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A L Silverman

Publications and source records attributed to A L Silverman.

28 records · Page 2Linked to original sources

Levels of hepatitis C virus RNA and liver histology in chronic type C hepatitis.

BACKGROUND: The clinical and pathologic significance of quantitative serum hepatitis C virus (HCV) RNA levels in patients with chronic type C hepatitis is unknown. The aim of this study was to determine whether serum levels of HCV RNA were associated with mode of viral transmission or with histological severity of liver disease. METHODS: A branched DNA signal amplification assay for HCV RNA was done on the sera of 127 patients with well-defined risk factors for viral hepatitis. Seventy persons acquired HCV infection by blood transfusion and 57 via tattoo application or former intravenous drug use. Group I included 42 patients with chronic persistent hepatitis, group II consisted of 39 patients with chronic active hepatitis, and group III included 40 individuals whose liver biopsies showed both chronic active hepatitis and cirrhosis, as well as six patients with clinically decompensated cirrhosis. RESULTS: The median HCV RNA level [equivalents/ml (eq/ml) x 10(5)] for patients who acquired infection from transfusion [73.5 x 10(5) (eq/ml)] was not significantly different from that of patients who reported prior intravenous drug use [50 x 10(5) eq/ml] (p = 0.283). The median HCV RNA level for groups I, II, and III was 29.5, 76, and 71, respectively. Group I differed significantly from groups II and III combined (median = 73) (p = 0.02). No difference was noted between group II and group III (p = 0.947). Age did not correlate with level of viremia (r2 = 0.01). No relationship was found between serum alanine aminotransferase and the level of viremia (p = 0.52). Multivariate analysis showed that only the histological severity of the disease proved to be predictive of HCV RNA level (p = 0.04). CONCLUSION: The lowest levels of hepatitis C viremia are, in general, associated with minimal liver disease. Overall, histological severity of chronic hepatitis C infection best predicts HCV RNA levels.

Biopsy↗

Lack of evidence for the heterosexual transmission of hepatitis C.

To determine the potential for sexual transmission of the hepatitis C virus (HCV), we specifically studied a cohort of 42 young adults (median age, 39 yr) with chronic HCV infection and their stable sexual partners. All HCV assays were supplemented with the four-antigen recombinant immunoblot assay, and 39 of 42 partners were tested for HCV RNA by the nested polymerase chain reaction. Ninety percent of the partners reported frequent and unprotected sexual intercourse with the index patients. Two of 42 partners tested positive for the anti-HCV antibody and both were HCV RNA positive; one had independent risk factors for viral hepatitis. Therefore, one of 41 partners, (2.4%; 95% CI, 0.6-12.9%) without independent risk factors for HCV was anti-HCV positive. This woman was one of five partners (20%; 95% CI, 1-66%) who reported frequent razor-sharing with the index patient. The partner frequently sustained skin lacerations, with bleeding, secondary to this shared razor blade. We conclude that heterosexual transmission of hepatitis C is extremely uncommon, despite frequent and unprotected sexual intercourse.

Adult↗

Abnormal methylation of the calcitonin gene in human colonic neoplasms.

Earlier studies of the methylation status of total genomic DNA and of specific genes have demonstrated, predominantly, hypomethylation in human neoplasms. However, we have recently documented the presence of new sites of methylation in the calcitonin gene in human lymphomas (100%), small cell lung carcinomas (92%), and acute myeloid leukemias (95%). We now report that these same novel calcitonin gene methylation sites are also a feature of DNA from human colonic adenomas (13 out of 14 studied), colon carcinomas (4/13), and established colon carcinoma cell lines (18/19), despite the presence of overall genomic DNA hypomethylation in these neoplasms. The data provide further evidence that regional increases in DNA methylation, like gene hypomethylation, occur in benign colonic neoplasms prior to malignant transformation. The fact that abnormalities of calcitonin gene methylation are less frequent in DNA from human colonic carcinomas than from adenomas and colon carcinoma cell culture lines is of special interest. This finding suggests that a more heterogeneous population of cells is present in the carcinomas and that the calcitonin gene hypermethylation may be inherent to cells which are initially selected for growth in culture or are capable of prolonged survival under culture conditions.

