Borderline Levels Research Articles

A Histopathologic Pattern of Centrilobular Hepatocyte Injury Suggests 6-Mercaptopurine-Induced Hepatotoxicity in Patients With Inflammatory Bowel Disease

Hepatotoxicity is an important side effect of thiopurine analog treatment for inflammatory bowel disease. A variety of histopathologic findings have been observed in patients with inflammatory bowel disease with thiopurine-induced hepatotoxicity, including nodular regenerative hyperplasia, vascular injury, and cholestasis. To describe the histologic features shared by 3 cases of thiopurine-induced hepatotoxicity in patients with inflammatory bowel disease. We identified 3 patients with inflammatory bowel disease who developed hepatotoxicity due to 6-mercaptopurine from the educational files of the Department of Pathology at Massachusetts General Hospital (Boston). Histology slides (stained with hematoxylin-eosin, trichrome, periodic-acid Schiff with diastase digestion, and iron stains) and patients' medical records were reviewed retrospectively. All 3 patients were receiving 6-mercaptopurine monotherapy at therapeutic doses, had normal thiopurine metabolite levels, and presented with elevated aminotransferase levels. Biopsies from all 3 cases exhibited a pattern of centrilobular hepatocyte injury characterized by ceroid-laden macrophages, hepatocyte anisonucleosis, and increased lipofuscin pigment, as well as centrilobular steatosis. Aminotransferase levels trended downward and either normalized or remained at borderline elevated levels after 6-mercaptopurine dose was reduced (in 1 patient) or discontinued (in 2 patients). Recognition of a pattern of centrilobular injury enables pathologists to suggest thiopurine-induced liver injury as the cause of elevated aminotransferases in patients with inflammatory bowel disease.

Improvement of Liver Function in Humans Using a Mixture of Schisandra Fruit Extract and Sesamin

This was a randomized, parallel, and placebo-controlled study. Forty subjects were divided into a test group and a placebo group. The study was focused on the potential effects of a mixture of Schisandra fruit extract and sesamin (hereinafter called 'SCH') in the subjects with borderline high levels (40-60 U/L) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Twenty subjects taking SCH (four tablets per day) and 20 subjects taking a placebo (four tablets per day) were studied. The effects of SCH on ALT, AST, total bilirubin, direct bilirubin, free radical levels, total antioxidant status, glutathione peroxidase, glutathione reductase, and the lag time for low-density lipoprotein oxidation were determined. The total test period was 5 months. Intervention of SCH clearly reduced the levels of ALT and AST, but it made no change in the total bilirubin and direct bilirubin. Intake of SCH also greatly increased the antioxidant capacity and decreased the values of thiobarbituric acid reactive substances, total free radicals, and superoxide anion radicals in the plasma. The activities of glutathione peroxidase and reductase in the erythrocytes were significantly increased. In addition, the lag time for low-density lipoprotein oxidation, an inflammatory marker, was evidently increased. Fatty liver was found to have been significantly improved in this study. SCH proved to have the effects of antioxidation and improving liver function.

Familial hypocalcaemia – think about calcium sensor receptor (CASR)

<h3>Aim</h3> Activating mutations of CaSR gene have been shown to cause hypercalciuric hypocalcaemia1. The CaSR plays a key role in maintaining calcium homeostasis by regulating parathyroid hormone (PTH) and renal calcium reabsorption. Activating mutation of CaSR causes increased sensitivity to Ca++ and hence down regulation of PTH secretion. <h3>Method</h3> This is a case series where we report a pedigree with clinical picture consistent with familial autosomal dominant hypoparathyroidism. The proband, an 18-month-old girl was found to have incidental hypocalcaemia. We identified 4 other affected individuals in the family, including the father of the proband and his twin brother. All affected individuals had mild hypocalcaemia, low normal serum parathyroid levels and borderline high phosphate levels. Treatment with vitamin D and oral calcium did not improve their serum calcium levels. The father of proband has shown evidence of hypercalciuria and has recently been treated for urolithiasis. Mutation analysis identified a novel activating mutation of the CaSR gene [c.407C&gt;T (p.Pro136Leu)] in all 3 family members who were tested. <h3>Conclusion</h3> Activating mutation of the CaSR inhibits PTH secretion and renal calcium reabsorption despite hypocalcaemia. Treatment with vitamin D and calcium can increase hypercalciuria leading to nephrocalcinosis and renal impairment1,2. Asymptomatic individuals should not be overtreated in an attempt to normalise serum calcium.

