The relationship between homovanillic/vanillylmandelic acid ratios and prognosis in neuroblastoma.

A total of 44 cases with neuroblastoma cases (excluding true positive cases detected in mass screenings) who were born from 1979 to 1991, and had data concerning the clinical stage and values of vanillylmandelic acid (VMA) and homovanillic acid (HVA) at diagnosis (microg/mg creatinine) were followed up until the end of 1994. Deaths were confirmed using the record of vital statistics of the Hokkaido Government. The 60-month survival rate of those who had an HVA/VMA ratio of 1-2 was 80.0%. Conversely, those with ratios <1 or >2 had respective survival rates of 24.1% and 5.3%. Most of those with a ratio >2 died within 24 months of diagnosis. Many of the cases with a ratio <1 lived over 12 months but died within about 36 months. Many tumors of those cases with a ratio of 1-2 originated in extra-adrenal glands, and had negative n-myc amplification. Most of the patients with a ratio >2 were diagnosed at 1 year of age or older. The HVA/VMA ratio at diagnosis is useful in estimating both the survival period and the prognosis.

[Clinical experience with cefadroxil powder for syrup in treatment of infections in children (author's transl)].

Clinical efficacy was studied with cefadroxil powder for syrup in 35 pediatric patients including 20 acute tonsillitis and pharyngitis, 6 scarlet fever, 2 cervical lymphadenitis and 7 urinary tract infections. The results indicated a 97% effectiveness when 'excellent' and 'good' ratings were combined. A mild skin rash was observed in 1 patient.

[Clinical evaluation of biapenem (L-627) in children].

Biapenem (L-627) was evaluated for its efficacy and safety. The following results were obtained. L-627 was given to 9 patients with infections: 3 with pneumonia, 1 with acute bronchopneumonia, 1 with acute bronchitis, 1 with bacteremia, 1 with tonsillitis, 2 with exceptional case. Therapeutic responses were excellent in 3, good in 4, with an efficacy rate of 100%. Adverse reactions were noted. No abnormalities were shown in laboratory data. It has been concluded that L-627 is a useful drug for the treatment of bacterial infections in children.

[Clinical results of cefotiam in the field of pediatrics (author's transl)].

We have administered cefotiam intravenously to 23 pediatric patients. The daily dose was 13-210 mg/kg. The clinical responses were excellent and good in 20 cases. Excluding 1 case with infectious mononucleosis, the efficacy rate of 90.9% (20/22 cases) was achieved As for side effect, diarrhea and eosinophilia were observed one each in 2 cases. In 2 cases, half lives were 24 and 53 minutes, urinary recovery rates were 88.3 and 91% over 6 hours.

[Clinical experience with cefotetan in the treatment of infections of children].

Twenty-five patients in hospital mainly with lower respiratory tract infections and urinary tract infections were treated with cefotetan (CTT). The drug was given intravenously in a dose of 20 mg per kg body weight 1 to 3 times per day. The response to treatment was satisfactory in the 21 patients (84%). There was slight changes in liver function tests in 2 patients and exanthem in 1 patient. CTT appears to be an effective antibiotic for the treatment of children with bacterial infection.

[Clinical evaluation of meropenem in children].

Meropenem (MEPM) was evaluated for its efficacy and safety. The following results were obtained. MEPM was given to 12 patients with infections: 5 with pneumonia, 1 with bacterial meningitis, 2 with pharyngitis, 4 with skin and soft tissue infections. Therapeutic responses were "excellent" in 5, "good" in 4 and "fair" in 3, with an efficacy rate of 75%. Adverse reactions were not noted. No abnormalities were shown in laboratory data. It has been concluded that MEPM is a useful drug for the treatment of bacterial infections in children.

[Clinical studies on 6059-S in the field of pediatrics (author's transl)].

