scispace - formally typeset
Search or ask a question

Showing papers by "Leicester General Hospital published in 2002"


Journal ArticleDOI
TL;DR: Postoperative cognitive dysfunction occurs frequently but resolves by 3 months after surgery, and may be associated with decreased activity during this period, as reported in subjective report overestimates the incidence.
Abstract: Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent. Metbods: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living. Results: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months. Conclusions: Postoperative cognitive dysfunction occurs frequently but resolves by 3 months after surgery. It may be associated with decreased activity during this period. Subjective report overestimates the incidence of POCD. Patients may be helped by recognition that the problem is genuine and reassured that it is likely to be transient.

368 citations


Journal ArticleDOI
01 Oct 2002-Gut
TL;DR: The colorectal cancer risk in patients with colonic Crohn's disease is similar to that in UC7,8 and thus the guidelines for UC should be equally applicable to such patients with Crohn’s disease.
Abstract: Patients with ulcerative colitis (UC) are at increased risk of colorectal carcinoma.1,2 Many clinicians practice colonoscopic surveillance in these patients in the hope of detecting dysplasia or an early cancer at a surgically curable stage. However, a recent audit of gastroenterologists showed such surveillance to be disorganised and inconsistent.3 Much debate surrounds the efficacy and cost effectiveness of surveillance programmes in UC4–6 because they were introduced without benefit of randomised controlled trials. The following guidelines should bring uniformity to the process and be of help to both surgeons and physicians. The colorectal cancer risk in patients with colonic Crohn’s disease is similar to that in UC7,8 and thus the guidelines for UC should be equally applicable to such patients with Crohn’s disease. 1. Surveillance colonoscopies should be performed when the disease is in remission. (Recommendation Grade: C). 2. All patients should have a screening colonoscopy after 8–10 years that will also clarify disease extent. (Recommendation Grade: C). 3. Regular surveillance should begin after 8–10 years (from onset of symptoms) for pancolitis and after 15–20 years for left sided disease. (Recommendation Grade: C). 4. As the risk of cancer increases exponentially with time, there should be a decrease in the screening interval with increasing disease duration. For patients with pancolitis, in the second decade of disease a colonoscopy should be conducted every three years, every two years in the third decade, and yearly by the fourth decade of disease. (Recommendation Grade: C). 5. Two to four random biopsy specimens every 10 cm from the entire colon should be taken with additional samples of suspicious areas. (Recommendation Grade: C). Patients with primary sclerosing cholangitis (including those with an orthotopic liver transplant) represent a subgroup at higher risk of cancer and they should have annual colonoscopy. (Recommendation Grade: C). Although it …

354 citations


Journal Article
TL;DR: There were consistent differences in several elements of process and outcome between general practitioners who consult at different rates and the evidence suggests that patients seeking help from a doctor who spends more time with them are more likely to have a consultation that includes important elements of care.
Abstract: The aim of the study was to examine differences in consultation process and health outcomes between primary care physicians who consult at different rates. A systematic review of observational studies was carried out, restricted to English language journal papers reporting original research or systematic reviews. Qualitative analysis with narrative overview of methodology and key results was undertaken, using MEDLINE (1966 to 1999), EMBASE (1981 to 1999), and the NHS National Research Register. Secondary references from this search were also considered for inclusion. Main outcome measures were objectively measured process or healthcare outcomes. Thirteen papers, describing ten studies, were identified. There were consistent differences in several elements of process and outcome between general practitioners (GPs) who consult at different rates. Although average consultation length may be a marker of other doctor attributes, the evidence suggests that patients seeking help from a doctor who spends more time with them are more likely to have a consultation that includes important elements of care.

258 citations


Journal ArticleDOI
TL;DR: It is indicated that even a small correction of serum HCO3 improves nutritional status, and evidence for down-regulation of BCAA degradation and muscle proteolysis via the ubiquitin-proteasome system is provided.

