Background electroencephalographic (EEG) activities of very preterm infants born at less than 27 weeks gestation: a study on the degree of continuity.

AIMS: To clarify the features of the background electroencephalographic (EEG) activities in clinically well preterm infants born at less than 27 weeks gestation and to outline their chronological changes with increasing postconceptional age (PCA). METHODS: EEGs of clinically well premature infants born at less than 27 weeks gestation were recorded during the early postnatal period. The infants were separated into three groups according to their PCA at the time of EEG recording (21-22 weeks PCA, 23-24 weeks PCA, and 25-26 weeks PCA). The mean and maximum duration of interburst intervals (IBIs), the mean duration of bursts, and the percentage of continuous and discontinuous patterns in each PCA group were evaluated. RESULTS: There were three infants at 21-22 weeks PCA, seven at 23-24 weeks PCA, and five at 25-26 weeks PCA. Eighteen EEG recordings were obtained. The mean and maximum IBI duration decreased with increasing PCA. The percentage of continuous patterns increased with increasing PCA. Conversely, the percentage of discontinuous patterns decreased with increasing PCA. CONCLUSIONS: In premature infants born at less than 27 weeks gestation, the characteristics of the background EEG activities were similar to those of older premature infants. These changes reflect the development of the central nervous system in this period.

[Evaluation of cardiac autonomic nerves by iodine-123 metaiodobenzylguanidine scintigraphy and ambulatory electrocardiography in patients after arterial switch operations].

The autonomic cardiac nerves reach the heart after passing through the vicinity of the aortic root and the pulmonary trunk. The arterial switch operation (ASO) completely transects the ascending aorta and the pulmonary trunk. Therefore, this surgical procedure virtually denerves the heart. Cardiac sympathetic denervation and reinnervation were evaluated in patients after ASO using iodine-123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and parasympathetic denervation and reinnervation using ambulatory electrocardiography [Holter electrocardiogram (ECG)]. MIBG scintigraphy was performed in 14 patients who underwent ASO (ASO group) and 3 patients who underwent other open heart surgery (control group). All patients in the ASO group underwent the operation in the neonatal or infantile period. Planar and single photon emission computed tomography (SPECT) images of the myocardium were obtained. Defect score was determined by the SPECT images as a semi-quantitative index. The mean interval between ASO and MIBG scintigraphy was 25.6 +/- 14.6 months. Holter ECG was also performed in 14 patients in the ASO group and 19 age-matched normal children. The Holter ECGs were plotted on a Lorenz plot. The H index, which is related to vagal tone for the cardiovascular system, was calculated from the R-R intervals. The mean interval between the ASO and Holter ECG was 8.3 +/- 9.7 months. MIBG scintigraphy in the control group demonstrated an almost normal homogeneous tracer uptake, but showed extremely reduced tracer uptake and significantly higher defect score in the ASO group. The extent and degree of the reduction of MIBG uptake improved with time after the ASO. The heart-to-mediastinum MIBG count ratio tended to increase with time. The H index of the ASO group was lower than that of normal children (< 12 months: Control group 0.0280 +/- 0.0068 vs ASO group 0.0219 +/- 0.0083), and gradually increased with time (1-3 years: 0.0470 +/- 0.0157 vs 0.0314 +/- 0.0124). These results indicate that MIBG scintigraphy reflects the presence of sympathetic denervation and the possibility of reinnervation after ASO, and that H index reflects the presence of parasympathetic denervation and the possibility of reinnervation after ASO. These are simple and useful methods for assessing the extent and degree of autonomic denervation and reinnervation.

Twin-to-twin transfusion syndrome with hydrops: a retrospective analysis of ten cases.

