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Biomedical subjects

E Duncan

Publications and source records attributed to E Duncan.

36 records · Page 2Linked to original sources

Vitamin E treatment of tardive dyskinesia.

OBJECTIVE: The authors studied the effects of vitamin E treatment of tardive dyskinesia; earlier studies have produced contradictory results. METHOD: Twenty-eight patients with tardive dyskinesia were treated in a double-blind, parallel-group comparison study of 8-12 weeks of treatment with vitamin E (1600 IU/day) or matching placebo capsules. RESULTS: The Abnormal Involuntary Movement Scale scores of the patients treated with vitamin E improved significantly compared to the scores of the patients given placebo. CONCLUSIONS: These results support earlier findings of the efficacy of vitamin E in treating tardive dyskinesia.

Ambulatory Care↗

Vitamin E in tardive dyskinesia: time course of effect after placebo substitution.

Alpha-tocopherol (vitamin E) has been found to be effective in the treatment of tardive dyskinesia (TD). Studies to date have been short in duration and have not found long-term carryover effects of vitamin E. The present study examined the persistence of the effects of vitamin E after longer term (36-week) treatment was discontinued. Vitamin E significantly improved TD over this period. However, the effects of vitamin E persisted so that TD scores approached baseline only after 12 weeks of placebo substitution.

Adult↗

Aspergillus fumigatus sternal wound infections in patients undergoing open heart surgery.

During a 21-month period (July 1986-April 1988), six patients who underwent open heart surgery at Holston Valley Hospital and Medical Center in Kingsport, Tennessee, developed sternal would infections caused by Aspergillus fumigatus. All patients required sternectomy, reconstructive surgery, and long term amphotericin B therapy; no patient died. By univariate analysis, the following were significantly associated with A. fumigatus sternal would infection: chronic lung disease, a recent history of pneumonia, a greater mean number of admission diagnoses, and a particular surgeon. However, multivariate analysis identified chronic lung disease as the only independent risk factor and the best predictor of A. fumigatus sternal wound infections. No factors related to the surgical procedure or operating room personnel were associated with infection. A review of the characteristics of the patients undergoing open heart surgery showed that since 1985, there had been a trend for these patients at Holston Valley Hospital and Medical Center to be older and sicker, which may have contributed to the occurrence of infections never observed before. Despite an extensive investigation, no environmental source for A. fumigatus was identified. A. fumigatus, however, grew from the bronchial washing of one patient at the time the sternal wound infection was diagnosed, and a prospective study showed that the rate of A. fumigatus colonization among open heart surgery patients was the same as the rate of sternal wound infections caused by A. fumigatus. These data suggest that patients with chronic lung disease and respiratory colonization with A. fumigatus are at increased risk for A. fumigatus sternal wound infections after open heart surgery.

Aged↗

Production of hydroxyl radicals and their disassociation from myocardial cell injury during calcium paradox.

The production of hydroxyl radicals during calcium paradox injury was investigated by measuring the production of 2,5-dihydroxybenzoic acid (2,5-DHBA) from salicylate. Four groups of rats were analyzed. In the first group, isolated hearts were perfused with calcium-free medium for 10 minutes followed by perfusion with medium containing Ca++ for 10 minutes. In the other groups, 0.25 microM N,N'-diphenyl-1,3-phenylenediamine (DPPD), 80 microM cytochrome c, or 450 U/ml catalase was added. Coronary effluent was analyzed for the presence of 2,5-DHBA, and tissue sections were examined using light microscopy. In the first group, 2,5-DHBA production began during the calcium-free period, peaked tenfold 60-90 sec. into the Ca repletion period, and declined thereafter. The increase in 2,5-DHBA was accompanied by severe cell damage. Cytochrome c reduced 2,5-DHBA production, and catalase almost completely inhibited 2,5-DHBA production, while DPPD had no effect on 2,5-DHBA production. None of the three additives provided any complete morphological protection. The data provide evidence for the production of hydroxyl radicals during calcium-paradox injury, that their production is dependent upon the presence of hydrogen peroxide, and that cell damage in the calcium paradox is not primarily mediated by the extracellular hydroxyl radicals.

