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Biomedical subjects

D Kirk

Publications and source records attributed to D Kirk.

At least 109 records · Page 6Linked to original sources

Intravesical formalin in intractable haematuria.

Eleven patients with bladder tumours classified T2 (2 cases), T3 (6 cases) or T4 (3 cases) - and 3 patients with radiation cystitis - were assessed as being beyond the scope of even palliative surgery, severe haemorrhage being present in all cases. One patient was treated by total cystectomy and urinary diversion 21 months after intravesical formalin installation. Palliative haemostatic treatment was instituted in all cases by intravesical instillation of a 10% formalin solution under general anaesthesia. Two patients received 3 and 5 instillations respectively, the former over 3 weeks and the latter over 9 months. The bladder was filled completely and an indwelling catheter introduced, the formalin solution being left in the bladder for from 3 to 20 minutes (mean: 13 minutes). Haematuria was absent after from one to 21 days (mean: 5.3 days) in 13 cases. The 14th patient died before arrest of haemorrhage. Survival after instillation was from 3 days to 32 months (mean 6.8 months). The outcome was fatal within 3 months or less in 8 cases and 6 patients died within 2 months of acute renal failure, one within 3 days of instillation. In 5 cases the treatment with formalin reduced bladder capacity to less than 100 ml. Other complications included acute infection of thigh, ruptured bladder, retroperitoneal fibrosis and severe frequency and nocturia (1 case each), and this procedure should therefore be reserved for terminal cases unable to support more aggressive therapy.

Aged↗

A serum-free culture system for studying solute exchanges in the choroid plexus.

Organ cultures of choroid plexus tissues from the lateral ventricle of juvenile rats have been maintained for periods up to 7 wk in a chemically defined, serum-free media. Of several media and various supplements evaluated, the best growth and survival was obtained with the Pasadena Foundation for Medical Research-4 media supplemented with three hormones: epidermal growth factor, insulin, and hydrocortisone. Autoradiographic studies demonstrated that the epithelial cells incorporated [3H]leucine and [3H]thymidine indicating active protein and DNA synthesis, respectively. The organ cultures were characterized by bulbous, vesicular outgrowths from the choroidal villi explants. The fluid-filled lumina of the vesicles reached diameters of 900 microns and were easily accessed by micropipettes. The walls of the vesicles were composed of single layers of epithelial cells in which the ultrastructural features in the in vivo tissue were well maintained. The in vivo polarity (apical end toward the media and basilar end of the cells toward the luminal cavity) was also maintained. This morphologically stable in vitro system seems to be a promising model for investigation of secretory mechanisms of choroidal tissue.

Animals↗

A colorimetric assay for the assessment of cytotoxicity of yeasts.

A colorimetric assay for the quantitation of microbial cytotoxicity has been developed using cells from a monocyte-like human cell line (U937), epithelial cells (Hela), and fibroblast-like cells (Vero) as targets. The fraction of surviving cells was determined by their content of the dye neutral red which is retained only by live cells and can be quantitated photometrically after controlled lysis. The neutral red retention assay was at least as sensitive as the 51Cr-release assay; it was considerably less laborious, faster, and avoided handling of radioactivity. Among the different Candida species tested, the highest cytotoxicity was associated with C. albicans and C. tropicalis; a lower degree of cytotoxicity was exhibited by C. glabrata, C. guilliermondii, C. krusei, C. parapsilosis, and C. pseudotropicalis. Among the strains of a given fungal species cytotoxicity varied by up to 40%.

Animals↗

Urethral stricture following cardiac surgery: a prospective study.

A prospective study was undertaken to assess the incidence of urethral stricture in 105 men undergoing coronary artery by-pass grafting. A pre-operative urological history was taken and peak urine flow rates measured before surgery, and 1 week and between 6 and 8 weeks after operation. All patients were catheterised in theatre with a standard type and size of urethral catheter and details recorded of the by-pass time and the degree of hypothermia. Postoperative urological problems such as urethral discharge and haematuria were noted. In addition, 100 patients completed a postal questionnaire about urinary symptoms between 4 and 12 months after surgery. The overall incidence of urethral stricture was 2%.

Adult↗

Differential growth regulation of human bladder tumor cells (J82) in culture by normal bladder cells from different aged human donors.

This study used an agarose gel culture system to study growth regulatory interactions between normal and neoplastic human bladder cells. The effects of normal human fibroblasts on tumor cell cloning efficiency in agarose was studied using 2 experimental protocols. In 1 system, the fibroblasts proliferated as anchored cells beneath the agarose, and in the other the fibroblasts were nongrowing cells embedded within the agarose as nonanchored cells. In contrast to the largely inhibitory effects of anchored fetal fibroblasts on tumor cell growth, their nonanchored counterparts were exclusively stimulatory. Similar experiments with normal fibroblasts derived from the bladders of increasingly older donors showed a progressive decline in their capacity to inhibit tumor cell growth in agarose. Further experiments modulating the growth rate of neonatal fibroblasts with fetal bovine serum have indicated that the diverse tumor responses elicited by anchored versus nonanchored cells, as well as those observed for the aged bladder fibroblasts, were a function of fibroblast growth rate. We concluded that there was an inverse regulatory relationship between the growth of normal and tumor cells; rapidly growing fibroblasts were inhibitory whereas nongrowing fibroblasts stimulated tumor cell growth in agarose culture.

