Search for the Θ+ pentaquark via the π(-)p→K(-)X reaction at 1.92 GeV/c.

The Θ(+) pentaquark baryon was searched for via the π(-)p→K(-)X reaction with a missing mass resolution of 1.4 MeV/c(2) (FWHM) at the Japan Proton Accelerator Research Complex (J-PARC). π(-) meson beams were incident on the liquid hydrogen target with a beam momentum of 1.92 GeV/c. No peak structure corresponding to the Θ(+) mass was observed. The upper limit of the production cross section averaged over the scattering angle of 2° to 15° in the laboratory frame is obtained to be 0.26 µb/sr in the mass region of 1.51-1.55 GeV/c(2). The upper limit of the Θ(+) decay width is obtained to be 0.72 and 3.1 MeV for J(Θ)(P)=1/2(+) and J(Θ)(P)=1/2(-), respectively, using the effective Lagrangian approach.

Suppressive effect of intravenous immunoglobulins on the activity of interleukin-1.

In order to study the effect of human immunoglobulin preparations for intravenous use (IVIg) on the production and activity of interleukin-1 (IL-1) derived from monocytes, we treated cultured monocytes with IVIg and examined the lymphocyte-activating factor (LAF) activity of IL-1 in the culture supernatants. The results showed that IVIg suppressed the activity from most healthy adults and some febrile children with acute respiratory disease or Kawasaki disease. Further studies revealed that intact Ig (whole molecular Ig) did not suppress the mRNA expression of IL-1 alpha or IL-1 beta in mononuclear cells, that intact Ig and pepsin-digested Ig inhibited the LAF activity of recombinant IL-1 (rIL-1) and also that intact Ig contains immunoglobulin (probably anti-IL-1 antibody) which binds with rIL-1 by dot blotting using biotin-streptavidin. These results suggest that IVIg suppresses neither IL-1 synthesis nor the release of IL-1 from monocytes but does neutralize IL-1 alpha and IL-1 beta activity by binding IL-1 proteins as an anti-IL-1 antibody.

[Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, and antibiotics in severe and/or refractory infections in pediatrics].

A newly developed human immunoglobulin liquid preparation for intravenous injection was studied for efficacy, safety, and usefulness in treating severe and/or refractory infections in children receiving antibiotic treatment. It is suggested that C-425 is a useful intravenous preparation of human immunoglobulin for the treatment of severe and/or refractory infections in pediatrics. C-425 was administered to 87 inpatients with severe and/or refractory infections at 23 institutions nationwide. The Committee selected 61 cases for the present analysis. Physicians in charge judged clinical efficacy of C-425 to be "excellent" in 23 cases (40.4%), "good" in 24 (42.1%), "fair" in 7 (12.3%), "poor" in 3 (5.3%), and "unknown" in 4. The efficacy rate was calculated at 82.5% when the "excellent" and "good" cases were combined, and 94.7% when the "fair" cases were also included. According to the Committee's judgement, the efficacy of C-425 was "excellent" in 27 cases (44.3%), "good" in 18 (29.5%), "fair" in 7 (11.5%), and "poor" in 9 (14.8%). The efficacy rate was 73.8% when the "excellent" and "good" cases were combined. The rate increased to 85.2% when the "fair" cases were added. Organisms were identified in 31 cases, and the time course was followed in 19 instances. Organisms were eliminated in 12 cases (63.2%), decreased in number in 2 (10.5%), and persisted in 5 (26.3%). Eradication rate was 63.2%. One of the 87 patients died of fulminant hepatitis 2 days after the end of the treatment. The remaining 86 cases were analyzed for the safety of C-425. A skin rash was observed in one case. Laboratory examination revealed increase in transaminase levels in a total of 8 cases; both in GOT and GPT in 5, in GOT alone in 2, and in GPT alone in 1. These findings were not clinically important.

[Clinical and pharmacokinetic study on cefodizime, a new cephalosporin antibiotic, in the pediatric infections].

Cefodizime (THR-221, CDZM), a new cephalosporin antibiotic, was evaluated for its safety and efficacy in 27 children with various bacterial infections. The episodes of infections included pneumonia (6 cases), bronchopneumonia (11 cases), lung abscess (1 case), acute pharyngitis (2 cases), cervical lymphadenitis (1 case), infected cephalohematoma (1 case), urinary tract infection (1 case), sepsis (2 cases) and purulent meningitis (2 cases). CDZM was effective in all but one, and its efficacy rate was 96.3%. The main etiologic pathogens were Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, Streptococcus agalactiae, Escherichia coli, Citrobacter freundii and Branhamella catarrhalis. The elimination rate was 92.3%. As adverse reactions or abnormalities, diarrhea was encountered in 4 cases. A slight elevation of serum transaminases or eosinophils was observed in 4 cases. The serum half-life was approximately 1.8-1.9 hours in children after intravenous bolus injections. Concentrations of CDZM in cerebrospinal fluids were well above MIC values of CDZM against those organisms responsible for the infections. The data suggest that CDZM is a safe and effective antibiotic when used in children with bacterial infections including purulent meningitis.