Immunogenicity of recombinant human erythropoietin in Korea: A two-year cross-sectional study

Immunogenicity of erythropoietin (EPO) is related with pure red cell aplasia (PRCA). We sought to determine the prevalence of antibody (Ab)-mediated PRCA in Korea and threshold diagnostic criteria by dual parameters: Ab titer and neutralizing activity. This study was a multi-center, cross-sectional study for two years. In the first year study (1 YS), 209 samples suspected to be EPO resistance were collected. In the second year study (2 YS), all the patients who consented to participate (N = 946) were enrolled. In 1 YS, we found three and six serum samples that were positive and borderline for anti-EPO Abs, respectively. The first three patients had neutralizing activity (NT) and were diagnosed as PRCA. In 2 YS, seven patients were anti-EPO positives and six had borderline levels. Among them, one patient with NT was diagnosed as PRCA and one with NT as aplastic anemia. The prevalence of PRCA was 0.106%. The correlation analysis of the 22 patients who had anti-EPO Ab showed that dual crossed cut-off lines (anti-EPO Ab titer ≥ 40 ng/ml, % NT ≥ 25%) were able to clearly isolate red cell aplasia. We suggest novel diagnostic criteria for diagnosis and prediction of Ab-mediated PRCA with data from both Ab titer assays and NT bioassays.

Home blood pressure monitoring may make office measurements obsolete

he conventional measurement of blood pressure(BP) in the office or clinic has been the cornerstonefor hypertension management for decades. How-ever, because of the white-coat and the masked hyper-tension phenomena, out-of-office BP monitoring withambulatory or home measurements is often required [1].ExtensiveresearchonambulatoryBPmonitoringhasestab-lished its role as the most accurate tool for hypertensiondiagnosis [1–3].Onthecontrary,despitetheincreasinguseof home BP monitoring by hypertensive patients in thedaily management of their high BP condition, research inthisfield,inparticularwhenconsideringoutcometrials,hasbeen delayed as compared to ambulatory BP monitoring[4,5].

P114 What factors might contribute to borderline faecal calprotectin levels?

Background: In adults, Faecal Calprotectin (FC) ELISA has a sensitivity and specificity of >93% for detecting IBD (1). However, small case series have shown that other factors (eg NSAIDs, cirrhosis, obesity etc) may lead to false +ve results. It is also unclear if immuno-suppressants, taken for non-GI indications can give false ve FC results. Aim: to determine the size and effect of possible factors which might contribute to borderline FC values to cause false +ve or ve results. Methods: Study population: any patient with a FC result held in the pathology database from May 2005 09 (n = 5943). Patient data were cross referenced to electronic records, radiology (PACS), endoscopy & pathology data sets (SnoMed CT). Exclusions: previous diagnosis of IBD or CRC, or aged 50mg/g and <150mg/g were included. Multivariate analysis (generalised linear model) was performed sequentially using SPSS with age, gender, BMI, ethnicity, medication, family history of IBD, smoking/alcohol consumption, liver disease. Histological severity of colonic inflammation was only included in the final model. Results: From 5943 patients, 569 (10%) were between 50 150 and met the inclusion criteria. 62% were female, mean age 51 yr, range 16 91 yr). Diarrhoea (50%) was the most common indication for testing. In the preliminary model FC values increased with age (B = 0.15, p < 0.04) and with a positive trend for liver disease (B = 7.7, p = 0.06); however neither variable remained significant in the final model, which was overwhelmingly dominated by the effect of mucosal inflammation (B = 41, p < 0.001). Immunosuppressant use (mainly for Rharthritis/SLE) was associated with lower FC values (p = 0.027). There was no effect from any of the other variables at any stage in either model.

