[Anticytokine therapy]. / Antizytokintherapie.

Anticytokine therapies have revolutionized the treatment of chronic inflammatory diseases, particularly autoimmune diseases such as rheumatoid arthritis. As the first introduced principle of cytokine blockade in the 1990s, tumor necrosis factor (TNF)-α antagonists still represent the leading anticytokine therapy. There are currently five TNF antagonists available with indications in the fields of rheumatology, dermatology, and gastroenterology. Other therapeutic approaches have been introduced in the last 10 years, e.g., the blockade of interleukin (IL)-1, IL-6, and IL-12/23. The advantages of cytokine blockers are their rapid onset of action with high response rates and a tolerable safety profile. Nevertheless, anticytokine therapy can cause increased rates of tuberculosis and hepatitis B infections or reactivation. An appropriate screening before therapy is mandatory, and thorough monitoring of the disease course before and during therapy is also important. The development of further anticytokine drugs for the induction and maintenance of remission is, therefore, required.

Quantification of periarticular demineralization and synovialitis of the hand in rheumatoid arthritis patients.

UNLABELLED: The bone mineral density (BMD) measurement of the hand in rheumatoid arthritis (RA) patients is no standard measurement method as yet. The aim was to contribute to the standardization of the hand BMD measurement, especially of periarticular regions. As results, we found best precision values for the wrist and a significant correlation between hand and spine/femur BMD depending on disease activity and disease duration. INTRODUCTION: This study was conducted to investigate (i) the precision of periarticular hand BMD measuring, (ii) the periarticular demineralization of the hand, (iii) the correlation between periarticular hand BMD and spine/femur BMD, and (iv) the correlation of hand BMD to hand synovitis. METHODS: A number of 52 RA patients were examined by BMD measurement of the femoral neck, spine, whole hand, metacarpophalangeal (MCP) joints II-V, personal identity profile (PIP) joints II-V, and wrist using dual-energy X-ray absorptiometry (DXA). Synovitis of the hand was examined by ultrasonography and magnetic resonance imaging (MRI). Three subgroups were further analyzed: early RA, established RA with moderate and with high disease activity. Early RA and established RA patients with high disease activity were Followed up after 12 months. RESULTS: We found (1) best precision of BMD measurement for the wrist, (2) BMD in RA significantly reduced if compared to normal controls, (3) a highly significant positive correlation between hand and spine/femur BMD and the power of correlation to depend on disease activity and disease duration (high correlation in RA with moderate disease activity and early RA, very high correlation in RA with high disease activity), (4) a negative correlation between hand BMD and hand synovitis in RA with high disease activity, and (5) a significant reduction of synovitis but no change in hand BMD after 12 months, respectively. CONCLUSIONS: This study shows a highly significant correlation between hand BMD and spine/femur BMD in RA patients depending on disease activity and disease duration. We conclude to measure BMD at different sites including hands in order to quantify bone loss in RA patients most properly.

Calorimeter with Bayesian unfolding of spectra of high-flux broadband x rays.

We report the development of a multipurpose differential x-ray calorimeter with a broad energy bandwidth. The absorber architecture is combined with a Bayesian unfolding algorithm to unfold high energy x-ray spectra generated in high-intensity laser-matter interactions. Particularly, we show how to extract absolute energy spectra and how our unfolding algorithm can reconstruct features not included in the initial guess. The performance of the calorimeter is evaluated via Monte Carlo generated data. The method accuracy to reconstruct electron temperatures from bremsstrahlung is shown to be 5% for electron temperatures from 1 to 50 MeV. We study bremsstrahlung generated in solid target interaction showing an electron temperature of 0.56 ± 0.04 MeV for a 700 µm Ti titanium target and 0.53 ± 0.03 MeV for a 50 µm target. We investigate bremsstrahlung from a target irradiated by laser-wakefield accelerated electrons showing an endpoint energy of 551 ± 5 MeV, inverse Compton generated x rays with a peak energy of 1.1 MeV, and calibrated radioactive sources. The total energy range covered by all these sources ranges from 10 keV to 551 MeV.

Contrast-enhanced ultrasonography is more sensitive than grayscale and power Doppler ultrasonography compared to MRI in therapy monitoring of rheumatoid arthritis patients.

