The clinical usefulness of treatment with erythromycin for diffuse panbronchiolitis (DPB) patients have been well reported to date, although its mechanisms remain unknown. In a previous study, we demonstrated that DPB patients were found to have large percentages of neutrophils in their lower respiratory tracts and suggested that neutrophils play an important role in the pathogenesis of DPB (Chest 99: 917-923, 1990).
While in vitro and in vivo studies have demonstrated that erythromycin decreases neutrophils directed migration.
In the present study, we performed bronchoalveolar lavage (BAL) on eight patients with DPB to clarify the cell populations in the lower respiratory tract before and after treatment with erythromycin. Neutrophils percentages in BAL fluid were significantly reduced after treatment with erythromycin (54.3±22.4% to 13.1±13.5%, p<0.01). No significant variance of BAL lymphocyte percentages was demonstrated after treatment with erythromycin.
These results suggest that a main mechanism of clinical usefulness of treatment with erythromycin for DPB may be inhibition of neutrophils migration into the lower respiratory tract instead of intrapulmonary bactericidal activity against organisms.

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The effects of antimalarial treatment on the blood oxygen-transporting properties and on the tissue hypoxia were investigated in severe murine malaria, using mice infected with Plasmodium berghei (NK65). Five week old male ddY mice were inoculated intraperitoneally with 1×10⁷ of P. berghei-infected red blood cells and treated with Fansidar _® (20mg/kg body weight sulfadoxine and 1 mg/kg body weight pyrimethamine orally) on day 5 after inoculation. Parasitemia in these mice decreased rapidly on day 1 after treatment. Blood hemoglobin concentration, however, decreased on days 1 and 2 of treatment, then began to increase. The actual oxygen equilibrium curve (OEC) in vivo (actual pH; actual Pco₂; 36.5°C) was calculated from the measured OEC and the results of blood gas analysis. Looking from arterial and venous Po₂ of each group, blood oxgyen-transporting properties decreased markedly on day 2 of treatment. This decrease resulted mainly from the decrease of hemoglobin concentration and also partly from the raised hemoglobin affinity for oxygen. Adenosine triphosphate concentration in liver tissues, however, began to increase on day 1 of treatment. Adenylate energy charge of liver tissues also recovered on day 1. Blood glucose concentration began to increase and blood lactate concentration began to decrease simultaneously on day 1 of treatment. Glucose concentration in liver tissues, in contrast, decreased on days 1 and 2 of inoculation. Lactate concentration in liver tissue decreased earlier on day 1. These data indicate that tissue hypoxia was removed on day 1 following antimalarial treatment although bloo oxygen-transporting properties decreased on days 1 and 2 after treatment. It was suggested the blood oxygen-transporting properties were compensated by another mechanisms.

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The pharmacokinetics of cefpirome (CPR), a new injectable cephem, were studied in 9 patients with various degrees (classified by Ccr.) of impaired renal function.
Serum and urinary concentrations of CPR were measured by bioassay. The pharmacokinetic analyses were based on a two compartment open model.
As renal impairment increased, higher serum concentrations were maintained in β-phase and higher urinary concentrations were kept over a long time, as well. As a conclusion, it is necessary to consider the adequate administration and dosage for patients with renal impairment to prevent side effects caused by the maintenance of cefpirome in serum over a long time.

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We examined the infectivity of the TK-1 strain of Coxiella burnetii against three strains of mice, athymic nude mice of BALB/c strain, several kinds of macrophages from these mice, and established cell lines.
All A/J, BALB/c and C57BL/6 murine strains were resistant against the intraperitoneal infection with TK-1 strain, but an enhancement of susceptibility of mice were revealed by the administration of cyclophosphamide (CPA) in BALB/c and A/J strains. CPA-treated BALB/c mice allowed an increase of TK-1 strain up to 1.7×10⁶ coxiellar particles/mg spleen. But athymic nude mice of BALB/c strain showed only a slight increase of coxiellar particles in spleen. The resident peritoneal macrophages from BALB/c and A/J, but C57BL/6, showed proliferation of the TK-1 strain in the large infected cell population, and a part of the infected macrophages allowed TK-1 strain to survive. On the other hand, the elicited peritoneal macrophages from resistant C57BL/6 showed the largest infected cell population, number of intracellular coxiellar particles, and following decrease of TK-1 strain in later stage of infection. These in vitro infectivity of TK-1 strain seemed to relate to the in vivo infectivity in mice, and indicated existence of macrophage subpopulation, in which destruction or proliferation of TK-1 strain occurred.

