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Biomedical subjects

M McIntosh

Publications and source records attributed to M McIntosh.

At least 37 records · Page 2Linked to original sources

Opposing actions of dehydroepiandrosterone and corticosterone in rats.

The purpose of this study was to determine the impact of dehydroepiandrosterone (DHEA) and corticosterone (CORT) treatment, using implants as a route of administration, on specific hormones, metabolites, and enzymes involved in energy metabolism. Sixty male Sprague-Dawley rats, 325 g initial weight, were implanted subcutaneously for 3 weeks with time-release pellets containing either DHEA or CORT at doses of 0, 10, 25, 50, or 100 mg in this 2 x 5 factorial experiment. In general, body weights and food intakes decreased as the level of steroid hormones increased. In contrast to DHEA treatment, rats receiving the 50- and 100-mg doses of CORT had lighter thymus glands and spleens and heavier epididymal and retroperitoneal fat pads than their controls. Rats treated with 100 mg of DHEA had lowered serum levels of triglycerides and lipid hydroperoxides whereas rats treated with 100 mg of CORT had higher levels of these blood lipids compared to their respective controls. In contrast to DHEA treatment, there was a dose-dependent increase in liver lipid content and the specific activities of the hepatic lipogenic enzymes glucose-6-phosphate dehydrogenase, malic enzyme, and fatty acid synthase in response to CORT treatment. Rats treated with 100 mg of DHEA had higher serum levels of IGF-1 than control rats. Conversely, rats treated with 100 mg of CORT had lower serum levels of IGF-1 and higher serum levels of testosterone, progesterone, and insulin than their controls. These data demonstrate the lipogenic actions of corticosterone in rats. Conversely, DHEA treatment reduced serum and hepatic lipids. Furthermore, these data suggest that using implants instead of bolus injections of steroids may be a more physiological approach for studying the influence of these steroids on lipid metabolism.

Animals↗

Missed opportunities: teenagers and emergency contraception.

OBJECTIVE: To determine American teenagers' awareness of and knowledge about emergency contraceptive pills and their likelihood to use them. METHODS: We conducted a nationally representative telephone survey between March 28, 1996, and May 5, 1996, of 1510 teenagers (757 girls and 753 boys), aged 12 to 18 years, living in the continental United States in households with telephones. The sample overrepresented African American, Latino, and low-income teenagers. The error attributable to sampling and other random effects for the total sample is +/-3 percentage points at the 95% confidence level. RESULTS: Of the 1510 teenagers, only about one quarter (23%) were aware that "anything" could be done after unprotected sex to prevent pregnancy. Slightly more (28%) had heard of "morning-after pills" or emergency contraceptive pills. Of the 423 teenagers who had heard of emergency contraceptive pills, one third (32%) did not know that a prescription is necessary to obtain them, and three quarters (78%) underestimated how long after unprotected intercourse the emergency contraceptive pill regimen could be initiated. Only 9% knew that emergency contraceptive pills are effective as long as 72 hours after unprotected sex. After being told about the option of emergency contraceptive pills, two thirds (67%) of teenaged girls said that they would be likely to use emergency contraceptive pills. Among the 66% of teenaged girls who had not previously heard of emergency contraceptive pills, 64% said that they would be likely to use them. CONCLUSIONS: Emergency contraceptive pills have great potential as a tool for reducing unplanned pregnancies among teenaged girls in the United States. Few teenaged girls were aware that this option exists. Once informed, teenaged girls reported being very interested in taking emergency contraceptive pills if needed.

Adolescent↗

Dehydroepiandrosterone attenuates preadipocyte growth in primary cultures of stromal-vascular cells.

