A study was made of 73 samples from 6 chronic hepatitis B patients, 2 out of the 6 cases were non-treated and the 4 cases were interferon treated HBeAg, HBeAb, s-ALT and HBV-DNA.
Detection of HBeAg and HBeAb were assayed by AxSYM system (Dainabot), which were based on microparticle enzyme immunoassay.
1) Fifty-three out of 73 samples showed positive for HBeAg; 45 samples showed only HBeAg positive (Group A) and 8 samples showed HBeAg and HBeAb positive (Group B). The positive ratios of HBV-DNA in each group 91.1%(41/45) and 50.0%(4/8), respectively and 4 out of the rest 20 samples that showed only HBeAb positive also showed HBV-DNA positive. The above 12 discrepant samples between HBeAg and HBV-DNA were collected from 4 chronic hepatitis B patients who became normal s-ALT levels after liver injury. The HBeAg S/N ratio (sample/negative control) of these samples were near the cutoff value (S/N =2.1).
2) Comparing the movement between HBeAg and s-ALT levels in 6 chronic hepatitis B patients, the changes of HBeAg S/N ratio were related with the changes of s-ALT. The changes of HBeAg S/N ratio were observed before the movement of s-ALT.
In conclusion, the detection of HBeAg/HBeAb by AxSYM system was useful to monitor the clinical course of chronic hepatitis B patients.

View full abstract

We analized the changes in frequency of bacterial isolates from the blood samples in our department from May 1987 to December 1993.
565 isolates from 4887 samples (11.6%) were detected. Among the detected microorganisms, the rate of gram-positivecocci (GPC) was much higher than the other kinds of the isolates each year. Especially, 80-90% of GPC were occupied by only 2 kinds of microorganisms, coagulase negative Staphylococci (CNS) and S. aureus. Among gram-negative-rods (GNR), constant increase of S. marcescens and transient increase of Enterobacter and P. aeruginosa were recognized. In 30 cases (5.3%), 2-3 kinds of microorganisms were isolated concomitantly, and in 55 cases (9.7%), the microorganisms, which was mainly cuased by CNS, S. aureus and Candida, was isolated from both blood samples and the tip of the IVH catheter concomitantly.
42.5% of the bacterial positive cases in 1933 underwent 2 more kinds of the indwelling catheters and 48.3% were administrated antibiotics. Most of the cases had underlying diseases including mainly malignant tumor (leukemia, solid tumor), cerebrovascular diseases, and multiple injuries.

View full abstract

A total of 446 Shigella strains consisting of 336 imported and 110 domestic strains isolated in Tokyo from 1990 to 1994 were examined for their species and serovar-distribution, and their drug-resistance. In both imported and domestic strains, S. sonnei was found to be the most prevalent species, followed by S. flexneri. In imported strains, however, the isolation frequency of S. flexneri, S. boydii and S. dysenteriae were higher than that of domestic strains, and the serovar of each species was distributed in a wider range than that of the domestic strains.
Provisional new serovar Shigella strains were isolated from 8 imported cases and 2 domestic cases.
The drug-resistance-test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM, and NFLX) showed that 82.7% of the imported strains and 89.1% of the domestic strains were resistant to any drugs examined. Drugs of a high resistant rate were SM, TC, ST for the both groups. Drug-resistance-patterns of the resistant isolates varied to 21 types. Among those, a triple drug-resistance-type with TC SM ST was found the most frequently in both groups. None of the strains were resistant to FOM or NFLX.

View full abstract

A new method for testing rifampicin (RFP) susceptibility of Mycobacterium tuberculosis was developed. This method is based on detection of the internal sequence derived from 71-kDa heat shock protein mRNA in tubercle bacilli heat-treated in the presence of RFP. The target sequence was amplified by reverse transcription and PCR, followed by agarose gel electrophoretic analysis. No amplification occurred in one RFP-susceptible strain by exposure to 45°C for 45 min in Middlebrook 7H9 broth containng RFP (10μg/ml) after overnight incubation at 37°C. On the other hand, an amplified 275-bp product was obtained from the RFP-resistant strain MY-129. In a subsequent trial using 65 clinical isolates, this method defined their RFP susceptibility levels as well as the verification of the MICs obtained by the conventional agar dilution method, with the exception of one RFP susceptible strain. Thus, this method provides a rapid and practical system to determine RFP susceptibility in M. tuberculosis.

