Acquired cystic disease of the kidney: an indication for renal transplantation?
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Adolescent↗
Biomedical subjects
G D Chisholm
Publications and source records attributed to G D Chisholm.
Androgen receptors in cancer of the prostate. Correlation with the stage and grade of the tumor.
The authors have measured the androgen receptor concentrations in the cytosol and nucleus of 13 carcinoma of the prostate (CaP) patients and compared these values to those in an age-matched group of 23 patients with benign prostatic hyperplasia (BPH). Histologic classification of the tumors was carried out and the receptor content was correlated to the grade and stage of the disease. The mean +/- SEM receptor values for BPH (cytosol: 115 +/- 18 fmol/g tissue; nucleus: 140 +/- 34 fmol/g tissue) were not significantly different from those measured in CaP (cytosol: 105 +/- 23 fmol/g tissue; nucleus: 83 +/- 23 fmol/g tissue). There was a positive correlation between nuclear and cytosolic receptors in both BPH and CaP. Our data revealed, however, the absence of any correlation between histologic grade in CaP and receptor content. If, however, the tumors were classified according to the stage of the cancer using the TNM system, "early disease" tumors maintained significantly lower Gleason score (4.4 +/- 0.61) and receptor levels (cytosol: 63.8 +/- 31.2 fmol/g tissue; nucleus: 46.2 +/- 26.5 fmol/g tissue) than those measured in the "late disease" (Gleason score: 7.0 +/- 0.56; cytosol receptor: 146.2 +/- 20.5; nuclear receptor: 117.2 +/- 31.6) (P less than 0.05); therefore the staging of the disease bears a great impact on the capacity of the tumor to specifically bind androgens.
Aged↗
Significance of immediate diuresis in relation to transplant kidney survival rate.
Transplant kidney survival of recipients with immediate diuresis (n = 19) is compared with recipients who did not have a significant post-operative diuresis (n = 53). There is statistically no significant difference between patients without significant early diuresis (survival rate 71%) and patients with immediate diuresis (survival rate 68%, p greater than 0.1). The renal function was not different in the survivors of the two groups at 12 months post-transplant as measured by creatinine clearance (p greater than 0.35).
Creatinine↗
Identifying leucocytes and leucocyte subpopulations in semen using monoclonal antibody probes.
An indirect immunoperoxidase technique employing specific monoclonal antibodies has been used to identify leucocyte subpopulations in cytocentrifuge smears of washed human ejaculate. Cells reacting with the pan antihuman leucocyte monoclonal antibody (HLe-1) were demonstrated in 63/67 specimens from subfertile patients with a mean count of 14.5 +/- 17.1 leucocytes per HPF (X 320). Cells with similar reactivity were observed in all specimens examined from 10 fertile men with a mean count of 41.6 +/- 26.3 leucocytes per HPF (X 320). Leu-T4+ cells (T-lymphocytes) were demonstrated in only 13/63 of the subfertile group with a mean count of 4.46 +/- 3.3 T-lymphocytes per HPF (X 320). Studies with the anti-leu 2a antibody revealed that these leu-4+ cells were mainly of the suppressor/cytotoxic phenotype. In contrast, no leu-4+ cells were detected in the control group. No leu-12+ cells (B-lymphocytes) were detected in any of the 80 specimens examined.
Antibodies, Monoclonal↗
Superficial bladder cancer: intravesical chemotherapy and tumour progression to muscle invasion or metastases.
Of 299 patients who presented with superficial bladder cancer (Ta, T1), 60 were treated by intravesical chemotherapy (Epodyl, methotrexate or mitomycin C). The rate of tumour progression to muscle invasion or metastases was identical for each intravesical regime. There was no evidence that mitomycin C promoted tumour progression. Carcinoma in situ in non-tumour-bearing urothelium was the most significant predictive factor for progression to muscle invasion or metastases.
Administration, Intravesical↗
Leucocytes in the ejaculate from fertile and infertile men.
The presence of leucocytes and their subpopulations was studied in the ejaculate from 69 men with an infertile marriage and 12 fertile men. Monoclonal antibodies specific for human leucocytes were used in an immunoperoxidase technique. In addition to the standard sperm analysis, each specimen was also tested for sperm antibodies, aerobic and anaerobic microorganisms, Ureaplasma urealyticum and Chlamydia trachomatis. Leucocytes were found in large numbers in the fertile men compared with the patients. Lymphocytes were found in 20% of the patients. Micro-organisms were cultured from a similar proportion of both groups. We found no correlation between leucocyte counts, sperm density and motility, sperm antibodies and growth of micro-organisms. Our results cast doubt on the conventional criteria of subclinical genital tract infection, namely positive culture and excess leucocyte counts.
Ejaculation↗
Results of surgery following radical radiotherapy for invasive bladder cancer.
