Presentation, pattern, and natural course of severe symptoms, and role of antibiotics and antibiotic resistance among patients presenting with suspected uncomplicated urinary tract infection in primary care: observational study.

OBJECTIVE: To assess the natural course and the important predictors of severe symptoms in urinary tract infection and the effect of antibiotics and antibiotic resistance. DESIGN: Observational study. SETTING: Primary care. PARTICIPANTS: 839 non-pregnant adult women aged 18-70 presenting with suspected urinary tract infection. MAIN OUTCOME MEASURE: Duration and severity of symptoms. RESULTS: 684 women provided some information on symptoms; 511 had both laboratory results and complete symptom diaries. For women with infections sensitive to antibiotics, severe symptoms, rated as a moderately bad problem or worse, lasted 3.32 days on average. After adjustment for other predictors, moderately bad symptoms lasted 56% longer (incidence rate ratio 1.56, 95% confidence interval 1.22 to 1.99, P<0.001) in women with resistant infections; 62% longer (1.62, 1.13 to 2.31, P=0.008) when no antibiotics prescribed; and 33% longer (1.33, 1.14 to 1.56, P<0.001) in women with urethral syndrome. The duration of symptoms was shorter if the doctor was perceived to be positive about diagnosis and prognosis (continuous 7 point scale: 0.91, 0.84 to 0.99; P=0.021) and longer when the woman had frequent somatic symptoms (1.03, 1.01 to 1.05, P=0.002; for each symptom), a history of cystitis, urinary frequency, and more severe symptoms at baseline. CONCLUSION: Antibiotic resistance and not prescribing antibiotics are associated with a greater than 50% increase in the duration of more severe symptoms in women with uncomplicated urinary tract infection. Women with a history of cystitis, frequent somatic symptoms (high somatisation), and severe symptoms at baseline can be given realistic advice that they are likely to have severe symptoms lasting longer than three days.

Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial.

OBJECTIVE: To assess the impact of different management strategies in urinary tract infections. DESIGN: Randomised controlled trial. SETTING: Primary care. PARTICIPANTS: 309 non-pregnant women aged 18-70 presenting with suspected urinary tract infection. INTERVENTION: Patients were randomised to five management approaches: empirical antibiotics; empirical delayed (by 48 hours) antibiotics; or targeted antibiotics based on a symptom score (two or more of urine cloudiness, urine smell, nocturia, or dysuria), a dipstick result (nitrite or both leucocytes and blood), or a positive result on midstream urine analysis. Self help advice was controlled in each group. MAIN OUTCOME MEASURES: Symptom severity (days 2 to 4) and duration, and use of antibiotics. RESULTS: Patients had 3.5 days of moderately bad symptoms if they took antibiotics immediately. There were no significant differences in duration or severity of symptoms (mean frequency of symptoms on a 0 to 6 scale: immediate antibiotics 2.15, midstream urine 2.08, dipstick 1.74, symptom score 1.77, delayed antibiotics 2.11; likelihood ratio test for the five groups P=0.177). There were differences in antibiotic use (immediate antibiotics 97%, midstream urine 81%, dipstick 80%, symptom score 90%, delayed antibiotics 77%; P=0.011) and in sending midstream urine samples (immediate antibiotics 23%, midstream urine 89%, dipstick 36%, symptom score 33%, delayed antibiotics 15%; P<0.001). Patients who waited at least 48 hours to start taking antibiotics reconsulted less (hazard ratio 0.57 (95% confidence interval 0.36 to 0.89), P=0.014) but on average had symptoms for 37% longer than those taking immediate antibiotics (incident rate ratio 1.37 (1.11 to 1.68), P=0.003), particularly the midstream urine group (73% longer, 22% to 140%; none of the other groups had more than 22% longer duration). CONCLUSION: All management strategies achieve similar symptom control. There is no advantage in routinely sending midstream urine samples for testing, and antibiotics targeted with dipstick tests with a delayed prescription as backup, or empirical delayed prescription, can help to reduce antibiotic use. STUDY REGISTRATION: National Research Register N0484094184 ISRCTN: 03525333.

Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study.

OBJECTIVES: To estimate clinical and dipstick predictors of infection and develop and test clinical scores; to compare management using clinical and dipstick scores with commonly used alternative strategies; to estimate the cost-effectiveness of each strategy; and to understand the natural history of urinary tract infection (UTI) and women's concerns about its presentation and management. DESIGN: There were six studies: (1) validation development for diagnostic clinical and dipstick scores; (2) validation of the scores developed; (3) observation of the natural history of UTI; (4) randomised controlled trial (RCT) of scores developed in study 1; (5) economic analysis of the RCT; (6) qualitative study of patients in the RCT. SETTING: Primary care. PARTICIPANTS: Women aged 17-70 with suspected UTI. INTERVENTIONS: Patients were randomised to five management approaches: empirical antibiotics; empirical delayed antibiotics; target antibiotics based on a higher symptom score; target antibiotics based on dipstick results; or target antibiotics based on a positive mid-stream specimen of urine (MSU). MAIN OUTCOME MEASURES: Antibiotic use, use of MSUs, rates of reconsultation and duration, and severity of symptoms. RESULTS: (1) 62.5% of women had confirmed UTI. Only nitrite, leucocyte esterase and blood independently predicted diagnosis of UTI. A dipstick rule--based on having nitrite or both leucocytes and blood--was moderately sensitive (77%) and specific (70%) [positive predictive value (PPV) 81%, negative predictive value (NPV) 65%]. A clinical rule--based on having two of urine cloudiness, offensive smell, reported moderately severe dysuria, moderately severe nocturia--was less sensitive (65%) (specificity 69%, PPV 77%, NPV 54%). (2) 66% of women had confirmed UTI. The predictive values of nitrite, leucocyte esterase and blood were confirmed. The dipstick rule was moderately sensitive (75%) but less specific (66%) (PPV 81%, NPV 57%). (3) Symptoms rated as moderately bad or worse lasted 3.25 days on average for infections sensitive to antibiotics; resistant infections lasted 56% longer, infections not treated with antibiotics 62% longer and symptoms associated with urethral syndrome 33% longer. Symptom duration was shorter if the doctor was perceived to be positive about prognosis, and longer with frequent somatic symptoms, previous history of cystitis, urinary frequency and more severe symptoms at baseline. (4) 66% of the MSU group had laboratory-confirmed UTI. Women suffered 3.5 days of moderately bad symptoms if they took antibiotics immediately but 4.8 days if they delayed taking antibiotics for 48 hours. Taking bicarbonate or cranberry juice had no effect. (5) The MSU group was more costly over 1 month but not over 1 year. Cost-effectiveness acceptability curves showed that for a value per day of moderately bad symptoms of over 10 pounds, the dipstick strategy is most likely to be cost-effective. (6) Fear of spread to the kidneys, blood in the urine, and the impact of symptoms on vocational and leisure activities were important triggers for seeking help. When patients are asked to delay taking antibiotics the uncomfortable and worrying journey from 'person to patient' needs to be acknowledged and the rationale behind delaying the antibiotics made clear. CONCLUSIONS: To achieve good symptom control and reduce antibiotic use clinicians should either offer a 48-hour delayed antibiotic prescription to be used at the patient's discretion or target antibiotic treatment by dipsticks (positive nitrite or positive leucocytes and blood) with the offer of a delayed prescription if dipstick results are negative.

Systematic review on urine albumin testing for early detection of diabetic complications.

