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ID PMID Title PublicationDate abstract
12212057 [Preliminary study on apoptosis and expression of apoptosis-related genes in peripheral bl 1999 Jun This study was conducted to explore the clinical implication of the relationship between systemic lupus erythematosus (SLE) and peripheral blood lymphocytes (PBL) apoptosis and apoptosis-related gene expression. Terminal deoxynucleotidyl transferase mediated nick end labelling technique and flow cytometry were used to detect the apoptotic cell; immunohistochemistry ABC was used to detect the expressions of bcl-2 and Fas in 29 cases of SLE. The results showed that the rate of apoptosis of PBL in SLE patients was significantly higher than that in normal control (P < 0.001), and that in patients with rheumatoid arthritis (P < 0.001). After 48 hour's culture, the apoptotic rate further increased in SLE patients (33.44%). There was a significant correlation between the SLE activity and the rate of apoptosis in vitro (r = 0.86, P < 0.001). The rate of apoptosis of PBL in SLE-nephritis patients was higher than that in non-SLE-nephritis patients (P < 0.01). Before and after the culture, the expressions of bcl-2 and Fas in PBL of patients with SLE were higher than those in normal control (P < 0.01, P < 0.001). So the authors suggest that increased rate of apoptosis may be used as an index for evaluating the severity of SLE cases.
11949737 The development and evaluation of the brief depression screen in medically ill disability 2001 OBJECTIVE: There is literature demonstrating elevated prevalence of depression in primary care. Yet there remains a need for a brief depression screen designed and evaluated specifically for use among medically ill patients. Our objective was to develop and validate a brief, unobtrusive screen for depression among severely medically ill long-term disability claimants. METHODS: The study sample consisted of 480 long-term disability claimants, less than 55 years of age, with one of the following illnesses: cancer, diabetes, myocardial infarction, rheumatoid arthritis, stroke, or multiple sclerosis. Each subject completed a questionnaire that included 26 potential screening items. A subset of subjects was administered the SCID, which served as the gold standard for the DSM-IV depression and dysthymia diagnoses. RESULTS: The Brief Depression Screen, a three-item screen for major depressive disorder and dysthymia, was developed. About 34 percent of the sample met criteria for major depressive disorder or dysthymia. The Brief Depression Screen detected 75 percent of those subjects in this sample. Furthermore, nearly half of the subjects with positive screen results met criteria for depression or dysthymia. These results are comparable to those of the eight-item Burnam screen, but not as sensitive as the more widely used, twenty item CES-D. CONCLUSION: The Brief Depression Screen was developed and evaluated for use with severely ill long-term disability claimants. In practice, a positive screen for depression is to be followed with a comprehensive diagnostic assessment that could be conducted by a trained clinician. Further research is warranted to determine whether the identification and treatment of depression in disability claimants with non-psychiatric medical illnesses will facilitate return to work, even in the presence of comorbid medical illnesses.
11798678 [Expression of interleukin-6 and its receptors in peripheral blood of patients with system 1999 Jul OBJECTIVE: To investigate the level of interleukin-6 (IL-6) and soluble-IL-6 receptor (sIL-6R) in serum of patients with systemic lupus erythematosus (SLE) and its correlation with disease activity and to explore IL-6 signal transduction pathways in SLE patients. METHODS: By using MTT colorimetry and ELISA, the levels of IL-6 and sIL-6R in serum from 16 patients with SLE (9 active, 7 inactive), 17 with active rheumatoid arthritis (RA) and 29 controls were measured. The expressions of acute phase reaction factor (APRF) in peripheral blood mononuclear cells (PBMCs) were also detected by using electrophoresis mobility shift assays (EMSA) after the PBMCs were isolated and then stimulated by IL-6. RESULTS: Serum IL-6 and sIL-6R levels in active SLE patients were significantly higher than those in normal controls (P < 0.01), but were significantly lower than those in active RA patients (P < 0.01). Serum IL-6 rather than sIL-6R level in active SLE patients was significantly higher than that in inactive ones (P < 0.01). Serum IL-6 was correlated positively with the anti-dsDNA antibody (r = 0.658, P < 0.01), but not with CRP (r = 0.041, P > 0.05). There were no expression of APRF in PMNC from SLE patients and 8 normal controls, whereas PMNC from 11 RA patients expressed APRF activity (11/17). CONCLUSION: The level of IL-6 is a useful parameter for monitoring disease activity of SLE. In active SLE, no significant elevation of serum sIL-6R and no expression of APRF in PMBCs may be responsible for mild CRP elevation.
