Extracellular serotonin levels change with behavioral state but not with pyrogen-induced hyperthermia.

Extracellular 5-HT in the anterior hypothalamus/preoptic area (AH/POA) and caudate nucleus of the freely moving cat was measured using in vivo brain microdialysis. Administration of 8-OH-DPAT, a 5-HT1A receptor agonist that decreases 5-HT neuronal activity, decreased extracellular 5-HT in both brain areas. Extracellular 5-HT levels were also examined in relationship to the sleep-wake cycle, because previous data from our laboratory have indicated that behavioral state is the primary determinant of 5-HT neuronal discharge. As with 5-HT neuronal discharge, extracellular 5-HT was increased during active behavioral states and decreased during somnolent periods. These first two sets of findings confirm the ability of the microdialysis technique to measure physiological fluctuations in extracellular 5-HT levels and support the hypothesis that neuronal discharge is a major determinant of extracellular 5-HT levels. Levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA) in the AH/POA were also responsive to changes in behavioral state and administration of 8-OH-DPAT, though fluctuations in extracellular 5-HIAA were less robust and temporally delayed. Finally, extracellular 5-HT and 5-HIAA were examined in the AH/POA during fever induced by systemic injection of the synthetic pyrogen muramyl dipeptide. Previous data from our laboratory have indicated that 5-HT neuronal activity is unaffected by this manipulation, though 5-HT has been implicated specifically in thermoregulation. Pyrogen-induced hypothermia produced no specific change in 5-HT efflux, because any changes noted could be accounted for by behavioral state changes. These data are consistent with the hypothesis that the brain serotonergic system is closely linked to the sleep-wake-arousal cycle. However, extracellular 5-HT may be involved in thermoregulatory processes as part of a global role in modulating neuronal activity in coordination with the behavioral state of the animal.     

Effects of dextromethorphan on regional cerebral blood flow in focal cerebral ischemia

Dextromethorphan (DM), a noncompetitive NMDA antagonist, has been demonstrated to reduce ischemic neuronal damage and edema, but DM's influence on cerebral blood flow has not been extensively studied. In this investigation, it is shown that DM has significant effects on regional cerebral blood flow (rCBF) patterns in a rabbit model of focal cerebral ischemia. rCBF was measured using radioactive microspheres following a 1 h permanent occlusion of the left internal carotid, anterior cerebral, and middle cerebral arteries in rabbits. Somatosensory evoked potentials (SEPs) were used to assess the degree of ischemia; only animals where SEPs were completely abolished were used for a frequency distribution analysis of rCBF. It was found that there were significantly more regions with lower flows in animals treated with normal saline (NS) (n = 7) compared to animals treated with DM (n = 7) (p less than 0.05, ipsilateral left side; p less than 0.001, contralateral right side). The frequency distribution medians were 27.5 ml 100 g-1 min-1 (left) and 70.0 ml 100 g-1 min-1 (right) in the NS group vs. 34.5 ml 100 g-1 min-1 (left) and 80.5 ml 100 g-1 min-1 (right) in the DM group. The left and right hemispheric regional means were 29.4 +/- 20 and 74.3 +/- 23 ml 100 g-1 min-1, respectively, in the NS group vs. 34.4 +/- 16 and 91.0 +/- 28 ml 100 g-1 min-1, respectively, in the DM group.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of age, sex, weight and height on the plasma concentrations in healthy subjects of the acidic metabolites of some biogenic monoamines involved in psychiatric and neurological disorders.

1. The plasma concentrations of unconjugated phenylacetic acid and m-hydroxyphenylacetic acid are lower in male than in female subjects. 2. The plasma concentrations of unconjugated phenylacetic acid and mandelic acid decrease with increasing weight and height for all subjects combined. The same relationships apply for both males and females but are significant only for males. 3. Homovanillic and vanillylmandelic acid concentrations in plasma increase with age. 4. The importance of using age, sex, weight and height matched groups in studies involving the plasma concentrations of some of the trace amine metabolites in psychiatric disorders has been demonstrated. This is particularly the case for phenylacetic acid, the major metabolite of phenylethylamine which is now thought to be a neuromodulator of catecholaminergic neurotransmission.     

Outcome and clinical course in inpatient bulimic women: a 2- to 9-year follow-up study

BACKGROUND: One previous follow-up study suggested that inpatient bulimic women do quite poorly; after an interval of 2 to 5 years, only 13% were recovered. To examine the course and outcome of a sample of patients with bulimia nervosa that was severe enough to require inpatient hospitalization, the authors conducted the following study. METHOD: Women (N = 52) with DSM-III-R bulimia nervosa were sought 2 to 9 years after hospitalization. Prior to contact, a retrospective chart review was conducted to determine global functioning and admission diagnoses. At follow-up, patients participated in a 4 to 6 hour interview that assessed current and lifetime Axis I disorders (SCID-I), current Axis II disorders (PDE), eating behaviors (EAT, BSQ, EDI, PSR), global functioning (GAF), social adjustment (SAS-SR), and treatment and medical problems experienced since discharge. To assess the significance of differences between the recovered and the currently bulimic women, Yates-corrected chi-square tests and two-tailed t tests were used. RESULTS: Of the 52 women, 46 were interviewed, 1 had died, and 5 could not be located. Of the 46 interviewed women, 39% had fully recovered, 20% had partially recovered, and 41% were currently bulimic. The likelihood of recovery increased with length of time since discharge. While medical problems related to the bulimia were few, treatment with phenelzine was associated with three reports of serious hypertensive episodes, one of which led to death. Global functioning before hospitalization, lifetime DSM-III-R Axis I diagnoses, and current Axis II diagnoses were not associated with outcome. CONCLUSIONS: These findings suggest that even severely ill bulimic patients have a significant chance of achieving full recovery.     

