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Biomedical subjects

R Hällgren

Publications and source records attributed to R Hällgren.

At least 19 recordsLinked to original sources
PubMed1992

Hereditary dysfunction of the third component of complement associated with a systemic lupus erythematosus-like syndrome and meningococcal meningitis.

OBJECTIVE: We describe a dysfunction of C3 in a patient with a systemic lupus erythematosus (SLE)-like syndrome. Alternative pathway complement function was absent, but classical pathway complement function was partially intact. METHODS: We used functional, preparative, and immunochemical techniques in the study. RESULTS: The patient's C3 proved normally susceptible to trypsin proteolysis and partially resistant to classical pathway, but completely resistant to alternative pathway, convertase-dependent cleavage. CONCLUSION: The dysfunction, thus, was caused by a failure of C3 to interact with the C3 convertases, rather than by a lack of a proteinase-sensitive cleavage site in the deficient protein.

Adult↗
PubMed1992

Jejunal secretion of secretory immunoglobulins and gliadin antibodies in celiac disease.

The aim of this study was to determine the secretion of secretory immunoglobulins and gliadin antibodies in the small bowel in celiac disease. Twenty-four patients were investigated by perfusion of a defined jejunal segment. Four of the patients studied had a serum IgA deficiency and had no measurable amounts of secretory IgA in the perfusion fluid. The other patients demonstrated a significant increase in the jejunal concentration of secretory IgA (median 28.5 mg/liter) compared with healthy controls (median 16 mg/liter, N = 16) and of IgM, celiac (median 12.3 mg/liter) compared to healthy controls (median 6.8 mg/liter, N = 16). Jejunal IgA gliadin antibodies were detected in all patients except those with an IgA deficiency. All patients had jejunal IgM gliadin antibodies, but none of the patients had measurable jejunal IgG gliadin antibodies. A positive correlation was detected between serum and jejunal IgA gliadin antibody levels in the celiac patients, (P less than 0.01). Calculation of the ratio between gliadin antibodies and total levels of IgA and IgM in serum and jejunal perfusate demonstrated that the jejunal synthesis of gliadin antibodies of IgA and IgM type is both more pronounced and persistent than the systemic humoral immune response to gliadin.

Adult↗
PubMed1992

Acute exposure of small intestine to ethanol induces mucosal leakage and prostaglandin E2 synthesis.

The small intestines of healthy volunteers were challenged with ethanol during regional perfusion of a defined jejunal segment. Infusion of 30 mL of 5000 mmol/L ethanol to the perfused jejunal segment gave a maximum ethanol concentration of 973 +/- 98 (SEM) mmol/L in the jejunum lumen. This ethanol challenge induced within 20-30 minutes a 10-fold increase in albumin (P less than 0.001) and a two-fold increase in the glycosaminoglycan hyaluronic acid (P less than 0.05) in the perfusion fluid. Later during the challenge and simultaneously with a decreased jejunal loss of albumin, the jejunal recovery of prostaglandin E2 increased fourfold (P less than 0.01). The jejunal fluid concentrations of histamine and eosinophil cationic protein remained stable during the ethanol challenge. No changes in the jejunal appearance of albumin or other measured substances were seen when the maximum jejunal fluid concentrations of ethanol were less than 400 mmol/L achieved during challenge with smaller amounts of ethanol. The increased jejunal fluid appearance of hyaluronic acid after ethanol challenge indicates increased leakage from the interstitial/lymph fluid of the gut wall due to altered mucosal permeability. The relatively larger jejunal losses of albumin suggest that ethanol induces increased microvascular permeability of the jejunum as well.

Adult↗
PubMed1992

Regional jejunal perfusion, a new in vivo approach to study oral drug absorption in man.

