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Biomedical subjects

G D Chisholm

Publications and source records attributed to G D Chisholm.

At least 37 records · Page 2Linked to original sources
PubMed1994

The management of bilateral ureteric obstruction and renal failure in advanced prostate cancer.

OBJECTIVES: To investigate the effect of upper tract decompression on the prognosis of uraemia secondary to bilateral ureteric obstruction in prostate cancer, with particular reference to the hormone dependency of the tumour. PATIENTS AND METHODS: Prospectively collected data, over the period 1978-1993, were selected from the departmental database and from hospital case code data. Inclusion criteria were: blood urea > or = 15 mM, radiological evidence of bilateral ureteric obstruction, a histological diagnosis of prostate cancer, and the exclusion of out-flow tract obstruction. Of the 820 patients recorded in the departmental database, 27 (3.3%) fulfilled the criteria. Thirty-six patients were identified in total. Statistical analysis was by the Mann-Whitney non-parametric test. RESULTS: Of the 36 patients with bilateral ureteric obstruction and renal failure, in those in whom androgen depletion had been undertaken after ureteric obstruction (i.e. androgen depletion was a treatment option), the mean survival was 646 days (n = 12, SD = 786). Among these patients upper tract decompression improved survival and reduced the amount of time patients spent in hospital. In those in whom androgen depletion had been carried out before obstruction (i.e. the tumour had escaped from hormonal control), survival was significantly worse (80 days, n = 24, SD = 86.8, P < 0.01). In this group the use of decompression improved survival little. Percutaneous nephrostomy was the commonest means of decompression (nephrostomy, 9; stent, 5; ureteroneocystostomy, 2). DISCUSSION: In patients for whom hormonal therapy remains an option, upper tract decompression offers a worthwhile improvement in terms of increased survival and reduced in-patient time. However, if ureteric obstruction is diagnosed after hormone manipulation has been used, upper tract decompression has little effect on survival and should only be used in exceptional circumstances.

Cyproterone Acetate↗
PubMed1994

Air insufflation versus water irrigation during flexible cystoscopy: a prospective randomized study.

OBJECTIVE: To compare air insufflation with water irrigation during routine diagnostic flexible cystoscopy. PATIENTS AND METHODS: A total of 200 consecutive patients scheduled for routine diagnostic flexible cystoscopy under topical anaesthesia were randomized prospectively to either air insufflation or water irrigation. Their tolerance to the procedure and post-operative symptoms were assessed from a questionnaire completed immediately after the procedure and then 1 week later. RESULTS: Air insufflation offered a better cystoscopic view than water irrigation. With regard to tolerance, in the air insufflation group, 72% reported the procedure to be comfortable, 22% uncomfortable and 6% painful compared to 44%, 45% and 11% respectively in the water irrigation group. This difference in favour of air insufflation was highly significant (Chi-square, P < 0.001). There was no statistical difference in either post-operative symptoms a week later or in the diagnostic yield between the two study groups. There were no complications in either group. CONCLUSION: Air insufflation cystoscopy is as safe and effective as water irrigation but better tolerated by patients. This, together with its more obvious advantages of the ease of administration and low cost, should prompt more routine use of air insufflation cystoscopy for day case procedures.

Carcinoma, Transitional Cell↗
PubMed1994

Induction of ICAM 1 expression on bladder tumours by BCG immunotherapy.

