[Regression of peripheral and pulmonary rheumatoid nodules under therapy with rituximab]. / Regression von peripheren und pulmonalen Rheumaknoten unter Rituximab-Therapie.

We report on a retrospective study of 16 rheumatoid arthritis (RA) patients with reduction in size of pulmonary and peripheral rheumatoid nodules following treatment with rituximab (RTX). The 8 female and 8 male patients had an average disease duration of 12.2 years, 88 % were anti-CCP positive and 94 % seropositive. Prior treatment included an average of 2.9 DMARD and 1.4 biological therapies. On average 6.1 rheumatoid nodules were found on hands and elbows and 5 patients had pulmonary nodules. In 6 out of 16 patients the nodules disappeared completely, in 2 patients a pulmonary nodule disappeared. In 10 out of 16 patients the size of the nodules decreased by approximately 50%, 1 out of the 16 patients with significant increase in size and number of nodules prior to RTX therapy showed a reduction in size but no new nodules occurred. The regression in size of the nodules occurred 34.2±39.1 weeks following RTX therapy, correlating with 1.3±0.59 RTX infusion cycles. Overall, increases in size or new nodules were reported in none of the patients. One nodule examined histologically following RTX therapy did not show any specific differences. RTX may lead to a marked reduction in size of rheumatoid nodules in RA patients. More studies are necessary to confirm whether this is an RTX-specific effect.

Cavitation dynamics of laser ablation of bulk and wire-shaped metals in water during nanoparticles production.

Although the first nanoseconds to microseconds rule the resulting process yield of laser ablation in liquid, a comprehensive view involving combination of time-resolved measurement techniques is still lacking. In this paper, fundamental aspects of laser ablation of metals in water during the production of nanoparticles are discussed. Three fast diagnostic methods have been applied simultaneously. These are Optical Emission Spectroscopy for the plasma characterization, fast shadowgraph for plasma and cavitation bubble dynamics and laser scattering for the mechanisms of delivery of the produced materials in the liquid. Moreover, in order to validate the discussion, the effect on cavitation dynamics of the ablation of bulk and wire-shaped targets has been investigated together with the relative nanoparticles production yield. Unusual arrow-bow ejection phenomena between the cavitation bubble and the wire result in suppressed material back-deposition, causing efficient ejection of ablated matter into the liquid. The presented nanosecond and microsecond-resolved analysis allows estimating the timescale and role of the basic mechanisms involved in laser ablation in liquids as well as the thermodynamic characteristics of the processes.

Actin and phosphoinositide binding by the ActA protein of the bacterial pathogen Listeria monocytogenes.

The surface protein ActA of the pathogenic bacterium Listeria monocytogenes induces actin-driven movement of bacteria in the cytoplasm of infected host cells and serves as a model for actin-based motility in general. We generated and purified soluble recombinant fragments of ActA and assessed their ability to interact with the acidic phospholipids phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate, both implicated in the regulation of actin polymerization. Purified ActA consisted of biologically active, elongated molecules with an alpha-helix and beta-sheet content of 11 and 32%, respectively. In the presence of either phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate, but not phosphatidylcholine, ActA molecules underwent a structural change that raised the alpha-helix content to 19% and lowered the beta-sheet content to 27%. Co-sedimentation experiments with phosphatidylcholine vesicles containing different acidic phospholipids demonstrated that ActA binds preferentially to D-3 phosphoinositides. The D-3 phosphoinositide binding activity was mapped to a small subregion in the N-terminal domain of ActA. This subregion comprised 19 amino acids and showed homology to cecropins. In addition, we found that amino acids 33 to 74 of ActA mediated actin binding by the whole, folded ActA molecule. These findings shed new light on ActA function.

[Methotrexate therapy of polymyalgia rheumatica]. / Methotrexattherapie der Polymyalgia rheumatica.

Twenty-seven patients with polymyalgia rheumatica were treated with methotrexate. In comparison with 295 patients with other inflammatory rheumatic diseases under methotrexate therapy, a favorable rate of therapeutic effect and a low rate of side-effects could be observed. Remissions appeared in the mean after 6 months (1-24 months). Therapeutic failures (1/27) or side-effects inducing breaking off the therapy (2/27) were rare. Methotrexate seems to be a useful possibility to supplement the corticosteroid therapy of polymyalgia rheumatica.

