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Biomedical subjects

S Narayanan

Publications and source records attributed to S Narayanan.

At least 37 records · Page 2Linked to original sources
PubMed2002

Cryopreserved versus freshly isolated lymphocytes in human biomonitoring: endogenous and induced DNA damage, antioxidant status and repair capability.

Lymphocytes are routinely used in human biomonitoring to assess the potential toxic and cytoprotective effects of diet on both DNA damage and repair and, by implication, health. Logistically, samples may require to be cryopreserved and stored. How this affects cells used in human biomonitoring is often not considered. In this study we have evaluated the influence of cryopreservation on endogenous and induced DNA strand breakage, altered bases (oxidized purines, oxidized pyrimidines and misincorporated uracil), antioxidant capacity and DNA repair capability in human peripheral blood lymphocytes. Neither isolation nor freezing increased DNA strand breakage above endogenous levels found in freshly isolated human lymphocytes. Oxidized bases (both pyrimidines and purines) and misincorporated uracil, were similar for fresh and frozen lymphocytes. Fresh and frozen lymphocytes responded almost identically to hydrogen peroxide. Quercetin-mediated cytoprotection against hydrogen peroxide-induced strand breakage was maintained in cryopreserved lymphocytes after short-term (24 h) and longer term (2 months) storage compared with freshly isolated and treated cells. Hydrogen peroxide-induced DNA strand breakage was repaired in fresh lymphocytes. Cryopreserved lymphocytes were unable to repair oxidant-induced DNA strand breaks. Frozen human lymphocytes can therefore be successfully used for most aspects of DNA damage biomonitoring, but not for repair.

Antioxidants↗
PubMed2002

Iatrogenic causes of falls in hospitalised elderly patients: a case-control study.

OBJECTIVE: To explore risk factors associated with falls and to evaluate a strategy used by nurses to predict and prevent falls in a hospitalised cohort of elderly patients. DESIGN: A case-control study of risk factors for falls in hospital. SETTING: A district general hospital in the UK. SUBJECTS: Altogether 181 patients in an acute integrated medical unit who had fallen were matched for age with 181 patients in the next bed who had not fallen. RESULTS: It was found that 46% (84 of 181) of the fallers were taking one or more benzodiazepines compared with 27% (48 of 181) of the control patients (p<0.001). More fallers 20% (34 of 181) had their benzodiazepines prescribed during their current admission compared with 7% (13 of 181) of the control patients (p<0.001). Temazepam was the main benzodiazepine used by over 95% of cases and controls. Overall 25% (45 of 181) of the fallers had fallen before during the current admission. The logistic regression analysis showed that only a previous fall, benzodiazepine intake, and the need for maximum assistance were significant predictors of falling in hospital, odds ratios were 5.6 (95% confidence interval (CI) 2.7 to 11.6), 2.3 (95% CI 1.4 to 3.7), and 3.1 (95% CI 1.9 to 5.2) respectively. Most fallers had been identified at risk of falling (125; 69%) by ward staff and in 113 (90%) of those preventive measures had been undertaken. Falls were least likely to occur during visiting hours with a peak incidence during night-time. CONCLUSION: There is a need for evidenced based successful fall prevention strategies but our study also reinforces an urgent public health message that an alternative to benzodiazepines should be sought for night sedation for older patients.

Accidental Falls↗
PubMed2001

Regiospecific synthesis of 2,3-disubstituted-L-histidines and histamines.

Regiospecific synthesis of 2,3-disubstituted-L-histidines and 2,3-disubstituted histamines starting from L-histidine methyl ester and histamine is reported. The key step involves homolytic free radical alkylation via silver catalyzed oxidative decarboxylation of alkylcarboxylic acids with ammonium persulfate.

Alkylation↗
PubMed2001

Insight into patient dissatisfaction with asthma treatment.

