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Biomedical subjects

Richard Harding

Publications and source records attributed to Richard Harding.

At least 73 records · Page 4Linked to original sources

Effects of sleep position, sleep state and age on heart rate responses following provoked arousal in term infants.

Previous studies have suggested that autonomic dysfunction may be involved in Sudden Infant Death Syndrome (SIDS). The major risk factors for SIDS are the prone sleeping position and maternal smoking. Our aim was to examine the effects of sleeping position and maternal smoking on the postnatal maturation of autonomic function by examining heart rate responses following arousal in healthy term infants. Twenty-four infants (11 born to mothers who smoked during pregnancy and 13 to mother who did not smoke) were studied using daytime polysomnography and multiple measurements of arousal threshold (cm H(2)O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep (AS) and quiet sleep (QS). We demonstrated no difference between smoking and non-smoking groups of infants in any of our measurements, and thus combined data from the groups. Baseline (BHR) was elevated in the prone compared to the supine position in quiet sleep (QS) at 2-3 weeks (p<0.001) and 5-6 months (p<0.001), and in active sleep (AS) at 2-3 and 5-6 months (p<0.05). BHR was significantly elevated in AS compared to QS in the supine position at all ages (p<0.01) and in the prone position at 2-3 (p<0.001) and 5-6 months (p<0.05). Increases in heart rate (deltaHR%) following arousal were significantly greater in the supine compared to the prone position in QS at 2-3 weeks (p<0.05) and in AS at both 2-3 (p<0.01) and 5-6 months (p<0.05). DeltaHR% was significantly greater in AS compared to QS in both supine (p<0.05) and prone (p<0.001) positions at 2-3 weeks and in the supine position at 2-3 months (p<0.001). We conclude that sleep state, sleep position and postnatal age affect the cardiac responses following arousal from sleep in healthy term infants. Impairment of heart rate control in the prone position may be important in understanding the increased risk for SIDS in this position.

Adolescent↗

Differential effects of maternal and fetal betamethasone injections in late-gestation fetal sheep.

OBJECTIVE: To determine the effects of single or repeated intramuscular injections of betamethasone, given maternally or directly to the fetus, on chronically catheterized, late-gestation fetal sheep. METHODS: Fetal or maternal sheep received either repeated intramuscular injections of betamethasone (0.5 mg/kg body weight at 104, 111, and 118 days' gestation), single betamethasone injection (at 104 days' gestation, followed by saline at 111 and 118 days' gestation), or repeated saline injections; n = 6 or 7 per group. At approximately 130 days' gestation fetuses were catheterized for serial measurements of heart rate, arterial pressure, blood gases, metabolites, and electrolytes. RESULTS: Repeated maternal betamethasone injections reduced birth weight (P =.03) without fetal hypoxemia or hypoglycemia. Circulating fetal calcium and lactate concentrations were reduced (P =.002 and P =.014, respectively) by repeated maternal betamethasone only. Fetal hematocrit tended to be lower after fetal (P =.3) and maternal (P =.07) betamethasone. CONCLUSION: Growth restriction caused by repeated maternal betamethasone treatments is not due to overt chronic placental insufficiency but may be caused by alterations in hormonal mediators of fetal growth or impairment of placental transport of specific nutrients.

Animals↗

Chronic placental insufficiency and foetal growth restriction lead to long-term effects on postnatal retinal structure.

The aim of this study was to determine the effects of foetal growth restriction on the retina after birth. Foetal growth restriction (FGR) was induced via umbilico-placental embolization (UPE) in ewes from 120 days of pregnancy until term (term approximately 147 days); controls were not exposed to UPE. Lambs were delivered and raised until 2 years of age when retinas were collected and processed for structural and neurochemical analysis. The foetuses exposed to UPE were hypoxemic and at birth were growth restricted. In 2-year-old FGR sheep, the total thickness of the retina and the number of tyrosine hydroxylase immunoreactive dopaminergic amacrine cells were reduced compared to controls (P < 0.05). It is concluded that restricted foetal growth leads to long-term structural and neurochemical changes in the retina. Of particular interest are the alterations to dopaminergic amacrine cell numbers, as alterations in this population may affect contrast sensitivity and have implications for the alterations in vision observed in very low birthweight infants.

