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Biomedical subjects

G D Chisholm

Publications and source records attributed to G D Chisholm.

At least 127 records · Page 7Linked to original sources
PubMed1985

DNA/RNA ratio in bladder cancer: a factor indicating the recurrence rate?

Flow cytometry (FCM) was used to monitor 24 patients receiving intravesical mitomycin C (MMC) therapy. The patients were selected for MMC therapy because of multiple low stage bladder tumours which had not been cleared by previous endoscopic management. The response to treatment was monitored with cystoscopy, cytology, mucosal biopsies and flow cytometry. Follow-up was for a minimum of 12 months and 19 patients (79%) remained free of tumour. Four patients developed recurrences 6 months after therapy (16.5%) and one showed no response. There were no partial responders. The flow patterns of the four patients who developed recurrence showed an increased RNA/DNA ratio; this was detected after the third MMC instillation and remained throughout the follow-up period. The patients who did not develop recurrence demonstrated either a 1:1 or decreased RNA/DNA ratio. The increased RNA/DNA ratio appears to precede cystoscopic, urine cytology or biopsy evidence of recurrence. If this is confirmed in a larger series it could be used to select patients at high risk for recurrence who would be suitable for alternative therapy.

Antibiotics, Antineoplastic↗
PubMed1985

The role of endoscopic treatment after radical radiotherapy for invasive bladder cancer.

In a 6-year period 232 patients were treated by radical radiotherapy for transitional cell cancer of the bladder. Fifty-eight patients had secondary surgical management to control either locally persistent or recurrent tumour. Endoscopic treatment alone was used in 31 patients with down-staged tumours and the survival of this group compared favourably with that of 27 patients selected for salvage cystectomy (5-year survival rate 88% cf. 44%). A group of patients with favourable prognostic factors may be identified in whom cystectomy can be avoided without prejudice to survival.

Carcinoma, Transitional Cell↗
PubMed1985

Prognostic significance of alkaline and acid phosphatase and skeletal scintigraphy in carcinoma of the prostate.

The prognostic significance of skeletal scintigraphy has been reassessed in relation to other tests by extended follow-up of 220 patients. Skeletal metastases increased in prevalence with T stage and were associated with shorter survival irrespective of age. Early disease, a normal acid or alkaline phosphatase at presentation and well differentiated tumours were associated with longer survival. Alkaline phosphatase alone accounted for all of the differences in survival. Scintigraphic change preceded elevation of the prostatic acid phosphatase in 81% of the patients whose initial scintigraphy and prostatic acid phosphatase were normal but who developed evidence of distant metastases on follow-up. The mean interval between scintigraphic conversion and the development of overt symptoms was 5.8 months. Our findings discount the value of skeletal scintigraphy for determining prognosis but do indicate that it is more sensitive than the acid phosphatase in identifying patients before they become symptomatic. Scintigraphy is indicated as a routine staging procedure in all new patients with carcinoma of prostate. In patients with a normal alkaline phosphatase, a baseline and regular follow-up are needed to identify patients likely soon to develop symptoms. If the alkaline phosphatase is elevated at presentation, scintigraphy is necessary to distinguish benign from malignant causes and to determine the extent of skeletal involvement.

Acid Phosphatase↗
PubMed1985

Prediction of response to radiotherapy for localised prostatic cancer.

Fifty-one patients with TO-4 NX MO carcinoma of the prostate were treated by external beam radiotherapy. Comparison with 40 patients with TO-3 NX MO disease, whose treatment was deferred initially, showed a higher incidence of local progression in the untreated patients. Age at presentation and initial T category did not have a significant influence upon the probability of disease progression after radiotherapy, whereas all but one of the irradiated patients with Gleason sum scores greater than or equal to 6 progressed. Treatment-related morbidity was appreciable and prolonged proctitis occurred in 31 patients. There was one treatment-related death. Biopsy 1 year after treatment did not yield information of prognostic significance. It is recommended that the selection of patients with localised carcinoma of the prostate for treatment by radiotherapy is based on histological grade. The Gleason score is a practical method for identifying those who would best be treated by other methods.

Aged↗
PubMed1985

Lymphocyte sub-populations in the male genital tract.