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DNA probe-assay using the Gen-Probe kit was carried out to detect Mycoplasma pneumoniae infections.
Fifteen children visited Ota General Hospital complaining of dry cough and high grade fever. Throat swabs of the patients were examined to detect M. pneumoniae ribosomal RNA by Gen-Prove kit. Five out of 15 patients were positive for DNA probe assay of M. pneumoniae. Clinical and laboratory data including serological examinations were compatible with M. pneumoniae infection in these cases. Following the improvement of clinical symptoms and signs by receiving erythromycine or minocycline, the positivity for DNA probe assay turned to negative.
Among the ten patients, who were negative for DNA probe assay, 2 cases were suspected of M. pneumoniae infection on the basis of clinical and laboratory findings. One patient had already taken antibiotics. Therefore, in these two patients, there was a possibility that the bacterial numbers were too small to be detected by DNA-probe assay.
The data described above support that DNA-probe assay is useful for the diagnosis of M. pneumoniae infections in the early stage. DNA-probe assay is also valuable to follow up the clinical course of the patients.

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A total of 184 strains of S. Enteritidis isolated from patients with sporadic cases of diarrhea during the period from April 1985 to March 1991 in Yamanashi Prefecture, were examined for their drug susceptibility, phage typing and plasmid profile.
The results can be summerized as follows:
1) In 1989, cases of sporadic diarrhea due to S. Enteritidis has drastically increased twentyeightfold from 4 to 112 cases.
2) The most predominant ages of S. Enteritidis isolates were that of 2 years age.
3) The predominant phage type (PT), accounting for almost 71% of the strains isolated, was PT 34 in 1989.
4) Eighty-two (73.2%) out of 112 strains of S. Enteritidis were resistant to SM single in 1989. In 1990, SM single resistant strains were 49 (90.7%) out of 54 strains of S. Enteritidis.
5) The predominant plasmid profile of S. Enteritidis isolates were 60, 55 Kbp plasmids.
6) In 1989, the characteristic of S. Enteritidis isolated from the cases of sporadic diarrhea were resistant to SM single, identified as belonging to PT 34 or PT 4. Almost S. Enteritidis strains of PT 34 carrying 60, 55 Kbp plasmids and many strains of PT 4 S. Enteritidis possessed only 60 Kbp plasmid.

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Vibrio cholerae non-01 was isolated at six locations on each of two different rivers in 1984 and 1985. A study of the strains isolated from these rivers according to antibiotic and metal susceptibility and the incidence of resistant strains produced the following results.
1) Tests to determine susceptibility to eight antibiotics (chloramphenicol, tetracycline, streptomycin, kanamycin, ampicillin, gentamicin, nalidixic acid and polymyxin-B) indicated that there was virtually no difference in the susceptibility of strains isolated from the two rivers. Of the 115 environmental strains, 81 (70.4%) showed resistance to one or more drugs. However, no strains were resistant to gentamicin. There was considerable variation in the concentration of susceptibility to polymyxin-B, and for this reason it was difficult to determine the resistance concentration.
2) 64.3%(74/115) of the strains isolated from the two rivers showed ampicillin resistance and produced β-lactamase.
3) 67.9%(55/81) of all resistant strains were resistant only to ampicillin, while 16.0%(13/81) were resistant to ampicillin and nalidixic acid. The rate of resistance to these substances was higher than to the other drugs.
4) The incidence of resistant strains differed according to environmental conditions along the two rivers. These variations appear to reflect the influence of environmental conditions in the catchment areas.
5) There was no metallic contamination in either the Sagami River, which has good water quality, or the Sakai River, which is heavily polluted. This meant that there was no variation in the metal susceptibility of the isolated strains according to differences in the degree of water pollution. Furthermore, none of the strains showed resistance to metals

