Search PubMed⌕ Search

Biomedical subjects

J A Cook

Publications and source records attributed to J A Cook.

At least 289 records · Page 16Linked to original sources
PubMed1983

Effects of a pyridine derivative thromboxane synthetase inhibitor and its inactive isomer in endotoxic shock in the rat.

1 We investigated the effects of a pyridine derivative thromboxane synthetase inhibitor and its inactive ortho isomer on arachidonic acid metabolism and pathophysiological sequelae of endotoxic shock. In vehicle-treated rats, 30 min after intravenous S. enteritidis endotoxin (15 mg/kg), plasma iTxB2 (the stable metabolite of thromboxane A2) increased from non-detectable levels (less than 100 pg/ml) to 763 +/- 250 pg/ml (n = 10). Plasma i6-keto-PGF1 alpha (the stable metabolite of prostacyclin, PGI2) increased to 1850 +/- 426 pg/ml, (n = 9) and plasma iPGE increased to 2350 = 560 (n = 5). Pretreatment with the pyridine active (PA) meta isomer (30 mg/kg i.p.) significantly (P less than 0.05) suppressed iTxB2 to 390 +/- 31 pg/ml (n = 10) although 6-keto-PGF1 alpha levels (1294 +/- 358 pg/ml, n = 5) and plasma iPGE (2847 +/- 1103 pg/ml, n = 5) were not significantly different from the shocked control values. In contrast, pretreatment with, the pyridine inactive (PI) ortho isomer did not significantly affect endotoxin-induced iTxB2 (1431 +/- 194 pg/ml, n = 5) or i6-keto-PGF1 alpha synthesis (628 +/- 266 pg/ml, n = 5). 2 Pretreatment of rats with the Tx synthetase inhibitor, PA, significantly enhanced (P less than 0.05) survival and prevented splanchnic infarction relative to both endotoxin shocked control rats and those pretreated with the PI isomer. 3 Significantly reduced lysosomal labilization, hepatocellular dysfunction and elevations in serum fibrin/fibrinogen degradation products were seen only in groups pretreated with the PA isomer. 4 The beneficial effects of the latter compound in endotoxic shock thus appear to be due to inhibition of Tx synthesis, since its ortho isomer did not inhibit TxA2 synthesis nor did it protect against endotoxic shock.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

A death in the family: parental bereavement in the first year.

This article examines parents' descriptions of their experiences in the first year after a child's death from cancer or a blood disorder. Interviews and questionnaires were used to gather information from 145 parents of children treated for oncologic or hematological diseases at a large, urban pediatric hospital who died during the years 1975 through 1979. Descriptive and survey data revealed differences between maternal and paternal mourning. Men and women differed significantly to the extent to which they encountered distance and lack of comfort in spousal relationships and difficulty during first year post-death holidays. Findings are discussed in light of the nature of relationships with the deceased child and other family members.

Adaptation, Psychological↗
PubMed1983

Immunogenicity of soluble and particulate antigens from Leishmania donovani: effect of glucan as an adjuvant.

The protective efficacy of glucan as an adjuvant with killed promastigotes of Leishmania donovani was compared with that of soluble or particulate fractions of the parasite. When these vaccine preparations were injected either intravenously or subcutaneously in CF-1 mice, glucan potentiated resistance against L. donovani infections as reflected by significant reductions in hepatic amastigote counts relative to infected control mice. The leishmanial antigens alone afforded no protection. Serum direct agglutination titers to leishmanial antigens were highest in all groups given the vaccine intravenously, whereas the delayed-type hypersensitivity response to the antigen was positive only in groups immunized subcutaneously with glucan as an adjuvant. Some index of protection and immune response against visceral infection with the parasite was seen in groups vaccinated with glucan and soluble antigens. However, the protection afforded by glucan and particulate antigens of L. donovani more closely paralleled the resistance of mice treated with glucan and unfractionated killed promastigotes. Further antigenic analysis of particulate fractions of L. donovani may optimize effective immunization when used with appropriate adjuvants, e.g., glucan.

Adjuvants, Immunologic↗
PubMed1983

Simplified intravenous nutrition using Intralipid-based mixtures in patients with serious gastrointestinal disease.

An Intralipid-based intravenous feeding mixture has been given to 20 patients with serious gastrointestinal disease who required parenteral nutritional support (mean duration 13.75 days). In half of the patients, only peripheral veins were used for infusion (mean duration 12 days), the infusion site being changed every 24-48 hr. Positive nitrogen balance was maintained in all but one individual and other parameters of nutrition improved. No serious complications due to intravenous feeding were encountered, although some patients did develop abnormal liver function tests and mild phlebitis at the peripheral vein infusion site. No abnormalities of pulmonary gas exchange attributable to the infusion were noted. We conclude that this mixture is safe, relatively simple to use and effective. Consequently, it may be especially appropriate for patients in general medical and surgical wards as well as those in specialist units.

