Biomedical subjects

R Hällgren

Publications and source records attributed to R Hällgren.

At least 37 records · Page 2Linked to original sources

PubMed1999

Enhanced expression of integrins and CD66b on peripheral blood neutrophils and eosinophils in patients with rheumatoid arthritis, and the effect of glucocorticoids.

The aim of this study was to elucidate signs of granulocyte activation by studying adhesion and phagocytosis receptors on peripheral blood granulocytes from patients with rheumatoid arthritis (RA), and to observe the effect of glucocorticoids. Analyses by flow cytometry showed elevation of the neutrophil and eosinophil expression of the alpha- and beta-chains of the beta2-integrin Mac-1 (CD11b/CD18) and of the CEA-gene family member 6 (CGM6, CD66b). Expression of the adhesion receptor antigens CD11a, CD29, CD49d, CD49f and CD44, and the Fcgamma receptors II and III, was unaffected. Treatment with low-dose prednisolone reduced the expression of CD11b on neutrophils and of CD11b, CD18 and CD66b on eosinophils to the same level as that found in healthy controls. Metyrapone treatment increased the surface expression of CD35 and CD49f on eosinophils, but did not affect surface expression on neutrophils. Activation of blood granulocytes may be important for the increased recruitment of neutrophils and eosinophils to the synovial cavity in RA. Treatment with low doses of glucocorticoids in RA normalizes the enhanced expression of the studied adhesion molecules in eosinophils but has minor impact on neutrophil activation. Endogenous glucocorticoid production seems to have minimal or no effect on the expression of adhesion and phagocytosis receptors on circulating granulocytes.

Adult↗

PubMed1999

Serum lysozyme: a potential marker of monocyte/macrophage activity in rheumatoid arthritis.

OBJECTIVE: Estimate the contribution of monocytes/macrophages to the disease process in rheumatoid arthritis (RA), by measuring the serum levels of the leucocyte-derived granular proteins: lysozyme, myeloperoxidase (MPO), lactoferrin and human neutrophil lipocalin (HNL). METHODS: Serum levels of these granular proteins were measured in patients with RA (n=23) and in healthy controls (n=27), and in 10 patients with RA after treatment with low-dose prednisolone. The serum levels of the granular proteins were also measured before and after treatment with metyrapone, a substance that inhibits the synthesis of cortisol in the adrenals. RESULTS: The serum levels of lysozyme and MPO were elevated in patients with RA, while the concentrations of lactoferrin and HNL were similar in both groups. Prednisolone treatment decreased the serum concentration of lysozyme and MPO. Metyrapone did not influence the level of the granular proteins measured. CONCLUSIONS: The increased serum levels of lysozyme and MPO, but not of HNL and lactoferrin in RA could indicate a stimulated secretory activity of mononuclear phagocytes. The measurement of serum lysozyme, as an indicator of monocyte/macrophage activity, might be used to study disease activity in RA.

Acute-Phase Proteins↗

PubMed1999

Increased intraluminal release of eosinophil granule proteins EPO, ECP, EPX, and cytokines in ulcerative colitis and proctitis in segmental perfusion.

OBJECTIVE: The role of the eosinophil granulocyte in bowel mucosa in inflammatory bowel disease still remains obscure. The present study was performed in order to elucidate the local eosinophil activity and activating cytokines in the inflamed lesions of colon and rectum in patients with ulcerative colitis and proctitis. METHODS: The activity of intestinal eosinophils with respect to the release of granule proteins was studied in 18 patients (10 with colitis and 8 with isolated proctitis) and 18 healthy controls, using intraluminal segmental perfusion of the sigmoid colon and rectum. The released amounts of eosinophil granule proteins: eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil protein X (EPX) to perfusion fluid were determined by radioimmunoassays. The intraluminal release of possible eosinophil priming cytokines granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 8 (IL-8), were analyzed by immunoassays. RESULTS: The mucosal release of ECP, EPO, and EPX was increased 10- to 20-fold in patients with colitis and proctitis compared with controls. The intraluminal release of GM-CSF and IL-8, was several-fold enhanced in patients with colitis and proctitis. We also found a correlation between all three eosinophil granule proteins and the levels of IL-8/GM-CSF in the sigmoidal segments of patients with colitis. CONCLUSIONS: We conclude that the increased release of ECP, EPO, and EPX to colorectal perfusion fluid indicate eosinophil involvement in the local disease in patients with colitis and proctitis. IL-8 and GM-CSF may play a role in eosinophil accumulation and priming in colitis.

Adult↗

PubMed1998

Eosinophil activation in ulcerative colitis: studies on mucosal release and localization of eosinophil granule constituents.

