ABSTRACT
OBJECTIVE: To compare the use of radiolabelled human monoclonal anti-TNF-α scintigraphy with clinical examination and MRI of hands and wrists joints in patients with active RA. METHODS: Eight patients with active RA, 28-joint DAS (DAS-28) ≥ 3.2 and a healthy volunteer underwent whole body and hand/wrist scintigraphy after the administration of anti-human TNF-α labelled with technetium-99m ((99m)Tc). One hundred and ninety-eight joints were examined. Patients were also given clinical examinations in addition to MRI of the hands and wrists. RESULTS: Of the 198 joints examined, signs of inflammation were detected by MRI in 49 (24.7%) and by scintigraphy in 48 (24.2%) joints, with agreement between the two methods in 44 joints. In five joints, MRI was positive and scintigraphy negative. In another four joints, scintigraphy was positive and MRI negative for signs of inflammation. MRI and scintigraphy were in agreement for negative results for 145 joints. The sensitivity and specificity of scintigraphy was 89.8 and 97.3%, respectively. When clinical parameters (presence of swelling and tenderness of joints) were compared with the MRI findings, lower correlation coefficients were observed (sensitivity of 59.2% and 65.3%, respectively). CONCLUSIONS: Scintigraphy using (99m)Tc-anti-TNF-α showed high correlation with the presence of inflammatory signs detected by MRI in the hands and wrists of patients with active RA, and demonstrated a greater sensitivity than clinical examination. These results can assist in better understanding of anti-cytokine therapy and support the achievement of evidence-based biologic therapy.
Subject(s)
Antibodies, Monoclonal , Arthritis, Rheumatoid/diagnostic imaging , Magnetic Resonance Imaging/methods , Technetium , Tumor Necrosis Factor-alpha/analysis , Wrist Joint/diagnostic imaging , Adult , Aged , Arthritis, Rheumatoid/pathology , Arthritis, Rheumatoid/physiopathology , Health Status , Humans , Middle Aged , Pilot Projects , Predictive Value of Tests , Radionuclide Imaging , Recovery of Function , Reproducibility of Results , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/immunologyABSTRACT
BACKGROUND: Bone marrow-derived cell therapy has been investigated in patients with severe liver disease. AIMS: To assess the feasibility, safety and cell kinetics of autologous bone marrow-derived mononuclear cells (BMMCs) infusion in cirrhotic patients. METHODS: BMMCs were isolated from autologous bone marrow and 10% of the cells were labelled with (99m)Tc-SnCl2. Whole body scintigraphy (WBS) was performed 3 and 24 h after infusion via the hepatic artery. Liver function and image were followed during 1 year. RESULTS: Eight patients received 2.0-15.0 × 108 cells. Three and 24-h WBS showed mean hepatic radiotracer retentions of 41 and 32% respectively. One case of dissection of the hepatic artery and one case of Tako-tsubo syndrome occurred as early complications. A patient developed a cutaneous immunomediated disorder and another patient developed hepatocellular carcinoma (HCC) 12 months after infusion. A reduction in bilirubin was shown at 1 week while serum albumin increased above baseline up to 1 month after infusion (P<0.05). CONCLUSIONS: BMMCs infusion is feasible and practical in a clinical setting. In vivo tracking of labelled cells demonstrated that the hepatic artery route successfully delivered BMMCs to the liver. The early improvement of laboratory indices of liver function should be interpreted with caution, because this study was not designed to evaluate efficacy. The median Model for End-Stage Liver Disease score had not deteriorated 1 year later. The occurrence of a graft-versus-host disease-like phenomenon highlights the importance of sustained vigilance even when giving autologous cells. Controlled studies are needed to determine whether BMMCs infusion affects HCC development in cirrhosis.
Subject(s)
Bone Marrow Transplantation , End Stage Liver Disease/therapy , Leukocytes, Mononuclear/transplantation , Liver Cirrhosis/therapy , Aged , Bone Marrow Transplantation/adverse effects , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/pathology , Feasibility Studies , Female , Humans , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Function Tests , Liver Neoplasms/etiology , Liver Neoplasms/pathology , Male , Middle Aged , Postoperative Complications , Treatment OutcomeABSTRACT
The immunomodulatory effect of juice obtained from leaves of Kalanchoe brasiliensis (Kb) on zymosan-induced inflammation was investigated. C57B110 mice received a subcutaneous injection of 150 microg zymosan in the footpad. After 7 days, there was an increase in footpad thickness from 176 +/- 4 to 236 +/- 9 x 10(-2) mm and in blood flow in the footpad area, monitored by 99mTc, from 98 +/- 4 to 694 +/- 59 counts per minute (cpm). Zymosan induced a severe infiltration of leukocytes into the articular tissues and a 13-fold increase in the adjacent popliteal lymph node (PLN) weight. Beginning 2 days after the injection, mice were treated daily for 5 days with different concentrations of lyophilised Kb juice dissolved in water. Treatment with 480 mg/kg/day reduced footpad thickness to 193 +/- 5 x 10(-2) mm, leukocyte infiltration and blood flow to 150 +/- 18 cpm in the footpad area. PLN weight in zymosan-injected mice decreased from 6.5 +/- 0.5 to 1.5 +/- 0.4 mg, similarly to the decrease after treatment with indomethacin (3 mg/kg/day). Flow cytometric analysis of lymph node cells showed an important reduction in B cell number in Kb-treated mice. Treatment over a period of 10 days was also effective at reducing zymosan-induced inflammation, even when started 7 days after injection. These data suggest anti-inflammatory and immunosuppressive effects of K. brasiliensis that may account for its popularity in folk medicine against rheumatic diseases.
