ABSTRACT
OBJECTIVE: To investigate the efficacy and tolerability of intravenous clodronate in patients with rheumatoid arthritis (RA). TREATMENT AND METHODS: Twenty-six patients with active RA were randomly allocated to receive either a single iv. infusion of placebo or 600 mg clodronate. Efficacy and safety were assessed weekly during the following three weeks by clinical and laboratory evaluations. RESULTS: Serum osteocalcin and carboxyterminal propeptide of type I procollagen (markers of bone metabolism) were significantly decreased in the clodronate group at the end of the study, whereas the indices of disease activity including number of swollen joints, number of tender joints, patient's and doctor's estimation of condition (visual analogue scale), erythrocyte sedimentation rate and serum C-reactive protein level were not affected by clodronate treatment. No serious adverse effects were observed. CONCLUSIONS: A single infusion of clodronate in patients with RA was safe and caused a decline in the markers of bone metabolism, but this short-term treatment did not suppress disease activity. Results from recent clinical and preclinical studies, however, suggest that the anti-inflammatory efficacy of clodronate requires liposome encapsulation.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Clodronic Acid/therapeutic use , Adult , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/adverse effects , Arthritis, Rheumatoid/pathology , Bone and Bones/drug effects , Bone and Bones/metabolism , Clodronic Acid/administration & dosage , Clodronic Acid/adverse effects , Double-Blind Method , Female , Humans , Infusions, Intravenous , Joints/pathology , Male , Middle Aged , Osteocalcin/blood , Treatment OutcomeABSTRACT
BACKGROUND: The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis. METHODS: 199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat. FINDINGS: 87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0.011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0.003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0.028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0.058) had clinically improved. The frequencies of adverse events were similar in both treatment groups. INTERPRETATION: Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis.
Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Adult , Aged , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/therapeutic use , Antirheumatic Agents/adverse effects , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , Male , Methotrexate/adverse effects , Methotrexate/therapeutic use , Middle Aged , Prednisolone/adverse effects , Prednisolone/therapeutic use , Remission Induction , Sulfasalazine/adverse effects , Sulfasalazine/therapeutic useABSTRACT
OBJECTIVE: To analyze the significance of cobalaminopenia (< 200 pmol/l) in patients with severe rheumatoid arthritis (RA). METHODS: We studied 42 patients with RA and cobalaminopenia (incidence 4%). Most patients had severe and longstanding disease. Concentrations of homocysteine, methylmalonic acid (MMA), gastrin, and pepsinogen 1 were analyzed in sera that had been stored frozen. A capillary gas chromatographic mass spectrometric technique was used to determine homocysteine and MMA. RESULTS: As a group, patients had significantly higher levels of serum homocysteine and serum MMA than laboratory reference probands (p < 0.0001 and p < 0.005, respectively). Individually, 20 of 39 patients had elevated serum levels of homocysteine (> 15 micromol/l). In 12 of 39 patients serum levels of MMA were elevated (> 0.37 micromol/l). Twenty of 42 patients had biochemical signs of disturbed gastric function. CONCLUSION: Our findings were compatible with the hypothesis that cobalaminopenia is one of several biochemical signs of gastrointestinal dysfunction in patients with severe RA. It is suggested that the hyperhomocysteinemia associated with vitamin B12 deficiency, folate deficiency, vitamin B6 deficiency, and impaired renal function may have a role in promoting high cardiovascular morbidity in patients with RA.
Subject(s)
Arthritis, Rheumatoid/blood , Homocysteine/blood , Methylmalonic Acid/blood , Vitamin B 12/blood , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/complications , Female , Humans , Male , Middle Aged , Pilot Projects , Retrospective StudiesABSTRACT
Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb < 100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb > or = 120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12 +/- 1.2 g/l vs 4 +/- 0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P < 0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18 +/- 1.1 g/l vs 7 +/- 1.1 g/l, P < 0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenuous efforts should have been made to control the disease itself.
