Biomedical subjects
Publications and source records attributed to D Morris.
Three horses were admitted for retrieval of polyurethane nasogastric tube fragments. The fragments were removed from the esophagus or stomach of 2 horses by manipulation of a snare introduced through the biopsy port of an endoscope. The fragments were surgically removed from the stomach of the third horse.
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Insomnia, a common complaint among the elderly, is generally treated with benzodiazepines. Long-acting benzodiazepines (e.g., flurazepam) often produce daytime somnolence and performance deficits, whereas short-acting drugs (e.g., triazolam) have been associated with marked rebound insomnia and anterograde memory loss. The authors designed a pilot study to evaluate the efficacy of an intermediate-acting benzodiazepine, estazolam (e.g., ProSom), as well as its side effects. The parameters studied were sleep, daytime performance, and memory. Ten geriatric patients (greater than 60 years of age) with insomnia participated in the study. They received placebo nightly for 2 weeks (baseline), estazolam 1 mg nightly for the next 4 weeks (treatment phase), and placebo again for 2 weeks (withdrawal period). Sleep was monitored by polysomnography the first two nights of each week in a sleep laboratory. Estazolam significantly decreased sleep latency, nocturnal awakenings, and wake time after sleep onset. Total sleep time increased an average of 63 minutes the first night of treatment. Significant improvements in wake time after sleep onset and total sleep time also were observed in the fourth week of estazolam treatment. Rebound insomnia occurred on the first withdrawal night only for wake time and total sleep time. By the next night, these sleep parameters returned to baseline. Neither day-time performance nor anterograde memory was adversely affected by estazolam treatment or its withdrawal. A 1-mg dose of estazolam appears to be a safe and effective hypnotic for elderly patients with insomnia.
The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial is a large scale international trial of new myocardial reperfusion strategies. The primary hypothesis is that early and sustained coronary artery recanalization will be associated with a significant reduction in mortality. The four regimens that are being tested are 1) streptokinase with subcutaneous heparin; 2) streptokinase with intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) with intravenous heparin; and 4) combination streptokinase, rt-PA and intravenous heparin. The planned recruitment of 41,600 patients in 1,500 sites from 15 countries is expected to be completed by December 1992 and will enable detection of a 15% reduction or 1% absolute difference in mortality compared with that associated with standard therapy (streptokinase and subcutaneous heparin). In designing the trial, two important issues were directly addressed. First, a strategy was developed to provide assurance of patient safety during large scale investigational use of an aggressive thrombolytic regimen. This includes fascimile transmission of a one-page safety summary form to the Data Coordinating Center within 24 h of death or discharge, acceptance of the concept of "net clinical benefit" and close surveillance of the trial's progress by the independent Data and Safety Monitoring Committee. Second, to avoid potential conflict of interest beyond elimination of any position of financial equity, the Steering Committee unanimously voted to prohibit any honoraria for speaking engagements, payment for consultancy or travel or reimbursement of any kind from any of the five corporate sponsors until 1 year after publication of the results. Incorporation of these approaches may facilitate the design of future large scale randomized trials in cardiovascular medicine.
OBJECTIVE: To investigate the effect of hyperprolactinemia on the androgen response to an oral glucose load in patients with normal and abnormal carbohydrate metabolism. DESIGN: Sixty-three women underwent a 75-g oral glucose tolerance test (OGTT) at approximately 6 weeks' postpartum. SETTING: University hospital setting. PATIENTS: Patients with a previous history of gestational diabetes. MAIN OUTCOME MEASURE: Adrenal and ovarian androgen response to oral glucose load. RESULTS: Results were stratified by the result of the OGTT (patients with impaired glucose tolerance or diabetes as a single group and patients with a normal OGTT as a separate group) and prolactin (PRL) level. All androgens decreased significantly over the 2-hour test in all groups except dehydroepiandrosterone sulfate (DHEAS) in the patients with both elevated PRL and abnormal glucose tolerance. CONCLUSION: Hyperprolactinemia and insulin resistance may act synergistically in the adrenal to alter DHEAS suppression and may result in chronically elevated circulating DHEAS levels.
Insulin resistance and glucose intolerance are common features of polycystic ovary syndrome (PCOS). We have investigated the effect of glucose on the fractional glucose disappearance in patients with PCOS and in age- and weight-matched control subjects. The minimal model method as applied to a frequently sampled intravenous glucose tolerance test was employed. The insulin sensitivity index (Si) and glucose effectiveness (SG) were calculated with the MINMOD program. Testosterone, androstenedione and free testosterone concentrations were significantly higher in PCOS subjects. Glucose-induced glucose clearance (SG) and insulin sensitivity were significantly lower in PCOS subjects than controls [SG: 2.7 +/- 0.3 versus 1.8 +/- 0.1 x 100/min; P less than 0.01; Si: 133.4 +/- 20.0 versus 65.6 +/- 6.4/min (nmol/ml)]. Six PCOS women had an SG value within the normal range (greater than 2.0 x 100/min) but had a similar Si to that found in PCOS women with abnormal SG. We suggest that independent alterations in both glucose- and insulin-mediated glucose uptake occur in patients with PCOS. The underlying disturbance in glucose effectiveness may be similar to that found in familial non-insulin dependent diabetes mellitus.
