Biomedical subjects

Rajinder Singh

Publications and source records attributed to Rajinder Singh.

At least 37 records · Page 2Linked to original sources

PubMed2004

Constituents of Pterocarpus marsupium: an ayurvedic crude drug.

Five new flavonoid C-glucosides, 6-hydroxy-2-(4-hydroxybenzyl)-benzofuran-7-C-beta-d-glucopyranoside (1), 3-(alpha-methoxy-4-hydroxybenzylidene)-6-hydroxybenzo-2(3H)-furanone-7-C-beta-d-glucopyranoside (2), 2-hydroxy-2-p-hydroxybenzyl-3(2H)-6-hydroxybenzofuranone-7-C-beta-d-glucopyranoside (4), 8-(C-beta-d-glucopyranosyl)-7,3',4'-trihydroxyflavone (5) and 1,2-bis(2,4-dihydroxy,3-C-glucopyranosyl)-ethanedione (6) and two known compounds C-beta-d-glucopyranosyl-2,6-dihydroxyl benzene (7) and sesquiterpene (8), were isolated from an aqueous extract of the heartwood of Pterocarpus marsupium. The structure has been established using spectroscopic data.

Flavonoids↗

PubMed2004

Detection of O6-carboxymethyl-2'-deoxyguanosine in DNA following reaction of nitric oxide with glycine and in human blood DNA using a quantitative immunoslot blot assay.

Previous research has shown that a range of nitrosated glycine derivatives react with DNA to form O6-carboxymethylguanine and O6-methylguanine DNA adducts [Harrison et al. (1999) Chem. Res. Toxicol. 12, 106-111). Nitrosated glycine derivatives may be formed in the gastrointestinal tract from the reaction of dietary glycine with nitrosating agents. The aim of this study was to further investigate the role of dietary glycine in the formation of O6-guanine adducts at physiologically relevant concentrations. In vitro studies were performed by reacting 10 microM to 50 mM glycine with nitric oxide in the presence of oxygen. An HPLC assay was developed to measure the resulting nitrosated glycine derivative, diazoacetate anion. The amount of nitrosating agent present in the reaction mixture was determined by colorimetric measurement of nitrite, the hydrolysis product of N2O3. Diazoacetate anion formation depended linearly on glycine concentration. Solutions of nitrosated glycine reacted with 2'-deoxyguanosine and calf thymus DNA to give O6-carboxymethyl-2'-deoxyguanosine and, at high concentrations of glycine and nitric oxide, O6-methyl-2'-deoxyguanosine. At physiological concentrations of glycine and nitric oxide, diazoacetate anion was not detectable. Studies with synthetic diazoacetate anion showed that concentrations < 14 microM did not give detectable O6-carboxyethylguanine in DNA, even when a sensitive immunoslot blot assay was used. However, O6-carboxymethylguanine was detected in human blood DNA samples obtained from three volunteers consuming a standardized high meat diet, using the immunoslot blot assay. O6-Carboxymethylguanine levels ranged from 35 to 80 (detection limit = 15) O6-carboxymethylguanine per 10(8) bases. These studies provide further evidence that nitrosated amino acids may be risk factors for gastrointestinal tract cancers.

DNA↗

PubMed2004

Effects of hemodialysis, dialyser type and iron infusion on oxidative stress in uremic patients.

Uremic patients undergoing hemodialysis (HD) are considered to face an elevated risk for atherosclerosis and cancer. This has been attributed in part to an increased oxidative stress. In this pilot study, oxidative cell damage in blood of HD-patients was compared to those of controls: total DNA damage (basic and specific oxidative DNA damage), modulation of glutathione levels (total and oxidized glutathione) and of lipid peroxidation were monitored via the Comet assay (with and without FPG), a kinetic photometric assay and HPLC quantification of plasma malondialdehyde (MDA), respectively. In some samples, leukocytes were analysed for malondialdehyde-deoxyguanosine-adducts (M1dG) with an immunoslot blot technique. HD-patients (n=21) showed a significant increase of total DNA damage (p<10(-12)), compared to controls (n=12). In a subset of patients and controls, GSSG levels and M1dG, however, only increased slightly, while tGSH and MDA levels did not differ. The influence of different low flux HD-membranes was tested in a pilot study with nine patients consecutively dialysed on three membrane types for four weeks each. In addition to the individual disposition of the patient, the dialyser membrane had a significant impact on oxidative stress. Total DNA damage was found to be almost identical for polysulfone and vitamin E coated cellulosic membranes, whereas a slight, but significant increase was observed with cellulose-diacetate (p<0.001). In patients receiving iron infusion during HD, MDA-formation (n=11) and total DNA damage (n=10) were additionally increased (p<0.005). Our results show an increased oxidative damage in HD-patients, compared to healthy volunteers. Significant influences were found for the dialyser membrane type and iron infusion.

