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Biomedical subjects

D Clark

Publications and source records attributed to D Clark.

At least 253 records · Page 14Linked to original sources

AIDS needs education.

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Acquired Immunodeficiency Syndrome↗

Spontaneous resolution of pulmonary stenosis.

Pulmonary stenosis diagnosed in infancy usually increases in severity with age or, if it is mild, may remain so for many years. We report the case of a child in whom moderately severe pulmonary stenosis in infancy appeared to completely resolve by the age of 8 years.

Female↗

Blood component therapy. New guidelines for avoiding complications.

Transfusion medicine is an expanding subspecialty that continues to be reshaped and redefined. The current indications for red blood cell (RBC) transfusion are the presence of tissue hypoxia or a hemoglobin level of less than 7 g/dL. Platelet concentrates should be given prophylactically for severe thrombocytopenia secondary to production defects. In the patient who is in need of an invasive procedure or is bleeding, therapeutic platelet transfusion may be needed if the platelet count is less than 50,000/microL or the bleeding time is twice the upper limit of normal or more. Both RBC and platelet transfusion should be avoided if specific therapy is available for the underlying condition. Transfusion of fresh frozen plasma is indicated for reversal of inherited isolated coagulation factor deficiencies, emergent reversal of the effects of warfarin sodium (Coumadin, Panwarfin, Sofarin), antithrombin III deficiency, and thrombotic thrombocytopenic purpura. No blood transfusion is without risk to the recipient. Two of the major transfusion-related complications are alloimmunization and graft-versus-host disease. Techniques for preventing these conditions are available.

Blood Transfusion↗

In vivo measurement of extracellular 5-hydroxytryptamine in hippocampus of the anaesthetized rat using microdialysis: changes in relation to 5-hydroxytryptaminergic neuronal activity.

The effect of manipulating the activity of central 5-hydroxytryptamine (5-HT) neurones on extracellular 5-HT in ventral hippocampus of the chloral hydrate-anaesthetized rat was studied using the brain perfusion method, microdialysis. Basal levels of 5-HT in the dialysates were close to the detection limits of our assay using HPLC with electrochemical detection. However, addition of the selective 5-HT reuptake inhibitor citalopram (10(-6) M) to the perfusion medium produced readily measurable amounts of dialysate 5-HT. Citalopram, therefore, was used throughout our experiments. Hippocampal dialysate levels of 5-HT sharply declined over the first hour after dialysis probe implantation, but then became constant. This stable output of 5-HT was reduced by 57% in rats treated 14 days previously with intracerebroventricular injections of the 5-HT neurotoxin 5,7-dihydroxytryptamine. Electrical stimulation (1-ms pulse width, 300 microA, 2-20 Hz) of the dorsal raphe nucleus for 20 min caused a rapid rise in hippocampal 5-HT output, which immediately declined on cessation of the stimulus and was frequency-dependent. Addition of tetrodotoxin (10(-6) M) to the perfusion medium reduced 5-HT levels to 75% of predrug values. Injection of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (0.5 and 2.5 micrograms) into the dorsal raphe nucleus caused a dose-related fall in hippocampal output of 5-HT compared to saline-injected controls. We conclude from these data that the spontaneous output of endogenous 5-HT into hippocampal dialysates, measured under our experimental conditions, predominantly originates from central 5-HT neurones and changes in accordance with their electrical activity.

5,7-Dihydroxytryptamine↗

Plasma amino acid concentrations in parenterally fed preterm infants.

One hundred and nine sick preterm infants were studied, and the data obtained show that hyperphenylalaninaemia is an extremely rare occurrence as long as an adequate source of energy is provided. High concentrations of the other aromatic amino acid (tyrosine) on the other hand, were often encountered and seem to be due to immaturity of an isolated hepatic enzyme as there was no correlation between phenylalanine and tyrosine concentrations. Possible adverse consequences of hypertyrosinaemia are discussed in relation to toxicity and the assessment of hepatic function. We provide reference centiles for plasma amino acid concentrations in this population.

Amino Acids↗

Dopamine (DA) autoreceptor efficacy of 3-PPP enantiomers after short-term synaptic DA deprivation.

