JAK2 mutation and acute coronary syndrome complicated with stent thrombosis

Acute coronary syndrome (ACS) could be a precious opportunity for patients to reveal concealed diseases other than conventional risk factors for ACS, such as hypertension, dyslipidemia, diabetes mellitus, etc. In the setting of ACS, the intracoronary and systemic prothrombotic environment has led to an increase in the risk of stent thrombosis of which mortality was higher among patients with ACS, especially with the highest mortality in patients with ST elevation myocardial infarction. The some specific conditions which were concealed beyond the cardiovascular pathophysiology except well-known risk factors for ACS and stent thrombosis might involve the onset of ACS. We describe a case of a 64-year-old man who was admitted to intensive care unit for chest pain. This case found the possibility that polycythemia vera with Janus kinase 2 (JAK2) V617F mutation might be a underlying disease of ACS with stent thrombosis, and highlighted the importance of recognizing polycythemia vera with JAK2 V617F mutation as concealed disease for cardiologists. We would like to report and review the relationship between ACS and polycythemia vera with JAK2 V617F mutation.     

Marked improvement of left ventricular function after parathyroidectomy in a hemodialysis patient with secondary hyperparathyroidism and left ventricular dysfunction.

A 52-year-old woman, a hemodialysis patient, was admitted because of exertional dyspnea. Echocardiography showed left ventricular (LV) dilatation and reduced contraction. Coronary angiography showed no fixed stenosis. She had elevated levels of parathyroid hormone (PTH) as a result of secondary hyperparathyroidism with advanced renal failure. After parathyroidectomy, marked improvement of LV function following immediate decrease of blood levels of PTH was observed. It is suggested that PTH might have a significant role in the pathogenesis of LV dysfunction and that parathyroidectomy might be effective as a therapy for heart failure in some patients with secondary hyperparathyroidism and LV dysfunction.     

Tissue-specific impairment of insulin signaling in vasculature and skeletal muscle of fructose-fed rats.

The relation between insulin resistance/hyperinsulinemia and cardiovascular diseases has attracted much attention. Insulin affects not only glucose metabolism, but also protein synthesis and cell growth. Insulin stimulates both the phosphatidylinositol 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) pathways, but the relationship between cardiovascular disease and selective insulin signal pathways is unclear. We investigated the tissue specificity and intracellular signal transduction selectivity of insulin resistance in the vasculature and skeletal muscle of fructose-fed rats (FFR). Sprague-Dawley rats were fed either normal rat chow (control rats) or fructose-rich chow. Normal saline with or without 1,000 (microg/kg) insulin was injected, and then the thoracic aorta or soleus muscle was removed under anesthetization. Insulin-induced tyrosine phosphorylation of insulin receptor beta subunit (IRbeta) and insulin receptor substrate-1 (IRS-1) and tyrosine/threonine phosphorylation of p44/42 MAPK (ERK-1/2) were evaluated. There were no significant differences in the degree of phosphorylation of IRbeta or ERK-1/2 in the thoracic aorta or in the soleus muscle between FFR and controls. However, tyrosine phosphorylation of IRS-1 in the soleus muscle of FFR was significantly reduced to 80% (p<0.001) of that in controls. The results suggest that PI3-K pathway in skeletal muscle is selectively impaired in FFR, and this impairment may induce hyperinsulinemia, which in turn may stimulate the MAPK pathway and lead to atherosclerosis. Thus PI3-K pathway may be one of the factors underlying the onset of cardiovascular disease in patients with insulin resistance.     

Effects of flecainide on the electrophysiological properties of atrial vulnerability in humans.