A series of monoclonal antibodies that react with human lymphocyte subsets was used in an indirect immunoperoxidase technique to study representative blocks from normal human testis, epididymis, vas deferens, prostate and seminal vesicles. Biopsies of testis, epididymis and vas obtained during surgical procedures directed at the investigation and treatment of infertile males were also studied. In all normal tissues, apart from the peripheral testis where no lymphocytes were identified, T lymphocytes were the predominant cell type (Leu 4+). These lymphocytes were largely of the suppressor/cytotoxic phenotype (Leu 2a+) and were more abundant in between the epithelial cells in the rete testis, epididymis, vas deferens, seminal vesicles and prostatic acini. Cells of the helper/inducer phenotype (Leu 3a+) were identified mainly within the interstitium of the epididymis and the prostate. B-lymphocytes (Leu 12+) were few in number and were mainly in the stroma of the prostate. In each organ the ratio of the T-cell subsets was determined and changes in this ratio were observed in epididymal and vasal biopsies from some infertile males. Finally, in testis biopsies from infertile men, suppressor/cytotoxic T-cells were demonstrated between the germinal epithelium and the fibrous tunica of the seminiferous tubules and as focal aggregates in the interstitium.

Antibodies, Monoclonal↗
PubMed1985

Nuclear retinoic acid binding protein in human prostate adenomas.

A retinoic acid binding protein has been detected in salt extracts of nuclei obtained from human prostate adenoma. The binding was characterized by competition experiments, temperature/time studies and saturation analysis. Substantial binding was only observed after sonication of nuclei and charcoal-pretreatment of a salt extract. The binding of radiolabelled all-trans-retinoic acid was displaced by all-trans-retinoic acid, retinol and to a lesser extent retinal and two synthetic retinoids, RO 10-1670 and RO 13-7410. Testosterone and dihydrotestosterone, at a 100-fold excess, had little effect on the binding. The association between retinoic acid and nuclear protein was both temperature and time dependent. At 37 degrees C, equilibrium was rapidly reached (30 min) whereas at 4 and 25 degrees C, ligand binding occurred at a slower rate. Saturation analysis performed under steady-state conditions yielded a dissociation constant of 15 +/- 2 nmol/l. Metabolism studies failed to show conversion of either radiolabelled all-trans-retinol or [3H]retinoic acid in vitro; these data suggest that both acid and alcohol forms of vitamin A are recognized by the extracted nuclear protein. The effect of three enzyme inhibitors on [3H]retinoic acid binding was studied. Binding was unaltered in the presence of aprotinin and phenylmethylsulphonyl fluoride but sodium molybdate (10 mmol/l) increased binding by 18%. The presence of a specific retinoid binding protein in prostate nuclei suggests that retinoids may play some role in the function of the gland.

Carrier Proteins↗
PubMed1984

The effect of anaesthesia and surgery for benign disease of the upper urinary tract on circulating leucocyte subpopulations identified with monoclonal antibodies.

Circulating lymphocyte subpopulations were monitored, using monoclonal antibodies and flow cytometry, in six patients undergoing surgery for benign disease of the upper urinary tract. A significant decrease in the total number of circulating lymphocytes was observed. This could be attributed to a significant decrease of T cells of both major subsets--the so-called T "helper" (Th) and T "suppressor/cytotoxic" (Ts) subpopulations. When the results of the T cell subsets were expressed as a ration (leu-3a+/leu-2a+, T "helper/suppressor") no significant change was noted. In contrast neither B cells nor natural killer (NK) and antibody dependent killer (K) cells were significantly affected. This selective loss of T cells from the circulation may be relevant to post operative infection and should be considered in the course of immunological monitoring.

Adolescent↗
PubMed1984

The effect of zinc on the 5 alpha-reduction of testosterone by the hyperplastic human prostate gland.

