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Biomedical subjects

J F Greden

Publications and source records attributed to J F Greden.

At least 19 recordsLinked to original sources

Shortened REM latency PostECT is associated with rapid recurrence of depressive symptomatology.

Electroconvulsive therapy (ECT) is highly effective in the treatment of major depressive disorder (MDD). The 1-year relapse rates are reported to be high and in the 30%-60% range, however. To test whether polysomnography (PS) can identify patients with a propensity for relapse we studied 20 patients, responders to a course of ECT, with PS studies. All patients met baseline diagnostic criteria for MDD, were treated with ECT following standardized protocols, had PS studies performed after the course of ECT in a medication-free state, received maintenance antidepressants postECT, and were followed periodically with phone interviews. The recurrence of depressive symptoms was determined at 3 months and 6 months after discharge. Fifty-five percent of the patients were symptomatic when evaluated 6 months after the ECT. Sleep Onset rapid eye movement (REM) periods were identified in 55% of the patients. As a group, patients who had experienced a recurrence of depressive symptoms by 6 months after discharge, had significantly shorter REM latencies after the course of ECT. A shorter REM latency after ECT identified patients who at six months demonstrated significant depressive symptomatology. Shortened REM latency after ECT in patients with MDD appears to be a correlate of vulnerability for relapse.

Adult

Selective inhibition by alcohol and cortisol of natural killer cell activity of lymphocytes from cord blood.

1. The immunosuppressive effects of drugs such as alcohol or hormones such as cortisol may be age-related. To test this hypothesis, the authors investigated the in vitro effects of ethanol (EtOH) and cortisol on Natural Killer (NK) cell activity of lymphocytes from normal cord blood in comparison with that of lymphocytes from normal adult peripheral blood. 2. K562, an erythroleukemia cell line, was used as a target in a 4 hr 51Cr release assay. 3. Ethanol at 0.3% (V/V) and cortisol at 0.05, 0.1 and 0.2 microgram/ml concentrations, added directly to a mixture of effector and target cells significantly suppressed the NK activity of cord blood lymphocytes in a dose dependent fashion, whereas similar concentrations of either EtOH or cortisol did not manifest significant immunoregulatory effects on NK cell activity of normal adult lymphocytes. 4. Pre-treatment of the target with either EtOH or cortisol for 4 hours did not affect cytotoxicity. Inhibition of cytotoxicity was also not due to direct toxicity of effector cells because lymphocytes treated with either EtOH or cortisol showed normal 51Cr release and their viability was comparable to that of untreated control cells. 5. This suggests a selective inhibitory effect of EtOH and cortisol on NK activity of neonatal lymphocytes that may be of clinical significance.

Adult

Suppression of tumor necrosis factor production by alcohol in lipopolysaccharide-stimulated culture.

Many studies have shown that alcohol consumption is associated with alteration in immune responses and increased incidence of infection in the host. Tumor necrosis factor (TNF) is a potent soluble mediator of immunoregulation and inflammation, and plays a very important role in host's defenses against infection and tumor. We propose that one of the mechanisms of alcohol-mediated immunosuppression may be due to a defect in the synthesis and release of the TNF. To determine this, we studied the direct effect of alcohol on lipopolysaccharide (LPS)-induced TNF production by whole blood and total mononuclear cell from normal subjects. Aliquots of blood samples (1 ml) or ficoll-hypaque separated total mononuclear cells (1 x 10(6)/ml) were cultured with different concentrations of either ethanol or acetaldehyde in the presence or absence of LPS for 4 hr at 37 degrees C. Plasma samples and culture supernatants were assayed for TNF levels in a bioassay using a TNF-sensitive WEHI 164 subclone 13 cell line. LPS at 10 micrograms/ml produced a maximal level of TNF compared with lower (1 micrograms/ml) or higher concentration (50 micrograms/ml) of LPS. Kinetics studies showed that an incubation time of 4 hr with LPS produced a maximum level of TNF production by blood. Alcohol, as low as 0.1% concentration, produced significant suppression of LPS-induced TNF production by whole blood, whereas alcohol at 0.2 and 0.3% concentrations were required to produce a significant suppression of TNF production by separated mononuclear cells. Anti-TNF-alpha antibodies significantly neutralized the LPS-induced TNF that suggests that blood monocytes may be the primary source of TNF production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Electroencephalographic sleep abnormalities in schizophrenia. Relationship to positive/negative symptoms and prior neuroleptic treatment.

