[Frequency of antiphospholipid antibodies and Leiden mutation of hemostasis Factor V in unexplained recurrent fetal and embryo loss]. / Chestota na antifosfolipidni antitela i Leidenova mutatsiia Faktor V na kr'vos'sirvaneto pri povtariashta se neobiasnima fetalna i embrionalna zaguba.

Object of the study are women with a history of unexplained recurrent embryo, fetal and early neonatal death, severe preeclampsia, fetal growth retardation, abruptio placentae, puerperal thromboses. Quite often placental insufficiency is linked to abnormal vascular system and hemostatic disturbancies. In about 65% of the women with a complicated and in 18% of the women with a normal pregnancy are observed different genetic anomalies that lead to a hypercoagulative state. A major place is taken by the Leiden mutation of hemostasis factor V, by protein C and protein S deficiency, etc. Another disease that leads to arterial and venous thromboses and is most often linked to recurrent miscarriage is the antiphospholipid syndrome. Many authors confirm the findings of large placental infarctions and thromboses in women who are positive for antophospholipid antibodies.

[Alpha-2 macroglobulin in serum and synovial fluid of patients with rheumatoid arthritis and osteoarthrosis]. / Alpha2-makroglobulin v syvorotke i sinovial'noi zhidkosti bol'nykh revmatoidnym artritom i osteoartrozom.

AIM: To study concentrations of alpha-2-macroglobulin (A-2-MG) in blood serum and synovial fluid (SF) in patients with rheumatoid arthritis and formulation of basic clinical, laboratory and x-ray criteria of RA activity. MATERIALS AND METHODS: A-2-MG levels were measured in the serum and SF from 151 RA patients and in the serum of 20 patients with osteoarthrosis (OA) and 62 healthy donors. The serum concentration for RA patients was 166 +/- 65.3 mg%, for OA patients--175.26 +/- 36.99 mg% and for healthy donors--177.772 +/- 50 mg%. Mean concentration of SF A-2-MG in RA patients was 98.77 +/- 82.43 mg%. CONCLUSION: Changes in the concentration of A-2-MG are unrelated to inflammation activity in the joints of RA and OA patients. Serum and synovial concentration of this protein corresponds to changes in the concentration of IgM and rheumatoid factors in RA patients.

Anticardiolipin antibodies in spontaneously hypertensive rats (SHR), stroke-prone SHR and normal Wistar rats.

1. Anticardiolipin antibodies (ACA) can be detected in the serum of patients with autoimmune disturbances, ischaemic heart disease, myocardial infarction, neurological disorders and other medical conditions. Elevated values of these autoantibodies can be associated with recurrent fetal loss, arterial and venous thrombosis and thrombocytopenia. 2. In the present study, we investigated the presence of ACA in three rat strains, namely normal Wistar rats (WR), spontaneously hypertensive rats Okamoto-Aoki (SHR) and stroke-prone SHR (SHRSP). All animals were examined at four ages: 1, 4, 10 and 12 months of age. Anticardiolipin antibodies were determined by ELISA. 3. Anticardiolipin antibody levels in normal WR, which were used as controls, were lowest at 1 month and increased significantly from the 4th month on. At the prehypertensive age (1 month), ACA levels in SHR and SHRSP were significantly higher compared with control WR, decreased with age and were significantly lower at 4, 10 and 12 months compared with age-matched WR. 4. These differences may be a result of immunological disorders in SHR.

[Spontaneous abortions in Sneddon's syndrome]. / Spontanni aborti pri sindrom na Sneddon.

Following the publications on the connection between Sneddon's syndrome and the antiphospholipid++ syndrome, the attention of researchers concentrated on the reproductive problems of women comprising the greater part of patients suffering from Sneddon's syndrome. One of the main indications of these almost coinciding syndromes are miscarriages for no obvious reason. It is supposed that the general mechanism is thrombosis. In a group of 38 patients with Sneddon's syndrome 32 (84%) are women. Twenty-eight of them have altogether given bright 43 times. Seven of them have suffered miscarriages for no obvious reason and three have habitual miscarriages. Three women have sterility problems.

Protein C activity in patients with antiphospholipid syndrome.

