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Biomedical subjects

E Kennedy

Publications and source records attributed to E Kennedy.

At least 19 recordsLinked to original sources

Inhibition of intimal hyperplasia in rat aortic allografts with cyclosporine.

The rat aortic transplant model of chronic rejection was used to study the effect of cyclosporine (CsA) on the development of intimal hyperplasia. ACI and Lewis rat strains were used to create isograft and allograft CsA nontreated and treated groups. After orthotopic abdominal aortic transplantation, recipients received either no treatment, CsA 2.5 mg/kg/day, CsA 5 mg/kg/day, or CsA 10 mg/kg/day by gavage. Treated grafts were harvested at 3 and 6 months after transplantation, and computer image digital analysis was used to measure intimal and medial areas of graft cross-sections. At 3 months, the reduction in percent intima was 62% (P = 0.005), 74% (P = 0.002), and 97% (P < 0.0001) for the 2.5-, 5-, and 10-mg/kg allograft groups, respectively. There was a 93% (P < 0.0001) reduction in percent intima at 6 months in the 10-mg/kg allograft group. CsA treatment also preserved the aortic media. In comparison to nontreated isografts, medial area in nontreated allografts was decreased by 37% at 3 months after transplantation. In contrast, medial area was not significantly changed in CsA-treated recipients (10 mg/kg/day) in comparison to nontreated isografts. More importantly, medial nuclear density was preserved in the CsA-treated recipients in comparison to nontreated allografts and was similar to treated or nontreated isografts. In conclusion, daily high dose CsA treatment was found to markedly inhibit intimal hyperplasia in rat aortic allografts up to 6 months after transplantation, which suggests that CsA at an adequate dosage can suppress chronic rejection.

Animals

What are American children eating? Implications for public policy.

As the health and demographic profile of the U.S. population changes, the food consumption patterns of American children have also changed. This review is organized around a series of policy issues looking at these new food consumption patterns, their relationship to the Dietary Guidelines, and their impact on children's health.

Adolescent

Beneficial cardiopulmonary effects of pentoxifylline in experimental sepsis are lost once septic shock is established.

OBJECTIVE: To determine the effects of pretreatment and posttreatment with pentoxifylline in a porcine model of gram-negative sepsis. DESIGN: Nonrandomized controlled trial. STUDY SUBJECTS: Young Yorkshire swine. INTERVENTIONS: Six groups of ventilated swine were studied for 5 hours. Group 1 swine (control, n = 8) received saline solution only. Group 2 swine (sepsis, n = 8) received a 1-hour infusion of Pseudomonas aeruginosa. Groups 3, 4, and 5 swine received the P aeruginosa infusion and a 20 mg/kg bolus followed by a 6 mg/kg per hour infusion of pentoxifylline. Group 3 swine (n = 6) received pentoxifylline prior to the onset of sepsis; group 4 swine (n = 6) received pentoxifylline at 1 hour and group 5 swine (n = 4) at 2 hours after the onset of the P aeruginosa infusion. Group 6 swine (control pentoxifylline, n = 3) received pentoxifylline only. OUTCOME MEASURES: Hemodynamic variables, neutrophil counts and CD18 expression, tumor necrosis factor activity, and arterial blood gases were measured hourly. Bronchoalveolar lavage was performed at 0 and 5 hours to measure neutrophil and protein content. RESULTS: All variables remained unchanged in the control and control pentoxifylline groups. Both pretreatment and posttreatment with pentoxifylline significantly attenuated lung injury and improved arterial PaO2. The cardiac index was significantly improved by administration of pentoxifylline in groups 3 and 4. Administration of pentoxifylline to group 5 animals in established septic shock caused uncontrolled, fatal systemic hypotension in two of the four animals. Plasma tumor necrosis factor activity, blood polymorphonuclear leukocyte counts, and CD18 expression were unaffected by the administration of pentoxifylline. CONCLUSIONS: Pentoxifylline protects against pulmonary and systemic hemodynamic derangements in fulminant sepsis and protects against pulmonary dysfunction. Pentoxifylline has a "therapeutic window" when given in established sepsis; if administration is delayed until overt septic shock occurs, it may then have deleterious effects.

Animals

Body mass index and economic productivity.

