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Biomedical subjects

D J Cook

Publications and source records attributed to D J Cook.

At least 253 records · Page 14Linked to original sources
PubMed1992

Effect of ketamine HCl on norepinephrine disposition in isolated ferret ventricular myocardium.

The purpose of this study was to determine if ketamine altered the release or disposition of norepinephrine at adrenergic nerve terminals in isolated ferret myocardium. In superfused right ventricular strips, the effect of ketamine on norepinephrine release and uptake was determined. Dihydroxyphenylglycol, the intraneuronally derived metabolite of norepinephrine, served as an index of neuronal uptake and was also measured in superfusate. Pharmacological manipulation of selective aspects of adrenergic transmission with corticosterone, yohimbine, clorgyline and desmethylimipramine allowed the primary site of action of ketamine to be established. Quantitation of tissue norepinephrine content after the experiments provided another means to evaluate ketamine's effect on norepinephrine release as well as to estimate the density of adrenergic innervation in ferret myocardium. Norepinephrine and dihydroxyphenylglycol were quantitated by high-pressure liquid chromatography with electrochemical detection. Ketamine increased norepinephrine overflow and decreased the efflux of dihydroxyphenylglycol in isolated myocardium. Studies in the presence of the clorgyline suggest that ketamine does not increase norepinephrine overflow by means of monoamine oxidase inhibition, and studies in the presence of desmethylimipramine and corticosterone indicate that ketamine does not augment norepinephrine release. Quantitation of tissue norepinephrine content demonstrates that ketamine does not cause depletion of myocardial catecholamines. The ketamine-induced increase in norepinephrine overflow and the observed decrease in dihydroxyphenylglycol production suggest that inhibition of the neuronal uptake of norepinephrine is the primary mechanism of ketamine's effect in isolated myocardium.

Animals↗
PubMed1991

Stress ulcer prophylaxis in the critically ill: a meta-analysis.

PURPOSE: To examine the differential effect of stress ulcer prophylaxis on overt bleeding, clinically important bleeding, and mortality in critically ill patients. DATA IDENTIFICATION: Computerized bibliographic search of published and unpublished research. STUDY SELECTION: Independent review of 168 articles identified 42 relevant randomized trials for inclusion. DATA ABSTRACTION: The validity, population, intervention, and outcomes of each trial were evaluated. RESULTS: Stress ulcer prophylaxis with antacids (odds ratio 0.40 [95% confidence interval (CI) 0.20 to 0.79]) or histamine-2-receptor antagonists (odds ratio 0.29 [95% CI 0.17 to 0.45]) decreases the incidence of overt gastrointestinal bleeding. Histamine-2-receptor antagonists are more effective than antacids at reducing overt hemorrhage (odds ratio 0.56 [95% CI 0.33 to 0.97]). A significant reduction in clinically important gastrointestinal hemorrhage is evident only with histamine-2-receptor antagonist therapy. There is a trend favoring antacids over sucralfate in the outcome of clinically important bleeding (odds ratio 0.65 [95% CI 0.16 to 2.49]); however, there are insufficient data to evaluate histamine-2-receptor antagonists versus sucralfate. No difference in mortality between treated and untreated patients was found. CONCLUSIONS: Overt gastrointestinal bleeding in critically ill patients is reduced by prophylaxis with antacids or histamine-2-receptor antagonists. Histamine-2-receptor antagonists are more effective than antacids at decreasing overt bleeding and are more effective than no treatment at reducing the incidence of clinically important bleeding. Mortality rates in the intensive care unit are not decreased by stress ulcer prophylaxis.

Critical Care↗
PubMed1991

CD18 adhesion receptors, tumor necrosis factor, and neutropenia during septic lung injury.