Amacrine Cells↗

Welfare rights advice in primary care: prevalence, processes and specialist provision.

BACKGROUND: Despite persistent poverty-related health inequalities, few sustained responses have been developed in primary care. Welfare rights provision has been proposed as one potential pathway to addressing health inequalities. OBJECTIVES: This study was set up to address the prevalence of welfare rights issues in general practice, and the practitioner response to unmet need. METHODS: A postal questionnaire was sent to practitioners in GP surgeries of an inner city health authority with high levels of deprivation. By means of a 'most recent case audit', data on welfare advice needs were collected. Practices with in-house welfare rights provision were compared with those surgeries with no such provision. RESULTS: Questionnaires were returned by 153 practitioners, describing their most recent case with a welfare rights need (mean 10.41 days ago). Of the respondents, 70.6% felt that there was a mental health element to this consultation, 49.8% of problems were described as urgent, and 65.8% of patients requested information or guidance. Those practitioners with specialist advisers in the surgery (n = 81) were significantly more likely to find referring patients to advisers easy, that quality of advice for patients was good, that welfare providers enhanced their ability to practice effectively and that such provision improves the health and well-being of patients. In those surgeries without provision (n = 72), patients were more likely to approach their practitioner for advice. GPs were more likely than nurses and other practising staff to see a case with welfare rights needs. Practitioners were more likely to raise the welfare issues if they had specialist advice in the surgery. CONCLUSIONS: A large amount of practitioner consultation time is spent on welfare rights-related issues. Although practitioners are skilled in detecting need, and their practice is enhanced by specialist support, expansion is needed to provide the advice which cannot be met by clinical consultation.

Counseling↗

Arousal responses to somatosensory and mild hypoxic stimuli are depressed during quiet sleep in healthy term infants.

STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic stimuli in sleeping human infants and to determine whether sleep state and postnatal age exerted similar changes in these arousal responses. DESIGN: We delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen) to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months during identified sleep states. Hypoxic challenges were terminated at arousal, when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse). RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of age. Arousal latency to hypoxia was significantly longer in QS than in AS at each study age; however, arousal latency was not affected by postnatal age. Arousal thresholds to somatosensory stimulation were significantly greater in QS than in AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to hypoxia and arousal thresholds to air-jet stimulation were not correlated within infants. CONCLUSION: We conclude that arousal responses of infants to somatosensory and respiratory stimuli are similarly affected by sleep state and postnatal age. Infants are less arousable to both stimulus modalities in QS than in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.

Arousal↗

Sustained changes in lung expansion alter tropoelastin mRNA levels and elastin content in fetal sheep lungs.

Our objective was to determine the effects of sustained alterations in fetal lung expansion on pulmonary elastin synthesis. In fetal sheep, lung expansion was either decreased between 111 and 131 days' gestation (term approximately 147 days) by tracheal drainage or increased for 2, 4, 7, or 10 days by tracheal obstruction, ending at 128 days' gestation. Lung tropoelastin mRNA levels were assessed by Northern blot analysis, total elastin content was measured biochemically, and staining of lung sections was used to assess the localization and form of elastic fibers. Tracheal obstruction significantly elevated pulmonary tropoelastin mRNA levels 2.5-fold at 2 days, but values were not different from controls at 4, 7, and 10 days; elastin content tended to be increased at all time points. A sustained decrease in lung expansion by tracheal drainage reduced pulmonary tropoelastin mRNA levels 2.5-fold; elastin content was also decreased compared with controls, and tissue localization was altered. Our results indicate that the degree of lung expansion in the fetus influences elastin synthesis, content, and tissue deposition.

Airway Obstruction↗

Determination of alveolar epithelial cell phenotypes in fetal sheep: evidence for the involvement of basal lung expansion.

