A case-comparison study of weight fluctuations during young adulthood and coronary artery disease during middle age

The hypothesis that large fluctuations in weight during young adulthood are associated with the degree of coronary artery disease was investigated by comparing patterns of weight change of patients with angiographically defined diseased or normal arteries. Participants (n = 823) were selected from men and women aged 40-74 years who had undergone angiography at North Carolina Baptist Hospital during 1987-88. Weight history from age 20 to 40 was assessed with a mailed questionnaire. Per cent prevalence of "yo-yo dieting" adjusted for age, race, and coronary disease risk factors in patients who had 0, 1, 2, 3, or more than 3 diseased arteries was 8.6, 8.8, 3.7, 5.6 and 7.1 per cent respectively (p = 0.313). These results do not support the research hypothesis. However, since the results may have been confound by neuroticism, they should not be interpreted as strong evidence against this hypothesis. ^

A PHARMACOLOGICAL EVALUATION OF THE MECHANISM OF CYTOTOXICITY OF 9-BETA-D- XYLOFURANOSYLADENINE IN CHINESE HAMSTER OVARY CELLS

The biochemical determinants of cytotoxicity of the purine nucleoside analog, 9-(beta)-D-xylofuranosyladenine (xyl-A) were studied in wild-type Chinese hamster ovary cells and in nucleoside kinase deficient mutants. It was found that {('3)H}xyl-A was readily phosphorylated to the triphosphate level in both the wild-type and deoxycytidine kinase deficient mutant, but not by the adenosine kinase deficient cells. Values for the apparent Km and Vmax of this uptake process were 43.9 (mu)M and 118.7 nmol/min/10('9) cells, respectively. Cloning procedures indicated that the viability of CHO cells was decreased 90 per cent by a 5-hr incubation with 10 (mu)M xyl-A. However, the toxicity of xyl-A was increased 100-fold by the addition of a nontoxic concentration (10 (mu)M) of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) to the medium. High-pressure liquid chromatographic analysis indicated that after 5 hr, the concentration of 9-(beta)-D-xylofuranosyladenine 5'-triphosphate (xyl-ATP) in cells incubated with xyl-A plus EHNA was 2.0 mM, four times greater than in those cells incubated with xyl-A alone. Incubation with xyl-A plus EHNA had no significant effect on the cellular concentrations of 5-phosphoribosyl-1-pyrophosphate after 1 hr whereas, treatment with 3'-dexoyadenosine (cordycepin) decreased the concentration of this metabolite. Determinations of the cellular nucleoside triphosphates indicated that under conditions that resulted in an intracellular accumulation of 500 (mu)M xyl-ATP, the endogenous concentrations of neither the ribonucleoside triphosphates nor deoxyribonucleoside triphosphates were significantly different from those of control cells. The ID(,50) for {('3)H}thymidine incorporation into DNA, 105 (mu)M xyl-ATP, was four-fold less than the ID(,50) for {('3)H}uridine incorporation into RNA suggesting that the process of DNA synthesis is more sensitive to the presence of xyl-ATP. When removed from exogenous xyl-A, CHO cells failed to recover their ability to synthesize RNA and DNA, although the intracellular xyl-ATP concentration decreased to less than 35 (mu)M. The selective inhibition of RNA synthesis by 6-azauridine did not prevent the expression of toxicity by xyl-ATP. However, the selective inhibition of DNA synthesis by ara-C significantly spared toxicity in cells that had accumulated an otherwise lethal concentration of xyl-ATP. It is shown that in cells which had accumulated 1.27 mM {('3)H}xyl-ATP, {('3)H}xyl-A was found to terminate cellular RNA chains at a frequency of 1.42 (mu)mol of {('3)H}xyl-A 3' termini per mol of mononucleotide. These results indicate that a general mechanism for the toxicity of xyl-A to CHO cells includes the cellular accumulation of xyl-ATP, which serves as a substrate for RNA synthesizing enzymes and subsequently is incorporated into nascent RNA transcripts as a chain terminator. A specific mechanism involving the premature termination of RNA primers required for the initiation of DNA synthesis is proposed to account for the inhibitory action of xyl-ATP on DNA synthesis. ^

Case-control study of factors associated with virologic failure in HIV-infected children on HAART in Botswana, a developing African country