PURPOSE: To evaluate wrist and finger joints in patients with rheumatoid arthritis (RA) by grayscale, power Doppler (PD) and contrast-enhanced musculoskeletal ultrasonography (US) and to compare these findings with MRI, clinical (DAS28) and laboratory (ESR; CRP) data. MATERIALS AND METHODS: US was performed at baseline (t0) and after three, six and twelve (t12) months before and after a change of medical treatment. MRI was carried out at t0 and t12 and used as the reference method. Contrast-enhanced US was used to assess one clinically most affected joint region. Different semiquantitative synovitis scores were calculated by grayscale and PD US. RESULTS: Contrast-enhanced US results evaluated by enhancement, slope and semi-quantitative assessment significantly correlated to each other, to grayscale US, CRP, as well as to MRI with the highest correlation coefficients for the used contrast-enhanced US modes (r = 0.56, r = 0.55, r = 0.57; each p < 0.05). Sum scores evaluated by grayscale US showed that synovial inflammation in finger joints was detected significantly more frequently in the palmar aspect than on the dorsal side (p = 0.001). Using power Doppler US, the wrists were significantly more inflamed from dorsal than on the palmar side (p = 0.0004). Significant longitudinal correlations between grayscale and power Doppler US scores were detected. CONCLUSION: Grayscale, power Doppler and contrast-enhanced US are accurate tools for the detection and follow-up of synovitis in RA wrist and finger joints, with contrast-enhanced US being most sensitive compared to MRI. All imaging methods reflected a good response to TNFα blocking therapy.

Compact spectroscopy of keV to MeV X-rays from a laser wakefield accelerator.

We reconstruct spectra of secondary X-rays from a tunable 250-350 MeV laser wakefield electron accelerator from single-shot X-ray depth-energy measurements in a compact (7.5 × 7.5 × 15 cm), modular X-ray calorimeter made of alternating layers of absorbing materials and imaging plates. X-rays range from few-keV betatron to few-MeV inverse Compton to > 100 MeV bremsstrahlung emission, and are characterized both individually and in mixtures. Geant4 simulations of energy deposition of single-energy X-rays in the stack generate an energy-vs-depth response matrix for a given stack configuration. An iterative reconstruction algorithm based on analytic models of betatron, inverse Compton and bremsstrahlung photon energy distributions then unfolds X-ray spectra, typically within a minute. We discuss uncertainties, limitations and extensions of both measurement and reconstruction methods.

Comparative macrorestriction and RFLP analysis of Mycobacterium avium subsp. avium and Mycobacterium avium subsp. hominissuis isolates from man, pig, and cattle.

In Germany, tuberculous lesions in slaughtered pigs due to infection with members of the Mycobacterium avium complex are increasingly reported. Contaminated food originating from pig or other livestock is discussed as potential source of human infection. M. avium isolates from man (n=45), pig (n=29), and cattle (n=13) were characterised by restriction fragment length polymorphism (RFLP) with respect to insertion sequences IS1245 and IS901 as well as by XbaI-based pulsed-field gel electrophoresis (PFGE) and the results were compared by computer cluster correlation analysis, to determine potential sources of infection in man. By PCR, 55% of animal isolates was identified as M. avium subsp. avium, and 45% as M. a. hominissuis. All human isolates belonged to M. a. hominissuis. IS1245-RFLP and PFGE resulted in two distinct main groupings reflecting the two subspecies, and dividing the isolates into several subgroups. Animal isolates of M. a. hominissuis were widely distributed within the subgroups of human isolates. M. a. avium isolates, further discriminated by IS901-RFLP, formed host-associated subgroups for animals. Comparison of RFLP patterns with those of PFGE resulted in different subgroups as well as different pairs of isolates with high similarities. Only two isolates exhibited identical patterns by both methods. In general, results of both methods support the possibility that M. a. hominissuis isolates from livestock represent a source of infection for man, probably by common environmental reservoirs. There was no evidence of human infections caused by M. a. avium in Germany.

Evidence for a Soft Nuclear Equation-of-State from Kaon Production in Heavy-Ion Collisions.

The production of pions and kaons has been measured in 197Au+197Au collisions at beam energies from 0.6 to 1.5A GeV with the kaon spectrometer at SIS/GSI. The K+ meson multiplicity per nucleon is enhanced in Au+Au collisions by factors up to 6 relative to C+C reactions, whereas the corresponding pion ratio is reduced. The ratio of the K+ meson excitation functions for Au+Au and C+C collisions increases with decreasing beam energy. This behavior is expected for a soft nuclear equation-of-state.

