Reproducibility of radionuclide left ventricular ejection fraction in patients awaiting cardiac transplantation

Radionuclide-derived left ventricular ejection fraction (LVEF) is used to assess LV systolic function, to follow trends in the natural history of dilated cardiomyopathy, and to prioritize patients waiting for cardiac transplantation. Reproducibility of LVEF at extremely low levels has not, however, been reported. To assess the reproducibility of radionuclide LVEF at levels below 0.30 EF U, 17 highly symptomatic patients (NYHA Class III/IV) with dilated cardiomyopathy were studied on two occasions, 72 hours apart. Sequential scans were analyzed by two independent observers. Mean LVEF was 0.18 +/- 0.06 U (scan 1) and 0.17 +/- 0.06 U (scan 2). Interoperator reproducibility (SD) was 0.03 U (R = 0.76), interscan reproducibility (SD) was 0.03 U (R = 0.62), and overall reproducibility (SD) was 0.04 U (R = 0.50). The interobserver variation of 0.03 (actually 0.027) was just over one half that seen in normal volunteers (variation 0.05, n = 29) studied previously in this department. A change of greater than or equal to 0.08 U (2SD) in either direction is highly likely to represent a real change in LV function in those with LVEF less than or equal to 0.30 units, compared with the change of at least 0.10 units required in those with normal LV function. Lower interobserver and interscan reproducibility should be taken into account when interpreting sequential scans in patients with severe LV dysfunction.     

Angeborenes Exanthem mit lividen disseminierten Papeln

Ohne Zusammenfassung     

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.     

健胃愈疡颗粒干预下大鼠胃溃疡黏膜乳癌相关肽和血小板活化因子的表达及与胃黏膜疏水性的相关性研究

目的:观察对胃溃疡复发有较好疗效的健胃愈疡颗粒对溃疡黏膜乳腺癌相关肽和血小板活化因子表达的影响,分析其可能的作用机制。方法:实验于2005-07/2006-07在湘雅医院中心实验室完成。SD大鼠110只,雌雄各半,随机抽签法分为5组,即正常对照组、假手术组、雷尼替丁组、健胃愈疡组,各20只;模型组30只。以Okabe改良法复制大鼠实验性胃溃疡,假手术组仅以生理盐水代替乙酸注入玻管内。造模后24h,雷尼替丁组、健胃愈疡组大鼠分别灌服盐酸雷尼替丁和健胃愈疡颗粒(药物组成为:柴胡、党参、白芍、延胡索、白芨、珍珠层粉、青黛、甘草,湖南湘雅制药有限公司生产)药液10mL/kg,分别相当于2.70,1.62g/kg,1次/d。假手术组、模型组灌服蒸馏水10mL/kg。10d后各组中随机取出10只大鼠剖腹取胃(处死前大鼠禁食24h),90d时将模型组20只大鼠再分为模型复发组和模型非复发组,各10只;除正常对照组、假手术组、模型非复发组大鼠腹腔内注射生理盐水外,其余各组大鼠腹腔内注射白细胞介素1,1μg/kg;在注射48h,大鼠禁食24h后,剖腹取胃。观察其对胃溃疡大鼠胃黏膜氨基己糖及磷脂含量、溃疡指数和胃黏膜血流的影响,并用RT-PCR观察乳癌相关肽乳癌相关肽和血小板活化因子表达的变化。结果:实验动物110只,全部进入结果分析。①模型组10,92d胃黏膜血流均低于正常对照组(P<0.01);健胃愈疡组同期胃黏膜血流均高于模型组(P<0.01)。②健胃愈疡组和雷尼替丁组10d溃疡指数均低于模型组(P<0.01,P<0.05);模型复发组、健胃愈疡组和雷尼替丁组92d溃疡指数均高于模型组(P<0.01);健胃愈疡组10,92d溃疡指数及复发率均低于雷尼替丁组(P<0.05,P<0.01)。③模型组10,92d氨基己糖和磷脂含量均低于正常对照组(P<0.01)。健胃愈疡组10,92d氨基己糖和磷脂含量均高于模型组和雷尼替丁组(P<0.01)。溃疡指数与氨基已糖、磷脂含量呈负相关(r=-0.957,-0.960,P<0.01)。④健胃愈疡组和雷尼替丁组10d乳癌相关肽mRNA表达较正常组和假手术组提高,血小板活化因子mRNA的表达下调(P<0.01),健胃愈疡组两指标表达变化较雷尼替丁组显著(P<0.01);模型复发组、健胃愈疡组和雷尼替丁组92d乳癌相关肽mRNA、血小板活化因子mRNA的表达同组10d比较差异无显著性意义(P>0.05);模型组乳癌相关肽mRNA、血小板活化因子mRNA的表达同组10d比较差异有显著性意义(P<0.01)。结论:健胃愈疡颗粒可提高乳癌相关肽mRNA及下调血小板活化因子mRNA的表达,影响胃黏膜氨基己糖及磷脂含量,可能是其促进溃疡愈合的机制之一。     

