Amanda L. Griffiths

Adrenal suppression from high-dose inhaled fluticasone propionate in children with asthma

and bacterial infiltration of the injured tissue. Finally, there is an endocrine or late phase characterised by proliferation with endothelium and vascular wall modelling (angiogenesis), which, in the case of healing, involves tissular regeneration or wound healing by scar formation [2–4]. Therefore, in an early or nervous phase, the nutrition of the injured tissue would be produced by diffusion (oedema), a mechanism with low energetic requirement that does not require oxygen (ischemia) or that is not correctly used (synthesis of reactive oxygen species (ROS)). Products derived from the degradation of macromolecules by the ROS action can constitute substrates that reach the cells by diffusion. In the intermediate or immune phase, the nutrition could be mediated by the inflammatory cells because both the neutrophils, as well as the macrophages, have a large capacity for intracellular (phagocytosis of debris) and extracellular (release of enzymes) digestion [5, 6]. Complex proteins, such as enzymes and debris, can be important sources of fermentation [7]. These inflammatory cells respond with respiratory burst and release high concentrations of superoxide anion radical, hydroxyl radical, hypochlorus acid, hypobromite and hydrogen peroxide [1]. The lymphatic circulation could predominate in these phases of the inflammation in detriment of the blood circulation. Finally, in the late or endocrine phase, blood circulation is involved in the nutrition [5, 6]. Angiogenesis makes it possible to acquire a capillary network that is specialised in supplying oxygen and substrates to cells, which, in turn, use them through oxidative metabolism [6, 8], thus producing regeneration. However, the wounds heal by scar formation, a process in which the fibroblasts, due to their phenotypic plasticity [9], could become intermediary cells of the epithelial nutrition. The deficient capacity of the fibroblasts for this trophic function could explain the defective quality of the epithelium obtained. Phases that are similar to the above-mentioned ones are commonly described in airway asthmatic inflammation [1, 9]. In this way, reactive oxygen species hyperproduction, whether by revascularisation or by reactive oxygen species release by the inflammatory cells during the respiratory burst, could represent primitive trophic mechanisms, which are used by the injured tissue when the use of oxygen by oxidative phosphorylation is not possible. More useful energy (adenosine triphosphate) can be generated through this latter pathway and it is a more elaborated trophic mechanism.This cross-sectional study was designed to examine the prevalence of adrenocortical suppression in children with asthma treated with high-dose inhaled fluticasone propionate (FP). Children and adolescents (n=50) with asthma, treated with inhaled FP at a dose of > or = 1,000 mg a day for > or = 6 months, were enrolled. Early morning serum cortisol was performed. Subjects with a serum cortisol of < 400 nmol x L(-1) had a tetracosactrin stimulation test. Fifty subjects of mean age 13.1 yrs were treated with a mean dose of 924.7 microg x m(-2) x day(-1) FP for a mean duration of 2 yrs. Of the 50 subjects, 36 (72%) had serum cortisol levels of < 400 nmol x L(-1) and underwent tetracosactrin stimulation test. Of these, 6 (17%) demonstrated a less than two-fold increase in serum cortisol from baseline and peak cortisol level of < or = 550 nmol x L(-1) at 30 or 60 min poststimulation. There was a significant negative correlation between the dose of FP x m(-2) and stimulated peak cortisol level. Biochemical evidence of adrenocortical insufficiency was demonstrated in 12% of the subjects, indicating that high-dose fluticasone propionate use may be associated with dose-dependent adrenocortical suppression.

Cystic fibrosis patients and families support cross-infection measures

A clonal strain of Pseudomonas aeruginosa (PA) was isolated in 1999 at the Royal Childrens Hospital, Melbourne, Australia, after five unrelated children with cystic fibrosis (CF) died from severe lung disease aged <5 yrs. Subsequently, more than half of the patients in the clinic with PA were found to harbour this strain, and segregation measures were instituted at the hospital to prevent further spread. The aim of this study was to assess CF parent and patient responses to the segregation measures to determine overall support. A questionnaire was sent out to the families of 291 CF children treated at the centre. A 65% response rate was obtained. The majority of parents (85%) and patients ≥12 yrs old (63%) were positive about the segregation measures instituted. A total of 11% of parents and 25% of patients were unsure, and 4% of parents and 12% of children gave negative responses. Those who were not happy listed reasons such as concerns about the emotional impact of not socialising with other CF children, inconclusive evidence about person–person spread of infection and feelings of alienation created in the clinic by the separation. In conclusion, the majority of responding cystic fibrosis patients and their families understand and are supportive of infection control measures instituted at the Royal Childrens Hospital, Melbourne, Australia.