OBJECTIVES: To determine whether microalbuminuria is an independent prognostic factor for the development of diabetic complications and whether improved glycaemic or blood pressure control has a greater influence on the development of diabetic complications in those with microalbuminuria than in those with normoalbuminuria. DATA SOURCES: Electronic databases up until January 2002. REVIEW METHODS: A protocol for peer review by an external expert panel was prepared that included selection criteria for data extraction and required two independent reviewers to undertake article selection and review. Completeness was assessed using hand-searching of major journals. Random effects meta-analysis was used to obtain combined estimates of relative risk (RR). Funnel plots, trim and fill methods and meta-regression were used to assess publication bias and sources of heterogeneity. RESULTS: In patients with type 1 or type 2 DM and microalbuminuria there is a RR of all-cause mortality of 1.8 [95% confidence interval (CI) 1.5 to 2.1] and 1.9 (95% CI 1.7 to 2.1) respectively. Similar RRs were found for other mortality end-points, with age of cohort being inversely related to the RR in type 2 DM. In patients with type 1 DM, there is evidence that microalbuminuria or raised albumin excretion rate has only weak, if any, independent prognostic significance for the incidence of retinopathy and no evidence that it predicts progression of retinopathy, although strong evidence exists for the independent prognostic significance of microalbuminuria or raised albumin excretion rate for the development of proliferative retinopathy (crude RR of 4.1, 95% CI 1.8 to 9.4). For type 2 DM, there is no evidence of any independent prognostic significance for the incidence of retinopathy and little, if any, prognostic relationship between microalbuminuria and the progression of retinopathy or development of proliferative retinopathy. In patients with type 1 DM and microalbuminuria there is an RR of developing end-stage renal disease (ESRD) of 4.8 (95% CI 3.0 to 7.5) and a higher RR (7.5, 95% CI 5.4 to 10.5) of developing clinical proteinuria, with a significantly greater fall in glomerular filtration rate (GFR) in patients with microalbuminuria. In patients with type 2 DM, similar RRs were observed: 3.6 (95% CI 1.6 to 8.4) for developing ESRD and 7.5 (95% CI 5.2 to 10.9) for developing clinical proteinuria, with a significantly greater decline in GFR in the microalbuminuria group of 1.7 (95% CI 0.1 to 3.2) ml per minute per year compared with those who were normoalbuminuric. In adults with type 1 or type 2 DM and microalbuminuria at baseline, the numbers progressing to clinical proteinuria (19% and 24%, respectively) and those regressing to normoalbuminuria (26% and 18%, respectively) did not differ significantly. In children with type 1 DM, regression (44%) was significantly more frequent than progression (15%). In patients with type 1 or type 2 DM and microalbuminuria, there is scarce evidence as to whether improved glycaemic control has any effect on the incidence of cardiovascular disease (CVD), the incidence or progression of retinopathy, or the development of renal complications. However, among patients not stratified by albuminuria, improved glycaemic control benefits retinal and renal complications and may benefit CVD. In the effects of angiotensin-converting enzyme (ACE) inhibitors on GFR in normotensive microalbuminuric patients with type 1 DM, there was no evidence of a consistent treatment effect. There is strong evidence from 11 trials in normotensive type 1 patients with microalbuminuria of a beneficial effect of ACE inhibitor treatment on the risk of developing clinical proteinuria and on the risk of regression to normoalbuminuria. Patients with type 2 DM and microalbuminuria, whether hypertensive or not, may obtain additional cardiovascular benefit from an ACE inhibitor and there may be a beneficial effect on the development of retinopathy in normotensive patients irrespective of albuminuria. There is limited evidence that treatment of hypertensive microalbuminuric type 2 diabetic patients with blockers of the renin--angiotensin system is associated with preserved GFR, but also evidence of no differences in GFR in comparisons with other antihypertensive agents. The data on GFR in normotensive cohorts are inconclusive. In normotensive type 2 patients with microalbuminuria there is evidence from three trials (all enalapril) of a reduction in risk of developing clinical proteinuria; in hypertensive patients there is evidence from one placebo-controlled trial (irbesartan) of a reduction in this risk. Intensive compared with moderate blood pressure control did not affect the rate of progression of microalbuminuria to clinical proteinuria in the one available study. There is inconclusive evidence from four trials of any difference in the proportions of hypertensive patients progressing from microalbuminuria to clinical proteinuria when ACE inhibitors are compared with other antihypertensive agents, and in one trial regression was two-fold higher with lisinopril than with nifedipine. CONCLUSIONS: The most pronounced benefits of glycaemic control identified in this review are on retinal and renal complications in both normoalbuminuric and microalbuminuric patients considered together, with little or no evidence of any greater benefit in those with microalbuminuria. Hence, microalbuminuric status may be a false boundary when considering the benefits of glycaemic control. Classification of a person as normoalbuminuric must not serve to suggest that they will derive less benefit from optimal glycaemic control than a person who is microalbuminuric. All hypertensive patients benefit from blood pressure lowering and there is little evidence of additional benefit in those with microalbuminuria. Antihypertensive therapy with an ACE inhibitor in normotensive patients with microalbuminuria is beneficial. Monitoring microalbuminuria does not have a proven role in modulating antihypertensive therapy while the patient remains hypertensive. Recommendations for microalbuminuria research include: determining rate and predictors of development and factors involved in regression; carrying out economic evaluations of different screening strategies; investigating the effects of screening on patients; standardising screening tests to enable use of common reference ranges; evaluating the effects of lipid-lowering therapy; and using to modulate antihypertensive therapy.

