Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population

Rheumatoid arthritis is a chronic autoimmune disorder associated with altered expression of pro- and anti-inflammatory cytokines in the affected tissues. The aim of this study was to investigate the association between promoter polymorphisms of TNFα and IL-10 gene with susceptibility, age of disease onset and disease severity in North Indian patients with rheumatoid arthritis (RA). SNPs at position −308 and −863 of TNF gene and −819/−592 and −1082 position of IL-10 gene were determined in 222 patients and 208 healthy controls using RFLP or ARMS method. Polymorphism TNF −308A was less prevalent among the patients (1.7%) than controls (4.9%; p = 0.01, OR: 0.32, 95% CI: 0.13–0.76). Among female patients, IL-10 −592A allele associated with higher baseline disease activity scores (5.77 ± 1.99) than −592C (5.57 ± 1.19; p = 0.04). Female patients carrying allele A of TNFα −863 had earlier age of onset of RA (33.99 ± 9.6 years) than those with allele C (36.15 ± 11.21 years; p = 0.043). In conclusion, allele A at TNFα −308 locus provides protection against RA in North Indian population while another TNF allele A at −863 position had weak association with earlier onset of disease in female patients. On the other hand promoter polymorphisms of IL-10 did not affect susceptibility but polymorphism at −819/−592A was associated with higher disease activity scores at baseline.     

Giant ruptured sinus of Valsalva aneurysm: diagnosis on echocardiography

A giant ruptured sinus of Valsalva aneurysm was diagnosed ontransthoracic and subsequent transesophageal echocardiography,in a 45-year-old man who presented with gradual onset shortnessof breath. Although the initial presentation was insidious,he later rapidly deteriorated. We discuss the unusual clinicalcourse in a patient with such a large aneurysm and discuss thelikely reasons.     

Population-based cancer incidence in Sikkim, India: report on ethnic variation

Background:

A Population-Based Cancer Registry (PBCR) was set up in Sikkim (a state in the North Eastern India) in 2003. We examined incidence rates by ethnic groups from 2003–2008.

Methods:

Age-adjusted incidence rates (AARs) per 100 000 person-years were calculated by direct method using the world standard population, and analysed by ethnic group (Bhutia, Rai and other).

Result:

There were a total of 1148 male and 1063 female cases of cancer between 2003 and 2008 on the Sikkim PBCR. The overall AARs were 89.4 and 99.4 per 100 000 person-years in males and females, respectively. Incidence rates were highest amongst the Bhutia group (AAR=172.4 and 147.4 per 100 000 person-years in males and females, respectively), and the largest difference in rates were observed for stomach cancers with AARs being 12.6 and 4.7 times higher in the Bhutia group compared with other ethnic groups in males and females, respectively.

Conclusion:

These observations call for further epidemiological investigations and the introduction of screening programmes.     

Quadricuspid Aortic Valve with Ruptured Sinus of Valsalva Aneurysm to the Right Atrium

A 32-year-old man with a sudden onset of chest pain and progressive dyspnea was found to have a ruptured sinus of Valsalva aneurysm to the right atrium with an associated quadricuspid aortic valve. Echocardiographic and angiographic images are presented, with real time transthoracic 3D echo. The patient was successfully operated.     

Differential expression of survivin-2B and survivin-DeltaEx3 is inversely associated with disease relapse and patient survival in non-small-cell lung cancer (NSCLC)

Although it was observed that inhibition of the antiapoptotic protein survivin expression in lung cancer cells induces apoptosis, the expression and role of survivin variants (survivin-2B and survivin-DeltaEx3) in lung cancer have not yet been characterized. We analyzed 24 non-small-cell lung cancer (NSCLC) samples by semi-quantitative RT-PCR. Surprisingly, our results revealed that high-level expression of survivin-2B is significantly associated with the patient category of "no relapse and alive" (p-value<0.0001). In contrast, high-level expression of survivin-DeltaEx3 is highly associated with the patient category of "relapse and dead" (p-value<0.0001). Consistent with this observation, exogenous expression of survivin-2B in A549 lung cancer cells inhibited cell growth, disrupted the mitochondria potential, and induced apoptotic cell death, while expression of survivin-DeltaEx3 protected the mitochondria potential and facilitated cell survival. These findings provide evidence that survivin-2B and survivin-DeltaEx3 play opposite roles in disease relapse and NSCLC cell survival, which is likely through the differential modulation of mitochondrial potential. Thus, controlling the differential expression of survivin-2B and survivin-DeltaEx3 may represent novel approaches for cancer therapeutics in NSCLC.     

