Catastrophic antiphospholipid syndrome and Kikuchi-Fujimoto disease: the first case reported

The case of a man with diagnosis of Kikuchi-Fujimoto disease (KFD) and catastrophic antiphospholipid syndrome (CAPS) is reported. He presented prolonged fever, lymphadenopathies, arthralgia, weight loss, hepatosplenomegaly and positive IgM for cytomegalovirus. While he was empirically treated with tuberculostatic drugs, he suddenly developed systemic inflammatory response syndrome, multiple organ failure and distal necrosis. On suspicion of severe sepsis, antibiotics, corticoids and recombinant human activated protein C (XIGRIS) were administrated. Exhaustive laboratory searching was negative. Histopathologic examinations of lymph node first disclosed malignant lymphoma but later KFD was confirmed. One month later, laboratory tests showed the presence of antiphospholipid antibodies (aPL). The patient was discharged after two months of hospitalization. This case exhibits a KFD complicated by definite CAPS. Cytomegalovirus could be involved in the development of both CAPS and KFD. Because of the severity of the case, we believe that XIGRIS noticeable improved the altered coagulation profile associated with CAPS.     

西罗奠司洗脱支架与絮杉醇洗脱支架用于冠状动脉血运重建的比较

背景：与裸金属支架相比，西罗莫司洗脱支架和紫杉醇洗脱支架都能降低再狭窄风险。但是，尚不清楚这两种药物洗脱支架在安全性和有效性上是否存在差异。方法：进行了一项随机、对照、单盲试验，在1012例行经皮冠状动脉介入（PCI）的患者中对比西罗莫司洗脱支架和紫杉醇洗脱支架。主要终点是行PCI9个月内的各种主要不良心脏事件（心源性死亡、心肌梗死和因缺血而需行靶血管血运重建）。1012例患者中有540例（53．4％）完成了随访冠状动脉造影检查。结果：两组的基线临床和冠状动脉造影特征相似。西罗莫司洗脱支架组和紫杉醇洗脱支架组的9个月时主要不良心脏事件发生率分别为6．2％和10．8％（HR0．56，95％CI0．36～0．86，P=0．009）。     

Altered expression of proteins of metabolic regulation during remodeling of the left ventricle after myocardial infarction

Non-infarcted myocardium after coronary occlusion undergoes progressive morphological and functional changes. The purpose of this study was to determine whether non-infarcted myocardium exhibits (1) alteration of the substrate pattern of myocardial metabolism and (2) concomitant changes in the expression of regulatory proteins of glucose and fatty acid metabolism. Myocardial infarction was induced in rats by ligation of the left coronary artery. One day and eight weeks after coronary occlusion, glucose and palmitate oxidation were measured. Expression of selected proteins of metabolism were determined one day to 12 weeks after infarction. One day after coronary occlusion no difference of glucose and palmitate oxidation was detectable, whereas after eight weeks, glucose oxidation was increased (+84%, P<0.05) and palmitate oxidation did not change significantly (-19%, P=0.07) in infarct-containing hearts, compared with hearts from sham-operated rats. One day after coronary occlusion, myocardial mRNA expression of the glucose transporter GLUT-1 was increased (+86%, P<0.05) and the expression of GLUT-4 was decreased (-28%, P<0.05) in surviving myocardium of infarct-containing hearts. Protein level of GLUT-1 was increased (+81%, P<0.05) and that of GLUT-4 slightly, but not significantly, decreased (-16%, P=NS). mRNA expressions of heart fatty acid binding protein (H-FABP), and of medium chain acyl-CoA dehydrogenase (MCAD), were decreased by 36% (P<0.05) and 35% (P=0. 07), respectively. Eight weeks after acute infarction, the left ventricle was hypertrophied and, at this time-point, there was no difference in the expression of GLUT-1 and GLUT-4 between infarcted and sham-operated hearts. However, myocardial mRNA and protein content of MCAD were decreased by 30% (P<0.01) and 27% (P<0.05), respectively. In summary, in surviving myocardium, glucose oxidation was increased eight weeks after coronary occlusion. Concomitantly, mRNA and protein expression of MCAD were decreased, compatible with a role of altered expression of regulatory proteins of metabolism in post-infarction modification of myocardial metabolism.     

