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Biomedical subjects

G D Chisholm

Publications and source records attributed to G D Chisholm.

At least 91 records · Page 5Linked to original sources

[Onset of and survival in adenocarcinoma of the prostate. Analysis of 48 consecutive cases studied over 10 years].

Four hundred and thirty-eight men with histologically confirmed prostatic adenocarcinoma were diagnosed consecutively and followed up closely for up to ten years. The mean age at presentation was 72.5 years and ranged from 45.3 to 91.0 years. Half of the total presented with symptoms of increasing urinary outflow obstruction and a quarter with acute urinary retention. One fifth of the total were diagnosed incidentally and these men had markedly less risk of progressing to skeletal metastases than those with localised, but clinically detectable disease. Most (60%) had locally advanced or metastatic disease at the time of diagnosis and the prevalence of skeletal metastases was seen to increase with local tumour stage. 40% had skeletal metastases at diagnosis and less than half of these patients survive two years. High grade tumours were associated with poor outcome, with a five year survival of less than 20% when the Gleason sum score was greater than seven.

Adenocarcinoma↗

Neurophysiological measurements in patients with genuine stress incontinence of urine and the relation of neurogenic defects to the presence of spina bifida occulta.

Neurophysiological measurements comprising surface electromyography (EMG) of the urethral and anal sphincters, measurement of the sensory thresholds of the dorsal nerve (DN) of the clitoris and the urethra and sacral reflex latencies from the dorsal nerve to urethra and anus and from the urethra to anus were performed in 44 females with genuine stress incontinence, in order to detect any relationship between the clinical disorder and a neurogenic defect in the innervation of the muscles involved in maintaining continence. Plain X-rays of the renal tracts (KUB films) were also studied to establish whether the prevalence of spina bifida occulta was increased in this group of patients and was a likely explanation for the nerve defects. Forty-three patients were found to have abnormal neurophysiological responses and the prevalence of spina bifida occulta was 50%, which compares with a prevalence of 17% in normal female controls. Genuine stress incontinence appears to be at least partly associated with defective innervation of the lower urinary tract and it is likely that in some cases the defect may be related to the presence of spina bifida occulta.

Adolescent↗

Age, and size and grade of tumour predict prognosis in incidentally diagnosed carcinoma of the prostate.

Of 403 consecutive cases of prostatic carcinoma 69 were diagnosed incidentally and were managed with a deferred treatment policy. The mean age at diagnosis was 74 years and mean follow-up was 42 months. Retrospective analysis confirmed that many such patients die of intercurrent disease before symptomatic tumour progression. However, patients aged 70 years or less at diagnosis with diffuse, high grade disease were shown to be at greater risk of symptomatic tumour progression. In this study 60% progressed to skeletal metastases within 3 years. Deferral of treatment in such patients appears inappropriate.

Age Factors↗

Neurophysiological abnormalities in genuine female stress urinary incontinence.

Perineal sensory and motor function was investigated in 28 women with genuine stress incontinence of urine and compared with a matched control group. Electrosensitivity of the dorsal nerve of the clitoris and of the urethral mucosa was significantly diminished in these patients (eight measurements 'insensitive'). Three different reflex latency measurements (dorsal nerve to external anal sphincter, dorsal nerve to urethral sphincter, urethral mucosa to external anal sphincter) were prolonged in incontinence (14 absent reflexes). Mean motor unit potential duration of the external anal sphincter was also prolonged, reflecting an early neuropathy. Anorectal manometry detected significantly weaker squeeze pressures in stress incontinence although other variables were unaffected.

Adult↗

Ultrasound as an alternative to intravenous urography in prostatism.

Seventy-five patients, with uncomplicated benign prostatic hypertrophy referred for pre-prostatectomy assessment, were studied to determine whether renal tract ultrasound combined with plain films of kidney, ureters and bladder could provide an acceptable alternative to intravenous urography (IVU). All patients had both IVU and ultrasound. Bladder residual urine volumes were calculated by ultrasound measurements. Fifty-nine (78%) patients had normal IVU and ultrasound. Twelve (16%) had both abnormal IVU and abnormal ultrasound. Four (6%) had positive findings on one examination not detected on the other: two of these occurred with ultrasound and two with IVU. Measurement of residual volume of urine in the bladder by ultrasound and IVU is discussed. The combination of ultrasound and a plain radiograph of the urinary tract provides more information and should replace IVU in the preoperative assessment of patients with uncomplicated benign hypertrophy of the prostate.

