Biomedical subjects
Publications and source records attributed to D Hrouda.
Symptomatic presentation of partial duplication of the ureter in adults is rare. However, there are reports of such conditions being treated with surgical correction with varying degrees of success. We present the case of a 23-year-old woman who underwent what is, to our knowledge, the first reported laparoscopic ureteropyelostomy for symptomatic "yo-yo" reflux.
OBJECTIVE: To evaluate the results of endopyelotomy in children, an established method in adult practice as a treatment for pelvi-ureteric junction (PUJ) obstruction. PATIENTS AND METHODS: Endopyelotomies undertaken between 1992 and 1999 by one surgeon in an established endourology unit were reviewed retrospectively. Children aged > 5 years presenting with pain and obstruction on isotope renography were selected for endopyelotomy. Patients with crossing vessels detectable on spiral computed tomography were treated by open pyeloplasty. Access to the renal pelvis was provided by a uroradiologist. Endopyelotomy was carried out through an Amplatz sheath of (median) 26 F. After applying traction to invaginate the PUJ an incision was made postero-laterally using electrocautery via an 11 F paediatric resectoscope. Stenting was maintained for 6 weeks. In all, 13 patients (median age 10 years, range 5-14) were treated; two had associated calculi. RESULTS: The symptoms resolved and the obstruction was relieved in only six patients, with a median (range) follow-up of 50 (26-68) months. The seven patients in whom endopyelotomy failed, as indicated by persistent pain, proceeded to open pyeloplasty at a median (range) of 4 (1.3-79) months. Of these, two had presented with associated multiple calculi and significant hydronephrosis (one with an associated duplex system) and three had crossing lower pole vessels at open operation. One developed a urinoma after the original endopyelotomy and one had a retained stent fragment removed at the time of pyeloplasty. CONCLUSIONS: Endopyelotomy in the symptomatic child requires a careful preoperative evaluation. Crossing lower pole vessels warrant an open pyeloplasty.
Advanced prostate cancer remains incurable with standard treatment options. Immunotherapy may be a realistic alternative given the growing evidence that the immune response can affect the growth of other solid tumours and the regulation of both specific and shared prostate cancer antigens. Early studies suggest that both non-specific and specific vaccines can effect relevant animal models and clinical trials based on these observations are now in progress. A number of other approaches including gene therapy with HSVtk are already undergoing clinical studies (Herman et al. Hum Gene Ther 1999; 10: 1239-1249). Prostate Cancer and Prostatic Diseases (2000) 3, 303-307
OBJECTIVE: To investigate cancer immunotherapy using whole allogeneic (differing tissue-type) tumour cells as vaccines in the rat prostate cancer model. Materials and methods Two rat models of prostate cancer were used; MAT-LyLu tumours which grow in Copenhagen rats and PAIII tumours which grow in Lobund-Wistar rats, with crossover of the cell lines to test allogeneic vaccination. The cell lines were immunologically characterized by flow cytometry. Irradiated tumour cells were administered as subcutaneous vaccines either before tumour challenge or after tumour establishment (both subcutaneous). A preparation of heat-killed Mycobacterium vaccae bacilli (SRL172) was used as an adjuvant to increase vaccine efficiency. RESULTS: Flow cytometry analysis of the cell lines showed that the PAIII cells had higher levels of major histocompatibility complex (MHC) class I and intercellular adhesion molecule (ICAM-1) expression than the MAT-LyLu cells. However, both tumour cell lines were rejected in their allogeneic hosts. Prophylactic vaccination with allogeneic MAT-LyLu cells protected against PAIII tumour challenge in Lobund-Wistar rats, with 80% of animals surviving for > 5 months, compared with 40% for animals receiving autologous cells. The immunity was prolonged, as rats were protected when rechallenged 5 months later. In Copenhagen rats allogeneic PAIII cells protected against the more aggressive MAT-LyLu tumour challenge only when the cells were combined with SRL172. Initial therapy experiments showed that vaccination with the cell lines mediated only limited tumour regression in the Lobund-Wistar rats. CONCLUSION: The allogeneic tumour cell vaccination model described is valuable for assessing the principle and efficacy of allogeneic prostate cancer cell vaccines for clinical use.
