Renal intravascular shockwave lithotripsy in complex mono Ch-EVAR.

BACKGROUND: Our objective is to present the Peripheral Intravascular Lithotripsy (IVL) System in the treatment of calcific renal artery stenosis (RAS) during Chimney Endovascular Aneurysm Repair (Ch-EVAR). The Ch-EVAR technique is a bail out procedure in treating aortic aneurysms with challenging anatomy regarding the proximal sealing zone. RAS typically involves varying degrees of calcification, and final treatment can be fraught with risk of vessel's damages and suboptimal results, particularly when renal angioplasty represents the only feasible course of action in Ch-EVAR. METHOD: We present a case of a patient with a complex juxtarenal abdominal aortic aneurysm and a pre-obstructive chalky stenosis of the right renal artery who underwent mono ChEVAR associated to visceral Intravascular Lithotripsy shockwave angioplasty. CONCLUSION: IVL is an attractive modality for the treatment of challenging, heavily calcified renal arteries that combines the calcium-disrupting capability of lithotripsy with the familiarity of balloon catheters to facilitate proper stent deployment. RESULT: We propose the IVL system as an additional tool in the vascular surgeon's armamentarium not only to obtain large-bore access to enable Transaortic Valve Replacement (TAVR) and EVAR but also to perform angioplasty of severely calcified visceral arteries during Ch-EVAR.

Ptchd1 deficiency induces excitatory synaptic and cognitive dysfunctions in mouse.

Synapse development and neuronal activity represent fundamental processes for the establishment of cognitive function. Structural organization as well as signalling pathways from receptor stimulation to gene expression regulation are mediated by synaptic activity and misregulated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been described in male patients with X-linked ID and/or ASD. The structure of PTCHD1 protein is similar to the Patched (PTCH1) receptor; however, the cellular mechanisms and pathways associated with PTCHD1 in the developing brain are poorly determined. Here we show that PTCHD1 displays a C-terminal PDZ-binding motif that binds to the postsynaptic proteins PSD95 and SAP102. We also report that PTCHD1 is unable to rescue the canonical sonic hedgehog (SHH) pathway in cells depleted of PTCH1, suggesting that both proteins are involved in distinct cellular signalling pathways. We find that Ptchd1 deficiency in male mice (Ptchd1-/y) induces global changes in synaptic gene expression, affects the expression of the immediate-early expression genes Egr1 and Npas4 and finally impairs excitatory synaptic structure and neuronal excitatory activity in the hippocampus, leading to cognitive dysfunction, motor disabilities and hyperactivity. Thus our results support that PTCHD1 deficiency induces a neurodevelopmental disorder causing excitatory synaptic dysfunction.

Integrative modelling for One Health: pattern, process and participation.

This paper argues for an integrative modelling approach for understanding zoonoses disease dynamics, combining process, pattern and participatory models. Each type of modelling provides important insights, but all are limited. Combining these in a '3P' approach offers the opportunity for a productive conversation between modelling efforts, contributing to a 'One Health' agenda. The aim is not to come up with a composite model, but seek synergies between perspectives, encouraging cross-disciplinary interactions. We illustrate our argument with cases from Africa, and in particular from our work on Ebola virus and Lassa fever virus. Combining process-based compartmental models with macroecological data offers a spatial perspective on potential disease impacts. However, without insights from the ground, the 'black box' of transmission dynamics, so crucial to model assumptions, may not be fully understood. We show how participatory modelling and ethnographic research of Ebola and Lassa fever can reveal social roles, unsafe practices, mobility and movement and temporal changes in livelihoods. Together with longer-term dynamics of change in societies and ecologies, all can be important in explaining disease transmission, and provide important complementary insights to other modelling efforts. An integrative modelling approach therefore can offer help to improve disease control efforts and public health responses.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'.

Genetic and environmental factors underlying comorbid bulimic behaviours and alcohol use disorders: a moderating role for the dysregulated personality cluster?