Adult↗

PubMed2004

Current management of gall bladder perforations.

BACKGROUND: Gall bladder perforation is a serious complication of acute cholecystitis. The purpose of the present study is to evaluate the presenting symptoms, diagnosis and management of patients with gall bladder perforations. METHODS: A retrospective study was undertaken of 31 consecutive patients with gall bladder perforation in a single unit of a tertiary referral hospital, between January 1996 and December 2001. RESULTS: The incidence of gall bladder perforation was 5.9% of all cases of acute cholecystitis. Associated comorbidity was quite common (58%). Ultrasound and computed tomography scans of the abdomen are sensitive investigations. Ultrasound guided percutaneous drainage helps in tiding over the emergency. The morbidity (35%) and mortality (9.6%) is considerable. CONCLUSION: The patterns of presentations, diagnosis and management of gall bladder perforation are changing. But there is scope for improvement.

Adult↗

PubMed2004

Computational and experimental studies on human misshapen/NIK-related kinase MINK-1.

We have studied the structure and function of Human Misshapen/NIK-related kinase (MINK-1) through a combination of computational methods and experimental approaches, including (1) fold recognition and sequence-structure alignment for each structural domain using the threading program PROSPECT, (2) gene expression and protein-protein interaction analysis of yeast homologs of human MINK-1 domains, and (3) yeast two-hybrid screening for proteins that interact with human MINK-1. Our structure prediction dissects MINK-1 into four domains: a conserved N-terminal kinase domain, followed by a coiled-coil region and a proline-rich region, and a C-terminal GCK domain. Gene expression and yeast two-hybrid analysis of yeast homologs of the MINK-1 domains suggest that MINK-1 may be involved in cell-cycle progression and cytoskeletal control. Consistent with these predicted functions, our in-house yeast two-hybrid screen for proteins that interact with human MINK-1 provides strong evidence that the coiled-coil and proline-rich domains of MINK-1 participate in the regulation of cytoskeletal organization, cell-cycle control and apoptosis. A homology model of the MINK-1 kinase domain was used to screen the NCI open compound database in DOCK, and chemical compounds with pharmaceutically acceptable properties were identified. Further medicinal chemistry compound structure optimization and kinase assays are underway.

Amino Acid Sequence↗

PubMed2003

An improved liquid chromatography/tandem mass spectrometry method for the determination of 8-oxo-7,8-dihydro-2'-deoxyguanosine in DNA samples using immunoaffinity column purification.

The analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) represents an important biomarker of oxidative stress. A sensitive method for the detection of 8-oxodG in DNA samples has been developed that utilizes immunoaffinity column purification of 8-oxodG followed by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) multiple reaction monitoring (MRM) mode analysis. An internal standard of stable-isotopically labelled 8-oxodG containing [(15)N(5)] was added prior to the enzymatic digestion of DNA to deoxynucleosides, which was then subjected to immunoaffinity column purification followed by microbore positive ion LC/MS/MS MRM. The 8-oxo-7,8-dihydroguanine (8-oxoG) base product ion at m/z 168 was monitored following cleavage of the glycosidic bond of the 8-oxodG [M+H](+) ion at m/z 284. Similar determinations were made for [(15)N(5)]8-oxodG by monitoring the [(15)N(5)]8-oxoG base product ion at m/z 173 formed from the [M+H](+) ion at m/z 289. The introduction of the immunoaffinity column purification step into the method represents a significant improvement for the accurate determination of 8-oxodG since all artefactual peaks that are observed following the direct injection of digested DNA onto the LC/MS/MS system are removed. The identity of these artefactual peaks has been confirmed to be 2'-deoxyguanosine (dG), thymidine (dT) and 2'-deoxyadenosine (dA). The presence of these artefactual peaks in MRM mode analysis can be explained as a consequence of a concentration effect due to their considerably higher relative abundance in DNA compared to 8-oxodG. The highest signal intensity was observed for the artefactual peak for dA due to the fact that the adenine base formed an adduct with methanol, which is a constituent of the mobile phase. The resulting [M+H](+) ion at m/z 284 (dA m/z 252 + CH(3)OH m/z 32) gave rise to a product ion at m/z 168 following the loss of deoxyribose in MRM mode analysis. Control calf thymus DNA was digested to deoxynucleosides and unmodfied deoxynucleosides were removed by immunoaffinity column purification; the enriched 8-oxodG was determined by LC/MS/MS MRM. The level of 8-oxodG in control calf thymus DNA was determined to be 28.8 +/- 1.2 8-oxodG per 10(6) unmodified nucleotides (n = 5) using 5 microg of digested DNA. The limit of detection of the microbore LC/MS/MS MRM for 8-oxodG was determined to be 25 fmol on-column with a signal-to-noise ratio of 3.5.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2003

Molecular epidemiology studies of carcinogenic environmental pollutants. Effects of polycyclic aromatic hydrocarbons (PAHs) in environmental pollution on exogenous and oxidative DNA damage.

Exposure to high levels of environmental air pollution is known to be associated with an increased carcinogenic risk. The individual contribution to this risk derived from specific carcinogenic chemicals within the complex mixture of air pollution is less certain, but may be explored by the use of molecular epidemiological techniques. Measurements of biomarkers of exposure, of effect and of susceptibility provide information of potential benefit for epidemiological and cancer risk assessment. The application of such techniques has been mostly concerned in the past with the carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) that are associated with particulate matter in air pollution, and has showed clear evidence of genotoxic effects, such as DNA adducts, chromosome aberrations (CA) and ras oncogene overexpression, in environmentally exposed Czech and Polish populations. We are currently extending these studies by an investigation of populations exposed to environmental pollution in three European countries, Czech Republic, Slovak Republic and Bulgaria. This pays particular attention to PAHs, but also investigates the extent of radically induced (oxidative) DNA damage in the exposed populations. Policemen, bus drivers and controls, who carried personal monitors to determine their exposures to PAHs have been studied, and blood and urine were collected. Antioxidant and dietary status were assessed in these populations. Stationary monitors were also used for ambient air monitoring. Amongst the parameters studied in the biological samples were: (a) exposure biomarkers, such as PAH adducts with DNA, p53 and p21(WAF1) protein levels, (b) oxidative DNA damage, (c) the biological effect of the exposure by measurement of chromosome damage by fluorescence in situ hybridisation (FISH) or conventional methods, and (d) polymorphisms in carcinogen metabolising and DNA repair enzymes. Repair ability was also measured by the Comet assay. In vitro systems are being evaluated to characterise the genotoxicity of the organic compounds adsorbed to air particles.

Biomarkers↗

PubMed2003

Attitudes of Canadian nephrologists, family physicians and patients with kidney failure toward primary care delivery for chronic dialysis patients.

BACKGROUND: Nephrologists have traditionally assumed responsibility for both nephrological and primary care health problems of their dialysis patients. However, given the increasing limitations of nephrology human resources, there is concern that traditional models may fall short of providing comprehensive care. METHODS: We studied this issue by distributing three different self-administered surveys to 361 members of the Canadian Society of Nephrology, 325 family physicians, and 163 chronic dialysis patients. RESULTS: The overall response rate was 61.3% for nephrologists, 51% for family physicians, and 90% for patients. More than 50% of Canadian nephrologists are spending approximately one-third of their time in primary care delivery. The majority of these nephrologists and family physicians agree that nephrologists should not be solely responsible for the primary care of patients on dialysis. Yet, both groups of physicians have concerns that family physicians do not have the knowledge/training and time to care for this complicated group of patients. The patients themselves have more confidence in the primary care that is delivered by their family physicians than by their nephrologists. Unfortunately, there is little communication between the two physician groups either between themselves or with their patients about the services that should be provided by their nephrologist or their family physician. CONCLUSION: Nephrologists and family physicians agree that more primary care for dialysis patients should be provided by family physicians. However, the lack of communication between physicians and patients may result in either a duplication or omission of services that are required by this patient population. Dialysis delivery systems in Canada must evolve to ensure that comprehensive chronic dialysis and primary care is provided to these patients through cooperation and communication with primary care physicians.

