Carcinoid syndrome with right-sided valve involvement - a case report and review of the literature.

BACKGROUND: The survival of patients with neuroendocrine tumors has substantially improved with modern treatment options. Although the associated carcinoid syndrome can be diagnosed early and controlled effectively, cardiologists still encounter patients with cardiac manifestations, particularly among individuals with persistently high levels of vasoactive mediators. Treatment options have been limited to surgical valve replacement in fully manifested disease. Since surgery is not always feasible, transcatheter valve implantation is becoming an interesting alternative. CASE: A case of a 50-year-old woman with carcinoid syndrome and right-sided valvular heart disease is presented. Moderate pulmonary valve stenosis and severe tricuspid valve regurgitation were diagnosed during the evaluation and treatment of neuroendocrine tumor. The possibility of rare valve involvement and the need for interdisciplinary cooperation in the diagnosis, monitoring and treatment of patients with neuroendocrine tumors producing vasoactive substances must be emphasized. CONCLUSION: The patient had a typically presenting carcinoid syndrome with a rare cardiac manifestation. Although monitoring and treatment were carried out in accordance with recommendations and appropriate to the clinical condition, rapid progression of the metastatic disease ultimately precluded invasive cardiac intervention.

Appendiceal tumors and pseudomyxoma peritonei: current recommendations for clinical practice.

Appendiceal tumors and pseudomyxoma peritonei (PMP) are rare tumors. Perforated epithelial tumors of the appendix are the most common source of PMP. This disease is characterized by the presence of mucin of varying degrees of consistency, partially adherent to the surfaces. Appendiceal mucoceles themselves are also very rare and usually their treatment involves only a simple appendectomy. The aim of this study was to provide an up-to-date review of the recommendations for the diagnosis and treatment of these malignancies according to the current guidelines of The Peritoneal Surface Oncology Group International (PSOGI) and the Blue Book of the Czech Society for Oncology of the Czech Medical Association of J. E. Purkyne (COS CLS JEP).

Primary Intracranial Sarcomas, Myxoid Meningeal Sarcoma - a Case Report and Literature Review.

BACKGROUND: Primary intracranial sarcoma is a rare disease. Due to the scarcity of evidence from randomized clinical trials, we follow the treatment guidelines of their extracranial counterparts or those published in case reports, while taking into consideration the specificity of radiotherapy within the brain, and the limit imposed on chemotherapy by the blood brain barrier. Nevertheless, surgery remains the golden standard of treatment for primary tumours, and also for recurrence. Even though there are usually narrow margins achieved in brain compared with the extracranial sarcomas. Despite significant effort, prognosis remains dismal. CASE: We present a 69-year old woman who was investigated for psychoorganic syndrome and paresis of the left hand. Magnetic resonance imaging revealed a tumour expansion in her frontal lobe with collateral oedema. Surgical resection was indicated. Histology of the specimen suggested a myxoid meningeal sarcoma. Early disease recurrence 4 months after primary resection was treated by reresection and 50 Gy of adjuvant radiotherapy to the tumour bed. Similarly, another recurrence 19 months after the second surgery was treated using the same approach. Systemic treatment has not been indicated so far. At this time, the patient is without evidence of any disease recurrence and continues with regular follow-up. CONCLUSION: Myxoid meningeal sarcoma represents a rare disease with a high risk of recurrence. Unfortunately, there is no clear recommendation for treatment algorithm. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Occurrence of serum antibodies against wheat alpha-amylase inhibitor 0.19 in celiac disease.