Women with bulimia nervosa (BN) frequently have co-occurring alcohol use disorders (AUDs). Studies of shared genetic transmission of these disorders have been mixed. Personality heterogeneity among individuals with BN may explain discrepant findings. Cluster analysis has characterized women with BN in groups on the basis of personality profiles. One group, the Dysregulated cluster, characterized largely by behavioural disinhibition and emotional dysregulation may be more closely linked etiologically to AUDs. This study examined whether genetic associations between BN and AUDs are the strongest among the Dysregulated cluster. Symptoms of BN and AUDs were assessed in female twins at ages 17 and 25 years from the Minnesota Twin Family Study. Personality clusters were defined using the Multidimensional Personality Questionnaire. Twin moderation models suggested small-to-moderate common genetic transmission between BN and AUDs. However, shared genetic effects did not differ by personality cluster. Findings suggest that personality clusters are unlikely to account for inconsistent findings regarding their shared aetiology.

The accuracy of the National Equine Database in relation to vector-borne disease risk modelling of horses in Great Britain.

REASONS FOR PERFORMING THE STUDY: The National Equine Database (NED) contains information on the size and distribution of the horse population, but the data quality remains unknown. These data could assist with surveillance, research and contingency planning for equine infectious disease outbreaks. OBJECTIVES: 1) To assess the extent of obsolete and missing data from NED, 2) evaluate the extent of spatial separation between horse and owner location and 3) identify relationships between spatial separation and land use. METHODS: Two questionnaires were used to assess data accuracy in NED utilising local authority passport inspections and distribution of questionnaires to 11,000 horse owners. A subset of 1010 questionnaires was used to assess horse-owner geographic separation. RESULTS: During 2005-2010, 17,048 passports were checked through local authority inspections. Of these, 1558 passports (9.1%; 95% confidence interval [CI] 8.7-9.5%) were noncompliant, with 963 (5.6%; 95% CI 5.3-6.0%) containing inaccurate information and 595 (3.5%; 95% CI 3.2-3.8%) classified as missing. Of 1382 questionnaires completed by horse owners, 380 passports were obsolete (27.5%; 95% CI 25.2-29.9%), with 162 (11.7%; 95% CI 10.0-13.4%) being retained for deceased horses and 218 (15.8%; 95% CI 13.9-17.7%) having incorrect ownership details. Fifty-three per cent (95% CI 49.9-56.1%) of owners kept their horse(s) at home and 92% (95% CI 90.3-93.7%) of horses resided within 10 km of their owners. CONCLUSIONS AND POTENTIAL RELEVANCE: Data from a small sample survey suggest the majority of data on NED are accurate but a proportion of inaccuracies exist that may cause delay in locating horses and contacting owners during a disease outbreak. The probability that horses are located in the same postcode sector as the owner's home address is larger in rural areas. Appropriate adjustment for population size, horse-owner spatial separation and land usage would facilitate meaningful use of the national horse population derived from NED for risk modelling of incursions of equine diseases into Great Britain.

Exploring the low-energy landscape of large-scale signed social networks.

Analogously to a spin glass, a large-scale signed social network is characterized by the presence of disorder, expressed in this context (and in the social network literature) by the concept of structural balance. If, as we have recently shown, the signed social networks currently available have a limited amount of true disorder (or frustration), it is also interesting to investigate how this frustration is organized, by exploring the landscape of near-optimal structural balance. What we obtain in this paper is that while one of the networks analyzed shows a unique valley of minima, and a funneled landscape that gradually and smoothly worsens as we move away from the optimum, another network shows instead several distinct valleys of optimal or near-optimal structural balance, separated by energy barriers determined by internally balanced subcommunities of users, a phenomenon similar to the replica-symmetry breaking of spin glasses. Multiple, essentially isoenergetic, arrangements of these communities are possible. Passing from one valley to another requires one to destroy the internal arrangement of these balanced subcommunities and then to reform it again. It is essentially this process of breaking the internal balance of the subcommunities which gives rise to the energy barriers.

Review article: intestinal lymphoid nodular hyperplasia in children--the relationship to food hypersensitivity.