Activation of eosinophil granulocytes (eosinophils) seems to contribute to the pathophysiology of several inflammatory conditions. This process was evaluated in 18 patients with ulcerative colitis and in 18 healthy controls using intraluminal segmental perfusion of the sigmoid colon and rectum and immunoanalysis for eosinophil cationic protein (ECP) in the perfusate. Immunohistochemistry for eosinophils and neutrophils was made in simultaneously taken biopsies and in biopsies from surgical specimens taken from additional 10 patients. The mucosal release of ECP was increased severalfold in patients with UC. The bowel biopsies demonstrated a lamina propria infiltrated with eosinophils. The degree of eosinophil activation/degranulation was related to the intensity of the inflammatory reaction. Activated eosinophils and extracellular deposits of ECP were, in particular, seen in crypt abscesses and in areas with damaged surface epithelium. Since ECP is highly cytotoxic, its release at the site of inflammatory bowel lesions might reflect a potential pathophysiological mechanism.

Adult↗

PubMed1998

Concordant message of different inflammatory markers in patients with rheumatoid arthritis.

The acute phase reaction is an unspecific response to inflammatory stimuli characterized by alterations in the concentration of several plasma proteins. It is of great clinical value to monitor the inflammatory state in patients with rheumatoid arthritis. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are the assays most widely used to measure the acute phase response, but there are also several other inflammatory markers (e.g., fibrinogen, haptoglobin, alpha 1-acid glycoprotein, alpha 1-antitrypsin, interleukins (IL), serum amyloid component A (SAA)). We have studied the interrelationships between several of these markers (ESR, Haptoglobin, Fibrinogen, CRP, SAA and IL-6) in rheumatoid arthritis patients. There was a good correlation between all acute phase markers in serum (p < .01). We found especially strong correlations between S-CRP and SAA (p < .000001) and between ESR and P-fibrinogen (p = .000004). The strong correlation indicates that P-fibrinogen could be used instead of ESR in monitoring rheumatoid arthritis patients. This would increase the specificity of the examination as ESR may be influenced by several factors other than the inflammatory response. There were no significant correlations between acute phase markers in serum or plasma and clinical index.

Acute-Phase Proteins↗

PubMed1997

Eosinophil cationic protein and histamine after intestinal challenge in patients with cow's milk intolerance.

BACKGROUND: Mast cells and eosinophils are key cells in the development of active symptoms in allergic diseases and other inflammatory conditions, and they mediate their action through the release of very potent granule constituents. METHODS: Five patients with milk-related gastrointestinal symptoms diagnosed by double-blind placebo-controlled milk challenges, but with negative responses to skin prick tests and RASTs with milk, and eight healthy control subjects were investigated. Repeated perfusion studies were performed with a two-balloon, six-channel tube by using milk, casein, and whey as antigens. Luminal eosinophil cationic protein, histamine, and albumin were measured by radioimmunoassay. RESULTS: Luminal cow's milk induced a pronounced increase in intestinal secretion of histamine and eosinophil cationic protein in patients, but not control subjects, during the first 20 minutes after challenge (histamine from 123 +/- 12 to 543 +/- 175 ng/cm, hr; eosinophil cationic protein from 80 +/- 23 to 686 +/- 262 ng/cm, hr). Albumin, as a marker of plasma leakage, was also significantly increased. CONCLUSION: These data indicate that mast cells and eosinophils are effector cells not only in patients with allergic disease but also in patients intolerant to foods and lacking circulating antibodies. The underlying mechanisms may be a reaction mediated by locally appearing antibodies or an immunologic activation resembling that found in intestinal disorders such as celiac disease.

Adult↗

PubMed1997

Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation.

An increased tissue accumulation of HYA occurs in several human and experimental inflammatory conditions. Such is the case in sarcoidosis, idiopathic pulmonary fibrosis and farmer's lung in man, and experimental bleomycin-induced lung damage in rats. Graft rejection in man and rats, experimental myocarditis in mice and myocardial infarction in rats follow the same pattern. Increased amounts of HYA also appear in gut luminal perfusion fluid in human inflammatory bowel disease. A transient accumulation of HYA is seen in wound healing, which is more sustained in fetuses. An increased accumulation of water and presentation of ligands for receptors on inflammatory cells are two consequences of the HYA accumulation.

Animals↗

PubMed1997

The timing of glucocorticoid administration in rheumatoid arthritis.