Cytometric and functional analyses of NK and NKT cell deficiencies in NOD mice.

Defects in NK and NKT cell activities have been implicated in the etiology of type 1 (autoimmune) diabetes in NOD mice on the basis of experiments performed using surrogate phenotypes for the identification of these lymphocyte subsets. Here, we have generated a congenic line of NOD mice (NOD.b-Nkrp1(b)) which express the allelic NK1.1 marker, enabling the direct study of NK and NKT cells in NOD mice. Major deficiencies in both populations were identified when NOD.b-Nkrp1(b) mice were compared with C57BL/6 and BALB.B6-Cmv1(r) mice by flow cytometry. The decrease in numbers of peripheral NK cells was associated with an increase in their numbers in the bone marrow, suggesting that a defect in NK cell export may be involved. In contrast, the most severe deficiency of NKT cells found was in the thymus, indicating that defects in thymic production were probably responsible. The deficiencies in NK cell activity in NOD mice could only partly be accounted for by the reduced numbers of NK cells, and fewer NKT cells from NOD mice produced IL-4 following stimulation, suggesting that NK and NKT cells from NOD mice shared functional deficiencies in addition to their numerical deficiencies. Despite the relative lack of IL-4 production by NOD NKT cells, adoptive transfer of alpha beta TCR(+)NK1.1(+) syngeneic NKT cells into 3-week-old NOD recipients successfully prevented the onset of spontaneous diabetes. As both NK and NKT cells play roles in regulating immune responses, we postulate that the synergistic defects reported here contribute to the susceptibility of NOD mice to autoimmune disease.

Intraoperative T staging in radical retropubic prostatectomy: is it reliable?

OBJECTIVES: During radical prostatectomy, wide local excision of the lateral prostatic fascia and neurovascular bundle on the ipsilateral side of the tumor is advocated if nerve sparing is likely to result in a positive surgical margin. Our intent was to validate whether intraoperative T staging can predict the presence of positive surgical margins and aid in the decision of whether to perform nerve-sparing prostatectomy. METHODS: One surgeon performed 100 consecutive radical prostatectomies, and one pathologist interpreted the pathologic findings. Topographic distribution of tumor within the specimen was assessed intraoperatively by palpation. The margin status was similarly assessed. This tactile clinical impression was compared with the final pathologic findings. RESULTS: The surgical margins were positive in 39 (39%) of 100 cases. The intraoperative assessment of the margin status had a high false-negative rate and a sensitivity of only 7%. However, the specificity was 96%, because few margins were falsely positive. The overall accuracy was 62%, with a negative predictive value of 62%. The sensitivity of the intraoperative assessment of tumor location was 73%, and the positive predictive value was 65%. CONCLUSIONS: The results of our study indicate that the intraoperative assessment of the margin status is not accurate and thus cannot help determine which patients require excision of the neurovascular bundle. We believe the decision to preserve the neurovascular bundle should be based on the preoperative prognostic factors and the presence of an intact capsule covering the region of the gland adjacent to this structure.

