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Biomedical subjects

A Scherer

Publications and source records attributed to A Scherer.

At least 19 recordsLinked to original sources

High-resolution multipinhole single-photon-emission computed tomography in experimental and human arthritis.

OBJECTIVE: To image inflammatory arthritic lesions in experimental arthritis and in patients with arthritis, using a newly developed high-resolution multipinhole single-photon-emission computed tomography (MPH-SPECT) technique. METHODS: Six interleukin-1 receptor antagonist-deficient mice with arthritis of the front and back paws and 2 control BALB/c mice were imaged with MPH-SPECT and scored macroscopically for arthritis. SPECT imaging was performed with a conventional gamma camera upgraded with a pyramidal lead collimator affixed with MPH apertures. All images were reconstructed, and uptake in the paws was quantified in counts/weight and injected activity. To transfer the imaging technique to humans we examined the clinically dominant hand of 6 individuals (3 with established rheumatoid arthritis [RA], 1 with early RA, 1 with osteoarthritis, and 1 healthy control). RESULTS: MPH-SPECT images were high-resolution 3-dimensional tomographic images, which allowed exact localization and quantifiable observation of increased bone metabolism. MPH-SPECT counts of inflamed joints in mice correlated with macroscopic scoring and histologic joint analysis postmortem. In humans, MPH-SPECT images depicted a detailed visualization of tracer accumulation in bony structures of hand and finger joints, and were also capable of imaging increased bone metabolism that had appeared normal with other imaging modalities, e.g., magnetic resonance imaging. CONCLUSION: The MPH-SPECT technique represents a new diagnostic tool in the detection of bone pathology in small-animal arthritis research. Compared with macroscopic scoring, this new method provides a more objective and higher-precision quantifiable measurement of bone reaction, allowing visualization of inflammatory processes of the whole skeleton in vivo. These results suggest that MPH-SPECT may be useful as a diagnostic instrument for monitoring experimental arthritis, with further potential for use in human studies of RA.

Aged↗

[Imaging methods in rheumatology: imaging in psoriasis arthritis (PsA)].

Conventional radiography is still the standard method of imaging in PsA since it displays many joints at the same time, thereby allowing different types of joint involvement to be recognized. Moreover, thanks to the high resolution of radiography, bony changes in a single joint are depicted in a brilliant way. Several features of psoriatic arthritis allow the distinction from rheumatoid arthritis, including the frequent involvement of the distal interphalangeal joints, asymmetry of joint involvement, axial involvement of finger joints, oligoarticular involvement; however, symmetric polyarthritis is also possible. At the level of the single joint, there are signs of severe destructive changes potentially leading to mutilation and at the same time signs of periostal bone proliferation and ankylosis may be present. Bony proliferation and/or osteolysis are not restricted to the joint region but can affect also the total phalanx with bone apposition or concentric osteolysis which may lead to a complete disappearance of phalanxes. For purposes of quantification of radiographic changes scoring methods are used that were originally developed for rheumatoid arthritis. So far, there is only one validated scoring method that was specifically designed for PsA and that takes into account both features of PsA, damage as well as proliferation of bone. In contrast to conventional radiography, MRI and sonography are able to visualize inflammatory processes within the soft tissue (joint capsules, tendon sheaths, tendon insertions, etc.), allowing an estimation of disease activity. Scintigraphy is nonspecific and can only be used to detect clinically silent inflammatory spots. The relatively frequent spinal (axial) involvement is similar to that seen in ankylosing spondylitis. However, unilateral sacroiliitis, asymmetry of syndesmophytes and development of parsyndesmophytes may distinguish PsA from ankylosing spondylitis. While conventional radiography demonstrates the bony consequences of inflammation in the spine, MRI also shows the active inflammatory changes in sacroiliacal joints and vertebrae.

Arthritis, Psoriatic↗

[Diagnostic imaging for connective tissue diseases].

Guidelines and diagnostic algorithms for the introduction of diagnostic procedures for connective tissue diseases have not yet been established and standardized. Diagnosis is often based on the patients's typical history, clinical symptoms and specific laboratory profiles. The use of diagnostic imaging procedures is relevant for differential diagnosis, for the assessment of disease activity and organ involvement, for defining the prognosis and monitoring responses to therapy and side effects. Experience with these techniques and diagnostic procedures, their application, indications and analysis represent the platform for rational and optimal diagnosis as well of defined therapy stratification.

