OBJECTIVE: We aimed to investigate whether persistence rates of Tumor necrosis factor (TNF) blockers in the early period was affected by the change in reimbursement guideline of Rheumatoid Arthritis (RA) using Korean National Health Insurance (NHI) claims database. METHODS: We identified patients with a diagnosis code of RA between January 2007 to December 2009 and who were 16 years of age or older, in a Korean NHI claims database. A subgroup RA patients who had recently started TNF blockers with 6 months of washout period in June 2007 (n=40), June 2008 (n=60), January 2009 (n=52) and June 2009 (n=68) were selected to compare the 6 months persistence rate. Also, we analyzed a change in prescriptions of TNF blockers in patients with RA for each 6 month period between 2007 and 2009. RESULTS: The persistence rates of TNF blockers during 6 months in each group was not statistically significant (67.5%, 75.0%, 73.1%, and 79.4%, p=0.22). However, when we compared the frequency of new patients started on TNF blockers in June 2009 to those in the same months in 2008 and 2007; there was a tendency to increase. During change in TNF blocker prescriptions between 2007 and 2009, the overall utilization of TNF blockers increased. CONCLUSION: The persistence rate of TNF blockers in the early period was not affected by change of reimbursement guidelines of RA. However, long-term design and multivariate analysis will be needed to identify the impact of change in reimbursement guideline on the persistence of TNF blockers.
Arthritis, Rheumatoid ; Humans ; Multivariate Analysis ; National Health Programs ; Prescriptions ; Tumor Necrosis Factor-alpha

Animals ; Female ; Male ; Rabbits ; Tumor Necrosis Factor-alpha ; analysis ; Vibration ; adverse effects

Chronic rheumatoid arthritis (RA) is characterized by the hyperplasia of synovial tissue, which results from the combined influence of the proliferation and antiapoptosis of the synovial cells. In this study, to identify candidate factors involved in the regulation of synovial hyperplasia, the expression profile of 205 apoptosis-related genes in a rheumatoid synovium was analyzed in comparison with that in an osteoarthritis (OA) synovium using a cDNA microarray. Upregulated genes in the RA synovium include TNFR2, GRB2, RBL2, CDC25B, MAPK p38, CDK-like kinase 2, and FLICE2, whereas 5 genes including SARP1 were down-regulated relative to OA. Among them, importantly, the expression levels of GRB2 and FLICE2 genes were remarkably enhanced in RA but not OA synoviocytes in response to TNF -alpha treatment. Therefore, TNF-alpha inducibility to GRB2 and FLICE2 genes abnormally enhanced in RA synoviocytes might represent the increased transcripts of these two genes in rheumatoid sunovial tissues. Moreover, these results suggest that RA-specific signals by TNF-alpha, including GRB2 and FLICE2, are involved in the pathogenic processes of synovial hyperplasia.
Arthritis, Rheumatoid* ; Hyperplasia* ; Mass Screening* ; Oligonucleotide Array Sequence Analysis ; Osteoarthritis ; Phosphotransferases ; Receptors, Tumor Necrosis Factor, Type II ; Synovial Membrane ; Tumor Necrosis Factor-alpha

OBJECTIVETo investigate the relationship between the presence of the TNF2 allele and plasma concentrations of tumor necrosis factor-alpha (TNF alpha) and soluble TNF receptor (sTNF-R) with the development of acute severe pancreatitis (ASP) and severe sepsis.

METHODSGenomic DNA was prepared from peripheral blood leukocytes. The TNF1 and TNF2 biallelic polymorphisms were identified by analyzing NcoI-digested DNA fragments obtained from PCR products. Plasma levels of TNF alpha and sTNF-R were measured by EASIA.

