PubMed Health⌕ Search

Biomedical subjects

M L Nicholson

Publications and source records attributed to M L Nicholson.

At least 19 recordsLinked to original sources
PubMed2006

The aetiology and pathogenesis of chronic allograft nephropathy.

Renal transplantation is the ultimate form of renal replacement therapy, and is the treatment of choice for many patients with end-stage renal failure. The advent of calcineurin inhibitor based immunosuppression resulted in the 1-year renal allograft failure rate dropping from around 50% twenty years ago to less than 10% in more recent times. Despite a massive improvement in renal allograft survival in the first year following transplantation 10-year graft survival can be as low as 50%. Chronic allograft nephropathy (CAN) is recognised as the main cause of renal allograft failure following the first year after transplantation. The diagnosis of CAN can only be made histologically. Typically biopsy specimens in grafts with CAN demonstrate an overall fibrotic appearance effecting the vascular endothelium, renal tubules, interstitium, and glomerulus. The risk factors for CAN are divided into alloimmune and alloimmune independent. Alloimmune dependent factors include acute cellular rejection, severity of rejection, subclinical rejection and HLA mismatch. Alloimmune independent factors such as delayed graft function, donor age, Cytomegalovirus infection, donor/recipient co-morbidity and of course calcineurin inhibitor toxicity are important in the development of CAN. The pathogenesis of CAN is complex, multifactorial, and unfortunately incompletely understood. There are a number of pivotal steps in the initiation and propagation of the fibrosis seen in biopsy specimens from kidneys with CAN. Endothelial activation in response to one or more of the aforementioned risk factors stimulates leukocyte activation and recruitment. Recruited leukocytes subsequently infiltrate through the endothelium and induce key effector cells to secrete excessive and abnormal extracellular matrix (ECM). Enhanced deposition of ECM is a histological hallmark of CAN. This paper aims to present a concise yet accurate and up-to-date review of the literature concerning the aetiological factors and pathological processes which are present in the generation of CAN.

Animals↗
PubMed2006

Tunnelled catheters for the haemodialysis patient.

Haemodialysis depends upon the establishment of a durable means of vascular access. Although the creation of a successful arterio-venous Fistulae (AVF) is the ideal, this is not always possible or practical. Tunnelled catheters play an important role as an interim/bridge technique for emergency access or while an AVF matures, but may be associated with significant morbidity. The aim of this review is to highlight recent evidence based developments in tunnelled catheters, including methods of placement, complications and possible management strategies.

Catheterization, Central Venous↗
PubMed2006

Effects of arterial pressure in an experimental isolated haemoperfused porcine kidney preservation system.

BACKGROUND: Normothermic preservation provides metabolic support to an ischaemically damaged organ before use as a kidney transplant. Optimal conditions for ex vivo preservation have not yet been established. This study examined the effects of arterial pressure on renal preservation using isolated haemoperfused kidneys. METHODS: An isolated organ preservation system, developed using cardiopulmonary bypass technology, was used to perfuse porcine kidneys with normothermic oxygenated blood. Groups of kidneys (n = 6) were perfused at a mean arterial pressure of 95, 75 or 55 mmHg. RESULTS: Kidneys perfused at the higher mean arterial pressures of 95 and 75 mmHg demonstrated improved renal function: mean(s.d.) area under the curve (AUC) for creatinine clearance 71(19) and 55(30) respectively versus 14(12) in the 55-mmHg group, P = 0.002; AUC for serum creatinine 938(140) and 1290(394) versus 2404(595), P = 0.003. The higher perfusion pressures were also associated with better acid-base homeostasis and improved renal haemodynamics. CONCLUSION: Mean arterial pressures of either 95 or 75 mmHg were capable of sustaining physiological renal function, but kidneys in the 95-mmHg group demonstrated superior renal function overall.

Animals↗
PubMed2006

Morbidity rates with reduced mycophenolate mofetil dosage: a single-center experience.

OBJECTIVE: Mycophenolate Mofetil (MMF) is a key component of available immunosuppressant regimens for transplantation. Traditionally a dose of 2 g/d is utilized, with the incidence of side effects, most notably gastrointestinal, being well known to transplant teams. The aim of this study was to assess the incidence of side effects and rejection rates with reduced doses compared to standard regimens of MMF. METHODS: Case notes of 117 renal transplants performed from 2002 to 2004 were reviewed retrospectively for the incidence of side effects and rejection rates for MMF doses of 1 g twice a day (n = 86) versus 500 mg twice a day (n = 27). RESULTS: All patients received MMF, steroids, and a calcineurin inhibitor or sirolimus. The incidence of side effects was higher at 1 g twice a day. Seventy-nine percent of the patients required dose reductions due to side effects. The incidence of acute rejection episodes was similar in both groups. CONCLUSION: The balance between adequate immunosuppression, side effects, and the risk of rejection is a constant dilemma faced by transplant surgeons. This study showed a reduced side effect profile with similar rejection rates when using a lower-dose regimen of MMF. This may have implications for future immunosuppressive protocols.

