Role of clinical, radiological, and neurophysiological changes in predicting the outcome of tuberculous meningitis: a multivariable analysis

OBJECTIVES: The role of EEG and evoked potentials has not been evaluated in predicting the prognosis of tuberculous (TB) meningitis. The present study was aimed at evaluating the prognostic significance of clinical, radiological, and neurophysiological variables using multi-variable analysis. METHODS: Patients with TB meningitis diagnosed on the basis of clinical, radiological, and CSF criteria have been prospectively evaluated. All the patients were subjected to a detailed neurological evaluation. The outcome was defined 6 months after starting treatment on the basis of the Barthel index (BI) score into poor (BI <12) and good recovery (BI> or =12). Death was included in the poor recovery group for statistical analysis. Thirteen clinical (age, sex, seizure, focal weakness, stage of meningitis, Glasgow coma scale score, methyl prednisolone therapy), CT (infarction, hydrocephalus, tuberculoma) and neurophysiological (EEG, motor and somatosensory evoked potentials) variables were evaluated employing single variable logistic regression followed by multivariable logistic regression analysis. The best set of predictors were obtained by stepdown logistic regression analysis. RESULTS: Fifty four patients were included in the present study. Their age ranged between 5 and 62 years, 11 were children younger than 12 years and 14 were female. Nine patients were in stage I meningitis, 12 in stage II, and 33 in stage III. On single variable logistic regression analysis the significant predictors of 6 months outcome of TB meningitis included focal weakness, Glasgow coma scale (GCS), motor evoked potential (MEP) and somatosensory evoked potential (SEP). On multivariable analysis the best set of predictors comprised focal weakness, GCS, and SEP. CONCLUSIONS: In patients with TB meningitis focal weakness, GCS, and SEP are the best predictors of 6 month outcome.     

A new surgical technique for ocular fixation in congenital third nerve palsy.

PURPOSE: To present a new technique of ocular fixation to restore and maintain the ocular alignment in primary position for patients with total third nerve paralysis. METHOD: We fixated the globe (medial rectus muscle insertion) to the medial palpebral ligament insertion at the anterior lacrimal crest by using nonabsorbable 5-0 polyester sutures in a prospective study of 5 patients (5 eyes) with congenital total third nerve paralysis. A large recession of the lateral rectus muscle (12 to 16 mm) was also performed in four patients. RESULTS: Four patients achieved satisfactory ocular alignment and one patient had residual exotropia. After an initial exotropic shift, no significant change in ocular alignment was observed during the follow-up period of 6 to 9 months. Mild fullness and congestion over the medial rectus muscle area was observed in the immediate postoperative period in all the patients, which resolved in about two months time. CONCLUSION: This technique of ocular fixation is easy, safe, and effective for the management of exotropia secondary to total third nerve paralysis.     

Radical aortic replacement employing simultaneous modified Bentall and elephant trunk procedure in Takayasu's arteritis

A case of Takayasu's arteritis resulting in extensive fusiform aneurysmal dilatation of the entire aorta extending from the aortic root to the abdominal bifurcation associated with aortic regurgitation is described. She underwent successful radical replacement of the aortic root, ascending, transverse arch and proximal part of the descending aorta employing simultaneous modified Bentall and Elephant trunk techniques. During aortic arch replacement the brain was protected by selective antegrade innominate perfusion under moderate hypothermia. A pattern to the best of our knowledge, has not been reported earlier.     

Expanding the living related donor pool in renal transplantation: use of marginal donors

PURPOSE: In a living related transplantation program it is not always possible to find an ideal donor. Sometimes the only available donor in the family has some benign disease or suboptimal renal anatomy or physiology, or is too old to be accepted and defined as a marginal donor. However, with proper screening the donor pool can be increased by accepting these marginal donors and treating the benign diseases which is beneficial to the donor. We evaluate the outcome of grafts from marginal donors. MATERIALS AND METHODS: From July 1988 to August 1997, 581 live related transplantations were performed. Of the donors 52 were older than 60 years and 34 had associated benign renal or nonrenal anomaly or disease. These donors were accepted after thorough questioning and consultation with family members. The recipients of graft from elderly donors were evaluated for the number of rejections, serum creatinine at last followup and graft survival. RESULTS: Of the recipients 52 received grafts from elderly donors with a mean age of 62.6+/-3.7 years. Mean followup was 34.14+/-0.7 months. The 2 and 5-year actuarial graft survival was 96% and 74%, respectively. Creatinine was normal (less than 1.5) in 37% of recipients and 1.5 to 2.5 mg.% in 46%. The rejection rate in postoperative month 1 was 29%. All donors underwent simultaneous surgery to treat the benign disease, and all did well after surgery. CONCLUSIONS: By accepting these marginal donors a 14.6% increase in the living related donor pool was achieved without compromising recipient or donor safety. Otherwise these recipients would have been forced to undergo unrelated transplantation or be maintained on dialysis, which is particularly difficult in a developing country. Donors with associated disease benefited from cure.     

