Rhythm Control in Heart Failure Patients With Atrial Fibrillation : Contemporary Challenges Including the Role of Ablation

Because nonpharmacological interventions likely alter the risks and benefits associated with rhythm control, this paper reviews the role of current rhythm control strategies in atrial fibrillation. This report also focuses on the specific limitations of pharmacological interventions and the utility of percutaneous ablation in this growing population of patients with concomitant atrial fibrillation and heart failure.     

Pharmacophore-based predictive model generation for potent antimalarials targeting haem detoxification pathway

Pharmacophore hypotheses were developed for molecules having antimalarial activities targeting the haem detoxification pathway of the malaria parasite. A training set consisting of 23 compounds was selected to generate these hypotheses, and their activities were evaluated for haem polymerization inhibition and against chloroquine-sensitive (3D7) as well as chloroquine-resistant (K1) strains of p. falciparum. The models were cross-validated by Fischer’s randomization test at a 95% confidence level. The model developed against chloroquine-resistant malaria parasites was found to yield the best predictions among the three models.     

Symphysis-fundal height measurement--a reliable parameter for assessment of fetal growth

Intrauterine growth retardation (IUGR) is one of the major causes of perinatal mortality in countries like India. Fundal height traditionally measured in relation to umbilicus and xiphisternum is of little value in predicting the fetal growth. Some workers have found that symphysis fundal height (SFH) measurements could be useful in screening pregnancies for growth retardation. A prospective study was taken up in 109 pregnant women attending the antenatal clinic of our Institution. Serial measurements of SFH, abdominal girth, double abdominal wall thickness (DAWT) and maternal weight gain were recorded. SFH measurements obtained were arranged on the basis of 10th, 50th and 90th percentile and represented graphically. Statistical analysis showed that the coefficient of variation was smallest for SFH as compared to abdominal girth and maternal weight gain. The babies (single born) delivered were between 2600 g and 3700 g irrespective of whether the maternal weight gain was 143 g/week or 424 g/week. The abdominal wall thickness had no influence on the measurement of SFH. An attempt was made to develop a nomogram of SFH for our population. This is a simple, reliable and inexpensive method in the screening of pregnancies for IUGR.     

Inhibition of tumorigenic potential and prostate-specific antigen expression in LNCaP human prostate cancer cell line by 13-cis-retinoic acid

Prostate-specific antigen (PSA) is a member of the kallikrein family and has been an important biological marker for prostate cancer. The mechanisms regulating PSA expression in prostatic cancer cells are unclear. The present study was designed to elucidate the role of 13-cis-retinoic acid (RA) in regulation of PSA and the tumorigenic potential of the human prostate cancer cell line LNCaP. The growth regulation of LNCaP cells was examined by DNA synthesis and doubling time. The tumorigenic potential of prostate cancer cells was analyzed by soft agar colony-forming assay, in vitro invasion assay, type IV collagenase assay and binding to extracellular matrix assay. The nuclear receptors for retinoic acid (RARα, -β, -γ and RXRα, -β,-γ) as well as PSA mRNA were determined by Northern blot using specific oligonucleotide probes. Our results suggest that 13-cis-RA significantly inhibits PSA secretion and expression both at the mRNA and protein levels compared with untreated cells. Electron microscopic studies suggest that after 13-cis-RA treatment, cells become more differentiated as they contain lumina, lined by plasma membrane and microvilli. Prostate cancer cell growth and tumorigenic potential after 13-cis-RA treatment was significantly decreased compared with controls. Nude mice tumorigenicity studies showed that 13-cis-RA-treated cells produced significantly smaller tumors compared with untreated cell tumors. There was also a significant increase in the expression of RXRa mRNA after 13-cis-RA treatment compared with untreated cells.     

Infant mortality in Pondicherry--an analysis of a cohort of 8185 births.

Infant mortality rate is one of the 12 global indicators for monitoring Health for All. Reliable data on infant mortality are not available for the majority of developing countries including India. To plan strategies for bringing down the rate and, later, to evaluate them, 'Cause Specific Rates' would be necessary. Pondicherry has achieved low rates of infant mortality. A study was conducted in the Anganwadis of Pondicherry to determine the causes of infant deaths. The 8185 children born between 1-4-1987 and 31-3-1988 in Pondicherry formed the study group. The Anganwadi workers collected information on the cause of death for the 222 children dying within the first year. The infant mortality rate was 27.1 per 1000 live births. Acute respiratory infections and diarrheal diseases accounted for 45% of the deaths.     