Dose-Response Relationship, Drug↗
PubMed2006

Comparison of techniques of vascular control in laparoscopic donor nephrectomy: The leicester experience.

BACKGROUND: The objective of this study was to compare the safety and efficacy of three different methods to secure the renal vessels during laparoscopic donor nephrectomy (LDN). METHODS: Vessel lengths and intraoperative vascular complications were compared in a prospective series of 106 LDNs in which the vessels had been secured using a stapling device, metal clips, or polymer clips. RESULTS: One hundred six patients underwent LDN (right = 25, left = 81). Renal vein lengths were not significantly different after stapling or using polymer clips (36 +/- 10 vs 37 +/- 9 mm; P = .463). Renal arterial length was shorter after stapling (30 +/- 7 mm) compared with both endoclips (34 +/- 10 mm; P = .030) and polymer clips (34 +/- 8 mm; P = .030). There was one major arterial bleed in the endoclip group, one episode of stapler malfunction, but no adverse events with polymer clips. CONCLUSION: Polymer clips are safe and yield greater vessel lengths during LDN.

Humans↗
PubMed2005

Comparison of renal allograft fibrosis after transplantation from heart-beating and non-heart-beating donors.

BACKGROUND: Renal transplants from non-heart-beating donors (NHBDs) yield acceptable function and allograft survival rates in the medium term. However, the long-term results are less certain and there is a paucity of information relating to the development of chronic allograft nephropathy. The aim of this study was to compare allograft fibrosis in kidneys transplanted from NHBDs and conventional heart-beating donors (HBDs). METHODS: A series of 37 NHBD and 75 HBD renal transplants were studied. Protocol renal transplant biopsies were performed at 6 and 12 months after transplantation. Biopsy sections were stained with Sirius red to demonstrate interstitial extracellular matrix. Renal allograft fibrosis was quantified using a computerized image analysis system. RESULTS: The mean first warm ischaemia time for kidneys from NHBDs was 24 min. A significant delay in graft function occurred in eight of 75 recipients in the HBD group and 31 of 37 in the NHBD group (P < 0.001). There were no significant differences in the level of allograft fibrosis between the two groups at any time point. CONCLUSION: Despite high rates of delayed graft function secondary to a prolonged warm ischaemia time, NHBD kidneys do not appear to be more susceptible to the development of renal allograft fibrosis. This study supports the growing body of evidence that kidneys from NHBDs are an acceptable alternative to those from HBDs.

Adult↗
PubMed2005

Randomized clinical trial of daclizumab induction and delayed introduction of tacrolimus for recipients of non-heart-beating kidney transplants.

BACKGROUND: Kidneys from non-heart-beating donors (NHBDs) have high rates of delayed graft function (DGF). Use of calcineurin inhibitors is associated with a reduction in renal blood flow, which may delay graft recovery from ischaemic acute tubular necrosis. METHODS: To assess whether daclizumab (DZB) could safely replace tacrolimus in the immediate postoperative period, patients were randomized to receive DZB induction and daily mycophenolate mofetil with steroids (DZB group) or standard tacrolimus-based triple therapy (control group). Tacrolimus was given to patients in the DZB group when the serum creatinine level dropped below 350 micromol/l. RESULTS: Fifty-one patients were recruited at two centres over a 2-year interval between 2000 and 2003. The overall rate of immediate function was 28 per cent (13 of 46 grafts), with the highest rate in recipients of machine-perfused kidneys treated with DZB (eight of 15 patients). CONCLUSION: Induction with DZB and delayed introduction of tacrolimus reduced the incidence of DGF in recipients of machine-perfused NHBD kidneys.

Adult↗
PubMed2005

Cyclosporine and rapamycin act in a synergistic and dose-dependent manner in a model of immunosuppressant-induced kidney damage.