View full abstract

Anaerobes, in particular Prevotella spp., are the predominant bacteria present in mixed respiratory infections. To study the virulence factor of Prevotella intermedia, we examined the effects of the culture filtrate of P. intermedia on the bactericidal activity of human polymorphonuclear neutrophils (PMNs). The culture filtrate significantly inhibited the phagocytic killing and the intracellular killing of Staphylococcus aureus by PMNs (p<0. 05), but the phagocytosis of PMNs was not affected. The boiled culture filtrate also inhibited the phagocytic killing of PMNs (p<0. 05), which suggests that the inhibitory effect may be mediated by heat-stable substances. Succinic and isovaleric acid were mainly detected from the culture filtrate by gas chromatography. The migration of PMNs was significantly inhibited by these short-chain fatty acids (15 mM succinic acid, p <0. 01 and 1 mM isovaleric acid, p <0.05). The phagocytic killing of PMNs was significantly inhibited by succinic acid (30 mM, p <0.05) and not by isovaleric acid. Therefore, these inhibitory effects on human PMN functions may be contributed to the virulence of the mixed infections with anaerobes.

View full abstract

A 71-year-old Japanese female, was found unconscious by drawing, in a hot spring spa, at around noon of 20 October 1994. She recovered by emergency cardiopulmonary resuscitation, and admitted to the Takinomiya General Hospital, with adult respiratory distress syndrome (ARDS). Although she recovered from ARDS within 4 days after her admission, she developed severe pneumonia accompanied with the second attack of ARDS. Ordinary bacteriological culture of her respiratory specimens failed to yield any significant pathogen for her pneumonia, and neither cefazolin nor imipenem/cilastatin was effective. Thus minocyclin was given on the 7th hospital-day and this was effective for blood gas and C-reactive protein (CRP) levels. Intratracheal exsudate inoculated on BCYEα agar plate yielded grayish white colonies. Cells of the colonies were clearly agglutinated by anti-Legionella pneumophila serogroup (SG) 3 serum. Antibody titers of patient's paired sera against the strain L. pneumophila SG3 Bloomington-2 and the patient's strain (Y-1) were determined by microplate agglutination test, and a significant rise from 1: 20 to 1: 320 was demonstrated. Patient recovered by erythromycin treatment and was discharged on the 59th hospital day. L. pneumophila SG3 organisms were again isolated from the spa water where the patient drawn. From these findings described above, we diagnosed the patient as pneumonia due to L. pneumophila SG3, and the spa water was the most probable source of infection.

View full abstract

To study the clinical significance of hepatitis B surface antigen (HBsAg) levels in chronic hepatitis B, sera from five patients with chronic hepatitis B HBsAg levels were measured quantitatively by counting immunoassay (CIA). CIA is an immunoassay that combines the latex agglutination method and particle counting technique.
The results were as follow:
1) In four patients with chronic active hepatitis, the increases of HBsAg levels were earlier than that of alanine aminotranseferase levels, and HBsAg levels had approximately the same changes as hepatitis B virus associated DNA polymerase (HBV DNA-p) activities.
2) In four patients treated with interferon-α or β, HBsAg levels after treatment decreased in the same manner as HBV DNA-p activities.
3) In a patient with chronic inactivate hepatitis. HBsAg levels were the same changes as HBV DNA-p activities.
These results suggested that quantitative analysis of HBsAg levels is useful to evaluate the prognosis and exacerbation for chronic hepatitis B.