11740352 Localization of cathepsins D, K, and L in degenerated human intervertebral discs. 2001 Dec 15 STUDY DESIGN: Localization of cathepsins D, K, and L in degenerated intervertebral discs was examined by immunohistochemistry. OBJECTIVES: To determine the involvement of cathepsins in the pathomechanism of intervertebral disc degeneration by monitoring the immunolocalization of cathepsins in degenerated intervertebral disc tissue. SUMMARY OF BACKGROUND DATA: Cathepsins D, K, and L are enzymes that contribute to the matrix destruction seen in the articular cartilage affected by osteoarthritis and rheumatoid arthritis. However, little is known about the contribution of these cathepsins to intervertebral disc degeneration. METHODS: Paraffin-embedded sections of degenerated intervertebral disc tissue collected at the time of surgery (13 discs from 12 patients) were immunohistochemically stained with antibodies for cathepsins D, K, and L. For further characterization of the stained cells, immunohistochemical detection of CD68 and TRAP staining were performed. RESULTS: Hematoxylin and eosin staining revealed obvious signs of degeneration in all sections. Cathepsins D and L were immunolocalized in disc fibrochondrocytes at various sites exhibiting degeneration. Cathepsins K were found in tartrate-resistant acid phosphatase-positive multinucleated cells, in particular near the cleft within the cartilaginous endplate. However, few cells were positive for these cathepsins in anulus fibrosus that maintained the lamellar structure of collagen fibers. CONCLUSIONS: Marked expression of cathepsins D and L was observed at the site of degeneration. Cathepsins D and K localized in tartrate-resistant acid phosphatase-positive multinucleated cells existed at the cleft between the cartilaginous endplate and vertebral body. The site-specific localization of these cathepsins suggests the association of these proteinases with endplate separation and disorganization of the anulus fibrosus in degenerative spinal disorders.
11726533 Vitamin D: its role and uses in immunology. 2001 Dec In recent years there has been an effort to understand possible noncalcemic roles of vitamin D, including its role in the immune system and, in particular, on T cell-medicated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. However, its highest concentration is in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. The significant role of vitamin D compounds as selective immunosuppressants is illustrated by their ability to either prevent or markedly suppress animal models of autoimmune disease. Results show that 1,25-dihydroxyvitamin D3 can either prevent or markedly suppress experimental autoimmune encephalomyelitis, rheumatoid arthritis, systemic lupus erythematosus, type I diabetes, and inflammatory bowel disease. In almost every case, the action of the vitamin D hormone requires that the animals be maintained on a normal or high calcium diet. Possible mechanisms of suppression of these autoimmune disorders by the vitamin D hormone have been presented. The vitamin D hormone stimulates transforming growth factor TGFbeta-1 and interleukin 4 (IL-4) production, which in turn may suppress inflammatory T cell activity. In support of this, the vitamin D hormone is unable to suppress a murine model of the human disease multiple sclerosis in IL-4-deficient mice. The results suggest an important role for vitamin D in autoimmune disorders and provide a fertile and interesting area of research that may yield important new therapies.
11715779 [Thalidomide--a dreaded drug with new indications]. 2001 Oct 20 BACKGROUND: Thalidomide was introduced as a non-toxic sleeping pill in 1957 and was prescribed in more than 20 countries. In 1961 the link between congenital limb defects and thalidomide use in pregnancy was proven, resulting in withdrawal of the drug. MATERIAL AND METHODS: On the basis of literature searches and personal experience we review the effects and use of thalidomide today. RESULTS: In vitro, thalidomide has immunoregulatory properties. This has lead to the administration of thalidomide in many immunological diseases. In 1964 it was discovered that thalidomide was effective against erythema nodosum leprosum. Thalidomide also has effect on aphthous stomatitis and Behçet's disease. The effect is more uncertain in graft-versus-host-disease, rheumatoid arthritis and Crohn's disease. Thalidomide reduces angiogenesis in experimental animals, and this has led to several studies of thalidomide as a possible anticancer drug. Advanced or resistant multiple myeloma may be a new target for thalidomide; at least 30% of these patients obtain response during treatment. Results indicate that patients with breast cancer and glioma do not benefit from treatment with thalidomide. INTERPRETATION: Thalidomide has proven to be effective in the treatment of erythema nodosum leprosum and aphthous stomatitis. It is also effective in advanced multiple myeloma, but not in other cancers.
