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Biomedical subjects

G D Chisholm

Publications and source records attributed to G D Chisholm.

At least 73 records · Page 4Linked to original sources
PubMed1990

Radio-immunoassay detection of interferon-gamma in urine after intravesical Evans BCG therapy.

Our previous studies suggested that interferon-gamma (IFN gamma) was produced in the local immune response to intravesical BCG. To confirm this we modified a commercially available radio-immunoassay for detection of this lymphokine in urine. The urinary levels of IFN gamma were compared in serial urine samples taken from six patients undergoing treatment with Evans strain BCG and seven patients receiving intravesical mitomycin C/epirubicin. IFN gamma was detected consistently in response to BCG with levels reaching a peak (mean 67.1 U/ml., range 7.9 to 155.9 U/ml.) four to six hours post-instillation whereas after other intravesical agents no IFN gamma was detectable after seven of 13 instillations. After the remaining six instillations lower levels were detected (mean 7.4 U/ml., range 0.6 to 22.4 U/ml.). The difference in peak levels between the two groups was statistically significant (p less than 0.001 Mann Whitney U test). These results are further evidence of specific cellular immune activity in response to intravesical BCG therapy and suggest anti-tumour mechanisms similar to allograft rejection and autoimmunity.

Administration, Intravesical↗
PubMed1990

Measures of mortality in prostatic cancer.

The use of different expressions of mortality in prostate cancer can lead to difficulty in comparing reported data. We have used different measures of mortality in the same group of 438 patients presenting consecutively with histologically proven adenocarcinoma of the prostate, in order to assess the values and deficiencies of each method. The use of expected and relative survival is shown to be valuable in allowing indirect but objective assessment of disease specific mortality in prostatic cancer.

Adenocarcinoma↗
PubMed1990

Production and response of a human prostatic cancer line to transforming growth factor-like molecules.

Serum-free media conditioned by the androgen insensitive human prostate cancer cell line DU145 showed immunological transforming growth factor-alpha (TGF alpha) activity, as well as competing activity in epidermal growth factor (EGF) radioreceptor assays (RRA). Furthermore, there were factors in the conditioned media which inhibited and stimulated DNA synthesis by DU145 cells in a dose-dependent fashion. Fractionation of the concentrated conditioned media by reverse-phase high performance liquid chromatography revealed several peaks containing EGF-like competitive activity only one of which demonstrated TGF alpha activity. However, none of the peaks corresponded to immunoreactive EGF. Measurement of EGF receptors on DU145 cells by competition and saturation analysis revealed high levels of receptors (mean +/- s.d. = 2.5 +/- 1 x 10(5) surface receptors per cell) which were of high affinity (Kd +/- s.d. = 1.0 +/- 0.5 nmol l-1). Although DU145 cells express high levels of EGF receptors, DNA synthesis was only minimally affected by exogenous EGF and TGF alpha.

Chromatography, High Pressure Liquid↗
PubMed1990

De-differentiation with time in prostate cancer and the influence of treatment on the course of the disease.

There is little information on histological changes in prostate cancer during the course of the disease. We have studied 74 patients with carcinoma of the prostate who required 2 transurethral resections of the prostate (mean interval between resections 2.4 years). They constituted 18.4% of all patients with carcinoma of the prostate presenting to our clinic between January 1978 and April 1988. All tumours were staged by conventional methods and graded using the Gleason system. The Gleason sum score in those patients with tumour in both specimens increased in 49, remained constant in 12 and decreased in 7. Within this group were 34 patients who were treated expectantly. The mean Gleason sum scores in this group increased, with a concomitant increase in local tumour stage and development of metastases. Although this was not a randomised trial, there was no significant difference in survival between patients having "deferred" management and those treated immediately, either from time of diagnosis or from time of second resection. There was, however, a significant difference in the time to second resection, with the "deferred" group requiring repeat resection on average 1 year earlier. This study confirmed the concept of tumour de-differentiation with time and showed that this phenomenon occurs in both treated and untreated tumours. Although overall survival was not influenced by the type of initial therapy or its timing, local progression, as assessed by the need for further TURP, occurred earlier in those not receiving immediate therapy.

Aged↗
PubMed1990

Morbidity following cystoscopy: comparison of flexible and rigid techniques.