Adult↗
PubMed1983

Immunization of mice against Leishmania donovani by subcutaneous injections of dead promastigotes.

Mice immunized by a series of intravenous, intraperitoneal or subcutaneous injections of formalin-killed Leishmania donovani promastigotes with glucan, a beta 1, 3 polyglucose, exhibited a significant degree of resistance against subsequent infection with viable promastigotes. Intramuscular immunization was not effective. Immunization via subcutaneous injections of dead promastigotes simultaneously with glucan elicited protective resistance, positive skin test responsiveness before and after challenge and increased antipromastigote antibody levels. Injections of glucan alone induced a lesser degree of resistance against infection without significant skin test or humoral responsiveness. Injections of dead promastigotes alone elicited increased antibody levels but no skin test responsiveness or resistance against infection.

Adjuvants, Immunologic↗
PubMed1983

Gentamicin and indomethacin in the treatment of septic shock: effects on prostacyclin and thromboxane A2 production.

We investigated the effects of the thromboxane synthetase inhibitor 7-(1-imidazolyl)heptanoic acid (7-IHA) and the fatty acid cyclooxygenase inhibitors indomethacin or ibuprofen in the treatment of fecal peritonitis in the rat. The effects of gentamicin alone and in combination with reduction of arachidonic acid metabolism by either treatment with indomethacin or essential fatty acid deficiency was also investigated. 7-IHA (60 mg/kg), administered i.p. 30 min before i.p. instillation of a fecal suspension, significantly reduced the plasma levels of immunoreactive (i) TxB2 from 1066 +/- 194 pg/ml (N = 14) to nondetectable (less than 200 pg/ml; N = 9) (P less than .01) at 1 hr and from 1695 +/- 218 (N = 16) to 508 +/- 56 pg/ml (N = 6) (P less than .01) at 4 hr after instillation of feces. In contrast, the levels of i6-keto-prostaglandin (PG)F1 alpha, the stable metabolite of prostacyclin, were significantly elevated by 7-IHA pretreatment from vehicle-treated septic control levels of 3777 +/- 414 (N = 16) to 5185 +/- 467 pg/ml (N = 9) (P less than .05) at 1 hr. Plasma i6-keto-PGF1 alpha at 4 hr in 7-IHA-treated rats (5503 +/- 665 pg/ml) (N = 6) was not different from vehicle-treated controls. Survival associated with fecal peritonitis was not altered by 7-IHA pretreatment. Indomethacin (10 mg/kg) or ibuprofen (5 mg/kg) administered i.p. 30 min before the fecal suspension significantly decreased both iTxB2 and i6-keto-PGF1 alpha, plasma levels when measured at 4 hr and prolonged survival time (P less than .05). Fibrinogen/fibrin degradation products were elevated (P less than .01) during fecal peritonitis and were reduced by indomethacin (P less than .01) or 7-IHA (P less than .05). Gentamicin significantly increased mean survival time from 8.6 +/- 0.2 (N = 50) to 23.8 +/- 2.6 hr (N = 16) (P less than .01). Gentamicin in combination with indomethacin or essential fatty acid deficiency further improved mean survival time and resulted in long-term survivals (greater than 48 hr) of 35 (N = 17) and 30% (N = 7), respectively (P less than .01 compared with gentamicin). Gentamicin pretreatment did not significantly alter plasma iTxB2 levels, but decreased i6-keto-PGF1 alpha from 9465 +/- 792 (N = 7) to 3096 +/- 1,174 pg/ml (N = 5; P less than .01) at 6 hr after induction of fecal peritonitis. These studies raise the possibility that inhibition of fatty acid cyclooxygenase may be a useful adjunct to antibiotic therapy in the treatment of septic shock.

Animals↗
PubMed1983

Arachidonic acid metabolism in endotoxin tolerance.