OBJECTIVE: To test the hypothesis that the timing of prednisolone administration might be critical in determining its effect on the diurnal rheumatoid inflammatory process. METHODS: 26 patients with rheumatoid arthritis were randomly divided into two equal groups and allocated to low doses of prednisolone at either 2.00 am or 7.30 am. Because of the diurnal variation in disease activity in rheumatoid arthritis, assessments of the two study groups were performed at 7.30 am both at the start of the study (day 1) and after four doses of prednisolone (day 5). The study protocol differences in the time period from the last dose of prednisolone to assessment were 5.5 hours in the 2.00 am group and 24 hours in the 7.30 am group. RESULTS: Administration of low doses of prednisolone (5 or 7.5 mg daily) at 2.00 am had favourable effects on the duration of morning stiffness (P < < 0.001), joint pain (P < 0.001), Lansbury index (P < < 0.001), Ritchie index (P < < 0.001), and morning serum concentrations of IL-6 (P < 0.01). The other study group showed minor but significant effects on morning stiffness (P < 0.05) and circulating concentrations of IL-6 (P < 0.05). Modest and similar improvements of C reactive protein, serum amyloid protein A, and erythrocyte sedimentation rate were seen in both study groups. CONCLUSIONS: Administration of low doses of glucocorticoids with a rather short biological half life seems to improve acute rheumatoid arthritis symptoms if it precedes the period of circadian flare in inflammatory activity, as defined by enhanced IL-6 synthesis. Further studies are needed to test the relative merits of different timing protocols of glucocorticoid administration in rheumatoid arthritis.

Aged↗

PubMed1997

Enhanced jejunal production of antibodies to Klebsiella and other Enterobacteria in patients with ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVE: To measure gut immunity directly in jejunal fluid in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). METHODS: Antibodies against three different Enterobacterias were measured in jejunal perfusion fluids (collected by a double balloon perfusion device) of 19 patients with AS, 14 patients with RA, and 22 healthy controls using enzyme linked immunosorbent assay. RESULTS: The AS patients had significantly increased jejunal fluid concentrations of IgM, IgG, and IgA class antibodies against Klebsiella pneumoniae, and IgM and IgA class antibodies against Escherichia coli and Proteus mirabilis compared with healthy controls. When compared with the patients with RA, the AS patients had higher concentrations of IgA and IgG class antibodies only against K pneumoniae. The RA patients had higher IgM class antibody concentrations against all three studied Enterobacterias, when compared with the healthy controls, suggesting an enhanced mucosal immune response in these patients. A three month treatment with sulphasalazine did not decrease enterobacterial antibody concentrations in the 10 patients with AS. CONCLUSION: There is strong direct evidence for an abnormal mucosal humoral immune response particularly to K pneumoniae in patients with AS.

Adult↗

PubMed1997

Renal accumulation and distribution of hyaluronan after ureteral obstruction.

In a unilateral ureteral obstruction model, a progressive accumulation of hyaluronan (HA) was observed in the renal papilla during the first 11 days of obstruction, after which the amount of HA decreased until the last day of observation, i.e. day 22. The initial accumulation of HA in the obstructed kidney probably reflects the attempts of the kidney to maintain osmotic balance. Consequently, when filtration ceases, HA synthesis decreases and the concentration of HA falls. In the papilla of the contralateral kidney, that had not been exposed to any mechanical damage, the HA content was found to vary in a similar way to that in the obstructed kidney. The explanation for this could be that the mesenchymal cells within the papilla increase their production of HA in order to meet the requirements of increased function necessary to also shoulder the function of the damaged kidney. In short similar variations in the HA content of the renal papilla was observed in both healthy and obstructed kidneys in a unilateral ureteral obstruction model.

Animals↗

PubMed1996

Experimentally-induced warm renal ischemia induces cortical accumulation of hyaluronan in the kidney.

An accumulation of the connective tissue component, hyaluronan (HA), is known to occur in both syngeneic and allogeneic kidney grafts during the early postoperative period. The presence of HA in the interstitial tissue of the grafts is paralleled by an increased water content, suggesting a role for HA in the development of the transplantation edema. In the present work, the kidney content and distribution of HA was studied in a model of warm renal ischemia in the rat to investigate whether renal ischemia is associated with HA accumulation. Seventy-two hours after a period of warm renal ischemia (30 or 60 min) significantly higher amounts of HA were observed in the left kidney that had been exposed to ischemia, than in the right, healthy kidney. The most pronounced increase was found to occur in the cortex (20 to 40 times), a structure where there normally is almost no presence of HA. In addition, there was a correlation between the relative water content of the kidney and the amount of HA possible to extract from the tissue. The renal accumulation of HA and water was prevented by daily intravenous administration of hyaluronidase. We conclude that renal ischemia induces an accumulation of HA that may increase the risk for the development of interstitial edema, a situation that may be circumvented by hyaluronidase treatment.

