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ID PMID Title PublicationDate abstract
1489490 Surface expression of heat shock protein 90 by blood mononuclear cells from patients with 1992 Dec Previous studies have indicated that blood mononuclear cells from 15-20% of patients with systemic lupus erythematosus (SLE) carry elevated levels of hsp90, a heat shock protein associated with steroid receptors in cells. We analysed surface expression of hsp90 on mononuclear cells (lymphocytes and monocytes) from patients with SLE by monoclonal antibody AC88 and flow cytometry. Whilst all blood mononuclear cells have intracellular hsp90, a significant proportion of patients with SLE expressed hsp90 on lymphocyte and monocyte surfaces. This was significantly higher on SLE lymphocytes than in laboratory controls and was positively correlated with disease activity. Comparison of total hsp90 with surface hsp90 in the same SLE patients' blood mononuclear samples indicated a correlation with a subgroup of patients. There was no correlation with expression of surface hsp90 by lymphocytes and activation markers. Patients with Sjögren's syndrome, rheumatoid arthritis, dermatomyositis and scleroderma were studied as disease controls and increased levels of shsp90 were detected in only three of the 53 patients studied. It is concluded that surface hsp90 expression is a feature of about 20% of patients with SLE and is correlated with high disease activity. The exposure of this hsp on the surface of some lymphocytes suggests that it is a candidate autoantigen in SLE.
1572909 Characterization of specific proteases associated with the surface of human skin fibroblas 1992 May Human skin fibroblasts were probed for cell surface protease activity. One activity removing dipeptides from the NH2-terminal end of Gly-Pro-pNA was specifically inhibited by di-isopropyl-fluorophosphate (DFP), phenylmethanesulphony fluoride (PMSF), and diprotin A, and thus was identified as dipeptidyl peptidase IV (DPP IV). A group of bestatin-sensitive N-exoaminopeptidase activities was also characterized when Ala-, Leu-, and Arg-pNA were used as chromogenic substrates. Using human monoclonal antibodies anti-CD 13 and anti-CD 26 that recognized, respectively, an N-Ala-aminopeptidase and DPP IV, it was found that human dermal fibroblasts expressed the CD 13 and CD 26 antigen on their surface. In addition, both peptidases were specifically immunoprecipitated by monoclonal antibodies anti-CD 13 and anti-CD 26 from plasma membranes. Cell surface proteolytic activities were also investigated in human fibroblasts derived from dermatological and rheumatic diseases (i.e., psoriasis, rheumatoid arthritis, and lichen planus). It was found that these fibroblasts also expressed both types of proteinases initially identified on normal skin fibroblasts and that the levels of Ala-aminopeptidase activities were similar in all cases. In contrast, the levels of Arg-, Leu-exoaminopeptidase, and DPP IV activities were significantly higher (up to 6.6-fold) in the three pathological fibroblast populations than in their normal counterparts. These proteolytic enzymes, therefore, can potentially serve as markers in dermatological diseases. Taken together, our results suggest that skin fibroblast-derived proteinases associated with both serine and N-aminopeptidase activities may play an important role by participating in the extracellular events associated with fibroblast behaviour.
