PubMed Health⌕ Search

Biomedical subjects

M Schäfers

Publications and source records attributed to M Schäfers.

At least 19 recordsLinked to original sources
PubMed2006

Molecular imaging of matrix metalloproteinases in vivo using small molecule inhibitors for SPECT and PET.

Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent secreted or membrane anchored endopeptidases. MMPs are involved in many physiological processes but also take part in the pathophysiological mechanisms responsible for a wide range of diseases. Pathological expression and activation of MMPs are associated with cancer, atherosclerosis, stroke, arthritis, periodontal disease, multiple sclerosis and liver fibrosis. Thus, noninvasive visualisation and quantification of MMP activity in vivo are of great interest in basic research and clinical application. This can be achieved by scintigraphic molecular imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) provided suitable radiolabelled tracers exist, e.g. radioactive inhibitors of matrix metalloproteinases (MMPIs). The approach to monitor MMP activity in vivo using radiolabelled small molecule inhibitors suitable for SPECT and PET is summarised in this review. Briefly, latest advances in scintigraphic imaging are introduced and followed by a report about the enzyme class of MMPs. The involvement of MMPs in cancer and atherosclerosis is exemplified and small molecule MMPIs are classified. Subsequently, the development of radiolabelled small molecule MMPIs, their synthesis and in vitro and in vivo evaluation is reviewed. Finally, an outlook on the clinical potential of labelled MMPIs in diagnostic algorithms is given.

Animals↗
PubMed2005

Non-invasive molecular imaging of beta-adrenoceptors in vivo: perspectives for PET-radioligands.

Recently, the spectrum of molecular imaging devices such as positron emission tomography (PET) was further expanded by the now clinically available combined imaging modalities such as PET-CT and the preclinically used small animal PET scanners. These are powerful tools that can bridge the gap between preclinical and clinical evaluation studies of new radiotracers for molecular imaging of healthy and diseased states in vivo. The beta-adrenoceptor (beta-AR) radioligands discussed in this review represent a class of molecular probes for the non-invasive in vivo assessment of beta-AR density eg. in the heart with PET. The beta-AR radioligands (S)-[11C]CGP 12177 (1) or (S)-[11C]CGP 12388 (2) are currently investigated in clinical studies with PET. Additionally, subtype-selective beta1-AR radioligands are used in preclinical research which show potential for the diagnostics of the "beta1-AR organ" as such the heart can be defined. Non-invasive quantification of beta-ARs could facilitate the accurate choice and control of therapeutic interventions. Here we summarize the state-of-the-art of the radiochemistry of radioactive beta-AR radioligands.

Adrenergic beta-Agonists↗
PubMed2005

Motion correction in PET/CT.

Motion in PET/CT leads to artifacts in the reconstructed PET images due to the different acquisition times of positron emission tomography and computed tomography. The effect of motion on cardiac PET/CT images is evaluated in this study and a novel approach for motion correction based on optical flow methods is outlined. The Lukas-Kanade optical flow algorithm is used to calculate the motion vector field on both simulated phantom data as well as measured human PET data. The motion of the myocardium is corrected by non-linear registration techniques and results are compared to uncorrected images.

Heart↗
PubMed2004

Clinical situations demanding weaning from long-term ventricular assist devices.

OBJECTIVE: Ventricular assist devices are increasingly used to treat patients with acute or chronic end-stage heart failure. We report on circumstances, exemplified on four cases, where a surprisingly favorable clinical course of the patients ultimately demanded early explantation of the device, which was not anticipated prior to its implantation. METHODS: The four patients were provided with implantable (Micromed BeBakey trade mark, Incor trade mark ) and external pneumatically driven (Thoratec trade mark, Excor trade mark ) devices under emergency conditions and were listed for heart transplantation. RESULTS: All four patients had an unexpected recovery of myocardial pump function. After careful diagnostic evaluation, all device components were completely removed without extracorporeal circulation. No stepwise weaning protocol was employed. CONCLUSIONS: Weaning patients from ventricular assist devices after recovery of myocardial pump function can become necessary. Diagnostic evaluation and the implementation of a weaning protocol is still a matter of debate, while complete surgical removal of all device components without extracorporeal circulation is possible with a low risk.

