A man with oral ulcers caused by hypereosinophilic syndrome and a good response to the tyrosine-kinase inhibitor imatinib

For the last 2 years, a 55-year-old man had painful, recurrent oral ulcers. Histological examination showed non-specific inflammation. Eosinophilia in the blood and bone marrow raised the suspicion of hypereosinophilic syndrome. No other specific organ involvement was observed. The diagnosis was confirmed by detection of the fusion gene 'FIP1-like-1-platelet-derived growth factor receptor alpha' (FIP1L1-PDGFRA) in the peripheral blood and bone marrow. Treatment with the tyrosine-kinase inhibitor imatinib resulted in a rapid response that has been maintained for more than 2 years. Hypereosinophilic syndrome is a rare haematological disorder. Until recently diagnosis was made by exclusion, and the course of disease was often fatal. Fusion of the FIP1L1 gene to the PDGFRA gene was identified recently in some patients with hypereosinophilic syndrome. The fusion results in a novel tyrosine kinase that is constitutively activated and may induce proliferation ofhaematopoietic cells. Treatment with imatinib targets this tyrosine kinase. These advances in our understanding of the molecular biology of the disease will lead to a new classification of hypereosinophilic syndrome with specific therapeutic options.     

Two patients with hypereosinophilic syndrome

Persistent eosinophilia was diagnosed in a 19-year-old woman with general malaise, dyspnoea attacks, coughing and episodes of angioedema and associated swallowing problems, and in a 21-year-old man with visual problems, dyspnoea, fatigue, reduced appetite, weight loss and gastrointestinal problems. Both had hypereosinophilic syndrome (a rare disease) with organ damage. In both patients, fluorescence-in-situ-hybridisation (FISH) was negative for the fusion gene FIP1L1-PDGFRA (FIPI-like-1-platelet-derived growth factor receptor alpha). The female patient's disease did not respond to either oral corticosteroids or imatinib, but did respond to hydroxycarbamide. The male patient successively received prednisone, interferon alpha and hydroxycarbamide. His eosinophilia progressed nonetheless, but responded partially to imatinib. In addition, the patient underwent an allogenic non-myeloblative stem cell transplantation from his HLA-identical sister. In patients with persistent eosinophilia accompanied by organ damage or organ dysfunction, hypereosinophilic syndrome can be diagnosed providing all secondary causes of the eosinophilia have been ruled out. Complementary investigations should include cytogenetic and clonal analysis to rule out haemopoietic malignancy. Prednisone, hydroxycarbamide, interferon alpha and the promising imatinib are all treatment options.     

Novel method in diagnosis of chronic myeloproliferative disorders--detection of JAK2 mutation

Chronic myeloproliferative disorders are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid cell lineages in the bone marrow. The WHO classification describes six major groups of chronic myeloproliferative disorders, as follows: chronic myeloid leukemia, chronic neutrophilic leukemia, chronic eosinophilic leukemia, polycythemia vera, essential thrombocythemia and chronic idiopathic myelofibrosis. The diagnosis of chronic myeloid leukemia and certain types of chronic eosinophilic leukemia are based on the detection of fusion genes (in chronic myeloid leukemia the BCR/ABL fusion gene, and in chronic eosinophilic leukemia the FIP1L1-PDGFRalpha gene). On the other hand molecular markers for polycythemia vera, essential thrombocythemia and chronic idiopathic myelofibrosis were lacking, making it difficult to identify these disorders clearly. The authors investigated the incidence of the newly identified somatic point mutation V617F of the Janus-2 tyrosine kinase in patients with polycythemia vera, essential thrombocythemia and myelofibrosis. Janus-2 kinase is a cytoplasmic, non-receptor protein-tyrosine kinase with a key role in signal transduction from multiple hematopoietic growth factor receptors. The mutant protein is constitutively phosphorylated and is able to activate its downstream signaling pathways in the absence of any cytokine, thereby contributing to the pathogenesis of chronic myeloproliferative disorders. The authors investigated DNA samples from 132 patients with chronic myeloproliferative disorders. The V617F mutation was detected by allele-specific polymerase chain reaction, and the patients were genotyped by a DNA tetra-primer amplification refractory mutation system assay. Approximately 73% of polycythemia vera, 60% of essential thrombocythemia and 67% of myelofibrosis showed the JAK2 V617F mutation. Using the amplification refractory mutation system assay, the frequency of homozygotes was 17.5% in polycythemia vera, 5.4% in essential thrombocythemia and 0% in myelofibrosis. The authors established an effective polymerase chain reaction based method for the identification of JAK2 mutation in the routine oncohematologic diagnostics.     

