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Biomedical subjects

A D Joyce

Publications and source records attributed to A D Joyce.

At least 19 recordsLinked to original sources

The impact of the Dornier Compact Delta lithotriptor on the management of primary ureteric calculi.

OBJECTIVE: To assess the effectiveness of the Dornier Compact Delta lithotriptor on the management of in situ primary ureteric stones. PATIENTS AND METHODS: 137 patients with primary ureteric stones were treated at a tertiary urological center using the latest Dornier Compact Delta lithotriptor between January 1999 and January 2002. Effectiveness of lithotripsy, retreatment rate, reasons for failure and complications were assessed. RESULTS: 102 males and 35 females with primary ureteric stones underwent ESWL treatment at our center. 74 patients had upper, 37 middle and 26 lower ureteric locations respectively. Mean stone size was 10 mm (range 8-25 mm). Mean numbers of sessions required were 1.8 (range 1-3). The retreatment rate was 33% in upper ureteric, 29% in mid ureteric and 26% in lower ureteric locations respectively. Complete clearance rate at 3 months was 86% for upper ureteric, 79% for mid ureteric and 79% for lower ureteric. 29 patients had auxiliary treatment in the form of double J ureteric stenting or percutaneous nephrostomies. 26 patients failed treatment and underwent ureteroscopic or ante grade percutaneous removal. Stone size was the only significant factor correlating with failure. The mean size of stones in the successful group was 12 mm as compared to 17 mm in failure group. The likelihood of success following a failed second session (no disintegration or disintegration with fragments more than 6 mm) of treatment was 13.4%. Complications including, steinstrasse, colic, UTI and petechial haemorrhage were seen in 35 patients. One patient developed pyonephrosis and subsequently required nephrectomy. CONCLUSION: An electromagnetic shock wave lithotriptor using the EMSE-150 shock wave emitter is an effective in situ treatment of primary ureteric stones. Patients with large stone size are likely to have a higher retreatment rate, more auxiliary procedures and complications. Having a failed second treatment session, the likelihood of a successful outcome after third session of ESWL is poor.

Adolescent↗

Isolation of germ cells from human testicular tissue for low temperature storage and autotransplantation.

OBJECTIVE: To develop a new protocol for conserving fertile potential in men undergoing sterilizing chemotherapy by low temperature banking of germ cells which can be returned to the patient's testes after thawing. DESIGN: Isolation of human and murine germ cells for comparing cellular viability after cooling to liquid nitrogen temperatures by the use of different cryoprotective agents and for infusion into the testis. SETTING: Laboratory research environment. PATIENT(S): Men undergoing routine surgery in a urology department. INTERVENTION(S): Testicular biopsy. MAIN OUTCOME MEASURE(S): Cellular viability and infusion of seminiferous tubules. RESULT(S): After isolation using a two-step enzymatic disaggregation protocol, 66% to 87% of germ cells from human and murine specimens, respectively, were still viable. Cell survival was similar in four commonly used cryoprotective agents after cooling to liquid nitrogen temperatures. Seminiferous tubules infused by back flow with dye solution via the rete testis were filled with an efficiency of 55%. CONCLUSION(S): Judging from the high viability of unfractionated germ cells, it is feasible to isolate germ cells from testicular biopsies for low temperature banking with the aim of attempting to restore fertility after iatrogenic sterilization.

Animals↗

The interaction of nitric oxide and prostaglandins in the control of corporal smooth muscle tone: evidence for production of a cyclooxygenase-derived endothelium-contracting factor.

