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P Mathur

Publications and source records attributed to P Mathur.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis, crystal structure, spectral studies, and catechol oxidase activity of trigonal bipyramidal Cu(II) complexes derived from a tetradentate diamide bisbenzimidazole ligand.

A new benzimidazole-based diamide ligand-N,N'-bis(glycine-2- benzimidazolyl)hexanediamide (GBHA)-has been synthesized and utilized to prepare Cu(II) complexes of general composition [Cu(GBHA)X]X, where X is an exogenous anionic ligand (X = Cl(-), NO(3)(-), SCN(-)). The X-ray structure of one of the complexes, [Cu(GBHA)Cl]Cl.H(2)O.CH(3)OH, has been obtained. The compound crystallizes in the monoclinic space group C2/c with unit cell dimensions a = 26.464(3) A, b = 10.2210(8) A, c = 20.444(2) A, alpha = 90 degrees, beta = 106.554(7) degrees, gamma = 90 degrees, V= 5300.7(9) A(3), and Z = 8. To the best of our knowledge, the [Cu(GBHA)Cl]Cl.H(2)O.CH(3)OH complex is the first structurally characterized mononuclear trigonal bipyramidal copper(II) bisbenzimidazole diamide complex having coordinated amide carbonyl oxygen. The coordination geometry around the Cu(II) ion is distorted trigonal bipyramidal (tau = 0.59). Two carbonyl oxygen atoms and a chlorine atom form the equatorial plane, while the two benzimidazole imine nitrogen atoms occupy the axial positions. The geometry of the Cu(II) center in the solid state is not preserved in DMSO solution, changing to square pyramidal, as suggested by the low-temperature EPR data g( parallel) > g( perpendicular) > 2.0023. All the complexes display a quasi-reversible redox wave due to the Cu(II)/Cu(I) reduction process. E(1/2) values shift anodically from Cl(-) < NO(3)(-) < SCN(-), indicating that the bound Cl(-) ion stabilizes the Cu(II) ion while the N-bonded SCN(-) ion destabilizes the Cu(II) state in the complex. When calculated against NHE, the redox potentials turn out to be quite positive as compared to other copper(II) benzimidazole bound complexes (Nakao, Y.; Onoda, M.; Sakurai, T.; Nakahara, A.; Kinoshita, L.; Ooi, S. Inorg. Chim. Acta 1988, 151, 55. Addison, A. W.; Hendricks, H. M. J.; Reedijk, J.; Thompson, L. K. Inorg. Chem. 1981, 20 (1), 103. Sivagnanam, U.; Palaniandavar, M. J. Chem. Soc., Dalton Trans. 1994, 2277. Palaniandavar, M.; Pandiyan, T.; Laxminarayan, M.; Manohar, H. J. Chem. Soc., Dalton Trans. 1995, 457. Sakurai, T.; Oi, H.; Nakahara, A. Inorg. Chim. Acta 1984, 92, 131). It is therefore concluded that binding of amide carbonyl oxygen destabilizes the Cu(II) state. The complex [Cu(II)(GBHA)(NO(3))](NO(3)) could be successfully reduced by the addition of dihydroxybenzenes to the corresponding [Cu(I)(GBHA)](NO(3)). (1)H NMR of the reduced complex shows slightly broadened and shifted (1)H signals. The reduction of the Cu(II) complex presumably occurs with the corresponding 2e(-) oxidation of the quinol to quinone. Such a conversion is reminiscent of the functioning of a copper-containing catechol oxidase from sweet potatoes and the met form of the enzyme tyrosinase.

Amides↗
PubMed2001

Relationship between tumour vascularity and circulating cancer cells in patients with colorectal carcinoma.

BACKGROUND: Colorectal cancer vascularity correlates with risk of metastasis. Greater tumour vascularity may increase haematogenous dissemination by providing a larger vessel area for tumour cell invasion into the circulation. We assessed whether the prevalence of tumour cells in the circulation of colorectal carcinoma patients (CTC) increased with tumour vascularity. METHODS: Pre-operative blood samples were assessed for circulating tumour cells using RT-PCR for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) mRNA. Vessel count and volume were morphometrically assessed from tumour biopsies after vasculature staining. RESULTS: Thirty-three colorectal cancer patients (M:F, 20:13; mean age 66 years, SD 11 years) were studied. One or more blood samples were RT-PCR positive for either CEA or CK20 mRNA or both, in 28 (85%) patients. There were no significant differences in the prevalence of RT-PCR positive patients between high and low tumour vascularity groups, or in tumour vessel counts or volume in RT-PCR positive compared with negative patients. CONCLUSIONS: These results do not support vascularity related variation in access of tumour cells to the circulation as an explanation for the correlation between tumour vasculature and metastasis. Tumour vascularity and metastatic potential may be linked phenotypes rather than cause and effect.

