PubMed Health⌕ Search

Biomedical subjects

H Tilson

Publications and source records attributed to H Tilson.

At least 19 recordsLinked to original sources
PubMed1999

Understanding the NIH review process: a brief guide to writing grant proposals in neurotoxicology.

During the past two years, the National Institutes of Health have made significant changes in the review process for investigator-initiated research grant applications in neurotoxicology. First, study sections that formerly dealt with toxicology and alcohol, respectively, have been merged. Neurotoxicology grant applications are now reviewed by ALTX-3, a study section in which the majority of members have expertise in the neuronal, biochemical or behavioral effects of alcohol, but usually not other neurotoxicants. Second, the NIH has instituted new review criteria, in which significance, approach, innovation, investigator expertise, and research environment must all be explicitly addressed by the reviews. In this article, past and present members of the ALTX-3 study section describe the NIH review process, with emphasis on how neurotoxicology applications are handled, and provide guidelines for preparing competitive applications.

Financing, Organized↗
PubMed1996

Risk assessment for neurobehavioral toxicity: SGOMSEC joint report.

Behavioral end points for neurotoxicity risk assessment have been developed and examined over the past three decades. They are now ready to move from simple qualitative guidelines, such as exemplified by reference doses, to more quantitative models, such as benchmark doses, based on dose-response information. Risk assessors, confronted by a wider array of methodologies and data than in the past, should be offered guidance in interpretation because now they have to deal with unaccustomed questions and problems. These include reversibility, susceptible populations, multiple end points, and the details of dose-response and dose-effect distributions.

Animals↗
PubMed1993

Record linkage to conduct an epidemiologic study on the association of rheumatoid arthritis and lymphoma in the Province of Saskatchewan, Canada.

The objective of this effort was to assess the utility of the large automated database in Saskatchewan as a resource for pharmacoepidemiologic studies. To this end a study was undertaken to test the hypothesis that rheumatoid arthritis (RA) increases the risk of cancer, especially lymphoma. This was done by performing a retrospective cohort study based on record linkage data from Saskatchewan Health. From hospital discharge diagnoses in the hospital file an exposed group (RA) and two comparison groups matched to the RA group by age and sex were identified: (1) the RA group consisted of people with a discharge diagnosis of rheumatoid arthritis; (2) the osteoarthritis (OA) group consisted of people with OA discharge diagnoses; and (3) a comparison (CN) group consisted of hospitalized people with no discharge diagnoses of arthritis. Drug exposures were determined by linkage with the Prescription Drug File, cancer outcomes were determined by linkage with the Cancer Foundation file, and length of eligibility in the health plan and demographics information were determined by linkage with the registration file. The data were checked for quality of linkages across files and consistency with study definitions. Of 13,333 identified subjects, 2.8% were excluded because of apparent incorrect assignment to study group or age group or because of ineligibility in health plan during the study period. In order to decrease the possibility of misclassification of exposure (rheumatoid arthritis), hospital discharge diagnoses were used to exclude subjects with any inflammatory rheumatic diseases (IRD) from the CN (7.8%) and OA (8.3%) groups and subjects with IRD other than rheumatoid arthritis (4.6%) from the RA group. To decrease selection bias, those who had cancer within 1 year of enrollment (to exclude those in hospital because of symptoms of undiagnosed cancer) were excluded. Because RA subjects hospitalized by a rheumatologist were most likely to have valid rheumatoid arthritis diagnoses, each analysis was run twice: once with the entire RA group (N = 1210) and once with those in the RA group who were rheumatologist-hospitalized (N = 646). Logistic regression of incidence was used to control for age, sex, and use of individual disease-modifying anti-rheumatoid drugs (DMARDs). For the rheumatologist-hospitalized RA group compared to the CN group, a significant 4-fold greater risk for lymphoma/myeloma was detected when DMARD use was not controlled for, and a 3.4-fold increase in risk was detected even when use of individual DMARDs was controlled for.(ABSTRACT TRUNCATED AT 400 WORDS)

Arthritis, Rheumatoid↗
PubMed1993

An international comparison of case definition of severe adverse cutaneous reactions to medicines.

There is substantial intercountry variation in the proportion of cases of toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) which are attributed to specific drugs. This study was undertaken to determine whether these differences might reflect biases in diagnosis of these conditions. A total of 138 reactions in 5 countries originally diagnosed as TEN or SJS were coded on to standardised forms. A single observer blind to the original diagnosis assessed each case according to specified criteria. This observer's diagnoses were compared with the original diagnoses. Overall, 111 of the 138 cases had information adequate for assessment. The blinded observer agreed with the diagnosis for 61% of cases where the original diagnosis was TEN and 58% of cases where the original diagnosis was SJS. There was no significant difference in rates of agreement when reactions attributed to sulphonamide antibiotics were compared with reactions attributed to other drugs. There were substantial and significant differences in percentage agreement between the blinded observer's diagnosis and the original diagnoses between countries. The lowest rates of agreement between the blinded observer and the original reports occurred in the US. Our results illustrate the difficulty in comparing reaction rates based on spontaneous reports between countries where the systems for gathering such reports vary. This illustrates the need for a minimum quantity of standard data and precise definitions of reactions if spontaneous reports of adverse reactions are to provide useful information about severe adverse skin reactions associated with drugs.

Adolescent↗
PubMed1991

Age-related changes in receptor-mediated phosphoinositide hydrolysis in various regions of rat brain.

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.

Aging↗
PubMed1990

Subchronic toxicity studies indicate that tris(2-chloroethyl)phosphate administration results in lesions in the rat hippocampus.

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.

Animals↗
PubMed1989

Repeated haloperidol administration changes basal release of striatal dopamine and subsequent response to haloperidol challenge.

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.

Animals↗
PubMed1989

Atracurium--a post-marketing surveillance study: U.K. study and discussion.

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.

Anesthesia Recovery Period↗
PubMed1988

Survival experience among patients with AIDS receiving zidovudine. Follow-up of patients in a compassionate plea program.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Dentate granule cells are essential for kainic acid-induced wet dog shakes but not for seizures.

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.

Animals↗
PubMed1986

Behavioral effects of centrally administered dynorphin and [D-ala2-D-leu] enkephalin (DADLE) in rats.

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.

Acoustic Stimulation↗
PubMed1986

Enkephalin contained in dentate granule cells is important for kainic acid-induced wet dog shakes.

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.

Animals↗
PubMed1983

Long-term effects of behavioral testing on serum hormones and brain weight.

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.

Aging↗
PubMed1977

Foodborne hepatitis A infection: a report of two urban restaurant-associated outbreaks.

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.

Adult↗