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     

Expression of atrial natriuretic polypeptide in ventricles of heart with hypertrophic cardiomyopathy: an immunohistochemical study of endomyocardial specimens]

To investigate the ventricular expression of atrial natriuretic polypeptide (ANP) in human hypertrophic heart, we conducted an immunohistochemical study using endomyocardial biopsy specimens obtained from the right side of the interventricular septum (RVB), left ventricular free wall (LVB), or both of 39 patients with hypertrophic cardiomyopathy (HCM), and 9 control subjects without hypertrophy. No HCM patients had apparent congestive heart failure. ANP was not present in control subjects' RVB or LVB specimens, but was found in HCM patients', showing its characteristic distribution patterns (RVB > LVB, p < 0.05); it was present in 15 of 36 RVB (42%) and 2 of 25 LVB (8%). No clinical data, including echocardiographic, hemodynamic and angiographic data, were directly related to ventricular ANP expression in HCM. According to histological data, however, ANP-present RVB specimens of HCM had larger myocytes, severer fibrosis and myofiber disarray than the specimens without ANP. This indicates that a failing state may not be a prerequisite for ANP expression in human hypertrophic ventricles, but that ventricular ANP expression may occur concomitantly with myocyte hypertrophy as an adaptive response to focal stress due to "histological overloads" such as disarray and fibrosis in HCM, which may be reflected in the characteristic distribution patterns of intraventricular ANP.     

Changes in insulin, somatostatin, and glucagon secretion during the development of obesity in ventromedial hypothalamic-lesioned rats

Changes in insulin, somatostatin, and glucagon secretion during the development of obesity in rats after ventromedial hypothalamic (VMH) lesions were evaluated by measuring fasting hormone levels and their secretion from the isolated perfused pancreas. Fasting peripheral insulin levels were not altered 1 week after the VMH lesions but became progressively elevated at 3-4, 8-9, and 11-12 weeks compared to the values in sham-operated and age-matched control rats. In the portal vein, insulin levels also progressively increased in VMH-lesioned rats, but the portal-peripheral gradient of insulin in the later phase of VMH obesity was significantly lower than in the early phase after VMH lesions. On the contrary, the arginine-induced insulin release from the perfused pancreas was highest at 1 week and gradually decreased thereafter, although it continued to remain higher than that of controls. The perfusate somatostatin response to arginine also was exaggerated in the VMH-lesioned rats. However, both the peripheral glucagon level and the glucagon secretion from the perfused pancreas of the VMH-lesioned rats were not significantly different from the controls. These results show that VMH lesions result in an increased insulin and somatostatin secretion. Using the cyclically perfused liver in situ, we have found that the hepatic extraction rate of insulin is indeed reduced in rats 8-9 weeks after VMH lesioning, and so have at least partly accounted for the decreased portal-peripheral gradient of insulin in the later VMH postoperative phase.     

Aplastic Anemia in a Patient with Cronkhite-Canada Syndrome

Cronkhite-Canada syndrome (CCS) is a rare polyposis disorder accompanied by alopecia and onychodystrophy. A 63-year-old man with a history of CCS and repeated embolism developed progressive thrombocytopenia and mild anemia. Laboratory testing, a bone marrow examination, and magnetic resonance imaging of the spine resulted in a diagnosis of concurrent aplastic anemia (AA). Paroxysmal nocturnal hemoglobinuria (PNH)-type cells were detected in a peripheral blood specimen. In addition, human leukocyte antigen (HLA) included DRB1*15:01 and DRB1*15:02. Mesalazine was discontinued in consideration of possible drug-induced pancytopenia. Immunosuppressive therapy ameliorated both the gastrointestinal symptoms of CCS and pancytopenia. A common autoimmune abnormality might underlie both CCS and AA.     

Antibody responses in Japanese volunteers after immunization with yellow fever vaccine

To monitor the development of specific and cross-reactive antibody response in twenty Japanese volunteers after vaccination with live yellow fever vaccine. Serum samples were collected on various days after vaccination and examined for hemagglutination inhibition (HI) antibodies against yellow fever virus (YFV), Japanese encephalitis virus (JEV) and dengue virus (DV), neutralizing antibodies against YFV and JEV, and IgM antibodies against YFV. None of the volunteers had been previously immunized with this vaccine. Fifteen of 20 had pre-vaccinated with JEV 7 to 40 years before. Ten of the 20 had neutralizing antibodies against JEV before immunization. None of the 20 had detectable antibodies against YFV or DV before vaccination. On day 10th after the vaccination, neutralizing antibodies to YFV were detected in 6 of 19 volunteers and IgM antibodies against YFV were detected in 7 of 19. On day 14th, HI, neutralizing, and IgM antibodies against YFV were detected in all the tested sera. Neutralizing antibodies against JEV were developed in 2 volunteers and HI antibodies against JEV were increased in 3 of 6 volunteers respectively. On day 29th, cross-reactive HI antibodies for JEV and DV were detected in all the tested sera. The results indicate that YF vaccine induces YFV-specific antibodies in all the tested volunteers and that it also induces HI antibodies cross-reactive for JEV and DV. The YF vaccine has a strong immunogenicity because it is a live vaccine, and induces antibody against YFV predominantly. The international certificate of yellow fever vaccination becomes valid 10 days after vaccination. On day 14th after vaccination, we detected neutralizing antibodies against YFV from all tested volunteers, however, only 6 of 19 volunteers had detectable neutralizing antibody on the 10th day after vaccination. Therefore, the vaccine may not be perfectly effective on day 10th after the vaccination.     

