stimulated hexose transport.

The mechanism(s) by which the oral sulfonylurea, tolazamide, exerts its extrapancreatic hypoglycemic effects was studied using rat epididymal adipose tissue maintained 20-44 h in the presence or absence of the drug. Insulin binding, hexose transport and glucose metabolism were compared in adipocytes isolated from the cultured tissue. In contrast to earlier reports that suggested that sulfonylureas alter the binding of insulin, neither receptor number nor affinity were changed by tolazamide treatment. The uptake of the glucose analogs 2-deoxyglucose and 3-0-methylglucose in the absence of insulin (i.e., basal) was also unchanged. However, exposure to tolazamide resulted in a potentiation of the stimulatory effects of insulin by approximately 30% at each hormone concentration assayed (0.4-40 ng/ml). This potentiation was dependent on the tolazamide concentration (0.003-0.30 mg/ml), with a maximal effect observed at therapeutic levels. A tolazamide analog hypoglycemic activity in vivo was found not to enhance either basal or insulin-stimulated uptake in vitro. Conversion of 0.1-5.0 mM glucose to CO2 and total lipids in the presence of insulin was also potentiated by tolazamide treatment. The inability of the drug to directly stimulate basal glucose uptake was paralleled by its lack of effect on glucose metabolism. At 50 mM glucose, where transport is no longer rate-limiting, tolazamide did not potentiate metabolism in the absence or the presence of insulin. These studies demonstrate that tolazamide in vitro alters postreceptor insulin action without influencing the receptor, and suggests insulin-stimulated hexose transport as the cellular process responsible for the hypoglycemic effect of sulfonyureas in adipose tissue.

Adipose Tissue↗
PubMed1980

Osteomalacia and weakness from excessive antacid ingestion.

A 60-year-old woman was evaluated for bone pain and incapacitating weakness. Initial laboratory studies showed a serum calcium level of 10.1 mg/dL, severe hypophosphatemia (1.1 mg/dL), and an elevated alkaline phosphatase level. X-ray films showed changes consistent with osteomalacia. Further studies revealed hypercalciuria (448 mg/24 hr) but absent urinary phosphorus. These data indicated phosphate malabsorption. Excessive use of an aluminum hydroxide-containing antacid was the cause of this patient's failure to absorb dietary phosphate. The features of this syndrome are reviewed to increase physicians' awareness of this illness, which occurs particularly in the elderly and is easily treated.

Alkaline Phosphatase↗
PubMed1980

Age-related abnormalities of circulating polyamines and diamine oxidase activity in cystic fibrosis heterozygotes and homozygotes.

Serum putrescine (Pu), spermidine (Sd), spermine (Sp), and plasma diamine oxidase ativity (DAO) were determined in cystic fibrosis (CF) homozygotes and heterozygotes plus age-matched controls. Mean (+/- S.E.) levels of Pu (0.51 +/- 0.06 nmoles/ml), Sd (0.63 +/- 0.07 nmoles/ml), and Sp (0.33 +/- 0.08 nmoles/ml) were higher (P < 0.001) in 17 control children versus 16 healthy adults (Pu = 0.15 +/- 0.04; Sd = 0.14 +/- 0.03; Sp = 0 in all). All 4 CF adults tested, but only 3 of 24 CF children, had increased polyamines relative to age-matched controls. Pu (0.33 +/- 0.04), Sd (0.33 +/- 0.05) and Sp (0.16 +/- 0.12) were increased (P < 0.001) in 11 adult heterozygotes; in turn, Pu (0.56 +/- 0.11; P < 0.025) and Sd (0.86 +/- 0.22; P < 0.005) were higher in the adult CF patients than in the heterozygotes. Plasma DAO was higher (P < 0.001) in 45 control children (9.3 +/- 0.7 units/ml) versus 61 healthy adults (5.7 +/- 0.07). Levels greater than or equal to +2 S.D. for controls occurred in 8 (21%) of 39 CF patients. Plasma DAO (19 +/- 4.8) was increased (P < 0.001) in 27 adult heterozygotes; 10 (37%) had values greater than or equal to +2 S.D. for normal adults. One or more polyamines and/or DAO were increased in each of 11 heterozygotes in whom all parameters were measured. These composite abnormalities might be considered as a potential means for identification of asymptomatic CF heterozygotes.