11698475 Accelerated Fas-mediated apoptosis of monocytes and maturing macrophages from patients wit 2001 Nov 15 Impaired handling of apoptotic cells has been suggested as an important factor in the development of systemic lupus erythematosus (SLE), and a role for complement in the removal of apoptotic cells was shown recently. We studied the in vitro function of macrophages from 40 patients with SLE and their matched controls in the removal of heterologous apoptotic cells opsonized by iC3b. Interaction index of apoptotic cells opsonized by iC3b was significantly lower in patients with SLE and averaged 71% +/- 37 of that of healthy individuals (p < 0.002) and 69% +/- 35 of patients with rheumatoid arthritis (p < 0.007). SLE patients had increased apoptosis of both freshly isolated monocytes (p < 0.001) and maturing macrophages (p < 0.04) that led to decreased density of monocyte-derived macrophages. Apoptosis was inhibited by adding soluble Fas receptor indicating Fas-mediated apoptosis. As demonstrated in both healthy controls and patients with SLE, decreased macrophage density by itself caused significant decreased uptake of apoptotic cells by the remaining macrophages. Maintaining normal density in SLE patients either by an increased initial density or by using soluble Fas restored the interaction capacity of the individual macrophages in the majority of patients. We concluded that impaired in vitro interaction of iC3b-opsonized apoptotic cells with macrophages from patients with SLE was mainly associated with Fas-dependent accelerated apoptosis of the monocytes/macrophages. Accelerated apoptosis of phagocytes may represent a novel in vitro mechanism of impairment of interaction with apoptotic cells that, apart from reducing the number of professional phagocytes, alters the function of the remaining macrophages.
11679603 Thirty-day mortality after elective total hip arthroplasty. 2001 Oct BACKGROUND: Previous reports on perioperative mortality associated with hip arthroplasty have not documented, to our knowledge, patient characteristics and surgical factors that increase the likelihood of death. The purpose of this study was to determine the prevalence of and associated risk factors for perioperative death after elective hip arthroplasty. METHODS: The records of 30,714 consecutive patients who had undergone elective hip arthroplasty at our institution from 1969 to 1997 were retrospectively reviewed to identify patients who had died within thirty days after the procedure. Mortality rates were determined according to age, gender, diagnosis, implant type, and fixation mode. RESULTS: Ninety deaths occurred within thirty days after elective total hip arthroplasty, for an overall mortality rate of 0.29% (ninety of 30,714). The thirty-day mortality rate was significantly higher for patients with preexisting cardiovascular disease (p < 0.0001), male patients (p < 0.0001), and patients who were seventy years of age or older (p < 0.0002). The mortality rate was slightly, but not significantly, higher for patients with an underlying diagnosis of rheumatoid arthritis (p < 0.36) and those receiving cemented implants (p < 0.57). There was no difference in the thirty-day mortality rate for revision as compared with primary hip arthroplasty (p < 0.92). CONCLUSIONS: Factors that are associated with an increased risk of mortality within thirty days after elective hip arthroplasty include an older age, male gender, and a history of cardiorespiratory disease. There has been a significant decline in the thirty-day mortality rate after elective hip arthroplasty in the last decade (p < 0.0002); during the 1990s, the overall rate at our institution was 0.15% (twenty-three of 14,989).