RESULTSThe overall TNF2 allele frequency in ASP patients was comparable to that found in healthy volunteers (29.2% vs. 29.3%, P > 0.05). Severe sepsis occurred in 26 of 72 patients. Patients with severe sepsis showed a significantly higher prevalence of TNF2 than those without (46.2% vs. 19.6%, P < 0.05). Plasma TNF alpha, sTNF-R I, and sTNF-R II levels were (36 +/- 31) pg/ml, (5.4 +/- 3.5) ng/ml, and (11.2 +/- 7.8) ng/ml, respectively, in patients with severe sepsis, and (31 +/- 25) pg/ml, (4.6 +/- 3.8) ng/ml, and (8.8 +/- 6.6) ng/ml in non-severe sepsis subjects. Differences in TNF levels were not statistically significant between patients with ASP and control group (P > 0.05). Moreover, there was no correlation between TNF2 allele frequency and TNFalpha levels [(37 +/- 31) pg/ml vs. (31 +/- 25) pg/ml in TNF2 group and TNF1 group, respectively, P > 0.05].

CONCLUSIONSOur results suggest that there is no relationship between ASP and the TNF2 allele, but that the TNF2 allele is associated with a susceptibility to severe sepsis as a result of ASP.

Acute Disease ; Adult ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis ; genetics ; Polymorphism, Genetic ; Receptors, Tumor Necrosis Factor ; blood ; Sepsis ; genetics ; Tumor Necrosis Factor-alpha ; analysis ; genetics

OBJECTIVETo determine the clinical significance of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha( TNF-alpha) in expressed prostatic secretions(EPS) for chronic prostatitis.

METHODSProstatic secretions IL-1beta and TNF-alpha were evaluated for 34 patients with chronic prostatitis, 10 with asymptomatic inflammatory prostatitis, 12 with benign prostatic hyperplasia (BPH) and 8 health controls by enzyme-linked immunosorbent assay (ELISA).

RESULTSIL-1beta and TNF-alpha levels in EPS in the patients of chronic prostatitis with WBC > or = 10/HP and asymptomatic inflammatory prostatitis were obviously higher than those of chronic prostatitis with WBC < 10/HP, BPH and health controls, (P < 0.05 and P < 0.02). There was a correlation between IL-1beta and TNF-alpha (P < 0.003) but none between WBC and IL-1beta or TNF-alpha.

CONCLUSIONCytokines are frequently elevated in EPS in men of chronic prostatitis with high WBC and asymptomatic inflammatory prostatitis, which provides a novel means different from traditional methods based on WBC for the identification of men with chronic prostatitis.

Aged ; Chronic Disease ; Humans ; Interleukin-1 ; analysis ; Male ; Middle Aged ; Prostate ; chemistry ; secretion ; Prostatitis ; immunology ; Tumor Necrosis Factor-alpha ; analysis

OBJECTIVETo observe changes in the concentrations of MIP-1alpha and TNF-alpha and their influence on sperm in the seminal plasma of infertile males.

METHODSWe measured the concentrations of MIP-1alpha and TNF-alpha in the seminal plasma of 110 infertile patients and 30 normal fertile men by ELISA and radioimmunoassay, and compared them with sperm concentration, sperm viability, sperm motility, leukocytospermia and serum anti-sperm antibodies (AsAb).

RESULTSThe infertility group, particularly the oligospermia cases, showed significantly higher concentrations of MIP-1alpha and TNF-alpha in the seminal plasma ([179.45 +/- 24.54] pg/ml and [4.66 +/- 2.01] ng/ml) than the normal fertile men ([89.64 +/- 13.27] pg/ml and [2.90 +/- 1.23] ng/ml) (P < 0.01). In comparison, the concentrations of MIP-1alpha and TNF-alpha were (196.04 +/- 23.54) pg/ml and (5.31 +/- 2.47) ng/ml versus (154.22 +/- 26.38) pg/ml and (3.94 +/- 2.09) ng/ml in the poor and normal sperm viability groups (P < 0.05 or P < 0.01), (210.39 +/- 21.43) pg/ml and (5.14 +/- 2.61) ng/ml versus (139.87 +/- 27.62) pg/ml and (4.11 +/- 2.26) ng/ml in the low and normal sperm motility groups (P < 0.05 or P < 0.01), (203.14 +/- 24.65) pg/ml and (5.28 +/- 2.66) ng/ml versus (155.76 +/- 21.42) pg/ml and (4.04 +/- 2.24) ng/ml in the leukocytospermia and non-leukocytospermia groups (P < 0.05 or P < 0.01), and (234.05 +/- 27.60) pg/ml and (5.63 +/- 2.31) ng/ml versus (124.85 +/- 23.56) pg/ml and (3.69 +/- 2.15) ng/ml in the serum AsAb positive and negative groups (P < 0.05 or P < 0.01), most significantly increased in the serum AsAb positive group.

