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Biomedical subjects

H Jeffery

Publications and source records attributed to H Jeffery.

At least 19 recordsLinked to original sources
PubMed2001

Enteral human IgG for prevention of necrotising enterocolitis: a placebo-controlled, randomised trial.

BACKGROUND: Neonatal necrotising enterocolitis is a serious, commonly fatal disease in premature neonates. Although feeding with expressed breast milk and other good nursery practices are partly protective, preventive measures are needed. Treating neonates enterally with a mixture of human IgA and IgG, prepared from donated blood, has been claimed to protect against necrotising enterocolitis. However, no IgA preparation is available in Australia. Our aim, therefore, was to identify whether or not enteral IgG could prevent the disorder. METHODS: We did a multicentre, double-blind, placebo- controlled trial. We randomly assigned 768 infants to receive human IgG 1200 mg/kg daily, and 761 to receive placebo, for up to 28 days. Treatment began at the same time as enteral feeding. The primary outcome measure was the proportion of infants who developed definite necrotising enterocolitis during the trial, and any deaths that resulted from the disorder in the treatment and placebo groups. Analysis was on an intention-to-treat basis. FINDINGS: 43 infants developed definite necrotising enterocolitis in the IgG group, ten of whom died. In the placebo group, 41 infants contracted the disorder and six died (p=0.47). 25 infants on IgG and 36 on placebo had suspect necrotising enterocolitis (p=0.14). INTERPRETATION: Supplementation of enteral feeds with human IgG does not reduce necrotising enterocolitis.

Double-Blind Method↗
PubMed2000

The role of gastro-oesophageal reflux in the aetiology of SIDS.

Gastro-oesophageal reflux (GOR) has been identified as a possible cause of SIDS. Several features of GOR unique to infants presenting with apparent life-threatening events (ALTEs) have led to its 'pathogenic' definition. One is that the life-threatening apnoea itself is initiated by GOR, another is that the ALTE relates to prolonged reflux during sleep, in a vulnerable sleep-state, and finally that the ALTE relates to excessive quantities of GOR. The presumption of GOR 'pathology' as a cause of SIDS however, is questionable in these susceptible infants for three reasons: firstly, GOR is physiological and occurs in most infants; secondly, there is no general consensus on what constitutes normal physiological reflux, and thirdly, variation in the recording technique and methods of data analysis and interpretation may account for the differences between study groups. It seems likely therefore if GOR is implicated in SIDS, additional factors are involved. Under certain circumstances, physiological GOR may trigger life-threatening apnoea in apparently healthy infants, that leads to SIDS. One mechanism that could explain such a death is reflex apnoea by stimulation of laryngeal chemoreceptors (LCR) during sleep. The conditions under which this could be fatal are the occurrence of gastric contents refluxed to the level of the pharynx during sleep, in the young infant who has depressed swallowing and arousal. That is, the occurrence of GOR to the level of the pharynx during sleep, an infrequent event that is usually innocuous, could be converted to a fatal event if swallowing is impaired and arousal depressed, by a variety of mediating factors such as prone sleeping, prematurity, sedatives, seizures or upper respiratory tract infections. The identification of LCR responses, particularly in prone sleeping and premature infants provide further evidence that this mechanism may be implicated in the aetiology of SIDS in apparently healthy infants.

Aging↗
PubMed1999

Role of ureaplasma urealyticum in lung disease of prematurity.

AIM: To examine the role of Ureaplasma urealyticum colonisation or infection in neonatal lung disease. METHODS: Endotracheal aspirates from ventilated infants less than 28 weeks of gestation were cultured for U urealyticum and outcomes compared in infants with positive and negative cultures. RESULTS: U urealyticum was isolated from aspirates of 39 of 143 (27%) infants. Respiratory distress syndrome (RDS) occurred significantly less often in colonised, than in non-colonised infants (p=0.002). Multivariate logistic regression analysis showed that in singleton infants, ureaplasma colonisation was the only independent (negative) predictor of RDS (OR 0.36; p=0. 02). Both gestational age (OR 0.46; p=0.006) and isolation of U urealyticum (OR 3.0; p=0.05) were independent predictors of chronic lung disease (CLD), as defined by requirement for supplemental oxygen at 36 weeks of gestational age. Multiple gestation was also a major independent predictor of RDS and CLD. CONCLUSIONS: Colonisation or infection with ureaplasma apparently protects premature infants against the development of RDS (suggesting intrauterine infection). However, in singleton infants, it predisposes to development of CLD, independently of gestational age. Treatment of affected infants after birth is unlikely to significantly improve the outcome and methods are required to identify and treat the women with intrauterine ureaplasmal infection, before preterm delivery occurs.

