Abnormal calcium, magnesium and zinc stores in peripheral blood cells from patients with inflammatory connective tissue disease.
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Arthritis↗
Biomedical subjects
R Hällgren
Publications and source records attributed to R Hällgren.
Ankylosing spondylitis: a chronic inflammatory disease with iron overload in granulocytes and platelets.
The cellular stores of iron in granulocytes and platelets isolated from 29 patients with ankylosing spondylitis were measured by the nuclear microprobe technique. The mean iron content in polymorphonuclear cells (PMNs) was 32 (SD 3) micrograms/g dry weight and in platelets 11 (2.6) micrograms/g dry weight. Corresponding values for age and sex matched healthy controls were 5.2 (1.9) and 4.6 (0.8) micrograms/g (p less than 0.001). Significant correlations were found in the patient group between (PMN) iron and the circulating levels of transferrin, total iron, and lactoferrin (p less than 0.05). PMN iron was not related to serum ferritin. Platelet iron correlated with transferrin (p less than 0.01) but not with the other iron binding proteins. Significant relationships were also found between the PMN iron stores and the inflammatory activity defined by erythrocyte sedimentation rate (ESR) and the immunoglobulins A and G. These data further illustrate the altered iron kinetics in chronic inflammatory disease and record the fact that the redistribution of iron associated with the inflammatory process also includes granulocytes and platelets.
Blood Platelets↗
Sulphasalazine in ankylosing spondylitis.
In recent years sulphasalazine has gained acceptance as an effective agent for the treatment of rheumatoid arthritis. Ankylosing spondylitis is a disease where remission inducing drugs so far have been lacking. In this double blind trial sulphasalazine was compared with placebo in 37 patients with ankylosing spondylitis. Evaluation after three months' treatment showed reduction of inflammatory activity and improvement of clinical variables. The side effects were mild. The results suggest that sulphasalazine is a potentially effective and safe drug in the treatment of ankylosing spondylitis.
Adult↗
Serum osteocalcin in rheumatoid arthritis and other inflammatory arthritides: relation between inflammatory activity and the effect of glucocorticoids and remission inducing drugs.
Osteocalcin, a vitamin K dependent protein synthesised by osteoblasts, was measured in serum by radioimmunoassay in patients with rheumatoid arthritis (n = 36) and seronegative spondyloarthropathies (n = 23). The serum osteocalcin levels were decreased in both patient groups compared with the levels measured in age and sex matched healthy controls. We found no relation between serum osteocalcin and the disease duration or inflammatory activity of the patients who were without drug treatment at the first examination. After administration of glucocorticoids (20 mg prednisolone a day) circulating osteocalcin decreased significantly after one week of treatment. During gradual reduction of the steroid dosage osteocalcin returned to pretreatment values. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) did not influence circulating osteocalcin. During treatment with chloroquine or penicillamine serum osteocalcin increased significantly, concomitant with a reduction of the acute phase reactants. Controversy persists about the abnormality of bone turnover in rheumatic diseases, but our data suggest that the overall bone turnover is decreased in patients with rheumatoid arthritis and other inflammatory arthritides.
Adrenocorticotropic Hormone↗
Pulmonary involvement in ankylosing spondylitis.
Thirty two patients with ankylosing spondylitis were investigated with a set of pulmonary function tests and the results compared with those for a control population. The patients had no complaints about lung symptoms and their chest radiographs were normal. The main pathological findings were reduced lung volumes, a raised closing volume/vital capacity ratio, and a decreased volumic airway conductance. The lung volume reduction correlated with disease duration, thoracic mobility, and degree of acute phase reaction. The stiff spondylitic thorax probably makes the main contribution to the impairment of lung function in these patients, but the findings in this study also suggest an involvement of the small airways. This type of pulmonary function testing seems valuable even in patients with ankylosing spondylitis without lung symptoms and it might be used as a tool in the staging of the disease, to evaluate treatment and to differentiate from fibrosis.
Adolescent↗
Patient reactions and granulocyte degranulation during hemodialysis with cuprophane and polycarbonate membranes. A double-blind study.
During dialysis with cuprophane or polycarbonate filters, a fall in neutrophil and eosinophil cell counts is observed. Total complement remains unchanged, but C3a increases indicating complement activation. Release of granular granulocyte proteins is observed indicating granulocyte activation. Patient reactions or biochemical findings indicate no significant difference when polycarbonate or cuprophane membranes are used, except perhaps less complement activation with polycarbonate. The biochemical observations may be due to complement activation or cell contact with the membrane.
Adult↗
Procollagen III peptide in bronchoalveolar lavage fluid. A potential marker of altered collagen synthesis reflecting pulmonary disease in sarcoidosis.
