Transformed lymphoma: an Achilles' heel of non-Hodgkin's lymphoma.

Transformed lymphoma has a reported incidence of 10-70% among patients with follicular lymphoma. Interpreting the wide-ranging estimates for incidence, survival, and effects of interventions from various studies is complicated by the use of different definitions of lymphoma transformation. Problems in defining histologic transformation will be addressed in this review. To date, there are no reliable markers of risk for transformation or factors predictive of survival. The prognosis for transformed lymphoma is generally poor, with most patients surviving only a few months, though some with limited disease that is chemosensitive may experience prolonged survival. Immunotherapy, particularly monoclonal antibodies and radioimmunoconjugates, holds promise but more experience is necessary. Approximately 200 patients are included in published series of autologous transplantation; of these, one-third remain disease free at 5 years, not dissimilar to reported outcomes for nontransformed disease. However, the treatment-related mortality is higher than in nontransformed disease, and there is a significant incidence of post-transplant myelodysplastic syndrome. The role of allogeneic transplant has yet to be pursued, but should be explored for its potential for a graft-versus-lymphoma effect. Advances in microarray gene analysis and biology may facilitate the understanding of mechanisms of transformation, development of a prognostic index and creation of tailored therapy.

Construction of an overproduction vector containing the novel srp (sterically repressed) promoter.

We report the design, synthesis, and evaluation of a novel Escherichia coli promoter intended for use in overproduction of proteins that are deleterious to the host. In this sterically repressed promoter (srp), the lac operator site is positioned between the -10 and -35 elements, where it can interfere sterically with RNA polymerase and thereby prevent assembly of a poised transcriptional complex. An srp-containing phagemid, pKEN1, and a tac-containing phagemid, pHN1, which has been widely used in protein overproduction but is often unstable, are compared with respect to levels of uninduced and induced protein expression. The level of uninduced protein synthesis by the srp promoter in vivo is approximately 50% of that observed with tac, whereas the levels of induced protein synthesis with the 2 vectors are approximately equal. A remarkable increase in stability of overproduction and growth was observed when the toxic Ada protein was overproduced in pKEN1, demonstrating the potential utility of this vector in overproducing toxic proteins.

Arbitration: preventive medicine for physician/hospital disputes?

This article discusses arbitration as one possible mechanism to equitably manage disputes between hospitals and physicians. The technique can be used to deal effectively with a variety of disputes, including appointment denials, disciplinary action, changes in physicians' privilege classifications, or other areas of internal disagreement.