Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and liver cancer. Previously, the consensus strategy against HCV infection was interferon mono-therapy. Now, pegylated interferon (PEG-IFN) with ribavirin combination therapy for 24-48 weeks is used against chronic hepatitis C and can achieve a sustained viral response (SVR) in about 50% of patients with genotype 1b and high viral loads. The number of elderly Japanese patients with chronic hepatitis C has increased compared to that in western countries. The efficacy of IFN therapy for elderly patients with genotype 1 and high viral titers is lower than in young patients, because the side effects of combination therapy with PEG-IFN and ribavirin are pronounced with a reduction in blood count. To avoid discontinuation of therapy and overcome the low SVR in elderly patients, ribavirin dosing, based on the total clearance of ribavirin (CL/F), may be considered to be increasingly valuable. Approximately 25% of HCV carriers have normal ranges of serum alanine amino transferase (ALT). The rate of SVR in patients with persistently normal serum ALT (PNALT) is almost as same as that in HCV carriers, in terms of IFN therapy. This evidence suggests that patients with PNALT should be considered for IFN therapy. Novel treatment options currently in development are focused on inhibition of HCV-specific enzymes, NS3 protease and NS5B polymerase, and several drugs have entered clinical trials. Now, patients with HCV and liver cirrhosis can be given IFN therapy, except in the case of genotype 1b and high viral loads. This therapy should contribute to an improvement in the prognosis. It would appears that interferon will remain an element of anti-HCV therapy for the immediate future, although new regimens will be necessary for advanced combination therapy. It is hoped that new forms of interferon that are more effective, less toxic, and more convenient can be developed.
Tachykinins are thought to mediate hyperpnea-induced bronchoconstriction (HIB). It was reported that tachykinin receptor antagonists, FK888 (a selective neurokinin 1 receptor antagonist) and FK224 (a dual neurokinin 1/ neurokinin 2 receptor antagonist) inhibited bronchoconstriction in asthmatics. To determine the role of tachykinin receptor antagonists on HIB, we tested the effect of FK888 and FK224 during dry gas hyperpnea challenge in sensitized guinea pigs. Sensitized guinea pigs. Sensitized guinea pigs, pretreated with FK888 and FK224 intravenously, were anesthetized and artificially ventilated with dry gas hyperpnea for 5 minutes. A control group was also studied. After the challenge, lung resistance was measured for 60 minutes. Bronchoalveolar lavage fluid was obtained for cell counts. Substance P, neurokinin A, nerve growth factor, prostaglandin E2, thromboxane B2, and 9α, 11β-prostaglandin F2 levels were determined in the lavage fluid using immunoassays. Five minutes after the hyperpnea challenges, lung resistance increased. FK224 pretreatment inhibited the increase in a dose-dependent manner, but FK888 pretreatment had no effect. FK224 (10 mg/kg) significantly decreased lavage fluid levels of substance P and nerve growth factor; other levels were unchanged. The numbers of eosinophils and epithelial cells in the lavage fluid of the hyperpnea challenge group were increased and FK224 (10 mg/kg) was effective in reducing the eosinophil count, while FK888 had no effect on lavage fluid cell counts. We found that FK224 inhibited HIB in guinea pigs, which was mediated by neurokinin 1 and neurokinin 2 receptors with substance P and nerve growth factor in neurogenic airway inflammation.
We analyzed the clinical and histological characteristics of 20 patients with extramammary Paget’s disease at Itabashi Hospital, Nihon University School of Medicine. Two out of 20 patients came to the hospital at an advanced stage (Stage III-IV) of disease. There is significant need for improvement of the diagnostic ability, and the patients need to understand the disease to recognize and initiate treatment as early as possible. Immunohistochemical staining of cytokeratin (CK) 7 and CK20 is useful in the diagnosis of the disease.
An 81-year-old woman with akinetic mutism, following diarrhea, appetite loss, nausea and vomiting, was admitted to our hospital after she had taken Lithium carbonate 600 mg/day for 3 years. Because the blood lithium concentration was high (2.02 mEq/L, effective level; 0.06-0.12 mEq/L) in addition to the clinical symptoms, she was considered to have chronic lithium toxicosis and treatment was started. On the 6th day after admission she began to suffer from high fever of over 38°C and severe discomfort of the chest, twisiting the upper half of her body. Remarkable negative T wave appeared on ECG on the next day. It was considered to be the emergence of cardiomyopathy and heart failure during the withdrawal of the lithium toxicosis.