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Bacterial meningitis is one of complications in the elderly with neurosurgical procedures. In an attempt to find the clinical features of this complication we analyzed 10 cases, which were found in 30 cases of the bacterial meningitis in Tokyo Metropolitan Geriatric Hospital from 1972 to 1989. The patients were 4 males and 6 females, 52-86 years old (the mean, 69).
While 2 Enterococcus species were isolated after craniotomy, Staphylococci were common pathogens (4 S. aureus, 4 S. epidermidis and 1 P. aeruginosa) in patients with shunt infection. Most of these patients lacked typical manifestations of meningitis except the fever. Symptoms occurred long after surgery with little abnormality in the data of serum and cerebrospinal fluid. However, blood cultures were positive in 75% of the cases. Removal of the infected catheter was effective in the cases of shunt infection.

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A polymerase chain reaction (PCR) with Chlamydia trachomatis-specific primers was applied for detection of C. trachomatis from urethral swab in male urethritis. The results were compared with those of culture method for detection of C. trachomatis. Of 18 clinical specimens tested in this study, inclusion bodies of C. trachomatis were detected in 11 specimens by the culture method. For PCR, sample DNA was prepared from transpot medium in which urethral smear was suspended and two oligonucleotides based on sequences within the major outer membrane protein gene from C. trachomatis serovar L₂ were used as extension primers. In 12 of the 18 specimens, 242bp DNA fragment was amplified by PCR and demonstrated to be the DNA fragment of C. trachomatis by Southern blot hybridization. No DNA of 242bp was amplified by PCR from five specimens in which any inclusion bodies of C. trachomatis were observed or from a specimen in which one inclusion body per cover slip was detected by culture method. C. trachomatis DNA of 242bp was amplified from all specimens in which 14 and more inclusion bodies per cover slip were detected by culture method. In two specimens concluded s negative by culture method, amplified C. trachomatis DNA were detected by PCR. Thus, the PCR would be a more simple and sensitive method for detection of C. trachomatis, compared with the culture method.

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The new Micro Particle Enzyme Immunoassay technique (META, IMx HBc-M, Abbott) had been recently introduced for the detection of IgM class antibody to hepatitis B core antigen (IgM anti-HBc).
To evaluate the feasibility of using the IMx HBc-M, we carried out comparison tests between this method. RIA and EIA using sera from acute hepatitis B and type B chronic liver disease.
Results obtained were as follows:
In the test of 98 sera from acute hepatitis B patients, 92 (93.9%) were positive for IgM anti-HBc by IMx HBc-M, 96 (98.0%) by RIA and 82 (83.7%) by EIA. The four sera which were positive by RIA, but not by IMx were ones obtained from 5 to 12 month after onset.
In the test of 267 sera from B type chronic liver disease patients, 93 (34.8%) were positive by IMx HBc-M, 109 (40.8%) by RIA and 23 (8.6%) by EIA. There was a difference in the positive rate between IMx HBc-M and RIA among type B chronic liver disease: the positive rate was higherin RIA than in IMx HBc-M among type B active chronic hepatitis, but only a little higher in IMx HBc-M than RIA among hepatocellular carcinoma.
IgM anti-HBc titer was significantly higher in acute hepatitis type B than in chronic liver disease, and was so even in the phase of HBsAg negative in acute hepatitis.
IgM anti-HBc was assayed within 45 minutes by IMx, and the procedure was simple because of the auto analyser used in this method.
These results indicate that the sensitivity of IMx is equivalent to that of RIA and higher than that of EIA, and that it is easier to use than either RIA or EIA.

