Differences associated with age at onset in early systemic sclerosis patients: a report from the EULAR Scleroderma Trials and Research Group (EUSTAR) database.

OBJECTIVE: The aim of this study was to analyse differences in clinical presentation in patients with early (< 3 years' duration) systemic sclerosis (SSc), comparing three age groups according to disease subsets. METHOD: Cross-sectional analysis of the prospective EULAR Scleroderma Trials and Research database (EUSTAR) was performed. Patients fulfilling preliminary American College of Rheumatology 1980 classification criteria for SSc, with < 3 years from the first non-Raynaud's SSc symptom at first entry, were selected. Patients with < 3 years from the first SSc symptom, including Raynaud's phenomenon, were also analysed. SSc-related variables, including antibodies, SSc subsets, and organ involvement, were examined. Age was categorized into ≤ 30, 31-59, and ≥ 60 years. We performed descriptive and bivariate analyses. RESULTS: The study included 1027 patients: 90% Caucasian, 80% women, and 40% with diffuse disease. In early stages of SSc, younger patients had significantly more anti-Scl-70 antibodies and diffuse disease. With increasing age, we observed more elevation of estimated pulmonary systolic pressure on echocardiography (5%, 13%, and 30%, respectively, in the three age groups), cardiac conduction blocks (6%, 6%, and 15%), and left ventricular diastolic dysfunction (4%, 12%, and 27%). The results were similar for 650 patients with < 3 years from first SSc symptom, including Raynaud's. CONCLUSION: In early stages of SSc, older patients showed data indicating more severe disease with greater cardiac involvement. The diffuse subset was more frequent in the younger subgroup. The identification of such differences may help in selecting appropriate management for individual patients in clinical practice.

There is a need for new systemic sclerosis subset criteria. A content analytic approach.

OBJECTIVES: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. METHODS: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. RESULTS: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). CONCLUSIONS: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

Educational recommendations for the conduct, content and format of EULAR musculoskeletal ultrasound Teaching the Teachers Courses.

OBJECTIVE: To produce educational guidelines for the conduct, content and format of theoretical and practical teaching at EULAR musculoskeletal ultrasound (MSUS) Teaching the Teachers (TTT) Courses. METHODS: A Delphi-based procedure with 24 recommendations covering five main areas (Duration and place of the course; Faculty members; Content of the course; Evaluation of the teaching skills; TTT competency assessment) was distributed among a group of experts involved in MSUS teaching, in addition to an advisory educational expert being present. Consensus for each recommendation was considered achieved when the percentage of agreement was >75%. RESULTS: 21 of 24 invited participants responded to the first Delphi questionnaire (88% response rate). All 21 participants also responded to the second round. Agreement on 19 statements was obtained after two rounds. CONCLUSIONS: This project has led to the development of guidelines for the conduct, content and format of teaching at the EULAR MSUS TTT Courses that are organised annually, with the aim of training future teachers of EULAR MSUS Courses, EULAR Endorsed MSUS Courses, as well as national and local MSUS Courses. The presented work gives indications on how to homogenise the teaching at the MSUS TTT Courses, thus resolving current discrepancies in the field.

Ultrasound elastography is a reproducible and feasible tool for the evaluation of the patellar tendon in healthy subjects.

OBJECTIVE: To evaluate the feasibility and reproducibility of ultrasound elastography (UE) in the assessment of healthy patellar tendon and to describe its UE pattern. METHODS: Twenty-two patellar tendons of 11 out of 16 healthy subjects who met the inclusion criteria were evaluated three times by ultrasound (US) and UE at their proximal, middle and distal portions, by two separate sonographers with different experiences in UE. RESULTS: In all tendon portions the color map analysis showed a predominance of green (highly elastic), with good values of intra-observer (Operator 1: P-values = 0.790, 0.864, 0.865; Operator 2: P = 0.642, 0.882, 0.613 for proximal, middle and distal portions, respectively) and inter-observer (P = 0.657) agreement. For both operators the intra-observer analysis of the elasticity ratio (ER) between the tendon and the subcutis showed high agreement values (P < 0.001 for both operators). The inter-observer analysis showed also high agreement values (P < 0.001 at proximal, P = 0.001 at middle, P = 0.005 at distal portions). The overall analysis of the ER of the tendon portions showed values of (mean ± SD): 1.47 ± 0.64, 4.38 ± 1.36, 3.32 ± 1.20 for proximal, middle and distal portions, respectively. The mean time to perform the UE evaluation for the inexperienced operator was 5 min at the beginning of the study but decreased to 2 min after a few examinations were done. The mean time for the expert was 2 min for the entire study. CONCLUSIONS: UE is a feasible and reproducible tool for the evaluation of the healthy patellar tendon and further data are needed to define its role in the assessment of tendon pathology.

