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Biomedical subjects

M S Robbins

Publications and source records attributed to M S Robbins.

At least 19 recordsLinked to original sources
PubMed1996

Five-year performance trends for older exercisers: a hierarchical model of endurance, strength, and flexibility.

OBJECTIVE: To examine 5-year trends in measures of physical performance, and the impact of disease upon performance, in three domains: cardiovascular fitness, musculo-skeletal strength, and flexibility among older adults participating in a medically supervised exercise program. DESIGN: Longitudinal analyses of data obtained in an observational cohort study. SETTING: Department of Veterans Affairs Medical Center in Durham, North Carolina. PARTICIPANTS: Seventy-three community-dwelling veterans between 64 and 90 years of age. INTERVENTION: Voluntary participation in a medically supervised outpatient exercise program meeting 3 days per week for 90 minutes per session. MAIN OUTCOME MEASURES: Changes over time in cardiovascular fitness, musculoskeletal strength, and flexibility. RESULTS: Forty-nine percent of the original study participants remained in the program for a full 5 years. They had lower baseline rates of cardiorespiratory and musculoskeletal diseases than did the dropouts. Dropouts were significantly more impaired in baseline measures of cardiovascular fitness (P = .038) and strength (P = .007). Changes over time for cardiovascular fitness and strength were similar. Only linear (P < .05) and quadratic time (P < .001) were significant. Only linear time was significant for measures of flexibility (P < .05). Baseline cardiorespiratory disease, baseline musculoskeletal disease, and interaction terms were not significant. Overall, measures of physical performance demonstrated gradual improvement for 2 to 3 years, followed by a gradual decline in performance irrespective of baseline disease status. CONCLUSION: Older adults who exercise regularly, including those with multiple chronic diseases, can achieve significant gains in measures of physical performance, and these gains can be sustained for 2 to 3 years.

Aged↗
PubMed1994

Sertraline intoxication in a child.

We describe severe sertraline intoxication in a child after accidental ingestion. Sertraline is a new antidepressant that has potent and selective inhibition of neuronal serotonin reuptake. Drug company-sponsored research has suggested little toxicity for this compound. Our patient exhibited prolonged tachycardia, hypertension, hallucinations, coma, hyperthermia, tremors of all extremities, and skin flushing. Clinicians should consider the possibility of serotonin syndrome among patients with similar clinical features and a recent history of sertraline or other serotonergic agent ingestion.

1-Naphthylamine↗
PubMed1994

The Gerofit Program: a VA innovation.

In 1986 Gerofit, an exercise and health promotion program for older veterans, was established. This paper describes the program in detail by summarizing the patient assessment protocol, the exercise program, and program evaluation, as well as observational outcomes for up to 5 years of follow-up. Our data suggest that exercise provides older veterans with beneficial gains in function that are maintained for 5 years.

Aged↗
PubMed1992

The future of positron emission tomography in clinical medicine and the impact of drug regulation.

Positron emission tomography (PET) was initially developed as a research tool for evaluating normal and abnormal physiology. Subsequently, the potential clinical utility of PET was recognized, and several specific clinical indications have been defined. PET has been demonstrated to be clinically useful in evaluating certain disorders of the brain and heart. PET holds significant promise for use in the evaluation of psychiatric illness and in multiple aspects of evaluation of malignancy. A major limiting factor for the growth of clinical PET is the absence of policies for reimbursement by third-party payers. Although rubidium-82 chloride is approved by the Food and Drug Administration (FDA), the lack of FDA approval of fluorine-18 2-fluoro-2-deoxyglucose (FDG) is hampering reimbursement for PET studies. The jurisdiction of the FDA over cyclotron-produced PET radiopharmaceuticals synthesized and used on site is a matter of debate because these drugs are not introduced into interstate commerce and because these activities appear to be permissible under certain exemptions in the Federal Food, Drug, and Cosmetic Act relating to the practices of medicine and pharmacy. The jurisdictional authority of the FDA in regulating these radiopharmaceuticals would be established with certainty only through litigation, but no individual or organization has elected to challenge the FDA at this time. The Institute for Clinical PET (ICP) is developing a Drug Master File that can be used in support of site-specific New Drug Applications (NDAs) for cyclotron-produced radiopharmaceuticals by any organization desiring an NDA. The ICP is optimistic that this method of obtaining FDA-approval of FDG and other cyclotron-produced PET radiopharmaceuticals will be successful and beneficial to sites using PET clinically.