The factors that control the differentiation of alveolar epithelial cells (AECs) into type-I and type-II cells in vivo are largely unknown. As sustained increases in fetal lung expansion induce type-II AECs to differentiate into type-I cells, our aim was to determine whether reduced fetal lung expansion can induce type-I AECs to trans-differentiate into type-II AECs. Chronically catheterised fetal sheep were divided into two age-matched control groups and three experimental groups (n = 5 for each). The experimental groups were exposed to either: (1) 10 days of increased lung expansion induced by tracheal obstruction (TO), (2) 10 days of TO followed by 5 days of reduced lung expansion induced by lung liquid drainage (LLD), or (3) 10 days of TO followed by 10 days of LLD. Following 10 days of TO, 5 days of LLD reduced the proportion of type-I AECs from 89.4 +/- 0.9 % to 68.4 +/- 2.8 %, which was similar to control values (64.8 +/- 0.5 %), and increased the proportion of type-II AECs from 1.9 +/- 0.3 % to 21.9 +/- 2.8 %, which remained below control values (33.4 +/- 1.7 %). The same treatment increased surfactant protein (SP)-A, SP-B and SP-C mRNA levels (expressed as a percentage of control values) from 26.7 +/- 6.0 %, 40.0 +/- 7.3 % and 10.3 +/- 1.8 % to 78.1 +/- 10.3 %, 105.8 +/- 12.7 % and 121.0 +/- 14.1 %, respectively. Similar results were obtained after 10 days of LLD, which followed 10 days of TO. These results indicate that the phenotypes of type-I and type-II AECs are strongly influenced by the basal degree of lung expansion in fetal sheep. Furthermore, the coincident increase in type-II AEC proportions and SP mRNA levels in response to LLD suggests that type-I AECs can trans-differentiate into functional type-II cells, and hence are not terminally differentiated.

Animals↗

Lung function, arterial pressure and growth in sheep during early postnatal life following single and repeated prenatal corticosteroid treatments.

BACKGROUND: Antenatal corticosteroid therapy is of great benefit to preterm infants, owing largely to effects on lung maturation. In sheep, repeated betamethasone injections given to the ewe improve lung function following preterm birth but also cause intrauterine growth restriction (IUGR). In humans and in animal models, IUGR is associated with impaired postnatal lung function. The effects on lung function of repeated prenatal betamethasone treatments and associated IUGR following term delivery are unknown. AIM AND STUDY DESIGN: To determine the effects of antenatal betamethasone treatments on postnatal arterial pressure, blood gases, ventilation, pulmonary gas volumes and compliance in serial studies of four groups of lambs until 4 weeks of age. SUBJECTS: Treatment groups were (1) maternal injections of saline at 104, 111 and 118 days of gestation, (2) a single maternal injection of betamethasone (0.5 mg/kg) at 104 days followed by saline at 111 and 118 days, (3) repeated betamethasone injections at 104, 111 and 118 days, or (4) no intervention (term is approximately 150 days). RESULTS: Repeated maternal betamethasone injections reduced birthweight and resulted in reduced postnatal body weights and arterial pressure throughout the first postnatal month. Lung function was not deleteriously affected by single or repeated maternal betamethasone treatments: blood gases, minute ventilation, lung volumes and compliance were not different between groups of lambs. CONCLUSIONS: The absence of alterations in postnatal blood gases contrasts with other models of IUGR in sheep and suggests that changes in lung structure caused by betamethasone may benefit IUGR neonates born at term.

Adrenal Cortex Hormones↗

Relation between oligohydramnios and spinal flexion in the human fetus.

