C-reactive protein and cardiovascular outcomes in smokers versus nonsmokers in non-ST-elevation acute coronary syndrome (from the TACTICS-TIMI 18 trial)

We investigated the role of inflammation, as measured by high-sensitivity C-reactive protein (CRP) levels, in cardiovascular risk in smokers who have acute coronary syndrome. Despite fewer traditional risk factors, smokers who had acute coronary syndrome had higher CRP levels than did nonsmokers (7.0 vs 5.1 mg/L, p <0.001). CRP was associated with adverse cardiovascular outcomes in smokers and nonsmokers, even when adjusted for the presence of pulmonary disease.     

Tubeless percutaneous nephrolithotomy: a prospective feasibility study and review of previous reports

OBJECTIVE: To evaluate the status of tubeless percutaneous nephrolithotomy (PCNL) in managing renal and upper ureteric calculi, from initial experience and a review of previous reports. PATIENTS AND METHODS: From September 2004 to December 2004, 46 patients were scheduled for tubeless PCNL in a prospective study. Patients with solitary kidney, or undergoing bilateral simultaneous PCNL or requiring a supracostal access were also enrolled. Patients needing more than three percutaneous access tracts, or with significant bleeding or a significant residual stone burden necessitating a staged second-look nephroscopy were excluded. At the end of the procedure, a JJ ureteric stent was placed antegradely and a nephrostomy tube avoided. The patients' demographic data, the outcomes during and after surgery, complications, success rate, and stent-related morbidity were analysed. Previous reports were reviewed to evaluate the current status of tubeless PCNL. RESULTS: Of the 46 patients initially considered only 40 (45 renal units) were assessed. The mean stone size in these patients was 33 mm and 23 patients had multiple stones. Three patients had a serum creatinine level of >2 mg/dL (>177 micromol/L). Five patients had successful bilateral simultaneous tubeless PCNL. In all, 51 tracts were required in 45 renal units, 30 of which were supracostal. The mean decrease in haemoglobin was 1.2 g/dL and two patients required a blood transfusion after PCNL. There was no urine leakage or formation of urinoma after surgery, and no major chest complications in patients requiring a supracostal access tract, except for one with hydrothorax, managed conservatively. The mean hospital stay was 26 h and analgesic requirement 40.6 mg of diclofenac. Stones were completely cleared in 87% of renal units and 9% had residual fragments of < 5 mm. Two patients required extracorporeal lithotripsy for residual calculi. In all, 30% of patients had bothersome stent-related symptoms and 60% needed analgesics and/or antispasmodics to treat them. CONCLUSION: Tubeless PCNL was safe and effective even in patients with a solitary kidney, or with three renal access tracts or supracostal access, or with deranged renal values and in those requiring bilateral simultaneous PCNL. The literature review suggested a need for prospective, randomized studies to evaluate the role of fibrin sealant and/or cauterization of the nephrostomy tract in tubeless PCNL.     

Molecular cloning and functional expression of a human cDNA encoding translation initiation factor 6

Eukaryotic translation initiation factor 6 (eIF6) binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. In this paper, we devised a procedure for purifying eIF6 from rabbit reticulocyte lysates and immunochemically characterized the protein by using antibodies isolated from egg yolks of laying hens immunized with rabbit eIF6. By using these monospecific antibodies, a 1.096-kb human cDNA that encodes an eIF6 of 245 amino acids (calculated M_r 26,558) has been cloned and expressed in Escherichia coli. The purified recombinant human protein exhibits biochemical properties that are similar to eIF6 isolated from mammalian cell extracts. Database searches identified amino acid sequences from Saccharomyces cerevisiae, Drosophila, and the nematode Caenorhabditis elegans with significant identity to the deduced amino acid sequence of human eIF6, suggesting the presence of homologues of human eIF6 in these organisms.     

Macrophage distinguishes Vibrio cholerae hemolysin from its protease insensitive oligomer by time dependent and selective expression of CD80-CD86

The monomeric and oligomeric forms of Vibrio cholerae hemolysin (HlyA), a membrane damaging toxin that forms transmembrane pentameric diffusion channels in target eukaryotic membrane, show a pronounced difference in protease susceptibility, presumably due to masking of sensitive peptide bonds during oligomerization. In this work, we examined if resistance of a protein to proteolytic processing affects the expression of costimulatory molecules, CD80 and CD86, on macrophage exposed to the same antigen. The murine peritoneal cavity macrophages expressed both CD80 and CD86 after 24 h of incubation with HlyA monomer but failed to express the costimulatory molecules when treated with the HlyA oligomer. The expression of CD80 molecule on macrophage after 48 h by the HlyA oligomer that failed to express the costimulatory molecules after 24 h indicates that proteolytic processing plays a decisive role in expression of CD80 and CD86 on cell surface.     

Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial.

OBJECTIVES: Our objective was to determine the timing of benefit with intensive statin therapy after an acute coronary syndrome (ACS) in two time windows: an early window soon after an ACS and a late window in more stable patients. BACKGROUND: The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial showed that the use of intensive statin therapy improved clinical outcomes over two years in ACS patients versus standard therapy. The relative contributions of early or late effects to the overall clinical efficacy of intensive therapy are presently unclear. METHODS: A total of 4,162 patients with ACS were recruited in the PROVE IT-TIMI 22 trial. Patients were randomized to intensive statin therapy (atorvastatin, 80 mg) or standard therapy (pravastatin, 40 mg). The composite triple end point of death, MI, or rehospitalization for recurrent ACS was determined in each group at 30 days. The composite triple and primary end points were assessed in stable patients from six months to the end of study, after censoring for clinical events before six months. RESULTS: The composite end point at 30 days occurred in 3.0% of patients receiving atorvastatin 80 mg versus 4.2% of patients receiving pravastatin 40 mg (hazard ratio [HR] = 0.72; 95% confidence interval [CI], 0.52 to 0.99; p = 0.046). In stable patients, atorvastatin 80 mg was associated with a composite event rate of 9.6% versus 13.1% in the pravastatin 40 mg group (HR = 0.72; 95% CI, 0.58 to 0.89; p = 0.003). CONCLUSIONS: Intensive statin therapy early after ACS leads to a reduction in clinical events at 30 days, consistent with greater early pleiotropic effects. In stable patients, intensive statin therapy provides long-term reduction in clinical events when compared with standard therapy. Thus, ACS patients should be started in-hospital and continued long-term on intensive statin therapy.     

Epidemiology of malaria transmission and development of natural immunity in a malaria-endemic village, San Dulakudar, in Orissa state, India

We describe the epidemiology of malaria in San Dulakudar, a village in Sundargarh District in the state of Orissa in eastern India. Malaria transmission is perennial with Plasmodium falciparum, accounting for greater than 80% of malaria cases. Transmission intensity varies with season with high transmission after the monsoon rains in autumn and winter, low transmission in summer, and intermediate transmission in spring. The anthropophagic mosquito Anopheles fluviatilis was identified as the main vector for malaria transmission. Based on observations of spleen rates and supported by data on malaria parasite prevalence and malaria incidence, San Dulakudar can be classified as a hyperendemic area for P. falciparum malaria. Parasite prevalence and malaria incidence rates decrease with age, suggesting that residents of San Dulakudar develop immunity to malaria. The study demonstrates the presence of regions in the Indian subcontinent such as Sundargarh District where P. falciparum is the primary cause of malaria and where malaria transmission rates are comparable to those found in many parts of Africa.     

Connexin 26 <Emphasis Type="Italic">(GJB2)</Emphasis> Mutations Associated with Non-Syndromic Hearing Loss (NSHL)

Objective

To determine the prevalence and spectrum of Connexin 26 (GJB2) mutations in pre-lingual non-syndromic hearing loss (NSHL) patients in authors’ centre and to review the data of Indian patients from the literature.

Methods

Sanger sequencing of entire coding region contained in single exon (Exon 2) of GJB2 gene in 15 patients of NSHL.

Results

GJB2 mutations were found in 40% (6/15) of NSHL patients, out of which mono-allelic were 33.3% (2/6). Bi-allelic GJB2 mutations were identified in 4 of 6 patients. Most common GJB2 mutation identified was c.71G?>?A(p.W24X), comprising 30% of the total GJB2 mutant alleles. Six studies involving 1119 patients with NSHL were reviewed and 4 of them have reported c.71G?>?A(p.W24X) as the commonest mutation while 2 studies found c.35delG as the commonest. GJB2 mutations accounted for 10.9%–36% cases of NSHL. Sixteen other mutations in GJB2 gene were reported in Indian patients out of which 6 mutations other than c.71G?>?A(p.W24X) viz., c.35delG, c.1A?>?G(p.M1V), c.127G?>?A(p.V43 M), c.204C?>?G(p.Y86X), c.231G?>?A(p.W77X) and c.439G?>?A(p.E147K) were identified in the present study.

Conclusions

Connexin 26 (GJB2) mutations are responsible for 19.4% of NSHL in Indian population. The c.71G?>?A(W24X) and c.35delG were the most prevalent GJB2 mutations accounting for 72.2% (234 of 324 total mutated alleles from 7 studies) and 15.4% (50 of 324 total mutated alleles from 7 studies) respectively. Thus, screening of these two common mutations in GJB2 gene by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) would greatly help in providing easy genetic diagnosis and help in genetic counseling of the families with NSHL.