181 citations


Journal ArticleDOI
TL;DR: Meeting or failing to meet the care patients hoped for is an important predictor of patient satisfaction with out-of-hours care, and purchasers and providers of out- of-hours services should consider whether and how patient expectation of service can be managed.
Abstract: Methods. We surveyed 3457 patients who requested out-of-hours care from five practices, two general practice out-of-hours co-operatives and a deputizing service in an English health authority during late 1997. The independent variables were: the service providing the care (service type), where out-of-hours care was given (location of care) and whether the care met the patient’s expectations. The independent variable was overall patient satisfaction with out-ofhours care. Results. Patients who received the care they hoped for (their idealized expectation was met) were more satisfied than those who did not. Patients who attended centres were more satisfied with the care received than those who had had home visits. Patients were more satisfied if they received care from the co-operative which did not employ assistants than from the deputizing service. Idealized expectation (care which was hoped for) match, location of care and service type explained 34, 2 and 4% of the variance, respectively. Age, sex, ethnicity, access to a car, normative/comparative expectation (care which was expected) and whether patients expected and received telephone advice, a home visit or domiciliary care, and the delay between request for care and care provision were not independently associated with satisfaction. Conclusions. Meeting or failing to meet the care patients hoped for is an important predictor of patient satisfaction with out-of-hours care. Purchasers and providers of out-of-hours care should consider whether and how patient expectation of service can be managed. This may reduce patient dissatisfaction with the service they provide. These findings also have important implications for the design of studies which use patient satisfaction as an outcome variable.

149 citations


Journal ArticleDOI
TL;DR: A better understanding of this process and the effect of disease may allow better selection of patients for partial hepatectomy and allow an insight into the possible application of clinical stimulation of regeneration.
Abstract: Background: Partial hepatectomy is the strongest stimulator of hepatic regeneration. The process of initiation and the control of the final size of the regenerated liver have been the subject of research for many years. A better understanding of this process and the effect of disease may allow better selection of patients for partial hepatectomy. It may also allow an insight into the possible application of clinical stimulation of regeneration. Methods: Data were reviewed from the published literature using the Medline database. Results: Most knowledge comes from in vitro studies and the study of resection in the rat model. A variety of cytokines, hormones and growth factors are involved in regeneration but very few have been found capable of stimulating regeneration in vitro. The exact interactions are not known, but there is probably a cascade involving different factors at differing stages of regeneration. Conclusion: Further in vivo research should allow greater understanding of liver regeneration, thereby providing a potential therapeutic tool in patients for whom regeneration has failed, or is likely to fail. Such research is also important in respect of liver support devices, which may inhibit liver regeneration by filtration of many of the factors involved. © 2002 British Journal of Surgery Society Ltd

145 citations


Journal ArticleDOI
TL;DR: FA(+)BSA is a more potent inducer of macrophage infiltration and cell death than FA(-)BSA, and may be the chief instigators of tubulointerstitial injury in protein-overload proteinuria.
Abstract: The role of the albumin-carried fatty acids in the induction of tubulointerstitial injury was studied in protein-overload proteinuria. Rats were injected with fatty acid-carrying BSA [FA(+)BSA], fa...

125 citations


Journal ArticleDOI
TL;DR: The study clearly demonstrates both the difficulties treating this fracture surgically and a procedure to be avoided (acromio-clavicular bridging), which, again has not been previously addressed.
Abstract: Symptomatic clavicular fracture non-union is rare. When it does occur, however, it may pose a difficult problem causing pain and functional impairment. The emphasis of this paper is on preopertive disabilities and the postoperative outcome and complications. Twenty patients with clavicular non-union treated operatively from 1989 to 1997 were reviewed, the average follow up was thirty-four months. Eleven fractures were midshaft, eight were lateral third and one medial third. A detailed proforma was completed with the patients documenting preoperative symptoms, outcome after surgery and complications. A literature search was carried out to find out the incidence of complications related to operating on post-traumatic clavicular non-union. All of the twenty fractures non-unions duly united after surgical intervention although three required early adjustment or change of metal work. The subjective and objective outcomes were good in 19 cases and poor in one. The postoperative complications included three implant failures, one stiff shoulder, two patients with numbness below the scar and one patient with an infected donor site wound. The literature search revealed that from 24 publications and 301 patients who had operations for clavicular non-union ther were 18 (6%) reported complications related to metal work, 45 (15%) reported complications related to soft tissues, seven (2%) complications related to the scar and 24 (8%) failures of union. Symptomatic clavicular non-union can cause severe disabilities. Good outcome, at low risk, can be expected from internal fixation and bone grafting of midshaft non-unions. Although there are only eight cases of lateral third clavicular non-unions, this is the largest series in the literature. Furthermore, the study clearly demonstrates both the difficulties treating this fracture surgically and a procedure to be avoided (acromio-clavicular bridging), which, again has not been previously addressed.