Adolescent↗
PubMed1979

Pituitary adrenal recovery following short-term suppression with corticosteroids.

To provide clinical guidelines for the use of high-dose short-term glucocorticoid therapy, we studied recovery of the hypothalamic-pituitary-adrenal axis in 10 normal men following the administration of suppressive doses of prednisone (25 mg twice daily for five days). Cortisol responses to insulin-induced hypoglycemia and synthetic ACTH before treatment were compared with responses two and five days after concluding the prednisone course when adrenal function was not influenced by the presence of exogenous steroid. Two days after prednisone therapy, peak cortisol responses to both hypoglycemia (11.0 +/- 0.9 microgram/dl mean +/- SEM) and synthetic ACTH (13.3 +/- 1.4 microgram/dl) were significantly reduced compared to pretreatment (20.6 +/- 1.6 and 27.3 +/- 2.5 microgram/dl, respectively, p less than 0.001). Five days after concluding the prednisone therapy, peak cortisol response to hypoglycemia had returned to near pretreatment levels although peak cortisol response in the adrenal gland to synthetic ACTH (22.3 +/- 1.1 microgram/dl) remained reduced (p less than 0.05). These data suggest that brief courses of high-dose prednisone therapy may limit the adrenal component of the hypothalamic-pituitary-adrenal response to stress for up to five days.

17-Hydroxycorticosteroids↗
PubMed1978

Studies of glucose transport system of fat cells: effects of insulin and insulin mimickers.

The rate of uptake of [U-14C]glucose or 3-O-[14C]methylglucose by isolated fat cells was rapidly measured (within 30 s) by an oil-centrifugation method. Insulin and the chemical agents, H2O2 (0.3 mM), vitamin K5 (48 micron), and spermine (0.3 mM), enhanced the uptake of both sugars. Each agent required a characteristic time period of incubation with the cells to produce maximum activation of transport. Insulin and the chemical agents increased the equilibrium exchange rate of methylglucose by the cells. The increase in rate elicited by the hormone and the reagents resulted primarily from increasing the Vmax of the exchange process. The Kt ranged from 7.5 to 10 mM after treatment of cells with insulin or the other agents. Basal Kt values were more difficult to measure, but in a sugar concentration range of 5-15 mM the values were similar to those found under conditions of stimulated exchange. Overall, these findings suggest that the chemical agents may be useful as probes to study certain aspects of insulin-mediated activation of glucose transport. However, because of the differences in time courses needed for activation, the actual steps that lead to stimulation may differ for the chemical agents and insulin.

Adipose Tissue↗
PubMed1978

Depressed plasma testosterone and fractional binding of testosterone in obese males.

Plasma testosterone (T), fractional binding of T to T-binding globulin (TeBG), LH, and FSH were evaluated in 22 obese men. Only 1 of 12 men weighing from 176-200% of ideal body weight (group I) had a low T concentration, while 9 of 10 men greater than 200% of ideal weight (group II) had plasma T concentrations 2 SD below the normal mean. The fractional binding of T to TeBG was equally and significantly decreased in both groups. As a result, the mean and individually calculated free T concentrations (free T index) were normal in group I. In contrast, the mean free T index in group II was significantly less than normal males and group I. Individually, 1 of 7 group II men had a free T index 2 SD below the normal mean. LH and FSH were normal in both groups. These studies indicate that in most obese males a low or low normal T is offset by decreased binding to TeBG, resulting in a normal free T index. However, some morbidly obese males are unable to alter their hypothalamic-hypophyseal-gonadal axis to maintain a normal free T index.

Adult↗
PubMed1978

[125I] Glucagon binding by liver membranes from young and adult rats.

We have previously shown that adipocytes from adult (between four and five months old) rats have reduced glucagon binding and glucagon-stimulated lipolytic activity when compared with cells from young (1.5 months old) animals. In the present study we measured specific [125I] glucagon binding by purified liver plasma membranes isolated from young and adult rats. When expressed on the basis of membrane protein content, 5'-nucleotidse activity, or specific [125I] insulin binding, the extend of [125I] glucagon binding by liver membranes was not influenced by aging. Furthermore, the degree of [125I] glucagon degradation was the same in both membrane preparations. These data describe a unique condition in which glucagon binding and hormone sensitivity diminish in one tissue but remain unaltered in another.

Aging↗