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Biomedical subjects

N Das

Publications and source records attributed to N Das.

At least 19 recordsLinked to original sources

Risk adjusted surgical audit in gynaecological oncology: P-POSSUM does not predict outcome.

AIMS: To assess the Physiological and Operative Severity Score for the enumeration of mortality and morbidity (POSSUM) and its validity for use in gynaecological oncology surgery. METHODS: All patients undergoing gynaecological oncology surgery at the Northern Gynaecological Oncology Centre (NGOC) Gateshead, UK over a period of 12months (2002-2003) were assessed prospectively. Mortality and morbidity predictions using the Portsmouth modification of the POSSUM algorithm (P-POSSUM) were compared to the actual outcomes. Performance of the model was also evaluated using the Hosmer and Lemeshow Chi square statistic (testing the goodness of fit). RESULTS: During this period 468 patients were assessed. The P-POSSUM appeared to over predict mortality rates for our patients. It predicted a 7% mortality rate for our patients compared to an observed rate of 2% (35 predicted deaths in comparison to 10 observed deaths), a difference that was statistically significant (H&L chi(2)=542.9, d.f. 8, p<0.05). CONCLUSION: The P-POSSUM algorithm overestimates the risk of mortality for gynaecological oncology patients undergoing surgery. The P-POSSUM algorithm will require further adjustments prior to adoption for gynaecological cancer surgery as a risk adjusted surgical audit tool.

Female↗

Increased cholecystectomy rate in the laparoscopic era: a study of the potential causative factors.

BACKGROUND: It has been suggested that an increased cholecystectomy rate in the laparoscopic era may be due to a reduced threshold for surgery or diagnostic confusion with irritable bowel syndrome (IBS). This study aims to determine the validity of these suggestions. METHODS: Questionnaires were sent to patients who had undergone cholecystectomy between 1988-1990 (open) and 1998-2000 (laparoscopic). Patients were asked about abdominal pain, fatty food intolerance, jaundice, and indigestion pre- and postoperatively. Questionnaires included Rome II criteria for the diagnosis of IBS and SF-36 quality-of-life data. Histological severity of gallbladder disease was assessed using a standard scoring system. RESULTS: A total of 124 of 196 patients in the open group and 264 of 400 patients in the laparoscopic group replied. There was no difference between the groups in gender, age at surgery, IBS incidence, or quality-of-life scores. The laparoscopic group reported a lower incidence of preoperative fat intolerance (45.8 vs 58.1%, p < 0.05) and a higher incidence of persistent postoperative abdominal pain (27.3 vs 17.7%, p < 0.05). Mean histopathology severity scores were higher in the open group (4.42 vs 3.95, p < 0.01). CONCLUSIONS: Increased cholecystectomy rate in the laparoscopic era cannot be attributed to diagnostic confusion with IBS. However, a reduction in the threshold for surgery may have contributed to the increased rate of cholecystectomy.

Abdominal Pain↗

Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p < 0.001). This suggests that use of ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

Animals↗

APOA1-75 G to A substitution associated with severe forms of CAD, lower levels of HDL and apoA-I among northern Indians.

Apolipoprotein A-I (APOA1 gene, apoA-I protein) is the major protein for plasma high density lipoprotein (HDL). The relationship of APOA1-75G/A polymorphism with lipid profile and coronary artery disease (CAD) is unclear. Out of 370 individuals initially recruited, 164 angiographically proven CAD patients (>/= 70% stenosis) and 36 individuals with normal coronaries or insignificant CAD (NCAD, </= 50% stenosis) from Delhi and adjoining areas were selected for analysis based on the set criteria. Polymorphism was determined by PCR followed by MspI restriction digestion. Lipid profile was estimated by enzymatic kit and apoA-I levels by immunoturbidimetry. A highly significant increasing trend in 'A' allele frequency was observed with the rise in severity of CAD: NCAD (0.097) < SVD (single vessel disease) (0.117) < DVD (double vessel disease) (0.223) < TVD (triple vessel disease) (0.291). In comparison to GG individuals, the OR of 'A' allele carriers to develop SVD, DVD, TVD was 1.3, 2.8 and 4.2 respectively (p(trend) = 0.007). Analysis of intergenotypic variations in the lipid profile revealed significantly lower levels of HDL and apoA-I among 'A' allele carriers as compared to GG (patients). Our study, first of its kind from India, suggests that 'A' allele may contribute to severity of CAD and low levels of HDL and apoA-I. However, an in depth study with a larger set of sample is necessary.

Age Factors↗

Laparoscopically assisted radical vaginal hysterectomy vs. radical abdominal hysterectomy for cervical cancer: a match controlled study.