Recent reports on the value of local anaesthetic flexible cystoscopy have emphasised excellent tolerance and preference for the technique over general anaesthetic rigid cystoscopy. However, no study has yet compared the post-operative morbidity rates of these procedures. Tolerance, preference and post-operative symptoms in 100 patients undergoing local anaesthetic flexible cystoscopy were compared with those in 100 patients undergoing general anaesthetic rigid cystoscopy. On initial questioning, 89% of patients found flexible cystoscopy painless and 92% expressed a preference for the same procedure on a future occasion; 98 patients who underwent flexible cystoscopy and 87 who underwent rigid cystoscopy returned a questionnaire on symptoms 1 week after the procedure. The incidence of post-operative symptoms was 33% following flexible cystoscopy and 76% following rigid cystoscopy. Patients in both groups who were undergoing check cystoscopy had a lower incidence of morbidity than those undergoing cystoscopy for other reasons. The results suggest that flexible cystoscopy was well tolerated and preferred by most patients. The morbidity associated with the procedure was also significantly less than that associated with rigid cystoscopy under general anaesthesia.

Adolescent↗
PubMed1990

The Burch Colposuspension operation for stress urinary incontinence.

One hundred and thirteen patients with genuine stress incontinence were treated by a modified Burch Colposuspension after having failed an adequate trial with medical management. Three-quarters of patients were evaluated with pre-operative video-cystometry (video-C.M.G.) while a third underwent post-operative video-cystometry. Flow rates were generally lower after surgery with 3 of the 113 patients developing post-surgery bladder instability. Previous incontinence surgery and higher parity produced statistically a greater number of failures. The overall subjective success of the operation was 80% with another 12% improved at 2 years. A 5 year long-term questionnaire follow-up did not demonstrate marked changes in these figures. The operation itself carries a 16% incidence of significant early complications, while late complications totalled 23%, the latter being primarily minor conditions. Patients left hospital after an average of 10 days.

Adult↗
PubMed1989

Prevalence of spina bifida occulta in patients with functional disorders of the lower urinary tract and its relation to urodynamic and neurophysiological measurements.

OBJECTIVE: To determine the relation between neurophysiological abnormalities and the radiological detection of spina bifida occulta in patients with dysfunction of the lower urinary tract. DESIGN: Blind assessment and subsequent decoding of mixed batch of abdominal radiographs from patients with and without urological symptoms for evidence of spina bifida occulta and comparison of results with those of previous control series. SETTING: Review study among tertiary referrals to an incontinence clinic of a city hospital. PATIENTS: One hundred and thirty eight adults with proved urodynamic abnormalities in whom neurophysiological measurements were available. INTERVENTIONS: None. END POINT: Correlation of neurophysiological abnormalities in lower urinary tract dysfunction with presence and type of spina bifida occulta and level of opening of posterior sacral arcs. MEASUREMENTS AND MAIN RESULTS: On decoding radiographs those from patients without urological symptoms showed a similar prevalence of spina bifida occulta to that in the control series (631/2707 controls; 23%). By contrast, patients with urological symptoms had a significantly increased prevalence of spina bifida occulta at S1 and S2 and a higher level of opening of posterior sacral arcs. The increased prevalence of the bony defect was particularly striking in men with urgency and instability and in women with stress incontinence. No significant correlation was found between any particular neurophysiological abnormality and the presence of spina bifida. CONCLUSIONS: In patients with dysfunction of the lower urinary tract neurophysiological abnormalities may be associated with congenital dysraphic lesions in the lower lumbar spine and sacrum. There appears to be no direct causal relation between the radiological and neurophysiological abnormalities but the findings suggest a common aetiological factor.

Adult↗
PubMed1989

Flow cytometric analysis of cellular DNA in human prostate cancer: relationship to 5 alpha-reductase activity of the tissue.

Flow cytometry of 20 prostate cancer specimens was carried out and the percentage DNA content in each phase of the cell cycle was correlated to the 5 alpha-reductase activity of the tumour. A group of 20 hyperplastic specimens was also entered into this study as control. Tumours were divided into 3 groups on the basis of their 5 alpha-reductase activity. This classification made it possible to identify a group of tumours of which none formed metastases (diploid tumours with 5 alpha-reductase activity greater than 20 pmol/mg protein/30 min and with less than 10% of the cells undergoing mitosis) and a second group of which 78% had metastasised at the time of presentation (diploid tumours with 5 alpha-reductase activity less than 10 pmol/mg protein/30 min and with more than 15% of the cells undergoing mitosis). DNA content within each of the 5 alpha-reductase groups appeared also to correlate with the histological grade of the cancer but no relationship was established with the stage of the disease. Our results suggest that a multi factorial discriminant combining DNA ploidy and 5 alpha-reductase measurements offers a good prognostic index for the assessment of disease progression in prostate cancer and that this might form the basis of a new approach to the treatment of this disease.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1989

Epidermal growth factor receptors in human prostate cancer: correlation with histological differentiation of the tumour.

