A method to differentiate between anti-C1q antibodies and C1q-binding immune complexes using collagenase-digested solid phase C1q.

A method for the detection of circulating immune complexes in the presence of autoantibodies to C1q is described. Solid phase C1q-digestion with bacterial collagenase results in the elimination of the collagen-like region of C1q. Binding of model immune complexes to this modified solid phase C1q is practically unaltered, while reactivity of anti-C1q antibodies is abolished by this procedure. In conjunction with an ELISA using the collagen-like region of C1q as antigen this modified C1q solid phase assay may be used to determine immune complexes and anti-C1q antibodies in the sera of patients with autoimmune rheumatic diseases.

HLA-DR1-positive patients suffering from rheumatoid arthritis are at high risk for developing mucocutaneous side effects upon gold therapy.

Population studies suggest an association between RA and, depending on the ethnic background, HLA-DR1 and/or -DR4. One standard regimen for the treatment of RA is the use of gold compounds like SATM to arrest progression of the disease. In the present study, the immunogenetic background of RA patients developing side effects upon SATM treatment was determined. A total of 53 patients under SATM therapy were tested for their HLA-DRB and -DQ alleles by DNA typing; a significantly higher frequency of HLA-DR1 (p < 0.004, uncorrected) was observed in patients presenting with mucocutaneous side effects (MCT) when compared with patients without MCT. The RR was 6.85. Thus, HLA-DR1 seems to be a marker for the susceptibility of gold adverse reactions.

Prediction of interstitial lung involvement in rheumatoid arthritis. The value of clinical data, chest roentgenogram, lung function, and serologic parameters.

We initiated the present study to predict interstitial lung involvement in rheumatoid arthritis (RA) by means of logistic regression analysis of clinical data, lung function, chest roentgenogram, and serologic parameters. Fifty-eight nonsmoking patients with RA were randomized from the rheumatologic unit and sent for investigation to the pulmonary department. Bronchoalveolar lavage (BAL) was performed in the middle lobe and the BAL fluid was considered abnormal in case of increased cell count per milliliter and/or lymphocytosis and/or neutrophil granulocytosis; these findings or combinations thereof were found in 42 (72.4 percent) of 58 cases. The patients' data that had an impact on the normality of BAL were the sex (p = 0.001), vital capacity (p = 0.028), peripheral blood T-helper cells (OKT4+) (p = 0.025), DR(+)-lymphocytes (p = 0.002), and antinuclear antibodies (p = 0.025). By means of the logistic regression analysis, it was possible to reach high significance in the prediction of interstitial lung involvement, with a sensitivity of 92.9 percent and a specificity of 75.0 percent (p less than 10(-6)). The efficiency of prediction was 87.9 percent. From these results, we conclude that interstitial lung involvement in RA is predictable from laboratory findings that have been yielded by noninvasive diagnostic techniques. These data should be used in clinical routine monitoring and they may help to facilitate the assessment of whether bronchoscopy is indicated.

Modulation of nitric oxide synthase activity by ibuprofen.

Inhibition of NO synthesis represents a new therapeutical approach in the treatment of inflammation. Clinical use of NOS inhibitors will necessitate the design of drugs selective for iNOS, because inhibition of constitutive endothelial NOS may cause adverse cardiovascular side effects. This study examines the effect of ibuprofen and its stereoeisomeric components on the activation of iNOS and cNOS as well as on the NO production by human umbilical vein endothelial cells. At therapeutic concentrations Ibuprofen activated iNOS and inhibited NOS. In endothelial cell culture experiments activation of NO production was seen especially at supratherapeutic ibuprofen concentrations. Both stereoisomeric components of ibuprofen showed comparable effects. This drug can therefore not be used for the selective inhibition of iNOS.

Inhibition of cytokine production and adhesion molecule expression by ibuprofen is without effect on transendothelial migration of monocytes.