Subject(s)
Anemia/drug therapy , Arthritis, Rheumatoid/complications , Erythropoietin/administration & dosage , Iron/administration & dosage , Adult , Aged , Anemia/etiology , Anemia/metabolism , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/physiopathology , Chronic Disease , Female , Humans , Inflammation/physiopathology , Iron/metabolism , Male , Middle Aged , Recombinant ProteinsABSTRACT
Developments concerning amyloidosis associated with rheumatic diseases or often causing musculoskeletal symptoms are reviewed. The pathogenesis, clinical manifestations, diagnosis, and therapy of amyloid A, amyloid light-chain, and amyloid beta 2-microglobulin amyloidosis are discussed from the standpoint of a clinical rheumatologist. The biology of the precursor protein serum amyloid A (SAA) has been extensively studied, and a new assay for SAA has been developed. In amyloid beta 2-microglobulin amyloidosis, modified beta 2-microglobulin may function as a pathogenic factor that initiates an inflammatory reaction in which macrophages produce cytokines that induce osteoclastogenesis and bone resorption. Further experience with serum amyloid P component scintigraphy in the diagnosis and monitoring of amyloidosis has accumulated. Guidelines for the dosage of colchicine in the treatment of amyloidosis associated with familial Mediterranean fever have been published. In amyloid light-chain amyloidosis, intensive chemotherapy in combination with bone marrow transplantation or autologous stem-cell infusion has potential therapeutic significance.
Subject(s)
Amyloidosis , Amyloidosis/epidemiology , Amyloidosis/physiopathology , Amyloidosis/therapy , Apolipoproteins/metabolism , Humans , Prevalence , Protein Precursors/metabolism , Serum Amyloid A Protein/metabolism , beta 2-Microglobulin/metabolismABSTRACT
Twenty-six patients with rheumatoid arthritis (RA) participated either in a 21 day, community sponsored, in-patient multidisciplinary rehabilitation program (N = 20) or; received traditional, out-patient physiotherapy designed by the patient's rheumatologist (N = 6). Clinical assessments were made (prior to, immediately after, and 6 months after rehabilitation) to evaluate the response to these two quite different rehabilitative measures that included: functional classification, joint score index, subjective VAS of pain, HAQ, pain disability index, Comprehensible psychopathological rating scale, hemoglobin, and CRP measurements. Economic assessments included salary, direct and community sponsored costs, for rehabilitation and costs for sick days and production losses. No clear-cut differences between the two rehabilitation modes were detected. Both modes showed improvement in different assessment parameters; patients with higher education and, therefore, with a less joint-disturbing work profile appeared to profit more from an extensive in-patient rehabilitation program. Patients with less education and a more manually-oriented working profile, did worse and had a higher tendency to seek medical pensioning, in spite of rehabilitative measures. As the total costs for out-patient rehabilitation only add up to 15.8% of the total costs for in-patient rehabilitation, this study setting cautiously suggests that out-patient rehabilitation might be an acceptable alternative to individualized patient groups that might not compromise clinical and vocational outcome. Larger patient groups are needed, however, to confirm these findings.
Subject(s)
Arthritis, Rheumatoid/economics , Arthritis, Rheumatoid/rehabilitation , Outpatient Clinics, Hospital/economics , Patient Admission/economics , Arthritis, Rheumatoid/diagnosis , Cost-Benefit Analysis , Follow-Up Studies , Humans , Outcome Assessment, Health Care/economics , Severity of Illness IndexABSTRACT
The purpose of the study was to evaluate the involvement of serine proteinases cathepsin G and elastase on pathomechanisms in synovial fluid (SF) of patients with reactive (ReA) and rheumatoid, (RA) arthritis. Cathepsin G, elastase, and their endogenous inhibitors alpha1-antichymotrypsin (alpha1-ACT) and alpha1-proteinase inhibitor (alpha1-PI) were identified immunohistochemically from SF and peripheral blood (PB) of patients with ReA and RA. Cathepsin G and elastase activities in SF and PB were measured spectrophotometrically. Dot-immunostaining was used to identify cathepsin G, elastase, but also alpha1-ACT and alpha1-PI from SF and PB. Cathepsin G and elastase-like activities (IU/I) were slightly elevated in ReA SF compared to the corresponding peripheral blood values (11.4 +/- 9.2 vs 4.8 +/- 1.7, NS, and 5.1 +/- 2.8 vs 2.3 +/- 2.2, NS), which was similar to what was seen in RA (16.4 +/- 6.2 vs 0.53 +/- 0.4, p < 0.05, and 6.51 +/- 1.8 vs 1.22 +/- 0.58, p < 0.05). Although some samples did not contain cathepsin G and/or elastase-like activities, all samples contained immunoreactive enzyme, but also alpha1-ACT and alpha1-PI. In ReA SF, in contrast to monocytes, all polymorphonuclear (PMN) cells contained cathepsin G and elastase. Cathepsin G and elastase activities correlated with each other (r = 0.78, p < 0.05) suggesting PMN / primary granules as their likely source. There was a closer association between the cathepsin G or elastase and SF leukocyte count in ReA than in RA. In ReA and RA SF elevated cathepsin G and elastase activities are detected compared to activity levels in PB suggesting local production mainly from PMNs. The co-existence of highly cellular SF and cathepsin G and elastase activity in the documented presence of endogenous inhibitors in ReA SF together with the, known, usually self-remitting clinical course of ReA, suggest a brisk and even exaggerated local PMN serine proteinase release; sparing of joints does not seem to be due to lack or inhibition of PMN responses but rather to a successful down-regulation or cessation of the responses initially elicited.
