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Biomedical subjects

S Davis

Publications and source records attributed to S Davis.

At least 235 records · Page 13Linked to original sources

Long-lasting effects of an acute stress on the neurochemistry and function of 5-hydroxytryptaminergic neurones in the mouse brain.

The present experiments investigated the effects of a novel stress challenge (6-min swim test) on behaviour (immobility) and the neurochemistry of cortical 5-hydroxytryptaminergic neurones in CD1 mice. The influence of previous experience of stress (once-daily saline injection) or administration of the noradrenaline and 5-hydroxytryptamine (5-HT) uptake blocker, sibutramine hydrochloride, on any changes was also evaluated. 5-HT2A receptor binding was unchanged 24 h after the last injection of either saline or sibutramine alone but immobility in the swim test was reduced to the same extent by these pretreatments. Seven days, but not 3 h, after the swim test, the density of 5-HT2A receptors and the frequency of 5-HT2A receptor-mediated head-twitches were increased significantly. These increases were prevented by saline injection, but sibutramine prevented the increase in head-twitches only. Sibutramine, but not saline, reduced 5-HT synthesis and 5-HT2A receptor-mediated head-twitches 3 h after the swim and increased synthesis at 7 days. The results indicate that a brief stress can have long-term effects on central 5-hydroxytryptaminergic neurones. Previous experience of stress or sibutramine has marked, but dissimilar, effects on these changes. These findings might be relevant to long-lasting CNS disorders provoked, or aggravated, by stress.

5-Hydroxytryptophan↗

Potentiation or depression of synaptic efficacy in the dentate gyrus is determined by the relationship between the conditioned and unconditioned stimulus in a classical conditioning paradigm in rats.

Learning a conditioned stimulus (CS)-unconditioned stimulus (US) association is accompanied by a variety of long-lasting changes in physiology and chemistry of the synapse in the dentate gyrus. To determine the time course of synaptic modification during learning, changes in the perforant path-dentate gyrus-evoked field potentials were measured in rats performing a classical conditioning (paired tone and footshock) or pseudoconditioning (unpaired tone and footshock) task. Over the course of 4 days of training, differential changes in the evoked response were observed in the two groups. In the conditioned group, there was an increase in the slope of the excitatory postsynaptic potential (EPSP) which started after five tone-shock paired trials and lasted for more than 40 min, outlasting the training session by 20 min. In contrast, a decrease in the slope of the EPSP which commenced after training and lasted for at least 1 h was observed in the pseudoconditioned group. In both groups there was a prolonged decrease in the amplitude of the population spike. The increase in the EPSP was reduced and the duration tended to shorten over days of training in the conditioned group, whereas in the pseudoconditioned group the decrease in the EPSP tended to increase. Off-line analysis of suppression of lever-pressing for food reward during the presentation of the tone, indicated that the conditioned rats had learned the tone-footshock association. Temperature was measured in the dentate gyrus of rats undergoing an identical procedure. In both groups slight temperature increases were observed, with no difference in amplitude and time-course between the groups. The differential effect of conditioning and pseudoconditioning on the evoked response and changes in temperature eliminate the possibility that effects of stress, arousal and muscular effort are the primary cause of the changes in the EPSP. The results suggest that behavioural events can exert bidirectional control of synaptic strength of entorhinal cortex inputs to the dentate gyrus and that the sign of synaptic modification is at least in part determined by the temporal relationship between these events. The data are discussed in terms of the type of neural activity that may mediate the processing of information in the dentate gyrus.

Animals↗

Childhood cancer occurrence in relation to power line configurations: a study of potential selection bias in case-control studies.

Several case-control studies have reported positive associations between childhood cancer and proximity to high-current residential power lines as defined by the Wertheimer-Leeper code. We conducted a study to evaluate whether or not differential nonparticipation of controls as a function of socioeconomic status is likely to account for the observed associations. We assessed the relation of annual family income to the Wertheimer-Leeper code in a sample of 392 households in western Washington state, and we evaluated the magnitude of bias that could occur from differential participation of low- and high-income eligible controls. Very-high-current configurations were most frequently located among households with self-reported family income of less than +15,000 per year, and very-low-current configurations were most frequently located among those with self-reported family income of more than +45,000 per year. In a hypothetical case-control study in which: (1) it was assumed that there is no true etiologic relation between power line configurations and cancer occurrence, and (2) controls with very low income were less likely to participate than others, observed (biased) odds ratios ranged from 1.03 to 1.24. If these results are applicable to other areas where case-control studies of cancer in relation to power lines have been conducted, they suggest that relatively lower participation among exposed controls (as a function of very low income) is not likely to account for the elevated risks of 1.5- to 3-fold that have been observed in these previous studies.

