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Biomedical subjects

Richard Harding

Publications and source records attributed to Richard Harding.

78 records · Page 5Linked to original sources

Palliative care in sub-Saharan Africa.

Control of pain and symptoms and terminal care are necessary for quality HIV and cancer care in sub-Saharan Africa. However, what constitutes feasible, accessible, and effective palliative care, and how to develop such services, remains to be resolved. Africa-specific palliative care includes components that carry resource implications. Home and community-based care has been largely successful, but community capacity and the resources and clinical supervision necessary to sustain quality care are lacking. Coverage and referrals must be primary concerns. Simple lay and professional protocols have been developed, but opioid availability remains a major constraint. Areas of good practice, and areas where further success may be achieved include: attention to community needs and capacity; explicit frameworks for service development and palliative-care integration throughout the disease course (including antiretroviral provision); further education and protocols; strengthening and dissemination of diverse referral and care systems; increasing advocacy; and funding and technical skills to build audit and quality assessment.

Africa South of the Sahara↗

Fetal responses to intra-amniotic endotoxin in sheep.

OBJECTIVE: Our aim was to determine the acute physiologic effects of intra-amniotic endotoxin administration in fetal sheep, and in particular, to determine whether intra-amniotic endotoxin causes an increase in fetal cortisol that could underlie the functional maturation of the fetal lungs previously reported in this model. METHODS: As in our previous experiments, ewes were randomly assigned to receive a single intra-amniotic injection of either endotoxin (20 mg, Escherichia coli [055:B5], n = 5) or saline (n = 5). Between 0.5 hours before endotoxin and 168 hours after its administration, we measured maternal and fetal arterial pressures and heart rates; fetal and maternal blood samples were collected for measurement of blood gases, electrolytes, glucose and lactate concentrations, white cell counts (total and differential), and plasma cortisol. RESULTS: Fetal arterial carbon dioxide tension and lactate concentration were significantly elevated 6 and 12 hours after endotoxin but returned to pre-endotoxin levels by 24 hours. Fetal plasma cortisol concentrations were significantly elevated at 4 hours and peaked 24 hours after endotoxin, returning to control levels by 2 days. Fetal white cell counts initially decreased (4 hours) and then increased (after 24 hours), becoming significantly elevated 6 days after treatment. Other fetal variables, and all measured maternal variables, were unaffected. CONCLUSIONS: Our data suggest that fetal sheep respond to intra-amniotic endotoxin with transient, mild physiologic alterations that follow a time course similar to inflammatory responses reported previously. The elevation in fetal cortisol is insufficient to be the cause of preterm lung maturation shown previously with this treatment.

Amnion↗

Pulmonary elastin synthesis and deposition in developing and mature sheep: effects of intrauterine growth restriction.

Hypoxia and nutrient restriction during gestation restrict fetal growth and alter lung development. As elastin is intimately involved in lung development, our aim was to assess pulmonary elastin synthesis and deposition following intrauterine growth restriction (IUGR) induced by umbilicoplacental embolization (UPE). Pulmonary tropoelastin expression and elastin content were examined at 128 days (5 days UPE) and 140 days (20 days UPE) of the 147- days gestation and at 8 weeks and 2.3 years after birth (both approximately 27 days UPE) in sheep. UPE induced hypoxemia, hypoglycemia, and fetal growth restriction but did not affect pulmonary tropoelastin mRNA levels or elastin deposition at any age; furthermore, elastin content was unaltered apart from being lower at 140 days. The authors conclude that hypoxemia and undernutrition associated with IUGR do not affect elastin synthesis and deposition in fetal lungs; alterations in lung structure following IUGR must have other causes.

Animals↗

Altered airway responsiveness in adult sheep born prematurely: effects of allergen exposure.

The aim of this study was to determine the effects of preterm birth per se on airway function in adult sheep. Preterm birth was induced at approximately 0.89 of term. At approximately 1 year of age the authors measured pulmonary resistance (RL) and airway responsiveness before and after house dust mite (HDM) challenge. Mature preterm sheep tended to have greater baseline RL than controls (P = .12): the smaller preterm sheep showed significantly greater RL than controls following bronchoconstrictor challenge. Preterm animals tended to have greater baseline total blood leukocyte count (P = .06). It was concluded that preterm sheep, especially with low postnatal growth, have greater airway responsiveness to bronchoconstrictor and higher baseline RL.

Airway Resistance↗

Generating the evidence base for the National Service Framework for Long Term Conditions: a new research typology.

The UK National Service Framework (NSF) for Long Term Conditions was published in May 2005. This article describes the challenges and some proffered solutions towards development of the evidence base to support best practice in the management of life-long neurological conditions, which are the principal focus of the NSF. The inherent limits in current systems for appraisal of evidence and their lack of applicability to these conditions are discussed. A new typology of evidence is proposed, which acknowledges the importance of expert opinion from users, carers and professionals as well as encompassing a broad range of research designs. To apply the typology, a brief evaluation tool is presented, which provides simple assessment of both qualitative and quantitative research evidence in terms of design, quality and applicability, and is practical for use by clinicians. Preliminary testing and application in development of the evidence base for the NSF are described.

Evidence-Based Medicine↗

Effects of intra-amniotic endotoxin on lung structure and function two months after term birth in sheep.

OBJECTIVE: Intra-amniotic endotoxin causes chorioamnionitis and results in improved lung function after preterm delivery in sheep. Our aim was to determine the effects on lung structure and function after term birth in lambs exposed to intra-amniotic or intra-allantoic endotoxin. METHODS: At 119 days' gestation, pregnant ewes bearing singleton fetuses received intra-amniotic or intra-allantoic injections of either saline (allantoic, n = 1; amniotic, n = 10) or Escherichia coli (055:B5) endotoxin (allantoic, n = 5; amniotic, n = 7). Amniotic or allantoic fluid was aspirated for white blood cell counts 24 hours after the injections. Ewes (n = 20) were allowed to deliver spontaneously. At 8 weeks' postnatal age we measured ventilation, lung volumes, and compliance in the offspring and collected their lungs for morphologic analysis. RESULTS: Higher amniotic or allantoic cell counts were confined to the fluid space into which endotoxin was injected. Saline injections did not increase amniotic or allantoic white blood cell counts. Gestation length, birth weight, and postnatal growth were unaffected by endotoxin treatments. Lung volumes and compliances at 8 weeks of age were not different between saline-treated and endotoxin-treated groups. Lung morphometry was not significantly altered by endotoxin, with one minor exception: interlobular septal volume was increased by intra-amniotic endotoxin, but this effect had no functional consequences. CONCLUSIONS: Intra-amniotic or intra-allantoic endotoxin caused a localized inflammatory response but did not cause preterm delivery or intrauterine growth restriction. The functional improvements and corresponding structural alterations in the lungs of preterm lambs, reported previously in this model, were not associated with improved or impaired lung function or marked alterations in lung structure 2 months after birth at term.

Aging↗