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Fc gamma receptors provide an essential link between cellular and humoral immunity, and little is known about their expression in monocytes of newborn infants. We compared baseline and gamma interferon (IFN-gamma)-induced expression of Fc gamma RI and Fc gamma RII protein and Fc gamma RI mRNA in monocytes from healthy, term infants and adults. Fluorescence-activated cell sorter analysis demonstrated that baseline expression of monocyte Fc gamma RI in newborn infants was not significantly different from that in adults, while Fc gamma RII protein expression in monocytes derived from newborns was significantly higher than that for adults (mean channel fluorescence [MCF] for newborns and adults, 5.53 and 4.50, respectively [P = 0.039]). In vitro treatment with recombinant IFN-gamma increased the expression of Fc gamma RI in monocytes of newborns and adults to the same extent (2.4- and 2.2-fold increase in MCF in newborns and adults, respectively, at 42 h). We developed a semiquantitative fluorescence reverse transcriptase PCR which demonstrated a significant increase in mRNA for Fc gamma RI in monocytes of newborns and adults with in vitro IFN-gamma exposure, indicating that IFN-gamma acts by increasing the transcription or transcript stability of Fc gamma RI mRNA. While there was no significant effect of IFN-gamma treatment on Fc gamma RII expression in monocytes from adults, there was a 20% increase in Fc gamma RII in monocytes from newborns (P = 0.009). Monocytes from healthy, term newborns and adults exhibit comparable baseline and IFN-gamma-induced levels of expression of Fc gamma RI and higher baseline and IFN-gamma-induced levels of expression of Fc gamma RII.

We studied the interaction between Candida albicans and mononuclear phagocytes derived from cord blood. In the presence of normal serum, the extent of phagocytosis and killing of candida by monocyte-derived macrophages was equivalent for newborns and adults. In the absence of serum both phagocytosis and killing by macrophages were reduced by half, but cord and adult cells were still equivalent. Mannosylated BSA and mannan inhibited ingestion of unopsonized candida by macrophages, suggesting a role for the mannose receptor. Exposure of cord and adult macrophages to IFN-gamma (10-500 U/ml) gave quantitatively different results in Candida killing, as well as in release of superoxide anion (O2-). Maximal increase in these functions with adult macrophages was achieved with 100 U/ml IFN-gamma. No enhancement with cord macrophages could be detected after treatment with 100 U/ml, and at 500 U/ml there was still significantly lower killing and O2- release compared with adult cells. Defective up-regulation of O2- release was also present in cord monocytes exposed to IFN-gamma on day 0. Studies of the surface expression of IFN-gamma receptors using a "nonblocking" mAb against the IFN-gamma receptor revealed a comparable number of receptors on cord and adult monocytes. When blocking Abs were used, however, there was a three times higher number of positive cells in cord monocytes. Specific binding of 125I-IFN-gamma to cord monocytes and macrophages was also higher compared with adult cells. These data suggest that neonatal macrophages have a normal capacity to ingest and kill both opsonized and unopsonized Candida but cannot be fully activated by IFN-gamma, a finding that could not be attributed to lower expression of IFN-gamma receptors on the neonatal cells.

We investigated the effects of glutathione (GSH), the major naturally occurring thiol, and a pharmacologic thiol precursor of GSH, N-acetyl cysteine (NAC), on the expression of human immunodeficiency type 1 (HIV-1) in primary cord blood and adult donor monocyte-derived macrophages (MDM). HIV-1 infection of cord blood and adult MDM was accomplished after incubating 10-15-d-old cultures for 4 h with a monocyte-tropic strain of HIV-1 (Bal). After 1 wk in culture cell supernatants were tested for reverse transcriptase (RT) activity. MDM were exposed to 5, 10 and 20 mM concentrations of both GSH and NAC before infection, during infection, and after infection was established. GSH and NAC suppressed the replication of HIV-1 in both primary cord blood and adult donor MDM in a concentration dependent fashion. These suppressive effects were more pronounced in cord-derived cells than in adult-derived cells. In cells treated with GSH or NAC before infection, there was no significant rise in RT activity as compared with controls. Similarly, when cells were treated with GSH and NAC and simultaneously infected, there was also no significant rise in RT activity after 1 wk in culture. In cells treated after infection was established, RT values were suppressed 80-90% that of untreated controls. This effect persisted for 1-2 wk after exposure to GSH and NAC. Untreated controls demonstrated syncytium formation and lost characteristics of spreading and elongation 2 wk after HIV-1 infection, whereas most of the treated cells remained free of syncytium and retained cytoplasmic spreading, adherence, and elongation. These data are consistent with other studies of thiol suppression of HIV-1 replication and demonstrate a similar observation for primary cultured cord MDM. These results may offer new approaches toward cellular protection after infection with HIV-1.