Evaluation of endometrial changes and p53 expression in tamoxifen treated women: Comparision of various methods.

Objective: To compare transvaginal sonography (TVS), sonohysterography (SHG), hysteroscopy and endometrial aspiration (EA) and p53 expression in assessing endometrial abnormalities in women on tamoxifen. Methods: In a cross sectional study of 50 pre- and post-menopausal women receiving tamoxifen for > 2 years, all participants underwent TVS and EA. Those with endometrial thickness > 4 mm on TVS underwent hysteroscopy and SHG. Serum p53 antibody and p53 immunohistochemistry were tested in all women. Results: The sensitivity and specificity when compared with histopathology as the reference standard were as follows: TVS 100% and 33.3%, SHG 85.7% and 50%, hysteroscopy 92.8% and 80.8%, serum p53 50% and 83.3%, and p53 immunohistochemistry 57.1% and 61.1%. Prevalence of endometrial abnormalities was not significantly different in asymptomatic and symptomatic women. Conclusion: Tamoxifen-users require routine testing for endometrial evaluation. TVS followed by hysteroscopy and biopsy is an effective option. p53 expression correlates with histological abnormalities. Key words: Tamoxifen, Sonography, Sonohysterography, Hysteroscopy, Endometrium, p53.     

SYNTHESIS OF THE RIGID ANALOGUES OF AN SSRI BENZENEPROPANAMINE

Several 1-(substituted phenoxy)-3-{[4-(4-trifluoromethyl) phenoxy] piperidin-1-yl} propan-2-ols (str.II) were prepared in a six-step reaction sequence starting from methylamine and ethyl acrylate and evaluated for antidepressant activity. The compounds were fully characterized by spectral and elemental analyses, and were tested for their effect on gross behavior, antireserpine and anorexigenic activity. No effect was observed on gross behavior and some of them showed fluoxetine like antireserpine and anorexigenic activity.     

Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications.

Activation of cell surface death receptors by their cognate ligands triggers apoptosis. Several human death receptors (Fas, TNF-R1, TRAMP, DR4, DR5, DR6, EDA-R and NGF-R) have been identified. The most promising cytokine for anticancer therapy is TRAIL/APO-2L, which induces apoptosis in cancer cells by binding to death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5. The cytotoxic activity of TRAIL is relatively selective to cancer cells compared to normal cells. Signaling by TRAIL and its receptors is tightly regulated process essential for key physiological functions in a variety of organs, as well as the maintenance of immune homeostasis. Despite early promising results, recent studies have identified several TRAIL-resistant cancer cells of various origins. Based on molecular analysis of death-receptor signaling pathways several new approaches have been developed to increase the efficacy of TRAIL. Resistance of cancer cells to TRAIL appears to occur through the modulation of various molecular targets. They may include differential expression of death receptors, constitutively active Akt and NFkappaB, overexpression of cFLIP and IAPs, mutations in Bax and Bak genes, and defects in the release of mitochondrial proteins in resistant cells. Conventional chemotherapeutic and chemopreventive drugs, and irradiation can sensitize TRAIL-resistant cells to undergo apoptosis. Thus, these agents enhance the therapeutic potential of TRAIL in TRAIL-sensitive cells and sensitize TRAIL-resistant cells. TRAIL and TRAIL-receptor antibodies may prove to be useful for cancer therapy, either alone or in association with conventional approaches such as chemotherapy or radiation therapy. This review discusses intracellular mechanisms of TRAIL resistance and various approaches that can be taken to sensitize TRAIL-resistant cancer cells.