Biomedical subjects
M Miller
Publications and source records attributed to M Miller.
Induction of mania by L-dopa in a nonbipolar patient.
The authors present a case of mania associated with the prolonged ingestion of large doses of L-dopa. Prior reports relating L-dopa therapy to mania in patients with bipolar disorders are discussed. The induction of a classic manic syndrome by catecholamine augmentation is possible in a nonbipolar individual.
Inhibition of photosynthetic oxygen evolution in non-vesicular preparations releases Mn2+ into a restricted aqueous compartment.
Release of Mn2+ following inhibition of the water-splitting enzyme by treatment with Zn2+ was studied in two preparations derived from chloroplasts: oxygen-evolving Photosystem II membrane fragments and Tween-20 treated thylakoid membranes. In both cases the released Mn2+ was retained in the membrane fraction on centrifugation in spite of the fact that the two preparations are known to be non-vesicular. This suggests that upon inhibition Mn2+ is released into an aqueous compartment more restricted than the thylakoid lumen. We propose that this compartment is formed from the various proteins of the Photosystem II complex.
Stop, look and listen.
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Adult respiratory distress syndrome associated with miliary tuberculosis. A case report.
In this report we describe a patient with miliary tuberculosis who presented with the adult respiratory distress syndrome. The diagnostic problems are discussed and the value of transbronchial lung biopsy is emphasized. Our experience with this patient stresses the need for maintaining a high index of suspicion for treatable causes of adult respiratory distress syndrome.
Risk factors related to bacterial contamination of indwelling vascular catheters in non-infected hosts.
Aerobic, anaerobic and fungal cultures were performed on 70 vascular catheters from 57 non-infected patients. Despite the exclusion of any patient who developed non-catheter-related foci of infection, 46% of all cannulae became contaminated, usually with relatively non-pathogenic organisms. Multiple organisms were observed in one-third of all infected catheters, and six patients developed probable catheter related bacteraemia. Of the risk factors studied, only duration of placement exceeding 3 days was significant. Obsessive aseptic measures did not reduce the rate of contamination.
Facilitated reversal learning of a spatial-memory task by medial septal injections of 6-hydroxydopamine.
To assess the role of hippocampal norepinephrine in learning and memory, rats were treated with medial septal injections of 6-hydroxydopamine either prior to or after acquisition of a spatial-memory task. No effect on acquisition learning or retention was observed. However, reversal learning was significantly enhanced in all treated animals regardless of whether treatment was prior to or after acquisition. Our results do not support a role of hippocampal norepinephrine in selective attention, but rather indicate a direct involvement in memory processes.
Theophylline metabolism: variation and genetics.
Variation of theophylline metabolism in 54 healthy, nonmedicated adults (13 monozygotic [MZ] twin pairs, 11 dizygotic [DZ] twin pairs, and 6 single individuals) was assessed by kinetic study. Elimination rate constant, clearance (Cl), t1/2, and apparent volume of distribution, as well as urine excretion of unchanged theophylline and of the three major metabolites (1-methyluric acid, 3-methyl-xanthine, and 1,3-dimethyluric acid) were studied. Smokers and men had increased theophylline elimination rates compared to nonsmokers and women. Identical (MZ) twins resembled each other more closely than nonidentical (DZ) twins in the various kinetic parameters, but mean intrapair differences between MZ and DZ twins for all but one of the serum and urinary parameters examined (including t1/2) were not statistically significant. Correspondingly, estimates of heritability and of intrapair correlation coefficients showed a smaller contribution of genetic factors to variation in theophylline metabolism than had been reported for other drugs investigated by twin studies. Nevertheless, in the family of the individual with the longest theophylline t1/2, the operation of a rare major gene retarding theophylline metabolism could not be excluded. A father and two out of four children had very slow Cls. This finding would be consistent with, but does not prove, monogenic inheritance.
Influence of phenytoin on theophylline clearance.
