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Biomedical subjects

A Gupta

Publications and source records attributed to A Gupta.

At least 73 records · Page 4Linked to original sources
PubMed2005

A novel non-toxic camptothecin formulation for cancer chemotherapy.

The use of a novel injectable biocompatible and biodegradable camptothecin-polymer implant for sustained intra-tumoral release of high concentrations of camptothecin is described. The drug delivery vehicle is an in situ thermogelling formulation, which is based on the natural biopolymer chitosan. This formulation, containing homogeneously dispersed camptothecin, was implanted intra-tumorally into a sub-cutaneous mouse tumor model (RIF-l). The effectiveness of treatment was measured in terms of tumor growth delay (TGD). Animals treated with the polymer implants containing camptothecin had significantly longer TGDs compared to untreated animals as well as to animals treated systemically with camptothecin by intra-peritoneal injection with no evidence of toxicity in terms of loss of body weight. The results indicate that this novel biodegradable polymer implant is an effective vehicle for the sustained intra-tumoral delivery of camptothecin which might also be suitable to deliver other insoluble anti-cancer drugs such as taxol.

Absorbable Implants↗
PubMed2005

A hand research fellowship training programme.

There are currently 68 hand surgery fellowship programmes known to the authors in the United States and many more throughout the world. To our knowledge, there are no hand fellowships which focus on research. Such a hand surgery research fellowship is being developed to provide this training. This paper outlines the goals and objectives of the intended 2 year training programme and includes a description of the fellowship. The first year would be mostly committed to learning research methods and the second would be a clinical hand fellowship. This will combine clinical expertise in hand surgery, practical research experience and formal research training. Hand researchers would learn research methods, develop innovative research ideas and begin an active research and academic career.

Education, Medical, Graduate↗
PubMed2005

Serogroup-reactive and type-specific detection of bluetongue virus antibodies using chicken scFvs in inhibition ELISAs.

Two bluetongue virus (BTV) serotype 10-specific single-chain Fv chicken antibody fragments (scFvs) were evaluated in a competitive ELISA. The binding of one (F3) to purified BTV was only inhibited by antibodies against the homologous serotype. The binding of the other (F10) was blocked by antisera to each of the 24 BTV serotypes. F10 recognised VP7, a major structural protein of the BTV core, but not if the protein was directly adsorbed to a plastic surface. It did, however, bind to recombinant VP7 that had been captured from suspension by rabbit IgG. This made it possible to develop an scFv based inhibition ELISA for BTV antibodies using recombinant VP7 without prior purification. The resulting immunoassay detected antibodies to 24 BTV serotypes, but not those directed against three serotypes of the related epizootic haemorrhagic disease virus. A phage library displaying fusion peptides expressed by fragments of the BTV genome segment 7 cDNA was constructed and screened using F10. Comparing selected peptides with the amino acid sequence of VP7 showed that recognition by the scFv required at least 131 residues representing the protein's upper domain. By providing well-characterised immunological reagents, recombinant antibody technology can contribute to the development of improved immunoassays for BTV diagnosis.

Animals↗
PubMed2005

Vimentin antibodies: a non-HLA antibody as a potential risk factor in renal transplantation.

Chronic allograft rejection is the major problem encountered in solid organ transplantation and is the end point of several complex processes. A number of recent studies show both alloimmune and autoimmune responses may have roles to play. The importance of HLA antibodies in transplantation is well documented, but despite the introduction of very sensitive HLA screening assays, antibody-mediated allograft rejection still occurs without detectable HLA antibodies. The target for antibody-mediated allograft rejection in these circumstances remains elusive, perhaps due to the variety of potential targets presented on endothelial cells. Recent studies identifying C4d and immunoglobulin deposits in patients undergoing late allograft loss provide evidence that chronic rejection involves humoral as well as cellular components. Several endothelial cell antigens that might be important in chronic rejection have been suggested, including MHC class I chain-related genes; Lewis; and the intermediate filament protein, vimentin. Vimentin is an ideal candidate antigen for antibody-mediated rejection as it is found in endothelial cells and is exposed to the immune system following surgery or by chronic allograft rejection due to endothelial cell breakdown, where the development of antibodies may cause further damage. We have developed a flow cytometric assay for the detection of antibodies to vimentin and have investigated whether HLA or vimentin antibodies are present in renal transplant recipients undergoing chronic rejection.

