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D E Neal

Publications and source records attributed to D E Neal.

At least 163 records · Page 9Linked to original sources
PubMed1994

Increased mdr1 gene transcript levels in high-grade carcinoma of the bladder determined by quantitative PCR-based assay.

Overexpression of the multidrug resistance (mdr1) gene has been implicated in resistance to a number of the chemotherapeutic agents currently used in the treatment of bladder cancer (doxorubicin, vincristine and epirubicin). We report the development and validation of a quantitative assay for the determination of mdr1 gene transcript levels based on reverse transcription and the polymerase chain reaction (PCR), sensitive to less than 2-fold variations in transcript levels. Using these techniques, mdr1 mRNA levels were investigated in 32 primary untreated transitional cell carcinomas of the bladder. mdr1 mRNA was detected in all samples, with levels varying between individual tumours over a 63-fold range. These variations were not associated with the proliferative status of the tumour. mdr1 mRNA levels were significantly higher in poorly differentiated high-grade (G3) tumours than in well- and moderately differentiated low-grade (G1 and G2) tumours (P = 0.0057). The results suggest that this relationship may extend to mdr1 mRNA levels being an indicator of poor prognosis, as anticipated on the basis of the observed relationship to tumour stage and grade. No evidence was found to implicate mdr1 mRNA levels as a predictor of tumour recurrence or progression. Given that mdr1 mRNA levels are increased in a proportion of high-grade bladder tumours that are routinely subjected to chemotherapy, we discuss the possibility that mdr1 mRNA levels may be clinically significant as determinants of chemotherapeutic response and outcome in bladder cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Endometriosis manifesting as a urachal tumor.

Endometriosis of abdominal wall scars is rare, especially in the postmenopausal woman. However, it must be considered as a possible cause of any abdominal wall mass in a woman who has had previous pelvic surgery and who is of reproductive age or taking exogenous hormones.

Abdomen↗
PubMed1994

Continent urinary diversion using the Mitrofanoff principle.

OBJECTIVE: To review the clinical and symptomatic outcome of patients undergoing cystectomy and continent urinary diversion using the Mitrofanoff principle. PATIENTS AND METHODS: There were seven men and five women (median age 62 +/- 21 years: range 21-79). The underlying diagnoses were: bladder carcinoma (8), neuropathic bladder disease (1), bladder exstrophy (1), tuberculosis (1) and interstitial cystitis (1). An ileo-caecal segment was used for construction of the reservoir. The appendix was used as a catheterizable conduit in 11 patients and a narrowed ileal tube in one patient. Symptomatic outcome was assessed by using a modified Visick grading. The median follow-up period was 15 +/- 10 months (range 6-39). RESULTS: The median hospital stay was 22 days. There were no post-operative deaths, but major post-operative complications developed in three patients and included intra-abdominal lymphocele (1), intra-abdominal abscess formation (1) and prolonged ileus (1). In the late post-operative period (> 30 days), four patients developed stenosis of the mucocutaneous junction and required dilatation. The overall symptomatic outcome was satisfactory in 11 patients. There were no deaths in the peri-operative period and none of the patients has since required revision. Urinary continence was achieved in all 12 patients during the day. One patient reported minimal, occasional leakage at nights. The median catheterization interval was 4 +/- 1 hours during the day (range 3-5) and 7 +/- 1 hours at night (range 6-9). CONCLUSION: Our experience with the Mitrofanoff procedure has been limited to a small number of patients. Despite this, the clinical outcome of the procedure was satisfactory. The procedure potentially offers an effective continence mechanism with acceptable post-operative morbidity.

Adult↗
PubMed1994

Written consent about sexual function in men undergoing transurethral prostatectomy.

OBJECTIVE: To review the written recording of consent about possible sexual dysfunction after transurethral resection of the prostate (TURP), and the incidence of sexual dysfunction in sexually active men after TURP, from a large scale audit of transurethral prostatectomy held in 12 hospital sites in the Northern Region. PATIENTS AND METHODS: Over an 8-month period data were collected from 12 separate hospital sites within the Northern Region by two independent nurse co-ordinators who travelled to each of the sites. Information was gathered from medical records, operation lists and theatre books using a standard proforma. The Nottingham Health Profile (NHP) was used as a quality of life instrument in a subgroup of patients who were asked about sexual function before and after operation. RESULTS: Advice about retrograde ejaculation was recorded infrequently, with only 30% of case notes including a statement about this (inter-site variations 0-78%). The mean age of patients in whom a written record was made was lower (70 [0.44 SEM] years) than those in whom there was no recording (72 [0.25] years; P < 0.001), but marital status did not appear to be a significant factor. No significant differences in NHP were found comparing men who did or who did not have written evidence about consent regarding retrograde ejaculation. In addition, in a subset of men who had been asked pre-operatively about sexual function, no significant differences were found in overall NHP measurements in those who did or who did not develop retrograde ejaculation. In men who were sexually active before operation, the incidence of major sexual problems, impotence and retrograde ejaculation were 12%, 11% and 24% respectively. CONCLUSION: The incidence of sexual dysfunction following TURP in this audit concurred with previously reported studies (4-40%), but despite this most urologists in our audit were not recording that they had advised their patients about this possible outcome.

