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ID PMID Title PublicationDate abstract
11352231 Activated human T cells directly induce osteoclastogenesis from human monocytes: possible 2001 May OBJECTIVE: To elucidate the direct role of human T cells in the induction of osteoclastogenesis in rheumatoid arthritis (RA), by studying human monocytes and the pathogenetic roles of receptor activator of nuclear factor kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG). METHODS: Synovial tissue obtained at total knee replacement was stained immunohistologically using anti-RANKL, CD3, and CD4 antibodies. Synovial fluid was obtained from patients with RA, osteoarthritis (OA), gout, or trauma. Concentrations of the soluble form of RANKL (sRANKL) and OPG in the synovial fluid were measured by enzyme-linked immunosorbent assay. Activated T cells from peripheral blood mononuclear cells (PBMC) of healthy volunteers were cultured with human monocytes from PBMC. RESULTS: Immunostaining of the synovial tissue of RA patients demonstrated that RANKL-positive cells were detected in a subset of fibroblast-like synoviocytes and infiltrating mononuclear cells. Double immunostaining revealed that RANKL-positive cells were detected in a subset of CD3+ cells and CD4+ cells. An increased concentration of sRANKL and a decreased concentration of OPG were detected in synovial fluid from RA patients. The ratio of the concentration of sRANKL to that of OPG was significantly higher in synovial fluid of RA patients than in synovial fluid of patients with OA or gout. The activated T cells expressing RANKL induced osteoclastogenesis from autologous peripheral monocytes. The role of RANKL in this osteoclastogenetic process was confirmed by dose-dependent inhibition by OPG. CONCLUSION: The present study is the first to demonstrate osteoclastogenesis using human-derived T cells and monocytes. In addition, the present findings suggest that excess production of RANKL by activated T cells increases the level of sRANKL in synovial fluid and may contribute to osteoclastic bone resorption in RA patients.
11549372 Differentiation of monocytes into multinucleated giant bone-resorbing cells: two-step diff 2001 Bone resorption in the joints is the characteristic finding in patients with rheumatoid arthritis (RA). Osteoclast-like cells are present in the synovial tissues and invade the bone of patients with RA. The characteristics of these cells are not completely known. In the work reported here, we generated these cells from peripheral-blood monocytes from healthy individuals. The monocytes were co-cultured with nurse-like cells from synovial tissues of patients with RA (RA-NLCs). Within 5 weeks of culture, the monocytes were activated and differentiated into mononuclear cells positive for CD14 and tartrate-resistant acid phosphatase (TRAP). These mononuclear cells then differentiated into multinucleated giant bone-resorbing cells after stimulation with IL-3, IL-5, IL-7, and/or granulocyte-macrophage-colony-stimulating factor. TRAP-positive cells with similar characteristics were found in synovial fluid from patients with RA. These results indicate that multinucleated giant bone-resorbing cells are generated from monocytes in two steps: first, RA-NLCs induce monocytes to differentiate into TRAP-positive mononuclear cells, which are then induced by cytokines to differentiate into multinucleated giant bone-resorbing cells.
10419373 Occipitocervicothoracic fixation for spinal instability in patients with neoplastic proces 1999 Jul OBJECT: Occipitocervicothoracic (OCT) fixation and fusion is an infrequently performed procedure to treat patients with severe spinal instability. Only three cases have been reported in the literature. The authors have retrospectively reviewed their experience with performing OCT fixation in patients with neoplastic processes, paying particular attention to method, pain relief, and neurological status. METHODS: From July 1994 through July 1998, 13 of 552 patients who underwent a total of 722 spinal operations at the M. D. Anderson Cancer Center have required OCT fixation for spinal instability caused by neoplastic processes (12 of 13 patients) or rheumatoid arthritis (one of 13 patients). Fixation was achieved by attaching two intraoperatively contoured titanium rods to the occiput via burr holes and Luque wires or cables; to the cervical spinous processes with Wisconsin wires; and to the thoracic spine with a combination of transverse process and pedicle hooks. Crosslinks were used to attain additional stability. In all patients but one arthrodesis was performed using allograft. At a follow-up duration of 1 to 45 months (mean 14 months), six of the 12 patients with neoplasms remained alive, whereas the other six patients had died of malignant primary disease. There were no deaths related to the surgical procedure. Postoperatively, one patient experienced respiratory insufficiency, and two patients required revision of rotational or free myocutaneous flaps. All patients who presented with spine-based pain experienced a reduction in pain, as measured by a visual analog scale for pain. All patients who were neurologically intact preoperatively remained so; seven of seven patients with neurological impairment improved; and six of seven patients improved one Frankel grade. There were no occurrences of instrumentation failure or hardware-related complications. In one patient a revision of the instrumentation was required 13.5 months following the initial surgery for progression of malignant fibrous histiosarcoma. CONCLUSIONS: In selected patients, OCT fixation is an effective means of attaining stabilization that can provide pain relief and neurological preservation or improvement.
