Parallel dose-response studies of the voltage-dependent Na+ channel antagonist BW619C89, and the voltage-dependent Ca2+ channel antagonist nimodipine, in rat transient focal cerebral ischaemia

We have compared two classes of putative neuroprotectants, the voltage-dependent Na+ channel antagonist BW619C87 [4-amino-2-(4-methyl-1-piperazinyl)-5-(2,3,5-trichlorophenyl) pyrimidine], and the voltage-dependent Ca2+ channel antagonist nimodipine, in a rat model of transient focal cerebral ischaemia. BW619C87 (10-50 mg/kg) or nimodipine (10-100 microg/kg) were injected intravenously 5 min before induction of 2 h transient focal cerebral ischaemia via intraluminal thread occlusion of the middle cerebral artery. BW619C87 was a potent neuroprotectant over the range tested, maximally reducing the volume of hemispheric ischaemic damage by 51% at the 50 mg/kg dose. Nimodipine maximally reduced ischaemic damage by 33% at the 50 microg/kg dose, although the maximal level of neuroprotection afforded by BW619C89 and nimodipine was not significantly different. This is the first study to compare these two classes of drug directly in a model of middle cerebral artery occlusion with reperfusion, and it supports the effectiveness of both as neuroprotectants.     

In vitro susceptibilities of Candida dubliniensis isolates tested against the new triazole and echinocandin antifungal agents

Candida dubliniensis is a newly recognized fungal pathogen causing mucosal disease in AIDS patients. Although preliminary studies indicate that most strains of C. dubliniensis are susceptible to established antifungal agents, fluconazole-resistant strains have been detected. Furthermore, fluconazole-resistant strains are easily derived in vitro, and these strains exhibit increased expression of multidrug resistance transporters, especially MDR1. Because of the potential for the development of resistant strains of C. dubliniensis, it is prudent to explore the in vitro activities of several of the newer triazole and echinocandin antifungals against isolates of C. dubliniensis. In this study we tested 71 isolates of C. dubliniensis against the triazoles BMS-207147, Sch 56592, and voriconazole and a representative of the echinocandin class of antifungal agents, MK-0991. We compared the activities of these agents with those of the established antifungal agents fluconazole, itraconazole, amphotericin B, and 5-fluorocytosine (5FC) by using National Committee for Clinical Laboratory Standards microdilution reference methods. Our findings indicate that the vast majority of clinical isolates of C. dubliniensis are highly susceptible to both new and established antifungal agents. Strains with decreased susceptibilities to fluconazole remained susceptible to the investigational agents as well as to amphotericin B and 5FC. The increased potencies of the new triazole and echinocandin antifungal agents may provide effective therapeutic options for the treatment of infections due to C. dubliniensis.     

Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19)

The effects of a long period of relatively high and nearly constant levels of Somatostatin (SRIF) on the control of food ingestion and body weight gain were investigated; weight gain occurs via concurrent modifications of food and fluid intake and in vitro gut motility. Fluid intake was not influenced by SRIF treatment. Food intake, body weight, body weight gain, and gut motility decreased after SRIF treatment, and, in some cases, these effects were dose-dependent. Food intake increased significantly during light phase of SRIF treatment. Thus, SRIF treatment produces facilitation of food intake in the light and inhibition in the dark. The suppression seen in the dark may be the result of a preferential activation of the inhibitory response. The increase of food intake during the light may be explained by a decreased availability of body fats as fuels for metabolism since SRIF inhibits GH release, which is involved is the breakdown of adipose tissue into fuels; lower fats synthesis during nocturnal feeding; or both. Decreased gastrointestinal motility also may explain the lower food intake and decreased body weight gain following SRIF treatment.     