Aged↗
PubMed1994

c-jun oncogene expression in transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To investigate c-jun oncoprotein expression in transitional cell carcinomas (TCCs) of the urinary bladder and to determine its relationship to tumour grade and stage, and to the expression of epidermal growth factor receptor (EGFR), c-erbB-2 and p53 oncoproteins. MATERIALS AND METHODS: The expression of c-jun was studied using immunohistochemistry in a series of 48 TCCs of known EGFR, c-erbB-2 and p53 status. RESULTS: Forty-four of 48 (92%) tumours showed c-jun specific nuclear immunoreactivity of variable intensity. The intensity of c-jun immunostaining was significantly related to tumour stage (P = 0.009) and EGFR status (P = 0.01). There was no correlation between c-jun oncoprotein expression and c-erbB-2 or p53 immunoreactivity. c-jun expression was not related to clinical outcome in terms of patient survival or rate of tumour recurrence. CONCLUSION: The c-jun oncoprotein is expressed in the majority of TCCs of the urinary bladder. There is a positive association between intense c-jun immunoreactivity and muscle invasive growth, and EGFR positivity in TCCs.

Aged↗
PubMed1994

Bladder function in healthy volunteers: ambulatory monitoring and conventional urodynamic studies.

OBJECTIVE: To obtain data on conventional artificial filling cystometry and ambulatory monitoring in healthy asymptomatic control populations. SUBJECTS AND METHODS: Seventeen healthy volunteers were assessed by means of artificial filling cystometry (CMG), filling at rates of 50 ml/min (CMG 50) and 100 ml/min (CMG 100), and ambulatory monitoring (AM). RESULTS: Significant differences were found between AM and CMG with respect to: the pressure rise on filling (P < 0.02), voided volumes (P < 0.01) and maximum detrusor pressure on micturition (P < 0.01). Detrusor instability was found in 38% of volunteers on AM, in 17% on CMG 50, but in none on CMG 100. CONCLUSION: A range of baseline urodynamic values has been established which could provide the basis for future studies of ambulatory monitoring.

Adult↗
PubMed1994

Frequency of H-ras mutations in human bladder cancer detected by direct sequencing.

OBJECTIVE: To determine the frequency of mutations of the H-ras gene in transitional cell carcinomas of the human urinary bladder using direct DNA sequencing based on the polymerase chain reaction (PCR) method and to compare the results with those of other methods. In addition, the relationship of the mutation frequency to tumour stage and grade was examined. PATIENTS AND METHODS: Bladder tumour samples, taken by cystoscopic resection from 50 patients with newly diagnosed transitional cell carcinoma of the urinary bladder, were analysed by PCR-based direct DNA sequencing for point mutations in the H-ras gene at codon 12. RESULTS: Point mutations were found in 9 of 50 tumours examined (18%). The most frequent mutation (8/9) was a G to T transversion converting GGC to GTC, which would result in a glycine to valine substitution. The remaining mutations was a G to A transition altering GGC to GAC, producing a glycine to aspartic acid substitution, which has not previously been reported in bladder cancer. In all tumour samples examined the wild-type allele (GGC) was also evident. Variation in the proportion of wild-type to mutated sequence was found within tumour samples. No relationship between mutations and tumor grade and stage was apparent. CONCLUSION: The frequency of H-ras mutations detected in this first large scale study using the highly sensitive and rapid PCR-based sequencing method was comparable to that reported by earlier studies with the nude mouse tumorigenesis variation of the 3T3 transfection assay. H-ras mutations can be early events in the development and progression of a significant proportion of human bladder cancer cases.

Base Sequence↗
PubMed1994

Abnormalities in p53 and DNA content in transitional cell carcinoma of the bladder.

