Renal Transplantation Is Not Associated with Regression of Left Ventricular Hypertrophy: A Magnetic Resonance Study

Background and objectives: Patients with end-stage renal failure (ESRD) have an increased risk of premature cardiovascular (CV) disease. Left ventricular hypertrophy is an independent risk factor for CV events and death in ESRD. Renal transplantation has been associated with reduction in CV risk and echocardiographic regression of left ventricular hypertrophy. However, echocardiography overestimates LV mass in ESRD patients. Cardiac magnetic resonance (CMR) provides more detailed, volume-independent, measures of cardiac structure. Changes in LV mass measured by CMR after renal transplantation were studied.Design, setting, participants, & measurements: Fifty patients underwent CMR on two occasions. Twenty-five were transplanted before the second scan. CMR was performed to measure LV mass index (LVMI), ejection fraction, end-diastolic and end-systolic volumes. Changes were expressed as percentage change over time. Patients with CV events between scans (e.g., acute coronary syndrome, myocardial infarction) were excluded. All transplant patients had serum creatinine <150 μmol/L.Results: There was no significant change in LVMI between patients who underwent renal transplantation and those who remained on dialysis (transplanted mean, 2.75%/yr, ± 9.1 versus dialysis, −3.6%/yr ± 16.7). In addition, there were no significant changes in end-diastolic volume (transplant, 0.1%/yr ± 19.5 versus not transplanted, −3.4%/yr ± 31.5), end-systolic volume (transplanted mean, 15.2%/yr ± 65.2 versus not transplanted, 3.0%/yr ± 55.5), or ejection fraction (transplant, 2.1%/yr ± 11.9 versus not transplanted, −0.4%/yr ± 5.3).Conclusions: Renal transplantation is not associated with significant regression of LVMI on CMR compared with patients who remain on the transplant waiting list.Patients with end-stage renal disease (ESRD), particularly those requiring dialysis and transplantation, have an increased risk of premature cardiovascular disease (CVD; (1)). Left ventricular hypertrophy (LVH) is a common feature of patients with ESRD, a component of uremic cardiomyopathy, and an independent risk factor for sudden cardiac death, heart failure, and cardiac arrhythmias in the general population and dialysis patients (2,3). Furthermore, successful renal transplantation (RT) is associated with lower cardiovascular morbidity and mortality compared with patients who remain on the transplant waiting list (4) and has been reportedly associated with significant echocardiographic regression of LVH (5,6).However, accurate echocardiographic estimation of left ventricular (LV) mass in ESRD patients is difficult because of large variation in intravascular (and hence intraventricular) volume during the interdialytic period and during dialysis therapy (7). Furthermore, geometric assumptions made during calculation of LV mass from conventional M mode echocardiography dimensions (8) result in greater inaccuracies because of geometric LV distortion in patients with LVH and ESRD (representing the majority of patients).Cardiac magnetic resonance (CMR) provides more detailed, volume-independent, measurement of cardiac structure and is considered the ′gold standard′ for assessing ventricular dimensions in patients, including those with stage 5 chronic kidney disease (9–11).The aim of this study was to compare changes in LV structure and function between patients that had undergone RT and those that remained on the transplant waiting list.     

Determinants of hypertension and left ventricular function in end stage renal failure: a pilot study using cardiovascular magnetic resonance imaging