Attitude of Health Personnel↗

PubMed2003

Near misses in bladder cancer - an airline safety approach to urology.

INTRODUCTION: Traditionally, surgical audit has identified and highlighted the incidence of adverse events complicating a patient's care. The airline industry has taken this concept a step further back by identifying and studying near misses, i.e. events that have the potential to do harm. We have applied this approach to patients with known or suspected bladder cancer. PATIENTS AND METHODS: A prospective study was performed by two urology firms on all patients with known or suspected bladder cancer over a 3-week period. Patients presented to either a central (hub) hospital, or to an associated (spoke) hospital. Four stages in bladder cancer care were considered: (i) diagnostic or check flexible cystoscopy; (ii) admission to hospital prior to TURBT; (iii) peri-operative period; and (iv) first out-patient consultation. A separate proforma, comprising various aspects of management was used for each of these stages of care. If any one criterion was not met, the episode was recorded as a near miss. Near misses were classified as due to capacity limitations in the system, clerical error, equipment failure, clinical error and patient failure. RESULTS: A total of 115 completed episodes were recorded. A near miss was recorded in 65 (56.5%) of all episodes. Capacity limitations accounted for 54%, clinical error for 23%, clerical error for 16%, patient failure for 5% and equipment failure for 2% of all recorded near misses. Of particular note is that near misses relating to diagnosis were more common at the spoke hospital, delayed referral from GPs accounted for more than 25% of clinical error, diagnosis of 5 new bladder tumours was delayed and availability of upper tract imaging was a problem at all phases of patient management. CONCLUSIONS: Near misses are very common in the management of patients with bladder cancer, and their identification should provide a useful framework for identifying potential areas for improvement in patient care.

Ambulatory Care↗

PubMed2002

Photochemistry of arylidene-beta-ionones: a highly efficient route to novel tricyclic ketones through intramolecular, exoselective photochemical (4 + 2) cycloadditions, occurring only in an aqueous-organic solvent.

(E,E)-Arylidene-beta-ionones (1a-f) are converted to 1,7,7-trimethyl-3-(E-2'-arylethenyl)-2-oxabicyclo[4.4.0]deca-3,5-dienes (3a-f, approximately 90%) by irradiating in anhydrous solvents. Irradiation of (3a-f) in aqueous methanol results in Z,E-arylidene-beta-ionones (2), through retro-electrocyclization, which undergoes an intramolecular, exo-selective [4 + 2] photocycloaddition leading to 11-(exo)-aryl-1,7,7-trimethyl-tricyclo[4.4.0.1(2,4)]undec-5-ene-3-ones (8a-f, 60-80%). The latter rearrange over silica gel to afford, quantitatively, 5-aryl-7,11,11-trimethyl-tricyclo[5.4.0.0(3,6)]undec-1-ene-4-ones (5a-f). Irradiation of 1a-f in aqueous methanol leads to 8a-f, except in case of 1c,f wherein formation, respectively, of tricyclic ketones 9c (55%) and 9f (80%), derived from photodeconjugation in 2, followed by intramolecular [4 + 2] cycloaddition, is observed.

Journal Article↗

PubMed2002

Surgical management of phaeochromocytoma.

