Haploidentical transplantation as a promising therapy for relapsed hemophagocytic lymphohistiocytosis in an older adult patient

Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe and often overwhelming systemic hyper-inflammatory syndrome generally presenting with unexplained fevers, hepatosplenomegaly, and progressive multi-organ dysfunction. Treatment of HLH has two major goals: Halting the triggering event and controlling the overactive immune system. However, patients with primary or recurrent secondary HLH should subsequently undergo allogeneic HCT for long lasting disease remission. Hereby we present the case of a 69 years old man with recurrent HLH who underwent a reduced intensity conditioning of fludarabine, cyclophosphamide and low dose total body irradiation followed by a haploidentical marrow graft and post-transplantation cyclophosphamide (PTCy), tacrolimus and mycophenolate mofetil as GVHD prophylaxis. He achieved a durable remission of HLH symptoms despite persistent myeloid mixed chimerism.The use of haploidentical donors and PTCy as tolerance inducing regimen is feasible in HLH. The achievement of mixed donor chimerism may be enough to control the clinical manifestations and to cure HLH.     

Toxocara infestations in humans: symptomatic course of toxocarosis correlates significantly with levels of IgE/anti-IgE immune complexes

Infestations of humans with the parasitic nematode T. canis are common in both developing and industrialized countries. Most infestations induce a clinically inapparent course of infection, however, severe clinical manifestations, i.e. visceral larva migrans (VLM) or ocular larva migrans (OLM) syndromes are observed. To find an explanation for the different courses of toxocarosis we examined several serological parameters: the expression of (i) specific IgE (Immunoblot, IB), (ii) specific IgG subclasses (IgG1–4, ELISA) and the formation of (iii) IgE/anti-IgE immune complexes. Serum samples were obtained from persons with symptomatic (VLM, OLM) and asymptomatic course (AS) of the infestation. As antigen, T. canis excretory/secretory (TES) antigen from L3 larvae was used. Reactivity of IgE against SDS-PAGE separated TES antigens was marginally higher in toxocarosis patients (35%) than in asymptomatics (24%), but without statistical significance. TES-specific IgG (1–4), predominant subclass in all three groups was IgG1, followed by IgG2, IgG4 and IgG3. Subclasses IgG1, 2, 4 showed significant differences between patients with VLM associated symptoms and asymptomatic persons ( P  < 0.001) but not between patients with OLM associated symptoms and asymptomatics. Significantly elevated levels of IgE/anti-IgE immune complexes were detected in sera of patients with symptomatic course of the disease, both VLM and OLM ( P  < 0.001). Whereas specific IgG may act via antibody dependent cell-mediated cytotoxicity mechanisms, IgE/anti-IgE immune complexes might possibly participate in VLM and OLM by inducing type III hypersensitivity.     

Analysis of deaths in patients awaiting heart transplantation: impact on patient selection criteria.

OBJECTIVE: To analyse the clinical characteristics of patients who died on the Stanford heart transplant waiting list and to develop a method for risk stratifying status 2 patients (outpatients). METHODS: Data were reviewed from all patients over 18 years, excluding retransplants, who were accepted for heart transplantation over an eight year period from 1986 to 1994. RESULTS: 548 patients were accepted for heart transplantation; 53 died on the waiting list, and 52 survived on the waiting list for over one year. On multivariate analysis only peak oxygen consumption (peak VO2: 11.7 (SD 2.7) v 15.1 (5.2) ml/kg/min, P = 0.02) and cardiac output (3.97 (1.03) v 4.79 (1.06) litres/min, P = 0.04) were found to be independent prognostic risk factors. Peak VO2 and cardiac index (CI) were then analysed in the last 141 consecutive patients accepted for cardiac transplantation. All deaths and 88% of the deteriorations to status 1 on the waiting list occurred in patients with either a CI < 2.0 or a VO2 < 12. In those with a CI < 2.0 and a VO2 < 12, 38% died or deteriorated to status 1 in the first year on the waiting list. Patients with CI > or = 2.0 and a VO2 > or = 12 all survived throughout follow up. Using a Cox's proportional hazards model with CI and peak VO2 as covariates, tables were constructed predicting the chance of surviving for (a) 60 days and (b) 1 year on the waiting list. CONCLUSIONS: These data provide a basis for risk stratification of status 2 patients on the heart transplant waiting list.     