1493027 Outpatient clinic referrals and their outcome. 1992 Mar A cohort of 392 patients referred to six outpatient clinics by general practitioners during 1987 with diagnoses of rheumatoid arthritis, osteoarthritis, peripheral vascular disease, psoriasis or eczema, were studied from the time of their first attendance until up to two years later. Six consultant clinics were studied in the three specialties: rheumatology, vascular surgery and dermatology. For each specialty a clinic in both a teaching hospital and a district general hospital were included. The cohort members were predominantly middle-aged or elderly people, with a greater proportion of women, except at the vascular surgery clinic where 65% of patients were men. The 392 patients made a total of 936 visits (median two, range one-eight) during the study period; 91 patients were still attending up to two years after the first visit. Patients referred by their general practitioner for therapy were less likely to be discharged than those referred for other reasons. The principal reason for continuing attendance as perceived by patients, general practitioners and hospital doctors was the necessity for consultant supervision, although agreement was far from complete in individual cases. Junior staff tended to see a higher proportion of patients at follow-up visits than did consultants, and were found to have lower discharge rates than consultants. Analyses of data showed that at the first visit, diagnosis, disease severity and the grade of doctor seeing the patient in the clinic was significantly associated with patient discharge at the P < 0.05 level of significance. Patients considered that their visits had produced improvement in their condition in 38% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)
8937133 [Effects of disease modifying antirheumatic drugs (DMARDs) and DEX on IL-1 beta and IL-6 p 1996 Oct To investigate the effects of disease modifying antirheumatic drugs (DMARDs) and DEX on production of IL-1 beta, IL-6 and TNF-alpha, synovial cells were observed after IL-1 beta administration in vitro. MATERIALS AND METHODS: Synovial tissue was obtained aseptically from 8 rheumatoid arthritis patients during joint surgery. The dissected tissue was treated with collagenase and adherent cells were passaged before using as samples. They were stimulated with IL-1 beta (1 ng/ml) and cultured with DMARDs and DEX in serum-free media. After 24 hours' incubation, the production of IL-1 beta, IL-6 and TNF-alpha in the supernatants was measured. RESULTS: DEX inhibited the production of IL-6. GST inhibited the production of IL-1 beta and IL-6. CONCLUSION: DEX and GST may modulate the disease activity by inhibiting the cytokine production from synovial cells.
8895157 Effect of a nonsteroidal antiinflammatory drug on synovial fluid in osteoarthritis. 1996 Oct OBJECTIVE: The use of nonsteroidal antiinflammatory drug (NSAID) therapy in osteoarthritis (OA) is controversial because of suggestions that pure analgesics can be as effective as NSAID for pain relief. In addition, there is incomplete information whether antiinflammatory effects have any longterm benefit in OA. NSAID have been known to affect synovial fluid (SF) prostaglandins in rheumatoid arthritis. We describe the first examination of the effect of an NSAID, etodolac, on SF prostaglandins, cytokines, and cells in OA. METHODS: Joint fluids were studied before and 2 weeks after initiation of therapy with etodolac 400 mg tid. Leukocyte counts, prostaglandin, interleukin 6, and tumor necrosis factor were measured. RESULTS: Pretreatment features of SF did not predict clinical response. We found no change in the relatively low leukocyte counts. However, SF prostaglandin levels and interleukin 6 levels were significantly decreased and tumor necrosis factor alpha levels were increased after therapy with NSAID. CONCLUSION: This NSAID had potentially important local effects that could be either beneficial or deleterious. Further studies on effects of this and other NSAID on a broader variety of SF and synovial cytokines may help predict longterm effects of NSAID on progression of OA.
8706331 Circulating levels of IL-11 and leukaemia inhibitory factor (LIF) do not significantly par 1996 Aug To investigate the contribution of IL-11 and LIF to acute-phase protein (APP) production, we first analysed the effects of IL-11 and LIF on production of C-reactive protein (CRP), fibrinogen, and haptoglobin by human primary hepatocytes. We also measured the serum levels of IL-11, LIF, and CRP in serum from patients with inflammatory rheumatic diseases to assess the role of these cytokines in the APP response in vivo. We included patients with conditions associated with a high APP response such as rheumatoid arthritis (RA) or spondylarthropathy (SpA), and others usually associated with a weak APP response such as systemic lupus erythematosus (SLE), in order to investigate whether these cytokines could account for the differences in APP responses. Our results showed that IL-11 and LIF induced only minimal stimulation on production of APP by human primary hepatocytes compared with IL-6, known as the major inducer. Serum levels of CRP were elevated in RA and SpA, and significantly higher than in SLE patients. Despite the presence of a high APP response in some of our patients and despite the fact that we used sensitive assays to measure IL-11 and LIF, serum levels of both cytokines were not detected in any of the tested sera. In conclusion, our results show that circulating levels of IL-11 or LIF do not contribute significantly to the production of APP in vivo, and that they do not account for the difference in APP response between SLE and other inflammatory rheumatic diseases.
