Lithium interactions: lithium and electroconvulsive therapy.
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Biomedical subjects
Publications and source records attributed to J G Small.
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Thirty-four hospitalized manic patients were randomized to treatment with either lithium carbonate or an average series of nine bilateral electroconvulsive treatments (ECTs), followed by maintenance with lithium carbonate. Weekly ratings of manic, depressive, and psychotic symptoms were obtained for eight weeks, and patients were followed up monthly for up to two years. Ratings by nonblind and blind observers indicated that the patients who underwent ECT improved more during the first eight weeks than did patients who were treated with lithium carbonate. This was especially true of patients with mixed symptoms of mania and depression and/or extreme manic behavior. Clinical ratings after eight weeks showed no significant differences between the lithium carbonate- and ECT-treated patients. Likewise, the two groups had comparable rates of relapse, recurrence, and rehospitalization during the follow-up period.
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THE DISTRIBUTION OF PYROPHOSPHATE: fructose 6-phosphate phosphotransferase (PFP) and ATP: fructose-6-phosphate 1-phosphotransferase (PFK) was studied in germinating bean (Phaseolus vulgaris cv Top Crop) seeds. In the cotyledons the PFP activity was comparable with that of PFK. However, in the plumule and radicle plus hypocotyl, PFP activity exceeds that of PFK. Approximately 70 to 90%, depending on the stage of germination, of the total PFP and PFK activities were present in the cotyledons. Highest specific activity of both enzymes, however, occurred in the radicle plus hypocotyl (64-90 nanomoles.min.milligram protein). Fractionation studies indicate that 40% of the total PFK activity was associated with the plastids while PFP is apparently confined to the cytoplasm. The cytosolic isozyme of PFK exhibits hyperbolic kinetics with respect to fructose 6-P and ATP with K(m) values of 320 and 46 micromolar, respectively. PFP also exhibits hyperbolic kinetics both in the presence and absence of the activator fructose-2,6-P(2). The activation is caused by lowering the K(m) for fructose 6-P from 18 to 1.1 millimolar and that for pyrophosphate (PPi) from 40 to 25 micromolar, respectively. Levels of fructose 2,6-P(2) and PPi in the seeds are sufficient to activate PFP and thereby enable a glycolytic role for PFP during germination. However, the fructose 6-P content appears to be well below the K(m) of PFP for this compound and would therefore preferentially bind to the catalytic site of PFK, which has a lower K(m) for fructose 6-P. The ATP content appears to be at saturating levels for PFK.
Thirty-eight chronically ill psychotic patients were treated with clozapine for indications of tardive dyskinesia, severe extrapyramidal side effects caused by other neuroleptics, or treatment-resistant psychosis. Fifty-five percent of all patients and 40% of schizophrenics improved with clozapine. Abnormal involuntary movements were suppressed during treatment and, with 1 exception, returned to baseline levels after clozapine was discontinued. Our results support the conclusion that clozapine's efficacy in refractory cases and its lack of neurological side effects make it a unique neuroleptic with advantages over conventional antipsychotic agents. The drug appears to be safe when treatment is accompanied by frequent clinical and hematologic monitoring.
In this paper we have described early applications of computerized EEG techniques in psychopharmacology. Perhaps our most remarkable finding was there were practically no differences between very chronic drug free schizophrenic patients and normals, which contradicts much of the EEG imaging literature. To us, the most likely explanation is that most of the anterior slowing observed in other studies was due to contamination from orbital artifacts, which we took exceptional pains to remove. Lingering effects of neuroleptic medications may also have contributed. Alternatively, EEG deviations in schizophrenia may recede when the illness reaches a very chronic stage, although this hypothesis is less tenable. There were significant differences between placebo and the three neuroleptics in terms of increased amplitudes in the delta and theta frequency bands in the anterior head regions, which is compatible with data from other studies. These changes were most pronounced with clozapine and least prominent with haloperidol, with chlorpromazine occupying an intermediate position. This order happens to parallel their relative antiserotonergic, antihistaminic and anticholinergic properties. The latter may have been partially obscured by the addition of benztropine. In a subgroup of patients who were recorded under each of the treatment conditions, there were more fast frequencies with clozapine than with the other neuroleptics agreeing with Roubicek and Major. This could be a function of clozapine's increased adrenergic activity as reported by Ackenheil. An unexpected finding was that patients who responded to clozapine had higher amplitudes in the alpha spectrum, most pronounced in the left anterior quadrant, than did the nonresponders. These differences between responders and nonresponders obtained whether patients were on placebo, haloperidol or clozapine. Curiously, Buchsbaum et al. found that anxious patients who responded to benzodiazepines also had higher alpha amplitudes in the same brain regions, which differentiated them from nonresponders. These findings clearly warrant future scientific investigation. In this regard, the generalizability of our data is limited by the extremely chronic, treatment-resistant population studied. However, promising directions for further research in EEG and psychopharmacology have been identified.
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Multiple variables were examined in relation to outcome of ECT in a complete population of 261 patients treated over a four-year period. Sixty-three percent were rated as much improved. Response to ECT was not predicted by identifying data, DSM-III Axes I, II and III, Research Diagnostic Categories (RDC) or the majority of the "blind" clinical ratings and neuropsychological and EEG data. ECT response was significantly associated with DSM-III Axis IV and V, history of substance abuse and the Brief Psychiatric Rating Scale (BPRS) withdrawal-retardation factor. Ratings of psychopathology and measures of intelligence improved with ECT, more in the patients who responded favorably than in those who did not. Scores on the neuropsychological test battery were better after ECT but remained within the brain-damaged range. Schizophrenic patients received the greatest number of treatments and showed the least variability in seizure duration. Electrical energy required for seizure induction was highest in depressed patients. Bilateral electrode placement was preferred for the majority of patients.