Type III procollagen N-terminal peptide was not detectable in bronchoalveolar lavage fluid from healthy volunteers but was present in fluid from the majority of patients with pulmonary sarcoidosis (N = 110); the mean concentration was 0.6 micrograms/liter returned fluid, range less than or equal to 0.2 to 19.5 or, expressed in relation to the amount of albumin recovered, 9.5 mg/gm albumin (range less than or equal to 1 to 45). The serum concentrations in the patients with sarcoidosis were normal. Significant inverse correlations were found between lavage fluid procollagen peptide and vital capacity (p less than 0.001), forced expiratory volume (p less than 0.01), and diffusion capacity (p less than 0.01). Lavage fluid procollagen peptide was also related to pulmonary radiological findings (p less than 0.001) and serum levels of angiotensin converting enzyme (p less than 0.001). These findings support the hypothesis that procollagen peptide in lavage fluid is a potential marker of activated pulmonary fibroblasts or an expanded fibroblast mass associated with interstitial lung fibrosis.
Adult↗
Peripheral blood T lymphocyte subsets in active rheumatoid arthritis--effects of different therapies on previously untreated patients.
Peripheral blood T lymphocyte subset levels were prospectively analyzed in previously untreated patients with active rheumatoid arthritis (RA) with different drug regimens. Before treatment the patient group had reduced numbers of Leu 2a+ lymphocytes compared with controls (p less than 0.001). During penicillamine and chloroquine treatment a marked reduction in absolute numbers of Leu 3a+ lymphocytes was seen (p less than 0.01), whereas treatment with nonsteroidal antiinflammatory drugs was characterized by increased absolute numbers of Leu 2a+ lymphocytes (p less than 0.02). Thus, there seems to be a predictable variation of T lymphocyte subsets in RA with certain drug regimens.
Adolescent↗
Renal interstitial fibrosis and vascular changes. Occurrence in patients with autoimmune diseases treated with cyclosporine.
Histologic examinations of kidney biopsy specimens from six patients with relapsing polychondritis (n = 1), Behçet's syndrome (n = 3), and chronic uveitis (n = 2) were performed after four to 36 months of treatment with cyclosporine. Five of the patients had a variable degree of focal interstitial fibrosis and tubular atrophy, with and without minimal interstitial inflammation. Arteriolar hyalinization was noted in four and glomerular sclerosis in two patients. These renal lesions could not be attributed to underlying autoimmune disease or previous drug therapy but were similar to those recently reported in kidney and heart recipients receiving long-term cyclosporine. The initial cyclosporine doses were 15 mg/kg body weight in one patient and 10 mg/kg in the others. The maintenance cyclosporine doses ranged from 2.5 to 7.5 mg/kg with appropriate trough cyclosporine plasma levels (60 to 130 ng/mL). A rough correspondence between the extent of the histologic renal changes and the cumulative cyclosporine was seen, whereas serum creatinine increase or the development of hypertension during treatment did not predict the degree of interstitial fibrosis or the presence of arteriolar changes. Neither did a rapid fall in the serum creatinine level after withdrawal of cyclosporine exclude focal irreversible renal lesions. Since the histopathologic changes found in the kidneys are potentially progressive, we believe that, until more is known, long-term cyclosporine treatment should be reserved for situations where more established immunosuppression has failed to control an autoimmune process threatening the function of vital organs.
Autoimmune Diseases↗
Hyaluronate in bronchoalveolar lavage fluid: a new marker in sarcoidosis reflecting pulmonary disease.
Hyaluronate (hyaluronic acid) was not detectable in bronchoalveolar lavage fluid from smoking or nonsmoking healthy volunteers but was present in fluid from 23 patients with sarcoidosis; the mean concentration was 16 micrograms/1 returned fluid (range less than or equal to 5-430) or, expressed in relation to the amount of albumin recovered, 0.22 micrograms/mg albumin (range less than or equal to 0.05-3.6). The serum hyaluronate concentrations in the patients with sarcoidosis were normal. There was a significant inverse correlation between vital lung capacity and hyaluronate concentrations in bronchoalveolar lavage fluid (p less than 0.001), and patients with abnormal lung volumes had hyaluronate concentrations that were on average six times higher than those in patients with normal vital capacity. Duration of disease, pulmonary radiological findings, and markers for macrophage activation (angiotensin converting enzyme) and lymphocyte activation (beta 2 microglobulin) were not correlated with bronchoalveolar lavage fluid hyaluronate. It was concluded that in sarcoidosis release of hyaluronate into the airways is related to lung volume and therefore to the course of the disease. Increased synthesis of hyaluronate in lung parenchyma may reflect activation of fibroblasts, and measurements of hyaluronate may have clinical value for prognosis and treatment.
Adult↗
Abnormal calcium and magnesium stores in erythrocytes and granulocytes from patients with inflammatory connective tissue diseases. Relationship to inflammatory activity and effect of corticosteroid therapy.