Antiphospholipid Syndrome↗

Analysis of radiation-pressure induced mechanical oscillation of an optical microcavity.

The theoretical work of Braginsky predicted that radiation pressure can couple the mechanical, mirror eigenmodes of a Fabry-Pérot resonator to its optical modes, leading to a parametric oscillation instability. This regime is characterized by regenerative mechanical oscillation of the mechanical mirror eigenmodes. We have recently observed the excitation of mechanical modes in an ultrahigh Q optical microcavity. Here, we present a detailed experimental analysis of this effect and demonstrate that radiation pressure is the excitation mechanism of the observed mechanical oscillations.

Journal Article↗

[Imaging techniques in rheumatology: conventional radiography in rheumatoid arthritis].

Conventional radiography is still regarded the gold standard for imaging techniques in rheumatoid arthritis (RA). It is a very important tool for the diagnosis, the differential diagnosis, and the evaluation of the course and prognosis of the disease. Special advantages of conventional radiography are the worldwide availability and experience with the method over decades and the relatively low costs. Moreover, x-rays can be stored and re-evaluated over long periods of time. Joint damage caused by RA can be quantified by means of scoring methods. The amount of destruction correlates well with functional disability over time. The inhibition of damage progression seen on radiographs is the most important characteristic of a DMARD. Typical radiographic changes are part of the ACR classification criteria of RA. Technically, bone structure can be demonstrated with a high local resolution better than with all other imaging techniques, whereas only indirect conclusions can be drawn concerning soft tissue and cartilage lesions. This review includes recommendations given by the "Commission on Imaging Techniques" of the German Society of Rheumatology regarding technical and personal preconditions, costs, indication as well as practical performance of radiography in RA. In addition, radiographic changes that can be expected in RA including destruction and repair are discussed briefly.

Arthritis, Rheumatoid↗

Vacuum Rabi splitting with a single quantum dot in a photonic crystal nanocavity.

Cavity quantum electrodynamics (QED) systems allow the study of a variety of fundamental quantum-optics phenomena, such as entanglement, quantum decoherence and the quantum-classical boundary. Such systems also provide test beds for quantum information science. Nearly all strongly coupled cavity QED experiments have used a single atom in a high-quality-factor (high-Q) cavity. Here we report the experimental realization of a strongly coupled system in the solid state: a single quantum dot embedded in the spacer of a nanocavity, showing vacuum-field Rabi splitting exceeding the decoherence linewidths of both the nanocavity and the quantum dot. This requires a small-volume cavity and an atomic-like two-level system. The photonic crystal slab nanocavity--which traps photons when a defect is introduced inside the two-dimensional photonic bandgap by leaving out one or more holes--has both high Q and small modal volume V, as required for strong light-matter interactions. The quantum dot has two discrete energy levels with a transition dipole moment much larger than that of an atom, and it is fixed in the nanocavity during growth.

Journal Article↗

[Comparison of incomplete (135 degrees ) and complete prone position (180 degrees ) in patients with acute respiratory distress syndrome. Results of a prospective, randomised trial].

BACKGROUND: Ventilation in the prone position is carried out for improvement of pulmonary gas exchange in patients with acute respiratory distress syndrome (ARDS). We compared the effects of an incomplete prone position (IPP, 135( degrees )) with a complete prone position (CPP, 180( degrees )) in patients with ARDS. PATIENTS AND METHODS: For this trial 59 patients with ARDS were randomly assigned and were positioned in a "cross-over" design: patients of group A were placed in IPP for 6 h and then immediately positioned in CPP for another 6 h. Patients in group B were positioned in reverse order. Blood gases, hemodynamic measurements, quasistatic respiratory compliance and assessments of side effects were performed before begin, 30 min and 6 h after first positioning, then 30 min and 6 h after second positioning and 2 after repositioning. RESULTS: Turning patients in IPP and CPP resulted in a significant increase in the arterial oxygenation index (p(a)O(2)/F(I)O(2)), but this effect was more pronounced in the CPP (before: 142+/-46 mm Hg, 6 h: 253+/-107 mm Hg) than in the IPP (before: 139+/-54 mm Hg, 6 h: 206+/-75 mm Hg), and compliance was improved only in CPP. The improvement in arterial oxygenation persisted 2 h after repositioning in the supine position in both groups. The oxygenation responder rate was lower during the IPP (70.3%) in comparison with the CPP (84.0%, p<0.05). The incidence of side effects tended to be increased during the CPP. CONCLUSION: Incomplete prone position improves oxygenation in ARDS patients, but less effectively than a "classic" CPP. In these patients the use of a CPP should be preferred.

