Predictive role of anti-gp210 and anticentromere antibodies in long-term outcome of primary biliary cirrhosis

Because some of the autoreactive T-cell clones specific for human PDC-E2 cross-react to mimicry peptides having an EIExDK motif derived from nuclear antigens such as human gp210 and sp100, we studied the clinical significance of antinuclear antibodies (ANA) in primary biliary cirrhosis (PBC) patients registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). We found that there are two different types of progression in PBC; one is a hepatic failure-type progression which is represented by positive anti-gp210 antibodies and the other is a portalhypertension-type progression which is represented by positive anticentromere antibodies. We discuss the predictive role of these ANA in the long-term outcome of PBC and the mechanisms by which two different PBC progression types occur based on molecular mimicry and aberrant expression of nuclear antigens.     

J-SAP study 1-2: outcomes of patients with stable high-risk coronary artery disease receiving medical-preceding therapy in Japan.

BACKGROUND: Stable coronary artery disease (CAD) is classified into 2 types: high-risk (ie, 3-vessel disease, left main trunk lesions, or ostial lesions of the left anterior descending (LAD)) and low-risk (1- or 2-vessel disease other than ostial lesions of the LAD). Generally, the former is treated with coronary artery bypass grafting-preceding therapy (CABG), but not medical-preceding therapy (Medical); however, this is based on evidence from 30 years ago or more and does not reflect the recent progression of Medical and CABG. In addition, a randomized study has not been performed in Japan. METHODS AND RESULTS: In high-risk CAD, the long-term outcomes of 77 Medical patients and age-, sex-, coronary-lesion-, symptom- and risk-factor-matched 99 CABG patients were surveyed over 3 years (mean: 3.4 years) starting in 2000 at 37 nationwide hospitals. The incidences of cardiac death and cardiac death+non-fatal acute coronary syndrome (9.1% and 11.7% in Medical, and 2.0% and 3.0% in CABG, respectively) were significantly higher and the improvement in clinical symptoms was significantly lower in Medical than CABG. CONCLUSIONS: CABG is recommended in patients with high-risk CAD from the view of long-term prognosis; however, it should be remembered that the long-term outcome in Medical has considerably improved.     

Clinical features of emergency electrocardiography in patients with acute myocardial infarction caused by left main trunk obstruction.

BACKGROUND: To diagnose left main trunk (LMT) infarction by 12-lead standard electrocardiogram (ECG) is an important emergency technique, but the features in LMT infarctions have not been clarified. METHODS AND RESULTS: The study enrolled 140 subjects who were divided into 4 groups according to the location of the culprit artery: 35 with LMT, 35 with left anterior descending artery (LAD), 35 with right coronary artery and 35 with left circumflex artery. Various parameters obtained from the ECGs were analyzed. Average QTc interval (0.51 +/- 0.06 s) in LMT group was markedly longer than that in the 3 other groups. Average QRS axis (-10 +/- 77 degrees) in LMT infarction showed a remarkable left deviation. ST-segment elevation in lead aVR occurred in 28 patients (80.0%) in the LMT group. The ECG features of the LMT group could be classified into 2 main groups: right bundle branch block (RBBB) with a marked left axis deviation (RBBB + LADEV type) and ST-segment elevation in leads V2-5, I and aVL without abnormal axis deviation (LAD type). CONCLUSION: Either ST-segment elevation in lead aVR and marked prolongation of both the QRS width and QTc interval with a prominent abnormal axis deviation or ST-segment elevation in the broad anterior precordial lead with a normal QRS axis strongly suggests LMT infarction.     

Paraneoplastic neurological syndrome accompanied by severe central hypoventilation and expression of anti-Hu antibody in a patient with small cell lung cancer]

A 65-year-old man was admitted to our hospital complaining of diplopia, dysarthria, difficulty in walking and progressive dysesthesia that developed in his left hand and leg. Brain MRI revealed high signal intensity regions on T2-weighted and FLAIR images of the hippocampus and the corpus amygdaloideum. After admission, the patient's neurological symptoms progressed to delirium and dementia with hallucinations. When he eventually developed severe respiratory failure requiring ventilatory support, brain MRI revealed new high signal intensity regions on T2-weighted images of the medulla oblongata and pons. Chest CT scans showed a mass under the aortic arch, and based on subsequent histopathological examination of a transesophageal endoscopic ultrasonography-guided fine needle aspiration biopsy of the tumor, a diagnosis of small cell lung cancer was made. In addition, anti-Hu antibody was found in the patient's serum, leading to a diagnosis of paraneoplastic encephalomyelitis/sensory neuropathy. One course of chemotherapy (carboplatin + etoposide) was administered; however, the protocol was not completed because the patient developed severe pneumonia. Given that neurological symptoms usually precede a diagnosis of malignancy in paraneoplastic neurological syndromes, it is important that these are considered carefully, as they may contribute to early diagnosis and treatment. Here we report a rare case of severe central hypoventilation in paraneoplastic encephalomyelitis/sensory neuropathy.     

A case of monocular blindness as the initial presentation of hepatocellular carcinoma with skull metastasis

A 52-year-old man suffering from monocular blindness, with light perception only, was admitted to our hospital. The symptom had begun as low vision and developed rapidly within 3 weeks into monocular blindness in the right eye, with no other systemic manifestations. Imaging examinations revealed multiple hepatocellular carcinomas in the cirrhotic liver, and tumors at the skull base and vertebra. A pathological and immunochemical study of specimens obtained by endoscopic transnasal tumor biopsy and laminectomy revealed them to be metastatic hepatocellular carcinomas (HCCs). Although the patient underwent radiation therapy and chemotherapy, he died 5 months after admission to our hospital. The cranial HCC, involving only the optic canal, may have disturbed the optic nerve in preference to the other cranial nerves. This is the first report of a HCC patient with monocular blindness as the initial presentation of the disease.     

