Biomedical subjects

R Hällgren

Publications and source records attributed to R Hällgren.

At least 127 records · Page 7Linked to original sources

PubMed1989

Hyaluronan (hyaluronic acid) in bronchoalveolar lavage fluid during the development of bleomycin-induced alveolitis in the rat.

Hyaluronan (hyaluronate or hyaluronic acid) was measured in bronchoalveolar lavage (BAL) fluid from rats during a 30-day period after a single intratracheal dose of bleomycin. An increase of hyaluronan (HA) in BAL fluid was apparent by 3 days after bleomycin administration. Peak HA values were reached on Day 5 and were about 75 times higher than in control animals. Analyses of urea in BAL and HA in serum indicated that the increased levels of HA in BAL, postbleomycin, could not be explained by plasma leakage. The HA recovered by lavage decreased progressively after Day 5 and returned to normal 3 wk after bleomycin treatment. The HA content and an increased influx of PMN in BAL fluid were correlated and showed a similar time dependence, suggesting that enhanced synthesis of HA in the smaller airways is linked to the early inflammatory phase of the bleomycin injury.

Animals↗

PubMed1989

A new technique for segmental jejunal perfusion in man.

A multichannel tube with two occluding balloons was developed for measurements of the secretion of different endogenous substances into a defined segment of the small intestine. The tube was inserted under fluoroscopic guidance with the aid of a guide wire and was in position in the proximal jejunum after 45-90 min. The overall success rate of the complete procedure was 90%. The system prevented contamination of the perfusate from gastric and pancreatic secretion. Major dilution of the intestinal secretion was avoided due to high recovery of the perfusion fluid. The jejunal secretion rates of high and low molecular weight substances, i.e., albumin, beta 2-microglobulin, hyaluronan, and histamine, were tested. The recovery of the effluent fluid and the volume marker 14C-PEG 4000 exceeded 95% and was also stable over the perfusion period. The mean secretion rates in 23 healthy controls of albumin (635 micrograms/cm/h), beta 2-microglobulin (0.87 microgram/cm/h), hyaluronan (1061 ng/cm/h), and histamine (70 ng/cm/h) were also stable during the perfusion period. Ten healthy controls were studied under steady state conditions for 3 h. The concentrations in jejunal perfusion fluid relative to serum levels were for albumin 0.06%, indicating the degree of passive leakage from the plasma compartment to the intestinal lumen. The appearance of the low-molecular weight protein beta 2-microglobulin in perfusion fluid was on average 3% of its circulating levels, suggesting that the concentrative transport from plasma is dependent on the molecular size. The jejunal fluid concentrations of histamine and hyaluronan exceeded their respective concentrations in plasma, indicating that local intestinal secretion/synthesis is mainly responsible for their appearance in jejunal fluid. In summary, the technique is simple, rapid, atraumatic, safe, and reproducible and, potentially, can accurately reflect biochemical processes in the small intestine.

Adult↗

PubMed1988

Cyclosporin-associated nephropathy in patients with autoimmune diseases.

Renal biopsy specimens were evaluated from patients with different autoimmune diseases treated with cyclosporin (CyA). Ten biopsies were done before CyA, 10 biopsies after low-dose (less than 7.5 mg/kg/day, initial dose or mean daily dose within the first month, respectively), and 9 after high-dose (greater than 7.5 mg/kg/day) treatment. Definite chronic CyA nephrotoxicity (cyclosporin-associated arteriolopathy and/or interstitial fibrosis striped form with tubular atrophy) was only present in the initial high-dose group. In this group a significant serum creatinine increase was noted and 8 of the 9 patients were hypertensive. No significant correlation was found between the severity of morphologic lesions and the mean daily dose during total treatment, cumulative dose, and duration of therapy. The morphologic changes in the low-dose group did not differ from the control biopsy specimens before CyA treatment. Based on these results, it can be concluded that major nephrotoxicity can be avoided by initial low CyA doses.

Adult↗

PubMed1988

Impaired glucose handling in active rheumatoid arthritis: relationship to peripheral insulin resistance.