The presence of specific and high affinity epidermal growth factor receptors (EGF-R) has been demonstrated in human prostate cancer (CaP). Scatchard analysis of the binding data revealed a linear plot consistent with a single class of binding sites with a mean dissociation constant (Kd) +/- s.d. = 1.6 +/- 0.4 nmol 1-1. Additionally the binding was specific for EGF since no other competitor than EGF was able to displace the binding of the labelled ligand from its receptor. Comparison of the concentrations of EGF-R in tissues from 19 patients with CaP with those measured in a group of 18 patients with benign prostatic hyperplasia (BPH) reveal that the expression of EGF-R was significantly higher in BPH (mean +/- s.d. = 125 +/- 7 fmol mg protein-1) than in CaP (52 +/- 11 fmol mg protein-1; P less than 0.01). Furthermore, in CaP the expression of EGF-R varied according to the histological grade of the cancer: well differentiated tumours demonstrated more receptors (84 +/- 13 fmol mg protein-1) than poorly differentiated tumours (22 +/- 5 fmol mg protein-1; P less than 0.01). Clearly the depletion in the expression of EGF receptors in CaP is a function of the histological grade of the cancer and as such EGF receptors could be used as a biochemical marker for tumour differentiation.

Aged↗
PubMed1989

Neurological defects of the voiding reflex arcs in chronic urinary retention and their relation to spina bifida occulta.

A group of 37 patients (24 female and 13 male) with chronic urinary retention and without demonstrable mechanical obstruction had neurophysiological measurements of their lower urinary tracts to detect any neurological abnormality which might relate to the disorder. These consisted of measurements of the electrosensitivity of the dorsal nerve of the penis/clitoris and of the urethra, measurement of the sacral reflex latencies (SRL) from dorsal nerve to urethra and to anus and between urethra and anus and EMG studies of the urethral and anal sphincters. The results suggest that female patients in particular have significant neurogenic defects in the voiding reflex arcs which find their clinical expression in detrusor underactivity with urinary retention. Plain X-rays of the renal tracts (KUB films) were also studied for the presence of spina bifida occulta. The prevalence of this defect was significantly higher than in normal controls, suggesting that in some of these patients the nerve defect might be related to a tethered cord in association with spina bifida occulta.

Adult↗
PubMed1989

Intravesical Evans Bacille Calmette-Guérin in the treatment of carcinoma in situ.

We report our experience in the treatment of carcinoma in situ of the urinary bladder using Evans strain Bacille Calmette-Guérin (BCG). The mean period of follow-up was 30 months; 18 patients received intravesical therapy and 16 of these were evaluable. They received 8 weekly instillations of 60 mg Evans strain BCG in 50 ml of saline. No intradermal BCG was given. The response rate was 93.75% at 3 months; this declined to 57% at 2 years. The complications of therapy were frequent but mild. Seven patients failed to complete the course. These results were comparable to those obtained with other strains of Bacille Calmette-Guérin.

Administration, Intravesical↗
PubMed1989

HLA-DR expression by high grade superficial bladder cancer treated with BCG.

The local immune response to intravesical BCG therapy for widespread carcinoma in situ and superficial bladder tumour was assessed using immunohistochemical methods on serial biopsies obtained during treatment. The main findings were the induction of a strong level of HLA-DR expression by urothelial cells which persisted for several months after completion of therapy. This coincided with a mononuclear cell infiltrate in the bladder wall consisting predominantly of activated helper T lymphocytes. Smaller numbers of macrophages, suppressor cytotoxic T lymphocytes and B lymphocytes were also found. These new findings confirm that the inflammatory response to BCG involves the urothelium in an immunological reaction and suggest that the success of immunotherapy with intravesical BCG may be due to enhanced tumour antigen recognition.

Administration, Intravesical↗
PubMed1989

A comparison of cyclosporin versus azathioprine treatment in renal transplants in Edinburgh.

Three year graft survival rates were calculated for 66 patients on cyclosporin and prednisolone immuno-suppression and compared to survival rates for 73 patients on azathioprine and prednisolone. There was a temporary early advantage for the cyclosporin treatment group up to four months post transplant. There was no further significant difference between the two treatment groups with graft survival rate of 81.4% in cyclosporin and 76.7% in azathioprine group at three years post transplant. Fewer of the patients on cyclosporin had acute episodes of rejection. There was no significant difference in serum creatinine or urea at one year, but the haemoglobin level was higher in cyclosporin treated patients. Cyclosporin does not appear to have increased the survival rate significantly in our centre where there is already a high graft survival with azathioprine.

Azathioprine↗