Aged↗

Thalidomide for the treatment of idiopathic myelofibrosis.

Except rare instances of allogeneic stem cell transplantation, treatment of idiopathic myelofibrosis (IMF) is only palliative and based on cytostatic treatment (hydroxyurea and anagrelide), androgen therapy, steroids and splenectomy. Thalidomide is an anti-angiogenic and immunomodulatory drug with a wide spectrum of activities, which are not clearly understood. Current data suggest that the action of thalidomide is related to several different mechanisms, including suppression of tumor necrosis factor, effects on basic fibroblast growth factor, vascular endothelial growth factor, interleukins and interferons, downregulation of selected cell surface adhesion molecules, and changes in the lymphocyte subsets. We administered thalidomide to 16 patients with IMF (15 men, one women) who had transfusion-dependent anemia, thrombocytopenia or symptomatic splenomegaly. Median age was 59 yr (range: 52-78). Patients received thalidomide at an escalating dose from 100 to 400 mg/d (median 300 mg). The drug was discontinued in four patients because of progressive disease (two) or polyneuropathy (two). Other adverse effects were obstipation (10), fatigue (eight) and edema (two). Clinical response has now been observed for a median duration of 9 months (range: 3-20). Fifteen patients are evaluable. Anemia improved in six of 10 patients who were anemic. Platelet counts improved in five of seven patients with thrombocytopenia. Splenomegaly regressed in three of 13 patients. Lactate dehydrogenase (LDH) decreased in seven of 12 patients, but increased in four patients. LDH levels were not correlated with clinical response. In summary, thalidomide appears useful in the treatment of IMF.

Aged↗

Acute disseminated encephalomyelitis and mucocutaneous ulcerations.

A 15-year-old Libyan girl developed typical findings of acute disseminated encephalomyelitis, unveiling characteristic symptoms of Behçet's disease by months. This disease course of neuro-Behçet's disease is quite exceptional in children, and an isolated, high-density MRI lesion of the corpus callosum, like in the present case, has not been described in neuro-Behçet's disease before.

Adolescent↗

[Imaging techniques in rheumatology: magnetic resonance imaging in rheumatoid arthritis].

Magnetic resonance imaging (MRI) is currently the most modern and, at the same time, most technically advanced instrument of sectional imaging in diagnostic radiology. MRI is superior to other radiological procedures because of its excellent soft-tissue contrast, the possibility of multiplanar imaging and the missing of ionizing radiation. Exact differentiation and imaging of soft tissue and bony alterations is of significant evidence in early diagnosis and monitoring of inflammatory joint diseases, such as rheumatoid arthritis (RA). Besides securing of technical quality management, the physician's qualification in indication, conduction and evaluation of MRI plays a pivotal role. This development of MRI for rheumatological purposes needs standardized recommendations and investigation protocols, which are now summarized and presented by the rheumatologists and radiologists of the study group of "diagnostic imaging procedures" of the German Society for Rheumatology (DGRh).

Arthritis, Rheumatoid↗

Co-ordinated expression of 5-HT2C receptors with the NCX1 Na+/Ca2+ exchanger in histaminergic neurones.

The different roles of Na+/Ca2+ (NCX) exchangers and Na+/Ca2+/K+ (NCKX) exchangers in regulation of the ionic homeostasis in neurones are poorly understood. We have previously shown that serotonin excites histaminergic tuberomamillary (TM) neurones by activation of 5-HT2C-receptors and Na+/Ca2+ exchange. With the help of single-cell RT-PCR (sc-RT-PCR) we have now determined the coexpression pattern of different subtypes of NCX and NCKX with serotonin receptors. The majority of TM neurones express NCX1, NCX2 and NCKX3. Serotonin 2C receptor-mRNA was detected in 70% while 5-HT2A mRNA was found in only 10% of TM neurones. In all neurones expressing the 5-HT2C receptor NCX1-mRNA was present. Double immunostaining revealed the presence of the NCX1 protein in histidine decarboxylase-positive neurones. In the majority of TM neurones one or two out of five isoforms, NCX1.4, NCX1.5, NCX1.7, NCX1.14, NCX1.15, were detected by cDNA sequencing and/or by restriction analysis. The alternative splicing region is important for the Ca2+ sensitivity and presumably for the modulation of NCX1 function by second messengers. We conclude that several exchanger-subtypes can be coexpressed in single neurones and that TM cells are heterogeneous with respect to their calcium homeostasis regulation.