11247866 Antibiotic prophylaxis for haematogenous bacterial arthritis in patients with joint diseas 2001 Apr OBJECTIVE: To assess the cost effectiveness of antibiotic prophylaxis for haematogenous bacterial arthritis in patients with joint disease. METHODS: In a decision analysis, data from a prospective study on bacterial arthritis in 4907 patients with joint disease were combined with literature data to assess risks and benefits of antibiotic prophylaxis. Effectiveness and cost effectiveness calculations were performed on antibiotic prophylaxis for various patient groups. Grouping was based on (a) type of event leading to transient bacteraemia-that is, infections (dermal, respiratory/urinary tract) and invasive medical procedures-and (b) the patient's susceptibility to bacterial arthritis which was increased in the presence of rheumatoid arthritis, large joint prostheses, comorbidity, and old age. RESULTS: Of the patients with joint disease, 59% had no characteristics that increased susceptibility to bacterial arthritis, and 31% had one. For dermal infections, the effectiveness of antibiotic prophylaxis was maximally 35 quality adjusted life days (QALDs) and the cost effectiveness maximally $52 000 per quality adjusted life year (QALY). For other infections, the effectiveness of prophylaxis was lower and the cost effectiveness higher. Prophylaxis for invasive medical procedures seemed to be acceptable only in patients with high susceptibility: 1 QALD at a cost of $1300/QALY; however, the results were influenced substantially when the level of efficacy of the prophylaxis or cost of prophylactic antibiotics was changed. CONCLUSION: Prophylaxis seems to be indicated only for dermal infections, and for infections of the urinary and respiratory tract in patients with increased susceptibility to bacterial arthritis. Prophylaxis for invasive medical procedures, such as dental treatment, may only be indicated for patients with joint disease who are highly susceptible.
11523903 Painless thyroiditis associated with severe inflammatory reactions in amyloid goiter: a ca 2001 Jun We report the case of a 64-year-old woman with rheumatoid arthritis (RA) associated with high grade fever, malaise, and painless swelling of thyroid gland. Laboratory findings showed severe systemic inflammatory reactions, including increases in various cytokines such as IL-6. Gallium-67 citrate imaging revealed intense uptake in the painlessly enlarged thyroid gland. Histologically, biopsied specimens of thyroid showed diffuse amyloid infiltrations, which included amyloid A (AA) protein. Biopsies of rectum and stomach revealed similar amyloid depositions, indicating that the amyloid had a secondary origin, potentially due to RA. All clinical symptoms were relieved by intravenous pulsatile administration of methylprednisolone followed by oral prednisone, resulting in prolonged hypothyroid status. To our knowledge, this is the first case report in Japan describing painless thyroiditis with severe inflammatory reactions in amyloid goiter.