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Bacterial colonization of the pharynx before and one week after operation, and contamination of the trachea during intubation in 7 patients who underwent operations were investigated. And bacterial colonization of pharynx, tracheas, and mechanical-ventilators in 7 ICU patients was investigated. Flora of palms of 10 ICU personnel was also examined
1) Oral bacteria began to be found in the trachea several hours after intubation.
2) In oropharyngeal flora, one week after operation, Neisseria and anaerobes whichbelong to normal flora decreased because of antibiotics, but no new resistant bacteria appeared.
3) Although isolates from pharnx of preoperative patients were normal flora, those of ICU patients were Staphylococcuse pidermidis, Enterococcu spp., gram-negative rods such as Pseudomonas aeruginosa, and yeast liked organisms etc, which were resistant to antibiotics.
4) From the trachea of intubated patients in ICU, oral bacteria were isolated.
5) Pseudomonas pickettii was isolated from the expiratory side of ventilator circuits in one patient, but it was not isolated from the patient.
6) From hands of ICU personnel, gram-positive bacteria such as coaglase negative staphylococci, Croyne bacterium spp. and Bacillus spp. were isolated.
7) One patient in ICU, who developed pneumonia due to resistant Bacteroides fragilis following oropharyngeal colonization, was reported.
These studies suggested the importance of environmental control, careful selection of antibiotics, and attention to change of flora.

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Distribution of Legionella spp. were surveyed two different times in Kinki District, Japan. The first time, eighty six building cooling tower waters were collected from Osaka, Hyogo and Nara Prefecture between April and December, 1987. The second time, thirty five waters were studied from Nishinomiya City in Hyogo Prefecture on July, 1989. BMPAα agar plate was used as the isolation medium for the first eighty six samples and MWY agar plate for the second thirty five samples.
Legionella were isolated from forty two samples (48.8%) of the first eighty six samples. Three different species of Legionellawere isolated simultaneously from one sample and two species from eight samples.L. pneumophilaserogroup 1 was the most predominant species.Twenty three samples (65.7%) were positive in culture from the second thirty five samples. Three different species of Legionella were isolated simultaneously from three samples and two species from eleven samples. Legionella anisa was more predominant than L. pneumophila serogroup 1 in this study.

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Ninety-eight cases of empyema thoracis admitted to Juntendo University Hospital between 1979 and 1990 were reviewed. Males accounted for 78 cases and females 20 cases. Thirteen pediatric patients ranged in age from 17 days to 4 years, while the 85 adult cases ranged from 16 to 89 years (mean: 58.4 years). The mortality rate increased with age. Fifty-three cases of community-acquired empyema thoracis consisted of 24 with no underlying disease (including 13 pediatric cases), and 29 with diabetes mellitus, alcoholic liver damage or chronic obstructive bronchopulmonary disease. Forty-five nosocomial empyema cases occurred after chest operation or thoracocentesis, or due to a subdiaphragmatic pathogenic condition or congestive heart failure complicated with aspiration pneumonia. In this series, 63 patients (64.3%) had para-or post-pneumonic empyema. Compared with the community-acquired infection cases, the mortality rate of the nosocomial infection cases was very high.
Seventy-eight cases were culture-positive, including 3 positive for Mycobacterium tuberculosis. The remaining 20 cases were culture-negative.
In 75 cases of culture-positive pleural fluid, aerobic bacteria were isolated from 31 cases (mortality rate: 22.6%), anaerobes mixed with aerobes from 21 cases (mortality rate: 52.4%), and anaerobes only from 23 cases (mortality rate: 21.7%). Thus, the mortality rate of mixed infected cases was highest.
Anaerobes were frequently isolated from the community-acquired empyema cases, and were often found in para-or postpneumonic lesions, including aspiration pneumonia.
The most commonly encountered aerobe was Staphylococcus aureus. Among the anarobes, Bacteroides spp., microaerophilic streptococcus, Peptostreptococcus and Fusobacterium spp. were most common. A single organism was isolated in pure culture from 39 cases. Single organisms isolated fromfluids were more frequently aerobes (25) than anaerobes (14).
The cases harboring Bacteroides spp. showed the worst outcome, with 11 deaths in 25 such cases.