Recently a new in vivo approach in man, using a regional intestinal perfusion technique, has been developed. The perfusion tube consists of a multichannel tube with two inflatable balloons, which are placed 10 cm apart. The tube is introduced orally and the time required for insertion and positioning of the tube is approximately 1 hr. In the present study eight healthy subjects were perfused in the proximal jejunum on three separate occasions. The first two perfusion experiments used the same flow rate, 3 ml/min, and the third experiment used 6 ml/min. Phenazone (antipyrine) was chosen as the model drug. The recovery of PEG 4000 in the outlet intestinal perfusate was complete in experiments 1 and 2, but slightly lower (90%) when the higher flow rate was used. The mean (+/- SD) fraction of phenazone absorbed calculated from perfusion data was 51 +/- 12% (3 ml/min), 64 +/- 19% (3 ml/min), and 42 +/- 27% (6 ml/min) for the three experiments, respectively. The mean fraction absorbed estimated by deconvolution of the plasma data was 47 +/- 16%, 51 +/- 19%, and 38 +/- 26%, respectively. The effective permeability of phenazone was 5.3 +/- 2.5, 11 +/- 6.8, and 11 +/- 12 (x 10(4) cm/sec, respectively. We have shown that it was possible to establish a tight intestinal segment which behaved as a well-mixed compartment. The low perfusion rate of 3 ml/min was preferred, since it resulted in the lowest variability in absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Response of anaemia in rheumatoid arthritis to treatment with subcutaneous recombinant human erythropoietin.

Eleven patients with chronic inflammatory arthritides and haemoglobin concentrations less than 105 g/l with symptoms from their anaemia were treated with a dose of 250 IU/kg/week of recombinant human erythropoietin for six weeks. The treatment was given as subcutaneous injections five days a week. All patients had active inflammatory disease. Nine patients responded to treatment with an increase in haemoglobin of more than 15 g/l. The mean (SD) haemoglobin concentration increased from 93.0 (8.0) g/l before treatment to 115.0 (12.0) g/l after six weeks. There was no correlation between the initial serum concentration of erythropoietin and the response. It was concluded that anaemia in chronic inflammatory arthritides responds to treatment with subcutaneous injections of recombinant human erythropoietin.

Administration, Cutaneous↗
PubMed1992

Effect of intrajejunal elemental diet perfusion on jejunal secretion of immunoglobulins, albumin, and hyaluronan in man.

The aim of this work was to study the jejunal secretion of immunoglobulins (Ig), albumin, and hyaluronan in response to jejunal perfusion of an elemental diet. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with a control electrolyte solution for 80 minutes and with an elemental diet (containing 20.5 milligrams of free amino acids and 104.2 milligrams of oligosaccharides) for 100 minutes. The jejunal fluid concentrations of albumin, IgG, monomeric IgA (m-IgA), polymeric IgA (p-IgA), IgM, secretory component, and hyaluronan were measured and their jejunal outputs calculated. Within 20 minutes of starting perfusion with the elemental diet there was a significant increase in the secretion rates of albumin (x3.3), IgG (x5), M-IgA (x3.7), p-IgA (x2), IgM (x2), and secretory component (x1.6), but the hyaluronan secretion rate was not changed. The increase in m-IgA, p-IgA, IgM, and secretory component output suggests that intestinal perfusion of an elemental diet results in stimulation of secretory immunity. The increase in albumin and IgG output probably reflects a nutrient induced leakage from the plasma compartment.

Adult↗
PubMed1992

Increased luminal release of hyaluronan in uninvolved jejunum in active Crohn's disease but not in inactive disease or in relatives.

Recently obtained data suggest that there is a subclinic inflammatory activity in the apparently uninvolved intestinal mucosa in Crohn's disease (CD). As CD is characterized by an activation of connective tissue and fibrosis, we investigated the extent to which hyaluronan (HA), an essential component of the connective tissue, was released into the lumen of an isolated jejunal segment in CD patients and in relatives. Patients with active CD of the terminal ileum (CD activity index, CDAI, > 150; n = 14), patients with CD in remission (CDAI < 150 n = 10), first-degree relatives of the CD patients (n = 21) and healthy controls (n = 43) were orally intubated with a catheter allowing occlusion and perfusion of a segment of the proximal jejunum. The jejunal fluid concentration of HA was 65 +/- 45 micrograms/l in patients with active CD in the terminal ileum, significantly higher than the value for 43 healthy controls (42 +/- 23 micrograms/l; p < 0.05), and the corresponding values for patients in remission (42 +/- 23 micrograms/l) and for first-degree relatives of the CD patients (53 +/- 52 micrograms/l), were not increased compared to the control group. To localize HA in the tissue, small bowel biopsies were taken during surgery from patients with CD and from controls and affinity stained for HA. There was an intense staining for HA in the lamina propria of the villi, both in biopsies from patients with CD and from controls, but no staining in the epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Alveolar accumulation of fibronectin and hyaluronan precedes bleomycin-induced pulmonary fibrosis in the rat.