Exogenous calcitonin gene-related peptide causes gubernacular development in neonatal (Tfm) mice with complete androgen resistance☆☆☆

It has been proposed that testicular descent is controlled indirectly by androgens acting on the central nervous system to mediate migration of the gubernaculum to the scrotum. Accumulating evidence suggests that the genitofemoral nerve may release a newly described neurotransmitter, calcitonin gene-related peptide (CGRP) to stimulate gubernacular motility during migration. This study aimed to determine whether exogenous CGRP could stimulate gubernacular migration in mice with complete androgen resistance (testicular feminization mouse [Tfm]). CGRP was injected into the right groin of neonatal Tfm mice at 2-day intervals until 2 weeks of age, when the length of the processus vaginalis was measured under a dissecting microscope. The processus vaginalis length in normal male littermates was 5.9 +/- 1.8 mm (mean +/- SD) while in the female it was 1.2 +/- 0.9 mm. Exogenous CGRP had no effect on either of these. In Tfm males CGRP caused a significant increase in the length of the processus vaginalis on the injected side (2.3 +/- 0.8 mm) compared with the uninjected side (1.4 +/- 1.0 mm). These results are consistent with the hypothesis that CGRP can replace, at least partially, the effect of androgens on gubernacular migration.

Double aortic arch presenting as severe bronchiolitis in a 2-week-old infant

Abstract:  A 2‐week‐old female infant was transferred from a regional hospital for mechanical ventilation after developing severe respiratory distress. Stridor had been present since the age of 1 week and was complicated by coryzal illness. Mechanical ventilation was difficult with marked inspiratory and expiratory flow obstruction recorded by the ventilator. Echocardiogram showed a normal heart. Flexible bronchoscopy revealed mid‐tracheal extrinsic compression (unchanged with positive end‐expiratory pressure) and advancement of the endotracheal tube by 2 cm completely corrected the flow obstruction. Repeat echocardiogram showed a double aortic arch. This case report emphasizes the importance of clinical history, examination findings and interpretation of the ventilator waveforms in the differential diagnosis of a difficult‐to‐ventilate infant with bronchiolitis.

Cytokine gene polymorphisms and severity of CF lung disease

BACKGROUND The search for modifier genes to explain inconsistencies in cystic fibrosis (CF) genotype-phenotype relationships has yielded mixed results. In a previous cross-sectional study from our centre the clinical effect (as described by FEV1, BMI z-score, admitted days and NIH score) of single nucleotide polymorphisms (SNPs) of four cytokine genes (IL-8, TNF-α, IL-1β and IL-10) was examined in 158 children with CF. No association between cytokine genotype and any biological outcome measure was found. In this present study a cross-sectional and longitudinal examination of this relationship was undertaken to test the hypothesis that pro-inflammatory SNPs would affect longitudinal changes in CF lung disease. METHODS Using the cohort examined in our earlier study we performed both longitudinal and cross-sectional data analyses examining the relationship between SNPs (TNF-α, IL-8, IL-10 and IL-1β) and clinical outcome measurements. In the first part of this current study, lung function data (annual decline of FEV1 percent predicted) was compared with the cytokine genotype over a 13 year period. In the second part of this current study multiple regression was used to assess associations between clinical outcomes (best FEV1 percent predicted and BMI at the age of 10 years) and alleles of cytokine genes, adjusting for gender, CF genotype and lung infection status. RESULTS A total of 152 patients with CF were analysed in the longitudinal study and data from 130 patients at the age of 10 years were analysed in the cross-sectional study. There was evidence for an association between pro-inflammatory SNPs of the IL-8, IL-10 and IL-1β genes and more severe lung disease. Multiple regression of the longitudinal data with a total of 10,956 lung function measurements showed an additional annual decline of the percentage predicted FEV1 of -1.15 (IL-8, p<0.001), -0.24 (IL-10, p=0.049) and -0.41 (IL-1β, p<0.001) for patients with any of the pro-inflammatory alleles. None of the cross-sectional data showed a significant association between the cytokine genotypes and the clinical outcomes. CONCLUSION Pro-inflammatory alleles of three cytokine genotypes, IL-8, IL-10 and IL-1β, appear to be associated with slightly more severe lung disease in patients with CF over a 13 year period. Further studies are required to exclude influence of confounders on the severity of lung disease.

