Time course and frequency of subtherapeutic anticoagulation for newly prescribed warfarin anticoagulation before elective cardioversion of atrial fibrillation or flutter.
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Aged↗
Biomedical subjects
S Jain
Publications and source records attributed to S Jain.
CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms.
Spinocerebellar ataxia 2 (SCA2) is an autosomal dominant neurodegenerative disorder that results from the expansion of a cryptic CAG repeat within the exon 1 of the SCA2 gene. The CAG repeat in normal individuals varies in length from 14 to 31 repeats and is frequently interrupted by one or more CAA triplets, whereas the expanded alleles contain a pure uninterrupted stretch of 34 to 59 CAG repeats. We have previously reported the presence of a limited pool of 'ancestral' or 'at risk' haplotypes for the expanded SCA2 alleles in the Indian population. We now report the identification of two novel single nucleotide polymorphisms (SNPs) in exon 1 of the SCA2 gene and their characterization in 215 normal and 64 expanded chromosomes. The two biallelic SNPs distinguished two haplotypes, GT and CC, each of which formed a predominant haplotype associated with normal and expanded SCA2 alleles. All the expanded alleles segregated with CC haplotype, which otherwise was associated with only 29.3% of the normal chromosomes. CAA interspersion analysis revealed that majority of the normal alleles with CC haplotype were either pure or lacked the most proximal 5' CAA interruption. The repeat length variation at SCA2 locus also appeared to be polar with changes occurring mostly at the 5' end of the repeat. Our results demonstrate that CAA interruptions play an important role in conferring stability to SCA2 repeat and their absence predisposes alleles towards instability and pathological expansion. Our study also provides new haplotypes associated with SCA2 that should prove useful in further understanding the mutational history and mechanism of repeat instability at the SCA2 locus.
Alleles↗
A clinical study of patients with genetically confirmed Huntington's disease from India.
BACKGROUND: Clinical data across the globe especially in genetic diseases like Huntington's disease (HD) is most helpful when collected using standardized formats. This helps in proper comparison of clinical and genetic data. METHODS: Herein, we report clinical data on 26 genetically confirmed HD patients from 19 Indian families predominantly from South India. Clinical data and evaluation was performed using standardized formats used by the Huntington Disease Study Group. RESULTS: Adult onset HD was commonest while Juvenile HD (onset <20 years) was observed in approximately 15% of patients. Chorea was the commonest presenting symptom (n=23, 88.5%) while remaining presented with psychiatric symptoms (n=3, 11.5%). Impairment of saccades was observed in approximately 75% of patients. Mean (SD) CAG repeats in the abnormal allele was 48.4 (8.7). Total motor score but not the total behavioral score worsens with duration of symptoms. The functional checklist score correlates with total motor score rather than with duration of symptoms. CONCLUSIONS: We detail clinical characteristics in genetically confirmed HD patients from a predominantly South Indian cohort. We observed a slightly higher occurrence of Juvenile HD. Functional disabilities in our patients correlate with worsening of motor rather than behavioral symptoms.
Adolescent↗
GRAB: a physiologic guanine nucleotide exchange factor for Rab3A, which interacts with inositol hexakisphosphate kinase.
Diphosphoinositol-pentakisphosphate (InsP7) and bis-diphosphoinositol tetrakisphosphate (InsP8) possess pyrophosphate bonds. InsP7 is formed from inositol hexakisphosphate (InsP6) by recently identified InsP6 kinases designated InsP6K1 and InsP6K2. We now report the identification, cloning, and characterization of a novel protein, GRAB (guanine nucleotide exchange factor for Rab3A), which interacts with both InsP6K1 and Rab3A, a Ras-like GTPase that regulates synaptic vesicle exocytosis. GRAB is a physiologic GEF (guanine nucleotide exchange factor) for Rab3A. Consistent with a role of Rab3A in synaptic vesicle exocytosis, GRAB regulates depolarization-induced release of dopamine from PC12 cells and nicotinic agonist-induced hGH release from bovine adrenal chromaffin cells. The association of InsP6K1 with GRAB fits with a role for InsP7 in vesicle exocytosis.
Adrenal Medulla↗
Peroxisome proliferator-activated receptor alpha-responsive genes induced in the newborn but not prenatal liver of peroxisomal fatty acyl-CoA oxidase null mice.
