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Biomedical subjects

J A Cook

Publications and source records attributed to J A Cook.

At least 235 records · Page 13Linked to original sources
PubMed1989

The effects of imminent minor surgery on the cognitive processing of health and interpersonal threat words.

Women in hospital for a laparoscopy and control subjects were examined on a version of the Stroop test in which the distracting effect of word content on speed of colour naming was examined. Both laparoscopy patients and controls were slowed by words related to interpersonal threat but only the laparoscopy patients were slowed by words that related to health threats. This suggests that a specific temporary threat can alter attentional biases.

Abdominal Pain↗
PubMed1989

Essential fatty acid-deficient rats are resistant to oleic acid-induced pulmonary injury.

Because leukotrienes and prostaglandins are inflammatory mediators derived from arachidonic acid, their potential role in oleic acid-induced lung injury was evaluated in control and in essential fatty acid-deficient (EFAD) rats depleted of arachidonic acid substrate. In control rats, oleic acid (0.06 ml/kg iv) increased the pulmonary permeability index (measured by scintigraphy) from -10 +/- 13 x 10(-6) s-1 to 217 +/- 20 x 10(-6) s-1 and 118 +/- 13 x 10(-6) s-1 at 5 and 50 min (P less than 0.05), respectively. It also caused arterial hypoxemia at 30 min (P less than 0.05). Compared with saline controls, oleic acid increased bronchoalveolar lavage fluid levels of immunoreactive (i) LTC4/D4, iLTB4, (P less than 0.01), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) (P less than 0.05). In EFAD rats, oleic acid failed to significantly increase the lung permeability index at 5 and 50 min. In contrast to control rats, oleic acid failed to cause hypoxemia in the EFAD rats. Bronchoalveolar lavage levels of iLTB4 and i6-keto-PGF1 alpha after oleic acid in EFAD rats were lower compared with oleic acid controls, whereas iLTC4/D4 in the oleic acid EFAD group was not decreased. Treatment with intraperitoneal ethyl arachidonate (400 mg over 2 wk) reversed the resistance of EFAD rats such that the pulmonary edema (P less than 0.05) was evident after oleic acid. This latter group also manifested a significant (P less than 0.05) rise in the bronchoalveolar lavage levels of iLTB4 and i6-keto-PGF1 alpha. These results suggest that arachidonic acid metabolites contribute to oleic acid-induced pulmonary permeability.

Animals↗
PubMed1989

Human platelets modulate edema formation in isolated rabbit lungs.

The role of platelet glucose-6-phosphate dehydrogenase (G-6-PD) in mediating the effects of human platelets on oxidant-induced edema in the isolated perfused rabbit lung was investigated using dehydroepiandrosterone, a specific steroidal inhibitor of G-6-PD. Xanthine oxidase (0.003 and 0.012 U/ml) caused lung edema that was attenuated by coinfusion of washed human platelets. Platelets that were incubated with DEA to inhibit G-6-PD activity augmented xanthine oxidase-induced lung edema and pulmonary hypertension at both doses of xanthine oxidase. Infusion of papaverine to maintain stable pulmonary artery (PA) pressures, incubation of G-6-PD-inhibited platelets with acetylsalicylate, or infusion of a thromboxane-prostaglandin endoperoxide receptor site antagonist, SQ 29548, into the lung perfusate prevented augmentation of lung edema and the PA pressor response by G-6-PD-inhibited platelets. It was concluded that antioxidant-intact platelets attenuate oxidant-induced lung edema by preventing increased membrane permeability, and that G-6-PD-inhibited platelets augment lung edema through hydrostatic mechanisms mediated by release of platelet cyclooxygenase products.

Animals↗
PubMed1989

Transient myeloproliferative disorder. In a neonate with Down syndrome. Immunophenotypic studies.

This report describes the results of bone marrow leukocyte immunophenotypic studies, DNA index measurement, and chromosome analysis in a newborn with Down syndrome and transient myeloproliferative disorder. The infant's initial leukocytosis with immature cells in the peripheral blood and thrombocytopenia resolved without treatment by 6 months of age, and he was well at 2 years of age. The lack of specific reactivity between the patient's morphologically immature cells and multiple monoclonal antibodies directed against lymphoid and myeloid leukemia cells may be characteristic of this disorder. Other cases should be examined for immunophenotype to correlate the results with chromosomal analysis and to provide a basis for comparison in those who subsequently develop true acute leukemia.

