Biomedical subjects
D E Neal
Publications and source records attributed to D E Neal.
Conservative management of prostate cancer.
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Long-term monitoring of bladder pressure in chronic retention of urine: the relationship between detrusor activity and upper tract dilatation.
We investigated 41 men with chronic retention of urine owing to bladder outflow obstruction by long-term monitoring of bladder pressure and conventional cystometry to determine the relationship between detrusor pressure and upper tract dilatation. We confirmed that high pressures during conventional filling cystometry were common in men with upper tract dilatation. However, important differences were demonstrated between long-term monitoring and conventional cystometry. The pressure increase during the natural filling phase of long-term monitoring was significantly smaller than that during conventional cystometry. Detrusor instability was found in 88 per cent of the men during long-term monitoring but in only 51 per cent during conventional cystometry (p less than 0.001). High frequency unstable detrusor contractions during long-term bladder pressure monitoring were associated significantly with upper tract dilatation (p less than 0.0001) and correlated significantly with impairment of glomerular filtration rate (rs equals -0.7339, p less than 0.001).
Urethral dilatation compared with cystoscopy alone in the treatment of women with recurrent frequency and dysuria.
The relative merits of cystoscopy alone and cystoscopy plus urethral dilatation were compared in a randomised study of women with recurrent frequency and dysuria. One hundred women were studied before and at least 6 months after operation. A detailed questionnaire was completed, the severity of the symptoms was scored and patients underwent urodynamic investigation. Forty-eight patients underwent cystoscopy alone and 52 underwent urethral dilatation. The two groups were well matched with regard to age, parity, menopausal status, previous gynaecological surgery and severity of symptoms. A significant improvement in symptoms was observed in both groups after treatment: 30% had no residual symptoms, 50% were improved and 20% were no better. However, no difference in final outcome was observed between those who had undergone cystoscopy alone and those who had undergone urethral dilatation. Furthermore, 7 patients who underwent urethral dilatation experienced transient stress incontinence of urine, a complication not observed in women who underwent cystoscopy alone. No benefit was observed from the addition of urethral dilatation to cystoscopy alone in women with recurrent frequency and dysuria.
Reproducibility of measurement of prostatic volume by ultrasound. Comparison of transrectal and transabdominal methods.
88 men undergoing elective prostatectomy were investigated by transrectal and transabdominal ultrasound. A repeat examination was performed by a second observer in 28 patients. The aims were to determine the correlation between transrectal and transabdominal ultrasonic estimation of prostatic volume and the degree of observer error. Transabdominal estimation of prostatic volume correlated well with the transrectal method (p less than 0.001) and good agreement between the two observers was found with both methods (p less than 0.001). In the individual patient, however, a wide variation in prostatic volume was found between the two observers and the two methods.
Preservation of the entire anal canal in conservative proctocolectomy for ulcerative colitis: a pilot study comparing end-to-end ileo-anal anastomosis without mucosal resection with mucosal proctectomy and endo-anal anastomosis.
Mucosal proctectomy with endo-anal pull-through anastomosis (MP + PTA) for ulcerative colitis reduces resting anal pressure and low RAP has been found to correlate with minor leakage of faeces or mucus. Our hypothesis was that conservative proctocolectomy with an end-to-end ileo-anal anastomosis (EEA) would result in higher anal pressure and less leakage. Twelve patients were studied after EEA and 24 after MP + PTA: each was in good health several months after operation. After EEA, maximal RAP decreased from a median 90 cmH2O (60-116 cmH2O) to 70 cmH2O (25-104 cmH2O, P less than 0.01), whereas after MP + PTA maximal RAP decreased from 85 cmH2O (70-125 cmH2O) to 40 cmH2O (22-80 cmH2O, P less than 0.003). RAP after EEA was significantly greater than RAP after MP + PTA (P less than 0.001). The pressure profile of the anal sphincter in the EEA group did not differ significantly from that of the pre-operative group at any point from 6 to 1 cm from the anal verge, and the sphincteric high pressure zone averaged 4 cm in length both before and after operation. After MP + PTA, resting anal pressure at stations 1 to 4 cm from the anal verge was significantly less than pre-operative pressure (P less than 0.001) and the sphincteric high pressure zone was only 3 cm in length compared with 4 cm before operation. Anal squeeze pressures were similar in the two groups of patients. After EEA 11 of 12 patients achieved perfect continence, day and night, whereas after MP + PTA 58 per cent of patients experienced minor faecal leakage (P less than 0.01). These findings suggest that the entire anal canal should be kept intact in the course of conservative proctocolectomy for ulcerative colitis.