Aged↗
PubMed2001

Sero-epidemiology of hepatitis E virus (HEV) in urban and rural children of North India.

OBJECTIVE: To estimate the prevalence of anti-HEV IgG and IgM antibodies to ORF3 peptide of Hepatitis E virus genome in an age stratified urban and rural population of children. DESIGN: Cross sectional survey. SETTING: Pediatric out-patient clinics in a tertiary hospital and a rural dispensary. METHODS: Study subjects between 6 months and 10 years with minor, non-hepatic illnesses were recruited for the study from March to December 1996. Baseline demographic details, drinking water source, sewage disposal methods, reasons for attending the hospital, histories of parenteral exposure in the past 12 months and acute hepatitis in the subjects and the family in the previous six months were obtained. Serum anti-HEV IgG antibodies were screened in all subjects, and in those who were positive, anti-HEV IgM antibodies were assayed as an indicator of recent infection. Serum aminotransferase (ALT) was estimated in those who were anti-HEV IgM antibody positive. RESULT: Out of 2160 subjects recruited, 2070 samples could be screened for anti-HEV IgG antibodies. In the urban population (n = 1065) anti-HEV IgG antibodies were detected in 306 subjects (28.7%; 95% CI 26.0-31.6) and of these 131 (42.8%; 95%CI 37.2-48.6) were anti-HEV IgM antibody positive. Amongst 1005 rural children, anti-HEV IgG antibodies were present in 239 (23.8%; 95% CI 21.1-26.4) and IgM antibodies in 113 (47.3%; 95% CI 40.9-53.7) children. The antibodies were present since the first year of age till 10 years of age and, increased with advancing age. Serum transaminases were raised in 7.5% (9/120) and 5.5% (5/88) of subjects with anti-HEV IgM antibodies in urban and rural centers respectively. Overall the seroprevalence of IgG antibodies against HEV were significantly more in urban as compared to that in rural subjects (p = 0.011). However, proportion of children with anti-HEV IgG carrying IgM antibodies was similar in the two study groups (p = 0.298). A model for estimating expected prevalence of anti-HEV IgG antibodies was developed. The observed antibody prevalence in both urban and rural subjects at each age interval after 48 months was less as compared to the expected levels and this gap increased with advancing age categories. It appeared that there was a decay of HEV antibodies with time. CONCLUSIONS: Children are susceptible to HEV infection since early infancy. The probability of exposure to HEV during childhood was higher in urban than rural population. Seropositivity to HEV antibodies increased by over 2 times beyond 4 years of age as compared to younger age. Anti-HEV IgG antibodies appear to wean off with increasing age.

Antibodies, Viral↗
PubMed2000

Randomized trial of regional plus systemic fluorinated pyrimidine compared with systemic fluorinated pyrimidine in treatment of colorectal liver metastases.

AIM: We report a prospective randomized study comparing survival, response and toxicity in colorectal liver metastasis (CLM) patients treated by either hepatic arterial floxuridine (HAI) plus continuous systemic fluorouracil/folinic acid or systemic fluorouracil/folinic acid. METHODS: Eighty-four CLM patients received either HAI plus systemic fluorouracil/folinic acid or systemic fluorouracil/ folinic acid. RESULTS: Significantly more HAI plus systemic, compared with systemic only, patients developed WHO grade 3 or 4 diarrhoea (P=0.004), but significant quality of life differences were not detected. Liver metastasis partial response at 4 months after randomization was significantly greater (P=0.003) in HAI plus systemic (13/29, 45%) compared with systemic only (7/30, 23%) patients. There was no significant difference between groups in the proportion of patients who died from extrahepatic disease progression, or in survival. CONCLUSION: Combining regional with systemic fluorinated pyrimidines did not improve survival compared with systemic fluorinated pyrimidine.

Aged↗
PubMed2000

Comparison of various calpain inhibitors in reduction of light scattering, protein precipitation and nuclear cataract in vitro.

