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Biomedical subjects

E Duncan

Publications and source records attributed to E Duncan.

At least 19 recordsLinked to original sources

Long-term treatment effects of vitamin E for tardive dyskinesia.

BACKGROUND: Several studies have found that alpha-tocopherol (vitamin E) can effectively treat tardive dyskinesia (TD). A limitation of these trials is their short treatment durations (maximum of 12 weeks), which do not allow us to address the effects of long-term treatment. METHODS: To participate, patients had to have TD and be on stable oral medications. The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo. RESULTS: Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of items #1-7) to measure TD severity, the study found a significant difference (3 points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of treatment and continuing through the full 36 weeks. We used linear mixed-effects regression to quantify the impact of several covariates, and found that treatment assignment. TD duration, and chlorpromazine equivalents had significant effects on decreasing the AIMS score. CONCLUSIONS: The study's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks. These findings are in direct contrast to those of VA Cooperative Study #394, a much larger, long-term, multi-site study, conducted by many of the same investigators, in which Vitamin E was not superior to placebo.

Antioxidants

Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment.

OBJECTIVE: To determine the relative effects of genetic and environmental factors in susceptibility to ankylosing spondylitis (AS). METHODS: Twins with AS were identified from the Royal National Hospital for Rheumatic Diseases database. Clinical and radiographic examinations were performed to establish diagnoses, and disease severity was assessed using a combination of validated scoring systems. HLA typing for HLA-B27, HLA-B60, and HLA-DR1 was performed by polymerase chain reaction with sequence-specific primers, and zygosity was assessed using microsatellite markers. Genetic and environmental variance components were assessed with the program Mx, using data from this and previous studies of twins with AS. RESULTS: Six of 8 monozygotic (MZ) twin pairs were disease concordant, compared with 4 of 15 B27-positive dizygotic (DZ) twin pairs (27%) and 4 of 32 DZ twin pairs overall (12.5%). Nonsignificant increases in similarity with regard to age at disease onset and all of the disease severity scores assessed were noted in disease-concordant MZ twins compared with concordant DZ twins. HLA-B27 and B60 were associated with the disease in probands, and the rate of disease concordance was significantly increased among DZ twin pairs in which the co-twin was positive for both B27 and DR1. Additive genetic effects were estimated to contribute 97% of the population variance. CONCLUSION: Susceptibility to AS is largely genetically determined, and the environmental trigger for the disease is probably ubiquitous. HLA-B27 accounts for a minority of the overall genetic susceptibility to AS.

Adult

Prostate simulation made easy.

A combination of computed tomography (CT) scan and retrograde urethrogram is routinely employed to simulate treatment portals prior to radiation therapy for prostate cancer. These procedures can be performed more efficiently with the use of a standard magnitude grid and a prepared urethrogram kit.

Humans

Control of infection: a survey of general medical practices.

BACKGROUND: The aims of the study were (1) to assess current infection control practice within general medical practices and establish a base line; (2) to identify potential infection control problems; (3) to assess the need for local infection control guidelines or standards related to general medical practice; (4) to assess the need for educational provision. METHODS: A survey was carried out, using questionnaire and structured interviews, of all general practices (92) within a Health Board area with a patient population of 561,300. RESULTS: Forty two (46 per cent) practices participated, serving 67 per cent of the patient population. Only three (7 per cent) practices had written infection control policies and only six (14 per cent) provided training on the subject. Thirty (71 per cent) practices had autoclaves; however, performance monitoring was poor. The majority of high-risk instruments were adequately decontaminated; of the medium-risk instruments, the auriscope speculum was the item most frequently inadequately treated [36 practices (88 per cent)]. Deficiencies were identified in treatment of blood spillage, and protective clothing provision was variable. The majority, 40 (95 per cent) practices, had systems to deal with clinical waste; however, only two (5 per cent) reported use of BS7320 sharps containers on domiciliary visits. Despite the recognized dangers, 23 (55 per cent) practices resheathed needles and only six (14 per cent) had first aid guidance for needlestick injuries. Only eight (19 per cent) practices knew and recorded staff immunity to hepatitis B following vaccination. CONCLUSIONS: Some deficiencies in infection control practice were identified and the need for policy guidance and staff training was highlighted.

