One hundred eight patients with hepatocellular carcinoma (HCC) underwent serologic testing for HBsAg, antibodies to HBs (anti-HBs), HBc (anti-HBc) and HCV (anti-HCV), and an assay for hepatitis B virus (HBV) DNA by the polymerase chain reaction (PCR). Ten (9.3%) of the 108 patients were positive for HBsAg and 96 (88.8%) were positive for anti-HCV. Both HBsAg and anti-HCV were present in 4 (3.7%) of the 108 patients. HBV DNA was detected in the serum of all patients who were positive for HBsAg and 9 (9.2%) of the 98 patients who were HBsAg-negative. Anti-HBc was positive and anti-HBs was negative in 8 of these 9 HBsAg negative patients with HBV DNA. HBsAg, HBV DNA and anti-HCV were negative in 6 (5.5%) of the 108 patients. These results suggest that HCV is highly associated with HCC and that HBV is occasionally associated with HCC even when HBsAg is negative.

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Two hundred eighty-seven episodes of septicemia which occurred in patients with hematological disorders between 1980 and 1993 were examined according to respective underlying diseases. The diagnosis of acute myelogenous leukemia (AML) was made in 155 patients, acute lymphocytic leukemia (ALL) in 45, chronic myelogenous leukemia (CML) in 29, malignant lymphoma in 36, adult T-cell leukemia (ATL) in 7, multiple myeloma (MM) in 8 and aplastic anemia (AA) in 7. Three hundred and two strains were isolated from 287 patients. Fifty two point three percent of the total isolates were gram-negative bacilli, 26.8% were gram-positive cocci, 17.2% were fungi and 3.6% were anaerobic bacteria. In ALL patients gram-positive cocci accounted for 42.0%. This rate was significantly higher than in other disorder. Additionally, oral mucositis or gingivitis was evaluated as clinical background in 36.1% of ALL cases. Forty-seven point two percent of organisms which caused septicemia in ALL patients were isolated from surveillance cultures of the throat just before the onset of septicemia. These data suggested that in ALL cases microbiological organisms more frequently invaded through injuries of oral mucosa. In ATL, CML, MM and AA patients, fungi accounted for more than 25% of causative organisms. The most common organism of all of the strains was Pseudomonas aeruginosa (21.9%), but in ATL and MM patients Escherichia coli was more common than P. aeruginosa. At the onset of the septicemia, neutrophil counts were less than 100/mm3 in 76.6% of all patients, and more than 3, 000/mm³ in only 5.0%. In contrast to this result, in 66.7% of ATL patients and 37.5% of MM patients, septicemia occurred even when neutrophil counts were more than 3, 000/mm³. Septicemia occurred in 28.2% of the total patients but died. The mortality rate in MM and AA patients (50.0% respectively) was higher than in other diseases. According to the mortality of each causative organisms, fungal septicemia had a terribly high mortality of 82.9% while other bacterial mortality was about 20%.

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Underlying diseases, pathogenic bacteria, clinical background and outcome were studied during 91 febrile episodes complicated by sepsis in 55 patients with hematological malignancies, who had been admitted to our hospital (Jikei University Kashiwa Hospital) betweeen January 1990 and December 1994. Particularly in patients with P. aeruginosa sepsis, we compared the prophylactic effect of ciprofloxacin (CPFX) alone with that of the combination of polymyxin B (PL-B) plus kanamycin (KM).
The major underlying diseases were acute myelocytic leukemia and malignant lymphoma, followed by myelodysplastic syndrome, acute lymphocytic leukemia and chronic myelocytic leukemia. Nearly two-thirds of the pathogenic microorganisms isolated were gram-positive bacteria (including coagulase-negative staphylococci and Staphylococcus aureus); approximately one-quarter were gram-negative bacteria (such as Pseudomonas aeruginosa), and the remainder were fungi. These microorganisms usually induced sepsis when granulocyte counts were decreased. Sepsis was a direct cause of death in about 60% of the patients and P. aeruginosa sepsis had the worst outcome. Oral administration of CPFX was more effective than PL-B plus KM in preventing P. aeruginosa sepsis. The difference in effectiveness might depend on the absorption profile of the drugs.