Mice deficient in fatty acyl-CoA oxidase (AOX(-/-)), the first enzyme of the peroxisomal beta-oxidation system, develop specific morphological and molecular changes in the liver characterized by microvesicular fatty change, increased mitosis, spontaneous peroxisome proliferation, increased mRNA and protein levels of genes regulated by peroxisome proliferator-activated receptor alpha (PPARalpha), and hepatocellular carcinoma. Based on these findings it is proposed that substrates for AOX function as ligands for PPARalpha. In this study we examined the sequential changes in morphology and gene expression in the liver of wild-type and AOX(-/-) mice at Embryonic Day 17.5, and during postnatal development up to 2 months of age. In AOX(-/-) mice high levels of expression of PPARalpha-responsive genes in the liver commenced on the day of birth and persisted throughout the postnatal period. We found no indication of PPARalpha activation in the livers of AOX(-/-) mice at embryonic age E17.5. In AOX(-/-) mice microvesicular fatty change in liver cells was evident at 7 days. At 2 months of age livers showed extensive steatosis and the presence in the periportal areas of clusters of hepatocytes with abundant granular eosinophilic cytoplasm rich in peroxisomes. These results suggest that the biological ligands for PPARalpha vis a vis substrates for AOX either are not functional in fetal liver or do not cross the placental barrier during the fetal development and that postnatally they are likely derived from milk and diet.
3-Hydroxyacyl CoA Dehydrogenases↗
Risk factors for adverse drug events among nursing home residents.
BACKGROUND: In a prospective study of nursing home residents, we found adverse drug events (ADEs) to be common, serious, and often preventable. To direct prevention efforts at high-risk residents, information is needed on resident-level risk factors. METHODS: Case-control study nested within a prospective study of ADEs among residents in 18 nursing homes. For each ADE, we randomly selected a control from the same home. Data were abstracted from medical records on functional status, medical conditions, and medication use. RESULTS: Adverse drug events were identified in 410 nursing home residents. Independent risk factors included being a new resident (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.5-5.2) and taking anti-infective medications (OR, 4.0; CI, 2.5-6.2), antipsychotics (OR, 3.2; CI, 2.1-4.9), or antidepressants (OR, 1.5; CI, 1.1-2.3). The number of regularly scheduled medications was associated with increased risk of ADEs; the OR associated with taking 5 to 6 medications was 2.0 (CI, 1.2-3.2); 7 to 8 medications, 2.8 (CI, 1.7-4.7); and 9 or more, 3.3 (CI, 1.9-5.6). Taking supplements or nutrients was associated with lower risk (OR, 0.42; CI, 0.27-0.63). Preventable ADEs occurred in 226 residents. Independent risk factors included taking opioid medications (OR, 6.6; CI, 2.3-19.3), antipsychotics (OR, 4.0; CI, 2.2-7.3), anti-infectives (OR, 3.0; CI, 1.6-5.8), antiepileptics (OR, 2.2; CI, 1.1-4.5), or antidepressants (OR, 2.0; CI, 1.1-3.5). Scores of 5 or higher on the Charlson Comorbidity Index were associated with increased risk of ADEs (OR, 2.6; CI, 1.1-6.0). The number of regularly scheduled medications was also a risk factor: the OR for 7 to 8 medications was 3.2 (CI, 1.4-6.9) and for 9 or more, 2.9 (CI, 1.3-6.8). Residents taking nutrients or supplements were at lower risk (OR, 0.27; CI, 0.14-0.50). CONCLUSIONS: It is possible to identify nursing home residents at high risk of having an ADE. Particular attention should be directed at new residents, those with multiple medical conditions, those taking multiple medications, and those taking psychoactive medications, opioids, or anti-infective drugs.
Aged↗
Formulation and process optimization to eliminate picking from market image tablets.