Family Practice

Amphetamine and negative symptoms of schizophrenia.

The purpose of this study was to assess further the effect of amphetamine on negative symptoms of schizophrenia. Thirty-seven schizophrenic males meeting DSM-III criteria were rated with the Brief Psychiatric Rating Scale, the Abrams and Taylor Scale, and the Abnormal Involuntary Movements Scale before and after double-blind administration of either amphetamine (n = 26) or placebo (n = 11). Our results indicated that amphetamine administration generally did not improve negative symptoms, even when accounting for changes in positive symptoms. However, greater baseline negative symptoms were associated with a modest diminution after amphetamine treatment. Therefore, amphetamine may modestly improve negative symptoms in those schizophrenics in whom this symptomatology is more severe.

Adult

An effective elimination of false positives isolated from differential display of mRNAs.

A reverse Northern analysis that effectively eliminates the false positives isolated from differential display of mRNAs (DD) is demonstrated. Preparation of probe by one-step labeling in reverse transcription reaction is found to be more effective and specific as compared to the preparation of probe by random priming of reverse transcribed cDNA pool. Reverse Northern assay of DNA fragments isolated from DD prior to their cloning into plasmid, analysis of multiple fragments on single slot blot, and requirement of RNA only in small amounts as compared to conventional Northern makes the protocol quick, effective, and economic.

3T3 Cells

Blunted change in cerebral glucose utilization after haloperidol treatment in schizophrenic patients with prominent negative symptoms.

OBJECTIVE: The purpose of this report was to determine 1) the effects of chronic haloperidol treatment on cerebral metabolism in schizophrenic patients, 2) the relation between negative symptoms and haloperidol-induced regional changes in cerebral glucose utilization, and 3) the relation between metabolic change and clinical antipsychotic effect. METHOD: Cerebral glucose utilization, as determined by position emission tomography (PET), was studied in 18 male schizophrenic subjects before and after chronic treatment with haloperidol at a standardized plasma level. RESULTS: Overall, haloperidol caused a widespread decrease in absolute cerebral glucose metabolism. The cerebral metabolic response to haloperidol was blunted in patients with high pretreatment negative symptom scores. CONCLUSIONS: Taken together with the results from a previously reported PET study of the effects of an acute amphetamine challenge (in which 14 of the current subjects participated), these data suggest that the negative symptom complex is associated with diminished cerebral response to change in dopaminergic activity. This deficit cannot be solely accounted for by structural differences.

Adult

Primary intracranial pleomorphic angioleiomyoma--a new morphologic variant. An immunohistochemical and electron microscopic study.

BACKGROUND: Angioleiomyomas usually are benign subcutaneous neoplasms that occur most often in extremities of middle-aged individuals. Very few cases have been described in other locations; none along the neuroaxis. An intracranial example of angioleiomyoma displaying unusual morphologic features not seen in the typical peripheral variants of this tumor is described. METHODS: The tumor was studied with conventional histology, immunohistochemistry with morphometric calculation of proliferation index, immunoelectron microscopy, and DNA flow cytometry. RESULTS: The tumor was composed of large epithelioid and pleomorphic cells filled with intermediate filaments positive for desmin and vimentin. Scattered cells also expressed myosin and muscle-specific actin. Smooth muscle cell differentiation was confirmed by ultrastructural demonstration of subplasmalemmal dense bodies, attachment plaques, and discontinuous basal lamina. The proliferation index with proliferating cell nuclear antigen (PCNA) monoclonal antibody was 75.78%, whereas it was only 4.22% with Ki67 monoclonal antibodies adopted to paraffin material (MIB-1). CONCLUSION: The tumor represents a unique morphologic variant of a pleomorphic angioleiomyoma. Cellular pleomorphism and a strong reaction for PCNA in numerous cells suggested that the lesion was malignant. However, the absence of mitotic figures, a small number of Ki-67-positive cells, a diploic DNA pattern, and a low proliferation index in flow cytometry all supported the concept that this neoplasm represented an unusual histologic variant of benign angiogenic leiomyoma. Encapsulation and demarcation of the surgical specimen and the survival of the patient for more than 4 years without recurrence after resection support this interpretation.

