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Biomedical subjects

D E Neal

Publications and source records attributed to D E Neal.

At least 127 records · Page 7Linked to original sources

The role of the nurse practitioner in a urology service.

OBJECTIVE: To evaluate the role of the nurse practitioner in urology and to determine the impact on the work of junior doctors. METHODS: Written criteria were defined before the postholder was appointed and subsequent performance was assessed against these criteria. Training was provided and the quality of work was assessed by direct observation. Senior House Officers (SHOs) were asked whether the post had increased their opportunities to attend theatre, outpatients and post-graduate training sessions and had decreased the number of 'inappropriate' tasks they had to perform. RESULTS: The nurse practitioner accomplished all the tasks that were defined before the appointment. The assessment of patients in pre-admission and haematuria clinics was satisfactory. The continuity of information, care of patients and counselling for patients receiving complex surgery were improved. Sixty-three per cent of all patients seen in the pre-admission clinic and all patients in a haematuria clinic were assessed initially by the nurse practitioner. Because the nurse practitioner was involved in setting up intravenous drug administration and infusions, administrative tasks and in obtaining results from the laboratory, the number of 'inappropriate' tasks performed by the SHOs decreased and they were able to attend more sessions of training and education. CONCLUSIONS: The nurse practitioner in clinical urological practice constitutes an effective use of resources and relieves junior medical staff from other tasks, allowing them to receive a more focused training. In addition, the quality of patient care was thought to be improved in some areas. The framework of a job plan for a nurse practitioner is described.

Humans↗

Peptide growth factors in the prostate as mediators of stromal epithelial interaction.

Peptide growth factors play a role in the maintenance of normal prostatic growth and differentiation (Fig. 2). It seems likely that the androgen sensitivity of human prostate is mediated by the production of peptide growth factors from stromal cells which act as the direct intermediate of androgen action on epithelial cells. TGF-beta 1 inhibition of epithelial cells is opposed by the stimulatory action of EGF, IGF and FGFs to maintain an equilibrium of epithelial cell numbers. The indirect mitogenic action of androgens appear to act by down-regulation of TGF-beta 1 and possibly EGF receptors. There is also interaction with the effects of IGF-II, produced by prostatic stromal cells and acting on epithelial cells to increase proliferation. The growth of normal prostatic fibroblasts is under the control of bFGF and TGF-beta 1. However, although our understanding of the actions of these growth factors in the normal prostate has improved over the last decade, their role in the development and maintenance of prostate cancer is less clearly defined. TGF-beta 1, classically considered to be inhibitory for epithelial cells, may be up-regulated in prostatic tumours, stimulating growth. Alternatively, autocrine production of such growth factors by tumour cells may lead to loss of inhibitory effects from exogenous TGF-beta 1, a mechanism also witnessed with TGF-alpha and bFGF. The role of EGF in the development of prostate cancer is confusing because results from the use of different cell types and experimental conditions is contradictory. It may be that a switch in the production of the predominant EGFr ligand from EGF to TGF-alpha is an important feature in the development and maintenance of the malignant phenotype. The presence of TGF-alpha autocrine loops has been shown clearly in some tumour cell lines. This switch in the production of a particular ligand may also be a feature of IGFs in prostate cancer. IGF-II may be replaced by IGF-I during malignant progression, both of which are able to act via the type 1 receptor. This change in IGF expression appears to be accompanied by altered expression of the IGF-BP2, with less detectable within prostatic tissues but elevated serum levels [58]. Basic FGF is normally produced by prostatic fibroblasts but is also produced by some prostatic cancer cell lines [64]. However, as with all growth factors, the expression of the bFGF protein and its receptor is dependent on the cell line examined. The autocrine and paracrine control of normal and abnormal prostatic growth by growth factors is important in determining their role in the development and maintenance of prostate cancer. Better understanding of such mechanisms is essential for the development of novel therapeutic strategies in the control and treatment of prostate cancer.

Cell Division↗

Breast and prostate cancer in the relatives of men with prostate cancer.

OBJECTIVE: To assess the risk of breast, ovarian and prostate cancer in the families of men with prostate cancer. PATIENTS AND METHODS: A case-control study was performed by interviewing patients with prostate cancer and obtaining detailed information on family histories of cancer. Controls were hospital-based patients, of a similar age to the cases, with bladder cancer or benign prostatic hypertrophy. RESULTS: A total of 209 cases and 322 controls were interviewed; of the cases, 22.5% had family members with a history of one or more of breast, ovarian or prostate cancers, compared with 15.2% of controls (P < 0.05). The odds ratio (OR) of having prostate cancer when there was a positive family history was 8.22 and the OR of a female relative of a patient with prostate cancer having breast cancer was 1.51. There was no apparent increased risk of ovarian or any other cancer. CONCLUSIONS: We confirm previous reports of an increased incidence of prostate cancer in the families of men with prostate cancer and report a similarly increased incidence of breast cancer in female relatives. We suggest that detailed family histories be taken routinely and intend to analyse blood samples provided from this study for genetic abnormalities.

