Is being resolute better than being pragmatic when it comes to breastfeeding? Longitudinal qualitative study investigating experiences of women intending to breastfeed using the Theoretical Domains Framework.

Background: In the UK, initiating then discontinuing breastfeeding before two weeks post-partum is common. The aim of this longitudinal qualitative study was to explore which psychosocial factors may influence discontinuation. Methods: A sample of 10 pregnant women intending to breastfeed were recruited. A longitudinal qualitative design was used to capture views prior to and two weeks following birth. Semi-structured interviews were conducted underpinned by the Theoretical Domains Framework to explore a comprehensive list of psychosocial factors. Results: Four women discontinued breastfeeding at the time of the second interview. Pre-partum differences were identified between maintainers and discontinuers; discontinuers appeared to have stronger intentions to breastfeed based on their self-determination, self-confidence and perception of fewer barriers to breastfeeding. Post-partum, discontinuers highlighted how they felt physically unable to carry on; their feeding experiences elicited negative emotions and pain. Negative emotions appeared to be exacerbated by original breastfeeding beliefs and advice given by healthcare professionals. Conclusions: The women in this study who discontinued breastfeeding showed less cognitive flexibility, which appeared to exacerbate post-partum emotional distress, when they encountered difficulties. Women with strong intentions and self-determination might benefit from support in anticipating potential barriers and identifying ways of overcoming them.

Children on long-term ventilatory support: 10 years of progress.

OBJECTIVES: To identify the number and current location of all children receiving long-term ventilation (LTV) in the UK, and to establish their underlying diagnoses and ventilatory requirements. DESIGN: Single time-point census completed by members of the UK LTV working party using an electronic-based questionnaire SUBJECTS: All children in the UK at home or in hospital who, when medically stable, continue to need a mechanical aid for breathing following a failure to wean beyond a 3-month period. RESULTS: 933 children under the age of 17 years in 30 regional centres were identified as receiving LTV. 88 children (9.5%) required continuous positive pressure ventilation by tracheostomy over 24 h, while 658 received ventilation while asleep only. Most children are ventilated by a non-invasive mask (n=704; 75%) or tracheostomy (n=206; 22%). Underlying conditions included neuromuscular disease (n=402; 43%), chronic respiratory (n=343; 37%) and central nervous system conditions (n=168; 18%). 129 (14%) children were aged 16 or over. 844 (91%) children were cared for at home with only 49 children listed as being in acute hospital units (n=34) or paediatric intensive care units/high dependency units (n=15). CONCLUSIONS: The last 10 years has seen a very significant increase in the number of children requiring LTV in the UK with an increasing number cared for at home. This reflects both improving technology and increasing clinical expertise in paediatric non-invasive ventilatory support, and a continuing change in attitude towards long-term support, particularly in children with neuromuscular diseases. There are a substantial number of children who soon will require transition to adult services, yet few such services currently exist.

Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone.

BACKGROUND AND AIMS: Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose. METHODS: Children recorded as prescribed FP > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l). RESULTS: A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6-19.3 years) were successfully tested. Of 194 receiving FP > or = 500 microg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of > or = 1000 microg/day. CONCLUSION: Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.

Respiratory management of the infant with type 1 spinal muscular atrophy.

A recent paper has highlighted the differences in the respiratory management offered to infants with type 1 spinal muscular atrophy (SMA-1). Current views appear polarised between those who would offer nothing, to those who would proceed as far even as tracheostomy and long term invasive ventilation for these infants. Here we offer a personal view, as a possible template for managing a vexed and emotional problem. The complex non-respiratory aspects of the holistic care of these infants will not be discussed.

Increased levels of superoxide in brains from old female rats.