自体骨髓干细胞移植治疗慢性肝衰竭研究

目的探索自体骨髓干细胞移植对肝衰竭患者的治疗作用,为干细胞移植的临床应用研究提供基础。方法35例慢性重症肝病患者,20例行自体骨髓干细胞移植治疗,15例作为对照。在无菌条件下,从患者髂后上棘抽取骨髓30～50ml,分离纯化骨髓干细胞。在局部麻醉下行肝动脉介入,将分离的骨髓干细胞移植于肝脏。患者在移植后1、2、4、8周进行肝功能检测。观察患者移植后不同时间症状改善情况及术后不良反应情况。结果在移植8周后,患者丙氨酸转氨酸逐渐降低,由平均181.7μmolL降至72.1μmolL;总胆红素由平均153.8μmolL降至80.2μmolL;直接胆红素由平均74.1μmolL降至40.5μmolL;白蛋白逐渐升高,由平均26.5μmolL升至31.5μmolL;与对照组相比有明显差异,表明移植后患者肝功能明显改善。干细胞移植后凝血酶原活动度逐渐上升,由术前平均28.2%上升至50.1%。进一步观察自体骨髓干细胞移植对肝衰竭患者生存率的影响,发现移植后1周生存率为100%,4周为95%(1920),8周后为90%(1820),12周后为85%(1720),较对照组生存率明显升高。移植后大多数患者有明显症状改善,移植后8周内腹水减轻10例(50%),食欲改善15例(75%),体力好转11例(55%),腹胀减轻9例(45%)。在20例移植患者中未发现严重并发症,术后有轻度恶心1例,发热1例。结论自体骨髓干细胞移植治疗后,患者肝功能和凝血机制明显改善,生存率提高,症状好转,表明骨髓干细胞移植对肝衰竭患者治疗有效,安全,不良反应少。     

Treatment of HCV patients before and after renal transplantation

Context

Patients with end-stage renal disease can easily acquire a hepatitis C virus (HCV) infection via several ways. An HCV infection is difficult to treat after renal transplantation due to the conflicting actions of immunosuppressant therapy to maintain the function of the transplanted kidney and viricidal interferon (IFN) or ribavirin (RBV) treatment. Antiviral therapy requires great caution to avoid the complex and potentially fatal pharmacological effects. In this review, we examined clinical challenges and potential solutions for this specific scenario.

Evidence Acquisitions

We searched Pubmed (NLM), LISTA (EBSCO), Web of Science (TS). The management of patients on waiting list, the indications and regimens about treatment were studied.

Results

More than forty papers about this topic were found, including seven small clinical trials. International consensus has been reached to test patients awaiting renal transplantation. HCV detection after renal transplantation warrants careful consideration of when to initiate antiviral therapy. Treatment will begin immediately if deteriorating liver function increases the risk for loss of renal function. The choice of regimen depends on the patient''s renal function and is individualized under close observation. The immunosuppressive regimen will be adjusted accordingly before antiviral therapy is initiated.

Conclusions

The effects of modified antiviral therapy on these patients varies because of individual characteristics and disease state, and also because of the difficulty associated with conducting a large clinical trial to obtain statistically sound conclusions. The management before transplantation is important and when antiviral therapy needs to start, careful consideration of risks and benefits is needed before initiating this type of treatment.     

