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S Brown

Publications and source records attributed to S Brown.

At least 37 records · Page 2Linked to original sources

A prospective analysis of extended endoscopic mucosal resection for large rectal villous adenomas: an alternative technique to transanal endoscopic microsurgery.

INTRODUCTION: Endoscopic mucosal resection is a safe resection tool for selected flat, sessile and lateral spreading tumours of the colon. Transanal microsurgical resection of select rectal neoplastic lesions is another accepted modality. Recent data suggests transanal microsurgery may have high complication rates. We conducted a prospective clinicopathological evaluation of an extended endoscopic mucosal resection technique for highly selected lesions of the rectum and assessed outcome data over a maximal 24-month period. PATIENTS AND METHODS: Eighty-three patients with known rectal neoplastic lesions underwent chromoscopic colonoscopy and on-table staging using a high-frequency (12.5 MHz) mini-probe EUS by a single endoscopist. Patients with T2 or node positive disease were referred for surgery. Following extended endoscopic mucosal resection patients were followed-up at 3, 6, 12 and 24 months post 'index' resection with chromoscopic endoscopy and EUS. Procedural complications, recurrence rates and outcome data were collected. RESULTS: Sixty-two patients fulfilled inclusion criteria. Median procedure time was 48 mins (range 32-126). Lateral spreading tumours (median diameter 30 mm; range 18-42 mm) and sessile lesions (median diameter 38 mm; range 25-86 mm) accounted for 19% and 81% of lesions, respectively. Ninety-seven percent of patients undergoing EMR were discharged within 6-h of procedure. Thirty-day re-admission and death rate was 0%. Bleeding complications occurred in 5/62 (8%) of patients with all achieving complete haemostasis using endo clips. None required transfusion. There were no procedural related complications or perforations. Overall 'cure' rate at a median follow-up of 16 months was 98%. CONCLUSIONS: Extended endoscopic mucosal resection for rectal neoplastic lesions can achieve superior results to those of per-anal excision and trans-anal microsurgery with regard to complications and recurrence rates. Extended endoscopic mucosal resection may be an alternative therapeutic modality in selected patients.

Adenoma, Villous↗

Characterisation of OXA-51, a novel class D carbapenemase found in genetically unrelated clinical strains of Acinetobacter baumannii from Argentina.

Acinetobacter baumannii is now one of the most frequently encountered nosocomial pathogens in intensive therapy units, and is renowned for being difficult to treat because of resistance to most antibiotics. Carbapenems are the remaining drugs of choice in many centres, but carbapenem resistance is now emerging in strains worldwide. Two subgroups of carbapenem-hydrolysing beta-lactamases, which differ in their amino-acid homology, have been found in some resistant strains. This report describes the emergence and characterisation of a novel carbapenemase (OXA-51) in genetically distinct carbapenem-resistant A. baumannii strains from Argentina. Enzyme kinetics and inhibitor studies were performed spectrophotometrically with purified beta-lactamase. Amplification of the gene was achieved with a two-step PCR method employing arbitrary partially degenerate and gene-specific primers. Transfer of imipenem resistance was attempted with the use of broth and membrane filter methods. Attempts to produce plasmid-cured variants were made in ethidium bromide curing experiments. OXA-51 was identified in two clones of A. baumannii, and was found to have < 63% amino-acid identity with subgroups 1 and 2. Enzyme kinetic studies confirmed that OXA-51 was a molecular class D enzyme with carbapenemase activity, and that it displayed the highest affinity for imipenem (Km value 11 microM). Sequence analysis of the gene identified distinct differences within conserved class D motifs when compared with subgroups 1 and 2. Attempts to transfer imipenem resistance and to determine a plasmid location for the gene failed. OXA-51 is the first of a new subgroup of carbapenemases to emerge in multiresistant clinical isolates of A. baumannii.

Acinetobacter Infections↗

The sequences of seven class D beta-lactamases isolated from carbapenem-resistant Acinetobacter baumannii from four continents.

Carbapenem resistance associated with class D beta-lactamases is an increasing problem in Acinetobacter baumannii. Most enzymes of this class reported so far belong to two subgroups, 1 and 2; however, a novel class D carbapenemase (OXA-51) has been reported recently which shares 56% and < 63% amino-acid identity with subgroups 1 and 2, respectively, and which belongs to a third subgroup. This study describes a further seven novel subgroup 3 beta-lactamases in carbapenem-resistant A. baumannii isolates from four continents.

