Factor XIII-A subunit Val34Leu polymorphism in fatal hemorrhagic stroke.

Blood coagulation factor XIII (FXIII) plays a key role in the protection of fibrin clot against fibrinolysis, in the cross-linking of fibrin and its mechanical strength. The role of the FXIII-A subunit Val34Leu polymorphism with fatal primary intracerebral hemorrhages (PICH) has not been studied. We evaluated retrospectively the prevalence of this polymorphism in stroke patients with fatal PICH and population control matched for age and gender. The prevalence of this polymorphism was determined for patients with fatal PICH (n = 98, female/male: 41/57) and controls. DNA was obtained from peripheral white blood cells in case of controls and from paraffin-embedded tissue sections in case of fatal PICH. The odds for increasing the risk of PICH against the control group were 5.429, 3.286, and 7.661 for total, female, and male patients, respectively. The Leu34Leu homozygous variant of the FXIII Val34Leu polymorphism significantly increased the risk of fatal PICH stroke in men.

Prothrombotic polymorphisms in patients with Raynaud's phenomenon and migraine.

We have investigated the prevalence and possible association of inherited prothrombotic risk factors in patients with primary Raynaud's phenomenon (PRP) and migraine. We performed genotypic analysis of FVLeiden, prothrombin G20210A, methyltetrahydrofolate reductase C677T and FXIII-A V34L mutations in these patients. Two hundred patients with primary Raynaud's phenomenon of Hungarian origin with migraine (57 female, one male, mean age of 43.8 ± 11.5 years) or without migraine (101 female, 41 male, mean age of 41.8 ± 14.5 years) were included in this study. Duration of PRP among migrainous patients was significantly longer than patients without migraine. The prevalence of methyltetrahydrofolate reductase T677 allele among patients with migraine was significantly higher than in patients without migraine (odds ratio 2.1, 95% CI: 1.4-3.3, p = 0.001). The prevalence of other thrombosis-associated alleles did not differ between patients with or without migraine. FVLeiden mutation, prothrombin G20210A mutation, and FXIII-A V34L polymorphism have no apparent effect on the occurrence of migraine in PRP.

Functional dyspepsia: still a serious challenge for medical practitioners and new drug investigators? A Belgian, French, German and Hungarian opinion.

The diagnosis of Functional Dyspepsia is based on the identification of long term specific symptoms and the absence of organic lesions. Many pathophysiological mechanisms are intricate and, at least, partially responsible for the syndrome. Widely accepted technical procedures for the identification of these mechanisms are missing. The final etiopathology is not yet established. The relationship between symptoms and putative mechanisms is unclear. At the moment of the prescription, the physician faces a real therapeutic gap. Moreover, Functional Dyspepsia is an evolving area of study and knowledge has to be updated regularly. As a result, consultations for Functional Dyspepsia are usually very challenging and patients look desperately for medical support. It is likely that this disease is both under-diagnosed and under-treated. Classifying patients into symptomatic subgroups is a promising approach proposed by Rome III. It is assumed that these subgroups are based on different pathophysiological mechanisms, and may allow for more specific therapeutic approaches. However the assessment of the symptomatic profiles of patients is time-consuming. It is also a risky process, because the Rome III subgroups have yet to be validated. There are currently no translations of the definitions in the different European languages. Interviews of the patients are biased by cultural, educational and subjective factors. Identification of suitable subjects for clinical trials is uneasy for the same reasons and can explain several recent Research and Development (R&D) failures. Therefore, there is a need for an updated, step by step approach, a real diagnostic algorithm of the consultation including the use of simple, clear, universal and cross-cultural validated tools, as word-figure questionnaires, designed to establish the symptomatic profiles of the patients.

Functional and morphological evaluation of hand microcirculation with nailfold capillaroscopy and laser Doppler imaging in Raynaud's and Sjögren's syndrome and poly/dermatomyositis.

