Supraventricular tachyarrhythmias after hematopoietic stem cell transplantation: incidence, risk factors and outcomes

Recent studies suggest that cancer patients may be at increased risk for supraventricular tachyarrhythmias (SVTA). We have observed clinically significant SVTA in patients undergoing hematopoietic stem cell transplantation occurring at a median of 6 days post transplant, manifesting as atrial fibrillation/flutter or regular narrow-complex tachycardia and persisting for a median of 3 days (range, 0-8). All patients received aggressive medical therapy and/or electrical cardioversion to restore sinus rhythm and to re-establish hemodynamic stability. Non-Hodgkin's lymphoma (NHL) was the most common diagnosis (53%), and a case control analysis in those patients demonstrated that SVTA occurred in 12% of patients and was associated with older age and pre-existing cardiac conditions. In conclusion, patients undergoing HSCT are at moderate risk for developing SVTA, particularly older patients with a diagnosis of NHL. These arrhythmias are clinically significant, and are a marker for increased mortality and prolonged hospital stay. Additional studies are needed to identify high-risk patients who may benefit from prophylactic anti-arrhythmic therapy.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

人芽囊原虫在不同培养基中生长状况的观察

目的筛选培养人芽囊原虫的最适培养基。方法将同一株人芽囊原虫阳性粪便标本以2×105细胞/管接种至RPMI1640、199和LES培养基中,加入20%小牛血清及青、链霉素,pH值为7.5,放置厌氧罐中于37℃恒温培养,每24h计数,每6d转种1次。观察人芽囊原虫在3种培养基中的存活时间、虫体密度和虫体形态。结果人芽囊原虫在RPMI1640培养基中存活时间最长、虫体密度最高,虫体以空泡型多见;在LES培养基中存活时间最短、虫体密度最低,但虫体形态清晰、规则;在199培养基中存活时间和虫体密度均介于前两者之间。结论RPMI1640培养基适宜人芽囊原虫的生长繁殖,为人芽囊原虫体外培养的首选培养基;LES培养基中虫体形态清晰、规则,可用于人芽囊原虫的形态学研究;199培养基也可用于人芽囊原虫的体外培养,但不作为首选。     

Improving care for patients with chronic heart failure in the community: the importance of a disease management program

STUDY OBJECTIVE: Utilizing a comparison group of patients with congestive heart failure (CHF) discharged to their primary care physicians, we sought to determine if disease management in a short-term, aggressive-intervention heart failure clinic (HFC) following hospital discharge is associated with improved outcomes. DESIGN: Chart review. SETTING: An integrated health-care center serving a tristate area. PATIENTS: Inclusion criteria were discharge from the hospital with a primary diagnosis of CHF, outpatient follow-up within the hospital system, and the presence of left ventricular systolic dysfunction as the basis for CHF. Patients were categorized into group 1 if they were referred to the HFC after hospital discharge, and into group 2 if follow-up care was provided by their primary care physician. MEASUREMENTS AND RESULTS: There were 38 patients in group 1 and 63 patients in group 2. There was a trend toward a shorter time to the first outpatient visit following discharge (11 days vs 15 days, p = 0.09), more outpatient visits within 90 days (10 visits vs 2 visits, p < 0.001), and more patient-initiated contacts (four contacts vs one contact, p = < 0.001) in group 1 compared to group 2, respectively. The combined hospital readmission and mortality rate at 90 days (10% vs 30%, p < 0.018) and 1 year (21% vs 43%, p < 0.02) was lower in group 1. There was a 77% relative risk reduction for 30-day hospital readmission in favor of group 1, and a statistically lower rate of readmissions at 90 days and 1 year. Utilization and maintenance of standardized CHF medications were significantly higher in patients who attended the HFC. CONCLUSIONS: A comprehensive disease management program for patients discharged with a diagnosis of CHF resulted in fewer rehospitalizations and improved event-free survival compared to patients followed up by their primary care physicians.     