OBJECTIVE: To investigate the interaction of endothelium-derived nitric oxide (NO) and prostaglandins (PGs) in regulating corporal smooth muscle tone in vitro. Materials and methods Strips of rabbit corpus cavernosum were mounted in organ chambers for the measurement of isometric tension. Strips were submaximally contracted with noradrenaline and concentration-response curves (CRCs) to acetylcholine (ACh) were constructed before and after treatment with 5 micromol/L atropine, 20 micromol of the cyclooxygenase inhibitor indomethacin and 10 micromol of the PGH2/thromboxane A2 receptor antagonist SQ29548. The NO synthase (NOS) inhibitors L-NG-monomethyl arginine (L-NMMA) and L-NG-nitroarginine (L-NOARG) were added to strips at tonic tension in the presence and absence of indomethacin, and after this CRCs to ACh were constructed. RESULTS: The addition of ACh to strips produced a concentration-dependent relaxation which was inhibited by atropine. Indomethacin, but not SQ29548, significantly increased relaxation to ACh. Relaxation to ACh was impaired by L-NMMA, but adding ACh to strips treated with L-NOARG resulted in contractile responses, whilst both effects were reversed by indomethacin. L-NMMA and L-NOARG led to increases in tonic tone which were unaffected by indomethacin. CONCLUSIONS: In rabbit corpus cavernosum there is a tonic release of NO which does not appear to be inhibited by a vasoconstrictor prostanoid. Endothelium-dependent relaxation to ACh results in the dual production of NO and a cyclooxygenase-derived endothelium contracting factor which acts in opposition to NO; this factor is unlikely to act on PGH2/TXA2 receptors.

Acetylcholine↗

The efficacy of a range of contact media as coupling agents in extracorporeal shockwave lithotripsy.

OBJECTIVE: To determine if the nature of the coupling agent normally used between the lithotripter and the patient affects the stone fragmentation rate during extracorporeal shock wave lithotripsy. MATERIALS AND METHODS: A jig designed to hold 'phantom' 10-mm stones at the focal point was fixed against the shock wave delivery point of an electromagnetic lithotripter (Dornier Compact, Germany). A layer of either petroleum jelly (Vaseline, Cheeseborough-Ponds Ltd, London, UK) ultrasonography jelly, a eutectic mixture of local anaesthetic (EMLA) cream, Instillagel (Farco-Pharma, Cologne, Germany) or a commercial water-soluble lubricating jelly was placed between the jig and shockwave head, and the number of shock waves required to fragment the stones was recorded. RESULTS: Significantly more shock waves were required to fragment stones when petroleum jelly was used as the coupling agent than with all the other agents under test, whereas significantly fewer shock waves were required when using Instillagel or lubricating jelly than for all other agents. CONCLUSION: The coupling agent used in water-free lithotripsy can affect the stone fragmentation rate and should not be considered inert. Ultrasonography jelly is probably the optimum agent available for use as a lithotripsy coupling agent.

Emollients↗

The effect of cyclic GMP on rabbit corporal smooth muscle tone and its modulation by cyclo-oxygenase products.

Corporal smooth muscle (CSM) tone is maintained by a finite balance between relaxant and contractile neurotransmitters. The aim of these experiments was to ascertain the degree to which cyclic GMP is involved in these interactions. We also sought to elucidate the pharmacological mechanism of action of MB in rabbit corpus cavernosum (RCC), an important tool in nitric oxide research. Using an organ chamber technique, strips of RCC were treated with the guanylate cyclase inhibitors Methylene Blue (MB) and LY83583; 100 microM MB led to increases in resting tension which were antagonized by indomethacin, nifedipine, phentolamine, but not superoxide dismutase (SOD). Contractile responses to noradrenaline (NA) were increased and relaxation to ACh was impaired by both MB and LY83583 and reversed with indomethacin, but not SOD. Pyrogallol had no effect on agonist-induced responses. The pharmacological action of MB in RCC does not depend on the generation of superoxide anions. Endothelium-dependent relaxation in RCC results in activation of soluble guanylate cyclase and release of a stable endothelium derived contracting factor(s), which is likely to be a constrictor prostanoid(s). Tonic production of cGMP in RCC inhibits the presynaptic release and contractile effects of NA and can be modulated by cyclo-oxygenase inhibition, demonstrating the important interaction and functional antagonism between cGMP and prostaglandins in the control of CSM tone.

Acetylcholine↗

Minimally invasive treatment of urinary tract calculi in children.