[Polymyalgia rheumatica in patients of a rheumatologic specialty practice. Clinical signs and etiological events]. / Polymyalgia rheumatica bei Patienten einer rheumatologischen Fachpraxis. Klinische Zeichen und auslösende Ereignisse.

Manifestations of polymyalgia rheumatica in 100 ambulatory patients of an internistic, rheumatological specialist's practice were investigated. In this group of patients, both the clinical course of the disease and its prognosis were found to be more benign than is commonly reported in the literature. Thus, for example, temporal arteritis was found in only three of the one hundred patients. Not all of the patients were found to have the markedly elevated ESR normally considered to be typical. For this reason, to establish inflammatory activity, in addition to ESR, C-reactive protein (CRP) should also be determined in order to ensure that atypical forms with less marked signs of inflammation are not overlooked. Thirty of the 100 patients reported possible triggering life events.

[Incidence of acral nodulosis with long-term methotrexate therapy in patients with inflammatory rheumatic diseases]. / Die Häufigkeit einer akralen Nodulosis unter Methotrexat-Langzeittherapie bei Patienten mit entzündlich-rheumatischen Erkrankungen.

The significance of acral nodulosis under methotrexate therapy is still controversial. Among patients with rheumatoid arthritis and methotrexate therapy this manifestation could be observed in 8/163 (5%). All cases were seropositive and already treated with other LAAD. Patients with other inflammatory rheumatic diseases under methotrexate therapy (n = 83) did not develop this nodulosis. The acral nodulosis is interpreted as a typical side-effect of methotrexate only in patients with rheumatoid arthritis. Histopathologically, these nodules do not differ from the typical rheumatoid nodule.

[Musculoskeletal manifestations in patients after bone marrow transplantation. Initial clinical rheumatologic observations]. / Manifestationen am Bewegungsapparat bei Patienten nach Knochenmarktransplantation. Erste klinisch-rheumatologische Beobachtungen.

From January 1986 through January 1989 69 adult patients received bone marrow transplants--20 with autologous, and 49 with allogeneic bone marrow. Ten patients after autologous and 33 patients after allogeneic transplantation (TX) could be examined for rheumatological complaints. None of the patients after autologous TX displayed rheumatological manifestations; 8/33 patients after allogeneic TX developed bone necrosis and they had to be treated for several months with high daily doses of prednisolon (mean: 55 mg/day). In 18/33 patients an oligoarthropathy of large joints could be observed after a significant reduction of prednisolon dosage over a period of 5 months. In addition 15/18 of these patients later developed a chronic g-v-h-disease. The TX arthropathy may be induced by cortico-steroid therapy (resp. reduction), but most important, it is a clinical sign for an imminent chronic g-v-h-disease.

[Detection of endotoxin in synovial tissue of patients with inflammatory-rheumatic diseases]. / Nachweis von Endotoxin im Synovialgewebe von Patienten mit entzündlich-rheumatischen Erkrankungen.

The etiology of inflammatory rheumatic diseases is unknown. The hypothesis, that bacteriae may play a part in the induction of a rheumatic synovialitis is further substantiated by the detection of Endotoxin (Lipid A) in the synovial membranes of five of eleven patients with early synovitis (disease duration shorter than 6 months) by using anti Lipid A monoclonal antibodies. Endotoxin (Lipid A) is a component of gram-negative bacteriae and Chlamydiae. It is a potent immunogen, and could be the link between infection of the gut or the urogenital system and the rheumatic synovialitis.

Reactive fibromatosis in pustulotic arthro-osteitis.

Sterno-costo-hyperostosis is an inflammatory rheumatic disease which is associated to pustulosis palmaris et plantaris. The origin of this disorder is unknown. We described the appearance as a "reactive" fibromatosis in connection with a hyperostosis of a clavicle, which could be demonstrated in a biopsy-probe and by NMR-technique.

[Scintigraphic studies of gonadal burden in radiosynoviortheses of the knee joint with yttrium 90]. / Szintigraphische Untersuchungen zur Gonadenbelastung bei Radiosynoviorthesen des Kniegelenkes mit Yttrium-90.