BACKGROUND: Measures of patient satisfaction or dissatisfaction with treatment are increasingly being used as indicators of quality of care. As these measures become more widely used, it is important to know if patient dissatisfaction is associated with important processes or outcomes of medical care. METHODS: Survey of patient-reported asthma management issues using the Asthma Therapy Assessment Questionnaire in a large health maintenance organization in the Pacific Northwest. Associations between patient dissatisfaction with asthma treatment and patient-reported measures of asthma control, patient-provider communication, and belief in asthma medications (self-efficacy) were examined. RESULTS: Of the 5181 adult members with asthma enrolled in the health maintenance organization, 30% indicated dissatisfaction with current treatment. Dissatisfaction was higher among patients with a higher number of asthma control problems, patient-provider communication problems, or belief in medication problems (eg, failure to believe their medications are useful and inability to take asthma medications as directed). The odds of dissatisfaction with treatment were 2.8 (95% confidence interval [CI], 2.4-3.3; P<.001) for asthma control problems, 2.0 (95% CI, 1.6-2.6; P<.001) for communication problems, and 8.0 (95% CI, 6.7-9.5; P<.001) for belief in medication problems compared with patients without these perceived problems. CONCLUSION: Patient dissatisfaction with treatment may be related to important asthma disease management issues.

Adult↗
PubMed2001

Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability.

OBJECTIVE: To assess axonal damage and its contribution to disability at different stages of multiple sclerosis (MS). BACKGROUND: Recent in vivo imaging and in situ pathologic studies have demonstrated that substantial axonal damage accompanies the inflammatory lesions of MS. However, the relation of axonal damage to the duration of MS and its contribution to disability at different stages of the disease remain poorly defined. DESIGN: We performed proton magnetic resonance spectroscopic imaging in 88 patients with a wide range of clinical disability and disease duration to measure N-acetylaspartate (NAA, an index of axonal integrity) relative to creatine (Cr) in a large central brain volume that included mostly normal-appearing white matter on magnetic resonance imaging. RESULTS: We observed that the NAA/Cr values were abnormally low in the early stages of MS, even before significant disability (measured using the Expanded Disability Status Scale [EDSS]) was evident clinically, and declined more rapidly with respect to EDSS at lower than at higher EDSS scores (P<.001). The correlation of NAA/Cr values with EDSS score was significantly (P<.03) stronger in patients with mild disability (EDSS score <5, Spearman rank order correlation = -0.54, P<.001) than in patients with more severe disability (EDSS score >/=5, Spearman rank order correlation = -0.1, P<.9). When similar analyses were performed in patients with MS grouped for duration of disease, the subgroup with early disease duration (<5 years) also showed central brain NAA/Cr resonance intensity ratios significantly lower than healthy controls (P<.001). CONCLUSION: Cerebral axonal damage begins and contributes to disability from the earliest stages of the disease.

Adult↗
PubMed2001

In vitro studies on antilithiatic activity of seeds of Dolichos biflorus Linn. and rhizomes of Bergenia ligulata Wall.

Soxhlet extracts of seeds of Dolichos biflorus and rhizomes of Bergenia ligulata were tested for their in vitro antilithiatic/anticalcification activity by the homogeneous precipitation method. The extracts were compared with an aqueous extract of cystone (a marketed preparation) for their activities. Also a combination of the extracts of the two plants was tested. Extracts of Dolichus biflorus showed activity almost equivalent to cystone while Bergenia ligulata showed less activity and the combination was not as active as the individual extracts.

Calcium Oxalate↗
PubMed2001

Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b.