OBJECTIVE: To report experience of a broad multimodality approach to the treatment of calculi in children using extracorporeal shock wave lithotripsy (ESWL), ureteroscopy/laser lithotripsy, lithoclast and percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: The treatment and outcome were reviewed in 43 children managed by a range of minimally invasive modalities, either singly or in combination, between 1990 and 1997. These patients represent a selected group deemed suitable for minimally invasive management during a period of developing experience with these techniques. Of this cohort, six children had previously undergone open stone surgery and contributory metabolic abnormalities were identified in seven. ESWL was the sole treatment modality in 24 children (56%). In five children (12%) ureteroscopy/laser lithotripsy was combined with ESWL, eight (18%) underwent ureteroscopy/laser lithotripsy alone, whilst three with bladder stones were treated with the lithoclast. Combined therapy including PCNL was required in three patients. RESULTS: Of the 43 children treated, 38 (88%) were rendered stone-free. Metabolic disorders accounted for three of the five cases of residual calculi. Complications requiring intervention occurred in two children (7%) and three subsequently underwent open pyelolithotomy or ureterolithotomy after unsuccessful minimally invasive treatment. CONCLUSIONS: Used selectively, the range of minimally invasive procedures available for adults, including ureteroscopy and PCNL, can be safely and effectively extended to the treatment of urinary tract calculi in children. The role of open surgery will diminish further with the availability of specialized instruments for paediatric PCNL.

Adolescent↗

Extra-anatomic stents in ureteric obstruction: experience and complications.

OBJECTIVE: To assess the role of extra-anatomic stents (EAS) as a means of urinary diversion in patients with ureteric obstruction secondary to malignancy. PATIENTS AND METHODS: The technique for inserting EAS in patients with ureteric obstruction was described previously; to date, 13 patients (seven women and six men, mean age 45.3 years, range 22-78) have been treated. All patients had ultrasonographic evidence of hydronephrosis and/or significant biochemical evidence of renal impairment. Patients had advanced malignancy and one patient an abdominal aortic aneurysm. RESULTS: Urinary diversion was successful in all patients; two survived for more than 1 year, with stent changes at 6-monthly intervals. In three patients the stents were replaced by percutaneous nephrostomies because of problems with leakage or infection. The remaining patients died with functioning EAS in situ. CONCLUSIONS: In patients with ureteric obstruction secondary to malignancy or medical conditions excluding them from more invasive surgery, EAS provide a further therapeutic option instead of a permanent nephrostomy, which has associated inherent problems. This technique is not without potential problems and careful selection of patients remains vital in this difficult area.

Adult↗

The evaluation of sexual function in men presenting with symptomatic benign prostatic hyperplasia.

OBJECTIVE: To evaluate quantitatively and qualitatively the degree of sexual dysfunction in an unselected population of men attending a prostate-assessment clinic using a sexual-function inventory, and to ascertain the degree of correlation between sexual dysfunction, urinary symptoms and age. PATIENTS AND METHODS: In all, 168 men with symptomatic BPH attending a prostate assessment clinic were investigated prospectively using the International Prostate Symptom Score (IPSS), BPH Impact Index (BPHII), a measurement of urinary flow rate and residual urine volume, and a sexual function questionnaire. The results were assessed using Spearman's rank order correlation to discern any correlations between the measured variables. RESULTS: The data from 140 patients were available for analysis; of these, low scores were obtained in 59% for sexual drive, in 56% for erections (with 46% of men satisfying the National Institute of Health criterion for impotence) and in 38% for ejaculation. There was a statistically significant rank order correlation between age and the sexual symptom scores for each of the three categories (sexual drive, erection and ejaculation), but no correlation between age and the problem assessment scores for these domains, suggesting that the older patients are just as bothered by their sexual dysfunction as the younger men. Furthermore, the BPHII scores correlated weakly but significantly with all aspects of sexual function, including overall sexual satisfaction, in contrast to the poor correlation seen with the total IPSS and sexual function scores. CONCLUSION: There is a significant number of patients with symptomatic BPH who have sexual dysfunction, with the proportion increasing with advancing age and with the older men still showing a high degree of bother from their symptoms. Sexual function scores were better correlated with BPHII scores than with the total IPSS, although some of the individual IPSS questions correlated well.

Adult↗

Cytokeratin 20 as an objective marker of urothelial dysplasia.

