Effectiveness of Homeopathic Medicines as Add-on to Institutional Management Protocol for Acute Encephalitis Syndrome in Children: An Open-Label Randomized Placebo-Controlled Trial.

BACKGROUND: Acute encephalitis syndrome (AES) is endemic to certain parts of India, with limited treatment options. In our initial exploratory comparative observational study of 151 patients with AES, there was significantly reduced mortality with adjunctive homeopathy compared to institutional management protocol (IMP). The present randomized placebo-controlled trial brings more statistical rigor to this research program. METHODS: This study was conducted at a pediatric unit from 2013 to 2015. Children aged > 6 months and ≤ 18 years and receiving IMP were randomized to receive adjunctive homeopathy (n = 325) or placebo as control (n = 323). The primary effectiveness analysis was based on Glasgow Outcome Scale (GOS). Morbidity was assessed using the Liverpool Outcome Score for Assessing Children at Follow-up. Analysis was by intention to treat. RESULTS: A total of 612 children were analyzed (Homeopathy [H] = 304; Control [C] = 308). The primary outcome, GOS, differed significantly between H and C groups. There was 14.8% death/neuro-vegetative state in the H group compared to 29.8% in the C group. Relative risk was 0.49 (95% confidence interval [CI]: 0.36 to 0.68), with absolute risk reduction of 15.0% (95% CI: 8.6 to 21.6%). Number needed to treat to prevent one additional death/neuro-vegetative state was 6.6 (95% CI: 4.6 to 11.6). Proportional-odds analysis also revealed a greater effect in the H group: odds ratio, 0.40 (95% CI: 0.27 to 0.60). The most frequently used medicines were Belladonna (n = 116), Stramonium (n = 33), Arsenicum album (n = 25), Sulfur (n = 18), Opium (n = 17), and Nux vomica (n = 10). CONCLUSION: Adjunctive homeopathic medicines may improve clinical outcomes associated with AES. Further randomized and controlled studies, using double-blinded trial design, are recommended to discover if the current findings may be corroborated.

A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: genetic risk is modulated by obesity.

Two common variants (rs1387153, rs10830963) in MTNR1B have been reported to have independent effects on fasting blood glucose (FBG) levels with increased risk to type 2 diabetes (T2D) in recent genome-wide association studies (GWAS). In this investigation, we report the association of these two variants, and an additional variant (rs1374645) within the GWAS locus of MTNR1B with FBG, 2h glucose, insulin resistance (HOMA IR), ß-cell function (HOMA B), and T2D in our sample of Asian Sikhs from India. Our cohort comprised 2222 subjects [1201 T2D, 1021 controls]. None of these SNPs was associated with T2D in this cohort. Our data also could not confirm association of rs1387153 and rs10830963 with FBG phenotype. However, upon stratifying data according to body mass index (BMI) (low ≤ 25 kg/m(2) and high > 25 kg/m(2)) in normoglycemic subjects (n = 1021), the rs1374645 revealed a strong association with low FBG levels in low BMI group (ß = -0.073, p = 0.002, Bonferroni p = 0.01) compared to the high BMI group (ß = 0.015, p = 0.50). We also detected a strong evidence of interaction between rs1374645 and BMI with respect to FBG levels (p = 0.002). Our data provide new information about the significant impact of another MTNR1B variant on FBG levels that appears to be modulated by BMI. Future confirmation on independent datasets and functional studies will be required to define the role of this variant in fasting glucose variation.

Homeopathy in chronic sinusitis: a prospective multi-centric observational study.

OBJECTIVE: The primary objective was to ascertain the therapeutic usefulness of homeopathic medicine in the management of chronic sinusitis (CS). MATERIALS AND METHODS: Multicentre observational study at Institutes and Units of the Central Council for Research in Homoeopathy, India. Symptoms were assessed using the chronic sinusitis assessment score (CSAS). 17 pre-defined homeopathic medicines were shortlisted for prescription on the basis of repertorisation for the pathological symptoms of CS. Regimes and adjustment of regimes in the event of a change of symptoms were pre-defined. The follow-up period was for 6 months. Statistical analysis was done using SPSS version 16. RESULTS: 628 patients suffering from CS confirmed on X-ray were enrolled from eight Institutes and Units of the Central Council for Research in Homoeopathy. All 550 patients with at least one follow-up assessment were analyzed. There was a statistically significant reduction in CSAS (P = 0.0001, Friedman test) after 3 and 6 months of treatment. Radiological appearances also improved. A total of 13 out of 17 pre-defined medicines were prescribed in 550 patients, Sil. (55.2% of 210), Calc. (62.5% of 98), Lyc. (69% of 55), Phos. (66.7% of 45) and Kali iod. (65% of 40) were found to be most useful having marked improvement. 4/17 medicines were never prescribed. No complications were observed during treatment. CONCLUSION: Homeopathic treatment may be effective for CS patients. Controlled trials are required for further validation.

In vitro and in vivo genotoxicity evaluation of hormonal drugs. I. Hydrocortisone.

