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S N Rasmussen

Publications and source records attributed to S N Rasmussen.

At least 91 records · Page 5Linked to original sources
PubMed1988

Diagnostic value of ascitic fluid cholesterol levels in the prediction of malignancy.

In a prospective study abdominal paracentesis with ascitic fluid aspiration was performed in 54 consecutive patients with ascites of unknown cause. The ascitic fluid was examined cytologically and bacteriologically. The total cholesterol concentration was measured with an enzymatic colorimetric method. Malignant disease was diagnosed in 34 patients. Two of them had both malignant disease and liver cirrhosis and were excluded. Seventeen patients had liver cirrhosis, one had acute pancreatitis, and two had decompensated heart disease. The diagnostic value of an ascitic cholesterol concentration greater than 1.2 mmol/l in terms of predicting malignant disease was 87.5% (95% confidence limits, 71.0-96.5). The predictive value of an ascitic cholesterol concentration less than or equal to 1.2 mmol/l in terms of benign disease was 80.0% (95% confidence limits, 56.3-94.3). It is concluded that ascitic cholesterol measurement is a valuable supplement to cytologic examination in distinguishing between ascites of malignant and benign origin.

Adult↗
PubMed1988

Pharmacokinetics of doxorubicin in man with induced acid or alkaline urine.

The common side effects of doxorubicin (DOX) treatment, i.e. vomiting and diarrhoea, would be expected to alter the pharmacokinetics of DOX in man, the efficacy of treatment, and further aggravate the side effects through acid/base disturbances. The pharmacokinetics were therefore investigated in 4 anthracycline naive females with advanced mammary carcinoma in 2 series of DOX monotherapy 70 mg/m2 administered with an interval of 4 weeks between the treatments. Sequential loading either with acid or base was instituted 2 days before and continued for 2 days after DOX infusion. Median urine pH was 5.0 or 8.0, and median arterial blood pH 7.30 or 7.43 respectively. Plasma and urine samples were analyzed by high performance liquid chromatography (HPLC). No difference was seen between the acid and alkaline condition for DOX or doxorubicinol with regard to clearance from blood plasma, area under the curve, renal clearance, renal drug clearance/renal creatinine clearance. Thus moderate acid/base metabolic disturbances did not alter the pharmacokinetics of DOX up to 48 h after DOX infusion.

Acid-Base Equilibrium↗
PubMed1988

Phase I study of 4-demethoxydaunorubicin by oral route in patients with advanced cancer.

In a phase I trial 4-demethoxydaunorubicin (4-dm DNR) was administered as oral capsules once a week to 51 adults with advanced mainly gastrointestinal solid tumors. No fatal toxicity was observed at doses up to 25.0 mg/m2. Dose-limiting granulocytopenia and non-hematologic toxicity developed at dosages greater than or equal to 22.5 mg/m2. No response to the therapy was observed. The plasma concentrations of 4-dm DNR were measured in 4 of the patients.

Administration, Oral↗
PubMed1987

Comparative responsiveness and pharmacokinetics of doxorubicin in human tumor xenografts.

The antineoplastic activity of the anthracycline antibiotic doxorubicin (Adriamycin) differs in its cytotoxic effectiveness against different types of human tumors. In the present study the effect of doxorubicin on the growth of two human lung carcinomas and one human mammary carcinoma transplanted into athymic mice was correlated with the pharmacokinetics of doxorubicin in the same tumors after intraperitoneal administration. Doxorubicin produced a greater inhibition of tumor growth in the lung carcinomas than in the mammary carcinoma. Furthermore, the pharmacokinetic characteristics of doxorubicin differed widely within the three human solid tumors. No apparent correlation was found to exist between the different tumor growth sensitivities to doxorubicin and the pharmacokinetic parameters of doxorubicin within the tumor tissue. It is suggested that the differences in the demonstrated antitumor effectiveness of doxorubicin may be due to differences in the "intrinsic sensitivity" of the three human solid tumors.

Animals↗
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

Randomised study of the influence of non-steroidal anti-inflammatory drugs on the treatment of peptic ulcer in patients with rheumatic disease.

Sixty-seven patients with rheumatic disease, treated with non-steroidal anti-inflammatory drugs (NSAIDs), entered a controlled trial with a diagnosis of duodenal (n = 51), gastric (n = 14), or gastric and duodenal (n = 2) ulcers. The main objectives of the study were a comparison of ranitidine and sucralfate in ulcer treatment, and to observe the influence of continued NSAID administration during peptic ulcer therapy. Ulcers healed within nine weeks in 52 patients. The mean healing time was similar in 27 patients given ranitidine 150 mg bd (4.9 weeks) and 25 patients given sucralfate 1 g qid (4.6 weeks). In patients with unhealed ulcers after nine weeks of treatment, healing was obtained in seven after further therapy for 3-9 weeks. Of the 30 patients who continued NSAIDs during treatment with either ranitidine or sucralfate, 23 ulcers healed (mean healing time: 5.0 weeks). Of 32 patients in whom NSAIDs were stopped, ulcer healing was documented in 29 (mean healing time: 4.6 weeks). The difference in healing rates was not statistically significant (p greater than 0.10). The outcome of ulcer treatment did not differ in patients with rheumatoid arthritis and patients suffering from osteoarthritis. During a 12 month follow up 14 symptomatic ulcer recurrences were recorded.

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↗
PubMed1987

5-Aminosalicylic acid in the treatment of Crohn's disease. A 16-week double-blind, placebo-controlled, multicentre study with Pentasa.

The response to 5-aminosalicylic acid (5-ASA) in mild and moderately active Crohn's disease localized in the small bowel was studied in a randomized, double-blind, placebo-controlled trial in four centres. Sixty-seven patients were included, of whom 30 were treated with 1500 mg slow-release 5-ASA/day (Pentasa) for a scheduled period of 16 weeks. In the 5-ASA group 40% of the patients improved, versus 30% of the placebo-treated group ('intent to treat' basis; p greater than 0.1). Four of the patients treated with 5-ASA left the study owing to disease deterioration, versus 10 of the placebo-treated patients (p greater than 0.2). Seventeen patients were secondarily excluded, and the remaining 50 patients (23 receiving 5-ASA) were reevaluated in greater detail. No statistically significant differences in outcome were shown. Three patients (one given 5-ASA) were withdrawn from the study because of presumed side effects, but no serious adverse reactions were recorded. The present results indicate that 5-ASA, at least in the dosage used, is not superior to placebo. Nevertheless, trends towards a beneficial effect in Crohn's disease in the small bowel justify further clinical trials with a larger dosage of 5-ASA.

Adolescent↗
PubMed1986

The colostomy plug: a new disposable device for a continent colostomy.

A new disposable device for colostomy control is described. It is a two-piece system consisting of an adhesive base plate and a disposable colostomy plug, attachable to the plate. The plug is made of a soft, pliable plastic material with open cells, containing a carbon filter which allows flatus to pass odour-free. It is packed and compressed in a water-soluble film, which disintegrates immediately after insertion, allowing the plug to expand and prevent the passage of faeces. The device has been tested in 53 patients. Faecal continence and the passage of flatus without noise or odour was achieved in 90%. The median application period until the plug became obstructed with mucus or faeces was 8 h (range 5-24 h or more), the application period being somewhat longer for patients who used bowel irrigation. Patients not using bowel irrigation applied a colostomy bag during the night.

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

The pharmacokinetics and protein binding of disopyramide in pigs.

The pharmacokinetics of disopyramide were investigated in 5 pigs. Disopyramide was administered as intravenous bolus injections at different doses and as intravenous infusions at different rates. By measuring the free and total concentrations in plasma of parent compound and desisopropyldisopyramide (the main metabolite in humans) and the amounts excreted in urine it was found that disopyramide had a concentration dependent protein binding and that free and total concentrations could be described by a two-compartment model with a t1/2, beta of approximately 2 hours. The free concentrations were found to be more valuable for estimating the kinetic parameters. The total clearance of disopyramide in the pig was found to approximately 3 ml/min./kg which is about 3 times greater than in man. In contrast to humans the free clearance in the pig increased with declining concentration. Apart from this the kinetics of disopyramide in the pig were very similar to those in man. In conclusion the pig could be a relevant model for studying the pharmacokinetics in humans.

Animals↗
PubMed1986

Medroxyprogesterone acetate pharmacokinetics following oral high-dose administration in humans: a bioavailability evaluation of a new MPA tablet formulation.

The pharmacokinetics of medroxyprogesterone acetate (MPA) in healthy female volunteers have been investigated following oral administration of single doses of six different high-dose MPA tablet formulations. Blood samples were obtained over 96 hrs following administration. The plasma was separated and analyzed in duplicate for MPA by radioimmunoassay (RIA) after extraction with petroleum ether. A two compartment open model with first order absorption was computer-fitted to the plasma concentration of MPA. Following oral administration MPA is rapidly transferred from the gastrointestinal tract to the blood circulation with a half-life of the absorption process of 15-30 min. The peak plasma concentration is reached 1-3 hrs after administration, and the biological half-life of MPA is 40-60 hrs. Following administration of 1000 mg MPA the areas under the plasma concentration-time curves (AUC 0-infinity) were calculated to (mean and S.E.): 3357 (438) nmol/l and 2403 (245) nmol/l for Leo formulation A and Farlutal, respectively (P less than 0.02). Following administration of 500 mg the areas were: 2325 (389) nmol/l, 1793 (312) nmol/l, 1778 (239) nmol/l, 1178 (209) nmol/l, and 556 (89) nmol/l for Gestapuran, Leo formulation A (P = n.s.), Leo formulation B (P = n.s.), Provera (P less than 0.001), and Lutopolar (P less than 0.001), respectively. The in vitro dissolution rates of MPA from the tablet formulations were determined and compared with the results of the bioavailability studies, indicating that a rapid dissolution rate as well as the particle size of MPA are two important factors to ensure optimal absorption of MPA from the gastrointestinal tract.

Administration, Oral↗
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

[Acute proctitis].

Explore the source record for details and available documents.

Acute Disease↗
PubMed1985

Single intravenous and oral doses of fenflumizole: pharmacokinetics and effects on prostanoid formation.

Fenflumizole is a substituted triaryl-imidazole with anti-inflammatory activity. Its disposition in man was studied after single intravenous and oral doses to 8 healthy male volunteers. Formation of the prostanoids thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha) in clotting blood was studied concomitantly. The pharmacokinetics after intravenous doses (0.1 mg/kg) could be fitted to a three compartment model and the half-lives (t 1/2) corresponding to the three phases were 2 min., 1 hour and 15 hours, respectively. The volume of distribution was 386 l and the plasma clearance 0.5 l per min. Oral doses (0.5 mg/kg) were rapidly absorbed (t 1/2 = 0.2 hr) and the following elimination from plasma had two phases with half-lives of 1 hour and 14 hours. Bioavailability was 50% due to a pronounced first-pass effect. The two metabolites mono- and didemethylfenflumizole were detected after both oral and intravenous doses and their maximum plasma concentrations occurred after 1-2 hours irrespective of the administration route. A concentration dependent depression of prostanoid formation was seen, the IC50 for TXB2 and 6-k-PGF1 alpha being 19 and 53 ng/ml respectively.

6-Ketoprostaglandin F1 alpha↗