Subject(s)
Arthritis, Reactive/enzymology , Cathepsins/metabolism , Pancreatic Elastase/metabolism , Serine Endopeptidases/metabolism , Adult , Aged , Arthritis, Reactive/physiopathology , Cathepsin G , Cathepsins/blood , Female , Humans , Immunoblotting/methods , Immunohistochemistry/methods , Linear Models , Male , Middle Aged , Pancreatic Elastase/blood , Prohibitins , Serine Endopeptidases/blood , Synovial Fluid/metabolismABSTRACT
To study the maternal immunogenetics in congenital heart block (CHB), 31 mothers of affected children were HLA typed for class I and II antigens, and the results were compared with the corresponding HLA types in 900 healthy controls, in 45 mothers with systemic lupus erythematosus (SLE) and in 21 mothers with primary SS who had healthy children. An enzyme-linked immunosorbent assay was used to study the autoantibody responses to the recombinant 52 and 60 kDa SS-A/Ro, and 48 kDa SS-B/La proteins, and to the affinity-purified SS-A/Ro and SS-B/La antigens. Mothers of children with CHB had HLA B8 and DR3 significantly more often than healthy controls [71 vs 10%; relative risk (RR) 9.8, P < 0.00001 and 74 vs 23%; RR9.8, P < 0.001, respectively]. HLA B35 was protective (RR 0.1, P = 0.0029). Compared to controls with SLE, mothers of children with CHB were more often HLA DR3 and DQ2 positive (RR 4.1, P = 0.0057 and RR 3.1, P = 0.031, respectively), and compared to controls with primary SS less often HLA B15 positive (RR 0.1, P = 0.010). In general, the HLA antigen profile in mothers of children with CHB was more closely related to primary SS than to SLE. Levels of antibodies to all three SS-A/Ro antigens were significantly higher in mothers of children with CHB than in controls with SLE and primary SS (P = 0.0001-0.0014). With regard to SS-B/La, the autoantibody responses were similar (P = 0.32-0.66).(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Antibodies, Antinuclear/blood , Heart Block/congenital , Histocompatibility Antigens Class I/blood , Lupus Erythematosus, Systemic/immunology , Maternal-Fetal Exchange , Sjogren's Syndrome/immunology , Adult , Aged , Child , Female , Heart Block/genetics , Heart Block/immunology , Humans , Lupus Erythematosus, Systemic/blood , Middle Aged , Pregnancy , Sjogren's Syndrome/bloodABSTRACT
BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) and colchicine have beneficial effects in primary biliary cirrhosis (PBC). The efficacy of colchicine and UDCA in PBC was compared in a 2-year placebo-controlled study (n = 90). METHODS: Clinical events, laboratory test results, and liver histology were recorded at the beginning and end of the trial. RESULTS: There were significantly fewer dropouts for hepatic reasons with UDCA than with placebo. Pruritus was reduced by both active drugs. Colchicine improved liver function test results only modestly, whereas UDCA significantly decreased the serum activities of aminotransferases, alkaline phosphatase, and gamma-glutamyltransferase compared with colchicine and placebo. Serum total bilirubin levels were decreased only by UDCA. Both colchicine and UDCA reduced serum cholesterol levels, and UDCA also reduced high-density lipoprotein cholesterol levels. Furthermore, UDCA reduced the serum levels of immunoglobulin (Ig) M and IgG, and colchicine reduced IgG levels compared with placebo. The elevated serum level of aminoterminal propeptide of type III procollagen remained unchanged by colchicine or UDCA, whereas the serum level of carboxyterminal propeptide of type I procollagen was significantly decreased by UDCA. UDCA significantly decreased ductular proliferation compared with colchicine or placebo. CONCLUSIONS: These data suggest that UDCA frequently is superior to colchicine and especially to placebo in the treatment of PBC.
