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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

At least 19 recordsLinked to original sources
PubMed2007

Immunogenicity of pneumococcal vaccine in renal transplant recipients--three year follow-up of a randomized trial.

Routine pneumococcal vaccination is recommended at regular intervals posttransplant. However, there is limited data on durability of vaccine response and the impact of vaccine type on antibody persistence. We determined the durability of response for patients enrolled in a randomized trial of conjugate (PCV7) versus polysaccharide (PPV23) pneumococcal vaccination. Response was defined as a twofold increase from baseline and a titer > or =0.35 microg/mL using a pneumococcal ELISA for seven serotypes (measured at 8 weeks and 3 years). Forty-seven patients were evaluated and had received either PPV23 (n = 24) or PCV7 (n = 23). Response rates and geometric mean titers varied by serotype but declined significantly at 3-years for 6 of 7 serotypes (p < 0.001). No significant difference in durability was found in patients that had received PPV23 versus PCV7. Compared to the 8-week response, 20.6% fewer patients had a response to at least one serotype by 3 years. The largest relative declines were seen for serotype 4 (response dropped from 40.4% at 8 weeks to 17.0% at 3 years) and serotype 9V (44.7% dropping to 21.3%). The only factor predictive of response durability was a strong multiserotype initial response (p < 0.001). In conclusion, vaccine responses decline significantly by 3 years and conjugate vaccine does not improve the durability of response.

Adult↗
PubMed2006

Review article: immune suppression and colorectal cancer.

BACKGROUND: Advances in immunology and molecular biology have shown that colorectal cancer is potentially immunogenic and that host immune responses influence survival. However, immune surveillance and activation is frequently ineffective in preventing and/or controlling tumour growth. AIM: To discuss potential ways in which colorectal cancer induces immune suppression, its effect upon prognosis and avenues for therapeutic development. METHOD: A literature review was undertaken for evidence of colorectal cancer-induced immune suppression using PubMed and Medline searches. Further studies were identified from the reference lists of identified papers. RESULTS: Immune suppression occurs at a molecular and cellular level and can result in a shift from cellular to humoral immunity. Several mechanisms for immune suppression have been described affecting innate and adaptive immunity with suppression linked to poorer clinical outcome. CONCLUSIONS: Colorectal cancer causes direct inhibition of the host's immune response with a detrimental effect upon prognosis. Immunotherapy offers a therapeutic strategy to counteract these effects with promising results seen particularly in precancerous conditions and early tumours. This review strongly suggests that immunotherapy should be incorporated into adjuvant therapeutic trials for stage 2 tumours and be considered as adjuvant treatment in conjunction with standard chemotherapy regimes for advanced disease.

Apoptosis↗
PubMed2006

Production of prolific microsheep by embryo transfer into large non-prolific sheep.

The Garole is a prolific breed of microsheep that possesses the FecB gene, which increases ovulation rate. The purpose of this study was to compare embryo production by multiple ovulation in seven Garole ewes with that in seven normal size, non-prolific Malpura ewes, and assess the influence of the large body size of Awassi crossbred recipient ewes on the birth-weight of Garole lambs. Oestrus was synchronised with two intramuscular injections of 7.5 mg prostaglandin F(2alpha) administered 10 days apart. The donor ewes were superovulated by the use of pregnant mare serum gonadotrophin and follicle-stimulating hormone. The onset and duration of oestrus were similar in both breeds. The Garole donors had higher total mean (se) ovarian responses (15.6 [3.6] v 9.1 [2.3]), ovulation rate (13.6 [3.1] v 8.4 [2.2]) and produced more transferable embryos (6.0 [3.5] v 4.0 [0.9]) than the Malpura donors, but the differences were not statistically significant. The Garole lambs produced by embryo transfer were on average 57.8 per cent heavier at birth than contemporary Garole lambs produced by natural mating.

Animals↗
PubMed2006

Knowledge, attitude and practice of complementary and alternative medicines for diabetes.

