ISSN:0007-1331    

DOI:10.1111/j.1464-410X.1995.tb07701.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Objective To establish whether the use of interferonalpha might result in improved survival, using two large series of patients with advanced renal cell cancer treated during studies of chemotherapy and biological therapy, respectively.Patients and methods Patients treated either in the Eastern Cooperative Oncology Group (ECOG) chemotherapy protocols (327 patients) or in protocols employing interferon as part of a European randomized study or phase II studies at the Norwegian Radium Hospital (231 patients) were retrospectively analysed. Groups for comparison were matched by exclusion of those with an ECOG performance status>2, no prior nephrectomy, brain metastases or prior chemotherapy. Univariate analysis of prognostic factors for survival was performed by the log rank method and multivariate analysis by Cox regression.Results Univariate analysis of the whole population showed that performance status, time from diagnosis to treatment, sites of metastases and the use of interferon carried the greatest prognostic significance. In multivariate analysis, the use of interferon remained a significant predictor of survival (P<0.001). Subgroup analysis suggested that the impact of interferon treatment was greatest in those patients with two of the following characteristics; good performance status, an interval of<2 years from diagnosis to treatment and no more than one site of metastasis.Conclusion Although a prospective randomized trial is needed to establish definite benefit from the use of interferon in advanced renal cell cancer, this analysis supports the rationale for performing such a trial, particularly in patients with relatively good prognostic features. Patients should be entered into the Medical Research Council study comparing interferon with medroxyprogesterone acetate.

ISSN:0007-1331    

DOI:10.1111/j.1464-410X.1995.tb07702.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Objective To demonstrate the specific distribution of muscarinic receptors in the rat urinary bladder and to investigate the effects of afferent and efferent denervation on the density and distribution of muscarinic receptors.Materials and methods Urinary bladders were obtained from female rats which had been injected with vehicle (control), or neonatally with capsaicin (NC, afferent denervation) or which had their pelvic plexus removed (post‐ganglionic denervation, PGD, efferent denervation). Tissue sections were used in radioligand‐binding studies and for autoradiography with the muscarinic receptor ligand l‐quinuclidinyl[phenyl‐4–3H]benzilate (QNB).Results Binding of QNB was saturable and specific to a single population of binding sites, with a mean dissociation constant (Kd) of 1.05 ± 0.14 nmin controls and 0.90 ± 0.13 nmin rats with PGD. Post‐ganglionic denervation caused a 37% increase in maximal binding (Bmax) of QNB from 437.1 ± 39.1 fmol/mg protein (control group) to 599.1 ± 4.5 fmol/mg protein (P<0.02). Autoradiograms revealed muscarinic binding sites over the smooth muscle, but none over the epithelium. Smooth muscle binding sites were doubled after PGD but were unchanged after NC treatment.Conclusion Muscarinic receptors were localized over the smooth muscle of the rat bladder and were increased after post‐ganglionic denervation. This increase may be responsible for the increased sensitivity to muscarinic agonists reported to occur after bl

ISSN:0007-1331    

DOI:10.1111/j.1464-410X.1995.tb07703.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Objectives To characterize [3H]α,β‐methylene adenosine 5′‐triphosphate ([3H]α,β‐MeATP, a radioligand for P2X‐purinoceptors) binding sites in the washed homogenates and membrane preparations of human urinary bladder and, using autoradiography, to localize [3H]α,β‐MeATP binding sites in human bladder.Materials and methods Specimens were obtained from the fundus of the urinary bladder of male patients aged 56–79 years. The washed homogenates or membrane preparations of the bladder specimens were incubated with [3H]α,β‐MeATP and the bound and free radioligand separated by filtration. For autoradiography, cryostat sections were incubated with 10 nM [3H]α,β‐MeATP, washed, dried and exposed for 2 weeks to emulsion‐coated coverslips. In both experiments, 100 μmβ,γ‐methylene ATP was used to determine non‐specific binding.Results Six of 16 specimens in the binding assay and three of seven specimens in the localization study showed specific [3H]α,β‐MeATP binding. The binding process was saturable and the specific binding sites were composed of a high‐and low‐affinity component. The specific binding to membrane preparations was reduced in the presence of Mg2+in the incubation medium. Competitive displacement experiments showed that the order of potency of the unlabelled ligands to displace the [3H]α,β‐MeATP binding was α,β‐methylene ATP<β,γ‐methylene ATP