120 citations


Journal ArticleDOI
TL;DR: The introduction of strategies designed to maximize secondary access patency is increasingly important as a means of prolonging patient survival on dialysis, reducing morbidity and reducing the escalating cost of such programmes.
Abstract: Background The recent expansion of renal replacement therapy programmes has been associated with an increase in the number and complexity of patients requiring permanent vascular access. The introduction of strategies designed to maximize secondary access patency is, therefore, increasingly important as a means of prolonging patient survival on dialysis, reducing morbidity and reducing the escalating cost of such programmes. Methods A review of the current literature on the planning of vascular access, access surveillance methods and treatment of the most common complications was performed. Results Multidisciplinary vascular access planning, increased use of preoperative imaging and the preferential use of autogeneous vein are essential to obtain the best long-term results. While vascular access surveillance, in particular protocols involving direct measurement of access flow, enables the prospective detection and treatment of venous stenosis, the precise indications for treating venous stenosis remain unclear. Surgical revision remains the gold standard for the treatment of failing arteriovenous fistulas, but recent advances in interventional radiological techniques along with the suitability of arteriovenous fistulas for percutaneous intervention may offer an effective alternative. The effect of both these interventions on access patency requires comparison in a randomized trial. Conclusion The introduction of strategies to improve access patency rates will change vascular access surgical practice away from the construction of new fistulas towards an increase in outpatient percutaneous intervention and surgical revisional procedures. The role of surgical interventions requires clearer definition. © 2000 British Journal of Surgery Society Ltd

116 citations


Journal ArticleDOI
TL;DR: Patients with heart failure are incorrectly diagnosed and inadequately treated with angiotensin‐converting enzyme inhibitors, a common clinical condition with high morbidity and mortality.
Abstract: Background: Chronic heart failure is a common clinical condition with high morbidity and mortality. Despite the evidence that appropriate treatment with angiotensin-converting enzyme inhibitors can improve morbidity, primary care studies show that patients with heart failure are incorrectly diagnosed and inadequately treated. Aim: To explore general practitioners' accounts of their management of patients with heart failure and identify the perceived obstacles to diagnosis and management. Methods: We conducted this qualitative study using semi-structured interviews in 18 general practices. The practices were stratified on the basis of size, location, and the level of practice development. The interviews were based on a schedule of open questions based on the literature on diagnosis and management of patients with heart failure. Transcriptions of the audiotaped interviews were independently analysed by two researchers and analysis was based on open coding using a constant comparative approach. Categories were reduced to major themes. Results: General practitioners suspect heart failure when patients present with breathlessness or ankle oedema. Many general practitioners reported that they would diagnose heart failure after respiratory examination and a positive finding of basal crepitations. Many general practitioners arrange a chest X-ray to establish the diagnosis and some arrange an electrocardiogram. A few general practitioners mentioned that they diagnosed heart failure with a trial of diuretics. Obstacles to diagnosis were mentioned by most general practitioners and included lack of facilities for appropriate investigations (especially echocardiography) and lack of time and expertise. Obstacles to management included lack of time, high cost of drugs, difficulty with diagnosis, selection bias towards younger patients and not having the confidence to initiate angiotensin-converting enzyme inhibitors. Many general practitioners were unaware of the impact angiotensin-converting enzyme inhibitors can have on morbidity and mortality. Conclusions: Although symptoms of heart failure are not sufficiently specific for diagnosing patients with heart failure, many general practitioners in European countries treat people with suspected heart failure on the basis of symptoms and signs alone. This study has identified many obstacles to the diagnosis and management of heart failure that may explain why patients are inadequately managed in primary care. Specific implementation strategies need to be tailored to overcome these obstacles.

94 citations


Journal ArticleDOI
TL;DR: The findings suggest that the changes in the ratio of Bax to Bcl-2 may contribute to the caspase-3 activation and the modulation of renal apoptosis associated with renal inflammation, tubular atrophy and renal fibrosis in experimental glomerulonephritis.