Humans↗
PubMed1996

Late-onset infections of infants in neonatal units.

OBJECTIVE: To examine regional variations in the incidence of late-onset neonatal infections in Australian and New Zealand neonatal units. METHODOLOGY: A longitudinal, prospective surveillance study of systemic sepsis (septicaemia or meningitis) in 11 neonatal units: 10 in the Australian States of the Northern Territory, New South Wales, Queensland, Victoria and Western Australia, and 1 in Christchurch, New Zealand. The results are reported of late-onset neonatal infection (defined as sepsis after 48 h) for the second year of prospective surveillance, data being collected from 1 October 1992 to 30 September 1993. RESULTS: Data were available on 24535 live births in Australia, representing approximately 10% of all live births in the country. There were 320 episodes of sepsis in Australian units affecting 294 babies. One hundred of these episodes (31%) were early-onset; 3.0% of babies admitted to six tertiary care neonatal units attached to maternity hospitals developed late sepsis, and this rate did not differ between units. The proportion of babies infected was inversely related to birthweight: 22.6% of babies under 1OOOg, but 0.6% over 2000g. Coagulase negative staphylococci were the commonest cause of late-onset sepsis. There were 26 episodes of S. aureus septicaemia, of which only one was due to MRSA. Meningitis occurred in 13 babies (5.9%) with late-onset sepsis. The mortality from late-onset sepsis was 7.7%. CONCLUSIONS: Coagulase-negative staphylococci are the commonest cause of late-onset sepsis of babies in neonatal units. There were no major regional differences in the incidence of, or the organisms causing, late sepsis.

Australia↗
PubMed1995

Protection of mice from Bordetella pertussis respiratory infection using microencapsulated pertussis fimbriae.

Conditions have been established which allow the efficient entrapment of Bordetella pertussis fimbriae in poly(lactide-co-glycolide) microspheres. Fimbriae released from the matrix were found to have retained some degree of conformational structure, as determined by assessing the capacity of fimbrial protein to bind to antibodies mapping to either conformational or denatured structures on the fimbriae, either encapsulated in microspheres with a mean diameter of 24 microns and an estimated in vitro protein release rate of approximately 42 days, or conventionally adjuvanted with alhydrogel, elicited vigorous immune responses in mice. The encapsulated fimbriae appear to elicit marginally lower serum antibody levels than those induced by equivalent amounts of alhydrogel-adjuvanted fimbriae. Mice immunised with both preparations were, however, protected against intranasal infection with live B. pertussis as evidenced by the significant reduction in levels of bacterial colonisation observed in the lungs and tracheas of immunised animals when compared to the immunologically naive controls.

Animals↗
PubMed1994

"Click test": rapid diagnosis of the respiratory distress syndrome.

Appropriate and early treatment with exogenous surfactant has clinical and economic benefits for neonates with pulmonary surfactant deficiency. In order to rapidly and reliably identify such neonates, we have evaluated the shake and click tests, biophysical tests of surfactant function, using 0.2 mL samples of tracheal (TA) and gastric aspirates (GA). Samples from 181 neonates with a gestational age range of 24-40 weeks were shaken with 95% ethanol. If bubbles formed (positive shake test) they were examined in air-free water under a microscope. In a positive shake or click test, the bubbles rhythmically increase and then decrease in size, denoting the presence of active surfactant. The probability of the tests to predict clinical surfactant deficiency was analyzed. The latter was defined as respiratory distress syndrome or transient tachypnea of the newborn diagnosed by chest radiography and clinical criteria. The click test on TA from preterm infants was most accurate, with a 100% positive predictive value and specificity, and a 93% and 94% negative predictive value and sensitivity respectively. These values for GA were 73%, 84%, 97%, and 95%, respectively. The test is quick, simple, inexpensive, reproducible, and unaffected by contamination with blood. The accuracy of this test on TA in diagnosing surfactant deficiency in neonates would permit early and optimal treatment with exogenous surfactant. When performed on GA, the test could aid decisions regarding transfer of neonates to tertiary level care.

Biophysical Phenomena↗
PubMed1994

The incidence of histological chorioamnionitis in IVF/GIFT preterm births.

