Adipogenic genes expression in relation to hepatic steatosis in the liver of two duck species.

Some studies have shown that expression of peroxisome proliferator-activated receptor gamma (PPARG), a key regulator of adipogenesis, and of some adipocyte-specific genes or adipokines are expressed in hepatic steatosis, leading to the concept of 'adipogenic hepatic steatosis' or 'hepatic adiposis.' Most of these studies were conducted in genetic obese mouse models or after manipulation of gene expression. The relevance of this concept to other species and more physiological models was here addressed in ducks which are able to develop hepatic steatosis after overfeeding. The expression of PPARG and other adipocyte-specific genes was thus analyzed in the liver of ducks fed ad libitum or overfed and compared with those observed in adipose tissues. Pekin (Anas platyrhynchos) and Muscovy ducks (Cairina moschata) were analyzed, as metabolic responses to overfeeding differ according to these two species, Muscovy ducks having a greater ability to synthesize and store lipids in the liver than Pekin ducks. Our results indicate that adipocyte-specific genes are expressed in the liver of ducks, PPARG and fatty acid-binding protein 4 being upregulated and adiponectin and leptin receptor downregulated by overfeeding. However, these expression levels are much lower than those observed in adipose tissue suggesting that fatty liver cells are not transformed to adipocytes, although some hepato-specific functions are decreased in fatty liver when compared with normal liver.

Regulation of LPCAT3 by LXR.

In this work we analyzed the transcriptome profiles of chicken hepatoma cells (LMH) in response to T0901317, a pharmacological agonist of the liver X receptor (LXR). Through an in silico search for LXRE (LXR response element) consensus sequences in the promoter of genes whose expression was shown to be sensitive to TO901317, we identified a LXRE in the promoter of the LPCAT3 (lysophosphatidylcholine acyltransferase 3). This motif is highly conserved between species. We further investigated the regulation of this gene and showed that the expression of LPCAT3 was induced both in chicken and human hepatoma cells (LMH and HuH-7, respectively) in response to T0901317. Transactivation and electrophoretic mobility shift assays allowed us to locate a functional LXRE in the chicken LPCAT3 promoter. Altogether these data evidence for the first time that the chicken LPCAT3 gene is a direct target of LXR and therefore suggest a new role for LXR in phospholipid homeostasis.

Liver X receptor alpha regulates fatty acid synthase expression in chicken.

Liver X receptor alpha (LXRalpha), also referred to as nuclear receptor subfamily 1, group H, member 3 is a member of the nuclear hormone receptor superfamily, and has recently been shown to act as a master transcription factor governing hepatic lipogenesis in mammals. Liver X receptor alpha directly regulates both the expression of other lipogenic transcription factors and the expression of lipogenic enzymes, thereby enhancing hepatic fatty acid synthesis (FASN). In birds, like in humans, fatty acid synthesis primarily occurs in the liver. Whether LXRalpha is involved in hepatic regulation of lipogenic genes remained to be investigated in this species. Here we show that fatty acid synthase and the expression of other lipogenic genes (sterol regulatory element binding protein 1 and steroyl coenzyme A desaturase 1) are induced in chicken hepatoma cells in response to a pharmacological liver X receptor agonist, T0901317. A detailed analysis of the chicken FASN promoter revealed a functional liver X response element. These data define the chicken FASN gene as a direct target of LXRalpha and further expand the role of LXRalpha as a regulator of lipid metabolism in this species.

Efficacy of biventricular sensing and treatment of ventricular arrhythmias.

While much is known concerning the hemodynamic effects of biventricular (BV) pacing, little has been reported concerning the efficacy of BV sensing and pacing in the detection and treatment of ventricular tachyarrhythmias. Two hundred nineteen heart failure (HF) patients with VT or VF and a QRS > or = 120 ms during sinus rhythm received an ICD capable of BV pacing and sensing. Detection times of induced VF and success rates for terminating induced VT were measured. The ICD system used a left ventricular epicardial lead implanted via thoracotomy (52 patients) or a specially designed percutaneous, over-the-wire lead inserted in the coronary venous system. VF detection times and VT termination rates by antitachycardia pacing (ATP) were compared with those measured in a population of recipients of ICD using a RV lead alone. Median induced VF detection times were comparable (2.0-s BV vs 1.8-s RV). Termination of induced VT on the first attempt was comparable with BV pacing (87.4%) versus RV pacing (89.6%). The time to detect induced VF was not different with ICDs using BV sensing versus conventional ICDs using RV sensing alone. Similarly, the rates of successful termination of induced VT by ATP with BV or RV pacing were comparable.