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This study had two objectives: 1) to establish magnetic resonance imaging (MRI) as a tool for measuring total and regional adipose tissue (AT) distribution in humans and 2) to assess the relationship between selected anthropometric variables and MRI-measured AT. Twenty-seven healthy men varying in age [40.8 +/- 14.5 (SD) yr], body mass index (28.5 +/- 4.8), and waist-to-hip ratio (WHR, 0.96 +/- 0.07) participated in the study. Total AT volume was determined using a linear interpolation of AT areas obtained on consecutive slices (n = 41) taken from head to toe (10-mm thickness, 50-mm centers). The mean change for repeated measures of total AT volume was 2.9% (range 0.9-4.3%). Large interindividual differences were observed for total AT volume (6.9-59.3 liters), subcutaneous AT (6.3-49.8 liters), and visceral AT (0.5-8.5 liters). Visceral AT represented 18.3% of the total AT. The single best predictor of total adiposity was waist circumference (R2 = 0.92). For visceral AT volume, WHR was the strongest anthropometric correlate (r = 0.85, P less than 0.01). When controlled for age and adiposity, however, WHR explained only 12% of the variation in absolute visceral AT and less than 1% of the variation in visceral-to-subcutaneous ratio. Age was a better predictor of visceral-to-subcutaneous ratio than level of adiposity or WHR. The results of this study demonstrate that MRI offers a reliable measure of regional and total AT distribution in humans and, thus, is of value as a research tool.
A selective gastrin receptor (GR) antagonist, L-365,260 is bound to the GR on AR42J cells with a potency 7.5-fold less than G17 (50% inhibitory concentration [IC50] G17, 6 x 10(-9) mol/l; IC50 L365-260, 4.5 x 10(-8) mol/l). G17 is mitogenic for AR42J cells, as assessed by 75Se-selenomethionine uptake and L-365,260 at concentrations of 2.5 x 10(-6) mol/l and 2.5 x 10(-7) mol/l, (55X and 5.5 X the dose required to displace 50% 125I G17, respectively), and reduced optimal G17 stimulated mitogenesis in 75% of experiments. The basal growth of two human colon cancer cell lines, LoVo and C146 was reduced by L-365,260 (2.5 x 10(-7) mol/l) after 5 days of treatment to 44% and 64% of the control, respectively. However, inhibition was followed by a rebound of growth to control levels. The growth of AR42J xenografts in nude mice was increased by administration of G17 (10 micrograms/mouse/d, P less than 0.027). This increase was blocked by coadministration of oral L-365,260 (5 mg/kg/d, P less than 0.034). L-365,260 could be an important therapeutic agent in slowing the growth of GR-positive, G17-sensitive gastrointestinal tumors.
Previous research has indicated that, while large parts of Middlesbrough and Sunderland appear to be equally severely deprived, premature mortality in the early 1980s was substantially worse in Middlesbrough. Postcoded mortality data from 1975 to 1986 were assembled, to ascertain whether this disparity reflected a temporary or consistent difference between these two towns. In addition, to enable detailed consideration of the differentials in premature mortality, data on cause of death for 23 cause-groups were assembled for the 6-year period 1978 to 1983. The results show that, throughout the 12-year period, death rates below the age of 65 years in Middlesbrough's poorer areas consistently exceeded death rates in comparable areas of Sunderland by a large margin. This disparity is demonstrated to affect both sexes and all age-groups below 65. Middlesbrough's excess mortality was evident for most causes of death (19 out of 22 causes among men, and 16 out of 23 causes among women), with cerebrovascular disease and genitourinary malignancy among women being the only major exceptions. Possible explanations for this wide difference are considered. The conclusions of research in Lancashire, suggesting that the antecedents of present differences may be found in infant health disparities from the 1920s and 1930s, do not seem to apply in this instance. The possibility that unmeasured differences in levels of poverty or the suddenness of its onset may be contributory influences remains problematic. Individual lifestyle is not considered a plausible explanation, but possible differences in the provision and use of health services between the two towns are thought worthy of closer investigation. It is also suggested that environmental differences, in terms of the built environment and atmospheric pollutants require closer scrutiny.
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Seventeen patients with acute mania were treated with the antiepileptic agent valproate under placebo-controlled, double-blind conditions for 7 to 21 days. No other psychotropics were allowed, except for lorazepam, up to 4 mg per day, as needed for agitation or insomnia for the first 10 study days only. Of the 17 patients, 12 (71%) showed some response, ranging from a 30 percent to a 100 percent decrease in scores on the Young Mania Rating Scale (MRS). The remaining 5 patients displayed no response to valproate treatment, with increases on the MRS of 3 percent to 13 percent. Compared with nonresponders, responders had an older age of onset and a shorter duration of illness and displayed a higher average serum valproate concentration on Study Days 3 through 6, but not on Study Day 15 or at termination. Degree of valproate response was greater for those patients with more severe sleep disruption at baseline. However, the majority of factors assessed, including a history of rapid cycling and high levels of dysphoria, were not associated with response to valproate.