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Using mainly changes in the amount of sputum as an index of the infectious course of chronic lower respiratory tract infection associated with purulent sputum over years, the disease was divided into stable and acute exacerbated phases and a bacteriological investigation using transtracheal aspiration (TTA) conducted. TTA was performed 107 and 45 episodes during stable phases and acute exacerbated phases respectively.
Monomicrobial and polymicrobial infection were detected most frequently during the stable and acute exacerbated phases repectively (p<0.01). During the stable phases, the single organisms detected most frequently were H. influenzae (26 episodes) and P. aeruginosa (20 episodes), while in the cases in which multiple organisms were detected during stable phases, combination including H. influenzaewere most common (19 episodes).
H. influenzae was the most frequently detected organism in cases showing single organisms during acute exacerbated phases (7 episodes). In the cases in which multiple organisms were detected as well, H. influenzae was the most commonly detected organism assumed to predisopse to exacerbation (7 episodes), while P. aeruginosa was not found.
These results suggest that in chronic lower respiratory tract infection. H. influenzae and P. aeruginosa are important as persistent infective organisms, while H. influenzae are important in acute exacerbation.

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In December 1989, an outbreak of gastroenteritis associated with cake consumption occurred in a day-care center with 60 children and 12 staff in Saitama prefecture. Children were served cakes at the Christmas party held in the day-care center and ate them with their families. Thirtythree of the 59 children (56%), 16 of the 74 families (22%) and 1 of the 10 staff (10%) eating the cakes became ill. Illness consisted primarily of nausea, vomiting, diarrhea and fever; the median incubation period was 31 hours.
Bacteriological analysis of stool specimens did not reveal a causative agent. Small round structured viruses (SRSV) were detected in fecal specimens from 10 of the 17 ill children (59%) and 2 of the 6 ill families (33%) by electron microscopy.
Cakes were purchased from a bakery where an employee who prepared he cake denied symptoms, and SRSV was not detected in the fecal specimen from the employee. Thus, it was not determined that the cake was contaminated by a food handler.

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Three chlamydial strains isolated from patients of otitis media with effusion were studied by comparing reactivity to monoclonal antibody (MAb) and polyclonal antibody (PAb) produced against one clinical isolate (named Mk), which was first isolated by Dr Mukai (Mukai Microbiological Research Laboratory, Yamato-shi, Kanagawa prefecture). Commercially supplied antibody (Microtrak ^® (S yva), Culture-set ^® (Ortho diagnostic system)) was also used. To isolate the Chlamydia spp, the yolk sacs of eggs were immediately inoculated with sample effusions (0.2 to 0.4 ml per sac) as soon as the samples were received. The eggs were observed every day for a period of 12 days thereafter for signs of life or death. One to two blind passages were first done in the eggs and then in HeLa 229 cells. The reactivity was examined by both micro-IF tests, among various strains of Chlamydia (C. trachomatis: L2. C.pneumoniae, C. psittaci: Budgerigar, Izawa, Meningopneumonitis (MP)) and by immunoblot analysis.
Chlamydia spp were isolated in two of the twenty-nine sample effusions (6.9%). These isolates were then tested for reactivity to MAb and PAb. It was found that MAb reacted with MP and Mk, but not with Budgerigar, Izawa and C. pneumoniae. The antibody of Culture-set ^® reacted with C.trachomatis C. pneumoniae and C. psittaci. No reactivity was observed in Mk by MicroTrak ^®. Immunoblot analysis revealed that MAb reacted with about 95 KDa protein of Mk, the two clinically isolated Chlamydia spp and MP. By using PAb from rabbits, similar blotting patterns were observed in Mk, the clinical isolates and MP. But the 70 KDa protein band which exists in Mk and MP was not observed in the clinical isolates. We could see a 40 KDa protein band in both Mk and the clinical isolaters, whereas the band was hardly visible in MP.
It has been well known that in human-to-human spreading of infectious diseases caused by Chlamydia, C. pneumoniae and C. trachomatis are the only causative agents. Our results indicate, however, that the clinical isolates belonged toC. psittaci and were similar to C. psittaci strain MP. This leads us to assume that the Chlamydia spp isolated here may be of mammal origin and may be acausative agent in human-to-human infection.

