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Biomedical subjects

S Balupuri

Publications and source records attributed to S Balupuri.

At least 19 recordsLinked to original sources

Outcome of gall bladder polypoidal lesions detected by transabdominal ultrasound scanning: a nine year experience.

AIM: To determine the outcome of polypoidal lesions within the gall bladder (PLG) diagnosed by trans-abdominal scanning. METHODS: A nine-year (1993-2002) retrospective case-note review of all patients who underwent ultrasound scanning after referral to a single Upper GI Surgeon at a District General Hospital was conducted. Patients who were diagnosed with a PLG were included in our study. A database was constructed and patient details, investigations including ultrasound scan (USS) findings, treatment and histology and final diagnosis were recorded. RESULTS: Twenty-three (out of 651) patients were diagnosed pre-operatively by USS to have a polyp-like gall bladder lesion (PLG). Post cholecystectomy histological examination revealed 12 gallstones, 7 cholesterol polyps, 3 adenocarcinomas within polyps and 1 normal gall bladder. The specificity of USS in the diagnosis of PLG was 92.3%. All the true polyps were malignant. Overall USS had 66.66% sensitivity and 100% specificity in the pre-operative suspicion of malignancy. Using size greater than 10 mm as measured on USS as a cut-off, we find 100% sensitivity and 86.95% specificity with a positive predictive value of 50% in the diagnosis of malignancy in PLG. CONCLUSION: A large number of PLG are in fact calculi within diseased gall bladder. In cases of gall bladder polyps more then 10 mm in size on USS further imaging (cross-sectional and/or EUS) is indicated prior to surgery. This will help in the optimal management of patients and avoid histological surprises.

Adenocarcinoma↗

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↗

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↗

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↗

Routine magnetic resonance cholangiopancreatography and intra-operative cholangiogram in the evaluation of common bile duct stones.

INTRODUCTION: Magnetic resonance cholangiopancreatography (MRCP) is a safe and sensitive investigation for the imaging of common bile duct pathology. When used to exclude common bile duct (CBD) stones, MRCP may obviate the need for intra-operative cholangiogram (IOC). In this prospective study, we looked at the single centre results of patients who underwent cholecystectomy with IOC following pre-operative MRCP. PATIENTS AND METHODS: Over a period of 18 months, 69 patients (24 male and 45 female; mean age 59 years [range, 19-86 years]) were investigated by MRCP prior to cholecystectomy. All patients underwent IOC. Inclusion criteria for MRCP consisted of derangement of liver function tests and/or history of jaundice in cases of ultrasound-proven cholelithiasis. RESULTS: Sixteen patients had suspected stones or filling defects on MRCP; all but two of these were confirmed to be stones on IOC. In only one patient was a stone visualised on IOC and not seen on MRCP. CONCLUSION: MRCP may be the only pre-operative investigation needed for exclusion of CBD stones, obviating the necessity for IOC.

Adolescent↗

Weight increase during machine perfusion may be an indicator of organ and in particular, vascular damage.

OBJECTIVES: Hypothermic machine perfusion preservation has been shown to improve the outcome of renal grafts from non-heartbeating donors. We have noticed that organs gain a variable amount of weight during perfusion. METHODS: All grafts, whether used or discarded, were assessed with respect to their weight gain. Primary outcome measures were the results of viability testing. Secondary outcomes were early transplant variables including incidence and duration of delayed graft function and histological examination of protocol graft biopsies. RESULTS: Weight increase data was available on 97 grafts. There were no significant differences in weight gain between kidneys used and discarded (17% vs 20%). 14 patients received grafts which gained over 30% of their initial retrieval weight. There were no significant differences in secondary outcome measures between this group of recipients and patients who had received less "waterlogged" kidneys. Histological changes including endothelial inflammation and oedema were observed. CONCLUSIONS: Kidney grafts which have gained over 30% of weight on hypothermic machine perfusion preservation can be transplanted successfully. Complex interactions between the period of warm ischaemia, in situ flushing, perfusion pressures and perfusate probably lead to the phenomenon of excessive graft weight gain.

Blood Vessels↗

Machine perfusion for kidneys: how to do it at minimal cost.

Due to a shortage of organs for transplantation, many centres use marginal grafts to increase their donor pool. As kidneys from non-heart-beating donors (NHBD) have sustained initial ischaemic damage, their viability is difficult to predict. Hypothermic pulsatile perfusion has not only been used to improve the condition of such grafts, but also allows viability assessment. Suitable systems are becoming more readily available, but they are expensive. We have used existing dialysis equipment with modified sterilised inserts to create a pulsatile hypothermic perfusion system. With this system, 41 NHBD kidneys were perfused for up to 8 h; their intravascular renal resistance (IRVR), flow characteristics as well as glutathione S transferase (GST) measurements were performed to assess viability. This hypothermic pulsatile perfusion system is now an integral component of our NHBD programme.

Costs and Cost Analysis↗

The trouble with kidneys derived from the non heart-beating donor: a single center 10-year experience.

