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Biomedical subjects

M Rosenbaum

Publications and source records attributed to M Rosenbaum.

At least 19 recordsLinked to original sources
PubMed1992

Proarrhythmic effects of procainamide and tocainide in a canine infarction model.

A canine model of myocardial infarction (MI) was used to study the type and frequency of ventricular antiarrhythmic and proarrhythmic effects due to procainamide and tocainide and the risk factors associated with development of proarrhythmia. An anterior MI was created by a 2-h occlusion of the left anterior descending artery (LAD) with complete reperfusion. Programmed ventricular stimulation was performed on two occasions after MI, on days 4-6 and on days 8-10, before drug and during antiarrhythmic drug infusion at three dose levels. The antiarrhythmic drugs were given in a randomized cross-over design. Only procainamide caused a dose-dependent increase in QRS, JTc, and right ventricular effective refractory period (ERP). Neither procainamide nor tocainide made sustained ventricular tachycardia (VT) noninducible, but procainamide slowed the tachycardia rate. Both drugs successfully made ventricular fibrillation (VF) noninducible: procainamide in 78% of trials and tocainide in 50% of trials. Proarrhythmia (development of inducible VT during drug when not present before drug or inability to terminate VT during drug administration) developed in 29% of dogs that received procainamide and 25% of dogs that received tocainide. There was no apparent correlation of QRS, JTc, and right ventricular ERP after drugs and proarrhythmia due to procainamide or tocainide. There was no significant difference in the size of MI between dogs with one or more proarrhythmic response to either drug and dogs that had no proarrhythmia. In this model, procainamide and tocainide had no antiarrhythmic efficacy for VT, but had moderate proarrhythmia potential that was unpredictable.

Animals↗
PubMed1992

Effects of systemic growth hormone (GH) administration on regional adipose tissue in children with non-GH-deficient short stature.

Chronic administration of exogenous GH to GH-deficient children is associated with a selective depletion of the abdominal sc fat depot and a resultant relative increase in gluteal, relative to abdominal, adipocyte lipid content. In GH-deficient children, the degree of this change in relative lipid content per adipocyte appears to be correlated with decreases in sensitivity of abdominal subcutaneous fat to the antilipolytic action of insulin. We studied abdominal and gluteal sc adipose tissue from 10 children with short stature (height less than 5% ile, growth velocity less than 5 cm/yr, bone age delayed at least 2 yr), who were not GH deficient based upon provocative testing (non-GH-deficient short stature) 1) before beginning and 2) after 3 months of therapy with exogenous GH (Humatrope, 0.1 mg/kg sc 3 times/week). In abdominal and gluteal adipocytes, we measured lipid content, rates of reesterification of fatty acids released by ongoing lipolysis and rates of in vitro lipolysis and lipogenesis in response to insulin, adenosine, and various adrenoreceptor agonists. These biochemical measures were correlated with measures of statural growth and adipose tissue distribution in each subject. We found that GH therapy was associated with a significant reduction in abdominal adipocyte size (0.48 microgram +/- 0.08 lipid per cell prior to therapy vs. 0.43 microgram +/- 0.08 lipid per cell after therapy, P less than 0.05) and a significant increase in responsiveness of gluteal sc adipose tissue to the lipogenic actions of insulin. The significant correlations of changes in abdominal adipocyte volume with changes in regional adipose tissue insulin sensitivity that were noted in GH-deficient children were not noted in this subject population, perhaps due to effects of endogenous GH on pretreatment insulin responsiveness of adipose tissue. These data reaffirm that GH has site-specific effects on regional adipose tissue depots.

Abdomen↗
PubMed1991

Violence in psychiatric wards. Role of the lax milieu.

In recent years there has been a marked increase in interest and publications dealing with violence in psychiatric facilities. There is general agreement that the increase in violent behavior is real despite underreporting prior to the late 1970s. The author proposes that the changes in structure and functioning of psychiatric facilities following the Community Mental Health Act of 1963 may be one of the factors responsible for the increase of violent behavior. To test this proposal, Index Medicus was searched for articles on violence in psychiatric facilities from 1935 through 1988. The first articles appeared in 1968. A review of leading textbooks of psychiatry during the same period revealed similar findings. The role of the lax milieu is discussed. It is proposed that the "medical model" as described in this paper be reinstituted in short-stay psychiatric facilities.

Crisis Intervention↗
PubMed1991

Regional differences in adrenoreceptor status of adipose tissue in adults and prepubertal children.