Animals↗

High levels of granulocyte and granulocyte-macrophage colony-stimulating factors in cord blood of normal full-term neonates.

Because several human hematopoietic growth factors have been identified and shown to be effective for treatment of congenital or iatrogenic neutropenias, and cord blood contains stimulatory activities for blood-forming cells, we postulated that identification of these factors and analysis of their regulatory role in normal neonates would provide a rationale for their use in treating neonatal infections associated with neutropenia. We studied the plasma levels of granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF, respectively) and the frequency of granulomonopoietic colony-forming cells (CFU-GM) in the umbilical cord blood of normal term neonates. Plasma growth factor levels were measured by a biologic assay. Circulating hematopoietic progenitors were assayed for colony formation with different recombinant growth factors used as exogenous growth stimulators. The cell cycle status of these progenitors was analyzed by the thymidine suicide technique. At birth the leukocyte count (mean +/- SD) was 11.0 +/- 3.9 x 10(9)L and the neutrophil count was 5.6 +/- 2.6 x 10(9)/L. The incidence of CFU-GM was significantly higher in umbilical cord blood than in normal adult peripheral blood (p less than 0.005) with up to 40% of the cells in S phase (less than 10% in normal adults). Plasma levels of G-CSF and GM-CSF at birth were 40.8 +/- 2.8 U/ml and 19.9 +/- 5.2 U/ml, respectively (normal adult plasma levels 2.5 +/- 1.5 U/ml for G-CSF and undetectable for GM-CSF). These high levels of G-CSF and GM-CSF in umbilical cord blood of normal neonates might play a role in maintaining adequate neutrophil production.

Adult↗

Nifedipine in the treatment of tardive dyskinesia.

There have been several case reports of improvement in tardive dyskinesia (TD) after treatment with calcium-blocking agents. We have conducted prior single-blind (rater-blind) studies of verapamil and diltiazem and found a statistically significant improvement in TD with verapamil, and a small improvement that did not reach statistical improvement after diltiazem treatment. We now report a single-blind (rater-blind) study of a third calcium antagonist, nifedipine, in the treatment of TD. Nifedipine (30-60 mg/day) was administered to eight schizophrenic patients with TD. Mean AIMS scores on items 1-7 decreased from 12.9 +/- 2.0 (SD) at baseline to 10.8 +/- 2.7 after treatment (t = 3.66, p = 0.01). All subjects were able to tolerate the maximal dose of nifedipine without significant side effects. TD is known to be affected by drugs that affect dopamine neurotransmission. Several lines of pre-clinical and clinical evidence suggest interactions between the calcium antagonists and the CNS dopamine system and provide a possible explanation for the effects on TD seen with calcium antagonists.

Adult↗

Effects of a specific beta 2-receptor blocker in neuroleptic-induced akathisia.

To assess the role of blockade of beta-receptor subpopulations in the treatment of neuroleptic-induced akathisia (NIA), the specific beta 2-antagonist ICI 118,551 was compared to placebo in a double-blind study. After a baseline evaluation on placebo, patients were treated with ICI 118,551 or placebo. Five of six patients treated with ICI 118,551 showed improvements in NIA, while only one of four patients improved on placebo. Patients were then treated openly with propranolol, a mixed beta 1, beta 2-antagonist. Compared to ICI 118,551, no further improvement on objective measures of akathisia was seen on propranolol. Mean subjective assessments of NIA declined on propranolol, but changes were variable and not statistically significant.

Adrenergic beta-Antagonists↗

Akathisia: selective beta-blockers and rating instruments.

beta-Blockers, particularly propranolol, have been shown to be an effective treatment for neuroleptic-induced akathisia (NIA). To examine the relative contribution of beta-1 and beta-2 receptor blockade to the therapeutic effect of propranolol, we studied a beta-1 selective agent (low dose metoprolol) and a beta-2 specific blocker (ICI 118,551). Both agents ameliorated NIA. To further evaluate instruments for quantifying NIA we compared (a) two sets of clinical ratings during the metoprolol study and (b) clinical and electromechanical ratings of NIA during the ICI 118,551 study. The changes in clinical ratings of NIA after metoprolol were similar for most patients; however, the changes in electromechanical and clinical ratings after ICI 118,551 were similar in less than half of the patients studied.