Sequestration of neutrophils (PMNs) in the pulmonary microvasculature and associated neutropenia are characteristic features of experimental models of septic lung injury. The etiology of altered PMN kinetics during septic lung injury is uncertain, but may be partially due to increased adhesiveness of activated PMNs to pulmonary endothelium. This study examines the relationship between the expression of PMN CD18 adhesion receptors, the evolving neutropenia, and plasma tumor necrosis factor (TNF) activity in a porcine model of septic lung injury. Acute lung injury was induced by infusion of live Pseudomonas aeruginosa (5 x 10(8) CFU/ml at 0.3 ml/20 kg/min) for 60 min (Group Ps, n = 6). Control animals (Group C, n = 3) received a 60-min infusion of sterile 0.9% saline. CD18 expression of circulating PMNs was measured by quantitative immunofluorescent flow cytometry. Plasma TNF activity was measured by L929 fibroblast cytolytic assay. Group Ps developed a significant neutropenia by 30 min (14.9 +/- 2.5 vs 23.4 +/- 3.3 x 10(3) cells/microliter at baseline, P less than 0.05, ANOVA) with circulating neutrophils exhibiting significantly increased CD18 expression by 60 min (6.34 +/- 0.72 vs 5.01 +/- 0.52 equivalent soluble fluorescence molecules (ESFM) x 10(3) at baseline, P less than 0.05, ANOVA). Group Ps demonstrated a significant increase in plasma TNF activity by 30 min (2.5 +/- 0.9 vs 0.7 +/- 0.3 U/ml at baseline). There was no significant change in PMN count, PMN CD18 expression, or plasma TNF activity in Group C. In complimentary in vitro studies, porcine PMNs stimulated with recombinant human TNF-alpha (n = 5) demonstrated a time- and dose-dependent increase in CD18 expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Mechanism of the positive inotropic effect of ketamine in isolated ferret ventricular papillary muscle.

Ketamine is a cardiovascular stimulant through its sympathomimetic effects; however, its direct inotropic effect has been reported as positive in rat and negative in rabbit ventricular myocardium. This study reexamines the effect of ketamine on the contractile properties of mammalian ventricular myocardium. In isolated, electrically stimulated ferret right ventricular papillary muscles, the authors assessed the inotropic effect of ketamine (10(-6) M to 3 x 10(-4) M in 0.5 log M increments) alone and in various pharmacologic conditions designed to delineate ketamine's site(s) of action. Ketamine exerted a positive inotropic effect that was maximal at 10(-4) M. Bupranolol (10(-7) M) abolished this positive inotropic effect, whereas phentolamine (10(-6) M) did not. Depletion of norepinephrine stores by reserpine also eliminated ketamine's positive inotropic effect, indicating that ketamine caused indirect activation of the beta-adrenoceptor. Ketamine did not exert a positive inotropic effect in the presence of simultaneous inhibition of neuronal norepinephrine uptake with desmethylimipramine (DMI) (5 x 10(-6) M) and extraneuronal uptake with corticosterone (5 x 10(-5) M). It is likely that ketamine's action is to inhibit norepinephrine uptake at the neuroeffector junction rather than to augment norepinephrine release. In the presence of corticosterone, ketamine exerted a smaller positive inotropic effect than that seen with ketamine alone. Ketamine produced a small increase in force development in the presence of DMI, but this did not reach statistical significance. Inhibition of neuronal catecholamine uptake appears to be the predominant mechanism of ketamine's positive inotropic effect.

Animals↗
PubMed1991

Nosocomial pneumonia and the role of gastric pH. A meta-analysis.

PURPOSE: To examine the differential effect of drugs used for stress ulcer prophylaxis on nosocomial pneumonia in critically ill patients. DATA IDENTIFICATION: Computerized bibliographic search of published and unpublished research. STUDY SELECTION: Independent review of 48 randomized controlled trials of prophylaxis identified eight relevant studies. DATA ABSTRACTION: The population, intervention, and outcomes were evaluated by duplicate independent review. RESULTS: The incidence of pneumonia was lower in critically ill patients receiving antacids and/or histamine-2-receptor antagonists as compared with patients receiving no stress ulcer prophylaxis (common odds ratio 0.42, 95 percent CI 0.17 to 1.11). When stress ulcer prophylactic therapy was titrated to achieve a gastric pH of 3.5 or greater, there was a trend favoring a decreased incidence of pneumonia (0.66, 95 percent CI 0.24 to 1.78). In trials comparing sucralfate with pH-altering drugs, the common odds ratio of 0.55 (0.28 to 1.06) suggests a 45 percent risk reduction with the use of sucralfate. CONCLUSION: Stress ulcer prophylaxis with drugs which raise gastric pH does not increase the incidence of pneumonia in comparison to placebo or control therapy. The use of sucralfate is associated with a lower incidence of nosocomial pneumonia in comparison to agents which raise gastric pH. However, methodologic deficiencies, small sample sizes, and the failure to examine the effects of antacids and histamine-2-receptor antagonists separately make a large prospective randomized trial necessary to confirm or refute these findings.

