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Introduction 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. Methods Cohort segregation was introduced in January 2000. PsA clonal strain was determined by pulse-field-gel-electrophoresis (PFGE) at the time of routine collection of airway specimens. Children with PsA underwent eradication treatment with anti-pseudomonal antibiotics over 2-3 months. We analyzed changes in prevalence and mortality from 1999 to 2016. Results The prevalence of AES1 declined from 69 (20%) in 1999 to 16 (5.4%) in 2006, to 1 (0.4%) in 2016. The prevalence of PsA overall diminished less over the same period, from 128 (37%) patients in 1999 to 57 (23%) in 2016. New acquisition of AES1 became less common over time, with no new cases identified from 2011. Those who contracted AES1 had a greater risk of death than those who did not (Odds Ratio 4.9, 95%CI 2.5-9.6). Patients with other AES PsA types were uncommon (AES2 n = 5, AES5 n = 2, AES14 n = 3, AES19 n = 1). Conclusions Cohort segregation was associated with reduction in AES1 prevalence ascertained by PFGE surveillance for patients in a single large pediatric cystic fibrosis center. Other alterations in practice such as early eradication treatment may also have contributed to reduced PsA prevalence. These factors combined with the transition of chronically infected patients over time to adult centers has eliminated AES1 from our clinic, with an accompanying mortality decrease.

Osteopathia striata with cranial sclerosis (OSCS) is a rare X-linked skeletal dysplasia characterized by linear striations of the long bones, osteosclerosis of the cranium, and extraskeletal anomalies. We report a female infant with OSCS diagnosed radiographically with molecular confirmation in the first year of life. The patient presented at 5 months with severe obstructive sleep apnea, which had progressed rapidly after the neonatal period and which responded favorably to mandibular distraction osteogenesis. This procedure has not previously been reported in association with OSCS, which is a rare cause of Pierre Robin sequence with dysmorphic features.

A clonal strain of Pseudomonas aeruginosa (PA) was isolated in 1999 at the Royal Children's Hospital, Melbourne, Australia, after five unrelated children with cystic fibrosis (CF) died from severe lung disease aged5 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 patientsor=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 Children's Hospital, Melbourne, Australia.

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 ≥1,000 mg a day for ≥6 months, were enrolled. Early morning serum cortisol was performed. Subjects with a serum cortisol of

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.

There is still controversy over whether androgens are involved in gubernacular migration during descent of the testis, prompting a review of anatomical events controlled by androgens. The gubernacular position in adult female, male, and testicular feminized male (TFM) mice (with complete androgen resistance) was observed macroscopically to determine its caudal limit and whether the adult TFM male still contained guvernacular bulk. The length of the processus vaginalis was measured, and the presence of a differentiated cremaster muscle was determined histologically. In 10 adult female mice there was neither a processus vaginalis nor a cremaster muscle, and the gubernaculum (round ligament of the ovary) attached to the external inguinal ring. In 10 adult TFM mice the gubernaculum ended at or just beyond the external ring, and was present in an amount corresponding to its size at the end of the outgrowth phase of development, with secondary infiltration by fat. The processus vaginalis was poorly developed, the cremaster muscle was undifferentiated, and there was no eversion of the cremaster sac. In 10 normal adult male mice the gubernaculum and testis had migrated to the scrotum, and the gubernaculum had regressed fully. Because gubernacular development in the androgen-resistant mouse cases after termination of transabdominal testicular migration, the anatomy of the adult confirms that, in the mouse, normal androgenic function is essential for eversion of the cremaster sac and gubernacular migration beyond the groin to the genital folds.

The effects of calcitonin gene-related peptide (CGRP) and CGRP 8-37 on the neonatal mouse gubernaculum were examined in organ culture, with the aim of seeing whether CGRP has a direct effect on the gubernaculum. A total of 440 gubernacula were studied. Two hundred and fifty gubernacula were treated with CGRP in concentrations ranging from 0-714 nM/liter. With increasing doses of CGRP the percentage of gubernacula showing vigorous contraction increased from 18-50%. The total percentage of gubernacula showing any form of contraction increased from 76-96%. One hundred and fifty gubernacula were exposed to the CGRP analog CGRP 8-37. Increasing concentrations of CGRP 8-37 from 179-714 nM/liter decreased the rate of vigorous contraction from 18-4%. The percentage of gubernacula showing any degree of contraction decreased from 76-14%. Forty gubernacula removed from testicular feminization (TFM) mice were exposed to varying concentrations of CGRP. In the absence of exogenous CGRP no contractility was observed. By contrast, in the presence of CGRP the gubernacula showed vigorous contractility increasing from 38-90%. The total number of gubernacula showing contraction increased from 75-100%. These studies demonstrated that the neonatal mouse gubernaculum exhibits a high level of endogenous contractility, which can be enhanced in a dose responsive manner with exogenous CGRP. CGRP 8-37 caused a dose responsive inhibition. The androgen-insensitive gubernaculum from the TFM mouse showed no endogenous contraction, but on exposure to CGRP showed an enhanced rate of contractility. These results are consistent with the hypothesis that androgens may control gubernacular migration indirectly via release of CGRP from the genitofemoral nerve in the inguinoscrotal region. The failure of gubernacular motility in vitro and migration in vivo in the TFM mouse may indicate lack of CGRP release from the genitofemoral nerve.