Adrenergic beta-Antagonists↗

Dipyridamole: pharmacokinetics and effects on aspects of platelet function in man.

1. The effect of dipyridamole on platelet function was measured in twelve normal subjects given 150 or 200 mg tablets as single and multiple doses, and in six subjects given single doses of 25, 50 and 100 mg and multiple doses of 50 mg 8 hourly. 2. Platelet aggregation was measured in response to ADP and collagen. In the subjects given 150/200 mg, the platelets were assayed for content of cyclic AMP and for formation of thromboxane after addition of collagen. The responses to ADP and collagen and the cyclic AMP content were assessed in both the presence and absence of added PGE1. The pharmacokinetics of dipyridamole were studied in all subjects. 3. One hour after 150/200 mg single doses of dipyridamole there was significant inhibition of platelet aggregation in response to both collagen and ADP. There was no detectable effect on aggregation at other time points or with lower doses of dipyridamole. The addition of PGE1 to platelets prior to testing did not enhance the effect of dipyridamole on platelet aggregation. 4. In multiple doses, dipyridamole (150/200 mg twice daily for 11 days) had no detectable effect on platelet aggregation. 5. Dipyridamole did not have any effect on platelet cyclic AMP content, whether or not PGE1 was added prior to assay. 6. Dipyridamole did not affect platelet thromboxane formation. 7. Plasma dipyridamole concentrations were maximal 1-2 h after ingestion, at the same time that inhibition of platelet aggregation was detected. The concentrations declined in a biexponential fashion, with a terminal half life of 24.1 +/- 1.9 h (mean +/- s.e. mean). In six of the 17 subjects, the mean steady state plasma concentration was less than 75% of the value predicted from the single dose data.

Adolescent↗

Legionnaires' disease in Kingport, Tennessee.

In August and September 1977 a discrete cluster of 27 serologically or pathologically confirmed cases of Legionnaires' disease, plus six highly presumptive cases were identified in the area of Kingsport, Tennessee. Three patients died. Most patients manifested severe pneumonia and fever; no mild or asymptomatic disease forms were recognized despite intensive case-finding efforts. Illness was epidemiologically associated with residing, visiting, or working in one geographic area of Kingsport, residence there being the factor most strongly associated. Although the attack rate for area residents was 0.64%, the randomly determined prevalence of serologic reactors was 5.2%, which is not significantly different from that in a nonimplicated control neighborhood. The epidemic did not correlate temporally with any identified environmental or demographic event. No source of the bacterium was found either by a detailed case-control study of area associations or by bacterial isolation from sentinel guinea pigs or environmental specimens. There was no evidence of person-to-person spread.

Disease Outbreaks↗

In vitro modulation of lymphocyte responses to phytohaemagglutinin by plasma in mother and baby at the time of birth. Increased lymphocyte responses in babies of mothers with lepromatous leprosy.

Peripheral blood lymphocytes from nineteen healthy mothers, mothers with borderline tuberculoid leprosy and fourteen mothers with borderline or polar lepromatous leprosy, and their newborn babies, were stimulated in vitro with phytohaemagglutinin (PHA). The responses in medium supplemented by serum from a pool of healthy non-pregnant individuals were compared with responses in medium supplemented by plasma from the mothers or from their babies, to assay for the presence of non-specific effects on T-cell responses. It was found that plasma from the mothers at the time of labour profoundly suppressed their own lymphocyte responses to PHA. However, the lymphocyte responses of healthy mothers were not significantly suppressed when cultivated in the presence of plasma from the babies, indicating that the suppressive factor(s) of normal pregnancy did not pass the placental barrier. Plasma from mothers with leprosy had a greater inhibitory effect on their babies' lymphocytes than plasma from healthy mothers. This raises the possibility that plasma from leprosy patients contains suppressive factors other than those associated with pregnancy. Babies of lepromatous leprosy mothers, who might have been exposed to mycobacterial antigens in utero, had higher PHA responses than the other babies, possibly due to a compensatory reaction to early stresses in the immune system.

Female↗