Acinetobacter baumannii↗

Perceptions of the impact of depression and anxiety and the medication for these conditions on safety in the workplace.

BACKGROUND: The number of people taking prescribed medication for anxiety and depression has increased greatly, but little is known of how this medication impacts on safety at work. AIMS: To examine the relation between anxiety and depression, prescribed medication, performance, and safety in the workplace. METHODS: The research involved nine focus groups with sufferers of anxiety and depression to investigate experiences of mental health problems and the impact of psychotropic drugs. A further three focus groups were conducted with staff in human resources, personnel, occupational health, and health and safety departments, to explore organisational perspectives. The sample comprised 74 individuals drawn from a wide range of occupational sectors. Finally, the results were presented to a panel of experts from occupational medicine, general practice, psychology, health and safety, and psychiatry, to consider the implications for practice. RESULTS: Workers reported that both the symptoms and the medication impaired work performance. Participants described accidents which they attributed to their condition or to the medication. Workers with responsibilities for others, such as teachers, healthcare workers, and managers appeared to present a particular safety risk. Healthcare workers believed that they placed themselves and their patients at risk when carrying out medical procedures. CONCLUSIONS: Respondents in this study felt that their symptoms of anxiety and depression and the medication they took to treat these conditions placed them at risk with respect to safety in the workplace. Drawing on the results, the authors outline areas for improvement in the management of mental health problems at work.

Accidents, Occupational↗

Childhood leukaemia incidence and the population mixing hypothesis in US SEER data.

We evaluated the infectious aetiology hypothesis of childhood leukaemia that rapid population influx into rural areas is associated with increased risk. Using data from the US SEER program, we found that in changes in rural county population sizes from 1980 to 1989 were associated with incidence rates for childhood acute lymphocytic leukaemia (ALL). The observed associations were strongest among children 0-4 years of age, born in the same state as diagnosis, in extremely rural counties, and when counties adjacent to nonrural counties were excluded. Similar analyses for brain and central nervous system (CNS) cancer in children, a disease less linked to this infectious hypothesis, provide evidence against methodologic bias. Similar evaluations for other decades were not meaningful due to limited sample sizes and, perhaps, increased population mobility.

Adolescent↗

Concerted changes in tropical forest structure and dynamics: evidence from 50 South American long-term plots.

Several widespread changes in the ecology of old-growth tropical forests have recently been documented for the late twentieth century, in particular an increase in stem turnover (pan-tropical), and an increase in above-ground biomass (neotropical). Whether these changes are synchronous and whether changes in growth are also occurring is not known. We analysed stand-level changes within 50 long-term monitoring plots from across South America spanning 1971-2002. We show that: (i) basal area (BA: sum of the cross-sectional areas of all trees in a plot) increased significantly over time (by 0.10 +/- 0.04 m2 ha(-1) yr(-1), mean +/- 95% CI); as did both (ii) stand-level BA growth rates (sum of the increments of BA of surviving trees and BA of new trees that recruited into a plot); and (iii) stand-level BA mortality rates (sum of the cross-sectional areas of all trees that died in a plot). Similar patterns were observed on a per-stem basis: (i) stem density (number of stems per hectare; 1 hectare is 10(4) m2) increased significantly over time (0.94 +/- 0.63 stems ha(-1) yr(-1)); as did both (ii) stem recruitment rates; and (iii) stem mortality rates. In relative terms, the pools of BA and stem density increased by 0.38 +/- 0.15% and 0.18 +/- 0.12% yr(-1), respectively. The fluxes into and out of these pools-stand-level BA growth, stand-level BA mortality, stem recruitment and stem mortality rates-increased, in relative terms, by an order of magnitude more. The gain terms (BA growth, stem recruitment) consistently exceeded the loss terms (BA loss, stem mortality) throughout the period, suggesting that whatever process is driving these changes was already acting before the plot network was established. Large long-term increases in stand-level BA growth and simultaneous increases in stand BA and stem density imply a continent-wide increase in resource availability which is increasing net primary productivity and altering forest dynamics. Continent-wide changes in incoming solar radiation, and increases in atmospheric concentrations of CO2 and air temperatures may have increased resource supply over recent decades, thus causing accelerated growth and increased dynamism across the world's largest tract of tropical forest.

