László Tóth

Diagnostic significance of HLA-DQ typing in patients with previous coeliac disease diagnosis based on histology alone

Coeliac disease is strongly associated with human leukocyte antigen (HLA)‐DQ2 or DQ8 genotypes. The diagnosis is based on demonstrating crypt‐hyperplastic villous atrophy, endomysial or transglutaminase antibodies and correlation of disease activity with gluten intake.

Catastrophic antiphospholipid syndrome in cancer

Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies resulting in arterial and venous thromboembolism. Apart from primary cases, this syndrome is often associated with autoimmune diseases. Around 50 cases of catastrophic antiphospholipid antibody syndrome have been reported as yet. Authors describe the first case of catastrophic antiphospholipid syndrome associated with gastric cancer. Apart from presenting the clinical case, authors also discuss the possible pathomechanism of this associated disorder including the role of immunological factors, as well as antiphospholipid antibodies.

Changes of local and systemic hemorheological properties in intestinal ischemia‐reperfusion injury in the rat model

The aim of this study was to investigate intestinal ischemia‐reperfusion and its local and systemic hemorheological relations in the rat. Ten anaesthetized female CD outbred rats were equally divided into 2 experimental groups. (1) Ischemia‐reperfusion (I/R): the superior mesenterial artery was clipped for 30 minutes. After removing the clip, 60 minutes of the reperfusion was observed before extermination. Blood samples were taken from the caudal caval vein and from the portal vein before ischemia, 1 minute before and after clip removal, and at the 15th, 30th, and 60th minutes of the reperfusion. (2) Sham operation: median laparotomy and blood sampling were done according to the timing as in I/R group. Hematological parameters, red blood cell aggregation, and deformability were determined. Leukocyte count and mean volume of erythrocytes increased slightly but continuously in portal venous samples during the reperfusion period. Red blood cell aggregation values were higher in portal blood by the end of ischemia, and then became elevated further comparing to the caval venous blood. Both in caval and portal venous samples of I/R group red blood cell deformability significantly worsened during the experimental period compared to its base and Sham group. In portal blood red blood cell deformability was impaired more than in caval vein samples. Histology showed denuded villi, dilated capillaries, and the inflammatory cells were increased after a 30 minutes ischemia. In conclusion, intestinal ischemia‐reperfusion causes changes in erythrocyte deformability and aggregation, showing local versus systemic differences in venous blood during the first hour of reperfusion.

Two germline alterations in mismatch repair genes found in a HNPCC patient with poor family history

The Bethesda guidelines may offer more useful criteria in patients’ selection for germline mismatch repair gene mutation analysis than guidelines merely based on family background. An early onset double primary colorectal cancer patient with poor family history with MSI-H status was investigated for MLH1 promoter methylation, expression of the MLH1 and MSH2 gene by immunohistochemistry and mutations in the MLH1 and MSH2 genes. The index patient carried two germline alterations, the p.Val716Met in MLH1 and the c.2210+lG>C in MSH2 genes, and both tumors failed to express MLH1 and MSH2 proteins. After subsequent analysis of the whole family of the index patient, the p.Val716Met variant can be defined as a rare polymorphism with the possible contribution of pathogenicity to tumor formation and c.2210+1G>C as a true pathogenic mutation causing an out-of-frame deletion of exon 13.

A new mutation in Muir-Torre syndrome associated with familiar transmission of different gastrointestinal adenocarcinomas

Hereditary Nonpolyposis Colorectal Carcinoma (HNPCC) is the most frequent inherited disease which can lead to the development of tumors in the colon and other locations. Its genetic basis is related to the germline mutation of the Mismatch Repair (MMR) genes. Muir-Torre syndrome is considered one of the subtypes of this disease, in which the HNPCC tumor spectrum is frequently associated with sebaceous carcinoma of the skin or keratoacanthoma. A 57 years old male patient is presented with a mucinous carcinoma of the caecum and an adenocarcinoma of the pancreas head. A malignant sebaceous carcinoma was removed from his left neck area. His family history was significant for two cases of colon carcinoma, two cases of stomach cancer and a case of metacron endometrial and skin tumor as well. Both the colon carcinoma and the skin tumor proved to be microsatellite unstable. An Arg>Pro switch missense mutation was found in codon 265 of the hMLH1 gene. This error was found in 4 other members of his family. The detected genetic alteration was considered pathogenic and was not published yet in English literature. The significance of this particular case is the rare tumor association in a patient with Muir-Torre syndrome (MTS). In cases of sebaceous skin lesions, evaluation of family history is of utmost importance in the early detection of HNPCC and in the follow up care of family members with the particular mutation.

Correlations between clinicopathological parameters and molecular signatures of primary tumors for patients with stage T3n0 colorectal adenocarcinomas: a single center retrospective study on 100 cases.