Glucose metabolism was studied after an intravenous glucose loading in normal-weighted, previously untreated patients (n = 14) with active rheumatoid arthritis (RA). The patients displayed an enhanced insulin response and impaired glucose handling compared with healthy controls (P less than .001). The insulin sensitivity, measured as the glucose utilization rate during steady state of euglycemia (M) was significantly decreased (P less than .01) among the patients compared to the controls (5.5 +/- 1.9 mg/kg BW/min [mean +/- SD] and 7.2 +/- 1.2, respectively). The corresponding values for the metabolic clearance rate (MCR) were 5.8 +/- 0.6 mL/kg BW/min and 8.2 +/- 0.4, respectively (P less than .01). In the patient group the k value correlated with the peripheral insulin sensitivity (P less than .01), which, in turn, was inversely related to the acute phase reaction (P less than .05). During 1 week of potent anti-inflammatory treatment with corticosteroids (prednisolone 20 mg daily) the k value improved P less than .001), the insulin sensitivity tended to improve and the insulin response increased (P less than .001) after an intravenous glucose loading. Five patients who had a remission of their disease on sulphasalazine as antirheumatic therapy were reexamined. A normalization of the inflammatory activity as well as the glucose handling and insulin sensitivity was achieved. The data obtained indicate that impaired glucose handling in active RA is related to insulin resistance. The linkage between inflammatory indices and glucose metabolism might reflect a special consequence of inflammation, but the influence of nonspecific disease manifestations, ie, malnutrition, inactivity, and myopenia, has to be considered.

Adrenal Cortex Hormones↗

PubMed1988

The acute effect of high dose corticosteroid treatment on serum osteocalcin.

Osteocalcin is a vitamin K-dependent protein that is synthesized by osteoblasts and present in circulation. We measured serum osteocalcin concentrations in nine asthmatics before and during treatment with high IV dosages of glucocorticoids, betamethasone 0.65 mg/h. This treatment induced within 13 +/- 1.5 (SEM) hours a reduction of serum osteocalcin form 2.6 +/- 0.3 (SEM) to 1.2 +/- 0.3 microgram/L (P less than .001). During the following 24-hour period the osteocalcin levels further declined and reached a level about 30% of the pretreatment level. Continued treatment did not induce a further reduction of serum osteocalcin. A positive correlation was seen between the pretreatment osteocalcin concentration and the steady-state osteocalcin value during steroid therapy. The corticosteroids did not influence the serum calcium and phosphate concentrations but induced a minor, significant (P less than .001) decrease of serum alkaline phosphatase. After completion of steroid therapy, the osteocalcin values remained depressed for another 24 hours but had reached the pretreatment levels after another three days. Our data suggest osteocalcin as a sensitive marker of the corticosteroid induced depression of osteoblast activity.

Adrenal Cortex Hormones↗

PubMed1988

Circulating inhibitor bound elastase in patients with ankylosing spondylitis and rheumatoid arthritis and the influence of sulphasalazine treatment.

The plasma concentration of granulocyte elastase in complex with alpha 1 proteinase inhibitor was determined in 42 patients with ankylosing spondylitis (AS) and 33 patients with rheumatoid arthritis (RA). Significantly raised levels of plasma elastase were found in patients with RA, whereas patients with AS had normal values. No correlation was seen between the elastase values and erythrocyte sedimentation rate (ESR), serum haptoglobin, immunoglobulins, or polymorphonuclear cell (PMN) count in either of the patient groups. A correlation was found between the Ritchie index and plasma elastase in patients with RA. After three months' treatment with sulphasalazine a clinical improvement was seen and this paralleled a reduction of the acute phase reaction in both patient groups. A reduction of the circulating elastase values was seen in the patients with RA, whereas no change was seen in patients with AS.

Acute-Phase Reaction↗

PubMed1988

Neutrophil and eosinophil involvement of the small bowel affected by chronic alcoholism.