Subject(s)
Colchicine/therapeutic use , Liver Cirrhosis, Biliary/drug therapy , Ursodeoxycholic Acid/therapeutic use , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Aspartate Aminotransferases/blood , Bilirubin/blood , Cholesterol/blood , Double-Blind Method , Female , Finland , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Liver/drug effects , Liver/pathology , Liver Cirrhosis, Biliary/blood , Liver Cirrhosis, Biliary/pathology , Liver Function Tests , Male , Middle Aged , Procollagen/blood , gamma-Glutamyltransferase/bloodABSTRACT
A randomized placebo-controlled 2-year study was performed in 69 patients with primary biliary cirrhosis (PBC) on serum lipids during ursodeoxycholic acid (URSO) and colchicine treatments. In addition to serum bilirubin and alkaline phosphatase (AFOS), two variables considered to reflect liver function, serum lipoproteins, cholesterol precursors (squalene, delta 8-cholestenol, lathosterol and desmosterol), markers of cholesterol synthesis, cholestanol and plant sterols (campesterol and sitosterol), markers of liver function and cholesterol absorption, were studied before and during the treatments. Serum bilirubin was inconsistently improved by URSO, whereas improvement of AFOS values was better by URSO than colchicine, especially in patients with initially more advanced PBC. Serum total cholesterol was reduced by both drugs, very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) cholesterol by URSO. Cholesterol precursor sterols were increased by both URSO and colchicine mainly in patients with initially less severe PBC. On the other hand, the cholestanol values were markedly increased initially, and the values were related to bilirubin during the 2-year period, were further increased in the placebo group, and reduced in the URSO and colchicine groups, so that the improvement was highest in the URSO-treated patients with the severe form of PBC. The increase of the serum plant sterols, particularly that of sitosterol, was retarded by the two drugs so that the campesterol/sitosterol ratio, which was related to serum bilirubin, was increased especially in the cases with initially more advanced PBC.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Cholestanol/blood , Cholesterol/biosynthesis , Colchicine/therapeutic use , Liver Cirrhosis, Biliary/drug therapy , Phytosterols/blood , Ursodeoxycholic Acid/therapeutic use , Alkaline Phosphatase/blood , Bilirubin/blood , Humans , Liver Cirrhosis, Biliary/blood , Middle Aged , PlacebosABSTRACT
In rheumatoid arthritis various pro-inflammatory metabolites of arachidonic acid (AA), such as leukotriene B4 (LTB4) and prostaglandin E2 (PGE2), contribute to tissue destruction and pain. In contrast to AA, which is an omega-6 fatty acid, the omega-3 fatty acids, after having been liberated from the cell membrane phospholipids, are further converted into the non- or anti-inflammatory eicosanoids LTB5 and PGI3. AA concentration is an important regulatory step in the synthesis of both prostanoids and leukotriens. Dietary supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has therefore been used to decrease the ratio of AA to EPA or DHA to obtain beneficial clinical effects. EPA and DHA are found in animal fat and are quite expensive compared to their precursor alpha-linolenic acid (alpha-LNA) found in flaxseed oil. We, therefore, performed a placebo-controlled trial with alpha-LNA in 22 patients with rheumatoid arthritis, using a linoleic acid preparation as a placebo. After a 3-month follow-up, the treatment group showed an increased bleeding time, but the clinical, subjective (global assessment, classification of functional status, joint score index, visual analogue scale, pain tenderness score) and laboratory parameters (haemoglobin, erythrocyte sedimentation rate, C-reactive protein) did not show any statistical alterations. AA, EPA and DHA did not change either in spite of a significant increase in alpha-LNA in the treatment group. Thus, 3-month's supplementation with alpha-LNA did not prove to be beneficial in rheumatoid arthritis.