According to the United Nations Program on HIV/AIDS (UNAIDS, 2008), in 2007 about 67 per cent of all HIV-infected patients in the world were in Sub-Saharan Africa, with 35% of new infections and 38% of the AIDS deaths occurring in Southern Africa. Globally, the number of children younger than 15 years of age infected with HIV increased from 1.6 million in 2001 to 2.0 million in 2007 and almost 90% of these were in Sub-Saharan Africa. (UNAIDS, 2008).^ Both clinical and laboratory monitoring of children on Highly Active Anti-Retroviral Therapy (HAART) are important and necessary to optimize outcomes. Laboratory monitoring of HIV viral load and genotype resistance testing, which are important in patient follow-up to optimize treatment success, are both generally expensive and beyond the healthcare budgets of most developing countries. This is especially true for the impoverished Sub-Saharan African nations. It is therefore important to identify those factors that are associated with virologic failure in HIV-infected Sub-Saharan African children. This will inform practitioners in these countries so that they can predict which patients are more likely to develop virologic failure and therefore target the limited laboratory monitoring budgets towards these at-risk patients. The objective of this study was to examine those factors that are associated with virologic failure in HIV-infected children taking Highly Active Anti-retroviral Therapy in Botswana, a developing Sub-Saharan African country. We examined these factors in a Case-Control study using medical records of HIV-infected children and adolescents on HAART at the Botswana-Baylor Children's Clinical Center of Excellence (BBCCCOE) in Gaborone, Botswana. Univariate and Multivariate Regression Analyses were performed to identify predictors of virologic failure in these children.^ The study population comprised of 197 cases (those with virologic failure) and 544 controls (those with virologic success) with ages ranging from 3 months to 16 years at baseline. Poor adherence (pill count <95% on at least 3 consecutive occasions) was the strongest independent predictor of virologic failure (adjusted OR = 269.97, 95% CI = 104.13 to 699.92; P < 0.001). Other independent predictors of virologic failure identified were: First Line NNRTI with Nevirapine (OR = 2.99, 95% CI = 1.19 to7.54; P = 0.020), Baseline HIV-1 Viral Load >750,000/ml (OR = 257, 95% CI = 1.47 to 8.63; P = 0.005), Positive History of PMTCT (OR = 11.65, 95% CI = 3.04-44.57; P < 0.001), Multiple Care-givers (>=3) (OR = 2.56, 95% CI = 1.06 to 6.19; P = 0.036) and Residence in a Village (OR = 2.85, 95% CI = 1.36 to 5.97; P = 0.005).^ The results of this study may help to improve virologic outcomes and reduce the costs of caring for HIV-infected children in resource-limited settings. ^ Keywords: Virologic Failure, Highly Active Anti-Retroviral Therapy, Sub-Saharan Africa, Children, Adherence.^

Survival of gastrointestinal and stromal tumor patients at UT M.D. Anderson Cancer Center

Objective. Gastrointestinal Stromal Tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract with spindled cell, epithelioid, or occasionally pleomorphic morphology. The primary objective of this paper is to describe the demographic and clinical characteristics and survival among GIST patients registered at the University of Texas M.D. Anderson Cancer Center (MDACC). ^ Methods. This cohort study includes 783 consecutive patients diagnosed with GIST from 1995 to 2007. Demographic, clinical and survival information were obtained from the MDACC cancer registry. ^ Statistical Analysis. Kaplan-Meier survival curves, univariate and multivariate Cox proportional hazards analysis were conducted to estimate survival and identify prognostic clinical factors associated with survival. Results. The age at diagnosis of MDACC GIST cases ranged from 17 to 91 with a mean of 57 years and a male-to-female ratio of 1.3:1. The racial distribution was whites 77%, African-Americans 9.5%, Hispanics 9.3% and other races 4.2%. Fifty per cent of the GISTs arose from stomach, 35% small intestine, 7% retroperitoneal space, 6% colorectal and 2% were omentum and mesentery. About half of the tumors were less than 10 cm in size. Fifty eight per cent of the tumors were localized whereas 36% were metastatic. MDACC GIST patients were generally comparable to SEER patients, but, on the average, were 7 years younger than SEER patients and were predominantly whites. ^ Stratification of 783 GIST cases by year of diagnosis based on the introduction of imatinib treatment in 2000 revealed that 60% of the GIST cases were first diagnosed between 2000 and 2007 whereas, 40% were first diagnosed between 1995 and 1999. There was a significant difference between the two cohorts in the distribution of race, GIST symptom, tumor size, tumor site, and stage of the tumor at diagnosis. The 1- and 5-year survival was 93% and 59% in the 1995–2007 cohort. Multivariate Cox regression analysis identified age at diagnosis (p<0.001), female sex (p=0.047), tumor size (p=0.07), multiple cancers (p=0.002), and GIST diagnosed between 2000 and 2007 (p<0.001) were significantly associated with survival. Approximately, 58% of the cases were treated with imatinib whereas 42% did not receive imatinib in 2000–2005 cohort. There was a significant difference in survival between imatinib and non-imatinib groups and in the distribution of tumor size categories, stage of the tumor at diagnosis and cancers before the diagnosis of GIST. The 1- and 5-year survival for imatinib patients was 99% and 73% and was 91% and 63% for non-imatinib patients. Multivariate Cox regression analysis of the 2000–2007 cohort identified, age at diagnosis and tumor stage as possible prognostic factors associated with survival.^