Insulin resistance is common in women with the polycystic ovary syndrome. We investigated the relationship between insulin resistance and the serum inhibin concentration in a group of 19 women with polycystic ovary syndrome and eight control subjects at different phases of the menstrual cycle. Insulin resistance was measured by the frequently sampled intravenous glucose tolerance test, and inhibin was measured by a specific radioimmunoassay. Insulin sensitivity (mean +/- SE) was significantly reduced in the polycystic ovary syndrome group compared with controls: reduced insulin sensitivity 46.7 +/- 5.0 min-1/(nmol/mL), normally insulin-sensitive 106.6 +/- 11.7 min-1/(nmol/mL) (P less than .01). The women with polycystic ovary syndrome had inhibin levels (126 +/- 15.2 microLEq/mL) comparable to those found during the early follicular phase of the control group (117 +/- 22.1 microLEq/mL), but significantly lower than late follicular phase (259 +/- 25.6 microLEq/mL) or luteal phase (448 +/- 91.8 microLEq/mL) levels in the control group. No association was found between the degree of insulin resistance and the inhibin concentration, which remained unaltered over a 3-hour period despite maximal stimulation of endogenous insulin secretion. The inhibin concentrations in polycystic ovary syndrome may reflect impaired follicular maturation. Inhibin secretion is not acutely affected by insulin secretion in normal or in hyperandrogenic women.
An antibody (RM) raised against the carboxyl-terminal decapeptide of the alpha subunit of the stimulatory guanine nucleotide regulatory protein (Gs alpha) has been used to study the interaction of Gs alpha with bovine brain adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. RM antibody immunoprecipitated about 60% of the solubilized adenylate cyclase preactivated with either GTP-gamma-S or AlF4-. In contrast, RM antibody immunoprecipitated about 5% of the adenylate cyclase not preactivated (control) and 15% of the adenylate cyclase pretreated with forskolin. Adenylate cyclase solubilized from control membranes or GTP-gamma-S preactivated membranes was partially purified by using forskolin-agarose affinity chromatography. The amount of Gs alpha protein in the partially purified preparations was determined by immunoblotting with RM antibody. There was 3-fold more Gs alpha detected in partially purified adenylate cyclase from preactivated membranes than in the partially purified adenylate cyclase from control membranes. Partially purified adenylate cyclase from preactivated membranes was immunoprecipitated with RM antibody and the amount of adenylate cyclase activity immunoprecipitated (65% of total) corresponded to the amount of Gs alpha protein immunoprecipitated. Only 15% of the partially purified adenylate cyclase from control membranes was immunoprecipitated. The presence of other G proteins in the partially purified preparations of adenylate cyclase was investigated by using specific antisera that detect Go alpha, Gi alpha, and G beta. The G beta protein was the only subunit detected in the partially purified preparations of adenylate cyclase and the amount of G beta was about the same in adenylate cyclase from preactivated membranes and from control membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Selective feticide was performed at 15 weeks' gestation in a twin pregnancy where one fetus was found to have beta-thalassaemia major after diagnosis by chorionic villus sampling at 10 weeks' gestation. The technical, medical, legal and psychological problems are discussed in relation to this case.
Of 141 women with twin pregnancies, 72 were randomly assigned to outpatient care and 69 to hospital admission between 26 and 30 weeks' gestation. There were no differences between the groups in the frequencies of major maternal complications in pregnancy and labour but more of those admitted to hospital than of the outpatient group had to be admitted after 30 weeks. There were no differences between the groups in the mean birthweights of the twins by birth order, or in their mean gestation at birth whether analysed by intention to treat or by the treatment given. 22 infants were delivered before 32 weeks' gestation in the inpatient group compared with 10 in the outpatient group. With the exception of small-for-dates infants, any trend towards greater morbidity or mortality was seen in the inpatient group. The policy of routine hospital admission of women with twin pregnancies from 26 weeks' gestation is not beneficial to mother or babies and should be abandoned.
Changes in the use of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) over the last several years have resulted in a new and different environment for the interventional treatment of coronary artery disease. This study explores these changes as applied to the treatment of chronic coronary artery disease. The study population comprised 14,078 patients undergoing diagnostic cardiac catheterization between 1981 and 1988. In 1981, 1,704 patients underwent a first known cardiac catheterization at Emory University Hospital or Crawford W. Long Hospital and were found to have significant coronary artery disease. Of these patients, 51.7% were treated medically, 44.0% by CABG and 4.3% with PTCA. A similar group comprised 1,719 patients in 1988. Of this group 41.2% were treated medically, 28.5% with CABG and 30.3% with PTCA. The data reveal a much more complex phenomenon than a simple increase in PTCA for the treatment of coronary disease at the expense of CABG. The CABG group aged such that the percent of the CABG population more than 65 years old increased from 26.0% of the total in 1981 to 44.9% of the total in 1988. The percent of patients with ejection fractions less than 50% in the CABG population increased from 24.5% in 1981 to 29.7% in 1988. The PTCA population had less severe disease, was younger and had better left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)