Aged↗

Prevalence and patterns of spina bifida occulta in 2707 normal adults.

Plain radiographs of the urinary tract on 2707 normal volunteers were reviewed to establish the prevalence and patterns of spina bifida occulta in the normal population. Abnormalities in the formation of the posterior arch were identified in 23%, and four different patterns are described. In this group of subjects the condition was twice as common in males as in females (P less than 0.001) and commoner in younger adults. The commonest defects were either in S1 alone or involved S1 and S2 together. Isolated defects at L5 or S2 were rare. The level of opening of the posterior sacral arcs was assessed and a high level of opening was shown to correlate with the presence of spina bifida occulta.

Adult↗

Immunocompetent cells in human testis in health and disease.

The authors have investigated lymphocyte subpopulations and macrophages in normal human testes and the testes of patients under investigation and treatment for subfertility. Specific monoclonal antibodies were used in an indirect immunoperoxidase technique. In normal tissues, T lymphocytes (Leu 4-positive cells) were present in the rete testis with a preponderance of cells of the suppressor/cytotoxic phenotype. In contrast, no lymphocytes were detected within the peripheral portions of the testis. Cells reacting with the anti-Leu M3 monoclonal antibody, which defines monocytes/macrophages, were detected in appreciable numbers in peripheral testis with a specific location around the seminiferous tubules. HLA-DR-positive cells (human leukocyte antigens--class II [DR] determinants of the major histocompatibility complex) also were identified and showed a similar pattern of distribution to that of the Leu-M3 positive cells. While no lymphocytes were seen in the normal peripheral testis, T lymphocytes were detected in testicular biopsies from subfertile patients. Suppressor/cytotoxic T cells (Leu 2a-positive) predominated in patients with oligozoospermia and obstructive azoospermia while T cells of the helper/inducer phenotype predominated in patients with unilateral testicular obstruction and in postvasectomy patients. Sperm antibody measurements correlated with these findings.

Adult↗

Indications for investigation of post-micturition dribble in young adults.

The endoscopic and urodynamic findings in eight male patients in whom post-micturition urinary dribble (PMD) was either the sole or predominant urinary symptom have been reviewed. In three patients whose only symptom was PMD, both endoscopic and videocystometric examinations were normal. In the remaining five patients with additional urinary symptoms, a functional or anatomical abnormality of the lower urinary tract was found in every patient. We conclude that in the assessment of patients with PMD, endoscopic and/or urodynamic investigation is of value only in those patients with multiple urinary symptoms.

Adolescent↗

Sacral reflex latency in acute retention in female patients.

Neurophysiological measurements of the innervation of the lower urinary tract were performed on 14 female patients presenting with unexplained acute urinary retention. The method consisted of (a) static electromyography (EMG) of the anal and urethral sphincter with the patient relaxed, coughing and gripping, (b) the study of sensory thresholds on the dorsal nerve of the clitoris and in the urethra, (c) the measurement of sacral reflex latencies (SRL) from the dorsal nerve of the clitoris to the anus and urethra and from the urethra to the anus. The results showed that all 14 patients had significant defects in the innervation of their lower urinary tract. These findings suggest that a neurological explanation for acute retention in women should always be sought before making any other diagnosis.

Acute Disease↗

Antibiotic prophylaxis for prostatic surgery. Single-dose cephradine compared with single-dose cefotaxime.

Several previous studies have attested to the value of antibiotic prophylaxis for prostatic surgery. We report a prospective randomised study which compared a single dose of cefotaxime with a single dose of cephradine given with the induction of anaesthesia. There was little difference between these regimens and it was concluded that either may be used, depending on availability and cost of the antibiotic. We have now completed a 5-year study of antibiotic prophylaxis for prostatic surgery and we also report the results of a long-term survey of the ward flora. There has been no significant change and there is no evidence for the emergence of resistant strains.

Aged↗

Local immune responses after intravesical BCG treatment for carcinoma in situ.

The lymphoid cellular infiltrates in the bladder biopsies from patients with carcinoma in situ before and after BCG intravesical therapy have been determined and characterised. This has been achieved using a panel of monoclonal antibody probes in an indirect immunoperoxidase technique. These studies have revealed the predominance of T-cells of the helper/inducer phenotype (T4+), beta-lymphocytes (B1+) and macrophages (Leu M3+, 3.9+) in bladder biopsies after BCG therapy. HLA.DR antigens were also expressed on the lymphoid cells infiltrate as well as the urothelial cells. These results suggest that the components of an active immune response were present and enhanced in the bladder wall after BCG therapy.

