The involvement of the renin-angiotensin system gene polymorphisms in coronary heart disease

INTRODUCTION AND OBJECTIVES: Previous studies angiotensin-converting enzyme gene insertion/deletion polymorphism ACE (I/D), angiotensinogen gene polymorphism, and angiotensin II AT1 receptor polymorphism in relation to coronary heart disease controversial results. This study was designed to analyze the association between these gene polymorphisms and the first coronary event in individuals residing on Grand Canary Island, Spain. PATIENTS AND METHOD: Case-control study. Case subjects (n = 304) were recruited at the first coronary event; age-matched controls (n = 315) were randomly selected from the Grand Canary population. Participants were examined for the usual risk factors. Blood samples were obtained for biochemical analyses and DNA extraction. Genotyping was performed by PCR and restriction analysis. RESULTS: Neither ACE (I/D) nor AT1 receptor polymorphism was associated with coronary heart disease, whereas the frequency distribution of AGT M235T genotypes among patients and control subjects (TT: 29% and 19%; MT: 48% and 50%; MM: 22% and 31%, respectively) was statistically different (p = 0.003). Multiple logistic regression analysis identified the TT genotype of the angiotensinogen gene (OR = 1.9; 95% CI 1.1-3.4), diabetes (OR = 4.4; 95% CI 2.0-9.4) and hypertension (OR = 2.1; 95% CI 1.3-3.3) as risk factors predicting the coronary event. CONCLUSIONS: Our results provide no evidence of an association between ACE (I/D) or AT1 receptor polymorphism and coronary heart disease. However, homozygosity for the T allele of the angiotensinogen gene, diabetes and hypertension independently place individuals at higher risk of experiencing a coronary event on Grand Canary Island.     

Quality of life in bridge-to-transplant patients with chronic heart failure after implantation of an axial flow ventricular assist device

Research suggests that ventricular assist devices improve quality of life for congestive heart failure patients awaiting heart transplantation. Axial flow ventricular assist devices like the Jarvik 2000 (Jarvik Heart, Inc., New York, NY) represent the newest type of ventricular assist device technology, but their effects on quality of life are not well understood. Therefore, the authors administered the Minnesota Living with Heart Failure Questionnaire to patients who had the Jarvik 2000 implanted as a bridge to heart transplantation. Patients completed the Minnesota Living with Heart Failure Questionnaire immediately before device implantation, 1 month after implantation, immediately before heart transplantation, and 1 month after transplantation. One month after implantation of the device, the nine patients who completed the study showed significant improvements in physical (p<0.008), emotional (p<0.02), and overall (p<0.008) quality of life. These improvements were maintained until the device was explanted. The authors conclude that implantation of the Jarvik 2000 ventricular assist device can substantially improve quality of life for patients awaiting heart transplantation.     

Intestinal pseudo-obstruction as an initial presentation of systemic sclerosis in two children

Two children are reported in whom intestinal pseudo-obstruction was the initial manifestation of systemic sclerosis. Gastrointestinal symptoms and skin changes resolved or improved in both children following treatment with prednisone and penicillamine (case 1) or methotrexate (case 2), although radiological changes of the gastrointestinal tract persisted at 3 and 2 yr of follow-up, respectively.      

Vulnerability to HIV Among Women Formerly Incarcerated and Women with Incarcerated Sexual Partners

HIV risk was assessed in association with a history of incarceration and having a sexual partner with a history of incarceration in a population sample of low-income young women residing in San Francisco. Of the 235 women surveyed, 23% reported prior incarceration and 42% reported having a sexual partner with a history of incarceration. Prevalence of sexually transmitted infections (STIs) (including HIV) was no higher among previously incarcerated women or those with a sexual partner with a history of incarceration. Women with a prior incarceration were significantly more likely to report injecting drugs, exchanging sex for money or drugs, and history of forced sex. Women reporting sexual partners with a history of incarceration were significantly more likely to report incarceration history, history of STIs, and history of forced sex. Interventions aimed at reducing substance abuse, STIs, commercial/survival sex, and the effects of sexual coercion need to be strengthened for women within and transitioning out of correctional facilities.     