OBJECTIVES: The technical feasibility of laparoscopically assisted radical vaginal hysterectomy has been well described, but its advantages over the open technique remain largely unproven. We reviewed and compared our experiences with both approaches. METHODS: All patients undergoing laparoscopically assisted radical vaginal hysterectomy (LARVH) between 1996 and 2003 were identified and matched for age, FIGO stage, histological subtype and nodal metastases using a control group of women who underwent radical abdominal hysterectomy (RAH) during the same time period. RESULTS: Fifty-seven women were listed for LARVH, resulting in five conversions. Fifty cases were matched successfully using the criteria above. The majority of cases were FIGO stage 1B1. Statistically significant differences (P < 0.05) were present when the following were compared for LARVH vs. RAH: duration of surgery (median 180 vs. 120 min), blood loss (median 350 vs. 875 ml), hospital stay (median 5 days vs. 8 days) and duration of continuous bladder catheterisation (median 3 days vs. 7 days). There were no statistically significant differences with regard to nodal yield, completeness of surgical margins or perioperative complication rate. Four major complications (8%, three cystotomies and one enterotomy) occurred in the LARVH group and three in the RAH group (6%, one pulmonary embolism, one ureteric injury and one major haemorrhage). Three women in LARVH group had seen a specialist regarding postoperative bladder dysfunction, versus 12 in the RAH group (P = 0.04). No patients in the LARVH group reported constipation requiring regular laxatives, versus six in the RAH group (P = 0.03). Median follow-up was 52 months for LARVH and 49 months for RAH. There was no significant difference between recurrence rates or overall survival (94% for LARVH vs. 96% for RAH). CONCLUSIONS: Despite the inherent limitations of LARVH and its associated learning curve, the procedure conveys many advantages over the open technique in terms of blood loss, transfusion requirement and hospital stay. In addition, the incidence of postoperative bladder and bowel dysfunction appears low-suggesting improved quality of life-without compromising survival.

Adult↗

Apolipoprotein C3 SstI polymorphism in the risk assessment of CAD.

Various population studies have reported the association of rare S2 allele of apolipoprotein C3 (APOC3) SstI polymorphism with hypertriglyceridemia (HTG) and coronary artery disease (CAD). We were the first to report an association of S2 allele with high triglyceride (TG) levels in healthy volunteers from Northern India. Since HTG is suggested to be a predominant risk factor for CAD among Indians, we have elucidated the relationship of APOC3 SstI polymorphism with the lipid profile and CAD. A total of 158 patients with > or = 70% stenosis in one or more coronary artery (angiographically proven CAD patients), 35 subjects with < 70% stenosis (NCAD) and 151 normal controls (free of heart disease) from Northern plains of India were recruited in the study. DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Lipid profile was estimated by enzymatic kit. We found a strong association of S2 allele with high TG levels, which was more significant in patients. Prevalence of S2 allele in normal controls and CAD patients were comparable, despite the fact that mean TG level was significantly higher in patients. A greater insight into this observation revealed that the prevalence of high TG, if not coupled with other risk factors (like high total cholesterol, low HDL), was comparable in patients and controls. Thus, our study reveals that rare S2 allele may be employed as a susceptibility marker for high TG. However, high TG or S2 allele alone may not contribute to the etiology of CAD.

Adult↗

Modulation of urinary CR1 in systemic lupus erythematosus.

The decline in the levels of erythrocyte complement receptor 1 (ECR1) in systemic lupus erythematosus (SLE) has been widely reported. The most probable cause for this decline is excessive proteolytic shedding of CR1 from the cell surface. Similarly a decline in glomerular CR1 (GCR1) has also been reported in SLE. Because CR1 is excreted in urine it is imperative to study the relationship of urinary CR1 (uCR1) with ECR1 and GCR1, and their overall correlation with disease activity. We have determined the levels of uCR1, ECR1 and GCR1 in SLE patients and compared them with normal controls and minimal change disease (MCD) patients. We found a significant decline in both uCR1 and GCR1 in SLE but not in MCD; levels of uCR1 in MCD were either comparable to those of controls or higher. Immunofluorescence for GCR1 was very high in MCD. We did not find any correlation between ECR1, uCR1 and kidney function tests on divariate scatter analyses. The correlation coefficient for uCR1 and GCR1 was highly significant and positive. Our findings thus suggest that uCR1 reflects the levels of GCR1 expression, which decline drastically in SLE. Therefore we envisage uCR1 as a potential marker for glomerular involvement in SLE.

Case-Control Studies↗

Genetic and structural polymorphism of complement receptor 1 in normal Indian subjects.