Patients with multiple sclerosis (MS) can benefit from treatment with interferon beta-1b. However, the mechanisms of action of this drug are incompletely understood and effects of interferon beta-lb on axonal injury are not known. A measure of axonal injury can be obtained in vivo using magnetic resonance spectroscopy to quantify the resonance intensity of the neuronal marker, N-acetylaspartate (NAA). In a small pilot study, we performed combined magnetic resonance imaging and magnetic resonance spectroscopic imaging on 10 patients with relapsing-remitting MS before and 1 year after starting treatment with subcutaneous interferon beta-lb. Resonance intensities of NAA relative to creatine (Cr) were measured in a large, central brain volume. These measurements were compared with those made in a group of 6 untreated patients selected to have a similar range of scores on the Expanded Disability Status Scale and mean NAA/Cr at baseline. NAA/Cr in the treated group [2.74 (0.16), mean (SD)] showed an increase of 5.5% 12 months after the start of therapy [2.89 (0.24),p = 0.05], while NAA/Cr in the untreated group decreased, but not significantly [2.76 (0.1) at baseline, 2.65 (0.14) at 12 months,p > 0.1]. NAA/Cr had become significantly higher in the treated group at 12 months than in the untreated group (p = 0.03). Our data suggest that, in addition to losing axons, patients with chronic multiple sclerosis suffer from chronic, sublethal axonal injury that is at least partially reversible with interferon beta-lb therapy.

Adjuvants, Immunologic↗
PubMed2001

Lysis of whole blood in vitro causes DNA strand breaks in human lymphocytes.

DNA damage in lymphocytes, as measured by alkaline single cell gel electrophoresis (pH 12.7), is greatly increased by the concurrent lysis of whole blood in both freshly isolated samples and in PHA-stimulated cultures over a period of 7 days. Further, there is a marked progressive increase in DNA damage with time in PHA-stimulated lymphocytes cultured in whole blood even when the lymphocytes are separated before analysis; no such increase is seen in lymphocytes cultured alone. This indicates that there are components in whole blood that can cause DNA damage in lymphocytes, with granulocytes and lysis of red blood cells likely candidates. The DNA damage is greatly reduced in granulocyte-depleted whole blood cultures, but even in these significant increases are seen at later sampling times. Consequently, careful sample preparation is of paramount importance if the Comet assay is to be successfully used to assess DNA damage in human peripheral blood lymphocytes. Further, the progressive increase in DNA damage in whole blood cultures may influence other methods using lymphocytes for population biomonitoring and may be significant for in vitro genotoxicity testing.

Blood Preservation↗
PubMed2001

Leishmaniasis diagnosed by liver biopsy: management of two atypical cases.

Two patients presenting with pyrexia of unknown origin were diagnosed as having visceral leishmaniasis based on the presence of Leishmania donovani bodies in liver tissue. Of particular interest is that these two case reports suggest that in patients with pyrexia of unknown origin, a liver biopsy for L. donovani bodies should be considered even when several months have passed since leaving an endemic area, when splenomegaly is absent, when bone marrow examination and serology are not diagnostic, and even when abnormal coagulation necessitates a transjugular liver biopsy.

Adult↗
PubMed2001

Evaluation of PCR using TRC(4) and IS6110 primers in detection of tuberculous meningitis.

We have evaluated a new set of primers (TRC(4)) in comparison with the IS6110 primers commonly used in PCR to detect tuberculous meningitis among children. The levels of concordance between the results of IS6110 PCR and TRC(4) PCR with cerebrospinal fluid specimens from patients with clinically confirmed tuberculous meningitis were 80 and 86%, respectively. Results with the two primer sets were concordant for 55 positive and 22 negative specimens (n = 98). We conclude that the sensitivity of PCR can be increased by using both IS6110 and TRC(4) primers.

Cerebrospinal Fluid↗
PubMed2001

Mutations in the rpoB gene of multidrug-resistant Mycobacterium tuberculosis clinical isolates from India.

Mutations in the 81-bp rifampin resistance-determining region (RRDR) of the rpoB gene were analyzed by DNA sequencing of 50 Mycobacterium tuberculosis clinical isolates (44 resistant and 6 sensitive) from various parts of India. Fifty-three mutations of 18 different kinds, 17 point mutations and one deletion, were observed in 43 of 44 resistant isolates. Three novel mutations and three new alleles within the RRDR, along with two novel mutations outside the RRDR, are reported in this study.