Impact of biventricular pacing on mortality in a randomized crossover study of patients with heart failure and ventricular arrhythmias.

Biventricular (BV) pacing is under clinical investigation for the treatment of heart failure. Its impact on mortality is unknown. Patients with heart failure and ventricular tachyarrhythmias received an implantable cardioverter defibrillator with BV pacing capability. Patients were randomized 1:1 to BV pacing or no pacing, then crossed over to the alternate mode after 3 months. All-cause mortality was measured in each arm up to the point of crossover. Fifteen of 222 patients died between implant and crossover. Five patients died while programmed to BV pacing and 19 died while programmed to no pacing. Survival in the BV pacing arm was 93 +/- 4% versus 86 +/- 6% in the no pacing arm (P = 0.18). In a patient population with symptomatic heart failure and ventricular arrhythmias, BV pacing does not appear to be associated with excess mortality. Larger and longer studies will be needed to determine if BV pacing confers a survival benefit.

A new and reliable method of individual ventricular capture identification during biventricular pacing threshold testing.

Biventricular (BV) pacing for the treatment of heart failure is in clinical investigation. In the absence of independent outputs for separate pacing of each ventricle, a method is needed to determine the respective LV versus RV thresholds. A technique was developed and validated to distinguish BV capture from LV or RV capture from a multilead surface ECG. The QRS axes were determined at the time of implant by comparing multilead surface ECGs during BV, RV, and LV pacing in 63 patients (42 men, age 63 +/- 12 years) who received pacemakers or ICDs capable of BV pacing. Differences between BV and LV, and between BV and RV axes were examined to determine which ECG leads best indicate a change from BV to univentricular capture. The axis shift from BV to RV pacing was positive while the axis shift from BV to LV pacing was negative. The morphology change associated with LV versus RV capture is best examined in the ECG lead that is perpendicular to the axis shift. A change from BV to LV capture was best identified as increasing positivity of the QRS in lead III, while a change from BV to RV capture was best recognized as increasing positivity of the QRS in lead I. When performing a BV pacing threshold test, mean QRS vector changes derived from standard ECG can be used to distinguish LV or RV capture from BV capture.

Performance of a new steroid-eluting coronary sinus lead designed for left ventricular pacing.

The Ventak CHF/CONTAK CD Biventricular Pacing Study is a prospective randomized trial to examine the safety and efficacy of biventricular (BV) pacing in patients with standard indications for an ICD, symptomatic heart failure, a LVEF < or = 0.35, and a QRS > or = 120 ms. Patients underwent implantation of a BV pacing and sensing system with backup defibrillation capability, which includes a steroid-eluting coronary venous lead that is advanced into the coronary venous vasculature by over-the-wire techniques. LV pacing threshold, BV impedance, and BV R wave amplitude were measured in 58 consecutive patients. Using a percutaneous over-the-wire insertion technique, steroid-eluting coronary venous leads were associated with satisfactory mean LV pacing threshold, BV impedance, and BV R wave amplitude acutely up to 4 months after implantation. Pacing threshold stabilized 2 weeks after lead implantation and sensing threshold remained stable from the time of implant.

Comparing the performances of Diggle's tests of spatial randomness for small samples with and without edge-effect correction: application to ecological data.

Diggle's tests of spatial randomness based on empirical distributions of interpoint distances can be performed with and without edge-effect correction. We present here numerical results illustrating that tests without the edge-effect correction proposed by Diggle (1979, Biometrics 35, 87-101) have a higher power for small sample sizes than those with correction. Ignoring the correction enables detection of departure from spatial randomness with smaller samples (down to 10 points vs. 30 points for the tests with correction). These results are confirmed by an example with ecological data consisting of maps of two species of trees in a West African savanna. Tree numbers per species per map were often less than 20. For one of the species, for which maps strongly suggest an aggregated pattern, tests without edge-effect correction enabled rejection of the null hypothesis on three plots out of five vs. on only one for the tests with correction.

