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Biomedical subjects

M Sharma

Publications and source records attributed to M Sharma.

At least 19 recordsLinked to original sources
PubMed2006

Comprehensive association analysis of the NOS2A gene with Parkinson disease.

Inducible nitric oxide synthase (NOS2A) may be involved in the oxidative stress pathology of Parkinson disease (PD). Two previous studies reported an association of a single nucleotide polymorphism (rs1060826) with PD. A replication study of 340 German patients and 680 controls showed no significant association between 12 genotyped polymorphisms and PD. NOS2A is therefore not a major susceptibility locus in our relatively young sample population.

Alleles↗
PubMed2006

Imaging growth dynamics of tumour spheroids using optical coherence tomography.

Optical coherence tomography (OCT) was used to monitor the dynamics of tumour spheroid formation by the hanging drop method. In contrast to microscopy, the estimates obtained using OCT for the volume of the spheroid, were consistent with the measured changes in cell number as a function of time. The OCT images also revealed heterogeneous structures in the spheroids of approximately 200 microm diameter. These corresponded to the necrotic regions identified by fluorescence of propidium iodide stained cells.

Cell Count↗
PubMed2006

Strong genetic evidence for association of TOR1A/TOR1B with idiopathic dystonia.

Recently, association of a TOR1A(DYT1)/TOR1B risk haplotype with common forms of idiopathic dystonia has been reported in the Icelandic population. Here we report a strong association of two single nucleotide polymorphisms within or in close proximity to the TOR1A 3'UTR, with the lowest p value being 0.000008, in a larger cohort of German and Austrian patients with predominantly focal sporadic dystonia.

Adult↗
PubMed2006

Possible gender-dependent association of vascular endothelial growth factor (VEGF) gene and ALS.

Individuals homozygous for haplotypes -2578-A/-1154-A/-634-G or -2578-A/-1154-G/-634-G in the promoter/5'UTR of the VEGF gene have a 1.8-fold increased risk of ALS in several European populations. We did not observe any significant association with single markers, or haplotype pairs, in a German sample of 580 sporadic ALS patients and 628 controls. However, the promoter SNP-1154 (rs1570360) was associated with affection status in women (p = 0.036), suggesting that the VEGF effect may be dependent on the sex ratio of the sample.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Synthesis and QSAR studies on 5-[2-(2-methylprop1-enyl)-1H benzimidazol-1yl]-4,6-diphenyl-pyrimidin-2-(5H)-thione derivatives as antibacterial agents.

A new series of 5-[2-(2-methylprop1-enyl)-1H benzimidazol-1yl]-4,6-diphenyl-pyrimidin-2-(5H)-thione derivatives [3a-q] has been synthesized and subjected to evaluate their antibacterial properties. All the synthesized compounds of the series displayed, remarkable activity in comparison to standard drug (ampicillin). A number of descriptors were tested to adjudge a quantitative correlation between activity and structural features. However, significant correlations have emerged between activity and physicochemical parameters viz. polarizability parameter (MR). Moreover, results are interpreted on the basis of multiple regression and cross-validation methodology.

Anti-Bacterial Agents↗
PubMed2006

Electrophysiological and behavioral evidence of auditory processing deficits in children with reading disorder.

OBJECTIVE: The aim of the research was to investigate auditory processing abilities in children with reading disorders using electrophysiological and behavioral tasks. METHODS: Differences in auditory processing between control, compensated (age appropriate reading skills with a history of reading disorder), and reading disordered groups were systematically investigated. RESULTS: The reading disorder group had significantly lower results than control and compensated reader groups for most tests in the reading and auditory processing test battery. All children with a reading disorder did not pass at least one behavioral test of auditory processing, and hence would be diagnosed clinically as having an auditory processing disorder (APD). The reading disorder group also had significantly smaller /ga/-evoked mismatch negativity (MMN) area than the control group. Compensated and control groups had similar results for the electrophysiological and behavioral auditory processing tests. Correlation analyses showed that reading fluency and accuracy and nonword scores (measured using Castle and Coltheart's word/nonword test) correlated significantly with most APD measures. CONCLUSIONS: The general profile of auditory processing deficits in children with reading disorder was a combination of deficits on frequency patterns (i.e. frequency pattern test) and absent or small /ga/-evoked MMN. Significant results from the correlation analyses support the co-morbidity of reading and auditory processing disorders. SIGNIFICANCE: Children with reading disorders are likely to have auditory processing disorders.

Acoustic Stimulation↗
PubMed2006

Efficacy of intrathecal adenosine for postoperative pain relief.

