Showing papers by "Catholic University of the Sacred Heart published in 2006"

The Mechanism of Diabetes Control After Gastrointestinal Bypass Surgery Reveals a Role of the Proximal Small Intestine in the Pathophysiology of Type 2 Diabetes

Abstract: Summary Background Data:Most patients who undergo Roux-en-Y gastric bypass (RYGB) experience rapid resolution of type 2 diabetes. Prior studies indicate that this results from more than gastric restriction and weight loss, implicating the rearranged intestine as a primary mediator. It is unclear, ho

The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study.

Abstract: BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the incidence and outcome of invasive fungal infections (IFI) in patients with hematologic malignancies. DESIGN AND METHODS: This was a retrospective cohort study of patients admitted between 1999 and 2003 to 18 hematology wards in Italy. Each participating center provided information on all patients with newly diagnosed hematologic malignancies admitted during the survery period and on all episodes of IFI experienced by these patients. RESULTS: The cohort was formed of 11,802 patients with hematologic malignacies: acute leukemia (myeloid 3012, lymphoid 1173), chronic leukemia (myeloid 596, lymphoid 1104), lymphoma (Hodgkin's 844, non-Hodgkin's 3457), or multiple myeloma (1616). There were 538 proven or probable IFI (4.6%); 373 (69%) occurred in patients with acute myeloid leukemia. Over half (346/538) were caused by molds (2.9%), in most cases Aspergillus spp. (310/346). The 192 yeast infections (1.6%) included 175 cases of candidemia. Overall and IFI-attributable mortality rates were 2% (209/11802) and 39% (209/538), respectively. The highest IFI-attributable mortality rates were associated with zygomycosis (64%) followed by fusariosis (53%), aspergillosis (42%), and candidemia (33%). INTERPRETATION AND CONCLUSIONS: Patients with hematologic malignancies are currently at higher risk of IFI caused by molds than by yeasts, and the incidence of IFI is highest among patients with acute myeloid leukemia. Aspergillus spp are still the most common pathogens, followed by Candida spp. Other agents are rare. The attributable mortality rate for aspergillosis has dropped from 60-70% to approximately 40%. Candidemia-related mortality remains within the 30-40% range reported in literature although the incidence has decreased.

Network Structure and Innovation: The Leveraging of a Dual Network as a Distinctive Relational Capability

Abstract: This paper employs comparative longitudinal case study research to investigate why and how strong dyadic interfirm ties and two alternative network architectures (a ‘strong ties network’ and a ‘dual network’) impact the innovative capability of the lead firm in an alliance network. I answer these intrinsically cross-level research questions by examining how three design-intensive furnishings manufacturers managed their networks of joint-design alliances with consulting industrial design firms over more than 30 years. Initially, in order to explore the sample lead firms’ alliance behavior, I advance an operationalization of interorganizational tie strength. Next, I unveil the strengths of strong ties and the weaknesses of a strong ties network. Finally, I show that the ability to integrate a large periphery of heterogeneous weak ties and a core of strong ties is a distinctive lead firm’s relational capability, one that provides fertile ground for leading firms in knowledge-intensive alliance networks to gain competitive advantages whose sustainability is primarily based on the dynamic innovative capability resulting from leveraging a dual network architecture.

A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease.

Abstract: Aims The role of aspirin in patients with coronary artery disease (CAD) is well established, yet patients happen to discontinue aspirin according to physician’s advice or unsupervised. We thus undertook a systematic review to appraise the hazards inherent to aspirin withdrawal or non-compliance in subjects at risk for or with CAD. Methods and results Electronic databases were systematically searched (updated January 2006). Study designs, patient characteristics, and outcomes were abstracted. Pooled estimates for odds ratios (OR) were computed according to random-effect methods. From the 612 screened studies, six were selected (50 279 patients). One study (31 750 patients) focused on adherence to aspirin therapy in the secondary prevention of CAD, two studies (2594) on aspirin discontinuation in acute CAD, two studies (13 706) on adherence to aspirin therapy before or shortly after coronary artery bypass grafting, and another (2229) on aspirin discontinuation among patients undergoing drug-eluting stenting. Overall, aspirin non-adherence/withdrawal was associated with three-fold higher risk of major adverse cardiac events (OR ¼ 3.14 [1.75–5.61], P ¼ 0.0001). This risk was magnified in patients with intracoronary stents, as discontinuation of antiplatelet treatment was associated with an even higher risk of adverse events (OR ¼ 89.78 [29.90–269.60]). Conclusion Non-compliance or withdrawal of aspirin treatment has ominous prognostic implication in subjects with or at moderate-to-high risk for CAD. Aspirin discontinuation in such patients should be advocated only when bleeding risk clearly overwhelms that of atherothrombotic events.

Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome

Abstract: Cardio-facio-cutaneous (CFC) syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. It phenotypically overlaps with Noonan and Costello syndrome, which are caused by mutations in PTPN11 and HRAS, respectively. In 43 individuals with CFC, we identified two heterozygous KRAS mutations in three individuals and eight BRAF mutations in 16 individuals, suggesting that dysregulation of the RAS-RAF-ERK pathway is a common molecular basis for the three related disorders.

The Effect of Family Control on Firm Value and Performance: Evidence from Continental Europe

Abstract: We investigate the relation between ownership structure and firm performance in Continental Europe, using data from 675 publicly traded corporations in 11 countries. Although family-controlled corporations exhibit larger separation between control and cash-flow rights, our results do not support the hypothesis that family control hampers firm performance. Valuation and operating performance are significantly higher in founder-controlled corporations and in corporations controlled by descendants who sit on the board as non-executive directors. When a descendant takes the position of CEO, family-controlled companies are not statistically distinguishable from non-family firms in terms of valuation and performance.

Gain-of-function SOS1 mutations cause a distinctive form of noonan syndrome

Abstract: Noonan syndrome (NS) is a developmental disorder characterized by short stature, facial dysmorphia, congenital heart defects and skeletal anomalies1. Increased RAS-mitogenactivated protein kinase (MAPK) signaling due to PTPN11 and KRAS mutations cause 50 percent of NS2-6. Here, we report that 22 of 129 NS patients without PTPN11 or KRAS mutation (17 percent) have missense mutations in SOS1, which encodes a RAS-specific guanine nucleotide exchange factor (GEF). SOS1 mutations cluster at residues implicated in the maintenance of SOS1 in its autoinhibited form and ectopic expression of two NS-associated mutants induced enhanced RAS activation. The phenotype associated with SOS1 defects is distinctive, although within NS spectrum, with a high prevalence of ectodermal abnormalities but generally normal development and linear growth. Our findings implicate for the first time gain-of-function mutations in a RAS GEF in inherited disease and define a new mechanism by which upregulation of the RAS pathway can profoundly change human development.

Determining global population distribution: methods, applications and data.

Abstract: Evaluating the total numbers of people at risk from infectious disease in the world requires not just tabular population data, but data that are spatially explicit and global in extent at a moderate resolution. This review describes the basic methods for constructing estimates of global population distribution with attention to recent advances in improving both spatial and temporal resolution. To evaluate the optimal resolution for the study of disease, the native resolution of the data inputs as well as that of the resulting outputs are discussed. Assumptions used to produce different population data sets are also described, with their implications for the study of infectious disease. Lastly, the application of these population data sets in studies to assess disease distribution and health impacts is reviewed. The data described in this review are distributed in the accompanying DVD.

Heart failure, chronic diuretic use, and increase in mortality and hospitalization: an observational study using propensity score methods