The human complement receptor 1 (C3b/C4b receptor, CD35, CR1), a polymorphic membrane bound glycoprotein, is differentially expressed on erythrocytes, eosinophils, monocytes, B and T-lymphocytes, dendritic cells and kidney podocytes. It also occurs in the plasma as soluble CR1 (sCR1) and in urine as urinary CR1 (uCR1). Different population studies have suggested the functional and physiological significance of the structural (CR1-A/190, CR1-B/220, CR1-C/160 and CR1-D/250 kDa) and genomic (HH, high erythrocyte CR1 expression, HL, intermediate and LL, low expression) polymorphisms in health and disease. However, simultaneous study on the structural and genomic polymorphism in the same group of study subjects is lacking. This is the first study on both quantitative and structural polymorphism in 101 healthy volunteers from different parts of India by random sampling. In our study, AA phenotype was found to be expressed in 84.2% of individuals and 14.8% carried AB phenotype. One individual (0.9%) was found to possess BB phenotype. Homozygous BB pattern was identified for the first time in Indian subjects. The relative gene frequencies for A and B allele were found to be 0.916 and 0.084, respectively. Pertaining to quantitative polymorphism, percentage distribution for HH, HL and LL phenotypes was found to be 23.7, 54.45 and 21.79%, respectively and the gene frequencies were 0.51 and 0.49 for H and L allele, respectively. The observations for quantitative as well as structural polymorphism showed a good probability of fitness with Hardy-Weinberg equilibrium, thus proving that both the types of CR1 polymorphic forms are encoded by autosomal co-dominant alleles. We found a higher frequency of HL and AA phenotypes in the study subjects. Our findings are unique as we found that gene frequencies for structural and quantitative polymorphism in our study subjects were a combination of those found in Caucasian and Oriental populations.

Adult↗

Contralateral groin node metastasis following ipsilateral groin node dissection in vulval cancer: a case report.

BACKGROUND: The majority of vulval cancers are of the squamous cell type. Current operative management strategies are based on modifications of radical vulvectomy and groin node dissection, enabling a more individualised and conservative approach to surgery. This has led to interesting dilemmas regarding the most appropriate management in certain individuals. CASE: We describe a case of a contralateral recurrence following unilateral groin node dissection for vulval cancer, with an initial single microscopically positive node. The patient did not receive adjuvant treatment. Evidence regarding the safety of this approach is discussed. CONCLUSION: The subject remains controversial, and further such cases should be recorded in the literature in order to gather more information on this difficult problem.

Aged↗

Hepatoprotective effect of Himoliv, a polyherbal formulation in rats.

The effect of Himoliv (HV) was evaluated in carbon tetrachloride or paracetamol induced hepatotoxicity in rats. Liver necrosis was produced by administering single dose of either carbon tetrachloride (CCl4, 1 ml/kg, 50% v/v with olive oil, s.c.) or paracetamol (PC, 1 g/kg, p.o.). The liver damage was evidenced by elevated levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and serum alkaline phosphatase (ALP) and hepatic thiobarbituric acid reacting substances (TBARS) and superoxide dismutase (SOD). HV pretreatment (0.5 and 1.0 ml/kg, p.o.) significantly (P < 0.001) reduced CCl4 or PC-induced elevations of the levels of SGOT, SGPT, ALP and TBARS, while the reduced concentration of SOD due to CCl4 or PC was reversed. Silymarin (25 mg/ kg, p.o.), a known hepatoprotective drug showed similar results.

Acetaminophen↗

Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians.

BACKGROUND: A close association between Sst I polymorphism in the 3' untranslated region of the apolipoproteinC3 (APOC3) gene and levels of plasma triglycerides (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a known risk factor for coronary artery disease (CAD) in the context of Asian Indians. We conducted a study on the relationship between APOC3 SstI polymorphism (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male healthy volunteers from Northern India. METHODS: DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Digested PCR products were run on 3% agarose gel and visualized by ethidium bromide staining. RESULTS: Rare S2 allele was highly prevalent in our study population (0.313) as compared to the Caucasians (0.00-0.11). The genotypic distribution was in agreement with Hardy-Weinberg equilibrium. S2 allele was almost two times more prevalent in the HTG group (N = 34) as compared to NTG group (N = 105) (p = 0.001). Multiple logistic regression revealed S1S2 individuals had age-adjusted odds ratio of 2.43 (95%CI = 0.99-6.01, p = 0.054) and S2S2 had 9.9 (95%CI = 2.66-37.29, p = 0.0006) for developing HTG in comparison to S1S1 genotype. CONCLUSIONS: Our study shows a significant association between rare S2 allele and HTG in Asian Indians.

Apolipoprotein C-III↗

Apolipoprotein E gene polymorphism in cerebrovascular disease: a case-control study.

