Search PubMed⌕ Search

Biomedical subjects

D E Neal

Publications and source records attributed to D E Neal.

At least 145 records · Page 8Linked to original sources

Expression of retinoblastoma gene product and p53 protein in bladder carcinoma: correlation with Ki67 index.

OBJECTIVES: To determine whether loss of the tumour suppressor gene retinoblastoma (Rb) and increased expression of the p53 protein were associated with increased tumour cell growth fraction. PATIENTS AND METHODS: Tumours from 105 patients (72 men, 33 women; median age 69 years, range 35-89) with newly diagnosed primary transitional cell bladder carcinoma were studied. Tumour samples were taken by means of cystoscopic resection. Expression of the retinoblastoma (Rb) and p53 gene products was assessed immunohistochemically in 98 of the carcinomas. The proportion of cells expressing the Ki67 antigen (Ki67 index which is a measure of growth fraction) was determined in 64 cases. RESULTS: p53 protein was detectable in 50% and Rb protein in 82% of the tumours. Staining for p53 and lack of staining for Rb protein were associated with muscle-invasive growth and high tumour grade (G3). The Ki67 index varied over a wide range (1-47%), but there were significant differences between mean indices for poorly differentiated (G3) and well or moderately differentiated (G1/G2) tumours, and between indices for muscle-invasive and the remaining tumours. The mean Ki67 indices for Rb-negative tumours and p53-positive tumours were approximately twice those for Rb-positive and p53-negative tumours. Only 10% of the tumours expressed high levels of p53 protein and failed to express Rb. CONCLUSION: These observations are consistent with the hypothesis that loss of Rb and mutation and overexpression of p53 are associated with an increased tumour cell growth fraction and that such changes may play a role in the de-regulation of cell proliferation in transitional cell carcinoma of the bladder.

Adult↗

The National Prostatectomy Audit: the clinical management of patients during hospital admission.

OBJECTIVE: To determine everyday practice in the hospital management of men undergoing prostatectomy and the extent of its variation. PATIENTS AND METHODS: A total of 5361 patients, who represented 89% of all those undergoing prostatic procedures in four health regions (Mersey, Wessex, Northern and South West Thames) and one test site (within Trent) were recruited by 103 (97%) surgeons. Clinical information was collected on a pre-coded data collection form which was completed during the hospital stay by the principal operator. Patient identification occurred at the time of surgery. RESULTS: Important findings included: (i) both older men and those of higher social class were more likely to undergo prostatectomy with fewer symptoms; (ii) men who waited longer for surgery had worse symptoms by the time of their operation; (iii) there were unexplained differences in routine pre- and post-operative investigation and treatment. Half the men had their flow rate or residual urine measured as part of their pre-operative assessment. About half the men received prophylactic antibiotics; (iv) when large groups were analysed, a consistent proportion of men throughout the study (12%) were undergoing the operation for a second time. The clinical course of men having a repeat operation differed in many ways from those having a first time procedure; (v) the larger proportion of men (62%) had surgery for strong indications as opposed to symptoms alone; (vi) although most operations were performed by consultants, emergency admissions, though symptomatically more severe and sicker, were more likely to be operated on by trainee surgeons; (vii) significant variation in mean pre-operative symptom severity and bother scores were seen between surgeons. CONCLUSION: The clinical management of prostatectomy has been defined in a large and representative UK sample. In some circumstances consistent variations have been identified. It is not yet clear whether these variations influence outcome. These data can be used by surgeons wishing to compare their own patient management with that described here.

Age Factors↗

Outcome of endoscopic bladder transection.