ISSN:0007-1331    

DOI:10.1111/j.1464-410X.1995.tb07704.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Objective To investigate dynamic changes in the obstructed rat ureter and to evaluate the usefulness of the rat model in the study of obstructive uropathy.Materials and methods Unilateral ligation of the ureter was performed in 26 rats. After ureteric ligation, four to seven rats were killed and examined after 1, 3, 7, 10, and 14 days. The severity of hydroureter and hydronephrosis was assessed by pyelography and the hydroureter‐hydronephrosis index. The middle portion of the ureter was prepared for light and electron microscopic observation. Five rats which received a sham operation were also examined as controls.Results The severity of hydroureter and hydronephrosis in the ligated ureters progressively increased during the period of obstruction (P<0.005) and reached a maximum 10–14 days after ligation. Hypertrophy of the smooth muscle layer developed on the third day after ligation and proliferation of submucosal connective tissue occurred on the 10th day after ligation. The changes in smooth muscle and connective tissue layers also progressed consistently during ureteric obstruction (P<0.001 and<0.005, respectively). The number and size of granular endoplasmic reticulum and Golgi apparatus in the smooth muscle cells increased after ureteric ligation and then caveolae exocytosis developed. Deposition of collagen fibres between muscle cells became apparent later.Conclusion The rat model of hydrouropathy demonstrated a clear temporal relationship between the severity of hydroureter and the dynamic changes in the obstructed ureter and could be used as a conventional method for the study of obstructive ure

ISSN:0007-1331    

DOI:10.1111/j.1464-410X.1995.tb07705.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Objective To investigate the role of urinary measurements of an angiogenic factor, basic fibroblast growth factor (bFGF), in the assessment of patients with bladder cancer.Patients and methods Urine from 83 patients was assayed using a commercially available ELISA for bFGF. Thirty‐eight patients had a bladder tumour and 21 had a history of bladder cancer but no disease at the time of testing. Twenty‐four patients acted as controls, 16 of whom were about to undergo transurethral resection of the prostate (TURP) for benign prostatic hypertrophy (BPH) and eight who had no urological disease.Results Median urinary bFGF was higher in patients with active bladder cancer than in those with a clear cystoscopy (5.20 and 2.13 ng/g creatinine, respectively;P<0.005). Median urinary bFGF was also elevated in patients about to undergo TURP (4.52 ng/g creatinine). Using a threshold value of 6.0 ng/g creatinine, the sensitivity of the test for detecting cancer was 42% and specificity was 88%. At a threshold value of 4.0 ng/g the sensitivity was 62% and the specificity 70%.Conclusion The relationship between urinary basic FGF and the presence of bladder cancer was significant. The test is not sufficiently sensitive or specific to use as a screening test for bladder cancer but may be very useful in monitoring the effectiveness of systemic therapies in bladder cancer. Elevated levels of bFGF in the urine of patients about to undergo TURP suggests a role for bFGF in the pathogenesis of

ISSN:0007-1331    

DOI:10.1111/j.1464-410X.1995.tb07706.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Objective To examine the place of pelvic exenteration in the palliation of advanced and recurrent pelvic tumours.Patients and methods The notes of patients referred for palliative exenteration were reviewed retrospectively. Fourteen patients (three men, mean age 52 years, and 11 women, mean age 61 years) with a variety of pelvic tumours associated with severe symptoms, had a laparotomy with a view to pelvic exenteration and 10 underwent total or anterior exenteration.Results Eight patients achieved excellent or good palliation based on survival and quality of life assessment, and two received no benefit. Four of eight patients were alive and apparently free of tumour at a mean of 17 months after surgery. Four were alive, symptom‐free but with evidence of malignancy at a mean of 19 months. Two patients who received no benefit died at 2 and 7 months after surgery. The planned exenteration was abandoned in four patients; three of these four patients were dead at a mean of 13 months and one was alive at 12 months.Conclusion Our results confirm that with careful selection and appropriate multi‐speciality care, aggressive pelvic surgery is of value in the palliation of some tumo

