Influence of some methylated hepatocarcinogenesis-related genes on the response to antiviral therapy and development of fibrosis in chronic hepatitis C patients.

Epigenetics involved in multiple normal cellular processes. Previous research have revealed the role of hepatitis C virus infection in accelerating methylation process and affecting response to treatment in chronic hepatitis patients. This work aimed to elucidate the role of promoter methylation (PM) in response to antiviral therapy, and its contribution to the development of fibrosis through hepatocarcinogenesis-related genes. A total of 159 chronic hepatitis Egyptian patients versus 100 healthy control group were included. The methylation profile of a panel 9 genes (SFRP1, p14, p73, APC, DAPK, RASSF1A, LINE1, O6MGMT, and p16) was detected in patients' plasma using methylation-specific polymerase chain reaction (MSP). Clinical and laboratory findings were gathered for patients with combined pegylated interferon and ribavirin antiviral therapy. Regarding the patients' response to antiviral therapy, the percentage of non-responders for APC, O6MGMT, RASSF1A, SFRP1, and p16 methylated genes were significantly higher versus responders (P<0.05). Of the 159 included patients, the most frequent methylated genes were SFRP1 (102/159), followed by p16 (100/159), RASSF1A (98/159), then LINE1 (81/159), P73 (81/159), APC (78/159), DAPK (66/159), O6MGMT (66/159), and p14 (54/159). A total of 67/98 (68.4%) cases of RASSF1A methylated gene (P=0.0.024), and 62/100 (62%) cases of P16 methylated gene (P=0.03) were associated with mild-degree fibrosis. To recapitulate, the PM of SFRP1, APC, RASSF1A, O6MGMT, and p16 genes increases in chronic hepatitis C patients, and can affect patients' response to antiviral therapy. The RASSF1A and P16 genes might have a role in the distinction between mild and marked fibrosis.

Gram-negative bacillary meningitis in Egypt.

BACKGROUND: Gram-negative bacillary meningitis (GNBM) is a rare disease with a high rate of mortality. OBJECTIVES: The aim of this study was to describe the clinical presentation and outcome of primary and secondary GNBM and to evaluate the efficacy of ceftriaxone (a third-generation cephalosporin) in the treatment of this disease. MATERIALS AND METHODS: A retrospective study was conducted including 95 patients with GNBM admitted to the Abbassia and Imbaba fever hospitals' meningitis wards in Egypt during the period from 1993 to the end of the year 2009. Their cerebrospinal fluid samples were subjected to conventional bacteriological methods for isolation of the causative Gram-negative bacilli. Forty-nine patients had primary GNBM (no predisposing cause of meningitis was detected) and 46 patients had secondary GNBM (with a predisposing cause of meningitis). RESULTS: Primary GNBM was characterized by an abrupt onset and was significantly associated with typical signs of meningeal irritation. The most common infecting organisms were Salmonella typhi in 16 (33%) patients and Escherichia coli in 15 (31%) patients. Of the patients with primary GNBM, 26 (53%) were cured, 11 (22%) developed neurological sequalae, and 12 (24%) patients died. Secondary GNBM was characterized by an insidious onset and significantly associated with unarousable coma. The most common infecting organisms were Proteus mirabilis in 17 (37%) patients and Pseudomonas aeruginosa in 16 (35%) patients. The most common predisposing factor of meningitis was otitis media and occurred in 26 (57%) patients. Of the patients with secondary GNBM, 15 (33%) were cured, 15 (33%) developed neurological sequalae, and 16 (35%) died. Primary GNBM was significantly associated with a higher cure rate than secondary GNBM. The duration of symptoms in patients with secondary GNBM was significantly higher than in those with primary GNBM. Ceftriaxone was the initial drug for treatment of these patients until the antibiotic sensitivity tests were reported. The overall resistance rate to the drug was 4%. CONCLUSION AND RECOMMENDATIONS: GNBM still has a high mortality rate and should be managed as a medical emergency. GNBM should be suspected in patients with otitis media, neurosurgical, and head trauma or who underwent spinal anesthesia and have disturbance in their level of consciousness, even if there are no signs of meningeal irritation. Ceftriaxone is still an effective drug and had a low rate of resistance in our study.