View full abstract

Antibody prevalence to B19 virus in Japan was previously reported with 1973 and 1984 serum collections. Since then we have had two big epidemics of erythema infectiosum in Japan: 1986-87 and 1991-92. In an attempt to estimate how much those epidemics have affected seroprevalence to B19 virus infection, we studied seroepidemiology in three separate areas using a newly developed ELISA system consisting of recombinant VP1 + VP2 particle antigen. Total of 900 sera obtained in 1993 from healthy individuals living in northern, central and southwest parts of Japan were assayed for the presence of and B19 IgG antibody. In the first, the new assay system was compared with our conventional assay system in which native B19 virus particles were used as antigen. Of 220 serum samples tested, 212 (96.4%) gave same results in both assays. Remaining 8 samples which gave variable results were those of near cut off values. We concluded that this new ELISA system can be recommended for seroepidemiological use. Antibody prevalence rates were 10%(0-4 y), 54%(5-9 y), 59%(10-14 y), 46%(15-19 Y), 38%(20-29 y), 48%(30-39 y), 64%(40-49y) and 76%(50 y-). No gender difference was observed. Comparison of antibody prevalences in 1973, 1984 and 1993 suggested that approximately 10%(about 8 million people) of the total population under 40 years of age acquired immunity to B19 virus during one epidemic period.

View full abstract

Objective: To evaluate the Gen-Probe ^® Amplified Mycobacterium tuberculosis Direst Test (MTD) for detection of Mycobacterium tuberculosis in clinical specimens other than sputum, especially cerebrospinal fluid (CSF) and pleural fluid (PF) specimens.
Design: Six CSF, 17 PF and 23 bronchoalveolar lavage fluid (BALF) specimens that were submitted to our clinical laboratory for detection of mycobacteria were subjected to MTD and conventional smear and culture examinations.
Results: Of 6 smear-negative CSF specimens, two were positive in MTD and culture examination. In PF specimens, two of 15 smear-and culture-negative specimens were positive in MTD, while one smear-negative but culture-positive specimen was MTD negative. Three of 20 smear-and culturenegative BALF specimens were positive in MTD. Three BALF specimens in which mycobacteria other than the M. tuberculosis complex detected by culture were negative in MTD.
Conclusion: MTD is vey useful for rapid detection of M. tuberculosis in clinical specimens other than sputum as well as sputum, and should be especially valuable for rapid diagnosis of tuberculous meningitis which requires prompt initiation of appropriate anti-tuberculosis drug treatment.

View full abstract

We evaluated the effect of hepatic fibrosis on the induction of hepatic 2', 5'-oligoadenylate synthetase (2-5AS) by interferon (IFN) in a rat model of liver cirrhosis, induced with thioacetamide. Although there was no difference in serum 2-5AS activity between the control and cirrhotic rats given murine IFN, 2-5AS activity in the liver homogenates of cirrhotic rats was significantly lower than in the controls (105±18.5 vs. 171±10.2 pmol/μg, p<0.01).These results suggested that hepatic fibrosis attenuated the effect of IFN and one of the reasons for this may be the decreased induction of hepatic 2-5AS activity after IFN administration in the presence of a cirrhotic liver.

View full abstract

We found a substance A in human serum by ELISA method, using anti-A antibody. The substance A was obtained from the membranes of A. laidlawii and this enhanced HIV replication. This substance in human serum was detected in the chloroform phase of the Bligh-Dyer method. Rf value in thin layer chromatography was 0.28. This substance clearly showed enhancement of HIV replication as well as the activity of the membranes of A. laidlawii, but did not induce TNF production. Furthermore, the activity which enhances HIV replication in human serum was reduced by anti-A antibody. These results suggest that the substance derives from human serum which possesses a similar active site as those of substance derived from the membrane of A. laidlawii.