We have investigated the susceptibility of cord blood monocyte-derived macrophages to human immunodeficiency virus type 1 (HIV-1) infection in vitro. Cord blood monocytes were maintained in vitro for 10 to 15 days and then infected with HIV-1. Syncytia were observed 14 days after infection by light microscopy. Viral proteins were detected by immunofluorescence assay. Electron microscopic examination demonstrated typical lentivirus particles within cytoplasmic vacuoles. The supernatants from the HIV-1-infected cultures also contained significant reverse transcriptase activity and p24 antigen. Like adult monocyte/macrophages, cord-derived monocyte/macrophages expressed the CD4 receptor molecule. Pretreatment with blocking antibody prior to infection with HIV-1 Bal significantly reduced or blocked infection of cord monocyte/macrophages. When cord and adult monocyte/macrophages were infected with HIV-1 Bal or Ada-M and directly compared, higher reverse transcriptase activities and p24 antigen expression were obtained with cord monocyte/macrophages. However, no significant difference was found between adult and cord monocyte/macrophages infected with HIV-1 IIIB. These observations suggest that cord monocyte-derived macrophages may be important in the pathogenesis of pediatric AIDS and that the increased susceptibility of cord monocyte/macrophages to HIV-1 infection in vitro may be relevant to the enhanced susceptibility of neonates to HIV-1 diseases in vivo.

Esthesioneuroblastoma can be regarded as a chemosensitive tumor based on multiple reports of response to treatment. Neoadjuvant therapy is seldom curative, however, and may be of no benefit in some patients. Individuals who respond to preoperative therapy have a greater chance of long-term disease-free survival. Platinum-based therapy has been the mainstay of treatment. Toxicity has been mild, and treatment failures have been treated with postoperative chemotherapy with or without bone marrow transplantation. Given the small number of cases of esthesioneuroblastoma diagnosed annually, it is unlikely that any consensus on this issue is forthcoming. Either post- or presurgical treatment of advanced stage or recurrent disease has become the standard of care, however.

Persistent pulmonary hypertension of the newborn causes systemic arterial hypoxemia because of increased pulmonary vascular resistance and right-to-left shunting of deoxygenated blood. Inhaled nitric oxide decreases pulmonary vascular resistance in newborns. We studied whether inhaled nitric oxide decreases severe hypoxemia in infants with persistent pulmonary hypertension.In a prospective, multicenter study, 58 full-term infants with severe hypoxemia and persistent pulmonary hypertension were randomly assigned to breathe either a control gas (nitrogen) or nitric oxide (80 parts per million), mixed with oxygen from a ventilator. If oxygenation increased after 20 minutes and systemic blood pressure did not decrease, the treatment was considered successful and was continued at lower concentrations. Otherwise, it was discontinued and alternative therapies, including extracorporeal membrane oxygenation, were used.Inhaled nitric oxide successfully doubled systemic oxygenation in 16 of 30 infants (53 percent), whereas conventional therapy without inhaled nitric oxide increased oxygenation in only 2 of 28 infants (7 percent). Long-term therapy with inhaled nitric oxide sustained systemic oxygenation in 75 percent of the infants who had initial improvement. Extracorporeal membrane oxygenation was required in 71 percent of the control group and 40 percent of the nitric oxide group (P=0.02). The number of deaths was similar in the two groups. Inhaled nitric oxide did not cause systemic hypotension or increase methemoglobin levels.Inhaled nitric oxide improves systemic oxygenation in infants with persistent pulmonary hypertension and may reduce the need for more invasive treatments.