The development of bleomycin-induced pulmonary fibrosis in rats was studied over a period of 30 days after an intratracheal instillation of bleomycin. Fibronectin was visualized in histological sections and quantified in bronchoalveolar lavage fluid (BALF) and related to simultaneous measurements of hyaluronan, collagen and albumin in BALF and/or lung tissue extracts. An increase in BALF fibronectin levels was noted after 3 days and the peak value a sixty fold increase was noted at day 7. Thereafter, the fibronectin levels declined and reached control values on day 21. A pronounced, patchily distributed staining for fibronectin appeared in the injured alveolar tissue parallel to the increased lavage fluid fibronectin levels on days 3-7. A fainter, streakily distributed fibronectin staining remained within the alveolar walls in areas with proliferating fibroblasts on days 14-30. Albumin in BALF increased to a peak level, 20 times control values, after 3 days and then rapidly declined. Thus, the ratio of fibronectin to albumin increased to a peak value of 43 times control values on day 7, indicating that plasma leakage cannot be the only source of the observed increase in lavage fibronectin. Lung tissue hydroxyproline increased between days 7 and 30, whereas extractable hyaluronan in lung tissue and bronchoalveolar lavage fluid peaked on days 3-7 and then gradually declined towards normal values on days 21-30. These data demonstrate that fibronectin accumulates in the alveolar tissue during the early inflammatory phase of the bleomycin-induced lung injury, parallelling hyaluronan accumulation and preceding the development of pulmonary fibrosis.

Animals↗
PubMed1992

A technique for segmental rectal and colonic perfusion in humans.

To enable a better characterization of pathophysiologic processes in colon and rectum, we have developed a perfusion technique for collection of soluble substances and cells from standardized intestinal segments. A tube with balloons attached to its outer wall was endoscopically introduced into the rectum and sigmoid colon, and its position ascertained fluoroscopically. The balloons delimited two segments, one in the sigmoid colon and one in the rectum. The segments were simultaneously perfused by a buffer at 37 degrees C. After a 30-min rinsing period, perfusate and cells were collected at 20-min intervals. Of 51 attempted perfusions, 45 were successfully completed. Recovered volumes equaled those infused. Leakage from the proximal intestine to the segments was negligible. In 18 healthy volunteers, the mean perfusate concentration from the rectal segment was 57.5 (27.5-120.2) mg/L for albumin, 1.3 (1.0-1.7) micrograms/L for eosinophil cationic protein, 5.1 (2.8-9.5) ng/L for prostaglandin E2, and 61.7 (41.7-89.1) micrograms/L for hyaluronan, and all values were lower in the sigmoid segment. Steady state conditions were achieved from the second perfusion period. The perfusate contained 4-80 x 10(4) cells, more than 95% of which were epithelial cells. The technique is safe, has a good subject compliance, and seems to be a valuable tool in investigations on quantitative release of soluble substances and cells in, e.g., colorectal inflammation.

Adult↗
PubMed1992

Class and subclass-associated specificity differences of anti-gliadin antibodies from mucosa and serum.

The class and subclass distribution of antibodies against gliadin in intestinal lavage fluid, saliva and serum was investigated in individuals with coeliac disease. Serum antibodies against gliadin were mainly or even exclusively of the IgA1 subclass. In intestinal lavage fluid and saliva, antibodies of both IgA1 and IgA2 subclasses were found. In patients with and without IgA deficiency, an IgG response was detected both in serum and intestinal lavage fluid with a predominance of IgG1 in selected patients. Specific IgG2, IgG3 and IgG4 antibodies were also detected in intestinal lavage fluid, while no specific IgG2, IgG3 or IgG4 antibodies were found in serum, suggesting a local production of specific IgG antibodies. In Western blot analysis, intestinal lavage fluid and serum IgA antibodies reacted against gliadin components with a MW between 33,000 and 42,000. Serum IgA1 antibodies directed against a gliadin component with a MW slightly higher than 42,000 were also observed. Specific IgG and IgM antibodies in both the secretion and serum against gliadin components with a MW between 33,000 and 42,000 were also detected. This study shows that mucosa-derived gliadin-specific IgA and IgG antibodies may be produced even when there is an absence of specific antibodies of the corresponding immunoglobulin subclass in serum. Furthermore, the specificity of serum and intestinal lavage fluid anti-gliadin IgA1 antibodies may differ.