11567172 Structure of lifestyle disruptions in chronic disease: a confirmatory factor analysis of t 2001 Oct BACKGROUND: The Illness Intrusiveness Ratings Scale (IIRS) measures the extent to which disease or its treatment or both interfere with activities in important life domains. Before comparing IIRS scores within or across groups it is crucial to determine whether a common underlying factor structure exists across patient populations. OBJECTIVE: To investigate the factor structure underlying the IIRS and evaluate its stability across diagnoses. METHODS: IIRS responses from 5,671 respondents were pooled from 15 separate studies concerning quality of life in eight patient groups: rheumatoid arthritis; osteoarthritis; systemic lupus erythematosus; multiple sclerosis; end-stage renal disease (maintenance dialysis); renal transplantation; heart, liver, and lung transplantation; and insomnia. Data were gathered by different methods (eg, interview, self-administered, mail survey) and in diverse contexts (eg, individual vs. group). RESULTS: Exploratory maximum-likelihood factor analysis identified three underlying factors in a randomly selected subset of respondents (n = 400), corresponding to "Relationships and Personal Development," "Intimacy," and "Instrumental" life domains. Confirmatory factor analysis corroborated the stability of this structure in an independent subsample (n = 2100). Complementary goodness-of-fit indices confirmed the consistency of the three-factor solution, corroborating that IIRS scores are uniquely defined across patient populations. Coefficient alpha was high for total and subscale scores. CONCLUSIONS: IIRS scores can be compared meaningfully within and across patient groups. Both total and subscale scores can be used depending on research objectives.
11399100 Modulation of bovine articular chondrocyte gene expression in vitro by oxygen tension. 2001 May OBJECTIVE: Adult articular cartilage is a physiologically hypoxic tissue with a proposed gradient of oxygen tension ranging from <10% oxygen at the cartilage surface to <1% in the deepest layers. This gradient may be disturbed during diseases of the joint, for example in rheumatoid arthritis when synovial fluid pO(2)falls. We investigated whether changes in oxygen tension modulate gene expression in articular chondrocytes. DESIGN: Bovine articular chondrocytes were cultured in alginate beads in medium maintained at <0.1, 5, 10 or 20% oxygen. A modified RNA arbitrarily primed polymerase chain reaction (RAP-PCR) technique was used to identify several genes whose mRNA abundance in articular chondrocytes was dependent upon oxygen tension. Northern hybridization slot blots were used to quantify changes in mRNA level relative to a housekeeping gene, beta-actin. RESULTS: Genes found by RAP-PCR to undergo up-regulation in hypoxia included TIMP-1 and integrin-linked kinase. Collagen V mRNA levels were down-regulated in hypoxic chondrocytes. This led us to examine mRNA levels for various cytokines, matrix structural molecules and beta1 integrin. Interleukin 1beta, transforming growth factor beta and connective tissue growth factor were all up-regulated by low oxygen tensions, as was beta1 integrin. Collagen II (COL2A1) was down-regulated by hypoxia but aggrecan mRNA levels remained unchanged. The mRNA levels for GAPDH, the archetypal hypoxia responsive gene, were not modulated in articular chondrocytes by changes in oxygen tension. CONCLUSIONS: Oxygen tension modulates the abundance of mRNAs encoding structural molecules, several cytokines, beta1 integrin and integrin-linked kinase in articular chondrocytes. This may be important during disease progression. Chondrocytes are unusual in their response to hypoxia, presumably because they exist physiologically in a low oxygen environment.
11372335 Revision total knee arthroplasty: planning, controversies, and management--infection. 2001 Routine blood work that includes ESR, CRP, and glucose levels, and plain radiographs and knee aspirations are obtained from our patients who have clinical suspicion of infection. If the culture result is positive and blood tests suggest infection, the surgical plan is a two-stage revision with an interval period of intravenous antibiotic administration. Risk factors are identified, and the patient's condition optimized. An infectious disease consultant is also involved in the treatment care plan and advises the patient about the best antibiotic, management of proper antibiotic levels, and home care. If culture results are negative, cultures are repeated every week for 3 to 4 weeks after the patient stops taking antibiotics. If the cultures yield positive results, a two-stage revision protocol is initiated. In patients who have 3 to 4 negative culture results, normal blood tests and radiographs, and no history of any immunocompromised state, such as diabetes or rheumatoid arthritis, diagnoses such as polyethylene wear or synovitis can be considered. If patients have any involved risk factor or blood tests, equivocal or suggestive, isotope scintigraphy is requested. We examine tissue in patients with positive scans and equivocal blood test results with clinical suspicion of infection. We prefer an open arthrotomy, which allows us to take multiple specimens for frozen section, assess fixation of the implant, and look for any other signs of infection. If the frozen section reveals more than 10 PMNLs per high-power field, we proceed to stage 1 revision after obtaining intraoperative cultures. If an organism grows in the cultures, stage 2 protocol is initiated. If no cultures are obtained at 7 to 10 days of incubation, we may consider earlier stage 2 revision at 4 to 6 weeks (Fig. 1). In patients in whom the frozen section reveals less than 5 PMNLs per high-power field, component fixation should be assessed, and if they are loose, revision of the knee should be initiated. As with a septic revision, use of antibiotic-impregnated cement can be considered for fixation. If the components are well fixed, a polyethylene tibial tray is exchanged. In either circumstance, intraoperative cultures should be obtained, and if they yield positive results, antibiotics should be continued for 6 to 12 weeks.
