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Biomedical subjects

R Hällgren

Publications and source records attributed to R Hällgren.

At least 145 records · Page 8Linked to original sources

Raised circulating levels of the eosinophil cationic protein in ankylosing spondylitis: relation with the inflammatory activity and the influence of sulphasalazine treatment.

The possibility of eosinophil involvement in ankylosing spondylitis (AS) was investigated by measuring serum levels of eosinophil cationic protein (ECP), a specific granule constituent of eosinophils. In a group of 48 patients with AS we found a threefold increase of the mean serum levels of ECP compared with a reference group (p less than 0.001). The blood eosinophil counts were similar in patients and controls. A correlation was found between ECP and inflammatory activity defined by erythrocyte sedimentation rate (ESR) and serum haptoglobin. Fifteen patients were studied before and after three months' treatment with sulphasalazine (2-3 g/day). The ECP levels decreased in 13/15 and this paralleled reduction of the acute phase reaction and improvement of clinical parameters. The results point to eosinophil activation as part of the inflammatory process in AS. The signs of reduced eosinophil activation during sulphasalazine treatment suggest either a drug mediated, direct effect on eosinophils or an effect on the inflammatory mechanism stimulating eosinophils.

Adult↗

Hyaluronic acid in bronchoalveolar lavage in rats exposed to quartz.

Hyaluronic acid, a connective tissue component, in bronchoalveolar lavage fluid (BAL) is correlated with decreased lung volumes in sarcoidosis. To investigate whether hyaluronic acid could be a marker of fibrosis in another interstitial lung disease, silicosis, the level of the substance in BAL fluid from rats exposed to crystalline silica (n = 3), amorphous silica (n = 3), and in one sham injected rat was measured. There was an increase in the total number of alveolar cells recovered in the rats exposed to crystalline silica and also a pronounced increase in the proportions of neutrophils and lymphocytes. In addition, the concentration of hyaluronic acid was high in this group of rats, and electron microscopic investigation of the lungs showed fibrosis. Thus hyaluronate in BAL fluid in rats exposed to crystalline silica seems to be a possible marker of fibrotic changes.

Animals↗

Hyaluronic acid in bronchoalveolar lavage fluid in patients with sarcoidosis: relationship to lavage mast cells.

Hyaluronate (hyaluronic acid), a potential marker for activated pulmonary fibroblasts, appears in increased concentrations in bronchoalveolar lavage fluid from patients with sarcoidosis. The mechanisms underlying fibroblast proliferation are largely unknown but activated alveolar T lymphocytes and macrophages probably play a part; the mast cell is also important for fibroblast proliferation. This study was designed to determine whether there is any association between pulmonary mast cells in lavage fluid, which are known to be increased in patients with sarcoidosis, and signs of pulmonary fibroblast activation. A strong correlation was found between lavage fluid hyaluronate and recovered mast cells (r = 0.72, p less than 0.001). Moreover, mast cell and hyaluronate estimations correlated inversely with lung volume and transfer factor for carbon monoxide, and both indices increased with advancing radiological sarcoid stage. Macrophage and granulocyte counts were normal in lavage fluid from patients with sarcoidosis and were not related to lavage fluid hyaluronate or laboratory signs of the disease in the lungs. Lymphocytes were recovered in increased numbers (p less than 0.001) and were related to the lavage fluid mast cells and hyaluronate. It is concluded that in sarcoidosis release of hyaluronate into the airways is related to the degree of lung disease and to the local inflammatory reaction in the lung as defined by increased numbers of mast cells and lymphocytes in lavage fluid. The findings may reflect a link between the immune system, activation of mast cells, and a pulmonary fibroblast proliferation.

Adult↗

Endotoxemia in chronic renal failure.