Forecasting↗
PubMed1991

Synthesis, characterization and myocardial uptake of cationic bis(arene)technetium(I) complexes.

A series of bis(arene)technetium(I) complexes has been synthesized from 99mTcO4- in order to study their organ distribution. Syntheses using either ultrasound/Al/AlCl3 or Zn/HCl gave products relatively free from transalkylation. The identity of the complexes was verified by comparison to the 99Tc complexes. Equivalence of the 99Tc and 99mTc complexes was demonstrated by HPLC techniques. Biodistribution studies in rats reveal substantial myocardial uptake for many members of the series, especially those containing benzene rings substituted with about four to six carbon atoms. The myocardial uptake is related to the lipophilicity of the complexes as measured by octanol/buffer partition ratios (OBPR). Optimal ranges of lipophilicity for maximal myocardial uptake occur for OBPR from 2 to 9. Rat and human plasma binding of the complexes increases with lipophilicity after a threshold value is exceeded.

Animals↗
PubMed1991

Comparison of in vitro RBC labeling with the UltraTag RBC kit versus in vivo labeling.

This study compared cardiac-gated equilibrium blood-pool imaging studies using in vitro technetium-99m- (99mTc) labeled red blood cells (RBCs) prepared with the UltraTag RBC kit to in vivo labeling with stannous (pyro- and trimeta-) phosphates. The in vitro labeling procedure takes approximately 25 min and does not require centrifugation to separate free from bound 99mTc. Imaging studies were performed in 30 patients using the in vitro labeling procedure and in 30 patients with in vivo labeling. Regions of interest were placed over the center of the left ventricle, inferior and lateral to the left ventricle (background), and over the right midlung. The mean +/- s.e. in vitro RBC labeling efficiency was 98.5 +/- 0.2%. The heart-to-background ratios were significantly higher with in vitro labeling. The heart-to-background ratios, averaged among two blinded reviewers, were 4.6 and 3.4 for the in vitro and in vivo methods, respectively. The heart-to-lung ratio was generally higher with the in vitro procedure (3.6) than that observed with the in vivo method (3.2) but failed to attain statistical significance (p = 0.059). These results demonstrate the superiority of the in vitro labeling procedure over in vivo labeling for gated equilibrium blood-pool imaging.

Erythrocytes↗
PubMed1989

Acute and subacute toxicity studies of ioversol in experimental animals.

The authors examined the acute and subacute toxicity of the low-osmolality nonionic radiographic contrast agent, ioversol. The median lethal dose (LD50) of ioversol administered intravenously to mice, rats, rabbits, and dogs was more than 12 g I/kg, which exceeds the maximal anticipated clinical dose by at least tenfold. When the acute intravenous toxicity of 35% I, wt/vol, ioversol was compared with 35% I, wt/vol, iohexol and 37% I, wt/vol, iopamidol in mice, no significant differences in LD50 values or general toxicity were found. Ioversol also was administered via intrathecal routes to rats, dogs, and monkeys. In a comparative study, acute intracisternal injections of 35% I, wt/vol, ioversol in rats demonstrated far less toxicity than 35% I, wt/vol, iohexol and 37% I, wt/vol, iopamidol, a result that may be due to the increased hydrophilic tendency of ioversol relative to iohexol and iopamidol. Acute intracisternal injections of 43% I, wt/vol, ioversol, 35% I, wt/vol, iohexol, and 37% I, wt/vol, iopamidol into dogs at 160 or 240 mg I/kg, demonstrated comparable, but only minimal, toxicity. Monkeys given lumbar intrathecal injections of ioversol tolerated 60 mg I/kg well with no resulting arachnoiditis. Subacute toxicity studies involving 4-week daily intravenous injections (0.2, 0.8, and 3.2 g I/kg/day) in rats and dogs showed ioversol to be well tolerated. The signs of toxicity included a reversible renal cytoplasmic tubular vacuolation in the rat at high doses and a reversible hepatocyte vacuolation in the dog at the same high dose. However, clinical chemistry tests showed no signs of renal or hepatic dysfunction, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Hemodynamic effects of ioversol in the dog and rat.

