Prebiotic-supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high-risk infants: a randomized controlled trial.

BACKGROUND: Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months, but evidence is mixed. Adding specific oligosaccharides may improve outcomes. OBJECTIVE: To evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF-OS) can prevent eczema in high-risk infants [ISRCTN65195597]. METHODS: We conducted a parallel-group, multicentre, randomized double-blind controlled trial of pHF-OS vs standard cow's milk formula. Infants with a family history of allergic disease were randomized (stratified by centre/maternal allergy) to active (n = 432) or control (n = 431) formula until 6 months of age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomized at 0-4 weeks (375 pHF-OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomized, immune markers at 6 months and adverse events. RESULTS: Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks of age, vs 93/324 (28.7%) control (OR 0.98 95% CI 0.68, 1.40; P = 0.90), and 107/347 (30.8%) pHF-OS vs 112/370 (30.3%) control in all infants randomized (OR 0.99 95% CI 0.71, 1.37; P = 0.94). pHF-OS did not change most immune markers including total/specific IgE; however, pHF-OS reduced cow's milk-specific IgG1 (P < 0.0001) and increased regulatory T-cell and plasmacytoid dendritic cell percentages. There was no group difference in adverse events. CONCLUSION: pHF-OS does not prevent eczema in the first year in high-risk infants. The immunological changes found require confirmation in a separate cohort.

Anaphylaxis to galacto-oligosaccharides--an evaluation in an atopic population in Singapore.

Anaphylaxis to galacto-oligosaccharides (GOS), a prebiotic, has been described in atopic patients following its supplementation in commercial milk formula in South-East Asia. The epidemiology of this usual allergy to a carbohydrate is unknown. This study evaluated the prevalence of allergy to two formulations of commercial GOS, Vivinal™ GOS (vGOS) and Oligomate™ , in an atopic cohort. Atopic subjects (n = 487) from two specialist allergy clinics were surveyed via structured questionnaire and underwent skin prick tests to GOS. Subjects with positive skin prick tests to GOS (n = 30, 6.2%) underwent basophil activation tests, and a subset (n = 13) underwent oral challenge tests to both formulations of GOS. Six subjects had positive challenges to vGOS; and none to Oligomate. By extrapolating the BAT and oral challenge results, the prevalence of allergy to vGOS is estimated at up to 3.5% (95% CI 2.2-5.5%) of our atopic population. Our findings show that GOS allergy may be common amongst atopics in Singapore.

Trophic size-structure of sailfish Istiophorus platypterus in eastern Taiwan estimated by stable isotope analysis.

To examine trophic dynamics over different size classes, an isotopic study of sailfish Istiophorus platypterus life-history stages was carried out. Samples were collected from eastern Taiwan and the South China Sea during April 2009 and February 2012. A total of 263 samples (111-245 cm, lower jaw fork length, LLJFL ) were examined for changes in trophic structure in relation to LLJFL by using stable isotope analysis of carbon (δ(13) C) and nitrogen (δ(15) N). The δ(15) N values for I. platypterus ranged from 7·51 to 14·19‰ (mean ± s.d. = 12·06 ± 1·16‰) and the δ(13) C values ranged from -22·04 to -15·48‰ (mean ± s.d. = -17·62 ± 1·10‰). The δ(15) N values were positively dependent on LLJFL (r(2) = 0·377), whereas δ(13) C were negatively dependent on LLJFL (r(2) = 0·063). There were significantly different seasonal changes in nitrogen and carbon isotopic concentration, but no significant differences in concentrations between eastern Taiwan and the South China Sea were reported. The trophic level (TL ) of each LLJFL class was correlated, starting from 2·84 TL for size class I (LLJFL < 140 cm) and reaching 5·03 TL for size class VI (LLJFL > 221 cm). The mean ± s.d. TL was 4·43 ± 0·19 for all samples. The results reveal that I. platypterus occupies a wide range of trophic levels and different size classes occupy different trophic positions in the pelagic ecosystem.

Predicting methicillin resistance among community-onset Staphylococcus aureus bacteremia patients with prior healthcare-associated exposure.