A tablet formulation when compressed using market image tooling may cause picking of powder. A D-optimal statistical experiment was designed to optimize the direct compression formulation and the process to alleviate picking of powder. The effects of levels of magnesium stearate, colloidal silicon dioxide (CSD), and lubrication time on picking were investigated using original compression tooling. These optimization results provided a small robust manufacturing region, hence a change in the cut angles of embossed letters and numbers from 70 degrees to 90 degrees in the modified compression tooling was evaluated. A statistical analysis of the data identified a robust manufacturing region that included formulations containing magnesium stearate 1-1.25% w/w, CSD 0.1-0.3% w/w, with a lubrication time of 5-10 min when compressed using modified compression tooling. The results indicate a significant reduction in picking by increasing the cut angles of embossed letters and numbers in the modified compression tooling. By evaluating interactions between various variables, we demonstrate a concentration dependent effect of CSD on the lubrication efficiency of magnesium stearate and compactability of microcrystalline cellulose containing formulation. In addition, the lubrication efficiency of magnesium stearate is maintained by blending CSD with powder blend prior to lubrication with magnesium stearate.
Drug Compounding↗
A model for the emergence of cooperation, interdependence, and structure in evolving networks.
Evolution produces complex and structured networks of interacting components in chemical, biological, and social systems. We describe a simple mathematical model for the evolution of an idealized chemical system to study how a network of cooperative molecular species arises and evolves to become more complex and structured. The network is modeled by a directed weighted graph whose positive and negative links represent "catalytic" and "inhibitory" interactions among the molecular species, and which evolves as the least populated species (typically those that go extinct) are replaced by new ones. A small autocatalytic set, appearing by chance, provides the seed for the spontaneous growth of connectivity and cooperation in the graph. A highly structured chemical organization arises inevitably as the autocatalytic set enlarges and percolates through the network in a short analytically determined timescale. This self organization does not require the presence of self-replicating species. The network also exhibits catastrophes over long timescales triggered by the chance elimination of "keystone" species, followed by recoveries.
Animals↗
Inadvertent tobacco advertising in physicians' offices.
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Advertising↗
The PDB data uniformity project.
The Protein Data Bank (PDB; http://www.rcsb.org/pdb/) is the single worldwide archive of structural data of biological macromolecules. This paper describes the data uniformity project that is underway to address the inconsistency in PDB data.
Databases, Factual↗
Molecular and clinical correlation in five Indian families with spinocerebellar ataxia 12.
Spinocerebellar ataxia 12 (SCA12) is a recently identified form of autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' untranslated region of the gene PPP2R2B. We analyzed 77 Indian families with autosomal dominant cerebellar ataxia phenotype and confirmed the diagnosis of SCA12 in 5 families, which included a total of 6 patients and 21 family members. The sizes of the expanded alleles ranged from 55 to 69 CAG repeats, and the sizes of the normal alleles ranged from 7 to 31 repeats. We believe our study is the first to demonstrate that SCA12 may not be as rare in some populations as previously thought.
Adult↗
Expression of macrophage-colony stimulating factor in normal and inflammatory bowel disease intestine.
Mucosal macrophages have been implicated in the pathogenesis of inflammatory bowel disease (IBD). Macrophage-colony stimulating factor (M-CSF) influences monocyte/macrophage proliferation, differentiation, and activation. Serum levels are increased in active IBD, but little is known about its role in mucosal inflammation. This study was undertaken to determine the distribution, frequency, and level of M-CSF expression in normal and IBD-affected intestine. RNA and tissue were studied from patients with Crohn's disease (CD) and ulcerative colitis (UC) as well as from histologically normal colon. Tissue from intestinal tuberculosis and ischaemic colitis patients served as controls. M-CSF mRNA and protein were examined by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridisation, and immunohistochemistry, respectively. M-CSF mRNA and protein were detected in histologically normal intestine, but their expression was largely confined to the mucosa. In active IBD, the frequency of M-CSF-expressing cells was significantly increased and their distribution markedly altered, although no increase in mucosal M-CSF mRNA levels in intestinal tissue was observed. The changes were not specific to IBD, as there were similar findings in intestinal tuberculosis and ischaemic colitis. The marked alteration observed in M-CSF expression in IBD and the importance of this cytokine in stimulating macrophage functions suggest that M-CSF may contribute to the pathogenesis of the IBD lesion.
Adult↗
Neuroprotective effects of Withania somnifera Dunn. in hippocampal sub-regions of female albino rat.