Journal ArticleDOI
TL;DR: The transposed autologous basilic vein to brachial artery arteriovenous fistula provides vascular access in the absence of adequate superficial vein.
Abstract: Background: The transposed autologous basilic vein to brachial artery arteriovenous fistula provides vascular access in the absence of adequate superficial vein. The long-term patency and complication rates of this conduit are largely unreported. Patients and methods: Seventy-four brachiobasilic fistulas were performed in 65 patients. This was a secondary or tertiary access procedure in 84 per cent of patients. Results: Of the 74 fistulas performed, 50 were successfully used for dialysis (68 per cent) and 24 (32 per cent) were never used, including 13 fistulas that failed without being used for dialysis. Of the 74 fistulas, 46 per cent failed (n = 34), 10 patients died with a functioning fistula (n = 10) and five were transplanted. The 30-day secondary patency was 73 per cent at 1 year, 53 per cent at 2 years and 43 per cent at 3 years rate was 96 per cent. Cumulative secondary patency was 73 per cent at 1 year, 53 per cent at 2 years and 43 per cent at 3 years. Nineteen (26 per cent) fistulas underwent a further 19 operative procedures. Fifty-one (69 per cent) fistulas developed complications. The most common complications were arm oedema (24 per cent), thrombosis (22 per cent) and bleeding (18 per cent). Conclusion: In high-risk patients the autologous transposed brachiobasilic fistula has equivalent patency and lower complication rates than those reported for polytetrafluoroethylene interposition grafts. © 2000 British Journal of Surgery Society Ltd

Journal ArticleDOI
TL;DR: A 34-year-old man with a 17-year history of Type 1 diabetes mellitus attended an annual review clinic in December 1999 and complained of a lump on his right thigh, which was found to be amorphous acellular eosinophilic material possessing a mild chronic inflammatory cell infiltrate.
Abstract: A 34-year-old man with a 17-year history of Type 1 diabetes mellitus attended an annual review clinic in December 1999 and complained of a lump on his right thigh. His diabetic control was moderate (HbA 1c 8.3%), and he displayed no long-term complications of diabetes. A firm well-defined 7-cm mass clinically distinct to adjacent areas of lipohypertrophy was found in the anterior aspect of his right thigh, an area that represented his current insulin injection site. Numerous smaller lesions of similar consistency were noted at other regular injection sites in his upper limbs and the contra-lateral thigh. No other clinical abnormalities were present and routine biochemical tests were unremarkable. Surgical excision was performed at a later date under general anaesthesia, revealing that the lesion was composed entirely of a waxy grey material. Histological examination showed the majority of the tissue to be amorphous acellular eosinophilic material possessing a mild chronic inflammatory cell infiltrate. The acellular matrix, when stained with Congo red and viewed through cross-polarized light, demonstrated the classical apple-green birefringent properties of amyloid (Fig. 1). This finding was corroborated by the appearance of non-branching fibrils on transmission electron microscopy. The association between the unusual and apparently localized soft tissue amyloid deposits and the insulin injection sites was considered and investigated further. Although parenteral drug abuse may occasionally result in reactive systemic (AA) amyloidosis by virtue of producing

Journal ArticleDOI
TL;DR: Bovine colostrum is a rich source of nutrients, antibodies and growth factors that can be used as a raw material for animal feed, as well as as a feed for humans.
Abstract: Summary Background : Bovine colostrum is a rich source of nutrients, antibodies and growth factors. Aim : To examine the efficacy of colostrum enemas in the treatment of distal colitis using a randomized, double-blind, controlled protocol. Methods : Fourteen patients (eight female), with a mean age of 45 years (range, 16–75 years) and mild to moderately severe distal colitis (Powell-Tuck scoring system), received colostrum enema (100 mL of 10% solution) or placebo (albumin solution) b.d. for 4 weeks. Both groups also received mesalazine (1.6 g/day) or, if already taking it, had a dose increment of 1.6 g/day. Disease activity was documented at 0, 2 and 4 weeks. Results : After 4 weeks, the colostrum group showed a mean reduction in symptom score of − 2.9 (95% confidence interval (CI), − 5.4 to − 0.3), whereas the placebo group showed a mean response of + 0.5 (95% CI, − 2.4 to +3.4). The histological score improved in five of the eight patients in the colostrum group (mean response, − 0.9; 95% CI, − 1.69 to − 0.03), whereas the histological scores only improved in two of the six patients in the placebo group (mean response, 0.2; 95% CI, − 2.4 to +2.6). Conclusions : Bovine colostrum enema shows potential as a novel therapy for left-sided colitis with additional benefits over using mesalazine alone. Further studies appear to be warranted.