The interaction between antiphospholipid antibodies and the protein C system may explain at least a part of the mechanisms underlying thrombosis in the antiphospholipid syndrome (APS). We evaluated the protein C activity, factor V Leiden mutation and the presence of several types of antiphospholipid antibodies in 60 patients with antiphospholipid syndrome. Nineteen patients (31.6%) and 5 controls (8.3%) had decreased protein C activity (95% CI, 10%-37%). 14 patients with high levels of antiphospholipid antibodies and normal factor V molecule (37.8%) and none of the patients with antiphospholipid antibodies in normal ranges and normal factor V molecule had decreased protein C activity (95% CI, 24%-52%; (x 510.4; p 5 0.001). Leiden mutation was found in 5 controls (8.3%) and in 4 patients (8.3%; 95% CI, 8-24%). We found a strong association between decreased protein C activity and presence of anticardiolipin antibodies and antibodies against b2-glycoprotein I. The decreased protein C activity depended on the antibody titre. Although abnormalities of the natural anticoagulant proteins like protein C and protein S seem to be involved in the pathogenesis of the APS, activation of protein C also occurs during the process of clotting. Studies such as we describe may help us identify subsets of patients whose clotting is dependent on protein C-antiphospholipid interactions that may lead to future novel therapies.

Prevalence of IgM-, IgA- and IgG-rheumatoid factors in seronegative polyarticular disease compared to pauciarticular disease in juvenile chronic arthritis as measured by ELISA.

OBJECTIVE: To determine the prevalence of the rheumatoid factor isotypes measured by enzyme-linked immunosorbent assay (ELISA) in polyarticular and pauciarticular juvenile chronic arthritis (JCA), and evaluate the diagnostic test qualities. PATIENTS AND METHODS: 53 patients with JCA (20 with seronegative polyarticular disease at onset, 21 with pauciarticular onset and course of disease and 12 with extended pauciarticular disease), as well as 125 control children (58 healthy controls and 67 patients with other diseases) were tested. ELISA for the detection of IgM-, IgA- and IgG-isotypes of RFs was used. The diagnostic characteristics of the tests were evaluated by means of clinical epidemiology methods. RESULTS: The prevalence of the ELISA for IgG-, IgA-, and IgM-RF for JCA patients vs all controls at optimal cut-off titres was 13%, 29%, and 32%, respectively. The test for IgG-RF was established to be of no significance. IgA-RF had higher prevalence in the polyarticular and extended pauciarticular form, 40% and 33%, respectively. IgM-RF showed a prevalence of 55% for the polyarticular and 42% for the extended pauciarticular form. No significant prevalence has been found in the pauciarticular form. CONCLUSION: Our results indicate that ELISA for IgG-RF is of no diagnostic value for JCA. The ELISAs for IgM- and IgA-RFs demonstrated a diagnostic significance for the polyarticular and extended pauciarticular form. Juvenile chronic arthritis (JCA) is a heterogeneous disease which encompasses different forms defined by the type of onset. There is evidence, supported by immunogenetic studies that the various subgroups may represent distinct disease entities [1, 2]. Numerous immunological abnormalities have been detected in JCA, but the most characteristic serological findings are ANA and IgM-rheumatoid factor, thought to be useful in the classification of patients and their management. Antinuclear antibodies are universal in JCA, most commonly found in children with early onset pauciarthritis and late onset seropositive polyarthritis [1, 2, 3]. In contrast, the IgM-rheumatoid factor, measured by conventional agglutination techniques, is a hallmark only of polyarthritis with late onset resembling adult rheumatoid arthritis. This group of patients with "seropositive" disease represents less than 20% of all JCA children. Of those patients with "seronegative" disease 20-30% have a systemic onset and the remainder have either a pauciarticular or polyarticular form [2, 3]. Following the introduction of more sensitive techniques, it has already been established that rheumatoid arthritis (RA) patients' sera contain not only the "classical" 19S IgM-RF, but also other isotypes of the rheumatoid factor (RF). A number of studies have emphasized the presence of IgG-, IgA-, IgM- and even IgE- RF in patients with "seronegative" RA [4, 5, 6]. The aim of this study is to determine the prevalence of IgG, IgM and IgA RFs and to attempt at evaluating the diagnostic and prognostic qualities of the ELISA-tests for rheumatoid factor isotypes in polyarticular and pauciarticular forms at onset of JCA.

Sperm, nuclear, phospholipid, and red blood cell antibodies and isotype RF in infertile couples and patients with autoimmune rheumatic diseases.

