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.     

Diffuse fibromatosis on the scalp in infancy: A variant of juvenile hyaline fibromatosis

Various types of fibromatosis have been reported in infancy and early childhood. We describe an infant with diffuse fibromatosis on the scalp. A one year and five months-old girl showed a diffuse and hard mass 3 × 5 cm in diameter and no tenderness on the scalp. Two months later, the size of the mass had increased and several other tumors appeared on the lateral head. The magnetic resonance imaging (MRI) disclosed that a large and diffuse tumor had spread from the frontal to occipital head; a ‘helmet-like’ configuration of the tumor was exhibited on sagittal MR images. The tumor showed high signal intensity on T2-weighted images and was enhanced with Gd-DTPA. Histological examination showed a fibroblastic proliferation with intervening thick collagen bundles. The patient was diagnosed as having diffuse fibromatosis. The tumor at the resection site immediately recurred, whereas the tumor in the frontal head showed marked regression. Three months after the resection, new tumors appeared in the occipital head. The size and number of these tumors have remained unchanged for more than 18 months. The sites and appearance of the tumors were identical to that of juvenile hyaline fibromatosis (JHF) in this patient. However, JHF usually includes fibroblasts associated with large amounts of hyalinized collagen-like material, which were not present in our patient. The different histology of JHF comparing our case and other reported cases may depend on the different phase of the disease progression at resection. Long-term observation is necessary for the appropriate diagnosis and evaluation of prognosis in this patient.     

Comparison of Injection Materials for the Elevation of Gastric Mucosa Prior to Endoscopic Mucosal Resection

Endoscopic mucosal resection (EMR), namely strip biopsy, to eradicate gastric mucosal lesions requires certain special techniques, including submucosal injection of appropriate agents. This experimental study using dogs was conducted to compare, with regard to the degree of duration of mucosal elevation and subsequent histologic changes of the gastric wall, three injection materials; physiological saline, hypertonic saline with epinephrine (HSE) and 10% soybean oil. The duration of mucosal elevation which should be sufficient for the EMR procedure did not differ between the three agents. The post-injection histologic changes included vessel dilatation in the peri-muscularis mucosae, dilatation of the lymphatic channels and vessel congestion. These changes appeared in all injection material groups, and the vessel congestion was found to be more conspicuous in the HSE group. All EMRs in this series were performed by single snare cutting, which was also evaluated. The margin of the stripped material was well limited to the submucosal layer in all cases, but the depth of the ulcers formed varied. The healing process of the ulcer for the first 4 weeks was delayed in the soybean oil group. Although there were few cases of perforation in this experiment and some subjects had adhesion between the gastric serosa and adjacent organs, the single snare method could be applicable for clinical use by skilled hands.     

Congenital chylothorax in a patient with 21 trisomy syndrome

A female infant with 21 trisomy syndrome associated with congenital chylothorax was reported. She was born at a gestational age of 34 weeks by Cesarean section because of fetal hydrothorax and hydrops fetus, confirmed by ultrasonography at 32 weeks. Emergent resuscitation and immediate thoracentesis were performed soon after birth. After beginning breast feeding, the serous pleural fluid became opalescent and a diagnosis of congenital chylothorax was made. Feeding was changed to medium-chain triglyceride (MCT) feeding and the production of pleural effusion disappeared after thoracentesis was performed several times. Accumulating evidence suggested that MCT feeding and intermittent thoracentesis under echo guide were effective. Some reports on patients, including this one, suggest that there may be more patients with 21 trisomy associated with congenital hydrothorax. Therefore, congenital hydrothorax might be listed as a complication of 21 trisomy.     

Epidemiological survey of foot diseases in Japan: Results of 30 000 foot checks by dermatologists

There has been no epidemiological survey of foot diseases in Japan. In this study we determined the prevalence of foot diseases, especially tinea pedis (TP) and tinea unguium (TU) in Japan. We conducted a randomized survey of outpatients who visited a dermatologist during the third week of May in 1999, 2000 and 2006. The most frequently reported condition was “fungal infection” in 8737 (40.0%) of 21 820 patients in 1999/2000, and 3848 (49.4%) of 7783 patients in 2006. The patients who visited a dermatologist for reasons other than superficial fungal infection but were diagnosed with TP or TU comprised 18.6% of the study population in 2000 and 24.1% in 2006. Of the patients with TP or TU, 63.2% used topical medication only. This survey showed that often patients are not aware of fungal infections and that their treatment is sometimes insufficient. Dermatologists should actively examine and treat patients with TP and TU.     