Pharmacological modulation of neuropeptides in peripheral mononuclear cells.

The concentrations of beta-endorphin and cholecystokinin were measured in fresh resting peripheral mononuclear cells obtained from rats and human subjects in basal conditions and after different pharmacological treatments. Both in the human and the rat, beta-endorphin concentrations in mononuclear cells, increased after treatment with serotoninergic agonists, decreased after dopaminergic or GABAergic drugs, while the respective antagonists exerted the opposite effect. In vitro, serotoninergic and GABAergic compounds confirmed their roles in the modulation of beta-endorphin in mononuclear cells. Cholecystokinin was never affected by the pharmacological treatments.     

Familial association of intracranial aneurysms and cervical artery dissections.

BACKGROUND AND PURPOSE: The familial occurrence of intracranial aneurysms and cervical artery dissections has been described in different families and supports the hypothesis that a primary arteriopathy may play a role in the pathogenesis of these disorders. Although the basis for this arteriopathy is generally not believed to be similar among cases of intracranial aneurysms and cervical artery dissections, several similarities exist in the epidemiology of these disorders and a common underlying arterial abnormality may be suspected. SUMMARY OF REPORTS: The medical records of all 175 patients with spontaneous dissections of the cervical arteries who were seen at the Mayo Clinic between 1970 and 1989 were reviewed to identify families in which intracranial aneurysms and cervical dissections coexisted. Three families were identified in which intracranial aneurysms and cervical artery dissections were observed among siblings. These families are described in detail. CONCLUSIONS: The familial occurrence of intracranial aneurysms and cervical artery dissections within the same families provides support to the importance of a common underlying arteriopathy in the pathogenesis of both these disorders. The underlying vascular defect may, at least in some cases, be inherited.     

Basic fibroblast growth factor prevents thalamic degeneration after cortical infarction

In the focal infarction model of the rat middle cerebral artery (MCA), the thalamus of the occluded side becomes gradually atrophic, mainly because of retrograde degeneration. We determined whether basic fibroblast growth factor (bFGF) administered intracisternally could prevent this thalamic atrophy. We occluded the left MCA through a small cranial opening, and animals were then divided into two groups. One group received intracisternal injections of recombinant bFGF (1 microgram dissolved in 0.1 ml of saline with 2% rat serum) starting 1 day after occlusion and repeated once a week to a total dose of 4 micrograms by four injections. The other group received vehicle solution by the same schedule. The animals were perfused and fixed at 28 days after occlusion, and histological examination was made at the level of the caudoputamen and thalamus. In the bFGF-treated rats, the area of the posterior ventral thalamus of the occluded side was 93% of that of the contralateral side, i.e., significantly larger than in the normal saline-treated rats (75%, p less than 0.01). The infarction size was not statistically different in the two groups. Microscopic observation indicated that normal-saline-treated animals showed shrinkage and disappearance of thalamic neurons, whereas bFGF-treated groups showed preservation of thalamic neurons. Computerized analysis of the cell size substantiated this observation. To assess the effect of bFGF on astrocytes, bFGF or vehicle solution was injected into normal rats, and their histology was evaluated at 1, 2, and 4 weeks after injection. The bFGF-injected group showed a significant increase in glial fibrillary acidic protein-positive astrocytes in the brain tissue facing the ventriculocisternal system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate effects of intravenous clomipramine on sleep and sleep-related secretion in depressed patients

An i.v. challenge dose of clomipramine (12.5 mg) was given to eight outpatients with major depression. The procedure facilitated the examination of all-night sleep and sleep-related neuroendocrine changes (cortisol, growth hormone, and prolactin). In comparison to baseline saline nights, the patients experienced a profound suppression of rapid eye movement (REM) sleep throughout the night with no rebound recovery in the second half of the night. Furthermore, REM-suppressing effects were noted on the following no-drug night. In contrast, little effect on delta wave sleep was found, except for increased consolidation of delta waves within stage 3 and 4 sleep. Delta sleep measures were significantly correlated with levels of cortisol and growth hormone.     

Studies on the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock

Patients treated with high doses of interleukin-2 (IL-2) because of cancer, develop hemodynamic and vasopermeability changes, that resemble those observed in sepsis. These patients thus provide a unique opportunity to study the early events in the development of septic shock. We analysed the changes that occurred in the contact system of coagulation in plasma from 4 patients, who together received seven 12-day cycles of high doses of IL-2. Levels of factor XII and prekallikrein during the cycles progressively fell to 50 and 30% of their initial levels, respectively, whereas significant increases in plasma factor XIIa- and kallikrein-C1-inhibitor complexes were not observed (in 3 out of 211 samples slightly increased levels of both complexes were found). The reductions in factor XII and prekallikrein were only in part due to protein leakage, since levels were still significantly lower, i.e., 80 and 50%, respectively, when corrected for albumin decreases. Levels of high molecular weight kininogen (HMWK) also decreased during IL-2 therapy, however, this decrease paralleled that of albumin. SDS-PAGE analysis of plasma HMWK did not reveal increased cleavage of this protein. The reduction of factor XII and prekallikrein, corrected for protein leakage, significantly correlated with albumin levels and inversely with daily cumulative weight gain in the patients. Thus, we demonstrate that factor XII and prekallikrein decrease during IL-2 therapy. As these decreases, already observed after 1 day treatment, were disproportional to that of albumin, a negative acute phase reactant, and correlated with signs of the vascular leak syndrome, we favor the explanation that they reflected activation rather than a decreased synthesis of the contact system proteins.(ABSTRACT TRUNCATED AT 250 WORDS)