We retrospectively studied 10 cases of twin-to-twin transfusion syndrome (TTTS) with fetal hydrops. TTTS was diagnosed sonographically between the 17-31 weeks of gestation. All twins were delivered by emergency cesarean section because of cardiac decompensation of one or both fetuses. The mean (+/-SD) age at diagnosis was 26.1 +/- 4.5 and the mean age at delivery was 28.8 +/- 2.0 weeks. Gestational age at birth was similar in survivors and nonsurvivors. However, surviving infants were diagnosed later in gestation (23.6 +/- 4.8 vs. 28.7 +/- 1.9 weeks; p < 0.01); and gestational age at appearance of hydrops were later in survivors (26.1 +/- 3.2 vs. 29.2 +/- 2.4 weeks; p < 0.05). Overall survival rate was 50% (10 of 20 infants). All survivors were delivered within 3 days after the appearance of fetal hydropic changes. Extrauterine treatment in earlier stages of TTTS might improve the outcome. Nevertheless, more aggressive intrauterine treatment should be considered in the most severe cases of TTTS developing before 24-25 weeks' gestation.

Oxygen uptake efficiency slope as a useful measure of cardiorespiratory functional reserve in adult cardiac patients.

In this study we aimed to elucidate the validity and usefulness of the oxygen uptake efficiency slope (OUES) in the evaluation of adult cardiac patients. Cardiopulmonary exercise tests were performed on a treadmill by 50 adult patients with chronic heart failure. The OUES was calculated from data for the first 75%, 90%, and 100% of exercise duration. The OUES is derived from the following equation: VO(2)=ax logV(E)+b, where VO(2) is oxygen uptake (ml/kg/min), V(E) is minute ventilation (l/kg/min), and the constant "a" represents OUES. We also determined the ventilatory anaerobic threshold (VAT). The correlation coefficient of the logarithmic curve-fitting model was [mean (SD)] 0.986 (0.009). The OUES could be used to discriminate effectively between New York Heart Association functional classes (P < 0.001). OUES and maximum VO(2) were significantly correlated (r=0.78, P < 0.01). Agreement between the OUES values for the first 90%, 75%, and 100% of the exercise was excellent (intraclass correlation coefficient = 0.99). Our results suggest that OUES is applicable to adult cardiac patients as an objective, effort-independent estimation of cardiorespiratory functional reserve.

Inhalation of low-dose nitric oxide to evaluate pulmonary vascular reactivity in children with congenital heart disease.

The objective of this study was to investigate the efficacy of low-dose nitric oxide (NO). The study used fifteen consecutive Japanese preoperative patients (7 males and 8 females) with congenital heart disease and pulmonary hyptertension (mean pulmonary arterial pressure >30 mmHg), 6 of these patients had Down's syndrome. Hemodynamic measurements were taken in room air, 100% oxygen, 5 and 40 parts per million NO (NO5 and NO40) by inhalation. The differences between two observations within the same group were determined by the two-tailed paired t-test. A pulmonary vascular resistance (Rp) regression curve was constructed by using linear regression analysis. The percentage change in pulmonary arterial pressure per systemic arterial pressure (Pp/Ps) with NO40 (Pp/Ps-40) exceeded that of Pp/Ps-5 (p < 0.0001). The percentage change for the Rp with NO40 (Rp-40) was larger than that for the Rp-5 (p = 0.0003). The percentage change of Pp/Ps-5 and that with oxygen were similar (p = 0.266). The relationship between Rp-5 and Rp-40 was linear. In conclusion, the effects of NO5 were equivalent to 100% oxygen but less than NO40. NO5 should initially be used to test pulmonary reactivity. If there is no response, patients should still be given NO40.

Cardiorespiratory response to exercise in patients with exercise-induced bronchial obstruction.