AIMS: To determine the expression of intercellular adhesion molecule 1 and 2 (ICAM 1 and 2) in transitional cell carcinoma cells before and after immunotherapy with Calmette-Guérin bacillus (BCG). METHODS: Frozen sections from 22 untreated bladder carcinomas were immunohistochemically examined with monoclonal antibodies to ICAM 1 and 2. Urinary cytospin slides were made for six patients for each of the six clinical instillations which constitute a therapeutic course. These slides were also stained for ICAM 1 and for leucocyte function associated antigen 1 (LFA 1). RESULTS: Bladder cancer cells did not essentially express either ICAM 1 or 2, but cells in the stromal areas surrounding tumour expressed both these antigens. After repeated instillations of BCG organisms ICAM 1 positive normal and neoplastic epithelial cells were observed in the urine. Cells obtained from the first three instillations expressed lower densities of ICAM 1 than those from the later instillations. Many neutrophils expressing LFA-1 and some lymphocytes were also noted in the cytospin slides and some of these were conjugated to tumour cells expressing ICAM 1. Six months after treatment a single maintenance dose of BCG induced ICAM 1 expression. CONCLUSION: Untreated superficial bladder carcinoma cells do not express ICAM 1 or 2, but these important immunological molecules were expressed in the stromal areas of tissue. Importantly, neoplastic cells in the urine expressed ICAM 1 after immunotherapy. This molecule can render bladder tumour cells vulnerable to non-antigen specific cytotoxicity mediated by activated lymphocytes.

Antigens, CD↗
PubMed1994

The TNM system of 1992. Comments from the TNM working group. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

The TNM working group acknowledges the multinational agreement reached in the 1992 TNM classification, but nevertheless gives some suggestions for modifications. The main interest of the group has been to evaluate parameters suitable for further ramification of the system. The group found that parameters such as DNA ploidy, PSA, nuclear roundness factor, are not yet ready for this purpose. Grade is an established parameter and should be incorporated into the TNM-categories of localized disease. In metastatic disease a number of parameters are available to subdivide this category according to prognosis, and these will be more uniformly and extensively studied in the several large trials that are now in progress.

Alkaline Phosphatase↗
PubMed1994

Control of leucocyte function-associated antigen-1-dependent cellular conjugation by divalent cations.

The control of integrin activation is fundamental to an understanding of the integrin-dependent cellular adhesion thought to be important for a plethora of basic cellular functions. Using a cell-cell conjugation assay the role of divalent cations in leucocyte function-associated antigen-1 (LFA-1)-dependent cellular adhesion was further investigated. The conjugation of interleukin-2 (IL-2)-activated lymphocytes to tumour cells was found to be energy dependent and required the presence of various divalent cations, removal of which decreased the level of conjugation. Increased concentrations of calcium, magnesium and manganese ions resulted in a corresponding increase in levels of conjugation. This increase in conjugation was LFA-1 dependent. Interestingly, when calcium ions were first removed from LFA-1, treatment of lymphocytes with magnesium and manganese ions gave significantly higher levels of conjugation than in the presence of calcium. Using a simple displacement study, calcium ions were shown to displace magnesium ions resulting in decreased conjugation. However, calcium ions were unable to displace manganese ions for binding to LFA-1. That manganese was exerting its effect via an LFA-1-dependent mechanism was confirmed using monoclonal antibodies to CD11a which negated the increased conjugation frequency due to manganese.

Antibodies↗
PubMed1993

Absence of 5 alpha-reductase activity in the gubernaculum during descent of the fetal pig testis.

To evaluate the hypothesis that testicular descent is mediated by the action of high local concentrations of dihydrotestosterone in the gubernaculum, testis, or epididymis, we obtained tissues from 30 male pig fetuses between 63 and 101 days of gestation. We assayed the 5 alpha-reductase activity in homogenates of pooled tissue by following the conversion of (3H)testosterone to (3H)dihydrotestosterone. The 5 alpha-reductase activity in the urethra and prostate increased prior to and during, but decreased after, the period of testicular descent. The 5 alpha-reductase activity in the gubernaculum remained constant throughout gestation and was not significantly higher than the background activity found in umbilical cord, testis plus epididymis, striated thigh muscle and heat inactivated samples of prostate and urethra. Prior to testicular descent, the 5 alpha-reductase activity was approximately 60 to 300 times higher in the urethra than in the gubernaculum, and approximately 20 to 55 times higher in the prostate than in the gubernaculum. These findings indicate that local conversion of testosterone to dihydrotestosterone in the gubernaculum or epididymis does not play a role in the mediation of testicular descent in the pig fetus.