Antibody Specificity↗
PubMed1992

Radiation-induced increase in hyaluronan and fibronectin in bronchoalveolar lavage fluid from breast cancer patients is suppressed by smoking.

Bronchoalveolar lavage (BAL) fluid was analysed from 21 patients with breast cancer, stage T1N0M0, who had undergone tumour resection and post-operative local irradiation (accumulated dose 56 Gy). The lavage was performed two months after radiotherapy, in the anterior part of the lingula (left side) or of the right middle lobe (right side), depending on which side had been exposed to radiation. The patients had significantly increased concentrations of fibronectin (FN) (p less than 0.001), hyaluronan (HA) (p less than 0.01) and albumin (p less than 0.05) in BAL fluid compared with the healthy controls (n = 19). However, when the patients were separated, according to smoking history, it was obvious that the inflammatory reaction occurred entirely in the nonsmoking patient group (n = 10), whilst no difference could be found between the smoking patients (n = 11) and the controls. In the nonsmoking patient group, there was a sevenfold increase in BAL concentrations of FN and a threefold increase in HA. Moreover, four patients had detectable levels of procollagen III peptide in BAL, all were nonsmokers. The smoking habits of the controls had no influence on the BAL measurements. These findings indicate that smoking interferes with the radiation-induced early inflammatory connective tissue reaction of the lung. Finally, the results justify further investigation of interaction of smoking with cancer treatment, both from the view of therapy effectiveness and reduction of adverse effects.

Albumins↗
PubMed1991

Eosinophil activation in systemic sclerosis.

Circulating levels of eosinophil cationic protein (ECP) were increased 4-fold in patients with systemic sclerosis (SSc) compared with those in healthy control subjects. There was no correlation between the ECP concentrations and laboratory indices of inflammatory activity or visceral involvement. Mean ECP levels were higher in patients with a history of occupational exposure to silica, even though patients who had no such history also had ECP levels higher than normal. The patients had increased bronchoalveolar levels of ECP, which correlated with impaired lung functioning. Skin infiltration with activated eosinophils and extracellular deposits of ECP were present in skin biopsy samples from the SSc patients. We conclude that eosinophil activation is part of the inflammatory process in SSc.

Adult↗
PubMed1991

Non-invasive assessment of systolic left ventricular function in systemic sclerosis.

Systemic sclerosis is a multisystemic disorder, also affecting the heart. To evaluate its influence on systolic left ventricular (LV) function, we investigated 30 consecutive patients (age 54.5 +/- 2.4 years, 15 men and 15 women) and 48 controls matched for age and sex. All subjects were investigated by phonocardiography, pulse curve recordings, M-mode echocardiography, and by pulsed and continuous wave Doppler. Heart rate, blood pressure and peripheral resistance did not differ, but patients weighed less than controls (P less than 0.01). Systolic time intervals indicated systolic impairment, with an increased pre-ejection period to LV ejection time (LVET) ratio (0.37 +/- 0.02 vs 0.30 +/- 0.01 P less than 0.001), and also an increased isovolumic contraction time to LVET ratio (0.17 +/- 0.02 vs 0.12 +/- 0.01, P less than 0.02). The latter difference remained when LVET was adjusted for heart rate. Echocardiographic E-point to septal separation was increased in patients (8.3 +/- 1.3 vs 4.8 +/- 0.3 mm, P = 0.001), also after adjustment for LV dimension (P = 0.0001), while septal fractional thickening was decreased (P less than 0.01). End systolic wall stress (P = 0.0002) and stress to volume ratio (P = 0.03) were lower in systemic sclerosis. Peak LV emptying rate was also lower in the patient group when measured by echocardiography (P = 0.03). There was no difference between groups regarding LV dimensions, fractional shortening or mean velocity of circumferential fibre shortening. While aortic Doppler peak emptying rate did not differ between groups, it occurred later in systole in the patient group (P less than 0.01) as did peak velocity (P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Bronchial hyperresponsiveness to methacholine in patients with primary Sjögren's syndrome.