Bone Marrow↗
PubMed1989

The role of eicosanoids in mediating blood flow alterations in endotoxin shock.

The vasoactive metabolites of arachidonic acid TxA2 and sulfidopeptide-leukotrienes appear to play a role in mediating hemodynamic alterations in endotoxic shock. The ultimate goal of these and other studies in shock is, however, to understand the mechanisms underlying the pathogenic changes in human shock states in order to develop effective treatment. Recent studies (see reviews by Ball, 1988) have implicated eicosanoids in pathogenesis of shock in man confirming the directions provided by the bolus endotoxin studies and suggest additional investigations of hemodynamics following interventions designed to alter eicosanoid synthesis in shock.

Animals↗
PubMed1989

The rat in sepsis and endotoxic shock.

Compared to the experimental studies, interpretation of eicosanoid levels in human sepsis is complicated by a large number of uncontrolled variables. Further clinical studies are needed to establish the relationship between the septic rat model and the human septic condition. The rat model is useful for uncovering fundamental pathophysiologic processes and should be useful in developing therapeutic interventions in human circulatory shock. Studies on the rat model offered the first indication that eicosanoids were involved in the shock syndrome (Cook et al., 1980). This led to clinical trials to determine the role of these mediators in human sepsis (Reines et al. 1982). The rat affords a model system which allows for pharmacologic manipulation and testing of a large number of hypotheses in a practical and cost effective manner. The recent evidence that leukotrienes are released during circulatory shock in the rat and that attenuation of this release alters the pathophysiologic outcome (Ball et al., 1986), lays the groundwork for future clinical studies. Finding that eicosanoids and leukotrienes are elevated in rat models of adult respiratory distress syndrome (Hammarstrom, 1983) has opened further new areas of clinical inquiry. Although rat models involving bolus endotoxin administration have not been predictive of the human septic syndrome, they have proven useful in the determination of the cellular sources and mechanisms of eicosanoid and leukotriene action. From the evidence presented, the septic shock rat model would seem to be the best model in predicting the outcome of therapies in human sepsis. Limited clinical trials have assessed the therapeutic efficacy of pharmacologic agents which alter eicosanoid and leukotriene metabolism in sepsis. In view of the continued high mortality of patients with septic shock and the failure of conventional therapies (Sprung et al., 1984; DuToit et al. 1985), further clinical and experimental studies are desirable.

Adrenal Cortex Hormones↗
PubMed1989

Alterations in Gc levels and complexing in septic shock.

Septic shock involves increased generation of eicosanoids from arachidonic acid. Gc (vitamin D-binding protein) has been recently found to bind the parent molecule arachidonic acid but can also complex actin released as a result of tissue damage which causes displacement of bound arachidonic acid. Possible changes in serum levels of Gc and extent of complexing were therefore investigated in patients with gram-negative sepsis. As compared to healthy controls, serum levels of Gc were significantly decreased in patients with septic shock (P less than 0.01). Moreover, the percentages of Gc circulating in complexed form were significantly increased (P less than 0.01) and correlated strongly with disease severity, with levels often greater than 90% in patients who died (normal mean 8% +/- 3). These results suggest a hitherto unsuspected role for Gc in septic shock syndrome.

Actins↗
PubMed1989

Alterations in plasma levels and complexing of Gc (vitamin D-binding protein) in rats with endotoxic shock.

