Expression and localization of osteopontin, homing cell adhesion molecule/CD44, and integrin αvß3 in mucoepidermoid carcinoma and acinic cell adenocarcinoma of salivary gland origin.

OBJECTIVE: Osteopontin (OPN) plays a role in tumor progression. This study aimed to determine the expression of OPN, CD44, and integrin αvß3 in pleomorphic adenoma (PA), acinic cell adenocarcinoma (ACA), and mucoepidermoid carcinoma (MEC). STUDY DESIGN: Immunohistochemistry was used to semiquantify the levels of expression of OPN and its receptors in normal salivary glands (NSG) (n = 20), PA (n = 20), ACA (n = 11), and MEC (n = 29). RESULTS: OPN expression was increased in ACA and MEC compared with PA and NSG (median scores, 6, 6, 4, and 4, respectively). CD44 expression was increased in ACA and reduced in MEC and PA compared with NSG (median scores, 8, 4, 3, and 5, respectively). Integrin αvß3 median scores were 5 in ACA, 1 in MEC, and 0 in PA and NSG. CONCLUSIONS: OPN is expressed in salivary gland tumors and is at higher levels in ACA and MEC.

Inherited metabolic diseases in the Southern Chinese population: spectrum of diseases and estimated incidence from recurrent mutations.

Inherited metabolic diseases (IMDs) are a large group of rare genetic diseases. The spectrum and incidences of IMDs differ among populations, which has been well characterised in Caucasians but much less so in Chinese. In a setting of a University Hospital Metabolic Clinic in Hong Kong, over 100 patients with IMDs have been seen during a period of 13 years (from 1997 to 2010). The data were used to define the spectrum of diseases in the Southern Chinese population. Comparison with other populations revealed a unique spectrum of common IMDs. Furthermore, the incidence of the common IMDs was estimated by using population carrier frequencies of known recurrent mutations. Locally common diseases (their estimated incidence) include (1) glutaric aciduria type 1 (∼1/60,000), (2) multiple carboxylase deficiency (∼1/60,000), (3) primary carnitine deficiency (∼1/60,000), (4) carnitine-acylcarnitine translocase deficiency (∼1/60,000), (5) glutaric aciduria type 2 (∼1/22,500), (6) citrin deficiency (∼1/17,000), (7) tetrahydrobiopterin-deficient hyperphenylalaninaemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency (∼1/60,000), (8) glycogen storage disease type 1 (∼1/150,000). In addition, ornithine carbamoyltransferase deficiency and X-linked adrenoleukodystrophy are common X-linked diseases. Findings of the disease spectrum and treatment outcome are summarised here which may be useful for clinical practice. In addition, data will also be useful for policy makers in planning of newborn screening programs and resource allocation.

Expression and localization of osteopontin, homing cell adhesion molecule/CD44, and integrin αvß3 in pleomorphic adenoma, polymorphous low-grade adenocarcinoma, and adenoid cystic carcinoma.

OBJECTIVES: Osteopontin (OPN) plays a role in tumor progression. This study aimed to determine the expression of OPN, CD44, and integrin αvß3 in pleomorphic adenoma (PA), polymorphous low-grade adenocarcinoma (PLGA), and adenoid cystic carcinoma (ACC). STUDY DESIGN: Immunohistochemistry was used to semiquantify the level of expression of OPN and its receptors in normal salivary glands (NSG; n = 20), PA (n = 20), PLGA (n = 16), and ACC (n = 22). RESULTS: OPN expression was increased in PLGA and intermediate-/high-grade ACC compared with PA and NSG (median scores, 6, 5, 4, and 4, respectively). CD44 expression was reduced in PA, PLGA, and ACC. OPN expression levels were moderately correlated with CD44 in PLGA. Integrin αvß3 was not expressed in PA and ACC and was seen in only 1 case of PLGA. CONCLUSIONS: OPN is expressed in salivary gland tumors but does not correlate well with CD44 and αvß3.

Respiratory viruses and atypical bacteria triggering severe asthma exacerbation in children.