The association between apolipoprotein E (apo E) polymorphism and stroke has been controversial. So far there are no studies reported on the polymorphism of apolipoprotein E in cerebrovascular diseases in the Asian Indians. A blinded case-control study was therefore undertaken and the apo E genotypes and lipid profile of a total of 120 subjects (63 stroke patients and 57 healthy controls) were done. The frequency distribution of apo E alleles and genotypes were assessed and their relation with the occurrence of stroke in Asian Indian subjects was determined. A significantly high frequency of apo epsilon4 allele (30%) was observed in the stroke patients than the controls (11%) (p < 0.005), and patients with epsilon4 allele had a fourfold higher odds to develop stroke OR (95%CI) 4.2 (1.8-10.1) (p < 0.005). On multivariate analysis, after adjusting for age, triglycerides and hypertension, the association of epsilon4 allele with stroke was found to be no longer statistically significant, OR (95%CI) 1.2 (0.4-4.5) (p = NS). On multiple logistic regression analysis age, OR (95%CI) 1.1 (1.1-1.2) (p < 0.001), and hypertension OR (95%CI) 15.1 (2.6-89.1) (p < 0.005) were found to be independent risk factors for development of stroke. This is the first report to have examined the association of apo E gene polymorphism with stroke in the Asian Indians. This study suggests that apo epsilon4 allele, triglycerides, age and hypertension are the predictors for stroke development.

Adult↗

Quercetin: critical evaluation as an antileishmanial agent in vivo in hamsters using different vesicular delivery modes.

Chemotherapy is still a major challenge for in vivo drug targeting to macrophages. Toxicity remains the major obstacle for the most potent drugs already known in the therapy of leishmaniasis. Thus, new drugs and new delivery systems are sought. By using different vesicular delivery modes e.g. liposomes, niosomes, microspheres and nanoparticles, attempts have been made to deliver an indigenous antileishmanial compound, quercetin, to treat experimental leishmaniasis in the hamster model so as to increase its efficacy as well as to reduce the toxicity. At equivalent quercetin concentration, the nanocapsulated quercetin was found to be the most potent in reducing the parasite burden in the spleen as well as in reducing hepatotoxcity and renaltoxicity compared to free drug or drug in other vesicular forms. An inverse relationship between the efficacy and the size of the vesicles was established. Such a drug vehicle formulation especially in the nanocapsulated form may be considered for clinical trials.

Algorithms↗

Unusual complications of ballooned feeding tubes.

Percutaneous Endoscopic Gastrostomy (PEG) and Feeding Jejunostomy (FJ) with a Foley catheter are well-established techniques for providing long-term nutritional support. Mechanical complications of these procedures are well recognised. We report two unusual complications of feeding tubes related to the balloon. Patient 1: A 23 years old female cerebral palsy patient had a PEG tube changed to a ballooned gastrostomy tube. Following this she developed abdominal cramps, vomiting and later on haematemesis. Contrast study showed migration of the balloon causing pyloric obstruction and a small prepyloric ulcer. Partially deflating the balloon and pulling it back to the original position corrected this. Patient 2: A 39 years old male cerebral palsy patient with a Foley catheter feeding jejunostomy developed obstructive symptoms within 48 hours of surgery. The balloon was deflated repeatedly without resolution. The catheter was impossible to withdraw and irrigate. Contrast instilled via the balloon channel demonstrated that the catheter was significantly stretched and the balloon was in terminal ileum. The balloon was fully deflated and easily withdrawn to be replaced with uninflated Foley catheter. Enteral feeding was easily reestablished. If a patient with a ballooned feeding tube develops intestinal symptoms balloon complications should be suspected. Contrast study through the feeding channel or balloon inflation channel is useful in diagnosing tube related complication. The threshold for imaging should be low, particularly in patients who are difficult to assess clinically.

Adult↗

Selectivity of protein oxidative damage during aging in Drosophila melanogaster.

The purpose of the present study was to determine whether oxidation of various proteins during the aging process occurs selectively or randomly, and whether the same proteins are damaged in different species. Protein oxidative damage to the proteins, present in the matrix of mitochondria in the flight muscles of Drosophila melanogaster and manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl-group antibodies. Aconitase was found to be the only protein in the mitochondrial matrix that exhibited an age-associated increase in carbonylation. The accrual of oxidative damage was accompanied by an approx. 50% loss in aconitase activity. An increase in ambient temperature, which elevates the rate of metabolism and shortens the life span of flies, caused an elevation in the amount of aconitase carbonylation and an accelerated loss in its activity. Exposure to 100% ambient oxygen showed that aconitase was highly susceptible to undergo oxidative damage and loss of activity under oxidative stress. Administration of fluoroacetate, a competitive inhibitor of aconitase activity, resulted in a dose-dependent decrease in the life span of the flies. Results of the present study demonstrate that protein oxidative damage during aging is a selective phenomenon, and might constitute a mechanism by which oxidative stress causes age-associated losses in specific biochemical functions.

Aconitate Hydratase↗