The alcohol-soluble fraction of wheat gluten (gliadins) induces in genetically susceptible individuals immunologically mediated celiac disease (CLD). However, gliadins and related cereal proteins are not unique foodstuff targets of CLD patients´ immune system. Non-gluten wheat alpha-amylase inhibitor 0.19 (AAI 0.19) has been found to be capable of activating human monocyte-derived dendritic cells and inducing pro-inflammatory status in intestinal mucosa of patients with celiac disease (CLD). The possible contribution of this reactivity in incomplete remission of CLD patients on a gluten-free diet (GFD) is matter of contention. In an attempt to characterize the antigenicity of AAI 0.19 in patients with active CLD, patients on a GFD and healthy controls we developed ELISA employing wheat recombinant AAI 0.19. Using this test we revealed a significant (P<0.001) elevation of IgA anti-AAI 0.19 antibodies (Ab) in patients with active CLD (12 out of 30 patients were seropositive) but also in CLD patients on a GFD (15/46), in contrast to healthy controls (2/59). Anti-AAI 0.19 IgG Ab levels were increased (P<0.001) only in patients with active CLD (14/30) in contrast to the controls. Interestingly, the levels of anti-AAI 0.19 IgG Ab were decreased in CLD patients on a GFD (P<0.001, 1/46) compared to the controls (1/59). Notably, 20 out of 30 patients with active CLD were positive either for IgA or for IgG anti-AAI 0.19 Ab. Thus, the majority of CLD patients developed a robust IgA and IgG Ab response against AAI 0.19. These findings may contribute to the broadening of the knowledge about CLD pathogenesis.

[A Patient with Primary Intraventricular Gliosarcoma and Long-term Survival - a Case Report]. / Pacientka s primárním intraventrikulárním gliosarkomem s dlouhodobým prezíváním - kazuistika.

BACKGROUND: Gliosarcoma is a rare, malignant CNS tumor with a very poor prognosis. Gliosarcoma is a variant of glioblastoma multiforme, which is characterized by the presence of both glial and mesenchymal components. The treatment strategy for gliosarcomas has not yet been determined clearly. CASE PRESENTATION: This case report presents a 23-year-old female patient who complained of increasing headaches, nausea and vomiting, and slight motor weakness in her left arm. An MRI scan of the brain showed a tumor filling the anterior part of the right lateral ventricle and extending into the right frontal lobe. Tumor extirpation was performed. Histology revealed gliosarcoma. Subsequently, the patient received concomitant chemoradiotherapy with temozolomide in the Stupp regimen. Following the fourth cycle of maintenance temozolomide chemotherapy, at eight months after diagnosis, an MRI scan detected progression of the tumor residue. The patient underwent another surgery and then received 10 cycles of second-line chemotherapy in the ICE (ifosfamide, carboplatin, and etoposide) regimen. She completed oncological therapy with minimal toxicity and follow-up MRI scans showed virtually no residual tumor. Another follow-up MRI scan, performed 28 months after diagnosis, demonstrated progression of the tumor residue again. A third tumor resection was performed 29 months after initial diagnosis. Histology again confirmed gliosarcoma. An early postoperative MRI scan showed subtotal resection with a tumor residue in eloquent areas and also suspected implantation metastasis in the spinal canal at the C2 level. From the neurological perspective, the patient was fully self-sufficient, and had only a very mild motor deficit in her left arm. Currently, at 31 months after initial diagnosis, the patient is in a stable condition and fully self-sufficient. CONCLUSION: Our case report shows that long-term survival can be achieved in a gliosarcoma patient exhibiting all the unfavorable features in clinical-pathological terms. The minimal recommended treatment is maximal resection followed by adjuvant radiotherapy. Our patient also underwent chemoradiotherapy with temozolomide in the Stupp regimen. Recurrence at eight months after diagnosis was managed by a repeat operation and high-dose combination chemotherapy, which kept the disease in remission for 20 months after the initial relapse. The lack of unequivocal rules for chemotherapy provides an opportunity to test less common treatment regimens.Key words: gliosarcoma - surgery - chemotherapy - radiotherapy - survivalThis study was supported in part by the grant No. NT13581-4/2012(86-91) of the Internal Grant Agency of the Czech Ministry of Health.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 26. 3. 2016Accepted: 27. 4. 2016.

[Multimodal Therapy of Recurrent Malignant Schwannoma]. / Kombinovaná lécba recidivujícího maligního schwannomu.