Graft Rejection↗
PubMed2005

A simple cardiovascular risk score can predict poor outcome in non-heart-beating donor renal transplantation.

A simple cardiovascular risk score used in our centre to plan cardiovascular work-up for renal transplantation can predict outcome in non-heart-beating donor (NHBD) renal transplantation. Patients in the higher-risk group, with a score of >12 of a maximum of 36 are likely to have a longer duration of delayed graft function, poorer glomerular filtration rate at 6 months, and inferior graft and patient survival, together with a relative rate of graft loss within 60 days of 4.514 (P = .019) and within 1 year of 3.511 (P = .036). Although a high cardiovascular risk score should not be regarded as a contraindication to NHBD transplantation, the score can be used to facilitate recipient selection.

Adult↗
PubMed2005

Evaluation of daclizumab to reduce delayed graft function in non-heart-beating renal transplantation: a prospective, randomized trial.

Daclizumab (DZB), an interleukin-2 receptor blocker, has been shown to reduce the rate of acute rejection, while non-heart-beating kidney recipients have high rates of delayed graft function that may be prolonged by high levels of calcineurin inhibitors. This study assessed whether DZB could safely replace calcineurin inhibitors in the immediate postoperative period and promote recovery from ischemic acute tubular necrosis. Patients were randomized into one of two groups: DZB induction and daily mycophenolate mofetil (MMF; 2 g) with steroids (20 mg prednisone) or standard triple therapy with tacrolimus, MMF, and prednisone. Patients in the DZB arm were converted to the control arm when either the serum creatinine dropped to <350 micromol/L or there was biopsy evidence of acute rejection. Over 2 years, Leicester and Newcastle non-heart-beating donor (NHBD) centers recruited 51 patients. There was one patient death in the DZB arm, during the study period, after a nonfunctioning graft was removed. A total of two (8%) grafts in the DZB arm and three (11.5%) grafts in the control arm failed to function. The overall rate of immediate function improved from around 5% (pre-2001) to 28%. There were no significant differences in the incidence of acute rejection or graft function (GFR) at 3 months. Machine-perfused kidneys in DZB-treated recipients had the highest rates of immediate function (53%, P = .015). We found that a calcineurin-sparing regime is safe and may be beneficial for recipients of machine-perfused grafts damaged by warm ischemia.

Antibodies, Monoclonal↗
PubMed2005

Does donor cardiopulmonary resuscitation time affect outcome in uncontrolled non-heart-beating donor renal transplants?

Uncontrolled non-heart-beating donors offer the opportunity to significantly expand the potential pool of kidney donors but are associated with a variable duration of cardiopulmonary resuscitation (CPR), where cardiac output is only 30% to 40% of normal. We were concerned that prolonged CPR would adversely affect the function of transplanted kidneys. In our series of 46 uncontrolled donors the mean duration of CPR was 60 minutes, which also represents a realistic cutoff point for CPR duration. Taking a cutoff point of 60 minutes, we found no differences in kidney discard rates following viability assessment, primary nonfunction rate, or duration of delayed graft function. We therefore conclude that if formal viability assessment is performed, kidneys may be retrieved from uncontrolled non-heart-beating donors irrespective of duration of CPR.

Cardiac Output↗
PubMed2005

Do recipients of kidneys from donors treated with streptokinase develop anti-streptokinase antibodies?

