Ramesh Jhaveri

Pharmacokinetics of cefoperazone in full-term and premature neonates.

The pharmacokinetics of cefoperazone were evaluated in 28 newborn infants who were being treated for sepsis. A dose of 50 mg/kg was administered intravenously on days 0 to 2 in all, with a second dose administered on days 5 to 7 in 14 infants. Cerebrospinal fluid penetration was also studied in seven neonates. The mean peak concentration of cefoperazone in the serum of premature infants less than 33 weeks of gestational age, 159 (standard deviation, +/- 22) micrograms/ml, was higher than concentrations in premature infants 33 to 36 weeks of age and full-term infants (110 +/- 41 and 109 +/- 29 micrograms/ml, respectively). The mean concentrations 24 h after dosage were similar in all three groups, 13 to 17 micrograms/ml. The mean serum half-lives were similar in the three subgroups and ranged from 7 to 9 h. After the dose at 5 to 7 days, mean blood levels in the subgroups at 0.5 h were 149, 112, and 112 micrograms/ml; 24-h levels ranged from 9 to 12 micrograms/ml. The mean serum half-lives ranged from 5 to 7 h. Cerebrospinal fluid levels in patients with meningitis ranged from 2.8 to 9.5 micrograms/ml and in patients without meningitis from 1 to 7 micrograms/ml. Peak blood levels were 15 to 1,000 times higher than the 90% minimal inhibitory concentration of common pathogens found in newborns. These observations support the potential efficacy of cefoperazone in treatment of infections, including meningitis, in newborn infants.

A new graph for insertion of umbilical artery catheters

THE LENGTH of insertion for umbilical artery catheters has been based on the graphs tabulated by Dunn 1 for total body length and shoulder umbilical length. Despite frequent use, these graphs have not been critically evaluated and have several potential limitations. They are based on the anatomic landmarks of the pathologist (the diaphragm) rather than those of the clinician (vertebrae). The original study included only eight of 25 patients with TBL _< 40 cm (fiftieth percentile for patients weighing 1,200 gin); and used only postmortem patients. Using live patients and including a larger number of low-birth-weight neonates, we re-evaluated Dunns graphs. In addition, new graphs for catheterization were calculated and their accuracy determined. METHODS

Pharmacokinetics and Safety of Cefamandole in Infants and Children

Cefamandole, a new cephalosporin antibiotic, has greater activity against common pathogens, including Escherichia coli, Haemophilus influenzae, and Proteus (including indole-positive strains), than available cephalosporin drugs. We have evaluated the safety and pharmacokinetics of this drug in 30 infants and children. Blood levels and urinary excretion of the drug were similar to those previously found in adults. The only side effects were mild and transient elevation of serum glutamic oxalacetic transaminase in 12 patients and of blood urea nitrogen in 1 patient in whom serum creatinine remained normal and unchanged.

α1 ANTITRYPSIN (AAT) ACTIVITY IN DEVELOPMENT OF BRONCHOPULMONARY DYSPLASIA (BPD)

Some of the toxic side effects of oxygen therapy are indirectly attributable to the release of proteases including elastases from PMNs. These may contribute to the pathogenesis of BPD. AAT inhibits elastases and if deficient may lead to an imbalance favoring proteolytic digestion of pulmonary connective tissue. We studied the possible role of AAT activity by measuring the trypsin inhibitory capacity (TIC) in prematures with IRDS who received oxygen.Twenty prematures with IRDS (m wt 1052 gms; m GA 29 wks; M/F = 12/8) had serial TICs drawn on days 1,3,7 and weeks 2-10. They were analyzed for severity of IRDS (mild: IMV ≤ 3 days, severe: IMV ≥ 4 days) and for the development of BPD using standard clinical and xray signs. Higher TICs were observed in 9 patients with mild IRDS (0.91 mg/ml) than in 10 with severe IRDS (0.36 mg/ml) (p<0.02) on day 1 but were comparable thereafter. In the 11 patients who did not develop BPD, TICs (1.05 mg/ml) were higher than in the 9 who did (0.31 mg/ml) (p<0.001) on day 1, week 4 (0.62 vs 0.33 mg/ml) (p<0.03), and week 8 (0.78 vs 0.47 mg/ml) (p<0.03).Decreased AAT activity was associated with the increased severity of IRDS on day 1 and with the occurrence of BPD on day 1 and weeks 4&8. However AAT activity was also directly related to gestational age (r = .6589; p<0.05). Hence AAT activity may play a pathogenetic role in the development of BPD, or may be a non specific marker, or both.

354 EFFECT OF INTRAUTERINE EXPOSURE TO NARCOTICS ON CORD BLOOD CONCENTRATIONS OF PROLACTIN (PRL), CORTISOL(C), AND THYROXINE (T 4 ) IN PRETERM INFANTS

PRL, C and T4 enhance fetal lung maturation, and decreased cord blood levels of these hormones have been found in infants with RDS. Use of narcotics during pregnancy may both decrease the incidence of RDS and affect the metabolism of these hormones.Cord blood concentrations were measured in 33 infants with a G.A. of 30 to 36 weeks. Ten were exposed to either heroin, methadone, or both and two of these developed RDS. Of the 23 non-narcotic exposed infants, 8 developed RDS and 15 did not.The following results (median and range) were obtained:The differences in PRL concentrations between the narcotic exposed and RDS groups were of borderline statistical significance (p=0.08), while levels of C were significantly higher in the no RDS than in the RDS or narcotic exposed groups (p<0.01). None of the other inter-group differences was statistically significant.Intrauterine exposure to narcotics may play a modifying role in the synthesis of pulmonary surfactants.

