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Biomedical subjects

D E Neal

Publications and source records attributed to D E Neal.

At least 19 recordsLinked to original sources
PubMed1996

C-erbB-2 in bladder cancer: molecular biology, correlation with epidermal growth factor receptors and prognostic value.

PURPOSE: To study the c-erbB-2 oncogene in primary transitional cell bladder cancer. MATERIALS AND METHODS: Ninety-five patients with known clinical follow-up and epidermal growth factor receptor (EGFr) status were studied for expression of c-erbB-2 by immunostaining. Possible mechanisms underlying increased staining for c-erbB-2 protein were investigated by analyzing DNA and RNA encoding c-erbB-2. RESULTS: Strong positive staining for c-erbB-2 was detected in 20 (21%) tumors, with weaker staining in a further 13 (14%). There was no correlation between increased staining for c-erbB-2 and tumor stage, grade, or EGFr status. There was a low rate of amplification of the c-erbB-2 gene (1 of 24) on Southern blotting with a higher rate of elevated c-erbB-2 mRNA (4 of 44) with dot blot hybridization. For pT1 tumors, the rate of recurrence was higher for those tumors which were positive for c-erbB-2. CONCLUSIONS: c-erbB-2 oncoprotein is expressed by a significant proportion of transitional cell tumors of the bladder. In this study, the prognostic significance of c-erbB-2 expression appears limited.

Blotting, Southern↗
PubMed1995

Transrectal ultrasound guided needle electromyography of the urethral sphincter in males.

Needle electromyography (EMG) of the urethral sphincter in males is commonly performed using a transperineal approach. The technique involves transcutaneous insertion of an EMG needle into the sphincter guided by the investigator's finger placed in the rectum. We describe a new method of needle placement into the urethral sphincter in males using transrectal ultrasound (TRUS). With the patient in the left lateral position, the apex of the prostate gland is identified in the longitudinal plane. Using the TRUS biopsy channel, a specially designed long EMG needle is inserted into the sphincter commencing approximately 1.5-2 cm distal to the prostatic apex in an oblique fashion. This method allows precise identification of the site for needle insertion, reducing blind attempts at localization. The transrectal route is much less uncomfortable to patients, potentially improving patient compliance and overall effectiveness of the technique.

Electromyography↗
PubMed1995

Urinary secretory immunoglobulin A and free secretory component in pyelonephritis.

The immune defense mechanisms of mucosal surfaces involve secretory immunoglobulin A (sIgA) antibodies and, to a lesser degree, other specific and nonspecific immune factors. These antibodies are dependent on a secretory component (SC) for their transmission through the epithelium. This SC is also secreted without Ig as free SC (FSC). The kidney does produce these proteins; however, the ability of the lower urinary tract to secrete them has not been shown. Thus, an upper urinary tract infection should produce more urinary sIg and possibly more FSC than a lower tract infection. To demonstrate this, urine was obtained from normal controls (N = 33), cystitis patients (N = 22), and pyelonephritis patients (N = 27). Monoclonal antibodies binding to specific conformational epitopes were used in an enzyme-linked immunosorbent assay to detect the levels of sIgA and FSC in these groups. Previous sIgA measurements have been hampered by lack of specificity of the capture antibody. Urine creatinine was obtained to correct for the effect of diuresis. A one-tailed Student's t-test for nonparametric populations was performed to assess differences. The sIgA levels in the normal and cystitis groups were equivalent (1.4 micrograms/mg/mL and 1.3 micrograms/mg/mL, respectively; P = 0.32). When these two groups were compared with the pyelonephritis group (24.1 micrograms/mg/mL), a statistically significant difference was seen (P = 0.012 and P = 0.011, respectively), with no overlap. There was a statistical difference in the levels of FSC in these same groups, but a large degree of overlap.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