Abstract: Aims Non-potassium-sparing diuretics are commonly used in heart failure (HF). They activate the neurohormonal system, and are potentially harmful. Yet, the long-term effects of chronic diuretic use in HF are largely unknown. We retrospectively analysed the Digitalis Investigation Group (DIG) data to determine the effects of diuretics on HF outcomes. Methods and results Propensity scores for diuretic use were calculated for each of the 7788 DIG participants using a non-parsimonious multivariable logistic regression model, and were used to match 1391 (81%) no-diuretic patients with 1391 diuretic patients. Effects of diuretics on mortality and hospitalization at 40 months of median follow-up were assessed using matched Cox regression models. All-cause mortality was 21% for no-diuretic patients and 29% for diuretic patients [hazard ratio (HR) 1.31; 95% confidence interval (CI) 1.11–1.55; P ¼ 0.002]. HF hospitalizations occurred in 18% of no-diuretic patients and 23% of diuretic patients (HR 1.37; 95% CI 1.13–1.65; P ¼ 0.001). Conclusion Chronic diuretic use was associated with increased long-term mortality and hospitalizations in a wide spectrum of ambulatory chronic systolic and diastolic HF patients. The findings of the current study challenge the wisdom of routine chronic use of diuretics in HF patients who are asymptomatic or minimally symptomatic without fluid retention, and are on complete neurohormonal blockade. These findings, based on a non-randomized design, need to be further studied in randomized trials.

Therapy With Gastric Acidity Inhibitors Increases the Risk of Acute Gastroenteritis and Community-Acquired Pneumonia in Children

Abstract: OBJECTIVE. Gastric acidity (GA) inhibitors, including histamine-2 receptor antagonists (H2 blockers) and proton pump inhibitors (PPIs), are the mainstay of gastroesophageal reflux disease (GERD) treatment. A prolonged GA inhibitor–induced hypochlorhydria has been suggested as a risk factor for severe gastrointestinal infections. In addition, a number of papers and a meta-analysis have shown an increased risk of pneumonia in H2-blocker–treated intensive care patients. More recently, an increased risk of community-acquired pneumonia associated with GA inhibitor treatment has been reported in a large cohort of adult patients. These findings are particularly relevant to pediatricians today because so many children receive some sort of GA-blocking agent to treat GERD. To test the hypothesis that GA suppression could be associated with an increased risk of acute gastroenteritis and pneumonia in children treated with GA inhibitors, we conducted a multicenter, prospective study. METHODS. The study was performed by expert pediatric gastroenterologists from 4 pediatric gastroenterology centers. Children (aged 4–36 months) consecutively referred for common GERD-related symptoms (for example, regurgitation and vomiting, feeding problems, effortless vomiting, choking), from December 2003 to March 2004, were considered eligible for the study. Exclusion criteria were a history of GA inhibitors therapy in the previous 4 months, Helicobacter pylori infection, diabetes, chronic lung or heart diseases, cystic fibrosis, immunodeficiency, food allergy, congenital motility gastrointestinal disorders, neuromuscular diseases, or malnutrition. Control subjects were recruited from healthy children visiting the centers for routine examinations. The diagnosis of GERD was confirmed in all patients by standard criteria. GA inhibitors (10 mg/kg ranitidine per day in 50 children or 1 mg/kg omeprazole per day in 50 children) were prescribed by the physicians for 2 months. All enrolled children were evaluated during a 4-month follow-up. The end point was the number of patients presenting with acute gastroenteritis or community-acquired pneumonia during a 4-month follow-up study period. RESULTS. We obtained data in 186 subjects: 95 healthy controls and 91 GA-inhibitor users (47 on ranitidine and 44 on omeprazole). The 2 groups were comparable for age, gender, weight, length, and incidence of acute gastroenteritis and pneumonia in the 4 months before enrollment. Rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was significantly increased in patients treated with GA inhibitors compared with healthy controls during the 4-month follow-up period. In the GA inhibitor-treated group, the rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was increased when comparing the 4 months before and after enrollment. No differences were observed between H2 blocker and PPI users in acute gastroenteritis and pneumonia incidence in the previous 4 months and during the follow-up period. On the contrary, in healthy controls, the incidence of acute gastroenteritis and pneumonia remained stable. CONCLUSIONS. This is the first prospective study performed in pediatric patients showing that the use of GA inhibitors was associated with an increased risk of acute gastroenteritis and community-acquired pneumonia in GERD-affected children. It could be interesting to underline that we observed an increased incidence of intestinal and respiratory infection in otherwise healthy children taking GA inhibitors for GERD treatment. On the contrary, the majority of the previous data showed that the patients most at risk for pneumonia were those with significant comorbid illnesses such as diabetes or immunodeficiency, and this points to the importance of GA suppression as a major risk factor for infections. In addition, this effect seems to be sustained even after the end of therapy. The results of our study are attributable to many factors, including direct inhibitory effect of GA inhibitors on leukocyte functions and qualitative and quantitative gastrointestinal microflora modification. Additional studies are necessary to investigate the mechanisms of the increased risk of infections in children treated with GA inhibitors, and prophylactic measures could be considered in preventing them.