A successful anticoagulation protocol for the first HeartMate II implantation in the United States

Bleeding and thrombus formation are common problems with life-threatening implications in patients receiving a left ventricular assist device. We describe the anticoagulation protocol for the 1st patient in the United States to undergo successful implantation of the HeartMate II left ventricular assist system.     

Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor

Background:

Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.

Methods:

We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

Results:

TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC₅₀ of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC₅₀ values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [¹¹C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [¹¹C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC₅₀ for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.

Conclusions:

These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.     

Self-perception of theoretical knowledges and practical skills by primary health care physicians in life-threatening emergencies according to their gender: A cross-sectional study

To assess the training received in Emergency Medicine (EM) by the Primary Health Care physicians of Asturias, as well as their perception of their own theoretical knowledge and practical skills in a series of procedures employed in life-threatening emergencies, and also to analyze the differences according to gender. The degree of preparation of Primary Health Care physicians for handling emergencies, according to the gender of the professionals, has never been studied before.Cross-sectional study of a sample of 213 Primary Health Care physicians from the Primary Health Care Service of Asturias, Spain, from among the total of 851 physicians on the staff of the Primary Health Care Service of Asturias. The survey was design ad hoc using the Body of Doctrine of Emergency Medicine proposed by the Spanish Society of Emergency Medicine, which indicates the theoretical and practical procedures that must be mastered by the Primary Health Care physicians.There are nonsignificant differences in the mean of theoretical knowledge and practical skills in many procedures or techniques studied depending on the gender.Female and male Asturian Primary Health Care physicians are generally well prepared to handle life-threatening emergencies. The degree of self-perception and acquisition of general theoretical knowledge and general practical skills for handling life-threatening emergencies is heterogeneous, and differences according to gender are not statistically significant.     

Measuring Emergency Care Survival: The Implications of Risk Adjusting for Race and Poverty

Objectives

We determined the impact of including race, ethnicity, and poverty in risk adjustment models for emergency care–sensitive conditions mortality that could be used for hospital pay‐for‐performance initiatives. We hypothesized that adjusting for race, ethnicity, and poverty would bolster rankings for hospitals that cared for a disproportionate share of nonwhite, Hispanic, or poor patients.

Methods

We performed a cross‐sectional analysis of patients admitted from the emergency department to 157 hospitals in Pennsylvania with trauma, sepsis, stroke, cardiac arrest, and ST‐elevation myocardial infarction. We used multivariable logistic regression models to predict in‐hospital mortality. We determined the predictive accuracy of adding patient race and ethnicity (dichotomized as non‐Hispanic white vs. all other Hispanic or nonwhite patients) and poverty (uninsured, on Medicaid, or lowest income quartile zip code vs. all others) to other patient‐level covariates. We then ranked each hospital on observed‐to‐expected mortality, with and without race, ethnicity, and poverty in the model, and examined characteristics of hospitals with large changes between models.

Results

The overall mortality rate among 170,750 inpatients was 6.9%. Mortality was significantly higher for nonwhite and Hispanic patients (adjusted odds ratio [aOR] = 1.27, 95% confidence interval [CI] = 1.19–1.36) and poor patients (aOR = 1.21, 95% CI = 1.12–1.31). Adding race, ethnicity, and poverty to the risk adjustment model resulted in a small increase in C‐statistic (0.8260 to 0.8265, p = 0.002). No hospitals moved into or out of the highest‐performing decile when adjustment for race, ethnicity, and poverty was added, but the three hospitals that moved out of the lowest‐performing decile, relative to other hospitals, had significantly more nonwhite and Hispanic patients (68% vs. 11%, p < 0.001) and poor patients (56% vs. 10%, p < 0.001).

Conclusions

Sociodemographic risk adjustment of emergency care–sensitive mortality improves apparent performance of some hospitals treating a large number of nonwhite, Hispanic, or poor patients. This may help these hospitals avoid financial penalties in pay‐for‐performance programs.