Although extracorporeal membrane oxygenation (ECMO) has been responsible for the improved survival of infants with cardiorespiratory failure, its use over the last decade has raised concern as to the health of the survivors and the severity of neurodevelopmental sequelae. Though infants meeting ECMO criteria have a variety of reasons prompting the use of this therapy, most studies to date have simply reported outcome on the entire population that has survived without regard to the original nature of the child's illness. The purpose of this study was to determine the type and extent of health-related problems and neurodevelopmental sequelae in infants requiring ECMO therapy and the association of these findings with the infants' primary diagnosis.Eighty-two neonates required ECMO therapy between May 1990 and December 1993. The most common diagnosis prompting ECMO therapy included 26% with meconium aspiration syndrome, 34% with congenital diaphragmatic hernia (CDH), 16% with persistence of the fetal circulation, and 9% with sepsis. Information concerning the hospital course was obtained through chart review, and the infants were seen at 6 and 12 months of age for medical and neurodevelopmental follow-up. Data were analyzed using descriptive statistics and Fisher's exact test, t-tests, and analysis of variance where appropriate. Assessment of hospital course and discharge data focused on the four main diagnostic groups, whereas follow-up data were further limited to the two most frequently encountered groups (meconium aspiration syndrome and CDH).Overall survival was 79%. Significant differences in survival were noted based on primary diagnostic category. Those with CDH fared the worst, with an overall survival rate of 68% and a more complicated hospital course with a longer duration of ECMO. At discharge, the CDH group demonstrated a greater incidence of bronchopulmonary dysplasia, gastroesophageal reflux, feeding dysfunction, and hypotonia. No significant differences were noted in the incidence of intraventricular hemorrhage, cerebral infarction, extra-axial fluid collection, or seizures. Hearing loss was uncommon. During the first year of life, although no differences were noted in growth rate, infants in the CDH group continued to experience a higher incidence of gastroesophageal reflux (43%) and feeding dysfunction, with 36% of this group requiring tube feedings for nourishment. Although 40% of the entire ECMO population was diagnosed with bronchopulmonary dysplasia before initial discharge, by 1 year of age, 50% of those with CDH versus 17% of those with meconium aspiration syndrome continued to be clinically symptomatic. Although the ECMO population as a whole scored in the normal range developmentally, CDH infants had significantly lower motor and slightly lower cognitive scores at 1 year of age. Despite finding abnormal muscle tone in a high percentage of the entire ECMO population at discharge, most demonstrated resolution by 1 year of age. Of the CDH infants, however, 75% continued to evidence some degree of hypotonicity, which affected acquisition and quality of gross motor skills.Despite the impact that ECMO has had on the survival of infants with severe respiratory failure, the efficacy of ECMO cannot be assessed accurately without an analysis of the extent and morbidity in the surviving population. Most centers are reporting relatively low morbidity for the entire ECMO population. However, upon separating this population into primary diagnostic categories, we found that the CDH population encountered a greater number of neurodevelopmental, respiratory, and feeding abnormalities during the first year of life. The reasons for these differences are unclear but may be related to the severity of the primary illness itself or the variables associated with prolonged ECMO therapy. Stratifying outcome by primary diagnosis gives the health care provider more information to improve

Schemes for predicting outcome in craniocerebral missile injury have ranged from Cushing's analysis that was based on the physical characteristics of the injury to complex logistic analyses that incorporate radiographic, laboratory, and clinical data. Generation of predictive scales is discussed, focusing on the utility of the Glasgow Coma Scale (GCS) score at presentation, presence or absence of coagulopathy, and radiographic evidence of the volume and type of tissue damage.