[Clinical and pharmacokinetic evaluations of aztreonam in children].

Aztreonam (AZT) was evaluated for its safety, clinical efficacy and pharmacokinetics in children. AZT was effective in all the 16 children with Gram-negative bacterial infections. The diagnoses included acute bronchitis and pneumonia (11), UTI (2), UTI with bacteremia (1), purulent meningitis (1) and acute mucositis (1). The etiologic agents were H. influenzae (10), B. catarrhalis (1), N. meningitidis group C (1), E. coli (3) and P. aeruginosa (2). The serum half-life was approximately 1.2 hours after intravenous bolus injection. Penetration into the inflamed cerebrospinal fluid was good not only in acute purulent meningitis but also in viral meningitis. From the present study, AZT is a safe and effective antibiotic when used in children with Gram-negative bacterial infections.

[Clinical evaluation of sultamicillin fine granules in pediatric infections].

Sultamicillin fine granules (SBTPC), a mutual prodrug of sulbactam (SBT) and ampicillin (ABPC), were administered to 16 pediatric patients with bacterial infections. The efficacy rate was 93.3%. MICs (10(6) cells/ml) of SBTPC against beta-lactamase non-producing strains were not significantly different from those of ABPC, and ranged from less than or equal to 0.05 to 1.56 micrograms/ml. MICs of SBTPC, however, were 2-4 fold smaller than MICs of ABPC against beta-lactamase producing strains. Diarrhea and loose stool as side effects were observed in 4 (25%) of 16 patients, but none of them were severe. After oral administration of SBTPC (10 mg/kg), serum levels of ABPC and SBT peaked at 3.41 micrograms/ml and 2.43 micrograms/ml after 0.6 hour, and declined with half-lives of 1.79 and 1.00 hours, respectively.

[Clinical evaluation of clarithromycin, a new macrolide antibiotic in children].

A new oral macrolide, clarithromycin (TE-031, A-56268), was evaluated for its safety, efficacy and pharmacokinetics in 33 children. TE-031 was effective in all cases of mycoplasmal pneumonia, pneumococcal pneumonia, streptococcal pharyngitis, pertussis and Campylobacter gastroenteritis. The pharmacokinetic availability of TE-031 granule and tablets was much better than the older macrolides; serum half-lives of TE-031 averaged 3.2 +/- 0.25 hours (for the granule preparation). No clinical adverse reaction was encountered, but cases of transient mild elevation of the serum GPT (2 cases) and eosinophilia (2 cases) were encountered. From these preliminary data, TE-031 seems to have a place in the treatment of pediatric infectious diseases.

[A comparative, well-controlled study of ceftizoxime suppository against ceftizoxime intravenous injection in infantile acute pneumonia].

We have attempted to clinically define the therapeutic usefulness of ceftizoxime suppository (CZX-S) in children with bacterial pneumonia, in a randomized trial. Intravenous injection of ceftizoxime (CZX) was used as the control. The results are summarized below. Subjects were inpatients with bacterial pneumonia, ranging in age from 9 months to 7 years and 10 months. As a rule, the daily dose was either four 250 mg (in potency) suppositories given at 6-hour intervals or 60 mg/kg body weight intravenous CZX (control) given in 4 injections at 6-hour intervals over a period of 7 days. The number of children in the study was 67. These children were divided into 2 dosage groups (suppository, 35; injection, 32) with matching pretreatment background factors. The severity of the target disease in the majority of the children was "moderate". The rate of therapeutic effectiveness was 97.1% for the suppository and 93.8% for the injection, and did not differ significantly between the 2 groups. Rates of efficacy by severity, presence or absence of underlying diseases, daily dose and/or complications were high without exception, and did not differ significantly between the 2 groups. Eradication rates for causative microorganisms, as studied in 16 children of each group, were both 93.8%. The 2 most frequently isolated causative organisms were Haemophilus influenzae and Streptococcus pneumoniae. Side effects were examined for 36 children of each group. The frequency of side effects did not differ significantly between the suppository group (2 with diarrhea and 1 with abdominal pain) and the injection group (1 with urticaria), and 8.3% and 2.8%, respectively. The frequency of abnormal laboratory test findings differed significantly (P less than 0.01) with respect to eosinophilia which occurred in 7 (20.6%) of the injected subjects but was not encountered in the subjects treated with suppositories. Other abnormal laboratory findings included thrombocytosis in 3 (14.3%) of the injection group and increased GOT in 1 (3.2%) of the suppository group. The suppository formulation of CZX appears to be a highly useful substitute for the injectable form, and should find a special use in children whose treatment with injections experiences some difficulty.