To develop and validate prediction rules to identify the risk of methicillin-resistant Staphylococcus aureus (MRSA) infection among community patients who have healthcare-associated (HA) exposure and S. aureus bacteremia. A total of 1,166 adults with community-onset S. aureus bacteremia were retrospectively enrolled. The background prevalence of community MRSA infection was extrapolated from 392 community-associated S. aureus bacteremia (CA-SAB) patients without HA exposure. Complete and clinical risk scores were derived and tested using data from 774 healthcare-associated S. aureus bacteremia (HA-SAB) patients. The risk scores were modeled with and without incorporating previous microbiological data as a model predictor and stratified patients to low-, intermediate-, and high-risk groups for MRSA infection. The clinical risk score included five independent predictors and the complete risk score included six independent predictors. The clinical and complete risk scores stratified 32.7 % and 42.0 % of HA-SAB patients to the low-risk group for MRSA infection respectively. The prevalence of MRSA infection in score-stratified low-risk groups ranged from 16.3 % to 23.3 %, comparable to that of CA-SAB patients (13.8 %). Simple decision rules allow physicians to stratify the risk of MRSA infection when treating community patients with prior HA exposure and possible S. aureus infection.

Differences between methicillin-resistant Staphylococcus aureus bacteremic isolates harboring type IV and type V staphylococcal cassette chromosome mec genes based on prior patient healthcare exposure.

This observational study enrolled adult patients with bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) who were treated at the emergency department of a teaching hospital from 2001 to 2007. MRSA isolates with type IV and type V staphylococcal cassette chromosome mec (SCCmec) genes (SCC IV/V-MRSA) were included in the final analysis. Healthcare-associated SCC IV/V-MRSA (HA-SCC IV/V-MRSA) and community-acquired SCC IV/V-MRSA (CA-SCC IV/V-MRSA) were defined as the identification of an SCC IV/V-MRSA isolate from a patient with and without healthcare-associated risk factors, respectively. Thirty-four cases of CA-SCC IV/V-MRSA (20 SCCmec type IV, 14 SCCmec type V) and 81 cases of HA-SCC IV/V-MRSA (59 SCCmec type IV, 22 SCCmec type V) bacteremia were identified. Vascular device-associated infections were a significant infection source in HA-SCC IV/V-MRSA bacteremia cases. SCCmec type IV HA-SCC IV/V-MRSA isolates (3.4%) were significantly less likely to carry the Panton-Valentine leukocidin (PVL) gene than SCCmec type IV CA-SCC IV/V-MRSA isolates (35.0%, p = 0.001). The 90-day cumulative probability of survival was 76% for patients with CA-SCC IV/V-MRSA bacteremia and 66% for patients with HA-SCC IV/V-MRSA bacteremia (p = 0.247, by the Wilcoxon rank-sum test). Significant differences in antimicrobial susceptibility were observed between bacterial isolates from patients with CA-SCC IV/V-MRSA bacteremia and HA-SCC IV/V-MRSA bacteremia.

An unusual cause of food-induced anaphylaxis in mothers.

BACKGROUND: Galacto-oligosaccharides (GOS) are prebiotics added to commercial milk formula of infants and mothers. In recent years, cases of allergy related to GOS in atopic children have been reported in the South East Asian region. CASE PRESENTATIONS: We describe a series of pregnant (n = 4) and lactating mothers (n = 2) who developed anaphylactic reactions after consumption of maternal milk formula containing GOS. All six subjects had pre-existing atopy and a positive skin prick test to GOS and 5/5 of the subjects who were tested had positive basophil activation tests to GOS. All of the mothers and their babies had normal neonatal outcomes after the reactions. CONCLUSIONS: The supplementation of GOS into milk and beverages in the Asian region should take into account the rare chance of allergenicity of GOS in the atopic population.

Should bleeding tendency deter abdominal paracentesis?

BACKGROUND AND AIMS: This study was conducted to evaluate the complications and bleeding associated with either thrombocytopoenia or prolongation of prothrombin time for ultrasound-guided abdominal paracentesis in the emergency department. STUDY DESIGN AND PATIENTS: In an emergency department of a tertiary centre, patients receiving ultrasound-guided abdominal paracentesis by the emergency physicians were prospectively enrolled. Patient characteristics, the preprocedure international normalised ratio for prothrombin time and the platelet count, and the procedure-related complications were collected and analysed. RESULTS: For a 2-year study period, a total of 410 abdominal paracenteses in 163 patients were investigated. The preprocedure international normalised ratio for prothrombin time was more than 1.5 in 142 paracenteses; the preprocedure platelet count was less than 50 x 10(3) microL(-1) in 55 paracenteses. Only two out of 410 procedures (0.5%, 95% confidence interval=0.1-1.8%) were associated with minor complications of cutaneous bleeding in the same patient (0.6%, 95% confidence interval=0.1-3.4%) at different visits. There was no significant procedure-related bleeding or complications even in patients with marked thrombocytopoenia or prolongation in international normalised ratio. CONCLUSIONS: Bleeding complication of ultrasound-guided abdominal paracentesis is uncommon and appears to be very mild, regardless of preprocedure international normalised ratio or platelet count. Routine correction of prolonged international normalised ratio or thrombocytopoenia before abdominal paracentesis may not be necessary.