Dual colour fluorescein analysis of peripheral blood T cells in auto-immune chronic active hepatitis

Both CD4 and CD8 T cells are subdivided into two phenotypically distinct sublineages via another two T cell markers, Leu-8 and CD11b antigens. The proportions of these four T cell subsets, CD4+Leu8+, CD4+Leu8-, CD8+11b+ and CD8+11b-, were studied in patients with auto-immune chronic active hepatitis (CAH) and compared with disease controls (hepatitis B surface antigen positive chronic active hepatitis) and healthy controls. We found that the proportion of CD4+Leu8+ cells was significantly reduced compared with controls (P less than 0.01), whereas those of the other cells were almost identical in all 3 groups. The absolute number of these CD4+Leu8+ cells was also lower than that of controls (P less than 0.01). Thus, the present study suggests that a reduced number of CD4+Leu8+ cells is associated with the aberrant immune response in auto-immune CAH.     

Immunoreactivity to M2 proteins in antimitochondrial antibody-negative patients with primary biliary cirrhosis

Abstract Although antimitochondrial auto-antibodies are characteristically present in the serum of patients with primary biliary cirrhosis (PBC), there is a discrepancy between the positivity for antimitochondrial antibody (AMA) and that for anti-M2 auto-antibody. In an attempt to explain the discrepancy, this study investigates the relationship between the AMA titre, determined by indirect immunofluorescence, and immunoreactivity to four inner mitochondrial membrance proteins (M2 proteins) with molecular weights of 70, 50, 47, and 40 kDa in 129 patients with PBC. Antimitochondrial antibody positivity was identified in 114 (88%) of 129 patients with clinically and histologically confirmed PBC. There were no significant differences between the AMA-negative and AMA-positive groups in clinical characteristics or histologically determined disease stage. Immunoblot analysis showed that all patients had anti-M2 auto-antibodies to one or more of the four M2 proteins. Nine (60%) of the 15 AMA-negative patients had antibodies to only one M2 protein (either 70 or 47 kDa). In contrast, 34 (53%) of the 64 patients with high AMA titres ( 1: 320) had antibodies to all four M2 proteins. There was a significant rank correlation between the AMA titre and the number of antibodies to M2 proteins ( P < 0.01). These findings indicate that the AMA titre is not influenced by the immunogenicity of M2 protein but by the number of M2 proteins that elicit an antibody response and that decreased immunoreactivity to M2 proteins may induce AMA negativity in PBC serum samples.     

Diastolic Mitral Regurgitation in Patients with First-Degree Atrioventricular Block

Diastolic mitral regurgitation has been observed in patients with DDD pacemakers when the atrioventricular (AV) delay was prolonged. However, diastolic mitral regurgitation associated with first-degree AV block has not been fully studied. We examined transmitral blood flow in 24 patients with first-degree AV block and normal cardiac function (ages 35.3 ± 17.4 years), and in nine patients with DDD pacemakers and normal cardiac function (ages 73.1 ± 8.1 years), using pulsed Doppler echocardiography. Diastolic mitral regurgitation was observed in 19 of 24 patients with first-degree AV block. Although PQ interval was shortened from 0.32 ± 0.06 to 0.20 ± 0.05 seconds (P < 0.01) after 1 mg atropine sulfate IV, the interval between P wave (ECG) and the beginning of diastolic mitral regurgitation did not change, while the duration of diastolic mitral regurgitation was shortened from 0.15 ± 0.03 to 0.05 ± 0.03 seconds (P < 0.01). There was a significant correlation between changes in PQ interval and changes in the duration of diastolic mitral regurgifation (r = 0.92, P < 0.001). Although cardiac output (3.9 ± 0.05 L/min) and pulmonary capillary wedge pressure (5.1 ± 1.5 mmHg) were normal in all patients with pacemakers, diastolic mitral regurgitation was observed when the AV delay was prolonged. The critical PQ interval for the appearance of diastolic mitral regurgitation was 0.23 ± 0.01 seconds. In patients with prolonged PQ intervals, delayed ventricular contraction following atrial contraction may be associated with mitral regurgitation in the presence of a reversed AV pressure gradient. The results of this study suggest that diastolic mitral regurgitation occurs not only in patients with DDD pacemakers, but also with AAIR pacemakers when the PQ interval is prolonged. The occurrence of diastolic mitral regurgitation is associated with the pacing mode or the setting of AV delay.