Streptokinase is used for preflush for non-heart-beating donors (NHBDs) in our center. The aim of this study was to evaluate whether the use of thrombolytic streptokinase results in the production of anti-streptokinase antibodies in the recipients after renal transplantation. Recipient sera taken prior to and at 1 and 6 months posttransplant were tested for the presence of antibodies to streptokinase using an enzyme-linked immunosorbent assay assay. No differences were detected between a group of 18 recipients who had kidneys from thrombolytic-treated NHBDs and a further group of 18 who received NHBD kidneys without such treatment.

Antibodies↗
PubMed2005

Variation in organ donation in northeastern England 1986 to 2003.

Renal transplantation is established as the best form of renal replacement therapy, but demand for kidneys exceeds supply from cadaveric donations. It is therefore important to make the best use of the pool of potential cadaveric organ donors. Donation rates are to a large extent dependent on public opinions, which may be influenced by external events. In northeast England from 1986 to 2003, there was a potential pool of 1170 brain stem-dead donors, of whom 190 (16%) could not be retrieved due to relatives' objections. From 1998 to 2003 we were referred 90 potential non-heart-beating donors, of whom relatives refused donation in 10 (11%). A major reason for not retrieving organs from a potential donor has been lack of consent from the relatives. Refusals appear to vary year by year and are consistently lower for non-heart-beating donors. This therefore raises the possibility that negative or positive media publicity plays a role in this variation.

Attitude to Death↗
PubMed2005

Anti-vimentin antibody detection in recipients of heart-beating and non-heart beating donor kidneys.

Alternative donor sources include non-heart-beating donors (NHBDs). There donors have been exposed to significant ischemia, so that it is common to utilize machine perfusion to either improve the organs or at least assess their viability. Both prolonged warm ischemia and machine perfusion can potentially damage the vascular endothelium, thereby exposing vimentin to antigenic recognition. The aim of this study was to determine whether anti-vimentin antibodies could be detected in the blood of renal transplant recipients at specific time points after transplant and whether they could be related to the donor source. Fifty-one recipients of NHBD kidneys were compared to 52 recipients of heart-beating donor (HBD) kidneys. All recipients had similar anti-vimentin levels pretransplant. However, at 1 month those kidneys from Maastricht category II NHB donors showed significantly higher levels. At 6 months both Maastricht category II and category III NHB donor recipients displayed significantly higher levels than recipients of HBD kidneys.

Adult↗
PubMed2005

Cardiovascular risk assessment scoring system for the determination of cardiovascular mortality in renal transplant patients.

It is well known that the greatest risk for mortality post-renal transplant is cardiovascular death. We compared a modified cardiac risk assessment system among renal transplant patients who subsequently died versus the group that survived. There was a good correlation between the low, medium, and high scores with survival. The deceased group had significantly greater cardiovascular scores than case controls.

Adult↗
PubMed2005

A simple cardiovascular risk score can predict poor outcome in NHBD renal transplantation.

A simple cardiovascular risk score used in our center to plan cardiovascular workup for renal transplantation can predict outcome in non-heart-beating donor (NHBD) renal transplantation. Patients in the higher risk group, with a score of >12 out of a maximum of 36 are likely to have a longer duration of delayed graft function, poorer glomerular filtration rate at 6 months, and inferior graft and patient survival, together with an relative rate of graft loss within 60 days of >4 (P = .053). Although a high cardiovascular risk score should not be regarded as a contraindication to NHBD transplantation, the score can be used to facilitate recipient selection.

Adult↗
PubMed2005

Circadian variation in stroke - a prospective hospital-based study.

A particular pattern of circadian variation of cardiovascular and cerebrovascular diseases has been reported in the literature. The circadian periodicity of ischaemic stroke with peak onset in the morning hours may not be a random event and could depend on some underlying precipitating and associated cardiovascular risk factors. In a prospective observational study, we observed that ischaemic stroke onset was significantly higher in late morning hours between 6.00 and 12.00 hours. Ischaemic heart disease and hypertension were significantly associated with the occurrence of late morning ischaemic strokes. Further studies in the future are needed to understand the significance of this association and whether these risk factors are implicated in the pathogenesis of stroke.