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Prostate cancer is one of the leading causes of cancer deaths in the western hemisphere. A number of different gene therapy strategies are currently being evaluated. The ex vivo and many of the in vivo therapies involve stimulating a specific antitumor immune response. Autologous vaccines involving interleukin-2 (IL-2)- or granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced whole tumor cells showed great promise in animal models. Clinical trials of these and other vaccine strategies are underway. In vivo gene therapies involving the replacement of mutant tumor-suppressor genes, antisense strategies, and the insertion of suicide genes are also being evaluated in prostate cancer.
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OBJECTIVE: To assess whether a new heat-killed Mycobacterium vaccae preparation (SRL172), which enhances cell-mediated immunity and has been proposed for use as an immunotherapeutic agent against cancer, is safe in patients with advanced hormone-refractory prostate cancer, can stimulate desirable cytokine changes in these patients and modulate the progression of the disease. PATIENTS AND METHODS: Ten patients were given SRL172 intradermally at regular intervals. The serum prostate specific antigen (PSA) level was used as a surrogate marker of response. The proportion of peripheral blood mononuclear cells (PBMC) secreting interleukin 2 (IL2), interferon gamma (IFNgamma) and interleukin 4 (IL4) was measured by flow cytometry (FACS) before and after vaccination to assess whether the treatment induced a Th2 (predominantly humoral) to Th1 (predominantly cell-mediated) switch. RESULTS: There were no significant adverse events. In five patients the serum PSA declined during the trial and in two of these there was no concomitant change of therapy apart from vaccination with SRL172. Before vaccination with SRL172 patients had a low proportion of PBMC producing IFNgamma and IL2 (all 10) and a higher proportion secreting IL4 (all three tested), suggesting a predominantly Th2 cytokine profile. After vaccination the proportion of IL4 secreting PBMC fell in all three patients tested. The proportion of IL2 secreting PBMC increased in three patients whose PSA fell. The proportion of IFNgamma-secreting cells remained depressed in nine of 10 patients. CONCLUSION: Two patients with advanced hormone-refractory prostate cancer had a PSA response to the vaccination with SRL172. The proportion of PBMC secreting IL2 is a potential marker of response to immunotherapy.
OBJECTIVE: To evaluate the potential of heat-killed Mycobacterium vaccae (SRL172) as a nonspecific immunostimulant and as an adjuvant to whole tumour cell vaccination in the rat model of prostate cancer. MATERIALS AND METHODS: SRL172 was used as a vaccine in the prevention and treatment of subcutaneous tumours in rats. Prevention experiments were conducted using subcutaneous MAT-LyLu tumours in Copenhagen rats, comparing vaccination with SRL172 alone, SRL172 plus autologous cells, and bacille Calmette-Guèrin (BCG) plus autologous cells before tumour implantation. Treatment experiments were conducted using subcutaneous MAT-LyLu tumours in the Copenhagen rat and subcutaneous PAIII tumours in the Lobund-Wistar rat. Tumours were induced by subcutaneous injection with tumour cells. Animals were then vaccinated with autologous cells, autologous cells plus SRL172, or SRL172 alone. RESULTS: SRL172 was effective as an adjuvant to autologous whole tumour cell vaccination in the prevention of MAT-LyLu tumours and the survival benefit was equivalent to that provided when the adjuvant was live-attenuated BCG. SRL172 alone did not reduce tumour take or tumour growth in this model and neither strategy was effective in delaying the growth of established MAT-LyLu tumours. In the Lobund-Wistar rat vaccination with autologous whole tumour cells and SRL172 significantly delayed the growth of established tumours. CONCLUSION: Mycobacterium vaccae deserves further evaluation as an adjuvant to whole tumour cell vaccination in a phase I clinical trial in patients with prostate cancer.
