The anatomy of the prostate: relationship with prostatic infection.
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Biomedical subjects
Publications and source records attributed to N J Blacklock.
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We are investigating the feasibility of photodynamic therapy in the treatment of localised prostatic cancer. Of major importance in this form of treatment is the extent to which light penetrates the target organ; hence, our interest in the optical properties of the human prostate gland. We obtained three whole prostates from autopsies of patients who died of non-urological causes. Red light was launched interstitially and detector fibres measured light intensity as a function of distance from the delivery fibre end. The optical constants derived from the three prostates were almost identical and indicated that light was predominantly scattered rather than absorbed (mean absorption and scattering coefficients 0.07 +/- 0.02 mm.-1 and 0.86 +/- 0.05 mm.-1 respectively). In a comparison of the tissue penetration by four different wavelengths, 633 nm red light was found to be transmitted best. Light propagation in the heavily absorbing tissue of the human liver was 4.3 times poorer than in the prostate. Such a combination of low absorption and high scattering characteristics in prostatic tissue would enhance the effectiveness of PDT. The optical constants derived will enable "light treatment planning" in patients with prostatic cancer.
A comparison of urinary fibrinolytic activity between 31 stone formers and 50 controls failed to demonstrate any significant difference and so failed to confirm an earlier independent observation. This may be due to methodological and design differences between the 2 studies, but does suggest reservations about the significance of lowered urinary fibrinolytic activity as a risk factor for renal stone disease. Dietary information from those taking part in the study suggests that a reduction of meat intake by stone formers might be associated with increased urinary fibrinolytic activity. This might account for the discrepancy between the 2 studies, in which case this observation could be of significance.
Stones were recovered from the urinary tract and their composition determined by X-ray diffraction before exposure to a pulsed dye laser beam. The resultant fluorescent emissions were recorded using a scanning reticon and they appeared to be specifically related to the composition of each stone. This technique has a practical application as it may allow identification of the composition of urinary tract stones in vivo, and so indicate the best mode of lithotripsy.
gamma-carboxyglutamic acid (GLA) is an amino acid with a high affinity for calcium. It is found in urine both as the free amino acid and incorporated into proteins such as osteocalcin. Free and bound GLA have been reported to be found at higher concentrations in the urine of stone formers than controls. We have investigated the effect of GLA and calcium, at physiological levels, on the crystallisation of calcium oxalate using a mixed suspension mixed product removal continuous crystalliser. GLA caused very significant changes in the crystallisation kinetics, but the effect was dependent on the calcium concentration. At 4 mM calcium, GLA decreased the growth rate and increased the nucleation rate; at 12 mM the reverse occurred. At all concentrations of calcium tested, GLA caused a significantly increased crystal mass to be produced. Our evidence supports the hypothesis that GLA modifies calcium oxalate crystallisation and could be a promoter of stone formation in vivo, particularly at moderately elevated levels of calcium excretion.
The pharmacokinetics of Casodex have been investigated in patients with prostatic carcinoma following single oral doses of 10 mg, 30 mg and 50 mg and during daily administration at these dose levels. Casodex displays prolonged absorption following a single dose, with peak plasma concentrations observed at up to 8 h for doses of 10 mg and 30 mg and up to 48 h for the 50 mg dose. The area under the plasma concentration-time curve increased linearly with dose, and Casodex was eliminated slowly from plasma (t1/2 about 6 days). During daily administration, Casodex accumulates about 10-fold in plasma at all dose levels; this is consistent with its long plasma elimination half-life, estimated by curve fitting of these multiple dose data to be 7-10 days. Trough plasma concentrations increased linearly with dose after both single and multiple dosing, achieving mean values of 1.80, 6.89 and 9.33 micrograms/ml for the 10 mg, 30 mg and 50 mg dose levels, respectively, after 12 weeks' dosing. Neither efficiency of renal function nor age had any apparent effect on the pharmacokinetics of Casodex. The pharmacokinetics of Casodex make it ideally suited to once-daily administration.
The effect of glycosaminoglycans on urinary stone formation was evaluated using a mixed suspension, mixed product removal (MSMPR) crystallisation system together with scanning electron microscopy (SEM) to examine the resulting crystals. Chondroitin sulphate was found to decrease the nucleation rate and to promote both the growth rate and suspension density. Results obtained with hyaluronic acid, although inconclusive, are similar to those given by chondroitin sulphate. Heparin sodium salt had a powerful inhibitory effect on both the nucleation rate and the suspension density, the effect increasing in proportion to the heparin concentration. SEM examination showed that the octahedral habit of calcium oxalate dihydrate was modified by the addition of heparin sodium salt and confirmed that the average crystal size in the presence of chondroitin sulphate and hyaluronic acid was significantly greater than the control or that found in the presence of heparin sodium salt.