Storage (irritative) and voiding (obstructive) symptoms as predictors of benign prostatic hyperplasia progression and related outcomes

OBJECTIVES: To assess the utility of voiding and filling symptom subscores in predicting features of benign prostatic hyperplasia (BPH) progression, including acute urinary retention (AUR) and prostate surgery. METHODS: The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year study designed to evaluate the effects of finasteride versus placebo in men with lower urinary tract symptoms (LUTS), clinical evidence of BPH, and no evidence of prostate cancer. A self-administered questionnaire was employed to quantify LUTS at baseline. Receiver operating characteristics (ROC) curves were used to assess baseline characteristics from patients treated with placebo as predictors of outcomes. The characteristics assessed included the overall symptom score (Quasi-AUA SI), separate voiding and filling subscores, prostate volume (PV) and serum prostate-specific antigen (PSA) levels. RESULTS: PV and PSA were superior to the symptom scores at predicting episodes of spontaneous AUR and all types of AUR. The Quasi-AUA SI and the filling and voiding subscores were effective at predicting progression to surgery; however, PSA was more effective at predicting this outcome. To better evaluate symptoms as predictors of surgery, patients who experienced a preceding episode of AUR were excluded from the surgery analysis. In the absence of preceding AUR, the best predictors of future surgery were the Quasi-AUA SI and the filling subscore. CONCLUSIONS: Among men with LUTS, clinical BPH and no history of AUR, the overall symptom score and storage subscore are useful parameters to aid clinicians in identifying patients at risk for future prostate surgery. PV and PSA were the best predictors of AUR, while PSA was the best predictor of prostate surgery (for all indications).     

Characteristics and lipid distribution of a large, high-risk, hypertensive population: the lipid-lowering component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) consisted of 42,418 participants randomized to one of four antihypertensive treatment groups: chlorthalidone, amlodipine, lisinopril, or doxazosin. A subset of these participants with fasting low-density lipoprotein cholesterol levels 100–189 mg/dL were randomized into a lipid-lowering component: 5170 to receive pravastatin (40 mg daily) and 5185 to receive usual care. This report describes the characteristics and lipid distribution of these participants. There were no important differences between the randomized treatment groups. Women had higher total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol than men. There was a similar finding for black participants compared with whites, except blacks had lower triglycerides. Diabetics had lower high-density lipoprotein cholesterol and higher triglycerides than nondiabetics, and patients with body mass index <25 kg/m² had higher high-density lipoprotein cholesterol but lower low-density lipoprotein cholesterol and triglycerides than patients with higher body mass index. The success of the randomization of this large, diverse population and the differences in the lipid distributions among its subgroups will allow further understanding of optimal lipid-lowering treatment.     

Magnesium-supplemented warm blood cardioplegia in patients undergoing coronary artery revascularization

BACKGROUND: Although there is growing evidence to suggest that the administration of magnesium (Mg2+) to patients undergoing coronary artery bypass grafting (CABG) and to patients after myocardial infarction is beneficial, the addition of Mg2+ to cardioplegic solutions remains controversial. The aim of this study was to compare the effects of intermittent warm blood cardioplegia with and without Mg2+ supplementation on the early postoperative clinical outcomes in patients undergoing both elective or urgent CABG. METHODS: Four hundred patients undergoing CABG were prospectively randomized to receive either blood cardioplegia without Mg2+ (BC, n = 200) or supplemented with Mg2+ (BC-Mg2+, n = 200). Serial plasma Mg2+ concentrations were recorded at base line and postoperatively from days 1 to 4. RESULTS: Patient characteristics were similar and no significant differences were found in early mortality and morbidity in the two groups. Analysis of 178 patients undergoing urgent CABG for unstable symptoms (BC = 95, BC-Mg2+ = 83) demonstrated a significantly lower requirement for internal defibrillation and temporary epicardial pacing in the BC-Mg2+ group. Furthermore, there was a nearly twofold lower incidence of new postoperative atrial fibrillation in the BC-Mg2+ group compared with the BC group (19% versus 34%, p = 0.03). Postoperative plasma Mg2+ levels were consistently lower in those patients who developed new postoperative atrial fibrillation compared with those who did not (p = 0.05). CONCLUSIONS: The addition of Mg2+ to warm blood cardioplegia resulted in a lower incidence of intraoperative and postoperative arrhythmias in patients undergoing urgent CABG for unstable angina.