NT-proBNP与呼吸衰竭及慢性肺源性心脏病的相关性研究

目的：研究N端脑钠肽前体（NT-ProBNP）与呼吸衰竭及慢性肺源性心脏病的相关性。方法：筛选和收集2012年1月-2013年12月本科收治的符合单纯呼吸衰竭（A组50例）和呼吸衰竭合并慢性肺心病（B组50例）诊断标准的患者。并选取在本院进行健康体检者（C组）的血样50份,进行血液NT-proBNP水平检测。比较三组的血液NT-proBNP水平,并对A、B两组治疗前后的NT-proBNP水平、血气指标进行比较。记录患者6个月内不良事件发生情况。结果：A、B两组治疗前、后的NT-proBNP水平均显著高于C组,差异均有统计学意义（P〈0.05）;B组在治疗前NT-proBNP水平显著高于A组,差异有统计学意义（P〈0.05）;A、B两组在治疗后的NT-proBNP水平比较无统计学意义（P〉0.05）。经过6-12个月随访,在100例呼吸衰竭患者中,因住院期间发生的病情加重需机械通气、心肺复苏或任何原因的死亡等不良事件共23次,因病情加重需再次住院有37次。发生相关不良事件的患者的NT-proBNP水平为（2849.7±394.7）pg/L显著高于未发生不良事件者的（988.7±93.1）pg/L,差异有统计学意义（P〈0.05）。结论：NT-proBNP水平与呼吸衰竭患者是否有肺心病及右心受累程度密切相关,是快速判断右心功能不全严重程度以及疗效判断的良好指标。     

Late postinfarction rupture of the interventricular septum

Postinfarction ventricular septal rupture complicates 1 to 2% of cases of acute myocardial infarction and accounts for 5% of early mortality. This severe complication usually occurs within two weeks after acute myocardial infarction, and the elderly are more susceptible. We present a case of late rupture of the septum. Case report: In a 75-year-old man, a ventricular septal defect developed more than two months after an extensive inferoseptal myocardial infarction due to occlusion of the right coronary artery. After more than two months of no symptoms he was referred to hospital due to symptoms of right ventricle failure. The diagnosis was made by echocardiography, pulmonary artery catheterization and ventriculography. Coronarography was also performed. Intraaortic balloon pump was introduced and the patient was transferred to the operating room. The defect was repaired using a circular polytetrafluoroethylene patch supported by buttressed interrupted sutures from both sides. Due to significant mitral valve regurgitation mechanical bileaflet mitral valve was implanted with preservation of the entire mitral apparatus and the left descending artery was revascularized using a saphenous graft. Conclusion: This case is reported to emphasize that later postinfarction rupture of the ventricular septum may occur with symptoms of right ventricle failure dominating the clinical course.     

Apocrine carcinoma of the breast

Apocrine carcinoma is a rare variant of breast carcinoma, and accounts for 0.3 to 1.0% of all breast cancers. A 55-year-old Japanese female patient presented with a right breast tumor, which had been detected by mass-screening, and she was admitted to our hospital. The physical examination revealed an elastic hard lump in the upper lateral quadrant of the right breast. The tumor size was approximately 1.0 cm in diameter, and the border was clear. There were no palpable axillary lymph nodes nor supraclavicular nodes. Fine-needle aspiration cytology revealed invasive ductal carcinoma. The patient underwent a partial resection of the right breast (breast conserving therapy) and a right axillary lymphadenectomy. Macroscopically, the resected specimen revealed a white tumor measuring 1.2 x 1.2 x 1.0 cm. The TNM classification was diagnosed as T1cN0M0 stage I. Histopathologically, the tumor revealed a proliferation of atypical epithelial cells with apocrine differentiation, arranged in a papillotubular or cribriform growth pattern with stromal invasion. The tumor cells showed irregular round-shaped nuclei often containing prominent nucleoli, and had particularly abundant eosinophilic granular cytoplasm. In the immunohistochemical analysis, these carcinoma cells were positive for Gross Cystic Disease Fluid Protein 15 and the androgen receptor, whereas they were negative for the estrogen and progesterone receptors. Immunohistochemical staining for Her2 using the HercepTest was found to be negative (score 0). Thus, the pathological diagnosis was apocrine carcinoma. There were no metastases in the axillary lymph nodes. The patient has had no recurrence in 8 years after surgery.     