OBJECTIVE: To determine the clinical, symptomatic and objective urodynamic outcome of patients undergoing endoscopic bladder transection. PATIENTS AND METHODS: The study included 20 men and 30 women (mean age of 50 +/- 15 years, range 20-86) who underwent endoscopic bladder transection. Their underlying diagnoses were idiopathic detrusor instability (41), enuresis with instability (6), multiple sclerosis (2) and Parkinson's disease (1). A full-thickness endoscopic transection of the bladder was performed under general anaesthesia. Subjective assessment was performed using symptom scores (0-14 points) and a Visick grading system (group A-E). Objective assessment was carried out using urodynamic studies. The mean follow-up period was 6 years (57 +/- 22 months, range 6-85). RESULTS: The mean hospital stay was 8 +/- 3 days (range 3-22). No patients died after the operation. Postoperative complications included extra-peritoneal extravasation (2), recurrent urinary tract infection (5) and urethral stricture (1). Symptom scores before and after the operation were 9 +/- 2 (range 4-14) and 8 +/- 3 (range 1-14) points respectively. The overall outcome of the procedure was satisfactory in only eight (16%) patients. The mean duration of symptomatic relief was 17 weeks (range 3-53). There was no significant difference between urodynamic results before and after the operation. Bladder instability observed in all patients before operating was demonstrated in 93% of patients after the operation. CONCLUSION: The results of our study suggests that endoscopic bladder transection produces only a transient symptomatic relief in a few of those patients who have failed to respond to pharmacological manipulations. We do not feel that its continued role is justified.

Adult↗

Nottingham health profile measurement in the assessment of clinical outcome after prostatectomy. Northern Regional Prostate Audit Group.

OBJECTIVE: To compare the changes in pre- and post-operative symptom scores with changes in Nottingham health profile (NHP) scoring, and thus determine whether NHP scoring offers a reliable assessment of outcome after transurethral resection of the prostate (TURP), and whether NHP scoring could usefully supplement the more traditional method of symptom scoring in this assessment. PATIENTS AND METHODS: An 8-month audit of 1396 TURPs, involving 12 hospital sites, was performed in the Northern region between April 1 and November 31, 1991. A cohort of 371 of these patients, for whom pre- and post-operative NHPs and irritative and obstructive voiding symptoms had been recorded, were investigated. RESULTS: There was a significant decrease in both obstructive and irritative voiding symptom scores 3 months after TURP and a significant fall in the NHP scores for all stations except social isolation. There were significantly higher irritative symptom scores both before and after operation in men with prostate cancer compared with those with benign prostatic hypertrophy, and significantly higher post-operative obstructive symptom scores in men with prostate cancer. However, there were no significant differences in the pre- and post-operative NHP scores for these two subgroups of patients. In patients who had a good outcome on symptom scoring, there was a significant reduction in NHP scores for all stations except social isolation. However, in those patients who had a poor outcome on symptom score, there was no correlation with changes in the NHP scores, with some NHP stations showing a significant reduction after operation. CONCLUSION: NHP quality-of-life scoring cannot replace symptom scoring in the assessment of outcome after TURP and when used alone, added little further information. However, for a comprehensive assessment of outcome, symptom scores and quality-of-life assessments should be used together.

Cohort Studies↗

Clinical outcome and quality of life following enterocystoplasty for idiopathic detrusor instability and neurogenic bladder dysfunction.