OBJECTIVE: To document the characteristics of the ventilatory response to exercise in patients with exercise-induced bronchial obstruction (EIB). EXPERIMENTAL DESIGN: Comparative study during the period between December 1993 and March 1994. SETTING: Ambulatory care in Ohgaki Municipal Hospital. SUBJECTS AND METHOD: We evaluated 11 children with EIB. Each subject under went symptom-limited cardiopulmonary treadmill exercise testing (Bruce protocol). RESULTS: Patients with EIB showed a significantly lower peak oxygen consumption (peak VO2) than the control subjects. Three patients with EIB developed relative hypoventilation during incremental exercise: an increase in end-tidal carbon dioxide partial pressure (PETCO2) and a decrease in VE/VCO2 were observed at the end-stage of exercise testing. CONCLUSIONS: These findings demonstrate that some patients with EIB develop bronchoconstriction during exercise.

Oxygen uptake efficiency slope: a new index of cardiorespiratory functional reserve derived from the relation between oxygen uptake and minute ventilation during incremental exercise.

OBJECTIVES: We investigated the usefulness of a new variable, oxygen uptake efficiency slope (OUES), as a submaximal measure of cardiorespiratory functional reserve. The OUES is derived from the relation between oxygen uptake (Vo2 [ml/min]) and minute ventilation (VE [liters/min]) during incremental exercise and is determined by VO2 = a log VE + b, where a = OUES, which shows the effectiveness of Vo2. BACKGROUND: Maximal oxygen uptake (VO2max) is effort dependent. There is no standard submaximal measurement of cardiorespiratory reserve that provides generally acceptable results. METHODS: Exercise tests, following a standard Bruce protocol, were performed on a treadmill by 108 patients with heart disease and 36 normal volunteers. Expired gas was continuously analyzed. The OUES was calculated from data of the first 75%, 90% and 100% of exercise duration. We also determined the following submaximal variables: the ventilatory anaerobic threshold (VAT), the slope of the regression line of the minute ventilation-carbon dioxide production relation (VE-VCO2 slope) and the extrapolated maximal oxygen consumption (EMOC). We analyzed the relation of OUES and other submaximal variables against VO2max and examined the effects of submaximal exercise on OUES. RESULTS: The correlation coefficient of the logarithmic curve-fitting model was 0.978 +/- 0.016 (mean +/- SD). The OUES and VO2max had a significant correlation (r = 0.941, p < 0.0001). The correlation between VO2max and OUES was stronger than that between VO2max and VAT, the VE-VCO2 slope or EMOC. The OUES values for 100% and 90% of exercise were not different from each other (at an alpha value of 0.05 and treatment effect of 170, the power of the test [1-beta] was 0.90); OUES for 75% of exercise was slightly lower (3.5%). CONCLUSIONS: Our results suggest that OUES may provide an objective, effort-independent estimation of cardiorespiratory functional reserve that is related both to pulmonary dead space and to metabolic acidosis.

[An operative case of bilateral partial anomalous pulmonary venous return using a direct anastomosis between the right atrial appendage and the superior vena cava].

We have experienced a case of bilateral partial anomalous pulmonary venous return without atrial septal defect. Right upper pulmonary vein returned to the superior vena cava and left upper pulmonary vein returned to the left brachiocephalic vein. This type of bilateral partial anomalous pulmonary venous return was extremely rare, and only 4 such cases have been reported in the Japanese literature. The patient, aged 3 years and 11 months, was successfully operated on, using a direct anastomosis between the right atrial appendage and the superior vena cava. This procedure is considered to be advantageous because both this right atriotomy line and suture line avoid injury of the sinus node and the sinuatrial node artery and no foreign material is used. A decrease in postoperative arrhythmia can also be expected from this procedure.

Oxygen intake efficiency slope: a new index of cardiorespiratory functional reserve derived from the relationship between oxygen consumption and minute ventilation during incremental exercise.