Adenosplenomegaly and prognosis in uncomplicated and complicated chronic lymphocytic leukemia. A study of 362 cases

Presence and size of lymph nodes and spleen, graded from 0 to , in 362 patients with CLL observed from diagnosis were evaluated. Statistical analysis showed a relationship with age, sex, anemia and thrombopenia, leukocytosis, and outlined two different groups: the one without organomegalies , with higher mean age (67 years), female prevalence, and better prognosis; the other with adenosplenomegaly graded ++/ , with lower mean age (57 years), clear male prevalence, and worse prognosis. Survival results were statistically different only between groups 0/+ versus group ++/ . Important chronic diseases were present at diagnosis in approximately 25% of the cases, with a severely reduced survival (median, 27 months), close to that of the cases with anemia and/or thrombopenia (22 months). Therefore it seems that in every prognostic grouping system, complicated cases should be taken into account and grouped with the anemic and/or the thrombopenic ones. The following prognostic groups are proposed: I: low risk: cases without or with adenomegaly and/or splenomegaly + (65% surviving at 100 months); II: intermediate risk: cases with adenomegaly and/or splenomegaly ++/ (median survival, 70 months); III: high risk: cases complicated by chronic diseases, or with anemia and/or thrombopenia (median survival, 25 months).     

A reversible bilateral renal artery stenosis in association with antiphospholipid syndrome

We describe a 26-year-old white female with a history of Raynaud phenomenon, erythema nodosum, polyarthralgias, migraine, vertigo, seizures, transient ischemic attacks, one fetal loss, and false positive VDRL, who developed milk hypertension without overt lupus nephritis. She had positive antinuclear antibodies (ANA) and double-stranded deoxyribonucleic acid (dsDNA) antibodies. The lupus anticoagulant test (LAC) and cardiolipins antibodies (aCL) were positive. She was diagnosed as having a Systemic Lupus Erythematosus-like illness (SLE-like) with 'secondary' antiphospholipid syndrome (APS). Renal spiral computed tomography (CT) with intravenous (IV) contrast showed bilateral renal artery stenosis. Anticoagulation with acenocumarol was started. She became normotensive without antihypertensive drugs five months later. A follow-up renal spiral CT showed complete recanalization of both renal arteries, making thrombosis the more likely culprit pathology in the stenosis. After two years follow up the patient is normotensive. She remains on acenocumarol.     

Reciprocal modulation of mitogen-activated protein kinases and mitogen-activated protein kinase phosphatase 1 and 2 in failing human myocardium

BACKGROUND: Mitogen-activated protein kinases (MAPKs), consisting of the ERK1/2, JNKs, and p38-kinase families, play a key role in the regulation of myocyte growth and apoptosis in vitro. The activity of MAPKs is regulated by dual-specificity MAPK phosphatases (MKPs). Because myocardial failure is associated with myocyte hypertrophy and apoptosis, MAPKs may play a pathophysiologic role in human myocardial failure. METHODS AND RESULTS: We measured MAPKs activities and the protein levels of MAPKs and MKPs (MKP-1 and MKP-2) in the myocardium explanted at the time of transplantation from patients with end-stage failure caused by idiopathic dilated cardiomyopathy (n = 5-7). Nonfailing donor hearts (n = 5-7) were used for comparison. Although the protein levels for JNK1/2 and p38-kinase in failing hearts were not different from levels in nonfailing hearts, the activities of both were decreased (P <.05). Despite a >3-fold increase in the protein level for ERK1/2 in failing hearts, ERK1/2 activity was not increased. Expression of MKP-2 was significantly increased in failing hearts, while expression of MKP-1 was increased in 5 of 7 failing hearts as measured by Western analysis. CONCLUSIONS: JNK1/2 and p38 activities are decreased in failing human myocardium. Increased expression of MKPs may therefore contribute to decreased MAPKs activity in failing human myocardium.     

Soluble thrombomodulin levels among women with a history of recurrent pregnancy loss, with or without antiphospholipid antibodies.

