Cardiac function in mice lacking the glucagon-like peptide-1 receptor

Glucagon-like peptide-1 (GLP-1) acts via its G protein-coupled receptor (GLP-1R) to regulate blood glucose. Although the GLP-1R is widely expressed in peripheral tissues, including the heart, and exogenous GLP-1 administration increases heart rate and blood pressure in rodents, the physiological importance of GLP-1R action in the cardiovascular system remains unclear. We now show that 2-month-old mice with genetic deletion of the GLP-1R (GLP-1R(-/-)) exhibit reduced resting heart rate and elevated left ventricular (LV) end diastolic pressure compared with CD-1 wild-type controls. At the age of 5 months, echocardiography and histology demonstrate increased LV thickness in GLP-1R(-/-) mice. Although baseline hemodynamic parameters of GLP-1R(-/-) did not differ significantly from those of wild type, GLP-1R(-/-) mice displayed impaired LV contractility and diastolic function after insulin administration. The defective cardiovascular response to insulin was not attributable to a generalized defect in the stress response, because GLP-1R(-/-) mice responded appropriately to insulin with increased c-fos expression in the hypothalamus and increased circulating levels of glucagon and epinephrine. Furthermore, LV contractility after exogenous epinephrine infusion was also reduced in GLP-1R(-/-) mice. These findings provide new evidence implicating an essential role for GLP-1R in the control of murine cardiac structure and function in vivo.     

Rice-ORS versus glucose-ORS in management of severe cholera due to Vibrio cholerae O139 Bengal: a randomized, controlled clinical trial

This study examined the comparative efficacies of rice-based oral rehydration solution (R-ORS) and glucose-based oral rehydration solution (G-ORS) in the management of severe cholera due to Vibrio cholerae O139 Bengal that causes epidemic cholera in many developing countries. Stool culture-proved adult male patients with severe cholera due to V. cholerae O139 Bengal were randomly assigned in a 1:1 ratio to receive either R-ORS or G-ORS after their initial rehydration with intravenous (i.v.) fluid and subsequently four hours of observation. They also received the usual hospital diet and tetracycline capsules (500 mg 6 hourly for three days) immediately after their enrollment in the study. The primary outcomes for observation were stool output during the first 24 hours after intervention and treatment failure as measured by the incidence of re-institution of i.v. fluid after initiation of trial therapy and duration of diarrhoea. Of 113 patients finally included in the study, 57 received R-ORS and 56 G-ORS. The admission characteristics of the two treatment groups were comparable. No significant differences in the first 24 hours of median (inter-quartile range) stool output [179 (67-206) g/kg in R-ORS group vs 193 (80-237) g/kg in G-ORS group; p = 0.52], incidences of unscheduled i.v. fluid requirement [21% (12/57) in R-ORS group vs 25% (14/56) in G-ORS group; p = 0.78], and median (inter-quartile range) duration of diarrhoea [32 (24-48) hours in R-ORS group vs 32 (24-56) hours in G-ORS group; p = 0.64] were observed. It is concluded that rice-based ORS is effective but not superior to standard glucose-based ORS in the management of adult males with severe cholera due to V. cholerae O139 Bengal.     

Dose distribution of asymmetric fields: comparison of the Helax-TMS with our developed 2D-program ASYMM

The purpose of this investigation was to compare the commercial 3D-treatment planning system Helax TMS to a simple 2D program ASYMM, concerning the calculation of dose distributions for asymmetric fields. The dose calculation algorithm in Helax-TMS is based on the polyenergetic pencil beam model of Ahnesj?. Our own developed 2D treatment planning program ASYMM, based on the Thomas and Thomas method for asymmetric open fields, has been extended to calculate the dose distributions for open and wedged fields. Using both methods, dose distributions for various asymmetric open and wedged fields of a 4-MV Linear accelerator were calculated and compared with measured data in water. The agreement of the Helax-TMS and the ASYMM with the experiment was good, whereas ASYMM showed a better accuracy for larger asymmetric angles. The explanation for this result is based on the consideration of beam hardening within the flattening filter and edges for different asymmetric settings in ASYMM algorithm. The TMS, however, owns the diverse possibilities that the 3D calculation and corresponding representation provide and holds better application opportunities in clinical routine.     