Before sexual differentiation occurs at seven weeks, the urological ridges develop in the embryo. These contain the primitive gonads, the mesonephros (embryonic kidneys) and the paired Wolffian (mesonephric) ducts, along with the Müllerian (paramesonephric) ducts. The fundamental mechanism of fetal sexual development was elucidated by Alfred Jost and is determined by the development of the gonad: where testes form in response to the testis-determining gene, and the male testicular hormones cause development of the male phenotype. If ovaries develop or the gonads are absent, female secondary sex characteristics are produced. Recently, the cloning of the putative human testis-determining gene on the Y-chromosome was reported. Assuming this is the true controller of testicular development, an understanding of the initiation of sexual differentiation at the genetic level should emerge in the near future. Of great importance will be the isolation of the testis-determining gene product and identification of other genes that it regulates.

The detection of a clonal Pseudomonas aeruginosa strain in 21% of children attending a cystic fibrosis clinic during 1999, which may have led to a worse prognosis, prompted strict infection control measures, including cohort segregation. We determined whether these strategies interrupted cross-infection within the clinic. Patients from 1999 were observed and a cross-sectional study of the 2002 clinic was performed. By 2002, the epidemic strain prevalence had decreased from 21 to 14% (p = 0.03), whereas the proportion of patients with nonepidemic P. aeruginosa strains was unchanged. The age- and sex-adjusted relative risk for epidemic strains among sputum producers in 2002 compared with 1999 was 0.64 (95% confidence interval, 0.47, 0.87; p = 0.004). Increased mortality or transfer to another clinic did not explain this reduction. Although children with epidemic strains may have had increased mortality (adjusted odds ratio, 2.0; 95% confidence interval, 0.6-6.8), they did not demonstrate greater morbidity than those with other P. aeruginosa isolates. Successful infection control measures provided additional indirect evidence for person-to-person transmission of an epidemic strain within the clinic. Further studies are needed to resolve whether cohort segregation completely eliminates cross-infection and if acquisition of epidemic isolates is associated with worse outcomes.

Significant concern remains over the long-term side effects of inhaled steroids. This cross-sectional study evaluates the effect of high-dose inhaled fluticasone propionate (FP) on biochemical markers of bone metabolism and bone density in children with asthma. Children with chronic asthma using FP >/= 1,000 mcg daily for at least 6 months, and healthy controls, were entered in the study. No children had taken oral prednisolone within the previous month. Fasting morning serum was analyzed for bone formation markers, and spot urine for bone resorption markers. Dual-energy X-ray absorptiometry (DEXA) results were reviewed in a subgroup of patients. Forty-nine children with asthma and 32 controls were recruited. The mean FP dose was 771.2 +/- 253.35 mcg/m2/day. Unpaired t-test analysis revealed no significant difference in biochemical markers studied. In subjects with asthma; 13 of 37 (35.1%) had lumbar spine density more than one standard deviation below the mean (P = 0.001). This fell to 6/37 (16.2%) with bone age correction (NS). In conclusion, no significant reduction in bone metabolism or bone age-corrected bone mineral density was observed in children with asthma on prolonged high doses of inhaled FP.

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.

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.

BackgroundThe 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.MethodsUsing 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 13year 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 10years) and alleles of cytokine genes, adjusting for gender, CF genotype and lung infection status.ResultsA total of 152 patients with CF were analysed in the longitudinal study and data from 130 patients at the age of 10years 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

Aim To evaluate changes in prevalence of an epidemic strain of Pseudomonas aeruginosa (AES-1, Australian epidemic strain, type 1) in a paediatric cystic fibrosis (CF) centre practising cohort segregation, to describe the patients' clinical characteristics at acquisition and observe mortality rates. Methods Cohort segregation was introduced in our paediatric CF clinic January 2000. The prevalence of AES-1 was analysed in 1999, 2002 and 2007. Age at acquisition, lung function, presence of bronchiectasis, hospitalisations, prior P. aeruginosa infection and mortality rates were collected. AES-1 infection was determined by pulse-field-gel-electrophoresis (PFGE) on airway specimen cultures taken three monthly. Results The prevalence of AES-1 declined from 21% in 1999 to 14% in 2002 (risk difference 7% (95% CI 1,13) p=0.0256) and to 6% in 2007 (risk difference 8% (95% CI 3,13) p=0.0018). New acquisitions after the introduction of cohort segregation were uncommon (10 by 2002 and another 7 by 2007) with a declining incidence of 3.3cases/year (1999 to 2002) compared to 1.4cases/year (2002 to 2007). Twenty-two of 32 (69%) deaths between 1999 and 2007 occurred in patients infected with AES-1. Conclusion Cohort segregation has been associated with reductions in the prevalence of AES-1 in our CF clinic. Mortality was higher in patients infected with AES-1 than other organisms.