9870875 Gelatin/chondroitin 6-sulfate microspheres for the delivery of therapeutic proteins to the 1998 Dec OBJECTIVE: To develop a biodegradable, inflammation-responsive microsphere system for the intraarticular delivery of therapeutic proteins. METHODS: Microspheres were synthesized by complex coacervation. Radiolabeled protein release and microsphere degradation were assessed by exposing the microspheres to human synovial fluids (SF) and recombinant gelatinase. Microsphere degradation was confirmed by scanning electron microscopy (SEM). Microsphere biocompatibility was evaluated in vitro by incubating the microspheres with human synoviocytes, and in vivo by injection into mouse joints. RESULTS: Optimal microsphere formulation was developed. Significant (up to 100%) release of encapsulated protein occurred in SF samples with measurable metalloprotease activity, while release was minimal in SF with negligible activity. Dissolution of microspheres exposed to gelatinase was confirmed by SEM. Microspheres were found to be noncytotoxic in vitro, and noninflammatory in vivo. CONCLUSION: Microsphere encapsulation is an inflammation-responsive and biocompatible system of protein delivery that holds promise for use in the delivery of therapeutic proteins to the joint.
10965368 [Immunology in the medical practice.XXXII. Transplantation of autologous hematopoietic ste 2000 Aug 12 The objective of this study was to document the experiences in the first Dutch pilot studies of the effect of transplantation of autologous haematopoietic stem cells in patients with therapy-resistant autoimmune disease. The first results in 21 adults and 14 children are promising: remission of the disease was achieved in 13 patients, while in the others a significant reduction of disease activity was seen with a corresponding improvement of the quality of life. Infectious complications were frequently observed. Two children with systemic juvenile idiopathic arthritis developed a fatal infection-associated macrophage activation syndrome. Multicentre randomised studies are necessary to study the effects of autologous stem cell transplantation and modifications such as T-cell depletion.
10555882 Tumor necrosis factor microsatellite markers TNFa5b5 and TNFa6b5 influence adverse reactio 1999 Nov OBJECTIVE: To investigate which HLA haplotypes identified by DRB1 or tumor necrosis factor (TNF) microsatellite markers are associated with adverse reactions to parenteral gold injections. METHODS: We retrospectively studied 193 Caucasian subjects with rheumatoid arthritis (RA) who had received parenteral gold injections from a university faculty outpatient practice (n = 163) and outpatient clinics at a Department of Veterans Affairs Medical Center (n = 30). DRB1 typing was done by several DNA based techniques. TNF microsatellite genotypes were derived by polymerase chain reaction amplification, sequencing-type gel electrophoresis, and silver staining. RESULTS: Seventy-six subjects had experienced adverse reactions to gold injections (other than nitritoid reactions), 18 of whom had 2 concurrent toxicities. The numbers with adverse reactions included: mucocutaneous (57), proteinuria (25), hematuria without proteinuria (5), thrombocytopenia (3), and miscellaneous (11). By frequency comparisons, no DR was associated with adverse reactions to parenteral gold (chi-squared 4.7, 6 df, NS). Specifically, there was no increased risk of proteinuria or mucocutaneous side effects in the DR3 positive RA group, almost all of whom had the DRB1 allele *0301. By logistic regression modeling controlling for sex and onset age, DR12 and the TNF microsatellite markers a5b5 and a6b5 were associated with mucocutaneous reactions (p < 0.05 for each). The odds ratios favoring mucocutaneous adverse reactions were 3.72 with TNFa5b5 and 2.03 with TNFa6b5. TNFa5b5 was commonly found on the HLA haplotypes bearing DRB1*0101, and TNFa6b5 was on the ones bearing DRB1 alleles of the DR1, DR2, DR3, DR5, or DR6 groups or the DRB1*0401 allele. CONCLUSION: HLA haplotypes conferring risk of gold induced mucocutaneous reactions were better identified by certain HLA class III markers, namely TNFa5b5 and TNFa6b5, than by any previously associated DR groups.
9354468 X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from hum 1997 Oct Genetic predisposition to rheumatoid arthritis (RA) is linked to the MHC class II allele HLA-DR4. The charge of the amino acid at DRbeta71 in the peptide-binding site appears to be critical in discriminating DR molecules linked to increased disease susceptibility. We have determined the 2.5 A x-ray structure of the DR4 molecule with the strongest linkage to RA (DRB1*0401) complexed with a human collagen II peptide. Details of a predicted salt bridge between lysine DRbeta71 and aspartic acid at the P4 peptide position suggest how it may participate in both antigen binding and TCR activation. A model is proposed for the DR4 recognition of collagen II (261-273), an antigen immunodominant in human-transgenic mouse models of RA.