The influence of phenytoin on theophylline elimination was studied in six healthy, nonsmoking subjects who were not taking any other drugs. Subjects were given an intravenous infusion of theophylline (aminophylline), 5 mg/kg, and several blood specimens were drawn over the following 24 hr for theophylline concentration determination. Subjects then began a 2-wk course on oral phenytoin, 300 mg/day, and on day 15 were again challenged with theophylline. For each subject theophylline clearance (ClT) was greater when taking phenytoin (range 31% to 65%). Mean ClT of the six subjects was 45% greater when taking phenytoin than when not taking phenytoin. In one subject, 24-hr urine collections were obtained in the untreated and treated state for analysis of theophylline metabolites. These results showed a general increase in excretion for each of the three major theophylline metabolites in the phenytoin pretreated state compared to the control state. Results indicate that phenytoin increases theophylline elimination. Patients taking phenytoin may require larger theophylline doses than recommended to achieve therapeutic blood theophylline concentrations.
Attitudes toward abortion as a means of sex selection.
A questionnaire was administered to 317 unmarried male and female college students in order to determine the acceptability of abortion as a means of achieving offspring of a desired sex. Respondents were given three hypothetical situations (first, second, and last child) to rate, comparing the present method of amniocentesis followed by abortion with proposed simpler methods. Acceptance ranged from 4.2% to 40.3%, being greatest among the less religious, male, and Protestant respondents. Proposed methods were only slightly more acceptable than the present one. Thus, simplifying the abortion procedure for the purpose of sex selection would not appear to increase its acceptability or utilization.
Kinetics and intermediates of marginal band reformation: evidence for peripheral determinants of microtubule organization.
The microtubules of the mature erythrocyte of the chicken are confined to a band at the periphery. Whole-mount electron microscopy after extraction reveals that the number of microtubules in each cell is almost the same. All the microtubules can be depolymerized by incubation in the cold, and the marginal band can be quantitatively and qualitatively reformed by return to 39 degrees C. These properties allow the reformation of the marginal band to be treated as an in vivo microtubule assembly reaction. The kinetics of this reaction and the intermediates detected during reformation suggest a mechanism of microtubule organization that is distinct from that observed in other cell types. Apparently only one or two growing microtubule ends are available for assembly--assembly is only detected at the cell periphery, even at early times--and there is no evidence of the participation of a microtubule-organizing center.
The evolution of beta-adrenergic dysfunction during the induction of canine cobalt cardiomyopathy.
This study was designed to investigate the changes in the beta adrenergic system during the induction of cobalt cardiomyopathy in dogs. Cobalt sulphate, at a dose of 5 mg X kg-1 X day-1 was administered intravenously with a low protein, low thiamine diet to 13 dogs. The percentage change of the left ventricular minor axis with systole by echocardiogram (% delta D) and dP/dtmax were used to monitor left ventricular function. Noradrenaline (NA) was measured in 24 h urine samples. Left ventricular (LV) free wall biopsies were assayed for noradrenaline (LV-NA), cyclic AMP, cyclic GMP and dopamine beta hydroxylase (LV-DBH). Lymphocytes were assayed for beta-receptor density. All dogs were studied at baseline and seven were studied after a midpoint cumulative dose of 60 to 90 mg X kg-1 of cobalt; the remaining six dogs were studied when they were in heart failure and had received more than 110 mg X kg-1. During the induction of heart failure the heart rate rose from 112 +/- 6 (means +/- SE) at baseline to 154 +/- 9 at the midpoint and 153 +/- 9 (both P less than 0.05) at the final measurement while the % delta D fell from 35 +/- 2% to 31 +/- 3% and 23 +/- 2% (P less than 0.05) and dP/dt fell from 333 +/- 40 kPa X s-1 at baseline to 254 +/- 46 kPa X s-1 (P less than 0.05) and 207 +/- 33 kPa X s-1 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Career planning and professional development: a unique course for nursing students.
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Risk in the vaginal delivery of the large fetus.