6059-S was administered to 32 children with various acute bacterial infections (bronchopneumonia 11, bronchitis 1, pyelonephritis 5, acute enteritis 6, purulent infection 4, secondary infection due to agranulocytosis 5) at the dose of 21 to 190 mg/kg/day for 2 to 12 days. The clinical response of 6059-S was very satisfactory in all 17 cases with the injection of respiratory tract or urinary tract infection, but it was not so favourable in 5 cases of secondary infection due to agranulocytosis. The overall clinical response was excellent in 5, good in 20, fair in 4, and failure in 3 with effective rate of 78%. As to side effect, each one case diarrhea and elevation of GOT and GPT was noted.

[Clinical results of 9, 3"-diacetylmidecamycin dry syrup in the pediatric field (author's transl)].

9, 3"-Diacetylmidecamycin (MOM), a new macrolide antibiotic, was administered to 28 patients: 6 with pharyngitis caused by Group A beta-Streptococcus, 2 with lacunar tonsillitis, 8 with upper respiratory tract infection, 6 with acute bronchitis, 3 with Mycoplasma pneumonia, 1 with primary atypical pneumonia, 1 with pneumonia caused by H. influenzae and 1 with whooping cough. MOM in the form of fine granules was administered at a daily dose of about 20-30 mg/kg divided into 3 doses. Isolated group A beta-Streptococcus strains were eradicated in only 1 out of 6 strain S. One strain of H. influenzae was eradicated. The clinical results could be obtained with 21 cases and the response was excellent in 1 case, good in 7, fair in 3 and poor in 10. Although diarrhea was found in 3 cases during the administration of MOM, it was not clear whether these phenomena were caused by MOM, because of the prevalence of diarrhea among the children treated by us at that time.

[A clinical study on cefpodoxime proxetil dry syrup in pediatric infections].

Clinical studies on cefpodoxime proxetil (CS-807, CPDX-PR) dry syrup were carried out in the field of pediatrics, and the results are summarized as follows. 1. Eleven year-old male and 12 year-old female were administered orally at a dose level of 5.6 and 6.0 mg/kg, respectively, after or before meal. Cmax and T1/2 were 5.0 micrograms/ml and 2.13 hours, respectively, for the male and 4.04 micrograms/ml and 1.63 hours, respectively, for the female. 2. Good clinical responses were obtained in 21 of 22 child patients with bacterial pharyngitis, tonsillitis, scarlet fever and urinary tract infections. One child with Mycoplasma pneumonia did not respond. As to bacteriological effects, eradication of pathogens was observed in 8 out of 11 strains, showing an eradication rate of 72.7%. 3. As to side effect, 1 case of loose stool was observed, but there was no need of discontinuing the drug treatment.

[Clinical evaluation of cefteram pivoxil fine granules in pediatric infections].

Cefteram pivoxil (CFTM-PI), in fine granules, was studied in pediatric infections and the results obtained are summarized below. It is concluded that CFTM-PI fine granule is an effective drug for the treatment of pediatric infections. 1. The pharmacokinetics of CFTM-PI fine granules was studied in 7 patients (5 males, 2 females) whose ages ranged from 9 to 15 years. (1) In 2 patients, administered with the drug at a dose of 3 mg/kg in the fasting state, serum peak concentrations of CFTM at 2 hours after administration were 0.66 and 0.53 micrograms/ml, and T 1/2 were 1.40 and 1.32 hours, respectively. Urinary recovery rates in the first 8 hours were relatively low at 5.8 and 10.8%, respectively. (2) In 1 patient, the drug administered at a dose of 6 mg/kg in the fasting state, serum peak concentration of CFTM at 2 hours after administration was 3.0 micrograms/ml, T 1/2 was 2.16 hours, and urinary recovery rate in the first 8 hours was 13.8%. In another 2 patients, CFTM-PI administered at a dose of 6 mg/kg after meal, serum peak concentrations of CFTM at 4 hours after administration were 5.8 and 2.5 micrograms/ml, T 1/2 of the latter was 1.93 hours, and urinary recovery rates in the first 8 hours were 27.0 and 14.4%, respectively. (3) In yet another 2 patients, CFTM-PI tablets was administered at a dose level of 150 mg after meal. Serum peak concentrations of CFTM were 1.7 and 1.6 micrograms/ml at 2 hours and 4 hours after administration, respectively, T 1/2 of the former was 1.38 hours, and urinary recovery rates were 24.1 and 15.5%, respectively. 2. Clinical results CFTM-PI as fine granules was administered to 18 patients, and the following results were obtained. (1) 12 cases (6 males, 6 females) with their ages ranged from 3 months to 12 years were administered with the drug at a dose of 10 mg/kg/day, divided into 3 equal portions. Clinical efficacies were fair in 1 case with bronchopneumonia, good in 3 cases with bronchitis and in 4 cases with tonsillitis/pharyngitis, excellent in 1 and good in another with scarlet fever, and good in 1 and poor in another with urinary tract infection (UTI) (2) Six cases (4 males, 2 females) with their ages were 6 and 7 years were administered with CFTM-PI at a dose of 20 mg/kg/day divided into 3 equal portions. Clinical efficacies were good in 1 case with bronchopneumonia, 2 cases with bronchitis and 3 cases with tonsillitis/pharyngitis.