The hemodynamic effects of selectively administered ioversol were examined in the dog and rat. At concentrations ranging from 32% to 37% I, wt/vol, ioversol was compared with nonionic (iohexol, iopamidol) and ionic (diatrizoate) contrast media for cardiovascular responses following injections into the femoral vein, right and left coronary arteries, left ventricle, and the pulmonary and femoral arteries of the dog, and into the carotid artery of the rat. Regardless of the intravascular route of injection, ioversol generally caused minimal effects on the heart rate, minimal to moderate decreases in myocardial contractility, left ventricular pressure, mean arterial pressure, pulmonary vascular resistance, and systemic vascular resistance. These effects of ioversol were comparable to those of iohexol and iopamidol, and were relatively less profound than those of diatrizoate. Under experimental conditions injections of ioversol exerted hemodynamic effects comparable to those of other nonionic agents, yet relatively diminished as compared with a representative high-osmolality ionic contrast agent. These results suggest that the nonionic contrast agent, ioversol, should be well tolerated in patients following injections via similar intravascular routes.

Animals↗
PubMed1989

Reproductive, developmental, and genetic toxicology of ioversol.

The authors examined the reproductive, developmental, and genetic toxicity of ioversol in several in vivo and in vitro systems. In Segments I, II, and III reproductive toxicity studies, ioversol did not produce teratogenic effects in either rats or rabbits at daily intravenous dose levels of up to 3.2 g I/kg/day. Daily intravenous injections in male and female rats did not adversely affect fertility or reproductive function. Offspring derived from dams treated with ioversol also developed and reproduced in a normal fashion. Four genetic toxicity studies employing bacterial and mammalian assay systems, and using both in vitro and in vivo methods, indicated that ioversol did not possess mutagenic or clastogenic activity.

Abnormalities, Drug-Induced↗
PubMed1989

Biodistribution and excretion of 125I ioversol in conscious dogs.

Radiolabeled ioversol was injected intravenously into two male and two female beagle dogs (6.7 to 10.4 kg) at two dose levels each (0.2 and 1.0 g I/kg). Blood levels of radioactivity were monitored at 2, 5, 10, 20, 40, 60, 90, and 120 minutes and at one and two days. Urine and feces were collected in metabolism cages for two days, at the end of which the dogs were killed and organs or tissues (kidneys, liver, spleen, lungs, thyroid glands, heart, gonads, and muscle) were sampled. Radioactivity in tissues and excreta was assayed. Biexponential disappearance of radioactivity from blood was observed in three of four dogs at each dose level. Distribution half-lives averaged 2.5 to 3.5 minutes. Elimination half-lives averaged 51 to 54 minutes. Volumes of distribution averaged 25% to 27% of body weight. No organ retention was evident at 48 hours. Recovery of ioversol in urine and feces averaged 86% to 88% of the administered dose, of which all but a few percent was recovered in urine. On chromatographic assay, ioversol accounted for an average of 103% to 109% of radioiodine, suggesting, within the experimental limits of the assay, that ioversol is excreted unchanged. No dose-related differences were evident in any of these measures. The pharmacokinetics and biodistribution of ioversol are consistent with those of other extracellularly distributed iodinated contrast agents that are excreted by the kidney.

Animals↗
PubMed1988

The effect of sodium on the fibrillatory potential of ioversol.

The spontaneous ventricular fibrillation (VF) potential of the nonionic contrast media, ioversol (IOV), with and without the addition of sodium was examined during right coronary artery (RCA) injections into anesthetized closed-chest dogs. Protocols included fixed volume (6 mL) and fixed rate (0.4 and 0.6 mL/sec) injections to compare two or more of the following: IOV, IOV + (0.075-0.9% wt/vol) NaCl, and sodium/meglumine diatrizoate (DIA). In these studies, the incidence of VF for IOV alone was either greater that with IOV + NaCl formulations or, if equivalent, the incidence of other arrhythmias was greater with IOV alone than with the sodium formulations. When DIA was included in the comparisons, the incidence of VF was always greater than IOV with or without sodium. There was a sodium-related concentration prolongation in QT interval that, at 0.9% NaCl, approximated that with DIA, even though the incidence of VF for the sodium formulation was 0/15 vs. 6/12 for DIA. Thus, the addition of sodium to IOV appears to reduce the propensity for sponteneous VF in the canine model.