The problem of the excessively weighted fetus was studied. For this purpose, over a period of 2 years, each delivery with fetal weight of 4,500 g or more was included in the study. The history and examination findings of the present pregnancy were reviewed following delivery. The postpartum outcome and later complications in both mothers and infants were investigated prospectively. A total of 82 deliveries of large babies were included in the study and the outcome was compared with that of parallel deliveries of babies within the normal weight range (2,500-4,000 g). Factors frequently associated with excessive fetal weight were identified. A relatively high perinatal mortality and morbidity relating to vaginal delivery were observed among the large infants. In all those cases who developed delay in the second stage of labour, Caesarean section is proposed when macrosomia is clinically suspected and confirmed by ultrasonic assessment. Moreover elective Caesarean section should be considered before labour, when macrosomia is associated with hyperglycaemia or other pathology.
Effects of beta-blockade on regional myocardial flow and function during exercise.
We examined the effects of a cardioselective beta-blocking drug on exercise-induced regional myocardial ischemia in 10 conscious dogs with chronic coronary artery stenosis. An ameroid constrictor, Doppler flowprobe, and hydraulic cuff were placed around the left circumflex coronary artery, and left ventricular pressure (LVP), systolic wall thickening (% delta WT; by sonomicrometry), and myocardial blood flow (MBF; microspheres) were measured during control standing, control treadmill exercise, and identical exercise after atenolol (1 mg/kg po). Prior to study, in every dog % delta WT and MBF in the ischemic area were normal at rest, indicating collateral development. During control exercise, % delta WT in the ischemic region markedly decreased from 27 to 4%, and transmural ischemia was evident in that region. Heart rate, systolic LVP, and LV (+)dP/dt were significantly lower during exercise after atenolol than during control exercise. % delta WT in the normal area was only 81% of that during control exercise, but dysfunction in the ischemic area was improved (77% increase compared with control exercise). Accompanying the improved function was a significant increase of MBF/beat and relative MBF in the ischemic zone; the endocardial-to-epicardial ratio increased from 0.27 to 0.47. Thus atenolol improved regional MBF distribution, thereby diminishing exercise-induced regional myocardial dysfunction and accelerating its recovery.
Social acceptability characteristics of learning disabled students.
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Dissociated patterns of nocturnal prolactin, cortisol, and growth hormone secretion after stroke.
The secretory activity of the hypothalamic-pituitary axis is influenced by suprahypothalamic regulatory mechanisms. To evaluate the effect of brain lesions on hormonal patterns, we investigated eight patients convalescing from hemispheric stroke and five sex- and age-matched healthy volunteers. Studies were conducted during two consecutive nights with continuous polygraphic recording and sequential blood sampling. Nocturnal plasma hormone measurements showed a normal rhythm of cortisol (a marker of ACTH), elevated prolactin concentrations (p less than 0.05) and low growth hormone values (p less than 0.05). The study suggests that major suprahypothalamic lesions influence hypothalamic function so as to facilitate prolactin secretion and inhibit growth hormone release. They have no effect on the more basic pattern of ACTH-cortisol secretion, however.
Heritability of quantitative variation at the group-specific component (Gc) locus.
Human group-specific component (Gc) is the plasma transport protein for vitamin D; in addition, polymorphic electrophoretic variants of Gc are found in all human populations. Because of its physiologic importance and in view of the extensive genetic variation at the Gc locus, we have determined the heritability of quantitative variation in Gc by comparing a series of monozygotic (MZ) and dizygotic (DZ) twins of known Gc genotype. The series included 31 MZ twin pairs, 13 DZ twin pairs, and 45 unrelated controls. Since Gc concentration is increased by estrogens, pregnant women and women taking oral contraceptives were excluded. We found no age-related differences in Gc concentration or differences between males and females, but the concentrations of Gc in the three electrophoretically determined genotypes were significantly different from each other. Using classical methods of heritability analysis, the overall heritability of variation in Gc concentration is approximately 70%. Heritability in males is greater than in females, probably reflecting the additional environmental effect of estrogens in women. To determine if the differences in Gc concentration between the three genotypes explain the high heritability, a new variance decomposition procedure was developed following classical methods in quantitative genetics. Application of this method suggests that 19% of the total variation in Gc concentration, combining both sexes, is due to electrophoretic differences between individuals (30% in females and 20% in males). Thus, the genetic component of variation in Gc concentration can be decomposed into a major gene component--the result of electrophoretic variation at the structural locus--and a second, unexplained, polygenic component.