Adult↗

Fractures of the radial head treated by internal fixation: late results in 26 cases.

Twenty-six patients, ranging in age from 14 to 57 years (average 29 years), were evaluated an average of 7 years and 4 months (range 1-14 years) after open reduction and internal fixation of a displaced radial head fracture. Using Mason's classification, there were 11 type II fractures, 9 type III fractures, and 6 type IV fractures with associated dislocation of the elbow. Seven patients had ipsilateral extremity injuries that included fractures of the coronoid process, capitellum, humerus, and distal radius. Using the Broberg and Morrey elbow score, good or excellent results were achieved in all Mason type II and type III fractures. Four of the six Mason type IV fractures were rated good or excellent. Fair results were obtained in two patients who had an associated dislocation of the elbow and multiple ipsilateral extremity injuries. In these two patients, secondary excision of the radial head relieved pain and yielded some improvement in flexion and forearm rotation.

Adolescent↗

Chronic carriage of multidrug resistant Salmonella typhimurium in a cat.

Gastroenteritis caused by a multidrug-resistant Salmonella typhimurium was diagnosed in a 12-week-old kitten. Although the kitten recovered from the acute episode after seven days, it continued to shed salmonella in its faeces for a further 12 weeks. Carriage was finally cleared by administering a 14-day course of treatment with parenteral enrofloxacin. The public health implications of an infection and subsequent carriage in a cat of a salmonella strain known to cause illness in humans is discussed.

Animals↗

Do caries explorers transmit infections with persons? An evaluation of second molar caries onsets.

UNLABELLED: Dental caries explorers may become contaminated during routine caries examinations with pathogenic organisms and thereby potentially transmit infections from one tooth to another within a patient. The purpose of this study was to test the hypothesis that the contamination status of explorers influenced the caries risk of second molars. Two explorer contamination statuses were defined: (1) contamination status 1--explorers which had probed a carious molar just prior to examining the second molar, and (2) contamination status 2--sterile explorers versus explorers which had probed several teeth. Caries examinations were performed by 4 dentists on a cohort of 4th grade students in Belize City. The examination dates and sample sizes (n) were: September-October 1989 (n = 1,277), January 1991 (n = 1,111), and January 1992 (n = 961), and January-February 1993 (n = 861). Within this cohort, there were 221 subjects who (1) had at least one pit and fissure carious onset on a caries-free second molar, (2) had no evidence of dental treatments, and (3) were examined by the same examiner during the entire study. After adjusting for confounding variables, the examination of a second molar with a dental caries explorer in either contamination status 1 or 2 had no substantial effect on the caries risk (rate ratio 0.95, 95% confidence interval: 0.77-1.18, and rate ratio 1.18, 95% confidence interval: 0.89-1.56, respectively). If a true rate ratio of 1.7 or greater was associated with the contamination status 1 and 2, these analyses had more than 99 and 80% probability of detecting it, respectively. CONCLUSIONS: Examining a sound second molar with a contaminated dental explorer either does not affect the caries risk, or results in such a small increase in caries risk that it can only be reliably identified in studies where the exposure of sound teeth to contaminated dental explorers is randomized.

Child↗

Nitro-L-arginine analogues. Dose- and time-related nitric oxide synthase inhibition in brain.

BACKGROUND AND PURPOSE: The purpose of the present study was to measure cortical nitric oxide synthase (NOS) activity and determine the appropriate doses of N omega-nitro-L-arginine methyl ester (L-NAME) or N omega-nitro-L-arginine (L-NNA) for near-complete enzyme inhibition in dogs, cats, and pigs. We anticipated that NOS inhibition was dose- and time-dependent and questioned if the dose-response relationship was related to the specific drug or animal species. METHODS: Saline or L-NAME or L-NNA in escalating doses was administered to pentobarbital-anesthetized pigs, dogs, and cats. Brain temperature and arterial blood gas, hemoglobin, and blood pressure levels were maintained within the physiological range. Cortical tissue was biopsied at baseline and 30, 120, and 360 minutes after agent administration for measurement of NOS activity by isotopic assay of the conversion of [14C]arginine to [14C]citrulline. RESULTS: L-NAME produced > 70% enzyme inhibition at a dose of 20 mg/kg across the species tested. Arterial blood pressure was elevated at 30 minutes after L-NAME treatment. However, consistent decreases in brain NOS activity required a longer period of time. Near-complete inhibition was apparent in most animals by 120 minutes and persisted for 6 hours after administration. A smaller dose of L-NNA was required for > 70% enzyme inhibition in the cats and dogs (10 mg/kg). Near-complete NOS inhibition was evident in most animals at 30 minutes after L-NNA administration, which also persisted for 6 hours. In pigs, this same level of inhibition required 20 mg/kg. CONCLUSIONS: These results suggest that administration of L-NAME and L-NNA diminishes brain NOS activity in a dose- and time-dependent manner and that the duration of effect is at least 6 hours.