BACKGROUND AND OBJECTIVE: Adenosine, by intravenous and intrathecal routes, is known to alleviate various types of pain. However, the role of intrathecal adenosine in providing postoperative analgesia has not been confirmed. The aim of the present study was to evaluate the efficacy of intrathecal adenosine for postoperative pain relief, and to determine its role for pre-emptive analgesia. METHODS: Ninety ASA I and II females, undergoing elective abdominal hysterectomy, were randomly divided into three groups of 30 patients each. Patients in the 'early adenosine' group received intrathecal adenosine 1,000 microg, 30 min before induction of anaesthesia. Patients in the 'late adenosine' group received the same dose before reversal of neuromuscular blockade. Control patients did not receive any test drug. A balanced general anaesthesia technique was used in all patients. Pain intensity scores using a visual analogue scale, sedation scores, time to first rescue analgesic and total morphine requirement were recorded. RESULTS: There was no significant difference in pain intensity scores, sedation scores, total morphine requirements and time to first rescue analgesic among the three groups. CONCLUSION: Intrathecal adenosine 1,000 microg is not effective as an analgesic for postoperative pain relief, and there is no pre-emptive effect.

Adenosine↗
PubMed2006

The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations.

BACKGROUND: Parkinson's disease is a genetically complex disease with mixed mode of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR) gene, which is located in the PARK3 linkage region, was shown to modulate age of onset of Parkinson's disease in sibships from North America. OBJECTIVE: To make a thorough assessment of the SPR gene region in sporadic Parkinson's disease. METHODS: A linkage study in 122 European sibship families with five microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around the SPR gene region, and an association analysis in 340 sporadic cases of Parkinson's disease and 680 control subjects from Germany with 40 SNPs. Linkage was evaluated by non-parametric linkage scores and genotypic or haplotype association was tested by regression analysis, assuming different risk effect models. RESULTS: Significant LOD scores between 2 and 3 were obtained at the two SPR-flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR gene. We found the previously reported promoter SNP rs1876487 also significantly associated with age of onset in our sib pair families (p-value 0.02). One strong linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was observed. Within this LD block all 14 inter-correlated SNPs were significantly associated with Parkinson's disease affection status (p-value 0.004). CONCLUSIONS: DNA polymorphisms in a highly intercorrelated LD block, which includes the SPR gene, appear to be associated with both sporadic and familial Parkinson's disease. This confirms a previous study showing that SPR potentially modulates the onset of or risk for Parkinson's disease.

Age of Onset↗
PubMed2006

Echinacea extracts modulate the pattern of chemokine and cytokine secretion in rhinovirus-infected and uninfected epithelial cells.

Extracts of Echinacea purpurea are among the most widely used herbal medicines throughout Europe and North America for the prevention or treatment of common cold, coughs, bronchitis and other upper respiratory infections. Popular preparations include expressed juice from the aerial parts of the plant (which contain polysaccharides) and alcoholic tinctures from roots (containing caffeic acid derivatives and alkylamides). Since immune modulation has been reported for similar extracts, cytokine antibody arrays were used to investigate the changes in the pro-inflammatory cytokines and chemokines released from a cultured line of human bronchial epithelial cells exposed to Rhinovirus 14 and two different chemically characterized Echinacea extracts. Virus infection stimulated the release of at least 31 cytokine-related molecules, including several important chemokines known to attract inflammatory cells. Most of these effects were reversed by simultaneous exposure to either of the two Echinacea extracts, although the patterns of response were different for the two extracts. These results could explain the antiinflammatory properties of Echinacea extracts. Furthermore, a number of these cytokines were stimulated by the same Echinacea preparations in uninfected cells. These observations therefore provide support for the alleged beneficial uses of Echinacea extracts.

Cell Line, Transformed↗
PubMed2006

Echinacea extracts modulate the production of multiple transcription factors in uninfected cells and rhinovirus-infected cells.