Hypertension, aging and a range of neurodegenerative diseases are associated with increased oxidative damage. The present study examined whether superoxide (O2*-) levels in brain are increased during aging in female rats, and the role of superoxide dismutase (SOD) and oestrogen in regulating O2*- levels. Young adult (3 month) and old (11 month) female spontaneously hypertensive stroke prone rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied. O2*- levels were measured in brain homogenates by lucigenin chemiluminescence and SOD expression by Western blotting. Ageing significantly increased brain O2*- levels in WKY (cortex +216%, hippocampus +320%, striatum +225%) and to a greater extent in SHRSP (cortex +540%, hippocampus +580%, striatum +533%). Older SHRSP showed a decline in cortical Cu/Zn SOD expression compared to young adult SHRSP. Oestrogen did not attenuate O2*- levels. The results show a significant age-dependent increase in brain O2*- levels which is exaggerated in SHRSP. The excess cortical O2*- levels in the SHRSP may be associated with a down-regulation of Cu/Zn SOD but are not related to a decrease in oestrogen.

Gene transfer of endothelial nitric oxide synthase but not Cu/Zn superoxide dismutase restores nitric oxide availability in the SHRSP.

OBJECTIVE: Previous studies from our group have shown a deficit in nitric oxide (NO) bioavailability and an excess production of the superoxide anion (O(2)(-)) in the stroke prone spontaneously hypertensive rat (SHRSP) compared to the normotensive Wistar Kyoto (WKY) strain. This present study has investigated whether adenoviral-mediated gene transfer of human eNOS or Cu/ZnSOD can alter the NO/O(2)(-) balance, thereby improving endothelial function. METHODS: A recombinant adenovirus, Ad/Hu/eNOS, containing the human eNOS cDNA fragment was generated by homologous recombination in 293 cells. Ad/Hu/eNOS or Ad/Cu/ZnSOD was delivered into SHRSP carotid arteries in vivo, using a titre of 2x10(9)-2x10(10) plaque forming units (pfu)/ml, and the effect on gene expression was observed 24 h later. RESULTS: Western blotting confirmed increased enzyme levels of eNOS and Cu/ZnSOD in the viral-infused vessels. Ex vivo, the pressor response to phenylephrine (PE) in the presence of L-NAME was increased in the eNOS-infused arteries relative to the contralateral controls, indicating restoration of basal NO availability to that observed in untreated control WKY rats. Infusion of the SOD virus produced a statistically insignificant increase in NO bioavailability. CONCLUSIONS: Our results support our previous findings obtained using a bovine eNOS recombinant adenovirus, that recombinant adenoviral gene transfer of human eNOS has a significant effect on NO bioavailability. In contrast, AdCu/ZnSOD gene transfer does not elicit an effect in our model. These results indicate that short-term overexpression of a recombinant eNOS, but not Cu/ZnSOD gene, in carotid arteries of the SHRSP is an effective means of locally increasing NO bioavailability to improve endothelial function.

Current status of long term ventilation of children in the United Kingdom: questionnaire survey.

OBJECTIVES: To identify the number and current location of children, aged 0 to 16 years, requiring long term ventilation in the United Kingdom, and to establish their underlying diagnoses and ventilatory needs. DESIGN: Postal questionnaires sent to consultant respiratory paediatricians and all lead clinicians of intensive care and special care baby units in the United Kingdom. SUBJECTS: All children in the United Kingdom who, when medically stable, continue to need a mechanical aid for breathing. RESULTS: 141 children requiring long term ventilation were identified from the initial questionnaire. Detailed information was then obtained on 136 children from 30 units. Thirty three children (24%) required continuous positive pressure ventilation by tracheostomy over 24 hours, and 103 received ventilation when asleep by a non-invasive mask (n=62; 46%), tracheostomy (n=32; 24%), or negative pressure ventilation (n=9; 7%). Underlying conditions included neuromuscular disease (n=62; 46%), congenital central hypoventilation syndrome (n=18; 13%), spinal injury (n=16; 12%), craniofacial syndromes (n=9; 7%), bronchopulmonary dysplasia (n=6; 4%), and others (n=25; 18%). 93 children were cared for at home. 43 children remained in hospital because of home circumstances, inadequate funding, or lack of provision of home carers. 96 children were of school age and 43 were attending mainstream school. CONCLUSIONS: A significant increase in the number of children requiring long term ventilation in the United Kingdom has occurred over the past decade. Contributing factors include improved technology, developments in paediatric non-invasive ventilatory support, and a change in attitude towards home care. Successful discharge home and return to school is occurring even for severely disabled patients. Funding and home carers are common obstacles to discharge.