BACKGROUND: Lymphoid aggregates are normally found throughout the small and large intestine. Known as lymphoid nodular hyperplasia (LNH), these aggregates are observed especially in young children and are not associated with clinical symptoms being considered 'physiological'. In children presenting with gastrointestinal symptoms the number and size of the lymphoid follicles are increased. Patients suffering from gastrointestinal symptoms (i.e. recurrent abdominal pain) should systematically undergo gastroduodenoscopy and colonoscopy. With these indications LNH, especially of the upper but also of the lower gastrointestinal tract has been diagnosed, and in some children it may reflect a food hypersensitivity (FH) condition. AIM: To review the literature about the relationship between LNH and FH, particularly focusing on the diagnostic work-up for LNH related to FH. METHODS: We reviewed literature using Pubmed and Medline, with the search terms 'lymphoid nodular hyperplasia', 'food hypersensitivity', 'food allergy' and 'food intolerance'. We overall examined 10 studies in detail, selecting articles about the prevalence of LNH in FH patients and of FH in LNH patients. RESULTS: Collected data showed a median of 49% (range 32-67%) LNH in FH patients and a median of 66% (range 42-90%) FH in LNH patients. Literature review pointed out that the most important symptom connected with LNH and/or FH was recurrent abdominal pain, followed by diarrhoea and growth retardation. Both LNH and FH are associated with an increase in lamina propria γ/δ+ T cells, but the mechanisms by which enhanced local immune responses causing gastrointestinal symptoms still remain obscure. CONCLUSIONS: When assessing FH, we rely on clinical evaluation, including elimination diet and challenge tests, and endoscopic and immunohistochemical findings. Considering the possible co-existence of duodenal and ileo-colonic LNH, upper endoscopy can be recommended in children with suspected FH, especially in those presenting with additional upper abdominal symptoms (i.e. vomiting). Likewise, lower endoscopy might be additionally performed in patients with suspected FH and LNH of the duodenal bulb, also presenting with lower abdominal symptoms (i.e. recurrent abdominal pain).

Primary and reactivated HHV8 infection and disease after liver transplantation: a prospective study.

Human herpesvirus 8 (HHV8) is pathogenic in humans, especially in cases of immunosuppression. We evaluated the risk of HHV8 transmission from liver donors, and its clinical impact in southern Italy, where its seroprevalence in the general population is reported to be as high as 18.3%. We tested 179 liver transplant recipients and their donors for HHV8 antibodies at the time of transplantation, and implemented in all recipients a 12-month posttransplant surveillance program for HHV8 infection. Of the 179 liver transplant recipients enrolled, 10.6% were HHV8 seropositive before transplantation, whereas the organ donor's seroprevalence was 4.4%. Eight seronegative patients received a liver from a seropositive donor, and four of them developed primary HHV8 infection. Two of these patients had lethal nonmalignant illness with systemic involvement and multiorgan failure. Among the 19 HHV8 seropositive recipients, two had viral reactivation after liver transplantation. In addition, an HHV8 seronegative recipient of a seronegative donor developed primary HHV8 infection and multicentric Castleman's disease. In conclusion, primary HHV8 infection transmitted from a seropositive donor to a seronegative liver transplant recipient can cause a severe nonmalignant illness associated with high mortality. Donor screening for HHV8 should be considered in geographic areas with a high prevalence of such infection.

A key role for abdominal ultrasound examination in "difficult" diagnoses of celiac disease.

PURPOSE: To evaluate the usefulness of abdominal ultrasound examination (US) for the diagnostic workup of cases of suspected CD involving negative serum antibodies and difficult diagnosis. MATERIALS AND METHODS: 524 consecutive patients with symptoms of suspected CD underwent an extensive diagnostic workup. 76 (14 %) were excluded since they were positive for serum anti-tTG and/or EmA antibodies. 377 were excluded since they were diagnosed with something other than CD or did not have the alleles encoding for HLA DQ 2 or DQ 8. A diagnosis of CD with negative serum antibodies was probable in 71 patients who underwent abdominal US and duodenal biopsy for histology evaluation. RESULTS: Intestinal histology and subsequent clinical and histological follow-up confirmed the CD diagnosis in 12 patients (GROUP 1) and excluded it in 59 subjects (GROUP 2). Abdominal US showed that the presence of dilated bowel loops and a thickened small bowel wall had a sensitivity of 83 % and a negative predictive value (NPV) of 95 % in CD diagnosis. Furthermore, in 11 of the 12 CD seronegative patients there was at least one of these two abdominal US signs. Therefore, considering the presence of one of these two signs, abdominal US sensitivity increased to 92 % and NPV to 98 %. CONCLUSION: Abdominal US is useful in the diagnostic workup of patients with a high clinical suspicion of CD but with negative serology.