A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma.

BACKGROUND: Current data suggest that chemotherapy combinations may be superior to single agents in biliary tract cancer. The epidermal growth factor receptor (EGFR) pathway appears to be associated with tumor stage, prognosis and response to therapy. This trial was designed to evaluate the tolerability and efficacy of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan. PATIENTS AND METHODS: Patients with advanced (unresectable or metastatic) cholangiocarcinoma, ECOG PS 0-2, and adequate organ function were treated with panitumumab (9 mg/kg) on day 1, and gemcitabine (1000 mg/m(2)) and irinotecan (100 mg/m(2)) on days 1 and 8 of a 21-day cycle. The primary objective was to evaluate the 5-month progression-free survival (PFS). Secondary objectives included overall response rate (ORR) and overall survival (OS). Mutational analyses of EGFR, KRAS and BRAF were carried out when feasible. RESULTS: Thirty-five patients received a median of 7 (0-30) cycles. The most common grade 3/4 toxic effects were neutropenia (10 patients, 29%), thrombocytopenia (10 patients, 29%), skin rash (13 patients, 37%) and dehydration (9 patients, 26%). Two patients had CR, 9 had partial response (PR), and 15 had SD for a disease-control rate of 74% (by RECIST) in 28 assessable patients. Two patients went on to have surgical resection. The 5-month PFS was 69%. The median PFS was 9.7 months and the median OS was 12.9 months. In 17 testable samples, no EGFR or BRAF mutations were identified; there were 7 KRAS mutations, with no difference in OS by KRAS status. CONCLUSIONS: This study showed encouraging efficacy of this regimen with good tolerability. Further study in this area is warranted. Clinical Trials Number: The trial was registered with the National Cancer Institute (www.clinicaltrials.gov identifier NCT00948935).

Analysis of disease activity, functional disability and articular damage in patients with juvenile idiopathic arthritis: a prospective outcome study.

OBJECTIVES: We longitudinally studied outcomes of patients with juvenile idiopathic arthritis (JIA) using the Childhood Health Assessment Questionnaire (CHAQ) for physical disability and the Juvenile Arthritis Damage Index for articular (JADI-A) and extra-articular damage (JADI-E), and we correlated them with various disease activity variables. METHODS: Eighty-seven patients with JIA were included in the prospective follow-up study with median age 14 years (4.6-18.0), disease duration 5.2 years (2.0-18.9) and follow-up of 4.0 years (2.0-5.2). Besides JADI-A and JADI-E, and the assessment of active joints count, joints with limited mobility, ESR, CHAQ and radiographic damage of joints was also done. A correlation analysis of CHAQ and JADI with various disease activity variables was performed. RESULTS: The patient's distribution of JIA subtypes were polyarticular (32), systemic onset (13), oligoarticular (31), and enthesitis related arthritis (11). After a follow-up period, 46% patients had active disease compared to 83% patients at baseline (p<0.01). The CHAQ disability index improved over baseline, while radiological damage (p<0.001) and JADI-A and JADI-E scores worsened (p<0.001). CHAQ and JADI significantly correlated with the majority of disease activity variables. CHAQ DI was significantly higher in the patients with coxitis (p<0.01) and wrist arthritis (p<0.001). The most pronounced deterioration in articular damage (JADI-A) was observed in patients with sJIA (3.69 at baseline vs. 5.69 at study endpoint). CONCLUSIONS: The improvement of functional disability (CHAQ DI) was observed over the course of the disease, whereas radiological joint damage, JADI-A and JADI-E scores worsened. Children with systemic JIA, wrist arthritis, coxitis and prolonged active disease are at higher risk of progression of severe disability.

