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Biomedical subjects

S H Hansen

Publications and source records attributed to S H Hansen.

At least 127 records · Page 7Linked to original sources
PubMed1985

Increased hepatic microsomal enzyme activity after surgery under halothane or spinal anesthesia.

Thirty-two fit patients scheduled for explorative arthrotomy of the knee were allocated randomly to either halothane/oxygen anesthesia or spinal anesthesia with bupivacaine 0.25 mg X kg-1. The day before and 1, 10, and 21 days after surgery, the aminopyrine breath test (ABT) was performed. The day before and 5, 10, and 21 days after surgery, the antipyrine clearance (APcl) was measured by the single sample saliva technique. The ABT as well as the APcl were increased significantly postoperatively (P less than 0.01). The day after surgery the ABT was increased by 13 +/- 21% in the spinal anesthesia group only, whereas a late increase by 14 +/- 31% was found in the halothane group. Five days after surgery, the APcl was increased by 36 +/- 45% in the spinal anesthesia group and by 21 +/- 28% in the halothane group. Both tests returned to base line values within 3 weeks postoperatively. In five volunteers following the same sampling scheme but receiving bupivacaine 0.25 mg X kg-1 im without surgery, no change in the ABT or the APcl was observed. The authors conclude that surgery may cause microsomal enzyme induction regardless of the anesthetic agent or technique used. The mechanism of this induction remains to be elucidated.

Adolescent↗
PubMed1985

Excitatory amino acids: studies on the biochemical and chemical stability of ibotenic acid and related compounds.

The complex pharmacological profile (excitation/inhibition) of ibotenic acid on single neurons in the mammalian CNS prompted studies on the stability of ibotenic acid and a number of structurally related excitatory amino acids under different in vitro conditions in the presence or absence of enzymes. Ibotenic acid, (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HPCA), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and (RS)-alpha-amino-3-hydroxy-4-bromo-5-isoxazolepropionic acid (4-Br-homoibotenic acid) were all inhibitors of (S)-glutamic acid decarboxylase (GAD) in mouse brain homogenates, but only ibotenic acid was shown to undergo decarboxylation during incubation with brain homogenates. The formation of the decarboxylated product, muscimol, which primarily occurred in a synaptosomal fraction, was dependent on the presence of pyridoxal-5-phosphate (PALP) and was inhibited by (S)-glutamic acid, 3-mercaptopropionic acid (3MPA), aminooxyacetic acid (AOAA), and allyglycine, suggesting that ibotenic acid is a substrate for GAD. The overall decomposition rate for ibotenic acid (8.7 nmol min-1 mg-1 of protein), which apparently embraces other reactions in addition to decarboxylation to muscimol, was higher than the rate of decarboxylation of (S)-glutamic acid (3.2 nmol min-1 mg-1 of protein). At pH 7.4 and 37 degrees C, but in the absence of enzymes, none of the excitatory amino acids under study underwent any detectable decomposition, whereas ibotenic acid and 7-HPCA, but not AMPA and 4-Br-homoibotenic acid, decomposed, partially by decarboxylation, at 100 degrees C in a pH-dependent manner. In the presence of liver homogenates, ibotenic acid was also shown to decompose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effect of ethanol, cimetidine and propranolol on toluene metabolism in man.

In a climatic exposure chamber four healthy volunteers were exposed to 100ppm toluene, 100ppm toluene + ethanol, 100ppm toluene + cimetidine, and 100ppm toluene + propranolol for 7h each at random over four consecutive days. A control experiment and 3.5h of exposure to 200ppm toluene were also performed. Ethanol inhibited toluene metabolism by 0.5 as expressed by the urinary excretion of two of the metabolites of toluene, namely o-cresol and hippuric acid. In agreement with this, the mean alveolar concentration of toluene was greater by 1.7 during ethanol exposure; 45 min after discontinuation of exposure the increase was by 3.3. Neither cimetidine nor propranolol changed toluene metabolism significantly. The results indicate that ethanol may prolong the time interval in which toluene is retained in the human body in persons simultaneously exposed to ethanol and toluene. When using o-cresol or hippuric acid in biological monitoring of persons occupationally exposed to toluene, the consumption of ethanol should be considered.