OBJECTIVES: Phaeochromocytoma is a rare tumour, which is benign but metabolically functional, with a potential for malignancy. Surgical resection is the primary treatment. The purpose of this study was to identify the presenting features, diagnostic tests and appropriate surgical approaches for phaeochromocytoma. METHODS: Retrospective analysis was performed on 26 patients with phaeochromocytoma who were admitted to General Surgery, Department of Postgraduate Institute of Medical Education and Research, Chandigarh, India from 1993 to 1999. RESULTS: Of the 26 patients, 15 were males and 11 were females. Their ages ranged from 13 to 60 years, with a peak phaeochromocytoma incidence in the second decade of life. Two patients had phaeochromocytoma as a manifestation of multiple endocrine neoplasia type 2 syndrome (MEN-2). Hypertension was present in 92% of patients. Six (23%) patients had extra-adrenal phaeochromocytoma. The incidence of bilateral tumour was 25% of adrenal tumour and 11.5% had malignant phaeochromocytoma. The diagnostic measurements were: 1) plasma catecholamines, 2) 24-hour urinary vanillylmandelic acid and 3) fractionated urinary catecholamines. Computed tomography of the abdomen was extremely accurate in diagnosing phaeochromocytoma (92% accuracy). Magnetic resonance imaging was performed in 2 patients with 100% accuracy. Preoperatively, all the patients were put on alpha adrenergic blocking agents to control blood pressure for varying periods of time. The transabdominal midline approach was used in all cases with excellent results. There was no surgical mortality. All the resected specimens were subjected to histopathological examination and phaeochromocytoma was subsequently confirmed. CONCLUSION: If preoperative diagnosis and localization of phaeochromocytoma is accurate, surgical resection can be done with minimal morbidity and mortality.

Adolescent↗

PubMed2002

Detection of malondialdehyde DNA adducts in human colorectal mucosa: relationship with diet and the presence of adenomas.

Colorectal biopsies from normal mucosa of participants in the United Kingdom Flexible Sigmoidoscopy Trial and European Prospective Investigation on Cancer (EPIC; n = 162) were analyzed for the presence of malondialdehyde-deoxyguanosine (M(1)-dG), a DNA adduct derived from lipid peroxidation. The aim was to investigate whether dietary factors can modulate M(1)-dG levels and whether M(1)-dG in normal mucosa is a risk factor for colorectal adenomas. Samples were analyzed using a sensitive immunoblot blot assay. This study has shown for the first time that M(1)-dG is present in human colorectal tissue. M(1)-dG levels ranged from undetectable (n = 13) to 12.23 per 10(7) total bases. Mean levels were 4.3 +/- 3 and 4.6 +/- 2.9 per 10(7) total bases in men and women, respectively. In men, there were positive associations of adduct levels with height and age, and inverse associations with body mass index. Legumes, fruit, salad, and whole meal bread were inversely associated with M(1)-dG adducts, whereas consumption of offal, white meat, beer, and alcohol were positively associated with elevated levels. In women, there was an inverse association of the adduct with the ratio of polyunsaturated:saturated fatty acids (P = 0.019) and a weak positive correlation with saturated fat (P < 0.061). When levels of adducts were compared in individuals with and without adenomas, there was a trend for higher levels in individuals presenting with adenomas especially in the highest category of M(1)-dG adducts (P < 0.005).

Adenoma↗

PubMed2002

Characterization of a defensin gene expressed in oil palm inflorescences: induction during tissue culture and possible association with epigenetic somaclonal variation events.

From differential display studies performed on oil palm (Elaeis guineensis Jacq.) tissue cultures bearing or lacking an epigenetic homeotic flowering abnormality, known as mantled, EGAD1, a gene coding for a putative plant defensin, has been identified and characterized. In whole plants, transcripts of the EGAD1 gene were detected only in inflorescences. The closest characterized relative of the oil palm EGAD1 gene is the Petunia PPT gene, which is expressed principally in the pistil of the flower. The 77 amino acid polypeptide encoded by the EGAD1 gene displays strong similarities with a number of plant defensin proteins, which are thought to play a protective role and which have been shown in some cases to possess antifungal properties. Oil palm tissue cultures exhibit a generally strong induction of accumulation of EGAD1 transcripts, which were detected to differing extents at all stages of the tissue culture regeneration process. The 5' flanking region of the EGAD1 gene was found to contain two different types of potential cis-acting DNA element previously identified in the promoters of plant defence-related genes, which may explain the observed expression in tissue cultures. At the callus stage of the in vitro regeneration procedure, a differential accumulation of EGAD1 transcripts was observed which correlated with the presence or absence of the mantled flowering abnormality. EGAD1 gene expression may therefore be a marker of epigenetic somaclonal variation events.

