Biomedical subjects

W A Thompson

Publications and source records attributed to W A Thompson.

At least 19 recordsLinked to original sources

PubMed1992

Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia.

The present study was undertaken to evaluate the extent to which an endogenous interleukin-1 (IL-1) response contributes to the hemodynamic and metabolic consequences of sublethal endotoxemia or lethal Gram-negative septic shock. Young, healthy baboons received either a sublethal dose of lipopolysaccharide (LPS) or an LD100 of live Escherichia coli bacteria, and one half of the animals in each group were continuously infused with IL-1 receptor antagonist (IL-1ra). Plasma IL-1 beta was not detected in this model of endotoxemia. Administration of IL-1ra had only minimal effects on the modest hemodynamic and metabolic responses to sublethal endotoxemia, and did not attenuate the plasma cytokine response. In contrast, high circulating levels of IL-1 beta (range 300-800 pg/ml) were seen during lethal E. coli septic shock. IL-1ra treatment significantly attenuated the decrease in mean arterial blood pressure (MAP) (from -72 +/- 8 to -43 +/- 6 mm Hg; P less than 0.05) and cardiac output (from -0.81 +/- 0.17 to -0.48 +/- 0.15 liter/min; P less than 0.05), and significantly improved survival from 43 to 100% at 24 h (P less than 0.05). The plasma IL-1 beta and IL-6 responses to lethal E. coli septic shock were also significantly diminished by IL-1ra treatment (P less than 0.05), whereas tumor necrosis factor-alpha (TNF alpha) concentrations were unaffected. We conclude that an exaggerated systemic IL-1 beta response is characteristic of lethal E. coli septic shock, and contributes significantly to the hemodynamic and metabolic consequences of E. coli septic shock. IL-1ra can significantly attenuate the cytokine cascade and improve survival.

Animals↗

PubMed1985

Pyrazoloquinoline benzodiazepine receptor ligands: effects on schedule-controlled behavior in dogs.

The effects of diazepam and the pyrazoloquinoline benzodiazepine receptor ligands CGS8216, CGS9896, and CGS9895 on schedule-controlled responding were studied in dogs. Responding was maintained under a multiple fixed-interval (FI) 5-min fixed-ratio (FR) 30 response schedule of food presentation. Diazepam (PO) produced dose-related decreases in response rates under FR component. Under the FI, rates first increased and then decreased with increasing doses of diazepam. Diazepam also produced a dose-related disruption of the temporal pattern of responding under the FI as measured by decreases in quarter-life values. CGS8216 IV produced dose-related decreases in response rates under both components. The highest oral dose of CGS8216 also decreased rates in both components. CGS8216 was approximately 100 times more potent by the IV route as compared to the oral route. CGS9896 IV had no significant effect on responding under either component of the multiple schedule. However, with increasing doses of CGS9896 PO, response rates under both components first decreased and then returned to control values. CGS9895 PO was without significant effect on responding. When CGS8216 was administered concomitantly with graded doses of diazepam, the former drug blocked the rate-decreasing effects of diazepam under the FR component, but not the rate-increasing effects of diazepam under the FI. The present results demonstrate that although these three pyrazoloquinolines are benzodiazepine receptor ligands, they do not exhibit diazepam-like effects on schedule-controlled behavior.

Animals↗

PubMed1984

Computed tomography of the gastroesophageal junction.

