Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

Management of pediatric pontine gliomas

We present 36 consecutive patients with intrinsic glioma of the pons. Tumors with exophytic expansion were excluded. There were 16 females and 20 males, ranging in age from 2 to 13 years, median 6 years. The most common presenting symptoms were cranial nerve dysfunction. unsteadiness of gait, and hemiparesis. Computed tomography (CT) showed a hypodense (17/21) or isodense (4/21) expansion of the pons. Five tumors had areas of contrast enhancement. Following information about prognosis and possible types of management, parents decided for or against radiation therapy: twentyfour children underwent irradiation and 12 did not. Median survival among children receiving a full course of irradiation was 280 days, compared to 140 days in an equivalent group of non-irradiated children. Hemiparesis presenting without cranial nerve symptoms and contrast enhancement on CT scan were poor prognostic factors, whereas sex, age, and duration of symptoms at diagnosis were unrelated to prognosis.     

Extracellular dopamine and neurotensin in rat prefrontal cortex in vivo: effects of median forebrain bundle stimulation frequency, stimulation pattern, and dopamine autoreceptors

In vivo microdialysis coupled with HPLC and radioimmuno-assay techniques were used to analyze dopamine (DA) and neurotensin (NT) in prefrontal cortical extracellular fluid following electrical stimulation of mesocortical axons. The release (overflow into the extracellular fluid) of both DA and NT increased with increasing number of impulses and with frequency. At the lowest frequency tested (2.5 Hz), DA release was significantly increased, while there was no significant increase in the release of NT. As the frequency of stimulation was increased from 2.5 to 20 Hz, the ratio of extracellular DA:NT decreased exponentially. Stimulation in a burst pattern produced greater release of both DA and NT than tonic stimulation when the number of impulses per second and the total number of impulses were held constant. Furthermore, blockade of DA autoreceptors with sulpiride stereoselectively increased the release of DA while decreasing the release of NT. These data suggest that the release of coexistent molecules (DA and NT) from mesocortical neurons can be influenced by physiological and pharmacological factors such that under certain conditions simultaneous or differential release may occur.     

Single-channel K+ currents recorded from the somatic and dendritic regions of cerebellar Purkinje neurons in culture

Voltage-sensitive K+ channels were studied in rat cerebellar Purkinje neurons in culture using the single-channel recording technique. Recordings in the cell-attached and outside-out configuration revealed multiple voltage-sensitive K+ channel types in patches from both the somatic and the dendritic regions. K+ channel types were present in all patches studied. The same channel types were observed in somatic and dendritic recordings. Channel types were identified by reversal potential, single-channel conductance, voltage sensitivity, and patterns of activity. In cell-attached patches recorded under physiological conditions, 3 channel types were identified. Mean single-channel conductances were 92, 57, and 12 pS. All 3 channel types were activated by membrane depolarization. Similar channel types were identified in inside-out and outside-out patches recorded under physiological conditions. Two additional channel types were identified in the outside-out patches, with mean single-channel conductances of 41 and 26 pS. In cell-attached recordings under symmetrical K+ conditions, 6 channel types were identified. Mean single-channel conductances were 222, 134, 39, 25, 14, and 15 pS. Channel types with mean conductances of 222, 134, and 39 pS required membrane depolarization for activation. A comparison of channel properties indicated that these channel types correlated with the 3 channel types observed in cell-attached patches under physiological conditions. The 3 smaller-conductance channel types (25, 14, and 15 pS) were active at potentials around rest or at hyperpolarized membrane potentials. Two K+ channel types (39 and 25 pS) were commonly associated with the late phase of extracellularly recorded spontaneous spike events, suggesting a functional role in the repolarizing phase of somatic and dendritic action potentials. These results demonstrate that voltage-sensitive K+ channels are a prominent component of both the somatic and the dendritic membrane of the cerebellar Purkinje neuron and support the view that multiple voltage-sensitive K+ channel types contribute to the membrane functions of both cellular regions in this CNS neuronal type.     

The effects of hyponatraemia and subarachnoid haemorrhage on the cerebral vasomotor responses of the rabbit

Impairment of cerebral autoregulation and development of hyponatraemia are both implicated in the pathogenesis of delayed cerebral ischaemia and infarction following subarachnoid haemorrhage (SAH) but the pathophysiology and interactions involved are not fully understood. We have studied the effects of hyponatraemia and SAH on the cerebral vasomotor responses of the rabbit. Cerebrovascular reactivity to hypercapnia and cerebral autoregulation to trimetaphan-induced hypotension were determined in normal and hyponatraemic rabbits before and 6 days after experimental SAH produced by two intracisternal injections of autologous blood. Hyponatraemia (mean plasma sodium of 119 mM) was induced gradually over 48 h by administration of Desmopressin and intraperitoneal 5% dextrose. Sham animals received normal saline. The cerebrovascular reactivity (% change +/- SD in cortical CBF/mm Hg PaCO2, measured by hydrogen clearance) of hyponatraemic (4.8 +/- 3.0%) and SAH (1.3 +/- 2.0%) animals was significantly less (p less than 0.05) than control (11.6 +/- 4.0%) and sham (8 +/- 2.0%) animals, whereas the reactivity of hyponatraemic-SAH animals was preserved (9.8 +/- 6.0%). Hyponatraemia and SAH alone each significantly impaired CBF autoregulation but their combined effects were not additive. Systemic hyponatraemia impairs normal cerebral vasomotor responses but does not augment the effects of experimental SAH in the rabbit.     

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.     

A benign tumor of the sciatic nerve: case report and review of the literature

Tumors arising from the sciatic nerve are a rare occurrence. A case is described of such a tumor developing as a large painless mass in the posterior right midthigh. The preoperative diagnosis was easily achieved by means of ultrasonography and computed tomography. Excision of the tumor, with preservation of the involved nerve, was performed. Microscopic examination showed a neurofibroma with however some features of a schwannoma. Problems of histological diagnosis and treatment are emphasized.     

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.