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Biomedical subjects

J Hawdon

Publications and source records attributed to J Hawdon.

12 recordsLinked to original sources

Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants.

BACKGROUND: Human milk has considerable short and long term benefits for preterm infants, but mothers may experience difficulties in expressing breast milk for infants too immature or sick to breast feed. Oxytocin has been used to assist breast feeding and milk expression, but few data are available to support this intervention in the neonatal unit setting. AIM: To test the hypothesis that oxytocin nasal spray increases early milk output in mothers expressing milk for preterm infants. METHODS: A randomised, double blind trial of oxytocin nasal spray (100 microl per dose) versus placebo was conducted in mothers delivering infants <35 weeks gestation. Sprays were used before expression of milk using an electric pump up to day 5. MAIN OUTCOME: Total weight of milk expressed while using spray (study powered to detect >1SD difference between groups). SECONDARY OUTCOMES: Pattern of milk production; number of pumping sessions; weight/fat content of milk expressed during a fixed 20 minute period on day 5 ("physiological study"); mother's opinion of expressing and spray assessed by questionnaire. RESULTS: Fifty one mothers were randomised (27 oxytocin, 24 placebo). Total milk production did not differ between groups. Repeated measures analysis of variance suggested significantly (p = 0.001) different patterns of milk production, with initial faster production in the oxytocin group then convergence between groups. Parity did not influence the response to the intervention. No significant differences were seen in milk weight or fat content in the physiological study nor in mothers' opinions of milk expression and treatment. CONCLUSIONS: Despite marginal differences in the pattern of early milk production, the use of oxytocin nasal spray did not significantly improve outcome. Most mothers believed they were receiving the active spray, suggesting a significant placebo effect (supported by limited data from historical controls) and benefits from the extra breast feeding support available during the study.

Administration, Inhalation↗

Low birth weight for gestation and airway function in infancy: exploring the fetal origins hypothesis.

BACKGROUND: Poor fetal growth has been associated with impaired airway function in adult life, but evidence linking birth weight and airway function in early childhood is sparse. We examined the hypothesis that low birth weight for gestation is associated with impaired airway function shortly after birth and that this is independent of impaired postnatal somatic growth. METHODS: Airway function was measured using the raised volume technique in healthy white infants of low (< or =10th centile) or appropriate (> or =20th centile) birth weight for gestation and was expressed as forced expiratory volume in 0.4 s (FEV0.4), forced vital capacity (FVC), and the maximal expired flow at 25% of forced vital capacity (MEF25). Infant length and weight, maternal height and weight, maternal report of smoking prenatally and postnatally, and parental occupation were recorded. RESULTS: Mothers of low birth weight for gestation infants (n=98) were lighter, shorter, and more likely to smoke and have partners in manual occupations. At 6 weeks their infants remained lighter and shorter than those of appropriate birth weight (n=136). FEV0.4, FVC, and MEF25 were reduced in infants of low birth weight for gestation, in those whose mothers smoked in pregnancy, or who were in manual occupations. After adjusting for relevant maternal and infant characteristics, infants in the low birth weight for gestation group experienced a mean reduction of 11 ml in FEV0.4 (95% CI 4 to 18; p=0.002), of 12 ml in FVC (95% CI 4 to 19; p=0.004), and of 28 ml/s in MEF25 (95% CI 7 to 48; p=0.03). CONCLUSIONS: Airway function is diminished in early postnatal life as a consequence of a complex causal pathway which includes social disadvantage as indicated by maternal social class, smoking and height, birth weight as a proximal and related consequence of these factors, and genetic predisposition to asthma. Further work is needed to establish the relevance of these findings to subsequent airway growth and development in later infancy and early childhood.

Bronchial Diseases↗

A common muscarinic pathway for diapause recovery in the distantly related nematode species Caenorhabditis elegans and Ancylostoma caninum.

Converging TGF-beta and insulin-like neuroendocrine signaling pathways regulate whether Caenorhabditis elegans develops reproductively or arrests at the dauer larval stage. We examined whether neurotransmitters act in the dauer entry or recovery pathways. Muscarinic agonists promote recovery from dauer arrest induced by pheromone as well as by mutations in the TGF-beta pathway. Dauer recovery in these animals is inhibited by the muscarinic antagonist atropine. Muscarinic agonists do not induce dauer recovery of either daf-2 or age-1 mutant animals, which have defects in the insulin-like signaling pathway. These data suggest that a metabotropic acetylcholine signaling pathway activates an insulin-like signal during C. elegans dauer recovery. Analogous and perhaps homologous cholinergic regulation of mammalian insulin release by the autonomic nervous system has been noted. In the parasitic nematode Ancylostoma caninum, the dauer larval stage is the infective stage, and recovery to the reproductive stage normally is induced by host factors. Muscarinic agonists also induce and atropine potently inhibits in vitro recovery of A. caninum dauer arrest. We suggest that host or parasite insulin-like signals may regulate recovery of A. caninum and could be potential targets for antihelminthic drugs.