We have compared the central dopamine (DA) autoreceptor-stimulatory properties of the 'atypical' DA agonist, (-)-3-PPP, its (+)-antipode and the reference DA agonist, apomorphine, following a 5 or an 18 h interruption of synaptic dopaminergic transmission by means of reserpine. The results are consistent with the notion that even a relatively short period (18 h) of synaptic DA deprivation results in a functional 'supersensitivity' of central DA synthesis-modulating autoreceptors. Interestingly, the data demonstrate a clearcut and significant enhancement of the intrinsic agonist efficacy of (-)-3-PPP in limbic and striatal parts after an 18 h as compared to a 5 h reserpine-induced impairment of synaptic DA transmission. In addition, there was a tendency towards a reduction in the doses of apomorphine and the 3-PPP enantiomers needed to inhibit DA synthesis in 18 vs. 5 h reserpinized rats in both brain regions. The findings indicate that the adaptive state of the DA autoreceptors had been altered, tentatively as a result of the reduced (endogenous) agonist occupancy. This is consistent with the suggestion that DA autoreceptors are influenced by a certain, albeit presumably low, endogenous dopaminergic tone under in vivo physiological conditions. The data obtained provide further support for the contention that receptor responsiveness is a critical determinant of the intrinsic efficacy displayed by DA receptor agonists such as (-)-3-PPP.

Animals↗

Relationship of locus of control to life style habits.

This study contrasted the life style habits of college students who were high and low on different dimensions of locus of control. The Levenson Locus of Control Scale was used to assess three locus of control dimensions (Internality, Powerful Others, and Chance); the Tennessee Self-Description Form (TSDF) assessed four areas of life-style (Work, Social, Health, and Leisure). High and low groups were formed for each locus of control dimension by taking the top 20% and bottom 20% of the distribution (total N = 162). For all three locus of control variables, a significant interaction was obtained between the high-low group variable and the four areas of life style. The High Internals, Low Powerful Others, and Low Chance groups obtained significantly higher Work and Health scores than did their counterparts.

Adult↗

Electrophysiological and pharmacological characterization of identified nigrostriatal and mesoaccumbens dopamine neurons in the rat.

Extracellular single-unit recording techniques were used to compare the basal activity and pharmacological responsiveness of identified nigrostriatal and mesoaccumbens dopamine (DA)-containing neurons. The projection area of each DA cell was determined by antidromic activation techniques. The forebrain stimulation used for the cell identification procedure did not alter the pharmacological responsiveness of DA neurons; the inhibitory effect of apomorphine (and d-amphetamine) was identical when stimulation was applied either prior to or following drug administration. Analysis of the spike discharge pattern revealed that a higher proportion of mesoaccumbens DA cells exhibited burst-firing activity. Although the firing pattern of the two populations of burst-firing DA cells was similar in many regards, mesoaccumbens DA cells exhibited a longer postburst inhibition than did nigrostriatal DA cells. Each of the DA agonists, apomorphine, pergolide, B-HT 920, and d-amphetamine, inhibited nigrostriatal and mesoaccumbens DA neuronal activity in a similar fashion. However, there was a marked population difference in the recovery of cell firing in the 10 minutes following apomorphine-induced inhibition; the recovery of mesoaccumbens spike discharges was considerably slower. Although this population difference was apparent to some extent following administration of pergolide or B-HT 920 (but not d-amphetamine), it was considerably less marked. The present findings are discussed with respect to the known regulatory control of midbrain DA neurons.

Action Potentials↗

Retinal/macular pigmentation in conjunction with ring 14 chromosome.

A number of constant features can be ascribed to patients who have a ring 14 chromosome. Recent publications have described pigmentation of the retinal/macular area of the eye and suggested that it may also be a constant feature of the syndrome. We describe a patient who has a ring 14 with a terminal deletion but no retinal pigmentation and compare our case with other informative cases. We suggest that a region on chromosome 14 proximal to q32.2 may be involved in controlling these changes.

Child, Preschool↗

Suppression of neuroleptic-induced persistent abnormal movements in Cebus apella monkeys by enantiomers of 3-PPP.

Effects of the enantiomers of the dopamine (DA) autoreceptor agonist 3-PPP (0.5-8.0 mg/kg body weight, i.m.) were studied in three Cebus apella monkeys with persistent abnormal movements induced by prior long-term treatment with fluphenazine enanthate. In 2 of the animals, (-)-3-PPP abolished the abnormal movements while producing only negligible acute motor effects (trembling and stereotypy). (+)-3-PPP, administered to one of these monkeys, also produced a dose-dependent suppression of the persistent abnormal movements, along with the appearance of acute motor signs including tongue protrusions, hyperkinesia, and stereotypy; at the highest dose, there was a biphasic effect. In the first phase, there were pronounced acute motor signs but no persistent abnormal movements. In the second phase, there were neither acute nor persistent abnormal movements. One monkey was unaffected by (-)-3-PPP or low doses of (+)-3-PPP; a higher dose (4 mg/kg) produced hyperkinesia and increased persistent abnormal movements in one experimental setting. The suppression of neuroleptic-induced persistent abnormal movements by 3-PPP enantiomers may be related to their ability to act as autoreceptor agonists, while the acute motor signs produced by higher doses of (+)-3-PPP may be due to activation of postsynaptic DA receptors. The present findings suggest that (-)-3-PPP and drugs with a similar pharmacological profile might be effective as symptomatic treatments for tardive dyskinesia, with little chance of inducing acute extrapyramidal side-effects.