Endotoxin-induced suppression of erythropoiesis: the role of erythropoietin and a heme synthesis stimulating factor

The regulation of erythropoiesis is primarily controlled by erythropoietin (Ep). Recently, however, other factors that both stimulate and inhibit erythropoiesis have been reported. Using an in vitro liquid culture of bone marrow cells, a factor in normal mouse serum was demonstrated that markedly stimulated heme synthesis by marrow erythroid cells. In this study, the role of this heme synthesis stimulating factor (HSF) and Ep in the erythropoietic suppression caused by endotoxin administration to mice was examined. Although HSF levels did not alter appreciably after endotoxin injection, marrow erythroid cells from these animals became unresponsive to the factor. This could be reversed if Ep was added to the culture in vitro or if the hormone was injected into the mice 18 hr prior to harvesting the marrow. This marrow erythroid cell response is identical to that seen in animals in whom Ep levels are markedly reduced, such as that found in exhypoxic polycythemia, and suggest a decrease in the hormone following endotoxin administration. Additional studies demonstrated that when Ep was injected into mice 6 hr after endotoxin administration, an increase in femoral erythroid colony-forming units (CFU-E), proerythroblast number, and 59 Fe incorporation into femoral marrow cells could be demonstrated. These findings, together with the marrow erythroid cell response to the hormone, suggest that the mechanism for suppression of erythropoiesis after endotoxin injection is a reduction in the level of circulating Ep.     

ProMACE/CytaBOM方案治疗难治性或复发性非霍奇金淋巴瘤的疗效观察

目的：探讨ProMACE/CytaBOM方案治疗难治性和(或)复发性非霍奇金淋巴瘤(NHL)的疗效。方法：采用ProMACE／CytaBOM方案治疗18例难治性和(或)复发性NHL患者，其中难治性NHL患者8例，复发性NHL患者10例。结果：5例难治性和(或)复发性NHL患者达到完全缓解(CR率为27．8％)，4例达部分缓解(PR率为22．2％)，总有效率为50．0％；目前12例仍生存，其中生存最长者26个月(2例)，仍处于CR期。毒副作用主要为消化道症状、轻度肝功能异常以及骨髓抑制。结论：ProMACE／CytaBOM方案对部分难治性和(或)复发性NHL患者仍有效，毒副作用较轻，可用于治疗对其他化疗方案无效的难治性和(或)复发性NHL。     

Protein N-myristoylation in Escherichia coli: reconstitution of a eukaryotic protein modification in bacteria.

Protein N-myristoylation refers to the covalent attachment of a myristoyl group (C14:0), via amide linkage, to the NH2-terminal glycine residue of certain cellular and viral proteins. Myristoyl-CoA:protein N-myristoyltransferase (NMT) catalyzes this cotranslational modification. We have developed a system for studying the substrate requirements and biological effects of protein N-myristoylation as well as NMT structure-activity relationships. Expression of the yeast NMT1 gene in Escherichia coli, a bacterium that has no endogenous NMT activity, results in production of the intact 53-kDa NMT polypeptide as well as a truncated polypeptide derived from proteolytic removal of its NH2-terminal 39 amino acids. Each E. coli-synthesized NMT species has fatty acid and peptide substrate specificities that are indistinguishable from those of NMT recovered from Saccharomyces cerevisiae, suggesting that the NH2-terminal domain of this enzyme is not required for its catalytic activity. By using a dual plasmid system, N-myristoylation of a mammalian protein was reconstituted in E. coli by simultaneous expression of the yeast NMT1 gene and a murine cDNA encoding the catalytic (C) subunit of cAMP-dependent protein kinase (PK-A). The fatty acid specificity of N-myristoylation was preserved in this system: [9,10(n)-3H]myristate but not [9,10(n)3H]palmitate was efficiently linked to Gly-1 of the C subunit. [13,14(n)-3H]10-Propoxydecanoic acid, a heteroatom-containing analog of myristic acid with reduced hydrophobicity but similar chain length, was an effective alternative substrate for NMT that also could be incorporated into the C subunit of PK-A. Such analogs have recently been shown to inhibit replication of certain retroviruses that depend upon linkage of a myristoyl group to their gag polyprotein precursors (e.g., the Pr55gag of human immunodeficiency virus type 1). A major advantage of the bacterial system over eukaryotic systems is the absence of endogenous NMT and substrates, providing a more straightforward way of preparing myristoylated, analog-substituted, and nonmyristoylated forms of a given protein for comparison of their structural and functional properties. The system should facilitate screening of enzyme inhibitors as well as alternative NMT fatty acid substrates for their ability to be incorporated into a specific target protein. Our experimental system may prove useful for recapitulating other eukaryotic protein modifications in E. coli so that structure-activity relationships of modifying enzymes and their substrates can be more readily assessed.     

