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Biomedical subjects

M Mitchell

Publications and source records attributed to M Mitchell.

At least 127 records · Page 7Linked to original sources
PubMed1985

Rapid plasma digoxin assay in outpatients--a useful routine technique?

In 25 outpatients taking digoxin for chronic atrial fibrillation (established for at least six months) a prospective study identified only one case in which rapid availability of the results of a plasma digoxin assay altered the dose which had already been selected on the basis of simple clinical assessment. No patient received more than 375 micrograms digoxin per day and none showed clinical evidence of toxicity even though seven had renal impairment. Six other patients had poorly controlled ventricular rates requiring larger doses of digoxin, but even in these patients the dose could be selected on clinical grounds alone. Despite the availability of a very rapid fluorescence polarisation immunoassay for digoxin, simple but careful clinical monitoring is an adequate basis for the selection of a suitable dose in most patients taking digoxin for atrial fibrillation.

Aged↗
PubMed1985

Stimulation of ovine placental lactogen secretion by arachidonic acid.

To determine whether arachidonic acid stimulates the secretion of ovine placental lactogen (oPL), arachidonic acid was infused as an intravenous bolus into pregnant ewes and fetuses. Plasma oPL concentrations were determined in mothers and fetuses before and for 5 h after infusion. The administration of 12.5 mg arachidonic acid (0.15-0.2 mg/kg, n = 11 experiments) to the pregnant ewes caused an increase in maternal plasma oPL concentrations of 73.9 +/- 15.6% (S.E.M.) and 60.8 +/- 18.1% above the pretreatment concentrations at 4 and 5 h respectively (P less than 0.01 in each instance). The infusion of 25 mg arachidonic acid (n = 8) caused increases of 96.0 +/- 19.1% and 100.3 +/- 26.4% (P less than 0.005), and the stimulation was not inhibited by the cyclo-oxygenase inhibitors indomethacin and ibuprofen. In contrast to arachidonic acid, vehicle alone or palmitic acid had no effects on plasma oPL concentrations. Despite the increase in maternal plasma oPL concentrations, plasma oPL concentrations in the fetus remained unchanged after the maternal infusions. The infusion of arachidonic acid (0.5-1.5 mg/kg) directly into six fetuses had no effects on either fetal or maternal oPL concentrations. These studies indicate that arachidonic acid stimulates maternal plasma oPL concentrations but has no effect on fetal oPL concentrations and the stimulation of oPL secretion is not due to the conversion of arachidonic acid to prostaglandins or other cyclo-oxygenase products.

Animals↗
PubMed1984

The pyrrolidine alkaloid, 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine, inhibits glycoprotein processing.

2,5-Dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP) is a pyrrolidine alkaloid that was isolated from the plant, Lonchocarpus sericeus. In the present study, DMDP was tested as an inhibitor of glycoprotein processing. MDCK cells were infected with influenza virus and the virus was raised in the presence of various amounts of DMDP. The glycoproteins were labeled by the addition of [2-3H]mannose or [1-3H]galactose to the medium. The virus was isolated by differential centrifugation and treated with Pronase to obtain glycopeptides. These glycopeptides were isolated by chromatography on Bio-Gel P-4, then digested with endoglucosaminidase H (Endo H) and rechromatographed on the Bio-Gel P-4 column. In the control virus, more than 70% of the glycopeptides were resistant to Endo H and were previously characterized as complex types of oligosaccharides. The remaining 20-25% are sensitive to Endo H and are of the high-mannose type. However, in the presence of DMDP (250 micrograms/ml), more than 80% of the glycopeptides are susceptible to digestion by Endo H. The oligosaccharide released by this treatment sized like a hexose11-12GlcNAc on a calibrated column of Bio-Gel P-4, and was only slightly susceptible to alpha-mannosidase treatment. This oligosaccharide was also labeled in the glucose moieties by growing the virus in [1-3H]galactose in the presence of DMDP. Following isolation, the oligosaccharide was subjected to complete methylation. Acid hydrolysis of the methylated oligosaccharide gave three methylated glucose derivatives, corresponding to 2,3,4,6-tetramethylglucose, 3,4,6-trimethylglucose, and 2,4,6-trimethylglucose in almost equal amounts. These data indicate that the oligosaccharide is a Glc3Man8-9-GlcNAc and that DMDP inhibits glucosidase I. Similar results were obtained with the cellular glycoproteins. DMDP did not inhibit the incorporation of [3H]leucine into protein in MDCK cells, nor did it inhibit virus production as measured by plaque counts or hemagglutination assays. DMDP did cause some inhibition of mannose incorporation into the lipid-linked monosaccharides, but incorporation into lipid-linked oligosaccharides was not greatly affected, and incorporation into protein was stimulated. These results suggest that the pyrrolidine alkaloids are a new class of processing inhibitors.

Alkaloids↗
PubMed1984

Uptake of heterologous DNA by Haemophilus influenzae.