The present study focusses on the effects of ibuprofen and its enantiomers on cytokine production by peripheral blood monocytes and endothelial cells as well as on the potential modulation of ADM-expression by human umbilical vein endothelial cells and the concomitant effects on monocyte transendothelial migration as measured by a cell migration assay system. This consists of an endothelial cell monolayer on a solid collagen substrate, i.e. an artificial vessel wall construct. We observed a significant inhibition by 100 microg/ml ibuprofen of VCAM-1 expression by endothelial cells while ELAM-1 and ICAM-1 expression was not influenced. However, we could not see any concomitant inhibitory effects on the spontaneous migration of monocytes after preincubating the endothelial cell monolayer with ibuprofen up to concentrations of 100 microg/ml and activating with suboptimal and optimal concentrations of TNF-alpha. Our monocyte transendothelial migration system reflects very sensitively endothelial cell-activation even by very low TNF-alpha concentrations. (S)- and (R)-ibuprofen were equal in their inhibitory/activating effects on cytokine production, with the exception of stronger IL-8 induction in endothelial cells by (R)-ibuprofen as compared to its chiral analogue.

[Baker cysts: an accompaniment of chronic diseases of the knee joint (author's transl)]. / Baker-Zyste: Begleitsymptom chronischer Erkrankungen des Kneigelenkes.

One hundred and twenty one Baker cysts demonstrated by arthrography have been analysed. Morphologically one must distinguish between distension cysts and dissection cysts. Distension cysts are more common with various diseases of the knee joint (68% of all cysts). Dissection cysts (32%) are found particularly with inflammatory-rheumatic diseases and are rarely of degenerative or post-traumatic origin. Acute rupture of the cyst was observed on ten occasions. Repeated rupture, which had only been suspected previously, was demonstrated by arthrography in four patients. It is pointed out that Baker cysts may imitate the features of acute thrombophlebitis.

[Technetium uptake in the parotid gland. Value of functional parameters in Sjögren's syndrome]. / Technetiumspeicherung der Parotis. Wertigkeit von Funktionsparametern beim Sjögren-Syndrom

Studies of the parotid function were performed on 22 subjects comprising 11 patients with Sjögren's syndrome and 11 normal controls using an Anger camera with digital data processing facility. After injection of 2 mCi of 99mTc-pertechnetate digital scintigrams of the face region were collected and stored onto magnetic tape. 50 minutes after injection the parotid glands were stimulated by administration of Pilocarpin. By subsequent processing of the data uptake curves were obtained for both parotid glands. In allowing for vascular activity three different methods were compared. The most satisfactory method with respect to discriminating the groups under study was using a background region located in the falx cerebri. From the corrected uptake curves a number of parameters were derived and their respective selectivity was investigated by statistical analysis. It is shown that the most suitable parameter characterizing the parotid function is given by the difference of maximum uptake before Pilocarpin stimulation and minimum uptake after stimulation.

The use of questionnaires in the evaluation of the functional capacity in rheumatoid arthritis.

The functional capacity of 46 patients with rheumatoid arthritis was assessed by means of two systems of investigation. Three different questionnaires were used. One set of each was filled out by the patient himself; the other with the help of the occupational therapist. The results obtained were tested for their reliability. In addition they were also compared to the Ritchie-Index (method of simple measurement of disease activity) of thirty patients. The disability of each patient could be assessed with sufficient precision. A correlation to the Ritchie-Index was also registered.

Development and evaluation of fuzzy criteria for the diagnosis of rheumatoid arthritis.

