Hemophagocytic syndrome (HPS) causes pancytopenia, increased blood LDH level, liver dysfunction, DIC, etc. with macrophages appearing in the bone marrow, spleen, lymph nodes, etc. Adult HPS is mostly secondary to various infections, malignant tumors, etc. and sometimes has a serious outcome. Particularly infection associated HPS (IAHS) is trigged by viral, bacterial and fungal infections. The cases of unknown primary disease and suspected IAHS of unindentified pathogenic microorganism are often encountered in the clinical setting.
The authors compared IAHS and malignant associated HPS (MAHS) and classified IAHS into viral associated HPS (VAHS), bacterial associated HPS (BAHS) and fungal types to compare the test values based on the test findings at the onset in the HPS cases treated at our Department. The patients consisted of 21 HPS cases, 11 IAHS cases (VAHS 4, BAHS 5, fungal 2) and 10 MAHS cases. Based on the test findings (WBC, Hb, Plt, LDH, ferritin, myelogram, cytokines, [IFNα, TNFγ, IL-6, sIL-2R, M-CSF], adhesion molecules [sICAM-1, sVCAM-1, sELAM-1, sL-selectin]) at the onset, a comparison between IAHS and MAHS and among the IAHS cases classified by pathogenic microorganism was made. In the comparison between IAHS and MAHS, the Hb value was significantlly decreased and sIL-2R tended to be increased at the onset in MAHS. When comparing the IAHS cases by pathogenic microorganism, Plt was significantly decreased and sICAM-1 and sVCAM-1 were increased at the onset in the BAHS, The BAHS cases had serious underlying diseases and poor prognosis with high incidence of DIC complications. We are going to accumulate more cases for early diagnosis and treatment of IAHS.

View full abstract

It is well-known that the biological characteristics of HIV-1 persistently infected in the host have often changed into a rapid growth in vitro, T-cell line tropism and marked syncytium inducing (SI) ability accompanied by the progress of clinical stages from AC to ARC or AIDS.
We have developed a follow-up diagnostic test using the clinical markers based on the virus phenotypes mentioned above, and reported that the test was significantly useful for determining the clinical status of HIV infected individuals. Recently, highly active antiretroviral therapy (HAART) was introduced into HIV-1 chemotherapy, and has been reported to be a markedly effective treatment for HIV infected individuals. In this study, we carried out an investigation to see whether the follow-up diagnosis was useful even after introducing the HAART in Japan in 1997. The results by the laboratory diagnosis on 139 HIV infected individuals who were clinically observed over a long period showed that the positive rate of virus isolation and MT-4 cell tropism in the isolates during the two years between 1997 and 1998 were significantly lower than that of the nine years from 1988 to 1996 before the implementation of HAART. In addition, we obtained data that the effect of HAART reflects the biological profiles of virus isolation more than the CD4+Tcell counts.
These results suggest that data of clinical examination using virus isolation as a parameter are useful not only for predicting the development of AIDS but also for evaluating the effects of HAART, particularly in patients showing no association between the CD4+Tcell counts and the plasma viral load.

View full abstract

The antiviral agent amantadine specifically inhibit influenza A virus infection, but the emergence of drug-resistant viruses occur more readily with amantadine treatment. In human influenza viruses, single amino acid changes at 4 sites spanning the transmembrane domain of the M2 protein can confer drug resistance. Amantadine was approved for treatment of Parkinson's disease in 1975, and for the influenza A virus infection in November 1998, in Japan. Annual consumption of amantadine for influenza treatment increased suddenly after the approval.
According to our previous report, the predominant genotype of resistant virus is the substitution S-31-N in M2 both in vitro and in clinical samples, as in the other reports. Based on the above findings, we focused on single amino acid change at position 31 (genotype S-31-N) and applied polymerase chain-reaction restriction fragment length polymorphism (PCR-RFLP), directly from throat swab samples, by using primers that insert a restriction site for Sca I. With this technique, we surveyed the incidence of amantadine resistant viruses in nursing homes, Niigata, Japan.
Thirty-one (22.0%) of 141 PCR positive samples from 8 nursing homes in 1998-99 season showed resistant patterns, and only 6 (19.4%) of them were after the administration of amantadine for treatment. All of these 8 nursing homes used amantadine for Parkinson's disease, but only half of them used the drug for influenza A infection. The incidence of resistant viruses was not significantly different from facilities with amantadine for influenza treatment to those without, 25.5% and 14.0% respectively. The occurrence of outbreaks and sporadic illness in those facilities, with different administration status were observed, but fortunately we could not find any evidence to relate the emergence of resistant viruses to the outbreaks.
This is the first report that the resistant influenza viruses already exist in nursing facilities where amantadine was used for not only influenza but also Parkinson's disease in Japan.

