40 results on '"Neal, DE"'
Search Results
2. Can we accurately identify men with low risk prostate cancer?
- Author
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Neal DE
- Subjects
- Aged, Biopsy, Needle, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Staging, Predictive Value of Tests, Prognosis, Prostatic Neoplasms diagnosis, Prostatic Neoplasms mortality, Risk Assessment, Sensitivity and Specificity, Survival Analysis, Mass Screening methods, Neoplasm Invasiveness pathology, Prostate-Specific Antigen blood, Prostatic Neoplasms pathology
- Published
- 2008
- Full Text
- View/download PDF
3. The bladder does not appear to have a dynamic secreted continuous mucous gel layer.
- Author
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N'Dow J, Jordan N, Robson CN, Neal DE, and Pearson JP
- Subjects
- Adult, Amino Acids analysis, Animals, Biopsy, Female, Gels, Humans, Ileum pathology, Intestinal Mucosa pathology, Male, Middle Aged, Postoperative Complications urine, Reference Values, Swine, Urinary Bladder chemistry, Mucins urine, Mucus metabolism, Urinary Bladder pathology, Urinary Diversion, Urothelium metabolism
- Abstract
Purpose: We determined whether the nature of any protective barrier in the bladder is composed of a secreted mucous gel layer., Materials and Methods: We collected 24-hour urine samples for analysis from 8 healthy 22 to 49-year-old volunteers and 5, 19 to 59-year-old patients treated with bladder reconstruction, in addition to scrapings from 100 freshly slaughtered pig bladders. Samples were subjected to homogenization, dialysis, freeze-drying, papain digestion, gel chromatography, equilibrium density gradient centrifugation, periodic acid-Schiff assay and amino acid analysis. Normal human bladder, pig bladder, normal ileum and transposed intestinal segments were studied for the presence of a mucous layer using a new method of histological analysis., Results: Mucin content in normal urine is 2.7 mg/24 hours, meaning that less than 0.6% of nondialyzable material in normal urine is mucin. The mucin content of urine from reconstructed bladders amounted to 86 mg/24 hours (5.2% of nondialyzable material). We observed that glycosaminoglycans accounted for 41% of the peak total elution volume of PAS positive material in normal urine. Mucin estimation in urine can be grossly overestimated if contaminating glycoconjugates are not removed. Biochemical analysis of material scraped off the pig bladder surface demonstrated that the maximum thickness of a continuous layer that could be achieved was 13.6 mum. While we could visualize an obvious mucous layer on control ileal samples and biopsies of transposed ileal segments from patients with bladder reconstruction, we were unable to note a distinct, measurable mucous layer lining the bladder surface in humans or pigs., Conclusions: Mucin levels in normal human and pig urine would be enough for slow turnover of a thin barrier but the large increase in mucin in the urine of patients with transposed intestinal segments demonstrates that any layer in normal bladder is much different than that lining the transposed intestinal segment. The most likely constituents of this barrier are membrane bound rather than secreted mucins along with the proteoglycan components of the glycocalix.
- Published
- 2005
- Full Text
- View/download PDF
4. Pentosan polysulfate sodium therapy for men with chronic pelvic pain syndrome: a multicenter, randomized, placebo controlled study.
- Author
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Nickel JC, Forrest JB, Tomera K, Hernandez-Graulau J, Moon TD, Schaeffer AJ, Krieger JN, Zeitlin SI, Evans RJ, Lama DJ, Neal DE Jr, and Sant GR
- Subjects
- Adolescent, Adult, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Chronic Disease, Diarrhea chemically induced, Double-Blind Method, Follow-Up Studies, Headache chemically induced, Humans, Male, Middle Aged, Nausea chemically induced, Pain Measurement, Pentosan Sulfuric Polyester adverse effects, Placebos, Quality of Life, Severity of Illness Index, Treatment Outcome, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Pelvic Pain drug therapy, Pentosan Sulfuric Polyester therapeutic use, Prostatitis drug therapy
- Abstract
Purpose: We evaluated the efficacy and tolerability of pentosan polysulfate sodium (PPS) for the treatment of men with chronic pelvic pain syndrome (CPPS), National Institutes of Health (NIH) category III., Materials and Methods: In a 16-week double-blind study 100 men with a clinical diagnosis of CPPS were randomized to receive 300 mg PPS or placebo 3 times daily. Clinical Global Improvement (CGI) was the primary outcome measure. Additional outcome measures were the NIH-Chronic Prostatitis Symptom Index (CPSI), Subjective Global Assessment and Symptom Severity Index assessment tools., Results: Significantly more patients receiving PPS experienced moderate to marked improvement based on CGI assessment (18 or 37% vs 8 or 18%, p = 0.04). However, mean CGI scores were not significantly different between the PPS group (1.0) and placebo groups (1.0 vs 0.6, p = 0.107). All NIH-CPSI domains suggested a positive effect for PPS and for total NIH-CPSI the difference approached statistical significance (-5.9 or 22% vs -3.2 or 12%, p = 0.068). The PPS group showed significantly greater improvement in NIH-CPSI quality of life domain scores than the placebo group (-2.0 or 22% vs -1.0 or 12%, p = 0.031). Of patients receiving PPS 67% and 80% of those receiving placebo completed the 16-week study. Diarrhea, nausea and headache were the most common adverse events., Conclusions: Pentosan polysulfate (900 mg daily) was more likely than placebo to provide relief for CPPS symptoms.
- Published
- 2005
- Full Text
- View/download PDF
5. Characterization of Escherichia coli strains causing urinary tract infections in patients with transposed intestinal segments.
- Author
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Keegan SJ, Graham C, Neal DE, Blum-Oehler G, N'Dow J, Pearson JP, and Gally DL
- Subjects
- Adult, Aged, Bacteriuria microbiology, Carrier State microbiology, Electrophoresis, Gel, Pulsed-Field, Escherichia coli genetics, Feces microbiology, Female, Genotype, Humans, Male, Middle Aged, Polymerase Chain Reaction, Recurrence, Virulence Factors genetics, Escherichia coli classification, Escherichia coli Infections microbiology, Urinary Reservoirs, Continent microbiology, Urinary Tract Infections microbiology
- Abstract
Purpose: Transposition of intestinal segments into the urinary tract predisposes to urinary tract infections. We characterized bacterial infections in these patients and examined the virulence genotype and persistence of Escherichia coli isolates., Materials and Methods: We followed 26 patients who underwent bladder reconstructive surgery using transposed intestinal segments. E. coli strains isolated from the urine of these patients were genotyped for established virulence determinants and the frequency of carriage was compared with E. coli strains isolated from community acquired urinary infections and the fecal flora of anonymous volunteers. A longitudinal study of E. coli strains in 9 patients was also done using pulsed field gel electrophoresis., Results: E. coli was the most frequently isolated organism, responsible for 59% (62 of 105) of monobacterial infections. Other bacteria isolated included Klebsiella species, Proteus species and Enterococcus faecalis. Community acquired E. coli strains were more likely to carry multiple determinants for particular adhesins (P and S fimbriae) and toxins (alpha-hemolysin and cytotoxic necrotizing factor) than fecal strains. Carriage frequency for bladder reconstruction strains was intermediary and not significantly different. The key finding was that E. coli strains persisted for prolonged periods, including 2 years in certain patients, often despite various antimicrobial treatments., Conclusions: This study highlights that further steps must be taken to prevent and treat urinary tract infections in this susceptible group. Particular attention should be given to the treatment of persistent infections.
- Published
- 2003
- Full Text
- View/download PDF
6. Transurethral prostate resection, noncontact laser therapy or conservative management in men with symptoms of benign prostatic enlargement? An economic evaluation.