The purpose of this study was to determine whether the antiobesity actions of dehydroepiandrosterone (DHEA) are due to an influence on preadipocyte proliferation and/or differentiation in primary cultures of pig and rat stromal-vascular (SV) cells. Pig SV cells were isolated from dorsal subcutaneous adipose tissue of 7-day-old pigs. For the proliferation assays, pig SV cells were grown for 4 days in plating medium containing DHEA at 0, 15, 50, or 150 microM. For the differentiation assays, pig SV cells were grown in plating medium for 3 days and then switched to a serum-free medium containing DHEA at 0, 15, 50, or 150 microM for the next 6 days. Rat SV cells were isolated from inguinal fat pads of 5-wk-old male rats. Rat SV cells were exposed to DHEA at 0, 5, 25, or 75 microM during proliferation. For the differentiation assays, rat SV cells were grown for 8 days in a serum-free medium containing DHEA at 0, 5, 25, or 75 microM. Preadipocyte differentiation [lipid staining, glycerol-3-phosphate dehydrogenase (GPDH) activity] and proliferation (preadipocyte-specific antigen staining) decreased with increasing levels of DHEA in cultures of pig SV cells. In cultures of rat SV cells, preadipocyte differentiation (lipid staining, GPDH activity) and proliferation ([3H]thymidine incorporation) were decreased in the 25 and 75 microM DHEA groups compared with the control and 5 microM DHEA groups. The level of expression of CCAAT enhancer binding protein-alpha, a master regulator of adipogenesis, in cultures of pig SV cells treated with 150 microM DHEA was 38% of control cultures. These data support the hypothesis that DHEA directly attenuates adipogenesis via attenuation of preadipocyte proliferation and differentiation.

Adipocytes↗

Are we making progress with emergency contraception? Recent findings on American adults and health professionals.

OBJECTIVES: To determine how awareness of and practices and attitudes toward emergency contraceptive pills (ECPs) have progressed among the American public and US health professionals. METHODS: In 1997, we conducted two nationally representative telephone surveys of Americans and health professionals of their knowledge, attitudes, and practices on ECPs and compared the findings to previous surveys. RESULTS: 66% of women and 51% of men 18 to 44 years old had heard of ECPs, up from 61% of women and 45% of men the same age in 1994. Only 1% of women surveyed reported having ever used this method, reflecting no change from 1994. Only 11% of women knew enough about ECPs to be able to use them. Americans named media as the primary source of information about ECPs. The proportion of physicians who had prescribed ECPs at least once in the preceding year increased significantly in 1997: 85% of obstetrician/gynecologists and 50% of family physicians compared to 69% and 34% in 1995. Almost all health professionals considered ECPs to be safe (99%) and effective (100%), yet relatively few discussed this option with their patients, and even fewer commonly prescribed it. CONCLUSION: Ongoing efforts are needed to improve awareness among the general public and to encourage health professionals to discuss and offer ECPs more widely.

Adolescent↗

The skeletonized body: suicidal inhalation of motorbike exhaust.

An adolescent boy who was being treated for psychiatric illness went missing. The body was discovered a year later, and he appeared to have committed suicide by inhaling the exhaust fumes from his motorbike. This report highlights the procedure used for the identification of his skeletonized body and the unusual nature of the source of exhaust fumes.

Administration, Inhalation↗

Parathyroid hormone, ionised calcium, and potentially interacting variables in plasma of an Old World primate.

Bone turnover and calcium homeostasis in man can only be modelled validly in Old World nonhuman primates. In order to interpret the models it is necessary to establish endocrine and biochemical parameters of bone mineral metabolism. This report is probably the first description of acute phase parathyroid responses to manipulations of blood ionised calcium, and of reference values for potentially interacting variables, in vervet monkeys. Plasma parathyroid hormone concentrations were measured in vervets under defined conditions, and ranges reported as normal for other nonhuman primates and man are summarised.

Animals↗

Effects of selective opioid receptor agonists and antagonists during myocardial ischaemia.

The antiarrhythmic activities of 16-methylcyprenorphine (M8008), nor-binaltorphimine (NBT) and naltrexone, which are relatively specific opioid receptor antagonists for delta, kappa and mu receptors, respectively, were examined during the 30 min following coronary artery occlusion in anaesthetised rats. The haemodynamic and electrocardiographic effects of the opioid receptor agonists [D-Ala2,D-Leu5]enkephalin (DADLE) (relatively selective for delta receptors), ICI-204448 (kappa) and glyol (mu) were also investigated over the 30-90 min post ligation period. When administered intravenously 5 min before ligation, M8008 (0.5 mg kg-1 and 2.5 mg kg-1) reduced the number of ventricular ectopic beats but had no effect on the incidence or duration of ventricular fibrillation. NBT and naltrexone were not antiarrhythmic at a dose of 0.5 mg kg-1 but at 2.5 mg kg-1 (a concentration at which both drugs block kappa receptors) the number of ventricular ectopic beats, the incidence of ventricular fibrillation and mortality were all reduced. All of the opioid receptor agonists caused a transient decrease in heart rate and in arterial blood pressure but none exhibited an arrhythmogenic effect. These studies suggest that the delta and kappa opioid receptor antagonists used may be antiarrhythmic as a result of blockade of the action of endogenously released peptides acting on these receptors or that they have a non-specific 'direct' antiarrhythmic action.