Intradialytic changes of plasma amino acid levels: effect of hemodiafiltration with endogenous reinfusion versus acetate-free biofiltration.

During hemodialysis, amino acids (AA) are lost in the ultrafiltrate with consequent modification of their plasma profile. The aim of this cross-sectional study was to evaluate intradialytic changes of plasma AA levels during a single session of hemodiafiltration with endogenous reinfusion (HFR) versus acetate-free biofiltration (AFB). 48 patients chronically treated with HFR or AFB were matched 1:1 for age, gender, Kt/V and diabetes. Blood samples were collected at the beginning and the end of dialysis. Baseline plasma levels (µmol/l) of total AA (3,176 ± 722), essential AA (889 ± 221), and branched chain AA (459 ± 140) levels in HFR were similar to those in AFB (3,399 ± 621, 938 ± 277, and 463 ± 71, respectively). Plasma intradialytic AA levels did not change in HFR, while in AFB there was a reduction by about 25%. In conclusion, as compared with AFB, HFR has a sparing effect on AA loss due to the lack of adsorption by cartridge and to their complete reinfusion in blood.

Determining the distance to monotonicity of a biological network: a graph-theoretical approach.

The authors use ideas from graph theory in order to determine how distant is a given biological network from being monotone. On the signed graph representing the system, the minimal number of sign inconsistencies (i.e. the distance to monotonicity) is shown to be equal to the minimal number of fundamental cycles having a negative sign. Suitable operations aiming at computing such a number are also proposed and shown to outperform all algorithms that are so far existing for this task. [Includes supplementary material].

First Report of Tomato torrado virus Infecting Tomato in Italy.

In 2009 and 2010, approximately 2% of plants had disease symptoms, including initial leaflet chlorosis that later developed into necrotic spots and general necroses along the leaflet. Fruit production on affected plants was substantially reduced and necroses were also present. Total RNA was extracted from five symptomatic plant samples using the RNeasy Plant Mini Kit (Qiagen, Hilden, Germany) and analyzed by reverse transcription (RT)-PCR with specific primer pair: TR2F (5' GAAGGACGAAGAGCGACTG 3'), and TR2R (5' AAGGTAGGTATGCGTTTGC 3') (1). The primers amplified a 575-bp fragment within the coat protein Vp23 of Tomato torrado virus (ToTV). No RT-PCR products were observed when water or asymptomatic tomato plants were used as controls. The RT-PCR products were purified and directly sequenced in both directions. Pair-wise similarity analysis confirmed the presence of ToTV with 99% similarity to isolate PRI-ToTV0301 (GenBank Accession No. DQ388880) and 98% similarity to isolate Kra (Accession No. EU652402). A representative sequence was deposited with GenBank (Accession No. GU903899). To further confirm the presence of ToTV, dsRNA analysis was conducted on all five symptomatic plants and one healthy tomato plant (2). Electrophoresis of dsRNA showed two bands of approximately 5,400 and 7,800 nucleotides long, typical of ToTV in all samples, while a third band between the other two (approximately 6,400 nt) was detected. Serological testing using double-antibody sandwich-ELISA was also conducted on the five symptomatic and 25 additional plants from the same greenhouse that displayed typical Pepino mosaic virus (PepMV) symptoms only. Antibodies used for serological testing screened for the presence of PepMV, Tomato spotted wilt virus, Cucumber mosaic virus, and Tomato mosaic virus (Loewe Biochemica, Sauerlach, Germany). These tests detected PepMV in all samples with disease symptoms typical of PepMV, and in three of the five samples with the newly described symptoms. To our knowledge, this is the first report of ToTV in Italy, and in some plants, co-infection with PepMV was likely. All ToTV-infected tomato plants in the greenhouse were destroyed. References: (1) H. Pospieszny et al. Plant Dis. 91:1364, 2007. (2) J. Sambrook et al. Molecular Cloning. A Laboratory Manual. 2nd ed. Cold Spring Harbor Laboratory Press, Woodbury, NY, 1989.