OBJECTIVE: To determine if transitional cell tumours of the bladder which contain mutations in the p53 gene have alterations in their DNA content. MATERIALS AND METHODS: In 33 transitional cell tumours of the bladder, DNA content was determined by flow cytometry and compared with expression of mutant p53 as assessed by immuno-histochemistry. RESULTS: Abnormal DNA content was associated with increased staining for p53 (P < 0.05), high tumour stage (P < 0.001) and increased histological grade (P < 0.01). Although positive staining for p53 was frequently associated with abnormal DNA content, a significant number of non-diploid tumours stained negatively for mutant p53. CONCLUSION: These data demonstrate that increased staining for p53 is associated with abnormalities in DNA content suggesting that mutation of the p53 gene is associated with an increased rate of chromosomal abnormalities and an increased rate of cell proliferation.

Carcinoma, Transitional Cell↗
PubMed1994

P53 expression, ploidy and progression in pT1 transitional cell carcinoma of the bladder.

OBJECTIVE: To investigate a potential role for overexpression of the p53 protein in the identification of pT1 bladder tumours destined to progress. PATIENTS AND METHODS: The protein expression of the tumour suppressor gene p53, nuclear ploidy and tumour grade were studied in 25 patients with pT1 bladder tumours. Follow-up data was available for 21 tumours over a 10 year period. p53 expression was determined by immuno-histochemistry on paraffin embedded sections and flow cytometry was performed on cell suspensions derived from the same blocks. RESULTS: Ten of 21 (48%) tumours progressed to muscle invasive disease. Nuclear staining for the protein was seen in 16 (64%) tumours and of these nine (56%) progressed. All tumours with abnormal DNA content and all high grade tumours demonstrated overexpression of p53. Significantly more patients with high levels of p53 expression (> 10% nuclear staining) progressed compared with tumours with less than 10% of nuclei staining (P = 0.007). However, grade was the most specific predictor of progression (100%), with all grade 3 tumours progressing and grade was also the most significant prognostic indicator in terms of survival (P = 0.025). CONCLUSION: Tumour grade is likely to remain as the most useful aid to management decisions in pT1 bladder tumours.

Aged↗
PubMed1994

Deaths and complications following prostatectomy in 1400 men in the northern region of England. Northern Regional Prostate Audit Group.

OBJECTIVE: To determine the degree of variation in mortality and major morbidity following transurethral resection of the prostate (TURP), and to assess intersite variation for mortality and morbidity over 12 sites within the Northern Region. Further, to determine whether the previously observed effects on morbidity of unit size, patient through-put and emergency admission were borne out in contemporary urological practice in the Northern Region. PATIENTS AND METHODS: For an 8 month period, 1 April 1991-31 November 1991, an independent audit of TURP was performed on 12 different hospital sites throughout the Northern Region. A constant data set was designed which was collected on each patient before and 3 months after operation by two independent clinical co-ordinators who travelled to each of the sites. All case notes were reviewed at 3 months after operation by the co-ordinators using a standard proforma, rather than depending upon self reporting by medical staff. Data on factors potentially affecting mortality and morbidity were collected, including emergency admission, diagnosis of prostate cancer, American Society of Anesthesiologists' co-morbidity scores, and age and differences in throughput in the 12 sites. The effect of through-put or 'volume' on mortality and morbidity was assessed by comparing morbidity and the number of cases performed. RESULTS: The early mean death rate was 13 of 1396 patients (0.9%), with an inter-site variation ranging from 0% to 3.8%. A mean of 2.0% of men were returned to theatre after TURP, 2.4% of patients received a blood transfusion (> 2 units) after operation, and 8.0% of patients developed post-operative sepsis; these complications varied sixfold, sevenfold and 17-fold across the different sites respectively. Those units performing < or = 100 operations over the audit period (equivalent to < 150 operation per year) had a significantly increased rate of deaths and complications which was not related to population differences, though some low volume units had good results. Elderly men who were admitted as emergencies or with prostate cancer were particularly vulnerable to complications. CONCLUSIONS: The overall early mortality rate after TURP for benign prostatic hyperplasia across the Region compares well with other reported large series. The significant variation in morbidity rates found in this study suggests that careful attention needs to be paid by Urologists, Purchasers and Providers to morbidity rates after prostatectomy.

Age Factors↗
PubMed1994

Androgen and oestrogen responsiveness of stromal cells derived from the human hyperplastic prostate: oestrogen regulation of the androgen receptor.