Carbon Dioxide↗

Pattern and process in Amazon tree turnover, 1976-2001.

Previous work has shown that tree turnover, tree biomass and large liana densities have increased in mature tropical forest plots in the late twentieth century. These results point to a concerted shift in forest ecological processes that may already be having significant impacts on terrestrial carbon stocks, fluxes and biodiversity. However, the findings have proved controversial, partly because a rather limited number of permanent plots have been monitored for rather short periods. The aim of this paper is to characterize regional-scale patterns of 'tree turnover' (the rate with which trees die and recruit into a population) by using improved datasets now available for Amazonia that span the past 25 years. Specifically, we assess whether concerted changes in turnover are occurring, and if so whether they are general throughout the Amazon or restricted to one region or environmental zone. In addition, we ask whether they are driven by changes in recruitment, mortality or both. We find that: (i) trees 10 cm or more in diameter recruit and die twice as fast on the richer soils of southern and western Amazonia than on the poorer soils of eastern and central Amazonia; (ii) turnover rates have increased throughout Amazonia over the past two decades; (iii) mortality and recruitment rates have both increased significantly in every region and environmental zone, with the exception of mortality in eastern Amazonia; (iv) recruitment rates have consistently exceeded mortality rates; (v) absolute increases in recruitment and mortality rates are greatest in western Amazonian sites; and (vi) mortality appears to be lagging recruitment at regional scales. These spatial patterns and temporal trends are not caused by obvious artefacts in the data or the analyses. The trends cannot be directly driven by a mortality driver (such as increased drought or fragmentation-related death) because the biomass in these forests has simultaneously increased. Our findings therefore indicate that long-acting and widespread environmental changes are stimulating the growth and productivity of Amazon forests.

Biodiversity↗

Effects of chlorinated solvents on four species of North American amphibians.

Tetrachloroethylene (PCE), a dry cleaning and degreasing solvent, can enter groundwater through accidental leaks or spills, and concentrations as high as 75 mg/L have been reported in Canadian aquifers. Amphibians in wetlands receiving contaminated groundwater may be exposed to PCE and its degradation products, but little information is available on the impacts of these compounds on indigenous amphibian species. Acute (96-h static renewal) exposures to PCE and its major degradation products, trichloroethylene (TCE) and cisand trans-dichloroethylene, were conducted on embryos of four North American amphibian species: wood frogs (Rana sylvatica), green frogs (R. clamitans), American toads (Bufo americanus), and spotted salamanders (Ambystoma maculatum). Subsequently, chronic exposures to PCE and TCE were conducted with the larvae of American toads. Both PCE and TCE were teratogenic to amphibian embryos; median effective concentrations (EC50s) for developmental deformities produced by PCE and TCE exposure for wood frogs and green frogs were 12 and 40 mg/L, respectively. Embryonic survivorship, however, was not compromised at these concentrations. American toads were less sensitive; the EC50 for developmental abnormalities was not attained at the highest test concentrations, 45 and 85 mg/L PCE and TCE, respectively. These results are pertinent in assessing the impact of groundwater pollution on an aquifer-fed wetland.

Amphibians↗

High-magnification chromoscopic pouchoscopy: a novel in vivo technique for surveillance of the anal transition zone and columnar cuff following ileal pouch-anal anastomosis.

