Alterations of ATPase activity and erythrocyte oxygen consumption in patients with liver-blood deficiency syndrome

ＡｌｔｅｒａｔｉｏｎｓｏｆＡＴＰａｓｅａｃｔｉｖｉｔｙａｎｄｅｒｙｔｈｒｏｃｙｔｅｏｘｙｇｅｎｃｏｎｓｕｍｐｔｉｏｎｉｎｐａｔｉｅｎｔｓｗｉｔｈｌｉｖｅｒｂｌｏｏｄｄｅｆｉｃｉｅｎｃｙｓｙｎｄｒｏｍｅＳＨＩＬｉｎＪｉｅ１，ＬＩＵＪｕｎＦａｎ２...     

A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases

Iron deficiency （ID）, with or without anemia, is often caused by digestive diseases and should always be investigated, except in very specific situations, as its causes could be serious diseases, such as cancer. Diagnosis of ID is not always easy. Low serum levels of ferritin or transferrin saturation, imply a situation of absolute or functional ID. It is sometimes difficult to differentiate ID anemia from anemia of chronic diseases, which can coexist. In this case, other parameters, such as soluble transferrin receptor activity can be very useful. After an initial evaluation by clinical history, urine analysis, and serological tests for celiac disease, gastroscopy and colonoscopy are the key diagnostic tools for investigating the origin of ID, and will detect the most important and prevalent diseases. If both tests are normal and anemia is not severe, treatment with oral iron can be indicated, along with stopping any treatment with non-steroidal anti-inflammatory drugs. In the absence of response to oral iron, or if the anemia is severe or clinical suspicion of important disease persists, we must insist on diagnostic evaluation. Repeat endoscopic studies should be considered in many cases and if both still show normal results, investigating the small bowel must be considered. The main techniques in this case are capsule endoscopy, followed by     

高血压病并发脑梗死患者红细胞变形性及细胞膜ATP酶活性的研究

目的：研究高血压病（EH）及并发脑梗死（HCI）患红细胞变形性（RCD）及细胞膜ATP酶活性的改变,方法：采用粘度法,化学比色法测定了20例正常人,30例EH及30例HCI患的红细胞变形指数（DI）,红细胞膜Na^ ,K^ -ATP酶和Ca2 -ATP酶的活性。结果：（1）EH组与正常对照组相比,DI值显升高,ATP酶活性降低,EH患DI与ATP酶活性呈负相关,与DBP呈正相关;（2）CHI组与EH组相比,DI显升高,ATP酶活性显降低;HCI患DI与ATP酶活性呈负相关。结论：（1）EH患RCD降低,并与细胞膜ATP酶活性降低及血压升高相关。（2）RCD降低可能与EH患脑梗死的发生有关。     

高血压病患者红细胞变形性改变和细胞膜ATP酶活性对其影响及卡托普利干预

目的 探讨高血压病患红细胞变形性（RCD）改变及细胞膜ATP酶活性对其影响,并观察血管紧张素转换酶抑制剂－卡托普利治疗后的变化。方法 采用粘度法、化学比色法测定了20例正常人、30例高血压病及30例高血压病并发脑梗死患的红细胞变形指数（DI）、红细胞膜Na^ ,K^ -ATP酶和Ca^2 -ATP酶活性。其中30例高血压病患接受卡托普利治疗,共24周。结果（1）高血压病组与正常对照组相比,DI值显升高,ATP酶活性降低;高血压病患DI与ATP酶活性呈负相关,DI与DBP呈正相关。（2）高血压病并发脑梗死组与高血压病组相比,DI显升高,ATP酶活性显降低;高血压病并发脑梗死病患,DI与ATP酶活性呈负相关。（3）卡托普利治疗后DI值显下降,ATP酶活性显升高。结论 （1）高血压病患RCD降低,并与细胞膜ATP酶活性降低及血压升高相关;（2）高血压病患并发脑梗死患RCD较高血压病患更低;（3）卡托普利治疗高血压病患在有效降压的同时,能显增加细胞膜ATP酶活性,增加RCD。     

