Association between Interleukin-6 (-174 G/C and -572 C/G) Promoter Gene Polymorphisms and Risk of Intracerebral Hemorrhage in North Indian Population: A Case Control Study.

Background: Interleukin-6 (IL-6), a pro-inflammatory cytokine is involved in various vascular pathologies including stroke. Till date, no studies have been reported for the association between IL-6 gene polymorphisms with the risk of Intracerebral hemorrhage (ICH). Objective: The aim of this present case-control study was to investigate the association between IL-6 (-174 G/C and -572 C/G) gene polymorphisms and risk of ICH in North Indian population. Methods: Genotyping was carried out by using SNaPshot method for ICH patients and 100 age-sex matched ICH free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between IL-6 (-174 G/C and -572 C/G) polymorphisms and risk of ICH. Results: Hypertension, diabetes, dyslipidemia, smoking and low socioeconomic status were found to be associated with the risk of ICH. The distribution of -174 G/C and -572 C/G genotypes was consistent with Hardy Weinberg Equilibrium (HWE) in the ICH and control subjects. Conditional logistic regression analysis showed a significant association between IL-6 -572 C/G gene polymorphism and the risk of ICH under dominant model (OR=3.7; 95%CI 1.05 to 13.1; p=0.004) and allelic model (OR=2.6; 95%CI 1.1 to 6.2; p=0.01). No significant association was observed for the association between IL-6 -174 G/C gene polymorphism and risk of ICH. Conclusion: Our results suggest that IL-6 (-572 C/G) polymorphism is significantly associated with the risk of ICH in North Indian population. Further prospective studies with large sample size are needed for independent validation.

Spinocerebellar ataxia 7 (SCA7) in Indian population: predilection of ATXN7-CAG expansion mutation in an ethnic population.

Background & objectives: spinocerebellar ataxia 7 (SCA7) is a rare form of neurodegenerative disorder with the clinical manifestation of cerebellar ataxia and retinal degeneration. In this study we describe the clinico-genetic characteristics of nine SCA7 families of Indian origin and cross compare these with other available worldwide studies. Methods: Thirty five individuals from nine SCA7 families were clinico-genetically characterized and CAG repeat distribution analysis was carried out in 382 control DNA samples from healthy controls (derived from 21 diverse Indian populations based on ethnic and linguistic and geographical location). Results: Of the nine families studied, 22 affected individuals and one asymptomatic carrier were identified. The average age at disease onset was 23.4±12.6 yr. The length of expanded CAG ranged from 40-94 with mean value of 53.2±13.9. The main clinical findings in affecteds individuals included cerebellar ataxia, and retinal degeneration along with hyper-reflexia (95%), slow saccades (85%) and spasticity (45%). Analysis of the association of number of CAG repeats with disease onset revealed that <49 repeats were associated with earlier age at onset in South East Asians compared to European populations. Further analysis of CAG repeats from 21 diverse Indian populations showed pre-mutable repeats (28-34) alleles in the IE-N-LP2 population. Six of the nine families identified in this study belonged to the same ethnic population. Interpretations & conclusion: Our results show that presenece of SCA7 is relatively rare and confined to one ethnic group from Haryana region of India. We observed a homogeneous phenotypic expression of SCA7 mutation as described earlier and an earlier age of onset in our patients with CAG <49. The identification of pre-mutable allele in IE-N-LP2 suggests this population to be at the risk of SCA7.

Autologous intravenous bone marrow mononuclear cell therapy for patients with subacute ischaemic stroke: a pilot study.

Background & objectives: Bone marrow mononuclear cell therapy has emerged as one of the option for the treatment of Stroke. Several preclinical studies have shown that the treatment with mononuclear cell (MNCs) can reduce the infarct size and improve the functional outcome. We evaluated the feasibility, safety and clinical outcome of administering bone marrow mononuclear cell (MNCs) intravenously to patients with subacute ischaemic stroke. Methods: In a non-randomized phase-I clinical study, 11 consecutive, eligible and consenting patients, aged 30-70 yr with ischaemic stroke involving anterior circulation within 7 to 30 days of onset of stroke were included. Bone marrow was aspirated from iliac crest and the harvested mononuclear cells were infused into antecubital vein. Outcomes measured for safety included immediate reactions after cell infusion and evidence of tumour formation at one year in whole body PET scan. Patients were followed at week 1, 4-6, 24 and 52 to determine clinical progress using National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), MRI, EEG and PET. Feasibility outcomes included target-dose feasibility. Favourable clinical outcome was defined as mRS score of 2 or less or BI score of 75 to 100 at six months after stem cell therapy. Results: Between September 2006 and April 2007, 11 patients were infused with bone-marrow mononuclear cells (mean 80 million with CD-34+ mean 0.92 million). Protocol was target-dose feasible in 9 patients (82%). FDG-PET scan at 24 and 52 wk in nine patients did not reveal evidence of tumour formation. Seven patients had favourable clinical outcome. Interpretation & conclusions: Intravenous bone marrow mononuclear cell therapy appears feasible and safe in patients with subacute ischaemic stroke. Further, a randomized controlled trial to examine its efficacy is being conducted.

An electromyographic study to assess the minimal time duration for using the splint to raise the vertical dimension in patients with generalized attrition of teeth.

Background: To investigate the effect of restoration of lost vertical by centric stabilizing splint on electromyographic (EMG) activity of masseter and anterior temporalis muscles bilaterally in patients with generalized attrition of teeth. Materials and Methods: EMG activity of anterior temporalis and masseter muscle was recorded bilaterally for 10 patients whose vertical was restored with centric stabilizing splint. The recording was done at postural rest position and in maximum voluntary clenching for each subject before the start of treatment, immediately after placement of splint and at subsequent recall visits, with splint and without the splint. Results: The EMG activity at postural rest position (PRP) and maximum voluntary clench (MVC) decreased till 1 month for both the muscles. In the third month, an increase in muscle activity toward normalization was noted at PRP, both with and without splint. At MVC in the third month, the muscle activity without splint decreased significantly as compared to pretreatment values for anterior temporalis and masseter, while with the splint an increase was seen beyond the pretreatment values. Conclusion: A definite response of anterior temporalis and masseter muscle was observed over a period of 3 months. This is suggestive that the reversible increase in vertical prior to irreversible intervention must be carried out for a minimum of 3 months to achieve neuromuscular deprogramming. This allows the muscle to get adapted to the new postural position and attain stability in occlusion following splint therapy.