The paper reviews the evidence to date on the nutritional links with productivity and then goes on to provide results from a multi-country study on the effects of increasing body mass index (BMI) on productivity. The research relating nutritional status to work capacity is more consistent than the research linking nutritional status to productivity. None of the studies to date elucidate the pathways through which improved nutrition improves economic productivity. In addition, many of the studies that have been conducted on the nutrition/wage links have been based on samples that contained a disproportionate number of male subjects. The few studies that have disaggregated data by gender report different results for men and women. Research conducted at IFPRI is presented to examine the trends in BMI for men and women across countries and for Kenya to examine the relationships between various measures of nutritional status--BMI and height--and energy expenditures in women. BMIs of men show a more consistent relationship with increasing household income than do the BMIs of women. In the case of the Gambia and Kenya, the mean BMI of women decreases with increasing household income. One reason for the apparently low response of BMI to increasing household income in Kenya is the time allocation patterns of women. Women in the Kenya sample spend the largest proportion of their day in home production activities which are energy intensive. In examining the relationship between nutritional indicators and the time devoted to work, the results suggest a significant, positive association between both BMI and height and the amount of time devoted to work. In the models presented, both BMI and height appear to increase the capacity to carry out work. It is difficult to value much of this work time since a disproportionate share is devoted to home production activities. Some of the more classic methods of measuring economic productivity, such as measuring wage rates, are not relevant for women in this setting. The data from Kenya suggest that more appropriate measures for specifying the value of women's work need to be developed in order to capture some of the nutrition/productivity links which may exist.

Body Mass Index

Assessing the linkages between low body mass index and morbidity in adults: evidence from four developing countries.

The study explores the relationship between low BMI and illness patterns in four developing countries. Using probit analysis, the study finds small but statistically significant effect of low BMI on proneness to morbidity in Pakistan and Kenya but none in the Philippines and Ghana. The circularity of causation between low BMI and illness was addressed by using the instrumental variable approach. The study also finds that the threshold at which morbidity begins to rise is not consistent with the suggested cut-off of BMI 18.5 kg/m2. The cut-offs were meaningful only in the case of Pakistan, but even here, the sizes of relationships are quite small although statistically significant.

Adolescent

Rapid heterologous desensitization of muscarinic and thrombin receptor-mediated phospholipase D activation.

Activation of the M3 muscarinic receptor in 1321N1 human astrocytoma cells leads to increased phospholipase D (PLD)-catalyzed hydrolysis of phosphatidylcholine, which is maximal within 1 min of exposure to agonist. Studies examining the kinetics of phosphatidylethanol formation indicate that there is no further PLD activation beyond this time. Thrombin, a mitogen for quiescent 1321N1 cells, also activates PLD only transiently. The PLD response does not recover for up to 1 hr and cells that have been exposed to carbachol or thrombin do not respond to subsequent challenge with the heterologous agonist. In contrast to the desensitization observed with agonists, phorbol-12-myristate-13-acetate induces a sustained stimulation of PLD. In addition, cells pretreated with carbachol or thrombin show a normal response to phorbol-12-myristate-13-acetate, suggesting that the enzymatic activity of PLD is not compromised. Guanosine-5'-O-(3-thio)triphosphate activation of PLD in cell-free homogenates is also unaffected by prior treatment of the cells with agonist. Agonist-stimulated PLD activation in 1321N1 cells is mediated by protein kinase C (PKC). Thrombin and carbachol cause comparable changes in redistribution of both PKC-alpha and PKC-epsilon. The increase in membrane-associated PKC-alpha is transient and is reinitiated by addition of the heterologous agonist, whereas PKC-epsilon remains membrane associated for at least 60 min and is not further increased by addition of the heterologous agonist. We suggest that desensitization of PLD activation results from the down-regulation of an as yet undefined mediator required for agonist receptor coupling to PLD and that PKC-epsilon might participate in this down-regulation.

Astrocytoma

Health and nutrition effects of cash crop production in developing countries: a comparative analysis.

The paper presents results of a comparative analysis of the health and nutritional effects of cash crop production in 6 countries--The Gambia, Guatemala, Kenya, Malawi, the Philippines, and Rwanda. The 6 country case studies were conducted during the same time period and used a similar, although not identical, research protocol. Participation in cash crop schemes resulted in increases in household income. Short-term increases in household income did not result in a decrease in the incidence of illness in preschool-aged children nor in the total time that preschoolers were ill. Increases in household income did result in increases in the preschooler's energy consumption; however, the income/calorie consumption links, although significant, were weak. The household income gains did not have an immediate or large impact on preschooler nutritional status. While, in the longer term, increases in income may bring about improvements in preschooler health, in the short term, it appears that increases in income must be accompanied by improvements in the health environment in order to have a significant effect in reducing preschooler morbidity and improving child nutritional status.

Agriculture

Cytotoxic effects of children's faeces: relation to diarrhoea due to Clostridium difficile and other enteric pathogens.