We investigated the usefulness of the oxygen intake efficiency slope (OIES) as a submaximal measure of cardiorespiratory functional reserve. OIES was derived from the relationship between oxygen consumption (VO2; ml/min) and minute ventilation (VE; l/min) during incremental exercise, which was determined by the following equation: VO2 = a logVE + b, where "a" represents OIES, which shows the effectiveness of ventilation. Maximal oxygen consumption (VO2max) is effort-dependent. There is no standard submaximal measurement of cardiorespiratory reserve that provides generally acceptable results. Exercise tests were performed by 17 normal volunteers on an ergometer using a symptom-limited Ramp protocol. Expired gas was continuously analyzed. OIES was calculated using the first 75%, 90%, and 100% of exercise data. We also determined the following submaximal parameters: the ventilatory anaerobic threshold (VAT), the slope of the minute ventilation-carbon dioxide production relationship (VE-VCO2 slope), and the extrapolated maximal oxygen consumption (EMOC). We analyzed the relationship between OIES, other submaximal parameters and VO2max, and examined the effects of submaximal exercise on OIES. The correlation coefficient of the logarithmic curve-fitting model was 0.991 +/- 0.006. OIES and VO2max were significantly correlated (r = 0.966, p < 0.0001). The correlation between OIES and VO2max was stronger than the correlation between VO2max and VAT, the VE-VCO2 slope and EMOC. OIES values for 100% and 90% of exercise were identical; OIES for 75% of exercise was slightly lower (3%). Our results suggested that OIES may provide an objective, effort-independent estimation of cardiorespiratory functional reserve.

Mapping of cyclosporin A binding sites in cyclophilin A by using synthetic peptides.

In order to map cyclosporin A (CsA) binding sites of cyclophilin (CyP), we synthesized the complete set of overlapping 157 octapeptides corresponding to human CyP A using the multi-pin peptide synthesis system. The pin-coupled synthetic octapeptides were examined in terms of binding ability to CsA by a modification of the enzyme-linked immunosorbent assay. Significant binding of CsA was detected with 35 synthetic N alpha-acetylated octapeptides possessing the N-terminal amino acids corresponding to the residues in positions 24-26, 42-44, 69-73, 75, 76, 89-91, 102, 116, 124-131, 144-151 and 152 in human CyP A, respectively. Other eight octapeptides showed moderate CsA binding activity. The distinct binding of octapeptides covering the C-terminal region of the CyP A was particularly significant. These data are to be compared with the information provided by X-ray and NMR studies on the CsA binding sites and furnish thus a test of the reported method. The present study also gave added insight into the CsA interaction sites of CyP.

[Laboratory and clinical evaluations of flomoxef sodium in neonates].

Flomoxef sodium (FMOX) was evaluated experimentally and clinically in neonates. 1. Serum concentrations and urinary excretions of the drug were examined after a bolus intravenous injection at 20 mg/kg to 22 neonates 1-30 days after birth (durations of pregnancy 31-43 weeks, weights at birth 1,650-4,040 g) and 5 infants 50-95 days after birth (durations of pregnancy 33-40 weeks, weights at birth 1,720-3,308 g). Serum concentrations were 10.8-67.6 micrograms/ml (mean 32.7 +/- 2.8 micrograms/ml) and 25.1-52.0 micrograms/ml (mean 38.9 +/- 4.3 micrograms/ml) in the neonates and the infants, respectively, at their peaks (0.5 hour value), decreased thereafter with half-lives of 0.96-5.59 hours (mean 2.20 +/- 0.26 hours value), and 0.97-1.54 hours (mean 1.22 +/- 0.12 hours value), respectively. Serum levels decreased to 0.2-17.1 micrograms/ml (mean 2.9 +/- 0.6 micrograms/ml) and N.D. -1.1 micrograms/ml (mean 0.4 +/- 0.2 micrograms/ml) after 8 hours, respectively. The urinary recovery rates of the drug in the first 8 hours after administration were 15.0-96.0% (mean 53.7 +/- 4.9%) and 29.9-73.3% (mean 62.4 +/- 9.4%) in the neonates and in the infants, respectively. 2. FMOX was administered to 78 neonates (durations of pregnancy 31-42 weeks, weights at birth 1,420-3,860 g) in whom bacterial infections were established or suspected, and clinical, bacteriological, and side effects were evaluated. In 47 neonates examined (1 with sepsis, 3 with acute upper respiratory infections, 18 with acute pneumonia, 1 with umbilical infection, 1 with impetigo, 4 with acute urinary tract infections, 1 with acute otitis externa, 1 with periproctal abscess, and 17 with intrauterine infections), the treatment was markedly effective in 41, and effective in 6, with an overall efficacy rate of 100%. The bacterilogical effects of the drug on 3 strains of Staphylococcus aureus, 1 strain of Streptococcus pneumoniae, 1 strain of Streptococcus agalactiae, 9 strains of Escherichia coli, and 2 strains of Haemophilus influenzae which were responsible for these infections were all rated as "eradicated". Moreover, the drug, administered with or without prophylactic intentions showed complete prophylactic effects in all 27 cases tested. No side effects were observed in any of the patients. Concerning abnormal clinical laboratory results, increases in GOT were noted in 2, eosinophilia in 1, and thrombocytosis in 1, but these abnormalities were invariably mild and the normalized in 1 patient without treatment. The results suggest that FMOX is useful and safe also in neonates.

