Frequency of food-dependent, exercise-induced anaphylaxis in Japanese junior-high-school students.

BACKGROUND: Food-dependent, exercise-induced anaphylaxis (FEIAn) is classified among the physical allergies. The pathophysiology of FEIAn remains unknown, as does the frequency of FEIAn in the general population. OBJECTIVE: We sought to study the epidemiology of FEIAn, especially its frequency in junior-high-school students in Yokohama, Japan. METHODS: A questionnaire asking about the occurrence of FEIAn in school students was sent to all 145 public junior-high-school nurses in Yokohama. RESULTS: One hundred thirty-two junior-high-school nurses responded to the questionnaire, and 13 (11 boys and 2 girls) cases of FEIAn among 76,229 junior-high-school students were reported. In addition, 24 (12 boys and 12 girls) subjects with exercise-induced anaphylaxis (EIAn) were detected. From this survey, the frequency of FEIAn was 0.017% in this population, and its frequency was significantly higher in boys than in girls (P < .05). The frequency of EIAn was 0.031%, and there was no difference according to sex. Only one third of junior-high-school nurses had any knowledge of FEIAn. We also performed provocation tests in 5 of the 13 cases with FEIAn after obtaining informed consent from the students and their parents and were able to confirm the diagnosis. CONCLUSION: This study showed that FEIAn and EIAn are relatively rare diseases among junior-high-school students in Yokohama. To avoid serious outcomes, we believe it is important that not only physicians but also school nurses and teachers of physical education be aware of these diseases.

[Hospital infection control in 21st century, the importance of networking with each division and clinical laboratory in the hospital. 1. From the aspect of clinical laboratory division].

Clinical laboratory division plays an important roll for the management of nosocomial infection. Staff from clinical laboratory division including technologist and/or medical doctor can work as a part of infection control team. Since the bacterial surveillance data from clinically isolated strains accumulates in the clinical laboratory division, these staff have a chance to notice outbreak in hospital at first time. While handling information from each strain, we need to feedback these data with additional information for physicians. From June, 2000, a national project started. That was a surveillance program for drag-resistant bacteria. We can compare information from local isolates and nation-wide isolates by this project. Genotypic methods especially pulsed-field gel electrophoresis(PFGE) is suitable for the identification of infection route in the hospital environment. And PFGE analysis for pathogenic strains works effective in our hospital.

[Molecular analysis of pathogens of upper respiratory tract infections in children--a study of nasopharyngeal S. pneumoniae and PBP genes in acute otitis media].

We have recently been confronted with refractory upper respiratory infections with an increasing prevalence of penicillin (Pc)-resistant S. pneumoniae. There has been a broad consensus that acute otitis media (AOM) is caused by migration of pathogens from nasopharynx and proliferation in the middle ear space, and thus it is, very important to study the bacterial environment in the nasopharynx as the source of middle ear infections. Eighty pneumococcal isolates from the nasopharynx of children with acute otitis media were evaluated by polymerase chain reaction (PCR) for mutation of Pc-binding protein (PBP) genes. The results showed mutation of all three PBP genes, pbp 1a, pbp 2x, and pbp 2b, in 30% of the isolates, while 74% were found to possess various PBP gene mutations, mostly in one-year-old children. Of the 46 isolates whose minimum inhibitory concentration (MIC) of Pc was < or = 0.06 microgram/mL, 43% were found to possess a pbp 2x mutaion, which affects cefem resistance. We genotyped each pneumococcal isolate from the nasopharynx of children with recurrent AOM by pulsed-field gel electrophoresis (PFGE). In 9 of 11 pairs (82%) of consecutive AOM episodes, the nasopharyngeal isolate in the second episode was different. In addition, discrimination of each isolate based upon the mutation profile of its PBP genes in 8 pairs (72%) of consecutive AOM episodes showed that the isolates were different, and there was little difference between the results of PBP gene mutation and PFGE analysis. These findings suggest that most nasopharyngeal isolates from children with AOM possess PBP mutations and that children with increased numbers of drug-resistant bacteria in their nasopharynx during AOM has been colonized or recolonized by different strains during each episode. We therefore emphasize that clinicians should assess the antibiotic susceptibility of nasopharyngeal isolates from children during each episode. PBP gene mutation analysis of S. pneumoniae is useful not only in providing valuable information on the antibiotic susceptibility of each strain but for assessing changes in causative strains in the sequential episodes of pneumococcal infection.