Animals↗

The electrophysiological effects of opioid receptor-selective antagonists on sheep Purkinje fibres.

The cardiac electrophysiological effects of 16-methylcyprenorphine (M8008), nor-binaltorphimine (NBT) and naltrexone, which are relatively specific opioid antagonists for delta, kappa and mu receptors, respectively, were studied in paced (1.5 Hz) sheep Purkinje fibres in vitro. M8008 (1 ng ml-1-10 micrograms ml-1) caused a concentration-dependent reduction in the maximum rate of depolarisation of phase 0 (MRD) and in the action potential duration measured at 50% repolarisation, APD50. Neither NBT (10 ng ml-1-10 micrograms ml-1) nor naltrexone (1 ng ml-1-10 micrograms ml-1) produced any significant effect on the cardiac action potential. In the presence of a physiological salt solution modified to mimic some of the changes that occur during myocardial ischaemia (i.e. hypoxia, acidosis, hyperkalaemia), M8008 caused a more marked reduction in MRD and prolonged rather than shortened APD50. These results suggest that the reported antiarrhythmic activity of M8008, but not NBT or naltrexone, may be, at least in part, explained by a direct cardiac electrophysiological action.

Acidosis↗

Aggressive early medical management by a specialist in physical medicine and rehabilitation: effect on lost time due to injuries in hospital employees.

Musculoskeletal injuries to hospital workers are both common and costly. Little advice has been written on how to decrease losses after injury. In a tertiary care hospital with 2700 employees a specialist in physical medicine and rehabilitation evaluated injured employees who were out of work for more than 2 days. Physician management emphasized increasing patient investment in the problem, early assessment of delayed recovery, and effective communication with the employer. There were 61 injuries averaging 6.7 days off per injury. In a previous year, 52 injuries averaged 11.8 days. Employees out for more than 2 days with back pain and seen by the physiatrist (52%) averaged 11 days off per injury whereas others averaged 14.9 days. In this hospital, early management by a specialist resulted in a substantial decrease in time off because of injury.

Absenteeism↗

Trends in psychotropic prescribing in general practice and general medical patients.

Psychotropic drug prescribing in 1280 medical inpatients between 1973-75 was compared with that in 1200 similar patients during 1982-83. Three benzodiazepines accounted for 64% of prescriptions in 1973-75 and nine benzodiazepines for 82% of prescriptions in 1982-83. Over the decade, use of psychotropic drugs fell from 56% to 38% (P less than 0.001), primarily due to a reduction in patients treated only in hospital (34% vs 16%, P less than 0.001). Before admission, the proportions of patients receiving these drugs were similar (17% vs 18%). During admission, concomitant administration of similar drugs declined from 22% of patients in 1973-75 to 11% in 1982-83 (P less than 0.001), while concurrent prescribing before admission increased from 13 to 19%. The marked fall in psychotropic drug use and in inappropriate concomitant therapy indicates an encouraging trend towards more rational drug use at least in hospital. This was achieved without fiscal control and further rationalization of prescribing habits may be achieved by self-audit within the profession without legislative action.

Adolescent↗

Conotoxin GI: disulfide bridges, synthesis, and preparation of iodinated derivatives.

The 13 amino acid toxic peptide from the marine snail Conus geographus, conotoxin GI, blocks the acetylcholine receptor at the neuromuscular junction. In this report, we describe a method for analyzing disulfide bonding in nanomole amounts of small cystine-rich peptides. The procedure involves partial reduction and a double-label alkylation of cysteine residues. Using this method, we show that the natural conotoxin GI has a (2-7, 3-13) disulfide configuration. The structure of conotoxin GI has been confirmed by chemical synthesis. The preparation and purification of molecularly homogeneous, iodinated derivatives of this toxin are also described. All derivatives, including the [diiodohistidine,diiodotyrosine]conotoxin GI, retained at least half of the biological activity of unmodified toxin. Since the tetraiodinated toxin, which is greater than 25% by weight iodine, retains considerable toxicity, unmodified histidine and tyrosine residues in conotoxin GI are not crucial for biological activity.

Amino Acid Sequence↗