- Author
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Noble SM, Coast J, Brookes S, Neal DE, Abrams P, Peters TJ, and Donovan JL
- Subjects
- Adult, Aged, Cost-Benefit Analysis, Health Resources statistics & numerical data, Humans, Male, Middle Aged, Prostatic Hyperplasia surgery, Quality-Adjusted Life Years, Laser Therapy economics, Prostatic Hyperplasia economics, Transurethral Resection of Prostate economics
- Abstract
Purpose: We evaluated the cost-effectiveness of noncontact laser therapy compared with transurethral prostate resection and conservative treatment in men with symptoms associated with benign prostatic enlargement., Materials and Methods: A total of 340 men with uncomplicated lower urinary tract symptoms participated in a large multicenter pragmatic randomized trial called the CLasP (Conservative management, Laser therapy, transurethral resection of the Prostate) study. Costs to the United Kingdom National Health Service and patients were determined from the time of randomization to the 7.5-month followup. Incremental cost-effectiveness ratios using conservative management as the base case were calculated for certain trial outcomes, including International Prostate Symptom Score (I-PSS), I-PSS quality of life score, maximum urinary flow, post-void residual urine volume, quality adjusted life-years and a composite measure of success based on I-PSS and maximum urinary flow. One-way sensitivity analysis of the basic costs and incremental cost-effectiveness ratios were done from the NHS viewpoint., Results: Mean costs per patient were greatest for noncontact laser therapy and least for conservative management. The incremental cost-effectiveness ratios showed that transurethral prostate resection was more cost-effective than noncontact laser treatment for all primary trial outcomes. The incremental cost-effectiveness ratios of transurethral prostate resection compared with conservative management were pound 81 per unit decrease in the I-PSS score and pound 1,338 per additional successful case per 100 patients. Sensitivity analysis showed that the initial results were robust., Conclusions: Noncontact laser was the mostly costly treatment option. Transurethral prostate resection was more cost-effective than noncontact laser therapy in terms of symptomatic improvement. In men wishing to delay treatment conservative treatment appears to provide a cost-effective alternative in the short term.
- Published
- 2002
- Full Text
- View/download PDF
7. Treatment of carcinoma in situ with intravesical bacillus Calmette-Guerin without maintenance.
- Author
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Griffiths TR, Charlton M, Neal DE, and Powell PH
- Subjects
- Administration, Intravesical, Aged, Carcinoma in Situ mortality, Carcinoma, Transitional Cell drug therapy, Carcinoma, Transitional Cell mortality, Disease Progression, Female, Humans, Male, Prognosis, Survival Rate, Urinary Bladder Neoplasms mortality, Adjuvants, Immunologic administration & dosage, BCG Vaccine administration & dosage, Carcinoma in Situ drug therapy, Urinary Bladder Neoplasms drug therapy
- Abstract
Purpose: Data concerning the relative efficacy of intravesical bacillus Calmette-Guerin (BCG) on subgroups of carcinoma in situ of the bladder are limited. We report the outcome of primary carcinoma in situ and carcinoma in situ associated with Ta or T1 transitional cell carcinoma of the bladder treated with BCG., Materials and Methods: Between 1987 and 1997, 135 patients (median age 70 years) with biopsy proven bladder carcinoma in situ underwent a standard course of 6 BCG instillations. Patients were divided into group 1-23 patients with primary carcinoma in situ, group 2-37 with carcinoma in situ associated with Ta transitional cell carcinoma and group 3-75 with carcinoma in situ associated with T1 transitional cell carcinoma., Results: Median followup was 41 months. For groups 1 to 3, complete response rates at 3 months were 74% (17 of 23 cases), 70% (26 of 37) and 75% (56 of 75), respectively. The overall progression rates at 5 years were 20% (3 of 15 cases), 18% (4 of 22) and 49% (25 of 51). Cancer specific survival rates were 83% (10 of 12 patients), 86% (12 of 14) and 59% (17 of 29), and the numbers of patients alive with the bladder intact were 60% (9 of 15), 58% (11 of 19) and 30% (12 of 40). Patients in group 3 treated with BCG had progression significantly earlier than those in groups 1 and 2 (log-rank test p = 0.013). A complete response to BCG in group 3 patients significantly delayed time to progression (Cox regression p = 0.001) but did not reduce death from transitional cell carcinoma. Indeed, only 38% (8 of 21) of complete responders were alive with the bladder intact at 5 years., Conclusions: A single course of BCG is remarkably effective for primary carcinoma in situ and carcinoma in situ associated with Ta transitional cell carcinoma but is suboptimal in patients with carcinoma in situ associated with T1 transitional cell carcinoma. Better outcomes in each of the 3 groups may have occurred with maintenance BCG.
- Published
- 2002
8. Penile injury.
- Author
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Losanoff JE, Neal DE Jr, and Jones JW
- Subjects
- Adult, Humans, Male, Rupture, Penis injuries
- Published
- 2001
9. Transurethral prostatic resection or laser therapy for men with acute urinary retention: the ClasP randomized trial.
- Author
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Chacko KN, Donovan JL, Abrams P, Peters TJ, Brookes ST, Thorpe AC, Gujral S, Wright M, Kennedy LG, and Neal DE
- Subjects
- Acute Disease, Aged, Aged, 80 and over, Confidence Intervals, Follow-Up Studies, Humans, Male, Middle Aged, Neodymium, Odds Ratio, Sensitivity and Specificity, Treatment Outcome, Urinary Retention diagnosis, Laser Therapy methods, Quality of Life, Transurethral Resection of Prostate methods, Urinary Retention surgery
- Abstract
Purpose: Transurethral resection of the prostate is the standard operation for acute urinary retention, although laser prostatectomy is reportedly effective and safe. The ClasP (conservative management, laser, transurethral resection of the prostate) study compared transurethral prostatic resection and noncontact neodymium (Nd):YAG visual laser assisted prostatectomy for treatment of acute urinary retention., Materials and Methods: This study was a multicenter randomized controlled trial, analyses were by intention to treat and followup was at 7.5 months after randomization. Primary outcomes were treatment failure, and included International Prostate Symptom Score, International Prostate Symptom Score quality of life score, residual urine and flow rate. Secondary outcomes included complications, and duration of catheterization and hospitalization., Results: A total of 148 men were randomized to transurethral prostatic resection (74) and laser (74). There were fewer treatment failures after prostatic resection (p = 0.008) and fewer men after resection required secondary surgery for poor results (1 versus 7, p = 0.029). Maximum flow rates after transurethral prostatic resection were better than after laser (mean difference 4.4 ml. per second). Comparison of symptom and quality of life scores demonstrated that any clinically significant advantage for laser could be ruled out. Patients stayed a mean of 2 extra days in the hospital after resection. The duration of catheterization was greater after laser but significantly fewer major treatment complications were found with laser therapy., Conclusions: Transurethral prostatic resection was more effective, resulted in fewer failures than laser treatment and remains the procedure of choice for men with acute urinary retention.
- Published
- 2001
10. A crossover randomized trial of transcutaneous electrical nerve stimulation and oxybutynin in patients with detrusor instability.
- Author
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Soomro NA, Khadra MH, Robson W, and Neal DE
- Subjects
- Adult, Aged, Cross-Over Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Muscle Hypertonia complications, Patient Satisfaction, Probability, Reference Values, Treatment Outcome, Urination Disorders etiology, Urodynamics, Mandelic Acids administration & dosage, Muscle Hypertonia diagnosis, Muscle Hypertonia therapy, Muscle, Smooth physiopathology, Transcutaneous Electric Nerve Stimulation methods, Urination Disorders therapy
- Abstract
Purpose: Management of idiopathic detrusor instability is difficult in most patients mainly due to the lack of a complete understanding of the pathophysiology. Oxybutynin and transcutaneous electrical nerve stimulation have been used but to our knowledge no direct comparisons have been made., Materials and Methods: Patients with frequency, urgency, urge incontinence and proved detrusor instability were studied with urodynamics, quality of life instruments, and frequency and volume charts. Patients were randomized to transcutaneous electrical nerve stimulation or oxybutynin. After 6 weeks of treatment, they were reassessed and after a washout of 2 weeks, they were started on the second arm of treatment and reassessed 6 weeks later., Results: A total of 13 male and 30 female patients were studied. Functional capacity had increased and number of voids daily had decreased significantly compared with before treatment in both arms (p <0.005). There were significant improvements in symptom specific quality of life measures but no changes were found on the global Short Form 36 (SF-36) quality of life questionnaire. The volume to first desire to void and first unstable contraction had increased significantly with oxybutynin but not with transcutaneous electrical nerve stimulation. Of 23 patients 7 were stabilized with treatment, including 2 with oxybutynin only, 2 with either nerve stimulation or oxybutynin and the remaining 3 with only nerve stimulation. Total bladder capacity did not change significantly with either treatment but patients noticed side effects more commonly with oxybutynin., Conclusions: Both treatments clearly improved subjective parameters. However, only oxybutynin showed significant improvements in objective urodynamic parameters. Transcutaneous electrical nerve stimulation can be used in patients who cannot take oxybutynin. Further studies are needed to show the long-term efficacy and cost analyses of nerve stimulation.