Extracts of Echinacea purpurea are widely used for the prevention and treatment of common colds, coughs, bronchitis and other upper respiratory infections, many of which are caused by rhinoviruses (RVs). Recent reports have indicated that rhinoviruses can stimulate the release of various pro-inflammatory cytokines and chemokines from cultured nasal and bronchial human epithelial cells, and several transcription factors (TFs) have been implicated in this process. The effects of Echinacea treatment and rhinovirus infection on the activation of a range of transcription factors were evaluated by means of a protein/DNA array analysis. The BEAS-2B cell line was used as the model, and nuclear extracts of uninfected cells and rhinovirus-14 infected cells were examined with and without treatment with one of two chemically different Echinacea extracts. It was found that both Echinacea extracts increased the nuclear content of more than 30 transcription factors, including the 12 pro-inflammatory factors examined, such as NFkB, AP-1, AP-2 and STATs 1-6. Virus infection resulted in a more dramatic increase in these same TFs. However, when RV-infected cells were treated with either of the two Echinacea extracts, TF levels were reduced to low levels, although the pattern of the reductions was different for the two extracts. These results indicate that rhinovirus infection of epithelial cells, and treatment with Echinacea extracts, led to profound effects on numerous transcription factors, which could explain the previously observed modulation of secreted cytokines and chemokines, as well as other signaling pathways. In addition, the results could help to explain the beneficial effects of Echinacea consumption.

Cell Line↗
PubMed2006

Impact of initial antibiotic choice and delayed appropriate treatment on the outcome of Staphylococcus aureus bacteremia.

The study presented here investigated the impact of initial antibiotic choice (beta-lactams vs vancomycin) on the outcome of 342 patients with Staphylococcus aureus bacteremia (50.9% with methicillin-resistant isolates) encountered between 1 January 2002 and 30 June 2003. Initial antibiotics were inappropriate (beta-lactams) in 60 (34.5%) methicillin-resistant cases and suboptimal (vancomycin) in 62 (36.9%) methicillin-susceptible cases. Time to effective antibiotic therapy was longer in methicillin-resistant cases (25.5+/-28.6 vs 9.6+/-16.6 h; p<0.0005). All-cause in-hospital mortality was higher with inappropriate therapy (35.0 vs 20.9%; p=0.02). Initial vancomycin treatment was associated with a higher incidence of delayed clearance (>or=3 days) of methicillin-susceptible bacteremia (56.3 vs 37.0%; p=0.03). The results indicate inappropriate initial therapy is associated with higher in-hospital mortality and initial vancomycin may delay clearance.

Adult↗
PubMed2006

Tacrolimus (Pan Graf) as de novo therapy in renal transplant recipients in India.

The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus has only recently been available in India. We report an initial experience using tacrolimus as de novo therapy in a living related renal transplant program. Fifty-two consecutive recipients of living renal allografts were treated with tacrolimus, mycophenolate mofetil, or azathioprine and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10 to 12 ng/mL in the first 3 months, 8 to 10 ng/mL in the next 3 months, and 5 to 8 ng/mL thereafter. Any evidence of graft dysfunction was evaluated by graft biopsy. The effect of this regimen on the lipid profile as well as the incidence of posttransplant diabetes mellitus was evaluated in an Indian population. All patients were followed for periods ranging from 6 to 72 weeks (mean = 29 weeks). The incidence of acute rejection was 3.84%; 17.3% developed posttransplant diabetes mellitus. Graft and patient survivals at the current follow-up were 100% and 96.26%. In conclusion, tacrolimus is a safe and effective immunosuppressant in a living related renal transplant program.

Adolescent↗
PubMed2006

School-based interventions for childhood and adolescent obesity.

The purpose of this article was to review population-based interventions for preventing childhood obesity carried out in school settings published between 1999 and 2004. A total of 11 such interventions were found from USA and UK. The grade of the interventions was from kindergarten, primary grades, middle school to high school. Most of these interventions targeted both physical activity and nutrition behaviours although there were some interventions that focused on only one dimension such as TV watching or restricting drinking of carbonated drinks or increasing physical education time in the school. Most of the interventions were based on some behavioural theory and the most popular theory was social cognitive theory. Most of the interventions focused on individual level behaviour change approaches. Most of the interventions focused on short-term changes right after the intervention. On the whole, interventions resulted in modest changes in behaviours and mixed results with indicators of obesity. TV watching seems to be most modifiable behaviour, followed by physical activity and nutrition behaviours. The outcome measures such as lowered BMI (body mass index), triceps skin-fold thickness and waist circumference have not been measured by all studies. Recommendations for enhancing the effectiveness of school-based childhood obesity interventions are presented.

Adolescent↗
PubMed2006

Rapid fixation of brains: a viable alternative?