Animals↗

PubMed1996

Increased mucosal synthesis of rheumatoid factor (RF) in coeliac disease.

Increased serum levels of RF have been reported in patients with gluten sensitivity. The objective of this study was to investigate the in vivo secretion of different isotypes of RF in the small bowel in coeliac disease. Nineteen patients were investigated by perfusion of a defined jejunal segment, and the jejunal perfusion fluid was analysed for the presence of IgA and IgM anti-Fc (IgG). Five of the patients studied had serum IgA deficiency. Patients with partial/subtotal villous atrophy but no IgA deficiency (n = 7) had a four-fold increase of IgM-RF (P < 0.001) and a three-fold increase of IgA-RF (P < 0.001) compared with healthy controls (n = 29). Patients with normal jejunal mucosa but no IgA deficiency (n = 7) had similar IgA-RF and IgM-RF concentrations to healthy controls. Patients with serum IgA deficiency had no IgA-RF detectable in jejunal fluid but the highest IgM-RF concentrations, in particular in active disease. The coeliac patients had serum levels of IgA-RF and IgM-RF within the reference ranges. Jejunal fluid levels of IgA-RF and IgA-anti-gliadin antibodies were significantly correlated (P < 0.001). The data indicate that enhanced jejunal mucosal production of RF occurs above all in active coeliac disease. The findings suggest that the immune response to gluten induces a mucosal RF synthesis.

Adult↗

PubMed1996

Increased levels of hyaluronan and albumin after intestinal challenge in adult patients with cow's milk intolerance.

BACKGROUND: The mechanisms for adverse reactions to foods in the gastrointestinal tract are poorly understood. Presently, only limited possibilities are available for identification of adverse immunological reactions to different foods. OBJECTIVE: The intestinal inflammatory reactions in adult patients with a history of milk-related gastrointestinal symptoms were studied after intestinal challenges by a jejunal perfusion technique and compared with the reactions in a control group. METHODS: Five skin-prick test and radioallergosorbent test negative and lactose tolerant patients with a history of milk-related gastrointestinal symptoms, verified by double-blind placebo-controlled challenge, and eight healthy controls were investigated. Perfusions were performed allowing analyses of a well-defined 'closed' jejunal segment. Milk perfusions were performed in patients and controls after an overnight fast. Ten millilitres of milk were administered to the segment at 3 mL/min. The jejunal fluid levels of hyaluronan (hyaluronic acid) and albumin were measured. RESULTS: In the five patients the milk challenges induced as a mean fivefold increased levels of hyaluronan compared with prestimulation values, whereas no such increases were seen in the control subjects. Albumin, as a marker of plasma leakage, was also increased in the patients but not in the control subjects. CONCLUSION: The underlying mechanisms for locally increased levels of hyaluronan and also albumin in the intestinal lumen may be secretion of lymph rich in hyaluronan and reflect the mucosal oedema. This capacity of the intestinal mucosa to react with lymph leakage towards a locally infused allergen may be a possible way to delineate gastrointestinal reactions in food-related disorders.

Adult↗

PubMed1996

Subcutaneous administration of hyaluronan reduces the number of infectious exacerbations in patients with chronic bronchitis.

Hyaluronan (HA) is a high molecular weight glycosaminoglycan found in large amounts in the skin, joints, and other organs. Previous studies have shown that HA stimulates neutrophil functions both in vitro and in vivo. The object of this study was to test the hypothesis that HA administration subcutaneously might reduce the number of bacterial infections in humans with an increased susceptibility to such infections. For this purpose we have studied 29 patients with chronic bronchitis and recurrent acute exacerbations of their disease. The patients were randomly separated into two groups. One group had HA for 6 mo followed by 6 mo of placebo, and the other group started with placebo treatment followed by HA. The treatment periods occurred during two consecutive winter periods. HA-treated patients had significantly fewer acute exacerbations (p = 0.01) than did placebo-treated patients. Likewise the consumption of antibiotics and other signs of bacterial infections were reduced. In the crossover study the placebo-treated patients again had much higher numbers of acute exacerbations than did the HA-treated patients (p < 0.0001). It is concluded that HA reduces the number of infectious exacerbations in patients with chronic bronchitis, possibly by enhancing cellular host defense mechanisms. HA is a new endogenous substance that can be used to stimulate host defense reactions and reduce the need of antibiotics. Before being recommended for clinical use, however, our results should be confirmed by further studies.

Aged↗

PubMed1996

Intact adrenocorticotropic hormone secretion but impaired cortisol response in patients with active rheumatoid arthritis. Effect of glucocorticoids.