Endothelium dependent and independent relaxation of aortic rings from Watanabe heritable hyperlipidemic rabbits after exposure to free radical generating system.

The effects of the xanthine oxidase/hypoxanthine free radical generating system on endothelium dependent and independent relaxation were compared in aortic rings from New Zealand white rabbits and heterozygous Watanabe heritable hyperlipidemic (WHHL) rabbits with mild atherosclerosis. Studies were carried out in young (3 months) and mature (18 months) animals. Plasma cholesterol levels were significantly higher in both 3 and 18 month WHHL animals. Endothelium independent relaxation to SNP did not differ between groups. However, the attenuation of relaxation to carbachol after xanthine oxidase/hypoxanthine treatment tended to be less in WHHL. This reached significance at 18 but not 3 months. We propose that this could be due to increases in levels of endogenous scavenger enzymes in these WHHL rabbits.

Core guidelines for the discharge home of the child on long-term assisted ventilation in the United Kingdom. UK Working Party on Paediatric Long Term Ventilation.

Paediatric home ventilation is a feasible option and can be successful in a wide range of conditions and ages. Advances in ventilator technology and an ethos of optimism for home care has increased the possibilities for discharging chronically ventilated children from intensive care units and acute medical beds. With careful planning the process can succeed, but difficulties often thwart the responsible team, especially when attempting discharge for the first time. These core guidelines aim to assist a smooth, swift and successful transfer. They were developed by a working party of interested professionals spanning a wide range of health care disciplines and represent a synthesis of views accumulated from the experiences of individual teams throughout the UK. Three case scenarios provide further illustrative detail and guidance.

Inducible L-arginine/nitric oxide pathway in human internal mammary artery and saphenous vein.

To characterize the L-arginine/nitric oxide (NO) pathway in human vascular smooth muscle (VSM), contractile responses of isolated internal mammary arteries (IMA) and saphenous veins (SV) were observed after induction of NO synthase by interleukin-1 beta (IL-1 beta) or by lipopolysaccharide (LPS). In IL-1 beta-treated endothelium-denuded rings, contractile responses to phenylephrine were reduced in SV rings only. Maximum phenylephrine-induced contraction was depressed by approximately 50%. This was not modified by the presence of indomethacin, NG-nitro-L-arginine methyl ester (L-NAME), or methylene blue (MeB). In LPS-treated vessels, contractile responses were depressed in both SV and IMA rings (40%), and this was not affected by indomethacin. In SV, L-NAME, NG-monomethyl-L-arginine, or MeB did not affect the inhibitory effect of LPS, whereas the effect was reversed in IMA by these inhibitors. In LPS-treated IMA, but not in SV, exogenous L-arginine evoked significant vasodilation (20%). We conclude that VSM of the human IMA possesses an L-arginine/NO pathway inducible by LPS. In SV, LPS or IL-1 beta treatment inhibits contraction by an unidentified system that is not dependent on NO synthase or on guanylate cyclase activities.

Signal transduction mechanisms of the vasoconstriction in hypertension.

We tested the hypothesis that vascular smooth muscle in genetic hypertension is characterised by hypereactivity to vasoactive agonists, by abnormalities in Ca2+ handling and the phosphoinositide signalling system. Activation of these signal transduction mechanisms by noradrenaline and endothelin-1 was compared in isolated perfused tail arteries from adult hypertensive and normotensive Wistar Kyoto rats. Basal cytosolic Ca2+ was greater in arteries from hypertensive rats, but basal perfusion pressure and basal inositol phosphate accumulation were unchanged. Contractile responses and Ca2+ mobilisation after noradrenaline, but not endothelin-1, were enhanced in arteries from hypertensive rats. Total inositol phosphates accumulation was similar in hypertensive and normotensive rats after either noradrenaline or endothelin-1 stimulation. In both hypertensive and normotensive rats, for a given Ca2+ mobilisation, higher contractile responses and higher levels of inositol phosphates were observed after endothelin-1 than noradrenaline stimulation. In conclusion, changes in contractility associated with modifications in the Ca2+ handling between hypertensive and normotensive rats suggested that alterations in the signal-transduction system occur with hypertension. The different effects of endothelin-1 and noradrenaline could be related to interactions with other signalling pathways.