The arachidonic acid metabolites thromboxane A2, a potent platelet aggregator, and prostacyclin, a potent vasodilator, are released early in endotoxin shock and may contribute to its pathologic sequelae. Plasma levels of thromboxane (Tx) A2 and prostacyclin were measured via radioimmunoassay of their stable metabolites immunoreactive (i) TxB2 and i6-keto-PGF1 alpha in tolerant and nontolerant rats after endotoxin. Long-Evans rats were made tolerant to endotoxin by four daily IV injections of S enteritidis (endotoxin) (0.1, 0.5, 1, and 5 mg/kg). In normal rats (N = 15) given LPS (IV, 15 mg/kg), only 11% survived at 24 h; in contrast, tolerant rats (N = 13) all survived even at a dose of 50 mg/kg. At 1 h, after endotoxin (15 mg/kg) IV, plasma i6-keto-PGF1 alpha in nontolerant rats was 1,005 +/- 149 pg/ml (N = 14) and continued to rise to 4,209 +/- 757 pg/ml (N = 5) (P less than 0.001) after 4 h. In tolerant rats, given endotoxin (15 mg/kg), plasma i6-keto-PGF1 alpha at 1 h was 800 +/- 203 pg/ml (N = 5) and was not significantly different (734 +/- 254 pg/ml) at 4 h. Plasma iTxB2 at both 1 and 4 h was significantly (P less than 0.01) lower in tolerant than nontolerant rats. Both iTxB2 and i6-keto-PGF1 alpha were significantly (P less than 0.01) lower in tolerant rats given 50 mg/kg IV endotoxin than nontolerant rats. Endotoxin-induced elevation in fibrin degradation products was significantly decreased (P less than 0.05) during endotoxin tolerance although there was no difference in the severity of thrombocytopenia. These composite observations demonstrate that endotoxin tolerance in the rat is associated with altered arachidonic acid metabolism.

Acid Phosphatase↗
PubMed1982

Plasma thromboxane concentrations are raised in patients dying with septic shock.

Central venous plasma concentrations of thromboxane B2 (TXB2) the stable metabolite of the vasoconstrictor platelet aggregator thromboxane A2, were measured in 12 patients with septic shock. In 8 patients dying with septic shock the concentration of plasma TXB2 (912 +/- 250 pg/ml) was ten times higher than that in 4 survivors of septic shock (92 +/- 25 pg/ml) and 6 controls (91 +/- 18 pg/ml). Prothrombin time and partial thromboplastin time were significantly prolonged in nonsurvivors compared with survivors. Similarly, the alveolar-arterial oxygen gradient was significantly raised in nonsurvivors (233 +/- 39 mm Hg) compared with survivors (112 +/- 47 mm Hg). This study demonstrates that the metabolism of arachidonic acid to thromboxanes is increased in patients dying of septic shock and this raises the possibility that thromboxanes may be involved in the disseminated intravascular coagulation and respiratory distress syndrome associated with severe sepsis.

Arachidonic Acids↗
PubMed1982

Glucan as an adjuvant for a murine Babesia microti immunization trial.

A vaccination protocol against murine Babesia microti infection, using glucan, a beta-1,3-glucopyranose derivative of yeast cell walls, and glutaraldehyde-fixed infected erythrocytes was evaluated. BALB/c mice were immunized intravenously four times at 2-day intervals with 2 X 10(8) fixed infected erythrocytes with and without glucan (0.45 mg). The mice were challenged 2 weeks after the last immunization with 10(8) viable infected erythrocytes. Peak parasitemia was significantly reduced (8.9 +/- 1.0%; P less than 0.001) in glucan-immunized mice as compared with nonimmunized controls (41.2 +/- 1.4%), glucan-treated controls (31.7 +/- 2.5%; P less than 0.05), or mice which received fixed infected erythrocytes without glucan (21.0 +/- 1.2%; P less than 0.01). Humoral and cellular immunity to B. microti was evaluated before challenge by measuring antibody titers and splenocyte blastogenic responses to B. microti antigens. The in vitro cellular response was inversely correlated with mean peak parasitemia (P less than 0.05). These observations demonstrate that glucan is an effective adjuvant in enhancing immunity to murine babesiosis.

Adjuvants, Immunologic↗
PubMed1982

Protective effect of glucan against visceral leishmaniasis in hamsters.

The effect of pre- or posttreatment with glucan, a reticuloendothelial stimulant, on the course of Leishmania donovani infection was assessed in highly susceptible hamsters. Intravenous administration of glucan before or after L. donovani infection significantly suppressed proliferation of amastigote-stage parasites in liver and spleen. Glucan-activated peritoneal macrophages in vitro also significantly reduced multiplication of the intracellular parasite. Ultrastructural studies revealed a well-defined hepatic granulomatous response to glucan, with hypertrophic Kupffer cells and reduced numbers of intracellular parasites compared to the control group. In additional studies, groups of hamsters were immunized by intravenous injections of glucan with Formalin-killed promastigote-stage L. donovani cells and challenged 60 days after the last immunizing injection. This treatment regimen significantly prolonged the mean survival time of those hamsters which died after infection, relative to untreated control groups. Hamsters stimulated with the glucan-killed promastigote preparation also exhibited significant reductions in splenic amastigotes on days 10 and 21 postinfection compared with all other control groups, but on day 35, splenic amastigotes did not differ significantly from those of control animals. Our composite observations provide evidence for glucan-enhanced nonspecific resistance of hamsters to visceral leishmaniasis.

Adjuvants, Immunologic↗
PubMed1982

Schistosome infections in humans: perspectives and recent findings. NIH conference.