Ancylostoma↗

Epidemiology of human geohelminth infections (ascariasis, trichuriasis and necatoriasis) in Lushui and Puer Counties, Yunnan Province, China.

Between April and June of 1998, the prevalence and intensity of geohelminth infections caused by hookworm, Ascaris and Trichuris were investigated in two rural Yunnan villages. In Liuku, a village of Lisu indigenous people in Lushui County, there was an overall geohelminth prevalence of 72% (48%, 43% and 16% for hookworm infection, ascariasis, and trichuriasis, respectively). The prevalence of ascariasis was greatest among preschool and school aged children, whereas the prevalence of trichuriasis was greatest among teenagers and the prevalence of hookworm increased until the age of 10-15 and then remained high throughout adulthood. In Linger, a village of Han Chinese, located in Puer County, there was an overall geohelminth prevalence of 77% (30%, 60% and 36% for hookworm infection, ascariasis, and trichuriasis, respectively). The differences in prevalence for hookworm and ascariasis were statistically significant. The prevalence of hookworm in Linger increased steadily with age and did not plateau, but there were no discernible patterns of prevalence versus age for either ascariasis or trichuriasis. Heavy trichuriasis infections were noted to occur in Linger. In both villages, more than 98% of the hookworm infections were of light and moderate intensity. Both by morphologic identification of third-stage infective larvae (L3) from eggs as well as identification of adult hookworms recovered from adult residents after treatment with quantrel, Necator americanus was identified as the exclusive hookworm in each village. Geohelminth infections caused by Ascaris, Trichuris and hookworm remain highly endemic to the rural areas of Yunnan Province in southwestern China.

Adolescent↗

Construction and analysis of cDNA library of Necator americanus third stage larvae.

OBJECTIVE: To obtain the genetic information on Necator americanus and to search for the purpose genes. METHODS: mRNA was isolated from the third stage larvae of Necator americanus maintained in hamsters. Double strand cDNA was synthesized and ligated to lambda ZAPII vector to construct the cDNA library. Expressed sequence tages (ESTs) were obtained by single pass sequencing of randomly isolated cDNA clones from the established library. RESULTS: A cDNA library of N. americanus was successfully constructed with high recombinant efficiency. The titer of unamplified library was 1 x 10(7). The insert size was about 750-3,000 bp. Of 11 ESTs obtained from the library, 7 have a significant homology with certain functional genes. CONCLUSION: A high quality and high representative cDNA library of N. americanus was constructed at the first time and some functional genes were identified from the library by ESTs.

Animals↗

Epidemiology of human hookworm infections among adult villagers in Hejiang and Santai Counties, Sichuan Province, China.

Hookworm infection as well as other intestinal nematodiases are endemic to Sichuan Province in China. In order to research the prevalence and intensity of these infections we visited two villages in Hejiang County (southern Sichuan Province) and Santai County (northwestern Sichuan Province) between July and October of 1997. Fecal examinations were performed on adult villagers over the age of 15 years (currently children under this age are dewormed annually with anthelmintic drugs). Among 310 residents of Lugao Village (Hejiang County), 87, 63 and 60% were infected with hookworm, Ascaris or Trichuris, respectively. The prevalence of hookworm determined to rise linearly with age (r = 0.97). High intensity infections with hookworm still occur in this region as 22% of the residents have over 3000 eggs per gram (PEG) of feces as determined by quantitative egg counts. The majority of these individuals harbored mixed infection with Necator americanus and Ancylostoma duodenale, although the former predominated when adult hookworms were collected from 30 village residents treated with pyrantel pamoate. In contrast, among the 334 Xinjian villagers examined (Santai County) the majority harbored predominantly light hookworm infections--66.1% of the residents has less than 400 EPG by quantitative fecal examination and only 3.7% exhibited greater than 3000 EPG. Again, N. americanus was the predominant hookworm seen after worm expulsion. We have round that despite economic development which is occurring in some parts of China, significant hookworm infections and clinical hookworm anemia still exist in areas of Sichuan Province. In Hejiang County we found that the intensity of hookworm infection has actually risen within the last 10 years. Hookworm is a medical problem among the elderly in Sichuan.

