The DISCOVERY PENTA study: a DIrect Statin COmparison of LDL-C Value--an Evaluation of Rosuvastatin therapY compared with atorvastatin

BACKGROUND: International guidelines emphasize the need to achieve recommended low-density lipoprotein cholesterol (LDL-C) levels in order to reduce morbidity and mortality associated with coronary heart disease (CHD). However, many patients with hypercholesterolemia fail to achieve LDL-C goals on treatment. OBJECTIVE: The primary objective was to compare the efficacy of rosuvastatin and atorvastatin for enabling patients to achieve National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goals. Secondary objectives were European LDL-C goal achievement, changes in the lipid profile, and safety. RESEARCH DESIGN AND METHODS: This 12-week, multicenter, multinational, randomized, open-label trial compared the efficacy and safety of rosuvastatin 10 mg with atorvastatin 10 mg in statin-na?ve and switched patients with primary hypercholesterolemia from Brazil, Colombia, Mexico, Portugal, and Venezuela. RESULTS: A total of 1124 patients with similar baseline characteristics were randomized to the two treatment groups. After 12 weeks of treatment, a significantly greater percentage of patients receiving rosuvastatin 10 mg compared with atorvastatin 10 mg achieved NCEP ATP III LDL-C goals (71.2% vs 61.4%, p < 0.001), 1998 European LDL-C goals (73.5% vs 59.2%, p < 0.001) and 2003 European LDL-C goals (58.9% vs 44.6%, p < 0.001). Rosuvastatin treatment was associated with significant reductions in LDL-C and total cholesterol (TC) and, in statin-na?ve patients, a significant increase in high-density lipoprotein cholesterol (HDL-C) compared with atorvastatin treatment. Both treatments were well tolerated with a similar incidence of adverse events. Clinically significant elevations in creatinine, creatine kinase or hepatic transaminases were low and similar between treatment groups. CONCLUSIONS: Rosuvastatin 10 mg is significantly more effective at achieving NCEP ATP III and European LDL-C goals, lowering LDL-C and TC in both na?ve and switched patients and increasing HDL-C in na?ve patients than atorvastatin 10mg, with a similar safety and tolerability profile. This study also provides evidence regarding the comparative effects of rosuvastatin versus atorvastatin in Latin American and Portuguese populations.     

Ectodermal dysplasia in females and inversion of chromosome 9.

Absence of sweat glands, hypotrichosis, hypodontia, characteristic facial features, and intolerance to heat, without dystrophia of the nails, are manifestations of sex linked hypohydrotic ectodermal dysplasia. Three males and two females were affected in a family in which the affected females were also carrying a pericentric inversion of chromosome 9. Those phenotypically normal females in this pedigree who were obligate carriers had normal karyotypes. One of the affected females (the proband) had, in addition, primary amenorrhoea, absence of the mammary glands, and rudimentary internal genitalia. The fact that clinical manifestations of ectodermal dysplasia in the carrier females of this family are only observed in those also carrying a pericentric inversion of chromosome 9 in peripheral blood leucocytes perhaps suggests that non-random inactivation of the paternal X chromosome has occurred as a consequence of the inversion.     

Presence of serotonin in the rat vas deferens: its influence on contractile responses

Serotonin has been detected in the rat vas deferens. Increase in the serotonin concentration by exposure of the rat vas deferens to L-tryptophan occurs in vitro. p-chlorophenylalanine partly blocks the increase in serotonin concentration induced by tryptophan in vitro but not in vivo. Chronic sympathetic denervation induces an increase in 5-HT concentration. Responses of the vas deferens to transmural stimulation are depressed by pretreatment of rats with p-chlorophenylalanine, and the depression is reversed by incubation in vitro with 5-hydroxytryptophan or serotonin. Serotonin can enhance the response to transmural stimulation at low concentrations but has no effect at higher concentrations. Physostigmine-induced enhancement of the response to stimulation is depressed only by higher concentrations of serotonin. The results raise the question whether endogenous serotonin can act as a modulator of neurotransmission in the rat vas deferens.     

Behavior of the ST segment, during isometric exercise, in chagasic patients with apical aneurysm of the left ventricle

In order to study the ST-segment changes during isometric exercise (IE) we have reviewed the hemodynamic and cineangiographic protocols of 13 with Chaga's disease patients. On the basis of the electrocardiogram (EKG) and the left ventricular cineangiogram, the chagasic patients were divided in two groups. Chagas' group I: 6 patients with left ventricular apical aneurysm, Chagas' II: 7 patients with multiple left ventricular dyskinetic segment and occasional premature ventricular contractions. Fourteen subjects with normal left ventricular cineangiograms and normal EKG's were used as controls. The IE was performed by all chagasic and control subjects 31.9 +/- 18 (M +/- SD) months after the cardiac catheterization. The IE was performed at 25% of maximum voluntary capacity for 5 minutes. The precordial leads (V1-V6) were simultaneously recorded, in the standing position, immediately before and after the IE. The ST-segment changes were assessed by measuring the distance of the 'J point, of the ST-segment, to the baseline in three consecutive sinus beats. Immediately before the IE, 5 patients of Chagas' group I (86%) has ST-segment elevation (leadas V1-V2). In the control group, only 2 subjects (14%) had ST-segment elevation, (P less than 0.007). After IE, the control subjects "normalized" their ST-segment elevation, whereas it persisted elevated in the 5 Chagas' group I patients (P less than 0.003). These results suggest that in chagasic patients, the ST-segment changes observed during isometric exercise could be related to the presence of left ventricular apical aneurysm.     