Excessive ethanol intake may affect the intestinal mucosa functionally and morphologically. The ethanol effect could partly be the result of inflammatory mechanisms, possibly reflected by an enhanced local granulocyte turnover. This study investigated habitual alcoholics by segmental perfusion of the jejunum and analysed the perfusion fluid content of granulocyte granule constituents. The mean jejunal secretion rate of myeloperoxidase (MPO), a neutrophil granule constituent, was 152 (26) (SE) ng/min/40 cm jejunal segment in the controls (n = 16). The MPO secretion rate in non-cirrhotic habitual alcoholics (n = 7) was on average 450 (103) ng/min and significantly increased compared with controls (p less than 0.001). In contrast alcoholics with cirrhosis (n = 6) had normal MPO secretion rate. The mean secretion rate of eosinophil cationic protein (ECP), an eosinophil granule constituent, was in the controls 77 (15) ng/min/40 cm jejunal segment. Corresponding values in non-cirrhotic and cirrhotic alcoholics were 141 (38) and 130 (93) ng/min, respectively (ns). The data suggest an enhanced neutrophil granulocyte turnover in the jejunum in alcoholics, possibly contributing to the ethanol induced affection of the small bowel. The lack of increased neutrophil activity in cirrhotic alcoholics may reflect a role of the liver for granulocyte activity.

Adult↗

PubMed1988

Predictive value of bronchoalveolar lavage cell analysis in sarcoidosis.

Patients with histopathologically proved sarcoidosis were studied serially by means of bronchoalveolar lavage, initially at the time of diagnosis and then six and 12 months later. Two years later they were evaluated by chest radiography and lung function tests and classified in terms of recovery or progression over the previous two years. The recovery of lymphocytes and granulocytes in lavage fluid was of limited prognostic value for persistent lung disease. In contrast, patients with increased numbers of mast cells recovered by lavage were more likely to deteriorate. Significantly increased mast cell counts (greater than or equal to 0.5% of total cells recovered) were seen in at least one lavage investigation in 15 of the 16 patients with more active and progressive disease, but in only eight of 23 patients with inactive disease (p less than 0.001). A persistent increase of mast cells on serial measurement occurred in nine of the 16 patients with active disease and in four of the 23 patients in whom the disease was inactive (p less than 0.02). The finding in the two subsequent lavages of lymphocytosis (lymphocytes greater than 30% of recovered cells) or neutrophilia (neutrophils greater than 15%) combined with mastocytosis (mast cells greater than or equal to 0.5%) occurred in nine of the 16 patients with active disease but in no patients with inactive disease.

Adult↗

PubMed1988

Redistribution of cellular mineral and trace element stores in HLA-B27 positive relatives of patients with ankylosing spondylitis--a marker of hidden inflammatory disease.

Subjectively healthy HLA-B27 positive 1st degree relatives (n = 14) of patients with ankylosing spondylitis (AS) were investigated concerning the mass fraction of calcium (Ca), magnesium (Mg), manganese (Mn), iron (Fe), zinc (Zn), strontium (Sr) and copper (Cu) in isolated blood cells using the nuclear microprobe technique. No relative had laboratory signs of inflammatory disease defined by acute phase plasma proteins. An accumulation of Mg, Ca, Mn and Fe was found in granulocytes compared with healthy controls. In platelets there was an accumulation of Fe and a reduction of the Cu content. In erythrocytes Ca was accumulated and the levels of Mg, Mn and Cu were reduced compared with the controls. Five of the relatives had radiological signs of sacroiliitis and 1 of these had sacroiliac tenderness. Relatives with and without radiological sacroiliitis showed no differences in the cellular metal amounts. When the alterations were compared with those previously found in patients with AS, a striking similarity was noted, although the changes were quantitatively less pronounced. In contrast B27 negative 1st degree relatives (n = 11) had normal mineral amounts in their cells. However, it seems less likely that altered metal handling could play a primary role for the disease susceptibility linked to HLA-B27 since B27 positive healthy controls (n = 12) without AS in the family had normal cellular stores of the measured elements. Rather our findings indicate that redistribution of cellular metals is an extremely sensitive marker of an inflammatory process not evident by clinical symptoms or increase of acute phase plasma proteins.

Blood Donors↗

PubMed1988

Bronchoalveolar mastocytosis in farmer's lung is related to the disease activity.