Management of cerebral gunshot injuries has changed considerably since Cushing's (1916) and Matson's (1948) classification schemes, developed during World War I and World War II, respectively. These military injuries are characterized by either very high mass, low-velocity shrapnel wounds or by high muzzle velocity missiles causing extensive destruction of tissue. The preponderance of low muzzle velocity weapons seen in clinical practice and the availability of computed tomographic (CT) evaluation within minutes after presentation has altered the range of prognostic indicators available to the neurosurgeon and the amount of relative importance placed on each factor. Raimondi and Samuelson (1970) noted this difference in wound ballistics and offered a classification scheme based on initial neurologic assessment. No well-defined classification system for civilian craniocerebral gunshot wounds has been proposed that evaluates and integrates clinical, laboratory, and neuroradiologic data. A retrospective study was performed on all 62 civilians with gunshot wounds to the head admitted to the University of Virginia Hospital between December, 1984, and November, 1990. The patient population consists of 86% males and 14% females, with an age range of 10-72 years; 60% self-inflicted wounds and 32% patients who died en route or immediately upon arrival at the hospital. The overall mortality rate was 55% at 1 week postinjury. Although we have demonstrated an association between some previously defined factors and prognosis in civilian injury, such as admission Glasgow Coma Scale (GCS) (p = 0.001) and initial pupillary response (p less than 0.001), we have also defined other significant predictors of outcome including abnormal coagulation states on admission (p less than 0.001) and the neuroradiologic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

The inflammatory response requires the localization of monocytic cells to sites of tissue injury through adherence to extracellular matrix molecules such as fibronectin (Fn), a nonimmune opsonin, which binds to collagen, fibrin, heparin and cell surfaces. Adherence to this molecule of two myeloid cell lines differing in their stage of differentiation, was studied. In the baseline state, U937 monocytic cells bound specifically to matrix-bound Fn, while HL-60 promyelocytic cells bound minimally. Exposure to Phorbol myristate acetate (PMA) dramatically increased binding of both U937 and HL-60 cells to Fn with plateau effects at 10 ng/ml for both cell lines and at 30 and 60 minutes for U937 and HL-60, respectively. Treatment with metabolic inhibitors suggests that PMA stimulation depends at least in part on intact energy metabolism, protein synthesis and cytoskeletal components. This system should help elucidate the early molecular and biochemical events involved in monocyte adherence to the extracellular matrix.

Fibronectin secreted by macrophages may contribute to the development of pulmonary fibrosis. Prostaglandins are important regulators of macrophage metabolism whose role in the regulation of fibronectin production is not known. In this study, we examined the effects of PGE1 and indomethacin on human monocyte-derived macrophages exposed to these agents in culture for 10 to 14 days. Indomethacin (10 micrograms/ml) reduced the ratio of supernatant fibronectin to adherent cell DNA by 32%, p0.01, and reduced lysozyme/DNA by 29%, p0.0001. Exogenous PGE1 (1 ng/ml) did not affect fibronectin, but increased lysozyme/DNA by 27%, p0.01. In additional experiments, supernatant fibronectin and total protein synthesized in the presence of 3H-leucine were measured. Indomethacin (10 micrograms/ml) had no effect on total supernatant protein radioactivity, but reduced fibronectin/DNA by 33%, p0.001, and reduced fibronectin/total protein by 19%, p0.01. Since indomethacin increases macrophage secretion of plasminogen activator and interleukin-1, these experiments add to the evidence that specific secretory products of macrophages are regulated independently. We conclude that indomethacin at 10 micrograms/ml decreases the production of fibronectin and lysozyme by monocyte-derived macrophages. The modest size of the effect, and its absence at lower doses of indomethacin, indicate that prostaglandins are unlikely to have a major role in the regulation of macrophage production of fibronectin.