Evaluation of epidermal growth factor receptors in bladder tumours.
Epidermal growth factor (EGF) receptor expression in 31 primary human bladder tumours was quantitated using both structural and functional assays and the EGF receptor gene in the same tumours was analyzed by Southern blot analysis. Immunocytochemical studies using the EGFR1 monoclonal antibody (Mab) showed a significant correlation between EGF receptor levels and the stage and grade of the tumours. Autophosphorylation assays employed to evaluate the receptor's tyrosine kinase activity gave results which in general were consistent with the immunocytochemical data. Using internally controlled immunocytochemical studies with two Mabs and Southern blot analysis of DNA isolated from the tumours, no evidence was obtained for the production of truncated receptors similar to those encoded by the v-erb-B oncogene. Gene amplification was not found in any of the superficial tumours, but one invasive tumour with high EGF receptor expression had an 8-10 fold amplification of the EGF receptor gene. The EGF receptor isolated from this tumour showed a normal pattern of tyrosine phosphorylation at all three major autophosphorylation sites. Our detailed study is consistent with the correlation previously found between EGF receptor expression and stage and grade of bladder tumours, and suggests that at this level of analysis EGF receptors in bladder tumours are not abnormal in structure or size, autophosphorylation activity, or gene structure.
Histochemical study of lectin binding in neoplastic and non-neoplastic urothelium.
A histochemical study of lectin binding was performed to assess staining with lectins and, therefore, the expression of complex carbohydrates in human neoplastic urothelium. Forty-seven patients with transitional cell carcinoma of the bladder and six controls were studied. Cryostat sections were stained with a panel of 10 biotinylated lectins by means of the avidin-biotin-peroxidase technique. Sixteen tumours were also studied after conventional formalin fixation and paraffin embedding. In general, staining by lectins of tumours was more intense than staining of control urothelium and staining of tumours invading bladder muscle was greater than that of superficial tumours (both P less than 0.001). A small but statistically significant diminution of staining was observed after formalin fixation and paraffin embedding (P less than 0.05). Four lectins--Bandeiraea simplicifolia (P less than 0.01), Vicia villosa (P less than 0.01), peanut agglutinin (P less than 0.001) and soyabean agglutinin (P less than 0.001) stained invasive tumours more frequently than superficial tumours in frozen sections. Thus, increased binding of certain lectins was found in human transitional cell tumours and correlated with muscle invasion and poor differentiation.
Relationship between voiding pressures, symptoms and urodynamic findings in 253 men undergoing prostatectomy.
Two hundred and fifty-three men (age 69.2 +/- 7 years) undergoing prostatectomy for bladder outflow obstruction were studied. The aims were to determine the distribution of voiding pressures and their relationship to presenting symptoms and urodynamic findings. Symptoms were scored by means of a standardised questionnaire and urodynamic studies were performed. Within this study group, high obstructive symptom scores were associated with low flow rates and high urethral resistance. However, high voiding pressures were not associated statistically with low flow rates or obstructive symptoms. Voiding pressures followed a unimodal, parametric distribution and a significant number of men had voiding pressures within the normal range: 9.1% had voiding pressures less than 55 cm H2O and 27.7% less than 75 cm H2O. Irritative symptoms, on the other hand, correlated significantly with obstructive symptoms, high voiding pressures and urethral resistance. Furthermore, high voiding pressures were associated with small cystometric bladder capacities, low compliance and detrusor instability. Whilst these clinical and urodynamic parameters were associated statistically with voiding pressures, none proved specific in being able to identify men with voiding pressures in the high or low end of the range.