In the past years dialyzers have been improved, and consequently pyrogenic reactions have become rare. However, some patients in our dialysis unit have shown symptoms during hemodialysis which we suspected could be caused by endotoxins. These patients, as well as controls without similar symptoms, had elevated levels of circulating endotoxin. We therefore measured endotoxin in blood from patients with chronic renal failure and different kinds of treatment. Serum samples were analyzed with a sensitive method described in the literature, using a chromogenic substrate and Limulus amebocyte lysate. In patients on hemodialysis (mean +/- SEM) the endotoxin value in samples taken immediately before dialysis was 40 +/- 4.7 ng/l and significantly elevated (p less than 0.001) compared with the endotoxin value (7 +/- 0.6 ng/l) found in the healthy reference group. Increased endotoxin levels were also seen in patients on hemofiltration (19 +/- 7.5 ng/l) and in patients with conservative treatment and various degrees of renal insufficiency (17 +/- 2.5 ng/l). Patients on peritoneal dialysis and renal-transplanted patients had levels not different from the controls. The mechanism behind endotoxemia in uremia is unknown but may partly be explained by reduced endotoxin elimination due to impaired liver macrophage function. The differences in endotoxin levels in patients on peritoneal or hemodialysis treatment may reflect that extracorporeal circulation enhances endotoxin entrance to the circulation and/or that endotoxin clearance is dependent on the dialysis regimen.

Adolescent↗

Circulating hyaluronate. A potential marker of altered metabolism of the connective tissue in uremia.

Hyaluronate, a glycosaminoglycan of connective tissue matrix, was measured in serum by radioassay in patients with renal insufficiency (n = 22) and with end-stage renal failure (n = 40). The serum hyaluronate levels were significantly increased in both groups compared with the levels measured in age- and sex-matched healthy controls. Significant correlations were found between serum hyaluronate and degree of impaired renal function. None of the patients had laboratory signs indicating affection of the liver, the major elimination route for circulating hyaluronate. No significant alteration of hyaluronate levels was seen during hemodialysis. Renal transplants, previously on dialysis treatment, had normal serum hyaluronate values. Data obtained indicate either an essential role of the kidneys for the elimination of circulating hyaluronate or an increased outflow of hyaluronate to the circulation in uremia or a combination of these two possibilities. The altered metabolism of hyaluronate in uremia was not only related to the azothemic state but also to the age of the patients. The mechanism may be qualitively similar to that underlying the age-dependent increase of serum hyaluronate seen in health. The hypothesis that elevated serum hyaluronate in uremia may reflect an accelerated ageing of the connective tissue is highly speculative, but has some support by the finding that cardiovascular and other clinical symptoms were linked to particularly high serum levels of hyaluronate.

Adult↗

The mast cell and signs of pulmonary fibroblast activation in sarcoidosis.

Hyaluronate and type III procollagen propeptide were assayed in bronchoalveolar lavage (BAL) fluids from patients with sarcoidosis. Levels were significantly elevated suggesting increased rates of synthesis of these connective tissue components in the lung. They were strongly related to each other (p less than 0.001) favoring the idea of a common cellular origin, as a suggestion activated fibroblasts. There was a significant inverse correlation (p less than 0.001) between lavage hyaluronate or procollagen propeptide and the clinical severity of the disease process defined by lung volume, diffusion capacity and pulmonary radiological findings. Correlation of clinical findings with lavage cell profiles was poor except for recovered mast cells (p less than 0.001). Lavage mast cell counts were also closely associated with BAL fluid hyaluronate and procollagen peptide (p less than 0.001). These findings may reflect a link between the mast cell, the activation of fibroblasts, and the progress of connective tissue changes in sarcoid lung.

Adult↗

Eosinophil activation in the lung is related to lung damage in adult respiratory distress syndrome.

The concentrations of eosinophil cationic protein (ECP), a specific granule constituent of eosinophil granulocytes, were measured in bronchoalveolar lavage (BAL) fluid from patients with adult respiratory distress syndrome (ARDS). The mean level was 163 +/- 85 (SD) micrograms/L and significantly increased (p less than 0.001) compared with the levels in control subjects (19 +/- 18 micrograms/L). The BAL fluid concentrations of myeloperoxidase (MPO) were also significantly increased in ARDS, indicating a local neutrophil activation. A significant correlation was found between BAL fluid ECP and MPO, suggesting a common activator of eosinophils and neutrophils. No relation was seen between BAL fluid ECP or MPO and degree of complement consumption, suggesting that other mechanisms besides complement activation may underlie granulocyte activation in ARDS. Lavage ECP levels correlated strongly with the severity of lung damage defined by pulmonary oxygenation index (PaO2/inspired fraction of O2). Activation of eosinophils, neutrophils, and the complement system is not specific for ARDS but was also observed in patients after major surgery, but at a significantly lower level (p less than 0.001). It is concluded that eosinophil activation is part of the inflammatory process in the lung in ARDS. The association observed between elevated lavage fluid levels of ECP and reduced pulmonary function in ARDS might reflect a pathophysiologic role for ECP and other cytotoxic eosinophil products in this syndrome and should be evaluated.