11256742 Mannose-binding lectin: structure, function, genetics and disease associations. 2000 Mannose-binding lectin (MBL), a serum protein characterised by both collagenous regions and lectin domains, plays an important role in innate immune defence. It binds to the repeating sugar arrays on many microbial surfaces through multiple lectin domains and, following binding, is able to activate the complement system via an associated serum protease, MASP-2. Serum levels of MBL are influenced by three mutations clustered in exon 1 of the gene and are further modulated by various promoter region polymorphisms. The exon 1 mutations lead to secondary structural abnormalities of the collagenous triple helix and a failure to form biologically functional higher order oligomers. There is an increased incidence of infections in individuals with such mutations and an association with the autoimmune disorders SLE and rheumatoid arthritis. Nevertheless, MBL genotyping of various populations has led to the suggestion that there may be some biological advantage associated with absence of the protein. These and other findings suggest that the concept of MBL as a protein involved solely in first line defence is an oversimplification and the protein should rather be viewed as having a range of activities including disease modulation.
10886239 Clustering of distinct autoimmune diseases associated with functional abnormalities of T c 2000 Jul To ascertain whether alterations of lymphocyte switching off may be associated with clustering of autoimmune diseases in children, Fas- and C2-ceramide-induced cell death was evaluated on T cell lines derived from three patients affected by clustering of autoimmune disorders. Three patterns were found: patient 3 was resistant to Fas- and C2-ceramide, patient 1 was resistant to Fas, but sensitive to C2-ceramide, patient 2 was resistant to C2-ceramide, but sensitive to Fas. By contrast, Fas- and C2-ceramide-induced cell death was normal in five children with systemic juvenile rheumatoid arthritis, five children with insulin-dependent diabetes and 10 age-matched healthy controls. Surface expression of Fas was low in patient 1, but normal in patients 2 and 3. Together with normal Fas transcripts, patients 2 and 3 displayed a transcript 152 bp longer than the normal one retaining intron 5. Our data indicate that polyreactive autoimmune syndromes may be associated with heterogeneous alteration of the immune response switching-off system.
10799835 Target molecules for anti-angiogenic therapy: from basic research to clinical trials. 2000 May There is growing evidence that anti-angiogenic drugs will improve future therapies of diseases like cancer, rheumatoid arthritis and ocular neovascularisation. However, it is still uncertain which kind of substance, out of the large number of angiogenesis inhibitors, will prove to be a suitable agent to treat these human diseases. There are currently more than 30 angiogenesis inhibitors in clinical trials and a multitude of promising new candidates are under investigation in vitro and in animal models. Important therapeutic strategies are: suppression of activity of the major angiogenic regulators like vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF); inhibition of function of alphav-integrins and matrix metalloproteinases (MMPs); the exploitation of endogenous anti-angiogenic molecules like angiostatin, endostatin or thrombospondin. Given the wide spectrum of diseases which could be treated by anti-angiogenic compounds, it is important for today's clinicians to understand their essential mode of action at a cellular and molecular level. Here we give an in-depth overview of the basic pathophysiological mechanisms underlying the different anti-angiogenic approaches used to date based on the most recent fundamental and clinical research data. The angiogenesis inhibitors in clinical trials are presented and promising future drug candidates are discussed.