The present studies were performed to evaluate the role of zinc in the regulation of testosterone 5 alpha-reduction by the 800 g supernatants prepared from human benign prostate hyperplasia specimens. The results show that when zinc is added at low concentrations the 5 alpha-reduction of testosterone is increased but at higher cation concentrations the metabolism is significantly inhibited. This decrease was mediated by both a non-competitive inhibition of the binding of testosterone to the 5 alpha-reductase enzyme and by a reduction in the formation of the NADPH cofactor. We have also demonstrated that the decreased synthesis of NADPH was produced by a competitive inhibition of both G6P and NADP binding to the G6PD enzyme. The data also suggests that the increase in testosterone metabolism observed at low zinc concentrations does not produce any changes in the binding of testosterone to the 5 alpha-reductase enzyme. In spite of the above observations we were unable to establish any correlation between the endogenous zinc content of the tissue and the in vitro capacity of the BPH samples to 5 alpha-reduce testosterone. The present study suggests a possible physiological role for the regulation of testosterone metabolism by zinc in the human prostate gland.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1984

A randomized trial of 48 hours of prophylactic cefotaxime versus single dose in transurethral prostatic surgery.

A previous randomized trial from this department demonstrated that there was significant reduction in morbidity and post-operative bacteriuria when men undergoing transurethral prostatectomy were given a prophylactic perioperative regimen of 48 h of cefotaxime compared with a no treatment control group. In this paper we report the results of a new randomized trial to determine whether a single dose of cefotaxime given with the induction of anaesthesia would be of equal efficacy to the previous 48 h regimen. We also investigated the ward bacterial flora for cefotaxime resistance before and during the trial. The 48 h regimen was significantly superior to the single dose in terms of the number of men who developed post operative complications and there was also a small but significant reduction in post-operative hospital stay. Forty-eight hours of prophylaxis covers the normal time of post-operative urethral catheterization and this may explain our findings. There was no evidence of emergence of cefotaxime resistant strains.

Bacteriuria↗
PubMed1984

Lymphocyte subsets in renal carcinoma--a sequential study using monoclonal antibodies.

Using monoclonal antibodies in conjunction with flow cytometry, circulating lymphocyte subsets with distinct functions in the regulation of the immune response were enumerated in 32 patients with proven renal carcinoma. Analyses were performed at presentation and sequentially during the clinical course of the patients. Untreated patients with advanced disease had a deficit of T cells with the "helper/inducer" phenotype (Leu-3a+) and this resulted in abnormal T "helper/suppressor" (Leu-3a+/Leu-2a+) ratios. Following nephrectomy, performed in 26 patients, there was a significant increase in the number of T cells with the "helper/inducer" phenotype and a significant increase in T "H/S" ratios. Subsequent follow-up at a minimum of 2 months after nephrectomy showed that the increase in T cells with the "helper/inducer" phenotype was maintained (with the exception of 6 patients with disease progression) and was then accompanied by a significant increase of the T cell subset with the "suppressor/cytotoxic" phenotype (Leu-2a+). Pre-operative renal arterial embolisation resulted in an early transient lymphopenia. The response to embolisation combined with nephrectomy was little different when compared with nephrectomy alone. These observations represent a novel view of the immunosuppressive effects of renal carcinoma and their relation to anaemia and disease progression are discussed.

Adult↗
PubMed1984

Is the incidence of renal carcinoma increasing?

An analysis of standardised incidence rates for renal parenchymal tumours over a 14-year period in Scotland demonstrated a significant increase in disease incidence for males but not females. Reasons are presented to support the contention that this increase is in part real.

Adolescent↗
PubMed1984

Intravesical methotrexate in the treatment of superficial bladder cancer.

Thirty patients with superficial bladder cancer (Tis, Ta, Tl) difficult to control by endoscopic means were given a total of 49 courses of methotrexate at fortnightly intervals. Four concentrations were investigated. In 14 courses this was the sole treatment and in the remainder the methotrexate was given as prophylaxis. Toxicity was not a problem but in both groups, although there was some evidence of anti-tumour activity, there were high recurrence rates and intravesical methotrexate cannot be recommended.

Carcinoma, Transitional Cell↗
PubMed1984

The stable state is not an objective response in hormone-escaped carcinoma of prostate.