In our nursery, we identified neonates with positive urine latex particle agglutination (LPA) tests for group B streptococcus (GBS) antigen who did not have corroborating cultural evidence of infection. To investigate the mechanisms underlying these apparent false-positive reactions, we examined the urine LPA test in an unselected population of neonates suspected of sepsis. Urine specimens for LPA testing and culture and simultaneous perirectal cultures were obtained from 134 neonates with suspected sepsis. Six infants had positive blood cultures for GBS; four of the six were positive by LPA testing. An additional 20 infants had positive LPA tests but negative blood cultures; of these, 13 had mothers who received antibiotic treatment prior to delivery. Two infants with positive LPA results and negative blood cultures had bacteria isolated from urine cultures obtained in a nonsterile fashion (GBS, Escherichia coli). GBS was not isolated from perirectal swabs of infants with positive LPA tests and negative blood cultures. In conclusion, (i) a high proportion of neonates evaluated for sepsis gave positive LPA tests and negative blood cultures, (ii) local contamination of the perirectal skin or urinary tract with GBS was an unlikely source of false-positive LPA reactions, and (iii) maternal antibiotic pretreatment during labor may represent an important cause of apparent false-positive LPA reactions.

Marked elevations in the vasopressin concentrations in human umbilical cord blood have been reported previously (4, 8). This could either be a part of generalized increase in the activity of fetal endocrine system at the time of birth, a phenomenon that has led to the concept of fetal participation in the onset of labor, or simply due to the stress of delivery. The present study is an attempt to examine the later possibility. Plasma vasopressin was determined by radioimmunoassay [9] in separately collected arterial and venous blood from the umbilical cords of 24 babies spontaneously delivered and 14 babies born after Caesarian Section in the absence of labor. Arterial acid-base determinations were done in each case. The Apgar Score was evaluated by one individual. In order to obtain a general idea of circulating concentration of this hormone in the neonatal period, vasopressin concentrations were determined in the systemic venous blood of 12 normal and 10 stressed babies. Vasopressin concentrations in the umbilical arterial blood of babies born after spontaneous delivery were remarkably high, as compared to all the other groups. Despite a wide range, between 5-2200 pg/ml, there was no correlation between the magnitude of vasopressin elevation and the severity of fetal asphyxia (Fig. 1). The present finding in part, confirms and expands previously observed increased vasopressin levels in the cord blood after spontaneous vaginal delivery. In addition, a lack of correlation between fetal asphyxia and the vasopressin levels suggests that these high levels may not be related to this form of stress.

The recent spread of hybridoma technology among laboratories has promoted the development of monoclonal antibodies against a wide variety of infectious disease agents. While monoclonal antibodies theoretically represent an excellent (perhaps superior) alternative to conventional antisera as diagnostic, therapeutic or laboratory reagents, traditional antisera may be preferable to monoclonal antibody in some circumstances because of the fixed affinity and specificity as well as the limited functional capacities of some antibodies. The acceptance of monoclonal antibodies by the clinical microbiologist and physician must await proof of their reliability, safety and efficacy.

