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.     

ATP sparing effect of isoflurane during ischaemia and reperfusion of the canine heart

Sustained dysfunction of myocardial contractility after shortperiods of coronary artery occlusion and reperfusion has beentermed "stunned myocardium". Isoflurane may improve the recoveryof regional myocardial contractility in stunned myocardium.The purpose of the present study was to determine if isofluraneprevents depletion of high energy phosphates after myocardialischaemia-reperfusion and if the reduction in cardiac work duringisoflurane anaesthesia contributes to the preservation of highenergy phosphate metabolism in an acute canine model. Mongreldogs were allocated to one of three groups: controls, anaesthetizedwith urethane and chloralose; ISO group, isoflurane administeredbefore ischaemia; and ISOc group, heart rate and mean arterialpressure controlled to approximately match baseline values.The left anterior descending (LAD) coronary artery was occludedfor 15 min and then reperfused for 60 min during 1.5% end-tidalisoflurane anaesthesia. Full thickness samples of myocardiumwere obtained from the reperfused area (supplied by the LAD)and the non-ischaemic area (supplied by the left circumflexcoronary artery). The concentrations of adenosine monophosphate(AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP),creatine phosphate (CP) and lactate in the endocardial portionof the myocardium were measured. Arterial pressure, aortic flowin the ascending aorta and rate-pressure product decreased significantlyafter isoflurane. Although the concentration of ATP of the reperfusedarea in the control group showed a significant reduction 60mm after reperfusion, the ISO and ISOc groups had significantlygreater concentrations. Isoflurane anaesthesia maintained myocardialhigh energy phosphate metabolism in reperfused myocardium. Weconclude that the reduction in cardiac work played only a minorrole in the ATP-sparing effect of isoflurane. (Br. J. Anaesth.1995; 74: 563–568)     

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.     

A Case of Neonatal McCune-Albright Syndrome with Cushing Syndrome and Hyperthyroidism

ABSTRACT. We describe a female newborn infant with McCune-Albright syndrome. In addition to the cutaneous pigmentation, she had apparent manifestations of hyperthyroidism and Cushing syndrome since birth. X-ray examinations showed many scattered lucencies in multiple bones. Endocrinological findings were as follows: serum T4 276 nmol/l; free T4 125 pmol/l; TSH <1 mU/l; serum cortisol >2210 nmol/l; plasma ACTH < 10 pg/ml; urinary free cortisol 865 nmol/day; estradiol 0.36 nmol/l. Regardless of treatment with antithyroid drugs and an inhibitor of 3β-hydroxysteroid dehydrogenase, the patient died of cardiac failure at the age of 4 months. Autopsy findings included a follicle cyst in the right ovary and multinodular hyperplasia in the thyroid and both adrenals. To our knowledge such a severe neonatal form of McCune-Albright syndrome has not been described in the literature.     

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.