红细胞膜ATP酶活性变化与糖尿病并发症的关系

目的 探讨红细胞胞膜ＡＴＰ酶（ＡＴＰａｓｅ）活性变化与糖尿工发症之间的关系。方法 将９７例糖尿病患者分为三组：Ａ组（无并发症）３７例,Ｂ组（并发酮症酸中毒）１５例,Ｃ组（慢性血管并发症）４５例。红细胞膜Ｎａ＋－Ｋ＝－ＡＴＰａｓｅ活性（红细胞膜ＡＴＰａｓｅ活性）分别用改良的Ｈａｎａｈａｎ法和Ｌｕｔｈｒａ法进行检测,并设４９例健康乾为对照组。结果 与对照组比较,各组糖尿病患工细胞膜ＡＴＰａｓｅ活性均明     

Donor-Type Myelodysplastic Syndrome with t(2;3) and Monosomy 7 after Allogeneic Peripheral Blood Stem Cell Transplantation and Liver Transplantation in a Patient with Severe-Type Aplastic Anemia

Secondary clonal hemaloiogical disease in donor cells has rarely been reported as a complication of allogeneic stem cell transplantation in hematological disease. We report a case of myelodysplastic syndrome that showed cytogenetic abnormalities of t(2;3) and monosomy 7, which developed 2 years after peripheral blood stem cell transplantation for aplastic anemia and 1 year after liver transplantation for drug-induced hepatic failure. This secondary malignancy of donor origin is most frequently seen in patients with leukemia. We suspect that the chromosomal abnormalities are related to hepatitis-associated aplastic anemia, administration of granulocyte colony-stimulating factor and erythropoietin for posttransplantion pancytopenia, and repeated infections after liver transplantation.     

Serial changes in endogenous erythropoietin levels in patients with myelodysplastic syndromes and aplastic anemia undergoing erythropoietin treatment

Summary Recombinant human erythropoietin (rhEpo) was administered to 14 patients with myelodysplastic syndrome (MDS) and seven patients with aplastic anemia (AA). In 19 patients, doses of 6000 units were given intravenously three times a week (t.i.w.) with the dose being doubled up to 24000 units every 8 weeks until a response was obtained. RhEpo was given subcutaneously in two patients. Seven patients, four with MDS and three with AA, showed a significant response with an increase of hemoglobin concentration during therapy. The response occurred at doses of 12000 units in five and 24 000 units in two patients. Responding patients with both MDS and AA had a relatively low serum Epo (s-Epo) level prior to Epo therapy. MDS responders had either refractory anemia (RA) or RA with ring sideroblasts (RARS), while two of the Epo responders in AA had a severe form of the disease. However, since some of the Epo responders had a high initial s-Epo concentration, a high s-Epo level does not preclude the use of rhEpo. Serial determination of s-Epo levels showed a progressive decline in six of the seven responders even when they were on rhEpo therapy, while the s-Epo levels remained elevated or further increased with time in most nonresponders. RhEpo was well tolerated by all patients. The results suggest that rh-Epo is a safe and effective treatment for a certain proportion of patients with MDS and AA. Moreover, serial determination of s-Epo during therapy may be useful in monitoring and predicting the therapeutic effect of rhEpo.This work was supported by grants (63480277, 03671185, 03151057) from the Ministry of Education, and Grants for Intractable Disease from the Ministry of Health of Japan     

Under-diagnosing and under-treating iron deficiency in hospitalized patients with gastrointestinal bleeding