The neuroprotective effects of W. somnifera were studied on stressed adult female Swiss albino rats. Experimental rats were subjected to immobilization stress for 14 h and were treated with a root powder extract of W. somnifera available as Stresscom capsules (Dabur India Ltd). Control rats were maintained in completely, non stressed conditions. Thionin stained serial coronal sections (7 microm) of brain passing through the hippocampal region of stressed rats (E(1) group) demonstrated 85% degenerating cells (dark cells and pyknotic cells) in the CA(2) and CA(3) sub-areas. Treatment with W. somnifera root powder extract significantly reduced (80%) the number of degenerating cells in both the areas. The study thus demonstrates the antistress neuroprotective effects of W. somnifera.
Animals↗
Applications of the telomerase assay in peritoneal washing fluids.
OBJECTIVE: The aim of this study was to detect telomerase activity in peritoneal ascites and to assess whether it can be used as an assistant tool for the early detection of ovarian cancer. METHODS: Telomerase activity was measured by TRAP assay in 47 patients with ovarian malignancies and 50 patients with benign uterine leiomyomas (control group). RESULTS: All 26 peritoneal washing cytology positive cases were telomerase positive. Of the 21 peritoneal washing cytology negative cases, 3 were telomerase positive. When these 3 were reevaluated for peritoneal cytology, malignant ascitis was identified in 1. All telomerase negative cases were negative for peritoneal washing cytology. The sensitivity and specificity of peritoneal cytology and telomerase testing in correlation with true malignant cells were 96 (26/27) and 100% (20/20) versus 100 (27/27) and 90% (18/20), respectively. The false negative rate of peritoneal cytology was 4.7% (1/21). The false positive rate of the telomerase test in relation to malignant ascites was 6.9% (2/29). CONCLUSION: Our preliminary results reveal a high sensitivity and specificity of both telomerase testing and conventional cytology in peritoneal fluids. Our data suggest that the telomerase test in peritoneal fluids can be used as an adjuvant to cytopathological methods in the diagnosis of malignant peritoneal ascites, particularly in cases of negative cytology. In these cases, a review of peritoneal histocytology is advised.
Adult↗
Negative predictive value of human papillomavirus test following conization of the cervix uteri.
OBJECTIVE: The goal of this study was to determine/evaluate the negative predictive value of human papillomavirus (HPV) testing following conization of cervix uteri. METHODS: A prospective analysis was undertaken on 79 cone biopsies of women with high-grade lesions (cervical intraepithelial neoplasia (CIN) III). HPV testing was performed on cervical smears before and after conization. We correlated the margin status (defined as positive cone margin or endocervical curettage status) and positive conization HPV status with the residual disease in a hysterectomy specimen. A Digene II kit was used to perform HPV testing. HPV detection was done by Hybrid Capture assay. RESULTS: Of the 79 patients, 47(59.5%) had positive margins after conization. HPV testing was positive in 37 cases (78.7%) and negative in 10 cases (21.3%). Residual disease was found in 31 of 47 (66%) postconization hysterectomy specimens. No residual lesions were found in HPV-negative cases. Of the 32 cases with negative margins following conization, HPV testing was negative in 25 cases (78%) and was positive in 7 cases (22%). Among these 25 cases with negative HPV tests, no residual lesion was detected, and in 7 HPV-positive cases, only one residual lesion was found. CONCLUSION: HPV testing is potentially an effective tool in predicting residual dysplasia after conization and could potentially assist in the decision between hysterectomy and conservative follow-up in women with CIN III.
Cervix Uteri↗
Prevalence of goitre in school-going children in Jabalpur.
