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Biomedical subjects

G D Chisholm

Publications and source records attributed to G D Chisholm.

At least 199 records · Page 11Linked to original sources

Renal angiography problems in live kidney donors.

We compared renal angiographic and operative findings in 88 live kidney donors. Fifty patients had normal arteriograms and uneventful nephrectomies. Abnormal renal parenchymal or main artery lesions were found in eight donors (9%). These included four renal artery stenoses; the kidney distal to the lesion was used for transplanting. Thirty one patients (35%) had multiple renal arteries. Only 24 of these (77%) were diagnosed at pre-operative angiography, though on review angiogram accuracy could be raised to 94%. Except for one patient the accessory renal arteries missed at angiography were tiny twigs; the small renal infarcts caused by ligating them did not impair transplant survival. There was one serious misdiagnosis of multiple renal arteries, preventable on review of the abdominal aortogram. We condiser pre-operative angiography an essential step for the live kidney donor. It is the most accurate way of ensuring that his remaining kidney will be structurally sound. Finding multiple renal arteries has a decisive impact on management. Abdominal aortography rather than routine selective arteriography is the safe and therefore preferable approach to these patients.

Humans↗

The tissue cage model in the distribution of antibacterial agents.

Developments in the measurement of interstitial tissue fluid using the tissue cage model are described. The design and physical characteristics of tissue cages are examined and evidence is presented to show that the fluid contained within these cages is representative of interstitial tissue fluid. The distribution of a variety of antibacterial agents into tissue cage fluid is examined and shows that this technique is a reliable experimental model for the study of drug distribution. The results also show that some antibacterial agents may never, normally, distribute into the tissue fluid and that the use of tissue homogenates, especially the kidney, is unreliable as a guide to the tissue concentration of a drug.

Animals↗

Receptor protein for dihydrotestosterone in nuclei of the female prostate of Praomys (Mastomys) natalensis.

An investigation was carried out to identify and characterize the binding of androgens within the nuclei of the prostate from female Praomys (Mastomys) natalensis. After in vivo and in vitro labeling with tritiated androgens, the tissue was subjected to cell fractionation and the nuclear fraction was purified. Gel exclusion chromatography and sucrose density gradient centrifugation of the nuclear extract showed the presence of a steroid receptor complex having a sedimentation coefficient of 3 S. Subsequent analysis of the bound radioactivity revealed that more than 90 per cent of the recovered tritiated steroid was dihydrotestosterone. This binding was found to be temperature dependent and could not be shown in liver tissue. The behavior of this nuclear steroid receptor complex is compared with that of the male Mastomys and the rat. It is suggested that the female Mastomys could be used as an experimental model for studying hormone effects on the prostate.

Animals↗

Investigations into the use of 77Br labelled 5alpha-dihydrotestosterone for scanning the prostate.

The potential use of a potent androgen labelled with a gamma emitting radionuclide for scanning the prostate was investigated. 2alphabromo 5alpha-dihydrotestosterone was synthesized and subsequently labelled with 77Br. The distribution of this compound was studied in rat and human tissues. The maximum concentration of radioactivity in the rat prostate at 1-4 h following the injection was found to be between 0.5-0.8% of the injected dose per gram of the tissue. In the human however, that value was 0.002-0.003%. Considering the overall results it was concluded that this compound is not appropriate for scanning the prostate.

Animals↗

Peptic ulceration, gastric secretion, and renal transplantation.

Fifty-four patients on haemodialysis for chronic renal failure underwent renal transplantation. Basal and maximum acid output and the incidence of peptic ulcer before transplantation were not significantly different from those of controls. But after renal transplantation the incidence of symptoms of peptic ulcer was high (22%) and four out of six patients who developed gastrointestinal bleeding died from this complication. In men peak acid output was significantly increased after renal transplantation and was associated with a 30% incidence of symptoms of peptic ulcer compared with 10% in women, who showed no significant change in mean basal or peak acid output. Peptic ulceration after transplantation was not associated with steroid dosage, hyperparathyroidism, or the height of blood urea concentrations. Given criteria of a history of dyspepsia, abnormal barium meal findings, or gastric hypersecretion, it was not possible to identify patients at risk from peptic ulceration or life-threatening complications after renal transplantation. Thus the routine screening of these patients for peptic ulcer has no practical value, and the incidence of fatal complications is not high enough to justify routine prophylactic anti-ulcer surgery aimed at reducing acid secretion before renal transplantation.

