Performance characteristics and comparison of Abbott and artus real-time systems for hepatitis B virus DNA quantification

Virological monitoring of hepatitis B virus (HBV) DNA is critical to the management of HBV infection. With several HBV DNA quantification assays available, it is important to use the most efficient testing system for virological monitoring. In this study, we evaluated the performance characteristics and comparability of three HBV DNA quantification systems: Abbott HBV real-time PCR (Abbott PCR), artus HBV real-time PCR with QIAamp DNA blood kit purification (artus-DB), and artus HBV real-time PCR with the QIAamp DSP virus kit purification (artus-DSP). The lower limits of detection of these systems were established against the WHO international standards for HBV DNA and were found to be 1.43, 82, and 9 IU/ml, respectively. The intra-assay and interassay coefficients of variation of plasma samples (1 to 6 log(10) IU/ml) ranged between 0.05 to 8.34% and 0.16 to 3.48% for the Abbott PCR, 1.53 to 26.85% and 0.50 to 12.89% for artus-DB, and 0.29 to 7.42% and 0.94 to 3.01% for artus-DSP, respectively. Ninety HBV clinical samples were used for comparison of assays, and paired quantitative results showed strong correlation by linear regression analysis (artus-DB with Abbott PCR, r = 0.95; Abbott PCR with artus-DSP, r = 0.97; and artus-DSP with artus-DB, r = 0.94). Bland-Altman analysis showed a good level of agreement for Abbott PCR and artus-DSP, with a mean difference of 0.10 log(10) IU/ml and limits of agreement of -0.91 to 1.11 log(10) IU/ml. No genotype-specific bias was seen in all three systems for HBV genotypes A, C, and D, which are predominant in this region. This finding illustrates that the Abbott real-time HBV and artus-DSP systems show more comparable performance than the artus-DB system, meeting the current guidelines for assays to be used in the management of hepatitis B.     

Renal allograft tuberculosis: report of three cases and review of literature

Renal transplant recipients are prone to a variety of infections due a persistent immunodepleted state. Incidence of tuberculosis in this population is much higher compared with the general population. While pulmonary tuberculosis still remains the commonest form in this population, renal allograft tuberculosis is very rare. We report two cases of isolated allograft tuberculosis and one case of allograft tuberculosis with coexistent pleuro-pulmonary and bone marrow involvement. All three cases had presented with pyrexia of unknown origin, wherein despite extensive investigations the cause was not found. In two cases the diagnosis was confirmed on histology. Two cases responded to non-rifampicin-based modified antitubercular treatment and one to conventional four-drug Rifampicin-based regimen. Graft function improved in two cases while in one case the graft was lost. Tuberculosis involving the renal allograft is a potential cause for graft dysfunction/loss and requires a high index of suspicion for diagnosis. Timely detection and early institution of therapy can help save the renal allograft.     

Effects of anxiety on TNF-alpha levels during psychological stress

OBJECTIVES: Psychological stress can influence the immune system, which may result in stress-related illnesses. In this study, we investigated the effect of psychological stress and the coping skill on plasma cytokine levels. MATERIALS AND METHODS: One hundred eighty-three students, at different stages of an academic year, participated in this study. Plasma tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-2 soluble receptor alpha, and IL-4 were measured and examined in relation to the measures of anxiety [State Anxiety Inventory (SAI)] and Bell Adjustment Inventory (BAI) score. RESULTS: SAI scores were significantly higher in both midterm students (MTS) and examination-taking students (ETS), compared with the freshly admitted students (FAS). In addition, TNF-alpha levels were significantly different between the high- and the low-anxiety groups of ETS but not in MTS or FAS. The correlation between SAI scores and the BAI emotional scores was highest in the ETS group. CONCLUSIONS: TNF-alpha level was significantly lower in the ETS group with high anxiety scores, and it is situation specific.     

Neuropsychological deficits in human immunodeficiency virus type 1 clade C-seropositive adults from South India

Most studies of cognitive functioning in human immunodeficiency virus type 1 (HIV-1)-seropositive (HIV-1+) subjects have been done in the United States and Europe, where clade B infections predominate. However, in other parts of the world such as South India, where clade C HIV is most common, the prevalence of HIV-1 is increasing. Standardized neuropsychological tests were used to assess cognitive functioning in a sample of 119 adults infected with clade C HIV-1 who were not on antiretroviral medications. The subjects did not have neurological or psychiatric illness and were functioning adequately. Neuropsychological test performance was compared with gender-, age-, and education-matched normative data derived from a sample of 540 healthy volunteers and a matched cohort of 126 healthy, HIV-1-seronegative individuals. Among the seropositive subjects, 60.5% had mild to moderate cognitive deficits characterized by deficits in the domains of fluency, working memory, and learning and memory. None of the subjects had severe cognitive deficits. The HIV-1+ sample was classified into groups according to the level of immune suppression as defined by CD4 count (<200, 201–499, and >500 cells/mm³) and viral load (<5000, 5001–30,000, 30,001–99,999, 100,000–1,000,000, and >1,000,001 copies). Although the most immunosuppressed group (CD4 count <200 cells/mm³ or viral load >1,000,001 copies) was small, their rate of impairment in visual working memory was greater when compared to groups with better immune functioning. Mild to moderate cognitive deficits can be identified on standardized neuropsychological tests in clade C-infected HIV-1+ adults who do not have any clinically identifiable functional impairment. The prevalence of cognitive deficits is similar to that reported in antiretroviral treatment-naïve individuals infected with clade B virus in the western world.     

Recent Update on Bacteria as a Delivery Carrier in Cancer Therapy: From Evil to Allies

Pharmaceutical Research - Cancer is associated with a comprehensive burden that significantly affects patient’s quality of life. Even though patients’ disease condition is improving...     