BACKGROUND: Malignant peripheral nerve sheath tumor schwannoma (MPNST), also known as malignant schwannoma, is a very rare tumor accounting for only 2% of all sarcomas. The prognosis is relatively poor, with a 5-year survival rate of 46-69%. The treatment of MPNST has not been standardized yet. Mainstay treatment is radical resection. Oncological adjuvant or neoadjuvant treatment has equivocal indications with unclear effects. CASE: The case report presents a 55-year-old patient who showed resistance in the medial-ventral area of the left lower limb. An MRI scan showed a tumor adjacent to the femoral nerve. Tumor extirpation was performed. Histology revealed malignant schwannoma (MPNST) and the resection was assessed as R0. Postoperative whole-body PET/CT revealed no viable tumor tissue. The patient was regularly followed-up. On a follow-up MRI scan, performed 53 months after initial surgery, tumor recurrence was detected in the left thigh. Extirpation of the recurrent tumor was performed. Histology confirmed MPNST and the resection radicality was assessed as R2. Postoperative PET/CT revealed tumor residues. Therefore, 58 months after the initial surgery, another operation of the residual tumor was performed with R0 resection. Three applicators for interstitial brachytherapy were placed in the resection cavity. Following the operation, radiotherapy with an interstitial brachytherapy boost of 18 Gy followed by external fractionated radiotherapy of 50 Gy were administered. The latest MRI scan, performed 66 months after the diagnosis of MPNST, showed no tumor tissue. The patient had no neurological deficit. CONCLUSION: The mainstay of treatment for MPNST is radical en bloc resection. The use of subsequent oncological therapy depends on the radicality of the resection. In our case, because of the good radicality of the initial surgery, adjuvant oncological therapy was postponed. As part of recurrence management, we again attempted to achieve the most radical resection possible and then apply adjuvant radiotherapy. In MPNST, as in all soft tissue sarcomas, high doses are chosen because of potential radioresistance. Given the confined nature of the disease, we chose this locally intensified therapeutic strategy, which resulted in this case in disease remission. Due to the low incidence of MPNST, it is not possible to test the efficacies of individual oncologic therapeutic procedures in larger patient cohorts.Key words: malignant schwannoma - soft tissue sarcoma - multimodal therapyThe authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 3. 2016Accepted: 25. 4. 2016.

Glioblastoma multiforme in patients with history of extracranial cancer: Case series.

OBJECTIVES: Significant progress in treatment strategies improves the expectations of patients with extracranial cancers. Metastases are the primary consideration in patients with cancer history. In the case of neurologic disorders, the patient should undergo brain MRI. A rationale is presented for surgery, whole-brain or stereotactic radiotherapy, or chemotherapy. Recently, we have encountered misdiagnosed primary malignant brain tumours in patients with oncologic history who had been admitted for surgery for brain metastases. The aim of our study is to evaluate the incidence of concurrent cancers, to assess the relationship between previous cancer staging and primary brain tumour evaluation as well as to determine treatment efficiency. METHODS: From January 2007 to December 2011, we prospectively followed up patients with concurrent history of both extracranial cancer and subsequent glioblastoma multiforme. Information was collected on the clinical condition, imaging, history of extracranial cancer, previous and present surgical and oncologic procedures, and GBM histologic, cytogenetic, and molecular genetic investigations. RESULTS: Five patients were recruited: three females and two males. The average patient age at the time of GBM diagnosis was 65.6 years. Three patients had a history of breast carcinoma, one of renal carcinoma and one of colorectal carcinoma. Following the diagnosis of carcinoma, three patients received chemotherapy and radiotherapy, one patient had radiotherapy alone, and one had no adjuvant therapy. In all the cases, surgery revealed primary GBM, with a standard occurrence of genetic abnormalities (Table 1). The average time from the diagnosis of extracranial cancer to that of GBM was 4 years. Four patients underwent chemoradiotherapy and one had palliative radiotherapy. Two patients completed oncotherapy and their OS was 27 months and 19 months, respectively. One patient had post-surgical progression of hemiparesis. One patient had pulmonary embolism during oncotherapy and one had paraplegia caused by a pathological fracture of vertebras T5 due to breast carcinoma metastases. The OS was 11.8 months (range 3-27 months). All the patients succumbed to GBM progression.

Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2.