Elimination of Australian epidemic strain (AES1) pseudomonas aeruginosa in a pediatric cystic fibrosis center

In this cohort study spanning an 18‐year period, we evaluated the prevalence and associated mortality rate of epidemic strains of pseudomonas aeruginosa (PsA), especially Australian Epidemic Strain Type 1 (AES1), in a pediatric cystic fibrosis center practicing cohort segregation and early PsA eradication.

Cytokine gene polymorphisms and severity of cystic fibrosis lung disease

Background Patients with end stage respiratory disease (ENSD) have an uncertain prognosis, deteriorate rapidly, over a period of days or hours, and commonly die in acute care settings. Introduction The St George end of life pathway was developed in response to evidence that current models of end-of-life care were failing to meet the needs of dying patients. This tool was designed to enable clinicians working in the acute care setting to integrate pivotal palliative care principles in the care of patients. Aim The aim of this observational study was to evaluate the benefits to patients and carers of the endof -life pathway implemented in an acutecare respiratory setting. Method A cohort of dying respiratory patients (n =13), who were placed on the end of life pathway in the period from November 2001 to November 2002, was examined to assess the acceptability and utility of the pathway. This was performed by chart review and staff reflection through a focus group. Results Completed care plans revealed the complexity of symptoms experienced by patients during this vulnerable period of their illness trajectory. Key areas for intervention included management of symptoms such as: pain, respiratory secretions, nausea and vomiting, dyspnoea, personal comfort, psychosocial and spiritual needs. 100% of patients had critical orders and no patients in this cohort received traumatic and unnecessary interventions such as intubation or arterial punctures. Staff described feeling more confident and having more guidance when caring for dying respiratory patients. Conclusion The end of life pathway has proved an important tool for good symptom management and delivery of holistic care. The tool has provided structure and information resources to assist clinicians to care of dying respiratory patients within the acute care setting. This review has confirmed the acceptability and the utility of the end-of-life pathway and underscored the importance of a multidisciplinary approach and a collaborative palliative care model. 01 Respirology (2003) 8, (Suppl.) A1–A65

Cohort segregation in the RCH CF clinic successfully reduces spread of the Melbourne “clonal strain” of Pseudomonas Aeruginosa

Background Patients with end stage respiratory disease (ENSD) have an uncertain prognosis, deteriorate rapidly, over a period of days or hours, and commonly die in acute care settings. Introduction The St George end of life pathway was developed in response to evidence that current models of end-of-life care were failing to meet the needs of dying patients. This tool was designed to enable clinicians working in the acute care setting to integrate pivotal palliative care principles in the care of patients. Aim The aim of this observational study was to evaluate the benefits to patients and carers of the endof -life pathway implemented in an acutecare respiratory setting. Method A cohort of dying respiratory patients (n =13), who were placed on the end of life pathway in the period from November 2001 to November 2002, was examined to assess the acceptability and utility of the pathway. This was performed by chart review and staff reflection through a focus group. Results Completed care plans revealed the complexity of symptoms experienced by patients during this vulnerable period of their illness trajectory. Key areas for intervention included management of symptoms such as: pain, respiratory secretions, nausea and vomiting, dyspnoea, personal comfort, psychosocial and spiritual needs. 100% of patients had critical orders and no patients in this cohort received traumatic and unnecessary interventions such as intubation or arterial punctures. Staff described feeling more confident and having more guidance when caring for dying respiratory patients. Conclusion The end of life pathway has proved an important tool for good symptom management and delivery of holistic care. The tool has provided structure and information resources to assist clinicians to care of dying respiratory patients within the acute care setting. This review has confirmed the acceptability and the utility of the end-of-life pathway and underscored the importance of a multidisciplinary approach and a collaborative palliative care model. 01 Respirology (2003) 8, (Suppl.) A1–A65

Length of intussusception as a function of mesenteric anatomy

Ileocolic intussusception presents with an abdominal mass or, occasionally, there may be bowel palpable in the rectum or protruding from the anus. Various factors have been proposed for the variations in the length of bowel involved. We tested the theory that the length of mesentry available to the intussusception is one of the factors limiting the length of the process. A postmortem study was carried out in eight children who died without congenital or acquired gut abnormalities. The distal ileum was intussuscepted using a blunt, flexible introducer. In nearly all cases, the distance between the proximal end of the intussusceptum and the superior mesentric trunk was significantly less than normal distance fron the cecum to the trunk. The length of the artificial intussusceptum was found to be proportional to the length of mesentery available. Points proximal to the ileocecal valve had more mesentry available and yielded longer intussuscepta. The superior mesentric trunk, the hub of the mesentery, proved to be limiting factor in all experimental intussusceptions.