Genotoxic evaluation of a widely used glucocorticoid, hydrocortisone, was undertaken using a battery of in vitro and in vivo test systems. Human lymphocyte cultures and mouse bone marrow studies (micronuclei and sister chromatid exchange analyses) showed the drug to be very potent clastogen. However, the Ames/Salmonella assay both with and without S9 did not show an increase in the His+ revertants.

In vitro and in vivo genotoxicity evaluation of hormonal drugs v. mestranol.

Genotoxicity of a widely used estrogen, Mestranol, was undertaken using in vitro, in vivo and host-mediated assay with bacteria as indicator organism. Analyses of chromosome aberrations and sister chromatid exchanges (SCEs) in human lymphocytes and chromosome aberrations, micronuclei and sister chromatid exchanges (SCEs) in bone-marrow cells of mice showed the drug to be capable of attacking the genetic material. However, both Ames Salmonella/S9 assay with and without S9 mix and host-mediated assay using same tester strains of Salmonella, did not show any significant increase/decrease in the His+ revertants.

In vitro and in vivo genotoxicity evaluation of hormonal drugs. II. Dexamethasone.

Genotoxicity evaluation of a widely used glucocorticoid medicine, dexamethasone, was undertaken using in vitro and in vivo assays. Analyses of chromosomal aberrations, sister-chromatid exchanges (SCEs) in human lymphocytes and micronuclei and SCEs in mouse bone marrow showed the drug to be capable of attacking the genetic material. However, the Ames/Salmonella assay, both with and without S9 mix, did not show any increase in His+ revertants.

Psychogenic factors in some genetic and non-genetic forms of infertility.

Five categories of patients suffering from different genetic and non-genetic forms of infertility and three categories of similarly affected, but potentially fertile, clinically normal individuals were studied. The Eysenck's Personality Inventory (1964), Ryle's Marital Patterns Test (1966) and Leckie and Wither's Inventory for Depressive Illness (1967) were used to determine the role played by psychogenic factors in causing infertility. No significant quantitative or qualitative differences were observed in the various groups studied. The psychogenic disturbances present in these individuals appear to be the result of the effect of persisting infertility rather than the cause of it.

Genetic heterogeneity of Oguchi's disease.

An analysis of the cases reported in Punjab, India, indicates the presence of genetic heterogeneity of Oguchi's disease, for which autosomal recessive inheritance has been documented earlier. The autosomal dominant inheritance pattern of this disease is associated with incomplete penetrance and a distinct sex bias towards females. This recognition is important for genetic counselling.

TCF7L2 polymorphisms are associated with type 2 diabetes in Khatri Sikhs from North India: genetic variation affects lipid levels.

Recently, the transcription factor-7-like 2 (TCF7L2) gene has been identified as the most important type 2 diabetes mellitus (T2DM) susceptibility gene. Common intronic polymorphisms in this gene have been found to be strongly associated with T2DM susceptibility showing marked reproducibility in multiple populations. The purpose of this study was to confirm the reported association of six TCF7L2 variants in a Khatri Sikh diabetic sample from North India. We genotyped six-associated SNPs in a case-control sample consisting of 556 T2DM cases and 537 controls. We also examined the impact of these variants on body mass index (BMI), waist to hip ratio (WHR), fasting insulin, and glucose and lipid levels. We report replication of association of four of the six SNPs with T2DM in this Khatri Sikh sample [rs7903146, (p = 0.010); rs11196205, (p = 0.011); rs10885409, (p = 0.002) and rs4918789, (p = 0.029)], under a dominant model conferring odds ratios (ORs) of 1.39, 1.44, 1.57 and 1.36, respectively. Haplotype analysis provided further evidence of association by showing a significant difference between cases and controls as revealed by the global omnibus test (chi(2)= 19.36; p = 0.0036). Multiple linear regression analysis also revealed the risk allele carriers of three of four significant SNPs (rs7903146, rs11196205, rs10885409) to be significantly associated with increased fasting total cholesterol (p value = 0.019, 0.025, 0.006) and LDL cholesterol levels (p value = 0.021, 0.018, 0.005), respectively. Our findings confirm that the TCF7L2 gene is a major risk factor for development of T2DM in Khatri Sikhs. It also provides new information about the significant impact of TCF7L2 gene variants on plasma cholesterol levels that appear to be independent of BMI.

Normal values for interpupillary, inner canthal and outer canthal distances in an Indian population.

Interpupillary distance (IP), inner and outer canthal distances (IC, OC) have been investigated in an Indian population to establish normal values for these parameters. In males, the mean values of IC and OC were found to be 3.15 +/- 0.2445 and 8.44 +/- 0.3172 cm, respectively. However, in females these values were 3.09 +/- 0.2862 and 8.17 +/- 0.3310 cm, respectively. IP, as derived by Pryor's formula, was found to be in close proximity with the observed IP values. IP was also estimated by a multiple linear regression technique. The normal IP values are useful in the identification of ocular hypo- or hypertelorism in various syndromes which might be otherwise obscured by the various somatometric traits of the face.

Genetic and segregation analysis of congenital cataract in the Indian population.