Activation of the locus coeruleus after amygdaloid kindling

PURPOSE: Substantia nigra (SN) and locus coeruleus (LC) neurons are implicated in the propagation and suppression of amygdaloid seizures. Both structures are activated concomitant with amygdaloid seizure discharges. Their mechanisms of activation, however, remain to be elucidated. SN firing is not associated with the induction of Fos immunoreactivity (ir), a marker of excitatory neuronal activation. LC has not been studied. The purpose of this investigation was to determine if amygdala-kindled generalized seizures could induce Fos-ir in the LC. METHODS: Female Sprague-Dawley rats were killed after generalized seizures induced by amygdala electrical stimulation and stained by using Fos immunocytochemistry. The number of Fos-ir neurons was compared between 15 animals with generalized seizures and four implanted, unstimulated controls. RESULTS: LC-ir neurons were significantly (p < 0.05) more prevalent after seizures than in control animals. Their numbers correlated very highly with Fos-ir in the central nucleus of the amygdala (p < 0.0001). No Fos induction was observed in LC in controls or in the SN in either group. CONCLUSIONS: Amygdala-induced generalized seizures result in Fos-ir in the LC but not in the SN. This is consistent with different mechanisms of activation possibly involving disinhibition in the SN and direct excitation in the LC.     

Path analysis of aptitude, personality, and achievement scores in Brazilian twins

Achievement at school and performance on the Dominoes test, the Differential Aptitude Tests (DAT), and Griéger's Characterological Questionnaire of 45 monozygotic and 46 same-sex dizygotic pairs of twins were analyzed using a new linear model for familial corrrelation. For 14 of the 20 sets of data, the genotype's contribution to the total variance is estimated to be higher than 50%. The effect of common environment seems to be important only for achievement in Arts.     

Estimating the impact of health services in a community

The advantages of clinical and mechanical combination of observations for prediction are mutually reinforced by an application of Bayesian statistics. The technique is shown to be particularly advantageous in a situation which is characterized by a paucity of observations available to suppliment a prior expert judgment. The approach also presents a basis for evaluating relative expertise and tracing the learning experience of experts. Taking the community as the organizational level of analysis, data on the classification of aged persons in Durham County, North Carolina, and data on the changes in classification of these individuals within the population over time are gathered and studied. These data are combined with clinical judgments of changes as a demonstration of the merits of the technique developed in this paper.     

A drug experience registry

The Drug Exerience Registry is a system for the recording and filing of drug-related patient events in a readily retrievable form. The purpose of the registry is to accumulate information on adverse drug reactions, unusual therapeutic successes of failures, and other experiences that may be useful for education, research or promotion of rational drug therapy. Data are recorded on case report forms which are categorized by organ-disease system affected, the clinical event and involved drug(s). These are then filed in the clinical event file along with literature synopses that serve as guides in evaluating the incidents and determining proper therapy. A drug file serves as a cross index to the clinical event file and allows one to quickly locate clinical events involving a drug. Both files contain sufficient hospital data to allow later retrieval of additional information if needed.     

Medical sculpture: a valuable aid to patient rehabilitation

Silicone rubber is the most satisfactory material for cosmetic prostheses. It has a soft, lifelike texture, is easily worked and easily colored and is strong enough to withstand frequent application and removal. Examples of patients referred to the medical sculptor include those with congenital defects of one or both ears, loss of the nose or an eye and orbit due to cancer surgery, loss or absence of fingers or parts of the hand and those who have had radical breast surgery.     

Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer

Many previous studies evaluating various hormone levels in males with subnormal semen analyses were performed when the normal semen parameters were considerably higher than now. This study evaluated sera levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TET), free TET, and prolactin (PRL) in 60 males with oligospermia and decreased motility according to recent World Health Organization standards. Three separate groups were evaluated: group 1, motile density (MD) < 5 x 10(6)/mL (but not azoospermia); group 2, 5 < or = MD < 10 x 10(6)/mL; group 3, MD > 10 x 10(6)/mL, but % motility < 30%. There were no significant differences in mean FSH levels between groups. Overall FSH was increased in 47.1% of the cases. In contrast, mean LH levels were normal in all three groups. Only 17.3% of the entire group had elevated LH levels. The TET level was below normal in 32.3% of the entire group, with a fairly equal distribution between the three groups. Overall, only 7.8% had elevated PRL levels, with the highest percentage found in group 3 (22.2%). Only a small minority of patients with increased FSH had low TET levels compared to 48.0% of those with normal FSH. These data demonstrate that when using the lower semen parameters, the most common serum hormone abnormality is increased FSH; men with MD < 5 x 10(6)/mL do not have a higher incidence of elevated FSH than those with higher MDs.(ABSTRACT TRUNCATED AT 250 WORDS)