Imaging assessment of children presenting with suspected or known juvenile idiopathic arthritis: ESSR-ESPR points to consider.

Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatic disease. It represents a group of heterogenous inflammatory disorders with unknown origin and is a diagnosis of exclusion in which imaging plays an important role. JIA is defined as arthritis of one or more joints that begins before the age of 16 years, persists for more than 6 weeks and is of unknown aetiology and pathophysiology. The clinical goal is early suppression of inflammation to prevent irreversible joint damage which has shifted the emphasis from detecting established joint damage to proactively detecting inflammatory change. This drives the need for imaging techniques that are more sensitive than conventional radiography in the evaluation of inflammatory processes as well as early osteochondral change. Physical examination has limited reliability, even if performed by an experienced clinician, emphasising the importance of imaging to aid in clinical decision-making. On behalf of the European Society of Musculoskeletal Radiology (ESSR) arthritis subcommittee and the European Society of Paediatric Radiology (ESPR) musculoskeletal imaging taskforce, based on literature review and/or expert opinion, we discuss paediatric-specific imaging characteristics of the most commonly involved, in literature best documented and clinically important joints in JIA, namely the temporomandibular joints (TMJs), spine, sacroiliac (SI) joints, wrists, hips and knees, followed by a clinically applicable point to consider for each joint. We will also touch upon controversies in the current literature that remain to be resolved with ongoing research. KEY POINTS: • Juvenile idiopathic arthritis (JIA) is the most common chronic paediatric rheumatic disease and, in JIA imaging, is increasingly important to aid in clinical decision-making. • Conventional radiographs have a lower sensitivity and specificity for detection of disease activity and early destructive change, as compared to MRI or ultrasound. Nonetheless, radiography remains important, particularly in narrowing the differential diagnosis and evaluating growth disturbances. • Mainly in peripheral joints, ultrasound can be helpful for assessment of inflammation and guiding joint injections. In JIA, MRI is the most validated technique. MRI should be considered as the modality of choice to assess the axial skeleton or where the clinical presentation overlaps with JIA.

Recommendations of the ESSR Arthritis Subcommittee for the Use of Magnetic Resonance Imaging in Musculoskeletal Rheumatic Diseases.

This article presents the recommendations of the European Society of Musculoskeletal Radiology Arthritis Subcommittee regarding the standards of the use of MRI in the diagnosis of musculoskeletal rheumatic diseases. The recommendations discuss (1) the role of MRI in current classification criteria of musculoskeletal rheumatic diseases (including early diagnosis of inflammation, disease follow-up, and identification of disease complications); (2) the impact of MRI on the diagnosis of axial and peripheral spondyloarthritis, rheumatoid arthritis, and juvenile spondyloarthritis; (3) MRI protocols for the axial and peripheral joints; (4) MRI interpretation and reporting for axial and peripheral joints; and finally, (5) methods for assessing MR images including quantitative, semiquantitative, and dynamic contrast-enhanced MRI studies.

Imaging and interpretation of axial spondylarthritis: the radiologist's perspective--consensus of the Arthritis Subcommittee of the ESSR.

This article reflects the radiologist's perspective on the imaging and interpretation of axial spondylarthritis (SpA). The arthritis subcommittee of the European Society of Skeletal Radiology provides a consensus for the following questions: When and how should we image? How should we analyze the images? How should we interpret the imaging findings? To answer these questions, we address the indications in imaging axial SpA and the different imaging techniques, with a special focus on magnetic resonance imaging protocols. The value of different imaging modalities is discussed. For adequate image analysis, knowledge of the anatomy and the pathologic changes in chronic and acute inflammation of the sacroiliac joints and the spine is mandatory. Differential diagnoses of inflammatory lesions of the sacroiliac joints and the spine are addressed due to their importance in image interpretation.