Circadian Rhythm↗
PubMed2005

Improved analgesia with clonidine when added to local anesthetic during combined spinal-epidural anesthesia for hip arthroplasty: a double-blind, randomized and placebo-controlled study.

BACKGROUND: The perioperative effects of intrathecal and epidural clonidine combined with local anesthetic were evaluated in 60 patients undergoing hip arthroplasty. METHODS: This was a double-blinded study and the patients were randomized into three groups, with 20 patients in each group. All patients received spinal anesthesia with 17.5 mg of plain bupivacaine with 15 microg of clonidine (Group BC-RC) or without clonidine (Groups B-R and B-RC). Postoperatively, epidural infusion was administered in the following way: Group B-R-ropivacaine 4 mg h(-1); Groups B-RC and BC-RC: ropivacaine 4 mg h(-1) and clonidine 40 microg h(-1). Sensory block was assessed with light touch, pinprick, transcutaneous electrical stimulation at T12 and L2 dermatomes, and perception of thermal stimuli. RESULTS: The maximal upper level of sensory block measured by pin-prick (T6-T7) did not differ between the groups while the partial sensory block for cold and warmth were increased two dermatomes above pin-prick level in the group with intrathecal clonidine compared to the other two groups (P < 0.05). Duration of anesthesia, analgesia and motor block were longer in Group BC-RC compared to Groups B-R and B-RC (P < 0.02). Postoperatively, both VAS score on movement and PCA-morphine consumption were higher in Group B-R than in Groups B-RC and BC-RC (P < 0.01). The arterial pressure and heart rate in Groups B-RC and BC-RC were significantly lower than in Group B-R at 10-24 and 15-24 h, respectively, after spinal injection. CONCLUSION: Low-dose intrathecal clonidine provided a better quality of anesthesia and longer-lasting analgesia. Epidural clonidine-ropivacaine infusion resulted in improved postoperative analgesia but was associated with a moderate decrease in blood pressure.

Adjuvants, Anesthesia↗
PubMed2005

Coagulation and inflammatory markers in Alzheimer's and vascular dementia.

Alzheimer's disease is classified as a degenerative dementia while vascular dementia is known to be associated with atherothrombosis and classical vascular risk factors. However, over the last decade, there is increasing evidence of the role of haemostatic factors and inflammatory mechanisms in the pathogenesis of Alzheimer's disease. Serum markers of hypercoagulability and markers of inflammation could lead to thrombosis, accelerated atherogenesis and resulting dementia of both Alzheimer's and vascular dementia. In this case control study, we studied these serum markers of coagulation and inflammation in patients suffering from dementia.

Alzheimer Disease↗
PubMed2005

Unidirectional whole body turning: a new lateralising sign in complex partial seizures.

BACKGROUND: The lateralising significance of unidirectional whole body turning in patients with complex partial seizures (CPS) arising from the temporal lobe was evaluated. METHODS: A total of 330 patients undergoing long term video-EEG study were included. "Unidirectional whole body turning" was defined as rotation of the trunk, head, and limbs by >90 degrees and lasting >10 s. EEG correlates, MRI, and SPECT findings were compared and outcome after surgery was noted for patients with follow up data for >1 year. RESULTS: Unidirectional whole body turning was observed in 13 patients with a mean age of 18+/-8 years. Concordance of the side of whole body turning with the EEG focus and MRI findings was observed in 11 of the 13 patients (84.7%) and in 26 of 28 seizures (92.8%). The six patients who underwent temporal lobectomy or resection of lesion, opposite to the direction of body turning, had good seizure outcome. CONCLUSION: Unidirectional whole body turning is a new lateralising sign in temporal lobe CPS with good predictive value for epileptogenic focus contralateral to the direction of turning.

Adolescent↗