Relationship between detrusor function and residual urine in men undergoing prostatectomy.
Two hundred and fifty-three men undergoing prostatectomy were studied by means of urodynamic investigation to determine the relationship between the volume of residual urine and detrusor function. Increased volumes of residual urine were associated significantly with increasing age, low peak flow rate and high urethral resistance. However, weak voiding pressures were uncommon and did not correlate with increased residual volumes. Increased residual volumes also correlated significantly with a high resting detrusor pressure and a high detrusor pressure rise during the filling phase, but there was a wide scatter of the results for pressure rise and patients could not be classified into groups on the basis of this parameter. Whilst detrusor decompensation was not manifest by weak voiding pressures in patients with increased residual volumes, impairment of the ability of the detrusor to empty the infused cystometric capacity during the subsequent voiding study correlated with increased residual volumes. These data are consistent with theories relating bladder outflow obstruction to the development of increased volumes of residual urine in men undergoing prostatectomy.
Effects of catheter size on urodynamic measurements in men undergoing elective prostatectomy.
Thirty men undergoing prostatectomy for symptoms of bladder outflow obstruction and low measured maximum flow rates (20 before and 10 after operation) were studied by means of urodynamic investigation. Paired studies were performed on each patient using a large catheter assembly (4 and 10 F) and a small catheter assembly (epidural line, outside diameter 1.1 mm). The order in which the studies were performed was varied randomly. Detrusor pressure at maximum flow rate was significantly greater in the large catheter study (73 +/- 30 cm H2O) than in the small catheter study (65 +/- 27 cm H2O; P less than 0.003). The maximum flow rate was significantly smaller in the large catheter study (8.9 +/- 9.5 ml/s) than in the small catheter study (12 +/- 7 ml/s; P less than 0.001). The increase in detrusor pressure at maximum flow that was noted during the large catheter study was confirmed in the 20 men who were studied before prostatectomy (mean increase 11 +/- 11 cm H2O; P less than 0.001) but no difference was found between the two methods in the 10 men studied after prostatectomy (50 +/- 19 cm H2O and 49 +/- 15 cm H2O). Using a large catheter assembly to perform urodynamic investigations has the advantage that repeated studies can be performed without recatheterisation, but it has the disadvantage of producing a small increase in detrusor pressure at maximum flow in men with symptoms of bladder outflow obstruction. Few errors in diagnosis should result, however, if laboratories using such catheters are aware of this effect and establish their own limit of normal for voiding pressures.
Immunological assessment of renal cancer patients as evaluated by the lymphocyte adherence inhibition test.
The lymphocyte adherence inhibition test was used to evaluate tumor immunity toward 2 types of soluble renal cancer antigens extracted from 3 different renal cancer specimens. These extractions were accomplished with either 3 molar potassium chloride or 2.5 per cent butanol, and were tested in 23 patients with renal cancer, 8 with benign renal disease and 9 with bladder cancer. In 62 tests of lymphocyte adherence inhibition reactivities toward 3 molar potassium chloride in renal cancer patients the mean value of lymphocyte adherence inhibition reactivity (32.7 +/- 15.4 per cent) was significantly greater compared to that observed in 20 examinations in patients with benign renal disease (17.6 +/- 9.4 per cent, p less than 0.001) and 24 tests in bladder cancer patients (15.4 +/- 4.4 per cent, p less than 0.001). With a lymphocyte adherence inhibition index of greater than 20 per cent as a positive response, there were 50 true positive findings (81 per cent) in the renal cancer group, while the combined benign renal disease and bladder tumor groups had 34 true negative responses (77 per cent). With the butanol extract the mean lymphocyte adherence inhibition reactivity of the 62 tests done on renal cancer patients (38.9 +/- 10.8 per cent) was significantly greater than either control group (7.1 +/- 6.2 per cent, p less than 0.001 for benign renal disease and 5.9 +/- 2.6 per cent, p less than 0.001 for bladder tumor). Moreover, of 62 tests done on renal cancer patients 59 (95 per cent) had true positive responses, while 43 of the 44 tests (98 per cent) in the combined control group showed true negative findings. These results suggest that immune responses in renal cancer can be assessed with the lymphocyte adherence inhibition test, and they may be useful in the diagnosis and management of renal cancer patients.