Subject(s)
Arthritis, Rheumatoid/diet therapy , alpha-Linolenic Acid/administration & dosage , alpha-Linolenic Acid/blood , Adult , Aged , Arthritis, Rheumatoid/blood , Double-Blind Method , Fatty Acids/analysis , Fatty Acids/blood , Female , Finland , Humans , Male , Middle Aged , Trace Elements/analysis , Trace Elements/blood , alpha-Linolenic Acid/therapeutic useABSTRACT
OBJECTIVE: To study fetal outcome in women with primary Sjögren's syndrome (SS) compared to that in women with systemic lupus erythematosus (SLE) and healthy women, and to study the possible association of fetal loss with anticardiolipin antibodies (aCL) and antibodies to SS-A/Ro and SS-B/La in women with primary SS. METHODS: A retrospective analysis of the fetal outcome in 55 pregnancies in 21 patients with primary SS compared to that in 100 pregnancies in 42 patients with SLE and 94 pregnancies in 42 healthy women matched for age, parity and the onset of the autoimmune disease with respect to pregnancy. IgG-, IgM- and IgA-aCL were determined by a cofactor-dependent ELISA and antibodies to SS-A/Ro and SS-B/La by ELISA using human recombinant antigens and affinity-purified antigens. RESULTS: Of all the 55 pregnancies in patients with primary SS, 8 (15%) occurred after the onset of primary SS symptoms. Eleven (20%) of the 55 pregnancies ended in fetal loss. The relative risk (RR) for fetal loss in patients with primary SS was 2.7 (95% CI 1.1-6.5; p = 0.023), and after the exclusion of the patient with four spontaneous abortions it was 2.0 (0.7-5.3; p = 0.18). In SLE the level of risk was 2.2 (0.9-5.0; p = 0.065). Fetal loss in patients with primary SS was not associated with elevated levels of anticardiolipin antibodies (aCL) or autoantibodies to SS-A/Ro or SS-B/La. Newborns of mothers with primary SS were not more premature or growth retarded than newborns of healthy women, but the absolute and the relative birth weights of the newborns of mothers with SLE was significantly lower than in healthy controls (P < 0.001 and P < 0.0001, respectively). CONCLUSION: We conclude that the majority of pregnancies in women with primary SS occur before the onset of the disease and that these women have an increased risk of fetal loss, which is not associated with elevated levels of ACL or antibodies to SS-A/Ro or SS-B/La. The risk of fetal loss in primary SS is similar to that in women with SLE, but fetal growth retardation appears to be more common in SLE than in primary SS.
Subject(s)
Pregnancy Complications , Pregnancy Outcome , Sjogren's Syndrome/physiopathology , Adult , Antibodies, Anticardiolipin/analysis , Antibodies, Antinuclear/analysis , Birth Weight , Case-Control Studies , Female , Fetal Death , Humans , Infant, Newborn , Infant, Premature , Lupus Erythematosus, Systemic/physiopathology , Middle Aged , Pregnancy , Reference Values , Retrospective Studies , Sjogren's Syndrome/immunologyABSTRACT
OBJECTIVE: To study the long-term outcome of mothers of children with isolated congenital heart block (CHB) and to characterize the maternal autoantibody response to SS-A/Ro and SS-B/La. METHODS: A retrospective clinical study of 33 mothers a mean of 11.2 years (SD 9.2 years, range 0-32 years) after the delivery of their first child with CHB. A clinical and immunologic study of 31 of these mothers, compared with 89 healthy mothers, 45 mothers with systemic lupus erythematosus (SLE), and 19 mothers with primary Sjögren's syndrome (SS), all of whom had healthy children. The specificity of the autoantibody responses to SS-A/Ro and SS-B/La was studied by enzyme-linked immunosorbent assays using purified human recombinant antigens and affinity-purified antigens. RESULTS: By the time of the analysis, 2 (6%) of the 33 mothers of CHB children had died and 6 (18%) had met the criteria for SLE. As a group, mothers of CHB children had clinical and immunologic characteristics more closely related to primary SS than to SLE or any other connective tissue disease. The predominant autoantibody response was to the SS-A/Ro antigens, notably to the 52-kd SS-A/Ro protein (prevalence 97%). Compared with controls with SLE, mothers of CHB children had higher titers of antibodies to recombinant 52-kd and 60-kd SS-A/Ro proteins and to the affinity-purified SS-A/Ro antigen (P < 0.05, P < 0.01, and P < 0.001, respectively). Compared with controls with primary SS, the autoantibody responses were similar. CONCLUSION: The predominant autoimmune disorder in mothers of children with CHB is subclinical primary SS. Antibodies to SS-A/Ro appear to be a prerequisite for the development of CHB.
