Apoptosis,PCNA and p53 in hepatocellular carcinoma

BACKGROUND/AIMS: The regulation of cell number is present in normal tissues but is lost in malignant neoplasms. The real meaning of these alterations is not well known. Apoptosis is the programmed cell death. p53, a tumor suppressor gene, has an important function in DNA repair and in regulation of apoptosis. Mutations of p53 were described in malignant tumors and can be the cause of the alterations of this balance. Proliferating cell nuclear antigen is an auxiliary protein present during G1-late phase and S phase. The aim of this study was to compare cell proliferation, apoptosis and expression of p53 in hepatocellular carcinoma. METHODOLOGY: Fifteen patients with hepatocellular carcinoma were included. Ten patients were men. The mean age of the patients was 55.53 years old. Cirrhosis was positive in nine patients, 5 were HBsAg positive and none were anti-HCV positive. The mean level of AST and ALT were respectively, 62.79 and 50.64. Formalin-fixed and paraffin-embedded tissues from these patients were examined retrospectively. Apoptosis were measured by counting the number of apoptotic bodies in 500 tumoral cells. The expression of p53 oncogene and the PCNA were determined by immunohistochemical method, using avidin-biotin method (DAKO). The p53 were considered positive when the number of positive nuclei was more than 5% of the tumoral cells. The proliferative activity was determined by proliferating cell nuclear antigen labeling index. RESULTS: The proliferating cell nuclear antigen-labeling index ranged from 0.48 and 0.95 (mean: 0.82). The p53 was positive in five patients. The number of apoptotic bodies counted ranged from 0 to 15 (mean: 4.20). There were no differences among p53 and the mean levels of proliferating cell nuclear antigen labeling index or p53 and the number of apoptotic bodies. CONCLUSIONS: A high index of proliferation has been shown in the patients studied. Positivity of p53 was seen in less than a half of the patients (35.71%). The index of apoptotic bodies observed was very low. Our results suggest that high-grade proliferation is not associated with increase of apoptosis in hepatocellular carcinoma.     

Efficacy and Toxicity Profile of Methotrexate Chloroquine Combination in Treatment of Active Rheumatoid Arthritis

Background

The present study was conducted to study the efficacy and toxicity profile of methotrexate chloroquine combination in treatment of active rheumatoid arthritis.

Methods

24 patients of rheumatoid arthritis confirming to revised American Rheumatism Association (ARA) criteria were studied prospectively for twenty months. Clinical evaluation was made every 3 months. Clinical disease variables measured at each visit were number of joints with swelling, number of joints with tenderness and pain, duration of morning stiffness and physician and patient assessment of disease activity. Blood counts, liver function tests and other adverse effects due to drugs were monitored every 2 months.

Results

10 patients demonstrated more than 50% improvement. 4 patients withdrew from study, 2 because of excessive nausea and vomiting and 2 because of noncompliance. Other side effects noted were hyperpigmentation, photosensitivity, skin rashes, raised transaminases and stomatitis.

Conclusion

Methotrexate chloroquine combination has good efficacy and toxicity profile. Gastrointestinal side effects are most common and usually responsible for the discontinuation of the drugs.Key Words: Rheumatoid arthritis, Methotrexate, Chloroquine, Efficacy, Toxicity     

Inverse association between dietary vitamin D and risk of cutaneous melanoma in a northern Italy population

The possibility of an inverse association between vitamin D and risk of cancer and, in particular, of cutaneous malignant melanoma has been suggested, but results of epidemiologic studies are still conflicting. We examined the relation between dietary vitamin D intake and melanoma risk through a population-based case-control study (380 cases, 719 controls) in a northern region of Italy, a country with an average vitamin D intake lower than that in northern Europe or the United States. We assessed average daily intake of vitamin D from foodstuffs using the European Prospective Investigation into Cancer and Nutrition (EPIC) semiquantitative food frequency questionnaire. In this population, levels of vitamin D intake were considerably lower than those observed in recent U.S. studies. We found an inverse relation between dietary vitamin D and melanoma risk in the sample as a whole, in both crude and adjusted analyses. In sex- and age-specific analyses, this association appeared to be stronger among males and among older subjects. These findings suggest that, at the relatively low levels of intake observed in this sample, an inverse relation between dietary vitamin D and risk of cutaneous malignant melanoma may exist.     

Pneumothorax preceding pulmonary blastoma in a child

Serial plain radiographic, ultrasound and CT findings of an unusual case of pulmonary blastoma are described with a review of the literature.     

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T- lymphotropic virus via the transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window- period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window- period donations is the number of post-screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window- period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.     

Factors associated with the intensity of liver fibrosis in renal transplant patients with hepatitis B virus infection

BACKGROUND: Hepatitis B may show a more aggressive course after kidney transplantation, but the factors associated with the progression of fibrosis in this group have not been identified. OBJECTIVES: To determine the influence of hepatitis B virus (HBV) viral load and host-related factors on the progression of hepatic fibrosis in hepatitis B virus-infected renal transplant recipients. PATIENTS AND METHODS: Renal transplant patients positive for HBV surface antigen (HBsAg) and submitted to a liver biopsy because of evidence of viral replication were included. Patients with advanced fibrosis (METAVIR F3-F4) were compared with patients with mild fibrosis (F0-F2) regarding sex, age, estimated time since infection, post-transplant time, donor type, history of renal transplantation, alanine aminotransferase, anti-hepatitis C virus, HBeAg and quantitative hepatitis B virus-DNA. Logistic regression analysis was applied to identify variables independently associated with more advanced fibrosis. RESULTS: Fifty-five patients (75% men, 41+/-11 years) with a mean post-transplant time of 5+/-4 years were included. HBeAg was detected in 67% of the patients and anti-hepatitis C virus in 35%. The median hepatitis B virus-DNA level was 2.8 x 10(8) copies/ml. Seventeen (31%) patients had advanced fibrosis. Using logistic regression analysis, the only variable that showed an independent association with more advanced stages of fibrosis was post-transplant time (P=0.03, odds ratio: 1.2, 95% confidence interval: 1.02-1.45). CONCLUSION: Hepatitis B virus viral load, although very high, and hepatitis B virus/hepatitis C virus coinfection are not related to the intensity of liver fibrosis in renal transplant patients infected with hepatitis B virus. Post-transplant time was the only factor independently associated with more advanced liver fibrosis, suggesting the influence of immunosuppression on the progression of liver disease in these patients.