OBJECTIVES: To investigate the current status of knowledge, attitude and practice of patients with diabetes relating to complementary and alternative medicine (CAM) in an Indian community, and to determine perceptions about the use of CAM and factors influencing knowledge and usage. SETTING: Endocrine clinic of Swaroop Rani, Nehru Hospital, Allahabad, India. STUDY DESIGN: Hospital-based cross-sectional study. PARTICIPANTS: Patients with diabetes attending the clinic for the first time. SAMPLE SIZE: A sample of 493 study participants selected by systematic sampling from a population of 6094 patients with diabetes. STUDY VARIABLES: Age, socio-economic status, educational status, religion, family history of disease, knowledge and practice of CAM, reasons for using CAM, method of use and perceived relief. STATISTICAL ANALYSIS: Normal test of proportions, chi(2) test, Kolomogorov-Smirnov test. RESULTS: Awareness of CAM among patients was high (71%). High prevalence of CAM use was found (67.7%) among all participants, and 95% among participants aware of CAM, mostly using 'naturopathy' (97.3% among users). No significant gap (P>0.10) between knowledge and practice in different categories was observed. Desire for quick and additional relief was the most common perceived reason for using CAM (86.8%). Higher levels of education and socio-economic status were significant positive correlates of CAM use. Knowledge of CAM was gained mainly from friends and neighbours. About 30% of users adopted CAM without allopathic treatment earlier. Only 42.2% of users perceived some relief by using CAM. Lowering of blood sugar was the most common perceived relief. CAM, along with diet control and exercise, resulted in maximum degree of satisfaction (61.9%) experienced by users. No relief was experienced by 53.6% of users of 'naturopathy'. CONCLUSIONS AND SUGGESTIONS: Use of CAM in diabetes is highly prevalent despite high levels of disappointment after its use. In this study, we suggest the need for health education relating to CAM and self-care in diabetes. Use of CAM should be explored with patients before clinical decisions are made.

Adult↗
PubMed2006

Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

Amino Acid Sequence↗
PubMed2006

Randomised double-blind placebo-controlled trial of aloe vera for irritable bowel syndrome.

Aloe vera (AV) is suggested to be beneficial in treating irritable bowel syndrome (IBS) symptoms, but no scientific trials exist to confirm this. We aim to assess the efficacy of AV on IBS in refractory secondary care patients. Patients with IBS were randomised to receive AV or matching placebo for a month. Symptoms were assessed at baseline, 1 and 3 months. Fifty-eight patients randomised, 49 completed the protocol to 1 month and 41 to 3 months. Eleven of thirty-one (35%) AV patients, and 6 of 27 (22%) placebo patients responded at 1 month (p = 0.763). Diarrhoea predominant patients showed a trend towards a response to treatment at 1 month (10/23 V 2/14, p = 0.07). There was no evidence that AV benefits patients with IBS. However, we could not rule out the possibility that improvement occurred in patients with diarrhoea or alternating IBS whilst taking AV. Further investigations are warranted in patients with diarrhoea predominant IBS, in a less complex group of patients.

Adolescent↗
PubMed2006

Systematic review: adipose tissue, obesity and gastrointestinal diseases.

BACKGROUND: Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. Insulin resistance is the most widely accepted link between obesity and disease, particularly colorectal cancer. The recognition that intra-abdominal fat is immunologically active sheds new light not only on the pathogenesis of obesity-related gastrointestinal conditions, but also on inflammatory conditions such as Crohn's disease. AIM: To describe the biology of adipose tissue, its impact on the immune system and explores the possible underlying mechanisms linking obesity to gastrointestinal diseases. It also looks at the role of mesenteric fat in determining severity and course of Crohn's disease. METHODS: Relevant English-language literature and abstracts cited on MEDLINE database were reviewed. RESULTS: Our recent finding of an association between obesity and subclinical bowel inflammation suggests that, apart from promoting generalized immune activation, fat also evokes local immune responses. We propose that the proinflammatory milieu promoted by obesity could underlie many of these associations and that the mechanism implicating insulin resistance may merely represent an epiphenomenon. In Crohn's disease, on the other hand, intra-abdominal fat may provide a protective mechanism. CONCLUSION: The potential of adipose tissue as a therapeutic target is vast and needs exploration.

Adipose Tissue↗
PubMed2006

The correlation between colorectal cancer rates of proliferation and apoptosis and systemic cytokine levels; plus their influence upon survival.