- Published
- 2001
11. Reducing mucus production after urinary reconstruction: a prospective randomized trial.
- Author
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N'Dow J, Robson CN, Matthews JN, Neal DE, and Pearson JP
- Subjects
- Administration, Intravesical, Administration, Oral, Cross-Over Studies, Double-Blind Method, Humans, Ileum surgery, Mucins metabolism, Mucins urine, Mucus drug effects, Prospective Studies, Quality of Life, Surveys and Questionnaires, Viscosity drug effects, Acetylcysteine administration & dosage, Aspirin administration & dosage, Intestinal Mucosa metabolism, Mucus metabolism, Ranitidine administration & dosage, Urinary Bladder surgery, Urinary Diversion
- Abstract
Purpose: After transposition into the urinary tract, intestinal segments continue to produce mucus. We determine the effectiveness of muco-regulatory drugs, including N-acetylcysteine, aspirin and ranitidine, in reducing mucus secretion and urine viscosity in patients with transposed segments., Materials and Methods: Our trial was a prospective randomized, double-blind placebo controlled crossover study involving 12 patients who underwent ileal conduit and 31 who underwent bladder reconstruction. Each treatment lasted 3 weeks with a 2-week washout. Pretreatment and posttreatment 24-hour urine samples were analyzed for mucin and viscosity after papain digestion, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and periodic acid-Schiff assay. A disease specific questionnaire and SF-36 quality of life survey were completed., Results: According to the questionnaire, mucus production did not decrease with time in 67% of patients. Mucin comprised 3% of the total nondialyzable material in urine (65 mg./24-hour for ileal conduit and 60 mg./24-hour for bladder reconstruction). Analysis of questionnaires and laboratory results failed to demonstrate any benefit of taking muco-regulatory agents compared with placebo., Conclusions: The use of N-acetylcysteine, aspirin and ranitidine did not result in a reduction in mucin production, urine viscosity or improvement in quality of life.
- Published
- 2001
12. Urethral recurrence after radical radiotherapy for bladder cancer.
- Author
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Cresswell J, Roberts JT, and Neal DE
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Transitional Cell pathology, Carcinoma, Transitional Cell surgery, Cystectomy, Female, Humans, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Staging, Prognosis, Retrospective Studies, Urinary Bladder Neoplasms pathology, Urinary Bladder Neoplasms surgery, Urinary Diversion, Carcinoma, Transitional Cell radiotherapy, Neoplasm Recurrence, Local prevention & control, Urethral Neoplasms prevention & control, Urinary Bladder Neoplasms radiotherapy
- Abstract
Purpose: Following cystectomy for bladder cancer, orthotopic reconstruction may result in a decreased risk of urethral recurrence compared to cutaneous diversion. We evaluate the rate of urethral recurrence after radical external beam radiotherapy., Materials and Methods: We reviewed the records of 214 men who had received radical radiotherapy at a single center from 1990 to 1995. Patients treated with chemotherapy were excluded from study., Results: A total of 214 men (median age 69 years, range 39 to 86) underwent radical radiotherapy for cure. Tumor stages were T1 in 7%, T2 in 41%, T3 in 42% and T4a in 10% of the patients. Median followup was 32 months (range 1 month to 8.4 years) and 5-year survival rate was 30%. Urethral recurrence developed in 7 (3.2%) cases and was detected within 18 months (median 10 months, range 3 months to 5 years) of followup in 5. In 2 of these 7 cases recurrence developed in the prostatic urethra, and when these 2 cases were excluded from analysis the recurrence rate decreased to 2.3%. A total of 64 men completed 5-year followup, with a 4.7% rate of urethral recurrence (3.1% excluding prostatic urethral recurrence). Multifocal disease, bladder neck involvement, prostatic disease and cis were possible risk factors for urethral recurrence., Conclusions: The risk of urethral recurrence after radical radiotherapy for transitional cell carcinoma of the bladder is comparable with that reported after orthotopic reconstruction. It is not possible to exclude completely that men at higher risk were offered cystectomy, but the data are consistent with the suggestion that continued contact with urine may be protective.
- Published
- 2001
13. Serum keratinocyte growth factor measurement in patients with prostate cancer.
- Author
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Mehta PB, Robson CN, Neal DE, and Leung HY
- Subjects
- Aged, Enzyme-Linked Immunosorbent Assay, Fibroblast Growth Factor 10, Fibroblast Growth Factor 7, Humans, Keratinocytes, Male, Predictive Value of Tests, Prostate-Specific Antigen analysis, Prostatic Hyperplasia blood, Prostatic Neoplasms diagnosis, Sensitivity and Specificity, Biomarkers, Tumor blood, Fibroblast Growth Factors, Growth Substances blood, Prostatic Neoplasms blood
- Abstract
Purpose: Keratinocyte growth factor (KGF) is a stromally derived growth factor important in mediating androgen induced activities in benign prostatic hyperplasia (BPH) and prostate cancer. We assessed whether serum KGF could be used as a molecular marker in patients with prostate cancer., Materials and Methods: Using a modified double sandwich enzyme-linked immunosorbent assay, we measured serum KGF in 56 men with prostate cancer and 81 men with BPH. Comparative analyses were made with total serum prostate specific antigen (PSA), disease stage and clinical grade., Results: Following optimization, a sensitive and reproducible assay for serum KGF measurement was developed. Serum KGF levels tend to be higher in men with BPH compared to those with prostate cancer (1,242 and 828 pg./ml., respectively). A weak but significant linear relationship between PSA and KGF (p = 0.034) was found in patients with BPH. There was no association between KGF and tumor grade or stage but there was a strong positive linear relationship between PSA and KGF (p = 0.006, R(2) = 68.3%) in low grade tumors. In those men with serum PSA less than 10 ng./ml. KGF levels were significantly higher in BPH compared to prostate cancer cases (965 +/- 245 and 133 +/- 61.3 pg./ml., respectively, p = 0.0058). Using a KGF threshold range of 500 to 900 pg./ml., specificity for detecting BPH was 88% to 100% and the positive predictive value was 92% to 100%., Conclusions: We have optimized a reproducible and sensitive enzyme-linked immunosorbent assay system for the measurement of serum KGF. Overall KGF levels tend to be lower in patients with prostate cancer than with BPH. In patients with serum PSA less than 10 ng./ml. serum KGF levels were significantly higher in the BPH compared to the prostate cancer group. A large prospective study is indicated to assess the role of serum KGF measurement in patients with prostate cancer.
- Published
- 2000
14. Mucin gene expression in human urothelium and in intestinal segments transposed into the urinary tract.
- Author
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N'Dow J, Pearson JP, Bennett MK, Neal DE, and Robson CN
- Subjects
- Adult, Female, Humans, In Situ Hybridization, Male, Middle Aged, Oligonucleotide Probes, Plastic Surgery Procedures, Up-Regulation physiology, Urinary Bladder metabolism, Gene Expression, Ileum surgery, Mucins genetics, Urothelium metabolism
- Abstract
Purpose: The repertoire of mucin (MUC) gene expression in the normal human urothelium is poorly defined and the alterations in MUC gene expression following transposition of intestinal segments into the urinary tract has not previously been studied. The aims of this study were to define MUC gene expression in the normal human urothelium; and in transposed intestinal segments., Materials and Methods: Non-isotopic in-situ hybridization was carried out using eight digoxigenin labeled oligonucleotide mucin gene probes (MUC 1 - 7). Immunohistochemistry using NCL-MUC1 and NCL-MUC2 monoclonal antibodies was performed on sections of paraffin-embedded tissues. Twenty-seven patients were investigated (normal human urothelium, n = 6; transposed ileal segments, n = 14 and normal ileal controls, n = 7)., Results: MUC1 and MUC4 were the predominant mucin genes expressed in the normal urothelium with MUC3 being expressed in a third of cases studied; MUC2, 5AC, 5B, 6 and 7 were not expressed. Despite the morphological changes seen in transposed ileal segments, MUC2 and MUC3 continued to be expressed in these segments albeit in a disorganised fashion. Both MUC1 and MUC4 were up-regulated in transposed ileal segments, genes expressed by the normal human urothelium. All eight mucin genes were expressed in an area of pyloric-type metaplasia found in one transposed ileal segment. In patients with clam enterocystoplasty there was evidence of increasing up-regulation of MUC2, 3, 4 and 5AC expression in the urothelium toward the anastomotic site., Conclusion: Transposition of ileal segments into the urinary tract results in up-regulation of MUC1 and MUC4, the predominant MUC genes expressed in the human bladder. The clinical implication of the up-regulation of some MUC genes toward the anastomotic site in patients with an enteroplasty and the aberrant expression of MUC5AC - MUC7 by transposed segments is at present unclear.