Acute Disease↗
PubMed2003

Spinal nerve ligation induces transient upregulation of tumor necrosis factor receptors 1 and 2 in injured and adjacent uninjured dorsal root ganglia in the rat.

Evidence indicates a role for tumor necrosis factor-alpha (TNF) in neuropathic pain. We correlated pain behavior in response to mechanical stimulation with immunoreactivity for TNF receptor (TNFR) 1 and 2 at 6, 24, 76 and 120 h following L5 and L6 spinal nerve ligation (SNL). Allodynia began in both L4 and L5 dermatomes within 6 h following SNL, peaking by 24 h. In L5 (injured) dorsal root ganglia (DRG), TNFR1 and TNFR2 levels displayed a bimodal increase, peaking at 6 and 120 h after SNL. In L4 (uninjured) DRG, TNFR1 and TNFR2 immunoreactivity peaked at 24 h returning to basal levels by 120 h. TNFR upregulation in injured and adjacent uninjured DRG neurons may be essential for mediating enhanced TNF effects and thus contribute to the development of pain-related behavior.

Animals↗
PubMed2003

Radioligands for imaging myocardial alpha- and beta-adrenoceptors.

Alpha- and beta-adrenoceptors play an important role in the control of heart function. According to their molecular, biological, and pharmacological characteristics, they are subdivided into alpha(1)-, alpha(2)- and beta(1)-, beta(2)-, beta(3)-, beta(4)-adrenoceptors. In cardiac disease, there is often a selective downregulation of beta(1)-adrenoceptors associated with a relative increase in beta(2)- and alpha(1)-adrenoceptors. Functional imaging techniques like single-photon emission tomography (SPECT) and positron emission tomography (PET) provide the unique capability for non-invasive assessment of cardiac adrenoceptors. Radioligands with high specific binding to cardiac alpha- and beta-adrenoceptors suitable for radiolabelling are required for clinical studies. The non-selective beta-adrenoceptor antagonist [(11)C]CGP-12177 was used to quantify beta-adrenoceptor density using PET in patients with heart disease. New non-selective ligands (e. g. [(11)C]CGP-12388, [(18)F]CGP-12388, [(11)C]carazolol and [(18)F]fluorocarazolol) are currently evaluated; beta(1)-selective radioligands (e. g. [(11)C]CGP-26505, [(11)C]bisoprolol, [(11)C]HX-CH 44) and beta(2)-selective radioligands (e. g. [(11)C]formoterol, [(11)C]ICI-118551) were assessed in animals. None of them turned out as suitable for cardiac PET. Potential radioligands for imaging cardiac alpha(1)-adrenoceptors are based on prazosin. Whereas [(11)C]prazosin shows low specific binding to myocardium, its derivative [(11)C]GB67 looks more promising. The putative alpha(2)-adrenoceptor radioligand [(11)C]MK-912 shows high uptake in rodent myocardium but has not yet been evaluated in man. A number of radioligands were evaluated for assessing cardiac adrenoceptors using PET. New radioligands are needed to provide more insight into cardiac pathophysiology which may influence the therapeutic management of patients with cardiovascular disease.

Carbon Radioisotopes↗
PubMed2003

[High non-specific binding of the beta(1) -selective radioligand 2-(125)I-ICI-H].

AIM: As results of cardiac biopsies suggest, myocardial beta(1) -adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac beta(2)-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess beta-adrenoceptors non-invasively. Among the novel racemic analogues of the established beta(1)-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to beta(1)-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective beta(1)-adrenergic radioligand in cardiac imaging. METHODS: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac beta-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-(125)I-ICI-H from the silylated precursor 2-SiMe(3)-ICI-H was established. The specific activity was 80 GBq/ micro mol, the radiochemical yield ranged from 70 to 80%. RESULTS: The unlabelled compound 2-I-ICI-H showed high beta(1)-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac beta-adrenoceptors. The radiolabelled counterpart 2-(125)I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac beta(1)-adrenoceptors in vivo. CONCLUSION: Because of its high non-specific binding 2-(125)I-ICI-H is no suitable radiotracer for imaging in vivo.

Adrenergic beta-Antagonists↗
PubMed2002

Mycophenolate mofetil in the therapy of polymyositis associated with a polyautoimmune syndrome.