Pulmonary thromboendarterectomy: an effective surgical treatment for cor pulmonale due to chronic pulmonary emboli

OBJECTIVE: To evaluate the initial experience with pulmonary thromboendarterectomy for cor pulmonale due to chronic pulmonary embolism. METHOD: In the period 1 April 1996 to 31 October 2001, 18 patients with right ventricular failure due to chronic thromboembolic pulmonary hypertension were operated on. Their mean age was 54 (SD: 14) years. Preoperatively, all of the patients were in functional New York Heart Association (NYHA) class III or IV. Pulmonary angiography revealed pulmonary hypertension with an increased pulmonary vascular resistance, as well as typical angiographic signs of unresolved chronic emboli. Pulmonary thromboendarterectomy was performed via median sternotomy, using extracorporeal circulation and intermittent deep hypothermic circulatory arrest. The patients were monitored via the outpatients' department. RESULTS: From a technical viewpoint, the procedure was performed successfully in all of the patients. Initially the pulmonary thromboendarterectomy was performed unilaterally (n = 7), which did not decrease pulmonary artery pressure significantly. The following 11 patients were treated bilaterally; in them thromboendarterectomy required an average of circulatory arrest totalling 64 (SD: 30) min with 161 (SD: 35) min of myocardial ischemia. After bilateral pulmonary thromboendarterectomy, the pulmonary artery pressure decreased from 45 (SD: 13) to 28 (SD: 9) mmHg (p = 0.001). Reperfusion pulmonary oedema, requiring prolonged ventilation, occurred in 3 patients. There was no operative or later mortality. At a mean follow-up of 28 (SD: 19) months, all but one of the patients were in functional NYHA class I or II. Echocardiography revealed reduced right ventricular dimensions and pulmonary artery pressures. One patient, with mainly distally located obstructions, exhibited no substantial improvement. CONCLUSION: The initial experience with pulmonary thromboendarterectomy for patients with cor pulmonale due to chronic pulmonary emboli demonstrated satisfactory mid-term follow-up data.     

Short coupled variant of "torsades de pointes" and sudden death

A case report of 38 year old man who experienced syncope and torsade de pointes is presented with the short coupled variant. The patient had a normal QT interval (QTC: 0.37 seconds) and multiform ventricular premature beats on the resting electrocardiogram. Under antiarrhythmic treatment (intravenous xylocaine), torsades de pointes suddenly appeared and cardiac arrest was followed. After cardioversion, sinus rhythm was restored. A cardiovascular disease was excluded, the echocardiography, the left and right ventricular angiography and coronarography were normal. Three months after, the patient presented at home a sudden cardiac death.     

Two sudden death cases of idiopathic ventricular tachycardia.

It is said that the prognosis of idiopathic ventricular tachycardia (IVT) without organic heart disease is good in general. In this paper, two sudden death cases of IVT are reported. The first case was a 44-year-old male, who was referred to our hospital for further examination and treatment of ventricular tachycardia. Echocardiography did not show obvious organic heart disease. After the patient was diagnosed with IVT, he was given drug therapy at the outpatient clinic. However, about six months later, he died suddenly while playing mahjong late at night. The second case was a 17-year-old male. He was also referred to our hospital by another hospital after being diagnosed with ventricular tachycardia. A diagnosis of IVT was made, for which he was given drug therapy at outpatient clinic. However, the patient discontinued receiving the drug therapy. The patient died suddenly about 3 months after discontinuation of the therapy. Some idiopathic ventricular tachycardia cases have poor prognosis like the present ones. It was considered necessary to thoroughly control and guide patients with their daily life and monitor them carefully about the ingestion of anti-arrhythmic agents.     

经导管介入封堵术治疗儿童室间隔缺损36例临床分析

目的探讨经导管治疗儿童先天性心脏病室间隔缺损封堵术的可行性及安全性,进行多方面综合疗效评价。方法通过经胸超声心动图（TTE）选择适合封堵术的先天性心脏病室间隔缺损（VSD）患儿36例,术前常规检测心电图（ECG）,胸部X线等,房间隔缺损（ASD）合并VSD 1例。在TTE及X线引导下行介入封堵术,术后通过胸片、心电图和TTE进行动态的随访观察。结果35例患儿封堵成功,技术成功率为97.2%,1例（2.8%）手术失败,改为体外循环下矫正畸形。术后5例病人有少量残余分流,2例出现房室传导阻滞（AVB）,1例出现完全性右束支传导阻滞（RBBB）,1例出现不完全性左束支传导阻滞（iLBBB）,封堵器脱落1例,心包填塞（PT）1例。VSD术前TTE测量值与术中X线测量值比较,差异无统计学意义。术后75%以上病人接受了3~6个月随访,35%以上病人接受了12个月随访,X线及TTE检查：全部显示肺血流量减少,右心房、右心室缩小,心电图提示无明显心律失常发生。结论经导管先天性心脏病封堵术治疗VSD具有很高的成功率及安全性;介入封堵术疗效好,并发症少,术后恢复快;TTE和X线可以准确地应用于先天性心脏病封堵术中。     

