Hugh E Evans

Aerosol inhalation teaching device

To facilitate teaching of inhalation technique to children, we have developed an aerosol inhalation teaching device by modifying the jacket of a canister nebulizer so that inhalation is accompanied by a horn sound and a flashlight is turned on when the canister is actuated. The device was evaluated in 33 children with asthma who had either never used a canister nebulizer (13 patients) or used incorrect technique (20 patients). The inhalation technique was first taught with conventionally, that is, verbal directions and demonstration with a canister nebulizer for 10 minutes. Only 10 (30%) of 33 children learned the technique. The remaining 23 were then taught with the special device. Twenty of 23 learned the technique within 10 minutes, but three others took longer. In a second study, 22 children, 11 of whom were beginners and 11 incorrect users, were instructed with the teaching device from the beginning. Seventeen (77%) learned the technique within 10 minutes; five others took longer. Most children can be taught the aerosol inhalation technique with this easily constructed device.

Oxidant-mediated lung disease in newborn infants***

High concentrations of oxygen are administered with increased airway pressure to most preterm neonates with respiratory distress syndrome (RDS). Among 20% to 30% of survivors a form of chronic lung disease, bronchopulmonary dysplasia (BPD), develops. Its pathogenesis may include tissue damage caused by the superoxide anion (O2-) and other free oxygen radicals. Animal experiments and other data suggested a rationale for superoxide dismutase (SOD) administration in an effort to prevent or ameliorate BPD. Our preliminary studies in 19 prematures with RDS demonstrated its safety in human newborns and permitted measurement of its plasma levels. No adverse clinical findings occurred, and laboratory parameters were unchanged. Subcutaneous administration (0.25 mg/kg) of bovine SOD led to detectable levels at 1 1/2 h (mean 0.22 microgram/ml), with a slight rise to a higher peak at 2 1/2-4 h and a plateau over the remainder of the 12-h interval. Following doses 2-5, peak levels of 0.64 microgram/ml occurred at 4-8 h. With this background, a prospective double-blind controlled study of 45 neonates (mean gestational age, 29 weeks; birth weight, 1,100 g) showed a statistically significant reduction in prevalence of clinical and X-ray signs of BPD with fewer days of continuous positive airway pressure required. The safety and pharmacokinetics of bovine SOD were confirmed.

Lung Tissue Elastin Composition in Newborn Infants with the Respiratory Distress Syndrome and Other Diseases

Amino acid analysis of human fetal lung elastin was undertaken in 49 instances of live-born neonates, ranging from 380 g to full term, and in 3 abortuses of 12-14 wk gestation. The data suggest that formation of the cross-linking agents, desmosine and isodesmosine, occurs early, between 14 and 22 wk. The ratio of neutral to charged amino acids remains low until the 36th wk when it attains adult levels. The composition of elastin was independent of sex and duration of survival. In three neonatal pulmonary diseases (respiratory distress syndrome, atelectasis, and hemorrhage) ratios were significantly lower than those found in nondiseased lungs. This may be a reflection of immaturity or may be a predisposing factor in neonatal lung disease. The latter hypothesis is attractive and receives indirect support from the association of a more polar elastin with other diseases, including adult emphysema and atheromatous aortic change.Our finding of relatively high polarity in elastin from human fetal lung is consistent with previous observations in a variety of fetal organs of other species.

Rates of cesarean section and perinatal outcome : perinatal mortality

A comparison of relevant statistics from National Maternity Hospital, Dublin, Ireland and University Hospital, Newark, New Jersey, USA, for the years 1983‐1989, revealed that after removal of major confounding factors, such as a fourfold difference in < 2500 gram births and an about tenfold discrepancy in the frequency of lethal congenital defects, the perinatal survival rates in all weight categories were significantly higher in the American center. The findings suggest that optimum perinatal results could not be achieved in an American high risk center with the approximately 6% abdominal delivery rate favored in Dublin. The same data also suggest, however, that the 17.5% rate of abdominal deliveries in Newark was unnecessarily high. The favorable impact of the relatively liberal use of cesarean section might have been derived in this study from a marked reduction of in utero losses, in the absence of an identifiable effect upon the rate of neonatal mortality.