Infants' tracking of objects and collections.

Recent research suggests that infants' understanding of the physical world is more complex and adult-like than previously believed. One of the most impressive discoveries has been infants' ability to reason about medium-sized, material objects. They are able to individuate objects in a scene, and to enumerate and reason about them. This article reports a series of experiments investigating 8-month-old infants' ability to reason about collections of objects. Experiment 1 shows a sharp contrast between infants' understanding of single objects versus collections. While infants detected the discontinuous ('Magical') disappearance of a single object, they did not detect the Magical Disappearance of a non-cohesive pile of objects. Experiments 2-4 found that infants' difficulty remained even when the distinct identity of each object in the collection was emphasized, but could be overcome if infants (a) first saw the individual objects clearly separated from each other prior to their being placed together in a pile, or (b) had prior experience with the objects making up the collection. Our findings suggest that infants' expectations about object behavior are highly specific regarding the entities they are applied to. They do not automatically apply to any and all portions of matter within the visual field. Both the behavior of an entity, and infants' prior experience play roles in determining whether infants will treat that entity as an object.

Anomalous results using countercurrent immunoelectrophoresis for the detection of pneumococcal antigen in Bactec blood culture media.

On examination of Bactec blood cultures for pneumococcal antigen by countercurrent immunoelectrophoresis the consistent presence of a non-specific protein band caused problems with the interpretation of results, even in laboratories experienced in performing countercurrent immunoelectrophoresis. When the Bactec blood culture system is used, countercurrent immunoelectrophoresis should not be relied on for the detection of pneumococcal antigen.

Serum soluble transferrin receptor reflects erythropoiesis but not iron availability in erythropoietin-treated chronic hemodialysis patients.

BACKGROUND: The diagnosis of iron deficiency using the current commonly used tests is usually difficult in hemodialysis patients. Soluble transferrin receptor (sTfR) has caught the attention of physicians recently as regards its use as a parameter for the evaluation of iron status. This study was conducted in order to evaluate the correlation of serum soluble transferrin receptor (sTfR) concentration with hematological parameters and iron profiles, in the role of identifying iron deficiency among dialysis patients. METHODS: Seventy-three patients having received chronic hemodialysis and stable maintenance recombinant human erythropoietin (rHuEPO) therapy were included. Iron, total iron-binding capacity, ferritin and sTfR were measured in the first week. Following this, these patients began to receive intravenous iron dextran (2 mg/kg/week) for 4 weeks. The hematocrit (Hct), hemoglobin (Hb) levels and reticulocyte counts were evaluated weekly. At the beginning of fifth week, the sTfR level was measured again. Patients were classified as belonging to one of the following groups: serum ferritin < 100 microg/L - absolute iron-deficient group; initial ferritin level > or = 100 microg/L with an increase in hemoglobin of greater than 1 g/dL at the end of the study occult iron deficiency group; others - non iron-deficient group. RESULTS: Seventy-one patients completed the study. The concentration of sTfR was positively correlated with Hct, Hb and reticulocyte index at the beginning (r = 0.236, p = 0.047; r = 0.257, p = 0.04; r = 0.401, p < 0.01, respectively) and at the end of the study (r = 0.384, p < 0.01; r = 0.338, p < 0.01; r = 0.427, p < 0.001, respectively). After 4 weeks of iron and rHuEPO therapy, the sTfR concentration increased, rather than declined, from 21.85 +/- 8.06 nM to 23.76 +/- 7.42 nM (p = 0.04) and the change was positively correlated with the changes in Hct, Hb and reticulocyte index. The administered rHuEPO doses did not differbetween the iron deficiency group (absolute deficiency, n = 3; occult deficiency, n = 10) and non-iron deficiency group (n = 58). The sTfR levels failed to identify the occult iron deficiency group because there was no difference between occult iron-deficient and non-iron-deficient patients (24.73 +/- 9.09 nM versus 21.60 +/- 7.89 nM, p = 0.34). Instead, transferrin saturation (TS) could be a differential marker between the 2 groups (19.0 +/- 10.9% versus 30.1 +/- 12.7%, p = 0.012). CONCLUSION: The serum sTfR concentration is indeed an appropriate marker for erythropoiesis. The erythropoitic effect of administered rHuEPO could mask the effect of iron status on the sTfR concentration. This might make the sTfR concentration no longer an appropriate index to identify the presence of occult iron deficiency. Thus, TS and ferritin currently remain better methods for the evaluation of iron status in rHuEPO-treated chronic hemodialysis patients.