PURPOSE: To compare effects of calpain inhibitors on in vitro light-scattering in rat lens soluble protein and calcium-ionophore (A23187)-induced cataract formation in cultured rat lenses. METHODS: Rat lens soluble protein was hydrolyzed for 24 hours by activation of endogenous lens calpain. Ten calpain inhibitors were tested in this model at 10 and 25 microM concentration. As an index of protein precipitation, light scattering was measured daily at 405 nm for 8 days. Lens proteins were analyzed by isoelectric-focussing. Subsequently, rat lenses were cultured for 5 days with 10 microM A23187. Calpain inhibitors (SJA6017, MDL28170, AK295 and PD150606), which inhibited light-scattering were tested at 100 microM concentration in this model. Cataract evaluation, isoelectric-focussing and calcium determinations were performed. RESULTS: At 25 microM concentration AK295, SJA6017, E-64, PD-150606 and MDL28170 produced greater than 25% inhibition of light-scattering. Isoelectric-focussing revealed that addition of Ca(2+) produced characteristic crystallin proteolysis and aggregation patterns. AK295, SJA6017, MDL28170 and E64c prevented these changes. Lenses cultured in A23187 exhibited nuclear cataract, elevated calcium and proteolysis and aggregation of crystallins. Co-culture with SJA6017, MDL28170 and E64c reduced A23187-induced nuclear opacities, proteolysis and aggregation of crystallins without affecting increased total calcium. CONCLUSIONS: Endogenous calpain-activation model and A23187-induced cataract model can be used sequentially to screen calpain inhibitors for potential anti-cataract activity. Proteolytic changes in lens cortex after exposure to A23187 are also due to calpain activation. AK295, SJA6017 and MDL28170 possess efficacy against calcium-induced models of rodent cataracts. Use of calpain inhibitors represents a promising approach to cataract therapy.

Animals↗
PubMed2000

Bronchoscopy training: current fellows' experiences and some concerns for the future.

OBJECTIVES: To determine current pulmonary fellows' perspectives about their bronchoscopy training. DESIGN: Survey of 59 pulmonary fellows selected by training program directors to represent their institutions. SETTING: "Hands-on" symposium at the CHEST 1998 annual meeting, Toronto, Canada. RESULTS: Fellows reported a mean (+/- SD) of 2.4+/- 0.7 years of training, estimated they had performed 77.7+/-34 bronchoscopies per year, and had generally high estimates of their bronchoscopy proficiency and training. Proficiency estimates correlated with number of procedures cited (r = 0.43, p = 0.001) or level of fellowship training (r = 0.40, p = 0.002). Proficiency ratings (r = 0.63, p = 0.0001) and procedure numbers (r = 0.45, p-0. 0004) correlated with program quality ratings. Approaches to bronchoscopy instruction varied, and most often consisted of one-to-one instruction by faculty (92.5%), lecture-based instruction (74.6%), and case discussions (72.9%). Use of bronchoscopy lectures (p = 0.008) or videos (p = 0.057) were associated with higher self-estimates of proficiency, whereas use of lectures (p = 0.002), a bronchoscopy text (p = 0.009), and one-on-one instruction (p = 0.05) were associated with more highly ranked programs. Major components of training varied among programs. Although most fellows had received instruction encompassed in basic bronchoscopy, fewer had experience with bronchoscopic intubation (71.2%), transbronchial needle aspiration (72.9%), quantitative bacterial culture (64.4%), stent placement (27.1%), laser photocoagulation (25.4%), or cryotherapy (6.8%). Components of bronchoscopy experiences correlated with fellows' estimates of bronchoscopy proficiency and program quality. CONCLUSIONS: Approaches to bronchoscopy instruction and the components of bronchoscopy experiences vary considerably among institutions and are associated with pulmonary fellows' perceptions of bronchoscopy proficiency and training program quality. Definition of an optimum bronchoscopy curriculum remains necessary.

Bronchoscopy↗
PubMed1998

Comparative analgesic activity of nimesulide and diclofenac by intramuscular route: correlation with pharmacokinetic profile of nimesulide.

Nimesulide, a selective cyclooxygenase-2-inhibiting nonsteroidal anti-inflammatory drug, has been found to be a potent anti-inflammatory and analgesic drug, when administered orally, rectally or topically. The aim of the present study was to evaluate the comparative efficacy of intramuscularly injected nimesulide with that of diclofenac and to elucidate the pharmacokinetic profile of this formulation. Swiss albino mice were used in the experiment. Analgesic activity was tested using the acetic acid writhing test and the tail-flick latency test. Plasma levels of nimesulide and its active metabolite, hydroxynimesulide, were determined by a HPLC method. A peak analgesic effect was observed between 60 and 120 min, while Cmax (10.6 +/- 3.8 micrograms/ml) of nimesulide was reached at 60 min (Tmax). Analgesia was induced within 15 min of administration of nimesulide and was significantly higher than that of diclofenac at 90 and 120 min posttreatment in the writhing reflex and at 60 and 90 min in the tail-flick latency test. The results indicate that intramuscularly injected nimesulide may be an alternative mode of administration in uncooperative patients or when immediate analgesic effects are warranted.