To determine the prevalence of goitre in school going children in Jabalpur city and critically evaluate clinical, biochemical and hormonal profile of goitrous children, 1205 children (800 boys and 405 girls) between 6 to 15 years of age were enrolled from 6 different schools located within the Jabalpur city limits. Conducting a Cross-sectional survey relevant family variables, eating habits (including type of salt used), anthropometry and general physical details were recorded in a pre-designed proforma. Thyroid gland was examined and graded as per standard technique. Spot urinary iodine excretion (UIE) of all goitrous children (n = 26) and randomly selected age and sex matched normal non-goitrous children (n = 63) was determined by dry-ashing method. Thyroid hormone profile of goitrous children was assessed by radio-immuno-assay. Student's t-test, z-test and proportionate test were employed to evaluate the statistical significance of the observations. It has been drawn a result that there was low prevalence of goitre in school going children of Jabalpur city. (2.4%, 26/1205). Girls had a higher prevalence (3.2%) than boys (1.6%), however the difference was statistically not insignificant. All goitrous children had small goitre (Grade I) 88.76% children had spot UIE > 100 mcg/l with as many as 13.4% having spot UIE > 150 mcg/l. No child had spot UIE < mcg/l. 11.23% of children had spot UIE of < 100 mcg/l with higher proportion of goitrous children (7/26, 26.92%) than the age matched, non-goitrous controls (3/63, 4.76%). The mean UIE of goitrous children was 109.6 +/- 22.1 mcg/l (range 80-150 mcg/l) and that of control children was 122.9 +/- 17.0 mcg/l (range 90-150 mcg/l). Thyroid hormone profile of goitrous children was in euthyroid range. Salt iodine content could not be done due to non-availability of kit. Jabalpur city is not endemic for iodine deficiency both by clinical as well biochemical criteria. The observed goitre cases are of sporadic variety.
Adolescent↗
Pattern of use and pharmacoeconomic impact of antihypertensive drugs in a north Indian referral hospital.
OBJECTIVE: The current study was designed to investigate drug utilisation and the pharmacoeconomics of hypertension in the hypertension clinic of a tertiary-care hospital. METHODS: The study was conducted in patients attending the hypertension clinic of Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh, India. A survey of prescriptions was carried out, and the information obtained was further corroborated by seeing the medical records as well as patient interviews. RESULTS: A total of 1,076 prescriptions were evaluated. Beta-adrenoceptor-blocking agents (51%), calcium antagonists (47%) and angiotensin-converting enzyme inhibitors (46%) were the most popular drugs. The utilisation of thiazides was less than expected. Combination therapy was used more commonly than monotherapy (53.8% vs 46.7%). Oral hypoglycaemic agents and lipid-lowering agents were commonly co-prescribed along with antihypertensive medications. About 30% of drugs were prescribed by generic name and 90% were from the national essential drugs list. Of the per capita income, 10.6% was spent on the treatment of hypertension. The mean monthly cost of various drugs ranged between US $0.8 and US $6.6. A total of 91 adverse drug reaction (ADRs) were encountered in the study; the added cost of treatment of these ADRs was US $211. CONCLUSION: In general, the treatment guidelines for hypertension were followed in our hospital. The utilisation of thiazides was an area requiring improvement. The cost of treatment of hypertension was substantial and imparted a significant economic burden on the patients.
Adrenergic beta-Antagonists↗
The polyglutamine motif is highly conserved at the Clock locus in various organisms and is not polymorphic in humans.
Circadian rhythms play a central role in diverse physiological phenomena and the recent years have witnessed the identification of a number of genes responsible for the maintenance of these rhythms. One of these is the Clock gene, which was first identified in mouse and subsequently in a large number of organisms, including humans. The human Clock gene has been proposed as a possible candidate for disorders affected by alterations of circadian rhythm, including bipolar disorder and schizophrenia. This gene contains a highly conserved polyglutamine motif, that in humans is coded for by CAG repeats. In view of the involvement of CAG repeat expansion in a number of neuro-psychiatric disorders, we have sought to determine the polymorphism status of CAG repeats at the Clock locus in humans. Our analysis of 190 unrelated individuals, who included patients suffering from bipolar disorder and schizophrenia, indicated that the repeat, which consisted of 6 CAG triplets, was not polymorphic in humans. An analysis of the repeat in non-human primates and other organisms revealed that the glutamine stretch is shortest in humans and baboons, and longest in Drosophila and zebrafish. A study of various Drosophila species revealed that the repeat number is highly polymorphic, ranging from 25 to 33 pure glutamine repeats. Unlike most other microsatellites, the CAG repeat stretch at the Clock locus in humans is smaller than its homologues in non-human primates. We propose that glutamine repeat size is functionally important in this gene and thus tightly regulated. The variation in repeat number is probably deleterious to the individual, resulting in the maintenance of a short and invariable repeat structure in the human population.
Amino Acid Sequence↗