Down-regulation of imidazoline sites in rabbit kidney.

The effects of 6 days treatment with guanabenz, clonidine, rilmenidine and idazoxan on [3H]idazoxan and [3H]clonidine binding to imidazoline sites on rabbit kidney membranes were compared. Guanabenz and rilmenidine treatment resulted in a decrease in Bmax for [3H]clonidine binding and guanabenz treatment for [3H]idazoxan binding consistent with the compounds in vitro affinities for the imidazoline binding sites. [3H]Idazoxan binding was also decreased by idazoxan treatment suggesting that idazoxan may act as an agonist at this site. These results show that imidazoline sites in kidney may be modified during chronic drug treatment and provide further evidence for differences between the sites labelled by the two ligands.

Imidazole binding sites in rabbit kidney and forebrain membranes.

1. The binding of [3H]-clonidine, [3H]-idazoxan and [3H]-yohimbine to rabbit forebrain and kidney membranes was compared. 2. Yohimbine bound exclusively to adrenergic sites, idazoxan to non-adrenergic sites and clonidine to both non-adrenergic and adrenergic sites. 3. Differences were observed between the ligands not only in binding at adrenergic and non-adrenergic sites but also between the non-adrenergic binding of [3H]-clonidine and [3H]-idazoxan. 4. However, no tissue specific differences were found.

Desensitization and down-regulation of brain alpha 2-adrenoceptors by centrally acting antihypertensive drugs.

Rabbits were treated with intravenous clonidine (8 mumol kg-1 day-1), guanabenz (20 mumol kg-1 day-1), rilmenidine (80 mumol kg-1 day-1) or vehicle via osmotic minipumps. After 6 days treatment mean arterial pressure (MAP), pressor responses to intravenous alpha-methyl noradrenaline and depressor responses to intracisternal clonidine were studied, and [3H]-yohimbine binding to forebrain and hindbrain examined in vitro. Clonidine, guanabenz and rilmenidine had similar effects on MAP and caused a similar attenuation of the depressor response to intracisternal clonidine, but only guanabenz attenuated pressor responses to intravenous alpha-methyl noradrenaline. Rilmenidine had no effect on [3H]-yohimbine binding to brain membranes. Clonidine treatment decreased binding in hindbrain while guanabenz treatment decreased binding in both fore- and hindbrain. Thus, the depressor effects of chronic treatment did not correlate with the effects on [3H]-yohimbine binding sites in rabbit brain suggesting that the blood pressure lowering effects of many centrally acting antihypertensive drugs are not necessarily dependent on binding to the alpha 2-adrenoceptor site labelled by [3H]-yohimbine.

The effects of calcium antagonists on blood pressure and responses to alpha-adrenoceptor agonists in hypertensive rabbits.

The effects of the calcium antagonists verapamil and nifedipine on mean arterial blood pressure, heart rate and pressor responses to a range of alpha-adrenoceptor agonists were examined in male normotensive New Zealand white rabbits and in rabbits with perinephritis hypertension. Verapamil and nifedipine caused a greater fall in mean arterial pressure in hypertensive compared to normotensive rabbits both when the fall was expressed as an absolute and as a percentage change. Effects on heart rate were similar in normotensive and hypertensive animals. Pressor responses to phenylephrine were attenuated by nifedipine and verapamil in normotensive and hypertensive rabbits. Pressor responses to alphamethyl noradrenaline were also attenuated by nifedipine, but pressor responses to BHT 920 were not significantly altered by either calcium antagonist in normotensive or hypertensive rabbits at the dose used. Thus the calcium antagonists had a greater effect on alpha 1 - than alpha 2-adrenoceptor mediated responses in both normotensive and hypertensive rabbits. Hypertensive animals showed an increased responsiveness to phenylephrine and alphamethyl noradrenaline but not BHT 920 compared to normotensives. This difference remained after treatment with both the calcium antagonists.