Pericarditis as primary manifestation of Mycobacterium bovis SSP. caprae infection.

A 76-year-old white male presented with progressive malaise, weight loss and dyspnea at rest. Echocardiography revealed a circular pericardial effusion and global hypokinesia. Pericardiocentesis showed a purulent exudate and microbiologic examination revealed Mycobacterium bovis fully sensitive to isoniazid, streptomycin, ethambutol, rifampin, and pyrazinamide. By spoligotyping the isolate could be further differentiated to M. bovis ssp. caprae. Antimycobacterial therapy was initiated but 3 weeks later the patient's circulation and renal function deteriorated and he died with clinical signs of sepsis despite intensive care treatment. Pericarditis is a rare manifestation of tuberculosis and can be fatal even when diagnosed and treated appropriately. In low incidence countries diagnosis is often delayed and even overlooked.

Reduced TH-1 cytokine release in an adult patient with chronic relapsing Mycobacterium malmoense infection.

An unusual course of infection with Mycobacterium malmoense is described in a patient receiving chronic but mild immunosuppressive therapy for rheumatoid arthritis. Symptoms mimicking Crohn's disease deteriorated under intensified immunosuppression and surgery. Judging from the patient's course under treatment specific for M. malmoense, the gastrointestinal symptoms were rather manifestations of a chronic relapsing mycobacterial infection. Detailed immunological investigation of the patient revealed a severely impaired TH-1 cytokine response as the immunological background for this uncommon course.

In-medium effects on phase space distributions of antikaons measured in proton-nucleus collisions.

Differential production cross sections of K+/- mesons have been measured in p + C and p + Au collisions at 1.6, 2.5, and 3.5 GeV proton beam energy. At beam energies close to the production threshold, the K- multiplicity is strongly enhanced with respect to proton-proton collisions. According to microscopic transport calculations, this enhancement is caused by two effects: the strangeness exchange reaction NY --> K- NN and an attractive in-medium K- N potential at saturation density.

Observation of different azimuthal emission patterns of K+ and of K- mesons in heavy-ion collisions at 1-2 A GeV.

Azimuthal distributions of pi+, K+, and K- mesons have been measured in Au+Au reactions at 1.5A GeV and Ni+Ni reactions at 1.93 A GeV. In semicentral collisions at midrapidity, pi+ and K+ mesons are emitted preferentially perpendicular to the reaction plane in both collision systems. In contrast for K- mesons in Ni+Ni reactions, an in-plane elliptic flow was observed for the first time at these incident energies.

[Pilot study for radiometric detection of mycobacteria in lymph nodes altered by tuberculosis in slaughtered animals]. / Pilotstudie zum radiometrischen Nachweis von Mykobakterien in tuberkulös veränderten Lymphknoten von Schlachttieren.

30 lymph nodes with tuberculous changes from slaughter animals were investigated, comparing radiometric and usual cultural methods for presence of mycobacteria. Mycobacteria were isolated with help of radiometric method (BACTEC 460-TB) from 24 lymph nodes ("sensitivity" 96%, "specificity" 83.3%), and with help of usual cultural method from 22 lymph nodes ("sensitivity" 88%, "specificity" 62.5%). The radiometric method is suitable for isolating of mycobacteria in veterinary medicine diagnostic also.

[Molecular biology methods in detection of mycobacteria. Improved and newly developed test systems for the diagnosis of mycobacteria]. / Molekularbiologische Methoden zum Nachweis von Mykobakterien. Verbesserte und neuentwickelte Testsysteme zur Mykobakteriendiagnostik.

In the coming years, the accurate and rapid microbiological detection of mycobacteria will gain in importance, since infections with Mycobacterium tuberculosis and ubiquitous mycobacteria are expected to increase, in particular in immunocompromised persons. In addition to the classical biochemical methods of detection involving the use of the microscope and cultures, molecular biological techniques are already being used today. The present overview therefore discusses the principles of the major methods. These include the use of the major DNA probes, DNA amplification techniques (PCR) with subsequent DNA sequencing for species determination, and RFLP analysis, which is employed to deal with epidemiological problems. Also described is the Bactec method for culturing in a liquid medium which forms the basis of various modern examination techniques.