Making a diagnosis of VWD.

A clear understanding of the molecular basis of VWD can guide the choice and interpretation of appropriate diagnostic tests. This review briefly describes the lifecycle and molecular interactions of VWF and how they lead to the current clinical classification. It also includes a brief discussion of the differential diagnosis and general workup of mucocutaneous bleeding, a review of the various VWD subtypes, and pertinent laboratory assays for each, including genetic tests. Finally, common testing pitfalls and diagnostic dilemmas are covered, including the challenge created by the overlap of borderline low VWF levels and mild bleeding.

246: Excess glucose levels limit first trimester trophoblast migration and induce an anti-angiogenic profile

migration and induce an anti-angiogenic profile Christina S. Han, Stephen F. Thung, Nancy Nickless, Charles J. Lockwood, Vikki M. Abrahams Yale University, Ob/Gyn & Reprod Sci., New Haven, CT OBJECTIVE: Diabetes mellitus (DM) confers a 3 to 11.7-fold risk of preeclampsia (PEC), but the underlying mechanisms for this association is poorly understood. Two leading hypotheses are: 1) impaired invasion and transformation of the maternal uterine vasculature by the trophoblast early in gestation, and 2) an altered angiogenic factor profile at the maternal-fetal interface, leading to an inadequate uteroplacental vascular system. The objective of this study was to determine the effects of excess glucose on first trimester trophoblast migration and secretion of angiogenic factors. STUDY DESIGN: The human first trimester trophoblast cell line (HTR-8) was treated with media containing glucose at 5 mM (normoglycemic), 10 mM (borderline hyperglycemic), or 25 and 50 mM (hyperglycemic). After 72 hours, supernatants were collected and assayed by ELISA for soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF). After 48 hours, a cell migration assay was performed using a two-chamber colorimetric assay. Statistical significance was determined by ANOVA. RESULTS: Compared to glucose at the normoglycemic level of 5 mM, borderline and hyperglycemic glucose levels (10, 25, and 50 mM) significantly up-regulated trophoblast secretion of the anti-angiogenic factors, sFlt-1 and sEng (p 0.001; n 3, Fig A & B). Borderline and hyperglycemic glucose levels significantly reduced trophoblast secretion of pro-angiogenic VEGF, but increased pro-angiogenic PlGF secretion, when compared to normoglycemic levels (p 0.001; n 3, Fig C & D). High levels of glucose (10 50 mM) also reduced trophoblast migration (P 0.001; n 3, Fig E) when compared to glucose at 5 mM. CONCLUSION: Exposure of first trimester trophoblasts to excess glucose generates an anti-angiogenic milieu and limits cell migration. Impaired invasion and vasculogenesis during this crucial period of placentation may contribute to the development of PEC in patients with pre-gestational DM. 247 Use of glucose stabilizer technology in the management of acute hyperglycemia in pregnancy Cornelia Graves, Patti Scott, Tracie Thibault, Tracie Wilder St. Thomas Health-Baptist Hospital, Obstetrics and Gynecology, Nashville, TN, Tennessee Maternal Fetal Medicine, Obstetrics and Gynecology, Nashville, TN, Tennessee Maternal Fetal Medicine, Ob/Gyn, Nashville, TN OBJECTIVE: Management of acute hyperglycemia continues to present a significant challenge. Web-based insulin software was initiated at a large, urban private hospital to improve glycemic control in patients with diabetes. There have been few studies in pregnancy that evaluate the effectiveness of web-based insulin software in pregnant patients. The purpose of this study is to evaluate the usefulness of this modality in pregnancy. STUDY DESIGN: Pregnant patients with gestational, Type I or Type II IDDM with hyperglycemia from July 1, 2010 through July 1, 2011 were eligible to be enrolled for use of the stabilizer. Optimal glucose value was defined as less than 110 mg/dl. The coefficient was calculated assuming that a pregnant patients insulin needs would be increased approximately 2-fold. To prevent error, a designated nurse specialist was available for assist with implementation. Data was collected and analyzed using the standard web-based software program. RESULTS: 25 patients with hyperglycemia were entered into this study. Type I-44%, Type II-36%; Gestational-20%. The average gestational age at the time of enrollment was 34.2 weeks. The average glucose at enrollment was 165.7 mg/dl. The average time to the target goal was 1.72 hours. There were no hypoglycemic episodes. CONCLUSION: Web-based insulin software provides a safe and effective way to treat acute hyperglycemia in the pregnant population.

