The MDR1 3435 polymorphism in patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a multifactorial disease, the pathogenesis of which involves immunological, genetic and environmental factors. P-glycoprotein (P-gp) encoded by the MDR1 gene, is an important transporter for many drugs, xenobiotics and cytokines and may be associated with many immunological processes and apoptosis. The activity of P-gp is genetically determined. Naturally occurring MDR1 polymorphisms have been described and correlated with potential clinical effects. Several mutations in the MDR1 gene have been recognized, but only some of them are associated with P-gp expression. The C3435T polymorphism was found to correlate with the activity of P-glycoprotein. The aim of the study was to evaluate the C3435T MDR1 polymorphism in patients with rheumatoid arthritis and to investigate a possible correlation with disease susceptibility, activity and severity. METHODS: The study was carried out in 92 patients with rheumatoid arthritis and 97 healthy subjects as a control group. The C3435T polymorphism was determined using the PCR-RFLP method. RESULTS: The distribution of C3435TT MDR1 genotypes in RA patients did not differ significantly from that in a control group and was as follows: 3435CC in 25 (26.9%) subjects, 3435CT in 50 (53.8%) and 3435TT in 17 (18.3%). The probability of remission of RA symptoms after therapy with methotrexate and glucocorticosteroids however, was 2.89-fold greater in patients with the 3435TT genotype compared to patients with the genotypes 3435CC and 3435CT. The risk of having an active form of rheumatoid arthritis resistant to therapy with disease-modifying antirheumatic drugs in patients with 3435CC and 3435CT genotypes was 2.89 times greater than in homozygous 3435TT subjects. CONCLUSION: We suggest that the C3435T MDR1 polymorphism is not an important genetic risk factor for RA susceptibility, but that this polymorphism may have an influence on the activity of the disease and its response to therapy with disease-modifying antirheumatic drugs.

[Neurological deficits in patients with primary and secondary anticardiolipin syndrome]. / Powiklania neurologiczne u chorych z pierwotnym i wtórnym zespolem antyfosfolipidowym.

27 patients (22 women, 5 men); age 17 to 56 yr. (mean age 37 yr.) were included in this study, 4 had primary antiphospholipid syndrome and 18 secondary antiphospholipid syndrome in the course of systemic connective tissue disease and in 5 cases increased levels of anticardiolipid antibodies were found which did not meet the criteria necessary for diagnosis of secondary antiphospholipid syndrome. The mean duration of the disease was 8 yrs. Among primary antiphospholipid syndrome patients two had ischaemic stroke, one migraine-like headache and seizures. 18 patients had lupus erythematosus, two mixed connective tissue disease, one rheumatoid arthritis, one Sjögren syndrome, one Behçet disease. In 55% of patients migraine-like headache, polyneuropathies, encephalophaties, stroke, seizures and vision disturbances were present. In 18.5% of patients EEG exam revealed focal lesions with tendency for generalisation. On brain stem auditory evoked potentials examination, in 11.1% of patients conductivity lesions in mesencephalon and pons were found, visual evoked potentials, in 11.1% of patients in visual tracts. In 37% of patients, neuropathy was found on EMG exam. Neurological symptoms are one of the most frequent disorders in systemic connective tissue disease associated with the presence of anicardiolipin antibodies.

[Antiphospholipid antibodies in high-risk pregnancy]. / Przeciwciala antyfosfolipidowe w ciazy wysokiego ryzyka.

UNLABELLED: Recently the connection of antiphospholipid antibodies (aPLs) presence with pregnancy loss and complications in pregnancy has been observed APLs related obstetric complications include: miscarriages after 10 weeks, IUGR, intrauterine foetal death, preeclampsia and severe preeclampsia. Our objective was to determine the aPLs prevalence in patients with recurrent pregnancy loss and/or complicated pregnancy. We examined 154 pregnant women aged 19-42 (average of 29.1) with recurrent pregnancy loss, current pregnancy complicated by preeclampsia and severe preeclampsia and/or IUGR, thrombotic episodes, thrombocytopenia or autoimmune disease. In all the patients anticardiolipin antibodies (aCL) were determined at least twice using ELISA and their coagulation system was tested including lupus anticoagulant (LA) test. In justified cases immunological examinations detecting connective tissue systemic diseases were conducted. Increased aCL titre was detected in 54 (34.4%) women. Statistically significant risk of increased aCL titre was observed in patients with autoimmunological diseases (RR = 4.3). Increased, but Statistically insignificant, risk of high aCL titre was observed in patients with venous thrombosis (RR = 2.45) as well as in patients with thrombocytopenia (RR = 2.45). LA prevailed significantly more often in patients with venous thrombosis episodes (RR = 6.33) and with autoimmunological diseases (RR = 17.4). Preterm deliveries were significantly more frequent in pregnant women with increased aCL titre and/or LA. Moreover, in this group foetal death and preterm stillbirth more often occurred. The above mentioned risks increased when aCL and LA coexisted. No relation between increased aPLs and miscarriage frequency was observed. CONCLUSIONS: 1) Increased aPLs titre prevail in multiparas with bad obstetrical anamnesis and with pathological course in present pregnancy, 2) increased aPLs titre prevail in patients with autoimmunological diseases, 3) increased aPLs titre are connected with pregnancy pathology manifested by frequent preterm deliveries and intrauterine foetal deaths.

[Backache and and related absenteeism]. / Bóle pleców i absencja chorobowa z tego powodu.

