Gordon B. Avery

Experimental use of cytosine arabinoside in congenital cytomegalovirus infection

Two infants with congenital cytomegalovirus infection were treated with cytosine arabinoside in an attempt to eradicate the virus and thereby possibly prevent further neurologic deterioration. Although in one case there appears to have been some modification of virus excretion during and after therapy, complete cessation of virus excretion was not achieved. The second patient apparently stopped excreting cytomegalovirus just prior to therapy but continued to harbor virus in white blood cells after therapy. Toxicities were vomiting, neutropenia, and thrombocytopenia.

Clostridium difficile in paediatric infections.

Summary Clostridium difficile , a major cause of antibiotic induced pseudomembranous colitis, has rarely been reported as a pathogen in paediatric patients. We report isolation of this organism from three children with various inflammatory conditions. These cases suggest that C. difficile may be pathogenic in paediatric patients.

Futility considerations in the neonatal intensive care unit

The purpose of this article is to summarize and comment on the history of medical decision making in the neonatal intensive care nursery, emphasizing considerations of futility. Several epochs will be described, with shifting roles of health care providers, the infants family, and proxies for society at large. Futility has been an issue in the intensive care of newborn infants throughout the last 35 years. Long before the Baby Doe regulations and the formation of ethics committees, neonatologists tried to determine which care measures were indicated. Given the frequency of severe malformations, birth asphyxia, and extreme prematurity, it has been a common event for the responsible physician to ask himself: will this treatment be beneficial or merely futile? As the therapeutic armamentarium became more powerful and complex, the choices from among a possible array of interventions became increasingly difficult. The autonomy of parents as decision makers was increasingly affirmed. In the 1980s, the federal government, the courts, and frequent malpractice suits set boundaries on medical decision making. In the 1990s, third party payors became increasingly assertive in limiting resource expenditure. These legal and societal mandates are frequently at variance with one another. Thus the issue of medical futility, as it applies to neonates in the United States, must be considered unresolved.

The fetal membranes as a barrier to transplantation immunity.

In order to investigate whether the fetal membranes of the mouse possess properties equipping them to form part of the barrier to transplantation immunity between fetus and mother, fetal membranes were grafted upon skin graft beds and overlaid with skin isogeneic to the adult host. When the inner surface of the membrane was down, grafts adhered to the bed, were promptly vascularized, and survived in good condition for 10 days. When the outer membrane surface was down, a cavity developed between membrane and bed, vascularization was delayed and occurred only from the cut edges of the graft, and the membrane epithelium degenerated after 6 days. Regardless of membrane orientation, brisk allograft reactions took place in pre-sensitized allogeneic hosts, demonstrating the presence of transplantation antigens in the fetal membranes. The resistance of the outer membrane epithelium to vascularization and its tendency to secrete amorphous material which created a cavity between it and the graft bed may be among the properties which normally prevent invasion of the fetal membranes by maternal blood vessels and the consequent wholesale exchange of transplantation antigens.

392 VITAMIN PREPARATIONS IN NEONATAL PARENTERAL NUTRITION (PN)

Toxicity to neonates from drug solvents is of concern. We reported serum hyperosmolarity due to Propylene Glycol (PG) in MVI-12. This study compared two groups of infants weighing < 1500 grams. Gr PG-received MVI-Conc. (with PG) 1 cc/d in their PN and Vit. E 50 u/wk IM. Gr Mann.-received MVI-Ped. (with Mannitol) 6.5 cc/d. Serum & urine osm. PG levels, BUN, creatinine, Na & glucose were measured days 0,2, 5, 12, 19, 26, 33 & 40 on PN. Weight, urine output, and fluid intake were measured daily. Vit E levels were measured on days 5, 26 & 33 on Pn. Mannitol levels were not measured. RESULTS: There were no differences between the groups in birth weight, gest. age, sex or age & wt. at start of PN. PG < 1000gm-serum mosm. correlated with serum PG during first 12 days of PN. (PG levels 2.4-108.4 mg/dl.) 14.2% of serum osmol. values were > 310mosmol/L. Mann, gr. < 1000gm-12.6% serum mosm. were > 310mosmol/L. No diuretic effect of Mannitol was detected. MVI-Ped. in recommended doses may produce higher than desirable vit. E levels.

1425 NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IMPROVE SURVIVAL IN GROUP B STREPTOCOCCAL SEPSIS

The mortality for newborns with early onset group B beta hemolytic streptococcal sepsis (GBSS) remains high (50-80%) despite specific antibiotic and pressor therapy. The four-to-five day old newborn rat model was used to evaluate two nonsteroidal anti-inflammatory drugs in the therapy of GBSS. We compared intraperitoneal (IP) indomethacin 3 mg/kg (INDO) and ibuprofen 4 mg/kg (IBUP) to sterile water controls in rats that had been injected subcutaneously (SQ) with two strains (GBS 1,GBS 2) of Type III group B strep grown to log-phase in Todd-Hewitt broth. The therapies (0.05cc IP) and micro-organisms (0.05cc SQ) were injected simultaneously. Per cent survival (% S) at 24 hours was recorded and lethal doses (LD) for controls were calculated:In the neonatal rat model, INDO significantly improved 24 hour survival in both the LD33 and LD85 groups. At an LD90, INDO failed to improve survival while IBUP did. This data suggests that after further studies INDO and IBUP--both prostaglandin inhibitors and anti-inflammatory agents--may become useful adjuvants to present treatment of early onset GBSS.