CONCLUSIONThe concentrations of MIP-1alpha and TNF-alpha in the seminal plasma are closely related with sperm count and function, and their detection helps to assess the severity of male infertility and improve its clinical treatment.

Adult ; Case-Control Studies ; Chemokine CCL3 ; analysis ; Humans ; Infertility, Male ; blood ; physiopathology ; Male ; Semen ; chemistry ; Tumor Necrosis Factor-alpha ; analysis

OBJECTIVETo investigate the level of tumor necrosis factor alpha (TNF-alpha) and epidermal growth factor (EGF) in patients with medicament-like dermatitis by trichloroethylene (DMLT).

METHODSUsing radioimmunoassay methods, serum TNF-alpha, EGF were measured in 39 patients with DMLT and in 20 controls.

RESULTSThe levels of serum TNF-alpha, EGF in patients with DMLT [(0.278 +/- 0.092) ng/L, (6.71 +/- 2.28) microg/L, respectively] were significantly higher than those of the controls [(0.128 +/- 0.029) ng/L, (4.31 +/- 1.13) microg/L respectively, P<0.05, P<0.01].

CONCLUSIONThe increased levels of serum TNF-alpha, EGF in patients with DMLT may be related to the following causes: (1) Trichloroethylene and its metabolite may irritate the macrophagocyte and monocyte in human body to release TNF-alpha into blood stream; (2) Severe damage of epithelial tissue in patients with DMLT may promote more EGF synthesis to accelerate the regeneration and repair of epithelial tissue.

Adolescent ; Adult ; Drug Eruptions ; blood ; Epidermal Growth Factor ; blood ; Female ; Humans ; Male ; Receptor, Epidermal Growth Factor ; analysis ; Trichloroethylene ; toxicity ; Tumor Necrosis Factor-alpha ; analysis

The ability to generate dendritic cells (DCs) in sizeable numbers has enormous implications for the development of clinically-effective antigen presentation procedures for cancer immunotherapy. We evaluated the generation of immunostimulatory DCs from peripheral blood CD34+ cells collected from healthy donors. CD34+ cells purified from leukapheresis product were seeded at 1 x 10(4) cells/mL in complete medium supplemented with GM-CSF, TNF alpha, IL-4, c-kit ligand, and flt3 ligand (FL). By day 14 of culture in the presence of GM-CSF + TNF alpha, the total cell number increased by 23.4 +/- 5.4-fold compared to the starting number of CD34+ cells. When the c-kit and FL were added to GM-CSF and TNF alpha, the cell number increased by 109.8 +/- 11.2-fold without affecting the immunophenotype of recovered cells. Flow cytometric analysis indicated that cells with the markers of mature dendritic cells, i.e., CD1a +CD14 -HLA-DR+, and CD80+CD86+HLA-DR+, constituted 49.0% +/- 7.5%, and 38.9% +/- 6.5%, respectively. This pattern of expression of surface antigen was unchanged whether the c-kit ligand and/or FL was added. The irradiated CD1a+HLA-DR+ cells recovered from in vitro cultures elicit a vigorous proliferation of allogeneic peripheral blood T-cells, irrespective of cytokine combinations. These findings provide advantageous tools for the large-scale generation of DCs that are potentially usable for clinical protocols of immunotherapy or vaccination in patients undergoing cancer treatment.
Antigens, CD34/analysis* ; Dendritic Cells/physiology* ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; HLA-DR Antigens/analysis ; Hematopoietic Stem Cells/physiology* ; Human ; Interleukin-4/pharmacology ; Tumor Necrosis Factor/pharmacology

Adult ; Female ; Hepatitis B ; immunology ; Humans ; Interferon-gamma ; blood ; Interleukin-12 ; blood ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha ; analysis

Bone Density ; Bone and Bones ; metabolism ; Hepatitis B ; complications ; Humans ; Liver Cirrhosis ; metabolism ; Male ; Tumor Necrosis Factor-alpha ; analysis