BACKGROUND: Persistence of underlying disease in the residual rectal mucosa and anal transition zone (ATZ) following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis and familial adenomatous polyposis provides a site for potential malignancy. For this reason endoscopic surveillance is performed, although conventional assessment may be unreliable. We hypothesized that the novel technique of high-magnification chromoscopic pouchoscopy (HMCP) may permit accurate anatomical localization of this high risk zone in vivo and permit improved biopsy accuracy. PATIENTS AND METHODS: We studied 132 patients with IPAA using HMCP. Three distinct zones were defined using magnification endoscopy: ATZ, appearing as a linear cellular marix; columnar cuff, identifiable by a type I crypt pattern; and ileal pouch body, appearing as villous projections. Quadrantic biopsies of these zones were taken in addition to biopsies of any other lesions noted. RESULTS: A total of 1586 biopsies were taken from zones 1-3 (median, 12; range, 5-16 per patient). Overall biopsy-targeting accuracies using magnification guidance as compared with histopathology were 82%, 73% and 91% for the ATZ, cuff and pouch body, respectively. No dysplasia was identified in the quadrantic surveillance biopsies. Histologically confirmed columnar metaplasia was visualized in vivo using magnification chromoscopy. Patients with IPAA >3 years' duration were more likely to have pouch reservoir columnar metaplasia as compared to those <3 years (p<0.01). Pouch reservoir metaplasia was associated with a pre-morbid diagnosis of high-grade dysplasia or carcinoma within the premorbid colectomy specimen (p<0.001). CONCLUSIONS: This is the first study to evaluate this novel application of high magnification chromoscopy. Magnification pouchoscopy is a valid predictor of ATZ and cuff anatomy, permitting accurate biopsy targeting. Further randomized studies validating this technique with an emphasis on dysplasia detection in larger cohorts are required.

Adult↗

Prognostic importance of the platelet count 100 days post allogeneic bone marrow transplant.

We assessed the prognostic importance of the platelet count 100 days post transplant of 107 consecutive patients receiving ablative allogeneic bone marrow transplant (BMT) between 7/96 and 12/00 who survived at least 100 days. Diagnoses included AML (n=36), chronic myelogenous leukemia (n=27), NHL (n=14), ALL (n=16), MDS (n=9), aplastic anemia (n=3), and one Hodgkin's disease and myelofibrosis each. In total, 64% were in remission or in chronic phase or had aplastic anemia (good risk), and 36% had active disease at the time of transplant (bad risk). In all, 70% were matched sibling transplants and 30% were matched unrelated donor transplants. The mean follow-up for the patients remaining alive is 48 months. Survival was powerfully influenced by the 100-day platelet count: 4-year survival was 19% for patients with a platelet count <30 x 10(9)/l; 41% for patients with a platelet count of 30-50; and 72% for those with a platelet count >50 (P<0.001; log-rank test). In a multivariable analysis, the most powerful risk factors for mortality after allogeneic BMT were low 100-day platelet count (P<0.001) and bad risk disease (P=0.009). We conclude that the platelet count 100 days post transplant is a powerful predictor of overall survival.

Adolescent↗

Expression of TNFalpha by CD3+ and F4/80+ cells following irradiation preconditioning and allogeneic spleen cell transplantation.

The pathogenesis of acute graft-versus-host disease (aGVHD) includes tumor necrosis factor-alpha (TNFalpha) expression by macrophages and T cells. However, the temporal comparison of donor vs host cells to TNFalpha expression in response to irradiation conditioning and alloreactivity has not been reported. This study compared intracellular TNFalpha expression in donor vs host spleen T cells and macrophages using a murine model of aGVHD. Total body irradiation conditioning alone resulted in increased frequency of F4/80+/TNFalpha+ cells, but no increase in CD3+/TNFalpha+ cells. Syngeneic transplantation resulted in an increased frequency of F4/80+/TNFalpha+ cells, while CD3+/TNFalpha+ cells increased on days 1 and 3 but declined on day 5. Allogeneic transplantation resulted in an increased frequency of donor CD3+/TNFalpha+ cells, while the frequency of host CD3+/TNFalpha+ cells declined. Similarly, donor F4/80+/TNFalpha+ cells also increased in frequency after allotransplantation, while the frequency of host F4/80+/TNFalpha+ cells was increased on day 1 and declined through days 3 and 5. In absolute cell numbers, CD3+/TNFalpha+ cells were greater than F4/80+/TNFalpha+ cells post allotransplantation. We conclude that (1) both donor and host CD3+ and F4/80+cells are present in the post transplant period and contribute to TNFalpha production and (2) in terms of frequency, the majority of TNFalpha producing cells in the spleen after allogeneic BMT are CD3+.