Therapeutic vaccination halts disease progression in BALB-neuT mice: the amplitude of elicited immune response is predictive of vaccine efficacy

The aim of this study was to evaluate the efficacy of genetic vaccination with rat ErbB2 antigen in a therapeutic setting for the BALB-neuT mouse model of mammary carcinoma and to establish immunological correlates with vaccine efficacy. To define an early therapeutic setting we performed imaging studies of mouse mammary glands with a high-frequency ultrasound system that allowed the diagnosis of tumor lesions before they become palpable, starting from week 13 after mouse births. An intensive immunization protocol of vaccination was implemented at this stage, consisting of four weekly DNA injections with electroporation followed by two injections of adenovirus carrying the codon usage-optimized cDNA encoding the extracellular-transmembrane domain of rat ErbB2. Immunological parameters were monitored in each individual mouse by analyzing peripheral blood leukocytes. The appearance of the first palpable tumor in vaccinated mice was delayed and there was a statistically significant time gap before additional masses developed, indicating disease stabilization. As a result of the immunization, antibodies and CD8(+) T cells to rat ErbB2 were detected and the amplitude of elicited responses correlated with the efficacy of vaccination. Moreover, the vaccination regimen specifically halted the rise in circulating myeloid suppressor cells (MSCs). All three parameters, that is, CD8(+) T cells, antibodies to rat ErbB2, and circulating MSCs, measured at the end of vaccination could be used as predictive biomarkers for future tumor development. This study emphasizes the potential of genetic vaccines for the therapeutic treatment of malignancies and suggests possible predictive biomarkers to be further validated in the clinic for the follow-up of vaccinated cancer patients.     

Polymorphisms in the IL6 gene in Asian Indian families with premature coronary artery disease--the Indian Atherosclerosis Research Study

Inflammation plays a major role in coronary artery disease (CAD). We investigated the polymorphisms in the interleukin 6 (IL6) gene and their effect on the expression of acute-phase proteins in premature CAD in Asian Indian families. One hundred and ninety affected sibling pairs (ASPs) were genotyped for three tag single nucleotide polymorphisms (SNPs) in the IL6 gene for linkage analysis. We observed suggestive logarithm of odds (LOD) score for one SNP (rs2066992) in a subset of 62 ASPs with the age at onset less than 45 years (LOD score=1.114, p=0.011 in linkage analysis; pi=0.55, p=0.008 in identity by descent; LOD score=1.06, p=0.014 in quantitative trait locus for plasma levels of high sensitivity C-reactive protein, hsCRP). This was followed by sequencing of the promoter region and haplotype analysis in 46 probands and 40 controls. Five out of the eight previously reported promoter SNPs were found to be polymorphic (rs1800797, rs1800796, rs7802307, rs7802308, rs1800795). Two novel sequence variants were also found. One promoter haplotype (GGAAG) was detected with an odds ratio (OR) of 3.676 (p=0.0017, 95% confidence interval [CI]: 1.68-8.045) and population attributable risk of 21.1% (95%CI: 9.2%-31.5%). The plasma levels of both hsCRP and fibrinogen exhibited significant association with these promoter SNP genotypes (p<0.001). In conclusion, IL6 gene polymorphisms appear to be important genetic factors in premature CAD, and in the regulation of key atherogenic markers in Asian Indian families.     

ProSeal as an alternative to endotracheal intubation in pediatric laparoscopy

BACKGROUND: The increasing use of laparoscopic surgery in children mandates a leak-free airway device during carboperitoneum for which tracheal tubes (TT) have been traditionally used. The pediatric ProSeal is a recent introduction to the laryngeal mask airway (LMA) family. The ProSeal LMA (PLMA) has been successfully used in adult laparoscopic procedures. We hypothesized that the ProSeal can be equally effective in achieving adequate oropharyngeal seal and pulmonary ventilation during elective laparoscopic procedures in children. METHODS: Sixty ASA I and II children, 6 months to 8 years, scheduled for elective laparoscopic surgeries (duration of carboperitoneum <60 min) were randomly assigned to two groups of 30 each (TT and ProSeal(TM)). Patients at risk of aspiration, difficult airway and upper respiratory tract infection were excluded. Anesthesia technique included 8% of sevoflurane/O(2)/N(2)O and neuromuscular blockade. Ventilation was set to 10 ml.kg(-1) with positive endexpiratory pressure of 5 cmH(2)O. Respiratory rate was adjusted to maintain endtidal CO(2) (P(E)CO(2)) between 4.6 and 5.8 kPa (35-45 mmHg). Carboperitoneum was achieved at 10 mmHg. Hemodynamic parameters, peak inspiratory pressure (PIP) and P(E)CO(2) were noted at different time points. Chi-squared test, Mann-Whitney U-test and Wilcoxan W-test were applied; P < 0.05 was considered significant. RESULTS: There were no statistically significant differences in SpO(2) and P(E)CO(2) between PLMA and TT groups before and after peritoneal insufflation. Significant change was seen in PIP (cmH(2)O) from induction to carboperitoneum in both groups (14.3 +/- 1.48 in PLMA, 14.2 +/- 1.46 in TT to 23.36 +/- 1.7 in PLMA, and 23.73 +/- 1.9 in TT); and in P(E)CO(2) (mmHg), from 32 +/- 2.2 to 48 +/- 3.6 in PLMA and 30 +/- 3.1 to 47 +/- 2.8 in the TT group. The changes were not significant; P > 0.05 between the groups. The first-time success rate for PLMA was 88%, mean oropharyngeal leak pressure was 29 +/- 3 cmH(2)O. CONCLUSIONS: The pediatric PLMA and TT have comparable ventilatory efficacy for elective short laparoscopic procedures.