OBJECTIVE: To investigate the dysregulation of cytokeratin 20 (CK20) expression in urothelial dysplasia and its potential as a diagnostic aid. PATIENTS AND METHODS: Twenty-two patients were selected on the basis that they had undergone one or more biopsies showing dysplasia before the development of a transitional cell carcinoma (TCC): 15 of these patients also had a prior history of TCC. The dysplasia was classified as mild in 12, moderate in 14 or severe dysplasia/carcinoma in situ in 10 patients, ensuring that a spectrum of morphological appearances was represented. Control biopsies were obtained from seven children undergoing bladder reconstructions and 23 patients with recurrent urinary tract infections, haematuria or functional bladder symptoms, but no history of TCC. RESULTS: The expression of CK20 was restricted to superficial 'umbrella' cells and occasional intermediate cells in the control biopsies, even in the presence of severe inflammation. In 31 of the 36 cases of dysplasia complete loss of restriction was seen at least focally with positive expression in all layers of the urothelium. CONCLUSION: The abnormal expression of CK20 is a reliable, positive marker of urothelial dysplasia in the urinary bladder. Immunostaining for CK20 is therefore a useful adjunct to morphology in the diagnosis of dysplasia, of particular value in the distinction from reactive states where diagnostic difficulties are greatest.

Aged↗

Cytokeratin 20 expression by non-invasive transitional cell carcinomas: potential for distinguishing recurrent from non-recurrent disease.

Although approximately 50% of patients with non-invasive (Ta) papillary transitional cell carcinoma show no recurrence of their disease, current histopathological approaches cannot distinguish this sub-group from those patients in whom the disease will recur. In this 5 year retrospective study, we have shown that cytokeratin 20 (CK20) was expressed in 19 of 29 (65.5%) of non-invasive papillary tumours of grades 1 or 2. CK20 expression patterns were predictive of disease non-recurrence in a sub-group of eight patients, representing 51.7% of patients with non-recurrent disease. In normal bladder mucosa, CK20 expression was restricted to the terminally-differentiated superficial cell. In eight CK20-positive tumours which showed no recurrence at 5 years, CK20 expression was either restricted to, or most intense in, the luminal cells of the papillae. This pattern of expression was not seen in any of the 15 tumours from the recurrent group. Disruption of normal CK20 expression was highly significantly correlated with recurrent tumours. These results suggest that changes in the expression of differentiation-associated antigens, such as CK20, may be useful in predicting benign versus malignant behaviour and may, therefore, be useful in defining treatment strategies.

Adult↗

Bromodeoxyuridine labelling of transitional cell carcinoma of the bladder--an index of recurrence?

Nineteen patients with newly diagnosed transitional cell carcinoma of the bladder consented to receive an intravenous bolus of bromodeoxyuridine (BrdUrd) 3 to 6 h prior to transurethral resection of bladder tumour. Routine paraffin embedded sections were stained with anti-BrdUrd monoclonal antibody in order to determine the S phase fraction of the bladder tumours and to correlate this with tumour grade, category and the development of recurrence during follow-up. BrdUrd labelling of nuclei was reliably detected in 100% of the tumours. The mean labelling index of Ta tumours (n = 8) was 3.14%; in T1 tumours (n = 7) it was 8.6% and in T2-3 tumours (n = 4) it was 16.4%. A similar correlation was found in association with tumour grade. The patients were followed up for a mean of 23 months (range 18-30). Seven of the 15 superficial tumours recurred during the period of follow-up. These tumours had a mean labelling index (at diagnosis) of 8.4%, whereas the tumours that did not recur had a mean labelling index of 3.4%. The in vivo determination of BrdUrd uptake in transitional cell carcinoma of the bladder may be useful in predicting which superficial tumours are likely to recur following resection and so rationalise both the time to follow-up and intravesical chemoprophylaxis.

Aged↗

[Urothelial cancer metastases after implantation of tumor cells under the kidney capsule].

In this study we used the subrenal capsule site of C57BL/6J mice to assess the tumorigenic and metastatic potential of established urothelial cell lines in a syngeneic murine model. High tumor take and subsequent removal of the primary tumor by nephrectomy resulted in the extended lifespan of the animals enabling the formation of secondary tumor growth. To test this model we have used a panel of cell lines expressing constitutively, or following transfection, ras oncogene products. All cell lines constitutively expressing ras oncogenes (K, H, or N-ras) were tumorigenic and metastatic in this assay. One non tumorigenic cell line (BBN3) and one tumorigenic but non-metastatic cell line (SH264), remained non-metastatic following transfection with the pSV2-neo gene but formed micrometastases in the lung when a ras oncogene was introduced in the same manner. Expression of altered ras proteins following transfection in these two cell lines was demonstrated using an H-ras specific antibody in Western blot analysis. This study demonstrates the value of the subrenal capsule site as a metastatic assay for bladder cancer and the potential involvement of ras oncogenes in urothelial cell metastasis.

Animals↗