Clinical and radiological dissociation of anti-TNF plus methotrexate treatment in early rheumatoid arthritis in routine care: results from the ABRAB study.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoinflammatory joint disease which leads to the destruction of joints and disability of the patients. Anti-tumour necrosis factor (anti-TNF) drugs can halt radiological progression better than conventional DMARDs even in clinical non-responders. METHODS: The efficacy of anti-TNF plus methotrexate (MTX) treatment versus MTX monotherapy on clinical and radiological outcomes were compared in early rheumatoid arthritis (RA) patients in clinical practice by retrospective analysis of an observational cohort.49 early RA patients (group A) on first-line MTX monotherapy and 35 early RA patients (group B) on anti-TNF plus MTX treatment were selected from an observational cohort and evaluated retrospectively focusing on their first twelve months of treatment. Data on disease activity (DAS28) and functional status (HAQ-DI) were collected three monthly. One-yearly radiological progression was calculated according to the van der Heijde modified Sharp method (vdHS). Clinical non-responder patients in both groups were selectively investigated from a radiological point of view. RESULTS: Disease activity was decreased and functional status was improved significantly in both groups. One-yearly radiological progression was significantly lower in group B than in group A. The percentage of patients showing radiological non-progression or rapid radiological progression demonstrated a significant advantage for group B patients. In addition non-responder patients in group B showed similar radiological results as responders, while a similar phenomenon was not observed in patients in group A. CONCLUSIONS: Clinical efficacy within our study was similar for tight-controlled MTX monotherapy as well as for combination treatment with anti-TNF and MTX. However MTX monotherapy was accompanied by more rapid radiological progression and less radiological non-progression. Anti-TNF plus MTX decreased radiological progression even in clinical non-responders supporting the advantage of anti-TNF plus MTX combination in dissociating clinical and radiological effects.

Pulsed laser light forces cancer cells to absorb anticancer drugs--the role of water in nanomedicine.

Anticancer drugs executing their function intracellularly enter cancer cells via diffusive processes. Complementary to these slow processes, cells can be forced to incorporate drugs by convection - a more efficient transport process. Transmembrane convection is induced by moderately intense pulsed laser light (or light emitting diodes) changing the structure of nanoscopic water layers in cells. This is a fundamental difference with the method of photodynamic therapy. In a model system we demonstrate that a total irradiation time of one minute is sufficient to completely inhibit proliferation of cancer cells. Transmembrane convection protects healthy cells from extended chemotherapy exposure, could be exploited to overcome multidrug resistance, and is a promising new tool in a variety of therapies as well as in skin rejuvenation.

Back pain and sacroiliitis in long-standing adult celiac disease: a cross-sectional and follow-up study.

There have been only scattered reports suggesting that musculoskeletal manifestations including back pain and sacroiliac joint involvement may be associated with celiac disease. In order to confirm this issue in a larger cohort, rheumatic manifestations were analyzed in 21 adult celiac patients using a comprehensive clinical, laboratory and radiological analysis. The diagnosis of celiac disease was based on the histopathology of jejunal biopsy specimens. The mean duration of celiac disease was 15 (0-31) years. All patients were currently on gluten-free diet and none of the patients had gastrointestinal symptoms at the time of the study. Using various imaging techniques, involvement of the sacroiliac joints was confirmed in 70% of celiac patients. Imaging revealed different morphological changes in the sacroiliac joint, e.g. accumulation of synovial fluid, synovitis, erosion with concomitant sclerosis, sacroiliitis or calcification of the ligament. These changes probably represent different clinical stages and/or manifestations of the same process. In a follow-up study of eight patients, after 11 years on a gluten-free diet, the great majority of patients had no clinical symptoms; yet, a subclinical progression of the sacroiliac joint involvement could be verified. Our results suggest the importance of regular rheumatologic follow-up of patients with celiac disease.

Quantum biology in low level light therapy: death of a dogma.