In 1987, the American Rheumatism Association issued a set of criteria for the classification of rheumatoid arthritis (RA) to provide a uniform definition of RA patients. Fuzzy set theory and fuzzy logic were used to transform this set of criteria into a diagnostic tool that offers diagnoses at different levels of confidence: a definite level, which was consistent with the original criteria definition, as well as several possible and superdefinite levels. Two fuzzy models and a reference model which provided results at a definite level only were applied to 292 clinical cases from a hospital for rheumatic diseases. At the definite level, all models yielded a sensitivity rate of 72.6% and a specificity rate of 87.0%. Sensitivity and specificity rates at the possible levels ranged from 73.3% to 85.6% and from 83.6% to 87.0%. At the superdefinite levels, sensitivity rates ranged from 39.0% to 63.7% and specificity rates from 90.4% to 95.2%. Fuzzy techniques were helpful to add flexibility to preexisting diagnostic criteria in order to obtain diagnoses at the desired level of confidence.

A prospective evaluation of the medical consultation system CADIAG-II/RHEUMA in a rheumatological outpatient clinic.

To evaluate the performance of CADIAG-II/RHEUMA as consultant in the primary evaluation of patients visiting a rheumatological outpatient clinic, a CADIAG-II/RHEUMA consultation was done for 54 patients and the list of generated diagnostic hypotheses was compared to each clinical discharge diagnosis. For 26 of a total of 126 rheumatological discharge diagnoses, no matching CADIAG-II/RHEUMA diagnosis was available. 94% of all other discharge diagnoses were found in the list of CADIAG-II/RHEUMA hypotheses, 82% among the first third of the list of hypotheses and 48% among the first five hypotheses. We identified the following factors limiting the ability of CADIAG-II/RHEUMA to generate a comprehensive and correctly ranked list of diagnostic hypotheses: (1) a large percentage of patients with early stages of not clearly identified rheumatological conditions; (2) the limited number of CADIAG-II/RHEUMA diagnoses compared to the large number of known rheumatological conditions; (3) the fact that rheumatological diseases are rarely characterized by a single pathognomonic feature but are usually diagnosed by combinations of rather unspecific findings.

The efficacy and safety of fentiazac and diclofenac sodium in peri-arthritis of the shoulder: a multi-centre, double-blind comparison.

In a double-blind parallel group comparison of efficacy and safety, 19 patients with peri-arthritis of the shoulder received 200 mg fentiazac twice daily and 19 received 50 mg diclofenac sodium twice daily, with both drugs given orally for 3 weeks. In both groups, observers' verbal rating scales of pain severity at rest and on movement showed decreases that were significant by week 1. Both groups also had significant improvement in abduction, external rotation, retroversion and anteversion. At week 1, the patients reported improvement, on a verbal rating scale, of global effectiveness, but there were no subsequent changes. There were no statistically significant differences between the treatments in any of these variables. Five (26%) fentiazac-treated patients and four (21%) diclofenac sodium-treated patients reported adverse effects, mostly gastro-intestinal. One case of rash in each group and one case of pruritus in a diclofenac sodium-treated patient were severe enough for the patients to be withdrawn from therapy. There were no clinically significant changes in laboratory values. It was concluded that fentiazac (400 mg/day) and diclofenac sodium (100 mg/day) were equally effective within 1 week in decreasing pain severity and improving shoulder mobility.

[Are antinuclear factors a contraindication for penicillamine treatment in patients with rheumatoid arthritis? (author's transl)]. / Das Auftreten antinukleärer Faktoren bei der chronischen Polyarthritis unter D-Penicillamin.

28 patients with rheumatoid arthritis undergoing treatment with penicillamine were investigated over a period of 7 to 72 months. Antinuclear antibodies were detected in 43% of patients before treatment, and 39% when treatment was completed. In all patients anti-native DNA antibodies were within the normal range. Precipitating antibodies to heat-denatured DNA were detected in 3 out of 16 patients at the end of therapy. There was no correlation between the detection of antinuclear antibodies, antibodies to native or denatured DNA and the occurrence of immunological side effects due to penicillamine (1 patient with pemphigus erythematosus, 3 patients with immune-complex nephritis).