Major salivary gland sonography in Sjögren's syndrome: diagnostic value of a novel ultrasonography score (0-12) for parenchymal inhomogeneity.

OBJECTIVE: To validate ultrasonographic criteria for examination of the major salivary glands in the diagnosis of primary Sjögren's syndrome (SS). METHOD: A total of 209 consecutive patients with rheumatic diseases were selected according to the American-European Consensus Group (AECG) classification criteria for SS. One hundred and fifteen patients had primary SS, 44 had secondary SS, and 50 had sicca symptoms, and 36 subjects served as asymptomatic controls. This cohort was analysed for size, echogenicity, parenchymal inhomogeneity, focal changes, and posterior borders of the major salivary glands by ultrasonography (US). A novel US score for parenchymal inhomogeneity (0-12) was assigned and its diagnostic accuracy evaluated. RESULTS: Ultrasonographic abnormalities of salivary glands were detected in 107/115 (93.0%) patients with primary SS, in 12/44 (27.3%) with secondary SS, in 25/50 (50.0%) with sicca symptoms, and in 4/36 (11.1%) asymptomatic controls. Area under the receiver operating characteristic curve (AUC-ROC) for US inhomogeneity score was highly significant [0.96 +/- 0.01; 95% confidence interval (CI) 0.94-0.99, p < 0.000] for primary SS, with a sensitivity to specificity ratio of 91/83 for parotid and 93/90 for submandibular glands. Setting the cut-off US inhomogeneity score at 6 resulted in the best ratio of specificity (90.0%) to sensitivity (95.1%), with a positive predictive value of 72% and a negative predictive value of 96%. A US inhomogeneity score >or= 6 was closely correlated with positive biopsy (p < 0.000) and scintigraphy findings (p < 0.000). CONCLUSIONS: We demonstrate the high diagnostic value of a novel US score for parenchymal inhomogeneity (0-12) that could serve as a useful single US criterion in the evaluation of salivary gland involvement in primary SS.

Induced sputum in systemic sclerosis interstitial lung disease: comparison to healthy controls and bronchoalveolar lavage.

BACKGROUND: Induced sputum (IS) is a noninvasive tool, which can be used to collect cellular and soluble materials from lung airways. OBJECTIVE: To evaluate if IS may be a useful and safe tool for the detection of airway inflammation in patients with interstitial lung disease (ILD) in systemic sclerosis (SSc). METHODS: Sixty-eight patients with SSc and ILD as well as 18 healthy individuals (controls) were selected and submitted to IS examination. In 34 of 68 patients with SSc, bronchoalveolar lavage (BAL) was also performed. Safety of IS was assessed by comparison of forced expiratory volume in the first second (FEV(1)), FEV(1)/forced vital capacity ratio and peak expiratory flow before and after the IS procedure. Cell composition in samples collected by BAL and IS was correlated, and IS total and differential cell count in SSc patients and controls were compared. RESULTS: The total number of cells was significantly higher in IS samples of SSc patients compared to those of healthy controls. Mean percentage of neutrophils was also higher in SSc patients (41.79 +/- 23.89 vs. 27.37 +/- 17.90), as well as lymphocytes (17.42 +/- 19.70 vs. 3.13 +/- 2.28) and eosinophils (2.35 +/- 4.43 vs. 0.41 +/- 0.46). On the other hand, mean percentage of macrophages was higher in healthy individuals (69.10 +/- 19.15 vs. 36.96 +/- 20.68). In fluid recovered by BAL, the most frequent cells were macrophages (67.89% +/- 17.26), while neutrophils (14.77 +/- 17.18%) and lymphocytes (15.62 +/- 13.46%) were less frequent and eosinophils (1.66 +/- 2.08%) were rare. A similar pattern of cell composition was found in IS samples (41.15 +/- 21.67% of macrophages, 39.72 +/- 23.15% of neutrophils, 15.28 +/- 19.46% of lymphocytes and 2.56 +/- 5.03% of eosinophils). Strength of correlation between BAL and IS was significant for macrophages and neutrophils. After IS procedure was performed, improvement of FEV(1) (mean value before IS was 85.09 +/- 14.44 and 88.93 +/- 16.40 after IS) and FEV(1)/forced vital capacity (mean value before IS was 98.53 +/- 12.11 and 105.22 +/- 10.78 after IS) was observed. CONCLUSION: The IS method may allow a noninvasive assessment of cell composition in airway fluid and may contribute to the better understanding of upper/medium airway inflammation in SSc. Future studies are needed to verify whether IS can replace invasive procedures for the detection and monitoring of lung inflammation in SSc.