Acetic Acid↗
PubMed1998

Comparative analgesic efficacy of nimesulide and diclofenac gels after topical application on the skin.

Nimesulide is a newer non-steroidal anti-inflammatory drug (NSAID) with selective cyclo-oxygenase (COX)-2 blocking property and has demonstrated a potent analgesic and anti-inflammatory activity on oral and rectal administration. However, the Cmax through both these routes is reached only after 3 h of administration. Dose-dependent gastrointestinal side effects also limit the concentration of drug that can be achieved at the site of inflammation when administered through these routes. The present study was conducted to evaluate the antinociception induced by a new gel formulation of nimesulide when applied on the skin. Efficacy of topical nimesulide gel 1% (w/w) was studied on mice in the acetic-acid-induced writhing, tail flick latency (TFL) test and formalin-induced pain models. The antinociceptive effect of nimesulide was compared to diclofenac gel (1% w/w). Both the drugs induced dose-dependent analgesia with peak effect seen between 90 and 120 min after treatment. Greater antinociceptive effect (expressed as percent maximum possible effect) was seen in the writhing test than in the TFL test, indicating the peripheral action of both drugs. Nimesulide evidenced significant protection in the first phase of formalin-induced pain indicating modulation of peripheral nociceptors unlike other conventional NSAIDs. This suggests that COX-2 may be a primary contributor to afferent evoked increase in prostanoid-mediated changes in pain processing. Antinociception seen following drug application on the skin was lower than that seen on intraperitoneal administration, indicating localised action following topical application. The findings of the present study suggest that the transgel formulation of nimesulide provides significant analgesic activity when applied topically.

Administration, Topical↗
PubMed1998

The circadian pattern of ischaemic heart disease events in Indian population.

A circadian variation of the onset of almost all ischaemic heart disease (IHD) manifestations with an increased incidence between 6:00 a.m. to 12:00 noon has been reported in several publications during the last decade. This study included 605 patients of various IHD subgroups, i.e., acute Q-wave myocardial infarction (n = 174), unstable angina (n = 266), non-Q myocardial infarction (n = 67), acute pulmonary oedema (n = 35) and sudden cardiac death (n = 63) proven to be due to IHD by electrocardiogram and/or autopsy. In overall, 33.55% (p < 0.0001) of patients had the IHD events with an increased frequency between 6:00 a.m. To 12:00 noon (2nd quarter of the day.) The distribution in the remaining, 1st 3rd and 4th quarters was 22.64%, 20.99% and 22.80%, respectively. Similar circadian rhythm (2nd quarter peak) was seen in males (n = 486), females (n = 119), patients ages < 60 years (n = 388), patients without past history of IHD (n = 434) and in those not on any medications (n = 359). However in patients with past history of IHD and diabetics, the circadian distribution did not differ from the random and the cases were distributed almost evenly in all the four quarters of the day. 39.08% of all the acute Q wave myocardial infarction (A-QMI), 33.45% of unstable angina and 36.5% of sudden cardiac deaths also occurred between 6:00 a.m. and 12:00 noon. However 51.42% cases of acute pulmonary oedema were encountered in the 4th quarter of the day and patients with non Q-myocardial infarction (non-QMI) did not show any particular pattern in relation to circadian rhythm. Thus it was inferred that in Indian population too the circadian pattern of IHD manifestations are similar to other population studies and morning appears to be the time, when the triggers (transient precipitating risk factors) that lead to these events are likely to be prominent. Study of these triggers and/or early morning pathophysiological changes may go a long way in understanding ischaemic heart disease and suggesting possible means of prevention.

Angina Pectoris↗
PubMed1998

The use of rectosigmoid stents in the management of acute large bowel obstruction.

The management of the acutely obstructed colon is controversial. Initial decompression of the bowel is still favoured by many surgeons, but the resulting colostomy has significant morbidity and mortality. Instead, stenting of the obstruction would permit defunctioning of the bowel, without the need for surgery and stoma formation. In this study we present our experience of the use of stents in the initial management of six patients with acute and sub-acute large bowel obstruction.

Acute Disease↗
PubMed1997

Cytosine methylation enhances DNA damage produced by groove binding and intercalating enediynes: studies with esperamicins A1 and C.