[Bacteriological, pharmacokinetic and clinical studies on clarithromycin in the pediatric field. Pediatric Study Group of Clarithromycin].

Clarithromycin (TE-031, A-56268), a new macrolide antibiotic agent, was evaluated bacteriologically and clinically for its efficacy and safety in pediatrics by a study group organized with pediatricians from all over the country. A summary of the results of the evaluation is as follows. 1. Absorption and excretion Pharmacokinetics of TE-031 was examined by single oral administration of 10% granules and 50 mg tablets at doses of 1, 5, 10 and 15 mg/kg. There were no significant differences between 10% granules and 50 mg tablets, and between administrations before and after meal. Peaks and half-life periods of blood level of TE-031 given once at doses of 5, 10 and 15 mg/kg (10% granules) before meal were 1.58, 4.37 and 3.79 micrograms/ml, and 2.53, 3.17 and 2.20 hours, respectively, and the urinary excretion in 6 hours after the administration were about 20-30%. 2. Antibacterial effects TE-031 was proved to have excellent antibacterial effect, i.e., inhibiting growth over 80% of strains of Streptococcus pneumoniae and Streptococcus pyogenes at 0.10 micrograms/ml, Branhamella catarrhalis at 0.39 micrograms/ml, and Campylobacter jejuni at 0.78 micrograms/ml. Against Staphylococcus aureus, TE-031 showed very similar activity spectrum to EM, and EM resistant strains were also resistant to TE-031. 3. Clinical results A total of 764 cases was studied. Clinical effects of TE-031 were evaluated in 717 cases out of the 764, excluding drop-outs and cases which did not meet specified protocols. Clinically, efficacies of TE-031 were "excellent" in 265 cases and "good" in 161 cases out of 453 cases of Group A in which causal agents were identified, with an efficacy rate of 94.0%, and out of 264 cases of Group B in which pathogens were not detected, clinical effects of TE-031 were "excellent" in 115 cases and "good" in 124 cases, with an efficacy rate of 90.5%. In terms of clinical effects of TE-031 classified by diseases when Group A and B were combined, efficacy rates were 91.6% for upper respiratory tract infection (217/237), 90.0% for bacterial pneumonia (108/120), 97.4% for Mycoplasma pneumonia (111/114), 100% for Chlamydia pneumonia (4/4), 85.0% for pertussis (34/40), 100% for scarlet fever (16/16), 83.9% for skin and soft tissue infection (26/31), and 98.9% for Campylobacter enteritis (87/88).(ABSTRACT TRUNCATED AT 400 WORDS)

[Clinical evaluation of sulbactam/ampicillin in the pediatric infections].

Sulbactam/ampicillin (SBT/ABPC) was administered to 33 pediatric inpatients with 34 bacterial infections. Clinical efficacies were judged to be good in 33 cases (97.1%) out of 34 which included 13 cases of 14 with infections caused by beta-lactamase-producing strains of organisms, and successfully cured by this drug. There were no particular side effects to comment except some cases of diarrhea and loose stool. These results indicated that SBT/ABPC would be useful in the treatment of pediatric infections as a first choice of drug. Serum half-lives of ABPC and SBT were 0.79 hour and 1.02 hours, respectively, hence, q.i.d. dosage regimen would be appropriate.

[Pharmacokinetic and clinical studies on cefodizime in the pediatric field. Pediatric Study Group of Cefodizime].