In some clinical trials the use of criteria of stable response of hormone-escaped prostate cancer is justified on the ground that it delineates patients with markedly improved survival, similar to that of partial regression patients. Forty-three patients with hormone-escaped prostate cancer were studied in order to identify other factors which might also predict improved survival. Fifteen patients received palliative treatment only, 17 secondary hormone therapy and 11 chemotherapy. Only one objective partial regression was seen. Thirty-seven patients have died of prostatic cancer, 3 have died of other causes and 3 remain alive. The mean initial hormone response was 14.8 months, the mean time from progression to death 11.3 months, and the mean time from symptoms to death 5.9 months. There was no significant correlation between length of initial response and survival following progression (r = 0.25). Six features of progression were reviewed. Patients presenting with one feature of progression had a significantly better mean survival, 14.8 months, compared with 8.2 months when multiple features indicated progression. It is concluded that the stable state is not an objective response in hormone-escaped carcinoma of prostate but a reflection of the patient's natural disease progression and that the mode of presentation may be a significant prognostic indicator.

Drug Resistance↗
PubMed1984

Maldescended testes and fertility: a review of 68 cases.

We report an analysis of 68 of 1112 couples who attended an infertility clinic where the man had past or present evidence of testis maldescent. The age at orchiopexy for these 68 men was later than would be expected, taking into account surgical practice in Scotland for the relevant time period and this supports the view that late orchiopexy is a risk factor for subsequent infertility. There was no evidence that antisperm antibodies are responsible for the damage to spermatogenesis in unilateral cases; however, measurement of the serum hormones showed elevations of LH and FSH which cannot be entirely explained as secondary to the damaged spermatogenesis. There was weak but nevertheless significant evidence that testis maldescent may be a poor prognostic factor as far as subsequent fertility is concerned and that this is independent of the length of time the couple have been trying and the man's motile sperm density. In two men there was intra-abdominal undescent and both were found to have testis tumours; we would re-emphasise that abdominal exploration is mandatory in such cases.

Adult↗
PubMed1984

Intra-epithelial lymphocytes in the normal epididymis. A mechanism for tolerance to sperm auto-antigens?

Using a monoclonal immunoperoxidase technique on frozen tissue sections of normal testis and epididymis, a distinctive distribution of lymphocytes has been identified. Almost all of the intra-epithelial lymphocytes were T cells and the majority of these belonged to the T8+ ("suppressor/cytotoxic") subset. The distribution contrasted with the predominance of the T4+ ("helper/inducer") subset in the interstitial tissues and in normal peripheral blood. The predominance of the "suppressor/cytotoxic" subset within the epithelium of the epididymis may exist in order to prevent the development of the immune response to auto-antigens on spermatozoa.

Adult↗
PubMed1984

Interaction between prolactin and zinc in the human prostate gland.

The interaction between prolactin and zinc was examined in vitro in the human prostate gland. The results indicated that prolactin did not modulate the acute uptake of zinc into benign prostatic hypertrophy tissue whereas zinc, in contrast, increased the uptake of prolactin into the prostate gland. Our study further showed that the augmented uptake of prolactin by zinc was partly due to an increase in the non-specific binding properties of the peptide hormone. We were also able to demonstrate that the specific binding of 125I-labelled human prolactin to the receptor was reduced in the presence of zinc by a competitive mechanism.

Drug Interactions↗
PubMed1984

The preparation, characterization and application of monoclonal antibodies to human prostatic acid phosphatase (PAP).

Hybridoma cells secreting anti-PAP were produced by fusion of NS-1 myeloma cells with spleen cells from immunized Balb/c mice. Three of 32 hybrids secreted antibodies. Dilution cloning of the two hybrids producing the highest antibody titres showed that each antibody was monoclonal. One clone from each hybrid (clones ES2 and ES8) was selected for further study. The specificity of the antibodies appeared satisfactory, no inhibition of 125I-PAP binding to antibody being seen with extracts of bone, intestine, kidney, leucocytes, liver or lung. The association constants of the antibodies from ES2 and ES8 were 1.7 X 10(8) and 1.7 X 10(9) l/mol respectively, both were of the IgG1 class. For the immunoradiometric (IRMA) assay of serum PAP 125I-labelled monoclonal antibody was incubated with serum and the PAP-labelled antibody complex was separated by addition of solid-coupled polyclonal anti-PAP. The wide working range of the response curve (0.3-400 micrograms/l) and the rapid analysis time (4 h) offer practical advantages over RIA procedures. Clinical evaluation of the assay is in progress. ES8 antibody also appears to have good specificity for immunocytochemical applications. Localisation of micrometastases in bone in prostatic carcinoma was readily achieved.

Acid Phosphatase↗