1. Respiratory viruses and atypical bacteria were detected in 51.0% of Hong Kong children with asthma exacerbations, which was significantly higher than the detection rate of 27.3% in children with chronic stable asthma. 2. Co-infections of two or more respiratory pathogens were more commonly found in children with asthma exacerbations (10.7%) than in patients with stable asthma (2.6%). 3. Human rhinovirus infection was a significant risk factor for asthma exacerbations. 4. There was no significant association between the severity of asthma exacerbations and respiratory viral or atypical bacterial infections. 5. Routine use of macrolide antibiotics in the treatment of childhood asthma exacerbations should be discouraged.

Scaling behavior in turbulent Rayleigh-Bénard convection revealed by conditional structure functions.

We show that the nature of the scaling behavior can be revealed by studying the conditional structure functions evaluated at given values of the locally averaged thermal dissipation rate. These conditional structure functions have power-law dependence on the value of the locally averaged thermal dissipation rate, and such dependence for the Bolgiano-Obukhov scaling is different from the other scaling behaviors. Our analysis of experimental measurements verifies the power-law dependence and reveals the Bolgiano-Obukhov scaling behavior at the center of the bottom plate of the convection cell.

Impact of the educational resource one life many gifts on attitudes of secondary school students towards organ and tissue donation and transplantation.

BACKGROUND: Increased awareness of organ donation/transplantation has been found to have a positive influence on organ donation rates. One Life … Many Gifts is a curriculum resource in Ontario, Canada, to educate and raise awareness for senior secondary school students about the importance of organ and tissue donation and transplantation. Teachers administered pre- and post- attitudinal surveys to senior secondary school students to evaluate changes in their attitudes toward organ and tissue donation and transplantation. In this study, the effect of the One Life … Many Gifts educational intervention on changing the attitudes and awareness of organ donation and transplantation of senior secondary students was assessed. METHODS: Mann-Whitney U tests were used to compare the pre- and post-surveys as a whole and then again for the data from individual schools. Kruskal-Wallis H-tests were used to compare data between schools. RESULTS: A total of 1832 pre- and 1440 post-educational surveys returned to Trillium Gift of Life Network were assessed in the 2008-2009 academic year. Overall, comparison of all pre- and post-educational program survey data showed significant improvement in the students' attitudes toward organs and tissue donation and transplantation (P = .00625). CONCLUSION: The One Life … Many Gifts program made an impact on changing the attitudes toward and awareness of organ donation among high school students in Ontario. Evaluation of its impact on donor registration and organ donation among the students and their parents is complex and remains to be seen.

Distribution of melamine in rat foetuses and neonates.

Pharmacokinetics of melamine has not been studied in pregnancies despite of the many reports on the effect on renal damage in adult and neonates. In this study, Sprague-Dawley rats have been used as a model to study the single-dose effect of melamine administration in late pregnancy and in neonates within 24h. Melamine concentrations in maternal serum, breast milk, whole foetus, amniotic fluid, neonatal serum and neonatal kidney was measured by liquid chromatography coupled with mass spectrometry. Melamine was detected in all the samples, including foetal rats and amniotic fluid in utero. Melamine was able to pass through placenta and reach the foetus, and to accumulate in lactating mammary gland and neonatal kidney. Moreover, melamine was eliminated through the placenta of the foetus and the kidneys of the neonates, and later excreted into the amniotic fluid. The study characterised for the first time the distribution of melamine in foetuses and neonates, providing reference for toxicological study of melamine during pregnancy.

Higher exercise frequency associated with lower blood pressure in Hong Kong adolescents: a population-based study.

The aim of this study was to determine the association between blood pressure and the frequency of structured physical training activity in Chinese adolescents. A total of 9558 students aged 11-18 years underwent anthropometric and blood pressure measurements in a cross-sectional growth study. Structured physical training activity was assessed by two simple self-administered questions and parents were asked to complete a questionnaire providing demographic information. Ninety per cent of eligible students participated in the study, of which 94% provided data on physical training frequency for final analysis. Of the boys, 22.6% and of the girls, 14.5% were physically active with extracurricular school exercise at least twice a week. Over half of the students did not regularly exercise except during physical education classes at school. Blood pressure had a positive correlation with body mass index (BMI). Both systolic blood pressure and diastolic blood pressure were substantially decreased with increased training frequency (P<0.05). Logistic regression adjusting for age, family history of hypertension, BMI and sleep duration showed that exercising two or more times a week had a negative relation with hypertension (odds ratio: 0.63, 95%CI 0.47-0.85). In conclusion, structured physical training activity of two or more times a week has a beneficial effect on blood pressure in Hong Kong children aged 11-18 years.