Animals↗
PubMed1993

The effect of recombinant cytokines on bladder cancer cells in vitro.

We have studied the Major Histocompatibility Class II-modulating and antiproliferative actions of recombinant interferon-gamma, tumor necrosis factor-alpha, interleukin-1 alpha, interleukin-2 and granulocyte macrophage-colony stimulating factor on bladder cancer cells in vitro. Indirect immunofluorescent staining employing monoclonal antibody probes in conjunction with flow cytometric analysis and tritiated thymidine incorporation assays were used. Interferon-gamma was a strong inducer and enhancer of class II antigens. Tumor necrosis factor-alpha could not induce the expression of class II antigens on tumor cells, which were initially class II-negative, but enhanced the expression on cells which already demonstrated low levels of the antigen. Interleukin-1, interleukin-2 and granulocyte macrophage-colony stimulating factor did not affect the major histocompatibility class II expression. Interferon-gamma and tumor necrosis factor-alpha both demonstrated powerful anti-proliferative effects on the bladder cancer cells, particularly those derived from low grade tumors (G1 and G2). Interleukin-1 alpha had no effect on tumor cell proliferation. In contrast interleukin-2 and granulocyte macrophage-colony stimulating factor had significant stimulatory effects on the proliferation of the low grade tumor cells (G1).

Antigens, Neoplasm↗
PubMed1993

Epidermal growth factor and transforming growth factor alpha concentrations in BPH and cancer of the prostate: their relationships with tissue androgen levels.

We measured immunoreactive EGF and TGF alpha in prostate tissue extracts obtained from 19 patients with benign prostatic hyperplasia (BPH) and 19 with cancer of the prostate (CaP). Whilst both BPH and CaP expressed EGF (BPH = 195.61 +/- 19.94 ng g-1 protein; CaP = 235.60 +/- 24.45 ng g-1 protein) and TGF alpha (BPH = 92.57 +/- 7.60 ng g-1 protein; CaP = 100.73 +/- 15.47 ng g-1 protein) in equal concentrations, the levels of EGF in any tissue extract were on average twice those of TGF alpha. Furthermore analysis of the individual growth factor data revealed a direct correlation between EGF and TGF alpha in both BPH (r = 0.72, P < 0.001) and CaP (r = 0.69, P < 0.001). When the tumours were classified according to their Gleason score, a slight but significant increase in growth factor concentrations was noted as the tumour became less differentiated. We also measured the concentrations of testosterone and dihydrotestosterone (DHT) in prostate extracts with a view of elucidating the relationship between androgen and growth factors in this gland. There was a small positive correlation only between testosterone and EGF (r = 0.62, P < 0.05) and testosterone and TGF alpha (r = 0.61, P < 0.05) in CaP. The absence of any similar correlation in BPH where DHT becomes the predominant hormone may suggest an indirect role for testosterone in the regulation of growth factor production.

Androgens↗
PubMed1993

Intra-operative myocardial ischaemia detected by biplane transoesophageal echocardiography during transurethral prostatectomy.

Recent studies have shown an increased late mortality rate due to cardiovascular causes after transurethral compared with open prostatectomy. This has been linked to the demonstration of haemodynamic changes during transurethral prostatectomy, which may cause ischaemic myocardial injury. We used transoesophageal echocardiography (currently the most sensitive modality for detecting myocardial ischaemia) to study 26 patients during prostatectomy under general anaesthesia. Evidence of myocardial ischaemia (as shown by the development of new regional wall motion abnormalities of the left ventricle) occurred in 4 of 22 patients during transurethral and in 3 of 4 patients during retropubic prostatectomy. An intra-operative fall in systolic as well as diastolic blood pressure occurred in 21 of 22 patients during the transurethral procedure and in all 4 patients during retropubic prostatectomy. The duration of anaesthesia and the operation, and the intra-operative blood loss did not differ significantly between patients with and without evidence of intra-operative myocardial ischaemia. However, the maximum intra-operative fall in systolic and diastolic blood pressure, as well as the mass of the prostatic tissue removed, were significantly greater in patients with than in those without evidence of intra-operative myocardial ischaemia, suggesting that the latter may be related to the extent of surgery and the degree of intraoperative hypotension. In this study, 7 of 26 patients (27%) showed evidence of myocardial ischaemia during prostatectomy. However, it remains difficult to explain why intra-operative myocardial ischaemia should result in an increased cardiovascular mortality rate several years after the operation.