Yttrium-90 radiosynoviorthesis of the knee joint in rheumatic inflammatory diseases shows favourable results. Because of the supposed exposure of the patients gonads, Yttrium synoviorthesis has rarely been performed in patients below the age of 40. Scintigraphic studies in 20 patients with rheumatoid arthritis showed no significant leakage of the radionuclide from the knee joint. Gamma camera measurements both phantom and in vivo in the regions of ovary and testes revealed a local dose of 1.05 microGy/MBq (3.9 mrd/mCi) or 1.1 microGy/MBq (4.1 mrd/mCi) of the injected radioactivity. Calculation of the maximum possible load of the gonads, supposing even total leakage of the injected 90-Yttrium from the knee joint, yielded a maximum possible dose of 6 mGy (600 mrd). We conclude from these studies and calculations that Yttrium-90 synoviorthesis of the knee joint can safely be carried out in patients below the age of 40.

[Determination of endotoxin in inflammatory rheumatic diseases--the effect of nonsteroidal anti-inflammatory agents on intestinal permeability]. / Endotoxinbestimmung bei entzündlich-rheumatischen Erkrankungen--Der Einfluss nichtsteroidaler Antiphlogistika auf die Darmpermeabilität.

We measured the amount of plasma endotoxin in 95 patients with inflammatory rheumatic diseases (42 with ankylosing spondylitis; 12 with possible ankylosing spondylitis; 41 with rheumatoid arthritis) and in 16 patients with Crohn's disease with a quantitative Limulus assay. Significantly increased mean values were found in inflammatory rheumatic diseases and in Crohn's disease. Between 31% and 50% of the patients had endotoxin values higher than 10 pg/ml--none of the controls had such values. Patients on regular treatment with NSAIDS had higher amounts of endotoxin again. From our results we discuss an intestinal involvement in inflammatory rheumatic diseases. An inflammation of the gut with an increased permeability seems to be responsible for the raised plasma endotoxin levels compared to healthy controls. NSAIDs probably contribute to the increased permeability of the gut.

Sonography and NMR imaging in rheumatoid gonarthritis.

Sonography and NMR imaging of the knee joint make it possible to obtain a visual representation of the thickened synovial membrane occurring in patients with rheumatoid gonarthritis, even before inflammatory deformation is radiologically detectable. Both methods can expose effusions and Baker's cysts. In NMR imaging, an indication of the inflammatory genesis can be obtained from the extended relaxation time T1. Due to the good representation of soft tissues, prognostic evidence may be gained of whether a mainly exudative or proliferative form is present.

Increased frequency of HLA-Bw62 and Bw35 CREG antigens in HLA-B27 negative ankylosing spondylitis.

67 patients with ankylosing spondylitis (AS) were tissue-typed for HLA-A, -B and -C antigens. HLA-Bw62 was found in 6 of 13 (46%) HLA-B27 negative patients, compared to 9% in HLA-B27 positive AS (p greater than 0.01) and 10% in healthy blood donors (p greater than 0.001). HLA-Bw62, a split of the previous HLA-B15, belongs to the HLA-Bw35 CREG antigens, 11 of 13 (85%) of HLA-B27 negative patients had an HLA-Bw35 CREG antigen. The present results are interpreted as an indication of a direct involvement of the HLA-B locus in the pathogenesis of AS.

HLA-B27 in possible ankylosing spondylitis with peripheral arthritis.

Among 86 patients selected as possibly having ankylosing spondylitis because of clinical symptoms and radiologically normal sacroiliac joints. HLA-B27 was positive in 41%. Four years later a representative sample of 38 individuals were re-examined and radiographed. HLA-B27 positive patients developed sacroiliitis as defined by radiological criteria twice as often (P less than 0.05). They also showed increased uptake of technetium 99 m upon quantitative scintigraphy with a region of interest method and more often probable or definite ankylosing spondylitis as defined by the New York criteria. Further differences between the HLA-B27 positive and negative follow-up groups concerned the frequency of clinical symptoms and peripheral arthritis. It is suggested that HLA-B27 typing may be helpful both in diagnosis and in judging the prognosis of possible or abortive ankylosing spondylitis.