Septic shock is known to involve increased metabolism of arachidonic acid and generation of certain eicosanoids. Recently, a new extracellular pool of unsaturated fatty acids including arachidonate has been found in relation to group-specific component (Gc), a vitamin D-binding plasma protein that sequesters monomeric G-actin. Since complexing with G-actin displaces fatty acids, possible alterations in plasma levels of Gc and extent of complexing were sought in serial samples obtained from rats with shock induced by Salmonella enteritidis endotoxin (12.5-15 mg kg-1). Gc levels in animals receiving endotoxin exhibited bimodal alterations, with a significant reduction (P less than 0.001) at 1 hour, followed by a progressive elevation to 160% of starting concentrations at 6 days in animals that survived, whereas in sham-injected animals the change observed was a continuous rise to 147% at 6 days. A statistically significant increase in the percentage of Gc complexed was observed in all endotoxemic rats from 2 hours onward (P less than 0.01), in contrast to sham-injected animals, in which the percentage of Gc complexed remained at less than 5%. Levels in survivors peaked at 30 +/- 5.2% at 8 hours and then decreased to normal (2 +/- 0.9%) by 6 days (n = 7), whereas in nonsurvivors complexed Gc continued to rise until time of death (66-80%) at 6-12 hours (n = 4). Correlation of these results with glucose, transaminases, and immunoreactive TXB2 and 6-keto-PGF1 alpha indicated that decreased absolute levels of Gc represent a consistent early change in endotoxic shock and that the percentage of Gc complexed is an accurate prognostic indicator of severity.

Actins↗
PubMed1989

A randomised comparison of two postoperative fluid regimens.

Postoperative paralytic ileus follows all significant gastrointestinal surgery. Its duration is variable and has led to a variety of empirical and time-consuming oral fluid regimens. We have compared a traditional method of fluid administration with an unstructured, simpler, patient-determined approach. A series of 102 patients on a general surgical ward who required intravenous fluids on the day after surgery were randomised by a closed envelope system to one of two protocols and followed prospectively. Of these, 12 patients were erroneously randomised or unable to fulfil trial requirements. The first, 'regulated' group (n = 41) received hourly aliquots of oral fluid as determined by twice daily ward rounds according to ward routine. The second, 'unregulated' group (n = 49) were given a jug of water and instructed to drink as desired. Patients in the regulated group received less of their postoperative fluids by the oral route at all stages of recovery but there were no significant differences in the mean durations of intravenous therapy, nasogastric intubation or hospital stay. Postoperative complication and mortality rates were also similar. Patients who underwent gastric or duodenal procedures (n = 14) showed a similar pattern of results. We conclude that 'patient-determined' regulation of postoperative oral fluid intake is safe and effective and may greatly simplify ward management.

Digestive System Surgical Procedures↗
PubMed1988

Effects of chronic pH 6.6 on growth, intracellular pH, and response to 42.0 degrees C hyperthermia of Chinese hamster ovary cells.

Culturing Chinese hamster ovary cells in low pH (6.6) medium for several months altered the reproductive survival of these cells to combined low pH treatments and 42.0 degrees C heating. We isolated new pH-resistant cells (identified as pHV-2) with enhanced ability to grow and divide under a low pH (6.6) environment. Their growth characteristics include (a) a plating efficiency of 70%, (b) a doubling time of 16 to 17 h, and (c) a steady state intracellular pH 0.12 pH units higher than for cells grown at a normal pH of 7.3. The pHV-2 cells had 100- to 200-fold increases in survival after 5 h of heating compared to cells incubated at low pH (6.6) for 4 h prior to and during the heat treatments. In addition, they developed a significant degree of thermotolerance. We measured a progressive decline in the intracellular pH as a function of time at 42.0 degrees C. However, the decrease in the intracellular pH did not seem to be correlated with the increased heat sensitivity. The ability to select for low pH variants may have important implications in the extrapolation of in vitro hyperthermic data to the in vivo situation.

Animals↗
PubMed1988

Effects of acute pH 6.6 and 42.0 degrees C heating on the intracellular pH of Chinese hamster ovary cells.

Incubation of Chinese hamster ovary cells in pH 6.6 medium for 4 h prior to and during 42.0 degrees C heating enhanced thermal cell killing compared to cells heated under normal pH 7.3 conditions. We examined the relationship between the extracellular pH and intracellular pH (pHi) of Chinese hamster ovary cells using a flow cytometer with the pH-sensitive fluorescent molecule 2,3-dicyanohydroquinone. Using either normal (7.3) or low (6.6) pH conditions, the mean pHi and population pHi heterogeneity was studied as a function of time at 42.0 degrees C. Cells incubated at pH 6.6 for 4 h had a resting pHi 0.14 to 0.19 pH units lower than cells at normal pH 7.3, indicating the presence of an active pHi regulatory system. Heating 1 h at 42.0 degrees C at normal pH caused an increase in the pHi of 0.14 pH units. With further heating the cells gradually returned to the unheated (7.3) control levels. Similar pHi changes were observed with the cells incubated and heated at pH 6.6. However, the mean pHi was always more acidic than cells heated at normal pH. Active pHi regulation was still possible for a substantial (greater than 30%) number of cells even after 10 h of heating under low pH conditions. These results suggest that a breakdown in pHi regulation is not the mechanism of low pH-induced heat sensitization.