Hypercalcemia due to adult T-cell lymphoma in a man from Surinam

A 48-year-old male patient from Surinam presented with anorexia, nausea and weight loss. An extreme hypercalcaemia of 5.08 mmol/l was found. Further diagnostic investigations showed that this patient had a HTLV-1 positive adult T-cell leukaemia/lymphoma (ATL/L). This is often associated with multilobularly nucleated lymphocytes, bone destruction and hypercalcaemia. Skin localisations are frequently observed. The combination of cytomorphology, immunophenotyping, HTLV-1 seropositivity and clinical findings points to the diagnosis. The patient was treated with 6 courses of chemotherapy consisting of cyclophosphamide, doxorubicin, teniposide, prednisone, vincristine and bleomycin. Upon inquiry it appeared that he had died elsewhere. Chemotherapy induces a short-lived remission in a minority of ATL/L patients. Antiviral therapy (alpha interferon, zidovudine) might offer new possibilities.     

充血性心力衰竭sFas/APO-1与心肌重塑的相关性及培哚普利的影响

目的观察充血性心力衰竭(CHF)患者sFas/APO-1与心肌重塑的变化及培哚普利对其的影响,探讨培哚普利改善CHF患者心功能的可能机制。方法选择CHF患者56例,随机分组,A组(26例)为常规治疗组,B组(30例)在常规治疗基础上加用培哚普利(4mg,Qd)治疗共3个月,分别于0、3个月末采用酶联免疫吸附双抗体夹心法(ELISA法)测定血清sFas/APO-1水平,采用超声心动图诊断方法测定左心室收缩末径(LVESD)、左心室舒张末径(LVEDD)、每搏输出量(SV)和左心室射血分数(LVEF)等,另设健康对照组20例。结果心力衰竭患者血清sFas/APO-1水平明显高于健康对照组,培哚普利组治疗3个月后,较常规治疗组血清sFas/APO-1水平明显下降,LVESD、LVEDD明显减低,SV与LVEF明显升高,差异均有统计学意义;sFas/APO-1水平与LVEF呈负相关。结论培哚普利可明显改善CHF患者心肌重塑与心功能,其作用机制可能与降低血清sFas/APO-1水平有关。     

Successful alemtuzumab treatment of a patient with atypical hairy cell leukaemia variant

Although hairy cell leukaemia and hairy cell leukaemia variant are characterized by much alike clinical features, these two diseases are disparate in nature and treatment. While hairy cell leukaemia responds quite well to 2-chlorodeoxyadenosine (cladribine) treatment, hairy cell leukaemia variant has much worse response rate and has no effective treatment option yet. With other treatment modalities, including monoclonal antibody treatment, we have less experience. Alemtuzumab (Campath-1H, MabCampath) treatment has been reported in a case with hairy cell leukaemia in relaps while there is no data with alemtuzumab therapy in the treatment of hairy cell leukaemia variant. The authors present their case of a 58 year-old male who has been diagnosed with hairy cell leukaemia variant upon clinical findings and lymphocyte phenotyping. Alemtuzumab treatment was started (3 x 30 mg/week s.c. for 12 weeks). After 8 weeks of treatment haematologic remission was achieved; flow cytometry has revealed only 1.5% malignant cells. Alemtuzumab treatment can be favourable in those cases of hairy cell leukaemia and hairy cell leukaemia variant which is dominated mainly by bone marrow infiltration and present no lymphadenomegaly or splenomegaly. In our case the p53 mutation had no influence on the outcome of alemtuzumab treatment.     

Secondary acute leukemia in Hodgkin's disease]

Two secondary acute leukaemias out of 166 patients with Hodgkin's disease were detected. At a young female patient treated only with chemotherapy the acute leukaemia developed 39 months following the diagnosis of Hodgkin's disease. Phenotype of leukaemic blast cells could not be determined exactly. After a short complete remission (1,5 month) the patient died because of the progression of her leukaemic process. The other young male patient treated with radio- and chemotherapy had six years disease free interval between the diagnosis of two malignant diseases. The combined cytostatic treatment of his acute lymphoblastic leukaemia resulted complete remission that lasted for one year but later the progression of leukaemia caused death. In connection with these cases the authors reviewed the current questions of treatment related acute leukaemias in Hodgkin's disease.     