BACKGROUND: It is shown that despite exponential increase in the number of clinically exciting results in low level light therapy (LLLT), scientific progress in the field is retarded by a wrong fundamental model employed to explain the photon-cell interaction as well as by an inadequate terminology. This is reflected by a methodological stagnation in LLLT, persisting since 1985. The choice of the topics is, by necessity, somewhat arbitrary. Obviously, we are writing more about the fields we know more about. In some cases, there are obvious objective reasons for the choice. Progress in LLLT is currently realized by a trial and error process, as opposed to a systematic approach based on a valid photon-cell interaction model. METHODS: The strategy to overcome the current problem consists in a comprehensive analysis of the theoretical foundation of LLLT, and if necessary, by introducing new interaction models and checking their validity on the basis of the two pillars of scientific advance (I) agreement with experiment and (II) predictive capability. The list of references used in this work, does contain a representative part of what has been done in the photon-cell interaction theory in recent years, considered as ascertained by the scientific community. RESULTS: Despite the immense literature on the involvement of cytochrome c oxidase (COX) in LLLT, the assumption that COX is the main mitochondrial photoacceptor for R-NIR photons no longer can be counted as part of the theoretical framework proper, at least not after we have addressed the misleading points in the literature. Here, we report the discovery of a coupled system in mitochondria whose working principle corresponds to that of field-effect transistor (FET). The functional interplay of cytochrome c (emitter) and COX (drain) with a nanoscopic interfacial water layer (gate) between the two enzymes forms a biological FET in which the gate is controlled by R-NIR photons. By reducing the viscosity of the nanoscopic interfacial water layers within and around the mitochondrial rotary motor in oxidatively stressed cells R-NIR light promotes the synthesis of extra adenosine triphosphate (ATP). CONCLUSIONS: Based on the results of our own work and a review of the published literature, we present the effect of R-NIR photons on nanoscopic interfacial water layers in mitochondria and cells as a novel understanding of the biomedical effects R-NIR light. The novel paradigm is in radical contrast to the theory that COX is the main absorber for R-NIR photons and responsible for the increase in ATP synthesis, a dogma propagated for more than 20 years.

Comparison of the femoral neck bone density, quantitative ultrasound and bone density of the heel between dominant and non-dominant side.

Our study was initiated to evaluate whether there are differences between the two sides, depending on hand dominance, in densitometry values and quantitative ultrasound parameters (QUS) of the lower limb. One hundred and six women and 44 men were involved. The hand dominance was determined by interview. The bone mineral density (BMD) of the left and the right femoral necks and the calcanei were measured by dual-energy X-ray absorptiometry (DXA). The QUS examination consisted of measuring the attenuation (BUA), the speed of the ultrasound (SOS) and quantitative ultrasound index (QUI) transversing the left and right calcanei. The density of the neck of femur of the non-dominant side did not differ from that of the dominant side. On the other hand, BMD, BUA and the QUI of the calcaneus were higher on the non-dominant side in both genders (p<0.05 for each parameter). No similar differences were seen for the SOS values. Our study has confirmed the side-to-side differences of the calcaneus in both genders, lower values were found on the dominant side. No similar differences were seen on the femur. The AUC values seemed to be higher on the dominant side, however, these differences were not strictly significant. In the case of peripheral site (heel) measurements, the practical significance of our observations is that they raise the possibility of performing peripheral DXA and QUS examinations of the calcaneus on the dominant side of the patient according to handedness.

Tuning the mitochondrial rotary motor with light.

Skin surface temperature has been proposed as an in vivo clinical biomarker for monitoring the detrimental effect of biostimulatory laser applications. In some cases, such as wound healing and cosmetic applications, the target of the irradiation is the skin surface. In other cases, the light has to reach deeper tissues, for instance, during the irradiation of internal body organs. Prerequisite for reproducible biostimulatory effects is that the light intensity surpasses a minimum threshold. Because of the loss of light intensity caused by absorption and scattering, targeting deeper tissues always implies that the intensity at the skin surface will be much higher than that at the target site. Derived from laboratory experiments which showed that virtually the same light which produces biostimulatory effects in cells in vitro and tissues in vivo is instrumental in reducing the viscous friction in nanoconfined systems, we arrive to a new understanding of the effect of biostimulatory levels of light on mitochondria. One immediate result is insight into strategies which promise to maximize the biostimulatory effect and minimize potential phototoxic effects during treatment of deeper tissues. Such optimization strategies are also promising for experimental and therapeutic in vitro applications, in particular in combination with cell-friendly microenvironments.