The combination of cyclosporine (CSA) and rapamycin (RAPA) is a potent and commonly used approach to immunosuppression following solid-organ transplantation. By applying varying doses of CSA and RAPA to the rat salt-depleted model, we aimed to find a dose combination that favored antiproliferation/antifibrosis rather than toxicity. Male Sprague-Dawley rats (350 to 500 g) were salt-depleted for 7 days prior to commencing CSA and RAPA treatment. Serum creatinine and urinary protein/creatinine ratios were measured. Fibrosis was estimated with Sirius red staining of extracellular collagen. mRNA expression of TGF-beta, MMP-2, MMP-9, TIMP-1, and collagen III was assessed with reverse transcriptase PCR. A rise in serum creatinine at 7 and 28 days was observed for CSA 15 mg/kg/d (P = .002) but not CSA 7.5 mg (P = .06) or RAPA 1 mg (P = .69) compared to controls. Twenty-four-hour urinary protein excretion was unchanged compared to controls for all drug doses and combinations. Of the dose combinations, CSA 7.5 mg/d + RAPA 0.5 mg/d produced the lowest serum creatinine for all time points, and inhibited profibrotic TIMP-1 (P = .017), while increasing antifibrotic MMP-2 (P = .009) mRNA expression, compared to CSA treatment alone. Expression of TGF-beta and collagen III was unaltered between groups. CSA treatment produced molecular and biochemical changes indicating renal damage. Addition of RAPA can attenuate this damage, but only with a dose reduction of both agents. The most favorable results were for the dose combination CSA 7.5 mg/kg/d plus RAPA 0.5 mg/kg/d.

Administration, Oral↗
PubMed2005

A consecutive series of 70 laparoscopic donor nephrectomies demonstrates the safety of this new operation.

Laparoscopic donor nephrectomy (LDN) has the potential to overcome some of the disincentives to living kidney donation. This study presents the results of a consecutive series of 70 LDN from a single center with an emphasis on postoperative complication rates and donor recovery times. There was no selection bias based on donor body mass index or because of difficult vascular anatomy. All donors received postoperative analgesia using a patient-controlled system and returned to activities and employment at their discretion. There was no donor mortality and no episode of thromboembolic disease. One operation was converted from open to LDN because of renal artery bleeding. Postoperative complications encompassed chest infection (6%), unilateral pulmonary edema (3%), ileus (3%), wound infection (3%), paraesthesia of L1 (4%), testicular pain (3%), persistent wound pain (1.4%), and reoperation for division of adhesions (3%). In conclusion, LDN is a safe procedure with low postoperative morbidity. There were some unexpected complications, but recovery time was short.

Female↗
PubMed2005

Laparoscopic donor nephrectomy yields kidneys with structure and function equivalent to those retrieved by open surgery.

The technical challenges of laparosopcic transperitoneal donor nephrectomy (LapDN) have raised concerns over the quality of the procured allografts. This study reports the anatomical and functional outcomes of kidneys retrieved from 60 live donors entered into a randomized controlled trial of open versus laparoscopic procurement. Open and laparoscopic donors were well matched for age (P = .18) and body mass index (P = .49). Operating time (P = .0001) and first warm ischaemic time (P < .001) were longer for the laparoscopic donors but total warm time was not different (P = .52). Left renal vein length (P = .14) and left renal artery length (P = .38) were similar. No differences in right vessel length were observed. Rates of acute rejection did not differ, and recipient renal function was similar in the two groups. This study demonstrates that LapDN yields kidneys that are structurally and functionally equivalent to those acquired by the open operation. This data may go some way towards allaying concerns over the effect of laparoscopic procurement on live donor kidneys.

Female↗
PubMed2005

Alterations in the practice of open and laparoscopic live donor nephrectomy at renal transplant centers in the UK and Ireland.

Live kidney donor (LKD) activity has increased over recent years. In response, the British Transplantation Society (BTS) has issued guidelines for best practice. This study involved two questionnaires sent to all renal transplant centers in the UK and Ireland to examine practice for the years 2000 and 2002. Findings were compared to BTS guidelines. There was a 100% response rate from 28 centers for both years. Twenty-seven centers performed LKD in the year 2000, falling to 24 in 2002. Consultants reported 356 procedures in 2000, representing 19% of all kidney transplants, and 403 in 2002, representing 23% of all kidney transplants. Three centers offered laparoscopic donor nephrectomy in 2000, and five did so in 2002. The majority of centers organize donor and recipient operations synchronously, and most have a consultant anaesthetist present for the donor procedure. There were variations in the use of thromboprophylaxis, and in donor follow-up. There is widespread practice of live kidney donation in the UK and Ireland, but BTS guidelines are not closely adhered to. Laparoscopic donor nephrectomy is offered at a small number of centers, but many have plans to introduce it.

Graft Rejection↗
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

Pre-incision infiltration of local anesthetic reduces postoperative pain with no effects on bruising and wound cosmesis after thyroid surgery.

Optimizing postoperative pain control is an important aspect in perioperative patient care. The aim of this study was to investigate the efficacy of preincision local anesthetic infiltration in postoperative pain management for thyroid surgery and its relationship to bruising and wound cosmesis. In a randomized single-blinded study, 39 consecutive patients listed for thyroid surgery were assigned into two groups. Group I (n = 19) received subcuticular preincision infiltration with 10 ml of bupivacaine (0.5%) and Group II (n = 20) received no infiltration. Postoperatively, the pain experienced was evaluated by two methods: verbal response scores and linear analogue scores (0-100 mm) at different time intervals following surgery. Bruising and cosmetic effects resulting from surgery were assessed using a linear analogue score at discharge. The two groups were well matched for confounding variables. Pain scores were significantly different at 6 hours post operatively (p = 0.0341) with mean scores Group I = 33 and Group II = 50, but this difference disappeared at 24 hours. No patients (0%) received IV morphine in Group I compared to 5 patients (25%) in Group II. There was no significant difference in the mean bruising scores (p = 0.8864) and mean cosmetic scores (p = 0.3339) at discharge. Preincision infiltration with bupivacaine provides easy and better analgesic control postoperatively in patients following thyroid surgery with no effects on bruising or wound cosmesis.

Acetaminophen↗
PubMed2005

A comparison of methods for determining genotypes at the tumour necrosis factor-alpha-308, interleukin (IL)-1beta+3953, IL-6 -174 and IL-10 -1082/-819/-592 polymorphic loci.

Induced heteroduplex genotyping (IHG) is one of many methods that can be used to determine single nucleotide polymorphisms (SNPs). It is relatively new in comparison to other polymerase chain reaction (PCR)-based techniques. The aim of this study was to compare the results of genotyping using IHG with the results of genotyping using either polymerase chain reaction-sequence-specific primers (PCR-SSP) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for SNPs in the tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10 genes. Ninety patients who consented to participate in the study had their genotypes determined by IHG and either PCR-SSP (TNF-alpha-308 and IL-10 -1082/-819/-592) or PCR-RFLP (IL-1beta +3953 and IL-6 -174). Results for each locus were compared between techniques by calculating the Kappa statistic as a measure of agreement. The IHG and more traditional genotyping methods produced very similar results at all loci. The Kappa statistics for each locus were as follows: TNF-alpha -308, K = 0.727; IL-1beta +3953, K = 0.886; IL-6 -174, K = 0.909; IL-10 -1082, K = 0.876; IL-10 -592, K = 0.920. IHG is a valid method for the determination of genotypes at the loci examined in this study and produces comparable results to those of more traditional methods of genotyping.

Cytokines↗
PubMed2005

Four gland parathyroidectomy without reimplantation in patients with chronic renal failure.

BACKGROUND: The optimal surgical management of patients in end stage chronic renal failure with secondary hyperparathyroidism is controversial. One approach advocated is four gland parathyroidectomy without reimplantation. The aim of this study was to review the medium term results of this procedure. METHODS: Fifty four consecutive patients with end stage chronic renal failure and secondary hyperparathyroidism who had a four gland parathyroidectomy without reimplantation were studied. The procedure was performed by a single surgeon with a median (range) follow up of 29 (0-70) months. RESULTS: Most patients (76%) developed postoperative hypocalcaemia but this was easily treated and doses of long term drugs necessary to prevent this were low. Pre-operative bone symptoms, hypercalcaemia, hyperphosphataemia, and an increased alkaline phosphatase were improved or resolved in most patients. Thirteen (24%) patients had an undetectable postoperative parathyroid hormone (PTH), (6 of 12 (50%) with a functioning renal transplant and 7 of 42 (17%) who required dialysis, p = 0.02). Median (range) postoperative PTH values in these groups were 0.1 (0.1-31) compared with 1.0 (0.1-24) pmol/l (p = 0.085) respectively. The remaining 41 of 54 (76%) patients had residual PTH secretion and postoperative hyperparathyroidism was identified in eight (15%) patients with only two requiring neck re-exploration. CONCLUSION: Four gland parathyroidectomy without reimplantation produced good medium term biochemical and clinical results. Most patients had minor residual PTH secretion that may contribute to this and mitigate concerns regarding adynamic bone disease. Endogenous PTH secretion is only completely lost in a few patients but occurs more often in those with a functioning renal transplant. Bone densitometry is required to investigate the long term impact of this procedure.

Administration, Oral↗