BACKGROUND: Oligohydramnios, a severe reduction in the volume of amniotic fluid, is associated with fetal lung hypoplasia but underlying processes are unclear. Studies in sheep suggest that oligohydramnios may lead to lung hypoplasia by causing increased flexion of the fetal spine, but this has not been demonstrated in the human, which has a different uterine anatomy. AIMS: Our aims were to quantify spinal flexion in the human fetus and to determine the relationship between oligohydramnios and the degree of spinal flexion. SUBJECTS AND METHODS: In 35 pregnancies, we used ultrasonography to assess amniotic fluid volume and to image the fetal spine so as to provide an index of mean spinal radius between the upper thoracic and lumbar spine. In 17 pregnancies with evidence of oligohydramnios resulting from premature rupture of membranes (mean +/- SEM gestation 28.8 +/-1.4 weeks), the mean radius of fetal spinal curvature between the upper thorax and sacrum was compared with values from 18 control fetuses with normal amounts of amniotic fluid (at 28.9 +/- 1.6 weeks). RESULTS: In each fetus, the spine could be imaged and the mean radius of curvature calculated. Oligohydramnios was associated with a significantly increased degree of fetal spinal flexion compared to controls. CONCLUSION: In human pregnancy, oligohydramnios is associated with increased flexion of the fetal spine, which is likely due to reduced uterine volume. This could contribute to the development of fetal lung hypoplasia, fetal immobility and other fetal anomalies.

Apgar Score↗

Test-retest reliability of the measurement of penile dimensions in a sample of gay men.

Both physiological and self-measurement methods have been employed to collect data on the dimensions of the erect penis. However, self-measurement using paper strips has often been favored as a less intrusive and time-consuming method, despite the recognition of the increased chance of bias through exaggeration. The current study aimed to establish the test-retest reliability of measurement of the erect penis using paper strips in a sample of 312 gay men. The men were issued with color-coded measuring strips printed with instructions but no calibrations, and asked to measure both the length and circumference of their partners' erect penis. Three months later they were asked to repeat these measures. Mean length on first measurement was 15.3 cm and 15.2 cm on second measurement. Mean girth at first measurement was 12.5 cm and 12.6 cm at second measurement. Test-retest reliability of measurement was found to be moderately low at r = .60 for length and r = .53 for girth. No relation was found between measurement discrepancy and the age, social class, education, ethnicity, or employment status of the partner taking the measurements. Although self-measurement strips are both convenient and acceptable, and widely reported in the literature, they only have moderate test-retest reliability. This may be due to both natural variability in penis size within subjects over time and unreliability of the measurement method.

Adult↗

Evaluation of welfare rights advice in primary care: the general practice perspective.

Income maximisation may reduce enduring poverty-related health inequalities. Specialist welfare rights advice in primary care has been proposed and, in some areas, implemented, but evaluation data from the general practice perspective is needed. The present study aimed to evaluate the impact on general practice of specialist welfare rights advice, comparing practices with and without in-house provision of welfare advice using a cross-sectional postal questionnaire. This study was conducted in general practice surgeries in an inner-London health authority with high indicators of deprivation. Questionnaires were sent to practice managers. Comparative data (according to whether specialist advice was currently offered) addressed processes of identifying and meeting welfare needs and outcomes in terms of efficiency of provision. Seventy-nine surgeries participated. Those with welfare rights advisers (n = 42) were significantly more likely to report that current provision was adequate, that it was easier for staff to access advice on their patients' behalf (and by patients themselves) and that the process of advice provision ran smoothly. Lack of funding and space were the principal reasons for not having in-house advice. Surgeries wish provision to be expanded within practices. Welfare rights advice in surgeries improves ability to meet welfare needs via specialist advisers. Referral processes are simplified, enabling general practitioners to ensure that relevant advice is provided without the need for welfare knowledge themselves. General practices welcome the expansion of provision, with the proviso that adequate resources are identified. The current lack of basic information in surgeries must be addressed (e.g. information on local providers, printed information detailing range and eligibility criteria of welfare benefits).

Cross-Sectional Studies↗

Amniotic fluid and fetal urinary responses to severe placental insufficiency in sheep.