[Gene examination methods (detection and genotyping of resistant genes)--MRSA].

Molecular diagnosis of MRSA infection including methods of detecting drag-resistant gene and genotyping is described. In Japan, MRSA is the major pathogen for nosocomial infections. For symptomatic patients with MRSA infection, rapid detection of mecA and spa gene by PCR is quite critical to their prognosis. In cases of carry-over contamination of PCR products and mixed infection with coagulase-negative Staphylococci, take precautions are needed while working with this examination. Analysis by restriction length polymorphisms using pulsed-field gel electrophoresis (PFGE-RFLPs) for MRSA nosocomial infection is also described.

[Why there were few isolations of tubercle bacilli in young children with pulmonary tuberculosis?].

We retrospectively evaluated the factors influencing the isolation of tubercle bacilli in 51 children under 14 years of age with pulmonary tuberculosis who were admitted to Yokohama City University Hospital from 1975 to 1998. Young children (0-6 years of age) with pulmonary tuberculosis were significantly less positive by smear and culture than elder children (7-14 years of age) with pulmonary tuberculosis. According to the Japanese Society for Tuberculosis classification of finding on chest X-ray film for pulmonary tuberculosis, the culture-positive patients with type II (cavitary lesions) were found in all, the culture-positive patients with type III (non-cavitary lesions) in 39.3%, and the culture-positive patients with type H (hilar and mediastinal lymphadenopathys) in 35.3%. Patients with cavitary lesions (type II) were significantly more positive by smear and culture than patients with non-cavitary lesions (type III + type H). Only 15.8% of the young children with pulmonary tuberculosis had received BCG vaccine and all had non-cavitary lesions (type III and type H). But, 84.6% out of the older children had received BCG vaccine and half had cavitary lesions. Taken together, the result was that there were few isolation of tubercle bacilli in young children with pulmonary tuberculosis because they had non-cavitary tuberculosis without delayed-type hypersensitivity to tubercle bacilli.

Early coding of reaching in the parietooccipital cortex.

Neural activity was recorded in the parietooccipital cortex while monkeys performed different tasks aimed at investigating visuomotor interactions of retinal, eye, and arm-related signals on neural activity. The tasks were arm reaching 1) to foveated targets; 2) to extrafoveal targets, with constant eye position; 3) within an instructed-delayed paradigm, under both light and darkness; 4) saccadic eye movements toward, and static eye holding on peripheral targets; and 5) visual fixation and stimulation. The activity of many cells was modulated during arm reaction (68%) and movement time (58%), and during static holding of the arm in space (64%), when eye position was kept constant. Eye position influenced the activity of many cells during hand reaction (45%) and movement time (51%) and holding of hand static position (69%). Many cells (56%) were also modulated during preparation for hand movement, in the delayed reach task. Modulation was present also in the dark in 59% of cells during this epoch, 51% during reaction and movement time, and 48% during eye/hand holding on the target. Cells (50%) displaying light-dark differences of activity were considered as related to the sight and monitoring of hand motion and/or position in the visual field. Saccadic eye movements modulated a smaller percentage (25%) of cells than eye position (68%). Visual receptive fields were mapped in 44% of the cells studied. They were generally large and extended to the periphery of the tested (30 degrees ) visual field. Sixty-six percent of cells were motion sensitive. Therefore the activity of many neurons in this area reflects the combined influence of visual, eye, and arm movement-related signals. For most neurons, the orientation of the preferred directions computed across different epochs and tasks, therefore expression of all different eye- and hand-related activity types, clustered within a limited sector of space, the field of global tuning. These spatial fields might be an ideal frame to combine eye and hand signals, thanks to the congruence of their tuning properties. The relationships between cell activity and oculomotor and visuomanual behavior were task dependent. During saccades, most cells were recruited when the eye moved to a spatial location that was also target for hand movement, whereas during hand movement most cells fired depending on whether or not the animal had prior knowledge about the location of the visual targets.

[A child of microscopic polyarteritis nodosa effectively treated with intravenous methylprednisolone pulses and serial cyclophosphamide pulse therapy].