[Avian mycobacteria]. / Aviäre Mykobakterien.

The avian mycobacteria have been identified first in relation to their virulence for hens. But this property was not definitely to correlate with serovars. Furthermore, this heterogenicity was to confirm on molecular level. Therefore it was necessary to introduce a M.avium complex beside true M.avium. M.avium has special relevance to AIDS patients. This fact shows that the reasons for infections by these facultatively pathogenic mycobacteria are more complicated as accepted.

[Demonstration of Mycobacterium africanum in a bull from North Bavaria]. / Nachweis von Mycobacterium africanum bei einem Rind in Nordbayern.

The isolation of Mycobacterium africanum from a mediastinal lymph node with tuberculous alterations of a young bull from a herd of cattle in Northern Bavaria is described for the first time. The source of infection was probably a member of the family of the owner of the animals.

Clinical evaluation of the automated COBAS AMPLICOR MTB assay for testing respiratory and nonrespiratory specimens.

We evaluated the COBAS AMPLICOR PCR system (Roche Diagnostics) for the routine detection of Mycobacterium tuberculosis complex (MTBC) in clinical specimens. Diagnostic culture, considered as the reference method, was performed with BACTEC, Löwenstein-Jensen, Stonebrink, and Kirchner media. Occasionally MB-Redox, ESP, or MGIT medium was also used. A total of 643 respiratory and 506 nonrespiratory specimens collected from 807 patients were investigated. Of the 95 culture-positive specimens, 80 were COBAS AMPLICOR MTB positive, and of the 1,054 culture-negative specimens, 1,044 were COBAS AMPLICOR MTB negative. After resolving discrepancies by review of the medical history, the overall sensitivity, specificity, and positive and negative predictive values for the COBAS AMPLICOR MTB assay, respectively, were 83.5, 98.8, 86.7, and 98.6% compared to those of diagnostic culture. In smear-positive specimens, the sensitivity of the COBAS AMPLICOR MTB assay was 96%, versus 48% for smear-negative specimens. No significant differences in the test performance between respiratory and nonrespiratory specimens were observed. The overall inhibition rate was less than 2%, excluding stool specimens. The clear advantages of the COBAS AMPLICOR PCR system are standardized procedures and reagents for specimen processing as well as an internal control for reliable monitoring of PCR inhibitors. By simplifying the work flow through a completely automated amplification and amplicon detection procedure, the COBAS AMPLICOR PCR system proved itself as a very useful component for routine diagnostic procedures.

Mycobacterium hassiacum sp. nov., a new rapidly growing thermophilic mycobacterium.

A new rapidly growing, scotochromogenic mycobacterium was isolated from urine. This strain is thermophilic (it grows at 65 degrees C), tolerates 5% NaCl, and was unable to utilize any of the sugars tested or citrate or to take up iron. The isolate splits benzamide, urea, nicotinamide, and pyrazinamide and is sensitive to streptomycin, ethambutol, cycloserine, ciprofloxacin, and chlarithromycin but resistant to isoniazid, rifampin, and prothionamide. These characteristics clearly place this organism in a new mycobacterial species, which was confirmed by the unique 16S rRNA nucleotide sequence. The high level of similarity between this rapid grower and Mycobacterium xenopi is surprising. For this new rapidly growing scotochromogenic and thermophilic mycobacterium we propose the name Mycobacterium hassiacum sp. nov.

[The epizootiology of tuberculosis of cattle in the Federal Republic of Germany]. / Zur Epizootiologie der Rindertuberkulose in der Bundesrepublik Deutschland.

Mycobacterial strains from different outbreaks of tuberculosis of cattle in Germany from 1996 to 2001 were differentiated by two molecular biological methods (Spoligotyping, RFLP IS6110). The causative agent was in one case Mycobacterium (M.) africanum, in 10 cases M. bovis and in 17 cases M. bovis ssp. caprae, respectively. The results of the molecular biological methods are discussed from the perspective of epizootiology and the particular importance of infections by M. bovis ssp. caprae emphasized. Direct contact of the animals, purchase from infected stocks, infected zoo animals and wildlife, as well as livestock handlers are discussed as possible sources of infection.