Biomedical subjects

O Ahrenstedt

Publications and source records attributed to O Ahrenstedt.

12 recordsLinked to original sources

PubMed1997

Defective elimination of C3b/iC3b-coated autologous erythrocytes in patients with primary biliary cirrhosis, alcoholic cirrhosis, and ulcerative colitis.

Delayed in vivo elimination of autologous erythrocytes coated with immunoglobulin G has been reported in autoimmune and inflammatory gastrointestinal diseases. Our aim was to elucidate whether impairment of the macrophages was restricted to the Fc receptors of the reticuloendothelial system or whether complement receptors were also affected. We studied elimination by complement receptors of autologous erythrocytes coated with fragments of C3 and C4 in patients with primary biliary cirrhosis, ulcerative colitis, and alcoholic cirrhosis. Impaired function was seen in all patient groups as compared with function in normal subjects, both concerning the mean half-life of the injected cells and the total number of eliminated erythrocytes. Neither of these parameters correlated with the levels of C3 fragments bound to the injected autologous erythrocytes. This is the first report of defective complement receptor function in ulcerative colitis and alcoholic cirrhosis. Immunoglobulin G-dependent elimination of erythrocytes was confirmed to be lowered in all patient groups. The results suggest severe macrophage functional aberrations involving both complement receptors and Fc receptors as the basis of phagocytic defects in autoimmune/inflammatory conditions. In contrast, a general loss of macrophages might cause the functional loss in alcoholic cirrhosis.

Adult↗

PubMed1995

The lack of effect of induced net fluid absorption on the in vivo permeability of terbutaline in the human jejunum.

The absorption mechanism(s) of terbutaline in the human jejunum was studied by using the intestinal perfusion instrument, Loc-I-Gut. The present study was divided into three parts. In Part I the absorption of 10 and 20 microM of both (+) and (-)-terbutaline enantiomers was studied. The influence of D-glucose (80 mM) on the net fluid transport across the intestinal wall and the effective intestinal permeability (Peff) of both (+/-)-terbutaline (10 microM) and antipyrine (0.5 mM) was investigated in Part II. The experimental design of Part III was similar to that in Part II, with the exception that the perfusion solution was hypotonic and had a D-glucose concentration of 80 mM. No statistical differences were found in the Peff between terbutaline enantiomers or their concentrations. D-glucose (80 mM) did neither affect net fluid transport nor the Peff of (+/-)-terbutaline and antipyrine in the human jejunum. In contrast, hypotonic D-glucose (80 mM) solution induced a net fluid absorption (p < 0.01). In parallel with this observation, the Peff -value of (+/-)-terbutaline was unchanged, whereas the absorption of antipyrine was found to be significantly increased (p < 0.05). The increased permeability of antipyrine during the net fluid absorption phase might be due to convective paracellular flow, but more likely is it a consequence of a higher concentration gradient of the drug close to the intestinal wall, and thereby increased transcellular absorption. Based on these findings we propose that the major route for the oral absorption of terbutaline and antipyrine might be passive transcellular diffusion.

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↗

PubMed1994

Intestinal drug absorption during induced net water absorption in man; a mechanistic study using antipyrine, atenolol and enalaprilat.