Different effects of pravastatin and cerivastatin on the media of the carotid arteries as assessed by integrated backscatter ultrasound.

BACKGROUND: Currently, there are various types of statins used in the treatment of hyperlipidemia and coronary artery disease. The purpose of this study was to compare the effects of a lipophilic statin (cerivastatin) with those of a hydrophilic statin (pravastatin) on the carotid arterial media using integrated backscatter (IB) ultrasound. Cerivastatin (C) has a strong anti-proliferative effect (APE) on smooth muscle cells (SMCs), whereas pravastatin (P) has a weak effect. METHODS AND RESULTS: The IB values in the media of 72 segments of carotid arteries were measured in 36 patients with hyperlipidemia before and after statin therapy or diet for 6 months (C, n=13: P, n=12: diet, n=11). In addition, IB values of 34 segments of carotid arteries were measured in 34 patients without coronary risk factors. Intima - media thickness (IMT) and arterial stiffness (stiffness beta) were measured by conventional echo at the same time. IB values did not significantly change in the P group (12.8+/-3.5 vs 12.7+/-2.7 dB), but decreased in the C group (12.1 +/-2.9 vs 10.0+/-2.7 dB, p<0.01). Also, stiffness beta did not significantly change in the P group (8.3+/-3.1 vs 7.6+/-2.5), but decreased in the C group (10.1+/-4.3 vs 7.9+/-3.3, p<0.05). IB values correlated with age (r=0.70, p<0.01) and stiffness beta (r=0.67, p<0.01) in the 34 patients without coronary risk factors. CONCLUSIONS: Statin therapy with cerivastatin, but not pravastatin, decreased the IB values of the carotid media and arterial stiffness. The difference between these 2 statins may be related to their effective dose range.     

Importance of recruitment of bone marrow-derived CXCR4+ cells in post-infarct cardiac repair mediated by G-CSF

OBJECTIVE: Granulocyte-colony stimulating factor (G-CSF) accelerates repair following myocardial infarction (MI). Recently, the beneficial effects of post-MI administration of G-CSF were reported to be mediated by direct activation of the Jak-Stat pathway in cardiomyocytes. Our aim was to test the hypothesis that bone marrow-derived cells recruited into the infarcted myocardium are the primary mediators of the beneficial effects by G-CSF. METHODS AND RESULTS: MI was induced using a 30-min ischemia-reperfusion protocol (day 0) in 40 rabbits treated with G-CSF (10 microg/kg/day from days 3 to 7) or saline. Another 40 rabbits received the same G-CSF or saline protocol but also received AMD3100 (200 microg/kg/day), a specific inhibitor of CXCR4. On day 28 post-MI, left ventricular ejection fractions and end-diastolic dimensions were significantly better in the G-CSF group than in the control saline group, and the scar area/left ventricular wall area ratio was significantly smaller in the G-CSF group. G-CSF administration also led to increased mobilization of CXCR4+ bone marrow cells, including RAM11+ macrophages, into infarcted areas. And within those areas there was significant upregulation of expression of stromal cell-derived factor (SDF)-1, a chemoattractant of circulating CXCR4+ cells, as well as of the collagenase matrix metalloproteinase-1. AMD3100 significantly inhibited all of these beneficial effects of G-CSF, but did not affect the upregulation of SDF-1 or phospho-Stat3. CONCLUSION: Recruitment of CXCR4+ cells into infarcted myocardial tissues via stimulation of the CXCR4/SDF-1 axis plays a critical role in the beneficial effects of G-CSF.     

Assessment of acute myocardial infarction in Japan by the Japanese Coronary Intervention Study (JCIS) Group.

BACKGROUND: Until now, large-scale nationwide surveys of acute myocardial infarction (AMI), such as those performed in Europe and America, have not been performed in Japan. Therefore, in 2000 the Japanese Coronary Intervention Study (JCIS) group conducted a nationwide survey on the incidence of AMI in Japan. METHODS AND RESULTS: Questionnaires were collected from 8,268 facilities throughout Japan. The total annual number of patients with AMI was 66,459 (52.4 patients/10(5) population), and the AMI incidence rate in Japan was approximately 25% of that in the United States. Most facilities with AMI patients treated less than 50 AMI patients annually, and that number was 45.0% of total AMI patients. The incidence of AMI patients was highest in Kochi, Kumamoto, and Wakayama prefectures, and lowest in Yamanashi, Saitama and Shiga prefectures. The ratio of the highest incidence to the lowest incidence was 2.0. A significant correlation was observed between the mean age of the prefectural population, as a coronary risk factor, and the incidence of AMI. CONCLUSIONS: The incidence of AMI in Japan is approximately 25% that in the United States and it varies considerably among the prefectures, one of the causes being the difference in the mean age. This provides important information for assessing the guidelines for Japanese patients with AMI.     

Sympathetic tone assessed by washout of iodine 125-labeled metaiodobenzylguanidine from the murine left ventricle-influence of immobilization stress and inhibition of the renin-angiotensin system

Background  

Because it is not metabolized as is norepinephrine (NE), most of the metaiodobenzylguanidine (MIBG) taken up by the heart is considered to be lost subsequently by release concomitant with sympathetic stimulation. Therefore we examined whether the washout of MIBG is influenced by sympathetic tone, which we modulated by using immobilization stress or activation of the renin-angiotensin system (RAS).