AIM: To determine whether patients hospitalized with gastrointestinal(GI) blood loss anemia are being checked and treated for iron deficiency. METHODS: Retrospective chart review was conducted for all patients admitted to a single tertiary care hospital between 11/1/2011 and 1/31/2012 for any type of GI bleeding. The primary endpoint was the percentage of patients who had their iron studies checked during a hospitalization for GI blood loss anemia. Secondary outcomes included percentage of anemic GI bleeders who had adequate documentation of anemia and iron deficiency, and those who were treated for their iron deficiency. Then we tried to identify possible predictors of checking iron studies in an attempt to understand the thought process that physicians go through when managing these patients. Iron deficiency was defined as Iron saturation less than 15% or ferritin level less than 45 μg/L. Anemia was defined as hemoglobin level less than 13 g/dL for males and 12 g/dL for females.RESULTS: Three hundred and seven GI bleeders were hospitalized during the study period, and 282 of those(91.9%) had anemia during their hospital stay. Ninetyfive patients(30.9%) had iron studies performed during hospitalization, and 45 of those(47.4%) were actually found to be iron deficient. Only 29 of those 45 iron deficient patients were discharged home on iron supplements. Of the 282 patients that had anemia during hospitalization, 50(17.7%) had no documentation of the anemia in their hospital chart. Of the 45 patients that had lab proven iron deficiency anemia(IDA), only 22(48.5%) had documentation of IDA in at least one note in their chart. Predictors of checking iron studies in anemic GI bleeders were lower mean corpuscular volume, documentation of anemia, having fecal occult blood testing, not having hematemesis or past history of GI bleeding. There were no significant differences between the teaching and non-teaching services in any patient characteristics or outcomes. CONCLUSION: Iron deficiency is under-diagnosed, under-recognized even when iron studies were checked, and under-treated in hospitalized patients with GI bleeding.     

再生障碍性贫血-阵发性睡眠性血红蛋白尿综合征与典型阵发性睡眠性血红蛋白尿症的临床对照研究

目的　研究再生障碍性贫血 -阵发性睡眠性血红蛋白尿综合征 (AA PNH综合征 )与典型阵发性睡眠性血红蛋白尿症 (PNH)临床特征的异同 ,加深对AA PNH综合征的认识。方法　回顾分析了 2 8例AA PNH综合征和 5 1例典型PNH的临床表现、实验室检查及治疗反应 ,并进行了对照研究。结果　AA PNH综合征与典型PNH相比 :①血栓形成、黄疸、肝脾肿大等临床表现均较轻。②网织红细胞虽较低 ,但仍高于正常 ;骨髓涂片及活检多表现为增生减低 ,但红系比例不低 ;③各溶血指标检查阳性率均较低 ,但CD5 5、CD5 9表达异常的检出率为10 0 % ,且其在红细胞、粒细胞、淋巴细胞中表达的百分率在两组患者中无明显差异。④免疫球蛋白、T细胞亚群的检测 ,两组患者均无异常。⑤两组患者对肾上腺糖皮质激素为主的治疗均反应良好。结论　AA PNH综合征虽临床表现有别于典型PNH ,但与典型PNH无本质区别 ;CD5 5、CD5 9的检测有助于提高AA PNH综合征的检出率     

沙棘油在体外对肾虚型再生障碍性贫血作用的实验研究

目的 观察沙棘油在体外对肾阳虚、肾阴虚不同证型再生障碍性贫血(AA)患者红系集落形成单位(CFU-E)、粒巨噬细胞系集落形成单位(CFU-GM)的影响.方法 20例AA患者(肾阴虚型组及肾阳虚型组各10例),正常对照组10例,取其骨髓分离单个核细胞,以琼脂半固体培养联合沙棘油的方法,培养3、7 d后分别对比各组CFU-E、CFU-GM集落形成情况.结果 不同证型AA患者的CFU-E、CFU-GM较正常对照组明显减低(P＜0.01);沙棘油能明显促进不同证型AA患者CFU-E、CFU-GM的集落生成,这种促进作用随沙棘油体积分数增加而增加;在体积分数不低于20%时,沙棘油对肾阳虚患者CFU-E、CFU-GM的疗效明显好于对肾阴虚患者的疗效(P＜0.05).结论 沙棘油在体外对AA患者CFU-E、CFU-GM有一定的促增殖作用,且高剂量时对肾阳虚证型患者的作用优于肾阴虚证型患者.     