OBJECTIVE: To study the hypothalamic-pituitary-adrenal axis in rheumatoid arthritis (RA) and the influence of glucocorticoid treatment. METHODS: Consecutive untreated patients with RA with moderately high inflammatory activity were studied and compared with healthy subjects of similar age. Subjects were studied both at baseline and after multiple releasing hormone (MRH) stimulations. Patients were reexamined one week after starting prednisolone. RESULTS: The baseline cortisol/adrenocorticotropic hormone (ACTH) ratio was significantly lower in patients with RA. After corticotropin releasing hormone (CRH) stimulation, their serum cortisol response was reduced during the later test phases in spite of intact ACTH response. The baseline and stimulated levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) were normal. An impaired prolactin response was seen after MRH stimulation. After one week of prednisolone therapy the absolute response of serum cortisol to CRH was decreased and the stimulated prolactin response was normalized. CONCLUSION: Impaired cortisol secretion in patients with RA in the presence of intact ACTH secretion is consistent with relative adrenal glucocorticoid insufficiency. Adrenal impairment may be secondary to the inflammatory disease process.

Adolescent↗

PubMed1995

Regional rectal perfusion: a new in vivo approach to study rectal drug absorption in man.

BACKGROUND: In vivo permeability measurements of drugs in the colonic/rectal region in humans are difficult. A new instrument for the perfusion of a defined and closed segment in the colon/rectum was developed. The objective of this study was to evaluate its use for studying drug absorption mechanisms in the human rectum and to investigate the effect of transmucosal water absorption on drug permeability. Six healthy subjects participated at 2 separate occasions by using a modified system for segmental rectal perfusion. The system consisted of a multichannel tube with inflatable balloons and was endoscopically introduced into the rectum. The technique was considered acceptable by the following criteria; (a) high and reproducible recovery of PEG 4000, (b) stable residence time of the solution within the test segment, (c) flux of electrolytes that agrees with previous reports, (d) mass-balance absorption of antipyrine across the rectal barrier, (e) and good acceptability to the subjects. The permeability of antipyrine in the rectal region was increased by inducing net water absorption. D-glucose was not absorbed during any study periods. The present technique is valuable for studying drug absorption from the human rectum.

Antipyrine↗

PubMed1995

Mucosal synthesis and release of prostaglandin E2 from activated eosinophils and macrophages in ulcerative colitis.

OBJECTIVE: To study the synthesis and release of prostaglandin E2 (PGE2) in diseased and healthy areas of the colon in ulcerative colitis/proctitis (UC) patients. METHODS: Perfusate fluid from rectal and sigmoid segments in patients with UC was analyzed for PGE2, eosinophil cationic protein, myeloperoxidase, and tumor necrosis factor-alpha concentrations. To further elucidate the cell-specific origin of mucosal PGE2 synthesis, double immunofluorescence staining as well as imaging analysis using antibodies reactive with prostaglandin H-synthase and cell-specific antigens were used on surgical colonic specimens from patients with active UC and from controls. RESULTS: The concentrations of PGE2 were, on average, 10-fold higher in perfusates from diseased areas in patients with UC than in perfusates from healthy areas in patients and controls. The PGE2 values correlated well with the released concentrations of eosinophil cationic protein, myeloperoxidase, and tumor necrosis factor-alpha. In the tissue specimens, there was a prominent colocalization in the expression of prostaglandin H-synthase on the one hand and CD 68 (a macrophage marker) and EG1/EG2 (eosinophil cationic protein markers) on the other hand, in both UC patients and controls. This did not apply to prostaglandin H-synthase and antibodies against B and T lymphocytes, neutrophils, or epithelial cells. CONCLUSION: The increased PGE2 production found in the inflamed mucosa in active UC may be caused by a fraction of activated eosinophils and macrophages.

Adult↗

PubMed1994

[Segmental intestinal perfusion. A "new" technique for human studies].

Intestinal release of inflammatory mediators and permeation of macromolecules were studied in patients suffering from Crohn's disease, celiac disease and food intolerance with the use of a system for segmental intestinal perfusion. Drug absorption and ion and bicarbonate transport were also studied in healthy subjects. Patients with Crohn's disease of the distal ileum revealed an increased release of inflammatory agents into the lumen of the proximal jejunum. Luminal provocation with different antigens in cases of celiac disease and food intolerance not only activated cells in the intestinal mucosa but also increased the leakage from plasma and lymph. Studies of drug absorption elucidated the kinetics of drug transport from intestine to plasma, and basal neurologic effects on ion and bicarbonate transport were determined.

Celiac Disease↗