OUT-OF-HOSPITAL CHILDBEARING CENTERS IN THE UNITED STATES: A DESCRIPTIVE STUDY OF THE DEMOGRAPHIC AND MEDICAL-OBSTETRIC CHARACTERISTICS OF WOMEN BEGINNING LABOR THEREIN 1972-1979

There is currently much interest in the appropriate use of obstetrical technology, cost containment and meeting consumers' needs for safe and satisfying maternity care. At the same time, there has been an increase in professionally unattended home births. In response, a new type of service, the out-of-hospital childbearing center (CBC) has been developed which is administratively and structurally separate from the hospital. In the CBC, maternity care is provided by certified nurse-midwives to carefully screened low risk childbearing families in conjunction with physician and hospital back-up.^ It was the purpose of this study to accomplish the following objectives: (1) To describe in a historical prospective study the demographic and medical-obstetric characteristics of patients laboring in eleven selected out-of-hospital childbearing centers in the United States from May 1, 1972, to December 15, 1979. Labor is defined as the onset of regular contractions as determined by the patient. (2) To describe any differences between those patients who require transfer to a back-up hospital and those who do not. (3) To describe administrative and service characteristics of eleven selected out-of-hospital childbearing centers in the United States. (4) To compare the demographic and medical-obstetric characteristics of women laboring in eleven selected out-of-hospital childbearing centers with a national sample of women of similar obstetric risk who according to birth certificates delivered legitimate infants in a hospital setting in the United States in 1972.^ Research concerning CBCs and supportive to the development of CBCs including studies which identified factors associated with fetal and perinatal morbidity and mortality, obstetrical risk screening, and the progress of technological development in obstetrics were reviewed. Information concerning the organization and delivery of care at each selected CBC was also collected and analyzed.^ A stratified, systematic sample of 1938 low risk women who began labor in a selected CBC were included in the study. These women were not unlike those described previously in small single center studies reported in the literature. The mean age was 25 years. Sixty-three per cent were white, 34 per cent Hispanic, 88 per cent married, 45 per cent had completed at least two years of college, nearly one-third were professionals and over a third were housewives. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI ^

THE EFFECT OF CAFFEINE CONSUMPTION ON MORTALITY IN HYPERTENSIVE INDIVIDUALS

The effect of caffeine consumption on mortality was evaluated in a historical cohort study of 10064 hypertensive individuals participating in the Hypertension Detection and Follow-Up Program (HDFP) from 1973 to 1979. The study cohort was stratified into caffeine consumption groups (none, low, medium and high) based on their total level of caffeine intake from beverages (coffee and tea) and certain medications at the One-year follow-up home visit. Stratification was also made by sex, race, type of care and age. The total relative risks (RRs) when computed across strata for each caffeine consumer group (low, medium and high) were not significantly different when compared to the noncaffeine consumer group for all-cause or cause-specific mortality rates. The point estimates and 95 per cent confidence intervals for relative risks of all-cause mortality when compared to nonconsumers were as follows: Low = 0.82 (0.65-1.03), Medium: = 0.82 (0.62-1.82) and High = 0.90 (0.63-1.28). For all sex, race combinations there was an increase in the per cent of current smokers within each caffeine consumer group as the level of caffeine consumption increased. Cigarette smoking was an important confounder correlated with caffeine consumption and associated with mortality in this cohort. When confounding by cigarette smoking was adjusted for in the analysis, no association was found between the level of caffeine consumption and all-cause or cause-specific mortality. ^