A 9-yr evaluation of carrier erythrocyte encapsulated adenosine deaminase (ADA) therapy in a patient with adult-type ADA deficiency

Adenosine deaminase (ADA) deficiency is an inherited disorder which leads to elevated cellular levels of deoxyadenosine triphosphate (dATP) and systemic accumulation of its precursor, 2-deoxyadenosine. These metabolites impair lymphocyte function, and inactivate S-adenosylhomocysteine hydrolase (SAHH) respectively, leading to severe immunodeficiency. Enzyme replacement therapy with polyethylene glycol-conjugated ADA is available, but its efficacy is reduced by anti-ADA neutralising antibody formation. We report here carrier erythrocyte encapsulated native ADA therapy in an adult-type ADA deficient patient. Encapsulated enzyme is protected from antigenic responses and therapeutic activities are sustained. ADA-loaded autologous carrier erythrocytes were prepared using a hypo-osmotic dialysis procedure. Over a 9-yr period 225 treatment cycles were administered at 2-3 weekly intervals. Therapeutic efficacy was determined by monitoring immunological and metabolic parameters. After 9 yr of therapy, erythrocyte dATP concentration ranged between 24 and 44 micromol/L (diagnosis, 234) and SAHH activity between 1.69 and 2.29 nmol/h/mg haemoglobin (diagnosis, 0.34). Erythrocyte ADA activities were above the reference range of 40-100 nmol/h/mg haemoglobin (0 at diagnosis). Initial increases in absolute lymphocyte counts were not sustained; however, despite subnormal circulating CD20(+) cell numbers, serum immunoglobulin levels were normal. The patient tolerated the treatment well. The frequency of respiratory problems was reduced and the decline in the forced expiratory volume in 1 s and vital capacity reduced compared with the 4 yr preceding carrier erythrocyte therapy. Carrier erythrocyte-ADA therapy in an adult patient with ADA deficiency was shown to be metabolically and clinically effective.     

Diagnostic and prognostic values of S-phase fraction and aneuploidy in patients with bone marrow aplasia

Aim  It is often difficult and challenging task to differentiate aplastic anemia (AA) from hypoplastic myelodysplastic syndrome (HMDS) among the patients with bone marrow aplasia. This is possibly because of the considerable clinical, cytological and histological similarities between these two disorders. As prognostic and therapeutic approach to AA and HMDS are different, it is imperative to differentiate them at the time of initial diagnosis. Various attempts have been made in the past to differentiate AA from HMDS. In the present study, we explored the value of certain new parameters i.e. S-phase fraction (SPF) and aneuploidy that could be used for this purpose. Materials and methods  The study included 46 consecutive patients with aplastic anemia, 15 patients with HMDS along with 32 age and sex-matched control subjects. S-phase fraction and aneuploidy analysis was carried out by flow cytometry using Mod Fit-LT V3.0 software. Results  The mean SPF value was significantly lower (p=0.02) in patients with AA and higher (p=0.01) in HMDS as compared to that of the control. Aneuploidy was present in 15.2% patients with AA and in 33.3% HMDS cases. During follow-up, 4 patients with AA developed MDS, out of these, three patients had aneuploidy as well as high SPF value at the time of diagnosis. Two patients with HMDS who had aneuploidy and high SPF, converted into AML. Eleven patients died during the study, in whom 8 had aneuploidy and high SPF value. Conclusion  We conclude that high SPF value and presence of aneuploidy favour the diagnosis of HMDS rather than AA. SPF and aneuploidy may be important parameters in patients with AA to predict their propensity to evolve into myelodysplastic syndrome and acute myeloid leukemia. SPF value may also be useful in the early diagnosis of HMDS before morphologically evidence of dysplasia is apparent.     