Female↗

Follow-up of prostate carcinoma with serial bone scanning using cyclotron-produced 18-fluorine.

Seventy-four patients with carcinoma of the prostate were studied annually by combined radiological and 18F scintigraphy over a 5-year period. Of the patients who have no radiological evidence of bone metastases, 25% have a positive 18F bone scan. Follow-up of these patients has shown that scan abnormalities perceded x-ray changes from between 1 to 4 years. False negative scans were not seen with 18F which allows for greater accuracy in the detection of skeletal metastases. Teh accurate staging of carcinoma of the prostate cannot be made without bone scanning. Preliminary results with 111In bleomycin as an adjunct to 18F have shown this to be a useful radio-pharmaceutical to distinguish metastases from benign lesions, and further studies are warranted.

Aged↗

Androgen receptors in the prostate of the Rhesus monkey.

The presence of an androgen receptor protein in the supernatant preparation of the prostate from Rhesus monkey (macaca mulatta) is described. The molecular weight of this receptor protein was found to be 2.8 - 2.9 X 10(5) daltons. The levels of free and bound androgen receptors were measured in the caudal and cranial lobes of the prostate by an exchange assay using methyltrienolone (R1881). The concentration of the free binding sites in the caudal lobe ranged between 3.7 - 23.7 fmol/mg proteial binding sites in the caudal lobe ranged between 36.0 - 112.7 and in the cranial between 21.2 - 55.0 fmol/mg. The bound receptor ranged between 43.3 - 109.0 and 19.1 - 47.3 fmol/mg protein for caudal and cranial lobes respectively. The level of both bound and free receptors was found to be significantly higher in the caudal lobe. This data suggests that the two lobes of the prostate in the Rhesus monkey can be equated with the two zones of the human prostate in respect of androgen responsiveness.

Animals↗

Identification of an androgen receptor in the cytosol of the female Mastomys prostate.

An in vivo and in vitro study was carried out on the prostate from the female Praomys (Mastomys) natalensis to identify and characterize the binding of androgens within the cytoplasm. The labelled cytosol was prepared and subjected to gel exclusion chromatography and density gradient centrifugation. A macromolecular protein associated with the radioactivity was isolated on Sephadex G-200. Subsequent analysis of the steroid receptor complex showed that the major part of the radioactive steroid (64 percent) was dihydrotestosterone. This binding was inhibited by unlabelled testosterone and could not be demonstrated in liver cytosol. Characterization of this dihydrotestosterone receptor complex revealed a sedimentation coefficient of 4.6 s in the presence of a high salt solution (0.4 M KCl). The complex aggregated in the absence of 0.4 M KCl and sedimented preferentially from 5.6-7.4 s together with polydisperse aggregates of higher sedimentation coefficients. The use of this animal as an experimental model for hormonal studies on the prostate is suggested.

Animals↗

The hormone response to a synthetic androgen (mesterolone) in oligospermia.

Forty subfertile men with oligospermia were treated with a synthetic androgen (Mesterolone). The effect of the drug was evaluated by measuring serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and analysing the semen before and after treatment. The results demonstrated that in twenty-three patients treated for 6-9 months there was a significant decrease in serum testosterone (P less than 0.01); the means +/- SEM before and after treatment were 17.05 +/- 0.95 and 14.7 +/- 0.95 (nmol/l serum) respectively. There was a pronounced increase in serum LH (P less than 0.01), the values being 2.73 +/- 0.26 and 3.61 +/- 0.3 (u/l) respectively. However, no significant difference was found in serum FSH before and after treatment. The sperm concentration showed a variable response to treatment. In twenty-one patients there was either no change or worsening in the sperm concentration, whereas in nineteen patients an improvement was observed. The analysis of variance of sperm concentration and motility for the periods before and after treatment, for all the patients, showed no significant difference in the sperm concentration F1.145 = 2.82 (P=0.1).

Dihydrotestosterone↗

Serum dihydrotestosterone in patients with benign prostatic hypertrophy.

Serum dihydrotestosterone (DHT) and testosterone were measured by radioimmunoassay in 24 normal men aged 60 to 80 years and in 25 patients with benign prostatic hypertrophy in the same age range. There was a significant increase in the level of dihydrotestosterone in patients with prostatic hypertrophy but no significant difference was found between the testosterone levels of the 2 groups. The scatter of the individual values for DHT indicated that this measurement has little practical clinical application in the diagnosis of prostatic hypertrophy. It is suggested that the increase in DHT may be due, at least in part, to a prostatic contribution to the circulating level and the relevance of this observation in relation to the aetiology of benign prostatic hypertrophy is discussed.