Animals↗

An evaluation of colorectal endoscopic mucosal resection using high-magnification chromoscopic colonoscopy: a prospective study of 1000 colonoscopies.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection provides an alternative to surgery for resection of sessile and flat colorectal lesions. High-magnification chromoscopic colonoscopy may allow early detection and anticipate histological diagnosis by identifying colonic crypt patterns. The aim of the present study was to assess the efficacy and safety of en-bloc endoscopic mucosal resection with high-magnification chromoendoscopy in the management of sessile and flat colorectal lesions </= 20 mm. PATIENTS AND METHODS: A single endoscopist using high-magnification chromoendoscopy prospectively examined 1000 patients attending for routine colonoscopy. Patients were selected for inclusion in the study if they were considered to be at high risk for underlying colorectal neoplasia or polyps. Within the study period, 1000 patients (29 %) qualified for entry from a total of 3480 colonoscopies conducted in our institution. Endoscopic mucosal resection was carried out in appropriate flat and sessile lesions. RESULTS: Endoscopic mucosal resection was carried out in 599 lesions. Complete histological resection was confirmed in 576 (96 %). Perforation occurred in one patient (0.2 %) and bleeding in 12 (2 %). A total of 254 lesions (40 %; excluding hyperplasia/metaplasia) were flat or depressed, and 374 (60 %) were sessile. Fifty-eight flat lesions (23 %) contained high-grade dysplasia or beyond, compared to 33 sessile lesions (9.0 %; P = 0.001). After resection, 21 lesions were upgraded histologically, with 17 being defined as adenoma with high-grade dysplasia or beyond. CONCLUSIONS: This study confirms that flat adenomas and carcinomas occur in the West and demonstrates the malignant potential of such lesions, which can be managed successfully using endoscopic techniques. Endoscopic mucosal resection with high-magnification chromoscopy is a safe and effective form of treatment for sessile or flat colorectal lesions. Complete resection can improve the accuracy of histopathological diagnosis. However, colonoscopists require training in these procedures in order to improve the rate of colorectal cancer detection.

Adenoma↗

Congenital muscular dystrophy with short stature, proximal contractures and distal laxity.

We report 5 cases (2 familial and 3 sporadic) who share a diagnosis of congenital muscular dystrophy (CMD) in association with short stature, proximal contractures, rigidity of the spine and distal joint laxity as well as early respiratory failure and mild to moderate mental retardation. The expression of collagen VI was confirmed to be normal on muscle biopsies of all 5 patients and in the informative family linkage to any of the three COL6 A loci was excluded. These findings extend the phenotypes within the CMD classification.

Adolescent↗

Effect of plasma insulin and branched-chain amino acids on skeletal muscle protein synthesis in fasted lambs.

The increase in fractional rate of protein synthesis (Ks) in the skeletal muscle of growing rats during the transition from fasted to fed state has been explained by the synergistic action of a rise in plasma insulin and branched-chain amino acids (BCAA). Since growing lambs also exhibit an increase in Ks with level of feed intake, the objective of the present study was to determine if this synergistic relationship between insulin and BCAA also occurs in ruminant animals. Six 30 kg fasted (72 h) lambs (8 months of age) received each of four treatments, which were based on continuous infusion into the jugular vein for 6 h of: (1) saline (155 mmol NaCl/l); (2) a mixture of BCAA (0.778 micromol leucine, 0.640 micromol isoleucine and 0.693 micromol valine/min.kg); (3) 18.7 micromol glucose/min.kg (to induce endogenous insulin secretion); (4) co-infusion of BCAA and glucose. Within each period all animals received the same isotope of phenylalanine (Phe) as follows: (1) L-[1-13C]Phe; (2) L-phenyl-[ring 2H5]-alanine; (3) L-[15N]Phe; (4) L-[ring 2,6-3H]Phe. Blood was sampled serially during infusions to measure plasma concentrations of insulin, glucose and amino acids, and plasma free Phe isotopic activity; biopsies were taken 6 h after the beginning of infusions to determine Ks in m. longissimus dorsi and vastus muscle. Compared with control (saline-infused) lambs, Ks was increased by an average of 40% at the end of glucose infusion, but this effect was not statistically significant in either of the muscles sampled. BCAA infusion, alone or in combination with glucose, also had no significant effect on Ks compared with control sheep. Ks was approximately 60% greater for vastus muscle than for m. longissimus dorsi (P<0.01), regardless of treatment. It is concluded that there are signals other than insulin and BCAA that are responsible for the feed-induced increase in Ks in muscle of growing ruminant animals.

