Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. Centers for Disease Control and Prevention.

Testing for the presence of antibody to hepatitis C virus (anti-HCV) is recommended for initially identifying persons with hepatitis C virus (HCV) infection (CDC. Recommendations for prevention and control of hepatitis C virus [HCV] infection and HCV-related chronic disease. MMWR 1998;47[No. RR-19] :1-33). Testing for anti-HCV should include use of an antibody screening assay, and for screening test-positive results, a more specific supplemental assay. Verifying the presence of anti-HCV minimizes unnecessary medical visits and psychological harm for persons who test falsely positive by screening assays and ensures that counseling, medical referral, and evaluation are targeted for patients serologically confirmed as having been infected with HCV. However, substantial variation in reflex supplemental testing practices exists among laboratories, and an anti-HCV-positive laboratory report does not uniformly represent a confirmed positive result. These guidelines expand recommendations for anti-HCV testing to include an option for reflex supplemental testing based on screening-test-positive signal-to-cut-off (s/co) ratios. Use of s/co ratios minimizes the amount of supplemental testing that needs to be performed while improving the reliability of reported test results. These guidelines were developed on the basis of available knowledge of CDC staff in consultation with representatives from the Food and Drug Administration and public health, hospital, and independent laboratories. Adoption of these guidelines by all public and private laboratories that perform in vitro diagnostic anti-HCV testing will improve the accuracy and utility of reported anti-HCV test results for counseling and medical evaluation of patients by health-care professionals and for surveillance by public health departments.     

Genetic polymorphisms and heart failure.

Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism. Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system. Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study gene-gene interactions and gene-environment interactions.     

p53 and skin carcinomas with skull base invasion: a case-control study.

BACKGROUND: Some skin carcinomas may be very aggressive. Increased expression of the protein p53 has been associated with tumor aggressiveness. In this study, p53 expression was evaluated in basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) with skull base invasion, and was compared to tumors with good outcome. STUDY DESIGN AND SETTING: Expression of p53 was immunohistochemically analyzed and it was reported as present or absent in 24 BCC and 11 SCC with skull base invasion. Control group (good outcome) included 23 BCC and 10 SCC. RESULTS: Expression of p53 was noted in 70.83% of BCC with skull base invasion, compared to 43.48% in the control group (P = 0.058). Regarding SCC, p53 positivity was noted in only 9.09% of SCC with skull base invasion, compared to 40.00% in the control group (P = 0.149). CONCLUSIONS: In this study, p53 expression was more common among BCC with skull base invasion, compared to controls with good outcome, and the difference was considered marginally significant. This proportion was reversed in SCC, but the difference was not statistically significant. EBM rating: B-3b.     

Effects of Ethanol on Human Natural Killer Cell Activity: In Vitro and Acute, Low-Dose In Vivo Studies

Chronic use of ethanol may cause a variety of immunological abnormalities in humans. In this study, we have determined the effects of an acute, low dose of ethanol (0.5 g/kg), administered either intravenously or orally, to normal, nonalcoholic male volunteers, on natural killer cell (NK) activity. We have also examined the effects of a 4-hr incubation with ethanol, in concentrations ranging from 0 to 320 mg/dl, on human NK activity in vitro. NK activity was measured by the ⁵¹Cr release assay technique in all of these studies, using peripheral blood mononuclear cells prepared from blood obtained from healthy, nonalcoholic volunteers. Eight subjects received ethanol in vivo; cells from nine subjects were used for the in vitro studies. Blood ethanol concentrations were determined at multiple time points before and after ethanol administration for the in vivo studies; for the in vitro studies, ethanol concentrations were measured from each assay sample both before and after the incubation period. Gas chromatography was used for determinations of both blood alcohol and medium ethanol concentrations. Results of the in vivo studies showed that a single dose of ethanol (0.5 g/kg), administered either intravenously (with resultant peak blood levels transiently up to 89 mg/dl) or orally (with resultant peak blood levels transiently up to 40 mg/dl at the time of the NK assay), did not alter NK activity. However, results of the in vitro studies showed a significant dose-dependent decrease ( p < 0.001) in NK activity when ethanol exposure was sustained for 4 hr at concentrations of 80 mg/ dl and above. We conclude that one of the possible causes for a higher incidence of certain viral infections and malignant tumors among chronic alcoholics may be due, in part, to this observed direct effect of ethanol on NK cytotoxicity.     

Natural history of morbid obesity without surgical intervention.

BACKGROUND: To study the mortality among morbidly obese patients qualifying for bariatric surgery. Mortality from bariatric surgery for morbid obesity has been widely reported; however, little is known about the mortality in morbidly obese patients who defer surgery. METHODS: Consecutive patients evaluated for bariatric surgery with an initial encounter between 1997 and 2004 were identified. The Social Security Death Index and office records were used to identify mortality through 2006. We conducted telephone interviews to determine whether the 305 patients who did not undergo bariatric surgery at our institution had undergone the surgery elsewhere. Using Cox proportional hazards models, we compared the mortality in patients undergoing surgery with that of those who did not. To evaluate bias resulting from missing data, we conducted analyses assuming that all patients with missing data had (1) undergone surgery and (2) not undergone surgery. RESULTS: A total of 908 patients underwent bariatric surgery (880 patients at our institution and 28 patients elsewhere). A total of 112 patients did not undergo surgery. Data regarding surgery on 165 patients could not be obtained. The mortality in those patients who did not undergo surgery was 14.3% compared with 2.9% for those who did undergo surgery. Adjusting for age, gender, and body mass index, patients who had undergone surgery had an 82% reduction in mortality (hazard ratio 0.18, 95% confidence interval 0.09-0.35, P <.0001). Sensitivity analysis, assuming that all patients with missing data received surgery resulted in an 85% mortality reduction (P <.001) and assuming that patients did not receive surgery resulted in a 50% mortality reduction (P = .04). CONCLUSIONS: Mortality among morbidly obese patients without surgery was 14.3% during the study period. Surgical intervention offered a 50%-85% mortality reduction benefit.     

DXA-Generated Z-Scores and T-Scores May Differ Substantially and Significantly in Young Adults

Central dual-energy X-ray absorptiometry (DXA) is the gold standard for non-invasive measurement of bone mineral density (BMD). Using this value and subject demographics, DXA software calculates T-scores and Z-scores. Professional society guidelines for the management of osteoporosis are based on T-scores and Z-scores, rather than on the actual BMD value. Although one expects T-scores and Z-scores to be very similar in young men and women for any given BMD measurement, little literature exists on this issue. Our clinical experience shows that some younger adult individuals (premenopausal women and men younger than 50 yr) have larger than expected difference between their DXA T-score and Z-score. This cross-sectional study evaluates the extent of this discordance between Z-scores and T-scores in a sample of 4275 men and women aged 20–49 yr. All subjects were scanned by central DXA using equipment manufactured by GE Lunar, GE, Madison, WI, or Hologic, Inc., Bedford, MA. Significant differences between Z-scores and T-scores were seen within individuals at the lumbar spine, total hip, femoral neck, and trochanter (p value < 0.001) for both DXA systems. Although these differences were less than half a standard deviation (SD) in most instances, the magnitude of difference was substantial at times, being 1 or more SD in up to 11% of cases (range: −1.95 to +1.54 SD). The smallest differences were seen at the total hip and the largest differences were seen at the femoral neck for both technologies. This is in part because there is no single standard Z-score definition, resulting in different methods of calculation across, and even within, DXA manufacturers. Standardization of Z-score definition and method of calculation is indicated. DXA Z-scores should be interpreted with caution in men and women aged 20–50 yr.