Subject(s)
Autoantigens/immunology , Heart Block/congenital , RNA, Small Cytoplasmic , Ribonucleoproteins/immunology , Adolescent , Adult , Antibody Formation , Autoantibodies/blood , Autoantibodies/immunology , Child , Child, Preschool , Female , Heart Block/blood , Heart Block/immunology , Humans , Immunoblotting , Immunodiffusion , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Infant, Newborn , Middle Aged , Mothers , SS-B AntigenABSTRACT
The ability of reactive oxygen species produced by triggered neutrophilic leukocytes, hypoxanthine/xanthine oxidase (HX/XAO), hydrogen peroxide, and hypochlorous acid/myeloperoxidase (HOCl/MPO) systems to degrade hyaluronate (HA) in human synovial fluid (SF) and purified umbilical cord HA was compared by measuring the molecular weight distribution of HA using high-performance liquid chromatography with a size-exclusion column. The exposure of noninflammatory SF to phorbol myristic acetate (PMA)-activated neutrophils or to hydrogen peroxide (H2O2) caused depolymerization of SF HA to the degree corresponding to that found in rheumatoid SFs. When HX/XAO was used as radical generator, the molecular weight of SF HA decreased from 3.42 x 10(6) to 1.40 x 10(4) daltons with concomitant decrease of SF viscosity to 36% from the original value. The HOCl/MPO system caused no depolymerization of SF HA, even at very high unphysiological HOCl concentrations that induced the precipitation of SF HA together with SF proteins. This effect was found to be comparable to conventional mucin clot formation in SF. However, purified human umbilical cord HA was easily depolymerized with HOCl/MPO or with H2O2, but these effects were sensitive to the hydroxyl radical scavenger mannitol and iron chelator desferrioxamine, indicating that the formation of reactive hydroxyl radical (OH.) is likely to participate in these reactions. Thus we conclude that in inflammatory SF HA is mainly depolymerized by OH. produced by decomposition of H2O2 catalyzed by iron, free or locally bound to HA itself. In contrast to what has been reported earlier, HOCl/MPO only depolymerizes purified umbilical cord HA (in a hydroxyl radical-dependent manner) but does not depolymerize HA in SF. As a matter of fact, HOCl/MPO has a scavenging action on SF HA by consuming H2O2 and thus preventing the formation of reactive hydroxyl radicals.
Subject(s)
Hyaluronic Acid/metabolism , Reactive Oxygen Species/pharmacology , Synovial Fluid/metabolism , Umbilical Cord/metabolism , Chemical Precipitation , Humans , Hydrogen Peroxide/pharmacology , Hypochlorous Acid/pharmacology , Hypoxanthine , Hypoxanthines/pharmacology , Neutrophils/metabolism , Peroxidase/pharmacology , Polymers , Xanthine Oxidase/pharmacologyABSTRACT
Fetal outcome in systemic lupus erythematosus (SLE) was retrospectively analysed in 242 pregnancies in 112 unselected patients, and the outcome was compared with that of 417 pregnancies in 192 control women matched for age, parity and socio-economic status. Relative risk for fetal loss after the diagnosis of SLE was 2.5 (95% confidence interval (CI), 1.4-4.5), for prematurity 5.8 (3.2-10.5) and for intra-uterine growth retardation (IUGR) 8.6 (3.0-24.3). Fetal outcome of pregnancy in patients with pre-existing stable lupus nephritis was no worse than in other SLE pregnancies. Relations of three lupus anticoagulant (LA) assays and tree anticardiolipin (aCL) enzyme-linked immunosorbent assays to fetal outcome were studied. Patients positive by any LA assay had a previous fetal loss more often than patients negative by all LA assays (odds ratio 3.4; 95% CI, 1.3-9.0; P = 0.01). Of the 41 patients whose antiphospholipid antibody (aPL) tests were all negative, five (12%) had a history of fetal loss (16% in controls). As a group, aCL was more sensitive for fetal loss than LA (64% vs 50%), but LA was more specific (77% vs 52%). Combinations of one aCL assay with one LA assay had a 41-73% sensitivity and a 64-73% specificity for a history of fetal loss. aPL did not correlate to prematurity or fetal growth retardation. In conclusion, fetal loss in SLE is 2.5 times more prevalent than in the normal population. The presence of LA indicates a high risk for