Age of Onset↗

The effect of prostatectomy on symptom severity and quality of life.

OBJECTIVE: To determine the effectiveness of prostatectomy in reducing symptom severity and bother and in improving disease-specific and general quality of life. PATIENTS AND METHODS: A prospective, cohort study was performed in National Health Service and private hospitals in the Northern, Wessex, Mersey, and South-West Thames Health Regions which comprised 5276 men undergoing prostatectomy recruited by 101 of the 106 (96%) surgeons (specialist and non-specialist) performing prostatectomy during a 6-month period. Patients were assessed using the American Urological Association (AUA) Symptom Index Score, the AUA symptom bother score, disease-specific and generic quality-of-life scores, the occurrence of adverse events (urinary incontinence, erectile impotence and retrograde ejaculation) and three global (general) questions on the results of their treatment. The outcome was assessed 3 months after surgery. RESULTS: Prostatectomy was effective in reducing both symptoms (initial mean score 20.1 reduced to 7.4, P < 0.001) and symptom bother (initial mean score 14.4 reduced to 4.3, P < 0.001). Not all men experienced a good reduction in symptoms; 121 (3.9%) were worse, 301 (9.6%) were the same, and 721 (23%) experienced only slight improvement. The type of operation, grade of principal operator and use of pre-operative investigations were not associated with the extent of symptomatic improvement. Changes in symptom severity were highly correlated with changes in bothersomeness++ and disease-specific quality of life but not with generic quality of life. A third of men who were continent before surgery reported some incontinence 3 months later, although only 6% found it a problem. Two-thirds of men experienced retrograde ejaculation and 31% experienced some erectile impotence following surgery. CONCLUSIONS: Prostatectomy is effective in reducing symptoms in most men. Men who experience a substantial reduction in symptoms were more likely to report a favourable outcome. The study confirmed that approximately one-third of men reported an unfavourable result 3 months after their operation.

Aged↗

High level expression of the multidrug resistance (MDR1) gene in the normal bladder urothelium: a potential involvement in protection against carcinogens?

It has been suggested that expression of the P-glycoprotein transmembrane efflux pump (PGP), encoded by the multi-drug resistance (MDR1) gene, may play a role in the protection of epithelial tissues from a variety of local and systemic toxins. We report that in approximately 50% (6/11) of the population, MDR1 messenger RNA levels in the normal urinary epithelium are comparable to those found in the highest expressing tissues in the body, and suggest a role for PGP in the normal bladder urothelium. MDR1 mRNA levels in the normal urothelium do, however, vary over a 60-fold range between individuals, and furthermore are uniformly significantly lower (about 6-fold, P</=0.01) in all low-grade bladder carcinoma samples. On the basis of these observations we conclude that low MDR1 mRNA levels are a uniformly consistent characteristic of low-grade bladder tumours, and hypothesize that high MDR1 expression plays a role in protection of the normal bladder from carcinogen exposure, and that individuals with low normal bladder MDR1 mRNA levels may consequently be at an increased risk of developing bladder cancer. Furthermore,the low level of MDR1 expression generally found in low grade superficial tumours may predispose them to additional carcinogen exposure and in this way contribute to possible tumour progression. In addition, MDR1 mRNA levels were observed to be elevated in a significant proportion (approximately 25%, 8/30, P = 0.015) of high grade tumours compared to low grade samples, and may therefore represent a marker of bladder tumour progression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Teaching the teachers--a needs assessment of tutors for a new clinical skills course.

There is an increasing trend in undergraduate education towards teaching clinical skills from a community base. A new clinical curriculum was introduced in Newcastle upon Tyne in 1995, beginning with an integrated clinical skills course. Although the attitudes and views of general practitioners (GPs) towards community-based clinical teaching have previously been reported, their perceived training needs have not been formally identified. The aims of this study were to identify the competencies needed by GPs for community-based clinical skills teaching, to compare and contrast these needs with their hospital colleagues, and to use the results to develop a teaching programme for the clinical tutors involved in the new course. In order of priority, the GPs and hospital tutors expressed similar needs: small-group teaching skills, assessing student needs, giving effective feedback and assessment of student performance, with a preference for the teaching to be organized within local teaching units. Most GPs and hospital tutors (73 and 69%, respectively) requested a distance-learning pack to complement the teaching. General practitioners rated resources for improving their individual clinical skills more highly than their hospital colleagues: for example, videotapes demonstrating examination techniques. Forty-six per cent of GP tutors had received some formal training in teaching methods compared to 29% of hospital tutors. The implications of the results for developing a 'Teaching the Teachers' course for clinical tutors are discussed.