9353999 Analysis of immunoglobulin deficiency cases: a five year study. 1997 Jul A total of 734 serum specimens from various clinical disorders along with 100 control samples from healthy subjects were processed for estimation of serum IgG, IgA and IgM employing single radial immunodiffusion procedure. Immunoglobulin deficiency, either selective or combined was noted in 31 males and 24 females in all age groups. Of the 55 cases encountered it was secondary immunoglobulin deficiency which was seen on a larger scale and encountered in patients with Multiple myeloma (16 out of 32) followed by Leprosy (14 out of 250), Lymphoma (5 out of 43), Malaria (4 out of 137), Burns (4 out of 52), Rheumatoid arthritis (2 out of 69) and non lymphoreticular malignancies (1 out of 41) in decreasing order of frequency. Primary immunoglobulin deficiency was observed in nine cases comprising of six belonging to Idiopathic late onset immunoglobulin deficiency, two of dysgammaglobulineamia and a solitary case of Ataxia telangiectasia. Panimmunoglobulin deficiency was observed in six cases, 11 had a dual deficiency while 38 showed deficiency of an isolated class with selective IgA deficiency in 20 cases. Furthermore, one patient each had total absence of IgG or IgA while IgM was not detectable in seven patients. A high suspicion index along with a regular rapport between the clinician and the laboratory personnel is necessary in the diagnostic set up of immunoglobulin deficiency states.
11703349 Increased circulating platelet-leucocyte complexes and platelet activation in patients wit 2001 Nov It is possible that platelet activation may play a pathogenic role in the increased risk of thrombosis associated with antiphospholipid antibodies (APA). In this study, levels of in vivo platelet activation were measured in 20 patients with primary antiphospholipid syndrome (PAPS) and 30 systemic lupus erythematosus (SLE) patients (14 of whom had secondary APS) using sensitive flow cytometry. Soluble P-selectin levels were also assayed. Platelet CD63 expression was significantly higher in PAPS than normal controls (P = 0.007), as well as SLE patients with and without secondary APS (P = 0.03 and P = 0.002 respectively). PAC-1 binding was significantly higher in PAPS than the control group (P = 0.007) and SLE patients without APS (P = 0.015). Platelet-leucocyte complexes were significantly higher in SLE patients than both PAPS and the control group, and platelet-monocyte complexes were significantly increased in PAPS compared with the control group. (Platelet-leucocyte complexes were also significantly higher than controls in 10 rheumatoid arthritis (RA) patients without APA). Soluble P-selectin levels were significantly higher in PAPS and SLE patients than the control group. Platelet CD62p expression, annexin V binding and platelet microparticle numbers were not increased in PAPS or SLE patients. We conclude that there is evidence of increased platelet activation in PAPS and SLE, and this is important to note as it may have potential therapeutic implications with respect to use of antiplatelet agents in these patients.
9557513 Aspirin: a neuroprotective agent at high doses? 1998 Jan Aspirin, acetylsalicylic acid, is routinely used in clinics as an analgesic, antipyretic and in the secondary prevention of stroke. These effects are caused by low doses of the drug (0.3-3.6 g/day) through the inhibition of cyclo-oxygenase, the enzyme responsible for prostaglandin synthesis. Higher doses of aspirin (4-6 g/day) are used in the treatment of inflammatory conditions such as rheumatoid arthritis and recent laboratory findings suggest that it could play a role in neuroprotection against glutamate excitotoxicity. This article reviews the possible mechanisms of action of high-dose aspirin in neuroprotection.