[Immunodiagnostic of liver echinococcosis].

Four immunological reactions of the liver echinococcosis are examined - Complement fixation test (CF), Latex agglutination test (LA), Bentonite agglutination test (BA) and Indirect haemagglutination test (IHA). The diagnostic "potentialities" of every sample are specified separately. IHA has given the best results, followed by LA. BA and CF in last place. The great significance of the immunodiagnostic with regard to diagnose of the disease is demonstrated and its place in the postoperative observation for clarifying of the prediction and for proving of the recidivation. It's obligatory to use several immunological samples, which complement one another. The immunological titers can stay at high rate in every stage of the illness, including during suppuration or partial calcification of the cyst.

[Attempt for etiopathogenic treatment of acute superior mesenteric artery occlusion by combination of small bowel resection and percutaneous artery stenting].

Acute mesenteric ischemia secondary to arterial occlusion is a highly lethal condition, mandating early diagnosis and prompt therapy, to prevent, or at least to minimize, bowel infarction. Progress in understanding the pathophysiology of mesenteric ischaemia has led to novel methods of treatment, so that in some circumstances therapy may be purely medical. More often surgery is demanded and is frequently life saving. Percutaneous transcatheter procedures are increasingly employed in both diagnosis and treatment. Close collaboration between surgeons, radiologists, physicians and anesthesiologists is therefore necessary if clinical outcome is to be improved. This conclusion is drawn by the presented case report.

Angiotensin-converting enzyme I/D polymorphism and macrovascular disease in systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by microvascular and macrovascular alterations. The D allele of the ACE I/D polymorphism is known to be associated with an increased incidence of atherosclerosis and has been recently proposed as associated with increased risk of SSc. This study evaluates the relationship between intima-media thickness (IMT), ankle-brachial pressure measurements (ABPI) and ACE I/D polymorphism in SSc patients. METHODS: According to the presence of ACE D allele (analysed by PCR), 53 SSc patients (47 females and 6 males; median age was 60.4 +/- 10.68 yrs; range 40-75 yrs) were divided in carriers of the D allele (DD + ID) (n = 46) and carriers of the I allele (II) (n = 7). In these patients, IMT and ABPI [calculated as the posterior tibial artery pressure (mmHg) divided by the brachial pressure] were obtained. Forty-three healthy controls (40 women and 13 men; median age 56.3 +/- 10.23; range 40-70 yrs) of the same ethnicity were recruited. RESULTS: SSc patients had IMT significantly higher than controls (0.85 +/- 0.03 vs 0. 68 +/- 0.01; P < 0.03). No significant differences (P > 0.3) in ABPI values between patients (1.018 +/- 0.10) and controls (1.091 +/- 0.11) were found. SSc patients with ACE DD and ID genotype showed an IMT significantly greater (0.89 +/- 0.03) than those carrying the II genotype (0.61 +/- 0.01) (P < 0.04). ABPI was not different among ACE gene genotypes. CONCLUSION: Our findings confirm an increased prevalence of macrovascular disease in SSc patients and show that IMT is greater in patients carrying the ACE DD and ID genotype in comparison with II homozygotes. This suggests that, in SSc, the presence of ACE D allele may predispose to an involvement of the macrovascular system.

The scleroderma Assessment Questionnaire (SAQ). A new self-assessment questionnaire for evaluation of disease status in patients with systemic sclerosis.

