Chronic hepatitis C in patients with persistently normal alanine transaminase levels.

BACKGROUND & AIMS: Many patients with chronic hepatitis C virus (HCV) have persistently normal serum alanine transaminase (ALT) levels. We compared characteristics of chronic hepatitis C patients with patients with normal and elevated ALT levels using data from 3 randomized phase III trials of peginterferon alfa-2a (40 kDa). METHODS: The characteristics of 480 patients with normal ALT values (on >or=3 occasions without any increases in ALT level over a 6- to 18-month period) and 1993 patients with elevated ALT levels were compared. Sixty-eight of the 480 patients with normal ALT levels were randomized to no treatment and monitored for 72 weeks. RESULTS: More patients with normal ALT levels than patients with elevated ALT levels were women (59% vs 32%; P<.01). The serum HCV RNA titer was significantly lower in patients with normal ALT levels (P<.01 vs in patients with elevated ALT levels). Patients with normal ALT levels had significantly lower inflammation and fibrosis scores on liver biopsy examination than patients with elevated ALT levels, but almost two-thirds had portal fibrosis and 10% had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA level, and liver histology was observed in patients with normal ALT levels. During the 72-week follow-up period, ALT activity elevated above the upper limit of normal in 53% of the untreated patients with normal levels of ALT. None became HCV RNA undetectable. CONCLUSIONS: Chronic hepatitis C patients with normal ALT levels should be evaluated in a similar manner as patients with elevated ALT levels because they are at risk for developing significant liver disease. The decision to treat with peginterferon alfa and ribavirin should be based on multiple factors, rather than on ALT levels alone.     

Significantly reduced expression of the proteoglycan decorin in Alzheimer''s disease fibroblasts

Aims—To investigate whether proteoglycan synthesis is altered in skin fibroblasts in patients with Alzheimer's disease compared with normal subjects.     

Ecological study of gastric cancer in Brazil:Geographic and time trend analysis

AIM:To investigate the geographic distributions and time trends of gastric cancer(GC)incidence and mortality in Brazil.METHODS:An ecological study of the DATASUS registry was conducted by identifying hospitalizations for GC between January 2005 and December 2010.The data included information on the gender,age,and town of residence at the time of hospital admission and death.RESULTS:The GC rates,adjusted according to available hospital beds,decreased from 13.8 per 100000in 2005 to 12.7 per 100000 in 2010.The GC rates decreased more among the younger age groups,in which the male-to-female difference also decreased in comparison to the older age groups.Although the lethality rates tended to increase with age,young patients were proportionally more affected.The spatial GC distribution showed that the rates were higher in the south and southeast.However,while the rates decreased in the central-west and south,they increased in the northern regions.A geographic analysis showed higher rates of GC in more urbanized areas,with a coast-toinland gradient.Geographically,GC lethality overlapped greatly with the hospital admission rates.CONCLUSION:The results of this study support the hypothesis of a critical role for environmental factors in GC pathogenesis.The declining rates in young patients,particularly males,suggest a relatively recent decrease in the exposure to risk factors associated with GC.The spatial distribution of GC indicates an ongoing dynamic change within the Brazilian environment.     

In vivo arrhythmogenicity of the marine biotoxin azaspiracid-2 in rats

Azaspiracids (AZAs) are marine biotoxins produced by the dinoflagellate Azadinium spinosum that accumulate in several shellfish species. Azaspiracid poisoning episodes have been described in humans due to ingestion of AZA-contaminated seafood. Therefore, the contents of AZA-1, AZA-2 and AZA-3, the best-known analogs of the group, in shellfish destined to human consumption have been regulated by food safety authorities of many countries to protect human health. In vivo and in vitro toxicological studies have described effects of AZAs at different cellular levels and on several organs, however, AZA target remains unknown. Very recently, AZAs have been demonstrated to block the hERG cardiac potassium channel. In this study, we explored the potential cardiotoxicity of AZA-2 in vivo. The effects of AZA-2 on rat electrocardiogram (ECG) and cardiac biomarkers were evaluated for cardiotoxicity signs besides corroborating the hERG-blocking activity of AZA-2. Our results demonstrated that AZA-2 does not induce QT interval prolongation on rat ECGs in vivo, in spite of being an in vitro blocker of the hERG cardiac potassium channel. However, AZA-2 alters the heart electrical activity causing prolongation of PR intervals and the appearance of arrhythmias. More studies will be needed to clarify the mechanism by which AZA-2 causes these ECG alterations; however, the potential cardiotoxicity of AZAs demonstrated in this in vivo study should be taken into consideration when evaluating the possible threat that these toxins pose to human health, mainly for individuals with pre-existing cardiovascular disease when regulated toxin limits are exceeded.     

Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: a case–control study

Objective. To analyze risk factors for Pneumocystis carinii pneumonia (PCP) in kidney transplant recipients. Study design. In a case–control study, 17 PCP cases diagnosed between July 1994 and July 2000 were matched with two controls each (previous and subsequent kidney transplant recipients who did not develop PCP during the same follow‐up period). Demographics, organ origin, human leukocyte antigen (HLA) mismatches, use of poly‐ or monoclonal anti‐CD3 antibodies (Po/MoAb) for induction or rejection treatment, rejection episodes, cumulative steroid dose for rejection treatment, immunosuppressive regimens, and other infections were analyzed. Results. No significant differences were seen in gender (male 10 vs. 15), mean age (39.7 vs. 35.4 years), organ origin (cadaver donor 13 vs. 19), HLA mismatches, or Po/MoAb use in induction treatment. Significant differences were observed in PCP cases for rejection history (P=0.02), and median and total number of rejection episodes (P=0.0018). The relative risks for PCP for 1, 2, and ≥3 rejection treatments vs. no such treatment were 1, 1.05, and 6.30, respectively (P=0.021). The relative risk for PCP for steroid‐resistant rejection was 4.34 (95% confidence interval [CI], 1.04–18.89) (P=0.019), and that for the use of Po/MoAb for rejection treatment was 7.23 (95% CI, 1.28–49.34) (P=0.006). The relative risk for PCP for 0, 1, and ≥2 previous or concomitant cytomegalovirus (CMV) infection vs. no such infections were 1.0, 2.32, and 13.0, respectively (P=0.012). The relative risks for PCP for tuberculosis (TB) was 18 (95% CI, 1.76–852.03), that for bacterial pneumonia was 14.22 (95% CI, 2.16–150.23), and that for hepatitis C virus infection was 5.25 (95% CI, 1.03–28.91). Immunosuppressive regimens with tacrolimus, mycophenolate mofetil (MMF), steroids (P=0.06), and MMF as a single variable (P=0.05) were more frequently used in cases. Primary trimethoprim‐sulfamethoxazole prophylaxis failure was observed in 12 patients in association with heavy immunosuppression and concomitant infections. Conclusions. The risk of PCP in kidney transplant recipients is related to the number and type of rejection treatments. It is also related to the occurrence of CMV infection, and to other immunomodulating infections such as TB and hepatitis C, and might also be increased with the use of newer and more potent immunosuppressive agents. Primary prophylaxis failure may occur in association with some of these risk factors.