De novo muscle invasive bladder cancer: is there a change in trend?

PURPOSE: We reviewed our radical cystectomy series to determine whether the majority of patients present with muscle invasive bladder cancer. MATERIALS AND METHODS: The records of 184 radical cystectomies performed by 1 surgeon from 1992 to 1999 were reviewed, and all slides of presenting pathology were reviewed by 1 pathologist. The pathological stage of the tumor at presentation was noted in each case, and the number of muscle invasive tumors at presentation was compared to 2 earlier series. RESULTS: Radical cystectomy was performed for muscle invasive transitional cell carcinoma of the bladder in 176 cases and for other histology in 8. There were 101 (57.3%) patients with muscle invasive cancer at presentation compared to 84% and 91% in the 2 earlier series, respectively, which was a statistically significant decrease (p <0. 0001) in the number of de novo muscle invasive bladder cancers. Women were more likely to be diagnosed with muscle invasion primarily than men (85.2% and 50.7%, respectively), and younger patients (younger than 50 years) were more likely to present with superficial bladder cancer compared to those older than 50 years who were more likely to present with de novo muscle invasive bladder cancer. CONCLUSIONS: Analysis of our data supports the findings of the earlier series that the majority of patients present with muscle invasive bladder cancer. However, there is a significant decrease in the percentage of tumors invading the muscularis propria at presentation. Although this observation is encouraging, we emphasize that it is not as dramatic as the stage migration associated with prostate cancer, which may be largely attributed to the widespread use of prostate specific antigen for early detection. Therefore, we support the suggestion that therapeutic gains might follow from improved education regarding the signs and symptoms associated with bladder cancer, with enhanced focus on women and consideration of screening methods for those at high risk for bladder cancer.

Identification of the Gasa3 and Gasa4 autoimmune gastritis susceptibility genes using congenic mice and partitioned, segregative and interaction analyses.

BALB/c mice thymectomized on their third day of life develop a high incidence of experimental autoimmune gastritis (EAG) which closely resembles human chronic atrophic (type A, autoimmune) gastritis. Linkage analysis of (BALB/cCrSlcxC57BL/6)F2 mice previously demonstrated that the Gasa1 and Gasa2 genes on distal Chromosome (Chr) 4 have major effects on the development of EAG in this murine model, while other loci displayed a trend towards linkage. Here, we implemented partitioned chi(2)-analysis in order to develop a better understanding of the genotypes contributing to susceptibility and resistance at each linkage region. This approach revealed that linkage of Gasa1 and Gasa2 to EAG was due to codominant and recessive BALB/cCrSlc alleles, respectively. To identify additional EAG susceptibility genes, separate linkage studies were performed on Gasa1 heterozygotes and Gasa2 C57BL/6 homozygotes plus heterozygotes so as to minimize the effects of these disease genes. The enhanced sensitivity of these analyses confirmed the existence of a third EAG susceptibility gene (designated Gasa3) on Chr 6. Epistatic interactions between the Gasa2 EAG susceptibility gene and the H2 were also identified, and the presence of an H2-linked susceptibility gene (Gasa4) confirmed by analysis of H2 congenic mice.

Management of urinary tract infection in general practice: a cost-effectiveness analysis.