Mitochondrial DNA haplogroup M is associated with late onset of hepatocellular carcinoma

The accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been associated with various types of cancer. The association of SNPs with cancer risk and disease outcome has been exhaustively studied. In this study, we investigated the association of age-at-onset and SNPs in the mitochondrial D-loop using a population-based series of hepatocellular carcinoma (HCC) patients. Haplogroup M (489C) and allele 235G were identified for their association with the late onset of HCC by the log-rank test. In an overall multivariate analysis, haplogroup M (489C) was identified as an independent predictive factor for the age-at-onset of HCC at borderline significant levels [relative risk, 1.736; 95% confidence interval (CI), 0.967-3.115; p=0.065]. Genetic polymorphisms in the D-loop are predictive markers for age-at-onset in HCC patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop may help to identify HCC patient subgroups at high risk of early onset of the disease.

Abstract P238: The Economic Burden of Hypertriglyceridemia

One-third of US adults has elevated triglyceride levels, but the medical care costs associated with this common lipid abnormality have not been described. Using an observational cohort design, we analyzed the comprehensive electronic medical records of all 108,324 individuals aged 18 or older who had triglyceride (TG) measurements in 2008 and were members of Kaiser Permanente Northwest for the entire year. After assigning patients to TG categories of &lt; 150, 150-199, 200-499, and ≥500 mg/dl, we calculated and compared annual direct medical costs. To isolate the independent contribution of TGs, we adjusted costs for age, sex, body mass index, blood pressure, smoking history, other lipid fractions, and health conditions such as cardiovascular disease, diabetes, and renal disease. Of the 108,324 study subjects, 64.1% had normal TG levels (&lt;150mg/dl), 16.4% had borderline high levels (150-199mg/dl), 18.0% had high TG levels (200-499mg/dl) and 1.5% had very high TG levels of ≥ 500mg/dl. Unadjusted costs followed a stepped association with TG levels. After adjustment, patients with TG levels ≥ 500mg/dl had significantly higher mean total costs ($8,567; 99% CI $7,034-10,100) than those with levels of &lt; 150mg/dl ($6,186; $6,058-6,314), 150-199mg/dl ($6,449; $6,196-6,702), or 200-499mg/dl ($6,376; $6,118-6,634). The differences were driven by both outpatient and pharmaceutical costs. Inpatient costs were also higher among those with TG levels ≥ 500mg/dl but did not reach statistical significance. Severe hypertriglyceridemia is associated with higher medical costs on the order $2,100 to $2,400 per annum (33-38%) independent of resource-intensive comorbid conditions.

Allergies and Adult Gliomas: Cohort Results Strengthen Evidence for a Causal Association

