PubMed Health⌕ Search

Biomedical subjects

D K Roy

Publications and source records attributed to D K Roy.

At least 19 recordsLinked to original sources
PubMed2005

Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study.

We have previously shown that center- and sex-specific fall rates explained one-third of between-center variation in upper limb fractures across Europe. In this current analysis, our aim was to determine how much of the between-center variation in fractures could be attributed to repeated falling, bone mineral density (BMD), and other risk factors in individuals, and to compare the relative contributions of center-specific BMD vs. center-specific fall rates. A clinical history of fracture was assessed prospectively in 2451 men and 2919 women aged 50-80 from 20 centers participating in the European Prospective Osteoporosis Study (EPOS) using standardized questionnaires (mean follow-up = 3 years). Bone mineral density (BMD, femoral neck, trochanter, and/or spine) was measured in 2103 men and 2565 women at these centers. Cox regression was used to model the risk of incident fracture as a function of the person-specific covariates: age, BMD, personal fracture history (PFH), family hip fracture history (FAMHIP), time spent walking/cycling, number of 'all falls' and falls not causing fracture ('fracture-free') during follow-up, alcohol consumption, and body mass index. Center effects were modeled by inclusion of multiplicative gamma-distributed random effects, termed center-shared frailty (CSF), with mean 1 and finite variance theta (theta) acting on the hazard rate. The relative contributions of center-specific fall risk and center-specific BMD on the incidence of limb fractures were evaluated as components of CSF. In women, the risk of any incident nonspine fracture (n = 190) increased with age, PFH, FAMHIP, > or =1 h/day walking/cycling, and number of 'all falls' during follow-up (all P < 0.074). 'Fracture-free' falls (P = 0.726) and femoral neck BMD did not have a significant effect at the individual level, but there was a significant center-shared frailty effect (theta = 0.271, P = 0.001) that was reduced by 4% after adjusting for mean center BMD and reduced by 19% when adjusted for mean center fall rate. Femoral trochanter BMD was a significant determinant of lower limb fractures (n = 53, P = 0.014) and the center-shared frailty effect was significant for upper limb fractures (theta = 0.271, P = 0.011). This upper limb fracture center effect was unchanged after adjusting for mean center BMD but was reduced by 36% after adjusting for center mean fall rates. In men, risk of any nonspine fracture (n = 75) increased with PFH, fall during follow-up (P < 0.026), and with a decrease in trochanteric BMD [RR 1.38 (1.08, 1.79) per 1 SD decrease]. There was no center effect evident (theta = 0.081, P = 0.096). We conclude that BMD alone cannot be validly used to discriminate between the risk of upper limb fractures across populations without taking account of population-specific variations in fall risk and other factors. These variations might reflect shared environmental or possibly genetic factors that contribute quite substantially to the risk of upper limb fractures in women.

Accidental Falls↗
PubMed2003

Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Age Distribution↗
PubMed2002

Falls explain between-center differences in the incidence of limb fracture across Europe.

There is important geographic variation in the occurrence of the major osteoporotic fractures across Europe. The aim of this study was to determine whether between-center variation in limb fracture rates across Europe could be explained by variation in the incidence of falls. Men and women, aged 50-79 years, were recruited from population-based registers in 30 European centers. Subjects were followed by postal questionnaire to ascertain the occurrence of incident fractures, and were also asked about the occurrence and number of recent falls. Self-reported fractures were confirmed, where possible, by review of the radiographs, medical record, or subject interview. The age- and gender-adjusted incidence of falls was calculated by center using Poisson regression. Poisson regression was also used to assess the extent to which between-center differences in the incidence of limb fractures could be explained by differences in the age- and gender-adjusted incidence of falls at those centers. In all, 6302 men (mean age 63.9 years) and 6761 women (mean age 63.1 years) completed at least one questionnaire concerning fractures and falls. During a median follow-up time of 3 years, 3647 falls were reported by men and 4783 by women. After adjusting for age and gender, there was evidence of significant between-center differences in the occurrence of falls. There was also between-center variation in the occurrence of upper limb, lower limb, and distal forearm fractures. Variation in the age- and gender-adjusted center-specific fall rates explained 24%, 14%, and 6% of the between-center variation in incidence of distal forearm and upper and lower limb fractures, respectively. Given the constraints inherent in such an analysis, in men and women aged 50-79 years, variation in fall rates could explain a significant proportion of the between-center variation in the incidence of limb fracture across Europe.

Accidental Falls↗
PubMed1996

Acquired systemic tolerance to rat cardiac allografts induced by intrathymic inoculation of synthetic polymorphic MHC class I allopeptides.