- Published
- 2000
15. A prospective randomized trial comparing transurethral resection of the prostate and laser therapy in men with chronic urinary retention: The CLasP study.
- Author
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Gujral S, Abrams P, Donovan JL, Neal DE, Brookes ST, Chacko KN, Wright MJ, Timoney AG, and Peters TJ
- Subjects
- Humans, Male, Middle Aged, Prospective Studies, Prostatic Hyperplasia complications, Severity of Illness Index, Urinary Retention etiology, Laser Therapy, Prostatic Hyperplasia surgery, Transurethral Resection of Prostate, Urinary Retention surgery
- Abstract
Purpose: We assessed the effectiveness of laser therapy versus transurethral prostatic resection in men with symptomatic chronic urinary retention secondary to benign prostatic enlargement., Materials and Methods: This trial was multicenter, pragmatic and randomized. Analysis was done by intent to treat. Laser therapy involved neodymium:YAG noncontact visual prostate ablation, while transurethral prostatic resection was performed by standard electroresection. Patients were included in our study if they reported moderate to severe lower urinary tract symptoms with an International Prostate Symptom Score (I-PSS) of 8 or more, benign prostatic enlargement and a persistent post-void residual urine volume of more than 300 ml. Followup was 7.5 months. Primary outcome measures included the I-PSS, I-PSS quality of life score, maximum urinary flow and post-void residual urine volume. Secondary outcome measures included treatment failure, complications, hospital stay and catheterization time., Results: A total of 82 patients agreed to be randomized to receive laser therapy (38) or transurethral prostatic resection (44). There were significant improvements in all primary outcomes in each group from randomization to followup. Transurethral prostatic resection was significantly better than laser therapy for I-PSS and maximum urinary flow values (p = 0.035 and 0.029, respectively) but there were no differences in post-void residual urine volume and I-PSS quality of life score between the groups. We noted significantly more treatment failures with laser therapy than resection (8 versus 0, p = 0.0014), although only 3 patients required resection after laser therapy because of persistent symptoms. In addition, hospital stay after resection was 2-fold that after laser therapy (ratio of geometric means 2.01, 95% confidence interval 1.54 to 2.61, p <0.0001). However, time to catheter removal was 9 times longer in the laser therapy group (p <0. 0001). Complication rates were significantly higher for transurethral prostatic resection (chi-square 5.05, 1 df, p = 0.025)., Conclusions: Transurethral prostatic resection is more effective than laser ablation in men with chronic urinary retention in terms of symptom score, maximum urinary flow and failure. However, men who underwent resection had significantly more treatment complications and were hospitalized longer than those who received laser therapy. This finding implies that laser ablation therapy may have a role in patients at higher risk who are willing to accept a lower level of effectiveness in exchange for decreased complication rates and hospital stay.
- Published
- 2000
16. A randomized trial comparing transurethral resection of the prostate, laser therapy and conservative treatment of men with symptoms associated with benign prostatic enlargement: The CLasP study.
- Author
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Donovan JL, Peters TJ, Neal DE, Brookes ST, Gujral S, Chacko KN, Wright M, Kennedy LG, and Abrams P
- Subjects
- Aged, Humans, Male, Severity of Illness Index, Laser Therapy, Prostatic Hyperplasia therapy, Transurethral Resection of Prostate
- Abstract
Purpose: We evaluated the effectiveness of a new technology (noncontact laser therapy) versus that of standard surgery (transurethral prostatic resection) and conservative management for lower urinary tract symptoms associated with benign prostatic enlargement., Materials and Methods: Men with uncomplicated lower urinary tract symptoms, that is no acute or chronic urinary retention, were randomized to receive laser therapy with a noncontact, side firing neodymium:YAG probe, standard transurethral prostatic resection or conservative management, including monitoring without active intervention, in a large multicenter pragmatic randomized controlled trial called the CLasP study. Primary outcomes were International Prostate Symptom Score (I-PSS), maximum urinary flow rate, a composite measure of success based on I-PSS and maximum urinary flow rate categories, I-PSS quality of life score and post-void residual urine volume. Secondary outcomes included treatment failure, hospital stay and major complications. Followup was 7.5 months after randomization. Intent to treat analysis was done using analysis of covariance, proportional odds models and the Newman-Keuls multiple comparisons procedure., Results: Of symptomatic patients 117, 117 and 106 were randomized to receive laser therapy, transurethral prostatic resection and conservative management, respectively. Baseline characteristics were similar. All primary outcomes indicated that transurethral prostatic resection and laser therapy were superior to conservative management, and resection was superior to laser therapy. As measured by combined improved symptoms and maximum urinary flow, a successful outcome was achieved in 81%, 67% and 15% of men who underwent transurethral prostatic resection, laser therapy and conservative management, respectively. Hospital stay was significantly shorter and complications fewer for laser therapy than for resection but catheters were in place significantly longer. Men treated conservatively did not have deterioration or treatment failure., Conclusions: Laser therapy and transurethral prostatic resection are effective for decreasing lower urinary tract symptoms and post-void residual urine volume as well as improving quality of life and maximum urinary flow in the short term in men presenting with moderate to severe symptoms. Transurethral prostatic resection is superior to laser therapy in terms of effectiveness but some patients may elect laser therapy due to the shorter hospital stay and lower risk of complications. Conservative management may be acceptable and safe in men with lower urinary tract symptoms since we observed no marked deterioration in the short term.
- Published
- 2000
17. Neural network analysis of clinicopathological and molecular markers in bladder cancer.
- Author
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Qureshi KN, Naguib RN, Hamdy FC, Neal DE, and Mellon JK
- Subjects
- Biomarkers, Tumor, Disease Progression, Follow-Up Studies, Humans, Neoplasm Staging, Predictive Value of Tests, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Survival Rate, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local mortality, Neural Networks, Computer, Urinary Bladder Neoplasms diagnosis, Urinary Bladder Neoplasms mortality
- Abstract
Purpose: To evaluate retrospectively the ability of an artificial neural network (ANN) to predict bladder cancer recurrence within 6 months of diagnosis and stage progression in patients with Ta/T1 bladder cancer, and 12-month cancer-specific survival in patients with T2-T4 bladder cancer., Materials and Methods: Data were analyzed using a NeuralWorks Professional II/Plus software package. The input neural data consisted of clinicopathological and molecular characteristics. Distinct patient groups were used for the prediction of stage progression and tumor recurrence in Ta/T1 bladder cancers, and 12-month cancer-specific survival for patients with T2-T4 tumors. ANN predictions were compared with those of four consultant urologists., Results: The accuracy of the neural network in predicting stage progression and recurrence within 6 months for Ta/T1 tumors and 12-month cancer-specific survival for T2-T4 cancers was 80%, 75% and 82% respectively; with corresponding figures for clinicians being 74%, 79% and 65%. On restricting the validation subset to patients with T1G3 tumors in relation to stage progression, the sensitivity of the ANN analysis increased to 100% with a specificity of 78% and an overall accuracy of 82%. The performance of the ANN in predicting stage progression in T1G3 tumors was significantly higher than that of clinicians (p = 0.25 for the ANN and p = 0.008 for clinicians, McNemar test)., Conclusions: Data analysis using an ANN has been shown to be a useful adjunct in predicting outcomes in patients with bladder cancer and out-performs clinicians' predictions of stage progression in the high risk group of patients with T1G3 disease.