[Clinical evaluation of cefixime in pediatric respiratory tract infections].

Cefixime (CFIX) was evaluated clinically in pediatric respiratory tract infections, particularly those caused by Haemophilus influenzae: 1. The total number of children in this study treated with CFIX was 232, out of which 215 cases were evaluated for clinical efficacy and 224 cases were investigated for safety. A daily dosage of 3-6 mg/kg/day was given divided into 2 to 3 times daily for 3-15 days. 2. Causative organisms were identified in 146 cases, out of which 128 cases were found to be single microbial infections and 18 cases were mixed infections. In single microbial infections, clinical efficacy was 100% for those caused by H. influenzae/Haemophilus parainfluenzae, and was 95% for Streptococcus pyogenes with an overall efficacy of 96.9%. In mixed infections, the clinical efficacy was 100% for those caused by a combination of H. influenzae and Streptococcus pneumoniae, and the overall rate was 94.4%. An involvement of H. influenzae was observed in 108 cases with a clinical efficacy rate of 99.1%, and definite involvement of beta-lactamase secreting strains of H. influenzae was found in 32 cases with a clinical efficacy of 96.9%. 3. Bacteriological effect was studied for 164 strains identified in 146 cases, and eradication rates were 89.5% for H. influenzae, 100% for H. parainfluenzae and S. pyogenes, and 71.4% for S. pneumoniae. The overall eradication rate was 91.4%. Superinfection was observed in 21 cases. MICs against 78 strains of H. influenzae were in a range of less than or equal to 0.10 microgram/ml regardless of beta-lactamase production, and far superior to cefaclor and amoxicillin. MICs against S. pyogenes and S. pneumoniae were in ranges of less than or equal to 0.10 microgram/ml and 0.39 micrograms/ml, respectively. 4. Clinical efficacy was 93.0% in 215 cases (excellent: 136, good: 64, fairly good: 10, poor: 5). CFIX attained a high efficacy in the range of 89.4-95.7% in acute pharyngitis, acute tonsillitis, acute bronchitis and acute pneumonia. 5. Safety was monitored in 224 cases and there were only one case of loose stool and another of diarrhea as side effects. There were no abnormal findings in 31 cases of the laboratory test. In conclusion, it was confirmed that CFIX is excellent and safe in the treatment of the respiratory tract infections.

[Pharmacokinetic, bacteriological and clinical studies on aztreonam in neonates].

