Faculty Bibliography
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department:Medicine. General Internal Medicine
recentyears:2
school:SOM
Total Results:
14792
Mutational analyses of epidermal growth factor receptor and downstream pathways in adrenocortical carcinoma
BACKGROUND:Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis and limited therapeutic options. Mitotane is considered the standard first-line therapy with only 30% of the patients showing objective tumour response. Defining predictive factors for response is therefore of clinical importance. The epidermal growth factor receptor (EGFR) has been implicated in the development of one-third of all malignancies. EGFR pathway members in ACC have been investigated, however, without available clinical data and relation to survival. METHODS:In this study, mutation status of EGFR and downstream signalling pathways was evaluated in 47 ACC patients on mitotane using direct sequencing, a TaqMan allele-specific assay and immunohistochemistry. Archival formalin-fixed paraffin-embedded tumour tissue was used for all analyses. Patient data were obtained anonymously, after coupling with the collected tumour tissue. RESULTS:One BRAF, two EGFR TK domain (c.2590> A, p.864A>T) and 11 TP53, but no PIK3CA or KRAS, mutations were found. No relationship was found between mutation status, immunostaining and mitotane response or survival. CONCLUSION/CONCLUSIONS:In conclusion, our data suggest that the role of EGFR tyrosine kinase inhibitors in ACC is limited. Treatment with EGFR monoclonal antibodies on the other hand might be beneficial for a larger group of patients. The possible efficacy of this therapy in ACC should be evaluated in future trials.
PMID: 23585556
ISSN: 1479-683x
CID: 4002912
Gender differences in cardiovascular mortality by C-reactive protein level in the United States: evidence from the National Health and Nutrition Examination Survey III
BACKGROUND: The association between C-reactive protein (CRP) and cardiovascular (CV) mortality by gender has not been previously described using a data set that is representative of the US population. METHODS: We used Cox proportional hazards models to explore gender differences in CRP-associated mortality via the National Health and Nutrition Examination Survey III 1988-1994 linked to the National Death Index with mortality follow-up through 2006. We examined CV mortality as well as all-cause mortality hazards. RESULTS: The final sample size included a total of 13,878 individuals (7,364 women and 6,514 men) with a median follow up of 18.2 years. All models controlled for race, age, smoking, high-density lipoprotein, hypertension, diabetes mellitus, waist circumference, and total cholesterol. Men with a CRP >3.0 mg/L relative to those with a CRP
PMID: 23816020
ISSN: 0002-8703
CID: 1071982
Exempting schoolchildren from immunizations: States with few barriers had highest rates of nonmedical exemptions
Rates of nonmedical exemptions from school immunizations are increasing and have been associated with resurfacing clusters of vaccine-preventable diseases, such as measles. Historically, state-level school immunization policies successfully suppressed such diseases. We examined state immunization exemption regulations across the United States. We assessed procedures for exempting schoolchildren and whether exemption rates were associated with the complexity of the procedures. We also analyzed legal definitions of religious objections and state legislatures' recent modifications to exemption policies. We found that states with simpler immunization exemption procedures had nonmedical exemption rates that were more than twice as high as those in states with more-complex procedures. We also found that the stringency of legal definitions of religious exemptions was not associated with exemption procedure complexity. Finally, we found that although there were more attempts by state legislatures to broaden exemptions than to tighten them in 2011-13, only bills tightening exemptions passed. Policy makers seeking to control exemption rates to achieve public health goals should consider tightening nonmedical exemption procedures and should add vaccine education components to the procedures by either mandating or encouraging yearly educational sessions in schools for parents reluctant to have their children vaccinated.
PMID: 23836745
ISSN: 0278-2715
CID: 508962
Correlates of Symptom Reduction in Treatment-Seeking Survivors of Torture
ISI:000322286700010
ISSN: 1942-9681
CID: 516102
Phenotypic variability of osteogenesis imperfecta type V caused by an IFITM5 mutation
In a large cohort of osteogenesis imperfecta type V (OI type V) patients (17 individuals from 12 families), we identified the same mutation in the 5' untranslated region (5'UTR) of the interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.-14C > T) and provide a detailed description of their phenotype. This mutation leads to the creation of a novel start codon adding five residues to IFITM5 and was recently reported in several other OI type V families. The variability of the phenotype was quite large even within families. Whereas some patients presented with the typical calcification of the forearm interosseous membrane, radial head dislocation and hyperplastic callus (HPC) formation following fractures, others had only some of the typical OI type V findings. Thirteen had calcification of interosseous membranes, 14 had radial head dislocations, 10 had HPC, 9 had long bone bowing, 11 could ambulate without assistance, and 1 had mild unilateral mixed hearing loss. The bone mineral density varied greatly, even within families. Our study thus highlights the phenotypic variability of OI type V caused by the IFITM5 mutation.
PMCID:3688672
PMID: 23408678
ISSN: 1523-4681
CID: 2229202
Antibiotics cut death rates in children with malnutrition [Note]
EMBASE:2013465165
ISSN: 1079-6533
CID: 1463512
GWAS of 126,559 individuals identifies genetic variants associated with educational attainment
A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) approximately 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for approximately 2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.
PMCID:3751588
PMID: 23722424
ISSN: 0036-8075
CID: 449662
MASP-2 activation is involved in ischemia-related necrotic myocardial injury in humans
BACKGROUND/OBJECTIVES: Insufficient blood supply to the heart results in ischemic injury manifested clinically as myocardial infarction (MI). Following ischemia, inflammation is provoked and related to the clinical outcomes. A recent basic science study indicates that complement factor MASP-2 plays an important role in animal models of ischemia/reperfusion injury. We investigated the role of MASP-2 in human acute myocardial ischemia in two clinical settings: (1) Acute MI, and (2) Open heart surgery. METHODS: A total of 187 human subjects were enrolled in this study, including 50 healthy individuals, 27 patients who were diagnosed of coronary artery disease (CAD) but without acute MI, 29 patients with acute MI referred for coronary angiography, and 81 cardiac surgery patients with surgically-induced global heart ischemia. Circulating MASP-2 levels were measured by ELISA. RESULTS: MASP-2 levels in the peripheral circulation were significantly reduced in MI patients compared with those of healthy individuals or of CAD patients without acute MI. The hypothesis that MASP-2 was activated during acute myocardial ischemia was evaluated in cardiac patients undergoing surgically-induced global heart ischemia. MASP-2 was found to be significantly reduced in the coronary circulation of such patients, and the reduction of MASP-2 levels correlated independently with the increase of the myocardial necrosis marker, cardiac troponin I. CONCLUSIONS: These results indicate an involvement of MASP-2 in ischemia-related necrotic myocardial injury in humans.
PMCID:3310957
PMID: 22178059
ISSN: 0167-5273
CID: 544852
THE DARKEST YEAR OF MEDICAL SCHOOL STUDENTS ARRIVE ALTRUISTIC AND EMPATHETIC. THEY OFTEN LEAVE JADED AND BITTER [Newspaper Article]
After two years of the predictable life of lectures, textbooks and exams, the students are plunged into the world of actual clinical medicine, where patients and their illnesses rarely go by the book. [...]as soon as students have figured out the ins and outs of the electronic medical record system, the names of the social workers and where the bathrooms are, they are shipped off to the next rotation -- in a different place, with a different medical team, with different patients, with different expectations and often an entirely new computer system to battle with
PROQUEST:1366359114
ISSN: 1068-624x
CID: 814422