Journal ArticleDOI
TL;DR: Tolterodine ER 4mg qd displayed a favourable safety, tolerability and efficacy profile during 12 months' treatment of patients with overactive bladder.

Journal ArticleDOI
TL;DR: The number of memory clinics in the British Isles has increased since the first survey in 1993, with a further increase in the number of clinics in Scotland.
Abstract: Background The number of memory clinics in the British Isles has increased since our first survey in 1993. Objectives The aim of this survey was to determine the memory clinics' characteristics and functions, and to compare these with the findings of our previous survey. Methods An expanded version of the 1993 questionnaire was sent to 102 possible memory clinics, identified by various means. There were 72 replies, 58 of which were from currently active clinics. Results There has been a substantial growth in the number of clinics since our previous survey in 1993, apparently stimulated by the licensing of cholinesterase inhibitor durgs for Alzheimer's disease (AD) and the development of services for early-onset dementia. Most of the new memory clinics have been set up within NHS old age psychiatry services, and they tend to be smaller and have less of an academic focus than the older clinics. However, they are similar in many aspects of their functioning, and have a similar range of practice with regard to patient assessment. Conclusions As memory clinics move out from academic centres into mainstream clinical services, there is potential for greater co-ordination of their activities, and the development of an agreed core data set for assessment that would be valuable in the national monitoring of new anti-dementia treatments in clinical practice. Copyright © 2002 John Wiley & Sons, Ltd.

Journal ArticleDOI
TL;DR: In this paper, the effects of two different immunosuppressive agents (cyclosporin and tacrolimus) on the expression of the genes controlling extracellular matrix deposition in renal transplant glomeruli were determined.
Abstract: Background Chronic allograft nephropathy is characterized by an excessive accumulation of extracellular matrix proteins leading to glomerular and interstitial fibrosis. The aim of this study was to determine the effects of two different immunosuppressive agents (cyclosporin and tacrolimus) on the expression of the genes controlling extracellular matrix deposition in renal transplant glomeruli. Methods Fifty-one renal transplant recipients were randomized to receive immunosuppression with either microemulsion cyclosporin or tacrolimus. Isolated glomeruli were plucked from protocol transplant biopsies performed 1 week, 3 months and 6 months after transplantation. Expression of the genes for collagen IVα2, collagen III, matrix metalloproteinase 2, tissue inhibitor of metalloproteinases (TIMP) 1 and TIMP-2, tenascin and transforming growth factor (TGF) β1 was studied by quantitative reverse transcriptase–polymerase chain reaction. Results The expression of messenger RNA (mRNA) for collagen III and TIMP-1 was significantly higher in patients receiving cyclosporin therapy than in those having tacrolimus (P < 0·01); this finding was accounted for by differences in the biopsy material at 1 week. A significant difference in collagen III, TIMP-1 and TIMP-2 mRNA expression was also detected between patients depending on the source of renal donor (cadaveric or living). There were no significant differences in the level of glomerular TGF-β1. Conclusion The data provide new in vivo evidence that tacrolimus may exert a less fibrogenic influence on transplant glomeruli than cyclosporin. © 2000 British Journal of Surgery Society Ltd

Journal ArticleDOI
TL;DR: Patients treated by patch excision and autologous venous reconstruction had the best outcome with a cumulative freedom from perioperative stroke/death or re-infection of 91% at 2 years, and the importance of close surveillance of early wound complications is emphasised.

Journal ArticleDOI
TL;DR: Atorvastatin was effective in achieving target LDL-cholesterol levels in a high proportion of the dyslipidemic CAPD patients studied at doses that are well tolerated.