This study extends the finding that intrathymic (IT) injection of 3M KC1 extracts of T cells induces transplant tolerance to the use of well defined polymorphic MHC class I allopeptides derived from the hypervariable domain of RT1.Au (WF MHC class I). While three of the six synthetic RT1.Au peptides were immunogenic, three others were nonimmunogenic when tested in ACI responders. In our initial studies, we examined the effects of IT injection of a mixture of equal concentrations of the three nonimmunogenic RT1.Au peptides on WF cardiac allograft survival in ACI recipients. The results showed that a single IT injection of 100 and 300 microg class I MHC allopeptides on day -7 relative to cardiac transplant did not significantly prolong graft survival in naive ACI recipients (MST of 9.8, and 12.3 days vs. 10.5 days in controls). In contrast, 600 microg allopeptides injected IT resulted in modest prolongation of graft to an MST of 19.5 days. However, IT injection of 600 microg allopeptides combined with 0.5 ml ALS on day -7 led to permanent acceptance (>200 days) of cardiac allografts in 7/9 ACI recipients compared with survival of 24.2 days in ALS alone treated controls. In contrast, similar treatment led to acute rejection of third party (Lewis) cardiac allografts. Intravenous injection of 600 microg allopeptides combined with ALS did not result in prolonged graft survival (26.8 days). The long-term unresponsive ACI recipients (>100 days) challenged with second-set cardiac grafts accepted permanently donor-type (WF) grafts while rejecting the third party (Lewis) grafts, a finding that confirms acquired systemic tolerance. These findings confirm the role of IT injection of synthetic polymorphic allopeptides in the induction of acquired thymic tolerance and provide the rationale for testing this strategy in large animals and eventually in man.

Amino Acid Sequence↗
PubMed1996

cAMP-mediated vascular protection in an orthotopic rat lung transplant model. Insights into the mechanism of action of prostaglandin E1 to improve lung preservation.

Prostaglandin E1 (PGE1) is often added to the donor pulmonary flush solution to enhance clinical lung preservation for transplantation. Although PGE1 is thought to act as a pulmonary vasodilator during the harvest period, the precise mechanism(s) of action whereby PGE1 enhances lung preservation is unknown. Because cAMP levels decline in endothelial and vascular smooth muscle cells exposed to hypoxia, we hypothesized that a PGE1-mediated increase in cAMP levels within the preserved lungs might improve pulmonary vascular homeostasis following lung transplantation. Rat lungs demonstrated a time-dependent decline in cAMP levels during hypothermic storage, with cAMP levels significantly increased by PGE1 supplementation (approximately 2-fold by 6 hours, P < .0005). To test whether augmenting cAMP levels may enhance lung preservation, experiments were performed using an orthotopic rat left lung transplant model. Compared with controls, supplementing the preservation solution with the membrane-permeable cAMP analogue dibutyryl-cAMP resulted in dose-dependent preservation enhancement, marked by reduced pulmonary vascular resistance (6.0-fold, P < .01), improved arterial oxygenation (3.0-fold, P < .01), reduced graft neutrophil infiltration (1.5-fold, P < .05), and improved recipient survival (7.0-fold, P < .005). Similar preservation enhancement was observed with another cAMP analogue (8-bromo-cAMP) or the phosphodiesterase inhibitor indolidan. Stimulating the cAMP second messenger system by PGE1 supplementation resulted in marked hemodynamic benefits and improved recipient survival, in parallel with reduced graft neutrophil infiltration, vascular permeability, and platelet deposition. These beneficial effects of PGE1 were abrogated by simultaneous administration of the cAMP-dependent protein kinase antagonist Rp-cAMPS. Although an arterial vasodilator (minoxidil) resulted in significant pulmonary vasodilation during harvest, it lacked other nonvasodilating effects of PGE1 and resulted in poor preservation. These data show that harvest vasodilation by itself is insufficient to enhance lung preservation and that PGE1 enhances lung preservation by stimulating the cAMP-dependent protein kinase and promoting non-vasodilatory mechanisms of pulmonary protection.

Alprostadil↗
PubMed1996

Hepatitis C antibodies in patients on peritoneal dialysis: prevalence and risk factors.