Microscopic polyarteritis nodosa (mPAN) is a rare disorder in pediatric field of systemic small vessel vasculitis, and affects skin and musculoskeletal system accompanied by progressive necrotizing glomerulonephritis. We described here a 15-year-old boy with positive anti-neutrophil cytoplasmic antibody (MPO-ANCA) and severe mPAN, who was effectively treated with intravenous methylprednisolone pulse therapy followed by monthly cyclophosphamide pulses for 1 year. The histologic examination of renal biopsy specimen showed a severely desolated disease characterized by fibrinoid necrosis, crescent formation of most glomeruli and interstitial infiltration of inflammatory cells. The elevated titers of MPO-ANCA were useful markers for diagnosis, and the serial determinations of the antibody titers were indicative of disease activity. Moreover, dramatic clinical improvement after the induction of the combinatorial therapy and the disappearance of MPO-ANCA was correlated in the disease course. In this report, the serial determination of MPO-ANCA constituted a useful diagnostic tool and a sensitive marker of disease activity.

Early coding of reaching: frontal and parietal association connections of parieto-occipital cortex.

The ipsilateral association connections of the cortex of the dorsal part of the rostral bank of the parieto-occipital sulcus and of the adjoining posterior part of the superior parietal lobule were studied by using different retrograde fluorescent tracers. Fluoro-Ruby, Fast blue and Diamidino yellow were injected into visual area V6A, and dorso-caudal (PMdc, F2) and dorso-rostral (PMdr, F7) premotor cortex, respectively. The parietal area of injection had been previously characterized physiologically in behaving monkeys, through a variety of oculomotor and visuomanual tasks. Area V6A is mainly linked by reciprocal projections to parietal areas 7m, MIP (medial intraparietal) and PEa, and, to a lesser extent, to frontal areas PMdr (rostral dorsal premotor cortex, F7) and PMdc (F2). All these areas project to that part of the dorsocaudal premotor cortex that has a direct access to primary motor cortex. V6A is also connected to area F5 and, to a lesser extent, to 7a, ventral (VIP) and lateral (LIP) intraparietal areas. This pattern of association connections may explain the presence of visually-related and eye-position signals in premotor cortex, as well as the influence of information concerning arm position and movement direction on V6A neural activity. Area V6A emerges as a potential 'early' node of the distributed network underlying visually-guided reaching. In this network, reciprocal association connections probably impose, through re-entrant signalling, a recursive property to the operations leading to the composition of eye and hand motor commands.

[Analysis of tuberculin reaction of tuberculous children below 4 years of age].

To clarify whether the size of tuberculin reaction could be used as an useful index of the severity of tuberculosis, we analyzed the sizes of tuberculin reaction (TR) of 60 children below 4 years of age with active tuberculosis at the time of diagnosis. Of 60 patients, 53 (88.9%) had positive reactions to tuberculin. The mean size of TR of 60 patients was 24.0 +/- 13.9 mm and maximum size was 60 mm. Seven patients who had no reaction to the tuberculin skin test consisted of three primary complex and four serious tuberculosis (two miliary tuberculosis and two tuberculous meningitis). The patients without BCG vaccination showed significantly smaller TR than the patients with BCG vaccination (p < 0.05). The patients less than 1 year of age showed significantly smaller TR than the patients of 4 years of age (p < 0.05). The patients with serious tuberculosis showed significantly smaller TR than the patients with primary complex (p < 0.05). Of patients with primary complex, there were no difference of the size of TR between the patients with pulmonary tuberculosis (III) and hilar lymphadenopathy (H). Together with, it did not necessarily mean that negative TR showed no infection with tuberculosis and the sizes of TR depended on the severity of tuberculosis in infantis and young children.

[Effective combination therapy of plasma exchange and subsequent cyclophosphamide pulses for catastrophic antiphospholipid antibody syndrome: a case report].

A 7-year-old girl with catastrophic antiphospholipid antibody syndrome was described. She firstly admitted to the local hospital with the complaints of persistent fever and abdominal pain, and was diagnosed as systemic lupus erythematosus with the laboratory findings as follows; positive for antinuclear antibody, anti-DNA antibody, and platelet-associated IgG, thrombocytopenia, and hypocomplementemia. 10 days after the initiation of oral prednisolone, she suddenly manifested tonic convulsion and unconsciousness accompanied by high fever. Because of the unresponsiveness to the methylprednisolone pulse therapy for supposed CNS lupus, she was transferred to our hospital. Her unconsciousness persisted, and pulsation on dorsalis pedis was not palpable on admission. Laboratory investigation revealed the falsely positive VDRL, a prolonged aPTT, positive for lupus-anticoagulant and antiphospholipid antibody. The magnetic resonance image demonstrated multiple spotty hyperintensity (T2) in the brain consistent with multiple hemorrhagic infarcts. Arteriogram demonstrated the infarct of dorsalis pedis, and coronary aneurysms. These findings were compatible with the criteria of catastrophic antiphospholipid antibody syndrome, she was diagnosed as catastrophic antiphospholipid antibody syndrome. The plasma exchange and subsequent cyclophosphamide-pulse therapy, which was given once a month for first 6 months, and later, at 3 months intervals, was effectively administered. This combination and oral anti-thrombotic therapy revealed effective for this kind of fatal disorder.

