B-cell growth factor receptor expression and B-cell growth factor response of leukemic B cell precursors and B lineage lymphoid progenitor cells

The purpose of this study was to analyze the expression of B cell growth factor (BCGF) receptors and to elucidate the biologic effects of biochemically purified natural BCGF at the B cell precursor stage of human B lineage lymphoid differentiation. The specific binding of radioiodinated high-mol-wt BCGF (125I-HMW-BCGF) and low-molecular-wt BCGF (125I-LMW-BCGF) to fresh marrow blasts from B cell precursor acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated BCGF molecules bound per blast ranged from undetectable to 24.3 X 10(3) for HMW-BCGF, and from 11.5 X 10(3) to 457.8 X 10(3) for LMW-BCGF. In 3H-TdR incorporation assays, 75% of cases showed a significant response to LMW-BCGF with a median stimulation index of 9.3. By comparison, only 33% of cases showed a significant response to HMW-BCGF with a median stimulation index of 2.4. Subsequently, B cell precursor colony assays were performed to assess and compare the biologic effects of BCGF on leukemic B lineage lymphoid progenitor cells. Among 28 cases studied, 57% responded to both HMW-BCGF and LMW-BCGF, 21% responded only to LMW-BCGF, and the remaining cases showed no proliferative response to either growth factor. The response patterns of virtually pure populations of FACS- sorted leukemic B cell precursors were essentially identical to the proliferative responses of unsorted leukemic B-cell precursors. Synergistic effects between HMW-BCGF and LMW-BCGF were observed in 80% of the cases that responded to both. The numbers of cell-bound radioiodinated BCGF molecules, the stimulation indices, as well as the number of B cell precursor colonies in BCGF-stimulated cultures showed a marked interpatient variation. Patients with structural chromosomal abnormalities (SCAs) involving 12p11-13 or patients with a Philadelphia chromosome showed a greater HMW-BCGF response at the level of leukemic progenitor cells than did other patients (P = .02). The LMW-BCGF response was significantly greater for patients with SCA than for patients without SCA (P = .04). The response of leukemic progenitor cells to HMW-BCGF or LMW-BCGF did not correlate with sex, age, disease status, FAB morphology, WBC at diagnosis, or immunophenotype. To our knowledge, this study represents the first detailed analyses of BCGF receptor expression and BCGF effects in B cell precursor ALL. The data presented provide direct evidence for the expression of functional receptors for both HMW-BCGF and LMW-BCGF in B cell precursor ALL.     

A prospective survey of risk factors in young adults with arterial occlusive disease

Few studies have presented a thorough analysis of young adults with symptoms of arterial occlusive disease. To learn more about the possible risk factors of vascular disease playing a role in these young patients, we have reviewed all patients of 45 years of age and younger with symptoms of arterial occlusive disease who had been referred to our department between 1978 and 1987. Thirty-seven patients (28 males and 9 females) were included in the study. The mean age at which the first symptoms occurred was 34 years. Most patients presented with chronic arterial obliterations of the lower extremities (31/37, 84%). In addition, 4 patients showed signs of ischaemic heart disease. A strongly positive family history of arteriosclerosis was obtained from 13 patients (35%). Hypertension was present in 7 patients (19%), diabetes in three (8%) and nicotine abuse was found in 27 patients (73%). Fifty-four percent of the patients (20/37) had undergone vascular reconstructive surgery, 19% (7/37) underwent transluminal dilatation, and 3 had had subsequent treatment of newly developed lesions. For this study, all patients were recalled to the outpatient clinic. A complete case history was taken followed by a physical examination and ECG. Laboratory examinations were performed to analyse parameters of: (a) coagulation; (b) fibrinolysis; (c) fat- and (d) methionine metabolism. Clear-cut laboratory abnormalities were found in 33 patients (33/37, 89%). Coagulation parameters were abnormal in 11 patients (30%) (protein S deficiency: 3 pts). Fibrinolysis was impaired in 15 patients (40%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Essential steps in developing best practices to assess reflective skill: A comparison of two rubrics

Purpose: Medical education lacks best practices for evaluating reflective writing skill. Reflection assessment rubrics include the holistic, reflection theory-based Reflection-on-Action and the analytic REFLECT developed from both reflection and narrative-medicine literatures. To help educators move toward best practices, we evaluated these rubrics to determine (1) rater requirements; (2) score comparability; and (3) response to an intervention.

Methods: One-hundred and forty-nine third-year medical students wrote reflections in response to identical prompts. Trained raters used each rubric to score 56 reflections, half written with structured guidelines and half without. We used Pearson’s correlation coefficients to associate overall rubric levels and independent t-tests to compare structured and unstructured reflections.