Adult↗

Hyaluronate in bronchoalveolar lavage fluid in sarcoidosis and its relationship to alveolar cell populations.

Hyaluronate is a potential marker of activated pulmonary fibroblasts and appears in increased amounts in bronchoalveolar lavage fluid from patients with sarcoidosis. This study was performed to investigate a possible link between the local immune response and pulmonary fibroblast proliferation. The median hyaluronate concentration in the lavage fluid from 23 sarcoid patients was 12.0 (interquartile range 7.5-28.5) micrograms/l. The hyaluronate concentration was positively correlated to the concentration and proportion of lymphocytes (p less than 0.001 and p less than 0.01, respectively) as well as to the concentrations of T lymphocyte subsets (OKT4+ p less than 0.01, OKT8+ p less than 0.05). No correlation was found between the hyaluronate concentration and the OKT4+/OKT8+ ratio. Furthermore, a significant correlation was observed in the lavage fluid between hyaluronate and angiotensin-converting enzyme, a marker of monocyte/macrophage activity (p less than 0.01). Thus, the intensity of the sarcoid alveolitis was associated with biochemical signs of pulmonary fibroblast proliferation/activation in sarcoidosis.

Adult↗

Redistribution of minerals and trace elements in chronic inflammation--a study on isolated blood cells from patients with ankylosing spondylitis.

The mass fraction of calcium (Ca), magnesium (Mg), manganese (Mn), iron (Fe). zinc (Zn), strontium (Sr) and copper (Cu) in isolated granulocytes, erythrocytes and platelets was measured using the nuclear microprobe technique. The cellular profile of metal variation was conspiciously altered in patients (n = 29) with ankylosing spondylitis compared with the profile found in age and sex matched healthy controls. Ca was accumulated in erythrocytes and granulocytes but decreased in platelets (p less than 0.001). Mg was increased in granulocytes but appeared in reduced concentrations in platelets and erythrocytes (p less than 0.001). The cellular amounts of Mn was increased in granulocytes (p less than 0.001), normal in platelets (p greater than 0.05) and subnormal in erythrocytes (p less than 0.001). Zn was reduced in all 3 cell types (p less than 0.001). Fe accumulation was evident in granulocytes and platelets (p less than 0.001). Sr was only measurable in granulocytes from patients. Cu was below the detection limit in the different cell types isolated from patients, but appeared in measurable amounts in erythrocytes and platelets from controls. The granulocyte amounts of Ca, Mg, Mn and Sr were strongly related to the acute phase reaction. Negative correlations were found between erythrocyte Mg and Zn and the inflammatory activity. The patients had increased serum levels of Cu, normal levels of Ca, Mg and Sr and decreased levels of Zn, Fe and Mn. No relationship was found between the serum concentrations of these elements and their respective cellular stores, except for a weak negative correlation between granulocyte and serum Fe.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pathophysiologic significance of lung granulocytes in human adult respiratory distress syndrome induced by septic or traumatic shock.

To evaluate the significance of lung granulocytes in the adult respiratory distress syndrome (ARDS), 12 ARDS patients were studied with bronchoalveolar lavage (BAL) within 4-12 hours after clinical diagnosis of the syndrome. The specificity of pulmonary granulocytes in ARDS was investigated in comparison with five patients requiring ventilator treatment for cardiogenic pulmonary oedema and 17 normal patients about to undergo cholecystectomy. The percentage of granulocytes among recovered BAL cells was significantly higher in ARDS (77 +/- 18, M +/- SD) than in the cardiac (7 +/- 4) or the normal (1.5 +/- 1.0) group. In serial BAL (48-hour intervals) in five ARDS patients, significant reduction of granulocytes 86 +/- 11----32 +/- 10%) accompanied clinical improvement. The percentage of granulocyte in BAL correlated significantly and inversely with the PaO2/FiO2 ratio (r = -0.98), and in ARDS it was significantly higher after septic than after traumatic shock (89 +/- 14 vs. 55 +/- 12). Myeloperoxidase, a specific constituent of neutrophils, was significantly and inversely correlated with PaO2/FiO2 ratio (r = -0.62). The findings suggest a role for activated granulocytes in the lung, with release of tissue-damaging substances, in initial ARDS pathogenesis, notably when the syndrome is sepsis-induced.

