Faculty Bibliography

BACKGROUND: Inadequate sterilization and reuse of medical equipment likely contributed to hepatitis C virus (HCV) transmission in the former Soviet Union (FSU). Although New York leads the nation in the number of immigrants from the FSU, the epidemiology of HCV infection has not been evaluated in this population. The aims of this study were to determine the prevalence of and risk factors for HCV infection among immigrants from the FSU in the New York metropolitan area. METHODS: We conducted a 3-day community-based HCV screening program in the two boroughs of the New York metropolitan area with the highest density of FSU immigrants (Brooklyn and Queens). Russian cable television was used to invite subjects to come in for free HCV testing. In the last 2 days of screening, each person also completed an HCV risk factor questionnaire. RESULTS: The overall prevalence of HCV seropositivity among the 283 subjects was 28.3% (95% confidence interval [CI] 23.0-33.5%). The prevalence of HCV infection was similar in men and women (30.3% vs 26.5%, P = 0.48) and was highest in subjects > or = 70 yr old (35.0%). HCV seropositivity was 11.1% in immigrants from Russia, 29.0% from Uzbekistan, 31.0% from the Ukraine, and 36.8% from other regions. Intramuscular injections (odds ratio 9.1, 95% CI 2.0-42.4) and blood transfusions (odds ratio 3.2, 95% CI 1.2-9.0) were the only variables that were significantly associated with HCV infection in the multivariable analysis. CONCLUSIONS: In this community-based screening program we found a high prevalence of HCV infection among immigrants from the FSU, and these infections likely resulted from inadequately sterilized medical equipment and blood transfusions. Universal HCV testing should be strongly considered for all FSU immigrants

While colonoscopy may detect early-stage colon tumors, a less invasive and more cost-effective technique would be beneficial. Stool, which picks up sloughed-off colonic epithelial cells, would be ideal for sampling the mucosa; shed tumor cells may display alterations in gene expression observed in intact tumors. It is first necessary, however, to show that RNA can be isolated from human feces and that this RNA contains human gene transcripts. We have therefore developed a method for the isolation of total RNA from freshly passed human stool, consisting of lysis in chaotropic agents, repeated extraction with phenol and phenol-chloroform, and absorption with an RNA-binding resin. After treatment with RNase-free DNase I, we assayed these preparations for the presence of human RNA by quantitative slot blotting, northern blotting, and reverse transcription-polymerase chain reaction (RT-PCR). We obtained 5-30 microg RNA per gram of stool from cancer patients, and about 5 microg RNA per gram of control stool. Quantitative slot blotting showed that about 10% of this RNA was of human origin. Both northern blotting and RT-PCR demonstrated the presence of human RNA in these samples. To unambiguously demonstrate the isolation of RNA from stool, we incubated a mixture of rat cells and control human stool at 37 degrees C for up to 24 hr. RT-PCR of the RNA isolated from this sample clearly revealed the presence of rat-specific mRNA. These experiments indicate that RNA can be isolated from human stool and that message encoded by human genes can be assayed in these preparations. This procedure may provide a powerful tool to identify patients at risk for colon cancer

Protooncogenes are cell cycle-related genes that are involved in cell growth of proliferation. Alterations in the level of expression of these genes, or expression of aberrant gene productions, have been observed in tumors and precancerous conditions. To determine if expression of these genes is altered in patients with inflammatory bowel disease (IBD) --who are at risk for development of colon cancer--we assayed transcripts of 15 protooncogenes in colonic epithelial cells of IBD patients and controls. Nine of these genes (H-ras, c-myc, c-fos, c-jun, junB, N-myc, c-abl, c-yes, and p53) were expressed in epithelial cells, whereas two (RB1 and N-ras) were not. expression of four other genes (c-src, K-ras, c-raf, and c-myb) was observed, but the intensity of these bands was too low for densitometric analysis. The steady-state levels of transcripts of H-ras and five nuclear protooncogenes (c-myc, c-fos, c-jun, junB, and N-myc) were lower in epithelial cells from involved or uninvolved IBD samples than in normal epithelial cells from either sporadic colon cancer or diverticulitis patients. The level of c-fos mRNA was two- to threefold higher in involved than in uninvolved areas of the colons of two ulcerative colitis (UC) patients, but not in one Crohn's disease (CD) patient. Message abundance of c-abl transcripts was two- to threefold lower in UC epithelial cells than in either the CD or control samples. The steady-state level of c-yes-encoded mRNA was considerably higher in IBD patients resected for colon cancer than in patients resected for active chronic IBD or in controls. The level of p53 message was constant in these samples. Increased levels of c-fos mRNA in involved UC relative to uninvolved UC may be related to the disease process. Decreased expression of c-abl transcript in UC may be a diagnostic marker for UC and may be related to the rate of cell turnover in these diseases. Enhanced expression of c-yes in IBD patients with tumors compared to active chronic IBD and controls suggests that expression of this gene may be a marker for development of colon cancer in IBD

A link between inflammation of the colon in inflammatory bowel disease (IBD) and the increased risk of colon cancer in ulcerative colitis (UC) may be provided by growth factor receptor genes. Their expression may be altered in response to growth factors present in the mucosa, and this, in turn, may induce further genetic changes, linked to carcinogenesis, in the cells of the colonic epithelium. To test this hypothesis, we assayed steady-state levels of eight growth factor receptor mRNAs in colonic epithelial cells of IBD patients and controls. Four of these genes (EGF-R, IGFI-R, CSF1-R, and PDGF-R-beta) were expressed in epithelial cells, whereas four (erbB-2, erbB-3, NGF-R, and met) were not. The level of the former in involved or uninvolved IBD was considerably lower than in normal epithelial cells from either sporadic colon cancer or diverticulitis patients. In contrast, expression was much higher in IBD patients with colon tumors than in active chronic IBD. The level of PDGF-R-beta mRNA was two- to fourfold higher in involved than in uninvolved areas of the colons of two UC patients, but not in one Crohn's disease patient. Message abundance of its ligand, PDGF-beta, however, was the same in paired UC samples. The pattern of expression of PDGF-beta and cripto was identical to that of EGF-R, whereas the level of mRNA of amphiregulin was the same in active chronic IBD and IBD patients with tumors. A fourth growth factor, Kfgf, was not expressed. Increased levels of PDGF-R-beta mRNA in involved UC relative to uninvolved UC may be related to the disease process in UC. Decreased expression of growth factor- and growth factor receptor-encoded mRNA in active chronic IBD may be related to the disease process, or it may be an effect of steroid therapy undergone by these patients. Enhanced expression of these genes in IBD patients with tumors compared to those without tumors suggests that this may be a marker for development of colon cancer in IBD

It is unknown whether beta adrenergic stress has adverse hepatic hemodynamic effects. Therefore, the authors studied the hemodynamic effects of beta adrenergic stimulation and subsequent blockade in 10 patients with cirrhosis (6 Childs A, 3 Childs B, and 1 Childs C) with known or suspected portal hypertension. Free and wedged hepatic vein pressures, hepatic venous pressure gradient, heart rate, mean arterial pressure, cardiac output, and azygos vein blood flow were measured at rest and after isoproterenol infusion (mean dose = 7.3 micrograms/min: target heart rate = 150% to 200% of resting heart rate). Esmolol, an ultra-short-acting beta blocker, was then infused (dose titrated to return heart rate to baseline), and all measurements were repeated. Based on the results, the authors conclude that beta adrenergic stress provoked by isoproterenol infusion significantly increases azygos vein blood flow and hepatic venous pressure gradient. Beta blockade with esmolol reduces azygos vein blood flow and hepatic venous pressure gradient significantly below baseline