Pharmacokinetic, bacteriological and clinical studies on aztreonam (AZT) were performed in neonates. The results obtained are summarized as follows. 1. Plasma levels and urinary excretion of AZT were determined in 18 neonates with ages between 1 and 30 days (gestation periods were 36 to 40 weeks and birth weights were 1,890 to 4,300 g) and in 2 infants with 54 and 60 days of age (gestation periods were 36 and 40 weeks, and birth weights were 2,300 and 3,300 g, respectively) upon one-shot intravenous injection of AZT 10 mg/kg (7 cases) or 20 mg/kg (11 cases) to the 18 neonates and 20 mg/kg to the 2 infants. Ampicillin (ABPC) 25 mg/kg was simultaneously injected to 5 cases of the neonates given AZT 20 mg/kg by one-shot intravenous injection and plasma concentrations of ABPC in these 5 cases were also studied. Plasma concentrations in neonates at 0.5 hour after intravenous injection of AZT 10 mg/kg were 11.5 to 27.6 micrograms/ml (average 20.3 +/- 5.5 micrograms/ml) and decreased with half-lives of 2.72 to 5.70 hours (average 3.81 +/- 1.28 hours), and the plasma levels at 8 hours after administration were 3.3 to 8.7 micrograms/ml (average 5.8 +/- 2.5 micrograms/ml). In the cases given AZT at 20 mg/kg, plasma levels at 0.5 hour were 12.4 to 48.8 micrograms/ml (average 35.9 +/- 11.6 micrograms/ml) and decreased with half-lives of 1.69 to 4.14 hours (average 2.94 +/- 0.76 hours) and AZT levels at 8 hours were 1.1 to 10.6 micrograms/ml (average 5.6 +/- 3.6 micrograms/ml). Urinary recovery rates in the first 8 hours after intravenous injection of the 10 mg/kg group were 15.5 to 61.9% (average 37.8 +/- 21.8%) and 16.3 to 62.2% (average 43.5 +/- 16.2%) for the 20 mg/kg group. Plasma concentrations in infants after administration of AZT 20 mg/kg were 33.0 to 35.6 micrograms/ml (average 34.3 +/- 1.8 micrograms/ml) at 0.5 hour and decreased with half-lives of 1.76 to 3.77 hours (average 2.77 +/- 1.42 hours) and AZT plasma levels at 8 hours were 1.4 to 5.8 micrograms/ml (average 3.6 +/- 3.1 micrograms/ml). Urinary recovery rates were 35.4 to 64.8% (average 50.1 +/- 20.8%). These results suggested that AZT shows a dose-dependent, high plasma concentration even in the neonatal period, as well as good urinary excretion from an early stage of the administration.(ABSTRACT TRUNCATED AT 400 WORDS)

[Pharmacokinetic, bacteriological and clinical studies of ceftizoxime in neonates].

Pharmacokinetic, bacteriological and clinical studies of ceftizoxime (CZX) were performed in neonates. 1. Serum concentrations and urinary excretion of CZX were investigated in 12 neonates ranging ages from 1 to 27 days (gestational age, 35-41 weeks; birth weight, 2,150-4,030 g) and 2 infants ranging ages from 55 to 57 days (gestational age, 39-40 weeks; birth weight, 2,320-2,650 g). Each of the subjects was given a single intravenous dose of 20 mg/kg by one shot. Serum concentrations of CZX in the neonates were 24.9-53.7 micrograms/ml at 1/4 hour after intravenous injection, with an average of 40.6 +/- 7.6 micrograms/ml. Serum half-lives of CZX were 1.32-4.75 hours and averaged 2.60 +/- 1.06 hours. Serum concentrations ranged from 2.01 to 14.6 micrograms/ml at 6 hours after injection with an average of 7.70 +/- 3.89 micrograms/ml. In the 2 infants, serum concentrations were 42.0 and 46.2 micrograms/ml at 1/4 hour (average: 44.1 +/- 3.0 micrograms/ml), and 2.91 and 5.04 micrograms/ml at 6 hours after injection (average: 3.98 +/- 1.51 micrograms/ml). Half-lives were 1.54 hours in 1 infant and 1.93 hours in the other (average: 1.74 +/- 0.28 hours). Furthermore, 6-hour urinary recovery rates were 28.5-71.7% (average: 49.3 +/- 12.8%) in the neonates and 42.1-55.5% (average: 48.8 +/- 9.5%) in the infants. The above results suggest that the following 3 points are accepted; 1) peak serum concentrations (at 1/4 hour) in neonates were similar to those in infants and older children irrespective of age (days after birth). 2) Serum half-lives of CZX in neonates shortly after birth were 4 or 5 times longer than those in older children, but decreased rapidly with the advance of day-ages. The half-life in neonates of 2 weeks of age or so became shorter to about twice the normal value in infants. Furthermore, half-lives of the drug in those at an age of the first half of infancy were similar to those in older children. 3) The urinary excretion rates tended to be somewhat low with neonates soon after birth, but became very similar to those in infants and older children at a relatively early stage.(ABSTRACT TRUNCATED AT 400 WORDS)

