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Biomedical subjects

M C Bishop

Publications and source records attributed to M C Bishop.

At least 37 records · Page 2Linked to original sources

Preclinical evaluation of copper-67 labelled anti-MUC1 mucin antibody C595 for therapeutic use in bladder cancer.

Transitional cell carcinoma of the bladder is the fifth commonest cause of death from cancer in men in the United Kingdom. Most patients present early with superficial disease, though with current treatment up to 20% progress to invasive disease, which has a poor prognosis. Better local treatments are required to limit this tumour progression. The ease of access to the bladder via a catheter provides the ideal opportunity for antibody (Ab) targeted therapy. We have previously shown that indium-111 labelled anti-MUC1 mucin Ab C595 selectively localises to bladder tumours after intravesical administration. We have selected copper-67 as an alternative radiolabel with suitable physical characteristics for radioimmunotherapy. This communication demonstrates that C595 can be reproducibly labelled with 67Cu and that the radioimmunoconjugate is both stable and maintains high immunoreactivity. Pilot studies on cystectomy specimens in a novel ex vivo system and in one patient confirmed the ability of this conjugate to localise to tumour after intravesical administration. On the basis of these studies we are now in a position to study the intravesical administration of 67Cu-labelled C595 in patients with bladder cancer with a view to a therapeutic trial.

Administration, Intravesical↗

Cystitis associated with tiaprofenic acid: a survey of British and Irish urologists.

OBJECTIVE: To quantify the extent and natural history of cystitis in relation to treatment with the non-steroidal anti-inflammatory drug (NSAID) tiaprofenic acid. METHODS: Anonymous postal questionnaires were sent to all UK and Irish consultant urologists enquiring about their awareness of the association between tiaprofenic acid (Surgam) and cystitis, and the number, nature and clinical details of patients with the diagnosis. RESULTS: Of the 357 urologists, 45.7% replied; 37.4% of those who responded had had cases of NSAID-concurrent cystitis, 35.6% replied that they had no personal experience but were aware of the possibility of an adverse drug reaction and 27% were unaware of the possibility of NSAID-related interstitial cystitis. There were 108 reported cases of cystitis; 55 (51%) were women, 12 (11%) were men and gender was not stated in 41 (38%). The median duration of treatment was 59 weeks (range 6 weeks-4 years). Symptoms abated completely on stopping the drug in 86% of patients, resolving in a median of 14 weeks (range 7 days-2 years). In seven cases (10%), resolution was incomplete; 17 patients had undergone reconstructive urological surgery. CONCLUSION: Tiaprofenic acid has caused at least 108 cases of cystitis and several of these patients underwent extensive urological surgery based on the assumption that they were suffering from chronic interstitial cystitis. Most cases were reversible on withdrawal of tiaprofenic acid, but 10% of patients had residual symptoms. Tiaprofenic acid causes a higher incidence of cystitis than any other NSAID and its withdrawal from the market should be considered.

Adult↗

Impact of cyclosporin on the incidence and prevalence of chronic rejection in renal transplants.

Over a 14-year period, 435 patients underwent renal transplantation. Chronic rejection has occurred in 58 (13%) of all grafts and has accounted for 18% of all graft losses. After the first 6 months following transplantation, chronic rejection was the most common cause of graft failure, accounting for 40% of losses. The median time (interquartile range) from transplantation to graft failure was 3 years (2-5.5 years). Comparison of azathioprine versus cyclosporin treated patients showed no significant difference in the incidence of graft loss (Cox regression score 2.55, P = 0.11). Furthermore, there were significantly more grafts with deteriorating function owing to chronic rejection in cyclosporin-treated patients (n = 16, 11% of surviving grafts) than in azathioprine-treated patients (n = 2, 3% of surviving grafts). These data suggest that cyclosporin does not prevent the development of chronic rejection in renal transplants.

Azathioprine↗

Experience with low-dose oestrogen in the treatment of advanced prostate cancer: a personal view.