Journal ArticleDOI
TL;DR: This study evaluated the effect of the kidney transplant ultrasonographic size to recipient body‐weight ratio (Tx/W) on the outcome of kidney transplantation.
Abstract: Background: The critical nephron mass needed to meet the metabolic demands of an individual depends on the body-weight. This study evaluated the effect of the kidney transplant ultrasonographic size to recipient body-weight ratio (Tx/W) on the outcome of kidney transplantation. Methods: A consecutive series of 104 cadaveric renal transplants was studied. Transplant cross-sectional area (TXSA) was measured ultrasonographically in the first week after transplantation as an index of renal size. A 'nephron dose' index (Tx/W) was calculated by dividing TXSA by recipient weight and was used to define three groups of patients, with high (more than 0.45), medium (0.3-0.45) or low (less than 0.3) Tx/W ratios. Isotope glomerular filtration rate (GFR) measurements were made at 1, 6 and 12 months after transplantation. Results: The serum creatinine level was significantly lower in the first 5 years after transplantation in patients with a high Tx/W ratio than in those with a medium or low ratio. GFR measurements were marginally higher in the groups with a high and medium Tx/W ratio compared with the low Tx/W group. A statistically significant association between Tx/W ratio and graft survival was not found. Conclusion: The renal transplant size to recipient weight ratio was an important determinant of long-term renal allograft function in this study. Extreme mismatching between allograft and recipient size should be avoided where possible, but the findings presented require confirmation in larger studies before clear recommendations can be made about size matching and kidney allocation.

Journal ArticleDOI
TL;DR: A course designed to initiate the process of reflection and recognition of how their attitudes and values might influence their care of patients at Leicester‐Warwick Medical School is reported on.
Abstract: Background Effective management of the doctor's role in relation to human sexuality requires sensitivity and tact, an ability to put patients at ease, use of appropriate language, and therapeutic, non-discriminatory attitudes. However, previous research suggests that medical students and doctors may hold negative attitudes towards homosexuality and some forms of sexual behaviour. Some educational programmes have started to help students develop communication skills for sexual health consultations, but little work has addressed the broader issue of attitudes and values which may underlie behaviour. It is vital that medical students begin early the process of reflection and recognition of how their attitudes and values might influence their care of patients. In this paper we report on a course designed to initiate this process at Leicester-Warwick Medical School (LWMS). Course description The course utilizes techniques of desensitization, problem-solving and reflection to enable the students to achieve the learning outcomes, which are primarily oriented towards reflection and self-development. It uses a variety of teaching and learning strategies, combining peer learning with self-directed learning, and small-group learning with whole class learning. Course evaluation We report observations and a before-and-after questionnaire study of students' views and attitudes. This evaluation suggests that the course is successful in reducing students' anxieties about human sexuality and improving their confidence in developing appropriate skills. Conclusions The LWMS course is one model which might be used to begin the process of encouraging medical students to develop ways of appropriately managing their responsibilities in relation to human sexuality.

Journal ArticleDOI
TL;DR: Experiences and health care needs of Gujarati Hindu patients with myocardial infarction appear different to those of non-Asians, and cardiac aftercare and rehabilitation services should take account of such information.
Abstract: Background: South Asian people living in the United Kingdom are at increased risk of coronary heart disease, have higher mortality rates and are less likely to be treated when compared to the white...

Journal ArticleDOI
TL;DR: It may be that use of an anti-EGFR therapy, in combination with more conventional treatment, provides a method of improving the prognosis for muscle-invasive bladder cancer.
Abstract: Muscle-invasive bladder cancer is a disease which causes significant morbidity and mortality. The two main forms of treatment for this disease include radical cystectomy and radical radiotherapy, but five year survival after treatment remains low at 40%. Many clinical and molecular risk factors have been shown to be associated with poor prognosis. One such factor is the expression of epidermal growth factor receptor (EGFR), which is overexpressed by many epithelial tumours, including bladder cancers. There are several methods of inhibiting the activity of EGFR and it may be that use of an anti-EGFR therapy, in combination with more conventional treatment, provides a method of improving the prognosis for muscle-invasive bladder cancer.