Diversity and Functional Consequences of Germline and Somatic PTPN11 Mutations in Human Disease

Abstract: Germline mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome (NS) and the clinically related LEOPARD syndrome (LS), whereas somatic mutations in the same gene contribute to leukemogenesis. On the basis of our previously gathered genetic and biochemical data, we proposed a model that splits NS- and leukemia-associated PTPN11 mutations into two major classes of activating lesions with differential perturbing effects on development and hematopoiesis. To test this model, we investigated further the diversity of germline and somatic PTPN11 mutations, delineated the association of those mutations with disease, characterized biochemically a panel of mutant SHP-2 proteins recurring in NS, LS, and leukemia, and performed molecular dynamics simulations to determine the structural effects of selected mutations. Our results document a strict correlation between the identity of the lesion and disease and demonstrate that NS-causative mutations have less potency for promoting SHP-2 gain of function than do leukemia-associated ones. Furthermore, we show that the recurrent LS-causing Y279C and T468M amino acid substitutions engender loss of SHP-2 catalytic activity, identifying a previously unrecognized behavior for this class of missense PTPN11 mutations.

Mechanisms of Recovery From Type 2 Diabetes After Malabsorptive Bariatric Surgery

Abstract: Currently, there are no data in the literature regarding the pathophysiological mechanisms involved in the rapid resolution of type 2 diabetes after bariatric surgery, which was reported as an additional benefit of the surgical treatment for morbid obesity. With this question in mind, insulin sensitivity, using euglycemic-hyperinsulinemic clamp, and insulin secretion, by the C-peptide deconvolution method after an oral glucose load, together with the circulating levels of intestinal incretins and adipocytokines, have been studied in 10 diabetic morbidly obese subjects before and shortly after biliopancreatic diversion (BPD) to avoid the weight loss interference. Diabetes disappeared 1 week after BPD, while insulin sensitivity (32.96 ± 4.3 to 65.73 ± 3.22 μmol · kg fat-free mass −1 · min −1 at 1 week and to 64.73 ± 3.42 μmol · kg fat-free mass −1 · min −1 at 4 weeks; P 2 ; P 2 ; P P P

Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III

Abstract: Hereditary angioedema (HAE) is characterized clinically by recurrent acute skin swelling, abdominal pain, and potentially life-threatening laryngeal edema. Three forms of HAE have been described. The classic forms, HAE types I and II, occur as a consequence of mutations in the C1-inhibitor gene. In contrast to HAE types I and II, HAE type III has been observed exclusively in women, where it appears to be correlated with conditions of high estrogen levels--for example, pregnancy or the use of oral contraceptives. A recent report proposed two missense mutations (c.1032C-->A and c.1032C-->G) in F12, the gene encoding human coagulation factor XII (FXII, or Hageman factor) as a possible cause of HAE type III. Here, we report the occurrence of the c.1032C-->A (p.Thr328Lys) mutation in an HAE type III-affected family of French origin. Investigation of the F12 gene in a large German family did not reveal a coding mutation. Haplotype analysis with use of microsatellite markers is compatible with locus heterogeneity in HAE type III. To shed more light on the pathogenic relevance of the HAE type III-associated p.Thr328Lys mutation, we compared FXII activity and plasma levels in patients carrying the mutation with that of healthy control individuals. Our data strongly suggest that p.Thr328Lys is a gain-of-function mutation that markedly increases FXII amidolytic activity but that does not alter FXII plasma levels. We conclude that enhanced FXII enzymatic plasma activity in female mutation carriers leads to enhanced kinin production, which results in angioedema. Transcription of F12 is positively regulated by estrogens, which may explain why only women are affected with HAE type III. The results of our study represent an important step toward an understanding of the molecular processes involved in HAE type III and provide diagnostic and possibly new therapeutic opportunities.

