TP53 polymorphisms in gliomas from Indian patients: Study of codon 72 genotype, rs1642785, rs1800370 and 16 base pair insertion in intron-3

Several single nucleotide polymorphisms of the TP53 gene have been reported, amongst which polymorphism in codon 72 (rs1042522) has received significant attention and shown to be associated with disease susceptibility in different cancer types. However, there are variable reports on this polymorphism in gliomas from worldwide with inconsistent results. In addition, the implications of other polymorphic loci are not much explored in gliomas. Hence, in the present study the TP53 sequence was analyzed for all polymorphism and mutations in a total of 84 gliomas of different types and grades from patients of Indian origin. The complete sequence of all coding exons (2 to 11) and introns 2, 3, 5 and 8 of TP53 gene were studied while for introns 1, 4, 6, 7, 9 and 10, only exon flanking regions could be studied. The polymorphic loci were compared with control population. In addition to the well known codon 72 polymorphism (rs1042522), three other polymorphisms rs1642785, rs1800370 and a 16 base pair insertion in intron-3 were found. At codon 72, our study showed higher Arg/Arg genotype in gliomas compared to normal population (38% versus 13%). The Arg allele frequency in glioma patients was comparatively higher than controls (0.55 versus 0.45; P = 0.037). The Arg allele frequency was also high in adult glioblastomas compared to paediatric counterparts (0.55 versus 0.36). However, there was no significant association of TP53 mutations with any genotype of codon 72. At rs1642785, the G allele frequency was significantly higher in gliomas than in control population (0.55 versus 0.36, P = 0.005). The genotype at a 16 base pair insertion in intron-3 was almost similar in case and control. However, the polymorphism at rs1800370 was exclusive to gliomas. This is the first report of TP53 gene polymorphism in glioma patients from India. Our study also delineates the frequency of four polymorphisms in gliomas for the first time. The codon 72 variant (rs1042522) and rs1642785 polymorphisms possibly poses risk to glioma development in Indian population. However, the functional significance of these polymorphism needs further elucidation.     

Comparison of bronchoscopic and non-bronchoscopic techniques for diagnosis of ventilator associated pneumonia

Background:

The diagnosis of ventilator associated pneumonia (VAP) remains a challenge because the clinical signs and symptoms lack both sensitivity and specificity and the selection of microbiologic diagnostic procedure is still a matter of debate.

Aims and Objective:

To study the role of various bronchoscopic and non-bronchoscopic diagnostic techniques for diagnosis of VAP.

Settings and Design:

This prospective comparative study was conducted in a medical ICU of a tertiary care center.

Materials and Methods:

Twenty-five patients, clinically diagnosed with VAP, were evaluated by bronchoscopic and non-bronchoscopic procedures for diagnosis. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of various bronchoscopic and non-bronchoscopic techniques were calculated, taking clinical pulmonary infection score (CPIS) of ≥6 as reference standard.

Results:

Our study has shown that for the diagnosis of VAP, bronchoscopic brush had a sensitivity, specificity, PPV and NPV of 94.9% [confidence interval (CI): 70.6–99.7], 57.1% (CI: 13.4–86.1), 85% (CI: 61.1–96) and 80% (CI: 21.9–98.7), respectively. Bronchoscopic bronchoalveolar lavage (BAL) had a sensitivity, specificity, PPV and NPV of 77.8% (CI: 51.9–92.6), 71.8% (CI: 24.1–94), 87.3% (CI: 60.4–97.8) and 55.5% (CI: 17.4–82.6), respectively. Sensitivity, specificity, PPV and NPV for non–bronchoscopic BAL (NBAL) were 83.3% (CI: 57.7–95.6), 71.43% (CI: 24.1–94), 88.2% (CI: 62.3–97.4) and 62.5% (CI: 20.2–88.2), respectively. Endotracheal aspirate (ETA) yield was only 52% and showed poor concordance with BAL (κ-0.351; P-0.064) and NBAL (k-0.272; P-0.161). There was a good microbiologic concordance among different bronchoscopic and non-bronchoscopic distal airway sampling techniques.

Conclusion:

NBAL is an inexpensive, easy, and useful technique for microbiologic diagnosis of VAP. Our findings, if verified, might simplify the approach for the diagnosis of VAP.     

A Review on Joint Carotid Intima-Media Thickness and Plaque Area Measurement in Ultrasound for Cardiovascular/Stroke Risk Monitoring: Artificial Intelligence Framework

Journal of Digital Imaging - Cardiovascular diseases (CVDs) are the top ten leading causes of death worldwide. Atherosclerosis disease in the arteries is the main cause of the CVD, leading to...     