BACKGROUND: Symptoms associated with urinary tract infection (UTI) are common in women in general practice and represent a significant burden for the National Health Service. There is considerable variation among general practitioners in the management of patients presenting with these symptoms. AIM: To identify the most appropriate patient management strategy given current information for non-pregnant, adult women presenting in general practice with symptoms of uncomplicated UTI. METHOD: A decision analytic model incorporating a variety of patient management strategies was constructed using available published information and expert opinion. This model was able to provide guidance on current best practice based upon cost-effectiveness (cost per symptom-free day). RESULTS: Empiric treatment was found to be the least costly strategy available. It saved two days of symptoms per episode of UTI at a cost of 14 Pounds. The empiric-and-laboratory strategy involves an incremental cost-effectiveness ratio of 215 Pounds per symptom day averted per episode of UTI. The remaining patient management strategies are never optimal. CONCLUSION: Empiric treatment of patients presenting with symptoms of UTI was found to be cost-effective under a range of assumptions for this patient group. However, recognition of the impact of this strategy upon antibiotic resistance may lead to the dipstick strategy being considered a superior strategy overall.

The use of liver transplant techniques to aid in the surgical management of urological tumors.

PURPOSE: Inferior vena cava tumor thrombus complicates radical nephrectomy. Various approaches have been used to deal with this problem, including venovenous and cardiopulmonary bypass. Applying organ transplant techniques enhances the exposure of urological tumors and may avoid bypass. MATERIALS AND METHODS: A total of 26 patients underwent surgery by techniques developed to facilitate orthotopic liver transplantation. Of the patients 15 with renal cell carcinoma and an intracaval tumor thrombus underwent piggyback style mobilization of the liver off of the retrohepatic inferior vena cava to allow enhanced access and vascular control, while 11 underwent conventional mobilization of the liver and retrohepatic inferior vena cava en bloc to allow enhanced access to various renal, adrenal and retroperitoneal tumors. RESULTS: In the 11 patients surgery was successful with a median blood loss of 200 ml. Postoperative ileus in 1 case was the only complication. We resected 5 infrahepatic thrombi without complications and with a median blood loss of 500 ml. In 7 patients with a retrohepatic inferior vena caval thrombus median blood loss was 1,500 ml., including 1 who died postoperatively, presumably due to a massive pulmonary embolus. Caval atrial tumor thrombus in 3 cases was successfully removed via a completely abdominal approach and sternotomy in 2. Cardiopulmonary bypass with hypothermic circulatory arrest was required in 1 of these cases. CONCLUSIONS: Liver mobilization was helpful for managing difficult urological tumors. Patients with a retrohepatic or even suprahepatic inferior vena caval thrombus may be treated without sternotomy or thoracotomy and cardiopulmonary bypass.

Incidental appendectomy during radical cystectomy: an interdepartmental survey and review of the literature.

OBJECTIVES: To survey and review the incidence of appendectomy performed during radical cystectomy and urinary diversion. We were interested in the reasons behind the decision and if continent diversions have changed the policy. METHODS: We performed a selective survey among urologists in academic centers throughout the United States regarding their practice of incidental appendectomy during radical cystectomy. We also reviewed the literature regarding the rationale for incidental appendectomy in general and during radical cystectomy in particular. RESULTS: Among the 13 departments and 26 urologists replying to the survey, 9 (69%) departments and 20 (77%) individual clinicians are not performing routine incidental appendectomy. In 2 departments, it is considered a matter of choice, and, in 4 (31%) departments, appendectomy is performed routinely. Many believe that the low risk of subsequent appendicitis does not justify the procedure and that the appendix may be useful for future reconstruction. A review of the literature suggests that incidental appendectomy during radical cystectomy is not necessary. CONCLUSIONS: Incidental appendectomy during radical cystectomy is not necessary and is no longer being performed in many academic centers. The risk of subsequent appendicitis is extremely low. The decision may depend on the form of urinary diversion planned.

Oral zinc for arterial and venous leg ulcers.