8690934 Serological diagnosis of visceral leishmaniasis by a dot-enzyme immunoassay for the detect 1996 Jun 14 Field medicine in tropical areas needs laboratory assays which are inexpensive and easy to perform. To meet this need a semi-quantitative dot-enzyme immunoassay (EIA) was developed for the detection of an L. donovani-related circulating antigen and tested for clinical relevance in the diagnosis of visceral leishmaniasis (VL). The dot-EIA probes serum spotted on nitrocellulose for the presence of the antigen using a monoclonal antibody raised against L. donovani promastigotes, a peroxidase-conjugated rabbit anti-mouse immunoglobulin antiserum and chloronaphthol as peroxidase substrate. The intensity of dot staining by chloronaphthol is read by eye and scored. The dot-EIA was used to test the following groups: 69 patients with VL from Brazil, Kenya, China and France, nine patients with cutaneous leishmaniasis, 38 patients with tropical diseases other than VL, five patients with rheumatoid arthritis and 40 health blood donors. The specificity of the assay was 96.7% (3/92 false positive) and the sensitivity 98.5% (1/69 false negative). A quantitative EIA for the detection of serum antibodies which makes use of a crude, soluble L. infantum promastigote extract as capture antigen and which was used as the reference method, proved to be more specific (98.9%) but similarly sensitive (98.5%). It should be possible to produce a kit, suitable for large scale application at low cost in order to facilitate routine use of the dot-EIA in the diagnosis of VL.
8612471 Tiaprofenic acid. A reappraisal of its pharmacological properties and use in the managemen 1995 Dec Tiaprofenic acid is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of patients with rheumatic diseases and other clinical conditions of pain and inflammation. Like other propionic acid derivatives, tiaprofenic acid is effective and generally well tolerated. Comparative studies in patients with rheumatoid arthritis or osteoarthritis receiving tiaprofenic acid 600 mg/day demonstrated improvements in pain intensity, duration of morning stiffness, articular index and other clinical variables which were similar to those achieved with alternative NSAIDs. Tolerability was also comparable between tiaprofenic acid and other NSAIDs in most trials; the most frequently reported adverse events involved the gastrointestinal tract. Some studies showed a trend towards fewer patient withdrawals because of adverse events with tiaprofenic acid than with NSAIDs such as indomethacin. Current evidence suggests that nonbacterial cystitis is more likely to be associated with tiaprofenic acid than with other NSAIDs. This reaction should, however, be considered in the perspective of its infrequent occurrence and its typical reversibility, and against the wider background of the established usage of tiaprofenic acid and its overall tolerability profile which is similar to that of other NSAIDs. Unlike indomethacin, tiaprofenic acid was not associated with increased cartilage degradation in a recently completed large clinical trial known as LINK, which evaluated the effects of long term administration in patients with osteoarthritis of the knee. Thus, tiaprofenic acid is an established option among the range of NSAIDs used in the treatment of patients with rheumatic diseases, with efficacy and tolerability profiles that are relatively well characterised. The availability of a sustained release dosage form of tiaprofenic acid, which has a similar efficacy and tolerability profile to the standard formulation, provides a convenient once daily dosage regimen.
8550645 One-stage anterior cervical decompression and posterior stabilization. A study of one hund 1995 Dec One hundred patients were managed with one-stage anterior decompression and posterior stabilization of the cervical spine. The underlying indication for the operation was cervical trauma in thirty-one patients; a neoplasm with a pathological fracture or an incomplete neurological deficit in fifty-five; and a miscellaneous condition, such as infection, rheumatoid arthritis, or cervical spondylotic myelopathy, in fourteen. The duration of follow-up ranged from twenty-four to 108 months (mean, thirty-two months) for the living patients. Sixteen patients had the procedure after the failure of an operation that had been performed elsewhere. The development of more biomechanically rigid cervical instrumentation did not obviate the need for a combined anterior and posterior approach. Twenty-six patients (26 per cent) had supplemental cervical instrumentation as part of the circumferential arthrodesis: seventeen had insertion of an anterior cervical plate and nine had insertion of a posterior facet plate. There were no iatrogenic neurological deficits. Of the seventy-five patients who had had a neurological deficit preoperatively, fifty-one improved one grade and six improved two grades according to the system of Frankel et al. Of the thirty-five patients who had not been able to walk preoperatively, twenty-one regained enough motor strength to walk postoperatively. Because the anterior and posterior procedures were performed during one session of general anesthesia, the prevalence of perioperative complications related to the airway was lower than that previously reported in the literature. No patient had an obstruction of the airway.