Colorectal cancer development is associated with a shift in host immunity with suppression of the cell-mediated immune system (CMI) and a predominance of humoral immunity (HI). Tumour progression is also associated with increased rates of cell proliferation and apoptosis. The aim of this study was to investigate whether these factors correlate and have an influence upon prognosis. Long-term follow-up was performed on 40 patients with colorectal cancer who had levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 measured from stimulated blood cultures before surgery. Their archived tumour specimens were analysed to determine a Ki-67-derived proliferation index (PI) and a M30-derived apoptosis index (AI). Tumour necrosis factor-alpha levels negatively correlated to tumour proliferation (rho=-0.697, P=0.01). Interleukin-10 levels had a positive correlation with tumour proliferation (rho=0.452, P=0.05) and apoptosis (rho=0.587, P=0.01). Patient survival correlates to tumour pathological stage (P=0.0038) and vascular invasion (P=0.0014). An AI< or =0.6% and TNF-alpha levels > or =8148 pg ml(-1) correlate to improved survival (P=0.032, P=0.021). Tumour proliferation and apoptosis correlate to progressive suppression of the CMI-associated cytokine TNF-alpha and to and higher levels of IL-10. Survival is dependent upon the histological stage of the tumour, vascular invasion, rates of apoptosis and proliferation and systemic immunity which are all interconnected.

Adenocarcinoma↗
PubMed2006

Systematic review of postoperative complications in patients with inflammatory bowel disease treated with immunomodulators.

BACKGROUND: This systematic review examined the use of immunomodulators and the risk of postoperative complications after abdominal surgery in patients with inflammatory bowel disease. METHODS: Electronic databases (PubMed, Embase, Ingenta, Zetoc and Ovid) were searched and the reference lists in all articles identified were hand-searched for further relevant papers. Studies were included if they evaluated postoperative complications and defined exposure to individual immunomodulators. RESULTS: All 11 studies that met the inclusion criteria were observational studies; two were reported only in abstract form. Five studies reported risks associated with azathioprine, five reported risks associated with cyclosporin and three reported risks associated with infliximab. None showed an increased risk of either total or infectious complications associated with immunomodulator use. However, subgroup analysis in one study, published as an abstract, suggested increased rates of anastomotic complications and reoperation associated with azathioprine. CONCLUSION: Available evidence does not suggest an increased rate of postoperative complications associated with immunomodulator use.

Aged↗
PubMed2006

Identification of a repetitive sequence belonging to a PPE gene of Mycobacterium tuberculosis and its use in diagnosis of tuberculosis.

A repetitive sequence specific to Mycobacterium tuberculosis was isolated from a lambda gt11 library of M. tuberculosis by DNA-DNA hybridization using genomic DNA of M. tuberculosis as probe followed by subtractive hybridization with a cocktail of other mycobacterial DNA. This led to identification of CD192, a 1291 bp fragment of M. tuberculosis containing repetitive sequences, which produced positive hybridization signals with M. tuberculosis DNA within 30 min. Nucleotide sequencing revealed the presence of several direct and inverted repeats within the 1291 bp fragment that belonged to a PPE family gene (Rv0355) of M. tuberculosis. The use of CD192 as a DNA probe for the identification of M. tuberculosis in culture and clinical samples was investigated. The 1291 bp sequence was present in M. tuberculosis, Mycobacterium bovis and M. bovis BCG, but was not present in many of the other mycobacterial strains tested, including M. tuberculosis H37Ra. More than 300 clinical isolates of M. tuberculosis were probed with CD192, and the presence of the 1291 bp sequence was observed in all the clinical strains, including those lacking IS6110. The sequence displayed RFLP among the clinical isolates. A PCR assay was developed which detected M. tuberculosis with 100% specificity from specimens of sputum, cerebrospinal fluid and pleural effusion from clinically diagnosed cases of tuberculosis.

Bacterial Proteins↗
PubMed2006

Pandemic influenza and its implications for transplantation.

Influenza viruses are important infections in transplant recipients. They may lead to complications including viral pneumonia, secondary bacterial infections and graft dysfunction. There has been a recent widespread outbreak of highly pathogenic H5N1 avian influenza among domestic poultry and wild birds along with a number of human cases with severe disease and high mortality. Genetic changes in the H5N1 virus may lead to efficient human-to-human transmission, heralding the onset of the next influenza pandemic. Discussed are the implications that such a pandemic may have on transplant patients. Logical inferences can be made from data on influenza in transplant patients and from experience with other respiratory virus outbreaks. In the event of a pandemic, it is likely that transplant patients will have more severe disease and higher mortality as compared to the general population. Vaccination and antiviral strategies may be less effective in this population. Implications for transplant programs in general are also discussed.