- Published
- 2000
18. A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice.
- Author
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Khadra MH, Pickard RS, Charlton M, Powell PH, and Neal DE
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Algorithms, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, Hematuria etiology, Urologic Diseases complications, Urologic Diseases diagnosis, Urologic Neoplasms complications, Urologic Neoplasms diagnosis
- Abstract
Purpose: The commonly accepted diagnostic algorithm for hematuria includes excretory urography (IVP) and cystoscopy. Some have suggested that ultrasound of the upper urinary tract is adequate and that cystoscopy is not necessary in younger patients with microscopic hematuria. We ascertain whether a less intensive algorithm could be adopted while retaining diagnostic efficacy., Materials and Methods: A total of 1,930 patients were enrolled prospectively in the study at a hematuria clinic between October 1994 and March 1997. Evaluation consisted of basic demographics, history and examination, routine blood tests, urinalysis and cytology. All patients underwent plain abdominal radiography, renal ultrasound, IVP and flexible cystoscopy., Results: A total of 1,194 males and 736 females with a mean age of 58 years (range 17 to 96) were included in the study. Overall, 61% of patients had no basis found for hematuria, 12% had bladder cancer, 13% had urinary tract infection and 2% had stones. Kidney and upper tract tumors were noted in 14 patients (0.7%), including 4 who presented with microscopic hematuria. If only ultrasound or IVP had been performed 4 of these cases would have been missed. Of 982 patients presenting with microscopic hematuria 51 had cancer. Bladder cancer was found in 7 patients younger than 40 years., Conclusions: Our findings suggest that cystoscopy cannot be safely avoided even in younger patients with microscopic hematuria. Only a combination of ultrasound and IVP detected all upper tract tumors.
- Published
- 2000
19. Contractions in human detrusor smooth muscle induced by hypo-osmolar solutions.
- Author
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Masters JG, Neal DE, and Gillespie JI
- Subjects
- Calcium Channel Blockers pharmacology, Diltiazem pharmacology, Dose-Response Relationship, Drug, Gadolinium pharmacology, Humans, Carbachol pharmacology, Isotonic Solutions pharmacology, Muscle Contraction drug effects, Muscle, Smooth drug effects, Muscle, Smooth physiology, Urinary Bladder drug effects, Urinary Bladder physiology
- Abstract
Purpose: The aim of this study was to investigate stretch activated channels in human detrusor using hypo-osmolar solutions to produce cell deformation. Stretch activated channels could provide another mechanism by which detrusor myocytes may be coupled., Materials and Methods: Human detrusor removed at surgery was dissected into strips and also enzymatically digested and cultured. Strips (5x1x1 mm.) were mounted in an organ bath and perfused with gassed Tyrode's. Hypo-osmolar solutions were made by removal of NaCl. Gadolinium (Gd3+), a blocker of stretch activated channels (SACs), and diltiazem, an L-type Ca2+ channel antagonist were used at 10 microM concentrations. Mean data +/- S.E.M. are expressed as a percentage of maximal tension produced by 1 microM carbachol for each patient. Enzymatically disaggregated, human detrusor was cultured in flasks, passaged and placed on glass coverslips. Once confluent the cells were incubated with the Ca2+ sensitive fluorochrome Fura-2AM. Coverslips were placed in a bath on the stage of EPI-fluorescence microscope and solutions were perfused through the bath (5 ml. per minute, 35C, pH 7.4). Changes in fluorescence emission ratio (proportional to changes in cytosolic Ca2+) were measured., Results: Hypo-osmolar solutions produced a tension increase in the strips and a Ca2+ influx in the cells. In the strips in paired experiments Gd3+ and diltiazem significantly reduced the response to hypo-osmolar solution (87%+/-16% v. 51%+/-12.5%, p = 0.003, n = 10 for Gd3+), and (69%+/-11% v. 37%+/-9%, p = 0.001, n = 9 for diltiazem). In Ca2+ free solution responses were significantly reduced (65%+/-10% v. 21%+/-8%, p = 0.001, n = 9). In the cells in paired experiments, 10 microM Gd3+ significantly reduced the elevation of cytosolic Ca2+ in response to hypo-osmolar solutions (median 0 v. 0.38 (62 cells, n = 7 bladders)), as did Ca2+ free hypo-osmolar solution (median 0 v. 0.44 (46 cells, n = 7)). 10 microM diltiazem (L-type Ca2+ channel antagonist) did not influence the response to hypo-osmolar solution (p = 0.14, median 0.5 v. 0.54 (31 cells, n = 4))., Conclusions: Hypo-osmolar solutions produced a tension increase in human detrusor that appears to be dependent on upon influx of Ca2+ through stretch activated channels (SACs), influx of Ca2+ through L-type Ca2+ channels and also on release of intracellular Ca2+.
- Published
- 1999
20. Bowel dysfunction after bladder reconstruction.
- Author
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N'Dow J, Leung HY, Marshall C, and Neal DE
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Gastrointestinal Transit, Humans, Intestinal Diseases physiopathology, Male, Middle Aged, Patient Satisfaction, Urodynamics, Intestinal Diseases etiology, Postoperative Complications, Urinary Diversion
- Abstract
Purpose: Bowel function may be disturbed after intestinal segments are used in urinary reconstruction. The etiology of this condition and its incidence in different patient groups is unclear. We studied the incidence of bowel disturbance in patients who underwent bladder replacement, continent diversion, enterocystoplasty for idiopathic detrusor instability and ileal conduit diversion., Materials and Methods: We evaluated 71 patients after ileal conduit diversion and 82 after bladder reconstruction, including clam enterocystoplasty for detrusor instability in 28, neurogenic bladder dysfunction in 26 and nonneuropathic conditions in 28. We noted the severity of symptoms, such as frequency of defecation, nocturnal diarrhea, flatus leakage, fecal urgency, fecal incontinence and explosive diarrhea, as well as quality of life., Results: Of the patients who underwent bladder reconstruction 24% had symptoms of bowel dysfunction preoperatively and 42% of those who were asymptomatic preoperatively described new bowel symptoms postoperatively. These symptoms were most common and severe in 54% of patients after clam enterocystoplasty for detrusor instability compared to 26% with neuropathy, 14% with a nonneuropathic condition and 15% with an ileal conduit. Compared to those in other groups patients who underwent enterocystoplasty for detrusor instability had a significantly higher incidence of nocturnal bowel movements (18 versus less than 4%, p <0.01), flatus leakage (29 versus less than 8%, p <0.01), fecal urgency (39 versus less than 12%, p <0.001) and fecal incontinence (32 versus less than 16%, p <0.001). The length of ileum used for clam enterocystoplasty was only slightly greater than that used for ileal conduit operations (25 versus 18 cm.). Of the patients who underwent enterocystoplasty for detrusor instability 29% regretted undergoing the procedure due to subsequent bowel symptoms., Conclusions: After enterocystoplasty for detrusor instability patients are at risk of significant bowel symptoms. The development of new bowel symptoms was associated with poor patient satisfaction.
- Published
- 1998
- Full Text
- View/download PDF
21. Transcutaneous electrical nerve stimulation and temporary S3 neuromodulation in idiopathic detrusor instability.
- Author
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Hasan ST, Robson WA, Pridie AK, and Neal DE
- Subjects
- Electrodes, Implanted, Female, Humans, Male, Middle Aged, Prospective Studies, Time Factors, Urinary Bladder physiopathology, Urinary Bladder, Neurogenic diagnosis, Urinary Bladder, Neurogenic physiopathology, Urodynamics physiology, Electric Stimulation Therapy, Spinal Nerve Roots physiology, Transcutaneous Electric Nerve Stimulation, Urinary Bladder, Neurogenic therapy
- Abstract
Purpose: We studied the effects of electrical stimulation on idiopathic detrusor instability., Materials and Methods: Between January 1993 and December 1994, 30 men and 41 women (mean age plus or minus standard deviation 48 +/- 16 years) underwent transcutaneous electrical nerve stimulation (TENS) of the S2-S3 dermatomes, and 13 men and 22 women (mean age 48 +/- 12 years) underwent S3 neuromodulation. Subjective assessment was performed using a diary and symptom score of 0 to 14. Objective outcome was analyzed with urodynamic studies., Results: Mean duration of TENS was 3 +/- 1 weeks (range 2 to 4). Although there were no major complications 31% of the patients reported local skin irritation. The overall urinary symptom scores improved from 10 +/- 2 (range 5 to 14) before the study to 7 +/- 3 (range 1 to 14) during stimulation. Urodynamic analysis revealed significant (p < 0.05) improvements in total bladder capacity and voided volume, and decreases in the number and frequency of unstable contractions. Mean duration of S3 neuromodulation was 6 +/- 1 days (range 4 to 8 days). Four procedures failed due to electrode displacement in 3 cases and procedure intolerance in 1. Hemorrhage from the puncture site occurred in 1 patient. Overall urinary symptom scores were 10 +/- 3 (range 5 to 14) before the study and 5 +/- 2 (range 2 to 10) during stimulation. Although symptomatic relief was more pronounced with S3 neuromodulation, no statistically significant differences were found regarding urinary symptoms compared to TENS., Conclusions: In patients with severe detrusor instability refractory to conservative treatments the use of TENS and S3 neuromodulation produced significant changes in urodynamic parameters and presenting symptoms. Our results appear to justify evaluation with neuromodulatory techniques before definitive surgical intervention in these patients.