The aims of this study were to evaluate the changes in the electrophysiological characteristics of the right atrium after the administration of flecainide and to clarify whether flecainide has a selective effect on human atrial tissue. Electrophysiological measurements were made in 38 patients, before and after intravenous administration of flecainide (2 mg/kg per 10 min). The effective refractory period of the right atrium (ERP-A), maximum conduction delay (Max.CD), repetitive atrial firing zone (RAFZ), fragmented atrial activity zone (FAAZ), and conduction delay zone (CDZ) were studied in the patients who were divided into 2 groups based on whether repetitive atrial firing (RAF) was induced in the baseline study. Flecainide significantly prolonged the ERP-A (202+/-22 to 238+/-33 ms, p<0.001) and shortened Max.CD (77+/-17 to 63+/-32 ms, p<0.05) in the patients with RAF, but not in those without RAF in the baseline study. After flecainide administration, there were significant reductions in the RAFZ (43+/-22 to 13+/-19 ms, p<0.0001), FAAZ (51+/-22 to 28+/-26 ms, p<0.001) and CDZ (70+/-21 to 48+/-30 ms, p<0.01) in the patients with RAF. However, atrial fibrillation (AF) was induced by stimulation after flecainide in 2 patients without RAF in the baseline study. There was a significant negative correlation between the ERP-A in the baseline study and the change in the ERP-A upon flecainide administration (r=0.45, p<0.01). Flecainide may preferentially activate the substrate for AF and RAF, but that action is mainly based on the electrophysiological characteristics found in the baseline study.     

Molecular features of non-B, non-C hepatocellular carcinoma: a PCR-array gene expression profiling study

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) usually develops following chronic liver inflammation caused by hepatitis C or B virus. Through expression profiling in a rare type of HCC, for which the causes are unknown, we sought to find key genes responsible for each step of hepatocarcinogenesis in the absence of viral influence. METHODS: We used 68 non-B, non-C liver tissues (20 HCC, 17 non-tumor, 31 normal liver) for expression profiling with PCR-array carrying 3072 genes known to be expressed in liver tissues. To select the differentially expressed genes, we performed random permutation testing. A weighted voting classification algorithm was used to confirm the reliability of gene selection. We then compared these genes with the results of previous expression profiling studies. RESULTS: A total of 220 differentially expressed genes were selected by random permutation tests. The classification accuracies using these genes were 91.8, 92.0 and 100.0% by a leave-one-out cross-validation, an additional PCR-array dataset and a Stanford DNA microarray dataset, respectively. By comparing our results with previous reports on virus-infected HCC, four genes (ALB, A2M, ECHS1 and IGFBP3) were commonly selected in some studies. CONCLUSIONS: The 220 differentially expressed genes selected by PCR-array are potentially responsible for hepatocarcinogenesis in the absence of viral influence.     

A Rare Case of Ectopic Adrenocorticotropic Hormone Syndrome with Recurrent Olfactory Neuroblastoma

A 40-year-old woman who had a history of recurrent olfactory neuroblastoma presented with full moon face, central obesity, buffalo hump, impaired glucose tolerance and bilateral cervical lymph node swelling. Laboratory tests showed morbidly elevated levels of adrenocorticotropic hormone (ACTH) and cortisol, which were not suppressed by high-dose (8 mg) dexamethasone. Biopsies of the enlarged cervical lymph nodes revealed ACTH-positive metastatic olfactory neuroblastoma, and ectopic ACTH syndrome was diagnosed. Metyrapone was used to suppress cortisol production and resulted in decreased levels of ACTH and cortisol. Bilateral cervical tumor resection further reduced the ACTH and cortisol levels, accompanied by a reduction in the metyrapone dosage. Cushing''s syndrome was alleviated through ACTH-producing tumor removal.     

Does a combination treatment of repetitive transcranial magnetic stimulation and occupational therapy improve upper limb muscle paralysis equally in patients with chronic stroke caused by cerebral hemorrhage and infarction?: A retrospective cohort study