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Eight multi-drug resistant mutants (4.94%) were found in 162 clinical isolates of P. aeruginosa after exposure to norfloxacin at different concentrations (1/4, 1/2, 1, 2 and 4 MICs) and were investigated for the mechanisms of drug resistance.
All the mutants were eight-times more resistant to norfloxacin than the respective parents, and showed the cross-resistance to the other fluoroquinolones. However, these mutants differed in the drug-resistant patterns; the 94-74 mutant was resistant to carbenicillin, ceftazidime and chloramphenicol, TA-15 mutant was resistant to imipenem, and the 93-183 was resistant to carbenicillin, ceftazidime and gentamicin.
TA-16 mutant only showed a marked decrease in the bacterial uptake of norfloxacin. Profiles of the outer membrane proteins of the mutants were analyzed by SDS-PAGE method. The six mutants, except for TA-52 and 93-183 mutants, increased the intensity of bands in the 46 KD region. Three mutants (TA-15, TA-16 and 93-183) decreased the intensity of 44 KD (OMPE) and also the former two decreased the intensity of 22 KD (OMP G). The gryA mutations associated with fluoroquinolone-resistance were investigated for the eight mutants, and the 93-183 mutant showed to have the gyrA mutation caused by the alteration in the amino acid sequence of gyrA; Thr-83 (ACC) to Ile (ATC).
The result of the present study indicate that multi-drug resistance of clinical isolates of P. aeruginosa develops through different types of mechanisms, and is not easily explained fully by the present results, and suggest that many factors attributed to the development of the resistances in those mutants remains to be clarified.

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An outbreak of diarrhea due to infection with Cryptosporidium occurred among the staff members and customers who visited one of the 10 public houses or a dancing school in a building in Hiratsuka, Kanagawa Prefecture, at the end of summer in 1994. The epidemiological surveys by a questionnaire revealed that 461 out of 736 persons investigated complained of cholera-like or flu-like illness. The clinical manifestations included mucous and/or watery diarrhea (96.7%), abdominal pain (61.6%), fever (54.2%: lower than 39°C= 84.1%, higher than 39°C= 15.9%), malaise (37.1%), nausea (32.8%) and headache (29.3%). The polluted drinking water was strongly suspected to be the immediate cause of infection. Although several species of pathogenic bacteria were isolated both from stool and water samples, they were not supposed to be linked to the outbreak. No known enteropathogenic virus was found in either of the samples. Oocysts of Cryptosporidium parvum were identified in 12 (48.0%) of the 25 stool samples. The oocysts were also found in tap water and other water samples from a receiving tank which was directly connected with the public waterworks, and an elevated tank on the roof, a wastewater pits, a soil pit and artesianspring water tank. These tanks and pits except for the elevated tank were built adjucent to each other on an underground floor of the building. These tanks and pits were connected with openings in the upperpart of the tank walls. These openings might have functioned to discharge excess of drinking water in the receiving tank to the wastewater pit. The water level of the wastewater pit is kept down below the openings by pumping out the sanitary sewage to the public drain. According to the declaration of the owner of the building, however, the wastewater pump was broken at the time of outbreak. Accidental malfunction of the drainage system caused contamination of drinking water with sanitary sewage through the connecting pipes.

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Rapid detection and identification method of mycobacteria from specimen with infected mycobacteriosis was established by the combination of polymerase chain reaction and alkaline phosphatase labeled oligonucleotide probe (PCR-ALPDH). We prepaired four kinds of probes: Mycobacterium tuberculosis complex, M. avium, M. intracellulare, and mycobacterial-probe other than tuberculosis. PCR-ALPDH was compared with conventional methods using 234 specimens which suspected mycobacteriosis. In culture, 68 specimens (29.1%) were positive and 166 specimens (70.9%) were negative. In PCR-ALPDH, 88 specimens (37.6%) were positive and 146 sepecimens (62.4%) were negative. In 68 specimens which were positive in culture, the agreement of results of conventional identification and PCR-ALPDH for each probes were: 39/40 (PCRALPDH/Culture, 97.5%) in M. tuberculosis 5/9 (55.6%) in M. avium, 6/6 (100%) in M. intracellulare and 22/28 (88.6%) in MOTT isolation. Among 166 negative culture specimens, 27 specimens were positive in PCR-ALPDH.
The results indicated that PCR-ALPDH method was applicable for the establishment of rapid and sensitive mycobacterial diagnostic system.

