Successfully treated unstable angina pectoris in a young Japanese female

A 25-year-old Japanese female complaining chest oppression and palpitation was admitted to hospital under the presumptive diagnosis of ischemic heart disease (IHD), although no obvious underlying disease associated with IHD was detected. Coronary angiography showed stenosis at the proximal site of left anterior descending artery (LAD), with dilatation and tortuosity at the bifurcation of the first and the second septal branches. Intravascular ultrasound imaging of the LAD showed intimal thickness without calcification at the site of stenosis. The stenosis was successfully and smoothly dilated by percutaneous transluminal angioplasty. Even with precise evaluation, the cause of the coronary artery disease in this young female patient was not clarified. Further careful follow-up is needed.     

Defense mechanisms against influenza virus infection in the respiratory tract mucosa

The respiratory tract mucosa is not only the site of infection for influenza viruses but also the site of defense against virus infection. Viruses are initially detected and destroyed non-specifically by innate immune mechanisms, but if the viruses escape the early defense mechanisms, they are detected and eliminated specifically by adaptive immune mechanisms. The major adaptive immune mechanisms are as follows. (i) Specific secretory-IgA (S-IgA) antibodies (Abs) and CTLs (CD8+ cytotoxic T lymphocytes) are involved in the recovery from influenza following viral infection of naive mice. (ii) Preexisting specific S-IgA and IgG Abs in the immunized animals are involved in viral elimination by forming virus-Ig complexes shortly after re-infection. By their polymeric nature, the S-IgA Abs, which are carried to the mucus by transepithelial transport used for dimeric IgA (dIgA) Abs, provide not only protection against homologous virus infection but also cross-protection against drift virus infection. The IgG Abs, which transude from the serum to the mucus by diffusion, provide protection against homologous virus infection. They are largely distributed on the alveolar epithelia to prevent influenza pneumonia. (iii) In the absence of Abs in the pre-immunized animals, the production of specific IgA and IgG Abs by B memory cells is accelerated after re-infection, and these antibodies play a role in viral elimination from day 3 onwards after re-infection. (iv) In epithelial cells of infected animals, specific dIgA Abs being trafficked through the epithelial cells may be involved in the prevention of viral assembly by binding to newly synthesized viral proteins. (v) In the pre-immunized animals, CTL production by memory T cells is also accelerated and these cells appear to participate in the killing of the host cells infected with different subtype viruses (within the same type) from day 3 onwards after re-infection. (vi) Similarly, memory Th1 cells that mediate an accelerated delayed-type hypersensitivity response are involved in blockade of virus replication by secreting IFN-gamma in mice challenged with different subtype viruses. These defense mechanisms suggest that the development of a mucosal vaccine, capable of inducing S-IgA Abs, which provide cross-protection against variant viruses within the same subtype, serum IgG Abs to prevent lethal influenza pneumonia and CTLs, which provide broad cross-protection against different subtype viruses, is strategically important to control influenza.     

Ultrasonography of gastric volvulus: "peanut sign"

We report a case of chronic gastric volvulus in which ultrasonography (US) was useful. An 81-year-old woman was hospitalized due to vomiting, and upper gastroduodenoscopy revealed that the stomach was spirally twisted and constricted. An upper gastrointestinal barium study demonstrated an organoaxial-mesenteroaxial combined type gastric volvulus. US showed constriction between the dilated upper stomach body and the lower stomach body similar to a "peanut". Thereafter, the patient's vomiting stopped and follow-up US demonstrated that the constriction of the stomach was loosened. Therefore, we believe that this characteristic US sign paralleled the symptoms of the patient.     

Liver disease in hepatitis C virus carriers identified at blood donation and their outcomes with or without interferon treatment: Study on 1019 carriers followed for 5–10 years

Aim: To portray liver disease and project outcomes in carriers of hepatitis C virus (HCV) in the general population. Methods: Liver disease was evaluated in 1019 individuals who were found with HCV infection at blood donation, and they were followed for 5-10 years with or without receiving interferon (IFN). Results: At baseline, chronic hepatitis was detected in 529 (51.9%) HCV carriers and more frequently in men than in women (62.6% [299/478]vs 42.5% [230/541], P < 0.01); cirrhosis was diagnosed in five (0.5% [three men included]) and hepatocellular carcinoma (HCC) in one (0.1% [man]). Of the carriers who were followed for 5 years or longer, loss of HCV-RNA from serum was achieved in 61 (31.0%) of the 197 treated with interferon (IFN) and only one of the 211 (0.5%) without IFN (P < 0.0001). HCC developed in 14 carriers including six ofthe 211 (2.8%) without IFN and eight of the 197 (4.1%) with IFN (six non-responders included). Follow ups of the 949 carriers identified age (P < 0.002), male gender (P < 0.01) and cirrhosis at the baseline (P < 0.0001) as factors contributing to the development of HCC. Cumulative incidence rates of HCC during 10 years among carriers found with chronic hepatitis increased in parallel with the age at the baseline. Conclusion: Identification of HCV carriers in the general population and treating those indicated with IFN would help decrease the development of HCC and lift its medical, as well as economic, burdens off society.     