Acid-Base Equilibrium↗
PubMed1988

Intracellular pH measurements using flow cytometry with 1,4-diacetoxy-2,3-dicyanobenzene.

1,4-Diacetoxy-2,3-dicyanobenzene (ADB) has been increasingly used for measurement of intracellular pH by flow cytometry. ADB rapidly enters cells and is cleaved to the fluorescent pH indicator 2,3-dicyano-hydroquinone (DCH). We have analyzed several potential problems that can affect its usefulness as a pH indicator. Hydrolysis of ADB in aqueous solutions reveals the temporary presence of a fluorescent species blue-shifted from DCH at the same pH. The presence of this species with DCH can lead to erroneous pH measurements. Stable pH measurements with ADB depend on the incubation conditions and esterase activity. Heated cells required 20 min for stable measurements, whereas control cells required 5 to 10 min. The reproducibility of pH measurements was excellent, with a resolution of less than or equal to 0.05 pH units in the range of 6.4 to 8.0. Absolute calibration curves of intracellular pH using the ionophore nigericin depended on matching the intracellular K+ concentration with the buffer, but relative measurements of intracellular pH were insensitive to K+. ADB was nontoxic to Chinese hamster ovary cells at up to 20 micrograms/ml. However, when cells loaded with dye were passed through a UV laser beam, concentrations of dye greater than 5 micrograms/ml were highly toxic. Viable cells could be sorted on the basis of intracellular pH if ADB were used at low concentrations.

Animals↗
PubMed1988

Effect of bacterial endotoxin on lipoxygenase and cyclo-oxygenase metabolites by rat neutrophils and correlation with cellular functional parameters.

The effect of Salmonella enteritidis endotoxin on in vitro rat neutrophil cyclo-oxygenase and lipoxygenase metabolism, phagocytic activity, superoxide (O2-) generation, and microbicidal activity was investigated. Incubation of polymorphonuclear leukocytes (PMN) with 5, 25, and 50 micrograms of endotoxin significantly enhanced synthesis of immunoreactive (i) leukotriene (LT)C4/D4 and thromboxane (Tx)B2 (P less than 0.001) as compared to control cells. Endotoxin 5 micrograms/ml produced optimal stimulation of the arachidonic acid metabolites. Calcium ionophore, A23187, significantly enhanced iLTC4/D4 and iTxB2 synthesis more than that elicited with endotoxin. Although phagocytic function was not significantly altered by endotoxin, intracellular killing of C. albicans demonstrated enhanced microbicidal activity at 5 micrograms/ml of endotoxin. Superoxide generation was significantly enhanced in neutrophils stimulated with phorbol myristate acetate (PMA). Endotoxin (5 micrograms/ml) further potentiated superoxide generation by these cells when stimulated by PMA. These findings demonstrate that endotoxin directly enhances neutrophil iLTC4/D4 and iTxB2 synthesis. The enhanced arachidonic acid metabolism elicited by endotoxin in these cells parallels increased microbicidal activity and superoxide generation.

Animals↗
PubMed1988

Effect of stressor intensity on habituation of the adrenocortical stress response.

Although it is known that the number of presentations of a stressor can influence the adrenocortical stress response, relatively little information exists on how stressor intensity affects this process. To evaluate this, we repeatedly presented rats with stressors of 3 different intensities and sampled blood for corticosterone. The first major finding was that the rat's initial adrenocortical responsiveness regardless of the stressor employed was a critical variable. Rats that showed a small corticosterone response showed no evidence of habituation or of differences due to stressor intensity. Rats that showed an initial robust response all showed partial habituation of their corticosterone response over time but the patterns varied with stressor intensity. Handled and prone restrained rats showed the same pattern but rats subjected to the more intense stressor of supine restraint showed delay in habituation and tonically elevated responses. These data indicate that individual differences in reactivity to stressors as well as stressor intensity can influence the pattern of the stress response over the course of repeated administration of the stressor.