With the use of highly competent Haemophilus influenzae cells, it was possible to demonstrate the uptake of heterologous DNAs. However, these DNAs, as expected, were only 1% or less as effective when competing for uptake with Haemophilus DNA. Escherichia coli DNA was removed from solution by competent cells to the extent expected if all the E. coli DNA particles contained at least one uptake recognition signal. The data were consistent with a model in which there was one uptake signal per 20 X 10(6) to 30 X 10(6) daltons of E. coli DNA. Since H. influenzae DNA has many more recognition signals, approximately one per 2 X 10(6) daltons (Danner et al., Gene 77:311-318, 1980; K. Vogt and S. H. Goodgal, submitted for publication), it has been suggested that the slower rate of E. coli DNA binding and the so-called specificity of Haemophilus DNA binding are due to the number of recognition signals per molecule of DNA as well as the nature of the DNA receptor (Vogt and Goodgal, submitted for publication). The specificity of native H. influenzae DNA binding does not apply to the uptake of denatured DNA in the transforming system (low pH) for denatured DNA.

Binding Sites↗
PubMed1984

Effect of castanospermine on the structure and secretion of glycoprotein enzymes in Aspergillus fumigatus.

Aspergillus fumigatus secretes a number of glycosidases into the culture medium when the cells are grown in a mineral salts medium containing guar flour (a galactomannan) as the carbon source. At least some of these glycosidases have been reported to be glycoproteins having N-linked oligosaccharides. In this study, we examined the effect of the glycoprotein processing inhibitor, castanospermine, on the structures of the N-linked oligosaccharides and on the secretion of various glycosidases. Cells were grown in the presence of various amounts of castanospermine; at different times of growth, samples of the media were removed for the measurement of enzymatic activity. Of the three glycosidases assayed, beta-hexosaminidase was most sensitive to castanospermine; and its activity was depressed 30 to 40% at 100 micrograms of alkaloid per ml and even more at higher alkaloid concentrations. On the other hand, beta-galactosidase activity was hardly diminished at castanospermine levels of up to 1 mg/ml, but significant inhibition was observed at 2 mg/ml. beta-Galactosidase was intermediate in sensitivity. Cells were grown in the presence or absence of castanospermine and labeled with [2-3H]mannose, [6-3H]glucosamine, or [1-3H]galactose to label the sugar portion of the glycoproteins. The secreted glycoproteins were digested with pronase to obtain glycopeptides, and these were identified on Bio-Gel P-4 (Bio-Rad Laboratories). The glycopeptides were then digested with endoglucosaminidase H to release the peptide portion of susceptible structures, and the released oligosaccharides were reisolated and identified on Bio-Gel P-4. The oligosaccharides from control and castanospermine-grown cells were identified by a combination of enzymatic and chemical studies. In control cells, the oligosaccharide appeared to be mostly Man8GlcNAc and Man9GlcNAc, whereas in the presence of alkaloid, the major structures were Glc3Man7GlcNAc and Glc3Man8GlcNAc. These data fit previous observations that castanospermine inhibits glucosidase I.

Alkaloids↗
PubMed1984

Midazolam and fentanyl-fluanisone: assessment of anaesthetic effects in laboratory rodents and rabbits.

The anaesthetic effects of a combination of midazolam, a water-soluble benzodiazepine, and fentanyl-fluanisone were assessed in laboratory rodents and rabbits. This combination of drugs produced good surgical anaesthesia in all of the species investigated. An important advantage of the combination was that it could be administered as a single intraperitoneal injection.

Anesthesia, General↗
PubMed1984

Accuracy versus speed in the generalized effort of learning-disabled children.

Reinforcement of effortful performance in a given academic task has been found to increase the subsequent performance of other academic tasks. The learned-effort hypothesis assumes that individuals learn which dimensions of task performance are correlated with reinforcement of high effort, and generalize across tasks. Therefore, reinforcement of increased effort in a given dimension of one task should result in greater generalized effort in the same dimension of transfer performance than in another dimension. In accord with this view, preadolescent learning-disabled students who received points for high reading accuracy subsequently produced more accurate drawings and stories than did students whose points had been based upon high reading speed or upon mere completion of the reading task. Students who received points for high reading speed subsequently constructed stories more quickly than did children whose points had been based upon high reading accuracy or upon reading-task completion. Consistent with the more explicit and frequent feedback for accuracy than for speed in most academic tasks, generalized accuracy was much more durable than generalized speed.

Child↗
PubMed1984

Chronic adaptations to physical conditioning in cardiac patients. Implications regarding exercise trainability.

Physical conditioning in patients with coronary heart disease can result in increased functional capacity, symptomatic relief of angina pectoris, favorable reduction of risk factors, enhanced psychological status, and improved quality of life. The mechanisms underlying the adaptations to training are poorly understood, but it is clear that several factors affect exercise trainability. Guidelines are available that suggest the appropriate intensity, frequency, and duration of exercise needed to obtain beneficial physiologic adaptations.

Adaptation, Physiological↗
PubMed1984

Cardiac exercise programs: role of continuous electrocardiographic monitoring.