Experience of appendicular thermal therapy applied to a patient with a left ventricular assist device awaiting heart transplantation

Thermal therapy for heart failure is recognized to improve clinical symptoms. We describe our experience with appendicular thermal therapy applied to a patient fitted with an extracorporeal left ventricular assist device (LVAD) who was wait-listed for a heart transplant. A 21-year-old male with end-stage heart failure due to dilated cardiomyopathy was fitted with a LVAD. His general condition stabilized after LVAD placement and the status of his heart failure has remained at NYHA class II for the past 13 months. However, his cardiac function did not sufficiently recover to discontinue LVAD support. We conducted appendicular thermal therapy using a steam foot bath and heated gloves for 2 weeks. Immediately after thermal therapy, his average sublingual temperature increased from 36.3 to 37.0 °C and the grade of mitral regurgitation, as well as LV ejection fraction and endothelial function improved. Furthermore, levels of oxidative and anti-oxidative stress markers decreased and increased, respectively, after 2 weeks of therapy. No complications developed. We conclude that appendicular thermal therapy was safe in this patient waiting for a heart transplant and who had an extracorporeal LVAD, and that the procedure might be beneficial for others with end-stage heart failure.     

Safety and efficacy of exercise training in a patient awaiting heart transplantation while on positive intravenous inotropic support

The safety and efficacy of exercise training in patients with congestive heart failure (CHF) is well established; however, the impact that exercise has on the subgroup of CHF patients awaiting heart transplant while on intravenous positive inotropic support remains largely unreported. This case study describes the safety and efficacy of exercise training in a patient awaiting heart transplant while on intravenous milrinone. Over a 1.2-year period, 246 exercise sessions were conducted with a total of 180.15 hours of aerobic exercise. During that time, the patient experienced only one hypotensive episode during exercise and had no other adverse events. The patient demonstrated a 38% increase in aerobic exercise time and a 34% increase in sustainable exercise workload. Research is needed to demonstrate the positive impact of exercise training on this subgroup of CHF patients.     

人自体骨髓干细胞移植治疗慢性肝功能衰竭的研究

研究应用患者自体骨髓干细胞作为供体，在体外分离纯化 后移植至患者体内，使干细胞在肝脏中生长分化为具有功能的 肝细胞，使损伤的肝功能得以恢复和重构，为干细胞的进一步 治疗研究打下基础。 一、资料与方法 1．病例选择：80例慢性乙型重型肝炎为我所住院患者，年     

Acute, reversible myocardial ischemia in a patient with an asthmatic attack

A 61-year-old woman with chronic asthma sustained an episode of dyspnea and chest heaviness and was brought to the emergency department. Her examination revealed tachypnea, tachycardia, hypotension, and diffuse prolonged respiratory wheezing. Arterial blood gas analysis showed severe hypoxemia and hypercapnia. A 12-lead electrocardiogram showed marked, downsloping ST-segment depression, with deep, negative T waves in leads I, II, III, and aVF and precordial leads V₃-V₆. After 15 minutes of therapy with oxygen, beta-agonists, and corticosteroids, the electrocardiographic abnormalities subsided and 2 hours later they had disappeared. Subsequent coronary angiography and ventriculography revealed normal coronary arteries and good left ventricular ejection fraction. It is concluded that an acute asthmatic paroxysm may produce transient myocardial ischemia even with angiographically documented normal coronary arteries.     

Adenovirus in the sinuses of an asthmatic patient with apparent selective antibody deficiencies

On two separate occasions 6 weeks apart, adenovirus type I was cultured from frontal and maxillary sinus tissue removed at surgery from a 37 year old man with bronchitis, reversible obstructive airways disease and pansinusitis. Cultures of nasopharyngeal and bronchial washings as well as samples of stool and urine failed to yield adenovirus. Subsequent immunologic evaluation revealed normal cell-mediated immunity, phagocytic and complement function. However, humoral immunity appeared selectively abnormal. Since viruses failed to grow in 30 surgically-removed sinus tissue samples from 22 similar patients, and since this is the first reported case in which an adenovirus or any other virus has been grown from chronically infected sinus tissue, we suspect that persistent virus infection in chronic sinusitis is an unusual event. In this case an immunologic deficiency may have been associated.     