Animals↗
PubMed1987

Comparison of technetium-99m MAG3 kit with HPLC-purified technetium-99m MAG3 and OIH in rats.

Technetium-99m (99mTc) mercaptoacetylglycylglycylyglycine (MAG3) in high (greater than or equal to 95%) radiochemical purity is prepared from lyophilized kits containing benzoylMAG3, sodium tartrate, lactose, and stannous chloride by adding sodium [99mTC]pertechnetate and heating the contents briefly. Constant-infusion renal whole-blood clearance obtained with [99mTc] MAG3 kits was compared with that obtained with high performance liquid chromatography (HPLC) pure [99mTc]MAG3 and with co-infused iodine-131 (131I) iodohippurate (OIH) in anesthetized rats. Average renal whole-blood clearance of [99mTc]MAG3 from kits was 3.9 +/- 0.4 ml/min/100 g body weight (mean +/- s.e.m. n = 5) and that for HPLC-pure [99mTc]MAG3 was 4.6 +/- 0.3 (n = 3). Renal whole-blood clearance ratios for [99mTc]MAG3 to co-infused iodine-131 (131I) OIH were greater than unity for both kit formulation (1.7 +/- 0.1) and HPLC-pure [99mTc]MAG3 (1.9 +/- 0.2). Differences in these two measures were not significant. Plasma binding (determined from blood drawn at the end of the infusion) of [99mTc]MAG3 prepared from both kits (75 +/- 2%, n = 4) and HPLC-separation (76 +/- 4%) were greater than that of [131I]OIH in corresponding plasma samples (31 +/- 1% and 32 +/- 2%) respectively). Renograms performed in anesthetized rats revealed no statistically significant differences between kit-prepared [99mTc]MAG3 and [131I]OIH in terms of time-to-peak renal activity (5.0 +/- 1.7 min, n = 6; and 2.2 +/- 0.2 min, n = 3, mean +/- s.e.m. for [99mTc]MAG3 and [131I]OIH, respectively), in terms of time to fall to half-maximal activity (15.3 +/- 2.4 min and 9.6 +/- 2.1 min, respectively), or in terms of fraction of peak radioactivity in right kidney (0.53 +/- 0.01 for both substances). To assess possible interference from hepatobiliary uptake and excretion in renal failure, radioactivity in liver regions of interest was followed by gamma camera scintigraphy for 30 min after intravenous injection of [131I]OIH and kit and HPLC-purified [99mTc]MAG3 in anesthetized rats rendered anephric by ligating renal peduncles. Liver activity was 25% of total for both preparations of [99mTc]MAG3 and was 22% of total for [131I]OIH. There were no significant differences among the substances.

Animals↗
PubMed1984

Effects of the interferon inducing agents tilorone and polyriboinosinic acid . polyribocytidylic acid (poly IC) on the hepatic monooxygenase systems of pregnant and fetal rats.