Chronic retention of urine. The relationship between upper tract dilatation and bladder pressure.
Twenty-five men with chronic retention of urine were studied in order to investigate the relationship between upper tract dilatation and bladder pressure. Each underwent assessment of upper tract dilatation and urodynamic investigation before bladder drainage. Patients were reassessed 3 or more months after operation. Residual urine and detrusor contraction pressure decreased significantly after operation (P less than 0.0001:P less than 0.01). A significant increase in effective cystometric capacity and a significant decrease in pressure rise during filling led to an improvement in compliance. At pre-operative assessment, patients with upper tract dilatation had a significantly greater resting bladder pressure (P less than 0.05), end filling pressure (P less than 0.002) and pressure rise during filling (P less than 0.02) than those without upper tract dilatation. In addition, statistically significant correlations were found between serum creatinine and end filling pressure (P less than 0.05) and between upper tract dilatation and both high end filling pressure (greater than 25 cm H2O) and high pressure rise during filling (greater than 15 cm H2O: both P less than 0.05). Whilst high end filling pressure and high pressure rise during filling were found to be closely associated with upper tract dilatation (sensitivity 93 and 100%), there was a high false positive rate (specificity 64 and 45%). Furthermore, statistical analysis demonstrated that these data had a continuous though skewed distribution, suggesting that it is not possible to make a clear distinction between high and low pressure chronic retention.
Comparison of long-term monitoring and standard cystometry in chronic retention of urine.
Twenty-eight men with chronic retention of urine were investigated by means of a standard medium fill cystometrogram and by long-term monitoring of bladder pressure whilst the bladder filled naturally. Effective cystometric capacity was greater in each patient during standard cystometry (297 +/- 180 ml) than during long-term monitoring (99 +/- 100 ml; P less than 0.002). The incidence of detrusor instability was also greater during long-term monitoring than during standard cystometry (P less than 0.01). During filling, the detrusor pressure increased significantly both in standard cystometry (27.9 +/- 22.8 cmH2O; P less than 0.002) and in long-term monitoring (4.9 +/- 6.5 cmH2O; P less than 0.002). The detrusor pressure rise during filling was significantly greater during the standard cystometrogram than during long-term monitoring (P less than 0.002). Even when the detrusor pressure rise was corrected to take account of the different cystometric capacities this difference persisted (P less than 0.05). High end filling pressures are common in men with chronic retention investigated by means of a standard cystometrogram but are not observed during long-term monitoring. Such high pressures are probably due to the unphysiological rates of filling and the large volumes of fluid instilled during standard cystometry.
Complications of ileal conduit diversion in adults with cancer followed up for at least five years.