7575667 Differential cytotoxic effects of mizoribine and its aglycone on human and murine cells an 1995 Sep 28 The growth inhibitory mechanisms of mizoribine, an immunosuppressive imidazole nucleoside used clinically to inhibit rejection reactions after renal transplantation and in the treatment of systemic lupus erythematosus and rheumatoid arthritis, were studied in human and murine cells. We found that (a) human cells were 20- to 60-fold more resistant than murine cells to both mizoribine and its aglycone, (b) adenine phosphoribosyltransferase (APRT)-deficient human cells were resistant to aglycone but not to mizoribine, (c) hypoxanthine phosphoribosyltransferase (HPRT)-deficient human cells were at least 100-fold more sensitive to both mizoribine and aglycone, and (d) the decrease in intracellular GTP broadly paralleled the cytotoxicity in each case. Therefore, data obtained from studies using non-human tissues should be interpreted carefully before clinical application. Results indicate that the growth inhibitory effect of the aglycone but not of mizoribine is mediated by APRT, and depletion of guanine nucleotides is responsible for the effects of both drugs. Our data also suggest that the drugs may reduce mutant HPRT-deficient somatic cells in vivo, and may cause enhanced adverse reactions in HPRT-deficient individuals. The drug may have altered effects in patients receiving other purine or pyrimidine analogs.
7591433 Antismooth muscle and antiparietal cell antibodies in Indians with alopecia areata. 1995 Aug BACKGROUND: Alopecia areata is suspected to be an autoimmune disease. We studied 104 consecutive patients with alopecia areata for the presence of autoantibodies and associated autoimmune diseases. METHODS: A detailed history and examination was carried out in all patients to look for associated atopy, diabetes mellitus, hypertension, rheumatoid arthritis, vitiligo, lupus erythematosus, and thyroid disorders, etc. in the patients or their family members. Venous blood for estimation of fasting and postprandial blood glucose was collected in 30 patients, especially in those with family history of diabetes mellitus. Antimitochondrial (AMA), antismooth muscle (SMA), antinuclear antibodies (ANA), antiparietal cell antibody (PCA), and antibody against thyroid microsome (TMA) were detected employing indirect immunofluorescence on a composite section of rat liver, stomach, kidney, and human thyroid. Skin biopsy was processed for direct immunofluorescence by a conventional technique. RESULTS: Disseminated discoid lupus erythematosus, lichen planus, urticaria, psoriasis, and seronegative spondylarthritis were associated with alopecia areata in one case each. Antismooth-muscle-antibodies and PCA were found in 36 (34.6%) and 44 (42.3%) patients respectively, followed by TMA in 8 (7.7%), AMA in 6 (5.7%), antithyroglobulin antibodies in 3 (2.8%), and ANA in 2 (1.9%) patients. The incidence of SMA was higher in men with alopecia areata (P < 0.001). Direct immunofluorescence carried out in 24 patients did not reveal significant findings, except for occasional immunoglobulin deposits around hair follicles and blood vessels. CONCLUSION: Alopecia areata in India is associated more often with antismooth muscle and antiparietal cell antibodies.