[Pharmacokinetic and clinical studies of cefdinir in pediatric field].

Cefdinir (CFDN) was evaluated for its efficacy and safety. The following results were obtained. 1. Pharmacokinetic study: CFDN was evaluated pharmacokinetically in 4 male children aged 9 to 13. CFDN was given orally to 3 children at a dose of 3 mg/kg. Peak plasma levels of 0.71 microgram/ml, 0.78 microgram/ml and 0.45 microgram/ml were attained in the 3 children, respectively, at 4 hours after dosing. Half-lives of CFDN in serum were 1.78 hours, 1.48 hours and 2.23 hours, respectively. The 12-hour urinary recovery rates of CFDN were 17.4%, 28.1% and 6.2%. When CFDN was given orally to the remaining child at a dose of 6 mg/kg, the peak plasma level was attained at 4 hours after dosing with a level of 1.16 micrograms/ml. T 1/2 was 1.78 hours. The 12-hour urinary recovery rate of CFDN was 15.0%. 2. Clinical study: CFDN 5 percent fine granules were given to 26 patients with infections; 2 with pneumonia, 4 with acute bronchitis, 1 with chronic bronchitis, 12 with pharyngitis, 4 with scarlet fever, 1 with otitis media and 2 with skin and soft tissue infections. Therapeutic responses were "excellent" in 15, "good" in 8, "fair" in 1 and "poor" in 2, with an efficacy rate of 88.5%. 3. Adverse reactions: As for adverse reactions, diarrhea was noted in 1 patient. It was concluded that CFDN is a useful drug for the treatment of the bacterial infections in pediatrics.

[A clinical study of rokitamycin dry syrup in pediatric infections].

A clinical study on rokitamycin (RKM) dry syrup was carried out and the results obtained are summarized as follows: 1. Good clinical responses were achieved with 30-40 mg/kg/day dose of RKM dry syrup. 2. Diagnostically, acute bronchitis and bronchial pneumonia responded better than other diseases examined. 3. The efficacy rate was low in the group of patients complicated by bronchial asthma.

[Clinical evaluation of imipenem/cilastatin sodium in children].

Nine pediatric patients with moderate or severe bacterial infections (3 septicemia or bacteremia, 2 pyelitis, 2 tonsillitis, 1 pneumonia and 1 pyothorax) in hospital were treated with MK-0787/MK-0791. The drug was administered intravenously by 30 or 60 minutes drip infusion in 3 or 4 divided doses totalling 24 mg/24 mg-70.2 mg/70.2 mg per kg/day. Clinical effectiveness were excellent in 4 cases, good in 2 cases, poor in 2 cases and not evaluated in 1 case. The overall efficacy rate was 75%. A slight decrease of WBC was observed in 1 case. It was concluded that MK-0787/MK-0791 was a useful antibiotic for the treatment of infections in pediatric practices. Pharmacokinetics of intravenously administered MK-0787/MK-0791 was studied in 2 other cases. The MK-0787/MK-0791 was administered intravenously by 30 or 60 minutes drip infusion to 2 cases at a dose of 10 mg/10 mg/kg. The mean half-life (T1/2) of MK-0787 was 1.03 hours and MK-0791, 0.69 hour. The mean urinary recovery rate of MK-0787 within 6.5-7 hours after administration was 62.5% and MK-0791, 76.7%.