Methylation of the C5 position of cytosine in CG dinucleotides represents an important element in the control of gene expression in eukaryotic cells. This major groove modification of DNA causes changes in DNA conformation that are recognized by DNA-binding proteins and DNA-damaging chemicals. We have observed that CG methylation affects the DNA damage produced by the enediyne esperamicin A1 and its analog lacking the intercalating anthranilate, esperamicin C. Fragments of the human phosphoglycerate kinase gene (PGK1) and the plasmid pUC19 were methylated with SssI methylase and subjected to damage by esperamicins A1 and C. Damage produced by esperamicin A1 was enhanced 1.5-2-fold near a single CG sequence at position -101 in PGK1 and in a region containing several methylated CG dinucleotides between positions -120 and -131. Esperamicin C-induced damage was enhanced to a similar degree in PGK1 but only at the site that contained multiple CG dinucleotides. There was enhancement of damage for both drugs in the pUC19 fragment at several sites near CG sequences. Analysis of the chemistry of esperamicin-induced DNA damage suggests that cytosine methylation does not affect the identity of drug-abstracted hydrogen atoms. The damage chemistry was also used to identify the DNA binding orientation of the esperamicins. The anthranilate of esperamicin A1 is predicted to intercalate in a CT step four base pairs in a 3'-direction to the CG sequence at -101 in PGK1 and in a CG dinucleotide at the site containing multiple CGs (positions -120 to -131). These observations are consistent with other studies that indicate a long range effect of cytosine methylation on DNA conformation.

5-Methylcytosine↗
PubMed1997

Endoscopic ultrasonography, fine-needle aspiration biopsy guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small-cell lung cancer: a comparison study.

BACKGROUND: Current methods for detecting mediastinal lymph node involvement with non-small-cell lung cancer can be inaccurate and are often invasive and expensive. OBJECTIVE: To assess the utility of endoscopic ultrasonography, fine-needle aspiration biopsy guided by endoscopic ultrasonography, and computed tomography for the detection of metastases to the posterior mediastinal lymph nodes in non-small-cell lung cancer. DESIGN: Prospective preoperative evaluation of the diagnostic operating characteristics of these procedures. SETTING: Referral-based academic medical center. PATIENTS: 130 consecutive patients with non-small-cell lung cancer who were otherwise good surgical candidates. INTERVENTIONS: All patients had initial computed tomography of the chest; those with enlarged nodes were referred for endoscopic ultrasonography. Endoscopic ultrasonography-guided fine-needle aspiration biopsy was done on suspicious contralateral posterior mediastinal or subcarinal lymph nodes identified by ultrasonography. At surgery, lymph nodes were dissected and categorized by location and underwent histopathologic evaluation. RESULTS: 52 patients were ultimately enrolled in the study: Thirty-one had thoracotomy with mediastinal dissection, and 21 had tumors considered unresectable on the basis of preoperative evaluation. Ultrasonography without aspiration biopsy had an overall accuracy of 84% for predicting metastasis to lymph nodes; computed tomography had an accuracy of 49% (P < 0.025). Twenty-four patients had ultrasonography-guided aspiration biopsy; 14 of 24 were ineligible for surgery because cytology showed malignancy. Results of surgical pathology correlated with negative aspiration cytology results in 9 of 10 patients, the one node with false-negative results contained a 2-mm focus of cancer. The accuracy of ultrasonography-guided aspiration biopsy in diagnosing metastasis to lymph nodes was 96%; the results of this test prompted a change in management in 95% of the patients who had the procedure. CONCLUSIONS: Endoscopic ultrasonography alone or with fine-needle aspiration biopsy adds useful diagnostic information in determining metastasis to posterior mediastinal or subcarinal lymph nodes in patients with non-small-cell lung-cancer. These procedures are especially helpful in the preoperative evaluation of patients with suspicious contralateral mediastinal or "bulky" subcarinal nodes.

Biopsy, Needle↗
PubMed1997

Topical aspirin provides protection against galactosemic cataract.

Effect of twice daily administration of aspirin eyedrops on the onset and progression of cataract induced by 30% galactose diet was studied. On the 30th day of galactose feeding while all control group rats showed complete stage IV opacity, those receiving aspirin eyedrops showed only mild cataractous changes of stage I. In vitro studies showed that addition of aspirin to the medium significantly decreased dulcitol formation (p < 0.01) and maintained glutathione levels (p < 0.02). Intraocular penetration studies using isolated goat cornea showed excellent penetration by salicylate indicating feasibility of topical administration. The results of the present study demonstrate that topical aspirin possesses significant anticataract activity in galactosemic cataract.

Administration, Topical↗