Cost-effectiveness analyses.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Tilson.
Explore the source record for details and available documents.
The effects of age on cholinergic markers and receptor-stimulated phosphoinositide hydrolysis was examined in the frontal cortex and striatum of male Fischer-344 rats. Choline acetyltransferase activity was decreased 27% in the striatum of aged (24 month) rats compared to young (3 month) controls. Muscarinic receptor density as measured by [3H]-quinuclidinyl benzilate binding showed a similar 26% decrease in the striatum of aged rats. Phosphoinositide hydrolysis was measured by the release of inositol phosphate (IP) from tissue slices prelabeled with [3H]myoinositol in response to carbachol, norepinephrine, and quisqualate. In the cortex, stimulated IP release was significantly greater in slices from aged rats compared to young rats for all three agonists. In contrast, stimulated IP release was significantly decreased in striatal slices from aged rats compared to young for all three agonists. These data indicate a differential effect of age on agonist-stimulated phosphoinositide hydrolysis in the cortex and striatum. The decreased responsiveness in the latter area may result from the age-related loss of postsynaptic receptors.
Tris(2-chloroethyl)phosphate (TRCP), a flame-retardant plasticizer used in plastics, polymeric foams and synthetic fibers, was studied as part of the National Toxicology Program's class study of phosphate flame-retardants. TRCP was administered at 0, 22, 44, 88, 175 and 350 mg/kg to both sexes of rats and 0, 44, 88, 175, 350 and 700 mg/kg to both sexes of mice in both fourteen day repeat dose and sixteen week subchronic studies. Results of these studies showed that TRCP toxicity in the 14-day studies was limited to modest increases in male rat kidney and female rat liver weights. Little evidence of toxicity was observed in mice in the 14 day studies. Toxicity observed in mice in the sixteen week studies was limited to increased liver weights in both sexes and decreased kidney weights in males. Administration of TRCP to rats for sixteen weeks resulted in increased mortality of both males and females, increased liver and kidney weights and a lesion in the hippocampal region of the brain. The lesion observed in rat brain appeared as loss of the pyramidal neurons of the CA1 region of the hippocampus and was both more common and more severe in female rats. This lesion, which was not observed in mice, is unusual for any chemical and is unique for a trialkyl phosphate such as TRCP. It is speculated that this highly directed toxicity of TRCP might be used as a chemical probe to investigate the role of the hippocampus in behavior and other functions.
The effects of acute or repeated administration of haloperidol on release of dopamine (DA) and homovanillic acid (HVA) from striata of awake rats were studied using a microdialysis probe. A single injection of haloperidol (1 mg/kg, i.p.) produced a time-dependent increase in DA and HVA in the perfusate. Comparative studies in rats anesthetized with 300 mg/kg of chloral hydrate given i.p. found that anesthesia decreased the basal release of DA, but not HVA, and significantly blocked haloperidol-induced increases in DA, while haloperidol-induced increases in HVA were not affected. Studies done in awake rats found that 21 repeated daily injections of haloperidol increased the basal release of DA, but not HVA. Subsequent challenge with haloperidol indicated a significant decrease in responsiveness to haloperidol-induced release of DA, but not HVA, in chronically dosed rats. These data suggest that repeated exposure to haloperidol causes a compensatory increase in extracellular DA release. That these compensatory changes may be associated with the increased therapeutic efficacy or extrapyramidal side effects of neuroleptics following repeated dosing warrants further study.
Two companion post-marketing studies have evaluated the frequency of adverse events amongst patients receiving atracurium. In this second report, we describe the Scottish study and discuss findings in both centres. In this study we compare the frequency of adverse events in 477 patients receiving atracurium with those in 484 patients who received vecuronium. The frequency of reported serious adverse events was low during surgery and in the recovery room. Although the overall incidence of adverse experiences was slightly lower after atracurium, there were no significant difference between the groups in frequency of major adverse events. This type of study is believed to be of value in the future surveillance of new drugs for hospital use.
Through a compassionate plea program (Treatment Investigational New Drug), 4805 patients with acquired immunodeficiency syndrome who previously had experienced Pneumocystis carinii pneumonia (PCP) received zidovudine (Retrovir, formerly azidothymidine). Overall survival at 44 weeks after initiation of therapy was 73% (+/- 2.1%). A positive association was found between survival and pretherapy clinical status as defined by hemoglobin level, functional ability, and stage of disease as measured by time since diagnosis of PCP. For patients with baseline hemoglobin levels of 120 g/L or greater, Karnofsky scores of 90 or greater, and PCP diagnosis within 90 days prior to initiation of therapy, 44-week survival was 88%. Adverse clinical experiences associated with zidovudine therapy were consistent with those from a double-blind, placebo-controlled trial. Survival experience of this large and diverse cohort is consistent with, and extends data from, this clinical trial. Comparison with available natural history data suggests that zidovudine therapy is associated with increased 44-week survival of post-PCP patients with acquired immunodeficiency syndrome.