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OBJECTIVE: To determine the current practice among British urologists for obtaining written consent for flexible cystoscopy and other minor procedures under local anaesthesia. METHODS: Postal questionnaires were sent to full members of The British Association of Urological Surgeons practising in the UK asking if they obtained written informed consent for local anesthetic procedures, e.g. flexible cystoscopy, urethral dilatation, and urethral catheterization for retention, for urodynamics or for intravesical chemotherapy. They were also asked whether they recorded that the risks and benefits of the procedure had been explained to the patient. RESULTS: Respondents were divided on whether they obtained written consent for flexible cystoscopy and urethral dilatation. Most did not obtain written consent for catheterization for retention, urodynamics, intravesical chemotherapy or suprapubic catheterization. The policy was inconsistent both between and within urologists. CONCLUSION: Given the medicolegal importance of informed consent, consensus among urologists is required so that national guidelines can be developed and a more rational policy applied.
OBJECTIVE: To examine whether a strategy of bladder conservation is reasonable in patients with multiple frequent superficial recurrences of transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Fifty-four patients with pTa/pT1. G1/G2 tumours at diagnosis, with five or more recurrences at two or more cystoscopies within 2 years of diagnosis and a minimum follow-up of 4 years were identified. The patients were categorized according to outcome, i.e. disease settled, continuing high-activity disease and disease progression. RESULTS: Forty-four patients did not progress, of whom 16 continued to have high-activity disease and 28 settled to a lower disease activity. One patient had a cystectomy for superficial disease. Nine patients progressed, six with muscle invasion in the bladder and three elsewhere in the urinary tract. Neither grade nor stage were predictive of recurrence. All but one of the patients with progression had both multicentric tumours at diagnosis and a positive cystoscopy at 3 months. Three patients died from their bladder cancer. CONCLUSION: A policy of endoscopic resections and intravesical chemotherapy or bacille-Calmette-Guèrin, with cystectomy reserved until muscle-invasive disease develops, does not significantly compromise survival in patients with high-activity superficial TCC. Cystectomy for superficial disease is rarely necessary.
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Prostate cancer is one of the leading causes of cancer deaths in the Western world and current therapies are of limited efficacy in advanced disease. Both ex vivo and in vivo gene therapy strategies offer exciting new possible approaches to the management of this disease. Ex vivo gene therapy involving interleukin-2 or granulocyte-macrophage colony-stimulating factor transduced whole tumour cell vaccines has shown great promise in animal models. The feasibility of in vivo corrective gene therapy involving the replacement of mutant tumour suppressor genes, antisense strategies and the insertion of suicide genes has been demonstrated in preclinical models. Several of these therapies are now entering phase I/II studies in patients with prostate cancer.
The associative network theory of memory [2] is outlined along with the concepts of mood congruity and state dependent learning. Two experiments are reported which investigate the occurrence of these effects where memory for pain is concerned. In experiment 1 the performance of 25 chronic pain patients was compared with that of 25 non-patient controls on a test involving both immediate and delayed recall of a mixed list of stimulus words of 3 types: pain-related, negative or neutral. No significant group differences were found in overall rates of immediate recall. As predicted, however, pain patients recalled more pain-related words than non-patient controls (P less than 0.001). On delayed recall the same significant group x word-type interaction was obtained (P less than 0.02), but in addition the non-patient controls recalled significantly more words overall (P less than 0.02). These results provide some evidence for the occurrence of a mood congruity effect. Experiment 2 investigated state dependent learning and mood congruity effects in experimentally induced pain. Twenty volunteer subjects were allocated to 1 of 4 conditions in which a wordlist (as in experiment 1) was presented following either a painful stimulus (cold pressor test) or a non-painful one (warm water) and was then recalled immediately following further exposure to stimulus conditions which were congruent with the original stimulus (warm/warm and cold/cold conditions) or non-congruent (warm/cold and cold/warm conditions). A 3-way split plot ANOVA yielded no significant main effects for group or word-type, but a significant interaction emerged between state at encoding and at recall (P less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)