Impairment of mucosal barrier integrity of small intestine might be causative in immune-mediated gastrointestinal diseases. We tested the markers of epithelial apoptosis - cytokeratin 18 caspase-cleaved fragment (cCK-18), and enterocyte damage - intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14) in sera of patients with untreated celiac disease (CLD), those on gluten-free diet (CLD-GFD), patients with autoimmune diabetes mellitus (T1D), T1D with insulitis (T1D/INS), and diabetes mellitus type 2 (T2D). We found elevated levels of cCK-18 (P<0.001), I-FABP (P<0.01) and sCD14 (P<0.05) in CLD when compared to healthy controls. However, the levels of cCK-18 (P<0.01) and I-FABP (P<0.01) in CLD-GFD were higher when compared with controls. Interestingly, elevated levels of cCK-18 and I-FABP were found in T2D and T1D (P<0.001), and T1D/INS (P<0.01, P<0.001). Twenty-two out of 43 CLD patients were seropositive for cCK-18, 19/43 for I-FABP and 11/43 for sCD14; 9/30 of T2D patients were positive for cCK-18 and 5/20 of T1D/INS for sCD14, while in controls only 3/41 were positive for cCK-18, 3/41 for I-FABP and 1/41 for sCD14. We documented for the first time seropositivity for sCD14 in CLD and potential usefulness of serum cCK-18 and I-FABP as markers of gut damage in CLD, CLD-GFD, and diabetes.

Modulation of phenotypic and functional maturation of dendritic cells by intestinal bacteria and gliadin: relevance for celiac disease.

DC maturation and functions are influenced by microbial and environmental stimuli, which could contribute to immune dysfunction. Here, we have investigated the role of enterobacteria (Escherichia coli CBL2 and Shigella CBD8) isolated from CD patients, bifidobacteria (Bifidobacterium longum CECT 7347 and Bifidobacterium bifidum CECT 7365), and gliadins on phenotypic and functional features of MDDCs and in coculture with Caco-2 cells. The ultimate goal of our study is to understand the roles played by specific components of the gut microbiota in CD. Enterobacteria induced marked alterations in MDDC morphology, inducing podosome dissolution and dendrites, and activated MDDC adhesion and spreading. Enterobacteria also induced inflammatory cytokine production (IFN-γ, TNF-α, and IL-12), partially resembling the gliadin-induced Th1-type cytokine profile. B. longum CECT 7347 and B. bifidum CECT 7365 induced minor MDDC morphological changes and activated adhesion and spreading and inflammatory cytokine production to a lesser extent compared with enterobacteria. B. longum CECT 7347 also induced lower CD86 and CD40 expression on MDDCs than the two enterobacteria. The aforementioned bifidobacterial strain also reduced gliadin-induced IFN-γ production and increased IL-10 secretion when both stimuli were combined. Similar trends were detected for MDDCs cocultured with Caco-2 cells. B. longum CECT 7347 reversed the gliadin-reduced ZO-1 expression in Caco-2 cells. Thus, our results suggest that specific components of the gut microbiota may influence phenotypic and functional maturation of DCs differently and their interactions with epithelial cells. This could ultimately define the role of DCs in CD progression.

A new approach to the isolation and characterization of wheat flour allergens.

BACKGROUND: The incidence of food allergy to wheat is increasing. Its diagnosis depends on the purity of major allergens and their inclusion in tests. Isolation and characterization of wheat allergens are therefore of utmost importance. OBJECTIVE: To purify and identify wheat flour allergens most frequently recognized by patients' IgE antibodies and to study their allergenicity. METHODS: Water/salt-soluble extracts from wheat flour were prepared and separated using a combination of ultrafiltration, isoelectric focusing and liquid chromatography. Purified proteins were analysed by immunoblotting using pooled sera from patients with atopic dermatitis who possessed IgE specific to wheat. Wheat proteins found to bind IgE were subsequently identified by matrix-assisted laser desorption/ionisation-time of flight mass spectrometry. The frequency and intensity of IgE binding of isolated proteins were tested using individual sera from patients and controls. RESULTS: We developed a procedure that allows isolation of wheat allergens from natural sources. Twenty-seven potential wheat allergens have been successfully identified; of these, the following seven are newly reported in food allergy: endogenous α-amylase/subtilisin inhibitor, trypsin/α-amylase inhibitor (AAI) CMX1/CMX3, thaumatin-like protein (TLP), xylanase inhibitor protein-1, ß-glucosidase, class II chitinase and 26 kDa endochitinase. TLP and wheatwin were shown to activate patients' basophils to a similar extent as two well-known allergens, lipid transfer protein (Tri a 14) and AAI 0.19 (Tri a 28.0101). CONCLUSION AND CLINICAL RELEVANCE: Our new approach enables the isolation of water/salt-soluble wheat allergens in their native form in amounts sufficient both for biological testing (in vivo and in vitro) and for physicochemical characterization. Such studies will lead to a more detailed knowledge of allergenicity of wheat proteins and to improved accuracy of diagnostic tests.