fetal loss, and the absence of aPL is an indication of a favorable pregnancy outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Lupus Erythematosus, Systemic/epidemiology , Pregnancy Complications/epidemiology , Pregnancy Outcome , Adolescent , Adult , Age Factors , Antibodies, Antiphospholipid/analysis , Antibodies, Antiphospholipid/physiology , Case-Control Studies , Female , Fetal Death/epidemiology , Fetal Death/etiology , Fetal Growth Retardation/epidemiology , Fetal Growth Retardation/etiology , Fetal Growth Retardation/immunology , Finland/epidemiology , Humans , Incidence , Lupus Coagulation Inhibitor/analysis , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/immunology , Middle Aged , Obstetric Labor, Premature/epidemiology , Obstetric Labor, Premature/etiology , Obstetric Labor, Premature/immunology , Pregnancy , Pregnancy Complications/immunology , Retrospective Studies , Social ClassABSTRACT
Since there are few data on the use of various birth control methods in systemic lupus erythematosus (SLE), we performed a cross-sectional study of the actual contraceptive practices in a group of 85 Finnish female SLE patients of reproductive age. We also recorded side-effects experienced during the use of oral contraceptives (OCs) and intrauterine devices (IUDs). The use of contraception was lower in SLE patients than in healthy women of the same age (59 vs 77%, P < 0.001). Sexually active SLE patients requiring contraception used more often barrier and natural methods (P < 0.001) and less often OCs (P < 0.05) than the corresponding healthy women. The risk of deep venous thrombosis in SLE patients while using oestrogen-containing OCs was slightly increased (RR 2.3, 95% CI 0.5 to 10.3). Twenty-five (78%) of the 32 patients, who had used progestagen-only contraceptives discontinued them because of side effects, which were mainly gynaecological. Major bleeding or pelvic infection did not occur during the use of IUDs.
PIP: Since there are few data on the use of various birth control methods in systemic lupus erythematosus (SLE), the authors performed a cross-sectional study of the actual contraceptive practices in a group of 85 Finnish female SLE patients of reproductive age. They also recorded side effects experienced during the use of oral contraceptives (OCs) and IUDs. The use of contraception was lower in SLE patients than in healthy women of the same age (59% vs. 77%, p .001). Sexually active SLE patients requiring contraception used barrier and natural methods more often (p 0.001) and OCs less often (p 0.05) than did the corresponding group of healthy women. The risk of deep venous thrombosis in SLE patients while using estrogen-containing OCs was slightly increased (RR 2.3, 95% Ci 0-5-10.3). 25 (78%) of the 32 patients who had used progestagen-only contraceptives discontinued them because of side effects which were mainly gynecological. Major bleeding or pelvic infection did not occur during use of IUDs.
Subject(s)
Contraception/methods , Contraceptives, Oral , Intrauterine Devices , Lupus Erythematosus, Systemic/epidemiology , Adolescent , Adult , Contraceptives, Oral/adverse effects , Cross-Sectional Studies , Female , Finland/epidemiology , Humans , Intrauterine Devices/adverse effects , Risk Factors , Thrombophlebitis/epidemiologyABSTRACT
We performed a 24-week open clinical study in which 12 patients with rheumatoid arthritis (RA) and anemia (mean hemoglobin (Hb) value 102 g/l, range 90-109 g/l) were treated with recombinant human erythropoietin (rHuEPO). rHuEPO was given as a subcutaneous injection twice weekly with an initial dose of 300 U/kg/week. Nine of the 11 patients who completed the study responded with an increase in Hb value of 15 g/l or more within 3 to 17 weeks. Three months after treatment the Hb levels were significantly lower than the highest Hb levels (p < 0.0001). There was an inverse correlation between the response rate and the mean serum concentrations of C-reactive protein and serum amyloid A protein (p < 0.001 and p < 0.003, respectively). We conclude that rHuEPO can correct anemia in patients with RA, but the response seems to be adversely influenced by the inflammatory activity of the disease.