BACKGROUND: Leg ulcers affect up to 1 per cent of people at some time in their life. Management includes care of the ulcer using dressings and treatment of underlying medical problems such as malnutrition, lack of minerals, vitamins, poor blood supply or infection. OBJECTIVES: To assess the effectiveness of oral zinc in healing arterial or venous leg ulcers. SEARCH STRATEGY: Searches of 19 databases, hand searching of journals and conference proceedings from 1948 onwards, and examination of bibliographies. The company manufacturing zinc sulphate tablets was asked for references to relevant trials. SELECTION CRITERIA: Randomised controlled trials comparing oral zinc sulphate with placebo or no treatment in patients with arterial or venous leg ulcers. There was no restriction on date or language. The main outcome measure used was complete healing of the ulcers. Trials were eligible for inclusion if they measured ulcer healing objectively, by time to complete healing, proportion of ulcers healed during the study, or healing rates of ulcers. DATA COLLECTION AND ANALYSIS: All data extraction and assessment of trial quality were done by both authors independently. MAIN RESULTS: There were six eligible trials. All are small and serum zinc was measured at baseline or during the trial in 4 trials. Overall there is no evidence of a beneficial effect of treatment with zinc sulphate on the number of ulcers healed at the end of the trials. There is some evidence that oral zinc might have a beneficial effect on healing of venous ulcers in people with a 'low' serum zinc level at baseline. REVIEWER'S CONCLUSIONS: Overall, oral zinc sulphate does not appear to aid healing of leg ulcers, although it might be beneficial in those with venous leg ulcers and low serum zinc. Further research is needed to ascertain the serum zinc concentration below which treatment with zinc might be beneficial, and the dose required. [This abstract was prepared centrally]

Nursing a fine line: patient privacy and sex discrimination.

Recent court decisions provide the only parameters for applying Title VII of the Civil Rights Act of 1964 to male nurse hiring and assignment. As the male nursing student population climbs toward 10%, nurses and health care providers struggle to define their employment rights.

Microvessel density as a prognostic marker for transitional cell carcinoma of the bladder.

OBJECTIVE: To investigate the prognostic significance of mean vascular density (MVD) in a variety of transitional cell carcinomas (TCC) obtained by biopsy and cystectomy, and thus determine the importance of vascular density as a prognostic indicator for vesical TCC. PATIENTS AND METHODS: Tumour vasculature was visualized using factor VIII immunohistochemistry. The MVDs of tumours from 42 cystectomy specimens were correlated with patient survival over a maximum follow-up of 156 months. The results were also compared with those obtained from initial bladder biopsy in a subset of 29 patients. RESULTS: Twenty-five patients had died over a mean follow-up of 32 months. The MVDs from cystectomy specimens ranged from 29 to 229 vessels per medium-power field (0.94 mm2) while that for biopsies before cystectomy ranged from 51 to 155 vessels. The MVD for both cystectomy and biopsy specimens showed a significant association with survival, but this was absent in a multivariate analysis that included tumour stage and grade, and there was a poor correlation between the MVD of cystectomy- and biopsy-derived tumours. CONCLUSION: The assessment of tumour vascularity appears to be of little clinical importance for vesical TCC.

Does oral zinc aid the healing of chronic leg ulcers? A systematic literature review.

OBJECTIVE: To determine whether oral zinc sulfate is an effective treatment for promoting healing of venous or arterial leg ulcers. DATA SOURCES: The search strategy of the Cochrane Wounds Group was used. This includes searches of electronic databases, conference proceedings, relevant bibliographies, and hand searching of journals. STUDY SELECTION: Studies were included if they were randomized controlled trials of oral zinc sulfate in the treatment of chronic venous or arterial ulcers with objective measures of healing. Six of the 10 studies initially identified were included in the review. DATA EXTRACTION: The trial method, participants, interventions, outcomes, baseline comparability, adequate reporting of withdrawals, and blinding of assessment were extracted by 2 reviewers independently. DATA SYNTHESIS: No trial showed a statistically significant benefit of zinc sulfate for healing leg ulcers. There is limited evidence to suggest that zinc might increase healing in individuals with a low serum zinc level, but more evidence is needed. CONCLUSIONS: There is no evidence of benefit from the general use of zinc sulfate in patients with chronic leg ulcers. There is a need for further research to see if oral zinc sulfate is beneficial in the treatment of patients with leg ulcers who have a low serum zinc level. If it is demonstrated to be beneficial, further trials are required to establish dose and duration of treatment.