Cardiovascular disease is the principal cause of mortality in patients with renal failure. Left ventricular (LV) abnormalities are adverse prognostic indicators for cardiovascular outcome. The aim of this study was to use cardiac magnetic resonance scanning (CMR) to define LV functional abnormalities in haemodialysis (HD) patients and clarify the determinants of blood pressure (BP) and the effect of anaemia in this population. We studied 44 HD patients and 11 controls with CMR performed following dialysis. Forty patients and 11 controls completed the study. LV mass (P<0.001) and estimated systemic vascular resistance (SVR) (P = 0.002) were significantly higher in the dialysis group compared to controls. LV ejection fraction (P = 0.002) and SV (P = 0.043) were lower than controls. In the HD patients, BP correlated significantly with cardiac output (CO; r = 0.569, P<0.001) and end diastolic volume (EDV; r = 0.565, P<0.001) but there was no correlation between BP and SVR (r = 0.201, P = 0.594). Haemoglobin was inversely correlated with both CO (r = -0.531, P<0.001) and EDV (r = -0.493, P = 0.001) and positively with SVR (r = 0.402, P = 0.009). HD patients had a higher LV mass and lower ejection fraction than controls. The relationship of BP with CO, but not SVR, supports the theory that a major determinant of BP is intravascular volume and CO rather than vascular resistance although there was a fixed increase in SVR in this population. Improved understanding of the mechanisms underlying increased SVR and improved control of CO and intravascular volume may allow better therapeutic strategies. CMR provides insights into the pathophysiology of hypertension and LV dysfunction in HD patients.     

Functional analysis and drug response to zinc and D-penicillamine in stable ATP7B mutant hepatic cell lines

AIM: To study the effect of anti-copper treatment for survival of hepatic cells expressing different ATP7B mutations in cell culture.METHODS: The most common Wilson disease (WD) mutations p.H1069Q, p.R778L and p.C271*, found in the ATP7B gene encoding a liver copper transporter, were studied. The mutations represent major genotypes of the United States and Europe, China, and India, respectively. A human hepatoma cell line previously established to carry a knockout of ATP7B was used to stably express WD mutants. mRNA and protein expression of mutant ATP7B, survival of cells, apoptosis, and protein trafficking were determined.RESULTS: Low temperature increased ATP7B protein expression in several mutants. Intracellular ATP7B localization was significantly impaired in the mutants. Mutants were classified as high, moderate, and no survival based on their viability on exposure to toxic copper. Survival of mutant p.H1069Q and to a lesser extent p.C271* improved by D-penicillamine (DPA) treatment, while mutant p.R778L showed a pronounced response to zinc (Zn) treatment. Overall, DPA treatment resulted in higher cell survival as compared to Zn treatment; however, only combined Zn + DPA treatment fully restored cell viability.CONCLUSION: The data indicate that the basic impact of a genotype might be characterized by analysis of mutant hepatic cell lines.     

大鼠胫骨骨折愈合过程中Ⅰ、Ⅱ型胶原蛋白的表达：失神经状态下Western blot方法测定

目的:揭示失神经骨折愈合中Ⅰ、Ⅱ型胶原蛋白表达的变化规律,探讨神经系统对骨折愈合机制的影响。方法:实验于2005-05/12在解放军第二军医大学动物实验室及细胞生物教研究室完成。40只SD大鼠按随机数字表法分成2组,每组20只。单纯左胫骨骨折组(胫骨骨折组),于左胫骨前弓状缘上0.3cm上1/3处咬断胫骨,从胫骨平台前缘插入一根直径0.8mm克氏针,制成胫骨骨折模型。T10脊髓完全性损伤并左胫骨骨折组(脊髓损伤并胫骨骨折组),在上述模型的基础上,横断切除T10段脊髓约0.3cm,制成T10脊髓完全性损伤大鼠胫骨骨折模型制备。分别于伤后1,2,4,5周采用Westernblot方法检测骨痂中Ⅰ、Ⅱ型胶原的蛋白表达。结果:40只大鼠全部进入结果分析。伤后第1周,两组Ⅰ、Ⅱ型胶原均有表达,脊髓损伤并胫骨骨折组两种胶原的表达程度均高于胫骨骨折组;伤后第2周,脊髓损伤并胫骨骨折组Ⅱ型胶原的表达达到峰值,高于胫骨骨折组(39.45±0.99,29.45±0.85,aP<0.05);伤后第4周,胫骨骨折组Ⅰ型胶原表达量达峰值,高于脊髓损伤并胫骨骨折组(31.69±1.42,26.33±1.11,aP<0.05),脊髓损伤并胫骨骨折组Ⅱ型胶原仍有高表达;伤后第5周,胫骨骨折组、脊髓损伤并胫骨骨折组Ⅰ、Ⅱ型胶原表达下降(Ⅰ型胶原2组依次为:20.32±0.56,13.57±0.44;Ⅱ型胶原2组依次为6.34±0.21,12.58±0.44)。结论:神经系统可能通过调节Ⅰ、Ⅱ型胶原的分泌而影响骨折愈合。     