OBJECTIVE: To develop a self-assessment questionnaire and estimate its validity in the evaluation of disease status in patients with systemic sclerosis. PATIENTS AND METHODS: The developed questionnaire (SAQ) consists of 23 questions divided into four groups related to symptoms of vascular, respiratory, gastrointestinal and musculoskeletal dysfunction. One hundred and five patients with systemic sclerosis filled in the SAQ. Answers were assessed on a 0-3 scale and Index of Vascular Status (IVS), Index of Respiratory Status (IRS), Index of Gastrointestinal Status (IGS), Index of Musculoskeletal Status (IMMS) and Index of Disease Status (IDS) were calculated. Mann-Whitney and Kruskal-Wallis tests were used to examine the correlation of index score for particular organ system with various disease damage indicators. RESULTS: Mean score for IVS was significantly higher in patients with finger-tip ulcers or finger-tip osteolysis than in patients without, and was also higher in patients who had more severe capillary damage. Mean score for IRS was significantly higher in patients with pulmonary fibrosis, also in patients with reduced FVC, DLCO and DLCO/VA. Patients with esophageal hypomotility had a higher mean score for IGS than patients with normal esophageal motility. The mean score for IMSS showed a strong correlation with the skin score and was significantly higher in patients with reduced hand motility, joint contractures, muscle weakness or arthralgia/arthritis. The mean score for IDS was significantly higher in patients who had multisystemic involvement. CONCLUSIONS: The Scleroderma Assessment Questionnaire (SAQ) is a sensitive measurement of disease status and level of impairment of different organ systems in patients with systemic sclerosis.

Liposomal-encapsulated chemotherapy: preliminary results of a phase I study of a novel liposomal paclitaxel.

Liposome encapsulation of antineoplastic drugs entered clinical testing in the late 1980s. As carriers for a variety of agents, liposomes can allow successful delivery of agents that may be subject to rapid degradation in the serum and can modify the toxicity profile. In general, liposomes have demonstrated an ability to attenuate toxicities by their different pharmacokinetic profile and pattern of distribution. Differences in the constitution of the liposome can greatly affect the pharmacokinetic profile resulting in different patterns of toxicity. Characteristics such as size, charge, composition, and integrity can affect performance of the liposome. Liposome encapsulation of doxorubicin has been shown to reduce cardiac toxicity. Preliminary data suggest that encapsulation of paclitaxel can greatly modify neurotoxicity without the need for cremephor.

Oral therapy for colorectal cancer: how to choose.

Either alone or in combination with other antineoplastics, fluorouracil (5-FU) has been the mainstay of treatment of gastrointestinal, breast, and head and neck cancers for the past 40 years. Numerous active 5-FU schedules are in clinical use, but erratic oral bioavailability has historically mandated intravenous administration. Recently, two methods have been used to overcome the poor oral bioavailability of 5-FU. The first involves the use of prodrugs that are absorbed intact in the gastrointestinal tract and are ultimately converted to 5-FU in normal or tumor tissues. An alternate approach involves the inhibition of gastrointestinal degradation via coadministration of an inhibitor of dihydropyrimidine dehydrogenase, the rate-limiting enzyme in 5-FU catabolism. The oral fluoropyrimidines currently in development result in prolonged exposure to 5-FU and, therefore, have the potential to achieve clinical benefits similar to those seen with protracted intravenous infusions of 5-FU, but without the cost, complications, and inconvenience of ambulatory infusion pumps. This review describes several oral fluoropyrimidine regimens with activity in colorectal cancer: capecitabine (Xeloda), tegafur, UFT, S-1, and eniluracil plus 5-FU. An understanding of the distinct mechanisms of action and toxicity patterns of each regimen may ultimately guide treatment selection when multiple choices become available.

Anticardiolipin antibodies and clinical spectrum of antiphospholipid syndrome in patients with systemic lupus erythematosus.