View full abstract

Hetero-VRSA was studied in 978 MRSA strains isolated from clinical samples during 1991 to 1998. Although no VRSA was detected, 23 strains (2.4%) were identified as hetero-VRSA by the vancomycin-resistance using MU3 agar plate. The frequency of hetero-VRSA was not increased in the course of time. MIC of the hetero-VRSA to vancomycin and teicoplanin was 1-2 μg/ml and 0.5-12μg/ml, respectively. All of the hetero-VRSA strains were confirmed as a heterogeneous strain by a population analysis.
Although 43% of the hetero-VRSA strains were coagulase type II, positive for TSST-1, and enterotoxin type C, others were various in the characteistics. In the gene analysis by pulse field gelelectrophoresis (PFGE), 4 sets of 2 strains were found to be identical among the 23 strains but the other 15 strains were genetically different.
We speculate that hetero-VRSA strains were generated in 1991 secondary possibly by use of β-lactam antibiotics.

View full abstract

An epidemiological investigation for methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcups neumoniae (PRSP) was performed at 22 medical institutes in Kinki area by the questionnaire from Kinki Infection Working Group in 1998.
The isolation frequencies of MRSA and PRSP, including penicillin-intermediate resistant S. pneumoniae (PISP), were 61.5 and 45.8%, respectively. As compared to the previous data of MRSA in the Kinki area of 1997, the increase of MRSA was recognized.
A single infection with MRSA was 49.5% and simultaneous pathogen detected with MRSA was Candida species. On the other hand, a single infection with PRSP including PISP, was 36.4% and simultaneous pathogen with PRSP was Haemophilus influenzae. Vancomycin, teicoplanin, ST and arbekacin showed good activity against MRSA. PRSP and PISP had low activity to ampicillin and erythromycin.

View full abstract

Five disinfectants were tested for virucidal activity on three DNA viruses and three RNA viruses in the presence or absence of serum protein. Disinfectants of the aldehyde and halogen groups had a virucidal activity on human herpes virus, bovine rhabdo virus, human immunodeficiency virus, human adeno virus, porcine parvo virus, and polio virus. Disinfectants of the invert and amphoteric soap groups, and biganide group had a destructive effect on RNA and DNA viruses possessing an envelope. The presence of serum protein exerted great influence upon the virucidal activity of disinfectants of the invert and amphoteric soap groups.

View full abstract

Our previous study found mistakes by some doctors in the choice of an assay for determining antibodies in Japan. To compare the positivity rates for antibodies by assays, we measured the antibodies of measles, rubella, chickenpox and mumps from the same sera using such methods as the EIA, HI and CF assays. The subjects were 175 nursing students. The positivity rates for measles, chickenpox and mumps by the EIA assay were 96.6%, 93.7%, and 83.3%, respectively. Those for rubella by the HI and CF assays were 92.0% and 10.1%. The sensitivity rates for measles, chickenpox and mumps by the HI and CF assays, based on the results of the EIA assay, were 75.1%, 102.4% and 69.2% in the HI assay, and 20.6%, 38.7% and 8.0% in the CF assay, respectively. Our previous study showed that the sensitivity of the HI assay for rubella antibody is same as that of the EIA assay in Japan. Currently an EIA assay should be chosen for these antibodies and the HI assay or IAHA assay should be possible selections for rubella and chickenpox. However, international comparison of the cutoff titers for these antibodies should be considered.

View full abstract

We found ten cases of human cytomegalovirus (CMV) infection who were intractable stridor. Their symptoms were not improved by the treatment with aminophyllin nor β stimulants. They were admitted repeatedly complaining of stridor, fever and diarrhea. In two cases, the immunological findings showed a decrease of bacterial sterilizing activity of the neutrophils. Additionally, blood count showed leukocytosis more than 15, 000/ul in all cases. Total serum IgE and specific IgE antibodies to many antigens were not elevated. Transaminase was elevated. Chest X-p findings of interstitial pneumonia or atelectasis continued for a long time in some cases. Virological examinations revealed high concentrations of specific IgM or CF antibodies against CMV in all cases. CMV DNA in saliva were examined by polymerase chain reaction (PCR) with primer sets for the immediate early (IE) region of CMV and showed positive in seven cases. CMV in bronchoalveolar lavage (BAL) was isolated in two cases, and CMV PCR in BAL was positive in three cases. The sequence of the CMV-PCR products showed almost same sequence except one point mutation in bp 1203.
We considered that CMV infections in infants may induce stridor for a long period.

View full abstract