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Various methods have been used clinically to assess prostatic function. We evaluated a number of ways of using zinc in post-prostatic massage urine (VB3) and found that the ratio of VB3 zinc concentration to initial urinary zinc concentration was a good indicator of prostatic secretory activity. This ratio can differentiate hormonally treated patients with carcinoma of the prostate from those untreated and from those with benign prostatic hypertrophy. The specificity is increased for individuals by repeat samples. Comparison of samples before and after resection showed no loss of function and no difference was found between groups treated with orchiectomy or LHRH agonist (Zoladex). The VB3/VB1 zinc concentration could be used in a prospective study of hormonal treatments directed against the prostate, where it could give objective evidence of a fall in secretory function of the gland.
The heterogeneous histology of the normal and diseased human prostate is well established. This study has investigated variations in cytosol androgen receptor (AR) content throughout the diseased gland to establish the most suitable sites to obtain tissue for AR assay. Only then can AR be investigated as a potential predictor of response to endocrine treatment. In a transverse slice of an enucleated prostate showing benign prostatic hyperplasia (BPH) AR levels in 1-g segments varied from 109 to 1,212 fmol/g tissue (mean 483 +/- 273; median 406), with no negative areas. Areas of higher receptor concentrations corresponded to the glandular regions of sections obtained from a slice taken in juxtaposition; areas of low receptor concentrations corresponded to the stromal regions. A significant correlation (P less than .02) was observed between AR concentration and the proportion of glandular components of each segment. Specimens were also obtained from each of three sites from 38 prostates; 45% of all specimens contained AR; however, distribution of receptor throughout the prostate was uneven. AR were significantly more likely to be measured in the peripheral zone (71% positive) than in periurethral tissue (39% positive) whilst only 24% of specimens taken from the limit of the resection possessed AR binding capacity. Similar distribution patterns were observed in both benign and malignant prostates, although 16% more specimens from carcinomatous prostates contained receptor than did those from benign glands; this difference was maintained at each site. In addition receptor levels were consistently lower in benign than in malignant specimens. It is therefore desirable to know the histological composition of specimens used for AR measurement.
High concentrations (272 +/- 33 ng/ml) of urogastrone-epidermal growth factor were measured in prostatic fluid from normal males by a specific radioimmunoassay. Significantly lower concentrations (155 +/- 24 ng/ml) were observed in the prostatic fluid of patients with benign prostatic hypertrophy than in the age-matched normal controls (2P less than 0.01). The growth factor content of seminal fluid was accounted for by the contribution of prostatic fluid. Immunochemical studies failed to show evidence of synthesis within the gland nor could high affinity receptors for the protein be demonstrated in membrane preparations of the gland.
Studies of 2 groups of patients 2 years and 8 years following vasectomy failed to demonstrate evidence of cell mediated immunity to sperm. Histological examination of testicular tissue from 11 patients undergoing reversal of vasectomy showed significant abnormalities in each. However, subsequent fertility within 15 months occurred in 7 (63.6%) of these patients. The nature of the testicular changes and the possible aetiological factors are discussed.
Between 1972 and 1977 vasovasostomy to reverse a previous vasectomy for contraception has been attempted in 27 cases. The procedure was abandoned as a technical impossiblity in only 1 case. The first 17 have been studied and in these there have been 11 pregnancies, 10 of which have already come to term with the birth of normal children, including one set of twins. Of the remainder, 2 are known to have oligozoospermia and 4 have been lost to follow-up although 2 of these were euspermic when last heard of. In spite of the encouraging results it is considered that there are no grounds for altering the present basis of vasectomy counselling in which the operation is described as likely to be irreversible.
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In the course of study of the influence of varying the amount of refined carbohydrate (sugar and sugar products) in an otherwise standardised diet in 18 normal subjects it was evident that the analysis of 24-h urine collections failed to show the profound diurnal variation in urinary electrolyte excretion and, in particular in this instance, calcium excretion. The analysis of individually voided specimens showed some normal subjects to have spontaneously high peaks of urinary calcium concentration throughout the day even whilst on a diet with low refined carbohydrate content. Increase in the refined carbohydrate content of the otherwise standardised diet caused significant increase in the number of urines with a calcium concentration above 9 mmol/1. Refined carbohydrate, a common cinstituent in Western diets, can therefore influence urinary electrolyte excretion in such a way that there may be an increased risk of over-saturation with calcium oxalate.
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