Aged↗
PubMed1993

Audit and its impact in the management of early prostatic cancer.

An analysis was made of a prospective database of 614 men with newly diagnosed carcinoma of the prostate who presented between January 1978 and December 1990; 3-monthly updates were available on their clinical, haematological and biochemical parameters and 6-monthly updates on chest X-rays, bone scans and skeletal X-rays. It was found that 107 men (mean age 73.5 years) had early disease at presentation. Their management was based on regular surveillance and the treatment deferred until disease progression or development of symptoms. The audit of outcome measured various clinical events. Four patients (3.7%) developed local failure, 11 (10.3%) developed bone metastases, 3 (2.8%) died of cancer with a median survival of 6.3 years, and 34 (31.8%) died of intercurrent disease with a median survival of 2.6 years. The observed survival for 12 years of the whole group was similar to the expected survival for an age-matched population in Scotland. The standardised mortality ratio was 81 (95% confidence limits 57-112).

Age Factors↗
PubMed1993

Audit and its impact in the management of advanced prostatic cancer.

From a prospective database of 614 consecutive men with newly diagnosed prostatic cancer an audit of outcome was studied in 169 men who presented with bone metastases and subsequently received hormonal manipulation in the form of monotherapy. The cohort was divided into 2 groups according to serum alkaline and acid phosphatase enzyme levels. Men with normal alkaline phosphatase levels (41.5%) had a better prognosis (median survival 38 months) than those with elevated levels at presentation (58.5%) (median survival 19 months). This difference was highly significant. A similar stratification on prostatic acid phosphatase levels did not yield any prognostic significance. With regard to cause-specific survival, serum alkaline phosphatase was an even more powerful prognosticator, with a median survival of 45 and 21 months for patients with normal and elevated levels respectively. Thus monotherapy is recommended for metastatic prostate cancer patients with normal serum alkaline phosphatase, but for those with elevated alkaline phosphatase the alternative avenues of treatment must be explored.

Acid Phosphatase↗
PubMed1993

Patterns of bone metastasis and their prognostic significance in patients with carcinoma of the prostate.

The different patterns of bone metastasis, metastatic load and their prognostic significance were examined in a consecutive series of 169 men with prostatic cancer and bone metastasis at presentation. Patients with an isolated metastasis in the pelvis or dorsal vertebrae had a better prognosis than those whose metastases were either diffuse or involved more distal sites such as the skull or the sternum, although all of these patients were classified as having M1 disease. Bone metastasis involving an area equivalent to 1 vertebral body equalled a metastatic load of 2. Based on their total metastatic load, 3 prognostic groups were identified with significant differences in case-specific survival despite receiving the same hormonal treatment. When comparing the potential efficacy of various treatments one must stratify the metastatic load, which is a powerful prognostic indicator of the outcome in patients with metastatic carcinoma of the prostate.

Bone Neoplasms↗
PubMed1993

Is the outcome of conservative management for localized prostate cancer acceptable? An overview.

The outcome of conservative management in a consecutive series of 107 localized prostate cancers (mean age 73.5 years) has been analyzed. Follow-up ranged from 1 to 12 years. Following regular surveillance and no initial treatment, 3 died from prostate cancer with a median survival of 6.3 years compared to 34 who died from intercurrent disease with a median survival of only 2.6 years. The observed survival for the whole group was similar to the expected survival for an age-matched population in Scotland. This was despite the fact that the nodal status and the capsular invasion were unknown.

Aged↗