A retrospective case control study was designed to investigate the role of subclinical infection as a risk factor for the high rate of preterm deliveries in IVF/GIFT pregnancies. The cases and the controls were identified from the records of consecutive livebirths of < 35 weeks' gestational age (GA), at King George V Hospital from 1987-1993. Fifty one singleton and 58 twin IVF/GIFT preterm births were matched for GA, year of birth, plurality, maternal age, parity, preclampsia and antepartum haemorrhage. As a marker of subclinical infection, the incidence of histological chorioamnionitis (HCA) in the 2 groups (as defined by the standardized, semiquantitative method of Benirschke) was compared. The matched variables did not differ significantly between the IVF/GIFT group and the control group. No significant difference in the incidence of HCA was detected between IVF/GIFT and control groups for singletons or twins. Overall 24% of IVF/GIFT and 30% of controls showed evidence of HCA, odds ratio (95% confidence intervals), 0.72 (0.40-1.31). This study showed no evidence that the incidence of HCA, is significantly increased in IVF/GIFT preterm births compared with other matched, preterm births. Therefore, we conclude that subclinical infection/inflammation cannot explain the 4-fold increase in preterm births in the IVF/GIFT population.

Adult↗
PubMed1993

Long-term antibody responses in mice following subcutaneous immunization with ovalbumin entrapped in biodegradable microparticles.

Ovalbumin (OVA) was entrapped in microparticles prepared from three different poly(lactide-co-glycolide) (PLG) polymers and the microparticles were administered subcutaneously to mice as a single dose. Two weeks after immunization, the serum IgG antibody response to OVA entrapped in microparticles was significantly greater than the response to soluble OVA. The response to OVA entrapped in microparticles peaked at week 10 and remained high for the full 1-year duration of the study. In a second study, the effect of particle size on the immunogenicity of PLG microparticles with entrapped OVA was assessed. Following booster immunizations in mice, microparticles of 1.5 microns were significantly more immunogenic than microparticles of 72.6 microns. Furthermore, although enhanced serum IgG responses were induced by immunization with OVA adsorbed to microparticles (1.0 microns), entrapment of the OVA in microparticles (1.5 microns) resulted in significantly better responses.

Animals↗
PubMed1993

The preparation and characterization of poly(lactide-co-glycolide) microparticles. II. The entrapment of a model protein using a (water-in-oil)-in-water emulsion solvent evaporation technique.

Poly(lactide-co-glycolide) (PLG) microparticles with entrapped antigens have recently been investigated as controlled-release vaccines. This paper describes the preparation of PLG microparticles with an entrapped model antigen, ovalbumin (OVA), using a (water-in-oil)-in-water emulsion solvent evaporation technique. In a series of experiments, the effects of process parameters on particle size and OVA entrapment were investigated. It was found that smooth, spherical microparticles 1-2 microns in diameter containing up to 10% (w/w) OVA could be produced using a small volume of external aqueous phase containing a high concentration of emulsion stabilizer and a 1:5 antigen:polymer ratio. PAGE analysis, isoelectric focusing, and Western blotting of OVA released from the microparticles in vitro confirmed that the molecular weight and antigenicity of the protein remained largely unaltered by the entrapment procedure.

Blotting, Western↗
PubMed1992

Risk factors for necrotising enterocolitis: the influence of gestational age.

Over a 7 year study period, 82 infants were identified who had necrotising enterocolitis (NEC). A case-control study of the 74 preterm infants was performed to determine those factors which contributed to the development of NEC. The 35 infants with NEC and gestation between 30-36 weeks, when compared with control infants matched for gestational age, had significantly lower birthweight centiles, cord pH, and 1 minute Apgar scores. By contrast, there were no significant differences between the 39 infants with NEC and controls in the 25-29 week group, except that fewer babies with NEC had received breast milk. The eight term babies all appeared to have an obvious predisposing event. We thus propose a model in which susceptibility to NEC is dependent on gestational age. In the 25-29 week range all babies are at risk on the basis of extreme prematurity. In the 30-36 week range asphyxiated and growth retarded babies are at increased risk, while at term a major predisposing event appears to be required.

Birth Weight↗
PubMed1992

Enhanced secretory IgA and systemic IgG antibody responses after oral immunization with biodegradable microparticles containing antigen.