BACKGROUND/AIMS To examine the clinical and protein expression characteristics of tumor tissues for prediction of prognosis in colorectal cancer (CRC). METHODOLOGY We retrospectively analyzed the clinicopathological data of patients with stage T3N0 CRC, operated between 1997-2003 and the surgical materials for the relation between disease prognosis and p53, p21, p16, β-catenin, E-cadherin, EGFR, hMLH1, hMSH2 and TS protein expressions. RESULTS A significantly shorter 3-year disease free survival was observed in patients under the age of 50. The worst 5-year overall survival (OS) observed for patients over 70. Tumor localization and number of processed lymph nodes significantly affected prognosis. The EGFR, hMSH2 and TS expressions and the 5-fluorouracyl treatment were not found to be of prognostic value; p53 and p21 positivity had significantly worse survival. When β-catenin membrane expression disappeared on tumor cells, the 5-year OS rate decreased and time to metastasis shortened significantly. Membrane β-catenin expression, processed lymph nodes number and age were detected as independent prognostic markers. CONCLUSIONS These results suggest that the evaluation of a clinicopathological profile, based on age, tumor localization, number of examined lymph nodes, p53, p21 and E-cadherin β-catenin expression appears to be useful in identifying high risk patients.

The beneficial effect of plasmapheresis in mixed connective tissue disease with coexisting antiphospholipid syndrome

The authors report a rare case of a female patient with mixed connective tissue disease (MCTD) with coexisting antiphospholipid syndrome (APS). Five years after the diagnosis of MCTD high concentrations of anticardiolipin (anti-CL) and anti-β2-glycoprotein (anti-β2GPI) autoantibodies were present in the patient’s serum without thrombotic events. Epstein-Barr virus (EBV) reactivation provoked APS, with the clinical manifestations of livedo reticularis, digital gangrene and leg ulcers. Skin biopsy from the necrotic area showed multiple fibrin microthrombi in the superficial vessels. Corticosteroid pulse therapy, and plasma exchange in combination with synchronized cyclophosphamide was administered, which led to improvement of the digital gangrenes, while no new lesions developed. The number of CD27high plasma cells decreased, and the previous high levels of autoantibodies also normalized in the peripheral blood. In the case of MCTD with coexisting APS combination therapy, including plasmapheresis has beneficial effects.

Morphological, hemodynamical and hemorheological changes of mature artificial saphenous arterio-venous shunts in the rat model

Artificial femoral arterio‐venous (AV) shunts are widely used in rodent models for studying shunt maturation and to optimize various surgical techniques. However, little is known about complex circulatory, microcirculatory, and hemorheological effects of end‐to‐side saphenous AV shunts. We aimed to study these parameters in mature AV shunts. Studying these questions in CD rats, end‐to‐side anastomoses were made between the left saphenous artery and vein. On the right‐side the nonoperated saphenous vessels served as own control. Furthermore healthy control animals were also investigated. On the 8th to 12th postoperative week microcirculatory and blood flow measurements were performed and blood samples were taken both from the shunts arterial and venous limbs and from the nonoperated side vessels. Hematological parameters, erythrocyte aggregation, and deformability were determined. The entire shunt and the control vessels were removed for histological examinations. The skin microcirculation on shunt side slightly increased on thigh and decreased on paws versus the nonoperated side. Blood flow measurements made directly on the vessels showed that arterial to venous blood flow rate ratio was 1.59 ± 0.29 on nonoperated side and 1.2 ± 0.13 on the shunt side, and 1.49 ± 0.05 in control animals. Erythrocyte aggregation and deformability worsened on the shunt side. Histologically increased number of smooth muscle elements and connective tissue were found in venous limb of the shunts. The artificial AV shunt between the saphenous artery and vein seems to be a suitable model for further functional‐morphological and hemorheological examinations of hemodialysis in various states and diseases.

Jerky magnetic noises generated by cyclic deformation of martensite in Ni2MnGa single crystalline shape memory alloys

It is shown that during periodic deformation of martensitic Ni2MnGa single crystalline alloy jerky magnetic noises are emitted. Above a threshold limit in the deformation amplitude, the noise energy per deformation cycle showed increasing tendency with increasing deformation. Energy and amplitude probability distributions of the noise were characterized by power law functions. The energy exponents were independent of the deformation amplitude in the investigated range. The decrease of the noise energy as well as power exponents with increasing magnetic field was interpreted by the decrease of the multiplicity of the martensite variants.

Testicular ischemia-reperfusion may alter micro-rheological parameters in laboratory rats

Ischemia-reperfusion-caused hemorheological alterations have been widely studied but the effect of testicular ischemia-reperfusion has not so far. In this study 14 Sprague-Dawley rats were involved. In the ischemia-reperfusion group under general anaesthesia the left testis was explored by opening the scrotum then the deferent duct and vasculature were clamped for 30 minutes. Testicular microcirculation was monitored by laser Doppler flowmetry. The right testis was untouched. In the control group: only anaesthesia was induced. Blood sampling occurred before and after ischemia, at the 60th minute of reperfusion and on the 1st postoperative day for determining hematological parameters (microcell-counter), erythrocyte deformability (slit-flow ektacytometer) and erythrocyte aggregation (light-transmission aggregometer). After the last blood sampling, testicles were removed for histological examination. Hematological parameter changes reflected inflammatory response. Erythrocyte deformability showed a worsening already at the 60th minute of reperfusion compared to base and control values. By the 1st postoperative day further decrease was observed. Erythrocyte aggregation significantly enhanced with great magnitude versus base and control values (p < 0.001). However, conventional histological examinations did not show marked testicular injury. The experienced changes can attract attention to the testicular ischemia-reperfusion causing significant effects on hemorheological parameters, which can lead to further harmful microcirculatory consequences.