Icahn School of Medicine at Mount Sinai

About: Icahn School of Medicine at Mount Sinai is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 37488 authors who have published 76057 publications receiving 3704104 citations. The organization is also known as: Mount Sinai School of Medicine.

Genomics and signaling pathways in hepatocellular carcinoma.

Abstract: Hepatocellular carcinoma (HCC) is a leading cause of death among cirrhotic patients and has become a major health problem in developed countries. There is an elemental understanding of the genes and signaling pathways involved in the initiation and progression of this neoplasm. The current hypothesis of the HCC cell origin includes both somatic cells (hepatocytes) and stem cells/progenitor cells. Unlike that in other malignancies such as breast, brain, or hematopoietic cancers, the implication of cancer stem cells in HCC pathogenesis is not yet supported by consistent data. Analysis of somatic genetic alterations and gene expression profiles in HCC samples has provided relevant information on the genes involved in hepatocarcinogenesis, pinpointing a seminal molecular classification of the disease. Nonetheless, a comprehensive genomic analysis of HCC samples using high-resolution platforms in precisely annotated HCCs is clearly needed. Recent data have identified different signaling pathways in liver carcinogenesis (e.g., Wnt-betaCatenin, Hedgehog, tyrosine kinase receptor-related pathways), providing an important potential source of novel molecular targets for new therapies. This review summarizes the most relevant information regarding structural and functional alterations in HCC and describes some of the key signaling pathways implicated in hepatocarcinogenesis.

Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report

Abstract: Hugh A. Sampson, MD, Roy Gerth van Wijk, MD, Carsten Bindslev-Jensen, MD, PhD, Scott Sicherer, MD, Suzanne S. Teuber, MD, A. Wesley Burks, MD, Anthony E. J. Dubois, MD, Kirsten Beyer, MD, Philippe A. Eigenmann, MD, Jonathan M. Spergel, MD, PhD, Thomas Werfel, MD, and Vernon M. Chinchilli, PhD New York, NY, Rotterdam and Groningen, The Netherlands, Odense, Denmark, Davis, Calif, Chapel Hill, NC, Berlin and Hannover, Germany, Geneva, Switzerland, and Philadelphia and Hershey, Pa

Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study.

Abstract: Summary Background Levodopa is the most effective therapy for Parkinson's disease, but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiological, intermittent administration of the drug, and can be reduced with continuous delivery. We aimed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube. Methods In our 12-week, randomised, double-blind, double-dummy, double-titration trial, we enrolled adults (aged ≥30 years) with advanced Parkinson's disease and motor complications at 26 centres in Germany, New Zealand, and the USA. Eligible participants had jejunal placement of a percutaneous gastrojejunostomy tube, and were then randomly allocated (1:1) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo. Randomisation was stratified by site, with a mixed block size of 2 or 4. The primary endpoint was change from baseline to final visit in motor off-time. We assessed change in motor on-time without troublesome dyskinesia as a prespecified key secondary outcome. We assessed efficacy in a full-analysis set of participants with data for baseline and at least one post-baseline assessment, and imputed missing data with the last observation carried forward approach. We assessed safety in randomly allocated patients who underwent the percutaneous gastrojejunostomy procedure. This study is registered with ClinicalTrials.gov, numbers NCT00660387 and NCT0357994. Findings From baseline to 12 weeks in the full-analysis set, mean off-time decreased by 4·04 h (SE 0·65) for 35 patients allocated to the levodopa-carbidopa intestinal gel group compared with a decrease of 2·14 h (0·66) for 31 patients allocated to immediate-release oral levodopa-carbidopa (difference −1·91 h [95% CI −3·05 to −0·76]; p=0·0015). Mean on-time without troublesome dyskinesia increased by 4·11 h (SE 0·75) in the intestinal gel group and 2·24 h (0·76) in the immediate-release oral group (difference 1·86 [95% CI 0·56 to 3·17]; p=0·0059). In the safety analyses 35 (95%) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events (five [14%] serious), as did 34 (100%) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group (seven [21%] serious), mainly associated with the percutaneous gastrojejunostomy tube. Interpretation Continuous delivery of levodopa-carbidopa with an intestinal gel offers a promising option for control of advanced Parkinson's disease with motor complications. Benefits noted with intestinal gel delivery were of a greater magnitude than were those obtained with medical therapies to date, and our study is, to our knowledge, the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study. Funding AbbVie.

A Prospective Study of Human Immunodeficiency Virus Type 1 Infection and the Development of AIDS in Subjects with Hemophilia

Abstract: We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (±SE) of 13.3±5.3 percent for ages 1 to 17, 26.8±6.4 percent for ages 18 to 34, and 43.7±16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 ...

Accuracy and calibration of commercial oligonucleotide and custom cDNA microarrays

Abstract: We compared the accuracy of microarray measurements obtained with oligonucleotide arrays (GeneChip, Affymetrix) with a laboratory-developed cDNA array by assaying test RNA samples from an experiment using a paradigm known to regulate many genes measured on both arrays. We selected 47 genes represented on both arrays, including both known regulated and unregulated transcripts, and established reference relative expression measurements for these genes in the test RNA samples using quantitative reverse transcriptase real-time PCR (QRTPCR) assays. The validity of the reproducible (average coefficient of variation = 11.8%) QRTPCR measurements were established through application of a new mathematical model. The performance of both array platforms in identifying regulated and non-regulated genes was identical. With either platform, 16 of 17 definitely regulated genes were correctly identified, and no definitely unregulated transcript was falsely identified as regulated. Accuracy of the fold-change measurements obtained with each platform was assessed by determining measurement bias. Both platforms consistently underestimate the relative changes in mRNA expression between experimental and control samples. The bias observed with cDNA arrays was predictable for fold-changes <250-fold by QRTPCR and could be corrected by the calibration function F(c) = F(a(cDNA))(q), where F(a(cDNA)) is the microarray-determined fold-change comparing experimental with control samples, q is the correction factor and F(c) is the calibrated value. The bias observed with the commercial oligonucleotide arrays was less predictable and calibration was unfeasible. Following calibration, fold-change measurements generated by custom cDNA arrays were more accurate than those obtained by commercial oligonucleotide arrays. Our study demonstrates systematic bias of microarray measurements and identifies a calibration function that improves the accuracy of cDNA array data.