- Published
- 1996
22. Conventional urodynamics and ambulatory monitoring in the definition and management of bladder outflow obstruction.
- Author
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Robertson AS, Griffiths C, and Neal DE
- Subjects
- Aged, Female, Humans, Male, Monitoring, Physiologic, Prospective Studies, Urinary Bladder Neck Obstruction physiopathology, Urodynamics
- Abstract
Purpose: We determined whether ambulatory urodynamics and new objective methods of defining bladder outflow obstruction might improve the classification of bladder outflow obstruction over conventional urodynamics (cystometrography), and whether such measures might improve prediction of the outcome of prostatectomy., Materials and Methods: A prospective study was performed of 122 men undergoing prostatectomy for symptoms and low flow rates. Cystometrography and ambulatory urodynamics were performed before and 6 months after prostatectomy but did not influence selection for operation. Methods of classifying obstruction included the Abrams-Griffiths nomogram, Schäfer linear passive urethral resistance relation and Griffiths urethral resistance factor., Results: The proportion of cases defined as obstructed did not differ on ambulatory urodynamics or cystometrography or when the Abrams-Griffiths nomogram was compared to the linear passive urethral resistance relation or urethral resistance factor. Significant improvements after prostatectomy were noted in flow rates (p < 0.001), residual urine (p < 0.001), voiding pressure (p < 0.001) and symptom scores (p < 0.001). Ambulatory urodynamics were more sensitive than cystometrography in detection of detrusor instability but detrusor instability did not correlate with outcome. Voiding pressures were greater during ambulatory urodynamics (p < 0.02). The outcome of obstructed cases (on Abrams-Griffiths nomogram during ambulatory urodynamics) was better (79% good outcome) than that of nonobstructed or equivocally obstructed cases (55% good symptomatic outcome, p < 0.05)., Conclusions: Men proved to have obstruction on the basis of pressure and flow measurements applied to a nomogram have better outcomes after transurethral resection of the prostate but sophisticated or computer derived methods of classification of obstruction did not improve prediction.
- Published
- 1996
23. C-erbB-2 in bladder cancer: molecular biology, correlation with epidermal growth factor receptors and prognostic value.
- Author
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Mellon JK, Lunec J, Wright C, Horne CH, Kelly P, and Neal DE
- Subjects
- Blotting, Southern, Carcinoma, Transitional Cell chemistry, Carcinoma, Transitional Cell mortality, DNA, Neoplasm genetics, Gene Expression, Humans, Immunoblotting, Oncogene Proteins v-erbB genetics, Prognosis, RNA, Messenger genetics, RNA, Neoplasm genetics, Urinary Bladder chemistry, Urinary Bladder Neoplasms chemistry, Urinary Bladder Neoplasms mortality, Carcinoma, Transitional Cell genetics, ErbB Receptors analysis, Genes, erbB-2, Neoplasm Recurrence, Local genetics, Oncogene Proteins v-erbB biosynthesis, Urinary Bladder Neoplasms genetics
- Abstract
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.
- Published
- 1996
- Full Text
- View/download PDF
24. Tanagho bladder neck reconstruction in the treatment of adult incontinence.
- Author
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Gallagher PV, Mellon JK, Ramsden PD, and Neal DE
- Subjects
- Adult, Epispadias surgery, Female, Humans, Male, Surgical Flaps methods, Treatment Outcome, Urethra injuries, Urethra surgery, Urinary Incontinence etiology, Urinary Incontinence physiopathology, Urinary Incontinence, Stress physiopathology, Urodynamics physiology, Urinary Bladder surgery, Urinary Incontinence surgery, Urinary Incontinence, Stress surgery
- Abstract
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.
- Published
- 1995
25. Long-term outcome related to epidermal growth factor receptor status in bladder cancer.
- Author
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Mellon K, Wright C, Kelly P, Horne CH, and Neal DE
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Male, Middle Aged, Multivariate Analysis, Neoplasm Recurrence, Local epidemiology, Neoplasm Staging, Predictive Value of Tests, Prognosis, Prospective Studies, Sensitivity and Specificity, Survival Rate, Time Factors, Urinary Bladder Neoplasms mortality, Urinary Bladder Neoplasms pathology, Urinary Bladder Neoplasms therapy, ErbB Receptors analysis, Urinary Bladder Neoplasms chemistry
- Abstract
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.
- Published
- 1995
26. The effect of antimicrobial therapy on testicular aspirate flow cytometry.
- Author
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Crotty KL, May R, Kulvicki A, Kumar D, and Neal DE Jr
- Subjects
- Animals, DNA analysis, Flow Cytometry, Male, Ploidies, Rats, Rats, Sprague-Dawley, Time Factors, Anti-Bacterial Agents pharmacology, Spermatogenesis drug effects, Testis cytology, Testis drug effects
- Abstract
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.
- Published
- 1995
27. Bilateral single ectopic ureters: diagnosis using transrectal ultrasound.
- Author
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Fannin O 3rd, Cammack JT, Crotty KL, and Neal DE Jr
- Subjects
- Adult, Choristoma complications, Humans, Hydronephrosis etiology, Male, Prostatic Neoplasms complications, Renal Insufficiency etiology, Choristoma diagnostic imaging, Prostatic Neoplasms diagnostic imaging, Ultrasonography methods, Ureter
- Abstract
An unusual case of bilateral, single ectopic ureters inserting into the prostate gland presenting with hydronephrosis and renal insufficiency is reported. The diagnosis was made by transrectal and abdominal ultrasound.
- Published
- 1993
- Full Text
- View/download PDF
28. Ambulatory monitoring of bladder pressure in low compliance neurogenic bladder dysfunction.
- Author
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Webb RJ, Griffiths CJ, Ramsden PD, and Neal DE
- Subjects
- Adolescent, Adult, Aged, Compliance, Female, Humans, Male, Middle Aged, Pressure, Urodynamics, Monitoring, Physiologic, Urinary Bladder, Neurogenic physiopathology
- Abstract
Upper tract dilatation is an important complication of neurogenic bladder dysfunction. Risk factors include incomplete bladder emptying with large residual volumes of urine and high tonic increases in bladder pressures during artificial filling. However, on natural bladder filling many of these patients do not have high tonic increases in detrusor pressures. We compared conventional urodynamic studies with ambulatory monitoring during natural bladder filling in 66 patients with low compliance neurogenic bladder dysfunction. There were marked differences in the tonic increase in bladder pressure during filling and in compliance during artificial bladder filling compared with ambulatory monitoring. Faster filling rates during artificial filling resulted in greater end filling pressures and lower compliance but the lowest increases in bladder pressure were found during ambulatory monitoring with natural bladder filling. During natural bladder filling significantly more patients had phasic changes in detrusor pressure; a high intensity of phasic activity during ambulatory monitoring correlated with high end filling pressures during artificial bladder filling. Upper tract dilatation was associated with large volumes of residual urine, high resting bladder pressures and low bladder compliance on filling at 100 ml. per minute. However, upper tract dilatation was most strongly associated with high intensity phasic pressure activity during natural bladder filling in combination with high residual urine volumes and high resting bladder pressures. On multivariate statistical analysis the intensity of phasic pressure activity during ambulatory monitoring was the best discriminator between patients with dilated and normal upper tracts. Our study has highlighted important differences in the results obtained by artificial filling cystometry and ambulatory monitoring during natural bladder filling. In particular, high increases in pressure did not occur during natural bladder filling, apparently being replaced by phasic activity. Within this group of patients who had the high risk factor of low bladder compliance measured during artificial bladder filling, a combination of greater residual urine volumes, greater resting pressures and greater phasic activity during natural bladder filling was found in patients with upper tract dilatation.