8587096 A critical appraisal of toxicity indexes in rheumatology. 1995 May Our objective was to design a grading system to judge the methodological quality of toxicity symptoms assessment in rheumatologic randomized controlled trials, and to use this grading system to evaluate rheumatology case report forms. For comparison, we also evaluated instruments derived in other clinical specialties. To further determine whether variability seen on the rheumatology case report forms would lead to variability of side effect measurement in a clinical trial setting, we conducted a survey of investigators and their coordinators in a multicenter randomized trial. We used Feinstein's definition of sensibility and a conceptual model of the process of toxicity measurement in the clinical trial setting to develop a grading system. Thirty case report forms were obtained from a convenience sample, and 7 other instruments from other disciplines were obtained through literature review. These forms were evaluated in a blinded manner by 3 reviewers. A survey of 30 trial staff from 15 centers involved in a multicenter, randomized trial of 2 active nonsteroidal antiinflammatory drugs (NSAID) in rheumatoid arthritis (RA) was undertaken to evaluate whether the variability identified in the review of the case report forms translated into variability in the measurement of side effects in clinical trial setting. The rheumatology case report forms had a mean score of 9.1 (SD = 2.6) out of 20, where 0 is the worst score and 20 is a perfect score. The structured instruments from other disciplines had a mean score of 14.9 (SD = 2.7). These means were significantly different, with p = 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)
7605385 Lp(a) lipoprotein, IgG, IgA and IgM antibodies to Chlamydia pneumoniae and HLA class II ge 1995 Apr 24 The associations previously found between lipoprotein(a) (Lp(a)) levels and atherosclerotic disorders, diabetes, rheumatoid arthritis and renal diseases suggest that Lp(a) may be involved in autoimmune reactions. The relation found between Lp(a) levels and the HLA class II genotype in males with early coronary artery disease (CAD) further support that assumption. It was suggested that an autoimmune process, perhaps triggered by a concomitant intracellular infection may occur especially in patients with inherited high Lp(a) levels in combination with certain inherited HLA class II genotypes. In this study a Chlamydia pneumoniae IgG titer > or = 32 was significantly more common (P = 0.036) in CAD patients than in matched controls. This is in agreement with previous reports by other investigators. In addition, an IgG titer > or = 256 in combination with an Lp(a) level > or = 120 mg/l was found to occur significantly more often (P = 0.011) in male patients than in male controls. Certain HLA class II DR genotypes in combination with high Lp(a) levels and C. pneumoniae titers occurred more frequently in both male and female patients than in controls. Some combinations were very common in male patients, and the difference in comparison with male controls was highly significant.
7640345 Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha 1995 Apr Results of clinical trials have indicated that cA2, a neutralizing mouse/human IgG1 chimeric anti-human TNF-alpha monoclonal antibody, may have therapeutic benefit for rheumatoid arthritis patients. Arthritic joints contain, in addition to elevated levels of soluble TNF-alpha, high numbers of CD4+ T cells and macrophages, cells known to express transmembrane TNF-alpha upon activation. For that reason, we sought to determine if cA2 binds to transmembrane TNF-alpha and what effects such binding may have on TNF-alpha-expressing cells. A cell line expressing a cell-surface, mutant form of transmembrane TNF-alpha was prepared for these studies. Analysis of these TNF+ cells by flow cytometry, direct binding, and competitive binding assays showed that cA2 binds to the transmembrane form of TNF-alpha with high avidity. Binding of the IgG1 isotype of cA2, but not an IgG4 version of cA2, resulted in efficient killing of the TNF+ cells by both antibody-dependent cellular toxicity and complement-dependent cytotoxicity effector mechanisms. These findings indicate that, in addition to blocking soluble TNF-alpha activity, cA2 can bind to transmembrane TNF-alpha in vitro and suggest that cA2 binding may lead to lysis of TNF-alpha-expressing cells in vivo.