Adult↗
PubMed1984

Dynamically-modified silica--an alternative to reversed-phase high-performance liquid chromatography on chemically bonded phases.

An alternative to the well known reversed-phase separations on chemically-bonded phases has been developed. The approach is based on a dynamic modification of bare silica with long chain quaternary ammonium ions. The influence of the concentration and type of the quaternary ammonium ion, the pH value and the ionic strength of the eluent on the selectivity towards test solutes has been investigated. The large number of parameters that can be varied in the system offers numerous possibilities by which the desired selectivity can be attained. Once established, a high degree of reproducibility of the selectivity between solutes is obtained even when using different brands of silica; this is in contrast to the situation when using chemically-bonded phases, such as, for example, different brands of octadecylsilyl-bonded silica materials.

Journal Article↗
PubMed1984

Hepatic drug metabolism and physical fitness.

Physical fitness, as expressed by maximal oxygen uptake (Vo2max), was measured in 14 subjects before and during physical education consisting of 4 to 8 hr of daily physical training. Mean pulse rate during training was 115 bpm. After 3 mo of physical training, Vo2max increased a mean 6% (range -5% to +23%). Corresponding mean increases in hepatic drug metabolism, as expressed by the metabolism of the model drugs antipyrine and aminopyrine, were 12% (range -12% to +59%) and 13% (range -21% to +47%). Changes in the two groups were still present 6 mo after physical education. There was only a moderately close but nonetheless significant correlation (r = 0.7) between the extent of change in Vo2max and the corresponding relative change in antipyrine metabolism during the 3-mo period of this investigation. The correlation between oxygen uptake and aminopyrine metabolism (r = 0.6) was slightly less and was not significant. Improved physical fitness associated with enhanced drug metabolism may lead to changes in drug efficacy and drug toxicity that may be clinically important in the case of drugs with low therapeutic indices.

Adult↗
PubMed1984

The prophylactic effect of 5-aminosalicylic acid and salazosulphapyridine on degraded-carrageenan-induced colitis in guinea pigs.

Experimental colitis was induced in guinea pigs by administration of 5% degraded carrageenan for 5 days. The prophylactic effect of a slow-release preparation of 5-aminosalicylic acid (5-ASA; 13 mg/100 g/day) was compared with approximately equimolar amounts of salazosulphapyridine (SASP; 26 mg/100 g/day) and placebo. Treatment was started 2 days before initiation of carrageenan administration. The drugs were administered through a chronic gastric fistula. At the end of the study concentrations of 5-ASA and acetylated 5-ASA (Ac-5-ASA) in cecal contents and in plasma were determined. In the placebo group, all guinea pigs developed many small punctiform ulcerations in the cecum (median, 30/cm2). In the 5-ASA group no protective effect was demonstrated, since the number of ulcerations was 37/cm2. The difference is not statistically significant. However, the SASP group presented significantly fewer ulcerations (4/cm2). The concentrations of 5-ASA and/or its acetylated metabolite were several times higher in the cecum content and twice as high in plasma in the SASP group, indicating a difference in the absorption patterns of 5-ASA and the two drugs. These results and the etiological difference between the human ulcerative colitis and the carrageenan model may account for the lack of prophylactic effect of the slow-release 5-ASA in this experiment.

Aminosalicylic Acids↗
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↗
PubMed1983

Urinary hippuric acid and orthocresol excretion in man during experimental exposure to toluene.

It is not known whether urinary excretion of hippuric acid (HA) or orthocresol (O-Cr) is to be preferred for the biological monitoring of workers with occupational exposure to toluene. To study this, 42 printing trade workers with more than 10 years' exposure to a mixture of organic solvents including toluene (0-20 ppm) and 43 control subjects matched by age, smoking habits, and living accommodation were investigated. Each matched pair was randomised to an experimental exposure of either 100 ppm or 0 ppm toluene for 6.5 hours under controlled conditions in an exposure chamber. Urinary excretion of HA and O-Cr was determined by high pressure liquid chromatography from samples obtained before exposure, during the first three hours, and during the last 3.5 hours of exposure. No difference in HA and O-Cr excretion was found between printing trade workers and controls. The median O-Cr excretion increased 29 times during exposure, whereas the HA excretion increased only five times. Thus only 3% of the O-Cr excretion originated from other sources than toluene whereas the corresponding value for HA was 19%. Standardisation of the concentrations of HA and O-Cr in relation to urinary creatinine reduced the relative variation by 29% and 56% respectively. This was not reduced further by expressing the excretions as average excretion rates based on total volume of urine collected. Background urinary O-Cr excretion was three to four times higher among smokers than non-smokers, probably due to the content of O-Cr in cigarettes. The O-Cr excretion in unexposed smokers was, however, 10 times lower that that of the non-smokers during the end of the experimental exposure to 100 ppm toluene.