The endothelial cells produce substances whose elevated plasma levels acquire predictive value for the development of events. For instance, soluble thrombomodulin (sTM) levels evidence endothelial cell injury. Under specific clinical conditions the levels of sTM are raised, such as in patients with certain autoimmune disorders, pre-eclampsia or antiphospholipid syndrome. The levels of sTM, as an endothelial injury marker, were evaluated in 65 women with a history of recurrent pregnancy loss (12 with autoimmune disorders, 19 pregnant women and nine with a history of gestational hypertension or pre-eclampsia or eclampsia); 13 of them had antiphospholipid antibodies. sTM levels could be used as a predictor of pregnancy loss in future prospective studies. We compared those levels with the levels found in control groups without recurrent pregnancy loss (20 healthy women and 14 women with autoimmune disorder). There were no statistically significant differences (P = 0.729) in the levels of sTM between the recurrent pregnancy loss group (31.1 ng/ml) and the healthy control group (31.4 ng/ml) or between the different subgroups with recurrent pregnancy loss (P = 0.873) and the healthy control group or the control group with autoimmune disorder (28.0 ng/ml). There were no statistically significant differences (P = 0.605) in the levels of sTM among the patients with recurrent pregnancy loss, with or without moderate or high antiphospholipid antibodies (32.0 versus 23.3 ng/ml). Consequently, the levels of sTM would not seem to be a useful tool, as an endothelial injury marker, in women with a history of recurrent pregnancy loss with or without antiphospholipid antibodies.     

Losartan but not enalaprilat acutely reduces reperfusion ventricular tachyarrhythmias in hypertrophied rat hearts after low-flow ischaemia

Based on clinical and experimental studies, angiotensin II receptor blockers and angiotensin converting enzyme inhibitors have been proposed to exert acute anti-arrhythmic effects in heart failure patients. Therefore, the goal of this study was to assess acute anti-arrhythmic effects of losartan and enalaprilat in hypertrophied rat hearts during low-flow ischaemia and reperfusion. In dose-finding experiments in non-hypertrophied isolated perfused hearts, we performed dose-response curves of losartan and enalaprilat studying monophasic action potential duration at 90% repolarisation (MAPD(90%)) and ventricular fibrillation (VF) threshold. Subsequently, we determined the effects of losartan and enalaprilat (in therapeutically relevant concentrations) on ventricular tachyarrhythmias induced by low-flow ischaemia/reperfusion in hearts demonstrating left ventricular (LV) hypertrophy 70 days after aortic banding. We found that neither drug significantly affected MAPD(90%) (1 nM-1 mM) or VF threshold (1 microM losartan and 10 microM enalaprilat) in non-hypertrophied hearts. Similarly in hypertrophied hearts, neither drug significantly affected the incidence or the duration of ventricular tachyarrhythmias (ventricular tachycardia and VF) during low-flow ischaemia. However, 1 microM losartan significantly reduced the duration of ventricular tachyarrhythmias during reperfusion. In conclusion, neither losartan nor enalaprilat is acutely anti-arrhythmic in hypertrophied rat hearts during low-flow ischaemia. During reperfusion, however, losartan but not enalaprilat exerts acute anti-arrhythmic effects.     

H(2)O(2) regulates cardiac myocyte phenotype via concentration-dependent activation of distinct kinase pathways

Reactive oxygen species (ROS) can act as signaling molecules to stimulate either hypertrophy or apoptosis in cardiac myocytes. We tested the hypothesis that the phenotypic effects of ROS are due to differential, concentration-dependent activation of specific kinase signaling pathways. Adult rat ventricular myocytes were exposed to H(2)O(2) over a broad concentration range (10-1000 microM). Low concentrations of H(2)O(2) (10-30 microM) increased protein synthesis without affecting survival. Higher concentrations of H(2)O(2) (100-200 microM) increased apoptosis (assessed by TUNEL). Still higher concentrations of H(2)O(2) (300-1000 microM) caused both apoptosis and necrosis. A hypertrophic concentration of H(2)O(2) (10 microM) increased the activity of ERK1/2, but not that of JNK, p38 kinase or Akt. An apoptotic concentration of H(2)O(2) (100 microM) activated JNK, p38 kinase and Akt, and further activated ERK1/2. The MEK1/2 inhibitor U0126 prevented the hypertrophic effect of 10 microM H(2)O(2). The apoptotic effect of 100 microM H(2)O(2) was inhibited bya dominant-negative JNK adenovirus, and was potentiated by U0126 or an Akt inhibitor. Thus, the concentration-dependent effects of ROS on myocyte hypertrophy and growth are due, at least in part, to the differential activation of specific kinase signaling pathways that regulate hypertrophy and apoptosis.