A total of 111 adults with malignant disease of the bladder were studied to determine the long term complications of ileal conduit diversion. Each patient had survived at least five years (mean 10 years) after cystectomy. At final follow up the radiological appearance of one or both kidneys had deteriorated in 50 (47%) of 107 patients: deterioration worsened significantly (p less than 0.01) with increasing duration of follow up. Eighteen patients (16%) developed biochemical evidence of impaired renal function, of whom four died of complications of renal failure. Bilateral upper tract dilatation was noted in 30 patients (28%), and in 21 its cause was obscure. Ten patients formed renal stones, and an additional 12 required further operations on the conduit or stoma. Despite the age of patients with bladder cancer and the poor prognosis of those with invasive tumours clinically important side effects were observed in a significant proportion of the long term survivors. Further efforts to determine the aetiology of upper tract dilatation in patients with an ileal conduit diversion are justified.
Epidermal-growth-factor receptors in human bladder cancer: comparison of invasive and superficial tumours.
The presence of epidermal-growth-factor (EGF) receptors in normal and neoplastic human urothelium was studied in 12 control patients and in 48 patients with transitional cell carcinoma of the bladder, 24 with invasive (pT3) and 24 with superficial tumours (9 pT1, 15 pTa). EGF receptors were identified on frozen sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the EGF receptor. Significantly more invasive tumours (21 of 24) than superficial (7 of 24) were stained positively for the EGF receptor (X2 = 14.49; p less than 0.001). Significantly more poorly differentiated tumours (18 of 21) than moderately differentiated tumours (10 of 27) were EGF-receptor positive (X2 = 9.6; p less than 0.01). No control sample stained positively for the EGF receptor. These findings suggest that the presence of a high intensity of staining for the EGF receptor in human bladder tumours is associated with poor differentiation and with invasion.
Electrically evoked activity in the human external anal sphincter.
Following electrical stimulation of perianal skin, short latency evoked electromyographic (EMG) responses from the external and sphincter have been interpreted as the electrophysiological correlate of the anal reflex. Delayed responses in patients with idiopathic faecal incontinence have been interpreted as evidence for denervation of the external anal sphincter. Electrically evoked responses were studied in normal subjects, either before and during spinal anaesthesia (n = 8), or before and during competitive neuromuscular blockade (n = 4), instituted for operative purposes. Short latency responses persisted unchanged in either latency or duration during spinal anaesthesia whereas long latency responses were completely abolished. Both short and long latency responses were abolished during competitive neuromuscular blockade. Short latency responses are not spinal reflex in nature, but due to stimulus activation of alpha-motoneuronal terminal branches. Delayed responses in incontinent patients cannot be interpreted as evidence for pudendal neuropathy. Long latency (i.e. greater than 40 ms) responses demand a functional sacral spinal cord and represent the true anal reflex. Their wide range of latency in normal subjects suggests this measurement will be of little use in confirming the presence or absence of pudendal neuropathy, and that other measures of neuropathy may be more appropriate.
Comparison of dynamic computed tomography, diuresis renography and DTPA parenchymal transit time in the assessment of dilatation of the upper urinary tract.
Three methods of assessment of upper urinary tract dilatation were compared prospectively. Forty-eight dilated renal units (35 patients) were studied, the majority being idiopathic pelvic hydronephrosis (69%). Dynamic computed tomography (CT) involves rapid sequence CT after injection of contrast medium. The maximum enhancement of a medullary region of interest (MMR) and its rate of enhancement (SMS) were derived from dynamic CT. Dynamic CT was compared with diuresis probe renography and measurement of parenchymal transit time (PTT) from DTPA imaging. The MMR (70.1 +/- 10.6 HU) and SMS (2.0 +/- 0.5 HU/s) in controls were significantly greater than in patients with upper tract dilatation (52.8 +/- 18.5 and 1.43 +/- 0.85 HU/s; both P less than 0.001). A significant association was observed between impairment of renal function in patients with upper tract dilatation and a low SMS and MMR (P less than 0.01). Statistically significant agreement was observed between the results of diuresis renography and PTT (P less than 0.025). However, no significant agreement was found when the results of dynamic CT were compared with either diuresis renography or with PTT. Dynamic CT as performed in the present study has no useful contribution to make in the diagnosis of patients with dilatation of the upper urinary tract.