人类项韧带的精细解剖结构

目的:观察人类项韧带的精细解剖结构及形态。方法:实验于2004-09/2005-04在大连医科大学解剖教研室及大连医大生物塑化有限公司科研部完成。观察对象为4具成人尸体的颈部,均有完整的颈部(椎)全段,包括颅骨后枕外隆突。其中1具尸体进行肉眼大体解剖;3具尸体取寰椎到C7水平,制作成P45(聚酯树脂)生物塑化薄片。所有标本及材料均由大连医大生物塑化有限公司及大连医科大学解剖教研室提供。观察大体标本及P45断层塑化薄片标本,记录各种新发现。最后将两部分的观察及影像结果合并,利用断层解剖知识,标注项韧带组织名称并进行分析。结果:在颈椎的不同平面,项韧带的浅层、背侧部和腹侧部分别由斜方肌、头夹肌、小(大)菱形肌和上后锯肌的腱膜纤维组成的一个整体,且绝大部分纤维走向为横行。结论:①项韧带的结缔组织纤维不是全部纵向走行的,是以横向走行为主的肌腱腱膜组织纤维。②P45生物塑化薄片技术的应用使项韧带精细解剖结构的全貌更直观。     

Patient differences related to management in general practice and the hospital: a cross-sectional study of heart failure in the community.

AIM: To compare patients treated for heart failure in relation to the management in general practices versus hospital admission. METHODS AND RESULTS: Twelve randomly selected general practices (GP) were screened for patients receiving ACE-inhibitor, digoxin, or loop diuretic treatment. The first 500 volunteers of 959 potential subjects were invited to a cardiac examination after exclusion of 235 frail, physically or mentally disabled patients. A diagnosis of heart failure during hospital admission (Hospital-HF, n = 102) was more related (p < 0.05) to male sex (45% vs. 21%), advanced age (73 vs. 70 years), breathlessness (75% vs. 62%), LV systolic dysfunction (47% vs. 20%), objective cardiac abnormality (92% vs. 65%) and higher 4-year mortality (33% vs. 15%) than patients taking loop diuretics due to signs and symptoms of heart failure in GP (GP-HF). Patients without clinical heart failure (n = 301) had the same survival but less symptoms and cardiac abnormalities than GP-HF patients. CONCLUSION: A surplus morbidity and mortality was related to a hospital-based rather than a GP based diagnosis of HF. Patients managed in GP were different from patients entering previous clinical trials of heart failure. We estimate that the pool of patients hospitalised with systolic heart failure would be increased from 1.3 to 1.4 more if all patients from primary care were included.     

Total body electrolyte composition in patients with heart failure: a comparison with normal subjects and patients with untreated hypertension.

Total body elemental composition was measured in 40 patients with well documented heart failure who were oedema-free on digoxin and diuretics. The results were compared with values for 20 patients with untreated essential hypertension matched for height, weight, age, and sex. Total body potassium alone was also measured in 20 normal subjects also matched for anthropomorphic measurements. Patients with hypertension had a very similar total body potassium content to that of normal subjects, but patients with heart failure had significantly reduced total body potassium. This could not be explained by muscle wasting because total body nitrogen, largely present in muscle tissue, was well maintained. When total body potassium was expressed as a ratio of potassium to nitrogen mass a consistent depletion of potassium was revealed in the group with heart failure. Potassium depletion was poorly related to diuretic dose, severity of heart failure, age, or renal function. Activation of the renin-angiotensin-aldosterone system was, however, related to hypokalaemia and potassium depletion. Such patients also had significantly lower concentrations of serum sodium and blood pressure. Serum potassium was related directly to total body potassium. Despite the absence of clinically apparent oedema total body chlorine was not consistently increased in heart failure, but the calculated extracellular fluid volume remained expanded in the heart failure group. Total body sodium was significantly increased in patients with heart failure, but less than half of this increase could be accounted for by extracellular fluid volume expansion. Potassium depletion in heart failure may account in part for the high frequency of arrhythmias and sudden death in this condition.     