Amino Acids, Branched-Chain↗

Development of a standardized susceptibility test for campylobacter with quality-control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem.

A standardized agar dilution susceptibility testing method was developed for Campylobacter that consisted of testing on Mueller-Hinton medium supplemented with 5% defibrinated sheep blood in an atmosphere of 10% CO2, 5% O2, and 85% N2. Campylobacter jejuni ATCC 33560 was identified as a quality-control (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36 degrees C for 48 hr and 42 degrees C for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all antimicrobial agents tested at both temperatures, 95-100% of the QC MIC results fell within recommended QC ranges. Twenty-one Campylobacter clinical isolates, encompassing five species of Campylobacter (C. jejuni, C. coli, C. jejuni, subsp. doylei, C. fetus, and C. lari) were tested in conjunction with the C. jejuni QC strain. While C. jejuni and C. coli could be reliably tested under both test conditions, growth of C. jejuni subsp. doylei, C. fetus, and C. lari isolates was inconsistent when incubated at 42 degrees C. Therefore, it is recommended that these species only be tested at 36 degrees C.

Campylobacter↗

Loss to follow-up of patients with malignant lymphoma.

Loss to follow-up (LTFU) in cancer patients is a serious problem, yet there is little data on this and on the underlying reasons. Of 144 paediatric and 431 adult patients with lymphoma diagnosed in 1997/1998 at King Faisal Specialist Hospital and Research Center, Riyadh (KFSHRC), 30% and 48.5%, respectively, were LTFU after 4 years (excluding patients known to have died). In 2001-2002, 196 paediatric and adult lymphoma patients at KFSHRC were enrolled in a prospective study in which explanations were obtained in detail for non-attendance at follow-up appointments (No Show). Sixteen months after commencement of the study, 49 patients were No Show, because of patient-based communication problems (20), transportation problems (8), patient not contactable (18), and personal reasons (3). In addition, patients were recorded incorrectly as No Show through hospital/patient communication problems. The No Show patients, especially the 23 who failed to keep a second appointment, are identifiable as potential LTFU during the 3 years in which this cohort will be followed. This study and, we suggest, other studies on LTFU should stimulate interest in this issue, in the predisposing factors, and in strategies to address them.

Adult↗

SCP1, a 356,023 bp linear plasmid adapted to the ecology and developmental biology of its host, Streptomyces coelicolor A3(2).

The sequencing of the entire genetic complement of Streptomyces coelicolor A3(2) has been completed with the determination of the 365,023 bp sequence of the linear plasmid SCP1. Remarkably, the functional distribution of SCP1 genes somewhat resembles that of the chromosome: predicted gene products/functions include ECF sigma factors, antibiotic biosynthesis, a gamma-butyrolactone signalling system, members of the actinomycete-specific Wbl class of regulatory proteins and 14 secreted proteins. Some of these genes are among the 18 that contain a TTA codon, making them targets for the developmentally important tRNA encoded by the bldA gene. RNA analysis and gene fusions showed that one of the TTA-containing genes is part of a large bldA-dependent operon, the gene products of which include three proteins isolated from the spore surface by detergent washing (SapC, D and E), and several probable metabolic enzymes. SCP1 shows much evidence of recombinational interactions with other replicons and transposable elements during its history. For example, it has two sets of partitioning genes (which may explain why an integrated copy of SCP1 partially suppressed the defective partitioning of a parAB-deleted chromosome during sporulation). SCP1 carries a cluster of probable transfer determinants and genes encoding likely DNA polymerase III subunits, but it lacks an obvious candidate gene for the terminal protein associated with its ends. This may be related to atypical features of its end sequences.

Amino Acid Sequence↗

ASCIA guidelines for prevention of food anaphylactic reactions in schools, preschools and child-care centres.

These guidelines have been developed by the anaphylaxis working party of the Australasian Society of Clinical Immunology and Allergy to provide advice for minimizing the risk of food-induced anaphylaxis in schools, preschools and child-care centres. The guidelines outline four steps for the prevention of food anaphylactic reactions in children at risk and food policy measures specific to school age and preschool age children.

Age Factors↗