We compared variations among Canadian provinces in rheumatoid arthritis (RA) initiating anti-tumor necrosis factor (TNF) therapy.
Data were obtained from the Optimization of Humira trial (OH) and from the Ontario Biologics Research Initiative (OBRI). Baseline characteristics were compared between regions: Ontario (ON), Quebec (QC), and other provinces (OTH). We compared Ontario OH to OBRI patients who were initiating anti-TNF therapy.
In 300 OH patients, mean age was 54.8 years (13.3). There were 151 (50.3%) ON patients, 57 from QC (19%), and 92 from OTH (30.7%). Regional differences were seen in the number of disease-modifying antirheumatic drugs (DMARD) ever taken (ON: 3.8 ± 1.4, QC: 3.1 ± 1.1, OTH: 3.3 ± 1.4; p
Cirrhosis represents a state of functional immune paresis with increased infection risk.
To investigate polymorphonuclear (PMN) leukocyte and monocyte function in ambulatory cirrhotics, and their potential relation with cirrhosis etiology or patient outcome.
Consecutive ambulatory cirrhotics without current or recent ( 0.05 for all). In Cox regression analysis, increased stimulated monocyte and PMN burst were independent predictors of sepsis, severe sepsis and ACLF occurrence. Also, increased stimulated monocyte burst was associated with worse transplant-free survival (p
Brachial artery blood flow reactions to hyperemia and hyperventilation (endothelium dependent vasodilation and vasoconstriction) were studied by doppler sonography in 60 persons aged 19-39 years with family history of atherosclerosis and risk factors of this disease. Reactivity of peripheral artery and risk factors of atherosclerosis development were found to be interrelated. The results allowed to suggest participation of atherogenic fractions of lipoproteins, triglycerides, proinflammatory cytokines, and monocyte derived NO in formation of pathological vascular reactions in persons with family history of atherosclerosis.
Cell-mediated immunity is essential for protection against the intracellular bacterium Francisella tularensis, which causes tularemia. Positive in vitro T-cell responses in the form of lymphocyte proliferation and lymphokine interleukin 2 (IL-2) and gamma interferon (IFN-gamma) secretion are found in memory immunity. Studies on the secretion of lymphokines with regard to the developing immunity to F. tularensis have not been published. Therefore, 14 subjects with no clinical history of tularemia were vaccinated with a live F. tularensis vaccine strain. The in vitro responses of five subjects (antigen-induced mononuclear cell and whole blood culture DNA synthesis and cytokine secretion) were measured twice a week throughout the period from 0 to 35 days after vaccination, and the peripheral blood lymphocyte subpopulations of nine subjects were determined between days 0 and 14. Positive reactions, i.e., responses exceeding those on day 0, were reached on day 10 with regard to the whole blood culture DNA synthesis response and IL-2 and IFN-gamma secretion and on day 14 with regard to the mononuclear cell DNA synthesis response and tumor necrosis factor alpha (TNF-alpha) secretion. No measurable IL-4 was found in either the immune or nonimmune supernatants. Since the secretion of TNF-alpha was related to immunization, this points to the specificity of the phenomenon, even though the type of secreting cell is not yet known. If it is shown later that specific T cells produce it, the TNF-alpha response and the negative IL-4 finding may speak for the importance of the Th1-like pattern in immunity to F. tularensis.
This paper analyzes the data of examination and the results of the treatment of 25 patients aged over 80 years (mean age 68.5+/-7 years) suffering from varicosity with long nonhealing trophic ulcers of the distal limb segments (CVI CMP C6) and 20 patients of the same age groups with CVI CEAP stages 3-5. All patients with CVI underwent either full-scope phlebectomy (64.4%) or partial truncal phlebectomy (35.6%), in which the trunk of the greater saphenous vein was stripped up to the upper third of the leg. A TCM-3 outfit (RADIOmeter, Denmark) was employed to measure oxygen tension in limb tissues. Parameters of lipid peroxidation and antioxidant tissue defence were measured intraoperatively in the capillary blood of the fingers as well as in the venous blood withdrawn from the cubital vein and the greater saphenous vein in the lower third of the leg near ulcer). The data obtained evidenced that lipid peroxidation activity was most pronounced in the soft tissues of the lower third of the leg in the group of patients with remarkable chronic venous insufficiency without trophic venous ulcers (GVI CEAP C3-5) and was significantly depleted after formation of varicose ulcers (CVI CEAP C6) associated with remarkable tissue hypoxia (TepO2 1.7-7.0 mm Hg). In all patients with CVI, the syndrome of lipid peroxidation was associated with the lowering of antioxidant defence activity. Patients with trophic venous ulcers had the signs of active inflammation in the soft tissues of the leg. The data obtained in the course of the study made it possible to optimize the treatment policy for elderly patients with trophic venous ulcers. In addition to the lowering of venous hypertension, the treatment included correction of microcirculatory disorders related to local hypoxia. Of special importance was reperfusion attenuation in the postoperative period.
