Effects of benzothiadiazine drugs on carbohydrate metabolism

The administration of chlorothiazide both to man and to rats results in hyperglycemia following a glucose load. Its administration to rats causes a decreased rate of glucose utilization by their adipose tissue in vitro. Chlorothiazide added directly to the incubating medium also decreases the rate of glucose utilization of rat adipose tissue. These effects of chlorothiazide are most likely due to both a direct action of the drug on tissue glucose metabolism and an indirect effect which is the result of chlorothiazide causing a decrease in the level of serum insulin-like activity which in turn diminishes the activity of insulin-dependent enzymes involved in glucose metabolism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32021/1/0000063.pd

Effect of furosemide on glucose metabolism

The administration of furosemide, a benzothiadiazine analogue, to rats results in elevation of the initial and 2-hour postglucose loading blood glucose levels. Furosemide given to rats causes a decrease in the rate of glucose utilization by their adipose tissue in vitro. Furosemide added directly to the incubational medium also decreases the rate of glucose utilization of normal rats' fat tissue in vitro. These effects of furosemide are similar to those produced by chlorothiazide and other benzothiadiazine compounds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33327/1/0000723.pd

Lung Screening Benefits and Challenges: A Review of The Data and Outline for Implementation

Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for almost a fifth of all cancer-related deaths. Annual computed tomographic lung cancer screening (CTLS) detects lung cancer at earlier stages and reduces lung cancer-related mortality among high-risk individuals. Many medical organizations, including the U.S. Preventive Services Task Force, recommend annual CTLS in high-risk populations. However, fewer than 5% of individuals worldwide at high risk for lung cancer have undergone screening. In large part, this is owing to delayed implementation of CTLS in many countries throughout the world. Factors contributing to low uptake in countries with longstanding CTLS endorsement, such as the United States, include lack of patient and clinician awareness of current recommendations in favor of CTLS and clinician concerns about CTLS-related radiation exposure, false-positive results, overdiagnosis, and cost. This review of the literature serves to address these concerns by evaluating the potential risks and benefits of CTLS. Review of key components of a lung screening program, along with an updated shared decision aid, provides guidance for program development and optimization. Review of studies evaluating the population considered "high-risk" is included as this may affect future guidelines within the United States and other countries considering lung screening implementation

Biotransformation of 9-[beta]-d-arabinofurano-syladenine by rat and human erythrocytes

Studies were performed to test whether 9-[beta]--arabinofuranosyladenine (ara-A) would accumulate in erythrocytes as a result of phosphorylation to the nucleotide level. When [3H]ara-A was incubated with whole blood from rat, monkey or man for 2 hr at 37[deg], the drug rapidly equilibrated between erythrocytes and plasma but did not concentrate in the cells. Incubation of [3H]ara-A with rat and human erythrocyte lysates for 2 hr followed by Chromatographie analysis showed that 2-5 per cent of ara-A was converted to nucleotides. In contrast, 10-35 per cent of [14C]adenosine was converted to adenine nucleotides under the same conditions. Incubation of [3H]ara-A with human erythrocyte lysates for 18 hr resulted in a conversion of approx. 40 per cent of the labeled drug to nucleotides. Additional chromatography revealed, however, that the nucleotide fraction contained almost no arabinosyl nucleotides. Rather, 90 per cent of the label in the nucleotide fraction was identified as IMP. These results indicate that only a minor amount, if any, of ara-A was phosphorylated by erythrocyte enzymes to yield arabinosyl nucleotides. An alternative pathway converted much of the labeled drug to ribosyl nucleotides via the deamination of ara-A to ara-hypoxanthine, cleavage to hypoxanthine and conversion of the free hypoxanthine to IMP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22270/1/0000709.pd

A Retrospective Study Assessing the Predictive Performance of a Lung Cancer Screening Risk Prediction Model in a Clinical Lung Cancer Screening Program

Background: United States Preventive Services Task Force (USPSTF) and Centers for Medicare & Medicaid Services (CMS) recommendations for annual screening for lung cancer with low dose CT (LDCT) scans rely on age and smoking history to identify those at high risk for lung cancer. The Tammemagi et al. six year lung cancer risk prediction model, PLCOm2012, developed and validated in large lung cancer screening clinical trials, demonstrated good predictive performance in screening selection. However, the model has not been validated in clinical practice. Validating the model in clinical practice would increase confidence in its ability to provide information for shared decision making discussions in the near term and would potentially allow for selection of other high risk groups, not currently recommended to be screened, in the future. Methods: Retrospective evaluation of the predictive performance of the Tammemagi et al. six year lung cancer risk prediction model in the Lahey Hospital & Medical Center, Lahey physician referred patients enrolled in the lung cancer screening program between January 1, 2012 and November 30, 2015 (n=2302). Predictor variable data were gathered from the program clinical data base and program participant clinic medical records. All patients met the National Comprehensive Cancer Network (NCCN) Lung Cancer Screening Guidelines Group 1 or Group 2 high-risk criteria. Results: The model six year mean risk for lung cancer was higher for participants with lung cancer, 4.56%, as compared to those without lung cancer, 3.55% (p=0.0265). Area under the curve (AUC) of the receiver operator characteristics (ROC) was 0.63 (95% CI 0.57 – 0.69). The mean absolute difference between observed and predicted risk was 0.013 or less for the first 9 deciles.At the 1.51% predicted risk recommended screening threshold; sensitivity = 85.7%, specificity = 29.7%, and PPV = 3.7%. In sub-group analysis, for NCCN Group 2 (younger, lighter smoking history, no limit on time quit and one additional risk factor) the mean predicted risk for participants with lung cancer was 2.39% as compared to 1.83% for those without lung cancer but the difference was not statistically significant; p=0.2507. However, the incidence of lung cancer was the same for NCCN Group 2 as for the complete sample. NCCN Group 2 model AUC was 0.634 (95% CI 0.522 – 0.746), the sensitivity and specificity of the model at the recommended screening threshold were 64.7% and 56.0%, respectively and PPV was 4.2%. Conclusions: Lung cancer risk prediction model, PLCOm2012noEd, predictive performance in a clinical lung cancer screening program was adequate to help patients and their physicians assess individual risk of lung cancer relative to the recommended model risk screening threshold (1.51%) and to supplement USPSTF and CMS screening program entry criteria for shared decision making discussions. Model risk predictive capability for the NCCN Group 2 subgroup did not match actual screening program lung cancer results

Pasión por lo que se hace

Los rosaristas María Paula Piedrahita y Andrés Camilo Borondy son un claro ejemplo de que en Colombia hay mucho talento deportivo. Pero sus historias también demuestran que ese talento debe hacer grandes esfuerzos para sobresalir, debido a la falta de apoyo.Rosaristas María Paula Piedrahita and Andrés Camilo Borondy are a clear example that there is a lot of sporting talent in Colombia. But their stories also show that such talent must go to great lengths to excel, due to a lack of support