OBJECTIVE: To study the long-term outcome of patients undergoing enterocystoplasty. PATIENTS AND METHODS: The study comprised 48 patients (17 men and 31 women; mean age 46 years) who underwent enterocystoplasty for idiopathic detrusor instability (DI, 35 patients) or neurogenic bladder dysfunction (13 patients). Symptoms were scored from 0 to 14 and the overall outcome and generic quality of life were assessed using a Visick grading system (groups A to E) and the Nottingham Health Profile (NHP). These assessments were carried out before, 3 months after operation and at the final follow-up (38 +/- 18 months, range 13-78). Urodynamic studies were performed before and after operation. RESULTS: No patient died after operation and there was minimal early morbidity. Late complications (> 30 days) included incisional hernia (3), anastomotic perforation (1), calculus formation (1) and urethral stricture (1). Clean intermittent self-catheterization (CISC) was performed by 36 (75%) patients. Early symptomatic outcome was good in 40 (83%) patients, moderate in seven (15%) and unsatisfactory in one (2%) patient. The mean symptom scores before and 3 months after surgery were 10 (range 2-14) and 3 (range 2-14), respectively (P < 0.001). There was a significant increase in total bladder capacity (307 +/- 140 to 588 +/- 217 mL; P < 0.001) and bladder compliance (37 +/- 50 to 169 +/- 162 mL/cm H2O; P < 0.001). DI persisted in 15 (31%) patients. NHP scores revealed significant improvements in all domains. Final assessment showed a less satisfactory situation, with recurrent urinary tract infection (UTI) in 17 (37%) patients, a need for long-term antibiotic therapy in seven (15%) and a change in bowel habit in 15 (33%) (13 DI, two with neurogenic bladder dysfunction). CISC was performed by 39 (85%) patients. The long-term outcome was good or moderate in 12 patients (92%) with neurogenic bladder dysfunction and good or moderate in only 19 patients (58%) with DI. CONCLUSION: Clam enterocystoplasty remains an effective management option in some patients with DI, but most patients with neurogenic bladder dysfunction do well. The procedure is, however, associated with long-term complications such as disturbance of bowel habit and recurrent UTIs, which impair the outcome in the long-term in patients with DI despite general improvements in irritative bladder symptoms.

Adult↗

P53 and ploidy assessed by flow cytometry in bladder washings.

OBJECTIVE: To determine p53 expression in cells in bladder washings and to relate this to DNA content and clinical outcome. PATIENTS AND METHODS: Washings from 102 patients (41 with newly diagnosed superficial tumours [pTa and pT1], 49 with recurrent superficial tumours and 12 with carcinoma invading bladder muscle) were studied. In 39 cases, the primary bladder tumour was also analysed. The rates of tumour recurrence and progression were determined for the new superficial tumours and related to both p53 expression and DNA content. RESULTS: Cells positive for p53 were detected in 22 of 90 (24%) washings from patients with superficial bladder cancer. P53 expression correlated with tumour stage (P < 0.05), grade (P < 0.05) and abnormal DNA content (P < 0.05). The analysis of pure urothelial (cyto-keratin-positive) cells improved the detection of DNA abnormalities (P < 0.001). In 74% of cases where both washings and tumour were analysed, the results for DNA content agreed. Of 41 new superficial tumours, 27 (66%) recurred (11 were p53-positive, 16 were p53-negative, P = 0.221; 17 had abnormal DNA content, 10 were diploid, P = 0.069). Four patients progressed (one was p53-positive, P = 0.315 and all had abnormal DNA content, P = 0.072). CONCLUSION: P53-positive cells can be detected in washings using flow cytometry and were more commonly detected in association with aneuploid tumours. At short-term follow-up, flow cytometric analysis of DNA content in washings had greater predictive value than had p53 expression. Few washings contained aneuploid cells when the primary tumour contained diploid cells, although the collection of washings is a convenient way of sampling tumour cells.

Aged↗

The feasibility and cost of a large multicentre audit of process and outcome of prostatectomy.

Objective--To determine the feasibility of performing multicentre process and outcome audits of common interventions taking prostatic procedures as an example. Design--Prospective, cohort study. Setting--All National Health Service and independent hospitals in Northern, Wessex, Mersey, and South West Thames health regions. Patients--5361 men undergoing prostatectomy identified by 103 of the 107 urologists and general surgeons performing prostatectomy in the study regions. Main measures-- Rates of participation by surgeons and patients; completeness of clinical data provided by surgeons; patient response rate and completeness of patient derived data; and cost. Results--Most surgeons (103,96%) agreed to participate. Overall, the proportion of eligible patients invited to take part was high (89%), although this was only measured in South West Thames, where dedicated data collectors were employed. Few men (80, 1.5%) declined to participate. Of those surviving for three months after surgery, 82.4% (4226) completed and returned the postal questionnaire. The response rate was higher in South West Thames (86.7%) than in the other regions (80.6%-80.8%). The audit was well received: 91% of patients found the questionnaire easy to complete and only 2.3% of them disapproved. Completeness of data was high with both the hospital and patient questionnaires. Missing data occurred in less than 5% of responses to most questions. The attributable cost was 34.50 pounds per patient identified or 44 pounds for patients in whom either the treatment outcome or vital status was known three months after their prostatectomy. Conclusions--This multicentre audit of process and outcome of prostatectomy proved feasible in terms of surgeon participation, patient identification, and the quantity and quality of data collection. Whether the cost was warranted will depend on how surgeons use the audit data to modify their practice.