Plasma lipolytic activity (lipoprotein lipase and hepatic lipase), free fatty acids (FFA), triglycerides, cholesterol, and glucose levels were measured in 21 premature infants [gestational age 26-37 weeks (mean +/- SEM 30.4 +/- 0.63 weeks), aged 1-8 days (mean +/- SEM 3.00 +/- 0.35 days)]. All infants were maintained on total parenteral nutrition with heparin (1 U/ml) and were given Intralipid, 1, 2, and 3 g/kg/day, over 15 h on days 1, 2, and 3, respectively. Blood samples were drawn before and at the end of Intralipid administration. Baseline plasma lipolytic activity, before the start of lipid infusion, was 1.54 +/- 0.24 U/ml (1 U = 1 mumol [3H]oleic acid released from tri[3H]olein/h). Lipolytic activity increased after lipid infusion to 4.04 +/- 0.96, 4.32 +/- 0.63, and 6.09 +/- 1.00 U/ml on days 1, 2, and 3 of the study. Hepatic lipase amounted to 38-47% of total lipolytic activity. During the 3 days of lipid infusion, there were dose-dependent increases in plasma FFA, triglyceride, and cholesterol. Whereas FFA and triglyceride concentrations returned to prelipid infusion levels 9 h after stopping the infusion of Intralipid, 1, 2, or 3 g/kg, there was a cumulative increase in plasma cholesterol and glucose concentrations. The close correlation between FFA concentrations and plasma lipolytic activity (r = 0.655, p less than 0.001) suggests considerable intravascular lipolysis. The positive correlation between plasma FFA and triglycerides (r = 0.632, p less than 0.001) and FFA and cholesterol (r = 0.582, p less than 0.001) indicate, however, that intravascular lipolysis does not prevent the lipemia associated with Intralipid infusion to low birth weight infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Deficiencies in both cellular and humoral immunity follow human bone marrow transplantation, predisposing recipients to life-threatening infections. Peripheral blood mononuclear cells (cells of donor marrow origin) from nine patients were collected serially at 3-month intervals during the first year post transplant and evaluated for proliferation and lymphokine (gamma interferon and interleukin-2) production in vitro. Cultures of patient cells or those of normal adult volunteers were stimulated by phytohemagglutinin (PHA) in vitro, and lymphocyte blastogenesis was assayed by tritiated thymidine uptake on day 2. PHA blastogenesis for peripheral blood mononuclear cell cultures from patients post bone marrow transplant achieved normal levels 3-6 months post transplant. Supernatants produced by cells from marrow recipients (less than 12 months post transplant) had lower-than-normal IFN-gamma activity and decreased IL-2 activity. Two patients with acute graft-vs-host disease (GVHD) had persistently depressed PHA blastogenesis, IFN-gamma production, and IL-2 production at 12 months post transplant.

The American Academy of Pediatrics currently recommends administering full-dose diphtheria, tetanus, pertussis, (DTP) vaccine to preterm infants, beginning at 2 months' chronologic age. Many physicians, however, continue to administer DTP vaccine at a reduced dosage in an attempt to lessen side effects. This study was designed to quantitate the immune response of 20 preterm infants immunized with half-dose DTP vaccine and to determine the nature and extent of side effects. Control subjects were 25 preterm infants immunized with full-dose vaccine. Although 96% of infants who received a full dose were able to mount a serologic response to pertussis after a second dose of DTP, 45% of infants who received a half dose were unable to mount a similar immune response to pertussis even after a third dose of DTP and required a full-dose (fourth dose of DTP) vaccine to better ensure protection. Serologic responses to diphtheria and tetanus were similar in the two groups. The incidence of side effects in preterm infants receiving both full-dose and half-dose DTP was less than that seen in a full-term population. Thus, the physician caring for the preterm infant should adhere to the American Academy of Pediatrics' recommendation for the immunization of preterm infants and offer full-dose DTP vaccine at the routine time intervals of 2, 4, 6, and 15 or 18 months' chronologic age to ensure adequate protection.

Rapid and accurate detection of neonatal bacteremia is an important part of the management of the neonate with suspected sepsis. This study compared the incidence of positive umbilical cord blood cultures (UCBCs) to the incidence of positive peripheral venous blood cultures and determined whether a meticulous UCBC technique prevented contamination of culture specimens. Six UCBCs of the 200 sampled were positive. Three cultures exhibited delayed growth (more than 48 hours) and were not considered clinically significant. In 2 of the 3 remaining positive cultures were organisms considered contaminants; the third culture correlated to the infant's peripheral venous blood culture (alpha-hemolytic streptococcus), showing evidence of bacteremia. From these data the authors conclude that 1) meticulous and fastidious collection of UCBCs prevents contamination of culture specimens, and 2) the UCBC may prove to be a satisfactory alternative to the postnatal peripheral venous blood culture for detection of neonatal bacteremia.