513 SERUM RETINOL AND RETINYL ESTERS IN PREMATURE INFANTS RECEIVING PARENTERAL ALIMENTATION

High doses of Vitamin A given during parenteral alimentation (PA), even if reduced by adsorption to plastic tubing, could cause toxicity if the retinyl ester (RtE) overwhelms the capacity of the storage mechanism. To check for significant serum RtE characteristic of Vitamin A toxicity, 9 infants were sampled while on peripheral PA for 1 to 31 days. On the day of sample, the mean daily Vitamin A dose per kg body wt: 3677 I.U. (S.D.1750) or 1103 ug (S.D.525). Mean gestational age: 30.2 wks (S.D.1.1), birth weight: 1222 g (S.D.264), day of age for sample ranged from 5 to 37 days and a total of 13 samples were collected. Serum RtE levels were uniformly low, i.e. 2.1 μg% or less. Serum Retinol before PA in 5 infants was 6.4 μg % (S.D. 3.8) and rose to 12.7 μg% (S.D. 5.3) during PA.Further work needs to be done to identify the optimal Vitamin A dose, but it is reassuring to know that the current dose does not appear to be excessive.

430 FAT DIGESTION IN THE STOMACH OF PREMATURE INFANTS: ORIGIN OF THE LIPOLYTIC ACTIVITY

Digestion of dietary fat in the adult is intitiated in the stomach by a lipase similar to that present in lingual serous glands (Hamosh et al. J. Clin. Invest. 55: 908, 1975; Lab. Invest. 37, 1977). Recently, we have reported similar activity in gastric aspirates of premature infants (Hamosh et al. Physiologist 20: 40, 1977). In order to determine the origin of the lipase, we have tested esophageal and gastric aspirates obtained from four infants with congenital esophageal atresia. Lipolytic activity (tested with doubly labeled 3H-glyceryl-14C-tripalmitin) was present in both esophageal (14.24 ± 10.6 n mol/ml/hr) and gastric (6.97 ± 2.31 n mol/ml/hr) aspirates; the reaction products were partial glycerides, glycerol and free fatty acids; pH optimum was 5.4. The data support previous observations that lipolytic activity in the stomach is due to enzymes secreted from the oro-pharynx (tongue). However, lipolytic activity in the stomach of these children strongly suggests the presence of a gastric lipase. (Supported by Grant NIH HD10823).

WHAT IS BEST PEEP

The interrelationships of compliance (CL), O2 transfer, CO2 excretion, and pulmonary circulation have not been explored in prematures with HMD. Using an esophageal balloon and pneumotach, CL was measured at intervals during titration of PEEP, together with arterial blood gases, in 7 prematures with HMD varying from 11h to 9d in age. As PEEP was varied stepwise upwards and downwards, an optimal value was found for CL. PaO2, and AaDO2. A 15 min. equilibration time was allowed at each PEEP setting, and the entire titration spanned 2-3 hrs. “Best PEEP” was different for CL, PaO2, and AaDO2, although best PaO2 and best AaDO2 were very similar. Interestingly, best PaO2 was at a significantly higher PEEP than best CL (mean 5 vs. 7.1cm H2O, P= < .05). PaCO2 rose at PEEPs of 6-9 in 4 patients, but was not limiting to “best PEEP.” The titration itself yielded an apparently beneficial “opening up” effect in 3 babies, in that repeat measurement of PaO2 and CL at the same PEEP showed improvement. Clinical estimations of PEEP were often not the same as recommended best PEEP, based on these titrations. In 3 cases PEEP was increased, in 2 it was decreased, and in 2 the previous setting was considered optimum. These data suggest that no single parameter defines “best PEEP,” but rather jt must be a judicious compromise.

Therapeutic intravenous galactose in glucose intolerant prematures

Small, sick prematures often require intravenous alimentation and are sometimes intolerant to concentrated glucose, with hyperglycemia and glycosuria. Animal studies have shown hetter glucose regulation in the presence of galactose, a normal product of lactose digestion. Possible benefit of IV galactose was studied.Blood galactose levels on 58 newborns taking milk by mouth showed prompt utilization with peak levels < 5 ng/dl. T1/2 was 45 min. with no significant effect of gestational age or time after birth, indicating necessary enzymes are present. Therapeutic infusions of equal conc. of glucose and galactose in 4 glucose-intolerant premies and 1 infant of a diabetic mother yielded promising results. All stabilized blood glucose in the normal range (70-120), 2 cleared significant urine glucose spills, 3 recovered from previous hyperglycemia, there was a tendency to tolerate higher CHO loads, and no clinical toxicity was noted. Blood galactose levels were monitored and remained below 20 mg/dl. These results suggest that IV galactose is feasible and may cause less hyperglycemia in sick prematures and less insulin stimulation in IDMs while allowing administration of additional calories as CHO.