[Pharmacokinetics in neonates and infants following administration of amikacin].

Sixteen neonates (at ages of 8 to 28 days) and 8 infants (at ages of 35 days to 1 year), who were in need of treatment with amikacin sulfate, were subjected to the present study. The drug was administered by intramuscular route (1.39 to 3.13 mg/kg) or by intravenous drip infusion over a 30 to 60 minutes period (2.94 to 6.00 mg/kg). Blood levels and urinary excretion of the drug were investigated with these subjects. The blood levels were also analyzed according to pharmacokinetic models. 1. When the drug was administered intramuscularly to neonates at average doses of 1.49 and 2.96 mg/kg and to infants at average doses of 2.97 mg/kg peak levels of 2.74, 6.53 and 8.55 micrograms/ml, respectively, were attained at 30 minutes after dosing. 2. When the drug was administered to neonates at average doses of 3.01 and 5.89 mg/kg by intravenous drip infusion over a 30 to 60 minutes period and to infants at average doses of 2.97 and 6.00 mg/kg in the same manner, peak levels of 7.70, 20.9, 9.40 and 23.0 micrograms/ml, respectively, were attained at the end of the intravenous drip infusion. 3. Urinary levels and recovery rates tended to increase with ages of these subjects. Urinary recovery rates for the neonates and the infants were 41.0 and 58.9%, respectively, on the average. 4. From a pharmacokinetic analysis of blood levels of the drug, it was concluded that, in any of the subjects who received the drug intramuscularly or by intravenous drip infusion, it would be possible to use the one-compartment open model. In the subjects who received the drug by intravenous drip infusion, however, it was determined the two-compartment open model would be the choice. 5. In the neonates and the infants, whose blood levels were analyzed according to the one-compartment open model, Ka values averaged 7.51 and 6.62 hr-1, respectively, with respective average Kel values of 0.32 and 0.66 hr-1. Average Vd values obtained were 0.36 and 0.26 L/kg, respectively. There was a negative correlation between the Vd values and the ages of the subjects, while there was a positive correlation between the Kel values and the ages. 6. Appropriate conditions for administering the drug by intravenous drip infusion to neonates and infants at ages of more than 1 week were investigated taking observed blood levels and achieved peak levels and trough levels calculated using the one-compartment open model into account.(ABSTRACT TRUNCATED AT 400 WORDS)

[Study on the use of cefotiam in neonates].

