Studies of neonatal calf diarrhoea. IV. Serum and faecal immune globulins in neonatal salmonellosis.
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The ketogenic potential of Intralipid was studied in two groups of infants: 12 were SGA and 15 AGA; all were clinically stable and less than 48 hours of age. During four-hour Intralipid tolerance tests, the SGA infants achieved significantly higher plasma TG and FFA levels. Both groups of infants significantly increased the concentration of ketone bodies; however, there was no difference in the levels achieved. In view of the slower clearance rate of TG and the higher levels of FFA in SGA infants, it is speculated that in addition to a possible defective lipoprotein lipase system and a decrease in number and size of the adipose cells, beta-oxidation of FFA to ketones may be occurring at a slower rate. The generation of high levels of ketones during Intralipid infusion period in both groups of infants indicates that SGA infants can handle ketone bodies as readily as AGA infants.
At 33 hospitals in the United States, a double-blind, randomized clinical trial was performed to compare one versus three prophylactic doses of synthetic surfactant in 700 to 1100 gm inborn infants. All 826 infants received an initial prophylactic dose of surfactant within 30 minutes of birth. Subsequently 410 infants received two doses of placebo (air) 12 and 24 hours later, and 416 infants received two additional doses of surfactant. By the age of 28 days, 70 infants who received one dose of surfactant and 40 infants who received three doses were dead, a 43% relative reduction in the mortality rate (30 fewer deaths; p = 0.002). By the age of 1 year after term, 87 infants who received one dose and 62 infants who received three doses were dead: a 29% relative reduction in the mortality rate (25 fewer deaths; p = 0.027). Infants who received three doses of surfactant required significantly less oxygen and less mean airway pressure for the first week of life. Necrotizing enterocolitis (9 vs 25 infants; p = 0.005), and use of high-frequency ventilation (13 vs 26 infants; p = 0.037); pancuronium (43 vs 62 infants; p = 0.045); and leukocyte transfusions (0 vs 4 infants; p = 0.042) were less frequent in the three-dose group, but air leak, bronchopulmonary dysplasia, intraventricular hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, and infections were not different. These results indicate that physiologic findings, mortality rates, and probably morbidity rates are improved by two additional prophylactic doses of synthetic surfactant.
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A survey is reported of 113 systematic reviews of therapies in neonatology, based on 559 eligible randomized trials in total. These reviews were prepared by the CNRG and were published in the Cochrane Library, Issue 3,2001. The median number of included trials per review was 3 (range 0 to 32) and participants 207 (range 0 to 5460). Among 90 reviews with a categorical primary outcome, the median number of outcome events per review was 54 (range 1 to 1284). Among reviews finding a statistically significant benefit of treatment, the effect size was large (median relative risk 0.55, range 0.09 to 0.93). Reviews of surfactant for prevention and treatment of respiratory distress syndrome were able to detect moderate-sized treatment effects (median relative risk 0.85) because of the large number and size of trials in this field. Among many reviews finding no evidence of treatment effect, large and potentially important benefits or harms could not be excluded. Most CNRG reviews were current. There is a continuing need to prepare systematic review of therapies not yet covered and to keep an increasing number of reviews up-to-date.
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Lambs sucking non-immunised ewes or ewes immunised 4-5 weeks before lambing with live attenuated, aromatic-dependent (aroA) Salmonella typhimurium (strain CS 332) were challenged orally at either 2, 4 or 7 days of age with virulent S. typhimurium (strain CS 94) at doses ranging from 10(9) to 10(13) colony forming units. No lambs displayed signs of clinical salmonellosis and all survived challenge but those sucking immunised ewes had organisms of the challenge strain in their faeces for much shorter periods of time than lambs of the control ewes. High titres of specific antibodies were measured in colostrum and milk of immunised ewes in comparison with very low titres measured in samples from control ewes; these differences were reflected by the titres of antibodies in the sera of corresponding lambs. At 2 days after lambing, the major antibody isotype in the colostrum of immunised ewes and sera of their lambs was IgM whereas at 7 days IgG1 was the predominant isotype. While it was clear that vaccination of pregnant ewes with the live attenuated vaccination conferred protection against experimentally-induced salmonellosis in their lambs, considerable protection was observed in control lambs in spite of there being very low titres of antibodies in the mammary secretion of their dams. The latter observation could be related to the presence of contain non-antibody potent bactericidal factors previously described in colostrum and milk.
