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.     

Quantitative structure–activity relationship (QSAR) study of elastase substrates and inhibitors

One hundred Suc-X-Y-Ala-pNA peptides (SUC: succinyl, pNA: p-nitroanilide, X, Y: Gly, Ala, Val, Leu, Ile, Phe, Pro, x-aminobutyric acid, norvaline, norleucine) were synthesized and their reaction constants with porcine pancreatic elastase (K_m, K_cat and K_cat/K_m) were determined. These reaction constants were quantitatively analyzed using the Free–Wilson/Fujita–Ban method. The contribution of amino acid side chains to the reaction constants K_m, K_cat and K_cat/K_m), expressed logarithmically, was found to be additive. On the other hand, 19 elastase inhibitors of the general formula CF₃CO-X-Y-Ala-pNA (X,Y: ten amino acids) were synthesized, and their inhibition constants were compared with the Michaelis constant for the corresponding substrates and analyzed using free-energy-related substituent constants. In the analysis of amino acid side chains in the Y position, the K_i value of the inhibitor was generally correlated to the K_m value of the substrate, which corresponded to the inhibitor, thus confirming the validity of the equation This study may serve as a prototypical approach to unraveling structure–activity relationships of peptide substrates and inhibitors of medicinal or agricultural importance.     

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.     

Adjuvant Immunotherapy for Malignant Brain Tumors

New methods of adjuvant immunotherapy were introduced for thetreatment of malignant brain tumors. Allogeneic bone marrowcell transfusion or local intratumoral infusion of allogeneicor autologous peripheral white blood cells were conducted on18 patients having malignant glioma, after ordinary treatmentof operation, radiation or chemotherapy. The survival rate ofthese patients was significantly prolonged when compared withthe rate normally expected. No side effects were noted. Morphologicalchanges of cells in the cerebrospinal fluid taken from the intratumoralcavity, before and after infusion of peripheral white bloodcells, were studied. Cytolysis and phagocytosis of tumor cellsby macrophages were observed. Suppressive mechanism of immunologicallycompetent cells on glioma cells was partly studied, cytologicallyin vitro.     

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.     

Sleep disorder in children with autism

Abstract Eighty-eight children with autism, living in a suburb of Tokyo, were examined by questionnaire from 21 July to 31 August. Experienced sleep disorders were observed in 56 children; 44 of whom had sleep disorders before 3 years old. The average age when sleep disorders were seen to have stopped was 5 years old. The most common problem was difficulty falling sleep ( n = 23), followed by frequent awakening during sleep time ( n = 19), then early morning awakening ( n = 11). Bed-wetting was observed in 22 children.     

Evaluation of the Actillume® wrist actigraphy monitor in the detection of sleeping and waking

Abstract This study evaluated the Actillume® instrument and the modified Action 3 sleep-wake scoring algorithm, in which the scoring factor (P) was set at 0.10, 0.14, 0.20, 0.30, 0.40 and 0.50. Fifteen subjects, each of whom underwent polysomnography with simultaneous wrist actigraphy four times, yielded a total of 60 sleep studies. The sleep data from each subject were divided into four groups. In the high sleep efficiency index groups of the calibration and validation samples, the accuracy of the algorithm significandy differed within six P-values and was highest at P = 0.14. In the low sleep efficiency index groups of both samples, however, there were no significant differences in the accuracy. Thus, these results indicate that P = 0.14 should be most appropriate for this actigraph and algorithm.