Five hundred and ninety-one of 889 patients with T1 to T4 transitional cell carcinoma of the bladder had persistent or recurrent cancer after radical radiotherapy. Durable local control was significantly poorer for patients with grade 1 or T4 cancer before radiotherapy. Three hundred and twenty-two patients received additional surgical treatment: 211 were endoscopically managed and 111 had secondary cystectomy. The survival of patients with residual or recurrent cancer after radiotherapy was significantly improved by secondary local treatment (P less than 0.0001). A comparison was made between endoscopic treatment and cystectomy after radiotherapy. Patients having secondary cystectomy were younger (mean age 60.0 years) than those managed endoscopically (66.8 years). The 5-year actuarial survival rate (from the date of radiotherapy) for patients who had endoscopic treatment was 47.1% compared with 62.5% for those who had cystectomy (P = 0.16). After both treatments survival was significantly correlated with the T category of the tumour before radiotherapy. Local tumour control was better after cystectomy; 85.6% of patients were locally tumour-free at the end of follow-up compared with 44.5% of those managed endoscopically. There was no overall difference in the subsequent risk of metastases between the two forms of surgery. However, seven of 12 patients managed endoscopically prior to secondary cystectomy died of their cancer. Five of these patients died from metastases even though they were locally disease-free. There was a significantly increased risk of metastases in patients managed endoscopically who were not locally disease-free after treatment (P = 0.0003). Caution is advised in persisting with endoscopic treatment after radiotherapy if local control is not readily achieved.
Aged↗
Immunohistochemical identification of lymphocyte subsets and macrophages in normal human urothelium using monoclonal antibodies.
Monoclonal antibodies were used to examine the pattern of distribution of lymphocyte subpopulations and macrophages in normal human urothelium. T lymphocytes (T11-positive cells) were demonstrated within the epithelium and within the lamina propria of both the ureter and the urinary bladder. Suppressor/cytotoxic T cells (T8-positive cells) predominated, with the average ratio of suppressor/cytotoxic T cells to the helper/inducer T cells being approximately 8.9 in the epithelium and 1.5 in the lamina propria. Leu M3+ cells (monocytes/macrophages) were detected in both epithelium and lamina propria. The character and distribution of these immunocompetent cells within the urothelium suggest a protective function, especially against infection and in tumour surveillance.
Antibodies, Monoclonal↗
Effect of a blood transfusion protocol and low dose steroid regime on renal transplant survival.
The effects of introduction of a low steroid regime and pre-transplant blood transfusion were evaluated. The kidney and patient survival rates for the period before such a policy was adopted were compared with the period after this policy. There has been a highly significant rise in patient survival rates to the present level of 95 per cent at three years. There was a similar rise in three year graft survival rates from less than 40 per cent to 66 per cent.
Actuarial Analysis↗
Evidence that human prostatic 5 alpha-reductase is located exclusively in the nucleus.
The 5 alpha-reductase activities in human prostatic nuclei and microsomes were compared. The activities in both subcellular fractions were identical with respect to pH dependence, heat inactivation and Michaelis constants for NADPH and testosterone. Subcellular distribution studies using DNA and nicotinamide mononucleotide adenyl transferase as nuclear markers showed that the amount of 5 alpha-reductase present in the microsomes was directly proportional to the amount of nuclear contamination. These results indicate that human prostatic tissue contains only one form of 5 alpha-reductase, which is located exclusively in the nucleus. This finding has important implications for the mechanism of steroid action in the prostate.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Treatment of advanced cancer of the prostate.
Advanced cancer of the prostate may be either locally advanced or distant. Staging methods available to define the extent of the disease are relatively imprecise; non-invasive methods rely on tumour markers and radioisotopes; invasive methods range from fine needle aspiration to lymph node dissection. Exact definitions of criteria of response to treatment are essential to evaluate different forms of treatment. Primary treatment of metastatic disease is based on hormone manipulation. Those who either never respond or relapse after primary treatment may show some response to further hormone therapy but usually require the combination of radiotherapy and analgesia to control their symptoms. The response rates to chemotherapy are disappointing.
Adrenalectomy↗
Solubilization of human prostatic 5 alpha-reductase.
A sensitive assay for 5 alpha-reductase was introduced which is capable of detecting at least 0.2 U of activity per sample. The assay was used in developing a method for the solubilization of human prostatic 5 alpha-reductase. Homogenisation conditions were devised under which 95% of the total prostatic 5 alpha-reductase was released into the microsomal fraction. A combination of 0.1 M sodium citrate, 0.1 M KCl, 20% (v/v) glycerol, 0.5 mM NADPH and 1 microM testosterone was found to stabilise 5 alpha-reductase in the presence of detergents. The effect of the presence of low concentrations of detergents in the assay on the activity of 5 alpha-reductase was studied. Triton X-100, Lubrol PX and Nonidet P-40, caused a concentration-dependent inhibition of activity. The ability of several detergents (Triton X-100 MEGA-9, Tween 20, Tween 80, digitonin, Lubrol PX and Nonidet P-40) to solubilise 5 alpha-reductase was studied. All detergents caused a concentration-dependent solubilization of 5 alpha-reductase. Significant amounts of active solubilized enzyme were recovered only with Lubrol PX at concentrations less than 1.1 mg/ml. Seventy percent of the 5 alpha-reductase was solubilized in an active form by extracting the membranes 3 times with 0.8 mg/ml Lubrol PX.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Evidence for the association between blood prolactin and androgen receptors in BPH.