Interferon inducing agents, including tilorone and polyriboinosinic acid . polyribocytidylic acid (poly IC), are known to depress hepatic cytochrome P-450-dependent monooxygenase systems and the induction of these systems by phenobarbital (PB) and 3-methylcholanthrene (MC) in mature male rats. The current study investigated the effects of tilorone and poly IC on the cytochrome P-450 systems of non-induced, PB-induced, MC-induced and pregnenolonecarbonitrile (PCN)-induced pregnant rats and their fetuses. Pregnant rats received either tilorone or poly IC and saline, PB, MC or PCN, and microsomes from their livers and those of their fetuses were examined for cytochrome P-450 content, aminopyrine (AP) N-demethylase activity and benzo[a]pyrene (BP) hydroxylase activity. The generalization can be made from these studies that, when the interferon inducing agents caused changes in cytochrome P-450 content or monooxygenase activities of either induced (PB, MC or PCN) or non-induced (saline) animals, decreases were seen in maternal livers and increases in fetal livers. Thus, in maternal livers tilorone depressed cytochrome P-450 and AP N-demethylase activity in non-induced and PB-, MC- and PCN-induced rats and BP hydroxylase activity in the induced animals; BP hydroxylase activity was not depressed in non-induced maternal livers. Poly IC depressed cytochrome P-450 and AP N-demethylase activity in non-induced and PB-induced rats but not in PCN-induced animals. BP hydroxylase was depressed by poly IC in both PB- and PCN-induced animals. Fetal hepatic cytochrome P-450 and monooxygenase activities were increased by tilorone in PB- and PCN-induced rats but not in non-induced or MC-induced animals. Poly IC increased cytochrome P-450 and both monooxygenase activities in PB- and PCN-induced fetal livers, whereas only BP hydroxylase activity was increased in the fetuses of non-induced rats. Several possible explanations are offered for the opposite effects produced by interferon inducing agents in maternal and fetal livers. Unlike maternally administered tilorone, which induced fetal cytochrome P-450 and monooxygenase activities in the liver, intrauterine tilorone depressed cytochrome P-450 and had no effect on AP N-demethylase or BP hydroxylase activities in the fetal liver. Intrauterine poly IC was without effect on the cytochrome P-450 systems of the fetal liver. Treatment of pregnant rats with tilorone on days 17-20 of gestation inhibited normal maternal weight gain and produced overt signs of toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminopyrine N-Demethylase↗
PubMed1984

Effects of the interferon inducing agents tilorone and polyriboinosinic acid . polyribocytidylic acid (poly IC) on the hepatic monooxygenase systems of the developing neonatal rat.

This paper describes the effects of the interferon inducing agents tilorone and polyriboinosinic acid . polyribocytidylic acid (poly IC) on the postnatal development of hepatic cytochrome P-450-linked monooxygenase systems of male rats from birth through early adolescence. The administration of tilorone to rats on days 1 and 2 postpartum modified the changes in the activities of hepatic monooxygenase systems that occur normally during the first four days postpartum. Thus, aniline hydroxylase activity, which develops very rapidly during the first 2 days postpartum, was depressed markedly by tilorone, ethylmorphine N-demethylase activity was depressed moderately, and benzo[a] pyrene hydroxylase, normally the slowest of the three monooxygenase activities to develop, was induced. These changes in monooxygenase activities occurred without a significant change in the cytochrome P-450 content. These observations suggest that not all species of neonatal cytochrome P-450 are affected equally by tilorone administration. By day 7 postpartum, the cytochrome P-450 content and all three monooxygenase activities were depressed in rats that had received tilorone on days 1 and 2 postpartum. All three monooxygenase systems were depressed by the administration of a single dose of poly IC (10 mg/kg) in 1-, 2-, 21-, 28- and 56-day-old rats. The length of the period between maximal depression and complete recovery of cytochrome P-450 systems was shown to be a function of the age of the rat; it increased from about 6 hr in 1-day-old rats to 48 hr in 56-day-old rats. Protein is synthesized more rapidly and degraded more slowly in neonate than in adult animals; this may account for the more rapid recovery of poly IC-induced depression of monooxygenase systems in neonates.

Aging↗
PubMed1981

Effect of muscimol on glucose-stimulated somatostatin and insulin release from the isolated, perfused rat pancreas.

This study examines the effect of muscimol, a high affinity, specific gamma-aminobutyric acid (GABA) agonist, on glucose-stimulated somatostatin and insulin release from the isolated, perfused rat pancreas. Perfusion with low glucose (50 mg/dl) conditions resulted in basal somatostatin release of 46 +/- 4 pg/ml. Basal insulin release was less than 20 microU/ml. High glucose (300 mg/dl) conditions stimulated somatostatin and insulin release. Steady-state levels of somatostatin and insulin release under high glucose conditions were 425 +/- 12 pg/ml and 419 +/- 18 microU/ml, respectively. Perfusion with medium containing 1 microM muscimol inhibited glucose-stimulated somatostatin release by 38%, whereas the course of glucose-stimulated insulin release was unaffected. Tentative conclusions from this study are (1) that GABA is potentially a modulator of islet somatostatin but not insulin release, and (2) the fact that somatostatin, an inhibitor of insulin, can be suppressed 38% without coincidental increase in insulin release seems to indicate that, under high glucose conditions, somatostatin is without a significant paracrine effect on the beta-cells.

Animals↗