The clinical presentation of stroke is usually more severe in patients with intracerebral hemorrhage (ICH) than in those with cerebral infarction (CI); recovery of stroke-related muscle paralysis is influenced and limited by the type of stroke. To date, many patients have been treated by neurorehabilitation; however, the changes in the recovery of motor paralysis depending on the type of stroke, ICH or CI, have not been established. This study aimed to determine this difference in improvement of upper extremity paralysis using 2-week in-hospital NovEl intervention Using Repetitive transcranial magnetic stimulation combined with Occupational therapy (NEURO).We scrutinized the medical records of all patients with poststroke (ICH or CI) upper extremity muscle paralysis using Fugl-Meyer assessments (FMAs) who had been admitted to 6 hospitals between March 2010 and December 2018 for rehabilitation treatment. This was a multiinstitutional, open-label, retrospective cohort study without control patients. We evaluated the effects of NEURO on patients with CI and ICH by dividing them into 2 groups according to the type of stroke, after adjustment for age, sex, dominant hand, affected hand side, time since stroke, and prediction of recovery capacity in the upper extremity.The study included 1716 (CI [n = 876] and ICH [n = 840]) patients who had undergone at least 2 FMAs and had experienced stroke at least 6 months before. The type of stroke had no effect on the outcomes (changes in the FMA-upper extremity score, F_[4,14.0] = 2.05, P = .09, partial η² = 0.01). Patients from all 5 groups equally benefited from the treatment (improvement in FMA scores) according to the sensitivity analysis-stratified analysis (F = 0.08 to 1.94, P > .16, partial η² < 0.001).We conclude that NEURO can be recommended for chronic stroke patients irrespective of the type of stroke.     

The Association of Cardio-Ankle Vascular Index (CAVI) with Biatrial Remodeling in Atrial Fibrillation

Aim: Arterial stiffness results in elevated left ventricular filling pressure and can promote atrial remodeling due to chronic pressure overload. However, the impact of arterial stiffness on the process of atrial remodeling in association with atrial fibrillation (AF) has not been fully evaluated. Methods: We enrolled 237 consecutive patients diagnosed with AF who had undergone ablation; data from 213 patients were analyzed. Cardio-ankle vascular index (CAVI) was used as a marker of arterial stiffness. The left atrial (LA) and right atrial (RA) volumes were determined by computed tomography imaging; atrial conduction and voltage amplitude were evaluated using a three-dimensional electromapping system used to guide the ablation procedure. Result: In univariate analysis, CAVI significantly correlated with atrial structural and electrical remodeling (LA volume index, r =0.297, P =0.001; RA volume index, r =0.252, P =0.004; LA conduction velocity, r =0.254, P = 0.003; LA mean voltage, r =−0.343, P =0.001, RA mean voltage; r =−0.245, P =0.015). Multivariate regression analysis revealed that CAVI and plasma levels of N-terminal B-type natriuretic peptide were independent determinants of LA and RA remodeling, respectively. On the other hand, age and LA conduction velocity were independent variables with respect to CAVI. Age-adjusted CAVI was highest in long-standing persistent AF when compared with measures of persistent or paroxysmal AF. Conclusion: CAVI was closely associated with biatrial remodeling in patients diagnosed with AF. These results suggest that arterial stiffness may play a significant role with respect to disease progression.     

A new Late Miocene great ape from Kenya and its implications for the origins of African great apes and humans

Extant African great apes and humans are thought to have diverged from each other in the Late Miocene. However, few hominoid fossils are known from Africa during this period. Here we describe a new genus of great ape (Nakalipithecus nakayamai gen. et sp. nov.) recently discovered from the early Late Miocene of Nakali, Kenya. The new genus resembles Ouranopithecus macedoniensis (9.6-8.7 Ma, Greece) in size and some features but retains less specialized characters, such as less inflated cusps and better-developed cingula on cheek teeth, and it was recovered from a slightly older age (9.9-9.8 Ma). Although the affinity of Ouranopithecus to the extant African apes and humans has often been inferred, the former is known only from southeastern Europe. The discovery of N. nakayamai in East Africa, therefore, provides new evidence on the origins of African great apes and humans. N. nakayamai could be close to the last common ancestor of the extant African apes and humans. In addition, the associated primate fauna from Nakali shows that hominoids and other non-cercopithecoid catarrhines retained higher diversity into the early Late Miocene in East Africa than previously recognized.