Amino Acid Sequence↗
PubMed2001

Characterization of endothelium-derived hyperpolarizing factor in the human forearm microcirculation.

The identity of endothelium-dependent hyperpolarizing factor (EDHF) in the human circulation remains controversial. We investigated whether EDHF contributes to endothelium-dependent vasomotion in the forearm microvasculature by studying the effect of K+ and miconazole, an inhibitor of cytochrome P-450, on the response to bradykinin in healthy human subjects. Study drugs were infused intra-arterially, and forearm blood flow was measured using strain-gauge plethysmography. Infusion of KCl (0.33 mmol/min) into the brachial artery caused baseline vasodilation and inhibited the vasodilator response to bradykinin, but not to sodium nitroprusside. Thus the incremental vasodilation induced by bradykinin was reduced from 14.3 +/- 2 to 7.1 +/- 2 ml x min(-1) x 100 g(-1) (P < 0.001) after KCl infusion. A similar inhibition of the bradykinin (P = 0.014), but not the sodium nitroprusside (not significant), response was observed with KCl after the study was repeated during preconstriction with phenylephrine to restore resting blood flow to basal values after KCl. Miconazole (0.125 mg/min) did not inhibit endothelium-dependent or -independent responses to ACh and sodium nitroprusside, respectively. However, after inhibition of cyclooxygenase and nitric oxide synthase with aspirin and NG-monomethyl-L-arginine, the forearm blood flow response to bradykinin (P = 0.003), but not to sodium nitroprusside (not significant), was significantly suppressed by miconazole. Thus nitric oxide- and prostaglandin-independent, bradykinin-mediated forearm vasodilation is suppressed by high intravascular K+ concentrations, indicating a contribution of EDHF. In the human forearm microvasculature, EDHF appears to be a cytochrome P-450 derivative, possibly an epoxyeicosatrienoic acid.

Administration, Oral↗
PubMed2000

Transcriptional analysis of inducible acetamidase gene of Mycobacterium smegmatis.

Isolation and analysis of strong and regulatable promoters of mycobacteria should be useful tools to aid the expression of cloned genes in mycobacteria. In the present study, we have mapped the transcriptional start site of the inducible acetamidase gene of Mycobacterium smegmatis and studied the mechanism of its regulation. Northern blot, reverse transcription-PCR and primer extension analysis studies were used to determine the position of the promoter.

Amidohydrolases↗
PubMed2000

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity.

OBJECTIVES: We investigated whether the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene modulates vasomotor tone and endothelial function. BACKGROUND: The deletion allele of the ACE I/D polymorphism has been associated with increased incidence of cardiovascular pathology. The risk is synergistically increased in patients who also possess the C allele at position 1,166 of the angiotensin type I (AT1) receptor gene. METHODS: In 177 patients with coronary atherosclerosis or its risk factors, we investigated endothelial function with intracoronary acetylcholine (ACH), endothelium-independent smooth muscle function with sodium nitroprusside (SNP) and basal nitric oxide activity with L-NG monomethyl arginine. RESULTS: Compared with ACE II genotype, patients with the ACE DD genotype had lower coronary microvascular and epicardial responses with SNP (coronary blood flow increase 196 +/- 26% vs. 121 +/- 11%, p = 0.003, and diameter increase 21.9 +/- 2% vs. 17 +/- 1%, p = 0.03, ACE II vs. DD, respectively). L-NG monomethyl arginine induced greater constriction in patients with the ACE DD compared with ACE II genotype (coronary blood flow -10 +/- 4% vs. 11 +/- 5%, p = 0.003, ACE DD vs. II and diameter constriction -6.3 +/- 1.2% vs. -1.9 +/- 1.2%, p = 0.01, respectively, in patients with atherosclerosis). No difference in ACH-mediated vasomotion was detected between the three ACE genotypes. The AT1 receptor polymorphism did not influence responses to either SNP or ACH. CONCLUSIONS: Patients possessing the D allele of the ACE gene have increased vascular smooth muscle tone. The enhanced tone appears to be counterbalanced by an increase in basal nitric oxide activity in patients with atherosclerosis.