- Published
- 1992
- Full Text
- View/download PDF
29. Cavernous tissue antibiotic levels in penile prosthesis surgery.
- Author
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Walters FP, Neal DE Jr, Rege AB, George WJ, Ricci MJ, and Hellstrom WJ
- Subjects
- Aztreonam analysis, Aztreonam therapeutic use, Gentamicins analysis, Gentamicins therapeutic use, Humans, Male, Vancomycin analysis, Vancomycin therapeutic use, Aztreonam pharmacokinetics, Bacterial Infections prevention & control, Gentamicins pharmacokinetics, Penile Prosthesis adverse effects, Penis chemistry, Prosthesis-Related Infections prevention & control, Vancomycin pharmacokinetics
- Abstract
A comparison of the delivery of several antibiotics (vancomycin, gentamicin and aztreonam) to the tissue site of prosthesis implantation was studied using cavernous tissue levels for each antibiotic. A total of 32 patients underwent penile prosthesis implantation. Intravenous antibiotics were administered 1 to 2 hours preoperatively, with vancomycin and aztreonam given to patients at the Tulane University Medical Center, and vancomycin and gentamicin given to patients at the New Orleans Veterans Administration Hospital. At operation the urine, serum and cavernous tissue were concurrently sampled and later analyzed for antibiotic concentration. The mean cavernous tissue level for vancomycin was 55.5 +/- 5.5 ng./mg. (standard deviation) for 20 patients, while the mean cavernous tissue levels for aztreonam and gentamicin were 8.9 +/- 2.1 ng./mg. for 10 patients and 4.7 +/- 1.2 ng./mg. for 12 patients, respectively. When the delivery of antibiotic to cavernous tissue was compared (quantitated as ng. antibiotic per mg. tissue per mg. drug administered), a statistically significant value (p less than 0.01) was observed with vancomycin (0.11 ng./mg./mg.) greater than gentamicin (0.06 ng./mg./mg.) or aztreonam (0.01 ng./mg./mg.), and with no significant difference observed between aztreonam or gentamicin. These findings suggest that cavernous tissue levels may be used as a method to determine optimal antibiotic prophylaxis against penile prosthesis infection.
- Published
- 1992
- Full Text
- View/download PDF
30. p53, c-erbB-2 and the epidermal growth factor receptor in the benign and malignant prostate.
- Author
-
Mellon K, Thompson S, Charlton RG, Marsh C, Robinson M, Lane DP, Harris AL, Horne CH, and Neal DE
- Subjects
- Aged, Biomarkers, Tumor analysis, Humans, Immunohistochemistry, Male, Middle Aged, Prostatic Neoplasms pathology, Receptor, ErbB-2, ErbB Receptors analysis, Prostatic Hyperplasia metabolism, Prostatic Neoplasms chemistry, Proto-Oncogene Proteins analysis, Tumor Suppressor Protein p53 analysis
- Abstract
Expression of the p53, the epidermal growth factor receptor (c-erbB-1) and c-erbB-2 protein was studied in 34 men with benign prostatic hyperplasia and 29 men with locally advanced prostate cancer by means of an immuno-histochemical method. Strong staining for p53 was found in five of 29 prostate cancers (17%; mean 21% +/- 7% of malignant cells stained in the positive tumours), but no staining was found in benign prostatic hyperplasia (p less than 0.05). On the other hand, the epithelium in benign glands was stained positively for c-erbB-2 in 18% (6/34) and for the epidermal growth factor receptor in 88% (30/34); whereas malignant epithelium stained strongly for c-erbB-2 in 21% (6/29) and for the epidermal growth factor receptor in only 17% (5/29). Prostate cancer was associated with a significant decrease in epidermal growth factor receptor staining (p less than 0.0001) and a significant increase in p53 staining (p less than 0.05). Most of the tumours were advanced and no significant relationship was observed between tumour stage and grade and expression of p53, the epidermal growth factor receptor or c-erbB-2. These findings demonstrate that altered expression of the epidermal growth factor receptor and p53 protein occurs in prostate cancer, but were not associated with other features of prognostic importance such as stage or grade.
- Published
- 1992
- Full Text
- View/download PDF
31. The outcome of prostatectomy on chronic retention of urine.
- Author
-
Styles RA, Ramsden PD, and Neal DE
- Subjects
- Aged, Chronic Disease, Humans, Male, Urinary Bladder Neck Obstruction complications, Urinary Bladder Neck Obstruction surgery, Urination Disorders etiology, Urodynamics, Prostatectomy, Urination Disorders physiopathology
- Abstract
A total of 68 men with bladder outflow obstruction and chronic retention (residual urine greater than 300 ml.) underwent investigation before and after prostatectomy with medium fill cystometry and natural fill long-term bladder pressure monitoring. Postoperatively, upper tract dilatation (present in 28 men preoperatively) resolved in all but 2 men and serum creatinine levels improved significantly. Irritative and obstructive symptom scores improved postoperatively (p less than 0.00006), although 17% of the men still had significant symptoms. Residual urine volumes decreased and flow rates improved (p less than 0.00006) but 32% of the men still had a residual urine of greater than 200 ml. Urodynamic parameters improved during medium fill cystometry and long-term monitoring. The main risk factors for upper tract dilatation are a pressure increase during bladder filling on conventional cystometry and the frequency of phasic detrusor activity during long-term monitoring, and they decreased postoperatively.
- Published
- 1991
- Full Text
- View/download PDF
32. Filling and voiding pressures measured by ambulatory monitoring and conventional studies during natural and artificial bladder filling.
- Author
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Webb RJ, Griffiths CJ, Zachariah KK, and Neal DE
- Subjects
- Aged, Humans, Male, Middle Aged, Pressure, Prospective Studies, Rectum physiopathology, Urethra physiopathology, Urinary Bladder Neck Obstruction physiopathology, Urinary Bladder physiopathology, Urodynamics
- Abstract
A total of 20 men awaiting elective prostatectomy for bladder outflow obstruction underwent conventional medium filling cystometry and ambulatory monitoring of bladder pressures during natural bladder filling. Total bladder capacity was similar during both tests (medium filling cystometry 256 +/- 138 ml. and ambulatory monitoring 248 +/- 120 ml., p not significant) as was the voided volume (medium filling cystometry 180 +/- 100 ml. and ambulatory monitoring 179 +/- 88 ml., p not significant). However, the peak urinary flow rate at the end of medium filling cystometry (4 +/- 6 ml. per second) was significantly lower than during ambulatory monitoring (9 +/- 4 ml. per second, p less than 0.05). The bladder contraction pressure during medium filling cystometry (79 +/- 44 cm. water) was significantly lower than during ambulatory monitoring (107 +/- 39 cm. water, p less than 0.005). Bladder pressures during voiding recorded after natural filling were significantly greater than after artificial filling. This finding may have significant implications for the use of conventional cystometry to study conditions such as outflow obstruction.
- Published
- 1991
- Full Text
- View/download PDF
33. Renin production after experimental extracorporeal shock wave lithotripsy: a primate model.
- Author
-
Neal DE Jr, Kaack MB, Harmon EP, Puyau F, Morvant A, Richardson E, and Thomas R
- Subjects
- Animals, Kidney physiopathology, Macaca mulatta, Renin-Angiotensin System physiology, Lithotripsy adverse effects, Renin blood
- Abstract
Since the advent of extracorporeal shock wave lithotripsy (ESWL) concern has surfaced as to the long-term risk of the development of hypertension, as well as risk to the developing kidney. To study this concern 8 infant and 3 adult rhesus monkeys (Macaca mulatta) underwent treatment with the XL1 experimental lithotriptor to 1 kidney varying the amount of voltage and shocks. Followup consisted of measurement of renin levels and quantitative renal scans, using 131iodine hippurate to calculate effective renal plasma flow. In the infants a slight change was noted in the absolute effective renal plasma flow of the treated kidney versus the untreated side but it was not statistically different. When indexed to body surface area in the growing animal, there was a statistically significant decrease in renal function. However, peripheral renin levels were markedly elevated in the infants at 3 weeks, and they gradually declined during the 6-month period, although levels remained elevated over baseline. The adults also had central renin levels drawn from the renal vein on the treated side, and there was a close correlation with the peripheral levels, which peaked at 3 weeks and returned to normal. Thus, it seems that at least in the short term renin production is increased in infants more than adults. This finding may be an indicator as to renal damage and is a possible explanation for hypertension occurring after ESWL.