Pivotal Advance: Bifidobacteria and Gram-negative bacteria differentially influence immune responses in the proinflammatory milieu of celiac disease.

CD is a chronic inflammatory disorder of the small intestine that presents in genetically predisposed individuals following gluten consumption. In this study, the effects of Bifidobacterium (Bifidobacterium bifidum IATA-ES2 and Bifidobacterium longum ATCC15707) and Gram-negative bacteria (Bacteroides fragilis DSM2451, Escherichia coli CBL2, and Shigella CBD8 isolated from CD patients), alone and in the presence of CD triggers (gliadins and/or IFN-gamma) on surface marker expression and cytokine production by PBMCs, were determined. These effects were also evaluated in cocultures of PBMCs and Caco-2 cells. The Gram-negative bacteria induced higher secretion of Th1-type proinflammatory cytokines (IL-12 and/or IFN-gamma) than the Bifidobacterium strains. Shigella CBD8 and E. coli CBL2 up-regulated mainly HLA-DR and CD40 expression involved in Th1 activation, and Bifidobacterium strains up-regulated CD83 expression. Specific interactions among the studied bacteria, gliadins, and IFN-gamma, which favored the CD immune features, were also detected. Therefore, intestinal bacteria could be additional factors that regulate the ability of monocytes recruited to the mucosa to respond to gliadins and IFN-gamma in CD patients, influencing the course of the disease.

Calreticulin is a B cell molecular target in some gastrointestinal malignancies.

Calreticulin, upon translocation to the cell surface, plays a critical role in the recognition of tumour cells and in experimentally induced cellular anti-tumour immunity. However, less is known about anti-calreticulin antibodies and their role in malignancies. Using enzyme-linked immunosorbent assay (ELISA), we found immunoglobulin (Ig)A and/or IgG anti-calreticulin antibodies in sera of approximately 63% of patients with hepatocellular carcinoma (HCC), 57% of patients with colorectal adenocarcinoma (CRA) and 47% of patients with pancreatic adenocarcinoma (PACA), while healthy controls, patients with viral hepatitis C and with chronic pancreatitis reached only 2%, 20% and 31% seropositivity, respectively. We found significantly elevated mean levels of IgA anti-calreticulin antibodies (P < 0.001) in patients with HCC (78.7 +/- 52.3 AU, mean +/- standard deviation), PACA (66.5 +/- 30.9 AU) and CRA (61.8 +/- 25.8 AU) when compared to healthy controls (41.4 +/- 19.2 AU). Significantly elevated mean levels of IgG anti-calreticulin antibodies (P < 0.001) were detected in patients with HCC (121.9 +/- 94.2 AU), gall bladder adenocarcinoma (118.4 +/- 80.0 AU) and PACA (88.7 +/- 55.6 AU) when compared to healthy controls (56.7 +/- 22.9 AU). Pepscan analysis revealed a large number of antigenic epitopes of calreticulin recognized by both IgA and IgG antibodies of patients with HCC and PACA, indicating robust systemic immune response. Moreover, significantly elevated levels of antibodies against peptide KGEWKPRQIDNP (P < 0.001) in these patients, tested by ELISA, confirmed the distinct character of antibody reactivity against calreticulin. The high occurrence and specificity of serum anti-calreticulin autoantibodies in the majority of patients with some gastrointestinal malignancies provide the evidence for their possible clinical relevance.

Anti-calreticulin immunoglobulin A (IgA) antibodies in refractory coeliac disease.