Adolescent↗

Vaccination with alum-precipitated recombinant Ancylostoma-secreted protein 1 protects mice against challenge infections with infective hookworm (Ancylostoma caninum) larvae.

Ancylostoma-secreted protein 1 (ASP-1) is the major protein secreted by infective hookworm larvae (Ancylostoma caninum). The Escherichia coli-expressed recombinant protein was evaluated as a vaccine antigen in a mouse model of ancylostomiasis. A. caninum larvae migrate through mouse lungs, with maximal migration occurring 48-54 h after oral infection. Quantitative larval recovery from the lungs at this time was used as an end point for vaccine evaluation. All mice developed antibodies to recombinant ASP-1 (rASP-1) after immunization and boosting with the alum-precipitated protein. The immunized mice had their worm burden reduced 79% (P < .0001) compared with controls. Immunization with rASP-1 in the presence of Corynebacterium parvum adjuvant also showed a vaccine effect (63% protection; P < .0001). The possibility that this protective effect resulted from delayed larval lung entry was excluded. rASP-1 offers promise as a hookworm vaccine antigen.

Adjuvants, Immunologic↗

Hyaluronidases of the gastrointestinal invasive nematodes Ancylostoma caninum and Anisakis simplex: possible functions in the pathogenesis of human zoonoses.

The gastrointestinal invasive stages of two parasitic nematodes, Ancylostoma caninum and Anisakis simplex, were each found to release in vitro a hydrolytic enzyme that degrades the glycosaminoglycan hyaluronic acid. The parasite hyaluronidases were partially purified by ion-exchange chromatography and biochemically characterized. The hyaluronidase from A. caninum adult worms had a molecular weight of 65,000 and a pH optimum of 6 with activity at neutral pH, while the hyaluronidase from A. simplex larvae had a molecular weight of 40,000 and a pH optimum of 4 with no activity at neutral pH. Both parasite hyaluronidases also degraded the glycosaminoglycan chondroitin sulfate A. Cupric sulfate and high concentrations of sodium chloride were inhibitory. The nematode hyaluronidases are postulated to have a role in tissue histolysis and mucosal invasion; their distinct biochemical properties have relevance to the pathogenesis of the zoonoses anisakiasis and eosinophilic enteritis.

Ancylostoma↗

Hookworm larval infectivity, arrest and amphiparatenesis: the Caenorhabditis elegans Daf-c paradigm.

Arrested development dramatically alters the life history of some species of soil-transmitted nematodes and elicits profound variations in the epidemiology of the infections they cause. Here, Peter Hotez, John Hawdon and Gerhard Schad show how an understanding of the cellular and molecular bases of arrested development may lead to new approaches for the control of ancylostomiasis and related infections.

Journal Article↗

Metalloproteases of infective Ancylostoma hookworm larvae and their possible functions in tissue invasion and ecdysis.

To infect their hosts, hookworm larvae must exsheath and migrate through connective tissue. A modified in vitro skin chamber was used to show that the human hookworm Ancylostoma duodenale and the zoonotic canine hookworm Ancylostoma caninum penetrate epidermis, basement membrane, and dermis in similar ways. These similarities in tissue invasion properties reflect the observed biochemical similarities in parasite protease composition. The larvae of both species contain protease activity that is inhibited by o-phenanthroline; this identifies the proteases as metalloproteases. The enzyme activities exhibit an alkaline pH optimum between pH 9 and 10. During modified sodium dodecyl sulfate-polyacrylamide gel electrophoresis in which a protein substrate (either casein or gelatin) was used, the protease activities resolved into a major band at an Mr of 68,000 and a minor band at an Mr of 38,000. Proteases were released by living A. caninum larvae in vitro and degraded purified and radiolabeled casein to smaller peptides. Motile hookworm larvae were also incubated with purified and radiolabeled connective tissue macromolecules in vitro. Both Ancylostoma species degraded human fibronectin to a 60,000-Mr polypeptide intermediate, but could not degrade solubilized bovine elastin or human laminin. In contrast, the obligate skin-penetrating nematode Strongyloides stercoralis degraded all three substrates. This biochemical difference may explain some observed differences in invasiveness.

Ancylostoma↗