7849313 Pharmacokinetic study of anti-interleukin-6 (IL-6) therapy with monoclonal antibodies: enh 1995 Feb 15 The use of inhibiting cytokine-binding-proteins (CBPs) such as soluble cytokine receptors and anticytokine antibodies is considered for the treatment of cytokine-dependent diseases. The pleiotropic cytokine interleukin-6 (IL-6) is a target for immunointervention in numerous pathologic situations, including multiple myeloma, B-cell lymphoma, and rheumatoid arthritis. An antitumor response was obtained in the treatment of a patient with multiple myeloma. A controversial issue is to evaluate whether the carrier effect of the CBPs might limit their efficiency in blocking the target cytokine. We analyzed the pharmacokinetics of radiolabeled IL-6 in mice treated with various combinations of anti-IL-6 antibodies. We show that injection of one or two antibodies led to the stabilization of the cytokine. Conversely, simultaneous treatment with three anti-IL-6 antibodies, binding to three distinct epitopes, induced the rapid uptake of the trimeric immune complexes by the liver and the elimination of IL-6 from the central compartment. The use of cocktails of three antibodies binding simultaneously to a cytokine thus provides a new means of enhancing the clearance of the target molecule and should help in the design of antibody-based clinical trials by overcoming the problem of the accumulation of the cytokine in the form of monomeric immune complexes.
7836774 Circulating forms of ICAM-3 (cICAM-3). Elevated levels in autoimmune diseases and lack of 1995 Feb 15 The intercellular adhesion molecule-3 (ICAM-3) has been identified as the third LFA-1 ligand in addition to ICAM-1 and ICAM-2. In this report we have identified circulating forms of ICAM-3 (cICAM-3) in human serum. Using a sandwich ELISA with two monoclonal anti-ICAM-3 Abs, we detected cICAM-3 in concentrations between 40 and 360 ng/ml in all of 112 healthy controls. An analysis of patient sera from 10 different immune-mediated diseases revealed a distinct pattern of expression. Significantly elevated cICAM-3 levels were found in rheumatoid arthritis, systemic lupus erythematosus, Guillain-Barré syndrome, and multiple sclerosis, but not in type I diabetes, Grave's disease, chronic autoimmune thyroiditis, ulcerative colitis, or Crohn's disease. cICAM-3 levels were significantly higher in systemic lupus erythematosus patients with active compared with nonactive disease. Despite their binding to the same integrin receptor, serum levels of cICAM-3 did not correlate with cICAM-1 concentrations in either normal persons or in patients. The majority of patients had either elevated cICAM-3 or cICAM-1 levels but not both. In conclusion, a circulating form of ICAM-3 is present in human sera. cICAM-3 expression is elevated in certain immune-mediated diseases but occurs independently of cICAM-1.
7994916 Characterization of naturally occurring autoantibodies against tumour necrosis factor-alph 1994 Dec Naturally occurring autoantibodies against cytokines exist in the sera of patients with autoimmune diseases as well as in the sera of normal individuals. We report here that affinity-purified autoantibodies against human TNF-alpha from one rheumatoid arthritis (RA) patient inhibited the cytotoxic effect of TNF-alpha on the mouse fibrosarcoma cell line WEHI 164, by 50%. In an attempt to predict the autoantibodies' recognition site on TNF-alpha protein we screened a random nanopeptide phage library with the affinity-purified TNF-alpha autoantibodies. Among 63 random selected clones, 46 clones carried the sequence ASSLLASSP, NSSPYLNTK or PQSPGSSFP. Frequency analysis of the relative occurrence of the 20 amino acids in the nanopeptides displayed by 50 random bacteriophages picked before selection and 63 after selection to bind to TNF-alpha autoantibodies indicated that proline (P < 0.0003) and serine (P < 0.04) are involved in the binding of the autoantibodies to the phages. Furthermore, we demonstrated that three synthetic peptides (ASSLLASSP, NSSPYLNTK and PPLKPVIDE) displayed by the selected phages reduced the binding of the autoantibodies to TNF-alpha protein by 50%. Interestingly, the sera of mice (BALB/c) immunized with phages displaying ASSLLASSP and NSSPYLNTK peptide showed an anti-TNF-alpha response as detected by ELISA. This response was not found in mice immunized with the wild type phage. Thus, the recombinant phages selected from the phage libraries could be used as carrier for immunization, and therefore as a tool for vaccine development. This work sets the stage for experiments designed to isolate ligands for protective antibodies.