Adrenal Cortex↗
PubMed1988

Development of acute tolerance to bumetanide: constant-rate infusion studies.

Bumetanide was administered intravenously to four mongrel dogs as a bolus of 8.7 micrograms/kg, immediately followed by a constant-rate infusion of 0.35 microgram/min/kg at 0.036 ml/min. Treatment A consisted of a 90-min equilibration period and first hour (Phase I) of study in which animals were maintained under euvolemic conditions. During the subsequent 3 hr of Treatment A (Phase II), animals were maintained under hydropenic conditions. These experiments were then repeated 1 week later (Treatment B) with the temporal aspects of hydration reversed (Phase III, hydropenia; Phase IV, euvolemia). Serial plasma and urine samples were assayed for bumetanide by high-performance liquid chromatography (HPLC) and for sodium by flame photometry. The bumetanide excretion rate was not significantly different during the 4 hr of Treatment A, although minor differences were observed between Phase III and Phase IV of Treatment B. The sodium excretion rate showed significant differences between euvolemic and hydropenic conditions of both treatments. A two- to threefold difference in the sodium excretion rate persisted even when slight differences (less than 20%) in bumetanide excretion rates were taken into account. These results demonstrate that an acute tolerance does develop to constant-rate infusions of bumetanide when inadequate fluid and electrolyte replacement occurs and that this tolerance can be reversed by rehydration.

Aldosterone↗
PubMed1988

Kinetics, dynamics, and bioavailability of bumetanide in healthy subjects and patients with congestive heart failure.

Four healthy subjects and six patients with congestive heart failure (CHF) were given 3 mg oral and intravenous doses of bumetanide in a random crossover fashion. Bumetanide was analyzed by HPLC, and sodium and potassium was analyzed by flame photometry. Aside from a modest reduction in renal clearance, the kinetics of bumetanide in CHF were similar to those in healthy subjects. The extent of bioavailability was 81%, with a variability of 20% to 25% about the mean for both groups. The cumulative dynamic responses to bumetanide, whether administered orally or intravenously, were essentially the same in each group. Pharmacodynamic modeling showed that there were no significant differences between healthy subjects and patients with CHF in either ER50 (bumetanide urinary excretion rate producing 50% of maximum drug effect) or S (slope), although the baseline effect was 15 times lower in CHF. The maximum effect attributable to bumetanide was twofold higher in healthy subjects and there was a significant correlation between this parameter and creatinine clearance (r = 0.964; p less than 0.001). Overall, these results indicate that a predictable transition from 3 mg intravenous to oral doses of bumetanide is possible in CHF.

Administration, Oral↗
PubMed1988

Human platelets attenuate oxidant injury in isolated rabbit lungs.

Because platelets contain active antioxidant systems, the capacity of platelets to attenuate oxidant lung injury was investigated. Purine and xanthine oxidase were infused into isolated perfused rabbit lungs (IPL) to generate H2O2, thereby causing increased membrane permeability edema. The coinfusion of washed human platelets (1.20 +/- 0.07 x 10(10) cells) attenuated the degree of edema formation as measured by lung weight gain and lung lavage albumin concentration. Electron microscopy of lung preparations demonstrated platelet adherence to capillary endothelial luminal surfaces of oxidant-injured lungs, but there was no evidence of vascular plugging with platelet macroaggregates. The platelet glutathione redox cycle or platelet catalase were inhibited before infusion of platelets into the IPL with purine and xanthine oxidase. Inhibition of the glutathione redox cycle with 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-chloro-2,4-dinitrobenzene, or buthionine sulfoximine prevented platelet attenuation of lung injury. Inactivation of platelet catalase with 3-amino-1,2,4-triazole, however, did not significantly reduce the platelet-induced lung protection. We conclude that the platelet glutathione redox cycle plays a major role in reducing enzymatically generated toxic O2 metabolites and attenuating lung injury.

Animals↗