Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and is often limited by side effects. Cyclosporine A (CsA) is a potent immunosuppressant widely used in organ transplantation. We conducted a pilot study to determine whether CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male: female = 9:1) who did not respond to IFN therapy previously and who had elevated serum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their mean duration of hepatitis was 15 years. Oral CsA was given for 3 months in a dose that was increased at 1 month intervals from 1.5–2.0 to 2.0–3.0 and 3.0–4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild non-symptomatic hypertension. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 ± 82 to 62 ± 48 IU/L; P < 0.02). The ALT levels fell to the normal range in five patients, although once therapy was discontinued the enzyme levels tended to return to pretreatment levels. Serum aspartate aminotransferase and g-glutamyl transpeptidase levels similarly decreased. The serum HCV-RNA titre, determined by competitive RT-PCR, did not change in any patient throughout the study period. There were no appreciable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkaline phosphatase levels. These findings suggest that CsA, even in a relatively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic-hepatitis C, although an antiviral effect was not noted.     

Diagnosis of Small Pancreatic Carcinoma

A retrospective analysis was performed to evaluate the clinicalsymptoms and abnormal test findings in small pancreatic carcinoma.Five hundred and thirty-six cases of pancreatic carcinoma withthe histology of duct cell carcinoma were collected from 14medical centers in Japan. In 440 of the cases, tumor size wasmeasured at the time of laparotomy or from the resected specimen.Three hundred and seventy-seven patients (86%) had a carcinomalarger than 3.0 cm; only 30% of these were resectable. Sixty-threepatients (14%) had a carcinoma of 3.0 cm or less, with resectabilityof 97%. Detecting a tumor of "3 cm or less" with a high probabilityof resectability is the objective of early diagnosis with theresulting possibility of a cure. In most cases these small carcinomaswere found easily when obstructive jaundice was present (73%).However, the estimated occurrence of obstructive jaundice associatedwith carcinomas of 3 cm or less was only 10% among the totalcases of pancreatic carcinoma studied. Therefore, it is necessaryfor early diagnosis to detect carcinomas of 3 cm or less presentingwithout jaundice. The symptoms of small carcinoma without jaundiceare weight loss, anorexia, upper abdominal pain, back pain anda palpable abdominal mass. Among the various available examinations,endoscopic retrograde cholangiopancreatography, computerizedtomography and ultrasonography were valuable in diagnosing thesesmall carcinomas.     

Acute disseminated encephalomyelitis associated with Mycoplasma pneumoniae infection

An 8 year old girl with acute disseminated encephalomyelitis (ADEM) is described. Elevated serum antibody titers suggested recent Mycoplasma pneumoniae infection. T2-weighted image of magnetic resonance imaging (MRI) disclosed multiple lesions of high signal intensity in bilateral basal ganglia and thalami as well as in the white matter. Postcontrast T1-weighted image revealed an enhanced lesion in the deep white matter. She showed rapid clinical improvement in response to corticosteroid therapy. The lesions had disappeared completely on MRI performed 10 weeks after the onset. ADEM is believed to be a demyelinating disorder of probable autoimmune etiology. MRI findings in this case may support the hypothesis that the primary pathological event is vascular injury and demyelination occurs only as a secondary phenomenon.     

Morphological comparison and functional reconstitution of rat hepatic parenchymal cells on various matrices

Four types of materials, type I collagen coat (Coat), acid-soluble type I collagen gel (Hardgel), pepsin-treated acid-soluble type I collagen gel (Softgel), and an extract of extracellular matrix of the murine Engelbreth-Holm-Swarm sarcoma (Matrigel), were used as matrices to culture rat hepatic parenchymal cells, and their morphological changes and adhesion were compared to the matrices by electron microscopic observations. Hepatic parenchymal cells cultured on Coat and Hardgel were extended and flattened, whereas cells cultured on Softgel and Matrigel assembled and formed aggregates. Such aggregates consisted of several hepatic parenchymal cells, with a recognizable bile duct-like alveolus on the inside. Morphologically, the aggregates were more spherical on Matrigel and oval shaped on Softgel. Microvilli of the cell surface were parallel to the matrix on Matrigel, but invaded into the gel on Softgel. Subsequently, investigation into how these morphological features affected the liver-specific functions, including secretion of albumin and induction of P450 by 3-methylcholanthrene, demonstrated that a high level of liver function was maintained in a long-term culture in hepatic parenchymal cells on Softgel. These results suggest that hepatic parenchymal cell interactions were stronger with Softgel than with Matrigel, and that Softgel appears to closely mimic the in vivo environment.     

PREVALENCE OF RAYNAUD'S PHENOMENON AND SPECIFIC CLINICAL SIGNS RELATED TO PROGRESSIVE SYSTEMIC SCLEROSIS IN THE GENERAL POPULATION OF JAPAN

Background. In order to evaluate the prevalence rates of Raynaud's phenomenon (RP) and specific clinical signs related to progressive systemic sclerosis (PSS) in the general population of Japan, inquiries were made concerning RP in the hands and dermatologic examinations were also conducted. Methods. One thousand and sixty-three subjects (332 men and 731 women) over 30 years of age who underwent inhabitants' health examinations in 1990 were considered for this study. Results. The prevalence of RP was 3.0% in men and 3.4% in women. In 8 men and 17 women with RP who received the blood tests, the positive rates of antinuclear antibody (ANA) were 12.5% and 35.3% in men and women, respectively. The prevalence rates of all five specific clinical signs related to PSS, sclerodactyly, pitting scars of the fingers, brown pigmentation of the body, shortened frenulum of the tongue, and flexion contracture of fingers, were under 2% in men and 3% in women. In women with RP the prevalence rates of sclerodactyly, pitting scars of the fingertips, brown pigmentation of the body, and shortened frenulum of the tongue were 16.0, 4.0, 4.0, and 16.0%, respectively. These values were significantly higher than those of persons without RP. Conclusions. Because some persons with primary RP may become typical cases of PSS within several years, a follow-up study, particulary for women who have positive titers of ANA with RP, should be carried out to find out whether the persons suffer from PSS or not.     