Patients (n = 10) at the acute phase of farmer's lung were investigated with chest roentgenography, lung function tests, and bronchoalveolar lavage (BAL) fluid analysis (n = 9). They had diffuse interstitial lung infiltrates and a reduction of the diffusion capacity. The dominating recovered cell types during BAL were lymphocytes; and in two patients, granulocytes. A prominent increase in mast cell numbers was seen in all patients. After avoidance of contact with moldy plant material for four to ten weeks (n = 7), lung function started to improve; and the BAL cell counts, to decrease. At clinical remission six to 14 months later (n = 7), the chest roentgenogram was normal and the diffusion capacity was slightly subnormal. The BAL numbers of mast cells and lymphocytes had further decreased but still remained increased compared with those in the healthy controls. Parallel to the normalization of the lung function and the recovery of BAL fluid cells, the increased BAL fluid concentrations of hyaluronic acid and procollagen III peptide started to decrease. These potential markers of fibroblast activation were significantly related to the mast cell number, but not to the lymphocyte number. The study has demonstrated that pulmonary mastocytosis is a prominent finding in farmer's lung and is related to the disease activity. The observed relationship between pulmonary mastocytosis and biochemical signs of lung fibroblast activation is further evidence to support the hypothesis of a mast cell interaction with lung connective tissue.

Adult↗

PubMed1987

Hyaluronate and type III procollagen peptide concentrations in bronchoalveolar lavage fluid as markers of disease activity in farmer's lung.

Ten patients were studied during an acute episode of farmer's lung. Prominent findings were an impaired diffusion capacity (on average only 51% of predicted) and substantially increased amounts of hyaluronate and type III procollagen peptide recovered during bronchoalveolar lavage; mean concentrations of these constituents in lavage fluid were 547 (range 137-1125) and 9.7 (2.8-19.4) micrograms/l, respectively. In bronchoalveolar lavage fluid from healthy controls (n = 21) hyaluronate concentrations were less than 15 micrograms/l and procollagen peptide concentrations less than 0.2 micrograms/l. Lavage fluid concentrations of these potential markers of fibroblast activation declined during the recovery phase of farmer's lung; four to 10 weeks after admission (n = 7) mean concentrations of hyaluronate and procollagen peptide were 154 (range 38-650) and 4.4 (0.6-15.8) micrograms/l, respectively. At clinical remission six to 14 months after admission concentrations of these markers had returned almost to normal, though slightly increased concentrations were still evident in about half the patients (n = 7). At that time lung volumes were normal but diffusion capacity remained slightly subnormal. It was concluded that in farmer's lung release of hyaluronate and type III procollagen peptide reflects activity of the disease. Increased synthesis of these connective tissue components continuing in a patient avoiding mouldy plant material may signal an increased risk of developing fibrotic lung disease. The abnormal accumulation of hyaluronate in the smaller airways in acute farmer's lung may be expected to immobilize water and thereby provide a possible mechanism of the interstitial inflammatory lung oedema with associated impaired gas diffusion. This hypothesis is supported by the relation found between hyaluronate in lavage fluid and reduced diffusion capacity.

Adult↗

PubMed1987

Circulating hyaluronic acid levels vary with physical activity in healthy subjects and in rheumatoid arthritis patients. Relationship to synovitis mass and morning stiffness.

We evaluated the possible influence of physical activity on serum levels of hyaluronic acid (HA), plasma levels of elastase, and serum levels of procollagen III peptide. In 15 healthy individuals, HA increased from 26 +/- 9 micrograms/liter (mean +/- SD) before arising from a night's sleep to 54 +/- 24 micrograms/liter 1 hour after arising and performance of normal morning activities (P less than 0.001). HA in 14 patients who had inflammatory arthritis increased from 124 +/- 104 micrograms/liter to 402 +/- 232 micrograms/liter under the same conditions (P less than 0.001). The elevation due to physical activity was significantly (P less than 0.001) higher in patients with rheumatoid arthritis (RA) than that found in controls. A slight increase of HA in the afternoon was also observed in healthy subjects who performed heavy exercise, but a marked increase was seen in RA patients who performed moderate exercise. In another group of 24 RA patients, a more standardized blood sampling was performed before arising and during normal morning activities. An increase in HA was significantly (P less than 0.001) correlated to the synovitis mass, estimated by the Ritchie articular index. Maximum increases of HA were seen 30 and 60 minutes after arising; thereafter, levels decreased to those measured at rest. During the morning activities, procollagen III peptide remained stable, while plasma elastase tended to increase. It is proposed that HA, produced in the joint tissue structures and accumulated at rest, is carried by the lymph vessels to the general circulation during physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

T lymphocytes in ankylosing spondylitis and the influence of sulphasalazine treatment.