18p- SYNDROME: CLINICIANS FANTASY

Since the advent of banding techniques, more than one hundred syndromes have been described based on just chromosomal abnormalities. In the majority of those cases a specific chromosomal abnormality could not be suggested by physical examination alone. However, after cytogenetic evaluation was completed, new syndromes were discovered. The 18p- syndrome is one such example whose clinical manifestations are so heterogeneious that by simply examining the patient, the abnormality of chromosome 18 was not even suspected. In fact, our patient was referred for cytogenetic evaluation to rule out Turner syndrome. The major clinical features included: mental and growth retardation, a few dysmorphic facial features, protruding ears, low hair line in the back, severe dental caries and behavioral problems. This is the first reported case of psychosis in this type of genetic abnormality. Primary and secondary amenorrhea are most frequently reported, however, our case had normal sexual development and normal menstruation. After reviewing the current literature, we concluded that it is impossible to establish a 18p- syndrome without chromosomal analysis.

ISCHEMIC INJURY TO NEWBORN RABBIT ILEUM: PROTECTIVE ROLE OF SUPEROXIDE DISMUTFISE (SOD)

Free oxygen radicals(superoxide anion, O2−) cause tissue damage in reperfusion injury of the intestine. The protective effect of a specific scavenger of O2− SOD, on weanling rabbit ileum during ischemia and reperfusion was evaluated. Twenty-three anesthetized weanling rabbits underwent laparotomy. The ileum was divided into 4 loops, each 8-10cm in length. Ischemia was induced in 2 loops by clamping the artery to the loop for 5mins; undamped loops served as controls. Eleven rabbits were pretreated with parenteral human SOD(5-10mg/kg, SC) at 0 and 16hrs. and surgery begun at 20hrs. Twelve received intraluminal SOD(10mg/kg) in 2 loops, and no SOD in 2 control loops. Animals were sacrificed 4 hrs. post surgery. Loops were fixed in formalin and examined histologically for the degree of mucosal necrosis by a pediatric pathologist who was blind to the conditions of the experiment. All rabbits given SC SOD had detectable serum levels of hSOD at 20 & 24 hrs. (.9-6.Omcg/ml).Reperfused ileal loops are protected from mucosal necrosis by both parenteral and intraluminal SOD. This may be an important etiology and therapeutic modality in NEC.

1611 EARLY NEONATAL URINARY TRACT INFECTION (EUTI) CONTROLLED STUDY OF MORPHOLOGY, BACTERIOLOGY AND NATURAL HISTORY

UTI during early neonatal period (under 2 weeks) has rarely been studied. Previous studies included older infants (even up to 3 months) and often lacked complete investigation and long term follow-up. We evaluated all infants with EUTI who were treated and prospectively studied regarding host factors and long term follow-up (mean 2.6 yrs.). Recurrences were classified as frequent (FR) (≥ 2 episodes in any 3 months) or infrequent (IR) if <2. The control group consisted of all neonates with late onset UTI (LUTI) (between 2 weeks and 2 months). M:F ratio, frequency of positive blood culture and abnormal urinalyses was similar. E. coli (EC) constituted only 33% cases of EUTI but 80% of LUTIs (P<0.01). Incidence of abnormal IVP was about double in EUTI (not statistically significant). Recur, rate was slightly lower in EUTI and number of recurrences less than ¼ compared to LUTI.In summary EUTIs are due to organisms other than EC, fever is an unusual sign (1/5 of cases), structural abnormalities are frequent (50%) but associated with fewer recurrences.

132 EFFECT OF CHEST SHIELDING DURING PHOTOTHERAPY ON THE INCIDENCE OF PATENT DUCTUS ARTERIOSUS (PDA) IN PREMATURE INFANTS

PDA is common among premature neonates, especially those <1500gms. In vitro, room light inhibits contraction of immature piglets ductal rings. Since phototherapy is used frequently on the first days of life, we compared the occurrence of PDA among prematures exposed to this intense light source with those whose chests were shielded. Sixty babies with IRDS were randomly assigned to either a treatment group (chest shielded with aluminum foil while on phototherapy-30 babies) or control group (no shield-30 babies). All were on radiant warmers, received mechanical ventilation for respiratory distress syndrome, and phototherapy (Air Shields Model #PTU 78–1) from day 1 of life. Irradiance was maintained at > 4.0uW/cm2/nn in all cases.The significant reduction of PDA with shielding (p< 0.035) suggests that phototherapy is a factor that may play a role in the occurrence of PDA in prematures. Shielding may be a practical method to decrease this common complication should this initial observation be confirmed.

1823 CERULOPLASMIN (CER) LEVELS IN PREMATURES AT RISK FOR BRONCHOPULMONARY DYSPLASIA (BPD)

Oxidant injury during ventilation therapy in prematures with RDS has been postulated as a possible cause of BPD. Antioxi-dants, such as ceruloplasmin (CER), may provide protection against the occurrence of BPD. CER serum levels have been correlated with the degree of severity of RDS and are capable of scavenging superoxide radicals in vitro. We have evaluated the potential role of serum ceruloplasmin levels in predicting the subsequent development of BPD in 30 prematures with RDS who required ventilator therapy.CER was not significantly lower in those patients who developed BPD when compared to those who did not.Although patients who developed BPD had lower birth weights (p<0.005), lower gestational age (p<0.03) and had more severe RDS (p<0.03), there were no significant differences in CER levels. In both groups CER levels ranged from 33–50% of pooled adult plasma. One way analysis of variance did not demonstrate that the CER levels were a significant predictor for the development of BPD.