Adenoma↗

Prevention of colon cancer in primary care practice.

Colorectal cancer is a common disease with a high mortality rate. Surgical resection in early stages is the only effective treatment, therefore, recent attention is focused on diagnosing early colon cancer by screening asymptomatic subjects. Principles and current technology supporting early detection of colorectal cancer are critically evaluated. Current guidelines for screening average risk asymptomatic subjects and high-risk groups are discussed.

Colonic Neoplasms↗

Clinical features, evaluation, and detection of colorectal cancer.

The most common presentation of colorectal carcinoma is in the symptomatic patient, most often with complaints of rectal bleeding, abdominal pain, or change in bowel habits. Symptomatic patients often have advanced disease and, because surgical resection is the only effective therapy at present, their chance for cure is poor. Until effective treatment is available, therefore, we must identify patients at high risk for lifelong screening. In addition, more effective means of surveillance of the general population need to be developed in order to diagnose patients at risk for sporadic colorectal cancer, given that this represents the majority of patients with disease. Tumor markers also would be useful to find residual disease while it is still resectable in patients who have undergone surgery for curative resection.

Colorectal Neoplasms↗

Screening and surveillance for colorectal cancer.

Pathologic reviews and clinical studies demonstrate that groups with increased cancer risk can be identified. It is estimated that about 3.5 per cent of colorectal cancers in this country are the result of known heritable cancer syndromes, such as familial polyposis. Much effort is currently being devoted to evaluation of biologic markers, such as cell surface antigens and their antibodies, ornithine decarboxylase, errors in DNA repair, abnormalities in metabolism of polyadenosine diphosphate, and application of molecular genetic techniques to identify patients with genetic cancer susceptibility.

Adult↗

Life after colectomy.

Animal and epidemiologic studies have raised hopes that effective chemoprevention of colorectal cancer in very high-risk patients may be possible in the future, but at present, the only established effective way to prevent colorectal cancer in very high-risk patients is colectomy. Advances in surgical techniques, improvements in stomal appliances, and medical advances in dealing with complications of colorectal surgery (such as impotence) have contributed to substantial improvements in the quality of life of patients who have had prophylactic colectomies.

Colectomy↗

Biochemical markers in colorectal cancer: diagnostic and therapeutic implications.

Markers that are now in use, including CEA and CA-19-9, are not specific or sensitive enough to detect early colorectal cancer. Newer tumor markers such as polyamines, ornithine decarboxylase, and altered blood group carbohydrate antigens may have a potential as future tumor markers. Additional studies of these markers as well as the development of new biochemical markers are warranted in the future to enhance the sensitivity and specificity of diagnosis of early colorectal cancer and those at risk for developing cancer. Finally, understanding events involved in abnormal cell proliferation (that is, elevated polyamines and ODC in colorectal cancer) may help direct future chemotherapy and possibly chemoprevention in high-risk groups such as adenomatous polyposis coli.

Antibodies, Monoclonal↗

Strategies for the control of colorectal cancer.

An overview of this issue is presented, with a discussion of its application to control of colorectal cancer. A brief update on new findings in molecular and genetic aspects is also given. Finally, strategies for control of colorectal cancer are discussed.

Colorectal Neoplasms↗

Biochemical markers in patients with familial colonic neoplasia.

Many potential markers, including biochemical markers, have been studied in an attempt to identify the presence of early colorectal neoplasia or risk of neoplasia, particularly in those families with hereditary colonic neoplasia syndromes. Unfortunately, most of these markers are useless in screening or diagnosis. Nevertheless, such markers as carcinoembryonic antigen (CEA) and CA 19-9 may have a role in pretherapeutic and posttherapeutic monitoring of disease or recurrence. The newer tumor markers, including the carbohydrate markers, ornithine decarboxylase (ODC) and the polyamines, are of great interest as potential tumor markers; ODC and the polyamines may also have a future potential as therapeutic targets. However, further studies are needed to determine their true sensitivity and specificity in hereditary colonic neoplasia syndromes, as well as in patients without genetic syndromes who are at risk for colorectal cancer.

Adenomatous Polyposis Coli↗