Our objective was to determine the prevalence of the antibody to hepatitis C (anti-HCV) in a population of end-stage renal failure patients on continuous peritoneal dialysis (CPD) and study the possible risk factors associated with anti-HCV seropositivity and seroconversion. A cross-sectional study included 155 adult patients enrolled in the CPD program in a single renal unit of a teaching hospital who were screened for anti-HCV by second-generation enzyme immunoassay, which was confirmed by recombinant immunoblot assay. Serum was also assayed for hepatitis B surface antigen (HBsAg). History of renal transplantation, blood transfusions, and exposure to hemodialysis was obtained from medical records. Ten of 155 patients (6.5%) in this study population were anti-HCV positive [anti-HCV(+)] and 11/155 (7.1%) were HBsAg positive; no patient was positive for both. All the anti-HCV(+) patients were on continuous ambulatory peritoneal dialysis (CAPD); no continuous cycling peritoneal dialysis (CCPD) patient was anti-HCV(+). Exposure to hemodialysis was a risk factor for anti-HCV seropositivity, with 7 out of 10 (70%) anti-HCV(+) patients having been on hemodialysis compared to 55/134 (41%) anti-HCV(-) (p < 0.05, Fisher's exact test). No difference was noted between anti-HCV(+) and anti-HCV(-) groups in relation to age, gender, duration on CPD, renal transplantation, or exposure to blood transfusions. Seroconversion occurred in only one patient after a mean observation period of 20 +/- 0.6 months. The prevalence of anti-HCV seropositivity in this population of CPD patients is 6.5%, and HBsAG 7.1%. Exposure to hemodialysis is a significant risk factor for development of anti-HCV seropositivity. Seroconversion rate appears to be low.

Adolescent↗
PubMed1995

Effects of immunosuppressive therapy on expression of inducible nitric oxide synthase (iNOS) during cardiac allograft rejection.

Recent studies have indicated a role for nitric oxide (NO) in alloimmune responses and in allograft rejection. iNOS mRNA, protein and enzyme activity are induced in myocardium during cardiac allograft rejection. NO produced by iNOS is negatively inotropic and has the potential to be cytotoxic to cardiac myocytes. To investigate whether immunosuppressive agents would alter the expression of iNOS during cardiac allograft rejection, hearts from Wistar-Furth rats were transplanted into the abdomen of Lewis recipients. At day 5 allografts from treated and untreated animals were removed for pathological and biochemical examination. At day 5 the untreated allografts exhibited histological evidence of marked rejection (edema, infiltration with macrophages and lymphocytes, necrosis of cardiac muscle fibers). Abundant iNOS mRNA was apparent in Northern blots and iNOS enzyme activity was increased in ventricular homogenates and in cardiac myocytes purified from the untreated rejecting allografts. Incubation of isolated purified cardiac myocytes from normal rats for 24 h with cytokines known to be present during allograft rejection (IL-1 beta, TNF-alpha and IFN-gamma) was also associated with increased iNOS mRNA and enzyme activity. When Wistar-Furth to Lewis allografts were treated from time of transplantation with FK 506, cyclosporine A, dexamethasone or a combination of all three drugs, histological evidence of rejection and the levels of iNOS mRNA and enzyme activity in ventricular homogenates were reduced significantly below those observed in the untreated allografts. The data in a rat model indicate that immunosuppressive drugs reduce myocardial iNOS mRNA and enzyme activity in rejecting cardiac allografts. The results are consistent with the hypothesis that the alloimmune response and cytokine release are involved in the expression of iNOS during cardiac transplantation rejection.

Animals↗
PubMed1995

Inhaled nitric oxide fails to confer the pulmonary protection provided by distal stimulation of the nitric oxide pathway at the level of cyclic guanosine monophosphate.

It has been suggested that inhaled nitric oxide gas may be beneficial after lung transplantation, because endogenous levels of pulmonary nitric oxide decline rapidly after reperfusion. However theoretical concerns remain about the formation of highly toxic oxidants during the quenching of nitric oxide by superoxide. To determine whether distal stimulation of the nitric oxide-cyclic guanosine monophosphate pathway at the level of cyclic guanosine monophosphate might confer the beneficial vascular effects of nitric oxide without its potential toxicities, we studied an orthotopic rat left lung transplant model. In this model, hemodynamic and survival measurements can be obtained independent of the native right lung. Lungs were preserved for 6 hours at 4 degrees C in Euro-Collins solution alone (control, n = 6) or supplemented with the cyclic guanosine monophosphate analog, 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic guanosine monophosphate (cGMP, n = 4). In additional experiments in which lungs were preserved with Euro-Collins solution alone, inhaled nitric oxide was administered during reperfusion (NO, n = 12). Thirty minutes after transplantation and ligation of the native right pulmonary artery, pulmonary vascular resistance, arterial oxygenation, graft neutrophil infiltration (myeloperoxidase activity), and recipient survival were evaluated. Cyclic guanosine monophosphate decreased pulmonary vascular resistance (1.1 +/- 0.2 vs 12.1 +/- 6.3 mm Hg/ml/min, p < 0.05), improved oxygen tension (369 +/- 56 vs 82.8 +/- 48 mm Hg, p < 0.05), reduced myeloperoxidase activity (1.7 +/- 0.3 vs 3.1 +/- 0.9 delta Abs 460 nm/min, p < 0.05), and improved recipient survival (100% vs 0%, p < 0.005) compared with Euro-Collins solution alone (control group). Animals receiving inhaled nitric oxide during reperfusion did not differ from control animals with respect to any of these parameters. These data suggest that distal stimulation of the nitric oxide-cyclic guanosine monophosphate pathway at the level of cyclic guanosine monophosphate has a protective effect that is not seen with inhaled nitric oxide in the immediate pulmonary reperfusion period.