The aim of this work was to compare the outcome of the questionnaire survey of low back pain with data on related sickness absenteeism. The questionnaire was responded by 585 (88.8%) employees. Of these number 288 (49.2%) respondents complained of low back pain. Sick leaves were given to 48 (16.7%) persons who had reported low back pains in the questionnaire and to 25 (8.4%) employees of 297 who had not reported the pain and also to 4 (5.4%) persons of 57 who had not responded to the questionnaire. Among those who had not complained of low back pain and were given sick leaves, mostly short ones, there were mainly men and blue collar workers. On the basis of our survey it seems that the analysis of sickness absenteeism due to low back pain does not completely reflect the prevalence of this disease, and that epidemiological studies of the prevalence should also take into consideration relevant sickness absenteeism.

Effects of ionic and non-ionic contrast media on platelet function as evaluated by plasma concentration of beta-thromboglobulin.

The aim of the study was to evaluate the effects of ionic and non-ionic contrast media on platelet function. In 44 patients who underwent angiography, the plasma concentration of beta-thromboglobulin (beta TG) was measured before and after ionic contrast medium (diatrizoate) administration in 22 patients and non-ionic contrast medium (iopromide) in the other 22 patients. A significant decrease in the plasma beta TG levels after intraarterial contrast medium injection occurred in both groups of patients. No significant beta TG level changes occurred in patients with normal pre-examination beta TG levels in both groups. In patients with elevated beta TG levels before arteriography, beta TG returned to normal values after contrast medium injection in both groups. There was no significant correlation between the amount of administered contrast medium and beta TG concentration after angiography. These results suggest that platelet function is not affected by either ionic or non-ionic contrast medium in patients with normal platelet activation. In patients with enhanced platelet activation, the activation became normal after contrast medium administration.

[Encephalopathy in the course of idiopathic hypereosinophilic syndrome -- clinical-morphological correlations]. / Encefalopatia w przebiegu zespolu hipereozynofilowego samoistnego--korelacje kliniczno-morfologiczne.

A case of 33-year-old man, who underwent numerous hospital admissions caused by multiple progressing disseminated neurological abnormalities is presented. At first multiple sclerosis was a tentative diagnosis. Because of persistent eosinophilia, after exclusion of other causes of increased eosinophil count, idiopathic hyperoesinophilic syndrome was diagnosed. The case was confirmed neuropathologically. The authors discuss causes of idiopathic hyperoesinophilic syndrome. Very exceptional history of the syndrome, with dominant CNS involvement, is discussed.

[Gastrointestinal non-Hodgkin's lymphomas. Personal observations]. / Chloniaki zlosliwe nieziarnicze przewodu pokarmowego. Obserwacje wlasne.

The localization, symptoms, endoscopic findings, histologic type, infiltration of bone marrow, lymphoma cell presence in the blood, and results of therapy were evaluated in 18 patients with gastrointestinal lymphoma. Only 9 patients met the criteria of primary gastrointestinal lymphoma, the remaining 9 presenting an extra-nodular localization of systemic disease, i.e. secondary lymphoma. The most common site of process was stomach, and most of the patients had histologically documented a high grade malignant lymphoma. Necessity of supplementing surgery with chemo- and/or radiotherapy was discussed. Such combined treatment should give a 10-year survival time in 60% of the treated patients (confirmed with the Kaplan-Meier's method). The authors concluded that stomach is the most common localization of gastrointestinal lymphoma, and that gastrointestinal non-Hodgkin's lymphoma diagnosis should include peripheral blood and bone marrow haematological examinations which clearly rise the reliability of differentiation between primary or secondary lymphomas.

[Ocular symptoms in Wegener's granulomatosis--personal observations]. / Objawy oczne w ziarniniaku Wegenera--obserwacje wlasne.

The authors present 10 patients treated for Wegener's granulomatosis. In 5 of of them (50%) the ocular changes were observed: in 3-infiltration of the orbit, including one case with infiltration of lacrimal ducts, and in 2-the recurrent bacterial conjunctivitis. On the account of the rareness of the disease and its various symptoms, the diagnosis, in some cases, was made fairly late. It was emphasized that the ocular lesions may be the first symptoms of Wegener's granulomatosis. The bacterial conjunctivitis, keratitis, scleritis, and orbital pseudotumor in patients with chronic respiratory tract and nasal sinuses changes should arouse suspicion of Wegener's granulomatosis and are an indication for detailed tests.

[Results of the treatment of Sjögren's syndrome with TFX (thymus factor X)]. / Ocena wyników leczenia preparatem TFX (thymus factor X) u chorych z zespolem Sjögrena.

Seven patients with Sjögren's syndrome (6 with primary and 1 with secondary form of the syndrome developing during SLE) were treated with TFX Polfa in ampoules of 10 mg during 6-12 month. Before the treatment, besides evaluation of the general clinical condition, the following immunological parameters were determined: IgG, IgA and IgM levels, absolute lymphocyte count, T-cell and B-cell counts, absolute neutrophil count, antinuclear antibodies, circulating immune complexes and skin tests with recall antigens (tuberculin and distreptase). The clinical condition of the patients was determined at monthly intervals and the immunological investigations were repeated after the treatment which lasted 6-12 months. In all patients alleviation was observed of the clinical manifestations of the disease with decreased proneness to infections. In some patients improvement was observed of the determined immunological parameters, in the first place, reversal of cutaneous tests from negative to positive.

Immunological profile in patients with non-Hodgkin's lymphomas.

In 51 cases with non-Hodgkin's lymphoma and in 25 healthy subjects, immunological state was determined by resorting to values of the following parameters of nonspecific immunity: the levels of G, A and M immunoglobulins, antistreptolysins, complement, T and B lymphocytes, monocytes, granulocytes and the skin test with recall antigens. The values were expressed according to the points system of Nagel et al. The results of studies revealed that in all but one case the values were lower than in controls. Also certain differences in immunological profile between respective lymphoma types were observed.