Animals↗

Epstein-Barr virus gene expression in nasopharyngeal carcinoma.

Epstein-Barr virus (EBV), an agent with growth transforming potential for human B cells, is associated with certain B cell lymphomas in man and also with an epithelial tumour, undifferentiated nasopharyngeal carcinoma (NPC). Since B cell growth transformation is associated with the constitutive expression of a small number of EBV-coded latent proteins, the nuclear antigens EBNA 1, EBNA 2, EBNA 3 and EBNA-LP and the latent membrane protein (LMP), the present work sought to determine whether this same pattern of virus gene expression occurred in NPC. Tumour biopsies were taken from NPC patients from three areas of differing tumour incidence (Kenya, Algeria, Britain) and immediately snap-frozen, as were biopsies of non-EBV-related carcinomas for controls. Immunoblotting of PAGE-separated proteins with selected human sera identified 24 NPC biopsies clearly expressing EBNA 1. When the analysis was extended using selected human sera with antibodies against the other EBNAs, there was no detectable expression of EBNA 2, EBNA 3 or EBNA-LP in any of these 24 biopsies; their EBNA 2-negative status was confirmed using a monoclonal antibody (MAb) PE2 which was reactive in immunoblotting and in immunoprecipitation with EBNA 2A and EBNA 2B proteins. Similar experiments with two different LMP-specific MAbs, CS1 to 4 and S12, revealed heterogeneity between NPC biopsies; 9/24 biopsies were demonstrably LMP-positive, the degree of expression varying considerably between individual tumours in a manner which was not related to the level of EBNA 1 expression. None of the 24 NPC biopsies expressed detectable amounts of EBV lytic cycle antigens. A nude mouse-passaged NPC cell line, C15, likewise expressed EBNA 1 and LMP but none of the other EBV latent proteins nor lytic cycle antigens. This work identifies a novel type of EBV-cell interaction in NPC cells which is distinct from that seen in in vitro transformed B cell lines and from that seen to date in EBV-positive B cell lymphomas.

Antibodies, Monoclonal↗

City size, quality of life, and the urbanization deflator of the GNP: 1910-1984.

The authors attempt to determine the net effect of city size on quality of life by developing a welfare measure of urbanization. "The estimation procedure suggested in the theoretical part of the paper (section II) is implemented in the empirical part (section III) using 1980 census data from the [U.S.] PUMS (Public Use Micro Data Sample). The results indicate there is no single optimal city size, but rather a worst city size, and about 90 percent of the U.S. population reside in cities smaller than worst city size. If quality of life is related to the degree of urbanization, then long-term trends in the locational distribution of the population should be accounted for in any welfare-oriented measure of national income. One application of our results is, as indicated, the derivation of a GNP welfare deflator reflecting changes in the degree of urbanization (section IV). The findings suggest an urban deflator on the order of six to seven percentage points, which is steadily increasing at a rate of about half a percentage point per decade."

Americas↗

Treadmill exercise test and ambulatory measures in panic attacks.

Treadmill exercise test performance and ambulatory heart rate and activity patterns of 40 patients with panic attacks were compared with 20 age-matched controls (control group 1) and 20 nonexercising controls (control group 2). All patients underwent a symptom-limited exercise stress test. Panic attack patients and control group 1 wore an ambulatory heart rate/activity monitor for up to 3 days. Panic patients had a significantly higher heart rate at 4 and 6 METS than either control group. The max METS were 11.2 +/- 2.3, 13.5 +/- 2.3 and 11.2 +/- 1.8 for the panic attack patients and control groups 1 and 2, respectively. One panic patient had ischemia on the treadmill at 12 METS. Panic patients had a significantly higher standing heart rate than controls. Furthermore, 11 of 39 panic patients had tachycardia on standing compared with 3 of 40 controls. Panic attack patients had higher wake and sleep heart rates than control group 1, but the differences were not significant. These results are consistent with autonomic dysfunction in panic patients but may also be due to differences in physical conditioning. The treadmill can be useful for reassuring patients and for identifying the rare patient with ischemia on exercise.

Adult↗