Natural history and predictors for progression of mild childhood obstructive sleep apnoea.

AIMS: The natural history of mild childhood obstructive sleep apnoea (OSA) was examined and factors associated with disease progression were identified. METHODS: Subjects were recruited from an epidemiological study which examined the prevalence of OSA in Chinese children aged 6-13 years. The first 56 consecutive children identified with mild OSA (apnoea-hypopnoea index 1-5) were invited for a repeat assessment 2 years after the diagnosis. RESULTS: 45 children participated in the follow-up study, in 13 of whom (29%) the OSA was found to have worsened. Compared with those in whom OSA had not worsened, the worsened OSA group had a greater increase in waist circumference, a higher prevalence of large tonsils (occupying > or =50% of the airway) at both baseline and follow-up, and a higher prevalence of habitual snoring at both baseline and follow-up. The presence of large tonsils had a positive predictive value of 53% and a negative predictive value of 83% for worsening OSA over a 2-year period. Multivariate linear regression analysis showed that the change in obstructive apnoea-hypopnoea index was associated with age at baseline (beta (SE) = -0.92 (0.34), p = 0.009), gender (male = 1; female = 0) (beta (SE) = 4.69 (1.29), p<0.001), presence of large tonsils at baseline (beta (SE) = 4.36 (1.24), p = 0.001), change in waist circumference (beta (SE) = 0.30 (0.09), p = 0.002) and persistently large tonsils (beta (SE) = 5.69 (1.36), p<0.001) over the 2-year period. CONCLUSIONS: Mild OSA in the majority of children does not resolve spontaneously. Subjects with tonsillar hypertrophy, especially boys, should be closely monitored to allow early detection of worsening OSA. Weight control should be stressed in the management of childhood OSA.

Cardiac remodelling and dysfunction in children with obstructive sleep apnoea: a community based study.

BACKGROUND: Childhood obstructive sleep apnoea (OSA) is suggested to be associated with cardiac structural abnormalities and dysfunction but existing evidence is limited and the treatment effect on echocardiographic outcome remains controversial. OBJECTIVE: To examine the presence of subclinical cardiac abnormalities in childhood OSA and the effects of treatment on cardiac changes. METHODS: Polysomnography (PSG) and echocardiographic examinations were performed in 101 children aged between 6 and 13 years who were invited from a community based questionnaire survey. They were classified into a reference group (apnoea-hypopnoea index (AHI) <1, n = 35), mild OSA group (AHI 1-5, n = 39) and moderate to severe group (AHI >5, n = 27) based on the PSG results. Treatments, including adenotonsillectomy or nasal steroids, were offered to the mild and moderate to severe OSA groups. RESULTS: The moderate to severe OSA group had greater right ventricular (RV) systolic volume index (RVSVI), lower RV ejection fraction (RVEF) and higher RV myocardial performance index (RVMPI) than the reference group. They also had more significant left ventricular (LV) diastolic dysfunction and remodelling with larger interventricular septal thickness index (IVSI) and relative wall thickness than those with lower AHI values. The moderate to severe OSA group had an increased risk of abnormal LV geometry compared with the reference group (odds ratio 4.21 (95% CI 1.35 to 13.12)). Log transformed AHI was associated with RVSVI (p = 0.0002), RVEF (p = 0.0001) and RVMPI (p<0.0001), independent of the effect of obesity. Improvement in RVMPI, IVSI and E/e' were observed in those with a significant reduction in AHI (>50%) comparing 6 month with baseline data. CONCLUSIONS: OSA is an independent risk factor for subclinical RV and LV dysfunction, and improvement in AHI is associated with reversibility of these abnormalities.

