The multiple drug resistance gene,MDR1: Expression at the protein and RNA levels

A comparison of three different approaches to detect MDR₁ expression in myeloid leukemia cells was undertaken. With respect to the 4 different antibodies studied, a high proportion of false positive reactions were detected. Substantial discordance between MDR₁ expression as indicated by Northern blot analysis, PCR, and immunohistochemistry was found. These findings complicate the clinical interpretation of data derived from these methods.     

Placental p,p''-dichlorodiphenyldichloroethylene and cord blood immune markers

Placental p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) concentration and cord blood atopic markers were determined in 19 neonates. Increased placental p,p'-DDE was associated with a statistically significant increase in cord plasma interleukin (IL)-13. Furthermore, both cord plasma IL-4/interferon (IFN)-gamma and IL-13/IFN-gamma ratios were significantly positively associated with placental p,p'-DDE concentration.     

An ELISA-based method for measurement of food-specific IgE antibody in mouse serum: an alternative to the passive cutaneous anaphylaxis assay

Passive cutaneous anaphylaxis (PCA) assay has been a gold standard method to measure allergen-specific IgE antibody (ASIgE Ab) levels in allergy mouse models. Many factors including stringent guidelines for laboratory animal use make PCA a difficult choice. Therefore, alternative methods are needed that can be readily applied for measurement of specific IgE antibody levels in mouse serum. Herein we describe a novel ELISA-based method that is more sensitive in comparison to PCA, IgE isotype-specific (because it has little cross-reactivity with IgG1 or IgG2a isotype) and highly reproducible (<10% inter- or intra-assay variation). Furthermore, we demonstrate the utility of this assay to measure specific IgE Ab against a variety of food extracts including chicken egg, peanut, almond, filbert/hazelnut and sweet potato. These findings are of particular interest to those who are seeking (i) to measure food-extract-specific IgE antibody in animal models and (ii) an alternative to the animal-based PCA method to measure mouse IgE antibodies.     

Presenting characteristics,comorbidities, and outcomes of patients coinfected with COVID-19 and Mycoplasma pneumoniae in the USA

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is spreading at a rapid pace, and the World Health Organization declared it as pandemic on 11 March 2020. Mycoplasma pneumoniae is an "atypical" bacterial pathogen commonly known to cause respiratory illness in humans. The coinfection from SARS-CoV-2 and mycoplasma pneumonia is rarely reported in the literature to the best of our knowledge. We present a study in which 6 of 350 patients confirmed with COVID-19 were also diagnosed with M. pneumoniae infection. In this study, we described the clinical characteristics of patients with coinfection. Common symptoms at the onset of illness included fever (six [100%] patients); five (83.3%) patients had a cough, shortness of breath, and fatigue. The other symptoms were myalgia (66.6%), gastrointestinal symptoms (33.3%-50%), and altered mental status (16.7%). The laboratory parameters include lymphopenia, elevated erythrocyte sedimentation rate, C-reactive protein, lactate dehydrogenase, interleukin-6, serum ferritin, and D-dimer in all six (100%) patients. The chest X-ray at presentation showed bilateral infiltrates in all the patients (100%). We also described electrocardiogram findings, complications, and treatment during hospitalization in detail. One patient died during the hospital course.     

Endoscopic treatment of biliary tract strictures in sclerosing cholangitis: a larger series and recommendations for treatment

We report a group of 35 patients with primary sclerosing cholangitis who had long-term follow-up after endoscopic treatment of major ductal strictures in the primary or secondary biliary ducts. Our patients were all symptomatic with ascending cholangitis or jaundice. There was significant improvement as measured by clinical parameters of hospitalization rates and laboratory data and comparable radiography. Long-term follow-up averaged 24 (+/- 2.8 months). We believe endoscopic treatment of sclerosing cholangitis should be attempted in selected symptomatic cases with major ductal strictures before liver transplantation.     

Cardiogenic shock: a summary of the randomized SHOCK trial

Cardiogenic shock is the most common cause of death for patients hospitalized with acute myocardial infarction. The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial randomly assigned 302 patients with predominant left ventricular failure following an acute myocardial infarction to a strategy of emergency revascularization or initial medical stabilization. Emergency revascularization by either coronary artery bypass grafting or angioplasty was required within 6 hours of randomization. Patients assigned to initial medical stabilization could undergo delayed revascularization at a minimum of 54 hours post-randomization. The primary end point of the study was 30-day all-cause mortality. Overall survival at 30 days did not differ significantly between the emergency revascularization and initial medical stabilization groups (53% vs. 44%; p=0.109). However, at the 6- and 12-month follow-up, there was a significant survival benefit with early revascularization (50% vs. 37%; p=0.027 and 47% vs. 34%; p=0.025, respectively). The benefit appeared to be greatest for those less than 75 years of age, with 20 lives saved at 6 months per 100 patients treated. According to the results of the SHOCK trial, the American College of Cardiology/American Heart Association guidelines for myocardial infarction now recommend emergency revascularization for patients younger than 75 years with cardiogenic shock.     

Pain on common bile duct injection during ERCP: does it indicate sphincter of Oddi dysfunction?

The reproduction of a patient's biliary-type pain upon initial injection of contrast material into the common bile duct during diagnostic ERCP is a dramatic experience for both patient and physician. The significance of this phenomenon is not clear, but it is touted by some to be a provocative test for sphincter of Oddi dysfunction. Sphincter of Oddi manometry was performed on 224 consecutive patients referred over a 2-year period for evaluation of post-cholecystectomy syndrome and suspected sphincter of Oddi dysfunction. All patients received only intravenous diazepam as premedication for ERCP. Delayed drainage time (greater than 45 min), bile duct dilation (greater than or equal to 12 mm), and a basal sphincter of Oddi pressure of greater than 40 mm Hg (mean +/- 3 SD) were considered elevated. We observed a reproduction of pain in 15 of 224 patients (6.7%) immediately following contrast injection. There was no correlation between pain on contrast injection and elevated basal sphincter of Oddi pressure, delayed common bile duct drainage, bile duct dilation, or abnormal liver enzymes. Therefore, we feel that reproduction of the patient's biliary-type pain associated with contrast injection of ERCP is not a provocative test for sphincter of Oddi dysfunction.     

Cardiovascular and Renal Outcomes of Newer Anti-Diabetic Medications in High-Risk Patients

Purpose of Review

We review the cardiovascular and renal outcomes and safety of newer anti-diabetic medications in high-risk patients. We examine the outcomes of the IRIS, EMPA-REG OUTCOME, CANVAS, LEADER, SAVOR-TIMI 53, and EXAMINE trials demonstrating the cardiovascular and renal benefits of thiazolidinediones, SGLT2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors.

Recent Findings

Diabetes mellitus is a leading risk factor for cardiovascular disease with rising prevalence and disease burden. The microvascular and macrovascular complications of diabetes are well-recognized and include increased risk of cardiovascular disease, myocardial infarction, and stroke. Newer diabetes medications have demonstrated significant cerebrovascular, cardiovascular, renal, and mortality benefits in high risk patients with diabetes. In addition to their glucose-lowering effects, the thiazolidinedione pioglitazone, SGLT2 inhibitors, GLP-1 agonist, and DPP-4 inhibitors have demonstrated significant cerebrovascular, cardiovascular, renal, and mortality effects.

Summary

The outcomes and safety data of newer diabetes medications from recent trials demonstrate cardiovascular and mortality effects with significant implications for clinical practice.