New indicators for delay in initiation of antiretroviral treatment: estimates for Cameroon

Objective

To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon.

Methods

We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d’Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010.

Findings

In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/μl (interquartile range, IQR: 66 to 210) in 2007–2009 to 163 cells/μl (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2).

Conclusion

The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful.     

Images of a Healthy Worksite: A Group-Randomized Trial for Worksite Weight Gain Prevention With Employee Participation in Intervention Design

Objectives. We assessed the effects of a worksite multiple-component intervention addressing diet and physical activity on employees’ mean body mass index (BMI) and the percentage of employees who were overweight or obese.Methods. This group-randomized trial (n = 3799) was conducted at 10 worksites in the northeastern United States. Worksites were paired and allocated into intervention and control conditions. Within- and between-groups changes in mean BMIs and in the percentage of overweight or obese employees were examined in a volunteer sample.Results. Within-group mean BMIs decreased by 0.54 kilograms per meter squared (P = .02) and 0.12 kilograms per meter squared (P = .73) at the intervention and control worksites, respectively, resulting in a difference in differences (DID) decrease of 0.42 kilograms per meter squared (P = .33). The within-group percentage of overweight or obese employees decreased by 3.7% (P = .07) at the intervention worksites and increased by 4.9% (P = .1) at the control worksites, resulting in a DID decline of 8.6% (P = .02).Conclusions. Our findings support a worksite population strategy that might eventually reduce the prevalence of overweight and obesity by minimizing environmental exposures to calorically dense foods and increasing exposures to opportunities for energy expenditure within worksite settings.Sixty-eight percent of adults residing in the United States are overweight or obese,1 and these conditions affect more than 1.4 billion adults worldwide.2 Traditional obesity control strategies, which have focused on changing diet and physical activity (PA) behaviors, provide significant individual benefits3 but are considered insufficient to reduce population disease burdens,4,5 for which broad, population-based approaches are needed.6 In addition to individual biology and behaviors, the physical, social, and cultural environment appears to contribute to the upward trend in population estimates of overweight and obesity7,8 by facilitating high-energy, low-nutrient diets and reducing the need to be physically active to perform activities of daily life.9Worksites are feasible self-contained environments with established communication systems in which interventions manipulating the food and PA environment and the social marketing of lifestyle changes can be implemented. Given that 58.4% of the US population aged 16 years or older is employed,10 worksite interventions have the potential to reach large number of adults11 and can foster the participation of employees in project development and sustainability.12–14 Moreover, participatory worksite interventions address workers’ needs, priorities, and interests and allow strategies to be adapted to the realities of individual sites.13 There is also a business case for weight control programs. In comparison with their nonobese counterparts, overweight and obese employees have higher absenteeism rates, have more work limitations, and are less productive.15–18With these issues in mind, the National Heart, Lung, and Blood Institute developed the Obesity Prevention in the Worksite initiative, a population-based approach to promoting behavioral change through environmental interventions that address prevention and control of weight gain.19 Prior to this initiative, worksite trials were either limited scope interventions, targeting a few aspects of the food or PA environment,9,20–23 or broader scope efforts simultaneously targeting risk factors for cardiovascular disease and cancer (e.g., smoking, diet).24–28 In addition, few studies addressed environmental influences related to excessive weight gain.Here we report the results of Images of a Healthy Worksite, one of the studies that is part of the Obesity Prevention in the Worksite initiative; this comprehensive nutrition and PA intervention was designed to promote healthy lifestyles and to stop the shift to the right of the population body mass index (BMI) curve. In this study, worksites were designated to receive an environmental intervention, and employees participated in intervention design. We hypothesized that mean BMIs among employees at the intervention worksites and the percentages of employees who were overweight or obese would not increase over a 2-year period or would increase less than at control worksites.