Predictors of sustained response to alpha interferon therapy in chronic hepatitis C.

OBJECTIVES: To utilize cytokine levels to predict sustained response (SR) to alpha interferon (IFN alpha) therapy in chronic hepatitis C patients, and to determine the relationship between serum tumor necrosis factor alpha (TNF alpha), interleukin (IL) IL 6, IL 8, IL 12, transforming growth factor beta (TGF beta 1) and the degree of liver damage as reflected by traditional markers. DESIGN AND METHODS: Serum cytokine levels were assessed using ELISA in 18 patients included in a controlled clinical trial of IFN alpha. RESULTS: Of the 18 patients, 27% were sustained responders (SR), 27% were response and relapse responders (RR), and 46% were non-responders (NR). Multivariate analysis showed that a low serum TNF alpha level and high serum IL 8 levels were independent factors associated with SR to IFN alpha therapy. Serum TNF alpha level highly correlated with viral load and genotype predictive values (p < 0.001). Therapy lowered the IL 6 and IL 12 profile. TGF beta 1 levels in serum are positively correlated with fibrinogenesis. CONCLUSIONS: IFN alpha therapy modulates immune response to hepatitis C virus, contributing to sustained response.

Cytokines as predictors for sustained response and as markers for immunomodulation in patients with chronic hepatitis C.

OBJECTIVES: (i) To characterize serum cytokine levels of tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL 6), IL 8 and IL 12 in non-cirrhotic patients with chronic hepatitis C, (ii) to correlate the levels of these cytokines with the degree of the disease at the basal level, (iii) to correlate these levels with the response to therapy, (iv) to compare profiles of cytokines in monotherapy (MT) versus combination therapy (CT), and (v) to compare the immunomodulatory effects of MT versus CT. DESIGN AND METHODS: 47 patients were enrolled in the study. The controls were 120 volunteers (recruited from students and staff) that did not present HCV RNA positive and were not known to suffer any other metabolic disease. Thirty patients formed the other group of controls, with alcoholic liver disease (ALD). Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: The sustained responders (SRs) have basal values much lower than relapsed responders (RRs) and non-responders (NRs) regardless of the therapy. CONCLUSIONS: Cytokines can be used as non-invasive markers for sustained response and as monitors for the outcome of therapy.

Estrogen replacement therapy and ovarian cancer.

Estrogen replacement therapy (ERT) has been shown to be of benefit for menopausal women, especially in prevention of coronary heart disease and osteoporotic fractures. Cancer fear is an important obstacle to use of ERT. From our literature review, there is a weak or no association between ERT and ovarian cancer risk. Individual risk of cancer should be considered before ERT use. The second issue in this review is ERT in patients with ovarian cancer. The majority of patients with ovarian cancer are postmenopausal or become menopausal after surgery. ERT is considered by many physicians to be contraindicated in patients with cancer. However, there is evidence that ERT in selected cancer patients may be of benefit for survival and quality of life. After weighing the evidence from studies on ERT in patients with ovarian, breast or endometrial cancer, we propose the use of ERT in selected ovarian cancer patients who are suffering from or are at a high risk of debilitating menopausal symptoms, osteoporosis, and coronary heart disease. The benefit of ERT to selected patient's health and quality of life appears to outweigh the risk of cancer recurrence.

Comparison of magnified chemiluminescent examination with incandescent light examination and colposcopy for detection of cervical neoplasia.

Magnified Chemiluminescent Examination (MCE) or speculoscopy is a new visual method for detection of cervical neoplasia. It utilizes low magnification and a special "blue-white" chemiluminescent light. The study includes 125 women with unhealthy cervix who were subjected to magnified examination with projected incandescent light (PIL) and chemiluminescent light (MCE). This was followed by colposcopy and directed biopsy from acetowhite areas. Of all 125 subjects, 20 patients showed cervical neoplasia of varying degree on histopathology. MCE could detect 18/20 neoplasias while PIL detected 11/20 cases. Sensitivity of MCE (90%) was significantly superior (P < 0.05) to PIL (55%) in detecting cervical neoplasia. Colposcopy, as compared to MCE, is better than speculoscopy as it facilitates grading of lesions due to higher magnification but antecedent MCE detected the acetowhitening in majority of patients (32/43). However, tendency to "overall" acetowhite lesions was significantly less during MCE when compared with colposcopy. Thus, MCE is a new diagnostic tool which is better than routine incandescent light examination and correlates well with colposcopy.

Do all grade I lesions on colposcopy need to be biopsied?

The present study intends to correlate grade I atypical transformation zone (ATZ) on colposcopy with cytology & histology in 51 patients by retrospective data analysis. Indications of colposcopy were inflammatory smears with unhealthy cervix (37/51). Atypical squamous cells of unknown etiology (2/51) & squamous intraepithelial lesions on cytology (12/51). All the patients exhibited grade I lesions on colposcopy & underwent directed biopsy. On histology chronic cervicitis was the commonest finding 70.6% (36/51) & CIN was found in 19.6% (10/51), out of which CIN II-III occurred only in 3.92% (2/51). Overcall rate of colposcopy for grade I lesions was 80.39%. Age, parity, the postcoital or contact bleeding did not correlate with the histological positivity of the lesions. Grade I ATZ with inflammatory smears revealed CIN II-III only in 2.7% (1/37) while with low grade SIL cytology there was no moderate or severe dysplasia. However Grade I lesions in association with high grade SIL exhibited CIN II-III lesions in 16.6% (1/6). Therefore grade I lesions in presence of inflammatory or low grade SIL smears can be observed & biopsied only if the changes persist. However association of high grade SIL with grade I ATZ calls for immediate biopsy.

Fetal Ebstein anomaly--a rare cause of non-immune hydrops.

A rare case of fetal Ebstein anomaly presenting as non-immune hydrops fetalis at 28 weeks of gestation is reported along with its review of literature.