DNA integrity of human leukocytes after magnetic resonance imaging.

PURPOSE: This study focuses on the effects of high-field (3T) magnetic resonance imaging (MRI) scans on the DNA integrity of human leukocytes in vitro in order to validate the study where genotoxic effects were obtained and published by Lee et al. MATERIALS AND METHODS: The scanning protocol and exposure situation were the same as those used under routine clinical brain MRI scan. Peripheral blood samples from healthy non-smoking male donors were exposed to electromagnetic fields (EMF) produced by 3T magnetic resonance imaging equipment for 0, 22, 45, 67, and 89 min during the scanning procedure. Samples of positive control were exposed to ionizing radiation (4 Gy of (60)Co-γ). Single breaks of DNA in leukocytes were detected by single-cell gel electrophoresis (Comet assay). Chromosome breakage, chromosome loss and micronuclei formations were detected by a micronucleus test (MN). Three independent experiments were performed. RESULTS: The data of comet tail DNA%, olive tail moment and micronucleus frequency showed no DNA damages due to MRI exposure. CONCLUSIONS: The results of the Comet assay and the micronucleus test indicate that the applied exposure of MRI does not appear to produce breaks in the DNA and has no significant effect on DNA integrity.

Nanobacteria, HIV and magic bullets--update of perspectives 2005.

In 1997 a Finnish group speculated on the presence of nanobacteria in vaccines. In 2001, a report on the identification of nanobacteria in a number of vaccines attracted much attention. Experiments indicated that viable nanobacteria are excreted via urine. Their extreme survivability suggests that prior to discussing any possible contamination of vaccines, sources and routes of natural infection need to be examined. In view of 30,000,000 HIV infections in sub-Saharan Africa, the recently reported occurrence of nanobacteria in HIV-infected patients deserves concern. Clearly, it could indicate the origin of a giant reservoir and dissemination cycle. Here we discuss novel therapeutic strategies to prevent or reduce nanobacterial infection. In regard of the rapid progress in this field, we start with a brief introductory summary, and analyze possible implications.

Living nanovesicles--chemical and physical survival strategies of primordial biosystems.

Life on Earth and Mars could have started with self-assembled nanovesicles similar to the present nanobacteria (NB). To resist extreme environmental stress situations and periods of nutritional deprivation, nanovesicles would have had a chemical composition protected by a closed mineralized compartment, facilitating their development in a primordial soup, or other early wet environment. Their survivability would have been enhanced if they had mechanisms for metabolic communication, and an ability to collect primordially available energy forms. Here, we establish an irreducible model system for life formation starting with NB.

A preliminary investigation into light-modulated replication of nanobacteria and heart disease.

OBJECTIVE: The purpose of this preliminary study is to evaluate the effect of various wavelengths of light on nanobacteria (NB). BACKGROUND DATA: NB and mitochondria use light for biological processes. NB have been described as multifunctional primordial nanovesicles with the potential to utilize solar energy for replication. NB produce slime, a process common to living bacteria. Slime release is an evolutionary important stress-dependent phenomenon increasing the survival chance of individual bacteria in a colony. In the cardiovascular system, stress-induced bacterial colony formation may lead to a deposition of plaque. METHODS: Cultured NB were irradiated with NASA-LEDs at different wavelengths of light: 670, 728 and 880 nm. Light intensities were about 500k Wm(-2), and energy density was 1 x 10(4) J m(-2). RESULTS: Monochromatic light clearly affected replication of NB. Maximum replication was achieved at 670 nm. CONCLUSIONS: The results indicate that suitable wavelengths of light could be instrumental in elevating the vitality level of NB, preventing the production of NB-mediated slime, and simultaneously increasing the vitality level of mitochondria. The finding could stimulate the design of cooperative therapy concepts that could reduce death caused by myocardial infarcts.