Animals↗
PubMed2005

A second locus for Aicardi-Goutieres syndrome at chromosome 13q14-21.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is an autosomal recessive, early onset encephalopathy characterised by calcification of the basal ganglia, chronic cerebrospinal fluid lymphocytosis, and negative serological investigations for common prenatal infections. AGS may result from a perturbation of interferon alpha metabolism. The disorder is genetically heterogeneous with approximately 50% of families mapping to the first known locus at 3p21 (AGS1). METHODS: A genome-wide scan was performed in 10 families with a clinical diagnosis of AGS in whom linkage to AGS1 had been excluded. Higher density genotyping in regions of interest was also undertaken using the 10 mapping pedigrees and seven additional AGS families. RESULTS: Our results demonstrate significant linkage to a second AGS locus (AGS2) at chromosome 13q14-21 with a maximum multipoint heterogeneity logarithm of the odds (LOD) score of 5.75 at D13S768. The AGS2 locus lies within a 4.7 cM region as defined by a 1 LOD-unit support interval. CONCLUSIONS: We have identified a second AGS disease locus and at least one further locus. As in a number of other conditions, genetic heterogeneity represents a significant obstacle to gene identification in AGS. The localisation of AGS2 represents an important step in this process.

Basal Ganglia Diseases↗
PubMed2005

Antioxidant activities of seabuckthorn (Hippophae rhamnoides) during hypoxia induced oxidative stress in glial cells.

The present study reports the cytoprotective and antioxidant properties of alcoholic leaf extract of seabuckthorn (SBT) against hypoxia induced oxidative stress in C-6 glioma cells. Exposure of cells to hypoxia for 12 h resulted in a significant increase in cytotoxicity and decrease in mitochondrial transmembrane potential compared to the controls. Further an appreciable increase in nitric oxide and reactive oxygen species (ROS) production was noted which in turn was responsible for fall in intracellular antioxidant levels and GSH/GSSG ratio. There was a significant increase in DNA damage during hypoxia as revealed by comet assay. Pretreatment of cells with alcoholic leaf extract of SBT at 200 mug/ml significantly inhibited cytotoxicity, ROS production and maintained antioxidant levels similar to that of control cells. Further, the leaf extract restored the mitochondrial integrity and prevented the DNA damage induced by hypoxia. These results indicate that the leaf extract of SBT has strong antioxidant and cytoprotective activity against hypoxia induced oxidative injury.

Antioxidants↗
PubMed2005

Cytoprotective and antioxidant activity of Rhodiola imbricata against tert-butyl hydroperoxide induced oxidative injury in U-937 human macrophages.

The present study reports cytoprotective and antioxidant activity of aqueous and alcoholic extracts of Rhodiola imbricata rhizome on tert-butyl hydroperoxide (tert-BHP) induced cytotoxicity in U-937 human macrophages. There was an increase in cytotoxicity and apoptosis significantly in the presence of tert-BHP over control cells. The tert-BHP induced cytotoxicity can be attributed to enhanced reactive oxygen species (ROS) production which in turn is responsible for fall in reduced glutathione (GSH) levels; further there was a significant decrease in mitochondrial potential and increase in apoptosis and DNA fragmentation. Both aqueous and alcoholic extracts of Rhodiola rhizome at a concentration of 250 microg/ml were found to inhibit tert-BHP induced free radical production, apoptosis and to restore the anti-oxidant levels to that of the control cells. The alcoholic extract of Rhodiola showed higher cytoprotective activities than aqueous extract. These observations suggest that the alcoholic and aqueous extracts of Rhodiola have marked cytoprotective and antioxidant activities.

Antioxidants↗
PubMed2005

Long-term morbidity following short-course, pre-operative radiotherapy and total mesorectal excision for rectal cancer.

AIM: Short-course pre-operative radiotherapy (SCPRT) and total mesorectal excision (TME) have been shown to reduce the rate of relapse and improve survival in patients with rectal cancer. Concerns about morbidity have limited its application in some centres. The aim of this study was to assess long-term toxicity of pre-operative RT in patients with rectal cancer. METHODS: Permanent toxicity was assessed in 20 patients who were alive >12 months after pre-operative RT (25Gy/ 5#), using a validated LENT SOMA scoring system. Ten patients with rectal cancer who had been operated on >12 months ago, but had not received pre-operative RT were assessed similarly. RESULTS: Patients who had received SCPRT appeared to have a significantly higher rectal toxicity, urinary and male sexual dysfunction, compared with the controls. No significant difference was noted in female sexual dysfunction. CONCLUSION: The combination of pre-operative RT and TME appears to be associated with significant long-term toxicity. Better methods of staging the tumours may improve selection of patients for SCPRT.

Adenocarcinoma↗