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.     

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.     

Personality and sexual anomalies

Test properties of the Millon Clinical Multiaxial Inventory (MCMI) were examined in a sample of 419 sex offenders and controls in three different settings. The offender group included sexual aggressives, pedophiles, incest perpetrators and miscellaneous cases. Nineteen of the 20 scales of the MCMI had alpha reliability over 0.60 and for 13 scales it was over 0.80. The scales showed satisfactory discriminant validity from age but 9 scales showed a moderate influence of intelligence scores and education. Criminal history did not influence scale results. The scales unfortunately did show significant correlations with MMPI validity scales. Although the scales were not susceptible to naive lying, they were influenced by social desirability especially. Four factors were extracted in principal axes factor analysis that accounted for 91.2% of the total variance. The first factor explained 58.2% of the variance and was labeled general psychopathology. The other three factors suggested psychotic tendencies, extraversion and the bipolar dependency-antisocial tendencies. When the groups were compared, almost all scales significantly differentiated them. When the MMPI F-K Scale was forced to enter a stepwise discriminant analysis first, five scales still were significant; Narcissistic, Schizoid-Asocial, Alcohol Abuse, Paranoid, & Dependent-Submissive scales. The MCMI taps important dimensions in sex offenders but suffers from validity problems.     

Paraimmunoblastic variant of small lymphocytic lymphoma/leukemia

We report 16 cases of a distinctive, biologically aggressive variant of small lymphocytic lymphoma/leukemia (SLL/L) that is characterized by the diffuse proliferation of cells normally comprising the pseudoproliferation centers (so-called paraimmunoblasts). Demographically, the patients differed in no significant regard from patients with SLL/L of usual type. Rapidly progressive, generalized lymphadenopathy was the dominant clinical finding in 15 of the 16 patients; one patient presented with symptoms related to lymphomatous involvement of the stomach and regional lymph nodes. Splenomegaly was observed in five patients. Seven patients, two of whom had a history of indolent-phase chronic lymphocytic leukemia, had an absolute lymphocytosis at diagnosis. In most patients, bone marrow involvement was noted at diagnosis. It consisted predominantly of small lymphocytic infiltrates indistinguishable from those observed in SLL/L of usual type; significant paraimmunoblastic infiltration was infrequent and generally occurred late in the disease course. Immunohistochemical and cytogenetic study further substantiated the hypothesized relationship of these cases to SLL/L. Findings included (a) coexpression of sIg and Leu-1 antigen in the majority of cases and (b) the presence of a t(11;14) (q13;q32) chromosome translocation in two of three cases with analyzable metaphases. Although treatment protocols were not uniform, follow-up data indicated an accelerated clinical course. Eleven patients have died of their disease between 3 and 39 months after diagnosis; the median survival was 28 months.