High resistive index of the radial artery is related to early primary radiocephalic hemodialysis fistula failure.

Forty-nine patients who had received radiocephalic hemodialysis fistula construction were evaluated with duplex Doppler ultrasonography to characterize the Doppler indices of the feed radial arteries just proximal to the site of anastomosis. Forty-four patients had fistulas with good function, and 5 patients had fistulas with inadequate blood flow or thrombosis within 4 weeks after the operation. A preliminary study showed extensive variability in peak systolic velocity and end-diastolic velocity in the feed arteries. The resistive index dropped significantly 1 week after the operation and remained relatively constant over the following 5 weeks. In the success group, the mean resistive index measured 1 week after operation was 0.40+/-0.06. It was higher than that of the failure group (mean resistive index: 0.52+/-0.06). Among patients with well-functioning fistulas, diabetic patients had higher resistive indices than did non-diabetic patients (0.44+/-0.04 vs. 0.37+/-0.06). Our results suggest that a higher resistive index of the feed artery is closely related to early autogenous primary hemodialysis fistula failure.

Academy of medicine, Singapore-Ministry of Health clinical practice guidelines: management of food allergy.

The Academy of Medicine, Singapore (AMS) and the Ministry of Health (MOH) publish clinical practice guidelines to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the AMS-MOH clinical practice guidelines on the Management of Food Allergy, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Academy of Medicine website: http://www.ams.edu.sg/guidelines.asp#foodallergy. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Paradoxical vocal cord dysfunction: when a wheeze is not asthma.

Vocal cord dysfunction (VCD) is an uncommon condition which often mimics asthma in presentation and severity. We present nine- and 11-year-old female siblings with vocal cord dysfunction, which is a dysfunction of the larynx involving unintentional paradoxical adduction of the vocal cords during inspiration. We evaluated the use of exercise testing in conjunction with pulmonary function testing in suspected vocal cord dysfunction. Although normal pulmonology function tests were elicited with the patient at rest, exercise testing revealed blunting of the expiratory loop with attenuation of the inspiratory loop unique to VCD. The child underwent video laryngoscopy in the specialised voice clinic, which confirmed vocal cord dysfunction. Exercise testing is a rapid and noninvasive means of diagnosing vocal cord dysfunction in a small subset of patients, but video laryngoscopy, with training manoeuvres to elicit paradoxical vocal cord movements in VCD, remains the gold standard of diagnosis of VCD.

The changing face of food hypersensitivity in an Asian community.

BACKGROUND: Food allergy seems to be increasing in Asia as well as world-wide. Our aim was to characterize food protein sensitization patterns in a population of Asian children with possible food allergy. METHODS: Children presenting to our allergy clinic over 3 years with symptomatic allergic disease and at least one specific food allergen sensitization documented on skin prick testing were included in the analysis. RESULTS: Two hundred and twenty-seven patients fulfilled inclusion criteria. Ninety (40%) of the positive skin tests were positive to egg, 87 (39%) to shellfish, 62 (27.3%) to peanut, 30 (13.2%) to fish, 27 (11.8%) to cow's milk, 21 (9.3%) to sesame, 13 (3.7%) to wheat and eight (3.2%) to soy. Peanut sensitization was the third most common sensitizing allergen, and seen mostly in young atopic children with multiple food hypersensitivities and a family history of atopic dermatitis. The median reported age of first exposure to fish and shellfish was 6 and 12 months, respectively. The mean age at presentation of children with shellfish hypersensitivity was at 6.7 years of age. The likelihood of shellfish sensitization was increased in children with concomitant sensitization to cockroaches. CONCLUSIONS: In contrast to previously reported low peanut allergy rates in Asia, in our review, peanut sensitization is present in 27% (62/227) of food-allergic children, mostly in patients with multiple food protein sensitizations. Temporal patterns of first exposure of infants to fish and shellfish are unique to the Asian diet. Shellfish are a major sensitizing food source in Asian children, especially in allergic rhinitis patients sensitized to cockroaches.

Increase of MMP-13 expression in multi-stage oral carcinogenesis and epigallocatechin-3-gallate suppress MMP-13 expression.