7976375 Leflunomide inhibits cytokine-induced DNA synthesis of rabbit synovial cells in culture. 1994 May The effects of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on DNA synthesis of rabbit synovial cells were studied. IL-1 beta 1000-10,000 U.ml-1, IL-6 10-1000 U.ml-1, TNF alpha 0.5-50 U.ml-1 and GM-CSF 1-100 ng.ml-1 concentration-dependently stimulated DNA synthesis in rabbit synovial cells in culture. Leflunomide (LFM) and its metabolite A77 1726 elicited an inhibitory effect on such cytokine-induced DNA synthesis of synovial cells. These results suggested that IL-1 beta, IL-6, TNF alpha and GM-CSF play a key role in the pathogenesis of rheumatoid arthritis. Inhibition of cytokine-induced proliferation of synovial cells by LFM may partially explain its antirheumatic activity.
8296191 [Old and current aspects of intravenous immunoglobulin therapy]. 1994 Jan 11 The natural variety of IgG isotype function suggests the use of IgG for therapeutic purposes. Whereas the clinical efficacy of substituting IgG through the i.m. and i.v. routes in combating infectious complications has long been known, the usefulness of i.v. IgG in comparatively high doses for the treatment of autoimmune disease states has been discovered serendipitously upon observing normalized platelet concentrates in IVIG-treated patients with immune thrombocytopenias. In such situations, a network of regulated humoral immune capacity, inherent to the large plasma pool of healthy donations, is conferred on the recipient and helps to reestablish homeostasis of deficient immune function. The indications for IVIG in diseases with abnormal immunity are rarely first choice but must be considered when conventional and cheaper options have failed. This is the case with the following diseases: idiopathic thrombocytopenic purpura, myasthenia gravis, Guillain-Barré disease, systemic lupus, rheumatoid arthritis, Evans syndrome, auto- and alloimmune cytopenias, polymyositis/dermatomyositis as well a haemorrhagic syndrome due to inhibitors against clotting factor VIII. In order to achieve synergism, a combination of IVIG with other therapeutic measures such as immunosuppressive agents, plasma exchange and/or immunosorption may be advisable. With such combinations, particularities in disease dynamics may be taken into account acceptable dosage recommendations for the treatment of autoimmune disease are not always available. The mechanisms of action of successful IVIG infusions are not yet completely understood. Those experimentally identified include: neutralization of autoimmune induction mechanisms; activity as anti-idiotypic agents; down-regulation of the Fc receptor apparatus, up-regulation of interleukin-1 receptor antagonist; deviation of complement activation to non-inflammatory targets and modulation of superantigens.
8158873 [A study of anemia and life activity in the elderly]. 1994 Jan One hundred senior citizens aged 80 years and over in homes for the aged were evaluated for the incidence of anemia (hemoglobin under 11.0 g/dl), Hb concentration, serum iron, and total iron binding capacity (TIBC). The subjects were classified into different groups according to age distribution (80-84, 85-89, over 90), as well as sex and life activity levels. In the 80-84 year age group, the Hb concentration was 0.5 g/dl higher than that in the other age groups. The Hb values of the male subjects were 1 g/dl higher than the corresponding values for female subjects. Subjects classified as bedridden had Hb values 1.2 g/dl lower than those in the groups that had higher activity levels (p < 0.001). The incidence of anemia was independent of sex and age differences; however, differences in activity levels were significant (p < 0.001). There are 53 patients with some diseases, urinary tract infections, bed sores (over 3 cm diameter), chronic bronchitis, progressive cancers and chronic rheumatoid arthritis, which may be origins of anemia. Seventy six percent of bedridden patients have one or two of the above diseases and 30% of non-bedridden patients have these diseases. The difference was statistically significant (p < 0.001). In the bedridden group, the differences of the mean Hb levels and the rates of anemia in patients with and without disease were not statistically significant (p > 0.1 in both factors). These facts indicate that the bedridden elderly have a high risk of anemia which is independent of some infectious and malignant diseases.