9324018 H-ras oncogene point mutations in arthritic synovium. 1997 Sep OBJECTIVE: To examine mutational activation of ras proto-oncogenes in synovial tissue from patients with rheumatoid arthritis (RA) compared with synovial specimens from patients with osteoarthritis (OA) or other arthropathies. Synovial samples from cadavers, without any signs of joint disease, were used as control material. METHODS: Using a combination of polymerase chain reaction (PCR) and automated sequencing of the amplified PCR product, regions around codons 12, 13, and 61 of the H-, K-, and N-ras proto-oncogenes were analyzed. Confirmation of mutations was based on restriction fragment length polymorphism analysis and/or oligonucleotide hybridization. RESULTS: Four (6%) of 72 patients with RA, 2 (13%) of 16 with OA, and 1 (8%) of 12 with other arthropathies harbored mutant H-ras proto-oncogenes, and were heterozygous at codon 13 for the GGT-->GAT (Gly-->Asp) change. An unexpected mutation was found in the H-ras gene, in which a heterozygous GTG-->ATG (Val-->Met) mutation was observed over codon 14. The incidence for this mutation was 39% (28 of 72) in RA patients, 94% (15 of 16) in OA patients, and 42% (5 of 12) in patients with other arthropathies. All samples carrying the codon 13 mutation of H-ras were also codon 14-mutated, i.e., double mutations existed. Identical point mutations were also detected in a few synovial specimens obtained from cadavers (n = 8), including a single case of double mutation. All specimens showed normal K- and N-ras loci. CONCLUSION: Activation of proto-oncogene H-ras by point mutation in codons 13 and 14 occurred in the synovial tissue of patients with RA, OA, or other arthropathies, as well as, to some extent, in the control synovia, indicating that the phenomenon is not specific for RA. In codon 14, incidence of the H-ras point mutation was highest in OA tissue. The possible significance of this codon 14-mutated H-ras gene needs to be clarified.
11673556 Chemokines regulate IL-6 and IL-8 production by fibroblast-like synoviocytes from patients 2001 Nov 1 Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce inflammatory cytokines and chemokines. The expressed chemokines are thought to be involved in the migration of inflammatory cells into the synovium. In this study we show that CCL2/monocyte chemotactic protein-1, CCL5/RANTES, and CXCL12/stromal cell-derived factor-1 enhanced IL-6 and IL-8 production by fibroblast-like synoviocytes (FLS) from patients with RA, and their corresponding receptors, CCR2, CCR5, and CXCR4, respectively, were expressed by RA FLS. The chemokines stimulated RA FLS more effectively than skin fibroblasts. Culture with CCL2 enhanced phosphorylation of extracellular signal-related kinase 1 (ERK1) and ERK2, but not phosphorylation of p38 or Src. Moreover, activation of ERK1/2 was inhibited by pertussis toxin, a G(i)-coupled protein inhibitor, and RS-504393, CCR2 antagonist, suggesting that ERK1/2 was activated by CCL2 via CCR2 and G(i)-coupled protein. On the other hand, CCL2, CCL5, and CXCL12 were expressed on RA FLS, and their production was regulated by TNF-alpha, IL-1beta, and TGF-beta1. Our results indicate that the chemokines not only play a role in inflammatory cell migration, but are also involved in the activation of FLS in RA synovium, possibly in an autocrine or paracrine manner.
10050673 Serum response elements activate and cAMP responsive elements inhibit expression of transc 1999 Jan Analyzing the induction kinetics and promoter elements regulating the expression of the transcription factor Egr-1, we found elevated levels of Egr-1-encoding mRNA in synovial fibroblasts of rheumatoid arthritis (RA) patients when compared to controls. By contrast, synovial lymphocytes and macrophages do not show an elevated Egr-1 transcription. Therefore, the overexpression of Egr-1 may serve as a diagnostic marker to characterize synovial fibroblasts of RA patients. To study the regulatory mechanisms controlling Egr-1 expression we analyzed the function of transcription factor binding sites located in the Egr-1 promoter. Individual transcription factor binding sites within the Egr-1 promoter were specifically mutated and Egr-1 promoter activity was tested using reporter gene constructs. Our experiments demonstrate that serum response elements are the main positive regulators and binding to a cAMP responsive element represents the major negative regulator for Egr-1 expression in synovial fibroblasts. In addition, we functionally defined a new element, which was not yet described in the human Egr-1 promoter and which serves as a second negative regulatory element for Egr-1 expression. Therefore increased serum response factor activity or failure of Egr-1 repressing signals may account for Egr-1 overexpression in RA synovial fibroblasts.