Assessment of the pharmacological effects of inotropic drugs on left ventricular pressure and contractility: an evaluation of the QA interval as an indirect indicator of cardiac inotropism.

INTRODUCTION: The ICH S7A and S7B guidelines require that effects of test substances on the cardiovascular system be assessed with respect to blood pressure, heart rate and electrocardiogram intervals. Where adverse effects are identified additional supplemental studies, including ventricular contractility, should be conducted as deemed appropriate. However, there is an absence of definitive guidance regarding when to pursue supplementary studies, in part due to ill-defined criteria of what constitutes an adverse effect and to surgical/technical monitoring limitations of study designs. However with advances in technology it is now feasible to develop models for assessing LVP and contractility in conjunction with standard assessments. The objectives of this study were to 1) develop a model for chronic evaluation of LVP and contractility, 2) illustrate changes in LV contractility without concurrent proportional changes in heart rate and/or systemic blood pressure and 3) determine if the QA interval, the time between the Q on the ECG and the beginning of the upstroke on the arterial blood pressure, can be used as a indicator of altered LV contractility. METHODS: Dogs (N=4) were implanted with a telemetry transmitter. LVP, contractility, ECG and BP were assessed prior to and up to 24 h following administration of Atenolol (10 mg/kg) and Pimobendan (0.45 mg/kg). RESULTS: Atenolol caused an approximately 30% decrease in HR, followed by a sustained decrease in maximum left ventricular contractility (+dP/dt mmHg/s). No effects were noted on blood pressure. Pimobendan caused a 100% increase in contractility (+dP/dt mmHg/s) which remained elevated for approximately 4 h. No effects were noted on blood pressure. Heart rate was highly variable initial decreasing, followed by a highly variable increase until 4 h postdose. Following administration of both compounds changes in maximum left ventricular contractility correlated with reverse changes in QA interval duration. DISCUSSION: This model demonstrates that evaluation of LV contractility complements measurements of heart rate and blood pressure as part of a more complete cardiovascular safety assessment strategy. Furthermore, we demonstrate an apparent correlation between dP/dt and QA interval and concluded that QA interval can be utilized as an indicator of a potential inotropic effect. However further confirmation should be assessed through additional in-vivo measurements of LVP and contractility.

Histomorphology of healthy oral mucosa in untreated celiac patients: unexpected association with spongiosis.

BACKGROUND: The jejunal mucosa is the major site involved in celiac disease, but modifications have also been found in the gastric, rectal and esophageal mucosa. Few studies have focused on the histomorphological features of the oral mucosa in celiac disease patients. Our objectives were: (i) to assess the presence, quality and intensity of lymphocytic infiltrate in clinically healthy oral mucosa and its relation to celiac disease severity (villous height to crypt depth ratio); and (ii) to detect any other histological features connected to celiac disease. METHODS: Twenty-one untreated celiac disease patients (age range 13-68 years) with clinically healthy oral mucosa were enrolled and compared with 14 controls. Intestinal and oral biopsies were carried out and specimens were evaluated after staining with hematoxylin and eosin. RESULTS: Intra-epithelial lymphocyte B and T infiltrates of the oral mucosa were found to be similar in both groups; likewise, intensity of the lymphocytic infiltrate in the lamina propria was similar in both groups and was not related to intestinal damage; important signs of spongiosis were found to be more significantly present in celiac disease patients compared with controls (P = 0.0002). CONCLUSIONS: Our study showed that the healthy oral mucosa of untreated patients does not reflect the intestinal damage by celiac disease, but it is unexpectedly affected by spongiosis, as being detected for the first time in the literature. This latter feature could be related to gliadin ingestion and could contribute to explain the higher susceptibility of celiac disease patients to suffering from oral mucosa lesions.