Adolescent↗

Serum lipoprotein in active rheumatoid arthritis and other chronic inflammatory arthritides. I. Relativity to inflammatory activity.

Lipoprotein metabolism was investigated in 69 patients with untreated active rheumatoid arthritis (n = 48) and in seronegative spondylarthropathies (n = 21). The patients had high inflammatory activity as measured by erythrocyte sedimentation rate and C-reactive protein (CRP). Serum cholesterol and cholesterol levels in the very-low-density lipoprotein (VLDL), low-density lipoprotein, and high-density lipoprotein fractions were reduced by 20% to 30% compared with healthy controls; and triglyceride levels in VLDL and high-density lipoprotein were reduced by 10% to 30%. There were significant correlations between the inflammatory activity and certain lipoprotein lipids, ie, between CRP and VLDL triglycerides, VLDL cholesterol, and serum triglycerides. The fractional elimination rate (K2) measured by an intravenous fat tolerance test was 30% higher in the patients than in the controls despite reduced tissue lipoprotein lipase activities. There was correlation between CRP and the K2 value. These findings suggest that it is the degree of inflammatory activity that governs the altered lipoprotein metabolism in untreated active chronic inflammatory arthritides. The relationships between CRP and VLDL and between CRP and K2 suggest that the VLDL particles may be altered by inflammatory process, and that the increased elimination may take place through the "scavenger pathway."

Adipose Tissue↗

Serum lipoprotein in active rheumatoid arthritis and other chronic inflammatory arthritides. II. Effects of anti-inflammatory and disease-modifying drug treatment.

Serum lipids and lipoprotein patterns were prospectively analyzed in 33 previously untreated patients with active chronic inflammatory arthritides during different anti-inflammatory and disease-modifying drug regimens. Before treatment the lipoprotein pattern was characterized by low cholesterol concentrations in all lipoprotein fractions and low triglyceride concentrations in the very-low-density lipoprotein fraction as well as in the high-density lipoprotein fraction. During treatment with prednisolone combined with azathioprine or cyclophosphamide (n = 10), a reduction of the disease activity was achieved and the lipoprotein pattern was normalized; similar results were noted in a small group of patients (n = 4) treated with prednisolone alone while nonsteroidal anti-inflammatory drug therapy (n = 9) neither significantly affected the lipoprotein pattern nor the inflammatory activity measured by the acute-phase reactants. The long-term treatment with penicillamine (n = 4) and chloroquine (n = 6) induced both a clinical remission of the disease and a reduction of the inflammatory activity. The lipoprotein concentrations started to reverse to the normal values during penicillamine treatment. In contrast, in the chloroquine-treated group the alterations in lipoprotein lipid concentrations were further pronounced, ie, the cholesterol and triglyceride concentrations in serum and the very-low-density lipoprotein fraction decreased.

Adolescent↗

Myocardial and skeletal muscle function in habitual alcoholics and its relation to serum myoglobin.

Lower-than-normal serum myoglobin levels are regularly found in habitual alcoholics without recent alcohol intake and were also confirmed in this study. It was hypothesized that these low levels reflect reduction in myocardial and skeletal muscle function. To study this hypothesis, heart and skeletal muscle function was evaluated and related to serum myoglobin levels. Myocardial function evaluated by noninvasive techniques was significantly decreased and heart muscle mass increased (p less than 0.001) in circulatory asymptomatic alcoholics compared with age- and weight-matched healthy male control subjects. The working capacity of the alcoholics was lower than expected during dynamic exercise testing (p less than 0.001), and maximal muscle power was reduced during isokinetic muscle testing (p less than 0.05). Myoglobin levels were correlated to the degree of myocardial diastolic dysfunction (p less than 0.01) but not to working capacity during dynamic or isokinetic exercise testing. The observation that myocardial affection was related to low serum myoglobin suggests that the mechanisms behind reduced myoglobin release are linked to the chronic muscle affection in alcoholics.