Refractory coeliac disease (RCD) is a very rare and dangerous form of CD, in which gluten-free diet loses its therapeutic effect and the damage of intestinal mucosa persists. Because of the adherence to the diet, serological markers of CD [immunoglobulin A (IgA) antibodies against gliadin, tissue transglutaminase (tTG) and endomysium] are often missing in RCD patients. We found substantially elevated levels of IgA anti-calreticulin (CRT) antibodies in the sera of almost all RCD patients tested. These sera were negative for IgA antibodies to gliadin and tTG and only some of them showed IgA antibodies to enterocytes. Analysis of patients' IgA reactivity to CRT fragments (quarters and halves) by Western blotting revealed differences in the specificity of IgA antibodies between RCD and CD patients. We therefore used the Pepscan technique with synthetic overlapping decapeptides of CRT to characterize antigenic epitopes recognized by serum IgA antibodies of RCD patients. Employing this method we demonstrated several dominant antigenic epitopes recognized by IgA antibodies of RCD patients on the CRT molecule. Epitope GVTKAAEKQMKD was recognized predominantly by serum IgA of RCD patients. Our results suggest that testing for serum IgA antibodies against CRT and its selected peptide could be a very useful tool in RCD differential diagnosis.

The intestinal microflora of childhood patients with indicated celiac disease.

The fecal short-chain fatty acids concentration was higher (154 +/- 46.9 mmol/L) in childhood patients than in healthy children (96.6 +/- 19.2 mmol/L). On the other hand, pH values were nonsignificantly lower in patients stool (6.78 +/- 0.75 vs. children 7.42 +/- 0.74). Using denaturing gradient gel electrophoresis specific for total bacteria, lactobacilli and bifidobacteria the microbial population was characterized in fecal samples and in duodenal biopsies. Bacteria adhering to duodenal biopsies were not dominating in stool samples. More than 50 % of detected bacterial species belonged to as yet uncultured strains.

Increased invasion of ED-1 positive macrophages in both ipsi- and contralateral dorsal root ganglia following unilateral nerve injuries.

There is an increasing evidence that unilateral nerve injury induces cellular and molecular changes in the associated DRG not only on the ipsilateral but also in the contralateral side. In this investigation, ED-1+ macrophages were quantified by image analysis in the naïve L5 DRG (nDRG) and compared with the ipsi- and contralateral ones 2 and 4 weeks after unilateral sciatic nerve ligature and ventral root transection (VRT). A few ED-1+ macrophages were found in nDRG but not closely associated with the neuronal bodies. In contrast, following nerve injuries ED-1+ macrophages and their processes were frequently located close neuronal bodies and became their satellite cells. Moreover, an increased number of ED-1+ cells was found in the ipsilateral DRG 2 weeks after unilateral sciatic nerve ligature or VRT, but no significant differences were measured between 2 and 4 weeks after both types of nerve lesion. Contralateral DRG displayed a significant enhanced number of ED-1+ cells no sooner than 4 weeks from sciatic nerve ligature. In contrast, VRT induced a significant increased invasion of the ED-1+ cells in the contralateral DRG as early as 2 weeks after operation. Our experiments indicate that a significantly higher number of ED-1+ macrophages remained in both ipsi- and contralateral DRG up to 4 weeks from nerve injury. Based on results from different models of nerve injury, we suggest that more than one mechanism operates to stimulate the invasion of ED-1+ macrophages into the DRG including retrograde transport of factors produced during Wallerian degeneration or their delivery by blood flow. Signaling for macrophage invasion into DRG contralateral to nerve injury may be mediated by lost motoneurons or by interneurones.

Interaction of mucosal microbiota with the innate immune system.

Organisms live in continuos interaction with their environment; this interaction is of vital importance but at the same time can be life threatening. The largest and most important interface between the organism and its environment is represented by surfaces covered with epithelial cells. Of these surfaces, mucosae comprise in humans approximately 300 m2, and the skin covers approximately 1.8 m2 surface of the human body. Mucosal tissues contain two effector arms of the immune system, innate and adaptive, which operate in synergy. Interaction with commensal bacteria, which outnumber the nucleated cells of our body, occurs physiologically on epithelial surfaces; this interaction could pose the risk of inflammation. The mucosal immune system has developed a complex network of regulatory signalling cascades that is a prerequisite for proper activation but also for a timely inactivation of the pathway. As demonstrated in gnotobiotic animal models of human diseases, impaired regulation of mucosal responses to commensal bacteria plays an important role in the development of several inflammatory and autoimmune diseases.

The serologic screening for celiac disease in the general population (blood donors) and in some high-risk groups of adults (patients with autoimmune diseases, osteoporosis and infertility) in the Czech republic.

The prevalence of celiac disease (CD) was determined in healthy blood donors and in high-risk groups of adults (a total of 1835 adults--randomly selected 1312 healthy blood donors, 102 patients with primary osteoporosis, 58 patients with autoimmune diseases and 365 infertile women). It was calculated on the basis of a two-step serologic screening method--in the first step IgA and IgG antigliadin antibodies (AGA) and IgA anti-gamma-glutamyltransferase ('transglutaminase') antibodies (ATG) were estimated, in the second step sera positive for IgA AGA and/or IgA ATG were examined for antiendomysial IgA (AEA) antibodies. Immunoenzymic assay (ELISA) was used for determining of AGA and ATG antibodies; immunofluorescence method, performed on human umbilical cord tissue, was used for assaying of AEA antibodies. Total serum IgA level in only IgG AGA positive subjects was measured by routine turbidimetric method. 0.45% of healthy blood donors, 0.98% of osteoporotic patients, 2.7% of patients suffering from autoimmune disease and 1.13% of women with infertility considered as immunologically mediated were found to be positive in both steps of serologic screening (AGA and/or ATG and antiendomysium positive). The presumed high prevalence of seropositivity for CD in apparently healthy Czech adult population was confirmed. In the high-risk groups, the prevalence of seropositivity for CD was approximately 2-4 times higher than in healthy blood donors. The real prevalence of CD in the tested groups, however, can be estimated after performing small intestinal biopsy in the seropositive patients.

[Autoimmune enteropathy with onset in early infancy: clinico-morphologic and immunologic manifestations]. / Autoimunní enteropatie se zacátkem v casném kojeneckém veku: klinicko-morfologické a imunologické projevy.

This paper describes a severely affected male infant with serious protracted diarrhoea caused by a rare autoimmune enteropathy. The disease began at 6 weeks of age of the child and it was associated with small bowel villous atrophy and the presence of circulating antienterocyte antibodies. The child was treated with steroids and with parenteral and special enteral nutrition. The patient showed clinical improvement as documented by decreased stool output and possibility to terminate the parenteral nutrition. The small biopsy samples showed a return to normal. Antienterocyte antibodies were negative after the treatment. The patient has been followed up for at least 18 months and was in a clinical remission. We recommend that autoantibodies tests should be performed in all infants with unexplained protracted diarrhoea. The use of potent immunosuppressive drugs and the increasing experience with parenteral and enteral nutrition can improve the perspective of these previously fatal disorders.

Serologic markers of untreated celiac disease in Libyan children: antigliadin, antitransglutaminase, antiendomysial, and anticalreticulin antibodies.

BACKGROUND: There are, as yet, no data available about the incidence of celiac disease in Libya. The aim of this study was to test the occurrence of serologic markers in a group of Libyan children with positive clinical and histologic findings indicative of celiac disease diagnosis. METHODS: Thirty-nine children with untreated celiac disease and 50 healthy school children, all younger than 14 years, were included in the study. Enzyme-linked immunosorbent assay for immunoglobulin G and immunoglobulin A (IgA) antigliadin, antitissue transglutaminase, and anticalreticulin antibodies was used to evaluate the serologic markers of the celiac patients. Immunoglobulin A antiendomysial antibodies were detected by indirect immunofluorescence using human umbilical cord tissue. RESULTS: Clinical symptoms at presentation were weight loss (82%), abdominal distension (61.5%), diarrhea or steatorrhea (59%), pallor (41%), abdominal pain (20.5%), constipation (15%), vomiting (10%), and short stature (7.7%). Most of these symptoms disappeared after introduction of a gluten-free diet. Of 39 patients, only 23 (59%) were endomysium positive and positive also in all other serologic markers. The second group of patients with positive clinical and biopsy findings but antiendomysial antibody-negative findings was subdivided into two subgroups according to the IgA antigliadin antibody results. Individuals in the IgA gliadin-negative subgroup also lacked IgA autoantibodies. CONCLUSIONS: The authors' findings stress the importance of serologic testing not only for screening but also for confirmation of celiac disease.