ISSN:0007-1331    

DOI:10.1111/j.1464-410X.1995.tb07707.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Objective To describe the long‐term results of treating patients with advanced urothelial cancer using a combination of methotrexate, vinblastine, doxorubicin and cisplatin (M‐VAC).Patients and methods Fifty‐one patients (37 men and 14 women, median age 66 years, range 41–82) with inoperable or metastatic carcinoma of the bladder, ureter or renal pelvis were treated with M‐VAC and their responses evaluated for up to 7 years. Relative dose intensity (RDI) was calculated by dividing the actual dose intensity by the projected total dose intensity and related to outcome. Overall survival was assessed from the date of initiation of treatment with M‐VAC, using the Kaplan‐Meier method.Results Of the 51 patients, 10 (20%) had a complete and 18 (35%) had a partial response, giving an overall response rate of 55% (95% CI, 41–68%). There was no significant difference in the median values of RDIs with response to the M‐VAC regimen. The median duration of response was 11.9 months for the 10 patients with a complete response and of these, eight relapsed at a median of 10 months after treatment and died at a median of 8.5 months from the time of disease recurrence. Survival of patients with a complete response differed significantly from those with no response at 1 year after the start of treatment, but not subsequently.Conclusion Long‐term follow‐up revealed a high relapse rate and poor prognosis in patients with a complete response who received the M‐VAC as induction therapy. Therefore, new adjunctive therapies are needed for patients with locally unresectable or metas

ISSN:0007-1331    

DOI:10.1111/j.1464-410X.1995.tb07708.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Objective To evaluate the efficacy and safety of tamsulosin 0.4 mg once daily (as a modified‐release formulation) compared with placebo in patients with benign prostatic enlargement, lower urinary tract symptoms and prostatic ‘obstruction’ (symptomatic benign prostatic hyperplasia [BPH]).Patients and methods Of 313 patients with symptomatic BPH enrolled in a 2‐week placebo run‐in period, 296 were subsequently randomized to receive either placebo (98 patients) or tamsulosin 0.4 mg once daily (198 patients) for 12 weeks. The primary variables assessed to determine efficacy were maximum urinary flow rate (Qmax) from free‐flow measurements and the total Boyarsky symptom score.Results Tamsulosin produced greater improvements in Qmax(1.4 mL/s, 13.1%) than did placebo (0.4 mL/s, 3.8%) (P= 0.028) and a greater decrease in total symptom score (3.4 points, 35.8% reduction) than did placebo (2.2 points, 23.7% reduction) (P= 0.002). Significantly more tamsulosin‐treated patients (67%) than placebo‐treated patients (44%) had a ≥ 25% decrease in total symptom score after 12 weeks (P<0.001). Treatment with tamsulosin for 12 weeks also produced significant improvements in average urinary flow rate (P= 0.040), irritative (P= 0.013) and obstructive (P= 0.014) symptom scores and symptoms of nocturia (P= 0.022) and hesitancy (P= 0.004). Tamsulosin was tolerated well by the patients. The incidence of adverse events emerging during treatment was comparable in the tamsulosin‐and placebo‐treated groups (34% and 24% respectively,P= 0.109), as was the incidence of cardiovascular‐related adverse events (5% and 7% respectively;P= 0.596). There were no significant differences in changes in blood pressure or pulse rates between the tamsulosin‐and placebo‐treated groups.Conclusion Tamsulosin 0.4 mg once daily is safe, well tolerated and clinically effective in improving symptoms and urinary flow rate in pa

ISSN:0007-1331    

DOI:10.1111/j.1464-410X.1995.tb07709.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Objective To evaluate the Memotherm™ (Angiomed) permanently implantable prostatic stent.Patients and methods Forty‐eight men (mean age 70.3 years, range 57–86) with symptoms and urodynamics suggestive of bladder outflow obstruction had a Memotherm™ stent inserted into the prostatic urethra. Subjective and objective follow‐up was performed at 1, 3 and 6 months.Results All but one patient was eventually able to void. Ten stents have been removed and three patients are awaiting stent removal. Subjective benefits bore no correlation with the maximum urinary flow rate and the findings on cystoscopy. Only 15 of the 48 patients had a satisfactory result.Conclusion Permanently implanted prostatic stents should be considered experimental and only marketed after intensive investigation. As a result of this study, the Memotherm™ stent is to undergo significant mo

ISSN:0007-1331    

DOI:10.1111/j.1464-410X.1995.tb07710.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY