Clinical features of liver disturbance in rheumatoid diseases: clinicopathological study with special reference to the cause of liver disturbance

Background: Background: Liver disturbance in rheumatoid diseases results not only from liver disease associated with the rheumatoid diseases themselves but also from various other causes. This study aimed to elucidate the clinical features of liver disturbance in rheumatoid diseases, focusing on the cause of this disturbance. Methods: A clinicopathological study was performed in 306 patients (106 with systemic lupus erythematosus, 71 with Sj?gren's syndrome, 59 with rheumatoid arthritis, 27 with scleroderma, 30 with polymyositis, and 13 with polyarteritis nodosa). Results: Liver disturbance occurred in 43% of these patients and resulted from various causes. Its degree and duration varied from one cause to another. Liver disease associated with rheumatoid diseases was the leading cause of the liver disturbance in these patients and was characterized by mild and transient liver disturbance (maximum alanine aminotransferase [ALT] level during the study period, 68 ± 8 IU/ml; maximum alkaline phosphatase [ALP] level, 410 ± 31 IU/ml; duration of liver disturbance, 6 ± 2 months). Most patients with this type of liver disease showed minimal change in liver histology, although two-thirds of those evaluated by the international scoring system for autoimmune hepatitis (AIH) were classified as “probable” or “definite”. Eight of 14 patients with histologically proven chronic hepatitis or cirrhosis were infected with hepatotropic virus (7 with hepatitis C virus [HCV] and 1 with hepatitis B virus [HBV]). Five of 9 patients in whom the hepatic lesion progressed had hepatotropic virus infection (4 with HCV and 1 with HBV), and the other 4 patients suffered from autoimmune liver diseases. Conclusions: Liver disease associated with rheumatoid diseases was the leading cause of liver disturbance in these patients and was characterized by mild and transient liver disturbance, whereas progressive liver diseases were often associated with hepatotropic virus, mainly HCV, or autoimmune liver diseases. Liver histology is indispensable for differentiating AIH from liver disease associated with rheumatoid diseases. Received: August 27, 2001 / Accepted: January 7, 2002     

Overexpression of interleukin-6 aggravates viral myocarditis: impaired increase in tumor necrosis factor-alpha

The process of inflammation and immune response is regulated by proinflammatory cytokines. Interleukin-6 (IL-6), one of the proinflammatory cytokines, plays a potentially critical role in viral-induced myocarditis. Our previous work demonstrates that exogenous IL-6 administration, given at the time of encephalomyocarditis virus (EMCV) inoculation in C3H/HeJ mice, has a protective effect on myocardium and improves survival rates. In the present study, we examined whether overexpression of IL-6 modified viral myocarditis. On day 3 and 10 after inoculation with EMCV, the ratio of heart weight to body weight and myocardial injury were significantly increased in IL-6 transgenic mice (IL-6TG). On day 3, a reduction of viral clearance was shown by the presence of elevated viral titers and viral replication in the heart of IL-6TG. The concentrations of serum tumor necrosis factor- alpha (TNF alpha) were dramatically increased in wild-type mice on day 1, in contrast, this change was not observed in IL-6TG. Treatment with recombinant human TNF (2 microg) significantly improved viral clearance in the IL-6TG hearts. Thus, overexpression of IL-6 promotes myocardial injury by interrupting both the cytokine network and viral clearance. These experiments suggest the possibility that IL-6 is one of the factors that accelerates tissue damage, including myocardial injury, in the viral myocarditis.     

Hormone replacement therapy causes a decrease in hepatocyte growth factor in hypertensive women

OBJECTIVE: Serum hepatocyte growth factor (HGF) is associated with blood pressure. We investigated whether the serum HGF level differs between hypertensive and normotensive postmenopausal women (PMW) and whether hormone replacement therapy (HRT) alters the serum HGF level and blood pressure in hypertensive and normotensive PMW. DESIGN: Prospective observational study. METHODS: A total of 33 PMW with mild to moderate essential hypertension controlled by antihypertensive treatment (mean age, 57 +/- 6 years) and 23 normotensive PMW (mean age, 57 +/- 7 years) received continuous HRT (0.625 mg of conjugated equine estrogen combined with 2.5 mg of medroxyprogesterone acetate) once a day orally for 12 months, and we measured serum HGF levels and blood pressure before and 12 months after the start of HRT. RESULTS: The baseline serum HGF level was significantly higher in hypertensive PMW than in normotensive PMW. HRT significantly decreased the serum HGF level in hypertensive subjects, from 2.85 +/- 0.64 pmol/l to 2.49 +/- 0.65 pmol/l (P < 0.001), but not in normotensive subjects. HRT did not change blood pressure in either group. CONCLUSIONS: Serum HGF level before the start of HRT was higher in the hypertensive PMW than in the normotensive PMW. Furthermore, HRT decreases serum HGF without decreasing blood pressure in hypertensive PMW. The HRT-induced decrease in serum HGF was greater in hypertensive PMW than in normotensive PMW, and the decrease was independent of blood pressure changes.     

Results of a survey of community-acquired-pneumonia and evaluation of old and new Japanese Respiratory Society guidelines]

We evaluated the usefulness of domestic and foreign guidelines for the diagnosis and treatment of patients with community-acquired-pneumonia at 23 institutions in 6 prefectures of the Tohoku Area, from December 2003 to November 2004. Based on the old and new Japanese Respiratory Society (JRS) guidelines, we evaluated severity, clinical efficacy and detection of atypical pneumonia. As for severity, the old guidelines led to the diagnosis of an excessive number of 'severe' cases. On the other hand, patients were appropriately diagnosed as having mild, moderate, severe, or very severe disease based on the new JRS guidelines (2005). The severity classification often correlated with the Pneumonia Severity Index (PSI) of the IDSA guidelines. The efficacy rate for patients who were prescribed the recommended drug according to the old JRS guidelines was 85.7% and for those who did not use the recommended drug it was 68.7% (p < 0.001).     

Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus

The role of cervical lymphadenectomy for thoracic esophageal cancer is controversial. This study evaluated the impact of cervical lymphadenectomy on the cervical lymph node metastasis (LNM) and survival rates of patients with esophageal cancer. We analyzed 199 patients who received radical esophagectomy with three-field lymphadenectomy. The overall 5-year survival rate was 49.4%. Cervical LNM was found in 36 (18.1%) out of the 199 patients. The 5-year survival rates of the patients with cervical LNM from upper and mid-esophageal cancers were 71.4% and 35.9%, respectively. However, none of the patients with cervical LNM from lower esophageal cancer survived more than 4 years after esophagectomy. The overall survival of patients with five or more metastatic nodes (5.9%) was significantly worse than that of patients with less than five positive nodes (45.5%). Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus, and with less than five positive nodes.     

Hypoxic ventilatory depression in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes

We describe a case of a 21-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who presented with hypoxic ventilatory depression. He had chronic hypoventilation, which was not explained by weakness of respiratory muscles. His hypercapnic ventilatory response was not impaired. In contrast, hypoxic ventilatory depression was observed in the isocapnic progressive hypoxic response test. After exposure to hypoxic conditions, his respiratory frequency decreased and tidal volume was unchanged. The hypoxic ventilatory depression was partially blocked by pretreatment with aminophylline. In conclusion, we need to be careful with patients with MELAS who are hypoxaemic because a vicious circle of hypoxia and hypoventilation can occur.     

Computed tomographic scan of the chest, latex agglutination test and plasma (1AE3)-beta-D-glucan assay in early diagnosis of invasive pulmonary aspergillosis: a prospective study of 215 patients

BACKGROUND AND OBJECTIVES: Blood and radiologic tests are frequently used for diagnosis of invasive pulmonary aspergillosis, but it remains unknown which is more useful for its early diagnosis. Aim of the study was to compare usefulness of computed tomographic (CT) scan of chest, latex agglutination (LA) test and determination of plasma (1-->3)-beta-D-glucan (BDG) levels for early diagnosis of invasive pulmonary aspergillosis (IPA). DESIGN AND METHODS: We treated 215 consecutive patients who underwent cytotoxic chemotherapy. From initiation of chemotherapy until death or discharge, blood samples were taken weekly and subjected to LA and BDG tests. We performed chest CT scans when patients had any signs of pulmonary infection or an antibiotic-resistant fever. RESULTS: Of the 215 patients, 30 (14. 0%) were diagnosed as having IPA. In sixteen cases the diagnosis was definite and in 14 it was suspected. In patient-based analysis, sensitivities of LA and BDG were 44% and 63%, respectively. Sensitivity tended to be lower in patients with IPA localized to the lung than those with disseminated invasive aspergillosis. Specificities were 93% and 74%, respectively. Either a halo or an air-crescent was observed in 7 of the 16 patients with IPA, and all of the IPA patients showed some abnormal signs on chest CT scans. On average, CT scan signs preceded a positive LA test by 7.1 days and a positive BDG assay by 11.5 days. In 6 of the 11 patients who became positive for either LA or BDG assay, CT scan signs preceded the positive results by more than seven days. INTERPRETATION AND CONCLUSIONS: Chest CT scan is more beneficial than the blood tests and X-ray for early diagnosis of IPA.