Acetylcholine↗
PubMed2000

Insertion-deletion polymorphism of the ACE gene modulates reversibility of endothelial dysfunction with ACE inhibition.

BACKGROUND: The aim of this study was to examine whether angiotensin-converting enzyme (ACE) inhibition improves coronary endothelial dysfunction in patients with atherosclerosis and its risk factors and whether this was related to the ACE insertion-deletion (I/D) polymorphism. METHODS AND RESULTS: In 56 patients with atherosclerosis or its risk factors, we studied endothelium-dependent responses with acetylcholine and endothelium-independent function with sodium nitroprusside, before and after ACE inhibition with enalaprilat. Enalaprilat did not alter either resting coronary tone or vasodilation with sodium nitroprusside. However, it potentiated the coronary microvascular and epicardial responses with acetylcholine; coronary blood flow increased from 82+/-7 to 90+/-8 mL/min (P=0.05) after enalaprilat. Patients with depressed endothelial function (P<0.001) and those with ACE DD or ID genotypes (P=0.002) but not those homozygous for the I allele had the greatest improvement by multivariate analysis. Similarly, acetylcholine-mediated epicardial vasomotion improved in segments that initially constricted (endothelial dysfunction): from -10.1+/-1% to -1.4+/-2% (P<0.001) after enalaprilat. No augmentation was observed in segments that dilated (normal endothelial dysfunction) with acetylcholine. Patients with the D allele, hypercholesterolemia, and smokers (all P<0.05) had greater improvement. CONCLUSIONS: Acute ACE inhibition improves coronary epicardial and microvascular endothelium-dependent vasomotion in patients with atherosclerosis or its risk factors who have endothelial dysfunction and presence of the D allele.

Acetylcholine↗
PubMed2000

Relating axonal injury to functional recovery in MS.

A patient was followed after the new onset of hemiparesis from relapse of MS with serial MR spectroscopy and functional MRI. The association of clinical improvement with recovery of N-acetylaspartate, a marker of neuronal integrity, and progressive reduction of abnormally large functional MRI cortical activation with movement demonstrates that dynamic reorganization of the motor cortex accompanies remission of MS.

Adult↗
PubMed2000

DNA stability and genomic methylation status in colonocytes isolated from methyl-donor-deficient rats.

BACKGROUND: Epidemiological studies report an inverse relationship between intake of the B vitamin folic acid and colon cancer. Folate is important for DNA synthesis and repair. Moreover, the production of S-adenosylmethionine (SAM), essential for normal DNA methylation and gene expression, is dependent on folic acid. Folate deficiency may increase the risk of malignant transformation by perturbing these pathways. AIMS OF THE STUDY: The principal aim of this study was to determine the effects of folate deficiency on DNA stability and DNA methylation in rat colonocytes in vivo. As the metabolic pathways of folate and other dietary methyl donors are closely linked, the effects of methionine and choline deficiency were also evaluated. METHODS: Male Hooded-Lister rats were fed a diet deficient in folic acid, or in methionine and choline, or in folate, methionine and choline for 10 weeks. DNA strand breakage and misincorporated uracil were determined in isolated colonocytes using alkaline single cell gel electrophoresis. Global DNA methylation was measured in colonic scrapings. Folate was measured in plasma, erythrocyte and liver samples. RESULTS: Methyl donor deficiency induced DNA strand breakage in colonocytes isolated from all experimental groups. Uracil levels in colonocyte DNA remained unchanged compared with controls. DNA methylation was unaffected either by folate and/or methionine and choline depletion. Rats fed a folate-deficient diet had less folate in plasma, red blood cells and liver than controls. CONCLUSIONS: Folate and methyl deficiency in vivo primarily affects DNA stability in isolated colonocytes of rats, without affecting overall DNA methylation.

Animals↗