Myocardial fatty acid metabolism during acute cardiac allograft rejection

Fatty acids are promptly taken up, metabolised and eliminated by healthy cardiomyocytes. Cardiomyopathy, coronary heart disease and chronic rejection are known to be associated with an impaired fatty acid metabolism. It was the aim of this study to investigate fatty acid metabolism in a rat heart transplant model and to correlate scintigraphic findings with histological changes. After right-side nephrectomy of Lewis recipients Brown Norway cardiac allografts were anastomosed to the renal vessels. Animals were given no immunosuppression. The metabolism of carrier-free 17-¹²³ jodo-heptadecanoic acid (¹²³J-HDA) with a specific activity of >2×10¹⁷ Bq/ml was scintigraphically measured between days 1 and 11. An increase in the grade of rejection was observed over time. Fifty-six frames of 30 s duration each were recorded. For the region of interest (native heart, transplanted heart, left kidney) frames 10–56 were superimposed, time-activity curves generated and monoexponentially fitted. Furthermore, elimination half-life and intercepts were calculated. Following scintigraphic evaluation the animals were killed and graft as well as native hearts excised for histological examination. The uptake of the tracer identified severe grades of rejection. Elimination half-life of the tracer was twice as long from hearts with mild rejection and more than 14 times as long in severe rejection compared with no rejection. Elimination half-life and amplitude did not permit discrimination between grades 1, 2 and 3 a, but significantly decreased in groups 3 b and 4. This method therefore seems to be a valuable tool for the noninvasive detection of severe acute cardiac allograft rejection. Since fatty acid metabolism is clearly stress-dependent it remains to be seen whether this method allows detection of earlier rejection in loaded hearts.     

Transfusion-related acute lung injury caused by an NB2 granulocyte- specific antibody in a patient with thrombotic thrombocytopenic purpura

HLA and granulocyte-specific antibodies have been implicated in the production of transfusion-related acute lung injury (TRALI). Reported here is a case that suggests that the patient's preexisting condition may play an important role in determining whether TRALI develops upon transfusion of blood products containing anti-white cell (WBC) antibodies. A 29-year-old woman with thrombotic thrombocytopenic purpura (TTP) underwent an uneventful 1.5-volume plasma exchange, which was followed by the transfusion of 2 red cell (RBC) units. At the end of the second RBC transfusion, the patient developed clinical signs and symptoms of noncardiogenic pulmonary edema. Serologic studies demonstrated that the serum from the second RBC donor had no HLA antibodies but did have a granulocyte-specific antibody (anti-NB2) that caused the agglutination of the recipient's granulocytes, which were NB2 positive. Serum from the donor of the first RBC unit and serum from the donors of units used in the exchange had no HLA or granulocyte-specific antibodies that reacted with the recipient's WBCs. Because the donor implicated in this reaction had a history of 21 blood donations, none of which had been associated with a transfusion reaction, we suggest that the patient's preexisting condition played a significant role in this episode of TRALI, owing to the granulocyte-specific antibody.     

认知矫正治疗对慢性精神分裂症患者临床症状和社会功能的影响

目的:观察认知矫正治疗对慢性精神分裂症患者临床症状和社会功能的改善作用。方法:选择2003-01/08在北京回龙观医院住院的慢性精神分裂症患者104例。均符合CCMD-Ⅲ及DSM-Ⅳ关于精神分裂症诊断标准;年龄25～55岁;病程≥2年;病情稳定,处于迁延、残留或部分缓解状态;药物治疗状况稳定,近期无换药打算;纳入对象或家属同意入组并签署知情同意书。应用随机数字表法将患者分认知矫正治疗组和对照组,每组52例。在相近药物治疗的基础上,认知矫正治疗组以Ann Delahunty和Rodney Morice等制定的神经认知矫正手册(汉化)为治疗工具,在治疗师的指导下进行认知作业练习,内容包括认知灵活性、工作记忆、计划执行功能3大功能模块。对照组予以相同时间的工娱治疗,主要包括有治疗师指导的操作性音乐治疗和舞蹈治疗。治疗前后两组患者分别进行PANSS、住院精神患者社会功能缺陷量表和护士观察量表的评定。结果:实验共纳入慢性精神分裂症患者104例,认知矫正治疗组44例,对照组46例进入结果分析,14例脱落。①治疗前后两组患者PANSS量表总分以及阴性症状量表、复合量表、一般精神病理量表、反应缺乏量表4个分量表的评分均有下降,组内比较差异有显著性意义(t=2.12～4.59,P<0.05);减分情况在两组间差异不明显(P>0.05)。②两组患者的社会功能缺陷量表总分在治疗后均有下降,与治疗前比较,差异有显著性意义(t=3.89,2.04,P<0.05);两组间比较,差异无显著性意义(P>0.05)。认知矫正治疗组治疗后护士观察量表的总病情以及总消极、迟滞2个分量表评分下降,与治疗前比较差异有显著性意义(t=1.49,1.19,2.81,P<0.05);其中迟滞项的减分在两组间比较,差异具有显著性意义(F=4.97,P<0.05)。③社会功能量表的改善与词语流畅性的改善呈正相关(R2=0.36,P<0.05),护士观察量表中总病情与积极两项评分的改善也与言语流畅性测验的改善正相关(R2=0.37,0.34,P<0.05)。结论:认知矫正治疗能在一定程度上改善精神分裂症患者的社会功能,并与部分认知功能的改善相关,但对临床症状无明显改善作用。     