感染性休克病人的血流动力学特点及意义

目的 了解感染性休克病人早期血流动力学改变的特点及预后关系。方法 临床前瞻性研究，监测感染性休克早期血流动力学改变并分析与预后的关系。结果 共连续观察48例病人，其中25例（52%）死亡。一些指标的水平在死亡者与生存者间差别较大，其中包括平均肺动脉压（MPAP)、肺动脉楔压（PAWP）、体/肺循环阻力指数（SVRI/PVRI）、左/右心做功（LCW/RCW）和左/右心每搏动（LCSW/RCSW）等血流动力学指标的氧合指数，动脉混合静脉血含氧量差（a-vDO2)、全身性为症反应综合征（SIRS）指标积分等。结论 感染性休克病情凶险，部分血流动力学指标对早期评估其预后有指标作用。     

Independent academic Data Monitoring Committees for clinical trials in cardiovascular and cardiometabolic diseases

Data Monitoring Committees (DMCs) play a crucial role in the conducting of clinical trials to ensure the safety of study participants and to maintain a trial's scientific integrity. Generally accepted standards exist for DMC composition and operational conduct. However, some relevant issues are not specifically addressed in current guidance documents, resulting in uncertainties regarding optimal approaches for communication between the DMC, steering committee, and sponsors, release of information, and liability protection for DMC members. The Heart Failure Association (HFA) of the European Society of Cardiology (ESC), in collaboration with the Clinical Trials Unit of the European Heart Agency (EHA) of the ESC convened a meeting of international experts in DMCs for cardiovascular and cardiometabolic clinical trials to identify specific issues and develop steps to resolve challenges faced by DMCs.The main recommendations from the meeting relate to methodological consistency, independence, managing conflicts of interest, liability protection, and training of future DMC members. This paper summarizes the key outcomes from this expert meeting, and describes the core set of activities that might be further developed and ultimately implemented by the ESC, HFA, and other interested ESC constituent bodies. The HFA will continue to work with stakeholders in cardiovascular and cardiometabolic clinical research to promote these goals.     

Acute myeloid leukemia M4 with bone marrow eosinophilia (M4Eo) and inv(16)(p13q22) exhibits a specific immunophenotype with CD2 expression

Extensive immunologic marker analysis was performed to characterize the various leukemic cell populations in eight patients with inv(16)(p13q22) in association with acute myeloid leukemia with abnormal bone marrow eosinophilia (AML-M4Eo). The eight AML cases consisted of heterogeneous cell populations; mainly due to the presence of multiple subpopulations, which varied in size between the patients. However, the immunophenotype of these subpopulations was comparable, independent of their relative sizes. Virtually all AML-M4Eo cells were positive for the pan-myeloid marker CD13. In addition, the AML were partly positive for CD2, CD11b, CD11c, CD14, CD33, CD34, CD36, CDw65, terminal deoxynucleotidyl transferase (TdT), and HLA-DR. Double immunofluorescence stainings demonstrated coexpression of the CD2 antigen and myeloid markers and allowed the recognition of multiple AML subpopulations. The CD2 antigen was expressed by immature AML cells (CD34+, CD14-) and more mature monocytic AML cells (CD34-, CD14+), whereas TdT expression was exclusively found in the CD34+, CD14- cell population. The eight AML-M4Eo cases not only expressed the CD2 antigen, but also its ligand CD58 (leukocyte function antigen-3). Culturing of AML-M4Eo cell samples showed a high spontaneous proliferation in all three patients tested. Addition of a mixture of CD2 antibodies against the T11.1, T11.2, and T11.3 epitopes diminished cell proliferation in two patients with high CD2 expression, but no inhibitory effects were found in the third patient with low frequency and low density of CD2 expression. These results suggest that high expression of the CD2 molecule in AML-M4Eo stimulates proliferation of the leukemic cells, which might explain the high white blood cell count often found in this type of AML.