Anti-Ulcer Agents↗
PubMed1991

Anti-CD18 antibody attenuates neutropenia and alveolar capillary-membrane injury during gram-negative sepsis.

Activated polymorphonuclear leukocytes (PMNs) are implicated in the pathogenesis of acute lung injury (ALI) associated with sepsis. Adhesion of activated PMNs to endothelial monolayers is mediated by the CD18 adhesion-receptor complex on the PMN cell surface. Monoclonal antibody 60.3 (MoAb 60.3) blocks CD18-dependent PMN-endothelial adhesion in vitro and in vivo. This study was designed to determine the role of CD18-dependent PMN adhesion in ALI associated with gram-negative sepsis. Anesthetized, ventilated (FiO2 0.5, positive end-expiratory pressure 5 cm H2O) pigs received sterile saline (control, n = 8) or live Pseudomonas aeruginosa, 5 x 10(8) colony-forming units/ml at 0.3 ml/20 kg/min (septic, n = 9) for 1 hour. A third group (n = 7) received MoAb 60.3, 2 mg/kg intravenously, 15 minutes before Pseudomonas infusion. Animals were studied for 300 minutes. MoAb 60.3 significantly (p less than 0.05) attenuated the neutropenia seen in sepsis (15 +/- 1 vs 6 +/- 1 x 10(3) PMNs/mm3 at 300 min). Alveolar-capillary membrane injury was assessed by bronchoalveolar-lavage protein content and extravascular lung water determination. MoAb 60.3 significantly (p less than 0.05) reduced BAL protein at 300 minutes (388 +/- 75 vs 1059 +/- 216 micrograms/ml in septic animals) and attenuated the increase in extravascular lung water to 240 minutes (7.1 +/- 2 vs 14.2 +/- 1.2 ml/kg in septic animals). Systemic hypotension, decreased cardiac index, pulmonary hypertension, and relative hypoxemia, all characteristic of this model, were not altered by MoAb 60.3. These data suggest that, in this model of septic ALI, neutropenia is, in part, CD18 dependent and that blocking CD18-dependent PMN adhesion protects the alveolar-capillary membrane independently of altered hemodynamic status.

Acute Disease↗
PubMed1990

Clinical assessment of central venous pressure in the critically ill.

To evaluate the accuracy of central venous pressure (CVP) assessment in critically ill patients, and measure disagreement amongst clinicians, 50 consecutive intensive care unit (ICU) patients with right internal jugular catheters were examined. CVP was measured by the indwelling catheter, and was assessed by: (1) one of three ICU staff physicians, (2) one of six medical residents, and (3) one of six medical students. There was no significant difference in CVP assessment between medical students, residents, and staff physicians. Although all clinicians tended to underestimate CVP, only the residents did so significantly (p less than 0.05). Sensitivity and specificity, and agreement and correlation between the clinicians' assessment and catheter measurements were higher when ventilated patients were excluded. All clinicians agreed more often and were better at identifying low CVP. In summary, considerable disagreement and inaccuracy exists in the clinical assessment of central venous pressure in critically ill patients.

Central Venous Pressure↗
PubMed1989

Liver trauma in a major peripheral hospital: analysis of management and mortality in 74 patients.

The management of liver trauma has improved considerably over the past 2 decades. However, much of the evidence for this improvement has emanated from major trauma centres. Little information is available from peripheral hospitals which deal with much of the trauma seen in Australia. This study set out to examine the management of liver trauma in Box Hill Hospital over the past 2 decades; 74 patients were treated for liver trauma during 1967-86, and the factors considered contributory to mortality rate were analysed. The overall mortality rate was 33.8%, but each 5-year period saw a reduction in mortality rate (25% in the 1982-86 period). The patient's age, associated injuries, transfusion requirements, degree of liver injury and postoperative haemorrhage all contributed to a higher mortality rate. This study indicated that management of liver trauma in a peripheral hospital results in mortality rates that are comparable with major trauma centres. Moreover, by highlighting treatment deficiencies through self-audit, improved treatment protocols should further enhance survival prospects.

Adolescent↗