Cardiovascular effects of chronic treatment with a β2-adrenoceptor agonist relieving neuropathic pain in mice.
ABSTRACT Neuropathic pain is often a chronic condition, disabling and difficult to treat. Using a murine model of neuropathic pain induced by placing a polyethylene cuff around the main branch of the sciatic nerve, we have shown that chronic treatment with β-AR agonists is effective against neuropathic allodynia. β-mimetics are widely used against asthma and chronic obstructive pulmonary disease and may offer an interesting option for neuropathic pain management. The most prominent adverse effects of chronic treatment with β-mimetics are cardiovascular. In this study, we compared the action of low doses of the selective β(2)-AR agonist terbutaline and of a high dose of the mixed β(1)/β(2)-AR agonist isoproterenol on cardiovascular parameters in a neuropathic pain context. Isoproterenol was used as a positive control for some heart-related changes. Cardiac functions were studied by echocardiography, hemodynamic measurements, histological analysis of fibrosis and cardiac hypertrophy, and by quantitative real time PCR analysis of atrial natriuretic peptide (Nppa), periostin (Postn), connective tissue growth factor (Ctgf) and β-myosin heavy chain (Myh7). Our data show that a chronic treatment with the β(2)-AR agonist terbutaline at low antiallodynic dose does not affect cardiovascular parameters, whereas the mixed β(1)/β(2)-AR agonist isoproterenol induces cardiac hypertrophy. These data suggest that low doses of β(2)-AR agonists may provide a suitable treatment with rare side effects in neuropathic pain management. This study conducted in an animal model requires clinical confirmation in humans.
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ABSTRACT: Autoimmune lymphoproliferative syndrome (ALPS) is associated with mutations that impair the activity of lymphocyte apoptosis proteins, leading to chronic lymphadenopathy, hepatosplenomegaly, autoimmunity, and an increased risk of lymphoma. We investigated the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) in discriminating benign from malignant lymphadenopathy in ALPS. We report that FDG avidity of benign lymph nodes in ALPS can be high and, hence, by itself does not imply presence of lymphoma; but FDG-PET can help guide the decision for selecting which of many enlarged nodes in ALPS patients to biopsy when lymphoma is suspected.American Journal of Hematology 03/2006; 81(2):81-5. · 4.00 Impact Factor
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ABSTRACT: To evaluate a single centre experience of endovascular treatment of mesenteric ischemia caused by vascular occlusion. Retrospective study. Between 1995 and 2002 17 patients (12 females; mean age 61 years) with symptoms of bowel ischemia were treated endovascularly for arterial occlusion. Vessels were evaluated with angiography and pressure gradient measured. A mean gradient of > 20 mmHg or a stenosis of > 50% was considered significant. Patient data were recorded prospectively and follow-up was supplemented with retrospective chart review. Fifteen patients had follow up imaging, median 10 months (3-29 months) postoperatively. Median clinical follow up was 14 months (5-42 months). Recanalisation was successful in 16 patients (94%). The average number of stents used was 1.6 per patient. For one patient recanalisation failed with subsequent SMA dissection. A celiac artery stenosis was stented but symptoms remained postoperatively. Perioperative mortality was 5.8% (n = 1). 14/17 patients (82%) displayed symptom relief/improvement. Six patients required secondary endovascular intervention; PTA (n = 3); stent/stentgraft (n = 3). Two of these patients required a third procedure. 4/6 patients that underwent secondary intervention were asymptomatic and of recurrent stenosis > 75% and a gradient > 15 mmHg mean pressure gradient on imaging. Two patients were treated because of a combination of angiographic findings and/or significant pressure gradient combined with clinical symptoms. Endovascular treatment of mesenteric ischemia due to vessel occlusion is feasible with acceptable short-term results and limited complications. Most patients experience relief/improvement of symptoms. A significant number of patients might need endovascular re-intervention because of restenosis.European Journal of Vascular and Endovascular Surgery 02/2005; 29(2):199-203. · 2.82 Impact Factor
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ABSTRACT: The aim of this prospective study was to compare fluorine-18 fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) with magnetic resonance imaging (MRI) in patients with early aortitis, at the time of initial diagnosis and during immunosuppressive therapy. The study population consisted of 15 patients (nine females and six males; median age 62 years, range 26-76 years) who presented with fever of unknown origin or an elevated erythrocyte sedimentation rate or elevated C-reactive protein and who showed pathological aortic [(18)F]FDG uptake. Fourteen of these patients had features of early giant cell arteritis (GCA), while one had features of early Takayasu arteritis. During follow-up, seven PET scans were performed in six patients with GCA 4-30 months (median 19 months) after starting immunosuppressive medication. The results of [(18)F]FDG imaging were compared with the results of MRI at initial evaluation and during follow-up and with the clinical findings. At baseline, abnormal [(18)F]FDG uptake was present in 59/104 (56%) of the vascular regions studied in 15 patients. Seven follow-up PET studies were performed in six patients. Of 30 regions with initial pathological uptake in these patients, 24 (80%) showed normalisation of uptake during follow-up. Normalisation of [(18)F]FDG uptake correlated with clinical improvement and with normalisation of the laboratory findings. All except one of the patients with positive aortic [(18)F]FDG uptake were investigated with MRI and MRA. Thirteen of these 14 patients showed inflammation in at least one vascular region. Of 76 vascular regions studied, 41 (53%) showed vasculitis on MRI. Of 76 vascular regions studied with both PET and MRI, 47 were concordantly positive or negative on both modalities, 11 were positive on MRI only and 18 were positive on PET only. MRI was performed during follow-up in six patients: of 17 regions with inflammatory changes, 15 regions remained unchanged and two showed improvement. Whole-body [(18)F]FDG PET is valuable in the primary diagnosis of early aortitis. The results of [(18)F]FDG PET and MRI in the diagnosis of aortitis in this study were comparable, but FDG imaging identified more vascular regions involved in the inflammatory process than did MRI. In a limited number of patients [(18)F]FDG PET was more reliable than MRI in monitoring disease activity during immunosuppressive therapy.European journal of nuclear medicine and molecular imaging 06/2003; 30(5):730-6. · 5.11 Impact Factor