A. W. S. Ritchie

Mechanisms responsible for diminished fragmentation of ureteral calculi : an experimental and clinical study

We molded 24 synthetic stones (mean weight 680 mg., range 641 to 715) from a commercial mixture of gypsum, silica, cellulose and polyvinyl acetate. Each stone was subjected to 400 shocks on a Wolf 2300 Piezolith and groups of 6 stones were treated in 4 different modes. Mean amounts fragmented were 243 +/- 18 mg. in a free environment, 62 +/- 18 mg. confined loosely in a latex tube, 22 +/- 8 mg. impacted in the tube and 30 +/- 8 mg. impacted alongside a 7F stent. During a 30-month period 118 patients received in situ extracorporeal shock wave lithotripsy for ureteral calculi using the same lithotriptor. The mean stone burden was 11.4 mm. (range 4 to 29). Success was greater for patients with calculi 10 mm. or less than for those with stones greater than 10 mm. (71% versus 51%, p less than 0.05), despite the former group receiving less shocks (5,404 versus 7,491). The influence of size was then excluded by studying the number of shocks delivered per mm. of calculus. Patients receiving 500 to 699 shocks per mm. showed a higher success rate than those receiving a smaller number of shocks per mm. Treatment with a greater number of shocks per mm. did not improve success rate. The experimental study demonstrated that confinement and impaction significantly diminish the rate of fragmentation of calculi. However, the clinical study suggested that there may be an optimum number of shocks per mm. that should be delivered. Treatment beyond this point fails to improve results. The 28% failure rate even in those receiving the highest number of shocks per mm. suggests that large, impacted calculi are unsuitable for treatment with in situ shock wave lithotripsy on this machine.

The Effects of Recombinant Human Intereron-Gamma on a Panel of Human Bladder Cancer Cell Lines

AbstractWe have examined the Major Histocompatibility Complex class II antigen inducing capabilities of recombinant human interferon-gamma, on a panel of human transitional cell carcinoma lines which have been raised from original tumours of varying histological grades: RT4 (grade 1), RT112 (grade 2) and MGH-U1 (grade 3). Cells were examined for class II antigens using an indirect immunofluorescent staining method and analysed on a fluorescence activated cell sorter.Twenty percent of RT4 cells constitutively expressed class II antigen. Both RT112 and MGH-U1 were repeatedly found to be negative for this antigen prior to treatment with interferon-gamma. Following treatment with interferon-gamma all three lines showed an increase in class II antigen expression, which was consistently dependent on both the length of incubation and concentration of interferon-gamma. A differential susceptibility was found amongst the three cell lines which may relate to the histological grade of the parent tumor.

An investigation of factors influencing the in vitro induction of LAK activity against a variety of human bladder cancer cell lines.

We investigated the sensitivity of transitional cell carcinoma cells, derived from the human bladder, to lymphokine activated killer cells. Recombinant interleukin-2 activated peripheral blood mononuclear cells were studied for their ability to mediate the cytolysis of a panel of four established human bladder transitional cell carcinoma cell lines. Lymphokine activated killer activity was assessed using a standard four hour chromium release assay. All four bladder cancer cell lines proved to be susceptible to lymphokine activated killer mediated cytolysis. This was found to be dependent upon the dose of cytokine and upon the duration of the activation period. The four cell lines were differentially susceptible to lysis (specific cytotoxicity at effector to target ratio of 40:1; RT112 = 22.9%, RT4 = 49.2%, MGH-U1 = 49.1%, EJ18 = 62.3%). The varying susceptibility of lymphokine activated killer mediated cytotoxicity was found to be independent of the histological grade of the parent tumour or the donor of effector cells. Both interferon-alpha and tumour necrosis factor-alpha also elicited lymphokine activated killer cell activity, although the maximum specific cytotoxicity achieved was considerably lower than that obtained with interleukin-2 alone. Interleukin-2, at optimal concentration, and tumour necrosis factor-alpha were found to behave synergistically in the generation of lymphokine activated killer effectors. However, concentrations of tumour necrosis factor-alpha higher than 100 Uml.-1 resulted in a decrease in specific cytotoxicity. These findings suggest a possible use of adoptive immunotherapy in human bladder cancer and indicate the optimum conditions for the generation of such effector cells.