5' Flanking Region↗

PubMed1996

Synthetic Ionophores. 13. Pyridine-Diamide-Diester Receptors: Remarkable Effect of Amide Substituents on Molecular Organization and Ag(+) Selectivity.

The N(Py).HN(amide) hydrogen bonding within the macrocyclic cavities in 9, 10, and 13 invokes their symmetrical electron-deficient structures ((1)H NMR) and consequently bind with water. This results in their poor ionophore characters. The steric requirement of methyl/benzyl substituents on amide N in 11 and 12 takes the substituents out of the cavity and thus positions the amide O toward the cavity ((1)H, (13)C NMR and X-ray analysis). This arrangement of two pyridine N and two amide O ((13)C NMR, IR) binding sites provides an appropriate environment for selective binding toward Ag(+) over Pb(2+), Tl(+), alkali, and alkaline earth cations. The increased spacer length in 14 leads to a lop-sided twist of pyridine rings (X-ray) and disturbs the above arrangement and leads to its poor binding character.

Journal Article↗

PubMedDate not supplied

Biliary mishaps in laparoscopic cholecystectomy.

AIM: To determine the incidence and types of biliary complications following laparoscopic cholecystectomy in our patients. METHODS: The clinical records of one hundred and fifty-five patients undergoing laparoscopic cholecystectomy were reviewed. RESULTS: Five patients developed biliary mishaps. The overall incidence of biliary complications was 3.2% (5/155). The incidence of major complications was 1.9% (3/155) and the incidence of minor biliary complications was 1.2% (2/155). In 3 out of 5 patients the mishap was attributed to developmental anomalies. Dense pericholecystic adhesions and cystic duct blow out were responsible for biliary complications in one patient each. Bilioenteric anastomosis was performed in two patients and restoration of continuity of the common hepatic duct over a T-tube was done in one patient. Side hole in an accessory duct was repaired over a T-tube and cystic duct blow out was managed with endoscopic biliary drainage alone. CONCLUSIONS: A high index of suspicion of developmental anomalies, cautions approach in difficult cases and readiness to consider conversion to open cholecystectomy are recommended to reduce the incidence of biliary complications in laparoscopic cholecystectomy.

Adult↗

PubMedDate not supplied

True epiphrenic diverticulum of esophagus secondary to tubercular adenitis.

Ephiphrenic esophageal diverticulum is rare and usually is a pulsion-type pseudodiverticulum that occurs in association with motility disorders of the esophagus. We report a 35-year-old man with tubercular lymphadenitis causing true traction type of epiphrenic diverticulum. Esophageal diverticulectomy and esophagomyotomy was done; he is doing well on antitubercular drugs.

Adult↗

PubMedDate not supplied

Multiple squamous cell carcinomas of esophagus.

Multiple tumors of the esophagus are reported only rarely. We describe three patients with double carcinoma of esophagus. They developed a second squamous cell carcinoma of esophagus more than 4 1/2 years after external radiation for a primary squamous cell carcinoma at a different site in the esophagus.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Postoperative pulmonary function in laparoscopic versus open cholecystectomy: prospective, comparative study.

BACKGROUND: Pulmonary complications remain a leading cause of morbidity after major abdominal operations. OBJECTIVE: To compare pulmonary function and the frequency of pulmonary complications after laparoscopic cholecystectomy (LC) and open cholecystectomy (OC). METHODS: Fifty-five patients with symptomatic gallstone disease undergoing elective cholecystectomy (LC 40, OC 15) under general anesthesia were evaluated using pulmonary function tests (forced vital capacity [FVC], forced expiratory volume at 1 second [FEV1], and forced expiratory flow at 25% to 75% [FEF25% -75%], chest X-ray and pulse oximetry before and after surgery. RESULTS: FVC, FEV1 and FEF25% -75% decreased by 21.5%, 21.2% and 30.3%, respectively, on postoperative day 1 following LC, and by 44.3%, 46.2% and 58.3%, respectively, after OC. Chest X-ray showed atelectasis in 15% of patients undergoing LC and 45% of those with OC. CONCLUSION: Impairment in pulmonary function after LC was less marked than after OC.

Adult↗