The evidence for an association between a history of allergies and a reduced risk of glioma has been emerging (1). In this issue of the Journal, Calboli et al. (2) analyze associations between prediagnostic plasma immunoglobulin E (IgE) levels and the risk of adult glioma by combining data from four large prospective cohort studies. The pooled data resulted in a modest number of 169 glioma cases, but for a rare disease, this is a substantial contribution to the literature. A statistically significant protective association with borderline elevated levels of total IgE (25–100 kU/L) relative to clinically normal levels ( 100 kU/L) was not observed. The findings are somewhat perplexing, but further our understanding of the biological underpinnings of the protection that allergies appear to provide in the development of brain tumors. The results of Calboli et al. (2) are consistent with one other cohort study that reported a statistically significant inverse associ ation between risk of glioma and borderline elevated levels of IgE, but inconsistent associations with elevated IgE levels (3). This study (2) estimated an odds ratio (OR) near unity at elevated total IgE levels, whereas Schlehofer et al. (3) reported a protective association with elevated levels of respiratory allergen–specific IgE. They observed that the higher the level of respiratory allergen– specific IgE, the stronger was the association, and an increased association was statistically significant in patients with high grade glioma (3). Together, these studies point to an association between prediagnosis IgE level and risk of glioma, but the biological mechanism underlying this association is still unclear. The suggestion that allergies may be associated with a reduced risk of developing of brain tumors was made in the early 1990s (4). Since then, 10 case–control and two cohort studies have investigated this association using self-reported data on the history of allergic conditions. Results showed an inverse association of glioma risk with any allergic conditions compared with nonallergic conditions (pooled estimated OR = 0.60, 95% confidence interval [CI] = 0.52 to 0.69) (1). The association was statistically significant when limited to asthma, eczema, and hay fever as a group, and the association remained when consideration of proxy reporting was introduced in the analysis (1). These estimates based on self-report of allergies are similar to that observed by Calboli et al. (2) (total IgE 25–100 vs <25 kU/L, OR = 0.63, 95% CI = 0.42 to 0.93).

Prevalence of Vitamin D Insufficiency and Risk Factors for Type 2 Diabetes and Cardiovascular Disease among African Migrant and Refugee Adults in Melbourne

Migration to industrialised countries poses a "double whammy" for type 2 diabetes among sub-Saharan African migrant and refugee adults. This population group has been found to be at an increased risk of obesity and type 2 diabetes, which may be further aggravated by inadequate vitamin D status. Thus, this study aimed to describe the demographics of vitamin D insufficiency, obesity, and risk factors for type 2 diabetes among sub-Saharan African migrants and refugees aged 20 years or older living in Melbourne, Australia (n=49). Data were obtained by a questionnaire, medical assessment, and fasting blood samples. The mean serum 25-hydroxyvitamin D level was 27.3 nmol/L (95% CI: 22.2, 32.4 nmol/L); with 25-hydroxyvitamin D levels <50 nmol/L occurring in 88% of participants. Participants displayed a cluster of risk factors for type 2 diabetes and cardiovascular disease: 62% were overweight or obese, 47% had insulin resistance (HOMA-IR >=2), 25% had low density lipoprotein cholesterol levels >=3.5 mmol/L, 24.5% had high density lipoprotein cholesterol levels <=1.03 mmol/L, 34.6% had borderline or high levels of total cholesterol (>=5.2 mmol/L), 18.2% had borderline or high levels of triglyceride (>=1.7 mmol/L), and 16% had hypertension (systolic blood pressure >=140 mmHg or diastolic blood pressure >=90 mmHg). These findings suggest that sub-Saharan African migrants and refugees may be at risk of type 2 diabetes and atherosclerosis-related diseases such as ischemic heart disease, stroke, and peripheral vascular disease. Well-designed vitamin D interventions that incorporate lifestyle changes are urgently needed in this sub-population.

Predictors of Bleeding Disorders in Children with Epistaxis: Value of Preoperative Tests and Clinical Screening