Suppression and recovery of the hypothalamic function after high-dose corticosteroid treatment in preterm infants.

BACKGROUND: High-dose systemic dexamethasone is effective in facilitating extubation of ventilated infants with bronchopulmonary dysplasia. Although the suppression and recovery of pituitary-adrenal response had been assessed after corticosteroid treatment in very low birth weight infants, its effect on hypothalamic function has not been longitudinally monitored. AIMS: This study was designed to assess the longitudinal hypothalamic response before, during and 4 weeks after a 3-week dose-tapering course of systemic dexamethasone treatment. PATIENTS AND METHODS: Twenty very low birth weight infants had blood collected for corticotropin-releasing hormone, ACTH and cortisol measurements immediately before starting dexamethasone (week 0), after receiving the maximum dose of treatment (week 1), at the end of the 3-week course (week 3) and 4 weeks after stopping corticosteroids (week 7). RESULTS: All circulating hormone concentrations were significantly suppressed during the treatment period at week 1 and week 3 compared with pretreatment concentrations at week 0 (p < 0.001). The recovery of pituitary function started early soon after week 1, whereas that of hypothalamus and adrenal functions started after the end of the dexamethasone course. Plasma ACTH concentration at week 7 had returned to the pretreatment level, but plasma corticotropin-releasing hormone (p < 0.05) and serum cortisol (p < 0.001) concentrations remained significantly suppressed. Partial recovery of hypothalamic and adrenal function was observed at week 7 (62 vs. 36% of their pretreatment levels, respectively). CONCLUSION: Our findings suggest that the hypothalamic function is suppressed during systemic corticosteroid treatment but partial recovery occurs 4 weeks after stopping therapy. Even in preterm infants, the hypothalamic-pituitary-adrenal axis behaves in a similar manner as in adult subjects and the pituitary function recovers earlier than that of hypothalamus and adrenals.

Ambulatory blood pressure in children with obstructive sleep apnoea: a community based study.

BACKGROUND: Childhood obstructive sleep apnoea (OSA) is increasingly being recognised. Its effects on blood pressure (BP) elevation and hypertension are still controversial. OBJECTIVE: To evaluate the association between OSA and ambulatory BP in children. METHODS: Children aged 6-13 years from randomly selected schools were invited to undergo overnight sleep study and ambulatory BP monitoring after completing a validated OSA questionnaire. OSA was diagnosed if the obstructive apnoea-hypopnoea index (AHI) was >1, and normal controls had AHI <1 and snoring <3 nights per week. Children with OSA were subdivided into a mild group (AHI 1-5) and moderate to severe group (AHI >5). RESULTS: 306 subjects had valid sleep and daytime BP data. Children with OSA had significantly higher BP than normal healthy children during both sleep and wakefulness. BP levels increased with the severity of OSA, and children with moderate to severe disease (AHI >5) were at significantly higher risk for nocturnal systolic (OR 3.9 (95% CI 1.4 to 10.5)) and diastolic (OR 3.3 (95% CI 1.4 to 8.1)) hypertension. Multiple linear regression revealed a significant association between oxygen desaturation index and AHI with daytime and nocturnal BP, respectively, independent of obesity. CONCLUSIONS: OSA was associated with elevated daytime and nocturnal BP, and is an independent predictor of nocturnal hypertension. This has important clinical implications as childhood elevated BP predicts future cardiovascular risks. Future studies should examine the effect of therapy for OSA on changes in BP.

In vitro and clinical immunomodulatory effects of a novel Pentaherbs concoction for atopic dermatitis.