Twenty-nine patients with ankylosing spondylitis (AS) were studied in an attempt to evaluate the role of T lymphocytes in this disease and a possible influence of treatment. The proportions of various T cell subpopulations in blood were assessed with monoclonal antibodies. Before treatment the proportions of Leu-4+ cells and Leu 3a+ cells were decreased while Leu-2a+ lymphocytes appeared in normal proportions. Leu-7+ cells appeared in increased proportions. An increased proportion of Leu-M1 positive cells were identified in the lymphocyte preparation from the patients, possibly reflecting the presence of activated granulocytes. Activation of the different cell types was studied with double staining technique. No activated Leu-3a+ or Leu-2a+ lymphocytes were present in blood when the patients were analyzed as one group, but when divided into subgroups according to inflammatory activity, the highest levels of activated Leu-2a+ lymphocytes were found in the group with active disease. Functional assays measuring DNA synthesis of T and B cells were normal. After three months treatment with sulphasalazine the patients showed clinical and laboratory improvement. The proportion of activated Leu-2a+ cells decreased during treatment, but no other changes occurred in the lymphocyte markers or lymphocyte functional tests. A patient control group showed no clinical improvement nor any changes in T cell markers. Our results support the concept that AS is a disease which affects the lymphocyte system and that the improvement induced by sulphasalazine may involve actions on this system.

Adult↗

PubMed1987

Impaired glucose handling in active rheumatoid arthritis: relationship to the secretion of insulin and counter-regulatory hormones.

An intravenous glucose tolerance test was performed in 45 untreated patients with active inflammatory rheumatoid arthritis and in age- and sex-matched healthy subjects. The mean k value in the patients, which correlated to the inflammatory activity, was 1.0 +/- 0.05 (SEM), which was significantly lower (P less than .001) than in the controls (1.8 +/- 0.09). The basal serum insulin concentration and the maximum insulin response to glucose loading were significantly higher (P less than .001 and P less than .01, respectively) in the patient group. The patients had a normal basal concentration of growth hormone in the serum, but during glucose infusion the concentration increased. The plasma glucagon level was significantly lower than in the controls (P less than .001). The urinary output of cortisol and catecholamines was normal. It is concluded that impaired glucose handling in active chronic inflammatory disease cannot be explained as a stress reaction but may be due to peripheral insulin resistance mediated by the inflammatory process. A paradoxical increase in growth hormone secretion during glucose infusion may suggest that this hormone is one factor that influences glucose handling in chronic inflammation. The pathophysiologic relevance of altered glucose metabolism and enhanced insulin secretion is uncertain but may reflect a possible link with the proposedly increased risk of atherosclerotic cardiovascular disease in rheumatoid arthritis.

Adolescent↗

PubMed1987

Impaired glucose handling in active rheumatoid arthritis: effects of corticosteroids and antirheumatic treatment.

Forty-two patients with active rheumatoid arthritis were studied serially with respect to glucose metabolism after the institution of different anti-inflammatory and antirheumatic therapies. Sixteen patients received 20 mg of prednisolone daily. After 1 week of treatment the mean k value in glucose tolerance tests increased from 1.0 +/- 0.1 (SEM) to 1.6 +/- 0.1 (P less than .001). The corticosteroid therapy thus restored the glucose tolerance to normal and significantly enhanced the insulin response (P less than .01). Corticosteroids also normalized the growth hormone response to glucose infusion but had no effect on plasma glucagon. Treatment with nonsteroidal anti-inflammatory drugs did not affect the k values nor the hormonal pattern either after short-term treatment or after three months of therapy, except for causing a minor increase in the plasma glucagon levels both before and after glucose infusion. The long-term effects of treatment with penicillamine (n = 4), chloroquine (n = 7), and immunosuppressive agents [corticosteroids combined with azathioprine or cyclophosphamide (n = 7)], were an improvement of the clinical state, a reduction of the inflammatory activity, and a reversal of the glucose handling to normal.

Anti-Inflammatory Agents↗

PubMed1987

Complement activation and increased alveolar-capillary permeability after major surgery and in adult respiratory distress syndrome.