Radiofrequency ablation of a left anterior accessory pathway in a patient with Wolff-Parkinson-White and major venous drainage anomaly

Anomalies of the venous system may impose serious limitations to the treatment of arrhythmias by means of ablation therapy. We describe a patient who had the Wolff-Parkinson-White syndrome with frequent episodes of antidromic supraventricular tachycardia in whom an ablation was performed. The patient was found to have no inferior vena cava, a hemiazygos vein draining in a persistent left superior vena cava, and a left anterior manifest accessory pathway.     

Tachycardiomyopathy in patients with and without subacute cardiac pathology. Experiences at the Cardiovascular Center of Merida, Venezuela]

We report our experiences with tachycardia-induced cardiomyopathy. Nine patients (3-56 years old) had incessant supraventricular tachycardia and congestive heart failure. The cardiac eco-Doppler evidenced a significant increase of cardiac volumes and mild tricuspid and mitral regurgitation. The ejection fraction (EF) was 0.31 +/- 0.12, the end diastolic volume was 162 +/- 48 cc and the end systolic volume, 116 +/- 54 cc. Four patients had accessory pathways, 3 atrial flutter, 1 A-V nodal reentrant tachycardia, and 1 ectopic atrial tachycardia. Two patients had Chagasic myocarditis. Only in one chagasic patient a decreased number of tachycardia episodes was achieved, this patient died. The autopsy revealed cerebellar and pulmonary emboli. In the other 8 patients the arrhythmia was well controlled. In these, the ventricular volumes decreased, the EF increased to 0.51 +/- 0.14 (p = 0.00006), and the congestive heart failure remitted. We conclude that incessant tachycardia produces a symptomatic dilated cardiomyopathy in patients with and without structural heart disease. The arrhythmia control is followed by an increase in cardiac function and a remission of heart failure symptoms.     

Left ventricular function and autonomic nervous system balance during two different stages of the menstrual cycle

We studied the left ventricular function and cardiac autonomic nervous system balance variations during two different stages of the menstrual cycle. These two variables, as well as plasmatic estradiol and progesterone concentrations, were measured in a drug-free state in 20 women (29+/-6 year-old) with regular menstrual periods. A clinical evaluation, an echo-Doppler and a Valsalva manoeuvre were performed in all the patients on the third day of their menstrual cycle (follicular phase) and three days prior to their next menstrual cycle (luteinizing phase). When comparing the results obtained in these two phases, a statistically significant increase was put forward in plasmatic estradiol (50.6+/-24 vs. 127.3+/-52.8 pg/ml) and progesterone (0.37+/-0.42 vs. 11.92+/-10.8 ng/ml) concentrations, Valsalva index (1.55+/-0.22 vs. 1.67+/-0.33; P=0.044) and E/A mitral wave ratio (1.63+/-0.36 vs. 1.75+/-0.35, P=0.02). The right and left atrial volumes, left ventricular volumes and ejection fraction were similar in the two menstrual phases studied. We conclude that the autonomic nervous system balance and the left ventricular diastolic function suffer significant changes during the luteinizing phase of the menstrual cycle in normal women.     

Value of the indices of myocardial contraction rate in patients with chronic mitral insufficiency]

Determinations of dp/dt max, Vec and Vmax were made in 20 patients with chronic mitral regurgitation of several degrees. Each of these results was correlated with the corresponding ejection fraction. Only dp/dt max showed adequated correlation and few scattering of individual results, demonstrating its true dependence on the intrinsec contractile state of the left ventricule. Vec. and Vmax. determinations also reflected contractility changes, but their variability and difficult clinical applicability does not allow to recommend its routine utilization in a clinical setting. We could not demonstrate any influence of the valvular lesion on the results of the measured contractility indicators.     

Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens

The control of nausea and emesis in cancer patients receiving chemotherapy poses a significant management problem. In this randomized, double-blind, placebo-controlled study, we evaluated the effect of serotonin S3 receptor blockade with ondansetron (GR 38032F) on the prevention of nausea and vomiting induced by cyclophosphamide-containing chemotherapy. Cyclophosphamide was given in doses of 500 to 600 mg/m2 and ondansetron as three intravenous (IV) doses of 0.15 mg/kg. Most patients had breast cancer. Cyclophosphamide was given in combination with doxorubicin (65% of patients) or with fluorouracil (85% of patients: 50% with Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] and 35% with methotrexate). All placebo-treated patients experienced vomiting, whereas 70% of patients treated with ondansetron did not vomit (P = .008). Median nausea scores were 8 mm on ondansetron and 65 mm on placebo (P less than .001). Seventy percent of patients treated with ondansetron retained their normal appetite, compared with 10% of placebo patients. Adverse events occurred in six placebo patients and one ondansetron patient. Diarrhea and headache were the most common events, both occurring more frequently in the placebo group. There were no extrapyramidal reactions, and the only significant biochemical change occurred in a placebo-treated patient. These results suggest that serotonin S3 receptor antagonists represent a novel, effective, and safe mode of therapy for nausea and emesis induced by cyclophosphamide-containing chemotherapies. In addition, our observations are compatible with the view that serotonin, acting on S3 receptors, mediates the nausea and emesis occurring after cyclophosphamide chemotherapy.