Congenital cataract is a major cause of blindness in children, and there is wide variation in the few reports available on the frequencies of its different inheritance patterns. Two hundred and fifty-two families with congenital cataract belonging to 13 different states of India, were clinically and genetically investigated to study their inheritance and segregation patterns. Twenty-one percent of the cases were autosomal recessive, 15% autosomal dominant, 63% were simplex cases, and in the remaining cases the inheritance pattern was not clear. A high incidence of consanguinity (50.9%) was observed in autosomal recessive cases. Out of 340 affected individuals, 222 (65.3%) were males and 118 (34.7%) were females. Segregation analysis showed good agreement in autosomal dominant and recessive families and the data are indicative of the prevalence rate for different inheritance patterns of congenital cataract within the Indian population.

The effect of cyclophosphamide on the centromere separation sequence in Chinese hamster spermatogonia.

The sequence of centromere separation in spermatogonial chromosomes of untreated and cyclophosphamide-treated Chinese hamsters is described. Centromeres of chromosome 1 and 2 separated much earlier than all other chromosomes, especially 6-8. Cyclophosphamide significantly inhibits the centromere separation in all chromosome groups but does not alter the sequence of separation.

The effect of cyclophosphamide and isoniazid (INH) alone and in combination on the centromere separation sequence in Chinese hamster bone marrow cells.

X-irradiation of Chinese hamsters with 50 and 200 rad delayed the centromere separation of bone marrow chromosomes. Combination of a treatment with 13.3 mg cyclophosphosphamide/kg body wt. and 50 rad did not result in an enhanced effect compared with the single treatments. Again, the separation sequence was not influenced. No delay was induced by a treatment with 125 mg isoniazid/kg, but a slightly and significantly earlier separation of the chromatids in both groups of metacentric and acrocentric chromosomes occurred. The separation delay seen after irradiation with 50 rad disappeared when the animals were pretreated with isoniazid. Independently of these results the asynchronous separation sequence was not altered in any of the experiments.

Comparative behavioural effects of benzodiazepine and non-benzodiazepine anxiolytics in rhesus monkeys.

Quantitative behavioural assessment of benzodiazepines (chlordiazepoxide, diazepam and lorazepam) and non-benzodiazepines (buspirone) anxiolytics were investigated in unrestrained rhesus monkeys (Macaca mulatta) living in social colonies. The different behaviour, categorised as social, solitary and abnormal were video recorded and analysed. Chlordiazepoxide (2.5-5 mg kg-1, p.o.), diazepam (2.5-5 mg kg-1, p.o.) and lorazepam (0.5-1 mg kg-1, p.o.) induced dose-dependent significant changes in certain social and solitary behavioural responses. Thus increases in social grooming, approach, contact, self grooming, feeding and resting with eyes open and decreased aggressiveness and vigilance. On the other hand buspirone (5-10 mg kg-1, p.o.) produced no significant alteration in social and solitary behavioural patterns. On the basis of the above findings the social and solitary behaviour protocol in non-human primates can be a useful tool for studying the effect of a new anxiolytic compound before clinical trial.

Prevalence of factor V Leiden mutation in various populations.

Resistance to activated protein C (APC) is the most common inherited risk factor for venous thrombosis. Most cases of APC resistance are caused by the point mutation nt 1691 G-A in factor V gene, referred to as factor V Leiden mutation. As initially shown in a Dutch population, this mutation has a carrier rate of 2.9%, the most frequent genetic disposition for thrombophilia and deep venous thrombosis. By large-scale epidemiological studies we have determined the prevalence of factor V Leiden mutation in populations from Poland (200), Argentina (215), Venezuela (126), Costa Rica (196), and India (150). The prevalences have been estimated for Poland (Warsaw) 5.0%, Argentina (Buenos Aires) 5.1%, Venezuela (Valencia) 1.6%, Costa Rica (San José) 2.0%, and India (Punjab) 1.3%. Based on worldwide distribution, it can be hypothesized that the factor V Leiden mutation has originated and accumulated in central European Caucasians and spread over the world by migration.

A novel form of "central pouchlike" cataract, with sutural opacities, maps to chromosome 15q21-22.

Congenital cataract is a clinically and genetically highly heterogeneous eye disorder, with autosomal dominant inheritance being most common. We investigated a large seven-generation family with 74 individuals affected by autosomal dominant congenital cataract (ADCC). The phenotype in this family can be described as "central pouchlike" cataract with sutural opacities, and it differs from the other mapped cataracts. We performed linkage analysis with microsatellite markers in this family and excluded the known candidate genes. A genomewide search revealed linkage to markers on chromosome 15, with a maximum two-point LOD score of 5.98 at straight theta=0 with marker D15S117. Multipoint analysis also gave a maximum LOD score of 5.98 at D15S117. Multipoint and haplotype analysis narrowed the cataract locus to a 10-cM region between markers D15S209 and D15S1036, closely linked to marker D15S117 in q21-q22 region of chromosome 15. This is the first report of a gene for a clinically new type of ADCC at 15q21-22 locus.