OBJECTIVES: Nailfold capillaroscopy is widely used in autoimmune patients to determine capillary morphology. Laser Doppler imaging (LDI) is a relatively new method for measuring the microcirculation of cutaneous perfusion. The aim of this study was to investigate the capillary morphology and microcirculation among patients with Sjögren's syndrome (SS) and poly/dermatomyositis (PM/DM) with these two non-invasive methods and to detect secondary Raynaud's syndrome (SRS) in these autoimmune diseases. METHODS: Thirty patients with primary SS, 30 patients with PM/DM, 30 patients with primary Raynaud's syndrome (PRS), and 30 healthy volunteers were included in the study. Nailfold capillaroscopy and LDI were performed on each patient. RESULTS: A comprehensive analysis was performed among the patients and healthy individuals. Among SS patients avascularity and among PM/DM patients avascularity and capillary morphology changes were most often detected by capillaroscopy. With LDI the mean steady-state cutaneous perfusion was 1.25 perfusion units (PU) in region of interest 1 (ROI1), 1.22 in ROI2, and 1.49 at the fingertips in PRS patients; the corresponding values were 1.2, 1.03, and 1.48 PU in SS, 0.91, 0.76, and 1.19 PU in PM/DM, and 1.79, 1.62, and 2.2 PU in the controls. The differences were significant between each autoimmune group compared to the control group (p<0.02, p<0.001, and p<0.001, respectively). CONCLUSIONS: By using nailfold capillaroscopy, abnormalities in capillary morphology can be detected, and by using LDI, the reduced blood flow in the capillaries can be detected. These investigations can be useful in the detection of SRS, or in distinguishing whether the reduced blood flow is due to primary/systemic autoimmune diseases.

Raynaud's syndrome: comparison of late and early onset forms using hand perfusion scintigraphy.

Primary Raynaud's disease is generally a disease of younger females; however, there are cases where symptoms present over the age of 40. These cases are described as late onset. In our current prospective study we compared the characteristics of early and late onset types of primary Raynaud's in 127 patients. In addition to the collection of medical records, we performed capillary-microscopy and hand perfusion scintigraphy using Tc-99 m DTPA to evaluate the microcirculation of each patient's fingers. Regarding the spectrum of the capillary-microscopic findings, we did not find any significant difference between the early and late onset forms. However, in hand perfusion examinations done using Tc-99 m DTPA, we measured a significantly lower finger/palm ratio (FPR) in the early onset group of patients. We also observed a correlation between the duration of the disease and the FPR, as well as between the age and FPR. Longer disease duration resulted in a significantly lower FPR. On the basis of our results, we believe that late onset Raynaud's should be treated as a separate entity. Due to its different characteristics found on examination and follow-up of our patients, functional hand perfusion examination should be recommended independently of the age-related characteristics of the disease.

Microcirculation of the fingers in Raynaud's syndrome: (99m)Tc-DTPA imaging.

AIM: We investigated the circulatory characteristics of patients suffering of primary and secondary Raynaud's syndrome. PATIENTS, METHODS: We examined 106 patients presenting with the classical symptoms of Raynaud's syndrom (47 primary, 59 secondary) by hand perfusion scintigraphy developed by our Department of Nuclear Medicine. After visual evaluation we analyzed the images semiquantitatively, using the finger to palm ratio. We statistically compared the patients with primary and those with secondary Raynaud's syndrome. RESULTS: By visual evaluation we constated regional perfusion disturbances in 42 from 59 patients with secondary Raynaud's syndrome. However, this was observed in only 3 from 47 patients with the primary form of this disease. This difference was statistically significant (p<0.001). Semiquantitative analysis showed that the finger/palm ratios (FPR) were significantly lower (p<0.05) for the patients with primary Raynaud's syndrome. No differences in the FPR values concerning sex or right and left side. CONCLUSION: The hand perfusion scintigraphy with (99m)Tc-DTPA is a noninvasive, cost effective diagnostic tool, which objectively reflects the global and regional microcirculatory abnormalities of the hands, and provides quantitative data for follow-up.

Five-year follow-up of 665 Hungarian patients with undifferentiated connective tissue disease (UCTD).