Results: Reflection-on-Action training required for two hours; two raters attained an interrater-reliability?=?0.91. REFLECT training required six hours; three raters achieved an interrater-reliability?=?0.84. Overall rubric correlation was 0.53. Students given structured guidelines scored significantly higher (p?<?0.05) on both rubrics.

Conclusions: Reflection-on-Action and REFLECT offer unique educational benefits and training challenges. Reflection-on-Action may be preferred for measuring overall quality of reflection given its ease of use. Training on REFLECT takes longer but it yields detailed data on multiple dimensions of reflection that faculty can reference when providing feedback.     

A population-based study of the extent of surgical resection of potentially curable colon cancer

Background We attempted to determine factors contributing to the extent of initial curative resection for colon cancer in a population-based cohort. Total abdominal colectomy with ileorectal anastomosis (TAC-IR) may be considered for young patients or those with a colorectal cancer family history to prevent metachronous lesions and facilitate surveillance. Methods All Ontario patients newly diagnosed with colon cancer over 12 months beginning in July 1997 were staged at the time of surgery. The extent of resection was compared with variables, including familial risk obtained from the Ontario Familial Colon Cancer Registry. Results Complete staging was possible for 86% of patients. A total of 1223 patients had a potentially curative resection: 17%, 46%, and 36% were stage I, II, and III, respectively. Patients were more likely to receive a TAC-IR if they were ≤50 years old (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8–6.6), if they had a synchronous lesion (OR, 28.37; 95% CI, 12.2–61.2), or if they were at a teaching hospital (OR, 2.8; 95% CI, 1.6–4.7), but not if they had a family history (OR, 7; 95% CI, 3–1.5). Conclusions Young age, teaching hospital, and multiple cancers but not family history were important factors for performing a TAC-IR.     

Serum blood urea nitrogen and long-term mortality in acute ST-elevation myocardial infarction

Older age is an independent predictor of mortality after percutaneous coronary intervention (PCI) in patients with Non-ST elevation Acute Coronary Syndrome (ACS). GPIIb/IIIa inhibitors are proved to improve outcome in high risk patients, but conflicting data are available about the effects of these inhibitors in elderly. Accordingly, we studied a consecutive population of elderly patients undergoing PCI for Non-ST elevation ACS. A total of 500 patients were divided in: GPI group (247 pts; mean age 77 ± 1.9 years) treated by stenting plus abciximab and, no GPI group (253 pts; mean age 77 ± 2.4 years) treated by stenting alone. Propensity analysis was used to account for the nonrandomized use of GPIIb/IIIa inhibitors. During hospitalization, incidence of death was similar among groups (3.2% vs 4.6%) without difference regarding incidence of major (1.6% vs 1.1%) and minor bleedings (4% vs 3%). At long-term follow-up the rate of death was significantly lower in GPI group (4.5% vs 12.3%; p = 0.002) as well as the rate of acute myocardial infarction (2.8% vs 11.1%; p = 0.0001), and pre-PCI (5.7% vs 13.4%; p = 0.003). Cox regression analysis identified abciximab use as an independent predictor of lower long-term major adverse cardiac event (MACE) after adjustment for propensity score (Exp (B) 0.620, 95%CI 0.394–0.976, p = 0.039). Our results suggest that addition of abciximab to stenting improves outcome in elderly patients with Non-ST elevation ACS, leading to an absolute benefit for reduction of death and MACE, with an acceptable rate of major and minor bleedings.     

Predictors of congruency between self-reported hypertension status and measured blood pressure in the stroke belt

BackgroundFew studies have comprehensively investigated the validity of self-reported hypertension (HTN) and assessed predictors of HTN status in the stroke belt. This study evaluates validity self-reporting as a tool to screen large study populations and determine predictors of congruency between self-reported HTN and clinical measures.MethodsCommunity Initiative to Eliminate Stroke project (n = 16,598) was conducted in two counties of North Carolina in 2004 to 2007, which included collection of self-reported data and clinical data of stroke-related risk factors. Congruency between self-reported HTN status and clinical measures was based on epidemiological parameters of sensitivity, specificity, and predictive values. McNemar’s test and Kappa agreement levels assessed differences in congruency, while odds ratios and logistic regression determined significant predictors of congruency.ResultsSensitivity of self-reported HTN was low (33.3%), but specificity was high (89.5%). Prevalence of self-reported HTN was 16.15%. Kappa agreement between self-report and clinical measures for blood pressure was fair (k = 0.25). Females, whites, and young adults were most likely to be positively congruent, whereas individuals in high risk categories for total blood cholesterol, low density lipoproteins, triglycerides, and diabetes were least likely to accurately capture their HTN status.ConclusionSelf-report HTN information should be used with caution as an epidemiological investigation tool.