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Biomedical subjects

N J Blacklock

Publications and source records attributed to N J Blacklock.

At least 19 recordsLinked to original sources

Photodynamic therapy for localised prostatic cancer: light penetration in the human prostate gland.

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.

Aged

Do stone formers have lower urinary fibrinolytic activity than controls?

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.

Creatinine

Identification of urinary stone composition by pulsed dye laser.

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.

Humans

Calcium oxalate crystallisation kinetics and the effects of calcium and gamma-carboxyglutamic acid.

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.

1-Carboxyglutamic Acid

The pharmacokinetics of Casodex in prostate cancer patients after single and during multiple dosing.

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.

Absorption

The effect of glycosaminoglycans on the crystallisation of calcium oxalate.

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.

Calcium Oxalate

Ratio of post-prostatic massage urinary zinc concentration to initial urinary zinc concentration. An improved method of assessing prostatic function.

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.

Humans

The role of magnesium in calcium oxalate urolithiasis.

The aim of this study was to evaluate the effect of magnesium on calcium oxalate crystal formation, both in physiological conditions and at slightly higher oxalate concentrations, using a mixed suspension mixed product removal crystallizer and scanning electron microscopy. True supersaturation ratios were calculated by allowing for complexation in solution. Magnesium inhibited the nucleation rate at all oxalate concentrations. It also inhibited the growth rate at oxalate concentrations of less than approximately 2.0 mmol/l but promoted the growth rate at higher concentrations. This suggests that, provided the oxalate concentration is sufficiently high, increase of magnesium concentration can increase the crystal growth rate. At physiological concentrations of oxalate, however, magnesium decreases both nucleation and growth rates. The SEM photographs showed that the predominant crystal was calcium oxalate trihydrate at low magnesium concentrations, with calcium oxalate dihydrate being observed in larger quantities at high magnesium concentrations.

Calcium Oxalate

Incidence of renal stones in 18 British towns. A collaborative study.

The geographical distribution of renal stones in England and Wales was investigated by selecting 18 towns which encompassed a range of social and economic conditions. Case registers of stone patients were maintained in the hospitals for 2 years; they included out-patients and in-patients. The annual registration rate was 22/100,000 population. Additional information was available for 1980 from Hospital Activity Analysis and the annual rate was 28/100,000. It is suggested that this is the best estimate of the incidence of renal stones in England and Wales. The rate ranged from 56/100,000 in Canterbury to 15/100,000 in Burton-on-Trent. The incidence of renal stones was higher in towns with better social and economic conditions. In comparison, climatic factors, latitude and water hardness were not important determinants of the distribution of renal stones.

Age Factors

Radiation dose to patient and staff during percutaneous nephrostolithotomy.

The radiation dose to the patient and to members of staff was monitored during 18 procedures for the percutaneous removal of renal stones. It was found that the radiation dose to the patient was minimal and was about the same as for an IVU. The overall dose to the staff was acceptably low and within safety limits. It was concluded that PCNL is a safe procedure from the radiation point of view but it may be advisable to take certain precautions if the workload is high.

Fluoroscopy

The role of Chlamydia trachomatis in epididymitis.

Microbiological studies have identified an infective micro-organism in 28 of 54 patients (52%) with epididymitis. Chlamydia trachomatis was the commonest infection isolated, occurring in 15 patients. An additional 17 patients (31%) who were culture negative had serological evidence which suggested recent chlamydial infection. Most patients with chlamydia were under 26 years of age, in contrast to patients over 35 years, in whom coliform infections predominated. Of the 12 consorts of patients with chlamydial epididymitis who were screened, nine were also positive for this micro-organism. These findings have important implications in the management of epididymitis, especially in young men.

Adolescent

Sucrose and idiopathic renal stone.

Idiopathic renal stone comprises more than 80 per cent of kidney stone disease. Whilst the incidence rate in the Western World is high, that in Africa south of the Sahara is very low. Epidemiological studies point to a dietary aetiology as the basis for stone formation in the kidney. A number of dietary constituents increase the urinary risk factors for stone formation and one of these is sucrose. The sucrose effect is exaggerated when it is consumed in certain forms. There is also the evidence that a third of a normal population responds in an exaggerated manner in respect of an increased excretion of urinary risk factors when sucrose is consumed and this phenomenon has been noted in over 70 per cent of idiopathic stone formers. In studying the mechanism of this, insulin was found to influence distal renal tubular function to increased calcium excretion. Stone formers with an exaggerated urinary risk factor response to sucrose were found to have abnormally high and sustained blood levels of insulin following a standard glucose test meal. Where sucrose or sucrose products are in abundance, quite apart from its effect in increasing urinary risk factors in the population in general, there is particular vulnerability of a significant sub group within the population with this type of insulin response. Sucrose furthermore is known to induce nephrocalcinosis in the kidney of the rodent and similar calcific lesions have been found in the kidney substance of man and these have been observed to begin to appear within the first decade of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium

Regional variation of cytosol androgen receptors throughout the diseased human prostate 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.

Cytosol

Urogastrone-epidermal growth factor concentrations in prostatic fluid of normal individuals and patients with benign prostatic hypertrophy.

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.

Chromatography, Gel