BACKGROUND: Matrix metalloproteinases (MMPs) play pivotal roles in tumor progression. MMP-13 (collagenase-3) digests collagen and other extracellular components. MATERIALS AND METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry and zymograph were used to study the roles of MMP-13 during the neoplastic process of oral squamous cell carcinoma (OSCC). RESULTS: Increase of MMP-13 mRNA and protein expression in OSCC cell lines relative to cultivated normal oral keratinocytes was found. MMP-13 mRNA expression in OSCC was significantly higher than in non-cancerous match tissue (NCMT) in 36 tissue pairs. Esophageal squamous cell carcinoma also exhibited high MMP-13 mRNA expression. The percentage of OSCC exhibiting strong MMP-13 immunoreactivity was significantly higher than pre-invasive lesion and NCMT. Treatment with >5 microm epigallocatechin-3-gallate (EGCG) to OEC-M1 cells suppressed the expression and activity of MMP-13. CONCLUSION: MMP-13 could be a potential tumor marker for OSCC. The effects of EGCG in tumor inhibition may act partially through the modulation of MMP-13.

Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases.

Proteinuria (albuminuria) reflects dysfunction of the glomerular permeability barrier in which inflammatory cytokines play a key role. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that possesses potent anti-inflammatory and immunomudulatory effects. This study evaluated the effectiveness of PTX to reduce proteinuria and inflammatory mediators in patients with proteinuric primary glomerular diseases. Seventeen patients with primary glomerular diseases, a persistent spot proteinuria exceeding 1.5 g/g creatinine (Cr) and a glomerular filtration rate between 24 and 115 ml/min/1.73 m(2) were treated with PTX 400 mg twice daily for 6 months. Before and after the treatment, serum Cr, plasma renin activity and aldosterone concentrations, plasma and urinary tumor necrosis factor (TNF)-alpha, interleukin-1beta and monocyte chemoattractant protein (MCP)-1, as well as urinary protein and Cr were measured. PTX significantly reduced urinary protein excretion, along with an increase of serum albumin. A significant correlation existed between the basal urinary protein/Cr and the basal urinary MCP-1/Cr ratios. PTX lowered the urinary MCP-1/Cr ratio, and the percent reduction of urinary protein/Cr ratio correlated directly with the precent decrease of urinary MCP-1/Cr ratio after PTX treatment. There was no significant change in blood pressure, renal function, biochemical parameters, plasma renin activity and aldosterone concentrations, or plasma TNF-alpha and MCP-1 levels during the study. In conclusion, administration of PTX 800 mg per day is safe and effective for reducing proteinuria in patients with proteinuric primary glomerular diseases. This beneficial effect occurs in close association with a reduction of urinary MCP-1 excretion.

Sensitization to dust mites in children with allergic rhinitis in Singapore: does it matter if you scratch while you sneeze?

BACKGROUND: Previously published data established Blomia tropicalis, as the major source of allergic sensitization in asthmatic children in tropical Singapore. Objective To define the prevalence, clinical characteristics and risk factors of species-specific mite sensitization in paediatric allergic rhinitis (AR) patients in this unique environment. METHODS: We performed a prospective evaluation of newly diagnosed AR patients, from 1 May 2003 to 30 April 2004, from the otolaryngology and allergy outpatient clinics of the Kendang Kerbau Children's Hospital in Singapore. Patients included in the study showed evidence of sensitization to at least one respiratory allergen source and completed a detailed questionnaire. Relative risk of sensitization and associated risk factors were calculated using logistic regression analysis with the forward stepwise model. Multivariate regression analysis was performed to adjust for confounding interactions. Continuous values were compared using anova, SPSS 9.0 for Windows (SPSS Inc., 1999). RESULTS: One hundred and seventy-five patients were included, 119 (68%) males, 142 (81%) Chinese, age mean 7.9 years (range 2-16). Sixty-eight patients (39%) reported a concomitant diagnosis and/or clinical complaints of bronchial asthma and 84 (48%) of atopic dermatitis. Skin prick test results were positive for traditional house dust mites (Dermatophagoides pteronyssinus. and D. farinae mix) in 85% of patients and for B. tropicalis in 62%. Overall mite sensitization was 98%, household pets 10%, moulds 9% and food proteins 12%. By far the single most significant factor associated with Dermatophagoides sensitization in this group was the presence of allergic eczema (odds ratio (OR) 31.8%, 95% confidence interval (CI) 3.6-285, P=0.002). Allergic eczema was negatively associated with B. tropicalis sensitization (OR 0.26%, 95% CI 0.14-0.5). CONCLUSIONS: Children with AR and concomitant atopic dermatitis show a preferential sensitization to the Dermatophagoides mites. In our population, B. tropicalis sensitization is more prominent in children with pure respiratory allergy.