Study of a cross-linked hydrogel of Karaya gum and Starch as a controlled drug delivery system

Abstract

A cross-linked hydrogel was synthesized using a hybrid backbone of karaya gum starch and grafted with polyacrylic acid. It showed a maximum swelling ratio (SR) of 30.5?g/g at pH 10 and was explored as an oral drug delivery carrier using paracetamol and aspirin as model drugs. In vitro release experiments revealed that maximum drug release at pH 7.4 in comparison to pH 1.2 (simulated intestinal vs gastric fluid) and neutral medium. The release profiles of these drugs showed no initial burst. It also showed good hemocompatibilty and non-cytotoxicity for its employment as a site specific drug delivery agent.     

Sex differences in inferior parietal lobule volume in schizophrenia

OBJECTIVE: The inferior parietal lobule is a heteromodal association cortical region that has been implicated in the pathophysiology of schizophrenia. Inferior parietal lobule gray matter volumes have been shown to differ between healthy male and female subjects, with male subjects having larger left volumes. The authors sought to determine whether these volumetric sex differences also exist in patients with schizophrenia. METHOD: The authors used magnetic resonance imaging to measure inferior parietal lobule volumes of 15 pairs of male and female schizophrenic subjects who were individually matched to each other and to 15 pairs of healthy male and female subjects. RESULTS: Male schizophrenic patients exhibited a reversal of the normal left-greater-than-right male asymmetry in this region and had left inferior parietal lobule gray matter volumes that were significantly smaller than those of healthy male subjects. Female schizophrenic patients did not differ significantly from healthy female subjects in left or right inferior parietal lobule volume or in asymmetry. CONCLUSIONS: This study provides further evidence of brain morphology sex differences in schizophrenia that possibly contribute to the differential clinical disease expression in men and women.     

Outcome after decompressive craniectomy in patients with dominant middle cerebral artery infarction: A preliminary report

Introduction:

Life-threatening, space occupying, infarction develops in 10-15% of patients after middle cerebral artery infarction (MCAI). Though decompressive craniectomy (DC) is now standard of care in patients with non-dominant stroke, its role in dominant MCAI (DMCAI) is largely undefined. This may reflect the ethical dilemma of saving life of a patient who may then remain hemiplegic and dysphasic. This study specifically addresses this issue.

Materials and Methods:

This retrospective analysis studied patients with DMCAI undergoing DC. Patient records, operation notes, radiology, and out-patient files were scrutinized to collate data. Glasgow outcome scale (GOS), Barthel index (BI) and improvement in language and motor function were evaluated to determine functional outcome.

Results:

Eighteen patients between 22 years and 72 years of age were included. 6 week, 3 month, 6 month and overall survival rates were 66.6% (12/18), 64% (11/17), 62.5% (10/16) and 62.5% (10/16) respectively. Amongst ten surviving patients with long-term follow-up, 60% showed improvement in GOS, 70% achieved BI score >60 while 30% achieved full functional independence. In this group, motor power and language function improved in 9 and 8 patients respectively. At last follow-up, 8 of 10 surviving patients were ambulatory with (3/8) or without (5/8) support. Age <50 years corresponded with better functional outcome amongst survivors (P value –0.0068).

Conclusion:

Language and motor outcomes after DC in patients with DMCAI are not as dismal as commonly perceived. Perhaps young patients (<50 years) with DMCAI should be treated with the same aggressiveness that non-DMCAI is currently dealt with.Key Words: Craniectomy, dominant, middle cerebral artery, outcome, stroke     

Thrombotic occlusion of the common carotid artery (CCA) in acute ischemic stroke treated with intravenous tissue plasminogen activator (TPA)

Although common carotid artery (CCA) occlusions are rare, acute clinical presentations vary from mild to devastating strokes primarily due to tandem occlusions in the intracranial arteries. Three patients with acute CCA occlusions were treated with systemic tissue plasminogen activator (TPA). Blood pressures were kept at the upper limits allowed with TPA therapy with fluid balance and the 'head-down' position. Recanalization occurred in intracranial vessels only. Marked early neurological improvement occurred in two of three patients. CCA occlusions should not be considered contra-indication to systemic thrombolysis.     

Study of central gray nmda receptors in nociceptive behaviour in rats

1. 1. Cannulae were implanted stereotaxically in the PAG area in rats.

2. 2. Nociceptive thresholds were assessed in these rats, by measuring the tail flick latencies after post - operative recovery.

3. 3. Micro-injections of NMDA, L — aspartic acid and L — glutamic acid were made in the central gray and the effects on tail flick latencies studied.

4. 4. Low dose of NMDA in the PAG did not significantly alter the tail flick latencies, higher doses produced hyperalgesia.

5. 5. L — glutamic acid, aspartic acid, and Mk 801 induced hyperalgesia in the doses used. Ketamine did not significantly affect the tail flick latencies.