OBJECTIVE: Our purpose was to test the hypothesis that severe placental insufficiency leads to reductions in fetal urine production and amniotic fluid volume in late-gestation fetal sheep. STUDY DESIGN: At 0.85 of gestation, chronically catheterized fetal sheep with ligated urachus were either embolized for 5 days by repeated injection of boluses of 15-microm microspheres into the common fetal umbilical artery until fetal arterial oxygen content was reduced by 50% (n = 6) or were infused with saline solution (n = 6). Amniotic fluid volume was measured daily before embolization by means of an indicator dilution technique and by drainage at autopsy. Fetal urine production, heart rate, and mean arterial blood pressure were measured continuously for 1 hour before embolization and 1 hour after embolization each day. Fetal arterial blood gases, oxygen content, electrolytes, and osmolality were also monitored. RESULTS: Five days of placental insufficiency, which reduced fetal arterial oxygen content by 50% and arrested fetal growth, resulted in a reduced amniotic fluid volume without a reduction in fetal urine production. Compared with that of controls, amniotic fluid volume was reduced over the 5-day period by 547 +/- 144 mL (-62%, P <.01). Amniotic fluid composition was also altered, with a significant increase in lactate and sodium concentrations and osmolality on days 4 to 5. On days 2 to 5, there was a progressive increase in amniotic fluid osmolality above that of controls, which paralleled the changes in amniotic fluid sodium concentration (P <.05). Fetuses became hypertensive on days 2 to 4 of embolization, although this response was attenuated by day 5. CONCLUSIONS: Chronic severe placental insufficiency caused a reduction in amniotic fluid volume not attributable to reduced fetal urine production. Changes in amniotic fluid composition induced by placental insufficiency suggest an excess intramembranous absorption of amniotic fluid water, in relation to solutes, into the fetal and maternal compartments, which may lead to the development of oligohydramnios.

Amniotic Fluid↗

Effect of intermittent umbilical cord occlusion on fetal respiratory activity and brain adenosine in late-gestation sheep.

It was hypothesized that intermittent umbilical cord occlusion (UCO) would inhibit ovine fetal breathing movements (FBM) in association with increased cerebral adenosine levels. To test this hypothesis, on two successive days during late gestation (133-134 days; term = 146 days), microdialysis samples were collected from the brains of 10 chronically instrumented fetal sheep during 2-h periods of complete UCO induced every 30 min (Day 1: 2-min UCOs; Day 2: 4-min UCOs). Control fetuses (n = 10) underwent no UCO. Tracheal pressure was measured throughout. This regimen resulted in a decrease in fetal arterial PO2 (PaO2) during each UCO to 7.3 +/- 0.8 mmHg (P<0.01; Day 1) and 8.4 +/- 1.1 mmHg (P<0.01; Day 2). Throughout each UCO period, fetal arterial pH (pHa) decreased to 7.28 +/- 0.02 (P<0.01; Day 1) and 7.11 +/- 0.07 (P<0.01; Day 2). The hourly incidence of FBM decreased significantly only on Day 2, from 38.6 +/- 4.1% to 4.1 +/- 1.6% (P<0.01). The frequency of deep isolated inspiratory efforts increased from 4.7 +/- 2.0 h(-1) to 17.6 +/- 6.1 h(-1) (P<0.05; Day 1) and from 2.2 +/- 0.9 h(-1) to 33.6 +/- 4 h(-1) (P<0.01; Day 2). The amplitude of both FBM and deep isolated inspiratory efforts increased during the UCO periods on both days. The concentration of cerebral extracellular fluid (ECF) adenosine during UCO increased by 219 +/- 215% (P<0.05; Day 1) and 172 +/- 107% (P<0.05; Day 2) over the baseline periods. In conclusion, the severity of the inhibitory effect of repeated UCO on FBM depends, in part, on the length of the occlusions. The inhibition of FBM during intermittent UCO may be mediated by the increase in ECF adenosine in the fetal brain. Furthermore, FBM and deep isolated inspiratory efforts appear to be regulated by different mechanisms.

Adenosine↗

Influence of intrauterine growth restriction on airway development in fetal and postnatal sheep.