Administration, Intravesical↗

Neurophysiological measurement of the voiding reflex arcs in patients with functional disorders of the lower urinary tract.

Neurophysiological measurements were carried out in 180 patients presenting to a Joint Incontinence Clinic with a history of lower urinary tract dysfunction. A full urodynamic assessment was performed along with neurophysiological measurement of the voiding reflex arcs. The majority of patients were shown to have significantly abnormal responses on neurophysiological measurement when compared with normal controls. Two particular groups, patients with acute retention and females with stress incontinence, were shown to have markedly poorer results than patients with other urodynamic problems. These results suggest that many patients with lower urinary tract dysfunction may have a neurological component.

Adolescent↗

Bladder cancer flow cytometry profiles in relation to histological grade and stage.

Flow cytometry was used as an additional measurement to monitor 59 untreated patients with bladder cancer. The findings indicate that tumours belonging to the same stage and grade can demonstrate different flow cytometric profiles. Using this technique, together with routine histological assessment, we were able to subclassify bladder tumours in respect of their progress. Flow cytometric profiles are recommended for additional information about the aggressiveness of the tumour and the potential response to treatment.

Aged↗

Localization of epidermal growth factor receptors in the human prostate by biochemical and immunocytochemical methods.

The receptor for epidermal growth factor (EGF) was characterized in the particulate fraction from human benign prostatic hyperplasia (BPH) and was present in 85% of tissues analysed. The uptake of 125I-labelled EGF by BPH was dependent on both time and temperature, with maximum specific uptake achieved after incubation for 90 min at 37 degrees C. Binding characteristics revealed two classes of binding sites of higher (mean dissociation constant (Kd) +/- S.D. = 0.8 +/- 0.2 nmol/l) and lower (Kd = 7.6 +/- 2.8 nmol/l) affinities. Competition studies demonstrated the specificity of the receptor assay since the binding of labelled EGF was abolished with excess unlabelled EGF but not with excess unlabelled human GH, human insulin, venom nerve growth factor, human FSH, human LH and human prolactin. There was a complex biphasic relationship between specific binding and protein concentration in the range 0.1-8 mg/ml. Subcellular fractionation of BPH homogenates demonstrated that the bulk of the specific binding was confined to the 800 g (crude heavy pellet) and 15,000 g (mitochondrial pellet) fractions. The 105,000 g (microsomal pellet) and the 105,000 g (cytosol fraction) exhibited low and variable binding capacities for the growth factor. The presence of EGF receptor was also confirmed by immunocytochemical staining of frozen sections from BPH using monoclonal antibody specific for EGF receptors. A positive correlation between 125I-labelled EGF binding and the intensity of staining was found. The presence of a specific EGF-binding receptor protein in human BPH tissues suggests that EGF may play a role in the pathogenesis of human BPH.

ErbB Receptors↗

Comparison of radioimmunoassay and immunoradiometric assay for serum prostatic acid phosphatase.

We have compared the laboratory performance of immunoradiometric (IRMA) and radioimmunoassay (RIA) methods developed in this laboratory for measurement of serum prostatic acid phosphatase (PAP). The IRMA utilizes a radiolabelled mouse monoclonal anti-PAP and a solid phased rabbit polyclonal anti-PAP. The same rabbit antibody is used in the RIA. The IRMA shows excellent precision over a much wider working range (0.25-1000 micrograms/l) than the RIA (0.73-14.0 micrograms/l), and can be completed in 5 h, while the RIA requires 3 days. Levels in healthy males and in patients with benign prostatic hypertrophy are similar in both assays, upper limits of normal being 1.8 micrograms/l (IRMA) and 4.7 micrograms/l (RIA). The two assay methods correlate very well (r = 0.97) when PAP is measured in serum from prostatic cancer patients, although IRMA results are generally lower than those obtained by RIA. About 20% of patients with non-metastatic prostatic carcinoma had elevated serum PAP, whereas about 80% of those with metastatic disease had raised levels. The diagnostic efficiencies of the RIA and IRMA appeared similar. The value of the IRMA in follow-up and staging remains to be determined.

Alkaline Phosphatase↗