Seizure control and treatment in pregnancy: Observations from the EURAP epilepsy pregnancy registry

Abstract: Objective: To analyze seizure control and treatment in pregnant women with epilepsy. Methods: Seizure control and treatment were recorded prospectively in 1,956 pregnancies of 1,882 women with epilepsy participating in EURAP, an international antiepileptic drugs (AEDs) and pregnancy registry. Results: Of all cases, 58.3% were seizure-free throughout pregnancy. Occurrence of any seizures was associated with localization-related epilepsy (OR: 2.5; 1.7 to 3.9) and polytherapy (OR: 9.0; 5.6 to 14.8) and for tonic-clonic seizures, with oxcarbazepine monotherapy (OR: 5.4; 1.6 to 17.1). Using first trimester as reference, seizure control remained unchanged throughout pregnancy in 63.6%, 92.7% of whom were seizure-free during the entire pregnancy. For those with a change in seizure frequency, 17.3% had an increase and 15.9% a decrease. Seizures occurred during delivery in 60 pregnancies (3.5%), more commonly in women with seizures during pregnancy (OR: 4.8; 2.3 to 10.0). There were 36 cases of status epilepticus (12 convulsive), which resulted in stillbirth in one case but no cases of miscarriage or maternal mortality. AED treatment remained unchanged in 62.7% of the pregnancies. The number or dosage of AEDs were more often increased in pregnancies with seizures (OR: 3.6; 2.8 to 4.7) and with monotherapy with lamotrigine (OR: 3.8; 2.1 to 6.9) or oxcarbazepine (OR: 3.7; 1.1 to 12.9). Conclusions: The majority of patients with epilepsy maintain seizure control during pregnancy. The apparently higher risk of seizures among women treated with oxcarbazepine and the more frequent increases in drug load in the oxcarbazepine and lamotrigine cohorts prompts further studies on relationships with pharmacokinetic changes. Risks associated with status epilepticus appear to be lower than previously reported.

A laparoscopy-based score to predict surgical outcome in patients with advanced ovarian carcinoma: a pilot study.

Abstract: Background Our objective was to set up a more objective quantitative laparoscopy-based model in predicting the chances of optimal cytoreductive surgery in advanced ovarian cancer patients.

Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients.

Abstract: Aims In patients recovering from acute coronary syndromes (ACS) the role of oral anticoagulation (and its intensity) in addition to aspirin remains controversial. We conducted a specific meta-analysis of randomized trials comparing aspirin plus warfarin (AþW) with aspirin alone in such patients. Methods and results MEDLINE and Cochrane databases yielded 14 (of 148 potentially relevant) articles enrolling 25 307 patients. Follow-up ranged from 3 months to 5 years. Irrespective of International normalized ratio (INR), AþW did not significantly affect the risk of major adverse events (MAE: all cause death, non-fatal myocardial infarction, and non-fatal thrombo-embolic stroke) when compared with aspirin alone [OR 0.96 (0.90–1.03), P ¼ 0.30], but increased the risk of major bleeds (MB): OR 1.77 (1.47–2.13), P , 0.00001. However, in studies with INR of 2–3, AþW was associated with a significant reduction of MAE [OR 0.73 (0.63–0.84), P , 0.0001, number needed to treat to avoid one MAE ¼ 33], albeit at an increased risk of MB [OR 2.32 (1.63–3.29), P , 0.00001; number needed to harm by causing one MB ¼ 100]. In both analyses, intracranial bleeding was not significantly increased by AþW when compared with aspirin alone. Conclusion For patients recovering from ACS, a combined strategy of AþW at INR values of 2–3 doubles the risk of MB, but is nonetheless superior to aspirin alone in preventing MAE. Whether this combined regimen is also superior to a ‘double’ anti-platelet strategy or to newer evolving treatments warrants further investigation.