BACKGROUND: The demand for renal transplantation has increasingly outstripped the supply of donor organs especially over the past 10 years. Although related and unrelated live donation is being promoted as one option for increasing the donor pool, it is unlikely that this will in itself be able to bridge the gap. Non-heart beating donors (NHBD) can provide an alternative supply of organs, which should substantially increase the donor pool. METHODS: In Newcastle, NHBD kidneys have been used for transplantation for a period of 10 years. In the early period (1988-1993) excellent results were obtained (90.5% success); however, these donors were controlled NHBD, Maastricht category III. In the second phase (1994-1998) increasing numbers of donors were obtained from the Accident and Emergency Department unit. These were failed resuscitation for cardiac arrest (category II). The rates of success in this period were poor (45.5% success) and the program was halted. The third phase of the program used machine perfusion of the kidneys and glutathione S transferase enzyme analysis to assess viability. RESULTS: Using such approaches renal transplants from largely category II donors produced a success rate of 92.3% which was significantly better than the phase II period of the program (P=0.023, Fisher two-tail test). CONCLUSION: Machine perfusion and viability assessment of NHB kidneys in phase III of the program has increased our donor pool as well as improved the graft survival. This is particularly relevant for the use of the category II NHB donor where the incidence of primary nonfunction was high, illustrated by phase II where machine perfusion/viability assessment was not used.

Adult↗

TGF-beta expression in renal transplant biopsies: a comparative study between cyclosporin-A and tacrolimus.

BACKGROUND: Chronic rejection is a major cause of graft dysfunction after kidney transplantation. This fibroproliferative disease may be promoted by overproduction of transforming growth factor beta (TGF-beta). Previous studies have suggested that CsA might increase production of this growth factor. The current study was designed to measure the expression of TGF-beta(b) in renal transplant biopsy specimens from patients undergoing immunosuppressive therapy with either CsA or tacrolimus (FK506). METHOD: Paraffin-embedded renal biopsy specimens were sectioned, dewaxed, and incubated with primary antibody against TGF-beta(b)1 latency-associated protein and active TGF-beta(b1). After washing, the sections were treated with secondary antibody conjugated with FITC. In each case, the sections were assessed by semi-quantitative scanning laser confocal microscopic method. RESULTS: There was no significant difference in latent TGF-beta(b) expression between biopsy specimens from patients receiving CsA and patients receiving FK506. However, biopsy specimens from patients receiving CsA expressed significantly more active TGF-beta(b1) than biopsy specimens from patients receiving FK506 (P<0.0001, Mann-Whitney test). DISCUSSION: The increased level of active TGF-beta1 expression in renal biopsy specimens of patients receiving CsA may indicate a mechanism of chronic rejection. However, these biopsies were performed to assess deranged renal function; therefore, the specimens may reflect events rather than differences in medication.

Biopsy↗

Early results of a non-heartbeating donor (NHBD) programme with machine perfusion.

Freeman Hospital, Newcastle upon Tyne restarted their non-heartbeating donor (NHBD) programme in September 1998 using machine perfusion, due to early poor results with conventional cold storage (45% graft survival, phase II). Since then, 15 NHBD kidneys have been transplanted. The retrieval protocol consisted of in situ perfusion with a double balloon triple lumen cannula in Maastricht category II male donors age range 13-59 years. Mean primary warm ischaemic time was 24.8 min (range 10-44). All kidneys were machine perfused through a locally developed perfusion system. The viability was assessed by serial measurements of total GST (maximum acceptable limit of 200 units/l) and intrarenal vascular resistance (IRVR) was recorded. Fifteen of the 22 kidneys (68.62%) were transplanted. Delayed graft function (DGF) was seen in ten recipients (66.6%), two kidneys had immediate function (IF), one organ was exported, two recipients died of unrelated causes and a further seven kidneys were discarded (two had high tGST, two were infected and three had poor flow characteristics). In phase III, a success rate of 91.7% was thus achieved, which was better than the phase II period (P = 0.027, Fisher 2-tail test). Machine perfusion has been successfully introduced in phase III to the Newcastle NHBD programme and facilitates viability assessment of NHBD kidneys.

Adolescent↗

Active TGF-beta1 expression in kidney transplantation: a comparative study of cyclosporin-A (CyA) and tacrolimus (FK506).

Chronic rejection is a major cause of graft dysfunction following kidney transplantation. This fibroproliferative disease may be promoted by overproduction of transforming growth factor beta (TGF-beta). Previous studies have suggested that cyclosporin-A (CyA) might increase production of this growth factor. The current study was designed to measure the expression of TGF-beta in renal transplant biopsies from patients immunosuppressed with either CyA or tacrolimus. Paraffin-embedded renal biopsies were sectioned, dewaxed and incubated with primary antibody against active TGF-beta1 antibody. After washing, the sections were treated with secondary antibody conjugated with fluorescein isothiocyanate (FITC). In each case the sections were assessed by semi-quantitative scanning laser confocal microscopy. Biopsies from patients receiving CyA expressed significantly more active TGF-beta1 than biopsies from patients receiving tacrolimus (P < 0.0001, Mann-Whitney test). The increased level of active TGF-beta1 expression in renal biopsies of patients receiving CyA may indicate a mechanism of chronic rejection.