Fibronectin is a large opsonic glycoprotein which promotes reticuloendothelial system clearance of bacteria, immune complexes, collagenous debris, and damaged platelets. The concentration of plasma fibronectin is decreased in the newborn infant; however, the role of fibronectin in the onset and course of neonatal sepsis is unknown. Serial plasma fibronectin levels were determined in 19 neonates with documented bacterial sepsis. Plasma fibronectin concentrations decreased significantly (P less than .001) in all study infants concurrent with the development of septicemia. Recovery of plasma fibronectin to normal levels occurred by day 5 in premature neonates and by days 7 to 10 in term neonates. Fibronectin deficiency and resultant reticuloendothelial system impairment may decrease the ability of newborn infants to resist or clear bacterial infections. An acute reduction in the concentration of plasma fibronectin may be a valuable marker for neonatal sepsis.

Photoisomerization of native bilirubin to more polar configurational isomers (Z,E-bilirubin) and structural isomers (lumirubin) was studied in 20 premature infants with physiologic jaundice to determine the effect of low-dose (6 microW/cm2/nm) v high-dose (12 microW/cm2/nm) phototherapy. Patients were assigned prospectively to receive either low- or high-dose treatment. Study groups were comparable with regard to birth weight, gestational age, and total bilirubin prior to the initiation of phototherapy. Treatment was administered with white light produced by a commercially available halogen-tungsten lamp. Dose was measured periodically during the study to ensure a uniform distribution of irradiance and constant exposure. Sera for photoisomers were obtained before initiation of treatment and at two, four, and eight hours. Photoisomers expressed as a percent of total bilirubin were determined using high-pressure liquid chromatography. Serum proportion of both configurational and structural isomers increased with the duration of phototherapy in both treatment groups. There was no significant difference between the percent of configurational isomers in low- and high-dose phototherapy groups. However, high-dose treatment produced a significantly higher proportion of the structural isomer lumirubin after four hours (0.7% low dose v 1.3% high dose, P less than .05). These data confirm that phototherapy results in both configurational and structural isomerization of bilirubin in vivo. Furthermore, the previously described "dose" effect of phototherapy may be attributed to the production of the structural isomer, lumirubin.

Thirteen percent of the newborns in our study group were colonized with group B streptococci on day 3. This colonization rate appeared constant during the first two weeks of life and then decreased to 5%. Of the babies colonized on day 3, 59% and 91% were culture-negative on days 14 and 42, respectively. Sixty-five percent of the babies carrying group B streptococci on day 14 acquired this microorganism following discharge (day 3). Babies colonized with staphylococci or Escherichia coli were found to have decreased probability of colonization with group B streptococci.

The physiology of the blood-brain barrier and its disruption by a variety of pathophysiologic processes in the development of experimental and clinical kernicterus are reviewed. The use of currently available methods for measuring free and bound bilirubin in developing strategies for the prevention of kernicterus and more subtle sequelae of hyperbilirubinemia also are presented.

Streptococci belonging to Lancefield group B are frequently recognized as the etiological agents of sepsis and meningitis in young children. Current methods of identifying these organisms have not been universally accepted because of the time and complexity in performing the studies and a lack of reference antisera. We have developed hybrid myeloma (hybridoma) cell lines which secrete large amounts of antibody against types II and III group B streptococci. Antibodies harvested from supernatants react only with the bacterial strain that was used initially to immunize the animals. We have used the hybridoma antibodies in an enzyme immunoassay and have shown it to be a sensitive and reliable technique for typing group B streptococci. The use of hybridoma antibodies in the enzyme immunoassay may permit early detection of group B streptococcal antigen before cultures are visibly positive.

Fibronectin, a large-molecular-weight glycoprotein present on cell surfaces and in human plasma, promotes cell adhesion and may modulate reticuloendothelial clearance of particulate debris and bacteria. Amniotic fluid is known to contain a heavily glycosylated variety of fibronectin, and cells derived from amniotic fluid synthesize and secrete fibronectin in tissue culture. The purpose of this study was to determine the relationship between the concentration of fibronectin in amniotic fluid and gestational age. Amniotic fluid samples, obtained from 54 women whose pregnancies ranged in gestation from 15-40 weeks, demonstrated a significant decrease in fibronectin levels with increasing duration of pregnancy (r = -0.70). Diminished concentrations of amniotic fluid fibronectin in the latter stages of pregnancy may represent either decreasing synthesis by amniocytes or a dilutional effect from fetal urine.