Rhabdomyolysis after the administration of itraconazole to an asthmatic patient with bronchopulmonary aspergillosis

It is known that the coadministration of itraconazole with cholesterol-lowering statins may induce muscle damage. We describe the case of a patient with steroid-dependent asthma, steroid-induced severe myopathy and allergic bronchopulmonary aspergillosis who developed rhabdomyolysis and acute renal failure following a approximately 6-week treatment with itraconazole, even without the concomitant use of HMG-CoA reductase inhibitors.     

Treatment of chronic renal insufficiency in the diabetic by dialysis and transplantation

The number of diabetics with end stage renal disease (ESRD) is growing. The best treatment at the lowest cost possible should be offered to all diabetics if therapeutic facilities are available. Such a policy requires that all dialysis methods and transplantation should be available and that transfer from one method to another should always be allowable. Results observed among insulin and non insulin-dependent diabetics are improving steadily, even in the older age group. However they are inferior to those observed in non diabetic people of the same age. Adequate medical care, including excellent control of high blood pressure and good control of blood glucose levels should reduce the frequency of severe complications including cardiac, ocular and peripheral vascular lesions. In diabetic patients under forty years of age, renal transplantation using a kidney from a cadaver or a related donor should be the first choice. However, for most patients dialysis methods are required as the only treatment or while waiting for a transplant. Very encouraging results are obtained with both hemodialysis and peritoneal dialysis. If home dialysis is considered, continuous ambulatory peritoneal dialysis (CAPD) offers the opportunity to treat many insulin-dependent or non dependent diabetics at home even those in the high risk population because of age and/or cardio-vascular instability. CAPD offers excellent control of blood glucose levels using the intraperitoneal route to administer insulin. Results obtained are discussed from data in the literature and from a survey of 124 insulin-dependent diabetic cases with ESRD treated in the Department of Nephrology of the Hospital de La Pitié from 1973 to 1984.     

Fulminant eosinophilic endomyocarditis in an asthmatic patient treated with pranlukast after corticosteroid withdrawal

Several cases of eosinophilic conditions including Churg-Strauss syndrome have been reported in association with the use of cysteinyl leukotriene receptor antagonists, including zafirlukast, montelukast, and pranlukast, in asthmatic patients. The case of a 26 year old woman with a three year history of asthma, rhinitis, and nasal polyps is reported in whom eosinophilia, pulmonary infiltrates, and fulminant eosinophilic endomyocarditis accompanied by cardiogenic shock developed during pranlukast treatment after corticosteroid withdrawal. Acute necrotising eosinophilic endomyocarditis was confirmed by endomyocardial biopsy. The patient recovered after intensive treatment, including mechanical assistance involving intra-aortic balloon pumping and steroid pulse therapy, along with the discontinuation of pranlukast. It is recommended that careful attention must be paid to signs of a systemic eosinophilic condition or even fulminant eosinophilic myocarditis in asthmatic patients who have begun treatment with antileukotriene drugs following withdrawal of steroids.


Keywords: fulminant eosinophilic endomyocarditis; asthma; pranlukast     

Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5‐year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice.     