The relative anatomical distribution of adipose tissue in central (abdominal) vs. peripheral (extremity) depots is highly correlated with the risk of adiposity-related morbidities, such as hypertension, cardiovascular disease, and diabetes mellitus. In adults, comparisons of the functional status of plasma membrane adrenergic receptors indicate that abdominal adipocytes are more responsive to the lipolytic action of beta 1-adrenergic agonists, while gluteal adipocytes are more responsive to the antilipolytic action of alpha 2-adrenergic agonists. To determine whether such regional differences in adipocyte adrenoreceptor status are present before puberty, we obtained needle biopsy samples of abdominal and gluteal sc adipose tissue in the post-absorptive state from 13 prepubertal children and 47 adults of varying body compositions (obese vs. lean). Lipolysis rates were measured in the basal state and in the presence of 10(-7) M norepinephrine (a mixed alpha- and beta-adrenergic agonist) and 10(-7) M isoproterenol (a beta-adrenergic agonist). In children, there were no significant regional differences in either the basal rate of lipolysis or the responses to adrenergic lipolytic and antilipolytic stimuli. In lean and obese adults, gluteal sc adipose tissue was strikingly more responsive to antilipolytic alpha-adrenergic stimulation (P less than 0.0001) and less responsive to lipolytic beta-adrenergic stimuli (P less than 0.005) compared to abdominal tissue. Abdominal sc adipocytes from children had a significantly lower rate of basal lipolysis (P less than 0.01) and were more responsive to alpha 2-adrenergic (antilipolytic) stimuli (P less than 0.05) than abdominal adipocytes in adults. These results suggest that peripubertal endocrine changes may mediate the striking regional differences in adrenoreceptor status of adult adipose tissue, and that a decrease in the preponderance of alpha 2-receptors (antilipolytic) in abdominal adipose tissue may account in part for the relative loss of central vs. peripheral fat that occurs during puberty.

Adipose Tissue↗
PubMed1990

The role of depression in couples involved in murder-suicide and homicide.

Twelve couples in cases of murder-suicide were compared to 24 couples in cases of homicide during the period 1978 to 1987 in Albuquerque, N.M. Data were obtained from police, the courts, hospital records, and interviews with friends and family of the deceased. The most striking findings were that perpetrators of murder-suicide were depressed (75%) and men (95%), while perpetrators of homicide were not depressed and one-half were women. The data indicate that the murder-suicide and homicide groups are two different populations.

Adult↗
PubMed1989

Acute inhibition of somatotroph response to human growth hormone-releasing hormone 1-44 occurs following three hours but not one hour of growth hormone infusion.

Our previous studies have demonstrated that a short-term (three hour) infusion of methionyl human growth hormone (met-hGH, 2 micrograms/kg/h) is associated with a rise in serum concentrations of free fatty acids and glycerol, and a blunting of somatotroph response to human growth hormone releasing hormone 1-44 (GRH) in normal volunteers. To gain more information on the time course of this blunting, and to determine whether it could be temporally dissociated from the GH-induced rise in serum concentrations of lipolytic products, the response to GRH (0.3 micrograms/kg) was measured in five normal adult volunteers from hours 1.0 to 3.5 of a 3.5-hour infusion of saline or met-hGH 2 micrograms/kg/h. Somatotroph response to the same dose of GRH from hours 3.0 to 5.5 of a longer (5.5-hour) infusion of saline or met-hGH (2 micrograms/kg/h) in five other volunteers was used for comparison. There was a significant blunting of somatotroph response following three hours, but not one hour of met-hGH infusion. The longer infusion was associated with a significant rise in serum concentrations of free fatty acids, and the shorter met-hGH infusion was too brief to provoke such a rise. Neither met-hGH infusion was associated with a significant rise in serum concentrations of glycerol, insulin, glucose, or insulin-like growth factors (IGF). This study provides further evidence that there is an association between circulating FFA and somatotroph function and suggests that FFA may act as messengers, which provide information to central systems regarding the energy balance of the organism.

Adult↗
PubMed1989

Recombinant growth hormone enhances muscle myosin heavy-chain mRNA accumulation and amino acid accrual in humans.

A potentially lethal complication of trauma, malignancy, and infection is a progressive erosion of muscle protein mass that is not readily reversed by nutritional support. Growth hormone is capable of improving total body nitrogen balance, but its role in myofibrillar protein synthesis in humans is unknown. The acute, in situ muscle protein response to an infusion of methionyl human growth hormone was investigated in the limbs of nutritionally depleted subjects during a period of intravenous refeeding. A 6-hr methionyl growth hormone infusion achieved steady-state serum levels comparable to normal physiologic peaks and was associated with a significant increase in limb amino acid uptake, without a change in body amino acid oxidation. Myosin heavy-chain mRNA levels, measured by quantitative dot blot hybridization, were also significantly elevated after growth hormone administration. The data indicate that methionyl growth hormone can induce intracellular amino acid accrual and increased levels of myofibrillar protein mRNA during hospitalized nutritional support and suggest growth hormone to be a potential therapy of lean body wasting.

Adult↗
PubMed1989

Intravenous refeeding blocks growth hormone (GH)-provoked rises in serum free fatty acids and blunting of somatotroph response to GH-releasing hormone in normal men.

