Gordon Williams

Malignant disease in patients with long-term renal transplants.

The incidence of de novo malignancy was analyzed in 274 renal transplant recipients whose graft had functioned for at least 3 years and who had been followed for 2622 patient-years and individually for up to 29 years. The actuarial incidence and relative risks (RR) of tumor development (compared with National statistics) were calculated. Subgroup analysis was performed according to age, sex, the number of years and type of immunosuppression, and the tumor type. Seventy one tumors occurred in 54 patients. Skin tumors were the most common, followed by lymphoma, renal, bladder, and bronchial carcinoma. The actuarial cumulative risks of tumor development were 18.4% (95% confidence interval [CI] 12.4-24.3%) at 10 years and 49.6% (95% CI 36.3-62.0%) at 20 years. The overall RR of developing a tumor was 6.2 but was higher for men (RR 7.3) than women (RR 4.9). The RR of developing skin cancers, but not other malignancies, increased from 6.6 at 5 years to 20 after > 15 years. There was no evidence that cyclosporine-treated patients had an increased incidence of tumors, indeed the risk may be less in patients treated with cyclosporine and low-dose azathioprine than in those treated with azathioprine and prednisolone alone after more than 5 years.

Renal transplantation following immunoadsorption in highly sensitized recipients

Five highly sensitized patients, with panel reactivity greater than 80% for 1.75-5 years, were treated by extracorporeal staphylococcal protein-A immunoadsorption, prednisolone, and cyclophosphamide. The five patients underwent treatment of 18-40 (mean 31) liters of plasma, respectively in 4-7 (mean 5.6) sessions. This reduced the titer of cytotoxic antibodies to sensitizing antigens to < 1/8 in all cases and abolished reactivity to crossreacting antigens. Two patients required retreatment following resynthesis of cytotoxic antibodies. All five patients have been transplanted, and four of these now have stable serum creatinines of 168 mumol/L at 34 months, 208 mumol/L at 29 months, 96 mumol/L at 5 months, and 125 mumol/L at 3 months posttransplantation. One patient had primary graft dysfunction due to acute tubular necrosis; the kidney was removed after eight weeks and showed cortical necrosis without evidence of acute rejection.

The incidence of immunosuppression-related skin disease in long-term transplant patients

One hundred and twenty-one patients who had received a renal allograft between 4 months and 21 years previously (mean +/- SD, 71 +/- 62 months) were studied. Seventy-two patients were conventionally immunosuppressed with azathioprine and prednisolone, and 36 had been exposed to the current regime of cyclosporine, azathioprine, and prednisolone. Forty-five patients had viral warts, of whom 20 had more than 10 warts. The presence of viral warts was significantly associated with pale skin type, excess sun exposure, and with duration of allograft. Viral warts were significantly more common in those on conventional immunosuppressive therapy, but this could be solely a reflection of the difference in duration of transplant between the 2 groups. Twelve patients were found to have developed dysplastic or neoplastic skin lesions since transplantation. The incidence of dysplasia increased with increasing age and was significantly associated with pale skin type, excess sun exposure, and duration of allograft. Despite the shorter duration of treatment in those on the new treatment regime, there was no difference between the 2 groups in the proportion of patients with dysplastic skin lesions. Immunosuppression-related skin disease may be a significant problem in allograft recipients in this country, and we suspect that patients taking cyclosporine will have similar problems to those on conventional immunosuppressive drugs alone. Immunosuppressed patients should be advised to avoid sun exposure, to use sunscreens, and should be monitored carefully for the development of dysplastic lesions.

Real-time ultrasound measurement of bladder volume: a comparative study of three methods

The accuracy of different ultrasound methods for determining the volume of urine in the bladder was compared using three methods in current use. Each method was applied to the same ultrasound images from 16 patients with prostatic hypertrophy. The calculated volumes were compared with the true volumes derived by measurement of voided and catheter-drained urine. All methods showed similar degrees of accuracy in quantifying bladder volumes. The range of errors of the best method tested was +/- 35% of true volume and this suggests that ultrasound measurement of bladder volume is not sufficiently accurate for many clinical and research applications.

The cost effectiveness of combined rapid tests (Multistix) in screening for urinary tract infections.

Urinary tract infections (UTI) are relatively common in the urology outpatients department and the renal transplant unit. Clinical diagnosis is imprecise and laboratory methods take time and are costly. Combined rapid tests (Multistix) were used to screen 400 consecutive mid stream specimens of urine: 200 from urology outpatients and 200 from renal transplant patients. All specimens were also tested in the laboratory. The negative predictive value for excluding UTI was excellent (> 98%) but positive predictive value for confirming presence of UTI was only 50%. However, with this simple screening method, up to 75% of urines can be excluded from laboratory analysis. Since there is a 20-fold difference in cost between dipstix and laboratory testing, the potential savings from this simple screening test is considerable.

Neuropeptide Y (NPY)-containing nerves in mammalian ureter

The distribution of neuropeptide Y in the ureter of the rat, rabbit, and man has been determined by radioimmunoassay and chromatographic analysis of the tissue extract. The localization of neuropeptide Y-immunoreactivity has been identified by immunocytochemistry. A regional distribution of neuropeptide Y was found; highest concentrations being present in the ureterovesical junction. Throughout the ureter, neuropeptide Y-immunoreactive nerve fibers were identified to surround the blood vessels and a few plexuses of neuropeptide Y-containing nerves were present within the muscle layers. Neuropeptide Y was not present within ganglion cells. Treatment of rats with 6-hydroxydopamine resulted in a significant reduction of neuropeptide Y concentrations in the upper, middle, and lower thirds of the ureter. This depletion in extractable neuropeptide Y was associated with morphologic changes typical of axonal degeneration of the neuropeptide Y-containing nerve fibers.