In a hepatitis B vaccination program (1982-1992), 705 infants born to HBsAg-positive mothers received HBIg within 2 h of birth and were vaccinated according to a three- or four-dose vaccination schedule, starting either at 3 months or directly after birth. Eight children HBsAg-positive during the first year of life (group 1: infected nonresponders). To determine whether failure of the hepatitis B vaccination was due to perinatal high-level maternal viraemia or genetically determined infant nonresponsiveness to the vaccine, we measured HBsAg and anti-HBs levels in infants and HBeAg and hepatitis B virus-DNA levels in maternal serum, and determined the HLA type of the infants. Controls included 14 infants with a normal anti-HBs response 1 year after vaccination (group 2: noninfected responders) and all eight infants without HBsAg and anti-HBs 1 year after vaccination (group 3: noninfected low responders). HBsAg, HBeAg and anti-HBs were measured by radioimmunoassay (Abbott Laboratories), hepatitis B virus-DNA was measured quantitatively by solution hybridization for groups 1, 2, and 3 (Abbott hepatitis B virus-DNA assay, Abbott Laboratories), and HLA was characterized by microcytotoxicity test for groups 1 and 3. All infants in groups 1 and 2 were born to HBeAg carrier mothers, and those in group 3 to HBeAg-negative mothers. Hepatitis B virus-DNA levels in maternal serum in group 1 were significantly higher than in group 2 (Wilcoxon rank-sum test: p < 0.01). Hepatitis B virus-DNA was not observed in group 3 maternal serum samples.(ABSTRACT TRUNCATED AT 250 WORDS)
A malar rash associated with severe gastrointestinal manifestations developed in a 4-month-old baby 3 months after a normal delivery. Serum complement and IgA levels were low during the active phase of the illness. An increased anticardiolipin antibody titer was demonstrated at the onset of disease and persisted for more than 6 months, at which time the skin and gastrointestinal manifestations subsided. The baby's mother, who had no symptoms, had an elevated Ro (SS-A) antibody titer and a moderately elevated anticardiolipin antibody titer.
Haematopoiesis and immune functions in cord blood (CB) are developmentally immature when compared with adult peripheral blood (APB). The defects in CB immune function and cytokine production may both contribute to the immaturity of CB immunity. We have studied the mechanisms associated with the dysregulation of myeloid lineage cytokines, GM-CSF and M-CSF, and lymphokines, IL-12, and IL-15 in activated CB when compared with APB MNC. Furthermore, we have studied the effects of IL-12 and IL-15 on induction of IFN-gamma and TNF-alpha production, NK, and LAK activities in CB and APB. GM-CSF, M-CSF, IL-12 and IL-15 protein and mRNA are decreased in activated CB MNC. These discrepancies are secondary, at least in part, to the altered post-transcriptional regulation. The impaired ability of CB to produce IL-12 and IL-15 in response to stimulation may contribute to the decrease in IFN-gamma, TNF-alpha production, NK and LAK activities. Furthermore, combination of low dose IL-12 and IL-15 may augment cytotoxic activities and minimize toxicity. These findings suggest that reduced cytokine expression from activated CB may contribute to the impaired CB cellular immunity and exogenous lymphokines may compensate for the immaturity in CB.
An Infant Breastfeeding Assessment Tool was used to assess the breastfeeding behaviour of 38 healthy, full-term newborn babies of multiparous women from birth until effective feeding was established. After data collection was completed, the babies were divided into a non-medicated group (n = 18) and an alphaprodine group (n = 20) based upon the medication profile of the mother. Inter-group differences were analysed using ANOVA and Dunnett's t-test. The dependent variables were the hours from birth to establishing effective breastfeeding and IBFAT scores at 12, 24, 36 and 48 hours after birth. The findings suggest that even small doses of the narcotic analgesic alphaprodine, when administered 1 to 3 hours prior to delivery, can delay effective feeding by several hours and in some cases, days.
We investigated whether gene transfer into hematopoietic cells could be achieved by direct injection of retroviral vector supernatant into the bone marrow space of newborn sheep. Six sheep (5 weeks old) were injected bilaterally with either 1 mL of G1nBgSvNa8.1 vector supernatant (titer: 1 x 10(7)) in each hip (n = 5) or with 3 mL of the same vector preparation/hip (n = 1). In addition, one 3-month-old sheep was injected unilaterally with 1 mL of the same vector preparation. Blood and marrow of these animals were analyzed for the transgene before injection and at intervals thereafter. At 1 week postinjection, an average of 11.6% of the lymphocytes and 25.5% of the granulocytes/monocytes in the marrow, and an average of 0.9% of the lymphocytes and 1.8% of the granulocytes/monocytes in the blood contained and expressed the LacZ gene. The presence/expression of the transgene has persisted for at least 13 months within the blood and bone marrow of these animals. These findings demonstrate that the direct injection of small volumes of high-titer retroviral supernatant into the bone marrow of newborn sheep results in transduction of hematopoietic cells that persists for at least 13 months postinjection.
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A model of vertical HIV transmission was developed using oral HIV-2(287) exposure of newborn Macaca nemestrina. The minimal Animal Infectious Dose for this oral route was found to be 10-fold higher than that for atraumatic viral transmission across other mucosal membranes (vaginal/rectal) of juvenile macaques. However, once infection was established, viral replication was rapid and plasma viremia could be detected by reverse-transcriptase polymerase chain reaction and viral co-culture within 1 week following exposure. No animal was resistant to infection and all macaques initially exposed to a subinfectious viral inoculum were subsequently infected by re-exposure of mucosal membranes. Higher viral load during primary infection correlated with a more rapid CD4 depletion; however, all HIV-2(287)-infected animals developed CD4 depletion during the observation period. This animal model can now be used to study early viral replication in the presence and absence of anti-retroviral agents to help identify conditions to reduce vertical HIV transmission in human newborns.
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