The concentrations of C3a des Arg were measured in bronchoalveolar fluid (BAL) and plasma from 12 patients with adult respiratory distress syndrome (ARDS). Compared with 32 controls, all patients had increased BAL fluid levels (p less than .001), and nine of 12 had increased plasma levels (p less than .001) of this split product from the third complement component. Reduced total hemolytic activity (CH50) in serum was seen in five patients (p less than .01). As an indication of damage to the alveolar-capillary barrier, ten of the 12 ARDS patients had elevated albumin concentrations in BAL fluid (p less than .001). These signs of complement activation and lung tissue damage are not specific for ARDS. Thus, in 15 patients investigated preoperatively and postoperatively, we found that major surgery induced a significant increase of BAL fluid C3a (p less than .01) and plasma C3a (p less than .02), a significant reduction of CH50 (p less than .001), and a significant increase of BAL fluid albumin (p less than .02). Similar values of CH50 and plasma C3a were seen in ARDS and after surgery (p greater than .05). Of the 12 ARDS patients, eight had increased BAL fluid concentrations of C3a (p less than .001), and ten had increased BAL fluid levels of albumin (p less than .001) compared with the post-surgical patients. Measuring complement consumption in blood by these techniques is of limited value in ARDS due to the lack of specificity. BAL fluid albumin has a similar degree of sensitivity and specificity for ARDS as does BAL fluid C3a.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1987

Serum erythropoietin in rheumatoid arthritis and other inflammatory arthritides: relationship to anaemia and the effect of anti-inflammatory treatment.

Serum erythropoietin (s-Epo) was measured with a sensitive radioimmunoassay method in 58 patients with classical rheumatoid arthritis (n = 41) or seronegative spondyloarthropathies (n = 17). Epo was significantly (P less than 0.001) increased and on an average two times higher than in a healthy population. A correlation was found between Hb and s-Epo (r = -0.46, P less than 0.005), indicating that these patients respond to anaemia with an increase in s-Epo. In order to investigate if inflammation has a direct influence on s-Epo levels a short period of corticosteroid treatment was given to rapidly decrease inflammatory activity. No increase in s-Epo was seen after 1 week. Furthermore, there was a correlation between s-Epo and ESR in all patients (r = 0.59, P less than 0.01). These results indicate that s-Epo is directed by the Hb level, which in turn is influenced by the inflammatory activity: a higher inflammatory activity gives a lower Hb and an increase in s-Epo. In comparison to previously published figures for the relation between Hb and s-Epo these patients seem to have an ordinary Epo response. We conclude that the anaemia of patients with chronic inflammatory joint disease is not caused by a diminished Epo production.

Adult↗

PubMed1987

Beta 2-microglobulin, lysozyme and lactoferrin in cerebrospinal fluid in patients with lymphoma or leukaemia: relationship to CNS involvement and the effect of prophylactic intrathecal treatment with methotrexate.

Central nervous system (CNS) involvement in patients with leukaemia or lymphoma presents a diagnostic problem. This study was conducted to test whether combined measurements of various cellular markers such as beta 2-microglobulin (beta 2m), lactoferrin (LF) and lysozyme (LYS) in the cerebrospinal fluid (CSF) might aid in the diagnosis of CNS involvement in such patients. Forty-two patients were studied. Sixteen were considered to have CNS involvement and 26 showed no signs of such involvement. In the group with symptoms or signs of CNS involvement, nine patients out of 12 had increased total protein in CSF, 14 of 14 increased beta 2m, 14 of 16 increased LYS and five of 15 increased LF. In patients without CNS involvement total protein was increased in four of 25, beta 2m in three of 21, LYS in four of 28 and LF in one of 28 patients. The differences were statistically significant (P less than 0.01, P less than 0.001, P less than 0.001 and P less than 0.05, respectively). Prophylactic intrathecal methotrexate treatment in patients with acute lymphoblastic leukaemia caused an increase in the CSF of beta 2m, LYS and LF but not of total protein, which may reflect a drug-induced inflammatory reaction in the CNS. We conclude that combined measurements of the three cell markers add to our understanding of the cellular reaction to malignant cells in the CNS in leukaemia and lymphoma and may be valuable supplements in the diagnosis of this CNS involvement.

Adolescent↗