First results of the THROMKID study: a quality project for the registration of children und adolescents with hereditary platelet function defects in Germany, Austria, and Switzerland

THROMKID is a quality project of the Paediatric Group of German Thrombosis and Haemostasis Research Society (GTH). Data from paediatric patients with hereditary thrombocytopathies (HT) treated in Germany, Austria, and Switzerland were obtained between May 2005 and August 2006. By evaluation of results of platelet function tests criteria were determined to assess the diagnosis in each patient into most likely, likely or unlikely. A total of 215 patients treated in 31 centers were identified. In 95 patients (44%) the diagnosis of HT was most likely, in 28 (13%) likely and in 92 (43%) unlikely. Taken the first two groups together (n = 123) the diagnoses were as follows: Glanzmann thrombasthenia (n = 39, 32%), Aspirin-like defect (n = 26, 21%), thrombocyte receptor defects (n = 21, 17%), storage pool disorders (n = 18, 15%), Bernard-Soulier syndrome (n = 10, 8%), Hermansky-Pudlak syndrome (n = 6, 5%) and MYH9-related hereditary makrothrombocytopenia (n = 3, 2%). The low prevalence of these diseases and the high percentage of patients with unclassified HT stresses the necessity for the establishment of a competence network for comprehensive care of these patients in the three German-speaking countries.     

IL-22 is produced by γC-independent CD25+ CCR6+ innate murine spleen cells upon inflammatory stimuli and contributes to LPS-induced lethality

IL-22 is a Th17 cytokine that plays a key role in immune responses against extracellular bacteria. In mucosal lymphoid tissues, IL-22 production is mainly due to an IL-23-responsive NK-like cell subset that shares some markers with lymphoid tissue inducer (LTi) cells. Here, we identified a new spleen cell population responsible for IL-22 production upon either in vitro stimulation by anti-CD3 antibodies or in vivo stimulation by lipopolysaccharide (LPS) via IL-2- and an IL-23-dependent mechanisms, respectively. These cells represent 1% of spleen cells from recombination activating gene (Rag2)-deficient mice, and correspond to a discrete innate lymphoid cell population expressing CD25, CCR6 and IL-7R. This population comprises 60-70% CD4(+) cells, which produce IL-22, and are still present in common γ chain-deficient mice; the CD4(-) subset coexpresses IL-22 and IL-17, and is common γ chain-dependent. The importance of IL-22 production for the LPS-triggered response is highlighted by the fact that IL-22-deficient mice are more resistant to LPS-induced mortality.     

Irbesartan-mediated reduction of renal and cardiac damage in insulin resistant JCR : LA-cp rats

Background and purpose:

Angiotensin II receptor antagonists (ARBs), originally developed for antihypertensive properties, have pleiotropic effects including direct vascular actions. We tested the hypothesis that the ARB irbesartan would be effective against micro- and macrovascular complications of the prediabetic metabolic syndrome using the obese, insulin-resistant JCR : LA-cp rat that exhibits micro- and macrovascular disease with ischaemic myocardial lesions and renal disease.

Experimental approach:

Obese male rats were treated with irbesartan (30 mg·kg⁻¹·day⁻¹, incorporated into chow) from 12 to 25 weeks of age.

Key results:

Irbesartan treatment caused no change in food intake or body weight. Fasting glycaemic control of the JCR : LA-cp rats was marginally improved, at the expense of increased plasma insulin levels (∼50%). Fasting plasma triglycerides were marginally reduced (∼25%), while cholesterol concentrations were unchanged. Elevated concentrations of adiponectin, monocyte chemotactic protein-1 and plasminogen activator inhibitor-1 were reduced along with severity of glomerular sclerosis. Macrovascular dysfunction (aortic hypercontractile response to noradrenergic stimulus and reduced endothelium-dependent relaxation) was improved and frequency of ischaemic myocardial lesions reduced (62%).

Conclusions and implications:

Irbesartan reduces markers of inflammation and prothombotic status, improves macrovascular function and reduces glomerular sclerosis and myocardial lesions in a model of the metabolic syndrome. Unlike pharmaceutical agents targeted on metabolic dysfunction, irbesartan reduced end-stage disease without major reduction of plasma lipids or insulin. The protective effects appear to be secondary to unknown intracellular mechanisms, probably involving signal transduction pathways. Understanding these would offer novel pharmaceutical approaches to protection against cardiovascular disease.