A prospective randomized controlled trial of perioperative antibiotic prophylaxis in renal transplantation

We have carried out a prospective, randomized controlled trial of perioperative prophylaxis with cefuroxime and piperacillin in 53 recipients of renal allografts. Twenty-seven patients received antibiotic prophylaxis with three doses of cefuroxime 750 mg and piperacillin 4 g, and 26 patients received no prophylaxis. Risk factors for infection were well matched. Infection rates were analysed for the periods 0-5 days and 0-14 days post-transplant. In the first 5 days, patients receiving antibiotics had fewer infections (3 vs. 11, P = 0.04) but by 14 days this difference was no longer apparent (21 vs. 30, P = NS). There was a total of 15 wound infections, which were more common in the control group both at 5 days (1 vs. 5, P = NS) and at 14 days (4 vs. 11, P = 0.027). Urinary infections were unaffected by prophylaxis. We conclude that perioperative antibiotic prophylaxis results in a modest but worthwhile reduction in the incidence of wound infections after renal transplantation.

Differences in Expression of Oligosaccharide Determinants by Phenotypically Distinct Sublines of the Dunning 3327 Rat Prostate Cancer

Oligosaccharides expressed by the 3327-H and 3327-MAT LyLu sublines of the Dunning rat prostate cancer model have been compared in formalin-fixed and routinely paraffin-embedded tumour tissues. Binding by lectins of defined specificity has been employed to identify expression of seven oligosaccharide structures by primary and metastatic prostatic carcinoma cells. Neuraminidase digestion was employed to reveal determinants masked by sialic acid. The presence of core Man alpha 1----3(Man alpha 1----6)Man beta 1----4GlcNAc beta 1----4 determinants recognised by Con-A (Canavalia ensiformis) confirmed expression of complex-type glycoconjugates by plasma membrane and cytoplasmic components of the 3327-H tumour but only by cytoplasmic determinants within 3327 MAT LyLu variant tumour-cells. The only other oligosaccharide freely expressed by either tumour-subline was (GlcNAc beta 1----4GlcNAc beta 1----4-)n, recognised by WGA (Triticum vulgaris). Prior to neuraminidase digestion, PNA (Arachis hypogaea) (which identifies Type I oligosaccharides: Gal beta 1----3GalNAc-) bound to pseudoluminal membranes of the 3327-H tumour. However, ECG (Erythrina cristagalli) (which identifies type II oligosaccharides: Gal beta 1----4GlcNAc-) did not bind to this tumour. Unmasked Type I (Gal beta 1----3GalNAc-) and Type II (Gal beta 1----4GlcNAc-) oligosaccharides were not identified in the MAT-LyLu variant. After neuraminidase digestion, PNA-binding was identified along pseudoluminal plasma membranes within 3327-H tumours but only within the cytoplasm of 3327-MAT LyLu primary and metastatic tumour cells. Following neuraminidase digestion, ECG-binding was observed along pseudoluminal plasma membranes of 3327-H tumours and heterogeneously within the cytoplasm of primary, but not metastatic 3327-MAT LyLu tumours. Terminal alpha/beta GalNAc- residues recognised by SBA (Glycine max) were not freely expressed by either subline. These structures were readily detected along luminal membranes of 3327-H cells and weakly detected within the cytoplasm of primary but not metastatic MAT 3327-LyLu tumour cells following neuraminidase digestion. Fucosylated Type II structures Fuc alpha 1----2Gal(GalNAc)-), recognised by UEA-1 (Ulex europaeus-1) and GalNAc alpha 1----3GalNAc- structures recognised by DBF (Dolichos biflorus) were not identified as a component of either tumour subline. The different patterns of oligosaccharide expression, identified by lectin-binding, clearly differentiated between the two tumour sublines and distinguished them from normal prostatic epithelium. The Dunning 3327 rat prostatic cancer sublines offer a useful model with which to examine the relationship between cell-surface oligosaccharide structures and phenotypic variants within a defined tumour-cell population.(ABSTRACT TRUNCATED AT 400 WORDS)

Wallstent endoprostheses for the relief of prostatic urethral obstruction in high risk patients

Twenty-one patients with prostatic urethral obstruction who were unfit for surgery were treated with self-expandable stainless steel endoprostheses inserted under fluoroscopic guidance. The procedure was technically successful in all patients, although in one case a second stent was required 2 months later. One patient developed a urethral stricture in the 12-16 month follow up period. One case of epididymoorchitis and one case of septicaemia after stenting were treated successfully with antibiotics. Endoprostheses represent a satisfactory alternative to prostatectomy in high-risk patients.

Carbohydrate residues in non-malignant prostatic epithelium as revealed by lectins

SummaryNon-neoplastic prostatic epithelium from 39 patients obtained at transurethral resection for outflow tract obstruction and 5 normal prostates from men under 35 years of age obtained at postmortem were formalinfixed and paraffin-embedded. The distribution of 8 lectin receptors were studied using a peroxidase anti-peroxidase method and an avidin-biotin method. Con A, WGA, and PNA bound to most epithelial cells. Con A,and WGA also showed major stromal binding. Approximately 5% to 10% of cells bound UEA1, GS1, DBA, and BPA. No major differences in lectin receptor expression were observed between normal and hyperplastic epithelium with either of the immunohistochemical techniques except that hyperplastic cells stained more strongly than normal epithelium.