OBJECTIVE: To determine the clinical symptoms and the panel of autoantibodies of patients with early undifferentiated connective tissue disease (UCTD) followed for at least 1 year. METHODS: 716 UCTD patients with manifestations suggestive but not diagnostic of specific connective tissue disease (CTD) were recruited and followed up between 1994-1999. The patients with early UCTD were subdivided into those with isolated Raynaud's phenomenon (RP) (50 patients), unexplained polyarthritis (31 patients) and "true" UCTD (665 patients). UCTD was diagnosed on the basis of clinical manifestations suggestive of a connective tissue disease and the presence of at least one non-organ specific autoantibody. The patients' sera were tested for anti-nuclear (ANA), as well as for nine different specific autoantibodies (anti-dsDNA, -Sm, -RNP, -SSA, -SSB, -Scl-70, -centromere, -Jo1 and -PM-Scl). RESULTS: The most common clinical manifestations of UCTD included RP, arthritis/arthralgias, pleuritis/pericarditis, sicca symptoms, cutaneous involvement (photosensitivity, rash), central nervous symptoms, peripheral neuropathy, fever, vasculitis, less pulmonary involvement and myositis. 230 of the 665 true UCTD patients (34.5%) developed a defined CTD (28 systemic lupus erythematosus [SLE], 26 mixed connective tissue disease [MCTD], 19 progressive systemic sclerosis [PSS], 45 Sjögren's syndrome, 3 polymyositis/dermatomyositis [PM/DM], 87 rheumatoid arthritis [RA], and 22 systemic vasculitis. 435 of 665 patients (65.4%) remained in the UCTD state, and 82 of 665 patients (12.3%) achieved complete remission with symptoms not reappearing within the 5-year period. The highest probability of evolution to a defined CTD was during the first 2 years after onset: of 230 UCTD patients 183 (79.5%) developed major organ symptoms and signs. In particular skin and cardiac complications seemed to spread during the follow-up period in those patients who progressed to SLE. The condition of 18/50 patients with isolated RP evolved to UCTD and 3 of 31 patients with unexplained polyarthritis progressed to definite CTD (2 patients RA and one MCTD). CONCLUSION: In our study most of the UCTD patients did not develop a definite CTD, but during the follow-up period we found new clinical and serological manifestations. One-third of the UCTD patients showed progress into different types of specific CTD.

A new giant pterosaur with a robust skull from the latest cretaceous of Romania.

A new giant pterosaur, Hatzegopteryx thambema, nov.gen., nov.sp., from the Maastrichtian Densus-Ciula Formation of Romania is remarkable for its very large size (estimated wing span > or = 12 m) and for the robustness of its large skull, which may have been nearly 3 m long. The stout skull bones contrast with the usually thin and slender skull elements of other pterosaurs, and raise the question of how the weight of the skull was reduced in order to make flight possible. The answer probably lies in the very peculiar internal structure of the bones, which consists of a dense network of very thin trabeculae enclosing small alveoli. This structure is reminiscent of expanded polystyrene and, like it, probably combined strength with lightness.

[Schoenlein-Henoch purpura in adulthood (gastrointestinal manifestation and endoscopy)]. / Die Schoenlein-Henoch-Purpura bei erwachsenen. (Gastrointestinale Manifestation und Endoskopie).

During a 15-year-period 62 adult patients were admitted with diagnosis of Schoenlein-Henoch purpura in our hospital. 25 female and 37 male patients ranged from 30-87 years (mean: 59.5 years) presenting with cutaneous, joint, renal and particularly abdominal involvement were investigated retrospectively. During the course of the disease, all patients developed purpuric rash (100 %), 14 (22,5 %) patients had joint symptoms and renal involvement occurred in 12 (19,3 %) patients. In this study, we discuss 15 (24 %) patients with gastrointestinal symptoms appearing in Henoch's purpura. Analysis of the gastrointestinal clinical features revealed: Abdominal pain 13 (86 %), massive colorectal bleeding 3 (20 %), occult blood loss 10 (66 %) vomiting 6 (40 %) and diarrhea in 3 (20 %) patients. Surgical consultation was obtained for 4 of the 15 patients and laparotomy was performed in 2 patients. All the patients underwent lower and upper endoscopic examination, in 3 cases the authors saw purpuric mucosal lesions in duodenum and in 8 patients were also found coin-like elevated lesions, additionally, biopsy from colonic lesions showed leukocytoclastic vasculitis. It is concluded that endoscopy may play a very important role in the diagnosis and treatment of Schoenlein-Henoch purpura.

