The clinical relevance of t(14; 18)/BCL-2 rearrangement and DEL 6q in diffuse large cell lymphoma and immunoblastic lymphoma

Background: t(14; 18)/bcl-2 gene rearrangement (R) is claimedto impart a worse rate of complete remission and disease-freesurvival in diffuse large cell lymphoma (DLCL). DEL 6q has alsobeen associated with poor outcome. Design: Retrospective studyof 54 patients with either diffuse large cell or immunoblasticlymphoma who had cytogenetics and/or molecular studies performed.Results: Patient characteristics, complete remission rate, andtime to treatment failure (TTF) were similar at three year follow-upfor groups with and without t(14; 18)/BCL-2R Survival was worsefor the former but the difference was not statistically significant.For DEL 6q, patient characteristics and survival rates weresimilar at three year follow-up for patients with and withoutthe abnormality. TTF was worse for the former but this was notstatistically significant. Conclusion: This study, with equalor greater number of patients with t(14; 18) than previous reports,fails to show a worse prognosis for patients with the t(14;18) chromosomal abnormality. A definite association will awaitfurther accrual of patients and a meaningul multivariate analysis. lymphoma, BCL-2, cytogenetics, DEL 6q     

Becoming an intentional teacher

This series of articles, Managing Your Academic Career, presents ways to intentionally improve your teaching. This first article explains the concept of becoming an intention teacher. Subsequent articles will deal with strategies that are useful in clinical teaching, such as preparing students to value and use research in practice, and providing feedback to students in the clinical setting.     

Poisoning with oxybutynin.

A case of poisoning with 100 mg of oxybutynin in a 34-year-old female is reported. The main features were anticholinergic effects, including stupor, followed by disorientation and agitation on awakening, dilated pupils, dry skin and retention of urine. She had a sinus tachycardia which resolved 3 h after admission, and in addition ventricular ectopics and bigeminy which continued for a further 30 h. She recovered fully on symptomatic treatment alone.     

Cell transplantation to improve ventricular function in the failing heart

Current therapies for congestive heart failure are limited in efficacy or in applicability. Cardiac cell transplantation offers a novel therapeutic approach to improve heart function. Although significant progress has been made over the past decade in the development of cell transplantation, only recently have investigators studied the changes in ventricular function following cell transplantation. This review article describes the latest research developments, evaluates recent studies of ventricular function after cell transplantation, and discusses the future directions of cell transplantation as a new therapy to ‘repair broken hearts’.     

Growth kinetics of microscopic hepatocellular neoplasms in carcinogen-resistant and carcinogen-responsive strains of mice.

The initiation and growth of microscopic hepatocellular neoplasms in C57BL/6 mice, considered relatively resistant to hepatocarcinogenesis, was compared with that of the more responsive C3H and B6C3F1 (C57BL/6 x C3H) strains. Tumors were induced by giving male mice injections of diethylnitrosamine when they were 15 days old. During the first 18 weeks postinjection, the growth rates of neoplasms in the three strains were almost identical (doubling time of 2.1 to 2.5 weeks). However, after that time, only the growth rates of the C57BL/6 neoplasms slowed; between 30 and 42 weeks the doubling time had increased to 13 weeks. In addition, at all sacrifice times the number of neoplasms in the C3H strain was at least 2.5 times higher than in the C57BL/6 and B6C3F1 strains. These results suggest that the genetic determinant(s) for inhibited tumor growth (expressed only in C57BL/6 mice) are recessive to those for unimpeded tumor growth (expressed in C3H and B6C3F1 mice), while the determinant(s) for large numbers of tumors (expressed only in C3H mice) are recessive to those for small numbers of tumors (expressed in C57BL/6 and B6C3F1 mice). In addition to the interstrain differences in tumor growth, two other types of tumor growth heterogeneity were identified. First, in each of the three strains, the largest tumors were found to grow faster than the smaller tumors. This suggests that the very broad range in tumor size that is seen in this model results from the long-term differences in the growth rates of individual neoplasms. Second, we found that in microscopic hepatic neoplasms in B6C3F1 mice, the thymidine labeling indices were 2.3 times greater in the outer 50-microns shell (2 cells thick) than in the next deeper 50-micron layer cells. This suggests that even in these minute neoplasms, gradients in blood-borne oxygen, nutrients, or growth factors are responsible for heterogeneous growth.     

Effect of Zonisamide (CI-912) on a Synaptic System Model

The effect of the experimental antiepileptic drug zonisamide (1,2-benzisoxazole-3-methanesulfonamide, ZNS) on the trigeminal complex of cats was compared with the effect of established antiepileptic drugs. Intravenous administration of 10-40 mg/kg ZNS significantly depresses descending excitatory mechanisms, as well as segmental and descending inhibitory mechanisms, but has only a minor effect on segmental excitatory mechanisms. This spectrum of activity is similar to that of valproate, and suggests that ZNS should also be a broad-spectrum antiepileptic drug. In agreement with our experimental observations, it has been found that ZNS is effective against complex partial, generalized tonic clonic, and myoclonic seizures. The antiepileptic profile of ZNS in conventional screening tests resembles that of carbamazepine (CBZ) and phenytoin. However, CBZ exacerbates rather than prevents myoclonic seizures. Our experimental model thus provides a more accurate prediction of ZNS's clinical spectrum of activity. The relationship of these findings to the mechanism of action of antiepileptic drugs is discussed.