Journal ArticleDOI
TL;DR: Tacrolimus has been shown to be less fibrotic than cyclosporin this paper, which may have implications for the choice of long-term immunosuppressant in renal transplantation.
Abstract: Background Cyclosporin is associated with significant chronic nephrotoxicity, manifest in the long term mainly as renal fibrosis. There have been claims that tacrolimus is a less fibrotic drug than cyclosporin, and this study was designed to determine the effect of the two drugs on the expression of fibrosis-associated genes. Methods Male Wistar rats underwent clamping of the right renal pedicle for 45 min together with left nephrectomy; this model has previously been shown to be associated with upregulation of fibrosis-associated genes. Experimental groups (six animals per group) received cyclosporin A 10 mg/kg daily, tacrolimus 0·2 mg/kg daily or no treatment. Animals were killed at 16 weeks, and the renal cortical expression of fibrosis-associated genes was studied by means of quantitative reverse transcriptase–polymerase chain reaction. Results Tacrolimus-treated animals developed significantly less proteinuria and had lower serum creatinine levels than those receiving cyclosporin. Tacrolimus administration also significantly reduced the expression of transforming growth factor β and tissue inhibitor of metalloproteinases 1, both the products of genes associated with fibrosis. Although cyclosporin treatment reduced levels of the matrix-degrading enzymes, matrix metalloproteinase (MMP) 2 and MMP-9, this was not statistically significant. Conclusion Tacrolimus has less nephrotoxicity than cyclosporin in this model. It also appears to have less fibrogenic potential, and this may have implications for the choice of long-term immunosuppressant in renal transplantation. © 2000 British Journal of Surgery Society Ltd

Journal ArticleDOI
01 Oct 2002
TL;DR: RHSA has a mitogenic effect on human PTCs, but fibronectin secretion was only induced by O-complexed rHSA and the O-rHSA effect was mediated via PKC activation, and involvement of PKC signal transduction pathway may be a novel therapeutic target for ameliorating proteinuria-induced tubular injury.
Abstract: Background. Proteinuric renal disease is associated with accumulation of tubulointerstitial matrix proteins. Human proximal tubular cells (PTCs) produce fibronectin in response to serum proteins but not albumin alone. It has been suggested that renal toxicity of filtered albumin depends on its lipid moiety. We therefore investigated the functional consequences of different fatty acids (FAs) carried on human albumin after exposure to human PTCs in culture. Methods. Confluent human PTCs were exposed to recombinant human serum albumin (rHSA) or palmitate (P)-, stearate (S)-, oleate (O)-, and linoleate (L)-complexed rHSA. In all experimental conditions, test media contained 1 mg'ml rHSA alone or carrying 100 mmol FAs. Mitogenic response was assessed by [ 3 H]thymidine incorporation. Cell culture supernatants were assayed for fibronectin. Protein kinase C (PKC) activity was assessed in cell lysates. Results. Apical exposure to rHSA alone or the O-rHSA complex stimulated a significant increase in [ 3 H]thymidine incorporation, whereas the L-rHSA complex was markedly inhibitory to human PTC growth. The L-rHSA complex was associated with severe cytotoxicity as assessed by lactate dehydrogenase release. Among all conditions, O-rHSA was the only test media that significantly increased fibronectin levels over control conditions (150.1 ± 10.6% over control, P<0.05, n=3). Pre-treatment of PTCs with PKC inhibitors before O-rHSA exposure resulted in a dose-dependent decrease in fibronectin secretion. O-rHSA activated PKC significantly compared with controls. Conclusions. We conclude that rHSA has a mitogenic effect on human PTCs, but fibronectin secretion was only induced by O-complexed rHSA and the O-rHSA effect was mediated via PKC activation. Involvement of PKC signal transduction pathway may be a novel therapeutic target for ameliorating proteinuria-induced tubular injury.

Journal ArticleDOI
TL;DR: Treatment with risperidone was associated with improvement in antisaccade errors and switching from conventional to ris peridone produced a reduction in errors, and vice versa.
Abstract: Objective: Antisaccade errors are consistently increased in schizophrenia. As they have been demonstrated only in cross sectional studies, it is unclear how they vary longitudinally or with different medications. In a previous cross sectional study, we reported a trend towards a reduction in error rates in a patient group treated with risperidone, compared with clozapine and sulpiride treated groups. Methods: Gap random and antisaccade paradigms were performed on two occasions in the same sample of DSM-IV schizophrenic patients (n=12) in transition between conventional antipsychotic drugs and risperidone. A cross over design was used with six patients switching from risperidone to conventional (group I) and six in the opposite direction (group II). A control sample (n=12) was also tested on two occasions and their performance compared. The effects of practice between first and second testing and of switching between conventional antipsychotic drugs and risperidone and vice versa was also evaluated. Results: A significant reduction in error rate was demonstrated during risperidone treatment (n=12), compared with conventional APD treatment. Switching from conventional to risperidone produced a reduction in errors, and vice versa. Conclusions: Treatment with risperidone was associated with improvement in antisaccade errors.