PROBLEM: To determine if measuring of nonorgan-specific autoantibodies is useful for better understanding and management of unexplained infertility. METHODS: Sera were obtained from 70 infertile couples, 57 rheumatic patients, and 76 fertile donors. Sperm antibodies (SA) were detected by the tests of Kibrick and Friberg, anti-histones, anti-cardiolipin antibodies, and RF isotypes by ELISA, antinuclear antibodies by indirect immunofluorescence, and anti-red blood cell antibodies by Capture-R. RESULTS: Multiple autoimmune reactivity (both partners positive and/or more than one type of autoantibody involved), higher than naturally occurring in fertile individuals, was found in 55% of the idiopathically infertile couples. IgA-RF was the dominant autoimmune marker. SA revealed similar rates in patients with rheumatic diseases and in infertiles with or without other autoantibodies. CONCLUSION: Although no single autoimmunity marker could predict occurrence of SA, the coincidence of enhanced polyclonal autoimmunity in both partners of infertile couples might potentiate their negative effect on reproduction.

[A rare case of gallbladder interposition in the extrahepatic bile ducts]. / Riaduk sluchai na interpozitsiia na zhluchniia mekhur v ekstrakhepatalnite zhluchni putishta.

This is a report on an exclusively rarely met with anomaly, consisting in interposition of the gallbladder within the extrahepatic bile ducts where ducti hepatici open into the gallbladder. Ductus cysticus assumes the role of ductus choledochus, and terminates in papilla duodeni major. Ductus hepaticus communis is completely lacking. The aforementioned anomaly of the biliary system in the female patient reported on is supplemented by a vascular variation, consisting in the following: a. hepatica dex. passes over the isthmus of the gallbladder, and after forming a kink it is directed to hilus hepatis. At the apex of the kink a. cystica divides with blood supply being secured by the latter and the branches of a. hepatica dex. A similar anomaly is described by Nell Krug (2), whereas J. Denes (1) reports on a case where only ductus hepaticus dex. opens into the gallbladder.

[The hemodynamic changes during preoperative acute normovolemic hemodilution (prospective, randomized and comparative research)]. / Izmeneniia gemodinamiki pri dooperatsionnoi ostroi normovolemicheskoi gemodiliutsii (prospektivnoe, randomizirovannoe i sravnitel'noe issledovanie).

Fifteen patients examined after preoperative acute normovolemic hemodilution (PANH) up to hematocrit value of 0.30 developed a significant increase in cardiac output (CO) and cardiac index (CI) and a decrease in total peripheral resistance (TPR), other hemodynamic parameters remained unchanged. In normal hemodynamics the patient's age is not a contraindication for PANH. Noninvasive monitoring of hemodynamic parameters, CO, CI and TPR in particular, during surgery employing PANH is obligatory for the early diagnosis and correction of impaired circulation.

[A modified technic of preoperative acute normovolemic hemodilution--the advantages and economic effect of its use in planned colorectal surgery]. / Modifitsirana tekhnika na predoperativna ostra normovolemichna khemodilutsiia--predimstva i ikonomicheski efekt ot prilozhenieto i v planovata kolo-rektalna khirurgiia.

In a prospective and comparative study were included 129 patients undergone planned operation for colorectal cancer. They were divided in two randomized groups: Group A consisted of 65 patients operated under conditions of preoperative acute normovolemic hemodilution (PANHD) by an own modified technique with Ringer-lactate and hemodex. Group B (control) included 64 patients operated with the use of homologous blood substitution. The results in the two groups were compared as to: intra- and postoperative blood transfusions; time (in days) of postoperative treatment; number of postoperative complications. Statistically significant differences (p less than 0.001) referrable to all three compared values were found. The modified PANHD technique in planned colorectal surgery is safer for the patients than the so far suggested techniques and may readily gain acceptance with the use of solutions of domestic produce. It leads to significant decrease in homologous blood transfusion, shortening the postoperative stay in hospital of patients subjected to hemodilution. The number of patients in whom postoperative complications developed was reduced.

[The postoperative changes in the cellular immune response in vivo in patients with colorectal carcinoma after preoperative acute normovolemic hemodilution--a randomized, prospective and comparative study]. / Sledoperativni promeni na kletuchniia imunen otgovor in vivo u bolni s kolorektalen kartsinom sled predoperativna ostra normovolemichna khemodilutsiia--randomizirano, prospektivno i sravnitelno prouchvane.