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The antimicrobial activities of vancomycin (VCM) or cefpirome (CPR) at sub-and above-MICs against clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) during the postantibiotic phase (PAE-phase) induced by CPR or VCM were examined. Antimicrobial activities were determined growth suppression (post antibiotic sub-MIC effect: PA SME) at sub-MICs, and bactericidal activity at sub-and above-MICs. During the PAE-phase induced by VCM, growth suppression and bactericidal activity of CPR were enhanced at sub-MICs, compared with the non PAE-phase. On the other hand, during the PAE-phase induced by CPR, not only were growth suppression and bactericidal activity of VCM enhanced at sub-MICs, but bactericidal activity were enhanced at above-MICs compared with non PAE-phase. These suggest that enhancement of growth suppression and bactericidal activity during PAE-phase was a factor of combination effect of VCM and CPR against MRSA.

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The importance of Group B streptococcal infection in elderly patiens has not been clearly defined.
We studied the annual incidence of Group B streptococci (GBS) isolated from sputum and urine of elderly patients who were admitted to Nagoyashi Koseiin Geriatric Hospital. The percentage of GBS isolated has increased since 1988. The type distribution of GBS isolates shows predominantly types Ia, Ib and JM9. The major clinical factors in patients from whom GBS was isolated from sputum were bedridden status, feeding tubes and tracheostomy. We also investigated the antibody to GBS in these elderly patients. The titers of GBS antibody were significantly higher in the group with GBS isolates than in the group without these pathogens.
These results suggest that GBS is one of the causative organisms of nosocomial infections in elderly patients.

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In 1992, we reported a new scheme for identifying 21 distinct serovars of E. faecalis by the bacterial agglutination reaction. In this study we isolated strains of E. faecalis from the urine of patients with urinary tract infections and serotyped. We also serotyped strains of E. faecalis isolated from the faces of healthy persons. The results showed that serovars 2, 7, 1 and 3 were the major serotypes a distribution on strains of E. faecalis isolated from patients. Serovars 2, 1 and 13 were the major serotypes of the fecal strains isolated from healthy persons. Single serovars were typable of all strains of E. faecalis isolated from patients in 80.6%(395/496) and in 62.4% of the fecal strains.
Examination of the hemolytic zone around colonies on horse/sheep blood agar plates showed that β-hemolytic strains on horse blood agar plate isolated from patients had 36.1% for all isolated strains from patients and 8.3% for fecal strains isolated from healthy persons.

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A survey study for Vibrio cholerae in imported seafood was conducted during January 1991 to December 1994. A total of 7, 439 specimens (approximately 20% of all imported food) were randomly picked up and examined for contamination of V. cholerae. Among these, V. cholerae 01 were isolated from 9 specimens, but they were all cholerae enterotoxin (CT)-negative. In terms of V. cholerae non-01, a total of 2, 803 specimens (37.4%) were contaminated with this vibrio. Shrimp, especially the ones still in their shells and imported from Asian countries such as India and Indonesia, were highly contaminated with V. cholerae. Although no strains of V. cholerae 01 isolated in this study produced CT, 2 strains of V. cholerae non-01 were proved to be CT-producers. Taking together the high contamination of V. cholerae in imported seafood and a part of those strains producing CT, we believe that careful survery for the possible contamination of V. choleare in imported seafood is necessary.

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This study was conducted to invesitigate the relative frequency of Staphylocossus spp. and coagulase negative Staphylococci (CNS) isolates from urine at Juntendo University Hospital in Tokyo.
The frequency of Staphylococci spp. was encountered in about 10% of the cases from 1984 to 1994 (except 1992 and 1993), and no significant annual changes were observed. The frequency of Staphylococcus aureus has been gradually increasing from 1986.
The relative frequency of CNS (321 strains) from 1989 to 1994 were as follows; Staphylococcus epidermidis 36%, Staphylococcus saprophyticus 26%, Staphylococcus haemolyticus 22%, Staphylococus caprae 8%, and other CNS 8%.