Coeliac disease: oral ulcer prevalence, assessment of risk and association with gluten-free diet in children.

AIMS: Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet. METHODS: A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet. RESULTS: Aphthous-like ulcers were found significantly more frequently in coeliac disease, in 22.7% (61/269) of patients with coeliac disease versus 7.1% (41/575) of controls (p=<0.0001; chi-square=41.687; odds ratio=4.3123; 95% confidence interval=2.7664:6.722). Most coeliac disease patients with aphthous-like ulcers and adhering strictly to gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free diet, with no or reduced episodes of aphthous-like ulcers (p=0.0003; chi-square=13.101; odds ratio=24.67; 95% confidence interval=2.63:231.441). CONCLUSIONS: The epidemiological association found between coeliac disease and aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be considered a risk indicator for coeliac disease, and that gluten-free diet leads to ulcer amelioration.

Oral pathology in untreated coeliac [corrected] disease.

BACKGROUND: Many coeliac disease patients with atypical symptoms remain undiagnosed. AIM: To examine the frequency of oral lesions in coeliac disease patients and to assess their usefulness in making coeliac disease diagnosis. PATIENTS AND METHODS: One hundred and ninety-seven coeliac disease patients and 413 controls were recruited and the oral examination was performed. RESULTS: Forty-six out of 197 coeliac disease patients (23%) were found to have enamel defects vs. 9% in controls (P < 0.0001). Clinical delayed eruption was observed in 26% of the pediatric coeliac disease patients vs. 7% of the controls (P < 0.0001). The prevalence of oral soft tissues lesions was 42% in the coeliac disease patients and 2% in controls (P < 0.0001). Recurrent aphthous stomatitis disappeared in 89% of the patients after 1 year of gluten-free diet. Multi-logistic analysis selected the following variables as the most meaningful in coeliac disease patients: dental enamel defects (OR = 2.652 CI = 1.427-4.926) and soft tissue lesions (OR = 41.667, CI = 18.868-90.909). Artificial Neural Networks methodology showed that oral soft tissue lesions have sensitivity = 42%, specificity = 98% and test accuracy = 83% in coeliac disease diagnosis. CONCLUSIONS: The overall prevalence of oral soft tissue lesions was higher in coeliac disease patients (42%) than in controls. However, the positive-predictive value of these lesions for coeliac disease diagnosis was low.

IgA anti-actin antibodies ELISA in coeliac disease: a multicentre study.

BACKGROUND: Previous studies have demonstrated that serum anti-actin antibodies are a reliable marker of intestinal damage severity in coeliac disease. AIMS: To validate in a multicentre study the clinical usefulness of serum IgA anti-actin antibody ELISA and its possible use in monitoring intestinal mucosa lesions during gluten-free diet. PATIENTS AND METHODS: Four centres recruited 205 newly diagnosed coeliac disease patients with villous atrophy, 80 healthy controls and 81 "disease" controls. Twelve coeliac disease patients on gluten-free diet but with persistent symptoms underwent serum IgA anti-actin antibody assay and intestinal histology evaluation. IgA anti-actin antibody ELISA was performed with a commercial kit. All coeliac disease patients underwent intestinal histology study. RESULTS: IgA anti-actin antibodies showed a sensitivity of 80% and a specificity of 85% in the diagnosis of coeliac disease patients with villous atrophy. The area under the receiving operator curve for anti-actin antibodies was 0.873 [95% C.I. 0.805-0.899]. Serum anti-actin antibodies values were significantly higher in coeliac disease patients than in healthy or "disease" controls (P<0.0001). Serum anti-actin antibodies were positive in 41 of the 60 coeliac disease patients with mild intestinal histology lesions (69%) and in 123 of the 145 with severe lesions (85.3%) (P<0.05). There was a significant inverse correlation between anti-actin antibody values and the villi/crypts ratio (r=-0.423; P<0.0001). In the 12 coeliac disease patients on gluten-free diet who underwent re-evaluation as they were persistently symptomatic, intestinal histology showed three cases with persistent villous atrophy: all of these were positive for serum anti-actin antibodies ELISA, whereas both serum anti-tTG and EmAs were negative. The other nine patients showed normal intestinal villi and were negative for serum anti-actin antibodies. CONCLUSIONS: Anti-actin antibodies are a reliable marker of severe intestinal mucosa damage in coeliac disease patients and a simple ELISA technique offers an accurate method for their determination. These antibodies seem to be a very reliable marker of persistent intestinal damage in coeliac disease patients.