Adult

Acute d-amphetamine challenge in schizophrenia: effects on cerebral glucose utilization and clinical symptomatology.

The effects of d-amphetamine (0.5 mg/kg orally) on regional cerebral glucose utilization were measured with positron emission tomography (PET) in 17 schizophrenics (along with a placebo-control group of an additional six schizophrenic patients). The acute d-amphetamine challenge tended to decrease glucose utilization throughout much of the brain, with a regional effect that was statistically significant in the left temporal cortex. There was no apparent relationship between the effects of amphetamine-induced changes in regional cerebral metabolism and psychotic symptom exacerbation. An exploratory analysis suggested that features characteristic of Crow's type II syndrome were significant predictors of cerebral hyporesponsivity to stimulant challenge, however.

Arousal

Persistent psychosis after reduction in pre- and post-synaptic dopaminergic function.

The purpose of this study was to evaluate the hypothesis that neuroleptic non-response in the face of "adequate" DA post-synaptic receptor blockade reflects failure of regulatory mechanisms to decrease DA pre-synaptic activity. Eight chronic schizophrenics, meeting rigorous criteria for neuroleptic non-response, were treated for four weeks with alpha-methylparatyrosine as an adjunct to their previously stable neuroleptic dose. Treatment with AMPT produced a prompt decrease in plasma HVA that was, on average, 72% lower at the end of the study. While there was also strong clinical evidence of reduction in central dopaminergic activity (both a significant reduction in dyskinetic movements and increase in extrapyramidal symptoms), there was virtually no change in severity of psychotic symptoms. Thus, in this group of non-responders, psychotic symptoms persisted despite both extensive dopamine post-synaptic receptor blockade and marked reduction of presynaptic activity. These symptoms may not be directly DA dependent.

Adult

Elevated PLA2 activity in schizophrenics and other psychiatric patients.

We measured serum phospholipase A2 (PLA2) activity in 39 schizophrenics, 26 psychiatric controls, and 26 normal controls using a radioenzymatic assay with phosphatidylcholine as precursor. Serum PLA2 activity was significantly higher in schizophrenics (p = 0.002) and other psychiatric (including substance abusing) patients (p = 0.032) than in normal controls. Enzyme activity did not differ between the schizophrenic patients and psychiatric controls. Fifty-one percent of the schizophrenics and 46% of psychiatric controls had PLA2 values above the highest value for normal controls. In the psychiatric control group higher than normal PLA2 activities were observed in all diagnostic categories, including major depression, bipolar disorder, posttraumatic stress disorder (PTSD), and substance abuse. In the context of others' findings of increased circulating PLA2 in infectious and inflammatory conditions, these increases must be viewed as disease nonspecific. The significance of these changes and their relationship to other acute-phase protein changes needs to be clarified in future research.

Adult

Plasma homovanillic acid in neuroleptic responsive and nonresponsive schizophrenics.

Changes in plasma homovanillic acid (HVA) were investigated in neuroleptic responsive and nonresponsive schizophrenics in order to delineate parameters of dopamine regulation, which may underlie differences in neuroleptic responsivity. Nineteen schizophrenics were treated with haloperidol for 6 weeks. HVA was sampled at baseline, 24 hr after initial neuroleptic dose, and after 6 weeks of treatment. Subjects were pretreated with debrisoquin in order to reduce the peripheral production of HVA. The responders had an initial rise in HVA at 24 hr after first neuroleptic dose, followed by a decline back to baseline over the 6 weeks of treatment. The nonresponders' HVA failed to rise at 24 hr after first neuroleptic dose. At 6 weeks of treatment their HVA had fallen to significantly below baseline. Thus, a rise in HVA 24 hr after the first dose of neuroleptic predicted treatment response; a fall in HVA at 6 weeks to below pretreatment values was associated with neuroleptic nonresponse.

Adult

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