Prevalence and risk factors associated with tuberculin skin test positivity among household contacts of smear-positive pulnionary tuberculosis cases in Umerkot, Pakistan.

STUDY POPULATION AND SETTING: Household contacts of acid-fast bacilli (AFB) sputum smear-positive tuberculosis patients in the Umerkot Taluka, Sindh, Pakistan. OBJECTIVE: To estimate the prevalence of and identify risk factors associated with tuberculin skin test (TST) positivity among household contacts of acid-fast bacilli (AFB) sputum smear-positive pulmonary tuberculosis cases. DESIGN: A cross-sectional study of household contacts of AFB sputum smear-positive tuberculosis cases, registered at the Umerkot Anti-Tuberculosis Association clinic from August 1999 to September 1999. The contact's Mycobacterium tuberculosis infection status was assessed using TST. On the day of the TST, a pre-designed questionnaire was administered to collect data on putative risk factors for TST positivity among contacts. The data were analysed using a marginal logistic regression model by the method of generalised estimating equations (GEE) to determine risk factors independently associated with TST positivity. RESULTS: The prevalence of TST positivity among household contacts of AFB sputum smear-positive index patients was 49.4%. The final multivariate GEE model showed that contact's age and sleeping site relative to the index case, the intensity of the index case's AFB sputum-smear positivity and the contact's BCG scar status were independent predictors of TST positivity among household contacts of AFB sputum smear-positive index cases. CONCLUSIONS: The results suggest that the household contacts of AFB sputum smear-positive tuberculosis patients in a poor neighbourhood of rural Sindh had a high prevalence of M. tuberculosis infection as determined by TST. Poor housing conditions seem to contribute to the spread of M. tuberculosis infection. Early diagnosis of pulmonary TB through evaluation of TST-positive household contacts, followed by appropriate therapy, may prevent further spread of M. tuberculosis infection. We recommend an awareness programme to prevent household contacts from acquiring M. tuberculosis infection from smear-positive pulmonary TB cases.     

Percutaneous closure of multiple atrial septal defects with three Amplatzer septal occluder devices

We report on the successful closure of three atrial septal defects with three Amplatzer septal occluders in a 55‐year‐old woman. Catheter Cardiovasc Interv 2004;62:526–529. © 2004 Wiley‐Liss, Inc.     

Recombinant Nonstructural 3 Protein,rNS3, of Hepatitis C Virus Along With Recombinant GP96 Induce IL-12, TNFα and α5integrin Expression in Antigen Presenting Cells

Background

Hepatitis C virus (HCV) infection is the main cause of chronic liver disease and to date there has been no vaccine development to prevent this infection. Among non-structural HCV proteins, NS3 protein is an excellent goal for a therapeutic vaccine, due to its large size and less variation in conserved regions. The immunogenic properties of heat shock proteins (HSPs) for instance GP96 have prompted investigations into their function as strong adjuvant to improve innate and adaptive immunity.

Objectives

The aim of this study was to examine additive effects of recombinant GP96 (rGP96) fragments accompanied by rNS3 on expression levels of α5integrin and pro-inflammatory cytokines, IL-12 and TNFα, in Antigen Presenting Cells (APCs).

Materials and Methods

Recombinant viral proteins (rNS3 and rRGD-NS3), N-terminal and C-terminal fragments of GP96 were produced and purified from E. coli in order to treat the cells; mouse spleen Dendritic Cells (DCs) and THP-1 macrophages.

Results

Our results showed that rNT-GP96 alone significantly increases the expression level of IL-12, TNFα and α5integrin in THP-1 macrophages and DCs, while IL-12 and TNFα expression levels were unaffected by either rNS3 or rRGD-NS3. Interestingly, the co-addition of these recombinant proteins with rNT-GP96 increased IL-12, TNFα and α5integrin expression. Pearson Correlation showed a direct association between α5integrin with IL-12 and TNF-α expression.

Conclusions

we have highlighted the role of rNS3 plus rNT-GP96 mediated by α5integrin in producing IL-12 and TNFα. It can be suggested that rNT-GP96 could enhance immunity characteristic of rNS3 protein via production of pro-inflammatory cytokines.     

Traumatic transverse atlantal ligamentous injury with posterior atlantoaxial instability in os odontoideum: Magnetic resonance features

The os odontoideum is an anomaly in which the odontoid is divided by a transverse gap, leaving the apical segment without support from its base. Because of its detachment from the axis body, os odontoideum can lead to hypermobility and instability. The following case report demonstrates rare magnetic resonance documentation of transverse atlantoaxial ligamentous injury with posterior atlantoaxial instability in a patient with os odontoideum.     

Changes in water metabolism in rats under the influence of naloxone: role of vasopressin

The effect of naloxone (0.6 mg; 1.2 mg; 2.4 mg X kg-1) were compared in normal Long Evans (N) and Brattleboro (D.I.) conscious rats. Naloxone did not change the values of drinking, diuresis, food intake, blood pressure, Na+ and K+ urinary excretion measured during 24 hours. During the two hours following drug injection, naloxone (1.2 and 2.4 mg X kg-1) reduced diuresis in normal as well as in D.I. rats. Water drinking was only modified in D.I. rats: this effect was shown to be a consequence of antidiuresis. These results suggest that the antidiuretic properties of naloxone are independent of vasopressin secretion. They do not support in a role of opiate receptors on vasopressin secretion in normal hydrated animals.     

Application of monolithic column in quantification of gliclazide in human plasma by liquid chromatography

A simple, rapid and sensitive isocratic reversed phase HPLC method with UV detection using a monolithic column has been developed and validated for the determination of gliclazide in human plasma. The assay enables the measurement of gliclazide for therapeutic drug monitoring with a minimum quantification limit of 10ngml(-1). The method involves simple, one-step extraction procedure and analytical recovery was complete. The separation was carried out in reversed-phase conditions using a Chromolith Performance (RP-18e, 100mmx4.6mm) column with an isocratic mobile phase consisting of 0.01M disodium hydrogen phosphate buffer-acetonitrile (52:48, v/v) adjusted to pH 4.0. The wavelength was set at 230nm. The calibration curve was linear over the concentration range 10-5000ngml(-1). The coefficients of variation for inter-day and intra-day assay were found to be less than 6.0%.     

The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers

Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Only MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers.