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Biomedical subjects

S Bondesen

Publications and source records attributed to S Bondesen.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cerebral blood flow velocity during high volume plasmapheresis in fulminant hepatic failure.

High volume plasmapheresis has previously been found to improve neurological statuses in patients with fulminant hepatic failure. We investigated the relationship between the neurological status and cerebral blood flow velocity (Vmean) during high volume plasmapheresis in 18 consecutive patients (ten females and eight males) with fulminant hepatic failure, with a mean age of 43 (range 9 to 57) years. The mean arterial pressure (MAP) and intracranial pressure (ICP) were also recorded. A total of 16% of body weight was exchanged with fresh frozen plasma per day. Thirty-six plasma exchanges wer performed with a median of 2 (range 1 to 8) per patient. Eleven of the patients survived (61%), nine after liver transplantation. Following the first high volume plasmapheresis, the coma score improved from 6 (1-8) to 2 (0-8) (p < 0.05), Vmean increased from 40 (14-152) to 62 (16-186) cm s-1 (p < 0.05), and MAP from 72 (35-118) to 94 (47-138) mmHg (p < 0.05). The intracranial pressure (ICP) was monitored and remained unchanged in nine patients whereas the cerebral perfusion pressure (MAP minus ICP) increased in the surviving group from 55 (40-74) to 80 (50-91) mmHg (p = 0.07) in contrast to no changes in the non survival group. In conclusion this study suggests that the neurological status, may improve during high volume plasmapheresis as MAP and Vmean increase the cerebral oxygen delivery.

Adolescent↗
PubMed1993

Identification of oxidation products of 5-aminosalicylic acid in faeces and the study of their formation in vitro.

The formation of three oxidant-derived products of 5-aminosalicylic acid (5-ASA) in vivo was demonstrated in patients with active ulcerative colitis as well as in healthy subjects. The products were isolated from faeces by preparative HPLC and their chemical structures were found to be oxidation products of 5-ASA using 1H-NMR spectroscopy and mass spectrometry. Reactions carried out in vitro between 5-ASA and oxidants suggested to be present in the inflamed bowel verified that the hypochlorite-mediated oxidation of 5-ASA as well as the haemoglobin-catalysed H2O2-dependent oxidation of 5-ASA resulted in the formation of a single oxidation product of 5-ASA. This product was similar to, but not identical to any of the products identified in faeces from patients receiving 5-ASA. Oxygen radical-mediated oxidation of 5-ASA gave several products, different from the products isolated. Finally, it was verified that the products formed in vivo are not formed as a result of autooxidation of 5-ASA either in faeces extract or in pharmaceuticals.

Aminosalicylic Acids↗
PubMed1991

Pharmacokinetics of 5-aminosalicylic acid in man following administration of intravenous bolus and per os slow-release formulation.

The fate of 5-aminosalicylic acid (5-ASA), which is used in the treatment of chronic inflammatory bowel diseases, was studied in six healthy volunteers receiving doses of 100 mg and 250 mg intravenous bolus as well as 250 mg per os (slow release). Following intravenous administration, the drug was rapidly eliminated with a plasma half-life of about 40 min, mainly due to rapid metabolism. No parent drug was recovered in feces, and the total recovery following oral administration (30%) was significantly lower than following the intravenous doses (77% and 72%). Nonlinear pharmacokinetics were suggested as the 2.5-fold increase in intravenous dose was followed by a significant relative increase (greater than 2.5) in the renal elimination of 5-ASA, as well as a significant decrease (less than 2.5) in the elimination of the metabolite N-acetyl-5-ASA. There was also a trend towards a decreasing total body clearance and metabolic ratio. The present study confirms earlier findings on the pharmacokinetics of 5-ASA and suggests a possible saturation of the N-acetylating system in the dose range studied. This may be of interest in the design of controlled-release formulations and dosage regimes for the treatment of diseases of the small-bowel, where 5-ASA is easily absorbed. Further, for the first time, a marked difference in the intestinal fate compared to the systemic fate of the drug is demonstrated, suggesting alternative presystemic metabolism of 5-ASA, which may bear relevance to its mode of action. Further studies on the pharmacokinetics of 5-ASA, preferably in patients, are warranted.

Administration, Oral↗
PubMed1991

Efficacy and outcome of an open access endoscopy service.

In a retrospective questionnaire-study, we have attempted to elucidate how open access endoscopy influences management of dyspeptic patients, with special focus on young patients (less than 40 year), since the proportion of examinations with findings not requiring medical treatment are consistently reported higher in this age group. During a one-year period, 436 patients referred for open access endoscopy and their general practitioners completed questionnaires giving details of medical treatment, consultation rate for dyspepsia and global assessment before and 6-18 months after the endoscopy. Relevant changes in medical treatment (stopped in patients with no or minor abnormalities or started in patients with major abnormalities) was found for 27% of the patients, irrespective of age group. The result of the endoscopy provided reassurance for 70% of the patients with no or minor abnormalities. Reassurance was coupled with a lower consultation rate and with fewer symptoms. Altogether, 83% of the young patients with no or minor abnormalities had a positive outcome of the endoscopy. As the endoscopy service introduced relevant and lasting prescription habits and reduced consultation rates at general practitioners, also for younger dyspeptic patients with no or minor abnormalities, the strategy generally proposed of a trial with H2-receptor antagonists before considering referral for endoscopy should be subjected to formal clinical trial evaluating all relevant levels of efficacy.

Adolescent↗
PubMed1990

Topical and systemic availability of 5-aminosalicylate: comparisons of three controlled release preparations in man.

The bioavailability of three pure 5-aminosalicylic (5-ASA) preparations (Asacol, Claversal, and Pentasa) was studied in 8 ileostomy patients and 12 normal subjects after 6 days of treatment with 2000 mg 5-ASA. The local bioavailability, reflected by the 5-ASA concentration was thereby measured at two clinically relevant areas of the gut: at the entrance to, and the exit from the colon. Estimates of the systemic bioavailability were obtained from the urinary excretions and the plasma values of 5-ASA and Acetyl-5-ASA (Ac-5-ASA) during the three regimens. The three preparations studied are designed to release 5-ASA at different levels in the intestine, but there was no significant difference in the 5-ASA concentrations in the ileostomy effluents (Asacol 1.8 mmol/L, Claversal 3.4 mmol/L, Pentasa 2.0 mmol/L, median values). However, we found a smaller urinary excretion of 5-ASA and Ac-5-ASA (5.2% vs Claversal 27.9% and Pentasa 23.0%, median values of ingested daily dose) and a lower concentration of Ac-5-ASA in the ileostomy effluents after Asacol treatment (0.8 mmol/L, median value) which indicates a more distal release from this preparation compared with Claversal (2.4 mmol/L, median value) and Pentasa (5.5 mmol/L, median value). In normal subjects a higher faecal water concentration of 5-ASA was found after Asacol (9.8 mmol/L, median value) compared with Claversal (5.0 mmol/L, median value), whereas no difference between the faecal water concentrations of Ac-5-ASA was found (Asacol 21.5 mmol/L, Claversal 21.6 mmol/L, median values). This can be explained by a larger systemic absorption of 5-ASA from Claversal, and accordingly Claversal treatment resulted in the largest urinary excretion of 5-ASA and Ac-5-ASA (43.7% vs Asacol 35.6% and Pentasa 31.6%, median values of ingested daily dose). The high Ac-5-ASA concentration in the ileostomy effluents and in the faeces after Pentasa, and the low plasma values, indicate a slow 5-ASA release from this preparation throughout the small and large intestine. The results of the study indicate that Asacol is released in the distal part of the small intestine, that Pentasa is gradually released in the small and large intestine, and that Claversal shows an intermediate release pattern.

Administration, Topical↗
PubMed1988

Absorption of 5-aminosalicylic acid from colon and rectum.

In order to clarify the characteristics of absorption of 5-aminosalicylic acid (5-ASA) from the colon, a neutral solution was instilled into the right part of the colon and the rectum, respectively, in six volunteers. A laxative (bisacodyl) and liquid meals were given prior to each instillation. No significant difference could be demonstrated between the two parts of the large bowel, but the absorption was considerably restricted compared with previous results obtained from the jejunum. The results confirm in a direct manner earlier observations on 5-ASA released from sulphasalazine.

Adult↗
PubMed1987

Lack of effect of 5-aminosalicylic acid on platelet aggregation and fibrinolytic activity in vivo and in vitro.

We have studied platelet aggregation and fibrinolytic activity in six patients with chronic inflammatory bowel disease treated with 5-aminosalicylic acid (mesalazine). There were no changes in these measurements during normal treatment, i.e. 1.5 g per day with a slow-release formulation, nor after an intravenous dose of 250 mg. Also in vitro tests were negative, in contrast to the inhibition seen with aspirin (acetylsalicylic acid). We conclude that treatment with mesalazine does not constitute a hazard to these patients in regard to prolonged bleeding time caused by an influence on platelet aggregation or fibrinolytic activity.

Adult↗
PubMed1987

Release of 5-aminosalicylic acid from Pentasa during normal and accelerated intestinal transit time.

The influence of intestinal transit time on the release of 5-aminosalicylic acid (5-ASA) from a peroral, slow-release preparation (Pentasa) was studied at steady state in seven healthy volunteers. Daily dose was 1500 mg Pentasa, normal transit time (NTT) was 24 h (16-26 h) and accelerated transit time (ATT), caused by a laxative, was 5 h (4-9 h). Median total recovery (24 h, 5-ASA + acetyl-5-ASA) was 87% (61-129%) (NTT) and 81% (56-100%) (ATT), respectively, (P greater than 0.10). The total faecal excretion of 5-ASA (per cent of dose) increased from 16%, (9-21%) (NTT) to 29%, (16-38%) (ATT) (P less than 0.02). Free 5-ASA rose from 12% (4-19%) to 17% (10-25%), the retained part (in granules) from 4% (2-5%) to 12% (4-24%). Urinary excretion decreased correspondingly from 32% (19-59%) to 21% (11-38%), predominantly as Ac-5-ASA (P less than 0.05). Mean plasma Ac-5-ASA concentration decreased from 1.42 micrograms ml-1 to 0.86 microgram ml-1 (P less than 0.05). An almost complete release of 5-ASA from Pentasa takes place during NTT. At ATT conditions about 88% is released, indicating Pentasa to be an acceptable source of 5-ASA in diarrhoeal states.

Adult↗
PubMed1987

Salazosulfapyridine and metabolites in fetal and maternal body fluids with special reference to 5-aminosalicylic acid.

In 7 pregnant women, treated prophylactically with salazosulfapyridine (SASP) 3 g/day, amniotic fluid (16th week, n = 4, maternal and cord plasma (n = 5) and breast milk (n = 3) were analysed for SASP and the metabolites sulfapyridine (SP), acetyl sulfapyridine (Ac-SP), 5-aminosalicylic acid (5-ASA) and acetyl 5-aminosalicylic acid (Ac-5-ASA). Amniotic fluid contained concentrations of SASP, SP and Ac-SP and partly also Ac-5-ASA comparable to those previously found by others, whereas 5-ASA concentrations were very low. The ratios of maternal to cord plasma for all SASP metabolites were about 1:1-1:2, except for 5-ASA, cord plasma being extremely low. In breast milk, only traces of 5-ASA were detected, while Ac-5-ASA was above the plasma level. Only negligible amounts of 5-ASA are thus transferred to the fetus/newborn, which is of significance for the future use of the new non-sulfa-containing 5-ASA preparations during and after pregnancy.

Adult↗
PubMed1986

5-Aminosalicylic acid in patients with an ileo-rectal anastomosis. A comparison of the fate of sulfasalazine and Pentasa.

The pharmacokinetics of 5-aminosalicylic acid (5-ASA) from sulphasalazine (SASP) and the slow-release 5-ASA preparation Pentasa was investigated in a cross-over study in 9 otherwise healthy patients with an ileo-rectal anastomosis. The 24-hour recoveries of the drugs were 90.5% and 84.7%, respectively. The median release of 5-ASA from SASP was 50% and from Pentasa 75%. Equal amounts of 5-ASA (18.0% vs 17.9%) were found in the faeces, and a significantly larger amount (4.4% vs 28.9%) of the metabolite N-acetyl-5-aminosalicylic acid (ac-5-ASA) was found in faeces following Pentasa. A larger amount of 5-ASA was absorbed and subsequently excreted in the urine, mainly as the metabolite (2.5% vs 20.5%) from Pentasa. This confirms previous results in ileostomized patients treated with Pentasa. The present findings also demonstrate that bacterial azo-reduction of SASP in patients with ileorectal anastomosis may be an adequate way to deliver 5-ASA in this type of patient. Both treatments may be used in these patients during a flare up of ulcerative colitis, but randomized studies are needed.

Aminosalicylic Acids↗
PubMed1986

Steady-state kinetics of 5-aminosalicylic acid and sulfapyridine during sulfasalazine prophylaxis in ulcerative colitis.

Fifteen adult and 19 pediatric outpatients with ulcerative colitis were studied to determine the steady-state kinetics of 5-aminosalicylic acid (5-ASA) released from salazosulfapyridine (SASP). Results of excretion in adults (mean 24-h recovery of 5-ASA, 21% in urine and 57% in feces) were compatible with those of healthy volunteers. Since mean SASP dose/kg body weight (about 50 mg/kg) and compliance (reflected in sulfapyridine recovery) were equal in adults and pediatric patients, the results of the patient groups could be compared. Near-complete azo reduction of SASP occurs in children. Absorption and excretion of 5-ASA and metabolism to acetyl-5-ASA did not differ statistically between pediatric and adult patients. However, the fecal excretion of the drug and its metabolites was significantly lower in young patients, although fecal concentrations were the same. The present results demonstrate that SASP is an excellent sustained-release drug for the delivery of 5-ASA to the lower part of the bowel system and provide a reference for comparison of 5-ASA kinetics after treatment with newer 5-ASA preparations.

Adolescent↗
PubMed1985

Plasma secretin in response to pure bile salts and endogenous bile in man.

The effect of exogenous bile salts on plasma concentrations of secretin was studied by infusion of chenodeoxycholate, cholate, glycocholate, and taurocholate into the duodenum of normal subjects. The effect of endogenous bile on plasma secretin was studied by ingestion of a liquid test meal, by reinfusion of postprandial duodenal aspirates with known contents of bile salts, and by stimulation of gallbladder contraction by cholecystokinin. Each experiment was performed in groups of seven subjects. The relative secretin-releasing potencies of glycocholate, cholate, taurocholate and chenodeoxycholate (2.25 mmol) were 1.0:1.3:1.9:3.2. Hydrochloric acid (0.5 mmol) was, on a molar basis, approximately ten times more potent than sodium cholate. The effect of taurocholate was diminished when a liquid meal was used as vehicle instead of saline. Endogenous bile did, in no circumstance, elicit release of secretin. It is concluded that although bile salts have the ability to stimulate secretin release, endogenous secretin release is of minor, if any, importance for secretin release when physiological conditions are approached.

Bile↗
PubMed1984

5-Aminosalicylic acid enemas in patients with active ulcerative colitis. Influence of acidity on the kinetic pattern.

Enemas containing 1000 mg 5-ASA were administered to patients with active distal colitis in three separate studies: as a single dose in a neutral solution (pH 7.4); as a single dose in a slightly acidic, buffered suspension (pH 4.8); and as multiple doses once a day for 10 days with the acidic enema. 5-ASA was relatively rapidly absorbed from the neutral solution, resulting in plasma concentrations of 5-ASA sometimes two to three times higher than those found after peroral salazosulphapyridine (SASP) treatment. In contrast, absorption from the acidic enema was reduced and/or prolonged, giving plasma concentrations similar to those found during oral SASP treatment. After repeated doses of the acidic enema, plasma concentrations after an enema resembled those seen after the single dose. Urinary excretion was significantly lower, suggesting a reduced fraction of absorption at steady-state conditions. No side effects were observed, and no local irritation was reported. An acidic buffer suspension with 5-ASA seems to be safe for use as enema and deserves further clinical testing for treatment of distal ulcerative colitis.

Adolescent↗
PubMed1984

Pregnancy in Crohn's disease.

Over a 13-year period, the course of 109 pregnancies in 68 women with Crohn's disease was studied. A total of 76 children were delivered. There were no gemellary deliveries, and none of the children had congenital malformations. Pregnancy entailed no increased risk of an exacerbation of the bowel disease. As compared with the reference population and with women with ulcerative colitis, the total material showed an increased risk of premature delivery and spontaneous abortion, but a further analysis showed that this was due only to an increased risk in women with active disease at the time of conception and in women who had undergone bowel resection during pregnancy. Birth weight and birth length corresponded to those in the reference population. The frequency of neonatal hyperbilirubinaemia was not higher in children of mothers with Crohn's disease than in children of healthy mothers. Treatment with sulphasalazine, salazosulphadimidine, and corticosteroids did not influence the course of pregnancy or the frequency of neonatal jaundice or malformations. Consequently, in Crohn's disease a pregnant woman should be given the same medical treatment as when not pregnant. Generally, the women should be advised preferably to conceive at a time when their bowel disease is inactive. The risk groups should be followed up with frequent obstetrical examinations throughout pregnancy.

Abortion, Spontaneous↗