Islet cell-activating protein reverses anti-fucosyl GM1 ganglioside antibody-induced inhibition of adenosine 3',5'-monophosphate production in FRTL-5 rat thyroid cells

Our previous study revealed that a specific antibody against fucosyl GM1 ganglioside (fGM1) inhibits basal and ligand-stimulated cAMP production in FRTL-5 rat thyroid cells. To further elucidate the mechanism of this inhibitory action of the antibody, the involvement of guanine nucleotide-binding proteins was studied using islet cell-activating protein (IAP) and cholera toxin. When FRTL-5 cells were pretreated with IAP and incubated with the antibody, the inhibitory activity of the antibody on cAMP production was completely abolished. Furthermore, the inhibitory activity of the antibody on TSH- or forskolin-stimulated cAMP production was also abolished by IAP preincubation. The inhibitory activity of the antibody by pretreatment of the cells was also reversed by the addition of IAP. Coincubation of FRTL-5 cells with the antibody and cholera toxin reduced the cAMP inhibitory action of the antibody. Similar results were obtained with anti-fGM1 pretreatment before cholera toxin stimulation. These results provide evidence that anti-fGM1 antibody acts via guanine nucleotide-binding proteins in inhibiting cAMP production in FRTL-5 cells.     

A Case Report of an Adult With Severe Hyperlipidemia During Acute Lymphocytic Leukemia Induction Therapy Successfully Treated With Plasmapheresis

Plasmapheresis for the treatment of hypertriglyceridemia has previously been performed in patients with sudden onset severe hypertriglyceridemia and acute pancreatitis; however, only a few reports of this procedure have been published. We report here on a case showing severe hypertriglyceridemia during asparaginase (Asp) treatment for acute lymphocytic leukemia (ALL), and give an overview of a lipid‐lowering apheresis therapy. To prevent the complication of pancreatitis due to hypertriglyceridemia, we performed plasma exchange (PE) three times using fresh frozen plasma. PE remarkably reduced both serum triglyceride and total cholesterol levels from 5430 mg/dL to 403 mg/dL and from 623 mg/dL to 204 mg/dL, respectively. The causes of severe hyperlipidemia in this patient were considered to include: the Asp treatment for ALL, and a genetic background with a heterozygote of familial lipoprotein lipase (LPL) defect syndrome, because the patient's plasma LPL level after intravenous heparin injection was low at 137 ng/mL. Hence, PE using fresh frozen plasma may be useful not only to remove lipoproteins, but also to supply defective factors, such as LPL, in similar cases.     

Restriction fragment length polymorphism (RFLP) of the human insulin receptor gene in Japanese: its possible usefulness as a genetic marker

Summary Restriction fragment length polymorphism of the human insulin receptor gene was analyzed with a 4.2 Kb cDNA probe in Japanese normal subjects and Type 2 (nonsulin-dependent) diabetic patients. Restriction endonuclease Rsa I digestion showed polymorphism of the human insulin receptor gene, with a band at 6.7 Kb, 6.2 Kb or 3.6 Kb. The frequency of the 6.7 Kb band was less than that in Caucasians. the Japanese subjects examined lacked a 3.6 Kb band, which is commonly found in Caucasians. We have also detected restriction fragment length polymorphism in the human insulin receptor gene by Pvu II or Stu I digestion. Although no significant association of restriction fragment length polymorphism with Type 2 diabetes was found in the present study, our results suggest that the restriction fragment length polymorphism in the human insulin receptor gene varies among ethnic groups, and that the restriction fragment length polymorphism linked to the human insulin receptor gene might be a useful marker for the linkage study of the genes located close to the human insulin receptor gene on chromosome 19.     

Patient satisfaction with sedation for flexible bronchoscopy

Background and objective:   Patient satisfaction with health care has increasingly been recognized as an important health outcome, but few studies have examined patient satisfaction with flexible bronchoscopy (FB). The purpose of this study was to assess patient satisfaction with FB conducted under conscious sedation and to identify the aspects of the procedure related to patient satisfaction.
Methods:   Patients' willingness to return for repeat FB was measured on a 5-point scale. Patients were asked whether they were bothered by the anaesthetic spray, scope insertion, shortness of breath, coughing, pharyngeal pain, chest pain or swallowing pain. Patients were asked to assess the quality of the physician, the institution and nursing, and their satisfaction with the privacy, waiting time and information provided about the procedure.
Results:   Of 161 consecutive eligible patients who underwent FB, 129 (80.1%) completed the questionnaire. Of the 129 patients, 65.8% reported that they would return for a repeat FB (12.4% would definitely return and 53.4% would probably return). Male gender, shorter examination time, excellent physician quality and not being bothered by coughing, pharyngeal pain or swallowing pain were related to greater patient satisfaction. The results of multiple logistic regression analysis showed that male gender was related to greater patient satisfaction.
Conclusions:   Bronchoscopists should try to recognize the factors that influence patient satisfaction and adjust their management accordingly.