1. The effect of induced water absorption on the intestinal permeability of antipyrine, atenolol and enalaprilat in the proximal jejunum was studied in eight healthy subjects with a regional intestinal perfusion technique. 2. The mean (+/- s.d.) net water flux changed from a secretory status of 1.2 +/- 1.2 ml h-1 cm-1 to an absorptive status of -3.7 +/- 3.5 ml h-1 cm-1 (P < 0.0025) on the introduction of a hypo-osmolar glucose-containing electrolyte solution. 3. The mean permeability values for the three drugs in the eight subjects were unchanged despite the increase in net water absorption (5.7 +/- 3.0 to 7.0 +/- 3.6 x 10(-4) cm s-1 for antipyrine, 0.1 +/- 0.2 to 0.2 +/- 0.2 x 10(-4) cm s-1 for atenolol and 0.3 +/- 0.3 to 0.1 +/- 0.2 x 10(-4) cm s-1 for enalaprilat). One subject showed a large change in the permeability for antipyrine and atenolol in parallel with a large increase in water absorption, but enalaprilat was unaffected. 4. The luminal recovery of PEG 4000 was similar before (100 +/- 4%) and during (101 +/- 7%) induction of water absorption, which indicates that the barrier function of the intestine appears to be maintained during glucose-stimulated fluid absorption in man. 5. We conclude that induced net water absorption in man does not influence the paracellular permeability of hydrophilic drugs or drugs with high molecular weight to any significant extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

The effect of L-leucine on the absorption of levodopa, studied by regional jejunal perfusion in man.

1. A new method for perfusing a 10 cm segment of jejunum in humans has been used in seven subjects to study the effect of the amino acid L-leucine (40 mM) on the intestinal absorption of levodopa (2.5 mM). The tube contains six channels and has two inflatable balloons, which enable a perfusion of a closed and defined segment of the proximal small intestine. 2. L-leucine decreased the intestinal absorption of levodopa from 40 +/- 19 to 21 +/- 15% but was without effect on the absorption of antipyrine, benserazide and D-glucose. 3. We confirm that levodopa is absorbed by the active transport system normally responsible for the absorption of large neutral amino acids (LNAA) in humans. Oral absorption by passive diffusion, probably by the paracellular route, might also occur for levodopa in the proximal part of the small intestine.

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

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↗

PubMed1991

Cell recovery during segmental intestinal perfusion in healthy subjects and patients with Crohn's disease.

The recovery of cells arising from small intestinal mucosa alone was studied during continuous perfusion of a closed segment of jejunum. The perfusion technique minimised the contamination of the perfused segment with, for example, proteolytic enzymes from pancreas, allowing recovery of viable cells. The use of hyaluronidase in the perfusion fluid increased the recovery of cells fivefold, the median recovery being 8 x 10(6) cells. The cells were analysed with monoclonal antibodies and flow cytometry. Nearly all cells (98-99%) recovered during perfusion of healthy control subjects and patients with Crohn's disease were epithelial cells. The jejunal cells expressed HLA-DR in similar proportions--around 30%--in patients and control subjects. The ratio between CD4+ and CD8+ lymphocytes was similar (0.2) in control subjects and patients with inactive Crohn's disease but decreased (0.03) in patients with active Crohn's disease in the ileum.

Adult↗

PubMed1990

Enhanced local production of complement components in the small intestines of patients with Crohn's disease.

There is evidence that complement components may be formed locally in inflammatory lesions containing monocytes and macrophages. To investigate the role of complement in Crohn's disease we measured jejunal-fluid concentrations of the complement components C4, C3, and factor B by perfusion of a closed segment of the jejunum in 22 patients with Crohn's disease thought to be limited to the terminal ileum. The mean (+/- SEM) jejunal-fluid C4 concentration was 2.0 +/- 0.3 mg per liter, significantly higher than the mean level in 35 healthy controls (0.7 +/- 0.1 mg per liter; P less than 0.001). The mean C3 concentration was 1.0 +/- 0.1 mg per liter in the patients and 0.7 +/- 0.1 mg per liter in the controls (P less than 0.05). The factor B levels were similar in the two groups. Calculated rates of intestinal secretion of these components showed differences of the same magnitude. Leakage of protein from plasma was not increased. The jejunal-fluid:serum ratios of these complement proteins indicated that their appearance in the lumen of the jejunum was due to at least in part to local mucosal synthesis. The increased jejunal secretion of C4, but not C3 or factor B, paralleled the clinical activity of Crohn's disease. Values were normal in first-degree relatives of the patients (n = 13), patients with celiac disease (n = 8), and patients with ulcerative colitis (n = 4). We conclude that increased secretion of complement by clinically unaffected jejunal tissue in patients with Crohn's disease reflects the systemic nature of this disorder and may be due to the stimulated synthesis of complement by activated intestinal monocytes and macrophages.