Aged↗

Can angiography stage renal carcinoma?

We have compared the staging of renal carcinomas in 36 patients as judged preoperatively by angiography (T stage) and postoperatively by histopathology (P stage). Using the standard abdominal aortogram and selective renal arteriogram we found a considerable error rate in T staging (40%). The commonest error was preoperative overstaging, and this is probably determined by the behaviour of renal carcinoma, rather than by inadequate angiography. We conclude that whilst renal arteriography remains a useful diagnostic aid, it cannot answer questions on tumour extent with any accuracy. Staging by histopathology is essential for proper assessment and management of these patients.

Angiography↗

The effect of antiandrogens and stilboestrol on the cytosol receptor in rat prostate.

The effects of 4 antiandrogens and stilboestrol on the cytosol receptor of the rat ventral prostate have been compared. Equimolar doses of cyproterone acetate, chlormadinone acetate, SC 9022 and flutamide inhibited the binding of dihydrotestosterone to the receptor complex in vivo by 44 to 50% whereas stilboestrol had no effect. In the in vitro studies an equimolar concentration produced similar effects to those observed in vivo with the exception of flutamide which had no effect. This technique provides a method for assessing and comparing the effectiveness of antiandrogens on the androgen receptor complex of the prostate.

Androgen Antagonists↗

Differential androgen uptake by the lobes of the rhesus monkey prostate.

The prostate of the rhesus monkey (Mucacca mulatta) consists of a cranial and a caudal lobe. The uptake of [3H] testosterone by these 2 lobes has been measured and compared with control tissues. A significantly higher uptake of radioactivity was found in the caudal lobe when compared to cranial as well as other control tissues. The uptake of radioactivity by the caudal and cranial lobes was suppressed when unlabelled testosterone was introduced into the incubation media. The relationship between these 2 lobes of the monkey prostate and the central and peripheral zones of the human prostate is described.

Animals↗

The treatment of oestrogen-escaped carcinoma of the prostate with estramustine phosphate.

30 patients with oestrogen-escaped carcinoma of the prostate have been treated with estramustine phosphate (Estracyt). 27% showed a partial objective response and 33% had a subjective response. The terms used for defining a response are challenged and it is recommended that comparative controlled trials are necessary to judge the place of this drug in the management of advanced prostatic cancer.

Clinical Trials as Topic↗

Relationships between spermatogenesis and serum hormone levels in subfertile men.

The measurements of serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were related to the sperm concentration and testicular biopsy in 137 subfertile men. The biopsies were classified into four histological groups: normal, focal tubular atrophy, maturation arrest and Sertoli-cell-only syndrome. A positive correlation was found between sperm concentration and the histological grade of spermatogenesis. FSH was directly related to the spermatogenesis and the values were significantly raised in maturation arrest and Sertoli-cell-only syndrome. This relationship was present, but to a much lesser extent, for LH. Serum testosterone levels remained unchanged and no relationship between testosterone and either sperm concentration or testicular biopsy was observed. These data indicate the value of FSH in the investigation of the subfertile male, but suggest that the routine measurement of testosterone is unnecessary.

Follicle Stimulating Hormone↗

Androgen concentrations in prostate and serum of the male and female Praomys (Mastomys) natalensis.

The levels of androgens in the male prostate, seminal vesicles, and serum, as well as in the female prostate and serum, were measured in the rodent Praomys (Mastomys) natalensis. Measurements were made in different age groups of both males and females using a sensitive radioimmunoassay. The results showed that the values for serum testosterone were 10 times greater in the male than the female. The concentration of serum dihydrotestosterone in the male was approximately one-tenth of the concentration of testosterone. The recovery of dihydrotestosterone from the prostate in the female and seminal vesicle in the male was low and these values were not considered. The concentrations of testosterone and dihydrotestosterone in the male prostate were 8.3 +/- 0.5 and 20.0 +/- 2.4 ng per g of wet tissue, respectively. The concentration of testosterone in the female prostate, 7.1 +/- 0.5 ng per g of wet tissue, was similar to that in the male. These studies have shown that the female Mastomys has a prostate which exists in a low androgen environment; it is suggested that this could be used as an experimental model for studying hormonal effects on the prostate.

Androgens↗