Pretreatment and on-treatment predictors of viral breakthrough in lamivudine therapy for chronic hepatitis B

Purpose  There are remarkable advances in the treatment of chronic hepatitis B (CHB) in the last few years. Unfortunately, prolonged antiviral treatment is associated with increasing risk of drug resistance/viral breakthrough (VBT), which may lead to flare-up and rapid decompensation. We have designed this study to predict the pretreatment and on-treatment factors responsible for development of VBT. Methods  This study was conducted during the period of February 2000 to November 2007. We have included 423 patients who received lamivudine (LAM) therapy for at least 1 year and at least 2 follow-ups at 6 months’ interval. Follow-up period was 12–78 months. Chi-square test, student's t test, and logistic regression analysis were performed to prove the validity. Results  Of the 423 study cases, 367 (86.8%) were of male patients and 261 (61.7%) patients were HBeAg positive; the age of the patients was 30.8 ± 12.9 years. Development of VBT was 4.4, 22.8, 45.3, and 74% at 1, 2, 3, and 4 or more years, respectively. Pretreatment high HBV DNA (P = 0.005) and female sex (P = 0.01) were associated with VBT and pretherapy ALT (P = 0.698), HBeAg status (P = 0.273), and age (P = 0.059) were not associated. Duration of treatment, failure to lose HBeAg at 1 year, and HBV DNA nonresponder at 6 months were significantly (P = 0.001) associated with development of VBT. Conclusion  Persistence of HBeAg at 1 year and HBV DNA nonresponder at 6 months are good predictors of development of VBT.     

Hysterosalpingography in the assessment of proximal tubal pathology: a review of congenital and acquired abnormalities

Tubal and peritoneal disease are the main causes of infertility. Tubal pathology can be either congenital malformation or acquired, proximal or distal, unilateral or bilateral and transient or permanent. Several imaging methods such as laparoscopy, fluoroscopy, saline infusion sonography, and hysterosalpingography (HSG) have been used in the assessment of tubal and peritoneal pathology. Although laparoscopy is the modality of choice for investigating tubal patency and pelvic structure in many infertility centers, HSG is usually the initial diagnostic method for infertility workup because of its ease of performance, accuracy, and minimal risk of complications. This method provides useful information about size, contour, and anatomy of the inner surface of the fallopian tubes and is the gold standard for evaluation of tubal lumen. Tubal and peritubal pathology show various imaging manifestations on HSG. This review illustrates the radiographic features of congenital and acquired structural abnormalities of the proximal tubal pathology and along with etiology of proximal obstruction or occlusion will be described.     

Associations Between Maternal Prenatal C-Reactive Protein and Risk Factors for Psychosis in Adolescent Offspring: Findings From the Northern Finland Birth Cohort 1986

Prenatal infection is associated with brain structural and functional abnormalities and may increase the risk for psychosis through a direct effect on neurodevelopment. Various infections may exert their effect through a proinflammatory immune response but studies of prenatal maternal inflammatory markers and offspring neurodevelopment are scarce. Using the longitudinal Northern Finland Birth Cohort 1986 study, we examined the associations of maternal prenatal C-reactive protein (CRP) levels with psychosis risk factors in adolescent offspring. CRP was measured in maternal sera collected in pregnancy. In offspring, school performance was measured at age 7 years, while school performance, psychotic experiences, and cannabis use were measured at age 16 years. We tested associations of CRP with offspring measures using regression analysis controlling for offspring sex, maternal education level, and prenatal maternal body mass index, smoking and alcohol use in pregnancy, place of birth, maternal psychiatric admission, paternal psychiatric admission, mothers age at birth, and gestational week of CRP sample. We also tested if adolescent cannabis use mediated the associations between maternal CRP and offspring outcomes. Controlling for covariates, maternal CRP was associated with academic performance at age 16 years (beta = .062, 95% CI = 0.036–0.088), but not with possible psychotic experiences at 16 years (odds ratio [OR] = 1.09, 95% CI = 0.96–1.24). Maternal CRP was also associated with adolescent cannabis use (OR = 1.24, 95% CI = 1.07–1.43). These findings suggest that prenatal inflammation may influence later mental illness risk by affecting neurodevelopment and also indirectly by increasing the risk of exposure to cannabis.