AIM: Recent events surrounding postmortem practices have necessitated several changes in the way necropsies are conducted both within the medicolegal and hospital settings. These changes have resulted in a striking reduction in the frequency of brain retention for neuropathological examination. Aberdeen Royal Infirmary, responding quickly to rising concerns among bereaved relatives regarding organ retention, instituted a change in practice regarding the examination of brains at necropsy as early as 2001. The new protocol involved subjecting the brain to rapid fixation using combined immersion and perfusion techniques. This allows return of the organ to the body without unreasonable delay to the funeral. In this article, we present the results of a retrospective audit comparing the efficacy of the new method against the conventional fixation protocol. METHODS: An equal number of postmortem brains were selected randomly from the year 1998 (following the usual fixation protocol), and from the year 2001 (following the new method). A three tier scoring system was devised to assess section and staining quality, and a single observer scored all the cases. RESULTS: No statistical difference was noted in the quality of sections prepared by rapid fixation those by conventional fixation. Furthermore, the rapid method was more frequently adequate for diagnosis (considering scores of 2 and 3 together) than the conventional method. CONCLUSION: Rapid fixation offers a viable alternative for detailed examination of brains at necropsy, without necessarily prolonging the retention of the organ.

Autopsy↗
PubMed2006

Microcatheter navigation and thrombolysis in acute symptomatic cervical internal carotid occlusion.

BACKGROUND AND PURPOSE: The treatment of acute stroke distal to an occluded cervical internal carotid artery (ICA) presents a challenge. We report our results of endovascular therapy in 7 patients presenting with acute symptomatic cervical ICA occlusion. PATIENTS AND TECHNIQUES: Among patients presenting with acute stroke at our institution from June 2001 to June 2005, we retrospectively identified 7 patients who underwent endovascular therapy of acute cervical ICA occlusion. The techniques used for vessel recanalization were analyzed. Postprocedure CT scans were reviewed for hemorrhage. The clinical outcomes were assessed by using the modified Rankin scale (mRS) with good outcomes assigned scores of < or =2. RESULTS: All 7 patients revealed cervical ICA occlusion, with additional intracranial thrombus in 6 of the 7 patients. In all patients, a guiding catheter was placed in the ipsilateral common carotid artery proximal to the occlusion and a microcatheter advanced through the ICA clot to deliver intra-arterial (IA) tissue plasminogen activator (in 6 patients, the microcatheter was also advanced intracranially for thrombolysis). Successful recanalization of the occluded ICA was achieved in 6 patients. In 3 patients, balloon angioplasty and stent placement of the cervical ICA was also performed. Follow-up CT in 6 patients showed small basal ganglia infarcts in 4, patchy parietal infarcts in one, and frontal lobe hematoma in one patient. At 1 month after the procedure, 5 patients had good clinical outcomes (mRS of 0 in 4 patients and 1 in one patient). CONCLUSION: Performance of IA thrombolysis by passing a microcatheter through an acutely occluded internal carotid artery may be an effective therapy in acute stroke.

Acute Disease↗
PubMed2006

Evaluation of enzymes in pyogenic and tuberculous meningitis.

OBJECTIVES: Lactic dehydrogenase (LDH), creatine kinase (CK) and gamma glutamyl transpeptidase (GGTP) were measured serially in cerebrospinal fluid (CSF) and serum in twenty five cases of meningitis and an equal number of age and sex matched healthy control subjects with an aim to find out their diagnostic and prognostic significance in cases of meningitis. METHODS: The enzymatic activity was measured serially (day 0, 4th and 7th) in cerebrospinal fluid (CSF) and serum in twenty-five cases of meningitis consisting of fifteen cases of pyogenic meningitis (PM) and ten of tuberculous meningitis (TBM) and an equal number of age and sex matched healthy control. The clinical details including the level of consciousness and neurological deficit were correlated with the enzymatic activity and prognosis. RESULTS: The levels of these enzymes were significantly elevated in all the cases of meningitis in serum as well as CSF as compared to control subjects. The activity was significantly higher in pyogenic than tuberculous meningitis (p<0.001) and it was higher in CSF than in serum (p<0.001). The maximum elevation in activity of GGTP and LDH were seen on the first day whereas CK was highest on 4th day and thereafter, the activity of all the enzymes declined in the majority of cases who had shown clinical improvement. However, in three cases of pyogenic and five cases of tuberculous meningitis, the enzymatic activity on subsequent estimation, increased serially. All these eight cases died. Further, the basal enzymatic activity in all these eight cases that died was higher as compared to those who survived. Of all the enzymes, CSF GGTP levels correlated best with the clinical picture. CONCLUSIONS: It is concluded that GGTP, CK and LDH were significantly elevated in cases of meningitis. It was not possible to differentiate the type of meningitis on the basis of enzymatic activity in any of them. However, it was possible to predict prognosis because higher basal activity and serial rise were associated with poor prognosis.

Adult↗