Cytotoxicity of faecal extracts was demonstrated in 47 of 88 children (54%) referred for microbiological investigation of stools. Cytotoxic Clostridium difficile and vertotoxigenic Escherichia coli (VTEC) were the pathogens identified most commonly but cytotoxicity was also found in association with Campylobacter jejuni, Salmonella spp, Shigella sonnei, Giardia lamblia, rotavirus, adenovirus and poliovirus type 1 which had been acquired by oral immunization. In two patients, one of whom had cystic fibrosis, cytotoxicity of faecal extracts was associated with isolation of Pseudomonas aeruginosa. In five of 13 patients with diarrhoea and cytotoxic C. difficile, other pathogens were also present, in agreement with the view that C. difficile are more readily recovered when the intestinal flora have been altered by colonization with other micro-organisms. There was no correlation between previous treatment with antibiotics and isolation of C. difficile. Cytotoxicity neutralized by antitoxin, usually to C. sordellii, is used to detect cytotoxic C. difficile. We suggest that cytotoxicity not neutralized in this way should be an indication for further investigation of stools for the presence of other pathogens such as VTEC or viruses.

Adolescent

Survival of patients with acquired immune deficiency syndrome and disseminated Mycobacterium avium complex infection with and without antimycobacterial chemotherapy.

The contribution of disseminated Mycobacterium avium complex (DMAC) infection to the morbidity and mortality of patients with acquired immune deficiency syndrome (AIDS) is unclear. Previous studies that suggested the decreased survival of patients with AIDS and DMAC had incomplete information on patient immunologic status and follow-up. We studied patients with AIDS and DMAC and compared their survival with that of AIDS patients without DMAC but with other comparable risk factors for survival. Case and control subjects were similar in terms of CD4 cell count, prior AIDS status, history of antiretroviral therapy, history of Pneumocystis carinii prophylaxis, and year of diagnosis. A group of 39 patients with untreated DMAC had significantly shorter survival, mean of 5.6 +/- 1.1 months (median 4 months), than 39 matched patients with AIDS but without DMAC, mean 10.8 +/- 1.3 months (median 11 months, p less than 0.0001). The survival of 16 additional patients with DMAC who received antimycobacterial therapy, mean of 9.5 +/- 1.4 months (median 8 months), was not significantly shorter than that of an additional 16 matched control subjects, mean 11.7 +/- 1.9 months (median 11 months, p = 0.58). Patients with treated DMAC survived significantly longer than those with untreated DMAC (p less than 0.01). We conclude that untreated DMAC significantly shortens survival. Moreover, these results indicate that patients with DMAC who receive antimycobacterial therapy do not experience the shortened survival seen in untreated DMAC.

Acquired Immunodeficiency Syndrome

Distribution of primaquine in human blood: drug-binding to alpha 1-glycoprotein.

To clarify the distribution of the antimalarial primaquine in human blood, we measured the drug separately in the liquid, cellular, and ultrafiltrate phases. Washed red cells resuspended at a hematocrit of 0.4 were exposed to a submaximal therapeutic level of 250 ng/ml of carbon 14-labeled primaquine. The tracer was recovered quantitatively in separated plasma and red cells. Over 75% of the total labeled drug was found in red cells suspended in saline solution, but only 10% to 30% in red cells suspended in plasma. The plasma effect was not mediated by albumin. Studies with alpha 1-acid glycoprotein (AGP), tris(2-butoxyethyl)phosphate, an agent that displaces AGP-bound drugs, and cord blood known to have decreased AGP established that primaquine binds to physiologic amounts of the glycoprotein in plasma. Red cell primaquine concentration increased linearly as AGP level fell and as the free drug fraction rose. We suggest that clinical blood levels of primaquine include the red cell fraction or whole blood level because (1) erythrocytic primaquine is a sizable and highly variable component of the total drug in blood; (2) this component reflects directly the free drug in plasma, and inversely the extent of binding to AGP; (3) the amount of free primaquine may influence drug transport into specific tissues in vivo; and (4) fluctuations of AGP, an acute-phase reactant that increases greatly in patients with malaria and other infections, markedly affect the partition of primaquine in blood. Because AGP binds many basic drugs, unrecognized primaquine-drug interactions may exist.

Carbon Radioisotopes

An examination of the relationship between childhood depression and social competence amongst primary school children.

Forty-three primary school children who scored in the clinical range of the Children's Depression Inventory were compared with 43 children who were categorized as fearful but not depressed and a control group of 43 children who were classed as nondepressed-nonfearful. Subjects were matched across groups on the basis of grade and sex. The analyses were performed twice, initially with a depressed sample that excluded any depressed-fearful children and again with a depressed group that included such children. The results revealed that, independent of whether the depressed category included children who were also fearful, the depressed group reported lower levels of assertiveness and greater submissiveness, less adequate social skills performance, received lower ratings of peer popularity, fewer positive nominations from peer sociometry and more negative nominations. Depressed children were much more likely to be rejected or isolated by their peers than were their fearful or control counterparts.

Child