Adult↗
PubMed1983

Treatment of Crohn's disease with peroral 5-aminosalicylic acid.

Eighteen patients with active Crohn's disease entered an open trial with 5-aminosalicylic acid in a slow-release preparation. All had lesions of the small bowel. Ten of them also had Crohn's disease of the colon. 5-Aminosalicylic acid, 500 mg three times daily, was administered for 6 wk. Even with meticulous monitoring, no side effects of any kind were observed, particularly no cases of renal affection, which could have been expected from animal studies. The clinical course was estimated as improved in 13 patients (72%), unchanged in 2 patients (11%), and aggravated in 3 patients (17%); 2 of these 3 were withdrawn from the study and switched to alternative treatment. The Crohn's disease activity index decreased from a median of 226 points to 99 points. On the basis of these results, large-scale controlled therapeutic trails seem warranted in order to establish clinical evidence for the benefit of peroral treatment with 5-aminosalicylic acid in patients with Crohn's disease.

Administration, Oral↗
PubMed1982

Determination of urinary hippuric acid and o-cresol, as indices of toluene exposure, by liquid chromatography on dynamically modified silica.

Two simple and sensitive high-performance liquid chromatographic methods for the determination of hippuric acid and o-cresol in urine have been developed. The chromatographic system is the same for the two methods and is based on dynamically modified silica. The detection limits were found to be 0.05 mg/ml and 0.05 microgram/ml of urine for hippuric acid and o-cresol, respectively, when using UV detection at 254 nm. The recovery for hippuric acid was about 100% and for o-cresol 33-36%. The detection limit for o-cresol could be lowered by a factor of ten by using fluorescence detection. The methods were used for investigations of the urine from persons exposed to 100 ppm toluene for 6.5 h. The method for o-cresol may also be used for determination of other phenols in urine.

Age Factors↗
PubMed1982

Mutagenic action of methyl 2-cyanoacrylate vapor.

Alkyl 2-cyanoacrylate adhesives were tested for mutagenicity in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1538. Both a normal spot test and a spot test specially designed to test volatile compounds were used. The adhesives were also tested in the plate incorporation assay. These investigations showed that methyl 2-cyanoacrylate adhesives are mutagenic in strain TA100. The spot test for volatile compounds showed that it is the vapors from the methyl 2-cyanoacrylate monomer that are responsible for the mutagenic effect. One can conclude that working with methyl 2-cyanoacrylate adhesives entails exposure to vapors with a mutagenic effect and may therefore pose a carcinogenic hazard. Because the adhesives are used in industry, their mutagenic effect has a special importance in work environment.

Cyanoacrylates↗
PubMed1982

5-aminosalicylic acid in a slow-release preparation: bioavailability, plasma level, and excretion in humans.

The release pattern, bioavailability, and kinetics of a 5-aminosalicylic acid tablet with sustained release were studied in humans. Six ileostomy patients received a single dose (500 mg). Eight and 48 h later, respectively, 58% and 65% of the dose was recovered in the ileostomy effluents, either as 5-aminosalicylic acid still retained in the preparation, free 5-aminosalicylic acid or acetyl-5-aminosalicylic acid. Fourteen healthy volunteers took 1500 mg of 5-aminosalicylic acid per day for 6 days and a steady state plasma acetyl-5-aminosalicylic acid concentration was reached on day 5 (1.1-2.9 microgram/ml). 5-Aminosalicylic acid was not detected in the plasma. At steady state, 40% of the 24-h dose was recovered from feces, and 53% from the urine. The sustained-release preparation studied provides sufficient amounts of 5-aminosalicylic acid to all parts of the gut and its curative effect in ulcerative colitis and Crohn's disease should be examined in controlled trials.

Adult↗