Population preference values for treatment outcomes in chronic lymphocytic leukaemia: a cross-sectional utility study

Background  

Given that treatments for chronic lymphocytic leukaemia (CLL) are palliative rather than curative, evaluating the patient-perceived impacts of therapy is critical. To date, no utility (preference) studies from the general public or patient perspective have been conducted in CLL. The objective of this study was to measure preferences for health states associated with CLL treatment.     

右室间隔部主动电极和右室心尖部被动电极的对照研究

目的 探讨采用主动固定螺旋电极行右室高位间隔部起搏的可行性和安全性.方法 采用随机对照临床研究,将需要放置心脏起搏器的64例患者,随机分成两组,34例采用主动固定电极行右室高位间隔部起搏(右室间隔部主动固定组),30例采用被动固定电极行右室心尖部起搏(右室心尖部被动固定组).对比两组患者在植入术中及术后起搏参数的变化. 结果(1)两组植入手术时间平均分别为(59.6±3.2)、(60.2±3.7)min,差异无统计学意义,但右室间隔部主动固定组X线曝光时间延长(P＜0.01).(2)右室间隔部主动固定组植入术中及术后1个月的起搏阈值高于右室心尖部被动固定组(P＜0.05或＜0.01),但术后3个月时比较差异无统计学意义.(3)植入术后1个月及3个月,右室间隔部主动固定组阻抗明显低于右室心尖部被动同定组(P＜0.01或＜0.05).(4)心室100%起搏时QRS时限右室间隔部主动同定组较右室心尖部被动固定组窄,但差异无统计学意义.(5)两组均顺利完成手术,未出现严重并发症.结论 使用主动固定螺旋电极行右室间隔部起搏是安全可行的.     

超声心动图对慢性阻塞性肺病患者右心室功能的评价

目的 应用应变率成像技术检测慢性阻塞性肺病(COPD)患者右心室功能,探讨该技术评价COPD患者右心室功能的可行性.方法 COPD患者84例,对照组70例,心尖四腔观测量右室前壁舒张末期厚度(RvFT)、右房舒张末期内径(RAEDd)、右室舒张末期内径(RVEDd)、右室舒张末期面积(RVEDa)、右室收缩末期面积(RVESa).结果根据肺动脉压将COPD患者分为无肺动脉高压组(NPAH)和肺动脉高压组(PAH);与对照组比较,PAH组RVFT显著增厚.RAEDd、RVEDd显著增大,RVFA及三尖瓣口E/A显著减小,NPAH组上述指标差异无统计学意义;与对照组比较,PAH组和NPAH组右室游离壁和室间隔SRs、SRe与SRe/SRa均显著降低,SRa无显著变化;与NPAH组比较,PAH组右室游离壁和室间隔SRs、SRe与SRe/SRa均显著降低,SRa无显著变化.COPD患者右室游离壁SRs与FEV1/FVC、DLco/VA呈显著正相关;而右室游离璧SRe、RVFA、三尖瓣口E/A与FEV 1/FVC、DLco/VA无显著相关性.结论 COPD患者无论有无肺动脉压增高,其右室功能已经受损;应变率成像技术可便捷、无创检测COPD患者右室功能.     

Baylisascaris procyonis–Associated Meningoencephalitis in a Previously Healthy Adult,California, USA

After severe neurocognitive decline developed in an otherwise healthy 63-year-old man, brain magnetic resonance imaging showed eosinophilic meningoencephalitis and enhancing lesions. The patient tested positive for antibodies to Baylisascaris spp. roundworms, was treated with albendazole and dexamethasone, and showed improvement after 3 months. Baylisascariasis should be considered for all patients with eosinophilic meningitis.     

Reactivation of hepatitis B infection due to glucocorticoids

A 55-year-old female started treatment with prednisone for peripheral facial nerve paralysis. After three months she was admitted to hospital with suspected cholecystitis. However, while in hospital her liver function deteriorated. Virological tests showed she had a hepatitis B infection. Another patient, a 71-year-old male, was treated with prednisone for polymyalgia rheumatica. A few weeks after starting therapy he was admitted to hospital with general malaise and weight loss. Laboratory results showed elevated values of liver function tests. Viral serology was positive for hepatitis B infection. Both patients proved to have reactivation of hepatitis B due to using prednisone. Neither patient had received preventive antiviral therapy. In patients with chronic hepatitis B infection, preventive antiviral therapy should be started before treatment with glucocorticoids is initiated.