Polysomnographic abnormalities in schizophrenia are not well characterized and their associations with schizophrenic symptomatology have not been adequately assessed. To address these issues, we recorded electroencephalographic sleep in 20 drug-naive schizophrenics, 20 drug-free but previously medicated schizophrenics, and 15 normal controls. Drug-naive and previously medicated patients had significantly greater impairment of sleep continuity and shorter rapid eye movement latency when compared with controls. In the previously medicated group, findings were significantly influenced by duration of drug-free status. Rapid eye movement latency was inversely correlated with the severity of negative symptoms (r = -.52) but was unrelated to depressive symptoms. Slow-wave sleep did not differ between schizophrenic patients and normal controls and was unrelated to any clinical parameter. Mechanisms underlying the observed associations between rapid eye movement sleep abnormalities and negative symptoms in the acute phase of schizophrenic illness need to be explored.

Adult

Measurement of depression and negative symptoms in schizophrenia.

The validity of the Hamilton Depression Scale (HAM-D) as a measure of depressive symptomatology in schizophrenic patients is questionable since it was not developed for this purpose, nor has it been validated in a schizophrenic population. Accordingly, 80 schizophrenic inpatients were administered the HAM-D, the 18-item Brief Psychiatric Rating Scale (BPRS), and the Scale for the Assessment of Negative Symptoms (SANS) at drug-free baseline and after 4 weeks of neuroleptic treatment. The findings revealed that the HAM-D total score was nonspecific, while individual HAM-D subfactors provided a better index of various symptom complexes. The HAM-D contained a depressive factor that correlated strongly with the BPRS depression factor and a negative symptom factor that correlated strongly with the SANS and the BPRS negative symptom factor. These findings suggest the need to utilize specific assessment techniques rather than global measures when assessing depression in schizophrenia.

Adolescent

Clinical predictors of 1-year outcome in schizophrenia.

To assess clinical predictors of 1-year outcome in schizophrenia, 63 patients were studied prospectively. Persistent negative and total symptoms after 4 weeks of neuroleptic treatment accounted for 62% of the variance of 1-year outcome, whereas baseline measures showed no relationship to outcome. Thus, 1-year outcome in schizophrenia can be reasonably predicted on the basis of symptoms persisting after 4 weeks of treatment.

Adult

Effect of anticholinergics on positive and negative symptoms in schizophrenia.

Anticholinergic drugs have been assumed to have no effects on schizophrenic symptomatology. Some studies suggest, however, that anticholinergic agents may antagonize the beneficial effect of neuroleptics on positive symptoms and partially ameliorate negative symptoms. Virtually all studies have been conducted in patients receiving concomitant neuroleptic treatment, raising the possibility that neuroleptics may obscure or modify any "true" anticholinergic effect on schizophrenic symptoms. To evaluate the hypothesis that anticholinergics may increase positive and decrease negative schizophrenic symptoms, we assessed the effect of biperiden on symptoms in the medication-free state. We studied the effect of biperiden 8 mg/day for 2 days on positive and negative symptoms in 40 otherwise drug-free schizophrenic inpatients. Biperiden produced a significant increase in positive symptoms (t = 6.7, p < .001) and reduction in negative symptoms (t = -3.4, p < .01). These data indicate that cholinergic modulation significantly affects positive and negative schizophrenic symptoms and suggest the need for systematic trials of cholinergic and anticholinergic agents in the treatment of positive and negative symptoms of schizophrenia, respectively.

Adult

Dexamethasone suppression test in schizophrenia: relationship to symptomatology, ventricular enlargement, and outcome.

To relieve confusion about the clinical correlates and prognostic implications of the dexamethasone suppression test (DST) in schizophrenia, we conducted a DST in 44 schizophrenic inpatients at drug-free baseline and approximately 4 weeks after neuroleptic treatment. Patients were rated on positive, negative, and depressive symptoms at both times. A head computed tomography (CT) scan was performed and measures of ventricle-brain ratio (VBR) obtained. Clinical improvement was monitored at four weeks, and longer-term outcome assessed at 1 year. Seventeen of the 44 patients were DST nonsuppressors at baseline, and five of these remained nonsuppressors at 4 weeks posttreatment. Postdexamethasone plasma cortisol levels were correlated with negative symptoms at baseline (r = 0.45; p less than 0.01), but not after 4 weeks of neuroleptic treatment. Postdexamethasone plasma cortisols were not related to global severity, positive, or depressive symptoms at either timepoint or to VBR. Persistent nonsuppression was associated with poor outcome, but baseline postdexamethasone cortisol levels were unrelated to outcome at 4 weeks and 1 year. The literature on DST in schizophrenia is reviewed and attempts are made to reconcile discrepant findings and to discuss pathophysiological implications.

Adolescent