Ukrain is a semisynthetic compound consisting of alkaloids from Chelidonium majus L. conjugated to thiophosphoric acid, with immunomodulatory and therapeutic properties in cancer patients. The present in vitro studies demonstrate that Ukrain is an effective biological response modifier augmenting, by up to 48-fold, the lytic activity of splenic lymphocytes obtained from alloimmunized mice. The lytic activities of interleukin-2 (IL-2) treated spleen cells and peritoneal exudate lymphocytes were also significantly increased by the addition of Ukrain to the cell mediated lysis (CML) assay medium. The highest Ukrain-induced enhancement of splenic lymphocytolytic activity in vitro was found to occur at day 18 after alloimmunization was dose-dependent and specific for the immunizing P815 tumour cells. Since Ukrain was present only during the CML assays, its mode of action is thought to be via direct activation of the effector cells' lytic mechanism(s). The effect of Ukrain on the growth of Balb/c syngenic mammary adenocarcinoma was also evaluated. Intravenous, but not subcutaneous or intraperitoneal, administration of this drug was found to be effective in delaying tumour growth in an actual therapeutic protocol initiated five days after tumour implantation. No deleterious side-effects were observed using these in vivo treatment modalities. The role of macrophages in the observed retardation of tumour development was investigated, using peritoneal exudate macrophages (PEM) in cytotoxicity assays. Previous studies showed that PEM of mammary tumour-bearing mice lose their capacity to kill a variety of tumour target cells including the in vitro cultured homologous tumour cells (DA-3). Pretreatment of PEM from normal mice with 2.5 microM Ukrain for 24 h, followed by stimulation with either IFN-gamma or with lipopolysaccharide (LPS) plus IFN-gamma enhanced their cytotoxic activity. Treatment of PEM from tumour-bearing mice with 2.5 microM Ukrain and LPS results in a reversal of their defective cytotoxic response against DA-3 target cells. Furthermore, Ukrain alone, in the absence of a secondary signal, induced the activation of tumouricidal function of PEM from tumour-bearing, but not from normal, mice. These data indicate that Ukrain's in vivo effects against the development of mammary tumours may be due, at least in part, to its ability to restore macrophage cytolytic function.
In regions where studded tyres and traction material are used during winter, e.g. the Nordic countries, northern part of USA, Canada, and Japan, mechanically generated particles from traffic are the main reason for high particle mass concentrations in busy street and road environments. In many Nordic municipalities the European environmental quality standard for inhalable particles (PM(10)) is exceeded due to these particles. In this study, particles from the wear of studded and studless friction tyres on two pavements and traction sanding were generated using a road simulator. The particles were characterized using particle sizers, Particle Induced X-Ray Emission Analysis and electron microscopy. Cell studies were conducted on particles sampled from the tests with studded tyres and compared with street environment, diesel exhaust and subway PM(10), respectively. The results show that in the road simulator, where resuspension is minimized, studded tyres produce tens of times more particles than friction tyres. Chemical analysis of the sampled particles shows that the generated wear particles consist almost entirely of minerals from the pavement stone material, but also that Sulfur is enriched for the submicron particles and that Zink is enriched for friction tyres for all particles sizes. The chemical data can be used for source identification and apportionment in urban aerosol studies. A mode of ultra-fine particles was also present and is hypothesised to originate in the tyres. Further, traction material properties affect PM(10) emission. The inflammatory potential of the particles from wear of pavements seems to depend on type of pavement and can be at least as potent as diesel exhaust particles. The results imply that there is a need and a good potential to reduce particle emission from pavement wear and winter time road and street operation by adjusting both studded tyre use as well as pavement and traction material properties.
The small bowel (SB), an organ replete with lymphocytes, may provoke graft-versus-host disease (GVHD) after transplantation (Tx). Since tumor necrosis factor (TNF) has been suspected of mediating the tissue lesions of GVHD, we sought to determine whether TNF could be detected in the serum of rats undergoing GVHD after SBTx or lymphocyte transfer. For this purpose, postoperative serum TNF activity was determined in Lewis x Brown Norway (LBNF1) hybrid rats suffering from GVHD after undergoing transplantation of an entire (group 1; n = 8) or a segmental (group 2; n = 4) Lew SB, or after i.p. injection with lethal doses (500 x 10(6)) of Lew lymphocytes (group 3; n = 3). Control LBNF1 received i.p. small doses (50 x 10(6)) of Lew lymphocytes (group 4; n = 4). Serum TNF activity was assessed using the WEHI bioassay. In rats with acute and lethal GVHD after entire SBTx (group 1) or injection with large doses of lymphocytes (group 3), TNF activity gradually increased and reached high levels by the time the rats were agonal. In segmental SBTx rats (group 2), GVHD was less severe than in entire SBTx rats. Similarly, the increase in TNF activity was less intense and only transient since it had returned to control levels by the time the rats had completely recovered from GVHD. In control rats primed with small doses of lymphocytes (group 4), GVHD did not occur and no increase in TNF activity was detected.(ABSTRACT TRUNCATED AT 250 WORDS)