A prospective evaluation for possible placenta accreta was performed in 34 patients with placenta previa and a history of one or more cesarean sections. Sonographic criteria used included (1) loss of the normal hypoechoic retroplacental myometrial zone, (2) thinning or disruption of the hyperechoic uterine serosa‐bladder interface, and (3) presence of focal exophytic masses. Of 18 patients with positive sonographic results, 14 had proof of placenta accreta and 16 of the patients underwent hysterectomy. Of 16 patients with negative sonographic results, only one had placenta accreta, and two patients required hysterectomy. Presence of numerous intraplacental vascular lacunae appears to be an additional risk criterion for placenta accreta, separate from the other criteria listed above.

an internationally acceptable grading system, which has al-A panel of recognized experts in liver transplantation ready been developed for kidney, 3 heart, 4 and lung. 5 At the pathology, hepatology, and surgery was convened for Third Banff Conference on Allograft Pathology, a group of the purpose of developing a consensus document for the specialists in liver transplantation from North America, Eugrading of acute liver allograft rejection that is scientifirope, and Asia met for this purpose. cally correct, simple, and reproducible and clinically useful. Over a period of 6 months pertinent issues were DEFINITION OF ACUTE REJECTION discussed via electronic communication media and a consensus conference was held in Banff, Canada in the In general, organ allograft rejection can be defined as, ''an summer of 1995. Based on previously published data and immunological reaction to the presence of a foreign tissue or the combined experience of the group, the panel agreed organ, which has the potential to result in graft dysfunction on a common nomenclature and a set of histopathologi-and failure.'' 2 This report is specifically concerned with acute cal criteria for the grading of acute liver allograft rejec-rejection, recently defined by the international consensus tion, and a preferred method of reporting. Adoption of document on terminology for hepatic allograft rejection 2 as, this internationally accepted, common grading system ''inflammation of the allograft, elicited by a genetic disparity by scientific journals will minimize the problems associ-between the donor and recipient, primarily affecting interlobated with the use of multiple different local systems. ular bile ducts and vascular endothelia, including portal Modifications of this working document to incorporate veins and hepatic venules and occasionally the hepatic artery chronic rejection are expected in the future. (HEPATOL-and its branches.'' 2 Early rejection, cellular rejection, nonduc-OGY 1997;25:658-663.) topenic rejection, rejection without duct loss, and reversible rejection are synonyms for acute rejection that appear in the literature, but their use is discouraged. The general clinical, The success of hepatic transplantation has resulted in its laboratory, and histopathological abnormalities listed below widespread use for treatment of many patients with endstage were derived from the international consensus document.2 liver disease; it is currently offered by more than 100 centers worldwide. One-year survival rates range from 70% to 90%; CLINICAL AND LABORATORY FINDINGSand long-term survival of 50% to 60% of patients is not unViewed from a biological perspective, any recipient's imcommon.1 Therefore, an increasing number of physicians, inmune system will likely be perturbed after transplantation, cluding pathologists, many of whom have no specific training resulting in immune activation. 2 However, viewed from a in transplantation biology, will become involved in the care clinical perspective, because of baseline immunosuppressive of organ all...

Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.

tients in the half-life of A77 1726, the known risk of toxic effects on the liver, and the requirement for doses that exceed recommendations for rheumatoid arthritis, this therapy should be monitored by fre-quent analysis of blood levels of the active metabolite and liver enzymes.

Leflunomide, a novel immunosuppressive drug, is able to prevent and reverse allograft and xenograft rejection in rodents, dogs, and monkeys. It is also effective in the treatment of several rodent models of arthritis and autoimmune disease. In vitro studies indicate that leflunomide is capable of inhibiting anti-CD3- and interleukin-2 (IL-2)-stimulated T cell proliferation. However, the biochemical mechanism for the inhibitory activity of leflunomide has not been elucidated. In this study, we characterized the inhibitory effects of leflunomide on Src family (p56lck and p59fyn)-mediated protein tyrosine phosphorylation. Leflunomide was able to inhibit p59fyn and p56lck activity in in vitro tyrosine kinase assays. The IC50 values for p59fyn (immunoprecipitated from either Jurkat or CTLL-4 cell lysate) autophosphorylation and phosphorylation of the exogenous substrate, histone 2B, were 125-175 and 22-40 microM respectively, while the IC50 values for p56lck (immunoprecipitated from Jurkat cell lysates) autophosphorylation and phosphorylation of histone 2B were 160 and 65 microM respectively. We also demonstrated the ability of leflunomide to inhibit protein tyrosine phosphorylation induced by anti-CD3 monoclonal antibody in Jurkat cells. The IC50 values for total intracellular tyrosine phosphorylation ranged from 5 to 45 microM, with the IC50 values for the zeta chain and phospholipase C isoform gamma 1 being 35 and 44 microM respectively. Leflunomide also inhibited Ca2+ mobilization in Jurkat cells stimulated by anti-CD3 antibody but not in those stimulated by ionomycin. Distal events of anti-CD3 monoclonal antibody stimulation, namely, IL-2 production and IL-2 receptor expression on human T lymphocytes, were also inhibited by leflunomide. Finally, tyrosine phosphorylation in CTLL-4 cells stimulated by IL-2 was also inhibited by leflunomide. These data collectively demonstrate the ability of leflunomide to inhibit tyrosine kinase activity in vitro, and suggest that inhibition of tyrosine phosphorylation events may be the mechanism by which leflunomide functions as an immunosuppressive agent.