Pharmacokinetic and clinical studies were carried out regarding the use of cefotiam (CTM) in the treatment of infections in newborn infants. Absorption and excretion: CTM was administered by bolus intravenous injection at a dose of 20 mg/kg to 9 newborns ranging in age from 1 to 28 days (gestational age, 34-40 weeks; birth weight, 2,000-3,380 g) and 6 infants aged 30 to 87 days (gestational age, 33 approximately 40 weeks; birth weight, 2,100-3,600 g) and its serum concentration and urinary excretion were determined. In the newborns, mean serum concentrations were 43.3 micrograms/ml at 1/4 hour, 36.7 microgram/ml at 1/2 hour, 27.8 micrograms/ml at 1 hour, 17.7 micrograms/ml at 2 hours, 8.8 micrograms/ml at 4 hours and 4.8 micrograms/ml at 6 hours, and in the infants, they were 44.5 micrograms/ml, 31.2 micrograms/ml, 19.1 micrograms/ml, 7.6 micrograms/ml, 2.2 micrograms/ml and 0.7 micrograms/ml at the above sampling times, respectively. Mean half-lives were 1.92 hours for the newborns and 0.96 hour for the infants, and mean urinary recoveries within 6 hours were 41.2% and 50.1% for the newborns and the infants, respectively. Taking individual differences into account, serum peak levels (at 1/4 hour) in newborns were very similar to each other irrespective of age (days after birth), and did not appear to be greatly different from those in infants. Half-lives, however, became shorter with aging, and the half-life of the serum CTM level in infants of about 1 month old should be close to those in young children or school-age children. From these observations, it is suggested to establish a standard regimen in which CTM is administered at a dose of 20 mg/kg once or twice a day to newborns within 3 days after birth, twice or 3 times a day to those aged 4 to 7 days, and 3 or 4 times a day to those aged 8 days or older. Clinical study: The CTM was administered to 11 patients with acute pneumonia, 2 patients each with suspected septicemia and with bullous impetigo, 1 patient with purulent lymphadenitis, 3 patients with idiopathic respiratory distress syndrome and 1 patient with pneumothorax, and its clinical effect was investigated. Excellent responses were observed in 12 of the 15 evaluated cases,good responses in 2, and a poor response in 1, thus an overall clinical effectiveness was 93.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

[Evaluation of latamoxef in neonates].

Basic and clinical studies were carried out on latamoxef (LMOX) in relation to the use of this antibiotic in the treatment of infections in newborn infants. The results were as follows. The MICs of LMOX were determined for various clinical isolates of Gram-negative bacteria: 22 strains of E. coli, 18 strains of K. pneumoniae, 4 strains of K. oxytoca, 19 strains of P. mirabilis, 4 strains of P. vulgaris, 5 strains of P. morganii and 3 strains of C. freundii and 60 strains of H. influenzae. The MIC distributions against all of these strains for each species were 0.1, 0.2, 0.1, 0.2, 0.1, 0.1, 6.25 and 0.78 microgram/ml or less, respectively. The antibacterial activity of LMOX against all of these Gram-negative isolates was thus found to be excellent. For 38 strains of P. aeruginosa, the MIC distribution was from 6.25 to 200 micrograms/ml; accordingly, although this antibiotic does show antibacterial activity against this microbe, it is not very potent. As Gram-positive bacteria, 28 clinical isolates of S. pyogenes and 34 strains of S. aureus were tested; their respective MIC distributions were 0.39--1.56 micrograms/ml and 3.13--25 micrograms/ml. Therefore, it is clear that the antibacterial activity of LMOX against these Gram-positive bacteria is not as good as against the above-mentioned Gram-negative species. LMOX was injected intravenously as a one-shot dose of 20 mg/kg to 5 newborn infants (ranging in age from 0 to 13 days) and to 2 suckling infants (49 and 60 days of age), and then the concentration of the drug in the serum was monitored with time. The mean serum concentrations in the newborn group at various times were as follows: 38.5 micrograms/ml at 0.5 hour, 31.6 micrograms/ml at 1 hour, 26.9 micrograms/m l at 2 hours, 17.8 micrograms at 4 hours and 15.5 micrograms/ml at 6 hours. For the 2 suckling infants, the mean values at those same time points were 30.5, 23.9, 16.3, 7.4 and 4.0 micrograms/ml. In addition the value for the mean serum half-life was 4.46 hours in the newborn infant group and 1.96 hours in the suckling infant group. The urinary recovery rate was 32.3% in the newborn infant group and 49.7% in the suckling infant group during 6 hours or 8 hours.(ABSTRACT TRUNCATED AT 400 WORDS)