Retrospective evaluation of 5-fluorouracil-interferon-a aTreatment of advanced colorectal cancer patients.

The authors describe the retrospective analysis of treatment by 5-fluorouracil and interferon-a aof 34 patients with advanced colorectal cancer. An average of 4.6 treatment cycles (3 12) was applied. Complete remission was not observed; partial remission was observed in 8 patients; in 13 patients no change occurred and progression was detected in 14 cases. Remission rate was 22.8%, mean response time was 5.2 (3 12) months, mean progress-free survival 5.6 (0 22) months. Mean survival from the start of treatment was 11.9 (1 42) months and from the establishment of the diagnosis 26.1 (3 60) months. Severe life-threatening side-effects did not occur; other side-effects such as fever, nausea, diarrhea, leucopenia, and anemia responded to drugs. Treatment by 5-FU and interferon, in accordance with other authors findings, improved survival and well-being of patients but no breakthrough has been achieved.

The clinical usefulness of the fingers-to-palm ratio in different hand microcirculatory abnormalities.

A non-invasive nuclear medicine technique was developed to screen patients with painful hands so as to separate patients with a normal from those with an abnormal microcirculation of the hands in different clinical conditions. Such a technique is important, as the other methods available are either subjective or rather complicated. The study population consisted of 10 healthy individuals, 23 patients with Raynaud's syndrome and 15 patients with mixed connective tissue disease (MCTD). Sixty gamma-camera images of the hands (1 s each) were recorded after a bolus injection of 99Tcm-DTPA via a dorsal foot vein. Regions of interest were drawn on the summed images around the fingers and the palmar region. The fingers-to-palm ratio was then calculated from the total counts inside these regions of interest separately for each hand. The mean fingers-to-palm ratio was 0.94+/-0.18 (0.71-1.25) for the healthy group, 0.57+/-0.22 (0.21+/-1.11) for the MCTD group and 0.40+/-0.14 (0.18-0.77) for the Raynaud's patients. Analysis of variance showed these differences to be highly significant (P < 0.001). There were also significant differences between 6 MCTD patients in an active (mean 0.48) and nine patients in an inactive (mean 0.66) clinical state (two-sample t-test: P < 0.05). There were no significant differences between the fingers-to-palm ratios of the left and right hands of the same patients (one-sample t-test). Of the 23 primary Raynaud's patients, capillary microscopic data were pathological in only eight (34%). We conclude that our method is able to differentiate between patients with normal and those with abnormal microcirculation of the hands. Although measurement of the fingers-to-palm ratio is not a specific method, it is useful both for staging and in the follow-up of patients.

[Clinical evaluation of local lipiodol chemoembolization therapy in primary and secondary hepatic tumors]. / Primer és szekunder májdaganatos betegek lipiodolos kemoembolizációval végzett helyi kezelésének klinikai értékelése.

The authors treated with locoregional lipiodol chemoembolization 32 patients suffering from primary and secondary liver malignancies. They present the clinical results of the 22 patients who received at least 2 treatments. Distribution of patients: 17 men, 5 women, mean age 56.2 (43-80) years. Seven patients suffered from primary liver carcinoma; regarding the Child's staging of the tumors 4 patients were in Child A, 3 patients in Child B. In 15 cases the treatment indication was secondary liver cancer. The primary tumors in these secondary liver cancer cases were: one case lung cancer, 11 colon (2 cases rectum) cancer, 2 cases pancreas cancer, one case gastric carcinoma. The 22 patients received in total 97 cycles of therapy. After the selective catheterisation of the hepatic artery adriamycin, mitomycin C, 5-fluorouracil or lipiodol was administered. During the mean follow up time of 9 months (3-15 months) remission could be observed in 6/22 patients. The side effects were preventable or medically treatable. It can be concluded that in the case of well-selected cases of non-resectable liver malignancies local chemoembolization could be beneficial, as it could slow down the progression of the underlying disease with the maintainment or even improvement of the quality of life.

[Raynaud syndrome and eradication of Helicobacter pylori]. / Raynaud-szindróma és Helicobacter pylori-eradikáció.