再生障碍性贫血和骨髓增生异常综合征患者骨髓CD34+细胞及其粒细胞集落刺激因子受体的研究

目的:检测再生障碍性贫血(AA)和骨髓增生异常综合征(MDS)患者CD34 细胞占骨髓单个核细胞(BMMNC)的比率及其表面粒细胞集落刺激因子受体(G-CSFR)的表达率。方法:用流式细胞术(FCM)检测13例AA、22例MDS及12例非血液病患者CD34 细胞占BMMNC的比率及其表面G-CSFR的表达率。结果:AA组与对照组、AA组与MDS组、MDS-难治性贫血(RA)组与难治性贫血伴原始细胞增多(RAEB)组BMMNC中CD34 细胞的比率比较差异有统计学意义(P<0.05),但G-CSFR的表达率差异无统计学意义(P>0.05)。多数重型AA(SAA)患者(3/4)及少数慢性AA(CAA)患者(1/9)BMMNC中的CD34 细胞少于0.1%。多数G-CSFR表达率低(<14%)的患者(7/9)外周血中性粒细胞减少;而表达率正常(14.0%~28.9%)的患者(1/6)很少见;表达率高(>28.9%)的患者(3/7)也可存在中性粒细胞减少。结论:造血干细胞减少是AA的主要发病机制之一,其表面G-CSFR的表达率不是影响AA的主要因素;MDS患者CD34 细胞比率升高是一个预后不良的指标,G-CSFR的检测可部分解释MDS患者外周血中性粒细胞减少的原因。     

Reduced in vivo skeletal muscle oxygen consumption in patients with chronic heart failure--a study using Near Infrared Spectrophotometry (NIRS)

AIM: We used Near Infrared Spectrophotometry (NIRS) during arterial occlusion to measure resting skeletal muscle oxygen consumption in chronic heart failure (CHF) patients and in age-matched healthy volunteers (HVs). METHODS: Fifteen CHF patients (ten males) and eleven HVs (six males) had echocardiographic evaluation followed by measurement of the oxygen consumption of the brachioradialis muscle using NIRS. This involved continuous measurement of the oxygenated haemoglobin concentration ([Oxy-Hb]) and deoxy-haemoglobin concentration ([Deoxy-Hb]) with an Oxiplex TS NIRS probe first under basal overnight fasted resting conditions followed by 1 min of forearm arterial occlusion. A linear decline was observed in [Oxy-Hb-Deoxy-Hb] during the arterial occlusion and the oxygen consumption rate was calculated from the initial slope observed. RESULTS: CHF patients were 59+/-2.8 years old with Left Ventricular Ejection Fraction (LVEF) 31%+/-2.2 and the HVs were 52+/-4.8 years old with LVEF 62%+/-2.5. The resting muscle oxygen consumption rate was significantly reduced in CHF patients versus HVs (0.04+/-0.01 mlO(2)/min/100 g versus 0.07+/-0.01 mlO(2)/min/100 g) p<0.005. CONCLUSIONS: There is a significant reduction in resting oxygen consumption per gram of tissue in skeletal muscle of patients with CHF.     

Global and regional myocardial oxygen consumption and blood flow in severe cardiomyopathy with left bundle branch block

OBJECTIVE: In patients with dilated cardiomyopathy (DCM), left bundle branch block (LBBB) is a common finding. The characteristic feature is an asynchronous septal wall motion and most frequently a delay of the lateral and/or posterior wall segments. With the onset of cardiac resynchronization therapy, there is a focus on the specific pathophysiology of a LBBB. However, quantitative data on regional myocardial oxygen consumption (MVO(2)) and blood flow (MBF) are missing. METHODS: We studied 31 patients with severe DCM and LBBB (ejection fraction 22.1+/-7.1%) and 14 patients with mild to moderate DCM without LBBB (ejection fraction 46.7+/-7.9%). Global and regional MVO(2) as well as MBF were determined from a dynamic (11)C-acetate positron emission tomography (PET) study. RESULTS: Global MVO(2) and MBF were lower in the DCM group with LBBB than in the control group (P<0.05). Regionally, the LBBB group revealed a higher (P<0.05) MVO(2) and MBF in the lateral wall than in the other walls. The control group did not show significant differences between the myocardial walls and demonstrated a smaller variability of the parameters. CONCLUSION: DCM patients with LBBB exhibit a more heterogeneous distribution of MVO(2) and MBF among the myocardial walls than DCM patients without LBBB. Due to the LBBB associated electromechanical alterations, the highest regional values of MVO(2) and MBF are found in the lateral wall.