Administration, Inhalation↗
PubMed1995

Enhanced preservation of orthotopically transplanted rat lungs by nitroglycerin but not hydralazine. Requirement for graft vascular homeostasis beyond harvest vasodilation.

Nitric oxide (NO) produced within the lungs maintains pulmonary vascular homeostatic properties, modulating leukocyte traffic, platelet aggregation, and vasomotor tone. Because reactive oxygen intermediates generated during reperfusion react rapidly with available NO, we hypothesized that the NO donor nitroglycerin (NTG) would enhance lung preservation for transplantation by improving graft blood flow and reducing graft neutrophil and platelet sequestration. By use of an orthotopic rat left lung transplant model, with ligation of the native right pulmonary artery to ensure that recipient survival and physiological measurements depend entirely on the transplanted lung, transplants were performed in 70 male Lewis rats after 6-hour 4 degrees C preservation in Euro-Collins solution (EC) alone or EC with supplemental NTG. Compared with EC alone, supplemental NTG significantly increased pulmonary arterial flow (2.2 +/- 1.4 to 21.4 +/- 2.9 mL/min, P < .01), decreased pulmonary vascular resistance (7.4 +/- 2.0 to 1.4 +/- 0.1 x 10(3) Woods units, P < .05), improved arterial oxygenation (163 +/- 57 to 501 +/- 31 mm Hg, P < .01), and enhanced recipient survival (17% to 100%, P < .001). These beneficial effects of NTG were dose dependent over a range of 0.001 to 0.1 mg/mL. Although NTG caused significant pulmonary vasodilation during the harvest/flushing period, the direct-acting vasodilator hydralazine caused greater vasodilation than did NTG but was associated with poor graft function, elevated pulmonary vascular resistance, and poor recipient survival. To explore nonvasodilator protective mechanisms of NTG, graft neutrophil and platelet sequestration were studied; supplemental NTG significantly reduced both neutrophil and platelet accumulation compared with either hydralazine or EC alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Occurrence of salmonellae in slaughtered pigs, goat meat, meat handlers and slaughtered-house workers.

Of 413 samples comprising 200 goat meat, 100 pig's faeces, 50 faeces of slaughtered-house workers, 13 faeces and 50 nailwashings of goat meat handlers collected from different shops of Calcutta Corporation, 25 (6.05 per cent) yielded 13 serotypes of salmonellae. The commonest serotypes was S. newport (24 per cent), followed by S. enteritidis (12 per cent), S. anatum (12 per cent) and S. typhimurium. Isolation rate of salmonellae was 12 (6 per cent) from goat meat, 10 (10 per cent) in pig's faeces and 3 (6 per cent) in nailwashings. S. newport (50 per cent) in goat meat and S. anatum (30 per cent) in faecal contents of pigs were the predominant serotypes. None of the faecal samples of goat meat handlers and slaughtered-house workers yielded salmonellae.

Abattoirs↗
PubMed1986

Changes of lipid spectrum in different tissues of Furadan-treated mice.

The effects of multiple intraperitoneal doses of Furadan (0.125 mg/kg, 0.25 mg/kg and 0.50 mg/kg, respectively) for the 2nd week, 4th week and 6th week of treatment on the concentrations of total lipid and its different fractions and lipase activity in mice were studied. The following were measured in liver, kidney, brain and serum; total lipid, cholesterol (total and free), phospholipid (total and its fractions--lecithin, lysolecithin, phosphatidyl ethanolamine and lysophosphatidylethanolamine), triglyceride, free fatty acid. Lipase activity was measured in liver and serum. Furadan caused biochemical disorders of the tissues. All the aforesaid lipid fractions (except free fatty acid) are elevated significantly in liver, kidney and serum of Furadan-treated mice. Free fatty acid increased significantly in serum and remain constant in other tissues of pesticide-treated mice. All the lipid fractions except phospholipid and its fractions remained constant in brain of treated mice; total phospholipid and its fractions decreased significantly in brain of treated mice. Lipase activity decreased significantly in liver and serum of treated mice. Such disorders of lipid levels in the aforesaid tissues might be associated with CNS depressant action and structural and functional toxicity of other tissues induced by Furadan.

Animals↗