[A multi-institutional study on the efficacy and toxicity of imipenem/cilastatin sodium in severe infections complicating hematological diseases and cancers in children. Study Group of Infectious Diseases in Pediatric Hematology/Oncology in Hokkaido].

A multi-institutional study was conducted between September 1990 and April 1992 to evaluate the efficacy and toxicity of imipenem/cilastatin sodium (IPM/CS) in severe infections in cases of granulocytopenia in children with hematological diseases and cancers. A total of 60 episodes of infection were treated with the drug, and an overall efficacy rate of 80% (48/60) was obtained. The efficacy rate in patients who were positive for Endospecy test was 90.0%. A group of patients who had previously received other antibiotics showed an efficacy rate of 79.2%, while the patients who had not received previous antibiotic treatment showed an efficacy rate of 80.6%. The difference between the 2 groups was statistically insignificant, however. Granulocyte counts appeared to have influence on the efficacy of the drug, but the influence was not strong. Three patients had nausea, vomiting and/or diarrhea, and 2 other patients showed abnormal liver function test parameters though they recovered soon after the cessation of the drug treatment. From these results, we have concluded that IPM/CS is an effective antibiotic for treatment of severe infections with hematological diseases and cancers in children.

[A clinical study of fluconazole-granules and -injectable in pediatric patients with deep-seated mycoses].

Fluconazole (FLCZ) is an antifungal agent of triazole class developed by Pfizer, Inc. Its oral and injectable forms have been available on the market since June 1989 in Japan. FLCZ exhibits potent antifungal activities against Candida spp., Aspergillus spp. and Cryptococcus spp. and, as orally or intravenously administered, is widely distributed into organs and tissues. For its low protein binding rate of about 10 per cent and long serum half life of about thirty hours in adults, FLCZ has been proved highly effective and useful in the treatment of deep-seated mycosis in adult patients. In the present study, we have investigated the clinical effectiveness and antifungal activities of FLCZ granules, a new dosage form of the drug, and of intravenous form in pediatric patients with deep mycosis. A total of 72 patients were treated either with granules orally or with intravenous injection and 47 patients among them were evaluable on the clinical efficacy of the drug. Also, a study on the pharmacokinetics of pediatric patients including premature/new born babies was conducted employing multiple dose regimens in a total of 27 patients. The clinical efficacy rates were 79.5% (35 patients out of 44) in candidiasis and 100.0% (3 of 3) in aspergillosis. The safety of the drug was assessed in 63 patients. No side effects were observed. Clinical laboratory test abnormalities were observed in some patients with an incidence of 9.7% (6 patients out of 62) but most of the abnormalities were only mild and transient. The pharmacokinetics at repeated doses indicated that a steady-state is reached in 4 days after the initial administration of either granules or intravenous form. From these results, it may be concluded that FLCZ is a very useful medication in the treatment of deep mycosis in pediatric patients.

[Pharmacokinetic and clinical studies with imipenem/cilastatin sodium in the pediatric field. Pediatric Study Group for Imipenem/Cilastatin Sodium].

