Antagonism of 5-HT3 receptors attenuates the effects of ethanol on extracellular dopamine

The effect of a 5-HT3 antagonist, ICS 205-930, on ethanol-induced changes in extracellular dopamine, was investigated with in vivo microdialysis. Pretreatment of rats with ICS 205-930 effectively attenuated the subsequent increases in dopamine, in both the nucleus accumbens and corpus striatum. This suggests that 5-HT may be involved in the effects of ethanol on dopaminergic systems.     

Diazepam-binding inhibitor and corticotropin-releasing hormone in cerebrospinal fluid

Diazepam-binding inhibitor (DBI) is a neuromodulatory peptide for gamma-aminobutyric acid (GABA) neurotransmission. Cerebrospinal fluid (CSF) levels of DBI have been found to be elevated in depression. CSF levels of the peptide corticotropin-releasing hormone (CRH) have also been found to be elevated in depression. Therefore, we examined for a relationship between DBI and CRH in human CSF. We found significant positive correlations between CSF levels of DBI and CRH in depressed patients, pathological gamblers, and normal controls. These data, along with the elevated CSF levels of DBI in depression, suggest the possibility that DBI may have a role in coordinating responses to stress in humans in addition to its possible role in the pathophysiology of depression.     

Use of simple tasks to test for impairment of complex skills by a sedative

Examination of the effect of three doses of pentobarbital on the comparative performance of a complex psychomotor taks with two simple neuromotor tasks, i.e., standing steady and pendulum eye tracking, revealed a high correlation. These simple tasks could be used as measures of intoxication since they do not require extensive training. Examination of the complex task impairment blood level ratio revealed that impairment relative to blood level was much greater in the absorption phase. This changing ratio underscores the point that blood levels alone are not an adequate estimate of intoxication.     

Lung endocrine-like cells in hamsters treated with diethylnitrosamine: alterations in vivo and in cell culture.

Diethylnitrosamine is known to cause squamous cell carcinoma and adenocarcinoma of the lung in Syrian golden hamsters. Sections of lungs obtained from hamsters treated with the systemic carcinogen diethylnitrosamine showed a significant increase in the number of argyrophilic cells of neuroepithelial bodies. The hyperplastic response was retained at least 4 weeks after cessation of treatment. To examine whether these affected cells exhibited enhanced survival in vitro, lung cells were dissociated with Pronase and grown in culture. After 7 days, argyrophilia, dense-cored vesicles, and corticotropin-like immunoreactivity were observed in many of the cells derived from hamsters treated for 5 or 8 weeks. These findings suggest that the endocrine-like cells of neuroepithelial bodies are affected by diethylnitrosamine as evidenced by a numerical increase in vivo and by the properties exhibited by cells in vitro. The relationship of this diethylnitrosamine-induced reaction to bronchial carcinoid tumors or small-cell carcinoma of the lung remains to be established.     

Effect of anticonvulsants on plasma haloperidol and thioridazine levels

Patients who had therapeutic plasma levels of phenobarbital and/or diphenylhydantoin had significantly lower plasma levels of haloperidol and mesoridazine, the active metabolite of thioridazine, than patients who did not receive anticonvulsants. Plasma thioridazine levels per se were not affected by concomitant anticonvulsant treatment. Biperiden, an antimuscarinic, antiparkinsonian agent, did not affect the plasma levels of these three neuroleptics.     

Effects of adinazolam and diazepam,alone and in combination with ethanol,on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers

Summary Effects on psychomotor and cognitive performance of adinazolam (15 or 30 mg), alone and in combination with ethanol (0.8 g/kg), were studied in healthy male volunteers and compared to effects of 10 mg diazepam.Adinazolam 30 mg produced relatively long-lasting impairments on tests of tracking, attention, verbal and nonverbal information processing, and memory. Adinazolam 15 mg resulted in descreased visual information processing. Adinazolam decreased supine mean arterial pressure, but only the 15 mg resulted in a tendency for decreased plasma norepinephrine concentrations.After standing for 5 min, 30 mg adinazolam was associated with increased heart rate.Although ethanol consumption produced additive decrements on a continuous performance task, there was little evidence to support a synergistic effect.Adinazolam 30 mg was accompanied by increased self-reports of side effects, especially drowsiness.     

Lack of relationship between in vitro tumor cell growth and prognosis in extensive-stage small-cell lung cancer

The ability to establish a continuously growing tumor cell line from fresh tumor specimens has been associated with shortened survival in some human malignancies. Therefore, we assessed the relationship between survival and in vitro tumor cell growth from specimens obtained during routine staging procedures in 68 consecutive patients with untreated, extensive-stage small-cell lung cancer (SCLC) who received etoposide/cisplatin chemotherapy. Three groups of SCLC patients could be distinguished: (1) 23 patients in whom a tumor cell line was established in vitro; (2) 28 patients in whom tumor-containing specimens were cultured but in vitro growth did not occur; and (3) 17 patients in whom no tumor-containing specimen could be procured. No significant difference in response rates to chemotherapy of the three groups was noted. Poor performance status (P2 = .001), male gender (P2 = .0008), liver metastases (P2 = .0033), brain metastases (P2 = .0152), and the ability to obtain a tumor-containing specimen from the patient for laboratory culture (P2 = .0005) were all significant independent predictors of decreased survival in this patient population. While the ability to obtain a tumor cell specimen for cell culture using routine staging and diagnostic procedures identified patients with shortened survival, we found no significant survival differences between patients whose tumor cell specimens grew in cell culture v those that did not (median survival of 7 months v 11 months, P2 = .72). Our study indicates that the clinical outcome of extensive-stage SCLC patients from whom tumor cell lines can be established is not significantly different than in those cases from whom tumor-containing specimens could not be grown in vitro.     

Plasma amine metabolites before and after withdrawal from neuroleptic treatment in chronic schizophrenic inpatients

Plasma catecholamine metabolites were measured in paired blood samples from 22 subjects with chronic schizophrenia. One sample was drawn while patients were on a stable dose of neuroleptic medication; the second was drawn 6 weeks after discontinuation of medication. In comparison with baseline values during neuroleptic treatment, there was a significant increase in the plasma concentration of the norepinephrine metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), and a trend toward an increase in the plasma concentration of the dopamine metabolite, homovanillic acid (HVA), in the medication-free subjects. There were no significant correlations between plasma MHPG or HVA concentrations and the corresponding ratings of psychopathology for these patients.