The in vivo changes in the cell-mediated immune response (CMIR) were studied in 40 patients undergone planned operation for colorectal cancer; delayed skin hypersensitivity test was used after intracutaneous application of standardized set of antigens produced at the Research Institute of Infectious and Parasitic Diseases in Sofia. The tests were performed, as follows: T0--2 days before the operation; T1--1 and T2--7 days after the operation. The tests were read after 48 hours, taking into consideration the sum of the mean diameters of the "positive" papules (in mm) and the number of antigens inducing positive skin response. Twenty patients received preoperative acute normovolemic hemodilution (PANHD)--group A, and the other 20--blood substitution by routine method--group B, control. Comparison of the results for T0 revealed no significant difference between the two groups. For T1 and T2 the mean sums of the mean diameters of positive papules in group B patients showed statistically significant decrease (p less than 0.001) both compared to T0 and to the respective values in group A patients. The following conclusions were made: 1. After PANHD the patients retained normal CMIR after operation: 2. Patients who received homologous blood substitution had statistically significant inhibition of CMIR on the 7. postoperative day.

[Continuous thoracic epidural analgesia in surgical interventions on the upper half of the abdomen--the noninvasive monitoring of the early hemodynamic changes]. / Produlzhitelna torakalna epiduralna analgeziia pri operativni namesi v gornata polovina na korema--neinvazivno monitorirane na rannite khemodinamichni promeni.

Operative interventions in the upper half of the abdomen have been performed in 32 surgical patients under thoracic epidural analgesia (TEA) with bupivacain at T4-L2 level, with the use of catheter technique. Before operation the patients were hydrated with 12.5 per cent of the circulating blood volume, calculated by nomogram. By noninvasive approach were monitored: pulse rate (PR), mean arterial pressure (MAP), minute cardiac volume (MCV), peripheral vascular resistance (PVR) and cardiac index (CI) for the following times; T0--basal preoperative value, T1--on the 5. min; T2--on the 10. min; T3--on the 15. min.; T4--on the 20 min.; T5--on the 50. min after application of bupivacain analgesia. The results were compared by variation analysis to T0. PVR was reduced with statistical significance for T2, T3 and T4 (p less than 0.01). MCV, CI and MAP tended to be reduced, while PR showed no significant changes. The results may be summarized, as follows: 1. Noninvasive monitoring of PR, MAP, MCV, CI and PVR in TEA is necessary for early detection and control of their pathologic changes; 2. The hemodynamic changes in TEA with bupivacain at T4-L2 level after premedication with vagolytic and hydration with Ringer-lactate (in amount 12.5 per cent of the circulating blood volume) are not significant and do not require additional treatment; 3, TEA at T4--L2 level allows performance of operative interventions in the upper half of the abdomen with adequate analgesia and relaxation, being particularly indicated for patients at risk.

[Changes in the level of urinary secretory immunoglobulin A in patients with recurrent pyelonephritis]. / Promeni v nivoto na urinniia sekretoren imunoglobulin a pri bolni s retsidivirashti pielonefriti.

The urine concentration of secretory immunoglobulin A was studied in 58 healthy persons (26 women and 32 men) and in 55 patients (44 women and 11 men) with chronic recurrent pyelonephritis before the beginning of the antibacterial treatment. An immunoenzyme method on a solid phase was used (ELISA). In 21 patients a lowered urine secretory immunoglobulin A level (IgA) was found, in 19 patients it was elevated and in 15 patients it was in normal ranges. In the group of patients with an elevated secretory IgA level the antibacterial treatment was successful in 89.5% of the patients while in the group of patients with a lowered secretory IgA level the treatment was successful only in 61.9% of the patients. In 12 patients the secretory IgA level was examined after the treatment and in 72.7% of them it was changed--in 38.2% of the patients the level was lowered and in 34.5% of the patients it was elevated. The local immune response of the organism against infections is discussed.

[Immunochemical studies in glomerulonephritis with mesangial immunoglobulin A precipitation]. / Imunokhimichni prouchvaniia pri glomerulonefriti s mezangialno otlagane na imunoglobulin A.

Serum IgA, C3 and circulating immune complexes were examined in 20 patients with morphologically proved chronic glomerulonephritis with mesangial IgA precipitates and in 39 clinically healthy controls. The immune complexes were analyzed. 10 patients were with Berger's disease, 8 patients--with secondary IgA glomerulonephritis accompanying chronic liver disease and 1 patient was with Henoch-Schönlein's purpura. No significant differences were found between the mean values of IgA, C3 and the circulating immune complexes in the patients and the healthy controls as well as between the actively ill patients and those in remission. IgA and IgM in the immune complexes were significantly higher in the patients than in the healthy controls. IgA level in the immune complexes was significantly higher in the patients with active disease than in the patients in remission. In the patients with liver disease C3 and C4 often were not found in the immune complexes. In these patients it is possible that aggregates of immunoglobulins are found instead of immune complexes. The IgA level in the immune complexes could serve as a criterion for the disease activity.