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This study was conducted to investigate the antimicrobial susceptibilities of the strains of coagulase negative Staphylococci (CNS) isolates from urine at Juntendo University Hospital in Tokyo from 1989 to 1994. The susceptibility testing were performed according to the broth dilution method standerdized by the Japan Society of Chemotherapy.
The following bacteria were tested; Staphylococcus epidermidis (59 strains), Staphylococcus haemolyticus (42 strains), Staphylococcus saprophyticus (30 strains). The antimicrobial agents tested wre as follows; Oxacillin, Cefazolin, Imipenem, Flomoxef, Gentanicin, Tobramycin, Arbekacin, Clindamycin, Tetracycline, Minicycline, Vancomycin, Sulfamethoxaxole-Trimethoprim and, Ofloxacin.
1. 100% of S. caprae, 62% of S. haemolyticus and 42% of S. epidermidis were resistant to Oxacillin. All strains of S. saprophyticus were sensitive to Oxacillin.
2. S. saprophyticus showed the highest sensitivities to all anti-microbial agents.
3. All strains of S. caprae were resistant to Tobramycin and Clindamycine.
4. Vancomycin and Arbecacin has strong antimicrobial activities to all CNS.
S. saprophyticus, which is the pathogen of acute urinary tract infections, showed high sensitivities to many antimicrobial agents.
On the other hand, S. haemolyticus and S. caprae, which are the predominate microorganisms of bacteriuria of inpatients, showed high resistance rates to antimicrobial agents.

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A case of catheter-related fungemia due to Hansenula anomala is reported. A 61-year-old male was diagnosed as having stage 3 ascending colon carcinoma stenosing the colon severely and was admitted to our hospital to receive an operation of the carcinoma. Just after admission, an intravenous hyperalimentation (IVH) catheter was inserted and IVH was started to prevent development of ileus and to prepare for laparotomy. Nine days later, he developed a fever. On the next day, the IVH catheter was removed and cultures of blood and the catheter revealed the presence of yeast-like organisms that were identified as H. anomala. Laboratory data showed hypogranulocytemia, slight disturbances of liver and kidney, a prolongation of PT, an increase of FDP and positive reaction of candida antigen by CAND-TEC^®. He improved after the removal of the catheter, and treatment with intravenous infusion of fluconazole 2 days after the removal was thought to be useful for recovery and to prevent the reappearance of infection though susceptibility to fluconazole was not good. Human infections due to H. anomala are rare and this is the 8th case of H. anomala fungemia in Japan. From this report and a review of the literature, risk factors for developing this fungemia include the use and abuse of central venous catheters such as IVH-catheter. It appears that H. anomala has recently emerged as a potential pathogen in the immunocompromised hosts and patients after insertion of cental venous catherters and that these organisms should be added to the growing list of unusual fungal pathogens in these patients.

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We experienced a 6 month-old infant who suffered from staphylococcal scalded skin syndrome (SSSS), whose mother used steroid ointment for the infant's erythematous skin rash for 2 days. On the 3rd day, the infant was admitted to our hospital with fever, erythema on the trunk and extremities, and flaccid blisters and erosions at periorificial areas and the neck. Nikolsky's sign was positive. S. aureus was cultured from the throat, conjunctival inflammatory lesion and exudates. The biological characteristics of the isolates were coagulase type I, enterotoxinnonproducing, TSST-1-nonproducing, protease pattern: D type, and plasmid profile: 563 kbp. The investigation of exfoliative toxin (ET) revealed negative for ET-A but positive for ET-B, proved by polymerase chain reaction (PCR). The isolated strain of S. aureus was demonstrated to be methicillin-resistant (MRSA), which was further defined to be positive for mec A gene by PCR method. It will be possible for such toxigenic ET-B producing MRSA to gain the dominant status in NICU or closed areas.

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