The effects of propofol, small-dose isoflurane, and nitrous oxide on cortical somatosensory evoked potential and bispectral index monitoring in adolescents undergoing spinal fusion

In this study we compared the effects of propofol, small-dose isoflurane, and nitrous oxide (N(2)O) on cortical somatosensory evoked potentials (SSEP) and bispectral index (BIS) monitoring in adolescents undergoing spinal fusion. Twelve patients received the following anesthetic maintenance combinations in a randomly determined order: treatment #1: isoflurane 0.4% + N(2)O 70% + O(2) 30%; treatment #2: isoflurane 0.6% + N(2)O 70% + O(2) 30%; treatment #3: isoflurane 0.6% + air + O(2) 30%; treatment #4: propofol 120 microg . kg(-1) . min(-1) + air + O(2) 30%. Cortical SSEP amplitudes measured during anesthesia maintenance with treatment #3 (isoflurane 0.6%/air) were more than those measured during maintenance with treatment #1 (isoflurane 0.4%/N(2)O 70%) (P < 0.0001) and treatment #2 (isoflurane 0.6%/N(2)O 70%) (P < 0.0052). Cortical SSEP amplitudes measured during treatment #4 (propofol 120 microg . kg(-1) . min(-1)/air) were more than treatment #1 (isoflurane 0.4%/N(2)O 70%) (P < 0.0001), treatment #2 (Iso 0.6%/N(2)O 70%) (P < 0.0007), and treatment #3 (isoflurane 0.6%/air) (P < 0.0191). In addition, average BIS values measured during treatments 1, 2, 3 and 4 were 62, 62, 61, and 44 respectively. Only treatment #4 (propofol 120 microg . kg(-1) . min(-1)/air) uniformly maintained BIS values less than 60. Our study demonstrates that propofol better preserves cortical SSEP amplitude measurement and provides a deeper level of hypnosis as measured by BIS values than combinations of small-dose isoflurane/N(2)O or small-dose isoflurane alone.     

Specificity analysis of sera from breast cancer patients vaccinated with MUC1-KLH plus QS-21

The mucin MUC1 is expressed on breast cancers in an underglycosylated form compared to normal tissues and is therefore a potential target for cancer immunotherapy. MUC1 contains multiple tandem repeats of the 20 amino acid (aa) peptide (VTSAPDTRPAPGSTAPPAHG). The APDTRPA epitope is particularly immunogenic since it is recognized by a variety of murine monoclonal antibodies and by some sera and cytotoxic T-cells from unimmunized patients with epithelial cancers. We have prepared a 30 aa peptide (C)VTSAPDTRPAPGSTAPPAHGVTSAPDTRPA with cysteine at the N-terminal end, and used the cysteine for chemical conjugation to keyhole limpet haemocyanin (KLH). Six breast cancer patients immunized with this conjugate plus the immunological adjuvant QS-21 have all produced high titre (by ELISA) IgG and IgM antibodies against the 30 aa MUC1 peptide, but these sera reacted moderately, or not at all, with MUC1-positive tumour cells. To understand this specificity better, we prepared a series of smaller peptides to determine the epitopes recognized by these immune sera in inhibition assays. Only peptides containing APDTRPA at the C-terminal end were able to completely inhibit ELISA reactivity for the full 30 aa peptide. No sera were completely inhibited by APDTR, APDTRP, PDTRPA or any other peptides that did not contain the full APDTRPA epitope. Remarkably, sera from all six patients recognized this same epitope and were completely inhibited by only this epitope. The specificity of these sera (1) primarily for C-terminal APDTRPA, and the absence of this epitope at the C-terminal end of any tumour mucins, and (2) the N-terminal APDTRPA alanine, which is normally buried in the beta turn MUC1 assumes in its secondary structure may explain the moderate to weak reactivity of these high titer sera against MUC1-positive tumour cells.