The Dodo Bird: Less a Verdict Than an Opportunity

I contend that although the Luborsky et al. findings on the Dodo bird verdict are noteworthy, the methodology on which they are based is significantly delimited. Amplifying Luborsky et al.'s moderate recognition of that delimitation, I propose a qualitative complement to the extant research. I call this complement "amalgamated" qualitative research and propose that it will deepen, clarify, and contextualize Luborsky et al.'s enigmatic findings. Until this amalgam is implemented, therapy research will be relegated to impressions rather than fine-grained illuminations.     

High-dose tamoxifen as an enhancer of etoposide cytotoxicity. Clinical effects and in vitro assessment in p-glycoprotein expressing cell lines.

Twenty-six patients with relapsed or drug-resistant cancer were treated with a combination of oral etoposide (300 mg day-1 for 3 days) and high-dose oral tamoxifen as a potential modulator of drug resistance (480 or 720 mg day-1 for 6 days beginning 3 days before etoposide). One patient with relapsed high-grade lymphoma and one with adenocarcinoma of unknown primary site has a partial response. Toxicity consisting of nausea, vomiting and subjective dizziness, unsteadiness of gait and malaise occurred during tamoxifen treatment. Serum levels of tamoxifen averaged 3-3.5 microM on day 4 of all courses of treatment at both 480 and 720 mg day-1. N-desmethyltamoxifen levels were lower than tamoxifen during the first course (2 microM) but increased to equal tamoxifen levels during the second course. Didesmethyltamoxifen levels remained below 1 microM. In vitro, both tamoxifen and the standard modulator of multidrug resistance, verapamil, produced minor enhancement of etoposide cytotoxicity in the MCF-7 wt cell line but produced no enhancement with any other cell line. High, intermittent doses of tamoxifen can be given with acceptable toxicity and produce serum levels that have been shown to modulate drug resistance in vitro. In vitro, however, such levels have no significant effect on etoposide cytotoxicity towards a range of wild-type and MDR cell lines.     

A multi-centre phase two study of intravesical epirubicin in the treatment of superficial bladder tumour

Epirubicin (4'-epi-adriamycin) was used in the treatment of widespread superficial carcinoma of the bladder. Thirty-seven patients received 50 mg in 50 ml of saline retained for 60 min. There was an overall response rate of 59% but this was of short duration. Thirty percent of patients progressed despite therapy. Therapy was associated with an incidence of side effects which necessitated therapy withdrawal in 12 (32.4%) patients. It is concluded that epirubicin, in the dose used in this study, cannot be recommended for routine intravesical chemotherapy and that further studies, at a reduced dosage, are necessary to evaluate this agent.     

Workshop on Late Renal Allograft Dysfunction

Despite continued improvement in incidence of acute immune injury and short-term graft survival, late allograft dysfunction remains a significant problem in the renal transplant population. Recent reports suggest that rates of renal function decline are quite varied in the overall recipient population, and that individual rates for many recipients may not change substantially over time. Moreover, analyses also reveal distinct predictive factors for both early and late functional decline. Long-term outcome studies for renal transplantation, however, might be significantly limited by incomplete data sets for assessing clinical endpoints. In view of the heterogeneous factors that may cause progressive allograft injury, more routine biopsy sampling would allow a more complete characterization of induced injuries. Elucidating mechanisms of renal fibrosis in response to injury, in experimental systems and humans, is also an important goal in better understanding chronic allograft damage. Regulation of cell senescence genes and epithelial to mesenchymal transition, studied in other models of renal fibrosis, are likely relevant to studies of renal allograft dysfunction. Recent technical advances in analyzing biological samples may play a pivotal role in identifying and validating surrogate markers of allograft function for future interventional trials in transplantation.