Molecular epidemiological study of Haemophilus influenzae serotype b strains obtained from children with meningitis in Japan.

We report an epidemiological study of 30 Haemophilus influenzae serotype b (Hib) strains derived from the cerebrospinal fluid of children with meningitis. The Hib strains were biotyped, tested for beta-lactamase production, and genotyped by long PCR-ribotyping, random amplified polymorphic DNA (RAPD) analysis, and genomic DNA restriction fragment length polymorphism (RFLP) analysis by pulsed-field gel electrophoresis (PFGE). The phenotypic study characterized 22 of the strains (73%) as biotype I. A genotypic study using long PCR-ribotyping with HaeIII restriction digestion showed no polymorphisms among these 30 Hib strains, but RAPD analysis with two sets of primers demonstrated two distinctive subtypes: one typical of the strains of biotype group II and the second characteristic of the strains of biotype groups I and IV. Each RAPD group was subtyped into several genotypic groups by PFGE-RFLP with SmaI digestion. The genotyping of clinically isolated Hib strains may help to elucidate transmission routes in community infections, endemicity, and the reasons for vaccine failure.

The influence of methicillin-resistant Staphylococcus aureus (MRSA) carriers in a nursery and transmission of MRSA to their households.

We examined two persistent MRSA-carrier nurses in a maternity hospital to elucidate the transmission of methicillin-resistant Staphylococcus aureus (MRSA) from healthcare providers to newborn infants and to the nurses' own families. Genotyping of the MRSA strains was performed by analyzing genomic DNA restriction length polymorphisms from pulsed-field gel electrophoresis (PFGE-RFLPs). The children of these nurses were carrying genotypically identical MRSA strains as their mother. Both MRSA carrier families remained asymptomatic over a two-year follow-up period. Eradication of nasal MRSA carriage from the two nurses resulted in declining MRSA carriage rates among infants in the nursery. Healthcare providers may become transient or persistent MRSA carriers whilst working in hospitals in which MRSA is endemic. They may then become a source of infection for patients as well as their own families. We recommend that healthcare providers should be examined for MRSA if an MRSA epidemic occurs in a hospital. The families of any such carriers should also be examined for MRSA.

[Computed tomography with normal chest radiography in childhood tuberculosis].

During the recent 2 years we experienced 5 children (2 months-5 years old) with lung tuberculosis, all of whom had positive tuberculin skin-tests, and were in close contact with their family members who had active tuberculosis. However, no abnormal findings on chest X-ray films were pointed out by 2 independent roentogenologists, and no increased levels of inflammatory markers including WBC numbers, CRP, and ESR were detected in all but one child. Moreover, mycobacterial examination of sputa and/or gastric aspirates by microscope, culture technique, and PCR amplification revealed no causative bacilli in 4 children. To clarify whether these children were affected by Mycobacterium tuberculosis, chest CT scan was applied. Surprisingly, all 5 children were revealed to have abnormal changes including primary complexes in the lung field. Taken together, it is important to pursuit the apparent lung tuberculosis in children with a positive family history and positive tuberculin skin-test.

[Improvement of the maintenance therapy after methylprednisolone pulse therapy--effect of prednisolone combined with immunosuppressants].