Adolescent↗

PubMed1990

The jejunal secretion of histamine is increased in active Crohn's disease.

Previous studies of mast-cell density and histamine content in biopsy specimens in patients with Crohn's disease have yielded conflicting results. In this in vivo study we have measured the jejunal secretion rate of histamine in patients with Crohn's disease (n = 15) of the terminal small bowel and in healthy controls (n = 24). The secretion studies were performed using a recently developed segmental jejunal perfusion system with a two-balloon, six-channel small tube. The histamine secretion rate was 152 +/- 29 (SEM) ng/cm small intestine per h in patients with Crohn's disease, which meant a significant increase (p less than 0.01) compared with the secretion rate in controls (71 +/- 11 ng/cm per h). Moreover, the secretion of histamine was related to the disease activity. Patients with active disease (n = 8) (i.e., Crohn's disease activity index greater than 150) had a mean histamine secretion rate of 193 +/- 47 ng/cm per h, while patients with inactive disease (Crohn's disease activity index less than 150) had a secretion rate not significantly increased compared with controls (105 +/- 24 ng/cm per h). The present data indicate increased mast-cell involvement of the small intestine in active Crohn's disease of the distal ileum. This finding might reflect the systemic nature of the disease process.

Adult↗

PubMed1985

The assault and battery panorama at a county hospital in Sweden.

All patients who had been assaulted and battered and who consulted the surgical emergency service at the county hospital were included. Forty seven cases were registered during a 5-month period, representing 1.1% of the surgical emergency patients. There were 31 males and 16 females. No case of child assault was recorded. About 55% of the males were between the ages of 20 and 29, whereas the females were relatively evenly distributed between 20 and 50 years of age. The patient material was analysed regarding social conditions, in what way the injury had originated and also the degree of severity of the injury. The social background and the presence of alcohol use or abuse were, as expected, important factors. Males were, as a rule, assaulted outside the home, females mostly at home. A few of the assault cases were legally prosecuted. The need for follow-up welfare measures was judged as considerable.

Adolescent↗

PubMedDate not supplied

Jejunal release of prostaglandin E2 in Crohn's disease: relation to disease activity and first-degree relatives.

Patients with Crohn's disease of the distal ileum show increased permeability to hyaluronan and increased release of histamine and complement components in uninvolved parts of the proximal jejunum. These abnormalities are related to disease activity, and are not found in first-degree relatives. Increased synthesis of prostaglandins has been observed in inflamed areas of the intestine in active Crohn's disease. Our purpose was to measure luminal prostaglandin release in patients with active and inactive Crohn's disease and their first-degree relatives. Twenty-four patients with Crohn's disease of the distal ileum (10 in remission and 12 with inflammatory activity) and 17 of their first-degree relatives were included and compared with healthy control subjects (n = 39). Ten centimetres of the proximal jejunum was isolated between balloons as described previously and perfused with a balanced electrolyte glucose-containing solution. Luminal concentrations of PGE2 and albumin were measured and their luminal release was calculated. Luminal release of PGE2 was significantly higher in patients with Crohn's disease than in control subjects [69.7 +/- 11.5 and 34.0 +/- 4.7 pg/cm per h (3.7 +/- 0.6 and 1.8 +/- 0.3 ng/L), respectively, P < 0.01]. The PGE2 levels, however, were not positively correlated to disease activity. Furthermore, there was a modest, but significant increase in luminal PGE2 in first-degree relatives [53.6 +/- 7.0 pg/cm per h (2.9 +/- 0.4 ng/L), P < 0.05]. These changes were not accompanied by significant changes in luminal permeation of albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