10752497 The differing patterns of subclinical pulmonary involvement in connective tissue diseases 2000 To explore common patterns of interstitial lung disease (ILD) in symptomless patients with connective tissue disease (CTD), we applied factorial analysis to determine the relationship among the factors. A selected cohort of 71 non-smoking patients with a confirmed diagnosis of CTD [24 with primary Sjögren's syndrome (pSS), 21 with systemic sclerosis (SS), 20 with rheumatoid arthritis (RA) and six with polymyositis/ dermatomyositis (PM/DM)] were identified. The diagnostic techniques included pulmonary function tests, bronchoalveolar lavage (BAL), chest radiographs and high-resolution computed tomography (HRCT). Disease extent and severity were assessed by a radiological and HRCT grading system. Three factors, accounting for 67% of the total variance, were extracted. The first factor (disease duration, diffusing lung capacity, neutrophils and CD8+ T cells on BAL, radiographic score and HRCT reticular score), with the highest percentage of variance (36.5%), defines a fibrotic lung pattern. The second factor (17.9% of variance) identifies an inflammatory lung pattern (macrophages, lymphocytes and eosinophils on BAL and HRCT ground-glass score). The third factor (12.6% of variance) represents a ventilatory function pattern (forced vital capacity, total lung capacity and forced respiratory volume in 1 s). The negative correlation between the fibrotic lung pattern and ventilatory function pattern, but not with the inflammatory lung pattern, suggests the presence of a significant derangement of the alveolar structures. In conclusion, application of factor analysis reveals various lung disease patterns in patients with CTD that might have different prognostic implications.
10719057 Quantitation of macrophage migration inhibitory factor (MIF) using the one-step sandwich e 2000 Apr We raised monoclonal antibodies against human macrophage migration inhibitory factor (MIF), and developed a one-step sandwich enzyme-linked immunosorbent assay (ELISA) method highly specific for human MIF. The ELISA system utilizes a solid phase monoclonal antibody as a capture antibody and a horseradish peroxidase-conjugated monoclonal antibody as a detector antibody. We used this ELISA method to evaluate the serum level of MIF in 240 healthy volunteers (140 males and 100 females). We found no significant difference in MIF concentration with respect to age. A significant difference was found with respect to sex, with the mean value (+/- SD) for male subjects of 5.3+/-2.3, and that for female subjects of 4.6+/-2.3 ng/ml (p<0.05). We next measured the serum MIF contents of patients with autoimmune diseases, and found that MIF levels were significantly elevated in patients with systemic lupus erythematosus and rheumatoid arthritis, 20.0+/-11.0 ng/ml and 21. 7+/-11.2 ng/ml, respectively. Using anti-MIF antibody-immobilized sepharose column chromatography, we discovered for the first time that MIF was present in erythrocytes. Taken together these results suggest that MIF plays a major role in autoimmune diseases and, moreover, potentially induces various patho-logical outcomes in cases of hemolytic disorders.
10707114 Time dependent influence of diazepam on the pharmacokinetics of ibuprofen in man. 1999 Circadian variation in the disease activity of rheumatoid arthritis has been established. Several nonsteroidal anti-inflammatory drugs have been studied for their chronokinetic behaviour. Time dependent influence of diazepam on the pharmacokinetics of diclofenac and naproxen has been reported. We report the time dependent influence of diazepam on the pharmacokinetics of ibuprofen in healthy subjects. Either ibuprofen or ibuprofen with diazepam was administered at 10.00 or 22.00 hours to eight healthy volunteers in a randomized crossover study. Serum ibuprofen levels were estimated by high performance liquid chromatography. There was a significant (p < 0.05) increase in mean elimination half life (2.39 +/- 0.42 to 3.59 +/- 0.35 h) following ibuprofen and diazepam administration compared to ibuprofen alone administered at 22.00 hours. The mean clearance of ibuprofen was therefore lowered from 62.7 +/- 8.9 to 41.7 +/- 2.6 ml/h/kg under the influence of diazepam during the night. Such a time dependent influence of diazepam on the pharmacokinetics of ibuprofen may be due to circadian variation in the pattern of protein production in the liver and/or competitive protein binding of the two drugs during the dark period.