The cardiofaciocutaneous syndrome

Abstract: The cardiofaciocutaneous (CFC) syndrome is a condition of sporadic occurrence, with patients showing multiple congenital anomalies and mental retardation. It is characterised by failure to thrive, relative macrocephaly, a distinctive face with prominent forehead, bitemporal constriction, absence of eyebrows, hypertelorism, downward‐slanting palpebral fissures often with epicanthic folds, depressed nasal root and a bulbous tip of the nose. The cutaneous involvement consists of dry, hyperkeratotic, scaly skin, sparse and curly hair, and cavernous haemangiomata. Most patients have a congenital heart defect, most commonly pulmonic stenosis and hypertrophic cardiomyopathy. The developmental delay usually is moderate to severe. The syndrome is caused by gain‐of‐function mutations in four different genes BRAF, KRAS, mitogen‐activated protein/extracellular signal‐regulated kinase MEK1 and MEK2, all belonging to the same RAS–extracellular signal‐regulated kinase (ERK) pathway that regulates cell differentiation, proliferation and apoptosis. The CFC syndrome is a member of a family of syndromes that includes the Noonan and Costello syndromes, presenting with phenotypic similarities. Noonan syndrome is caused by mutations in the protein tyrosine phosphatase SHP‐2 gene (PTPN11), with a few people having a mutation in KRAS. Costello syndrome is caused by mutations in HRAS. The protein products of these genes also belong to the RAS–ERK pathway. Thus, the clinical overlap of these three conditions, which often poses a problem of differential diagnosis, is explained by their pathogenetic relatedness.

Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis

Abstract: No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46–1.21, P=0.16) and death (HR=0.85, 95%CI=0.49–1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=–3.4–14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=−7.0–9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival.

The Public Sector Pay Gap in France, Great Britain and Italy

Abstract: We investigate public-private pay determination using French, British and Italian microdata. While traditional methods focus on parametric methods to estimate the public sector pay gap, in this paper, we use both non-parametric (kernel) and quantile regression methods to analyse the distribution of wages across sectors. We show that the public-private (hourly) wage differential is sensitive to the choice of quantile and that the pattern of premia varies with both gender and skill. In all countries the public sector is found to pay more low skilled workers with respect to the private sector, whilst the reverse is true for high skilled workers. The effects are more pronounced for females.

Efficacy and safety of non-invasive ventilation in the treatment of acute cardiogenic pulmonary edema – a systematic review and meta-analysis

Abstract: Introduction Continuous positive airway pressure ventilation (CPAP) and non-invasive positive pressure ventilation (NPPV) are accepted treatments in acute cardiogenic pulmonary edema (ACPE). However, it remains unclear whether NPPV is better than CPAP in reducing the need for endotracheal intubation (NETI) rates, mortality and other adverse events. Our aim was to review the evidence about the efficacy and safety of these two methods in ACPE management.

Review article: safe amounts of gluten for patients with wheat allergy or coeliac disease

Abstract: For both wheat allergy and coeliac disease the dietary avoidance of wheat and other gluten-containing cereals is the only effective treatment. Estimation of the maximum tolerated amount of gluten for susceptible individuals would support effective management of their disease. Literature was reviewed to evaluate whether an upper limit for gluten content in food, which would be safe for sufferers from both diseases, could be identified. When setting gluten limits for coeliac disease sufferers, the overall potential daily intake should be considered, while for wheat allergy limits should be based on single servings. For coeliac disease sufferers this limit should lie between 10 and 100 mg daily intake. For wheat allergy, lowest eliciting doses for children lie in the lower milligram range, while for adults they are most significantly higher. Gliadins (part of the gluten proteins) not only trigger coeliac disease, but are also major allergens in wheat allergy. Therefore, measurement of gliadins with validated enzyme-linked immunosorbent assay methods provides an appropriate marker for assessing gluten and/or wheat protein contents in food. Available data suggest that a maximum gluten content for 'gluten-free' foods could be set, which protects both wheat allergy sufferers and coeliac patients.