The influence of physical restraint or fasting on plaque-forming cell response in mice

Abstract This study was designed to investigate the effects of 1- and 3-day (16 h/day) physically restrained or fasting on immunological and endocrine responses in CBF1 mice. The influence of stressors on these responses was evaluated using anti-sheep red blood cell plaque-forming assay, and by examining T cell subsets, thymus weight and endocrine hormone levels. The results revealed that a significant elevation of the plaque-forming cells (PFC) was found in spleen cells in 1-day restrained mice, that the PFC were conversely suppressed following 3-day physically restrained stress, and that the PFC were not affected by 1- or 3-day fasting stress. Serum levels of norepinephrine were found to be significantly increased only in 1-day physically restrained mice. No change of T cell subsets and thymus weight was found in 1-day physically restrained mice. A significant increase in serum corticosterone levels was elicited in both 1- and 3-day physically restrained mice, and 3-day fasting mice, while increased Lyt2-positive T cells and thymic atrophy were found only in 3-day physically restrained mice. These findings suggest that immune function was differentially affected by the duration and types of stressors.     

Surveillance interval of endoscopic examinations for colorectal cancer screening

Background: There have been a few evidence‐based studies concerning the relationship between the length of the surveillance interval of colonoscopic examinations and the risk of colorectal cancer (CRC). The aim of the present study was to assess the appropriate interval between endoscopic examinations for CRC screening in a retrospective cohort study. Methods: The cohort included subjects in whom cancer was not detected at the initial endoscopic examination and in whom endoscopic examination(s) was subsequently performed one or more times. The results of the endoscopic examinations performed in the mass screening for CRC between November 1983 and March 1999 were analyzed. The study end point was the detection of CRC and the detection rates of cancer were assessed among those who underwent examinations at various intervals between successive endoscopic examinations. Results: Among the 117 636 cohort subjects, 63 invasive cancer cases and 112 mucosal cancer cases were found. The odds ratio (OR) for invasive cancer was not significantly elevated even when the interval between successive examinations was over 5 years. The OR for mucosal or invasive cancer was significantly elevated among the subjects in whom the interval between successive examinations was over 5 years (OR, 1.71; 95% confidence interval (CI), 1.07–2.73), than among those in whom the interval was 1 year. Conclusions: Since prolongation of the interval between endoscopic examinations of up to 5 years did not result in any change in the cancer risk among persons who are at average risk for CRC, 5 years may be an adequate interval between endoscopic examinations in the mass screening for CRC.     

The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis

Background and objective: In this study the prevalence, lung function and prognosis of IPF combined with emphysema were evaluated. Methods: Consecutive patients with usual interstitial pneumonia (UIP) on high‐resolution computed tomography (HRCT), with or without emphysema, were assessed retrospectively. The area of fibrosis in the base of the lungs was assessed by HRCT as minimal (<2 cm from the subpleura), moderate (≥2 cm from the subpleura, <1/3 of the area of the base of the lungs) or severe (≥1/3 of the area of the base of the lungs). Results: Among 660 patients with UIP on HRCT, 221 showed upper‐lobe emphysema. Pulmonary function results for patients with UIP and UIP/emphysema, respectively, were: FVC, 71.8% and 87.1%; FEV1%, 86.7% and 87.9%; and DL_CO, 74.3% and 65.2% of predicted. The relationship between FVC, the extent of fibrosis and survival was investigated in 362 patients with records of pulmonary function tests and no lung cancer at the time of entry into the study. Although the extent of fibrosis was similar between the groups, 71.3% of UIP patients met the lung volume criteria for IPF (FVC <80% of predicted), whereas only 26.5% of UIP/emphysema patients met the lung volume criteria for IPF. Median survival was 7.5 years in the UIP group and 8.5 years in the UIP/emphysema group. Conclusions: Emphysema was a common finding in patients with UIP. Patients with UIP and emphysema had greater lung volumes and better survival compared with those with UIP alone.     

Early detection of cutaneous microcirculatory change during hemorrhage using a laser Doppler flowmetry

The purpose of the present study was to evaluate the usefulness of cutaneous microcirculatory monitoring during hemorrhage. We observed changes in cutaneous blood volume, velocity and flow of five adult rabbits during hemorrhage by using a laser Doppler flowmetry. Mean arterial blood pressure, heart rate and blood gas values were measured. Cutaneous blood volume, velocity and flow decreased significantly after drawing 10 mL/kg of blood, while heart rate, mean arterial blood pressure and blood gas did not change. The decrease of cutaneous blood velocity preceded that of blood volume and was associated more deeply with the reduction of blood flow. In conclusion, cutaneous microcirculatory monitoring using laser Doppler flowmetry is a sensitive technique for detecting early changes of circulatory failure caused by hemorrhage.