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As a follow-up to pilot observations that six manic patients who failed to respond to unilateral electroconvulsive therapy (ECT) recovered rapidly when switched to bilateral treatment, a retrospective study was conducted. Twenty-five patients who responded after switchover from unilateral to bilateral ECT, 25 age- and sex-matched controls, and 25 concurrent controls who responded to right unilateral ECT alone were evaluated. Demographic variables and DSM-III diagnosis did not discriminate between the groups, nor were they different in terms of electroencephalographic (EEG) findings, neuropsychological test results, numbers of ECT, and duration of seizure discharges. Standard assessments of psychopathology performed by independent psychiatrists showed no differences in ratings of psychosis or depressive phenomena. However, scales assessing manic symptoms showed highly significant differences with many more features of unrestrained behavior, elevated mood, hurried speech, and other typical features of mania in the patients who were switched from unilateral to bilateral ECT. Although there were no differences in prescribed drugs, the use of prn medications for sleep was greater in the experimental-switched patients than in controls. Patients who responded to unilateral ECT alone exhibited virtually no manic features, whereas those who demonstrated these characteristics failed to respond to unilateral ECT but benefited when switched to bilateral treatment.
Gluconeogenesis in Citrullus lanatus seeds is a post germinative event. Increases in isocitrate lyase activity and incorporation of radioactivity from [2-(14)C]acetate into sugars occur only after radicle emergence. During germination, the seeds appear to rely on carbohydrate as the respiratory substrate. At this time, glycolysis, the pentose phosphate pathway, and the tricarbocyclic acid cycle seem to be functional. Utilization of raffinose during germination appears to be important.Water stress, which completely inhibits germination, has a marked effect on carbohydrate metabolism. The rate of (14)CO(2) release from [2-(14)C]acetate, [1-(14)C]glucose, and [6-(14)C]glucose is lower in the stressed seeds than the control seeds during the respiratory lag phase. However, in the stressed seeds neither glycolysis, the pentose phosphate pathway, nor the tricarboxylic acid cycle is completely inhibited. In contrast to the control seeds in which raffinose content sharply declines after 12 h of incubation, raffinose content in the stressed seeds remains fairly constant.The respiratory lag phase of the control seeds coincides with a lower reducing substance content, glucose content, and fructose content than in the stressed seeds during the corresponding incubation period.
In a double-blind, long-term follow-up study, 117 bipolar patients received lithium carbonate, imipramine hydrochloride, or both and 150 unipolar patients received lithium carbonate, imipramine, both lithium carbonate and imipramine, or placebo. With bipolar patients, lithium carbonate and the combination treatment were superior to imipramine in preventing manic recurrences and were as effective as imipramine in preventing manic recurrences and were as effective as imipramine in preventing depressive episodes. The combination treatment provided no advantage over lithium carbonate alone. With unipolar patients, imipramine and the combination treatment were more effective than lithium carbonate and placebo in preventing depressive recurrences. The combination treatment provided no advantage over imipramine alone. The lithium carbonate-treated group had fewer manic episodes than the other groups. Treatment outcome, which was evaluated primarily in terms of the occurrence of major depression or manic episodes, was significantly related to characteristics of the index episode, ie, the episode that brought the patient into the study.
Elicitation of pattern reversal evoked potentials (PREPs) was added to routine clinical EEG examinations in 100 consecutive adult psychiatric admissions. Latencies and correlations between the peaks and troughs of the triphasic complex were examined with particular reference to current hypotheses about neurophysiologic dysfunctions in schizophrenia and other psychiatric illnesses. PREP data also were examined in relation to age, sex, handedness, concurrent medications, and the clinical EEG findings. The results obtained indicated that age, sex, handedness, neuroleptic and anticholinergic medications and underlying EEG characteristics exert minimal influences upon the PREP. Schizophrenics showed lower hemispheric correlations and greater response stability than did patients with other diagnoses. No lateralized differences in relation to diagnosis were identified.
A group of 759 patients with final DSM-I and -II diagnoses of schizophrenia was identified among a cohort of 1494 adults who were hospitalized between 1965 and 1972. Admission EEG recordings were done in each patient during waking, activation procedures, drowsiness, and sleep. All cases were reclassified according to the Feighner et al. criteria, and relationships between the EEG, reassigned diagnosis, and outcome were examined. One-third of the schizophrenics were rediagnosed as having affective, organic, or other disorders. EEG abnormalities predicted diagnostic change and relatively favorable prognosis. Mean alpha frequencies were slower in schizophrenics than in patients with other DSM I-II disorders, and less in patients with Feighner et al. diagnoses of schizophrenia than in some rediagnosed categories. In 1980-82, matched samples from the original cohort with affective, schizophrenic, and mixed Feighner et al. diagnoses were followed and evaluated blindly with the SADS-L. RDC follow-up diagnoses were significantly correlated with the index EEG findings in terms of higher alpha average frequencies proportional to the amount of affective psychopathology. A subgroup of high functioning individuals within the RDC schizophrenic category was identified with affective symptomatology early in the course of illness, normal EEGs, and high alpha average frequencies. Patients with a consistent diagnosis of schizophrenia according to the three nosologic systems were shown to function better in some areas if the index EEG was abnormal. Discriminant function analysis established that DSM-I and -II categories possessed the greatest long-term predictive accuracy which was enhanced by the EEG diagnosis and alpha average to a level of more than 50%. The Feighner et al. and RDC diagnostic systems were not as relevant for prediction of long-term follow-up status.
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