Journal ArticleDOI
TL;DR: Laparoscopic donor nephrectomy is associated with less postoperative pain and a substantial improvement in donor recovery times and it is not yet clear whether or not the outcome of the recipient kidney transplants are the same after ODN and LDN and much more experience is required.
Abstract: Laparoscopic donor nephrectomy has the potential to lessen the burden placed on live kidney donors. This study describes the first British comparison of donor morbidity and recovery following conventional open donor nephrectomy (ODN) and laparoscopic donor nephrectomy (LDN). An initial series of LDN (n=20) was compared to a historical control group of ODN (n=34). Laparoscopic operations were performed via a transperitoneal approach, the kidney being removed through a 6–12 cm Pfannensteil incision. Open operations were performed using a retroperitoneal flank approach with resection of the 12th rib. Postoperatively, donors were managed with a patient controlled analgesia system. LDN was associated with shorter mean (SD) inpatient stay (6 (2) v 4 (1) days; p=0.0001) and lower parenteral narcotic requirements (morphine 179 (108) v 67 (54) mg; p=0.0001). Laparoscopic donors started driving their cars sooner (2 (1.5) v 6 (4) weeks; p=0.0001) and returned to work more quickly (5 (3) v 12 (6) weeks; p=0.0001) than open nephrectomy donors. There were no differences in recipient serum creatinine levels at three months post-transplant but two recipients of transplant kidneys retrieved laparoscopically (10%) developed ureteric obstruction, whereas this complication did not occur after ODN (p=0.13). LDN is associated with less postoperative pain and a substantial improvement in donor recovery times. It is not yet clear whether or not the outcome of the recipient kidney transplants are the same after ODN and LDN and much more experience is required before the place of this new technique can be defined.

Journal ArticleDOI
TL;DR: In this paper, the availability of suitable vein, maturation rates, patency and complication rates of autogeneous elbow fistulas in diabetics and non-diabetics at a single centre where an autogeneous vein only policy is employed.

Journal ArticleDOI
TL;DR: The aim of the present study was to assess the incidence of wound sepsis following closure of ileostomie and colostomies in this institution.
Abstract: Background: The aim of the present study was to assess the incidence of wound sepsis following closure of ileostomies and colostomies in our institution. Methods: Circumferential subcuticular wound approximation was used in 51 patients in our institution. Evidence of wound sepsis (assessed by the presence of cellulitis, induration and or purulent discharge) was documented both in the postoperative period and in outpatient follow-up. Results: A wound infection rate of 0% was achieved, both in the immediate postoperative period and upon 6-week follow-up. Conclusions: Circumferential subcuticular wound approximation is, therefore, a safe and efficacious technique for dealing with the skin woundafter stomal closure, virtually abolishing wound sepsis.

Journal ArticleDOI
TL;DR: The potential for aspirin therapy to reduce complications of primary thrombosis and chronic allograft nephropathy following renal transplantation is examined.
Abstract: Background: Primary thrombosis and chronic allograft nephropathy are important causes of early and late graft loss, respectively, following renal transplantation. This study examined the potential for aspirin therapy to reduce these complications. Methods: A consecutive series of 105 cadaveric renal transplants treated with aspirin 150 mg daily for the first 3 months after transplantation was compared with an untreated historical control group (n = 121). Protocol needle-core biopsies were performed on all transplants in both groups at 1 week and 12 months after transplantation. Needle-core allograft biopsies were performed at 3, 6 and 12 months after transplantation, and serum creatinine was measured at each outpatient attendance for the duration of follow-up. Results: There was a significantly lower rate of primary allograft thrombosis in patients treated with aspirin (none of 105) compared with that in the control group (six (5 per cent) of 121; P = 0·03). There were no differences in renal function or 2-year allograft survival between the two groups. Aspirin-treated patients had a lower incidence of chronic allograft nephropathy at 1 year than controls although this did not reach statistical significance (16 versus 26 per cent; P = 0·075). There were no major bleeding complications in either group in association with peptic ulcer disease or following renal transplant biopsy. Conclusion: Aspirin reduced the rate of early graft thrombosis of renal transplants in this series but did not improve renal function or graft survival. A trend towards a lower rate of chronic allograft nephropathy was noted with aspirin treatment. These findings require confirmation in a prospective randomized trial. © 2001 British Journal of Surgery Society Ltd