10808970 A technique for isolated arthrodesis for inflammatory arthritis of the talonavicular joint 2000 Apr There are few reports in the literature documenting the efficacy of isolated arthrodesis for inflammatory arthritis of the talonavicular joint. Accordingly, we reviewed a single surgeon's experience with this procedure in twenty consecutive cases from this patient population. A technique using indirect joint distraction and the combined use of screw and staple fixation was employed. Solid arthrodesis was noted radiographically in 19 of 20 feet (95%) at an average of 11 weeks. Complications included one non-union, one deep venous thrombosis, and one superficial wound infection. Objective results were graded as excellent in 16 cases, good in 3 cases, and poor in one case. Subjectively, 18 patients were satisfied and one patient dissatisfied with the results of the procedure. It is concluded that isolated arthrodesis is an effective procedure for the treatment of inflammatory arthritis of the talonavicular joint, offering significant pain relief and improved function. Additionally, the use of indirect joint distraction and fixation with screws and staples is a reliable technique associated with an excellent fusion rate.
10321597 Methotrexate-induced papular eruption in patients with rheumatic diseases: a distinctive a 1999 May BACKGROUND: In the past few years, low doses of methotrexate have been used for treatment of patients with rheumatoid arthritis and other collagen vascular diseases, mainly as an immunosuppressive and corticosteroid-sparing drug. Several cutaneous adverse reactions have been described in association with methotrexate therapy. OBJECTIVE: We describe the clinical and the histopathologic features of distinctive cutaneous lesions that appeared in 4 patients with acute bouts of collagen vascular diseases who were receiving methotrexate therapy. METHODS: We clinically and histopathologically evaluated cutaneous lesions caused by methotrexate therapy in 4 patients, 2 with systemic lupus erythematosus, 1 with rheumatoid arthritis, and 1 with Sharp syndrome. RESULTS: Clinically, lesions consisted of erythematous indurated papules most commonly located on proximal areas of the extremities. Histopathologic examination of these papules showed an inflammatory infiltrate mainly composed of histiocytes interstitially arranged between collagen bundles of the dermis, intermingled with few neutrophils. In some foci of deeper reticular dermis, small rosettes composed of clusters of histiocytes surrounding a thick central collagen bundle were seen. Cutaneous lesions showed a direct chronologic relationship with methotrexate therapy, and they disappeared when the drug was tapered or withdrawn and corticosteroids were increased. CONCLUSION: Patients receiving low doses of methotrexate for acute bouts of collagen vascular diseases may experience characteristic cutaneous lesions with distinctive clinical and histopathologic findings shortly after methotrexate administration. We discuss the differential diagnosis with other dermatoses showing similar histopathologic findings that have been described in patients with collagen vascular diseases.
9704213 Management of collagen vascular diseases in childhood. 1998 Jul Collagen vascular diseases seen in children include systemic, discoid and neonatal lupus, dermatomyositis, scleroderma, juvenile rheumatoid arthritis, and, in rare cases, Sjogren's syndrome. Although these diseases are uncommon in children, when seen, they are associated with significant morbidity. This review describes the clinical features of each condition and provides an overview of treatment options now available. These include numerous systemic treatments which can be used as steroid-sparing agents.