Recombinant interferon-α-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study

Abstract: To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-α-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-α-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p=0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p=0.0035) and platelet count (p=0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10⁵ copies/ml and serum platelet level above 15×10⁴/μl was 71%, whereas that in patients with a serum HCV-RNA level above 10⁵ copies/ml and serum platelet level less than 15×10⁴/μl was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.     

Noninvasive localization of accessory pathways by magnetocardiographic imaging

The magnetocardiogram (MCG) is a newly developed method that helps localize a cardiac current source. To test the clinical accuracy of a 7-channel biomagnetic system in the localization of early ventricular depolarization sites, the MCGs of 14 patients with Wolff-Parkinson-White (WPW) syndrome were recorded in a radiofrequency-shielded room. The locations of early ventricular depolarization sites were classified by standard 12-lead electrocardiograms (ECGs) and body surface iso-potential mapping. The accessory pathways of 3 patients with WPW syndrome were located in the right free wall and in 11 patients in the left free wall. The three-dimensional (3-D) dipole location was computed every 2 ms from the onset of the QRS complex by the least-square method. These 3-D dipole locations were projected onto a gated magnetic resonance image in order to visualize the propagation of the calculated ventricular source. The results were compared with those obtained by body surface isopotential mapping, and electrocardiographic and electrophysiologic studies. The location of the deduced current dipole at 20 ms correlated well with the location of the accessory pathway by the body surface mappings in 12 of the 14 patients with WPW syndrome. The MCG is capable of precisely determining the 3-D location of a current source in a noninvasive manner and may be of potential benefit in the treatment of WPW syndrome by catheter ablation.     

Serological and virological studies of Japanese encephalitis in the Terai region of Nepal.

In 1987 and 1990, serum samples were collected from people living in the two districts (Itahari and Chitwan) of the Terai region of Nepal. Antibodies against Japanese encephalitis (JE) virus in these sera were detected by the hemagglutination inhibition (HI) and neutralization (N) tests. By the HI test, 26 out of 172 (15.1%) sera from Chitwan and 15 out of 137 (10.9%) sera from Itahari showed positive titers. Higher positive rates were shown by the N test, where 46 out of 172 (26.7%) sera from Chitwan and 22 out of 137 (16.1%) sera from Itahari had antibodies against JE virus. A JE strain was isolated from a blood specimen of a pig raised in Kathmandu. When the nucleotide sequence of the pre-M region of the strain was compared to the same region of the other JE virus strains reported, the highest similarity was observed to the strains isolated in Nepal in 1985. These results suggest that the Terai region has been an epidemic area of JE.     

Role of ghrelin in streptozotocin-induced diabetic hyperphagia

Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, was originally purified from the rat stomach. We have previously reported that central administration of ghrelin increases food intake and body weight. To investigate the role of ghrelin in the hyperphagic response to uncontrolled diabetes, adult male rats were studied 14 days after administration of streptozotocin (STZ) or vehicle. STZ-treated diabetic rats were markedly hyperphagic. This hyperphagia was accompanied by hyperglycemia, hypoinsulinemia, and reduced plasma GH levels. Treatment of diabetic rats with insulin reversed these changes. Plasma ghrelin concentrations in untreated diabetic rats were significantly higher than in control rats and were normalized by insulin treatment. The ghrelin gene expression in the stomach was also higher in STZ diabetic rats than in control rats, but this difference was not significant. In contrast, plasma leptin was markedly reduced in STZ diabetic rats. This reduction in plasma leptin levels was reversed by insulin treatment. In addition, hypothalamic NPY mRNA levels were increased in STZ-treated diabetic rats and were reversed by insulin treatment. Furthermore, the hyperphagia was partially reversed by the administration of a ghrelin-receptor antagonist. Therefore, we conclude that the elevated plasma ghrelin levels, along with decreased plasma leptin levels, could contribute to the diabetic hyperphagia in part by increasing hypothalamic NPY. This is the first report to show the pathophysiological significance of ghrelin in diabetes.