Objective: Children with recurrent epistaxis despite medical therapy may be at higher risk of having a bleeding disorder. The objective of this study was to identify the prevalence of previously undiagnosed bleeding disorders in children with severe epistaxis who failed medical therapy requiring intraoperative nasal cautery. Method: Retrospective chart review from October 15, 2006 to December 31, 2010. Inclusion criteria: children (&lt;19 years) with epistaxis referred to otolaryngology, no known bleeding disorder, and failed medical therapy requiring nasal cautery. Data collected: duration and severity of epistaxis, bleeding history, family history of bleeding. Screening CBC, PT and PTT were performed on all of patients. Results: Of 248 subjects referred for epistaxis, 47 met study inclusion criteria (mean age 8.6 ± 3.8 years; male:female ratio 29:18). Coagulation studies revealed 12.8% (6/47) prolonged PT, 8.5% (4 /47) prolonged PTT, 10.6% (5/47) prolonged PT and PTT. Three with borderline levels proceeded to surgery. Twelve were referred to hematology secondary to abnormal coagulation studies. Of these, five patients (5/12, 42%) were diagnosed with a bleeding disorder (3-type 1 von Willebrand’s disease (VWD), 1-platelet aggregation disorder, and 1-factor VII deficiency). Overall, 6.4% (3/47) had VWD in this cohort, which is higher than the reported prevalence of 1%. Conclusion: Knowledge of whether a child has a coagulopathy prior to surgery can limit complications. In this highly selected group of patients with persistent epistaxis, 10.6% (5/47) had a bleeding disorder. It is important to consider hemostatic testing in high risk patients.

Global epidemics of childhood obesity is hitting a ‘less industrialized’ corner in Asia: a case study in Macao

Childhood obesity prevalence amongst children is rising virtually in all countries with rapid acceleration in major cities in China. A cross-sectional study was conducted amongst 2,015 primary and secondary students in Macao to investigate the nutritional status and analyzed for the relationship of overweight and other cardio-metabolic risk factors. Subjects were randomly selected in proportion to the gender and age of the population. A total of 26.4% of boys and 13.9% of girls were overweight or obese with the highest prevalence around 40% among boys aged 9-12 and girls aged 10 and 11. Some 18.1% of boys and 20.4% of girls were found to have borderline LDL levels; a further 9.3% and 10.4% were found to have high-risk, respectively. For those students with overweight and obesity, a significant higher proportion of them had cardio-metabolic risk factors. Based on this evidence, there is a concern that obesity and its associated co-morbidity could reach epidemic proportions in the 'less industrialized' cities of China.

Lipid profile and cardiovascular risk factors among first-year Brazilian university students in São Paulo.

The surveillance of cardiovascular risk factors has been recommended worldwide. The current study is aimed to estimate the prevalence of cardiovascular risk factors among first-year students from a public university in the city of Sao Paulo, Brazil. A cross-sectional study of 56 first-year students, of both genders, was performed. Information about demographic characteristics, family history of chronic diseases, smoking, and physical activity was obtained by means of a standardised questionnaire. Anthropometrical parameters (BMI, waist circumference, body fat percentage), metabolic parameters (glycaemia, serum lipid profile), and dietary data (total energy intake, percentage of total energy from macronutrients, cholesterol and dietary fiber) were assessed. The risk of cardiovascular diseases was characterised by family history of cardiovascular diseases (44.6%), smoking (10.7%), physical inactivity (35.7%), borderline high total cholesterol and LDL-c levels (16.1% and 5.4, respectively), decreased HDL-c levels (8.9%), increased triglyceride levels (8.9%), and overweight and obesity (17.8% and 7.1%, respectively). The diet of the students was inadequate: it was high in fat and protein, and low in carbohydrate and dietary fibre. The prevalence of risk factors for cardiovascular diseases in young adults draws attention to the need to adopt preventive plans in the university setting.

Absolute and Attributable Risks of Atrial Fibrillation in Relation to Optimal and Borderline Risk Factors