In this work, the effect of eradication of Helicobacter pylori on complaints and symptoms of infected, primary Raynaud's syndrome patients was studied. Altogether 92 Helicobacter pylori positive patients with gastric complaints and with primary Raynaud's syndrome received eradication therapy. In this prospective study, before and after the eradication the severity and frequency of the complaints and symptoms of the patients were recorded. The eradication was performable in 89 patients; in 75 cases the eradication was successful. In the eradicated patients frequency and duration of Raynaud attacks were improved related to those of the not eradicated group. These results might suggest a potential etiopathogenetical role of Helicobacter pylori infection in the pathogenesis of the primary Raynaud's syndrome.

[Comments on Raynaud syndrome based on laser-Doppler studies]. / Eszrevételek a Raynaud-szindrómáról lézer Doppler-mérésekkel szerzett tapasztalatok alapján.

The authors have in their care 286 Raynoud syndrome patients. They present their experience in the study of the microcirculation and the treatment of these patients. In 81% (232 patients, 196 women and 36 men) of the cases they did not find any underlying diseases. In the group of the patients with secondary Raynaud's syndrome (35 women and 19 men) underlying diseases, possibly leading to microcirculatory disturbances, could be identified. In the primary Raynaud's syndrome group the main capillary diameter measured by capillary microscopy was 15 +/- 4 micron. In patients with progressive systemic sclerosis the mean diameter was 43 +/- 9 micron. In the group of women with primary Raynaud's syndrome the authors performed laser Doppler measurements of the nailfold microcirculation. During the reactive hyperaemia test basal values (18.2 +/- 6.2 Perfusin Units, P. U.) and reactive hyperaemia values (a mean of 180% growth compared to the basal values) were similar to that perfusion values referred in the literature. In the progressive systemic sclerosis group the basal flow (9.3 +/- 3.3 P. U.) and the reactive hyperaemia (a mean of 20% increase compared to basal values) were significantly lower. Concerning the fact that the progression of Raynaud's syndrome into systemic autoimmune disease--mainly to progressive systemic sclerosis may be predicted, it is important to follow up carefully all patients with Raynaud's syndrome.

Higher-order spectral analysis in laser-Doppler flowmetry signal processing.

This paper presents an application of higher order statistics and spectra to the problem of laser-Doppler Flowmetry (LDF) for microcirculation monitoring. The proposed signal processing technique computes the bispectra of LDF signals after appropriate pre-processing and extracts features which can be used for classification of the signals to a normal or patient category. Bispectra are defined in terms of the third-order moments or cumulants of signals and are shown to contain valuable information for the above classification of LDF signals. Experimental studies, including (a) a set of 17 normal subjects and 69 patients with Raynaud's phenomenon and (b) 50 LDF-signals separated to four groups from patients that have different pathologic characteristics, are described and results are presented which illustrate the performance of the proposed approach when applied to the LDF signals.

Postoperative chemoembolism treatment of primary and metastatic malignant hepatic tumours.

Between 1992 and 1996 62 patients were operated for primary malignant and metastatic hepatic tumours. After the operation 31 patients received cytostatical treatment, 9 patients were treated with the method of chemoembolism. 46 patients are alive 30.7 (5-54) months after the operation. 9 patients died 12.5 (3-27) months after the resection of the liver. Authors have favourable experiences on the treatment of chemoembolism.

Fibrinolysis-resistant fibrin deposits in minor labial salivary glands of patients with Sjögren's syndrome.

Minor labial salivary glands obtained at biopsy from 12 patients with Sjögren's syndrome were investigated by immunomorphological methods for the presence of fibrinolysis-resistant fibrin deposition. Fibrin could be found in extracellular localization between individual inflammatory cells infiltrating minor salivary glands. In the areas surrounding mononuclear infiltrations the labeling for fibrin showed an essentially fibrillar pattern. Staining for factor XIII A was observed over fibrin deposits and in large, stellate cells not showing reaction for fibrin. Here it is demonstrated that factor XIII A+ tissue macrophages are in an intimate relationship with fibrin deposits. The authors suggest that tissue macrophages may play a regulatory role in fibrin accumulation in association with autoimmune inflammation and consequently in demarcation of the inflamed tissue.