Intragastric immunization may lead to the induction of antibodies in the secretory immune system including saliva. The antibody response is usually short-lived. The objectives of this study were to see whether oral immunization with biodegradable microparticles containing antigen might lead to enhanced mucosal responses. Ovalbumin (OVA) was entrapped in a novel antigen delivery system comprising poly (D,L-lactide-co-glycolide) (PLGA) microparticles. Salivary IgA and serum IgG responses after three daily oral immunizations in BALB/c mice were assayed by ELISA at weekly intervals and compared with those to soluble antigen. Low levels of salivary IgA antibodies were detected at Weeks 2 and 3 in both groups and no significant differences were found. After a secondary series of intragastric immunizations at Week 4, marked differences were apparent between the groups. The mean salivary IgA titre at Week 6 was 959 +/- 494 U compared with 30 +/- 5 in the soluble OVA group (P less than 0.0001). Significant differences were still apparent at Weeks 7-8 through the value was falling. Serum IgG antibodies were detectable and were significantly greater in the particle group (at Weeks 4 and 8) than in controls (P less than 0.001). These results suggest that microparticles are taken up by antigen-presenting cells in Peyer's patches, then slowly degrade in vivo and release entrapped antigens, and thus can function as potent antigen delivery systems giving rise to both mucosal and systemic responses. Microparticles have considerable potential as a controlled released antigen delivery system for the induction of longer-term immune responses at mucosal surfaces.

Administration, Oral↗
PubMed1991

Controlled release microparticles for vaccine development.

The primary and secondary sera IgG antibody responses to ovalbumin (OVA) entrapped in biodegradable poly(lactide-co-glycolide) (PLGA) microparticles were compared with the responses obtained with soluble OVA. In addition, OVA in PLGA microparticles was also administered after dispersion in an immunostimulatory vehicle, Freund's incomplete adjuvant (FIA). The primary IgG responses to OVA in microparticles/FIA were significantly greater than the responses to soluble OVA from day 14 to day 42, when booster immunizations were administered. From day 49 to the end of the study at day 84, the responses to OVA, both in microparticles alone and in microparticles/FIA, were significantly greater than the responses to soluble OVA. Nevertheless, the responses obtained for OVA in microparticles or microparticles/FIA were, in general, not as high as those obtained with OVA in Freund's complete adjuvant.

Animals↗
PubMed1991

Biodegradable microparticles as controlled release antigen delivery systems.

A model but poor immunogen, ovalbumin (OVA), was entrapped in a novel antigen delivery system comprising poly (D,L-lactide-co-glycolide) (PLGA) microparticles. Both the primary and the secondary IgG antibody responses obtained with OVA in microparticles were compared to those obtained with OVA emulsified in Freunds' adjuvants by two routes of immunization, intraperitoneal (i.p.) and subcutaneous (s.c.) injection. Following single i.p. or s.c. injections, the IgG serum antibody responses to OVA in microparticles were significantly greater than the responses to OVA in Freunds' complete adjuvant (FCA) for up to 10 weeks. After s.c. booster doses of OVA, the secondary IgG antibody responses to OVA in microparticles remained greater than the secondary responses to OVA in Freunds', but not significantly so. Furthermore, the primary IgG responses to OVA in microparticles obtained 8-12 weeks after a single i.p. injection were greater than the secondary responses to OVA in Freunds' obtained by repeat s.c. injections at Weeks 0 and 6. These results demonstrate that microparticles can function as potent antigen delivery systems for an entrapped antigen. Due to their ability to degrade slowly in vivo and to release entrapped antigens, microparticles have considerable potential as controlled release antigen delivery systems for the induction of long-term immune responses.

Animals↗
PubMed1989

Perinatal cocaine intoxication.

This report describes a case in which cocaine abuse during pregnancy was related temporally to abruptio placentae, preterm labour and to rapid delivery. The neonate developed respiratory distress with features of persistent pulmonary hypertension of the newborn and also signs of neurological dysfunction. He was managed by supportive therapy and has been followed-up to nine months of age. Perinatal cocaine intoxication, either directly or indirectly, is discussed as a cause of his cardiorespiratory and neurological maladaptation. As cocaine abuse appears to be an escalating problem in Australia, increased public awareness of the dangers of both acute and long-term abuse of the drug is seen as a priority in preventive care.

Adult↗
PubMed1987

Is C-reactive protein really useful in preterm premature rupture of the membranes?

In a prospective blind study 380 daily serum samples from 55 women with preterm premature rupture of the membranes were analysed for C-reactive protein (CRP). Although the last CRP before delivery was higher in patients with histological chorioamnionitis (P = 0.007), considerable overlap between infected and non-infected pregnancies occurred, precluding the use of CRP as a diagnostic test if published normal levels were used. When upper limits were set at 30, 35, or 40 mg/l, the last CRP before delivery proved 90, 95 and 100% specific and 88, 92 and 100% positively predictive of infection in singleton pregnancies. Such high specificities are needed to prevent inappropriate intervention based on false positive results. We therefore propose upper limits for single estimations of 30, 35, or 40 mg/l depending on the relative risks of preterm delivery versus infection at various gestational ages. In addition, consecutive values greater than 20 mg/l appeared highly predictive of infection.

C-Reactive Protein↗