The purpose of the present study was to determine the value of telemetry monitoring for detection of new and significant electrocardiographic (ECG) or blood pressure abnormalities during outpatient cardiac exercise therapy. Following preliminary graded exercise testing, 177 cardiac patients underwent a four-week monitored exercise program three days per week. During 2248 training sessions, 12 of the 177 patients (7%) showed significant ECG or blood pressure abnormalities not evident on initial exercise testing, eight (5%) requiring change in medical therapy. Abnormalities included significant (greater than 2mm) ST-T displacement (two patients), ventricular arrhythmias (seven patients), and hypertensive exercise response (three patients). Eleven of the abnormalities (92%) appeared during the first three weeks of the program. Results indicated that continuous ECG and blood pressure monitoring offered a small but significant diagnostic yield not evident on preliminary graded exercise testing. One-year experience suggested that short-term (four weeks) exercise monitoring may be adequate for cardiac patients who undergo careful preliminary screening.

Adult↗
PubMed1983

Possible impact of audit on chest X-ray requests from surgical wards.

Use of chest X-rays in the surgical wards of two district general hospitals was monitored from 1976 to 1980. Utilisation fell by 42% in one hospital and by 26% in the other. There was no evidence that substantial reduction in the use of chest X-rays was associated with increased postoperative morbidity (as reflected in postoperative length of stay) or mortality. Indeed in one hospital there was a significant fall in postoperative length of stay and postoperative mortality during the study period. It is likely that publicity given to the overuse of preoperative chest X-rays and to the guidelines for more effective use which subsequently emerged has played an important part in bringing about the observed reduction in use of this investigation.

Costs and Cost Analysis↗
PubMed1983

The effect of iron on mixed infection of Bacteroides fragilis and Escherichia coli in mice.

Survival of an infected animal is improved in a mixed infection when Bacteroides fragilis is the bacterial species acting as a microbial antagonist against Escherichia coli. The protective effect afforded an animal by B. fragilis against E. coli is altered when ferric ammonium citrate is added to the injected mixed culture. In mice an E. coli concentration of 10(9) produced zero survival; the concentration 10(8) produced 40% survival; the concentration 10(7) and less produced 100% survival. Bacteroides fragilis concentrations of 10(8) and less did not kill the 15- to 20-g mouse within 5 days. Mice were given ip injections of the constant amount of 10(8) E. coli and serially diluted amounts of B. fragilis beginning with 10(8) organisms/ml. There was 40% survival in the 10(8) E. coli controls and 96% survival in the animals receiving 10(8) E. coli plus B. fragilis. The addition of ferric ammonium citrate to 10(8) E. coli plus B. fragilis reduced animal survival from 96 to 63%.

Animals↗
PubMed1983

Neurochemical effects of long-term ingestion of ethanol by Sinclair (S-1) swine.

Sinclair (S-1) miniature swine were given access to a mixture of ethanol and beer for three years. Control swine were fed an isocaloric diet with corn starch substituted for ethanol. Both groups had free access to tap water. The alcohol group consumed about 4 g ethanol/kg/day (about 50% of their caloric intake) resulting in plasma ethanol concentrations of about 100 mg/dl. Brain membranes were prepared for analysis of neurotransmitter receptor binding, membrane lipid composition and physical properties. Receptor studies demonstrated an increase in the binding of 3H-GABA to cortical and cerebellar membranes from the alcoholic pigs as compared to control. Binding of 3H-ligands to muscarine cholinergic, beta-adrenergic, alpha-adrenergic, dopamine and benzodiazepine receptors was not changed by chronic ethanol ingestion. These results are similar to those obtained in studies of human alcoholics by other investigators. The cholesterol content of myelin and synaptic plasma membranes was not altered by ethanol consumption. The fluorescence polarization of diphenylhexatriene, a measure of membrane order, did not detect any differences in the membranes from control or alcohol-treated swine either before or after in vitro exposure to ethanol. These results are different from those reported for rodents after short-term ethanol treatments and emphasize the importance of evaluating different models of experimental alcoholism.

Alcohol Drinking↗
PubMed1983

Injectable anaesthetic techniques in 2 species of gerbil (Meriones libycus and Meriones unguiculatus).

The effects of a range of injectable anaesthetic agents were assessed in two species of gerbil (M. libycus and M. unguiculatus). The drug combination of metomidate and fentanyl was the only preparation that consistently produced surgical anaesthesia. Considerable species variation in drug response was noted, indicating that caution should be exercised in recommending standard anaesthetic dose rates for these animals.

Anesthesia, General↗
PubMed1983

Neuroleptanalgesia in the rabbit.

The efficacy of the neuroleptanalgesic combinations of fentanyl-fluanisone with diazepam; and etorphine-methotrimeprazine, either alone, or with diazepam, was investigated in the rabbit. The effects of these drugs on some cardiovascular variables were studied in chronically catheterized rabbits. Fentanyl-fluanisone and diazepam produced good surgical anaesthesia. Although respiratory depression occurred, this had little effect on blood gas values. In contrast, etorphine-methotrimeprazine and diazepam produced severe respiratory depression with consequent hypercapnia and acidosis.

Acidosis↗