The purpose of this study was to investigate the relationship between prostatic androgen receptors and plasma prolactin and testosterone in patients with benign prostatic hyperplasia. Cytosolic and KCl extractable nuclear androgen receptors were measured in 22 patients and these were in turn correlated to the hormone concentrations in blood specimens taken on the morning before the day of operation. The mean +/- S.E.M. concentrations of cytoplasmic androgen receptors, KCl extractable nuclear androgen receptors, plasma testosterone and plasma prolactin were respectively 115 +/- 18 fmoles/gm. tissue, 198 +/- 40 fmoles/gm. tissue, 15.6 +/- 1.2 nmol./l. and 128 +/- 17 mU/l. Plasma prolactin was highly correlated with cytosolic androgen receptors (r = 0.784, p less than 0.01; no. = 15) though not with nuclear androgen receptors (r = 0.453, p greater than 0.05; no. = 15). However, when the androgen receptor levels were expressed as fmoles/mg. protein both cytosolic and nuclear levels were proportional to plasma prolactin (p less than 0.01 and p less than 0.02 for both the cytosolic and nuclear receptors respectively; no. = 15). There was no correlation between either cytosolic and nuclear androgen receptors and plasma testosterone levels. The results suggest that plasma prolactin may be involved in the regulation of androgen receptor content in the benign prostate.
Aged↗
A comparison of retinol binding in human hyperplastic and malignant prostate.
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Aged↗
5 Alpha-reductase activity in human prostate cancer is related to the histological differentiation of the tumour.
We have measured the activities of two androgen metabolizing enzymes in tissue obtained from thirty-nine patients with carcinoma of the prostate (CaP). The enzyme activities were correlated to the histological differentiation of the tumours based on the Gleason Score and also compared to the activities measured in fourteen age matched patients with nodular prostatic hyperplasia (BPH). Although the mean values for the 5 alpha-reductase in CaP (9.29 +/- 1.47 pmol/mg protein/30 min) were found to be significantly lower than the corresponding values in BPH (16.26 +/- 3.04 pmol/mg protein/30 min) (P less than 0.05), there were nonetheless significant differences within the cancer group and these were totally dependent on the degree of differentiation of the tumour. A progressively suppressed enzyme activity was measured as the carcinomatous tissue became more anaplastic. No correlation was, however, observed between tumour bulk which was also estimated histologically and 5 alpha-reductase, indicating that the activity of this enzyme is purely a function of the histological grade of the cancer and as such 5 alpha-reductase could be used as a biochemical marker for tumour differentiation. We also measured the 3 alpha (beta)-hydroxysteroid dehydrogenase activities in cancer of the prostate but our findings indicated no significant differences between the various stages of the cancer. Furthermore we were unable to correlate the activities of this enzyme with that of the 5 alpha-reductase. Nonetheless two interesting patterns relating to the 3 alpha (beta)-hydroxysteroid dehydrogenase emerged.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxysteroid Dehydrogenases↗
Cis-platin and methotrexate in the treatment of transitional cell carcinoma of the urinary tract.
Nineteen patients with recurrent or metastatic transitional cell carcinoma of the urinary tract were treated with a 3-weekly combination of methotrexate 200 mg/m2 as a 24-h infusion with folinic acid rescue and cis-platin 100 mg/m2. An objective response rate of 68% was obtained, with 4 patients (21%) achieving complete remission. Pulmonary disease and lymph node metastases were particularly sensitive to this therapy. The median duration of response was 21 weeks with a median survival of 54 weeks in the responding patients. This regimen warrants further investigation in the treatment of invasive bladder carcinoma.
Aged↗
Patterns and significance of the sacral evoked response (the urologist's knee jerk).
Neurological examination may fail to demonstrate any abnormality in patients who have neurogenic bladder dysfunction. Standard clinical methods will include full examination of segmental nerves to the level of S1 but will not include the lower sacral segments which control sphincter function. We describe a simple method of measuring the integrity and function of these segments of the cord. The method and the common patterns of response are described. The stimulus is physiological (not supramaximal), the response is measured with surface mounted electrodes at the urethral and anal sphincters and each measurement is the average response after 100 stimuli.
Anal Canal↗
Neurophysiological measurements in primary adult enuretics.
The nerve supply of the lower urinary tract was studied in 25 primary adult enuretics by full urodynamic assessment and neurophysiological measurements. The latter consisted of the measurement of static EMG, sensory thresholds and sacral reflex latencies (SRL). All patients were normal on clinical neurological examination. All neurophysiological measurements were within normal limits in only three patients and the remaining 22 had at least one abnormal response. The commonest abnormality was a high or even absent urethral sensory threshold. These defects in sensory and motor innervation correlated with the clinical dysfunction. It was concluded that this is a valuable method for the detection of nerve defects in the lower urinary tract, especially when the clinical neurological examination is normal.
Adolescent↗