In this paper we analyzed the clinical manifestation and course of the disease in 47 patients with systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) during prospective follow-up that lasted 2-5 years (mean 3.4). The most frequent features of APS were thrombosis (51%) thrombocytopenia (46.8%), and neuropsychiatric disorders (40.4%). These features were predominantly associated with elevated concentrations of IgG aCL isotype or with the presence of both IgG and IgM isotypes. Spectrum of neuropsychiatric disorders included mainly cerebrovascular ischemic disease (63%), but also some other, such as mental disorders and seizures, and, rarely, atypical migraine and transverse myelopathy. Thrombotic events in APS are the most significant for therapeutic and prognostic considerations. The treatment of basic disease (SLE) and conventional management of thromboembolic manifestation with heparin and/or dicoumarol (or warfarin) prevented neither the recurrent thrombosis in 9 patients (37.5%), nor the fatal outcome in 6 patients (12.8%). Further investigations and perhaps more aggressive approach to APS treatment are needed for better clinical care of these patients.

[Antinuclear antibodies detection in both HEp-2 cells and tissue section of the rat liver using indirect imunofluorescence]. / Okkrivanje antinukleusnih antitela indirektnom imunofluorescentom metodom na humanim epitelijalnim celijama-dva i tkivnim iseccima jetre pacova.

Having in mind the importance of indirect immunofluorescence in antinuclear antibodies detection, the study was aimed to compare characteristics of fluorescent visualization and specificity of HEp-2 cells with tissue cryosections of the rat liver. The study included 76 serum samples obtained from patients with systemic connective tissue diseases. Out of that number, fluorescence findings on HEp-2 cells and rat liver tissue were positive in 74 and 54 patients, respectively. At the same time, only foyr basic types of fluorescence were manifest in tissue samples, while HEp-2 cells revealed 3 mixed types, and within the patchy type, several subgroups were evidenced. Out of the 20 serum samples which enabled positive results only with HEp-2 cells, they all belonged to the group of patchy fluorescence. In addition to the better fluorescence visualization, owing to its more complexs antigenic structure. HEp-2 cells revealed significantly higher specificity when compared to the rat liver tissue thus enabling definitive identification of sertain specific autoantibodies, or they were used as screening methods for its further detection.

[Anticardiolipin antibodies in patients with systemic lupus erythematosus]. / Antikardiolipinska antitela kod bolesnika sa sistemskim eritemskim lupusom.

The aim of the study was to determine the prevalence and to evaluate clinical significance of anticardiolipin antibodies in cohort of 60 patients with systemic lupus erythematosus. The measurement of autoantibodies was carried out by standardized ELISA method using MELISA anticardiolipin IgG and IgM kits (Walker Diagnostics, Cambridgeshire, UK) A positive result indicated a value in GPL or MPL U/ml more than 3 SD above the mean value obtained with control sera of 48 healthy pearsons. IgG isotype alone, and both isotupe of anticardiolipin antibodies were found in 30 percent, in 6,7 percent and in 11,7 percent of patients, respectively. High or medium levels of IgG anticardiolipin antibodies were found in all 6 patients with actual venous or arterial thrombosis, but in only 3 out of 10 patients with history of thromboembolic features. All 6 patients with actual thrombocytopenia and 3 female with recent spontaneus abortion also had elevated levels of the same isotype. Total anticardiolipin antibodies (IgG and IgM) were significantly associated with recent or history of thrombocytopenia. In conclusion, we emphasize the association of IgG anticardiolipin antibodies with recent events of antiphospholipid syndrome in patients with systemic lupus erythematosus.

Origin of laminin in the extracellular matrix of human tumor xenografts in nude mice.

Monoclonal antibodies reacting exclusively with laminin of human origin and a polyclonal antibody reacting with both murine and human laminin were used to immunohistochemically study the extracellular matrix of four human tumors grown as xenografts in nude mice: a lung carcinoma and a yolk sac carcinoma because they produced cell associated laminin in vitro; and two hepatocellular carcinomas which did not produce cell associated laminin in vitro. The extracellular matrix of the xenografts of the lung carcinoma and the yolk sac carcinoma contained laminin of both human and murine origin. Xenografts of liver carcinoma contained only laminin of mouse origin. This shows that the malignant cells capable of laminin production in vitro contribute this glycoprotein to the extracellular matrix of the solid tumor formed by them in vivo.