OBJECTIVES: We investigated the effect of the combination therapy of prednisolone (PSL) and immunosuppressants after methylprednisolone pulse therapy. METHODS: A protocol of PSL (15-20 mg/day) and mizoribine (150-200 mg/day) after methylprednisolone (mPSL) pulses was used for 2 years to treat 7 patients (PSL + MZB group). Cyclophosphamide (CYC) pulse therapy was added to the combined therapy in 4 patients with severe lupus nephritis. The total dose of predinisolone, and side effects were compared with those in 6 patients who were treated with PSL (30 mg/kg) alone after mPSL pulse therapy (PSL group). RESULTS: No relapses occurred in the PSL + MZB group, although all of 6 patients relapsed in the PSL Group. The total doses of PSL in the PSL + MZB group was about 70% of the PSL Group. There were two patients with Herpes-Zoster infection and one patient with liver dysfunction as side effects, with no differences in the frequency of side effects between the was groups. CONCLUSIONS: Combination maintenance therapy with prednisolone and immunosuppressants after methylprednisolone pulse therapy was effective in preventing relapse.

[Evaluation of a PCR assay commercial kit for quantification of human immunodeficiency virus type-1 RNA].

We studied a basic evaluation of the reliability and usefulness of the test results to assess the validity of the kit "AMPLICOR HIV-1 Monitor" as a laboratory tool, by determining the reproducibility, linearity on dilution, possible effects of interference on the results, and correlation with the results obtained at outside facilities. Furthermore, we compared the HIV-1 RNA load between blood samples obtained from HIV-1 subtype B and E. The HIV-1 RNA load measurement was made according to the pre-determined methods of this kit, in blood samples obtained from HIV-positive outpatients. Simultaneous reproducibility was 23.08%-32.95% in C.V.% and linearity was maintained between 110 copies/ml and 2,184,277 copies/ml, demonstrating favorable performance of the kit. The institution correlation between two facilities were also favorable. Fluctuation of measurement by interference was absent for bilirubin, hemoglobin and chyle, but was significant for heparin.

[Bleeding infectious enteritis].

A recent trend on bleeding intestinal infections in Japan was described. Salmonella Enteritidis infection occupied over 42% of food-borne diseases in 1996. Salmonella Enteritidis is the most popular infectious agent for food-borne outbreak in Japan. Salmonella Typhimurium DT104 which is widely spread in Europe and in U.S.A. is not common in Japan. We experienced large outbreak of foodbore EHEC/VTEC O157: H7 infections in 1996. Since then, diagnostic and therapeutic studies on EHEC/VTEC infection and haemolytic uremic syndrome are promoted by the Government. HACCP may take an important roll for the prevention of large outbreaks of foodbore EHEC/VTEC infections.

Epidemiological study of a food-borne outbreak of enterotoxigenic Escherichia coli O25:NM by pulsed-field gel electrophoresis and randomly amplified polymorphic DNA analysis.

This study investigated the applicability of molecular epidemiological techniques to the identification of the causal agent of an outbreak of diarrhea caused by ingestion of food contaminated with enterotoxigenic Escherichia coli (ETEC). The outbreak occurred at four elementary schools in July 1996 and affected more than 800 people. Illness was most strongly associated with eating tuna paste (relative risk, 1.79; 95% confidence interval = 1.16 to 2.79; P = 0.0001). To evaluate the epidemiological characteristics of the pathogen, the DNAs from numerous isolated ETEC strains were subjected to randomly amplified polymorphic DNA analysis, pulsed-field gel electrophoresis of nuclease S1-treated plasmid DNA, and analysis of genomic DNA restriction fragment length polymorphisms. All ETEC isolates were of the O25:NM (nonmotile) serotype, which carries a heat-stable enterotoxin Ib gene. Genotypic analysis demonstrated that the strains isolated from the patients at all four schools were identical. The isolates of ETEC O25:NM obtained from the tuna paste that had been served for lunch at these schools were genetically indistinguishable from those isolated from the patients. Results suggest that this outbreak was food borne. The molecular biology-based epidemiological techniques used in this study were useful in characterizing the causal agent in this food-borne epidemic.

[A case of macrophage activation syndrome developed with systemic juvenile rheumatoid arthritis].

We reported a child of macrophage activation syndrome (MAS) associated with the course of systemic juvenile rheumatoid arthritis (sJRA). The clinical and laboratory findings in our case was ascribed to the overproduced inflammatory cytokines especially TNF-alpha by activated macrophages. Moreover, macrophage-colony stimulating factor (M-CSF) was also elevated in the active phase of the disease, and decreased in the convalescent phase, indicating that M-CSF can be the most potent stimulator of macrophages to produce inflammatory cytokines. Cyclosporine A along with plasmaexchange and corticosteroid, instead of VP16 or other immunosuppresive agents, was effecting in the management of this severe, life-threatening MAS.