Stromal cells derived from collagenase-digested benign hyperplastic adult prostates were isolated and grown in culture. Androgen and oestrogen receptor status were determined and growth in response to mibolerone (a synthetic androgen) and oestradiol-17 beta was measured. In addition, the ability of oestrogens to regulate the androgen receptor in stromal cells was investigated. [3H]Thymidine incorporation into DNA was stimulated by mibolerone in primary and secondary cultures, but sensitivity was lost with subsequent passages. Androgen stimulation of [3H]thymidine incorporation was consistently inhibited by the anti-androgen cyproterone acetate. Oestradiol-17 beta also stimulated [3H]thymidine incorporation into DNA, and this effect was inhibited by the anti-oestrogen tamoxifen. Sensitivity to oestradiol was lost with subsequent passages. A combination of mibolerone and oestradiol was not synergistic in increasing [3H]thymidine incorporation into DNA, but maximal stimulation occurred at 100-fold lower concentrations of mibolerone and oestradiol when the two hormones were applied in combination. Specific high-affinity [3H]mibolerone- and [3H]oestradiol-binding sites were demonstrated by radioligand binding in intact cells. The affinity for oestradiol binding to its receptor exceeded that quantified for mibolerone binding to the androgen receptor, whilst the number of oestradiol-binding sites was approximately tenfold less than that quantified for mibolerone. Treatment with oestradiol down-regulated the number of [3H]mibolerone binding sites 1.7-fold (P < 0.005) as early as day 2 after oestradiol treatment. In conclusion, we successfully cultured stromal cells derived from hyperplastic prostates which retained sensitivity to androgen and oestrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1994

Surgical trainees as anatomy demonstrators.

The aim was to determine whether anatomy demonstrators had increased first-time pass rates in the ABS part of FRCS compared with other candidates and to determine what anatomy departments will do if changes resulting from the Calman/Bottomley report on medical training lead to a decrease in the number of surgical trainees who wish to work as anatomy demonstrators. A questionnaire was sent to departments of anatomy in the UK and Ireland regarding: numbers of demonstrators, career background, funding, employment terms, training and first-time pass rate in ABS. Twenty-six of 32 departments responded, 89 per cent of 206 anatomy demonstrators were surgical trainees. Full-time posts were largely funded by universities and part-time posts largely by private hospitals. Nine departments had a total of 40 posts integrated with local surgical rotations, but only five provided ABS courses in all subjects. For the period 1990-1993 the first-time pass rate of demonstrators in ABS was 75 per cent, compared with the overall pass rate of 37 per cent for UK candidates at The Royal College of Surgeons of candidates at The Royal College of Surgeons of England. Changes brought in by the Calman/Bottomley report may result in fewer surgical trainees working as anatomy demonstrators. This will have major consequences for undergraduate anatomy courses. Anatomy departments will have to develop innovative methods of teaching which do not rely on surgical trainees. We believe that surgical trainees require and desire training in the basic sciences, which include anatomy, physiology, biochemistry and pathology. These objectives could be met by medical schools offering comprehensive taught courses in basic sciences in conjunction with four-month contracts as anatomy demonstrators.

Anatomy↗
PubMed1993

Changes in seminal fluid zinc during experimental prostatitis.

Patients with prostatitis have been found to have decreased prostatic fluid zinc (PF Zn). It is unclear whether changes of prostatitis are due to an inherent lack of Zn in some patients or whether the changes, including reduced PF Zn, are due to the infectious process itself. Six nonhuman primates were infected with 1 x 10(5) E. coli JR340, a clinical isolate known to cause prostatitis in the monkey. After infection, seminal fluid for culture and zinc assay was obtained by electroejaculation. Zinc was measured by colorimetric analysis. Blood counts, quantitative renal scans and urine cultures were also monitored. The animals were followed for 4 weeks and then sacrificed. The histopathology showed resolving prostatitis and fibrosis. Zinc levels dropped with acute infection, and variably recovered as the infection cleared. Controls showed slight variability with respect to PF Zn. It appears that PF Zn decreases as a result of the infectious process.

Animals↗
PubMed1993

Absence of long-term gonadotoxicity in primates receiving extracorporeal shock wave application.

Extracorporeal shock wave lithotripsy (SWL) is becoming popular in the management of lower ureteral calculi; however, the quantity of data on its potential gonadotoxic effects are limited. Eight nonhuman primates had baseline measurements of testicular volume, semen analysis, serum testosterone and FSH assays, and DNA flow cytometric analysis of testicular aspirates. The anesthetized primates were lowered into a Dornier XL-1 lithotripter and at a 20 kV power setting had various numbers of shocks (0, 500, 1500) directed at each testis. Sequential studies were done at 6-week intervals for 9 months. The control group showed no significant change in any measure. Semen analysis, testosterone, and FSH results were variable and without statistically significant differences. There were changes in the DNA histograms, with the tetraploid (4N) group of cells being the most sensitive. All changes caused by SWL application returned to baseline by 9 months. Data from this primate study document no apparent long-term male gonadotoxicity from SWL, but the authors suggest measures to protect the testis during clinical use.

Animals↗
PubMed1993

Polyorchism.

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Adult↗