We measured the serum GH responses to GHRH (1 micrograms/kg) in six normal men who had been rendered hyperinsulinemic and hypolipidemic by 10 days of total parenteral nutrition (TPN subjects) with a 25% dextrose-amino acid solution. The men underwent GHRH testing after 3 h of infusion of NaCl or Met-human (h) GH (2 micrograms/kg.h). The results of these tests were compared with those of five men tested in the post-absorptive state (PA subjects). The serum GH response to GHRH during NaCl infusion was significantly lower in the TPN subjects than in the PA subjects. During the Met-hGH infusion, the serum GH response to GHRH in the PA subjects was significantly lower than that after the NaCl infusion, whereas in the TPN subjects the response was similar to that during the NaCl infusion. The mean integrated areas under the GH response-time curve after GHRH treatment were 3963 +/- 2086 min/micrograms.L following NaCl infusion and 413 +/- 64 min/micrograms.L following Met-hGH infusion in PA subjects; they were 1127 +/- 500 min/micrograms.L following NaCl infusion and 1456 +/- 682 min/micrograms.L during Met-hGH infusion in the TPN subjects. The Met-hGH infusions resulted in a significant increase in serum FFA concentrations in the PA, but not the TPN, subjects. These results suggest that hyperalimentation induces a metabolic background which inhibits GH secretion, as manifested by a diminished serum GH response to GHRH administered after NaCl infusion. The absent FFA response to Met-hGH infusion in the TPN subjects may explain why the Met-hGH infusion in them did not result in a reduced serum GH response to GHRH as occurred in the PA subjects. Hence, FFA may play an important role in the effects of short term Met-hGH infusion on GH secretion.

Adult↗
PubMed1989

Metabolic clearance rates of synthetic human growth hormone in children, adult women, and adult men.

The MCR of biosynthetic human GH was studied in 12 prepubertal children, 9 adult women, and 13 adult men. Subjects received a constant infusion of biosynthetic GH, and clearance was calculated by dividing the infusion rates by steady state serum concentrations of GH. We found that adult men have a significantly more rapid MCR of human GH than women (125.2 +/- 7.6 mL/min.m2 in men; 89.4 +/- 7.7 mL/min.m2 in women) and that both men and women have a significantly more rapid MCR of human GH than prepubertal children (66.8 +/- 7.7 mL/min.m2). Sex differences in GH clearance rates may account at least in part for the lower mean serum GH concentrations in pubertal, but not prepubertal, males compared to those in females. The differences in clearance between prepubertal children and adult women and men suggest that the male-female differences in GH clearance are due to androgen effects on GH clearance or on the relative proportions of free and protein-bound GH in serum.

Adult↗
PubMed1989

Effects of systemic growth hormone (GH) administration on regional adipose tissue distribution and metabolism in GH-deficient children.

Chronic administration of exogenous GH to GH-deficient children is associated with a redistribution of adipose tissue from an abdominal (android) to a more peripheral (gynoid) distribution. We studied abdominal and gluteal sc adipose tissue from seven GH-deficient children 1) before beginning and 2) after 3 months of therapy with exogenous GH (0.1 mg/kg, sc, three times per week). In abdominal and gluteal adipocytes, we measured lipid content and rates of in vitro lipolysis and lipogenesis in response to insulin and various adrenoreceptor agonists. These results were correlated with measures of statural growth and adipose tissue distribution in each subject. We found that GH therapy was associated with a significant reduction in abdominal adipocyte size (0.68 +/- 0.09 micrograms lipid/cell before therapy vs. 0.49 +/- 0.07 after therapy; P less than 0.05), a significant reduction in overall basal rates of lipogenesis (0.43 +/- 0.06 mumol [14C]acylglyceride synthesized/10(6) cells.2 h before therapy vs. 0.27 +/- 0.09 after therapy), and with variable desensitization of abdominal sc adipose tissue to the antilipolytic effect of insulin. The extent of this decrease in insulin action was significantly correlated with changes in abdominal adipocyte lipid content (r = 0.77; P less than 0.05), and with the changes in the anatomical distribution of fat during the study period (r = 0.97; P less than 0.001), as measured by the relative lipid content per adipocyte at each site. We conclude that the site-specific changes in adipose distribution during GH administration are due in part to anatomical site-specific GH-mediated changes in insulin responsiveness of adipose tissue and that exogenous GH therapy is associated with a decrease in de novo triglyceride synthesis in GH-deficient children.

Adipose Tissue↗
PubMed1988

Influence of substrate background on peripheral tissue responses to growth hormone.

To evaluate the effects of substrate and hormonal background on the peripheral response to methionyl human growth hormone (met-hGH), metabolic measurements were performed in 10 normal subjects before and at the end of a 6-hr infusion of met-hGH. Five subjects were studied in the postabsorptive state and five were studied on the 10th day of intravenous repletion. Measurements of hormonal levels, serum amino acid levels, and free fatty acid levels, as well as extremity amino acid and free fatty acid fluxes, were performed. Met-hGH in the postabsorptive setting had no effect on extremity amino acid flux but significantly increased extremity free fatty acid efflux. In contrast, met-hGH in the background of intravenous feeding produced a significant extremity uptake of total amino acids but had no effect on free fatty acid flux. These data suggest a relationship between the substrate background and the actions of met-hGH on both peripheral protein and lipid metabolism. Therefore, the adequacy and composition of the feeding regimen may be important when considering growth hormone as an adjunct to nutritional therapy.

Adult↗