Amino Acid Oxidoreductases↗

Repeated episodes of umbilical cord occlusion in fetal sheep lead to preferential damage to the striatum and sensitize the heart to further insults.

The effect of repeated episodes of asphyxia on the fetal cardiovascular system and CNS was examined. The umbilical cord was occluded for 5 min, four times, at 30-min intervals in 11 chronically instrumented fetal sheep (118-126 d). Fetal electrocorticogram (ECoG), cortical impedance, ECG, heart rate, and blood pressure were continuously recorded for 3 d, after which neuronal loss was determined histologically. Each occlusion resulted in fetal hypoxemia and bradycardia accompanied by increased T/QRS ratio. Progressively severe hypotension and lactic acidosis developed during successive occlusions. The ECoG was depressed and cortical impedance increased with each occlusion. During the final occlusion, blood pressure fell to 3.5 +/- 1 kPa and heart rate to 93 +/- 9 bpm, T/QRS ratio increased to 0.44 +/- 0.3, and lactate rose to 7.2 +/- 1.2 mM/L. Three animals died from cardiac fibrillation during recirculation after the third or fourth occlusion. After the asphyxial episodes, blood pressure and heart rate returned to normal, and the T wave was inverted for 310 +/- 155 min. Lactate returned to baseline within 24 h. The ECoG remained depressed for 90 +/- 35 min, and intermittent seizures developed at 3.3 +/- 1.4 h after the last occlusion. Neuronal loss was primarily found in the striatum. The extent of neuronal loss correlated with the degree of hypotension, increase in T/QRS ratio, duration of postasphyxial ECoG depression, and number of seizures. These results indicate that transient asphyxial episodes compromise the ability of the heart to tolerate additional insults and further suggest that neuronal loss is a consequence of cardiovascular compromise secondary to asphyxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of hypergravity on immunologic function.

The purpose of this study was to compare the effects of hypergravity exposure (2g) with those of exposure to space flight in the Cosmos 2044 flight. To do so, rats were centrifuged continuously for 14 days. Two different experiments were carried out on tissue obtained from the centrifuged rats. In the first experiment, rat bone marrow cells were examined for their response to recombinant murine colony stimulating factor-granulocyte/monocyte (GM-CSF). In the second experiment, rat spleen and bone marrow cells were stained in with a variety of antibodies directed against cell surface antigenic markers. These cells were preserved and analyzed on a flow cytometer. The results of the studies indicated that bone marrow cells from centrifuged rats showed no significant change in response to GM-CSF as compared to bone marrow cells from control rats. Spleen cells from flown rats showed some statistically significant changes in leukocytes subset distribution, but no differences that appeared to be of biological significance. These results indicate that hypergravity did not greatly affect the same immunological parameters affected by space flight in the Cosmos 2044 mission.

Animals↗

Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma.

Adenocarcinomas of the esophagus and gastric cardia were once rare. However, for unknown reasons, their incidence has been increasing rapidly over the past 15 years in the United States and parts of Western Europe. In contrast, the incidence of esophageal squamous cell carcinomas has remained relatively constant. To investigate possible reasons for these diverging incidence rates we analyzed data from two population-based case-control studies of cancers of the esophagus and gastric cardia that were conducted among male and female residents of western Washington between 1983 and 1990. Information on body mass index, cigarette use, alcohol intake, and other possible risk factors was collected via personal interviews with 404 cases or their next of kin (including 298 adenocarcinomas and 106 squamous cell carcinomas) and 724 controls identified by random digit dialing. Use of alcohol and cigarettes were significant risk factors for both histological types. The increase in risk for current smokers of 80 or more pack-years compared to nonsmokers was substantially higher for squamous cell cancer [odds ratio (OR) = 16.9; 95% confidence interval (CI) = 4.1-69.1] than for adenocarcinoma (OR = 3.4; 95% CI = 1.4-8.0), as was the increase for persons who typically drank 21 or more drinks/week compared to those who drank <7/week (OR = 9.5; 95% CI = 4.1-22.3 versus OR = 1.8; 95% CI = 1.1-3.1). For squamous cell carcinoma, body mass index was inversely associated with risk, whereas for adenocarcinoma, the highest risk was observed among persons who were in the highest decile of body mass index (OR = 1.9; 95% CI = 1.1-3.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Is consensus reproducible? A study of an algorithmic guidelines development process.