The mass fraction of Ca and Mg in isolated erythrocytes and granulocytes was measured using the nuclear microprobe technique. Conspicuous abnormalities were observed in cells from patients with rheumatoid arthritis and other inflammatory arthritides. Compared with the normal cellular content, total Ca was increased an average of 3 times in erythrocytes and 5 times in granulocytes. Total granulocyte Mg was increased about 3 times, whereas erythrocyte Mg was reduced to as much as 60% of normal. These abnormalities were less prominent or were absent in scleroderma patients, except for levels of granulocyte Ca, which were increased more than 3 times beyond normal in this patient group. A significant positive correlation was found between serum haptoglobin and erythrocyte or granulocyte Ca content among these patients, but not between haptoglobin and erythrocyte or granulocyte Mg values. During corticosteroid treatment, a significant increase in erythrocyte Mg and a significant reduction in erythrocyte Ca were noted, but normalization of these levels was not achieved. Granulocyte Ca was also significantly reduced, while granulocyte Mg remained unaltered. Serum levels of Ca and Mg were within normal ranges and were not influenced by corticosteroid therapy. The results indicate that at least Ca abnormalities in erythrocytes and granulocytes are associated with the intensity of the inflammatory process and that the amounts of Ca and Mg in these cells are influenced by potent antiinflammatory therapy.
Adrenal Cortex Hormones↗
Increased in vivo secretory activity of neutrophil granulocytes in patients with psoriasis and palmoplantar pustulosis.
The relationship between psoriasis and palmoplantar pustulosis (PPP) is uncertain, as is the role of the neutrophil granulocyte in these conditions. In a previous comparative study of the rate of polymorphonuclear leucocyte (PMN) phagocytosis of IgG- and IgG-C3b-coated particles, an increased uptake rate was found in both diseases. Further information on the in vivo activity of PMNs in these conditions may be obtainable by determining the level of lactoferrin (LF) in serum from such patients, since LF serves as a specific marker of the turnover and activity of the circulating pool of neutrophils. In this study on 19 patients with psoriasis and 20 patients with PPP, elevated levels of LF were found in both conditions. In contrast, the levels of lysozyme and beta 2-microglobulin, which are markers of monocyte-macrophage and lymphocyte activity, respectively, were normal. This suggests the selective activation of neutrophils in these disorders. LF was significantly correlated (P less than 0.05 and 0.001, respectively) to the rates of phagocytosis of IgG- and IgG-C3b-coated particles, but not to the chemotaxis of isolated PMNs. There was no correlation between the severity of the disease and the levels of serum LF. The data suggest the increased in vivo activity of neutrophils in psoriasis and PPP.
Adolescent↗
Reduced zinc in peripheral blood cells from patients with inflammatory connective tissue diseases.
By the use of the nuclear microprobe technique, the concentrations of zinc in isolated erythrocytes, platelets, and granulocytes were measured in patients with rheumatoid arthritis, other inflammatory arthritides, and scleroderma. Markedly reduced cellular zinc values were found compared to those measured in healthy subjects. No relation was found to inflammatory activity or disease duration. Plasma zinc was reduced in the majority of the patients and was negatively correlated to the inflammatory activity estimated by ESR and serum orosomucoid. No relation was found between total zinc values in plasma or cells or disease duration. Corticosteroid therapy was instituted in a number of the patients with inflammatory arthritides and induced a significant elevation of total zinc in all cell types, although normalization was not achieved. Plasma zinc values remained unchanged during the treatment.
Adult↗
Is 125I iothalamate an ideal marker for glomerular filtration?
The triiodinated angiographic contrast medium, iothalamate, has (usually labelled 125I) been used extensively as a marker for glomerular filtration. We have studied the renal handling of 125I iothalamate (IOT) in vivo and in vitro in several species. In renal cortical slices from chicken, rabbit, rat, and monkey, the tissue-to-medium ratio of IOT was twice that of 51Cr-EDTA (EDTA) at 37 degrees C; a difference that was abolished at 0 degree C and markedly reduced by added o-iodohippurate or iodipamide. In five chickens the steady-state renal clearance of IOT (CIOT) was twice (P less than 0.05) that of EDTA (CEDTA) or 3H inulin (C1); a difference that was abolished by administration of 100 mg/kg/hr of novobiocin, an organic anion transport inhibitor. CEDTA was similar to C1 before as well as after transport inhibition. Utilizing the Sperber technique the mean apparent tubular excretion fraction (ATEF) of IOT was 8%, while that of EDTA was 1% (P less than 0.01; N = 10). After novobiocin coinfusion (new steady-state) ATEFIOT was significantly reduced (P less than 0.01) and not different from that of EDTA (-1%). In the same animals the total urinary recovery of IOT was 84 and 57% (P less than 0.01) before and after novobiocin, respectively, while corresponding values for EDTA was unchanged by the inhibitor. In seven rats the renal extraction of IOT was reduced from 29 to 17% (P less than 0.05) by coinfusion of probenecid (5 mg/kg/hr). Corresponding extractions were 82 to 34% (P less than 0.005) and 22% (unchanged) for PAH and EDTA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Serum osteocalcin levels in normal subjects and patients with primary hyperparathyroidism.