Pharmacokinetic and clinical studies of imipenem/cilastatin sodium (MK-0787/MK-0791), a new carbapenem antibiotic and a dehydropeptidase-I inhibitor, respectively, were carried out in a joint study in the pediatric field by a study group consisting of investigators at 16 institutions. The results were summarized below. Pharmacokinetic studies Peak plasma concentrations of MK-0787/MK-0791 were 27.7-190.0/28.3-216.4 micrograms/ml at doses of 10/10-50/50 mg/kg administered by a 30 or 60-minute drip infusion. The above findings proved that dose response was clearly observed. Over a period of 6 or 7 hours, the urinary excretion of MK-0787 and MK-0791 totaled 54.2-88.0% and 53.6-89.0% of the dose administered, respectively. Plasma half-lives of MK-0787 and MK-0791 in the beta-phase were 0.87-1.05 hours and 0.59-0.95 hour, respectively. The cerebrospinal fluid (CSF) levels of MK-0787 in patients with purulent meningitis were 2.0-14.4 micrograms/ml; however, the penetration rate of the drug into the CSF was relatively poor in patients with normal meninges. Clinical study Clinical efficacy was evaluated in 283 patients. In 112 patients the daily dosage ranged from 30/30 mg/kg to 59/59 mg/kg, and in 138 patients it ranged from 60/60 mg/kg to 99/99 mg/kg. The maximum dose administered was 222/222 mg/kg. The drug was administered either 3 or 4 times per day. The clinical efficacy rate was 92.5% among 187 patients with identified etiologic pathogens. The drug was effective in 3 out of 4 patients with purulent meningitis and in 7 out of 10 patients with septicemia. The clinical efficacy rate was 96.7% in 90 patients with respiratory tract infection (pneumonia, lung abscess, etc.), 96.5% in 57 patients with urinary tract infection, 90.9% in 11 patients with SSTI. The clinical efficacy rate in those with no identified etiologic pathogen was 97.0% among 101 patients. Bacteriologically, the eradication rate for S. aureus was 87.9% of 33 isolates. Comprehensively, the eradication rate for Gram-positive bacteria was 94.7% of 75 isolates. The eradication rate for P. aeruginosa was 87.5% of 8 isolates. Including these strains, the eradication rate for Gram-negative bacteria was 90.3% of 134 isolates. The MK-0787/MK-0791 exhibited an eradication rate of 91.9% among a total of 211 Gram-positive and Gram-negative bacteria including anaerobes.(ABSTRACT TRUNCATED AT 400 WORDS)

[A clinical study of fluconazole in the treatment of systemic mycosis associated with immunocompromised children].

Efficacies of fluconazole (FLCZ) were evaluated in 8 cases of systemic mycosis (1 case each of candidemia, candiduria, 4 cases of pulmonary candidiasis, and 2 cases of suspected fungemia) complicated in immunocompromised children. Enrolled in the study were 3 patients with acute leukemia, 1 with malignant lymphoma, 2 with congenital immunodeficiency syndrome, 2 with other disorders. The clinical efficacies were good in 6 out of 7 cases. No side effects were observed. FLCZ is a very good and safe agent for the treatment of systemic mycosis complicated with immunocompromised children.

[The first-three year report of the Tuberculosis Control Project, Lumbini, Rupandehi].

The Tuberculosis Control Project, Lumbini, Rupandehi (TCPLR) is a bilateral cooperative venture between two NGO's, the Nepal Anti-Tuberculosis Association (NATA) and the Japan Anti-Tuberculosis Association (JATA), which consists of planning and implementing pilot tuberculosis control activities in Lumbini, Rupandehi district in Nepal, aiming at achieving high cure rate of newly detected smear-positive pulmonary tuberculosis patients before introducing DOTS strategies. Between December 1993 and July 1996, 349 tuberculosis (TB) cases were enrolled in the TCPLR. The categories of cases were as follows: 138 cases (40%) of new smear-positive pulmonary TB [new Sm(+) PTB], and 54 cases (15%) of smear positive pulmonary TB other than new Sm(+) PTB [other Sm(+) PTB] including such cases as continued treatment and relapse, 106 cases (30%) of new smear-negative TB [new Sm(-) TB], and 51 cases (15%) of other smear-negative TB other than New Sm(-) PTB [other Sm(-) TB]. The number and proportion of new Sm(+) PTB cases enrolled in the project have been increasing [6 cases (23%) for the first year, 102 cases (54%) for the third year] although the proportion is still low (40% overall). The regimens of chemotherapy in the initial intensive and the continuation phases of treatment according to the categories of TB were as follows: New Sm(+) PTB; 2HRZE(S)/6HE, other Sm(+) PTB; 2HRZES/1HRZE/5HRE, and Sm(-) TB; 2HRZ/6HE. The proportion of cases treated by the appropriate regimen of chemotherapy has increased. The cohort analysis of the treatment outcome of the cases enrolled in the project showed the following. The proportion of cured cases plus smear-unconfirmed cases completing treatment among new Sm(+) PTB was 74% overall, however, the proportion of defaulters increased in the third year. The proportion of cured cases plus smear-unconfirmed cases completing treatment among other Sm(+) PTB cases was 66% overall, which is slightly lower than that of new Sm(+) PTB cases, however, the difference was not so marked. The proportion of treatment completed cases among smear-negative pulmonary TB cases was 77% overall, however, proportion of defaulters increased in the third year. The treatment outcome in this report was obtained before the adoption of DOTS strategies: However, it showed that cure and treatment completion rates were comparable to those obtained in the SEARO countries which adopt DOTS strategies. The treatment outcome could be improved after the introduction of DOTS strategies in 1997.

