Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Treatment of normal individuals with granulocyte-colony-stimulating factor: donor experiences and the effects on peripheral blood CD34+ cell counts and on the collection of peripheral blood stem cells

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) has been used in patients to increase the level of circulating hematopoietic progenitors. Although G-CSF has been administered to some healthy individuals, the kinetics of mobilization of peripheral blood stem cells (PBSCs), the optimum dose schedule and the incidence and nature of adverse reactions in normal individuals are not completely defined. STUDY DESIGN AND METHODS: Normal individuals (n = 102) who received G- CSF for 5 or 10 days at doses of 2, 5, 7.5, or 10 micrograms per kg per day were studied. The subjects were observed for symptoms and physical changes, and blood samples were obtained for a variety of laboratory tests. After 5 or 10 days of G-CSF treatment, PBSCs were collected by apheresis and analyzed. RESULTS: Overall, 89 percent of the individuals completed the 5-day treatment protocol and 88 percent completed the 10- day protocol without modification of the dose of G-CSF administered. Ninety percent of donors experienced some side effect of G-CSF. The most frequent effects noted were bone pain (83%), headache (39%), body aches (23%), fatigue (14%), and nausea and/or vomiting (12%). The dose of G-CSF administered directly affected the proportion of people with bone pain (p = 0.025) or body aches (p = 0.045) or who were feeling hot or having night sweats (p = 0.02) or taking analgesics (p = 0.01). With the 5-day dose schedule, several changes in serum chemistries occurred, including increases in alkaline phosphatase (p = 0.001), alanine aminotransferase (p = 0.0013), lactate dehydrogenase (p = 0.0001), and sodium (p = 0.0001). Decreases occurred in glucose (p = 0.045), potassium (p = 0.0004), bilirubin (p = 0.001), and blood urea nitrogen (p = 0.0017). In donors who received G-CSF for 5 days, the absolute neutrophil count was increased after one G-CSF dose, and it reached a maximum on Day 6, as did the number of CD34+ cells (64.6 +/? 55.9 × 10(6) cells/L). In those same donors, the platelet count after apheresis on Day 6 was 32 +/? 13 percent lower than pretreatment values (250 +/? 42 × 10(9) cells/L). In donors receiving G-CSF for 10 days, the neutrophil count reached a maximum on Day 8, but the number of CD34+ cells peaked on Day 6 (58.3 +/? 52.1 × 10(5) cells/L) and then declined. The platelet count decreased from pretreatment values by 28 +/? 12 percent prior to apheresis on Day 11. When individuals were treated for 5 days with G-CSF, the quantity of CD34+ cells collected was directly related to the G-CSF dose. When 5 micrograms per kg per day was given, 2.80 +/? 1.81 × 10(8) cells were collected, compared with collection of 4.67 +/? 3.11 × 10(8) cells when 10 micrograms per kg per day was given (p = 0.04). More important, PBSCs collected after 10 days of G-CSF administration (5 micrograms/kg/day) had significantly fewer CD34+ cells (0.82 +/? 0.37 × 10(8) cells, p = 0.01) than did PBSCs collected after 5 days of G-CSF (5 micrograms/kg/day). CONCLUSION: Most normal donors receiving G-CSF experience side effects, but these are mild to moderate in degree. Some alterations in blood chemistries occur, but none were clinically serious. Because of the symptoms associated with G-CSF, these individuals must be monitored closely. The treatment of normal donors with G-CSF for more than 5 days significantly decreased the number of circulating CD34+ cells and the quantity collected by apheresis.     

维持性血液透析患者钙磷乘积与营养状态的关系

目的回顾性分析维持性血液透析患者钙磷乘积与营养状态的关系。方法对武汉市第一医院维持性血液透析110例终末期。肾脏病患者的临床资料进行回顾性分析,统计其透析前血清钙磷和一般营养状态等指标。钙磷乘积≤55（mg／d1）^2为A组,〉55（mg／d1）^2为B组,比较两组的差异。结果与A组相比,B组血磷（P）明显较高（P〈0．01）;血浆白蛋白（Alb）、透析前尿素氮（BUN）、总胆固醇（TC）、三酰甘油（TG）的含量均较高（P〈0．05）;血钙（Ca）、血红蛋白（Hb）、甲状旁腺激素（iPTH）无统计学意义（P〉0．05）。结论血液透析患者钙磷乘积的升高,可能与营养状态的改善,血磷摄入增加有关。     