10376785 Nutritional parameters and short term outcome in arthroplasty. 1999 Jun OBJECTIVE: Advances in surgical techniques and management of arthroplasty patients have contributed to a significant reduction in surgical complication rates. Preoperative nutritional status has a significant impact on surgical outcome. Studies have reported improved outcomes in burn and hip fracture patients receiving nutritional supplementation during their recoveries. Our objective was to assess the effects of preoperative nutritional status on the incidence of complications, resource consumption, and length of stay of patients undergoing hip and knee replacement surgery. METHODS: One hundred and nineteen patients were evaluated. Standard preoperative laboratory tests were performed on all patients. Medical severity of illness was assessed on all patients using the Charlson Comorbidity Index. Anesthesia and surgical time was recorded. Short term outcome was assessed utilizing hospital charges as a measure of resource consumption, length of stay (LOS), in-hospital consults and the presence and number of complications during hospitalization. Non-parametric Kruskall Wallis and chi-square statistical analyses were performed. A p value <.05 was considered significant. RESULTS: Mean age was 64.6 years +/-15.62. 52.9% had osteoarthritis (OA), 4.2% had rheumatoid arthritis (RA), 5.9% had osteonecrosis (ON), 9.2% had a hip fracture and 28% had a failed total knee arthroplasty (TKA) or total hip arthroplasty (THA). Mean albumin and total lymphocyte count (TLC) were 38.5 g/L +/-4.78 SD and 1884 cells/microL +/-762 SD, respectively. Patients with albumin levels less than 34 g/L had 32.7% higher charges ($50,108+/-8203 SE vs. $33,720+/-1128 SE, p<.006), higher medical severity of illness (p = .03) and longer LOS (8.6+/-1.7 SE vs. 5.2+/-.356 SE days, p<.001). Patients with TLC less than 1200 cells/microL had higher charges ($32,544+/-1050 SE vs. $42,098+/-3122 SE, p = .004), longer LOS (5.7+/-.531 vs. 5.4 days +/-.368, p = .004) and anesthesia (242.85+/-17.55 SE vs. 198.6 min. +/-6.06 SE, p = .02) and surgical times (177.14 min. +/-17.57 SE vs. 120.21 min. +/-6.22 SE, p = .002) when compared with patients with TLC higher than 1200 cells/microL. These findings were still significant when adjusted for medical severity of illness and age. CONCLUSIONS: Our data demonstrate that preoperative nutritional status is an excellent predictor of short term outcome. Serum albumin and TLC correlate with resource consumption, length of stay and operative time in patients undergoing joint replacement surgery. These parameters may be improved with nutritional supplementation prior to surgery.
11422907 In vitro evaluation of an enhanced human serum amyloid A (SAA2) promoter-regulated soluble 2001 Jun Tumour necrosis factor (TNF)-alpha contributes to the pathogenesis of many inflammatory diseases. Recombinant soluble TNF receptor fusion proteins (sTNFR:Ig) are potent TNF antagonists, both in vitro and in vivo. The concentration of serum amyloid A (SAA) increases by up to 1000-fold during inflammation, largely owing to cytokine-driven transcriptional upregulation. A reporter plasmid, comprising the proximal 0.7 kb of the human SAA2 promoter fused to a luciferase gene, was used in transient transfection experiments in human HepG2 hepatoma cells to assess the quantitative and qualitative TNF antagonist properties of a construct in which sTNFR:Ig synthesis is under the control of a chimera of the SAA2 promoter and a tat/HIV element. The SAA2-tat/HIV-sTNFR:Ig construct retained the fine-tuned cytokine responsiveness of the SAA2 promoter, while exhibiting the quantitatively enhanced level of protein expression conferred by the tat/HIV element. It produced a biologically significant TNF inhibition that was at least as strong as that achieved using a CMV promoter-driven sTNFR:Ig construct. There was a dose- and time-dependent relationship between the pro-inflammatory cytokine used, and the generation of TNF antagonist activity by SAA2-tat/HIV-sTNFR:Ig. Although sTNFR:Ig protein can be induced by either TNF-alpha or interleukin (IL)-1beta, its antagonist activity is limited to the former cytokine. The SAA2-tat/HIV-sTNFR:Ig construct, and derivatives thereof, may therefore be ideally suited to gene therapy applications that require the local production of potent and specific immune modifiers only when there is active pathology. It may consequently be of particular use in the future treatment of diseases such as rheumatoid arthritis.