BACKGROUND: Our group recently reported a randomized and placebo-controlled clinical trial on the efficacy of a twice-daily concoction of five herbal ingredients (Pentaherbs formulation, PHF) in treating children with atopic dermatitis (AD). OBJECTIVES: To investigate the immunomodulatory effects that may be induced by PHF treatment. METHODS: We investigated the effects of PHF on cytotoxicity and proliferation of phytohaemagglutinin (PHA)- and staphylococcal enterotoxin B (SEB)-stimulated peripheral blood mononuclear cells (PBMC) isolated from buffy coat of blood donors. PHF-induced immunomodulation for five inflammatory mediators in cultured PBMC was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The effects of a 3-month, open-label study of PHF on circulating inflammatory mediators in children with AD were also assessed. RESULTS: PHF at up to 1 mg mL(-1) dose-dependently suppressed PBMC proliferation. The addition of PHF to cultured PBMC reduced supernatant concentrations of brain-derived neurotrophic factor (BDNF), interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in response to PHA, and BDNF and thymus and activation-regulated chemokine (TARC) following SEB stimulation. PHF increased epithelial cell-derived neutrophil activating peptide-78 levels in culture supernatants. At the RNA level, PHF suppressed the transcription of BDNF, TARC, IFN-gamma and TNF-alpha. Twenty-eight children with AD were treated with PHF for 3 months, and their mean plasma concentrations of BDNF and TARC decreased significantly from 1798 pg mL(-1) and 824 pg mL(-1) at baseline to 1378 pg mL(-1) and 492 pg mL(-1) (P = 0.002 and 0.013, respectively) upon study completion. CONCLUSIONS: PHF possesses in vitro and in vivo immunomodulatory properties that may mediate the clinical efficacy observed in AD treatment.

Efficacy and tolerability of a Chinese herbal medicine concoction for treatment of atopic dermatitis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: There has been considerable interest in traditional Chinese herbal medicine (TCHM) as a treatment for atopic dermatitis (AD). A twice-daily concoction of an ancestral formula containing five herbs has been found to be beneficial in an open study. OBJECTIVES: To assess the efficacy and tolerability of the concoction in children with AD. METHODS: Following a 2-week run-in period, children with long-standing moderate-to-severe AD were randomized to receive a 12-week treatment with twice-daily dosing of three capsules of either TCHM or placebo. The SCORing of Atopic Dermatitis (SCORAD) score, Children's Dermatology Life Quality Index (CDLQI), allergic rhinitis score, and requirement for topical corticosteroid and oral antihistamine were assessed before and at weeks 4, 8, 12 and 16 after treatment. Adverse events, tolerability, haematological and biochemical parameters were monitored during the study. RESULTS: Eighty-five children with AD were recruited. Over 12 weeks, the mean SCORAD score fell from 58.3 to 49.7 in the TCHM group (n = 42; P = 0.003) and from 56.9 to 46.9 in the placebo group (n = 43; P = 0.001). However, there was no significant difference in the scores at the corresponding time points between the two groups. The CDLQI in TCHM-treated patients was significantly improved compared with patients receiving placebo at the end of the 3-month treatment and 4 weeks after stopping therapy (P = 0.008 and 0.059, respectively). The total amount of topical corticosteroid used was also significantly reduced by one-third in the TCHM group (P = 0.024). No serious adverse effects were observed between the groups. CONCLUSIONS: The TCHM concoction is efficacious in improving quality of life and reducing topical corticosteroid use in children with moderate-to-severe AD. The formulation was palatable and well tolerated.

Which aeroallergens are associated with eczema severity?

We investigated if a correlation exists between aeroallergen sensitization and the severity of eczema. Data on aeroallergen response to skin-prick testing (SPT) and disease severity of children with eczema (n = 119) were evaluated. Atopy, as defined by at least one positive response to aeroallergen skin prick testing, was found in > 90% of eczema patients. House dust mite was the most commonly sensitized aeroallergen, followed by cat fur. Dermatophagoides pteronyssinus and Dermatophagoides farinae sensitization were associated with eczema severity (present in 67% of the mild and 97% of the severe group; P = 0.001). However, there was no association between eczema severity and higher strengths of SPT response (defined as SPT > 1+ to dust mites or dust). Atopy to moulds, Bermuda grass, cockroach, cat and dog was less prevalent and was not associated with eczema severity. It is sensible to advise parents on specific avoidance strategies only in severely affected children who have a definitive history of eczema exacerbation by specific aeroallergens and who are not responsive to conventional treatment.