The purpose of this study was to determine the role that dentate granule cells play in wet dog shakes (WDS), behavioral seizures, and hippocampal cell loss caused by systemic administration of kainic acid (KA). Rats were given bilateral injections of colchicine (COL) into the hippocampal formation to selectively lesion dentate granule cells. Two weeks later, they were injected subcutaneously with KA and were observed for WDS and seizures. Seizures were terminated with pentobarbital 2.5 hr after KA injection, and the rats were killed 48 hr later. The integrity of hippocampal cell populations and projections to the hippocampal formation from entorhinal cortex was assessed with radioimmunoassay and immunostaining for methionine-enkephalin (ME) and dynorphin (DYN) A, as well as with Timm and Nissl staining. Results indicate that COL injections eliminated KA-induced WDS, did not affect the latency to onset of seizures, and potentiated KA-induced cell loss in the CA3 region of hippocampus. COL lesions eliminated ME and DYN immunostaining of granule cells, but not ME immunostaining of entorhinal afferents to the dentate gyrus or Ammon's horn. These findings indicate that granule cells are an essential neuronal link in the expression of KA-induced WDS, but that seizures propagate along other pathways in the limbic system.
Dynorphin and [D-ala2-D-leu]enkephalin (DADLE) were administered directly into the cerebrolateral ventricles of rats and effects on various indices of sensorimotor function and retention of a passive avoidance task were measured. Dynorphin markedly suppressed exploratory motor activity and decreased responsiveness to an acoustic stimulus. Although increases in latency to respond to a noxious thermal stimulus were seen in rats after dynorphin, these changes were always associated with alterations in motor capacity. Injection of dynorphin immediately after a passive avoidance training trial had no significant effect on retention 1 week later. The physiological effects of DADLE were clearly different than those of dynorphin. DADLE produced a biphasic decrease followed by an increase in motor activity and an increased acoustic startle reactivity. DADLE had no effect on reactivity to a noxious thermal stimulus. Posttrial administration of DADLE significantly impaired retention of a step-through passive avoidance task 1 week after training. These data indicate different neurobiological roles for kappa and delta opiate receptors in the central nervous system.
Kainic acid (KA) caused an initial decrease and a subsequent rebound in hippocampal enkephalin (ENK) in rats exhibiting wet dog shakes (WDS) without behavioral convulsions. Antibody to methionine-enkephalin but not dynorphin A(1-8) injected into lateral ventricles attenuated KA-induced WDS, as did naloxone. Granule-cell destroying injections of colchicine into ventral but not dorsal hippocampus caused a 60% reduction of hippocampal ENK and a complete elimination of KA-induced WDS. These studies suggest that release of granule cell ENK, which is 3 times more concentrated in ventral than dorsal hippocampus, plays an important role in KA-induced WDS.
The effects of prior behavioral testing on endocrine function, brain weight, and neurotransmitter receptors were examined. Rats with a history of behavioral testing were significantly different from comparatively naive animals. Prior tested male and females had lower prolactin levels than nontested animals, and serum luteinizing hormone and corticosterone levels were elevated in males. In both sexes, hippocampal brain weight was greater in previously tested animals. However, estimates of brain membrane protein content and neurotransmitter receptors were unaffected by prior testing. These data suggest that prior tested animals respond as if they had experienced a history of chronic stress. Therefore, past history of the organism must be considered in studies designed to evaluate any agent's effect on neuroendocrine or neurochemical parameters.
The cities of Portland, Oregon, and Buffalo, New York, each experienced a restaurant-associated foodborne outbreak of viral hepatitis type A during 1975. Although there were several food handlers ill with viral hepatitis A in each of the restaurants involved, each outbreak was the apparent result of food contamination by a single food handler. In the Buffalo outbreak, food contamination was documented to have occurred for a brief period of time six days prior to onset of any symptoms in the index case. These outbreaks point out the uncommon occurrence of food contamination by individuals ill with type A viral hepatitis, the usefulness of two types of food questionnaires in identifying the vehicle(s) of transmission, and the apparent lack of benefit of widespread immune serum globulin administration as a control measure in this setting.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.