Oral mucosa of coeliac disease patients produces antiendomysial and antitransglutaminase antibodies: the diagnostic usefulness of an in vitro culture system.

BACKGROUND: Antiendomysial (EmA) and antitransglutaminase (anti-tTG) antibodies are the most specific indirect marker of coeliac disease (CD). It is not known whether the oral mucosa of patients with CD is able to produce these antibodies or not. AIMS: To evaluate the ability of the oral mucosa of patients with CD to produce antibodies in an in vitro culture system. PATIENTS AND METHODS: Twenty-eight patients with new diagnosis of CD (15 adults and 13 children) and 14 adult subjects with other diseases (controls) were studied. All underwent oral mucosa biopsy and subsequent EmA and anti-tTG assays on the mucosa culture medium. RESULTS: Sensitivity and specificity of EmA and anti-tTG assayed in the oral mucosa culture medium for CD diagnosis were 54% and 100% and 57% and 100%, respectively. The CD clinical presentation, such as the presence of oral mucosa lesions, did not influence the results of the EmA and anti-tTG assays in the oral mucosa culture medium. There was an association between positivity of antibodies and greater severity of the oral mucosa lymphocyte infiltration. CONCLUSION: This study demonstrates that the oral mucosa contributes to EmA and anti-tTG production in untreated patients with CD.

Gluten-free diet impact on leptin levels in asymptomatic coeliac adolescents: one year of follow-up.

Coeliac disease, daily more frequently diagnosed in our population, involves many organs also in oligosymptomatic patients and with an adequate nutritional regime. Possible endocrine implications include failure to thrive, pubertal delay and reproduction diseases due to deregulation of GH, FSH and LH secretion. Leptin, an adipose tissue hormone, can be decreased as well and its deficiency could be related to growth and puberty anomalies. We studied 14 asymptomatic coeliac patients in peripubertal age (7.5-13.8 years) and tested their leptin levels in order to correlate them with endocrine and anthropometric data. Before the diet was started leptinaemia (M+/-DS) was: 4.94+/-5.53 ng/ml. In 10/14 patients (71%) leptinaemia was

Review article: Chronic constipation and food hypersensitivity--an intriguing relationship.

BACKGROUND: Chronic constipation is common in the general population. Some studies have shown that in children cow's milk protein hypersensitivity can cause chronic constipation unresponsive to laxative treatment. AIMS: To review the literature and summarize the data that point to a relationship between refractory chronic constipation and food hypersensitivity, and to discuss the hypothesis that the pathogenesis of constipation due to food hypersensitivity. METHODS: A search in the U.S. National Library of Medicine was performed, matching the key words 'chronic constipation, food intolerance and allergy'. RESULTS: Thirty-three papers were found but only 19 of them were related to the topic of this review. Most of the data indicated a relationship between constipation and food allergy in a subgroup of paediatric patients with 'idiopathic' constipation unresponsive to laxative treatment. There was only one study in adults that demonstrated the resolution of chronic constipation on hypoallergenic diet in four patients. CONCLUSIONS: An increasing number of reports suggest a relationship between refractory chronic constipation and food allergy in children. Similar data in adults are scarce and need to be confirmed. Further studies should be performed to obtain firmer evidence for the role of allergy in constipation and clarify the pathogenetic mechanisms involved.