The prevalence of bronchial hyperresponsiveness (BHR) to methacholine inhalation in a consecutive series of 21 patients with primary Sjögren's syndrome was studied prospectively. Slight to severe BHR was seen in 12/20 (60%) of the patients. Ten of 12 patients with BHR (83%) had a non-productive cough, wheezing, or intermittent breathlessness. Bronchial hyperresponsiveness was more common in patients with extraglandular symptoms (10/14, 71%) than in those with only glandular symptoms (29%). Spirometrically 29% (6/21) of the patients had 'small airways' disease', and all those had BHR. Of 6/21 (29%) who had diffuse interstitial lung disease, two had BHR. Three of the four patients with obstructive lung function were challenged with methacholine and two of them had BHR. Only two patients with BHR had normal spirometry findings. The data showed that respiratory disease--mostly mild or moderate but even severe bronchial hyperresponsiveness--is commonly seen in patients with primary Sjögren's syndrome.

Adult↗
PubMed1991

Hypoxanthine, xanthine, and urate in synovial fluid from patients with inflammatory arthritides.

As nucleotide catabolism increases during tissue injury the appearance of purine metabolites in inflamed synovial fluid might be of value in understanding the joint damage in inflammatory arthritides. In this study, therefore, synovial and plasma concentrations of hypoxanthine, xanthine, and urate in 16 patients with rheumatoid arthritis (three with psoriatic arthropathy) were analysed. It was found that their plasma concentrations of hypoxanthine were greater than those of a reference group of healthy subjects. The synovial fluid concentrations of hypoxanthine, xanthine, and urate were higher than corresponding concentrations in plasma. Positive correlations were found between the respective plasma and synovial fluid values of xanthine and urate. These findings indicate a local enhanced purine metabolism in inflamed joint tissue and diffusion of oxypurines from joint cavity to plasma. No relation was found between measured metabolites and disease duration, radiological joint findings, or synovial fluid cells. Except for a weak correlation between plasma urate and serum haptoglobin, measured purine metabolites were not related to laboratory measures of systemic inflammation.

Adult↗
PubMed1991

Neutrophil function in patients with primary Sjögren's syndrome: relation to infection propensity.

The function of neutrophils was studied in 23 consecutive patients with primary Sjögren's syndrome and in 35 healthy controls. Nineteen patients (83%) had extraglandular symptoms and nine patients (39%) had recurrent bacterial infections. The patients had a marked reduction of neutrophil adherence, especially those with recurrent bacterial infections, and reduced opsonic activity of plasma. Increased random migration of isolated neutrophils was found in the patients with a propensity for bacterial infections. Chemotaxis and chemokinesis, phagocytosis, chemiluminescence production, and the intracellular neutrophil contents of lactoferrin and lysozyme were normal. The various aspects of neutrophil function tested in this study were not related to disease duration or to inflammatory disease activity. The impaired neutrophil adherence may play a part in the increased propensity for bacterial infections seen in patients with primary Sjögren's syndrome.

Adult↗
PubMed1991

Deposition of eosinophil cationic protein in vascular lesions in temporal arteritis.

The possible role of the eosinophil and its cytotoxic granule proteins in the vascular lesions seen in temporal arteritis was elucidated. Sixteen sections of biopsy specimens from arteria temporalis showing giant cell arteritis were stained for eosinophil cationic protein (ECP) by polyclonal antibodies and the immunoperoxidase method. Activated eosinophils were identified by monoclonal antibodies linked to alkaline phosphatase. Activated eosinophils and secreted ECP were seen in all layers of the inflamed vessels and were most evident in necrotic lesions and thrombi. Only a small number of granulocytes seen in the adventitia were immunoreactive for cathepsin G, and no extracellular deposits of this neutrophil granule protein were seen. A few immunoreactive eosinophils were found in the adventitia in two of five negative temporal artery biopsy specimens from patients with polymyalgia rheumatica. All eight coronary artery biopsy specimens with atherosclerotic lesions showed no activated eosinophils or secreted ECP. These findings indicate that eosinophils are involved in the vascular lesion in temporal arteritis and suggest that cytotoxic eosinophil granule proteins may contribute to the necrotic lesions and the development of thrombi.

Aged↗