UNLABELLED: A multi-center open study was conducted to investigate cefodizime (CDZM), a newly developed cephem antibiotic, from pharmacokinetic, bacteriological and clinical aspects, in the pediatric field with the participation of 17 institutions and their related facilities. The results are summarized as follows: 1. Serum concentrations and urinary excretion: The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg, via a bolus intravenous injection or intravenous drip infusion over 30 or 60 minutes. The results were nearly the same as those in adult patients. Mean serum concentrations 5 minutes after a bolus intravenous injections were: 105.5, 264.0 and 461.7 micrograms/ml with 10, 20 and 40 mg/kg, respectively, and T 1/2 (beta)'s for the 3 dosages were 1.75, 1.92 and 1.88 hours, respectively. With 30-minute intravenous drip infusion, mean serum concentrations at the end of infusion were: 90.5 micrograms/ml with a dose level of 10 mg/kg, 178.3 micrograms/ml with 20 mg/kg, and 322.8 micrograms/ml with 40 mg/kg, and T 1/2 (beta)'s for these dosages were 1.90, 2.15 and 1.93 hours, respectively. With 60-minute intravenous drip infusion, mean serum concentrations at the end of infusion were: 66.3 micrograms/ml with a dose level of 10 mg/kg, 136.0 micrograms/ml with 20 mg/kg and 259.2 micrograms/ml with 40 mg/kg, and T 1/2 (beta)'s for these dosages were 1.43, 2.05 and 1.46 hours, respectively. In 8 hours after administration of CDZM, urinary excretion rates were 82.1, 77.7 and 76.5% for bolus intravenous injections of 10 mg/kg, 20 mg/kg and 40 mg/kg, respectively, and 83.3, 71.3 and 68.1% for 30-minute intravenous drip infusions of 10 mg/kg, 20 mg/kg and 40 mg/kg, and 84.4 and 84.3% for 60-minute intravenous drip infusions of 20 mg/kg and 40 mg/kg, respectively. 2. Concentrations in cerebrospinal fluid: Penetrations into cerebrospinal fluid in patients with purulent meningitis reached levels of 1.96-9.48 micrograms/ml with administration of CDZM at 50 mg/kg in acute cases within 6 days after onset. The penetration rates of CDZM were about a median range among injectable beta-lactam agents. 3. CLINICAL RESULTS: Of 457 cases treated with CDZM, 53 cases were excluded from the clinical evaluation. Clinical efficacies were evaluated as "excellent" in 126 and "good" in 78 out of 221 case from which causative agents were isolated, with an efficacy rate of 92.3%. Efficacies were "excellent" in 97 and "good" in 69 out of 183 cases from which pathogens were not isolated giving an efficacy rate of 90.7%.(ABSTRACT TRUNCATED AT 400 WORDS)

[Clinical evaluation of a new oral cephem, cefpodoxime proxetil in children].

Cefpodoxime proxetil (CPDX-PR, CS-807) was evaluated for its efficacy, safety and pharmacokinetics in children. CPDX-PR was effective in 93.6% of 47 cases with respiratory tract, middle ear, skin or urinary tract infections. Twice or 3 times daily administration of 3 mg/kg each was sufficient to treat streptococcal pharyngitis and Haemophilus influenzae infections. No severe adverse reaction was encountered in 52 cases treated with CPDX-PR. The serum half-life was approximately 2.17 +/- 0.24 hours after oral administration.

[Outbreaks of asthma attack and meteorological parameters--comparison between two areas].

The correlation between patient visits and meteorological parameters were analyzed regarding asthmatic children who visited the outpatient emergency clinics at Teikyo University Hospital in Tokyo and Ogaki Municipal Hospital in Gifu, during the two years of 1986 and 1987. The yearly climatological changes are quite similar in both areas. Moreover, variations in the number of patient visits were also remarkably similar in both areas. High temperatures and high vapor pressure significantly correlated with increased numbers of visits in both areas. High humidity and high barometric pressure had some correlation with increased numbers of visits in both areas. As for wind direction, northerly synoptic winds had a significant correlation with increased numbers of visits in Tokyo, while contrarily, southerly winds produced the same effect in Ogaki. Precipitation and cloud density showed no correlation with the number of patient visits in either area.

[Outbreaks of asthma attacks and meteorological parameters--multivariate analysis].

The correlation between patient visits and meteorological parameters was analyzed among asthmatic children who visited the out-patient emergency clinic at the Teikyo University Hospital during the three years from 1984 to 1986. Data were analyzed with the method of multivariate analysis (quantification theory type II). The major factors affecting the frequency of visits were an air temperature at more than 15 degrees C, a relative humidity at more than 65%, a vapor pressure at more 1013 mb and a wind speed at less than 3.5 m/sec. Multivariate analysis of seven meteorological parameters, the four parameters shown above plus sea level pressure, cloud density and precipitation, revealed that discrimination ratios with the Lag 3, Lag 2, Lag 1 and Lag 0 values were 63.8%, 68.5%, 68.5% and 63.6%, respectively. These results indicate that asthma forecast is possible by the multivariate analysis of meteorological conditions.

The increase of non-MHC-restricted cytotoxic cells (gamma/delta-TCR-bearing T cells or NK cells) and the abnormal differentiation of B cells in Wiskott-Aldrich syndrome.

The objective of this study was to analyze the configuration of the lymphocytes in Wiskott-Aldrich syndrome (WAS) by studying the surface antigens from nine cases using dual-color immunofluorescence analysis. All the patients showed the increase of non-MHC-restricted cytotoxic cells, namely CD3+ WT31- delta TCS1+ (gamma/delta-T cell receptor (TCR)-bearing cells) and/or CD16+ natural killer cells. The gamma/delta-TCR+ cells of WAS, however, were unique since they did not express CD5, which is present on ordinary gamma/delta-TCR+ cells. A reduced number of CD4+ cells and an increased percentage of CD11b+ Leu7+ cells within a CD8+ subset were observed in all cases. With regard to B cell subpopulations, most cases showed reduced Fc epsilon R2-bearing B cells, despite an elevated serum IgE.