[Preliminary results with a new non-steroidal antirheumatic drug (author's transl)]. / Erste Erfahrungen mit einem neuen nichtsteroidalen Antirheumatikum

Thirty patients with classical or definite rheumatoid arthritis were treated over a 4-week period with diftalone, a new non-steroidal antirheumatic drug. The daily dosage ranged from 500 to 1000 mg. A good objective response was achieved in 69% of the patients. Diftalone was well tolerated. Side effects were noted in 11.8% of patients on 500 mg diftalone daily and in 18.8% of cases treated with the highest dosage (1000 mg daily). The optimum daily dosage appears to be 750 mg.

[The implementation of a computerized documentation system for the evaluation of spa therapy in patients with rheumatoid arthritis (author's transl)]. / Der Einsatz einer EDVA in der Erfolgsbeurteilung von Kuren bei Patienten mit chronischer Polyarthritis

A previously-described documentation system for articular examination was applied to evaluate the results of spa treatment in 20 patients with rheumatoid arthritis during 3 separate treatment periods. Physical joint findings were documented and indices were compiled by means of a computer before, during and after treatment with thermal water the first year, normal water the second year (or vice versa) and without baths at all in the third year. These indices were compared statistically. Each kind of treatment produced a statistically-significant improvement in the disease, there being no significant difference in the results achieved by the 3 therapeutic regimens.

[Measles antibodies in systemic lupus erythematosus (author's transl)]. / Masernantikörper bei Lupus erythematodes disseminatus.

30 patients with systemic lupus erythematosus (SLE), 19 patients with rheumatoid arthritis (RA) and 34 controls were investigated with regard to measles antibodies (AB). The titres were compared with clinical and immunological parameters. As previously reported by several authors we found increased measles AB titres more frequently (kappa 2-test, p less than 0.05) in patients with SLE than in those with RA and controls. No significant correlation was found between immunoglobulins, antinuclear antibodies, CH50 or rheumatoid factor, and an elevation of the measles AB titre. A trend was noted, however, towards a positive correlation between measles antibodies and IgM. An elevated measles AB titre in SLE can be explained on the basis of several mechanisms. However, hyperimmunoglobulinaemia with non-specific, secondary AB elevation can be ruled out as a cause of elevated measles AB titre according to our results.

[Clinical experience with levamisole treatment of patients with systemic lupus erythematosus (author's transl)]. / Erste klinische Erfahrungen mit Levamisol bei der Behandlung von Patienten mit systemischem Lupus erythematodes.

Levamisole treatment was started in 8 patients with inactive SLE. Four patients, who have now been followed up for over 12 months, have not shown clinical deterioration. Three of these patients received concomitant maintenance corticosteroid therapy, the dosage of which could be reduced in each case. A decrease in anti-DNA antibodies was observed in all 4 patients. Levamisole had to be withdrawn in the other 4 patients. One patient developed an exacerbation of her LE skin manifestations after two months, whilst in another patient fever and skin rash (probably drug-induced) were observed after one month. The cooperation of the 2 other patients was not satisfactory and the drug had, thus, to be withdrawn. In conclusion, 4 out of 8 patients with SLE showed a beneficial response to levamisole therapy.

CADIAG: approaches to computer-assisted medical diagnosis.

CADIAG-1 is a medical expert system, based on a symbolic logic representation of medical relationships. Strong relationships such as confirming, excluding or obligatory occurrence are applied to confirm or exclude diagnoses. Weak relationships are represented by facultative and not confirming relationships (FN-relationships). Diagnostic hypotheses are established by systematic combination of symptoms showing FN-relationships. CADIAG-2, a medical expert system based on fuzzy set theory and fuzzy logic, allows detailed specification of medical relationships. Here the diagnostic process also provides confirmed and excluded diagnoses as well as diagnostic hypotheses. Hypotheses are calculated by considering fuzzy relationships between medical entities. 426 cases with rheumatic and 47 cases with pancreatic diseases were tested. For CADIAG-1, the overall accuracy for confirmation and hypothesis generation is calculated with 91.1% for rheumatic diseases and 100% for pancreatic diseases. CADIAG-2 reached an overall accuracy of 93.7% for rheumatic cases and 91.5% for pancreatic cases.