Biopsy↗

The impact of cytomegalovirus serology for 7-year graft survival in cadaveric kidney transplantation--the Newcastle experience.

To analyse the contribution of cytomegalovirus (CMV) serology to long-term graft survival in cadaveric kidney transplantation, 404 transplants from a single centre were divided into four subgroups with respect to the combination of donor and recipient CMV antibody status. Graft survival was estimated according to Kaplan-Meier for 1, 3, 5 and 7 years post-transplantation. The single-centre results confirm a negative impact of CMV-positive donor organs for initial graft survival in CMV-negative recipients within the first 3 years after transplantation. However, when 5- and 7-year long-term graft survival was studied, Donor +/Recipient - pairs showed a favourable long-term result, whilst D +/R - pairs had surprisingly a poorer outcome. Therefore, the concept of avoiding transplantation in the D +/R + CMV serology group should be ignored whereas attempts could be made to improve the poor long-term outcome of D +/R + pairs or to reduce its size by organ allocation.

Adolescent↗

Comparison of proteolytic enzymes and glutathione S-transferase levels in non-heart-beating donors' (NHBD) kidney perfusates.

UNLABELLED: In order to identify biochemical markers of kidney damage prior to transplantation, we determined the levels of activity of a range of proteolytic enzymes in kidney perfusate samples from non-heart-beating donor (NHBD) cases. Urinary protease activities have been described as indices of kidney damage in renal disease; their potential as markers of tissue damage in kidneys before transplantation has not been assessed. In an attempt to identify additional/improved biochemical markers, the present study compared the levels of total glutathione S-transferase (GST) with corresponding levels of several proteolytic enzymes in perfusate fluid from machine perfused NHBD kidneys. Proteases were selected to represent factors that may influence enzyme efflux, such as intracellular localization or molecular size. METHODS: Perfusate samples were obtained over an 8-hour period from machine-preserved NHBD kidneys. Protease activities in these samples were determined by fluorometric assays and comparison made with total GST activity. Individual proteases were analysed in the transplanted and non-transplanted kidney groups (discarded on the basis of other viability parameters). RESULTS: A correlation between protease activity and total GST was obtained for only leucyl- and pyroglutamyl aminopeptidase. Furthermore, in the transplanted group, it was possible to set nominal upper limits of activity for alanyl-arginyl- and dipeptidyl IV-aminopeptidase (AP). In the non-transplanted kidney group protease levels were increased above "normal" upper limits for the same enzyme types. By the use of alanyl AP it was possible to discriminate 75% of unsuitable kidneys discarded by the use of other criteria. CONCLUSION: The lack of correlation between total GST and protease activity for most of the enzymes investigated and alanyl AP levels in perfusate samples could be related to differences in cellular localisation, suggesting that assays of alanyl AP may give complimentary biochemical information relating to kidney tissue damage. Quantification of alanyl AP in machine perfusate samples may be a valuable additional independent biomarker of tissue damage.

Endopeptidases↗

Assessment of non-heart-beating donor (NHBD) kidneys for viability on machine perfusion.

UNLABELLED: The shortage of organs has resulted in renewed interest in organs from non-heart-beating donors (NHBD). Viability assessment of such organs may reduce the incidence of delayed graft function and primary non-function. In Phase III of the NHBD programme, introduction of machine perfusion enabled the assessment of these marginal donors. Since then the graft survival has been 88.4% compared with the previous phase where machine perfusion or viability assessment was not done (45.5%). The parameters used were total glutathione S-transferase (GST) in the perfusate, the intrarenal vascular resistance (IRVR) and flow characteristics over time. METHODS: All NHBD kidneys were machine perfused through a locally developed perfusion system. The viability was assessed by serial measurements of the above-mentioned parameters. RESULTS: Forty-two local NHBD kidneys were retrieved and one kidney was imported, of which 19 donors (i.e. 38 kidneys) were of the uncontrolled (category II) donors. After viability assessment on machine perfusion; two kidneys were discarded due to positive tests for syphilis, four kidneys had high total GST levels, five kidneys due to high IRVR and poor flow characteristics and one did not flush on retrieval. Three kidneys were exported after viability tests. In 28 NHBD kidney recipients, immediate graft function was seen in two kidneys, 22 (84.6%) developed delayed graft function. One kidney had primary non-function, and two recipients lost their grafts, due to chronic rejection and renal vein thrombosis. There were two deaths, unrelated to transplantation. Graft survival was achieved in 88.4% (23/26 graft survival in phase III) of cases. CONCLUSION: Machine perfusion and assessment of NHBD kidneys has been successfully introduced to the Newcastle NHBD programme. This approach, using renal transplants from largely category II donors produced a success rate of 88.4% which was significantly better than the phase II period (45.5%) of the program (p=0.023, Fisher 2 tail test).

Humans↗