CORRECTION OF DEFECTIVE NEUTROPHIL CHEMOTAXIS BY SYSTEMIC VITAMIN C (VC) THERAPY IN NEWBORN INFANTS (NB)

Vitamin C has been shown to improve defective chemotaxis in Chediak - Higashi Syndrome. We evaluated its effect on NBs whose predisposition to sepsis is partly attributable to defective chemotaxis. Ten term NBs were treated with 4 doses of 100 mgs of VC q6 hrs starting on day 2 of life. Blood was obtained for study immediately before and after VC treatment. Chemotactic index (CI) and random migration index (RM) were determined by a modified Boydens chamber technique. PMNs were deposited on a 3 μ millipore filter which divided the chamber into an upper compartment filled with Hanks solution (HS), and lower filled with a mixture containing AB serum, endotoxin and HS. Following incubation and staining a ratio of migrated cells to total cells was determined and termed CI. In a parallel run with HS on either side the ratio was termed RM. The result (table) indicates that CI and RM increased about 64% followingVC therapy, a difference significant at P<0.02. We conclude that Vitamin C by improving the PMN qualitatively may be a useful adjunct to the treatment of sepsis in NB infants in general and in leukopenic infants in particular.

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.

NEUTROPHIL (PMN) MIGRATION IN RESPONSE TO CHEMOTACTIC FACTORS GENERATED BY THE INVADING PATHOGENS IN ACUTE BACTERIAL ENTERITIS (ABE)

The role of chemotactic and random migration(RM) in ABE is not known. They were determined in 9 pts with ABE due to shigella or salmonella between days 3&5 of admission and 9 controls. One day prior to study each isolate was grown in medium 199 to generate specific chemotactic factors (SCF). Leukocytes were harvested from heparinized blood and 1.0×106PMNS were deposited on to 3 u millipore filter which was placed in the Boydens chamber. The upper compartment of the chamber was filled with Hanks solution (HS) and the lower with SCF 100uL/mL of HS. Three simultaneous chambers were also set up with endotoxin activated serum (EAS), E. coli generated factors (ECF) and HS alone in the lower compartments. After 3hrs incubation filters were stained and cells which migrated to lower surface were counted. A ratio of migrated to total cells with SCE, EAS & ECF was termed as chemotactic index(CI) and RM with HS alone. In 4 pts studies were repeated after therapy. Mean (±1SD) values are presented (table): Mean CIs of patients with all the 3 factors were significantly lower than those of controls and significantly increased after therapy. RM was similar. Supression PMN chemotaxis may be one step in the pathogenesis of ABE. Counteracting it with drug/agents may improve the outcome.

421 EFFECT OF IN VITRO AND SYSTEMIC VITAMIN C (VC) ON THE NEUTROPHIL FUNCTION IN SICK NEWBORNS (NBs)

VC has been shown to improve chemotaxis in normal newborns. We evaluated its effect in vitro on 11 sick term NBs, including 8 on antibiotics for undocumented sepsis, on day 2-3 of life. WBCs, separated from the blood, were divided into 2 aliquots. One was incubated for 30 min with Hanks solution (HS) containing 20 μg/ml VC and the other with HS alone.In a separate study 10 different term NBs with suspected sepsis were treated with 4 doses of lOOmgs of VC q6h starting on day 2 of life. Blood was drawn before and after VC treatment. Chemotaxis was determined by a modified Boydens chamber technique. PMNs were deposited on a 3μ millipore filter which divided the chamber into an upper compartment filled with Hanks solution (HS), and lower filled with a mixture containing AB serum, endotoxin and HS. Following incubation and staining a ratio of migrated cells to total cells was determined (CI). In a parallel run with HS on either side the ratio was termed RM.Mean CI increased 64% following VC incubation and VC therapy. RM remained unchanged in both studies. VC may be a useful adjunct to therapy of NBs with sepsis but more studies are needed.

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.

553 ETHNIC DETERMINATION OF THE PATHOGENS IN URINARY TRACT INFECTION (UTI) IN INFANTS AND CHILDREN

The role of ethnicity in UTI has not been studied. We analysed the prevalence of organisms causing initial UTI in 550 cases including blacks (200 cases), Hispanics (330 cases) and white (20 cases) based on race, sex and urinary tract (UT) structure (table). Whites were too few to evaluate. Incidence of E.coli(EC) (>80%) was similar in black and Hispanic females (F) however in males (M)>50% were caused by organism other than EC Proteus Mirabilis (PM) was more prevalent in Hispanic M than Hispanic F, black M or F (P < 0.001, each). Among Hispanic M, PM was less common with abnormal UT (AUT) than with normal UT (NlUT) S.epid and all gram+ were most prevalent in black M compared with other groups (P<0.01). Among black M Gm+ was seen in 33% with AUT and only 13% with NlUT (P > 0.05). Incidence of AUT was similar (about 24%) in hispanic and black. In conclusion, PM is primarily a pathogen of Hispanic M and more common with NlUT and rare among blacks. Gm+ are most common among black M and is associated with malformation. Ethnicity thus has major impact on the prevalence of pathogen in UTI.