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Case I: A middle-age homosexual male developed AIDS with Pneumocystis carinii pneumonia (PCP) and esophageal candidiasis in 1986 during his stay in an European country about five months prior to transfer to Tokyo Metropolitan Komagome Hospital, Tokyo, in 1987.He was also diagnosed as having cryptosporidiosis presenting with mild diarrhea a month following the diagnosis of PCP. Diarrhea was successfully treated with spiramycin. On transfer to Tokyo Metropolitan Komagome Hospital, he was febrile but had no diarrhea. Serum HIV and TPHA were positive and his blood lymphocyte subset T4a was markedly decreased. On the 13th day after transfer to the hospital, watery diarrhea appeared. Cryptosporidium oocysts were detected from the feces taken on the 17th hospital day. The patient died of Escherichia coli septicemia on the 38th hospital day. Autopsy finding yieldedCryptosporidium infection widely spread over the stomach, ileum, bile and pancreatic ducts.
Case II: A 31-year-old previously healthy female presented with abrupt onset of mucous stool five times daily. Mucous passage continued on the subsequent days despite administration of loperamide, and the passage increased to 20 times daily with mucous to watery diarrhea associated with mild abdominal cramps and nausea on the 4th day after onset of illness. On the 6th day of illness, she visited Tokyo Metropolitan Komagome Hospital. She denied close contact with pet animals or contact with any person presenting diarrhea. She had no recent history of travelling anywhere outside Tokyo. On examination she was an apparently healthy woman except for a slightly distended abdomen with localized tenderness in the right upper quadrant. Microscopic examination of her watery stool by sugar flotation technique yielded numerous Cryptosporidium parvum oocysts. Acetylspiramycin 1.2g daily was started from the 9th day of illness and was administered for 14 days. She recovered from diarrhea within several days. Blood tests for HIV and syphilis, conducted with the informed consent of the patient, were negative.

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Three patients with hepatic fascioliasis are presented.
(case 1) A 36-year-old female was admitted in January, 1988, because of intermittent high-grade fever. Laboratory findings included white blood cell count 8, 050/mm³ with 29% eosinophils, and CRP9.5 mg/dl. There was a positive intradermal reaction to Fasciola hepatica antigen. Liver biopsy revealed eosinophilic abscess, granulation and many Charcot-Leyden crystals.
(case 2) A 54-year-old male was admitted in June, 1985, because of abdominal fullness. Marked hepatomegaly was noticed. Laboratory findings included white blood cell count 10, 200/mm³ with 26%eosinophils, and CRP 2.2 mg/dl.
(case 3) A 48-year-old male was admitted in March, 1989, because of intermittent high-grade fever. Hepatomegaly was noticed. Laboratory findings included white blood cell count 7, 310/mm³ with30.3% eosinophils, and CRP 3.5 mg/dl. His condition was complicated by pleuritis with invasion of Fasciola hepatica.In all patients, stool specimens were negative for ova and immunoelectrophoresis was positive forF. hepatica antigen. Computed tomography demonstrated multiple low-density areas in the periphery of the liver in cases 1 and 3, and disseminated areas in case 2. After treatment with bithionol 40mg/kg every other day for 40 days, all three patients became asymptomatic.

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