Mycophenolate mofetil 1.5 g daily (30 mg/kg body weight) was given to a patient with ankylosing spondylitis, ulcerative colitis, and severe refractory polymyositis after conventional treatment regimes had failed. No severe side effects occurred. Considerable improvement of clinical symptoms and electromyographic findings were seen within 6 months after the initiation of mycophenolate mofetil, allowing for tapering and discontinuation of methylprednisolone. Mycophenolate mofetil may be considered as an useful alternative in the treatment of polymyositis when standard therapeutic regimens fail.

Anti-Inflammatory Agents↗
PubMed2002

[Methods and clinical applications in nuclear cardiology: a position statement].

Nuclear cardiological procedures have paved the way for non-invasive diagnostics of various partial functions of the heart. Many of these functions cannot be visualised for diagnosis by any other method (e.g. innervation). These techniques supplement morphological diagnosis with regard to treatment planning and monitoring. Furthermore, they possess considerable prognostic relevance, an increasingly important issue in clinical medicine today, not least in view of the cost-benefit ratio. Our current understanding shows that effective, targeted nuclear cardiology diagnosis--in particular for high-risk patients--can contribute toward cost savings while improving the quality of diagnostic and therapeutic measures. In the future, nuclear cardiology will have to withstand mounting competition from other imaging techniques (magnetic resonance imaging, electron beam tomography, multislice computed tomography). The continuing development of these methods increasingly enables measurement of functional aspects of the heart. Nuclear radiology methods will probably develop in the direction of molecular imaging.

Cardiology↗
PubMed2001

Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy.

We investigated the anti-hyperalgesic effect of neutralizing antibodies (AB) to tumor necrosis factor-alpha (TNF) in two murine models of neuropathy, the chronic constrictive sciatic nerve injury (CCI) which has a strong epineurial inflammatory component, and the partial sciatic nerve transection (PST), a 'pure' nerve injury model. In both models a single AB injection intra-operatively as well as on day 4 reduced thermal hyperalgesia significantly, whereas mechanical allodynia was only reduced with intraoperative but not with delayed treatment.

Animals↗
PubMed2001

Combined epineurial therapy with neutralizing antibodies to tumor necrosis factor-alpha and interleukin-1 receptor has an additive effect in reducing neuropathic pain in mice.

Monotherapy with antibodies to tumor necrosis factor-alpha (TNF) or interleukin-1 receptor 1 (IL-1R1) reduces hyperalgesia in an animal model of painful neuropathy. Here we investigated whether combined therapy with epineurial anti-TNF and anti-IL-1R1 antibodies produces a further advantage. C57BL/6 mice with a chronic constrictive injury of one sciatic nerve were treated epineurially with neutralizing antibodies to either IL-1R1 or TNF alone or with a combined application of neutralizing antibodies to TNF and IL-1R1. Combined treatment with anti-IL-1R1 and anti-TNF antibodies markedly reduced thermal hyperalgesia and mechanical allodynia more effectively than monotherapy with either antibody. There were no detectable differences in IL-1beta and TNF endoneurial protein expression between animals with monotherapy and combined treatment. We conclude that combined anti-cytokine therapy may be a useful strategy in the treatment of neuropathic pain.

Animals↗
PubMed2001

Sigmoid and transverse sinus thrombosis after closed head injury presenting with unilateral hearing loss.

Sinus thrombosis has rarely been associated with closed head injury; more often, thrombosis of the sigmoid or transverse sinus is caused by otogenic inflammations or tumours, or occurs during pregnancy. Symptoms are frequently vague, while untreated thrombus progression may be fatal due to venous congestion and infarction. We report a 32-year-old man presenting with right hearing loss, tinnitus and headache 2 days after a closed head injury. Neurological examination showed no additional abnormality. The EEG showed focal bifrontal slowing. CT revealed a fracture of the occipital bone. MRI and MRA demonstrated complete thrombosis of the right sigmoid and transverse sinuses. After 2 weeks of intravenous heparin therapy followed by warfarin, the patient's hearing improved and MRI and MRA showed complete recanalisation of the sigmoid and transverse sinuses. Venous sinus thrombosis can be an undetected sequel to head injury. Appropriate imaging studies should be carried out to enable therapy to be started as soon as possible.

Adult↗