Approximately 200 million persons are infected with schistosomes. Of those infected, a small proportion develop serious chronic disease, usually after years of intensive exposure and infection. Schistosoma mansoni and Schistosoma japonicum reside in the mesenteric veins and produce liver fibrosis, which results in portal hypertension and bleeding esophageal varices but little hepatocellular dysfunction. Schistosoma haematobium resides primarily in the pelvic veins and produces mass lesions in the bladder and ureters, which lead to hydroureter and hydronephrosis. The intensity of infection is a major factor determining development of disease, but differences in worm strain and host response may also be important. In acute schistosomiasis there is an intense response to the parasite, which is suppressed as the infection becomes chronic. The marked inflammatory response seen in early and acute schistosomiasis becomes less intense and fibrotic lesions predominate. The recent advent of safe, effective, and easily administered chemotherapeutic reagents will aid in the control of schistosomiasis.

Animals↗
PubMed1982

Thromboxane and prostacyclin production during septic shock.

We investigated a rat fecal peritonitis model of acute intraabdominal sepsis in order to evaluate the potential role of arachidonic acid metabolites in septic shock. Immunoreactive TxB2, the stable metabolite of thromboxane A2, and i6-keto-PGF1 alpha, the stable metabolite of prostacyclin, were measured by radioimmunoassay. Plasma levels of iTxB2 rapidly increased from nondetectable (ND less than 200 pg/ml) to 1,052 +/- 208 pg/ml, one hour after feces injection. iTxB2 then increased to 1,681 +/- 248 pg/ml at four hours and remained unchanged through six hours. Plasma i6-keto-PGF1 alpha increased from ND to 3,848 +/- 489 pg/ml a one hour. Four hours after feces, i6-keto-PGF1 alpha levels rose to 7, 450 +/- 933 pg/ml then continued to rise to 9,465 +/- 792 pg/ml at six hours. Either essential fatty acid deficiency (arachidonic acid depletion) or indomethacin treatment (cyclo-oxygenase inhibition) significantly decreased (P less than 0.01) the elevation of plasma iTxB2 and i6-keto-PGF1 alpha associated with fecal peritonitis. Thrombocytopenia occurred within six hours after injection of feces and was significantly improved (P less than 0.05) by indomethacin. Elevated fibrin degradation products at six hours (18 +/- 3 micrograms/ml) were significantly reduced in essential fatty acid-deficient (7 +/- 2 micrograms/ml; P less than 0.05) and indomethacin-treated (4 +/- 0.7 micrograms/ml; P less than 0.01) rats. Survival time (8.6 +/- 0.2 hours) was significantly enhanced by essential fatty acid-deficiency (10.2 +/- 0.4 hours; P less than 0.01) or indomethacin treatment (13.3 +/- 0.6 hours; P less than 0.01). These studies show that fecal peritonitis is associated with increased synthesis of thromboxane A2 and prostacyclin and suggest that these arachidonic acid metabolites may play a role in the pathophysiology of septic shock.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Value of individual household water supplies in the maintenance phase of a schistosomiasis control programme in Saint-Lucia, after chemotherapy.

Between 1970 and 1975, the incidence of new Schistosoma mansoni infections was reduced in 5 villages after each household was provided with its individual water supply and community laundry shower units were made available. In 1975, 1976, and 1977 chemotherapy with oxamniquine was offered to persons found to be infected. Transmission was reduced further and remained at a low level for the next 4 years, with no sign of an increase in spite of the reservoir of infection remaining after therapy and a poor level of sanitation in the villages.Thus, properly maintained water supplies appear to be effective in maintaining transmission at a low level during the maintenance phase of a schistosomiasis control programme, after chemotherapy. Sporadic new infections must be anticipated among children, but these will probably be of low intensity and associated with minimal morbidity.

Adolescent↗
PubMed1982

Effect of pharmacist counseling on drug information recall.

The effect of counseling by pharmacists on patients' long-term recall of drug information was studied. Clinic and hospital neurological patients were counseled by a physician regarding a drug newly prescribed for them. Each patient in the study was then given a 15-item multiple-choice pretest specific for the new medication. Patients in the control group were given a posttest identical to the pretest eight weeks later. Test group patients were counseled by a pharmacist and were given the posttest eight weeks later. Specific information was categorized as to source. The mean scores of the test group patients increased 26.2 percentage points between pretest and posttest. Scores on information covered by the physician and reinforced by the pharmacist increased 19.6 percentage points, and scores on information presented only by the pharmacist with written reinforcement increased 30.6 percentage points. Scores of the control group patients showed no improvement between pretest and posttest. Pharmacist counseling had a significant effect on patients' recall of drug information after eight weeks.

Age Factors↗