Adult↗

Bactericidal proteins and neutral proteases in diabetes neutrophils.

Reduced bacterial killing by polymorphonuclear leucocytes has been reported in patients with diabetes mellitus. Whether this is due to reduced content of bactericidal granular proteins has not been determined. We therefore immunochemically measured the content of myeloperoxidase, lactoferrin, lysozyme, cathepsin G and elastase in polymorphonuclear leucocytes from 50 insulin-treated diabetic patients. The peroxidase activity was also measured. Normal contents of myeloperoxidase and lactoferrin as well as normal peroxidase activity were found. The average contents of cathepsin G, elastase and lysozyme were 2.5, 3.2 and 2.6 micrograms/10(6) polymorphonuclear leucocytes, respectively, and thus 14, 45 and 18% higher than the contents of normal polymorphonuclear leucocytes. The results indicate that reduced intracellular killing of bacteria demonstrated in previous studies in diabetic patients does not appear to be related to a reduction in the content of bactericidal proteins.

Age Factors↗

Lethal adult respiratory distress syndrome after meningococcal septicemia biochemical markers in bronchoalveolar lavage.

A lethal case of Adult Respiratory Distress Syndrome (ARDS) consequent to meningococcal septicemia is clinically and physiologically described. Very high levels of eosinophil cationic protein and lactoferrin in bronchoalveolar lavage were observed in spite of peripheral eosinopenia and neutropenia. These findings provide support for the hypothesis that activated granulocytes are involved in the pathogenesis of septic-induced ARDS.

Adolescent↗

The predictive and discriminative value of biologically active products of eosinophils, neutrophils and complement in bronchoalveolar lavage and blood in patients with adult respiratory distress syndrome.

To determine whether biologically active products of eosinophils, neutrophils and complement contribute to the development of adult respiratory distress system (ARDS) we measured eosinophil cationic protein (ECP), lactoferrin (LF) and C3a in bronchoalveolar lavage (BAL) and blood by means of radioimmunoassays. Seventeen patients served as controls. Fifteen patients were studied before and after major surgery to evaluate the influence of the surgical procedure, and 12 patients with ARDS were investigated 4-12 h after the onset of the disease. Major surgery per se significantly increased ECP in BAL, LF in serum and C3a in BAL and plasma. ECP, LF and C3a levels in BAL and blood were all significantly higher in ARDS patients as compared with levels in controls and those observed after major surgery. The higher ECP levels in BAL were associated with the more severe ARDS as was also the case for C3a in BAL and plasma and LF in serum. One out of 15 patients subjected to major surgery developed ARDS postoperatively and had very high levels of ECP, LF and C3a in BAL and blood at sampling 3 h prior to onset of ARDS, and these levels were similar to those observed in ARDS patients. One out of 12 ARDS patients died from the disease and this patient had the highest level of ECP in BAL and serum. Our results strongly support the role of activated polymorphonuclears, and notably the activated eosinophils, in the pathogenesis of ARDS. Evidence is also presented that ECP can be used as a predictor of impending ARDS.

Adult↗

Ethanol reduces myoglobin release during isokinetic muscle exercise.

Changes in serum myoglobin concentrations were studied in 12 healthy males performing a standardized isokinetic 2-min exercise test. The test was performed on three separate occasions: in the habitual state, during moderate ethanol intoxication and one day after ethanol intake. Although the performed muscle work, maximal heart rate, and blood lactate levels did not differ between the three test occasions, the serum myoglobin increments after exercise were significantly reduced (p less than 0.05) in the ethanol-intoxicated state and also 10-15 hours after ethanol intake. The reduction of the exercise-induced myoglobin increment was not explained by increased elimination of the protein. The mechanism, therefore, is likely to be a reduction of myoglobin release from skeletal muscle due to an ethanol-induced alteration of the muscle cell membrane, possibly by means of adenylate cyclase activation.

Adult↗