Corpectomy for multi-level cervical spondylosis and ossification of the posterior longitudinal ligament

The choice of a surgical approach for multi-level cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) is still a controversial issue. While most of the surgeons are still performing decompression by laminectomy some are doing multi-level anterior decompression. Few neurosurgeons are performing decompression by corpectomy. We have treated 26 patients by median cervical corpectomy during the last 4 years. These patients were followed up for a mean period of 25 months. Twenty one (80%) patients had a good outcome, 2 patients remained unchanged and 3 expired. Review of the literature and our experience indicates that patients with CSM and OPLL should be operated by median cervical corpectomy (anterior approach).     

Enhanced molecular volume of conservatively pegylated Hb: (SP-PEG5K)6-HbA is non-hypertensive

Recent studies have suggested that the "pressor effect" of acellular Hb is a consequence of perturbation of the macro-and microcirculatory system in multiple ways, and that PEGylation is an effective approach for controlling the same. In an attempt to confirm this concept, a new and simple thiolation mediated, maleimide chemistry-based conservative PEGylation protocol has been developed to conjugate multiple copies of PEG-chains to Hb. This approach combines the high reactivity of maleimides towards thiols with the propensity of iminothiolane to derivatize the epsilon-amino groups of proteins into reactive thiol groups, with conservation of their positive charge. One of the PEGylated products, namely (SP-PEG5K)6-HbA, that carries on an average six copies of PEG5000 chains per Hb, is non-hypertensive in hamster top load and in rat 50% exchange transfusion models. This hexa-PEGylated-Hb has (i) a hydrodynamic volume corresponding to that of an oligomerized Hb of 256kDa, (ii) a molecular radius of approximately 6.8 nm, (iii) high oxygen affinity, (iv) lowered Bohr effect, and (v) increased viscosity and colloidal osmotic pressure. These properties of (SP-PEG5K)6-HbA are consistent with the emerging new paradigms for the design of Hb based oxygen carriers and confirm the concept that the "pressor effect" of Hb is a multifactorial event. The thiolation mediated maleimide chemistry-based PEGylation protocol described here for the generation of (SP-PEG5K)6-Hb is simple, highly efficient, and is carried out under oxy conditions. The results demonstrate that a non-hypertensive PEG-Hb can be generated by conjugation of a lower number of PEG chains than previously reported.     

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy

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Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases

The expansion of trinucleotide repeat sequences is associated with several neurodegenerative diseases. The mechanism of this expansion is unknown but may involve slipped-strand structures where adjacent rather than perfect complementary sequences of a trinucleotide repeat become paired. Here, we have studied the interaction of the human mismatch repair protein MSH2 with slipped-strand structures formed from a triplet repeat sequence in order to address the possible role of MSH2 in trinucleotide expansion. Genomic clones of the myotonic dystrophy locus containing disease-relevant lengths of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two types of slipped-strand structures by annealing complementary strands of DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex slipped structures or S-DNA) or (ii) different numbers of repeats (heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of either CTG or CAG repeats were structurally distinct and could be separated electrophoretically and studied individually. Using a band-shift assay, the MSH2 was shown to bind to both S-DNA and SI-DNA in a structure- specific manner. The affinity of MSH2 increased with the length of the repeat sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat sequences, implicating a strand asymmetry in MSH2 recognition. Our results are consistent with the idea that MSH2 may participate in trinucleotide repeat expansion via its role in repair and/or recombination.      

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

Development of a composite indicator to prioritize districts for implementation of human immunodeficiency virus programmes in Maharashtra,India

A key recommendation of the National AIDS Control Programme‐IV of India was to develop new strategies for geo‐prioritization of the human immunodeficiency virus (HIV) epidemic. We conducted this study to categorize the districts in Maharashtra (India) based on a multidimensional framework for geo‐prioritization of services. Programmatic data on trends of HIV prevalence, coverage of marginalized populations and vulnerability factors were included. A composite indicator based on these was developed, and the cumulative score was calculated for each district. HIV prevalence among general population has declined steadily from 0.60% in 2007 to 0.33% in 2017. The programme coverage was stable but inadequate for men who have sex with men (MSM). The coverage for female sex workers (FSWs) was inadequate and reduced over time. Nine districts were categorized as high priority, 13 as moderate priority and 11 were classified as low‐priority districts based on burden and vulnerability for HIV. The high‐priority districts were Pune, Solapur and Yavatmal for FSW interventions and Pune, Thane and Latur for MSM interventions. This multidimensional indicator is based on existing programmatic data, dynamic and can be made state‐specific. It is useful to categorize and prioritize districts for allocation of resources and geo‐prioritization of services in resource limited settings.     

IMPORTANCE OF DONOR SELECTION IN RENAL TRANSPLANTATION

Renal transplantation has become a treatment of choice for patients with end stage renal disease. A successful transplant is the result of a combination of several factors acting synergistically, such as the degree of HLA compatibility between donor and the recipient, pretransplant blood transfusions, the recipient''s state of immunoreactivity and sensitization, immunosuppressive therapy given in post operative period etc. Donor selection appears to be the most critical factor for the long term success of the organ graft. In this brief review, some of the important parameters of donor selection in renal transplantation are highlighted.KEY WORDS: Histocompatibility (HLA) matching, Cross match, Sensitization     

A ten year serological survey of hepatitis A, B and C viruses infections in Nepal

BACKGROUND: In 1987, we reported that the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Nepal was low, as compared to hepatitis A virus (HAV) infection, and that no human T-lymphotropic type-1 (HTLV-1) infection was found in Nepal. OBJECTIVES: To determine changes in the prevalence of HAV, HBV, and HCV infections between 1987 and 1996 in inhabitants of Bhadrakali (suburban) and Kotyang (rural) villages in Nepal. STUDY DESIGN: We did a cross-sectional survey of 458 inhabitants of two Nepalese villages, to assess the prevalence of antibody to HAV (anti-HAV), antibody to hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg), antibody to HCV (anti-HCV), and antibody to HTLV-I (anti-HTLV-I). RESULTS: Anti-HAV was detected in 454 (99.1%), HBsAg in 5 (1.1%), anti-HBc in 33 (7.2%) and anti-HCV in 8 (1.7%) of serum samples tested in 1996. Statistically significant differences by gender or age group were nil. The prevalence of HCV infection was significantly higher in 1996 than in 1987 after adjusting for age of subjects living in the two villages (p < 0.01). The prevalence of HBsAg was significantly higher in 1996 than 1987 in Bhadrakali after adjusting for the factor of age (p < 0.05). Between 1987 and 1996, evidence for HTLV-1 positive residents was nil. CONCLUSION: These results suggest that HAV has been endemic in Nepal for long time while not of HBV, and that HCV infection tends to be increased recently.