Alternative Splicing↗

Optimized protocol for linear RNA amplification and application to gene expression profiling of human renal biopsies.

Gene expression analysis using high-density cDNA or oligonucleotide arrays is a rapidly emerging tool for transcriptomics, the analysis of the transcriptional state of a cell or organ. One of the limitations of current methodologies is the requirement of a relatively large amount of total or polyadenylated RNA as starting material. Standard array hybridization protocols require 5-15 micrograms labeled RNA. To obtain these quantities from small amounts of starting RNA material, RNA can be amplified in a linear fashion. Here we introduce an optimized protocol for rapid and easy-to-use amplification of as little as 1 ng total RNA. Our analysis shows that this method is linear and highly reproducible and that it preserves similarities as well as dissimilarities between normal and disease-related samples. We applied this technique to the RNA expression profiling of human renal allograft biopsies with normal histology and compared them to the profiles of renal biopsies with histological evidence of chronic transplant nephropathy or chronic rejection. Among others, complement component C1r was found to be significantly up-regulated in chronic rejection and chronic transplant nephropathy biopsies compared to normal samples, while fructose-1,6-biphosphatase showed lower-than-normal expression.

Gene Expression Profiling↗

Vertebral fractures in multiple myeloma: first results of assessment of fracture risk using dynamic contrast-enhanced magnetic resonance imaging.

The objective of this study was to evaluate dynamic contrast-enhanced magnetic resonance imaging (d-MRI) as a prognostic indicator of lumbar vertebral fractures in patients with multiple myeloma. d-MRI of the lumbar spine was performed in ten patients with multiple myeloma. A fast gradient echo sequence (turbo fast low-angle shot, two-dimensional) was used, together with controlled bolus injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). The maximum increase in signal intensity [amplitude (A),arbitrary units (a.u.)] was assessed for each lumbar vertebra. About half a year later (median: 6.2 months) magnetic resonance imaging was repeated to detect new fractures. Amplitudes of vertebrae which fractured after the initial d-MRI were compared with amplitudes of vertebrae which did not fracture during follow-up. Six of ten patients (7 of 50 lumbar vertebrae) showed new fractures. Five patients fractured one vertebra each, whereas one patient had several vertebrae involved. The initial d-MRI showed significantly higher amplitudes (p<0.0001) in those vertebrae that subsequently fractured (A: 33.1+/-8.1 vs 16.7+/-4.2). On retrospective analysis, a cutoff level of 25 a.u. discriminated without overlap between vertebrae that fractured during follow-up and those which did not. The maximum increase in signal intensity (the amplitude) on d-MRI appears to be a prognostic marker capable of predicting vertebral fractures of the lumbar spine in patients with multiple myeloma. d-MRI may therefore be helpful in identifying patients who might benefit from localized radiation therapy or surgical intervention.

Adult↗

Quantification of total abdominal fat volumes using magnetic resonance imaging.

The purpose of this study was to develop a rapid and reliable method for the measurement of total abdominal fat volumes in diabetic patients using magnetic resonance imaging (MRI). Total volume coverage of the abdomen was obtained using T1-weighted images in 37 diabetic patients (age 48 +/- 13 y mean +/-SD). Quantification of intraabdominal (IAF), subcutaneous (SCF), and total abdominal fat volumes (TAF) was performed using a semiautomated computer assisted analysis. The variability of image analysis for fat measurements between two observers and within observers was assessed. Mean volumes (+/- SD) for IAF, SCF and TAF were 10.5 l (+/- 5.0 l), 15.1 l (+/-7.3 l) and 25.7 l (+/-11.5 l), respectively. Reliability of measurements was excellent for both observers (observer I: intraobserver reliability IAF, SCF and TAF: r = 0.999, r = 0.999 r = 1.0, observer II: r = 0.999, r = 0.999 and r = 1.0), as well as between both observers (interobserver reliability IAF, SCF, and TAF: r = 0.999, r = 0.999, r = 1.0). A single computer analysis required about 9 min in addition to 7 min scan time. The developed analysis method of MR images allows a rapid and reliable determination of total intraabdominal, subcutaneous and total fat volumes. This method has the potential to be very valuable in respective studies in patients with diabetes.

Abdomen↗