Efficacy and safety relative to placebo of an oral formulation of cetirizine and sustained-release pseudoephedrine in the management of nasal congestion.

BACKGROUND: The aim of this study was to assess the clinical efficacy of an oral formulation of cetirizine 5 mg with sustained-release pseudoephedrine (PSE) 120 mg relative to placebo in patients with nasal congestion. METHODS: Twenty-four patients with perennial rhinitis due to house-dust-mite (HDM) allergy were recruited in this crossover study. A treatment period of 1 week, in which cetirizine/PSE was administered twice daily, was followed by a washout period of at least 2 weeks and a further period of 1 week in which the alternative treatment was given to each patient. Immediately after the first dose of each medication (day 1), nasal congestion and related symptoms were assessed during a 7-h challenge with HDM feces, with the Vienna Challenge Chamber (VCC), to investigate onset of action of the preparation. A second challenge of 3-h duration, carried out at least 12 h after the final dose, was undertaken after 1 week (mean) of twice-daily treatment to assess residual effects of the formulation after achievement of steady state. RESULTS: The oral formulation of cetirizine/PSE was significantly (P<0.001) superior to placebo in improving nasal obstruction during both challenges. The improvement in nasal airflow and nasal patency was significantly greater with cetirizine/PSE than with placebo (P<0.02). In addition, subjective assessment of nasal symptoms showed that cetirizine/PSE was significantly superior to placebo in both challenges for the sum of nasal obstruction scores (P<0.01). Both medications were well tolerated, and no serious adverse events occurred during the study. CONCLUSIONS: In this study, cetirizine/PSE relieved nasal congestion and other objective and subjective symptoms to a significantly greater extent than placebo. No serious adverse events occurred, and both regimens were equally well tolerated.

The effect of cetirizine on symptoms and signs of nasal polyposis.

Forty-five patients with residual or recurrent nasal polyposis after ethmoidectomy were treated with either cetirizine at twice the daily recommended (20 mg) dose or placebo for three months. The number and size of polyps remained unchanged during the study period. Cetirizine was found to reduce nasal sneezing and rhinorrhoea effectively. The drug also had a beneficial effect on nasal obstruction in the latter part of the study. The side effects of 20 mg (double the recommended daily adult dose) of cetirizine were few and comparable to placebo.

[Study of statistical test connections in non-orthogonal analysis of variance]. / Etude des liaisons statistiques de tests en analyse de variance non orthogonale.

In the Analysis of Variance, we quite often split up the model to test different hypotheses about the model. However, when we analyse the results, we must not forget that the statistics used for the tests are not stochastically independent, either for an orthogonal design, because the test statistics have the same denominator, or for non-orthogonal design. In the latter case, test statistics have not only the same denominator but also not-independent numerators. The links between test statistics have been studied for orthogonal designs (Dall'Aglio, 1962) and for symmetrical Incomplete Block Design (Ballas and Webster, 1966). We shall give here results for the general case of the Analysis of Variance, treat more particularly the case of the Incomplete Block Design and show the joint distribution of two test statistics and, more simply, their correlation coefficient.

Sulfalene with pyrimethamine and chloroquine with pyrimethamine in single-dose treatment of Plasmodium falciparum infections. A trial in a rural population in northern Nigeria.

A comparative trial was carried out in northern Nigeria of the ability of the drug combinations chloroquine-pyrimethamine and sulfalene-pyrimethamine to clear the peripheral blood stream of asexual forms of P. falciparum within 7 days. The reappearance of asexual P. falciparum forms within the 70-day follow-up period and the occurrence of vomiting during the 2-3 hours following administration of the drugs were also recorded. The purpose of the trial was to choose the more suitable of the two drug combinations for repeated mass administration in the intervention phase of a collaborative field research project in the epidemiology and control of malaria in the African savannah. No differences were observed between the two drug combinations from a parasitological point of view. However, the sulfalene-pyrimethamine combination was found easier to administer and occasioned fewer records of vomiting. It was therefore recommended for use in the project.