The serum concentrations of osteocalcin were measured by a radioimmunoassay method in 95 apparently healthy subjects of both sexes with ages from 20 to 80 years and in 16 patients with primary hyperparathyroidism. There were no differences for the values between healthy males and females before the age of fifty, whereas the levels were higher in postmenopausal females. The osteocalcin levels were inversely related to age in premenopausal females but not in elder females or in males. The serum osteocalcin levels were raised in patients with primary hyperparathyroidism but with a large overlap against normal values. In all groups there was a positive correlation with the serum alkaline phosphatases. Variations with age should be considered in the interpretation of measurements in females. Furthermore, the increase in the immediate postmenopausal period might have implications for postmenopausal bone loss.
Adult↗
Circulating hyaluronate in psoriasis.
A radioassay method allowing measurements of low concentrations of circulating hyaluronate was used in a study of serum hyaluronate concentrations in 44 patients with psoriasis. Twenty-three of them had only skin lesions and 21 had both skin lesions and arthropathy. In both of these groups significantly elevated serum levels of hyaluronate were found. The highest values were observed in those with widespread and active skin disease and/or active arthritis. Serum hyaluronate positively correlated with the plasma concentrations of alpha 1-antitrypsin and haptoglobin and also with ESR, which may indicate a relationship between acute inflammation and increased production of hyaluronate. Seven patients with widespread atopic dermatitis included for comparison had normal hyaluronate values. In blister fluid from lesional skin in two patients with acute psoriasis, very high concentrations of hyaluronate were found, in comparison with the concentrations in blister fluid from non-involved skin. The increased concentration of serum hyaluronate in psoriasis indicates involvement of dermal and synovial tissue in psoriasis, in addition to the epidermal changes.
Adult↗
The role of polymorphonuclear leucocytes in the pulmonary dysfunction induced by complement activation.
To determine the role of polymorphonuclear leucocytes (PMNs) in the pulmonary reaction induced by complement activation, pigs were infused with complement-activated plasma (CAP), cell-free supernatant from PMNs activated in vitro, or washed PMN aggregates produced in vitro. Infusion of CAP resulted in transient peripheral leucopenia, a reversible rise in pulmonary vascular resistance (PVR) and decreased arterial oxygen tension (PaO2). Indomethacin did not influence the CAP-induced drop in PMN count or the accumulation of PMNs in the lung, but significantly counteracted the rise in PVR and fall in PaO2. Antihistamines did not prevent the cellular or pulmonary reactions to CAP infusion. Methylprednisolone did not inhibit the decrease in PMN count, but modified the pulmonary reaction to CAP, although it did not prevent the rise in PVR to the same extent as indomethacin; it counteracted the fall in PaO2. Infusion of supernatant from activated PMNs did not influence the PMN count, but caused a reversible increase in PVR and a drop in PaO2. Indomethacin counteracted the pulmonary reaction to this infusion. Infusion of washed PMN aggregates did not result in any cellular or physiological changes. These findings suggest that the pulmonary reaction induced by complement activation is mediated by humoral components generated and/or released during activation of PMNs. Arachidonic acid metabolites play an important role and it is likely that substance(s) released from activated PMNs trigger prostanoid synthesis in other cells. It is conceivable, however, that PMNs exposed to activated complement factors also directly synthesize and release arachidonic acid metabolites.
Animals↗
Circulating hyaluronate in rheumatoid arthritis: relationship to inflammatory activity and the effect of corticosteroid therapy.
The mean serum hyaluronate concentration in a group of patients with rheumatoid arthritis (n = 37) was 232 +/- 182 (SD) microgram/l and significantly greater (p less than 0.001) than that of age and sex matched healthy controls (mean level 42 +/- 25 micrograms/l) as well as that of patients with ankylosing spondylitis (mean level 58 +/- 33 micrograms/l). In rheumatoid arthritis positive correlations were found between serum hyaluronate and acute-phase plasma proteins, while neither rheumatoid factor titre nor the presence of circulating immune complexes were related to the hyaluronate levels. Increased serum hyaluronate could not be explained by impaired renal or liver function or by drug therapy. During treatment with corticosteroids but not with non-steroidal anti-inflammatory drugs the serum hyaluronate concentrations were significantly reduced. The data obtained suggested an increased production of hyaluronate in rheumatoid arthritis, and the increase seems to be related to the activity of the inflammatory process.
Acute-Phase Proteins↗