View full abstract

A 51-year-old female was admitted with complaints of fever and general fatigue. Chest X-ray showed diffuse bilateral fine nodular shadows and infiltrates. Complication of hepatic and muscular injury was suspected from increased levels of GOT, GPT and CPK in the seurm. Arterial blood gas analysis revealed hypoxemia. Because hypoxemia aggravated despite treatment with intravenous minocycline (200 mg/day), corticosteroids and mechanical ventilation were started, and the administration of minocycline (400 mg/day) and sparfloxacin was added. Consequent, chest X-rays and several laboratory data improved gradually. The final diagnosis was established with a significant rise of both IgG and IgM antibody against Chlamydia psittaci with MIF and identification of Chlamydia with the cell culture method. Chlamydia was successfully isolated from BALF of this patient obtained 5 days after commencement of minocycline treatment.
Psittacosis should be considered as a possible cause of severe respiratory failure necessitating emergency care including mechanical ventilation.

View full abstract

We reported a case who suffered from tuberculous meningitis at 10 months of age, and progressed to basal tuberculoma despite intensive drug therapy with isoniazid, rifampin, and streptomycin. Pan-hypopituitaliam due to basal tuberculoma was effectively replaced by the administration of anti-diuretic hormone (DDAVP) and levothyroxine sodium. Basal tuberculoma was finally removed by surgical operation. Histopathological examination of the tuberculoma revealed Mycobacterium tuberculosis and Langhans giant cells. During the 6 years after te operation, her growth rate was found to be retarded, and the administration of human growth hormone was started. Remarkable catch-up growth was demonstrated. We like to emphasize that infantile tuberculosis, mostly a result of intafamilial transmission, may manifest meningitis in the early phase of the disease, and it sometimes progresses to basal tuberculoma unresponsive to anti-mycobacterial drug therapy.

View full abstract

In 1992, some 90 countries or territories where 42% of the world's population resided were considered malarious and estimation of deaths from malaria worldwide per year were in the order of 1.4 of 2.8 million. The higher the number of Japanese who go abroad becomes (the total number in 1994 was 13, 578, 934: Records of Statistical Division of the Ministry of Justice), the greater is the risk of their contracting malaria. Indeed, the reported annual number of imported malaria cases increased to not less than 100. Now, malaria should first be presumed if a patient complains of a high fever after a visit to a tropical country. And the importance of instituting prompt diagnosis and proper treatment should also be stressed.
One of the antimalarials which has been highlighted for its effectiveness is halofantrine. This drug has been used for treatment of human malaria since 1984, and to date clinical trials have involved about 3.4 million patients in more than 30 countries (personal communication). Several patients successfully treated with halofantrine without any treatment failure have also been documented in Japan. However, in 1993, a clinical study involving 400 patients on the Thai-Burmese border revealed cardiac effects of antimalarial treatment with halofantrine, including one sudden death after the treatment. There have also been some spontaneous reports of serious ventricular dysrythmiasis with prolongation of the QT intervals, rarely associated with death The pharmaceutical company producing Halfan ^® has reported 8 cardiac arrests, leading to 6 deaths, when a higher dose than recommended was used, there was recent or concomitant treatment with mefloquine, there was pre-existing prolongation of the QT interval or the patient had a thiamine deficiency. Finally, the World Health Organization (WHO) announced a “drug alert” on halofantrine advising a change in recommendations for its use. In the present paper, we discuss the first Japanese vivax malaria patient whose QT interval was prolonged after treatment with halofantrine.

View full abstract

A case of itraconazole-induced hypokalemia with pulmonary aspergilloma is reported. A 68-year-old female who had been followed for rheumatoid arthritis, gastric ulcer and pulmonary aspergilloma was admitted to our hospital because of a cough, low grade fever and hemosputum. She was treated with itraconazole (100 mg/day) for pulmonary aspergilloma of the left upper lobe. Fifty seven days after starting the treatment, her serum potassium was 2.33 mEq/l. Since there was no history of diarrhea, vomiting or abuse of drugs known to cause hypokalemia, itraconazole-induced hypokalemia was suspected. Thirty one days after the discontinuation of the treatment with itraconazole, her serum potassium increased to 3.57 mEq/1 without potassium supplement. The lymphocyte stimulation test for itraconazole was negative. This case suggests that serum potassium should be monitored in the patients treated with itraconazole.

View full abstract