Intraperitoneal administration of a sublethal dose of E. coli endotoxin to fasted rats produced within 12 hrs a rise in plasma ammonia, urea, glutamine, glutamate and aspartate as compared to controls. At this time, hepatic ureagenesis also increased as did the levels of glutamate, glutamine, aspartate, alanine and asparagine. However, liver glucose and ketone levels were unchanged. Hepatic [ATP]/[ADP] ratios declined in endotoxin-treated animals and there was an oxidation of mitochondrial pyridine nucleotides and a reduction of cytosolic pyridine nucleotides. The results suggest that impairment of nitrogen metabolism is an early effect of endotoxemia.

Plasma levels of FFA, TG and CHOL were measured in 21 premature infants (gest. age 26-35 wks.), aged 1-8 days, maintained on total parenteral nutrition with heparin (1 U/ml) and given 1, 2 and 3 g IL/kg/day (over 15 h) on day 1, 2 and 3 respectively. Blood samples were drawn before and at the end of IL administration.

In excitable cells, cellular Na+ levels are kept low by Na-pump activity of the cell membrane. Since Na-pump activity affects vascular tone, we measured cell NA+ levels and Na-pump activity in umbilical (UA) and chorionic plate arteries (CPA) from term vaginal deliveries and compared them to “normal” adult arteries using rabbit carotid arteries (RCA). Contiguous arterial segments (2.5mg) were obtained from the various sites and used for cell Na+ measures using a LiCl wash followed by flame photometry. Na-pump activity was measured using an ouabain sensitive 86Rb uptake procedure. These results indicate that human UA & CPA contain high (CPA) to extraordinarily high (UA) cell Na+ levels compared to RCA and that resting Na-pump activity is maximally turned on in UA and elevated in CPA versus RCA. Rings of arteries isolated in-vitro and contracted with serotonin in K+free media completely relax when the NA-pump is activated with KCl. Taken together these results suggest a cellular basis for maintenance of placental vascular vasodilation.

We have previously documented decreased oxygenation during infusion of 1 g/kg Intralipid (IL) over 4 h (0.25 g/kg/h) in premature infants with respiratory illnesses (Pediatr. 66:26,1980). To examine the effect of slow infusion rates and lipid dosage on oxygenation, 16 AGA premature infants with RDS (BW mean ± SEM - 1.26 kg ± 0.04; EGA 29.9 wks ± 0.34; Postnatal age 4.0 days ± 0.26 - p = NS vs. previous study group) maintained on total parenteral nutrition were given 1, 2 and 3 IL g/kg/day over 15 h (IL g/kg/h = 0.067, 0.133, 0.20) on day 1, 2 and 3 respectively. Arterial blood gases (for calculation of alveolar-arterial oxygen gradients-AaDO2) and blood for free fatty acid (FFA) and triglyceride (TG) analysis were drawn before and at the end of IL infusion. There was a significant effect of IL infusion rate on ΔAaDO2 (p

Colostrum was obtained about 3 hours after breast feeding from 27 healthy mothers, 1-3 days after delivery. The phagocytic cell concentration of colostrum varied considerably amongst different donors. Ten samples were hypercellular (>5×106/ml); 6 were cellular (1-5×106/ml) and 11 were hypocellular (

Plasma levels of lipase (LPL, HL) and free fatty acids (FFA) were measured in 21 infants (gest. age 26-35 wks) aged 1-8 days, maintained on total parenteral nutrition with heparin (1 U/ml) and given 1, 2 and 3 g IL/kg/day (over 15 h) on day 1, 2 and 3, respectively. Blood samples were drawn before and at the end of IL administration.