Intra-articular hyaluronic acid: duration of effect and results of repeated treatment cycles.

An open-label, multicenter study was designed to evaluate the effects of intra-articular (IA) hyaluronic acid in patients given a diagnosis of osteoarthritis of the knee. Patients (n = 108) received five weekly IA injections of hyaluronic acid 20 mg (Hyalgan) under sterile conditions, and were observed for up to 12 months after the last injection. Some patients received a second series of injections after 4 to 8 months. For the 59 patients who were observed for 12 months after the first treatment cycle, evaluation of pain according to a visual analog scale showed significant improvements lasting 12 months, with pain during load, pain at rest, and duration of walking ability compared with a baseline evaluation. Patients who required a second treatment cycle showed a further amelioration. Significant improvements were also seen in knee function and in global evaluations by both patient and investigators. Relief of symptoms of osteoarthritis of the knee was seen as early as 4 weeks after treatment in 68% of patients receiving IA hyaluronic acid. In 55% of these patients, relief was maintained until the end of the 12-month follow-up.

[Systemic manifestations in rheumatoid arthritis. A multivariate analysis of 122 patients (author's transl)]. / Organmanifestationen bei chronischer Polyarthritis. Eine multivariate Analyse bei 122 Patienten

In a retrospective study the case reports of 122 patients with rheumatoid arthritis (RA), were analyzed by computer with respect to systemic manifestations and the possible relationship of these manifestations to clinical findings. Bromsulphthalein retention, lung and kidney function were studied in other smaller unselected groups of RA patients and the results compared with the relevant clinical data. It was observed that nearly all systems can be involved in RA. High rheumatoid factor titres seem to be of great importance with regard to prognosis, but the duration and activity of the disease do, however, also influence the occurrence of systemic complications. Functional impairment of the different organs investigated was found in a high percentage of RA patients. Usually these disturbances are subclinical and not of great significance to the patient. Effects of antirheumatic drug therapy are difficult to evaluate, but they obviously do play an important role in the aetiology of the observed functional disturbances. Nevertheless, it must be stressed that the detection of systemic manifestations and functional disorders at the earliest possible stage of the disease is needed in the determination of the therapy of choice and is of great prognostic importance, thereby justifying detailed and often costly investigation.

The concentrations of markers of bone turnover in normal pregnancy and preeclampsia.

BACKGROUND: The purpose of our study was to investigate the concentrations of markers of bone turnover in normal pregnancy and preeclampsia. MATERIAL AND METHODS: Forty-five pregnant patients with preeclampsia, 78 healthy pregnant women (26 in first, 26 in the second, and 26 in third trimester of pregnancy), and 20 nonpregnant women were included in the study. Serum concentrations of osteoprotegrin (OPG), receptor activator of nuclear factor kappa B ligand (sRANKL), and the markers of bone turnover, osteocalcin and CrossLaps-degradation products of type I collagen, were determined using the ELISA method. Statistical analysis was performed using Mann-Whitney U-test. RESULTS: The concentrations of sRANKL and OPG were significantly higher in the second trimester of normal pregnancy when compared to the first and the third trimesters and to nonpregnant controls. The concentrations of osteocalcin were significantly higher in the first trimester of physiological pregnancy in comparison with nonpregnant women and with second and third trimesters of pregnancy. The concentrations of CrossLaps were significantly higher in the second trimester of normal pregnancy when compared to the first and third trimester. In preeclampsia, the sera concentrations of osteocalcin and CrossLaps were significantly higher when compared to the third trimester of normal pregnancy. CONCLUSION: The results suggest that the bone formation is increased in the first trimester, whereas the bone resorption is increased in the second trimester of normal pregnancy. Furthermore, the results suggest that the bone turnover is increased in patients with preeclampsia when compared to healthy normotensive pregnant women.