Aged↗

Tanagho bladder neck reconstruction in the treatment of adult incontinence.

We studied the effectiveness of tubularized bladder neck reconstruction in the treatment of 8 patients with complex incontinence using urodynamic and clinical methods. The patients had undergone Tanagho bladder neck reconstruction within the last 10 years. Three of the 8 patients were judged unsuitable for artificial sphincter implantation because of severe scarring, and loss of urethral and vaginal tissue. There were 7 women with epispadias or severe urethral damage as a consequence of obstetrical or gynecological procedures. Five patients underwent 7 concurrent procedures at the time of bladder neck reconstruction, including colposuspension (4), and closure of a fistula involving the bladder neck (1) and urethra (1) plus vaginal reconstruction (1). Of 8 patients 5 (63%) were completely continent and satisfied, 2 underwent ileal conduit diversion (1 because of incontinence and 1 refused clean intermittent self-catheterization), and 1 is incontinent and awaiting further treatment. The best results were noted in patients with a healthy bladder and periurethral tissues. Four of 5 patients (80%) deemed potentially suitable for artificial urinary sphincter insertion were satisfied compared to only 1 of 3 (33%) unsuitable for artificial urinary sphincter insertion. The Tanagho bladder neck reconstruction is a useful addition to the procedures that may be used by the reconstructive urological surgeon in the treatment of carefully selected patients with complex incontinence, particularly in women with epispadias who for various reasons may wish to avoid the long-term potential complications of an artificial urinary sphincter.

Adult↗

Long-term outcome related to epidermal growth factor receptor status in bladder cancer.

For bladder cancer we currently lack accurate methods of predicting outcome, although clinical stage and histological grade are broad determinants of prognosis. Preliminary data have indicated that assessment of epidermal growth factor receptor status is a method of further subclassifying bladder cancer. We assessed prospectively the clinical significance of determining epidermal growth factor receptor status in 212 patients with newly diagnosed bladder cancer who were followed for 1 to 96 months (mean 26.5). In multivariate analyses epidermal growth factor receptor was confirmed to be an independent predictor of survival (p = 0.004) and stage progression (p = 0.0004). Most importantly, epidermal growth factor receptor status was found to be 80% sensitive and 93% specific in predicting stage progression in T1, grade 3 bladder cancer. We conclude that epidermal growth factor receptor status is a useful molecular marker in patients with bladder cancer, especially those without infiltration of the detrusor muscle at presentation.

Adult↗

The effect of antimicrobial therapy on testicular aspirate flow cytometry.

Many antibiotics have been shown to have adverse effects on spermatogenesis. Deoxyribonucleic acid (DNA) flow cytometry of testicular aspirate has been shown to be an effective method of quantitatively evaluating testicular function. To assess this problem, DNA flow cytometry of testicular aspirate was performed on 8 groups of rats, each of which received antibiotics via daily gavage for 10 days. Aspirations were performed on days 0, 11 and 56. Data thus obtained were analyzed using a two-way ANOVA with repeated measures. Antibiotics studies included ciprofloxacin 15 mg./kg./day, sulfamethoxazole (SMX) 20 mg./kg./day (with trimethoprim (TMP) 4 mg./kg./day), nitrofurantoin 7 mg./kg./day, ofloxacin 10 mg./kg./day, lomefloxacin 6 mg./kg./day, doxycycline 3 mg./kg./day and norfloxacin 10 mg./kg./day. One group received the same SMX/TMP dose, together with folate 0.014 mg./kg./day. A statistically significant change in aspirate content on day 11 as compared with baseline existed in groups receiving TMP/SMX (p = 0.00025), nitrofurantoin (p = 0.0000043), ofloxacin (p = 0.000075) and doxycycline (p = 4.89 X 10(-9). Control rats and the group receiving TMP/SMX with folate showed no significant change. On day 56 the abnormality persisted in groups TMP/SMX (p = 0.042), nitrofurantoin (p = 0.001), ofloxacin (p = 0.036) and doxycycline (p = 0.003). Controls and groups receiving ciprofloxacin, norfloxacin and lomefloxacin continued to show no statistically significant difference from baseline on day 56. These data suggest that SMX/TMP, nitrofurantoin, ofloxacin and doxycycline significantly alter spermatogenesis. Ciprofloxacin, norfloxacin and lomefloxacin had no apparent effect on spermatogenesis as measured by DNA flow cytometry.