Background— Atrial fibrillation (AF) is an important risk factor for stroke and overall mortality, but information about the preventable burden of AF is lacking. The aim of this study was to determine what proportion of the burden of AF in blacks and whites could theoretically be avoided by the maintenance of an optimal risk profile. Methods and Results— This study included 14 598 middle-aged Atherosclerosis Risk in Communities (ARIC) Study cohort members. Previously established AF risk factors, namely high blood pressure, elevated body mass index, diabetes mellitus, cigarette smoking, and prior cardiac disease, were categorized into optimal, borderline, and elevated levels. On the basis of their risk factor levels, individuals were classified into 1 of these 3 groups. The population-attributable fraction of AF resulting from having a nonoptimal risk profile was estimated separately for black and white men and women. During a mean follow-up of 17.1 years, 1520 cases of incident AF were identified. The age-adjusted incidence rates were highest in white men and lowest in black women (7.45 and 3.67 per 1000 person-years, respectively). The overall prevalence of an optimal risk profile was 5.4% but varied according to race and gender: 10% in white women versus 1.6% in black men. Overall, 56.5% of AF cases could be explained by having ≥1 borderline or elevated risk factors, of which elevated blood pressure was the most important contributor. Conclusion— As with other forms of cardiovascular disease, more than half of the AF burden is potentially avoidable through the optimization of cardiovascular risk factors levels.

Circulation: Clinical Summaries

Circulation: Clinical Summaries

“Normal” range of alanine aminotransferase levels for Asian population

BecauseALTis continuously distributed in populations and might be influ-enced not only by liver disease, but also various medical condi-tions unrelated to liver disease, and demographic determinants(age, sex, and body mass index), the cut-off serumALT value thatdiscriminates between healthy and diseased livers has not beenclearly defined.

Distress tolerance moderates the relationship between negative affect intensity with borderline personality disorder levels

A number of studies have suggested that negative emotionality and negative affect intensity play key roles in the development and maintenance of borderline personality disorder (BPD). However, more recent research indicates that one's response to affective discomfort may be an even more important variable in the pathogenesis of BPD than either negative emotionality or negative affect intensity per se. As such, the current study aimed to empirically test the moderating role of 2 well-validated laboratory measures of the ability to tolerate psychological distress (distress tolerance) in the relationship of negative emotionality and negative affect intensity with BPD levels. Results provide laboratory-based evidence for a moderating effect of distress tolerance on the relationship of negative emotionality and negative affect intensity with levels of BPD. Specifically, the 2 former variables were related to levels of BPD among those with low distress tolerance. The current results add support to existing developmental frameworks of BPD and suggest the importance of modifying one's response to affective distress along with levels of negative emotionality in treatment settings.

First Salivary Screening of Celiac Disease by Detection of Anti‐transglutaminase Autoantibody Radioimmunoassay in 5000 Italian Primary Schoolchildren

The high prevalence of celiac disease (CD) prompted us to evaluate a new, noninvasive disease screening strategy. The aim was to identify CD in 6- to 8-year-old children for a timely diagnosis, start gluten-free diet (GFD) in compliant subjects, achieve the growth target, and prevent CD complications. Five thousand subjects were invited to participate in the study. Four thousand forty-eight saliva samples were tested for anti-tissue transglutaminase (tTG) immunoglobulin (Ig)A using a fluid-phase radioimmunoprecipitation method. Positive children were tested for serum radioimmunoassay tTG IgA, enzyme-linked immunosorbent assay tTG IgA, and anti-endomysium IgA. Children confirmed as positive by serum assays underwent endoscopy with duodenal biopsies and, at the diagnosis of CD, were suggested to start GFD. Consent was obtained from 4242 parents (84.8%) for the screening to be performed, and adequate saliva samples were collected from 4048 children (95.4%). Thirty-two children were found to be salivary tTG IgA positive and 9 with borderline autoantibody levels. Thirty-one of the 32 and 3 of the 9 subjects were also serum positive. Twenty-eight children showed villous atrophy when undergoing intestinal biopsy, whereas 1 had Marsh 1 lesions; 3 children were suggested to start GFD without performing endoscopy. CD prevalence in the population investigated (including 19 CD known cases) was 1.16%. The ratio between screening-detected patients and those diagnosed before the screening was 3:2. The ratio between symptomatic and asymptomatic patients was 1:1.6. We demonstrated that it is possible to perform a powerful, simple, well-accepted, and sensitive CD screening using saliva. Until now, the compliance with GFD in children with CD has been optimal.