Epidemiologic studies suggest that intrauterine growth restriction (IUGR) can lead to impaired lung function, yet little information exists on the effects of IUGR on airway development. Our objectives were to characterize morphometrically effects of IUGR on airway structure in the fetus and to determine whether alterations persist into postnatal life. We used two groups of sheep, each with appropriate controls; a fetal group was subjected to IUGR by restriction of placental function from 120 to 140 d (term approximately 147 d), and a postnatal group, killed 8 wk after birth, was subjected to IUGR from 120 d to birth at term. In both fetuses and postnatal lambs, IUGR did not alter lung weight relative to body weight. In IUGR fetuses, the luminal areas and basement membrane perimeters of the trachea and larger bronchi (generations 0-8, trachea = 0) were smaller than in controls. Airway wall areas, relative to basement membrane perimeters, were reduced in IUGR fetuses compared with controls, largely due to reduced areas of cartilage and epithelium. At 8 wk after birth, there were no significant differences in airway dimensions between IUGR and control lambs. However, the number of profiles of bronchial submucosal glands, relative to basement membrane perimeters, was lower in IUGR lambs than in controls and the area of epithelial mucin was increased. We conclude that restriction of fetal growth during late gestation impairs the growth of bronchial walls that could affect airway compliance in the immediate postnatal period. Although airway growth deficits are reversed by 8 wk, alterations in mucus elements persist.

Animals↗

White matter injury after repeated endotoxin exposure in the preterm ovine fetus.

Intrauterine infection has been linked to neurologic injury in preterm infants. However, a reproducible model of white matter injury in the preterm fetus in a long gestation species that can be monitored in utero is currently unavailable. Thus, our objective was to determine the effects of bacterial endotoxin (lipopolysaccharide, LPS) on physiologic and inflammatory responses and brain structure in the preterm ovine fetus. At 0.7 of gestation, six catheterized fetuses received three to five intravenous injections of LPS (1 micro g/kg) over 5 d; seven fetuses served as controls. Fetal responses were monitored and brain tissue examined 10-11 d after the initial LPS injection. After LPS on d 1 and 2, fetuses became transiently hypoxemic and hypotensive and blood IL-6 levels were increased, but these responses were smaller or absent after subsequent LPS exposures. Neural injury was observed in all LPS-exposed fetuses, most prominently in the cerebral white matter. Injury ranged from diffuse subcortical damage to periventricular leukomalacia, and in the brainstem the cross-sectional area of the corticospinal tract was reduced by 30%. Thus, repeated exposure of the preterm ovine fetus to LPS causes neuropathology resembling that of cerebral palsy and provides a robust model for exploring the etiology, prevention, and treatment of white matter damage.

Animals↗

Climate feedbacks at the tundra-taiga interface.

Feedbacks, or internal interactions, play a crucial role in the climate system. Negative feedback will reduce the impact of an external perturbation, a positive feedback will amplify the effect and could lead to an unstable system. Many of the feedbacks found in the climate system are positive; thus, for example, increasing CO2 levels will increase temperature, reduce the snow cover, increase the absorption of radiation and hence increase temperature further. The most obvious feedbacks, such as the snow example quoted above, are already included within our models of the climate and earth system. Others, such as the impact of increasing forest cover due to global warming, are only just being included. Others, such as, the impact of global warming on the northern peatlands and the impact of freshwater flows on the Arctic Ocean are not yet considered. The contrast in surface characteristics between low tundra vegetation to high taiga forest is considerable. The contrast is greatest in the winter, when the tundra is snow covered but the trees of the taiga protrude through the snow pack, and is probably the greatest contrast found on the land surface anywhere. This variation causes massive changes in the energy fluxes at the surface and hence the temperature conditions on the ground and within the atmosphere. There will be large resultant changes in the vegetation development, the carbon fluxes, the permafrost and the hydrology. The Arctic is already experiencing change and it is essential for us to understand the basic processes, and how these interact, to be confident of our predictions of environmental change in the future.

Air↗

A multi-professional short-term group intervention for informal caregivers of patients using a home palliative care service.

Informal carers of home palliative care patients have high unmet needs. However, interventions for carers are few. This research-based short-term group intervention addresses the information and support needs of carers. Multiprofessional informal teaching is combined with peer support. The intervention was designed by integrating the findings from a qualitative study and the evidence on needs and interventions, in order to address the key issues of feasibility, acceptability, and accessibility. Qualitative data from attendees showed that identifying with other carers and validating feelings, asking questions of professionals, and providing each other with support and encouragement were valuable outcomes from the group.

Adaptation, Psychological↗