Animals↗

Evaluation and results of treatments for prostatism.

Men with symptoms of prostatism form a heterogenous group. The best treatment of proven obstruction or retention in fit men remains transurethral prostatectomy (TURP). Men presenting with symptoms of prostatism may have bladder outflow obstruction, detrusor instability or weak bladder contraction leading to low pressure/low flow voiding so it is perhaps not surprising that only 75% of men selected for TURP purely on the basis of symptoms have a good outcome. Pressure flow studies are the only precise method of diagnosing outflow obstruction. The problem of accurately diagnosing obstruction before treatment is started applies particularly to trials of new treatments such as lasers, high energy focused ultrasound and drugs. Laser treatment is producing short term results that are slightly inferior to TURP but may have less morbidity. The role of conservative treatment is important in selected men. Men who have severe intercurrent illness may be treated by means of intra-prostatic stents. In order to accurately assess a new treatment it is necessary to determine the short-term mortality, the morbidity, complication rate and outcome as well as the cost-effectiveness, long-term outcome and patient preference. These conditions have not yet been met for any of the new treatments for prostatism.

5-alpha Reductase Inhibitors↗

Pediatric urolithiasis: review of research and current management.

The treatment of urolithiasis in children has changed dramatically in recent years. With the proven safety and efficacy of extracorporeal shock wave lithotripsy (ESWL), percutaneous lithotripsy and ureteroscopy in adults, these modalities are now in the forefront of the treatment of pediatric urinary stones. Our research in the juvenile non-human primate with ESWL indicates that renal damage in most cases is neither significant or persistent. In addition, technological advances in instrumentation have cleared the way for the use of percutaneous lithotripsy and ureteroscopy in most pediatric patients. Today, open surgical procedures for stone disease in children should be a last resort.

Child, Preschool↗

Use of terazosin in prostatodynia and validation of a symptom score questionnaire.

OBJECTIVE: The purpose of this trial was to study the use of terazosin in nonbacterial prostatitis/prostatodynia, and to evaluate a new symptom score sheet for this disease. METHODS: Twenty-five patients who presented with lower urinary tract symptoms suggestive of prostatitis were evaluated for evidence of bacterial infection by Meares-Stamey criteria and found to be negative. They were then treated with the alpha-blocking drug terazosin in doses from 1 to 10 mg. A symptom score index for prostatitis was developed, tested in these patients, and validated against patients with benign prostatic hyperplasia. Normal control patients, who presented for vasectomy, were studied as well. RESULTS: Nineteen patients (76%) responded to one month's therapy, with 11 (58%) remaining asymptomatic three months later. The symptom score index, as measured by Cronbach's alpha measure of index reliability, was excellent at 0.78 and logistic regression analysis demonstrated each prostatitis question to have independent validity (P < 0.001) but not to the extent of the combined score. CONCLUSIONS: Terazosin appears effective in treating patients with nonbacterial prostatitis/prostatodynia. This new symptom score is one way to evaluate and track patients with this disease. A randomized, placebo-controlled clinical trial has been initiated to study this.

Adrenergic alpha-Antagonists↗