Aged↗

Extraurinary manifestations of chronic pyonephrosis.

Twenty-five patients who underwent nephrectomy for chronic pyonephrosis were studied retrospectively. Such patients may present with a wide range of symptoms. Marked haematological and biochemical abnormalities are found, the most striking being a gross elevation of plasma viscosity (or ESR) and a raised alkaline phosphatase. The resulting picture often suggests extrarenal disease, and diagnostic confusion occurred in a number of patients.

Adult↗

Comparable growth regulation of five human tumor cell lines by neonatal human lung fibroblasts in semisolid culture media.

Cellular growth interactions were studied between neonatal human lung fibroblasts (NLF-13) and human tumor lines derived from carcinomas of the prostate (PC-3, DU145), bladder (J82), and endometrium (HEC-1A) and from a glioma (Hs 683t). NLF-13 were interacted with tumor cells in soft agar or agarose media using two experimental protocols. In one system, NLF-13 cells were grown as anchored monolayers proliferating under the tumor cell layer. In the second, NLF-13 were embedded directly (nonanchored) into the agar or agarose layer with the tumor cells. The results from both interaction systems were similar for all five tumor lines. Anchored NLF-13 caused a dose-dependent inhibition of tumor growth, whereas nonanchored cells produced a dose-dependent growth stimulation. A time exposure experiment indicated that tumor stimulation and inhibition were biphasic responses to NLF-13. It was concluded that low concentrations of a diffusible NLF-13 product(s) accelerated tumor growth, whereas high concentrations were inhibitory. Further, the production of the active NLF-13 substance(s) was positively correlated with NLF-13 growth rate. Tumor cell inhibition was irreversible after a 5-day exposure to proliferating NLF-13 cells. Another line of normal neonatal human lung fibroblasts (NLF-147) showed inhibitory properties similar to those described for NLF-13. However, preliminary studies with fibroblasts from the skin of a Down's syndrome neonate (DS-172) and from a human kidney tumor (KTF-130) have shown both these fibroblast types to have a reduced ability to inhibit tumor cell cultures (J82) compared to the neonatal lung fibroblasts (NLF-13 and NLF-147).

Agar↗

The effect of 5-azadeoxycytidine on cell growth and DNA methylation.

By growing cells in the presence of 3 mM thymidine and 5-azadeoxycytidine up to 20% of DNA cytosines have been substituted with azacytosine. No substitution was obtained on incubating with 5-methyldeoxycytidine. Azacytosine-substituted DNA has a very low level of 5-methylcytosine and cells, which survive azadeoxycytidine treatments maintain this low level of methylation in the absence of the drug. The DNA of such cells is undermethylated fairly evenly in all classes of DNA e.g., satellite and unique DNA. Incubation of cells in azadeoxycytidine leads to high cell mortality which is not related to the lack of DNA methylation but may be linked to the altered interactions of proteins with the substituted DNA. This effect, rather than reduced DNA methylation, may be the cause of differentiative changes observed on treatment of cells with 5-azacytidine.

Animals↗

Arterial embolisation in renal carcinoma: a useful procedure?

Twenty-eight patients underwent embolisation over a 2-year period. III effects followed embolisation in 16 (57%), 2 of whom died. Attention is drawn to the intolerance of many patients to the length of the procedure. Of 24 patients undergoing operation, one case was inoperable and difficulty was encountered in 9. No perirenal plane of oedema was identified. No specimen examined histologically showed complete infarction. The tumour tissue was more resistant to infarction than normal kidney and 8 tumours (35%) appeared to have escaped completely. It is concluded that the role of embolisation is limited and that a combination of methods for achieving adequate arterial occlusion must be used for the optimum effect.

Embolization, Therapeutic↗

Growth control of prostatic carcinoma cells in serum-free media: interrelationship of hormone response, cell density, and nutrient media.

Two established prostatic carcinoma cell lines have been grown in long-term culture in a defined medium (PFMR-4) free of serum, hormones, or growth factors. Growth of both lines in serum-free medium was population dependent. This cell-density requirement could be replaced by mitomycin C-inactivated feeder cells, homologous conditioned medium, or fetal bovine serum, but not by hormones or growth factors. The cells responded to these factors only at high density. The nature of this hormonal response was dependent on the kind of basal nutrient medium used. Growth in PFMR-4 with added insulin was more rapid than that in DME/F12 medium with any combination of hormones or growth factors and was substantially greater than growth in DME/F12 medium with insulin alone. The results demonstrate that whereas these two prostatic carcinoma lines (PC-3 and DU 145) do not require hormones for survival or growth, they do respond to certain hormones under appropriate conditions. These conditions include both the type of basal nutrient medium used and the population density.

Animals↗