[Nine month chemotherapy with INH and rifampicin for non-cavitary pulmonary tuberculosis].

In order to know the adequate duration of the chemotherapy with two drugs (INH + RFP) for pulmonary tuberculosis with non-cavitary minimal radiological findings (minimal case), 278 cases with minimal lesion which had completed 9 months' chemotherapy, were observed for more than six months up to 5 years (mean duration = 54.4 months). Of them, 60 cases were bacteriologically confirmed by smear and/or culture examination. Many cases showed further improvement in radiological findings even after the end of the chemotherapy. Of 180 cases of initially infiltrative type (GAKKEN B type), 10 cases showed the enlargement of shadow radiologically, but were not regarded as relapsed cases, because they remained bacteriologically negative and the shadow improved in 1-2 months without additional chemotherapy. Only 3 cases (1.1%) were regarded as relapsed cases because of the positive bacteriological conversion and aggravation of the shadow. They were initially sputum negative. It can be concluded that for radiological minimal cases, nine months is enough for the duration of chemotherapy when the INH-RFP regimen is used.

[A study of ambulatory treatment for pulmonary tuberculosis in foreigners residing in Japan].

We studied 130 cases of pulmonary tuberculosis in foreigners residing in Japan to obtain the results as follows; 1. Of the cases of pulmonary tuberculosis in foreigners who are registered and receiving treatment in Japan, 20.3% were treated at three dispensaries of the Japan Antituberculosis Association in Tokyo. 2. The nationality of the cases treated was China in more than half of them, followed by the Republic of Korea. 3. The number of days taken from entry into Japan to the start of treatment was about 11.4 months; 0.9% of the total number of cases examined by chest radiophotography required medical treatment. 4. Their living conditions in Japan according to questionnairing are: 56.2% have jobs in Japan; working hour, 4.99 +/- 1.19 hours a day; 64.4% take night work; 57.6% work in food/drink service industry; living space is 12.5 m2; 52.4% share the same house with other persons, living together with 1.6 persons. 5. As for the type of illness at the start of treatment, GAKKAI classification type III accounted for 90% and spread 1 83.8%. GAKKAI classification type II accounted for 10%, consisting of many relatively mild cases. 6. The defaulter rate was high at 40.8%. The reason for defaulting was broken down to discontinuation on his own 68%, repatriation 15% and side-effects 19%. The time to default was average 3.2 +/- 3.1 months after the start of treatment. They defaulted 1.2 +/- 0.4 times on the average. 7. To reduce the defaulter rate to the minimum in treating the foreigners residing in Japan, the following may be needed. a. To give guidance on the regimen including the need of treatment and risk associated with discontinuation of treatment at the first visit. b. Measures to reduce the amount to be born by the individual in the medical expenses. c. Preparation of a pamphlet for therapeutic guidance in foreign languages.