OBJECTIVE: To re-evaluate the treatment of advanced prostatic carcinoma with diethylstilboestrol (DES) in low dosage in relation to the degree of suppression of plasma testosterone. PATIENTS AND METHODS: The study comprised 106 patients with advanced carcinoma of the prostate (89 with T3/4 M1 and 17 with T3/4 N0/1 M0) who were treated with 1 mg/day of DES. The response was assessed clinically and by the change in plasma prostate specific antigen, prostatic and phosphatase and alkaline phosphatase, and plasma testosterone was monitored regularly. In a few patients it was possible to reduce the dose to 0.5 mg/day DES; in others, the initial response was not sustained and they were treated with an increased dose of DES or bilateral orchidectomy. RESULTS: Seventy patients (Group 1) showed a sustained response to 1 mg/day of DES (0.5 mg/day in three) and 50 remained in remission at a mean of 21 months of treatment. Of the 36 patients offered secondary treatment, 12 (Group 2) responded with a second remission. Only 27% of patients had mean testosterone levels in the castrate range (0-2 nmol/L) but most in Group 1 had mean levels of < 10 nmol/L, whilst in 10 of the 12 patients in Group 2, the level was > 10 nmol/L. Overall times to progression and death were comparable with the results of conventional monotherapy or combination treatment and complication rates were acceptable. CONCLUSION: Low-dose oestrogen therapy (1 mg/day of DES) is cheap, effective and caused few side-effects, none of which was life-threatening. In many patients, only minimal suppression of the plasma testosterone was required and the response appeared to be qualitative, although there was considerable variation in the threshold of response. A randomized trial of oestrogen, in a minimal dose adjusted to the requirements of the individual patient, against conventional hormone treatment now seems justified.

Aged↗

Overseas electives.

Explore the source record for details and available documents.

Education, Medical↗

Targeting of bladder cancer with monoclonal antibody NCRC48--a possible approach for intravesical therapy.

OBJECTIVE: To determine the localization of the anti-MUC1 mucin monoclonal antibody (mAb) NCRC48 to bladder cancer following intravesical administration. PATIENTS AND METHODS: mAb NCRC48 (330-500 micrograms) radiolabelled with 111indium (11-17 MBq) was administered intravesically to 12 unselected patients with radiological evidence of bladder cancer. Tumour localization was assessed by gamma-camera imaging and by tissue biodistribution studies on biopsies obtained at cystoscopy at about 2 or 24 h after the procedure. After 24 h, whole blood radioactivity was measured and 3 weeks after the procedure the serum level of human anti-mouse antibodies was estimated using an ELISA method. RESULTS: Eleven patients had tumours confirmed at cystoscopy (grades 1-3, stages pTa-pT2). The mean uptake of NCRC48 by tumour and by normal urothelium (expressed as the percentage of the instilled dose/g x 10(3) +/- SD) at 2 h was 3.42 +/- 3.68 and 0.41 +/- 0.77 (P < 0.05). After 24 h, the values for tumour and normal urothelium were 1.17 +/- 1.18 and 0.17 +/- 0.11, respectively. Areas of increased activity on the scintigrams were consistent with the position of the tumours at cystoscopy. No radioactivity was detected in blood at 24 h and there was no evidence of a human anti-mouse antibody response. CONCLUSION: The MUC1 mucin may be a suitable antigen to study the potential of therapeutic strategies based on monoclonal antibody targeting of superficial bladder cancer and may allow the development of more effective agents in the treatment of this condition.

Aged↗

Effect of human leucocyte antigen matching on the incidence of acute rejection in renal transplantation.

The influence of human leucocyte antigen (HLA) matching on the incidence of acute rejection and graft survival was examined in 181 consecutive patients receiving cadaveric renal transplants. Allografts with better HLA-DR and HLA-B matching showed significantly lower rejection rates than less well matched grafts on both univariate (rejection rates 25, 62 and 82 per cent for zero, one and two DR mismatches; P < 0.001) and multivariate analysis. Rejection episodes occurred earlier in mismatched grafts (P < 0.001). Superior matching was associated with improved graft function at 1 year after transplantation (mean serum creatinine level 137, 180 and 225 mumol l-1 for zero, one and two DR mismatches; P < 0.05). No association was, however, demonstrated between the degree of matching and overall graft survival. Good HLA matching reduces the number of acute rejection episodes, producing significant savings in drug costs and hospital stay. Long-term graft function is improved and minimizing early graft damage helps to avoid later development of chronic rejection.

Acute Disease↗

The use of DNA typing to clarify the origin of metastatic carcinoma after renal transplantation. A clinical and medico-legal problem.

We present an unusual diagnostic problem in a transplant patient whose failed renal transplant was found to contain undifferentiated carcinoma. When the patient later developed metastatic renal carcinoma, he began legal proceedings against the hospital for the transmission of a tumour with his renal transplant. He subsequently died of carcinomatosis. Post-mortem examination revealed acquired renal cystic disease in his native kidneys with a 1-cm adenocarcinoma arising from the wall of one of the cysts. We used DNA typing to determine the origin of the metastatic tumour and resolve the medico-legal problem.

Adenocarcinoma, Clear Cell↗

Urosurgical management of urinary tract infection.

A wide range of abnormalities in the genito-urinary system predispose to infection and surgical solutions may be appropriate. This review considers the investigation of obstruction and the relationship between urinary infections and renal damage, chronic renal disease, renal abscesses, reflux, calculi, catheterization and instrumentation, the neuropathic bladder and prostatitis as well as the role of antibiotic prophylaxis in urological surgery. Recommendations for the urosurgical management of urinary infection are made.

Humans↗