- Published
- 1991
- Full Text
- View/download PDF
34. Tamm-Horsfall autoantibodies in interstitial cystitis.
- Author
-
Neal DE Jr, Dilworth JP, and Kaack MB
- Subjects
- Adult, Biopsy, Chronic Disease, Cystitis diagnosis, Cystoscopy, Enzyme-Linked Immunosorbent Assay methods, Female, Humans, Male, Middle Aged, Mucoproteins isolation & purification, Urinary Bladder pathology, Uromodulin, Autoantibodies blood, Cystitis immunology, Mucoproteins immunology
- Abstract
Interstitial cystitis presents a diagnostic and therapeutic challenge. Although many etiologies, including autoimmunity, have been proposed its pathogenesis remains obscure. Tamm-Horsfall protein has been identified in the superficial urothelium of patients with interstitial cystitis demonstrating abnormal urothelial permeability. Eight patients with a clinical diagnosis of interstitial cystitis underwent cystoscopy and bladder biopsy. Characteristic cystoscopic findings were present, and each patient had chronic inflammation and mast cells by histopathological analysis. Preoperative anti-Tamm-Horsfall protein serum antibody (IgG) titers were determined by enzyme-linked immunosorbent assay (range 500 to 8,000, mean 2,750). A control group of 8 patients with a negative urological history also had titers of 0 to 500 (p = 0.02). The humoral response to Tamm-Horsfall protein in these patients suggests a role for Tamm-Horsfall protein in interstitial cystitis. Measurement of serum Tamm-Horsfall protein antibody may prove to be useful as a noninvasive diagnostic test in patients with this disease.
- Published
- 1991
- Full Text
- View/download PDF
35. Immunological assessment of renal cancer patients as evaluated by the lymphocyte adherence inhibition test.
- Author
-
Mori K, Neal DE Jr, and Lamm DL
- Subjects
- Adult, Aged, Carcinoma, Renal Cell diagnosis, Female, Humans, Kidney Diseases immunology, Kidney Neoplasms diagnosis, Lymphocytes immunology, Male, Middle Aged, Urinary Bladder Neoplasms immunology, Carcinoma, Renal Cell immunology, Immunologic Techniques, Kidney Neoplasms immunology, Leukocyte Adherence Inhibition Test
- Abstract
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.
- Published
- 1986
- Full Text
- View/download PDF
36. Ambulatory monitoring of bladder and detrusor pressure during natural filling.
- Author
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Griffiths CJ, Assi MS, Styles RA, Ramsden PD, and Neal DE
- Subjects
- Adult, Equipment Design, Evaluation Studies as Topic, Female, Humans, Male, Pressure, Rectum physiopathology, Urinary Bladder Diseases physiopathology, Urodynamics, Urologic Diseases physiopathology, Ambulatory Care, Monitoring, Physiologic instrumentation, Urinary Bladder physiopathology, Urinary Tract physiopathology
- Abstract
We have developed a system to perform fully ambulatory monitoring studies of the bladder. Bladder and rectal pressures are recorded during natural filling of the bladder for up to 6 hours. This system has been evaluated in 19 studies performed on 15 patients. The mean duration of the studies was 3 hours 51 minutes (standard deviation +/- 1 hour 3 minutes) and the mean number of voids per patient was 3.8 +/- 2.2. Visual inspection of the recorded data showed that subtraction of the rectal trace from the bladder trace provided a useful detrusor trace when subjects were ambulant as well as resting. When ambulant, movement caused typical peak-to-peak pressure variability in the bladder and rectal traces of approximately 30 +/- 20 cm. water (mean and standard deviation of peak-to-peak pressure for typical ambulant 5-minute sections for each patient), which after subtraction was reduced on the detrusor trace to 10 +/- 5 cm. water. The equivalent figures when resting were 9 +/- 5 cm. water, subtracting to less than 5 cm. water for the detrusor. Further measurements also were calculated for the whole of each trace. The system provided good quality recordings and should prove useful in future evaluations of natural fill urodynamic studies.
- Published
- 1989
- Full Text
- View/download PDF
37. Long-term monitoring of bladder pressure in chronic retention of urine: the relationship between detrusor activity and upper tract dilatation.
- Author
-
Styles RA, Neal DE, Griffiths CJ, and Ramsden PD
- Subjects
- Aged, Dilatation, Pathologic, Humans, Male, Pressure, Urinary Bladder Neck Obstruction pathology, Urinary Bladder Neck Obstruction physiopathology, Urinary Tract pathology, Urodynamics
- Abstract
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).
- Published
- 1988
- Full Text
- View/download PDF
38. Epidermal growth factor receptor in human bladder cancer: a comparison of immunohistochemistry and ligand binding.
- Author
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Neal DE, Smith K, Fennelly JA, Bennett MK, Hall RR, and Harris AL
- Subjects
- Adult, Aged, Aged, 80 and over, Biopsy, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Staging, Radioligand Assay, Urinary Bladder Neoplasms pathology, Epidermal Growth Factor analysis, ErbB Receptors analysis, Urinary Bladder Neoplasms metabolism
- Abstract
Epidermal growth factor receptors were measured in biopsies from patients with newly diagnosed bladder cancer. Two methods to detect these receptors were compared: immunohistochemical staining of frozen sections, and a ligand binding study using radiolabeled epidermal growth factor and tumor cell membranes. We studied 101 patients by immunohistochemistry and 47 patients by both methods. An association was found between immunohistochemical positivity for epidermal growth factor receptors and high tumor stage (p less than 0.001). Thus, most of the muscle invasive tumors were positive (35 of 49, 71 per cent) and more stage pT1 tumors were positive (8 of 18, 44 per cent) than were stage pTa tumors (5 of 34, 15 per cent, p less than 0.05). The ligand binding study was slightly more sensitive in detecting receptors than immunohistochemistry (30 of 47, 64 per cent and 25 of 47, 53 per cent, respectively). Greater amounts of receptors were found in muscle invasive tumors compared to tumors not invading muscle (p less than 0.05). A significant association was found between the 2 methods in the detection of receptors (p less than 0.001) and no discrepancies were found between the 2 methods in tumors containing high levels of receptors. Immunohistochemistry provides a satisfactory method to detect receptors in tumors with high levels of receptors, although ligand binding is more sensitive in tumors with low levels of receptors.
- Published
- 1989
- Full Text
- View/download PDF
39. Urodynamic investigation of the ileal conduit: upper tract dilatation and the effects of revision of the conduit.
- Author
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Neal DE
- Subjects
- Adult, Aged, Dilatation, Pathologic etiology, Dilatation, Pathologic physiopathology, Humans, Ileum physiopathology, Ileum surgery, Middle Aged, Peristalsis, Pressure, Radiography, Reoperation, Ureteral Diseases diagnostic imaging, Ureteral Diseases etiology, Ureteral Diseases physiopathology, Urinary Catheterization, Urinary Incontinence surgery, Urinary Diversion adverse effects, Urodynamics
- Abstract
Urodynamic studies of the ileal conduit were performed in 36 patients with normal upper urinary tracts (controls) and in 32 who had progressive upper tract dilatation within 6 years preceding the study. In controls the conduit emptied mainly by means of low pressure, to-and-fro activity. In contrast, high frequency, high amplitude peristaltic activity was found commonly in patients with upper tract dilatation, such activity being consistent with obstruction of the distal conduit. Of the 32 patients with upper tract dilatation 17 underwent reoperation on the conduit as well as postoperative urodynamic studies. Among these 17 patients a decrease was observed in basal pressure in the conduit postoperatively compared to preoperatively (5 +/- 4 and 12 +/- 6 cm. water, p less than 0.001). A decrease also was found postoperatively in the frequency (4 +/- 6 and 36 +/- 28 per hour, p less than 0.001) and amplitude (34 +/- 47 and 61 +/- 28 cm. water, p less than 0.001) of peristaltic activity. Radiological improvement in the appearance of the upper urinary tracts was found in 9 patients (53 per cent) postoperatively. These findings support the hypothesis that upper tract dilatation in certain patients with an ileal conduit may be caused by high pressure activity in the presence of free ureteral reflux. Such abnormalities, which are probably the result of obstruction of the distal conduit, may be detected by means of urodynamic evaluation and may be corrected by revision of the conduit.
- Published
- 1989
- Full Text
- View/download PDF
40. In vivo transfer of an R-plasmid in a urinary tract infection model.
- Author
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Neal DE Jr, Moody EE, Thomas VL, Gander R, and Radwin HM
- Subjects
- Animals, Culture Media, Drug Resistance, Microbial, Female, Fimbriae, Bacterial, Papio, Urine, Escherichia coli genetics, Escherichia coli Infections microbiology, R Factors genetics, Urinary Tract Infections microbiology
- Published
- 1989
- Full Text
- View/download PDF
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