Serum hepatocyte growth factor as an index of extensive catabolism of patients awaiting liver transplantation

BACKGROUND: Whole body catabolism as the result of intrahepatic metabolic derangement is common in liver transplant candidates. However, individual nutritional assessment parameters lack sensitivity and specificity in determining energy status of these patients. Recently, serum hepatocyte growth factor (HGF) has been shown to reflect the recovery of hepatic energy metabolism after liver transplantation. AIMS: The relation between preoperative levels of serum HGF and metabolic variables was investigated to clarify the clinical value of measuring HGF in evaluations of the catabolism. PATIENTS/METHODS: Blood samples were obtained from 30 liver transplant recipients, and biopsy specimens were taken from each recipient's rectus muscle and the explanted liver. Preoperative serum concentration of HGF was determined. Whole body energy metabolism was assessed by measuring glycogen contents of biopsy specimens and plasma or serum levels of glucose, insulin, total ketone bodies, total carnitine, and amino acids. RESULTS: Serum HGF concentration was elevated in 22 of 30 patients and correlated with the Child-Pugh score. It showed a negative association with muscle glycogen content, and a positive correlation with serum levels of glucose, total carnitine, and total ketone bodies. Patients with elevated serum HGF concentrations had higher preoperative plasma levels of aromatic amino acids and branched chain amino acids, associated with lower branched chain to aromatic amino acid ratios. CONCLUSIONS: The elevated serum concentration of HGF in liver transplant candidates reflected inhibition of peripheral glucose storage, enhanced lipid oxidation, and increased peripheral release of branched chain amino acids, and thus extensive energy catabolism.     

三位一体支气管哮喘教育管理模式对病情控制水平和生命质量的影响

目的评估三位一体支气管哮喘(简称哮喘)教育管理模式对患者病情控制水平和哮喘生命质量的影响。方法北京大学人民医院三位一体哮喘教育管理模式由哮喘专业门诊、哮喘宣教中心和哮喘患者协会构成。2005年4月至6月选择北京大学人民医院接受三位一体哮喘教育管理的门诊患者为教育组(56例);选择另一家三级医院未接受系统哮喘教育管理的门诊患者为对照组(30例)。采用面对面问卷方式调查两组近8周的病情控制水平和生命质量评分并进行对比分析。结果两组病情的良好控制率分别为61%(34例)和10%(3例),教育组优于对照组,差异有统计学意义(χ2=20.50,P<0.01);两组哮喘患者生命质量总评分分别为(155±12)分、(132±24)分,教育组亦优于对照组,差异有统计学意义(t=5.17,P<0.01)。结论三位一体哮喘教育管理模式可以有效提高哮喘患者的病情控制水平和哮喘生命质量。     

激活骨髓自体移植治疗白血病和淋巴瘤的疗效分析

目的 探讨激活骨髓自体移植治疗恶性血液病的疗效及影响因素。方法 ４４例为白血病和非霍奇金淋巴瘤（ＮＨＬ）患者进行激活骨髓自体移植,观察移植后造血与免疫功能重建,移植后完全缓解（ＣＲ）,移植后相关死亡、肿瘤复发率和长期无病生存率及移植物抗宿主产产表现及毒副作用。选用Ｋａｐｌａｎ－Ｍｅｉｅｒ生存曲线评估一３、５年无病生存率、ＣＯＸ回归模型分析性别、年龄、疾病种类、移植前状态（ＣＲ与未ＣＲ）,预处理方案     

自体骨髓单个核细胞移植对8例异常Q波扩张型心肌病患者心功能的影响

目的研究自体骨髓单个核细胞(ABMMNCs)经冠状动脉移植对伴有异常Q波的扩张型心肌病(DCM)患者心功能的影响。方法选择2005年6月至2006年5月在哈尔滨医科大学附属第二临床医学院心内科住院的8例体表心电图伴有异常Q波的原发性DCM患者,在常规抗心衰药物治疗的同时,进行冠状动脉造影并进行ABMMNCs移植;在术前和术后3个月、6个月分别行体表心电图及超声心动图检查。结果术后3个月和6个月,8例患者左室射血分数(LVEF)、左室舒张末期内径(LVDd)、左室收缩末期内径(LVSd)虽然较术前有所改善,但差异无显著性意义(P>0.05)。患者术后心电图仍存在异常Q波,与术前无差异。结论经冠状动脉移植ABMMNCs,未证明能改善伴有Q波的DCM患者的心功能。