Clinical Competence↗

Ca2+ signalling in cultured smooth muscle cells from human bladder.

It has been suggested that the isolation and culture of human detrusor smooth muscle cells may provide useful insights into the physiology of the intact detrusor muscle. In the present paper, data are presented from cultured human bladder smooth muscle cells isolated from small, routinely available biopsies. Since the initiation of contractions involves a rise in intracellular Ca2+, this study has focused on the mechanisms involved in the rise of Ca2+ in cultured cells. Exposure of cells to bathing solutions with elevated K+ concentrations resulted in an increase in Ca2+ consistent with the presence of voltage-activated Ca2+ channels. Agonists, including carbachol, histamine and ATP, also activated repetitive transient increases in Ca2+ in the presence and absence of external Ca2+. Spontaneous Ca2+ transients were recorded in 31% of cells isolated from normal bladders. Such spontaneous and agonist-induced oscillations were not abolished in depolarized cells, suggesting that the mechanisms underlying the oscillations are not dependent on the cyclical operation of voltage-operated Ca2+ channels. However, the spontaneous activity was inhibited by the Ca2+ blocker verapamil, pointing to the presence of Ca2+ channels. The operation of an IP3-sensitive Ca2+ release mechanism was examined using saponin-permeabilized cells, which demonstrated that IP3 increased the rate of 45Ca2+ efflux. The conclusion from this study is that many of the mechanisms described in the intact tissue are operational in cultured cells.

Adenosine Triphosphate↗

Bladder cancer.

Bladder cancer is the fourth most common cancer in England and Wales. The most common presenting symptom is macroscopic haematuria. The management options for superficial and invasive bladder cancer depend on the stage at presentation. Most superficial bladder cancers are managed by transurethral resection and cytoscopic follow-up. The prognosis for patients with invasive bladder cancer is less good. The role of chemical, radiotherapeutic and surgical intervention are discussed.

Antineoplastic Agents↗

Surface localization of sacral foramina for neuromodulation of bladder function. An anatomical study.

A method is described for percutaneous localization of the sacral foramina, for neuromodulation of bladder function. We carried out an anatomical study of 5 male and 5 female human cadaver pelves. Using the described surface markings, needles were placed percutaneously into all sacral foramina from nine different angles. Paths of needle entry were studied by subsequent dissection. We observed that although it was possible to enter any sacral foramen at a wide range of insertion angles, the incidence of nerve root/vascular penetration increased with increasing angle of needle entry. Also, the incidence of nerve root penetration was higher with the medial approach compared with lateral entry. The insertion of a needle into the S1 foramen was associated with a higher incidence of nerve root penetration and presents a potential for arterial haemorrhage. On the other hand the smaller S3 and S4 nerve roots were surrounded by venous plexuses, presenting a potential source of venous haemorrhage during procedures. Our study suggests a new method for identifying the surface markings of sacral foramina and it describes the paths of inserted needles into the respective foramina. In addition, it has highlighted some potential risk factors secondary to needle insertion.

Electric Stimulation↗

Benign prostatic stromal cells are regulated by basic fibroblast growth factor and transforming growth factor-beta 1.

The current study was undertaken, using cultures of prostatic epithelial and stromal cells, to determine the functional interactions between androgens, basic fibroblast growth factor (FGF2) and transforming growth factor-beta 1 (TGF beta 1) and their importance in maintaining stromal homeostasis. Treatment of stromal cells with TGF beta 1 significantly increased intracellular FGF2 and FGF2 sequestered to the extracellular matrix. FGF2 was also detected in stromal conditioned medium (SCM), but at levels 70-fold less than found in cell lysates. TGF beta 1 (0.1 ng/ml) treatment caused an initial increase of 86% in secreted FGF2 levels, but high concentrations of TGF beta 1 (5 ng/ml) decreased FGF2 levels by 38%, relative to the untreated control. Further studies showed that epithelial conditioned medium (ECM), androgen-treated, stromal conditioned medium (ASCM), but not SCM were mitogenic for stromal cells. Both ECM and ASCM caused a threefold increase in DNA synthesis. FGF2 may be the mediator of these interactions, since the mitogenic effect of both ECM and ASCM was significantly reduced by the addition of anti-FGF2 neutralising antibody. We hypothesise that the lack of response of stromal cells to SCM is due to TGF beta 1 blocking the mitogenic effect of FGF2. Thus down-regulation of TGF beta 1 synthesis, by androgens, results in stromal proliferation by ASCM.

Cell Division↗

Conventional urodynamics and ambulatory monitoring in the definition and management of bladder outflow obstruction.

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.

Aged↗

Transcutaneous electrical nerve stimulation and temporary S3 neuromodulation in idiopathic detrusor instability.

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.

Electric Stimulation Therapy↗

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

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

Electromyography↗

Urinary secretory immunoglobulin A and free secretory component in pyelonephritis.

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

Adult↗