10614777 Characterization of a CSF-induced proliferating subpopulation of human peripheral blood mo 1999 Dec The phenotype of a subpopulation(s) of human monocytes which has been shown to proliferate in vitro in response to macrophage colony-stimulating factor (M-CSF or CSF-1) and granulocyte-macrophage CSF (GM-CSF) is as yet unknown. To identify this proliferating subpopulation(s) we demonstrated first that DNA synthesis was occurring under culture conditions suitable for flow cytometric evaluation. Flow cytometric analysis of surface antigen expression identified that after 5 days of culture the proliferating subpopulation of monocytes expressed CD14, CD13, CD33, CD11b, CD11c, CD87, HLA-DR, CD45RO, and did not express CD86, CD34, CD80, CD4, CD16, and CD56. In addition, these proliferating monocytes (representing approximately 5% of total monocytes) were shown to produce the proinflammatory cytokines interleukin-6 and tumor necrosis factor alpha in response to lipopolysaccharide stimulation. Further characterization and subsequent isolation of this subpopulation of monocytes may provide new and important information necessary to understand inflammatory diseases such as rheumatoid arthritis, where local proliferation at the site of inflammation may be a key factor contributing to the chronicity of the disease.
10611859 The Frank Stinchfield Award. Sudden death during primary hip arthroplasty. 1999 Dec The records of 23 patients who died intraoperatively during hip arthroplasty at the authors' institution were reviewed. Of the 38,488 hip arthroplasties in 29,431 patients performed between 1969 and 1997, there were 23 deaths during surgery. There were 15 women and eight men with a mean age of 80.9 years. Preoperative diagnoses were acute hip fracture (13 patients), pathologic fracture (four patients), femoral neck nonunion (one patient), osteoarthritis (four patients), and rheumatoid arthritis (one patient). Eleven patients undergoing cemented total hip arthroplasty died and 12 patients undergoing cemented hemiarthroplasty died. All deaths occurred because of irreversible cardiorespiratory disturbances that were initiated during cementing. There were no deaths among 12,551 patients receiving 15,411 uncemented hip arthroplasties during the 28-year period under review. Autopsy was performed in 13 patients. Bone marrow microemboli were seen in the lungs of 11 of 13 patients in whom an autopsy was performed and methylmethacrylate particles were seen in the lungs of three of 13 patients. These data suggest that elderly patients with preexisting cardiovascular conditions undergoing cemented arthroplasty, especially for fracture diagnosis, are at increased risk for intraoperative death compared with patients undergoing elective hip arthroplasty. In the latter years of the current study, modifications of the operative techniques designed to minimize intramedullary hypertension were associated with a reduction greater than three-fold in overall intraoperative mortality rate. These changes in surgical technique should be considered when cement fixation is used in patients thought to be at risk for having cardiopulmonary disturbances develop from venous embolization of marrow contents.
10598881 Inhibition of human B cell activation by a novel nonsteroidal anti-inflammatory drug, indo 1999 Nov Indometacin farnesil (INF) is a prodrug of indomethacin (IND) designed to reduce the occurrence of side-effects by esterification of the carboxyl group on IND with farnesol. Previous studies have shown that INF has the characteristics of disease-modifying anti-rheumatic drug (DMARD) in that it has a component of slow-acting effect in treatment of rheumatoid arthritis (RA), in which abnormal B cell functions are considered to be involved. The current studies therefore examined the effects of INF on human B cells. Ig production was induced from highly purified B cells obtained from healthy donors by stimulation with Staphylococcus aureus Cowan I (SA) plus IL-2. T cell proliferation and IFN-gamma production were induced from highly purified T cells by stimulation with immobilized mAb to CD3. At pharmacologically attainable concentrations, INF, but not IND, suppressed the production of IgM and IgG of B cells, whereas neither suppressed the T cell proliferation and IFN-gamma production. The inhibition of Ig production by INF is not due to its IND structure, but is most likely due to its farnesil component, since farnesol alone comparably suppressed the Ig production. INF and farnesol did not suppress the expression of early activation markers, including CD98, CD25, and CD71, on SA-stimulated B cells, but appeared to inhibit the maturation of B cells following the initial activation. These results indicate that INF preferentially suppresses the human B cell functions. Thus, the data suggest that INF may have more beneficial effects than IND in treatment of RA.