The authors evaluated the reproducibility of a clinical algorithm consensus development process across three different physician panels at a health maintenance organization. Physician groups were composed of primary care internists, who were provided with identical selections from the medical literature and first-draft "seed" algorithms on the management of two common clinical problems: acute sinusitis and dyspepsia. Each panel used nominal group process and a modified Delphi method to create final algorithm drafts. To compare the clinical logic in the final algorithms, the authors applied a new qualitative and quantitative comparison method, the Clinical Algorithm Patient Abstraction (CAPA). Dyspepsia algorithms from all physician groups recommended empiric anti-acid therapy for most patients, favored endoscopy over barium swallow, and had very similar indications for endoscopy. The average CAPA comparison score among final physician algorithms was 6.1 on a scale of 0 (different) to 10 (identical). Sinusitis algorithms from all groups proposed empiric antibiotic therapy for most patients. Indications for sinus radiographs were similar between two algorithms (CAPA = 4.9), but differed significantly in the third, resulting in lower CAPA scores (average CAPA = 1.9, P < 0.03). The clinical similarity of the algorithms produced by these physician panels suggests a high level of reproducibility in this consensus-driven algorithm development process. However, the difference among the sinusitis algorithms suggests that physician consensus groups using a consensus process that a health maintenance organization can do with limited resources will produce some guidelines that vary due to differences in interpretation of evidence and physician experience.

Acute Disease↗

A qualitative approach to the evaluation of a cardiac education follow-up program.

The purpose of this study was to evaluate a Cardiac Education Follow-Up Program from the consumer's perspective. Nine cardiac patients between the ages of 51 and 70 participated. All had diagnoses of myocardial infarction and had taken the Program within the previous month. Patton's (1986) utilization-focused approach to evaluation provided the conceptual orientation and the Davis Patient Interview Guide (DPIG) was used for data collection. Results indicated that four aspects of the Program were of predominant interest/concern: information; support; the cardiologist's session; and the room in which the class was offered. Recommendations for program modification, using the results of the consumer's evaluation, are identified.

Aged↗

Regulation of the expression of NR1 NMDA glutamate receptor subunits during hippocampal LTP.

Several isoforms of the NMDA receptor 1 (NR1) subunits of the ionotropic NMDA (N-methyl-D-aspartate) glutamate receptor contain a consensus site for phosphorylation by protein kinase C (PKC) which, once phosphorylated results in an increased conductance through the receptor channel. Using in situ hybridization, we investigated the expression of NR1 subunits sensitive or insensitive to modification by PKC in the granule cells of the dentate gyrus of the hippocampus, following the induction of long-term potentiation (LTP). A selective 50% increase only in the levels of mRNA NR1 subunits containing this consensus sequence for PKC phosphorylation was seen 48 h after LTP induction. The change in the expression of PKC-sensitive NR1 subunits may be the molecular basis for the increased response of the post-synaptic cell to released glutamate during the maintenance phase of LTP.

Animals↗

Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity.

The EPH-related transmembrane tyrosine kinases constitute the largest known family of receptor-like tyrosine kinases, with many members displaying specific patterns of expression in the developing and adult nervous system. A family of cell surface-bound ligands exhibiting distinct, but overlapping, specificities for these EPH-related kinases was identified. These ligands were unable to act as conventional soluble factors. However, they did function when presented in membrane-bound form, suggesting that they require direct cell-to-cell contact to activate their receptors. Membrane attachment may serve to facilitate ligand dimerization or aggregation, because antibody-mediated clustering activated previously inactive soluble forms of these ligands.

Amino Acid Sequence↗

Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components.

A recently defined family of cytokines, consisting of ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), and interleukin-6 (IL-6), utilize the Jak-Tyk family of cytoplasmic tyrosine kinases. The beta receptor components for this cytokine family, gp130 and LIF receptor beta, constitutively associate with Jak-Tyk kinases. Activation of these kinases occurs as a result of ligand-induced dimerization of the receptor beta components. Unlike other cytokine receptors studied to date, the receptors for the CNTF cytokine family utilize all known members of the Jak-Tyk family, but induce distinct patterns of Jak-Tyk phosphorylation in different cell lines.

Animals↗