Genomic screen for loci associated with tobacco usage in Mission Indians

Background  

The prevalence of tobacco usage in Native American adults and adolescents is higher than any other racial or ethnic group, yet biological risk and protective factors underlying tobacco use in this ethnic group remain unknown. A genome scan for loci associated with tobacco use phenotypes was performed with data collected from a community sample of Mission Indians residing in Southwest California.     

Cytochrome P450 3A4 Activity in Premenopausal and Postmenopausal Women,Based on 6-β-Hydroxycortisol:Cortisol Ratios

Study Objective . To characterize cytochrome P450 (CYP) 3A4 activity in premenopausal and postmenopausal women by evaluating the urinary 6-β-hydroxycortisokcortisol ratio. Design . Prospective study. Subjects . Thirteen premenopausal and 13 postmenopausal women who were healthy and not receiving drugs known to affect CYP3A4 activity. Interventions . Beginning on day 2 of menses, premenopausal women collected first morning urine samples every other day for a complete menstrual cycle. Postmenopausal women collected first morning urine every other day for 28 days. Measurements and Main Results . Mean weekly 6-β-hydroxycortisol:cortisol ratios did not differ during the phase (week) of the menstrual cycle. Daily ratios did not differ in postmenopausal women. No difference between premenopausal and postmenopausal women was found on comparing overall median ratios. Conclusion . Cytochrome P450 3A4 activity as measured by 6-β-hydroxy cortisol:cortisol ratio did not differ by week of menstrual cycle, suggesting no menstrual cycle-related changes. Menopause does not appear to be associated with differences in CYP3A4 activity, compared with premenopause.     

No impact of repeated endoscopic screens on gastric cancer mortality in a prospectively followed Chinese population at high risk.

BACKGROUND: Gastric cancer (GC) is the leading cause of cancer deaths in China. Our study prospectively evaluated the impact of repeated endoscopic screens on GC mortality in a high-risk population in China. METHODS: Between 1989 and 1999, a population-based gastroscopic screening was conducted in 4,394 residents of Linqu County, China, a region with the highest rates of GC worldwide. Residents ages 35 to 64 years received initial gastroscopies with biopsies in 1989. Repeated endoscopies were performed in 1994 and 1999. Cancer occurrences and deaths were actively monitored throughout the entire period until July 2000. Mortality from GC was compared with expected values based on mortality rates obtained for Linqu in the 1990-1992 Chinese Cancer Mortality Survey. RESULTS: Between March 1989 and July 2000, 39,303 person-years were accumulated; 85 new GCs occurred, 29 (34.5%) were in early stage. Fifty-eight cases (68%) were identified at one of the screens. The number of observed deaths from GC (37) was close to the expected (36.8). The standardized mortality ratio was 1.01 (95% CI 0.72-1.37) for the entire cohort, 1.13 (95% CI 0.77-1.57) for males, and 0.65 (95% CI 0.26-1.32) for females. CONCLUSIONS: Despite high population coverage with repeated screens, no reduction in GC mortality was observed in this high-risk population in China.     

INTELLECTUAL FUNCTIONS OF PATIENTS WITH CHILDHOOD-ONSET EPILEPSY

The intellectual functions of 64 epileptic patients who had had an initial evaluation between five and 16 years of age, including the WISC, were re-evaluated after a period of at least five years. In general the seizure states had improved, and 50 per cent were in remission for between two and eight years. All but four were still taking at least one anticonvulsant drug. WISC IQ estimates showed a slight decrease. Verbal and performance areas could be differentially affected, and a gain in one could be offset by a loss in the other, so the Full-scale IQ might not be a reliable measure of day-to-day performance. Those whose seizures remained uncontrolled had a statistically significant decrease in performance IQ, whereas in general it was stable or increased for patients in remission. There was evidence that decreased IQ indicated slower mental growth rather than loss of previously acquired function. Phenobarbital but not phenytoin levels were inversely correlated with IQ, suggesting that the upper limit of the 'therapeutic range' of phenobarbital may already be toxic with regard to learning abilities. To optimize an epileptic child's functioning in school and to prevent long-term intellectual problems, it is advisable that IQ testing should be part of the routine initial evaluation, and that drug levels should be checked at regular intervals.     

Asymmetric dimethyl-arginine and coronary artery calcification in young adults entering middle age: the CARDIA Study.

BACKGROUND: Normal endothelial function depends on nitric oxide (NO) release by endothelial cells. Asymmetric dimethylarginine (ADMA), by competing with L-arginine, inhibits NO production and may lead to endothelial dysfunction and atherosclerotic development. Our aim was to ascertain the association between ADMA and coronary artery calcification (CAC), a marker of atherosclerotic coronary disease burden. DESIGN: A nested case-control study within the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, an observational study among young adults residing in four US cities. METHODS: Participants were 263 white and black male and female cases with the presence of CAC and 263 sex and race-matched controls without evidence of CAC by computed tomography, 33-47 years old in 2000-2001. RESULTS: The median level (range) of ADMA was significantly higher in cases (0.55; 0.20-2.22 micromol/l) than in controls (0.53; 0.32-1.30 micromol/l; P=0.03). In conditional logistic regression adjusting for age, field center, educational attainment, smoking status, alcohol consumption, body mass index, waist circumference, hypertension, diabetes, low-density lipoprotein and high-density lipoprotein-cholesterol, triglycerides, renal function and C-reactive protein, the highest tertile of ADMA, compared with the lowest tertile, was associated with 1.80 (95% confidence interval 1.03-3.15) increased odds of the presence of any CAC. By linear regression, a significant independent relationship was also found between ADMA and the degree of CAC. CONCLUSION: These results support a role for ADMA as a biochemical marker of CAC.     

Short term correlates of the Neuro Emotional Technique for cancer-related traumatic stress symptoms: A pilot case series

Introduction As many as one quarter of all cancer survivors report traumatic stress symptoms from cancer-related experiences. While the majority of these patients do not meet the criteria for posttraumatic stress disorder (PTSD), there is growing evidence that subsyndromal symptoms can significantly contribute to functional impairment and negative health outcomes. Treatment options for the hallmark symptoms of traumatic stress—unpleasant, intrusive thoughts and avoidant behaviors—have not been well investigated for the cancer survivorship population. Materials and methods Seven female cancer survivors with traumatic stress symptoms from cancer-related experiences and no other major psychopathology, were enrolled to receive three sessions of Neuro-Emotional Technique (NET), a brief, targeted treatment that combines traditional desensitization principles with complementary modalities. Results Psychological outcome measures (Impact of Event Scale (IES) and Subjective Units of Distress (SUD) and physiological measures (Heart Rate (HR) and Skin Conductance Level (SCL) demonstrated the following changes: 71% on IES, 88% SUD, 74% on HR, and 65% on SCL following the intervention. Statistically significant changes were observed for all four parameters, and effect size g for proportion improved were 0.50 each for IES, SUD, and HR, and 0.20 for SCL. Conclusions These cases suggest feasibility of the NET intervention for cancer-related traumatic stress and the potential for change in symptoms and physiological reactivity. Further investigation is needed to determine the specific and long-term effects of such an approach. Implications for cancer survivors Traumatic stress from cancer-related experiences might represent a constellation of symptoms that are amenable to brief, targeted interventions. This study was supported by the O.N.E. Research Foundation     

IDEC-131 (Anti-CD154), Sirolimus and Donor-Specific Transfusion Facilitate Operational Tolerance in Non-Human Primates

CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.