沙利度胺预防ERCP术后胰腺炎的实验研究

目的评价具有促进TNF-αmRNA降解的免疫调节剂沙利度胺在预防ERCP术后胰腺炎中的作用。方法建立ERCP术后胰腺炎模型，治疗组术前8天起沙利度胺灌胃，并设立假手术组、无治疗组和赋形物对照组。24h后比较血清淀粉酶水平、胰腺水肿程度以及组织学炎症评分，并比较胰腺组织TNF-αmRNA表达情况。结果沙利度胺显著降低血清淀粉酶、减轻胰腺水肿及组织学炎症评分，并显著降低胰腺组织中TNF-αmRNA的表达。结论TNF-α可能在ERCP术后胰腺炎的发生发展中起着重要作用．预防性使用沙利度胺能有效减轻ERCP术后胰腺炎的严重程度。     

The Effect of Major and Minor Depression on Medicare Home Healthcare Services Use

OBJECTIVES: To examine the associations between major and minor depression and categories of Medicare home healthcare use.
DESIGN: Observational prospective study (1997–1999).
SETTING: Visiting nurse agency in suburban New York State.
PARTCIPANTS: Five hundred thirty-nine new Medicare admissions aged 65 and older (mean age 78.4), 65.1% female, and 15.0% nonwhite. Approximately 13.5% were diagnosed with major depression and another 10.8% with minor depression.
MEASUREMENTS: Consensus "best estimate" Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnoses for major and minor depression assessed using Structured Clinical Interviews for DSM-IV (SCID) plus medical charts.
RESULTS: Major and minor depression appear to have little association with probability and amount of use of the types of Medicare home health care (skilled nurse, home health aide, therapist (physical, occupational, and speech), and medical social services). Overall, patients with minor depression appear to have utilization similar to that of patients with major depression.
CONCLUSION: It seems likely that any potential incremental depression effect on utilization is being offset by the transitional medical state of the patients that entered Medicare home healthcare directly from a hospital, nursing home, or rehabilitation facility, and the overall severity of disability and chronic illness present in long-term home healthcare patients. Further research is required to determine whether similar findings occur in other home healthcare agencies and whether these are present under the current Medicare Prospective Payment System reimbursement mechanism.     

One‐Year Follow‐Up of Nonrandomized Comparison between Coronary Artery Bypass Grafting Surgery and Drug‐Eluting Stent for the Treatment of Unprotected Left Main Coronary Artery Disease in Elderly Patients (Aged ≥75 Years)

Purpose: The present observational study compares in‐hospital and 12‐month clinical outcomes in elderly patients with unprotected left main coronary artery disease treated either with coronary artery bypass grafting or drug‐eluting stent. Methods: From January 2004 to December 2007, 211 patients (pts) with unprotected left main coronary artery (ULMCA) stenosis, aged 75 or older, underwent coronary revascularization either with coronary artery bypass graft (CABG) (106 pts) or drug‐eluting stent (DES) (105 pts). The decision to treat with CABG or percutaneous coronary intervention (PCI) was dependent on the patient's and the physician's choice. The occurrence of major adverse cardiac or cerebrovascular events (MACCE: death, nonfatal myocardial infarction, or stroke) and revascularizations was recorded after 1 year of follow‐up. A multivariate logistic regression analysis was performed using a propensity score method to take potential baseline differences between groups into account. Results: In‐hospital MACCE rates were 5.7% and 3.8% in the CABG and PCI groups, respectively (P = 0.748). After 1 year of follow‐up, these rates were, respectively, 13.9% and 14.9% (P = 0.841), and rates for target vessel revascularization at 12 months were 1.0% and 13.9% (P < 0.001). The PCI group was significantly associated with older age, dyslipidemia, history of cancer, high Euroscore, elevated creatininemia, single‐vessel disease, fewer chronic occlusions of the left anterior descending artery, and more LMCA stenosis ≥70%. The multivariate logistic regression analysis was adjusted for age, diabetes, left ventricular ejection fraction, Euroscore, and plasma creatininemia and stratified on the score of propensity to be treated with PCI. In the subgroup below median propensity score, the adjusted odds ratio for 1‐year MACCE was OR = 0.91 (95% confidence interval: 0.14 to 5.98; P = 0.924) whereas OR was 0.16 (0.04–0.69; P = 0.013) in the subgroup above median propensity score. Conclusions: In patients with a high probability of being treated with PCI (older age, high Euroscore, high creatininemia, single‐vessel disease, …), the 1‐year risk of MACCE was significantly lower in PCI‐ than in CABG‐treated subjects. No significant difference was found in other cases.     

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.