Computed tomography (CT) of the chest and abdomen has proved to be helpful in the preoperative staging of both esophageal and gastric carcinoma. The gastroesophageal junction however, is a difficult area to evaluate as variations in normal anatomy may mimic pathological processes. Pseudomasses at the gastroesophageal junction can be confused with neoplasm. The CT appearance of the GE junction was evaluated in 150 normal patients. CT scans were also performed on 15 patients with carcinoma involving the GE junction. Twenty cases of benign diseases of the GE junction were also studied by CT. Anatomy--The normal anatomy of the gastroesophageal junction will be illustrated with both line diagrams and CT images. The hepatogastric ligament and the caudate lobe of the liver will be demonstrated and their use in locating the GE junction will be shown. Technique--A short segment describing the appropriate technique for CT of the gastroesophageal junction will follow. The use of oral and intravenous contrast will be discussed. The need for distension of the stomach with effervescent agents and oral contrast as well as the use of decubitus and prone positioning will be emphasized when a mass-like density is seen at the GE junction. Examples will be provided. A pseudomass at the GE junction on a supine CT will be shown that disappears with distension and decubitus scanning. This will be used to lead into the next section on neoplasm in which the first example will have an identical appearance on supine CT images. Neoplasm--The relative incidence of gastric adenocarcinoma and esophageal squamous cell carcinoma at the GE junction will be briefly reviewed. The similar CT appearance of the neoplasms will be described and liberally illustrated. Metastatic involvement of lymph nodes adjacent to the GE junction will also be shown. The staging classification for CT evaluation of GE neoplasms will be reviewed. The utility of preoperative staging of esophageal and gastric neoplasms will be briefly reviewed and applied to the GE junction. Our series of patients with cancer of the GE junction will be discussed. The importance of the CT detection of criteria of inoperability will be demonstrated with examples of metastatic involvement of the liver and lymph nodes as well as direct invasion of adjacent organs. Benign Disease--Examples of benign stricture, hiatal hernia, and achalasia will be illustrated. Our cases where CT scans helped rule out a malignant process that had been suggested on barium studies will be reviewed. Summary and Conclusions--Important points of technique, normal anatomy, benign and malignant disease will be briefly reviewed.

Adenocarcinoma↗

PubMed1984

Behavior maintained under fixed-interval and second-order schedules by intravenous injections of endogenous noncatecholic phenylethylamines in dogs.

The effectiveness of i.v. injections of the endogenously occurring amines beta-phenylethylamine (PEA), N-methyl phenylethylamine (NMPEA) and phenylethanolamine in maintaining schedule-controlled behavior was investigated in dogs. Behavior was maintained under either a fixed-interval (FI) 5-min schedule of i.v. drug injection or a second-order FI 5-min schedule where every fifth response (FR 5) resulted in a 2-sec visual stimulus and the first FR 5 completed after the interval elapsed resulted in both the visual stimulus and i.v. drug injection [FI 5-min (FR 5:S)]. Experimental sessions, with 10 intervals per session, were conducted 5 days/week. Each drug injection was followed by a 5-min timeout period to minimize the direct effects of the drugs on responding. As the dose per injection increased, rates of responding maintained under both schedules by PEA and NMPEA first increased and then decreased. When saline was substituted for drug, responding occurred at very low rates. PEA and NMPEA were approximately equieffective and equipotent in maintaining responding under the FI 5-min schedule. PEA maintained somewhat higher rates under the FI 5-min (FR 5:S) schedule; rates maintained by NMPEA under the second-order schedule were comparable to those maintained under the simple FI schedule. Phenylethanolamine failed to consistently maintain responding under either schedule. Injections of PEA and NMPEA controlled overall patterns of positively accelerated responding under both schedules, whereas the local pattern of responding under the second-order schedule was under the control of both the brief stimulus presentations as well as drug delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Mutagenicity in the vicinity of a lead smelter.

The mutagenicity of the environment in the vicinity of a lead smelter was examined for 3 years by studies of changes in the frequencies of male germinal mutations of the waxy-C system of Zea mays and somatic mutations of the stamen hair system of Tradescantia. A transect was run at 0.3, 1.7, 3.2, 7.4, and 11.4 km predominantly downwind from the smelter. The mutagenic responses vary between years, within a year, and with distance. Mutation frequencies are both directional and nondirectional with distance. Concentrations of Pb, Cd, Cu, and Zn measured in soil samples show directional changes with distance each of the 3 years, and joint monotonicity is observed in some cases between mutation frequency with distance and metal concentrations with distance. Of a total of ten experiments with both Zea mays and Tradescantia, eight show significantly higher mutation frequencies at one or more locations close to the smelter than at locations more distant or at other controls.

Environmental Pollutants↗

PubMed1977

On the treatment of grouped observations in life studies.

Assuming a model of proportional failure rates, Cox (1972) presents a systematic study of the use of covariates in the analysis of life time. The treatment of tied observations is a particularly troublesome point in both theory and application. It appears that grouping rather than discrete time is the right way to handle ties. This paper studies methodology for grouped observations. A logistic model, which makes explicit use of Cox's earlier binary data methods, is introduced and illustrated with a numerical example. The model leads back to Cox's proportional failure rates when the lengths of the grouping intervals approach zero. This limiting process provides some enlightenment on controversial issues such as ignoring intervals in which no failures occur, determining whether the covariates may be functions of time, and treating ties.

Humans↗

PubMed1976