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Biomedical subjects

M Johansen

Publications and source records attributed to M Johansen.

At least 19 recordsLinked to original sources
PubMed1994

Severe chronic inflammation of the mucous membranes in the eyes and upper respiratory tract due to work-related exposure to hexavalent chromium.

Chronic inflammation of the skin and mucous membranes following prolonged exposure to high doses of toxic hexavalent chromium is well known in the occupational medical literature. Perforation of the nasal septum is a cardinal clinical feature. Late development of cancer in the respiratory system is established. A recently diagnosed case with an unusually severe affect on the eyes is described. The industrial usage of chromium and its toxicological profile is reviewed.

Aged↗
PubMed1992

Column-switching high-performance liquid chromatographic detection of pholcodine and its metabolites in urine with fluorescence and electrochemical detection.

A sensitive and selective method for the detection of pholcodine and its metabolite morphine in urine using high-performance liquid chromatography is described. It involves on-line clean-up of urine on a trace enrichment column packed with a polymeric strong cation-exchange material. Pholcodine and its metabolites were separated on two analytical columns with different selectivities. Pholcodine was detected by a fluorescence detector and morphine was detected electrochemically. One system, based on reversed-phase chromatography, applied a polystyrene-divinylbenzene column and gradient elution. The other system was based on normal-phase chromatography with a silica column and isocratic elution. Morphine was confirmed to be a metabolite of pholcodine by reversed-phase chromatography and electrochemical detection. Two unidentified metabolites of pholcodine were separated from pholcodine by normal-phase chromatography and detected by fluorescence detection.

Antitussive Agents↗
PubMed1992

Macromolecular prodrugs. XX. Factors influencing model dextranase-mediated depolymerization of dextran derivatives in vitro.

Endo-dextranase-mediated depolymerization of dextran and dextran derivatives under various experimental conditions in vitro was determined. By a simultaneous determination of Mn and MW of dextrans treated with the enzyme in aqueous buffer, an initial increase of the polydispersity of the polysaccharide sample was observed, indicating that dextranase cleaved the dextran molecules into chains which differed significantly in length. A pH optimum of 5 for the enzyme action was found. However, in the pH range 5-8, which prevails in the colon, the initial depolymerization rates differed by a factor of less than 2. Dextranase treatment of a dextran sample resulted in a constant increase of the concentration of terminal reducing glucose residues per time unit suggesting, that the initial depolymerization reaction followed zero-order kinetics. For degrees of substitution below 12 the efficacy of dextranase fragmentation of dextran conjugates decreased almost linearly with increasing DS. The chemical nature of the attached drug did not significantly affect the depolymerization rates. Maximally depolymerized dextran derivatives were obtained by the combined action of dextranase and various alpha-glucosidases. Treatment of such solutions with: a) model esterases b) 80% plasma and c) 20% liver homogenate did not give rise to an acceleration of the initial drug regeneration, as compared to identical experiments carried out in pure buffer solution (pH 7.4 and 37 degrees C).

Animals↗
PubMed1991

[Attitudes and knowledge among parents who do not want their children to be vaccinated against measles, mumps and rubella (MFR-vaccination)].

In a questionnaire investigation concerning attitudes to and knowledge about MFR vaccination among 81 parents who did not want their children to be vaccinated against measles, mumps and German measles, the parents could be divided into two main groups with reasons formulated in advance: 41% stated that "infectious diseases are beneficial for children" including here their somatic and mental development and the parent-child relationship. The remaining parents based their attitudes on defective knowledge about MFR vaccination, fear of side effects, erroneous contraindications and attitudes such as: the MFR diseases are not serious and vaccination may cause serious disease, does not protect effectively or lowers the resistance of the population and that economy is a poor argument in favour of vaccination. Parents who were critical about the total information concerning the MFR programme were also more critical about their general practitioner than the remaining parents. 80% stated that the MFR programme had been introduced because it involved social economy while 56% thought that health benefits were the reason. It is concluded that further well-directed information about the MFR programme is essential, if the necessary vaccine coverage is to be obtained.

Child↗
PubMed1991

[Attitudes to and knowledge of contraindications against measles, mumps and rubella vaccination. (MFR-vaccination) among general practitioners].

A questionnaire investigation among general practitioners revealed that 29% of these were less positive about vaccination for measles, mumps and German measles (MFR vaccination) than for the remainder of the vaccination programme for children. Knowledge about contraindications for MFR vaccination was incomplete. Thus, only 26% of the general practitioners would advise vaccination if the parents stated that the child was hypersensitive to eggs. Only 70-80% of the general practitioners would advise vaccination if the child had cystic fibrosis, hydrocephalus, ventricle septum defect or had a cold but was apyrexial. Conversely, only 74% and 81% replied negatively to recommend vaccination if the child had had a previous anaphylactic reaction to eggs or was receiving treatment for leukemia. The replies given by the general practitioners were compared with present guidelines for contraindications to MFR vaccination and it is concluded that general practitioners should become more familiar with the knowledge about the MFR programme available at present and that further information from the official health authorities is required.

Child↗
PubMed1991

Metabolic study of pholcodine in urine using enzyme multiplied immunoassay technique (EMIT) and capillary gas chromatography.

A study of pholcodine metabolism in man is reported. Three subjects received a single therapeutic oral dose of 50 mg pholcodine and urine samples were collected as long as a positive opiate response could be detected by EMIT (16-26 days). Pholcodine was found to conjugate with glucuronic acid and 15% (13-17%) of the pholcodine dose was excreted in urine as the glucuronide, and 29% (24-35%) as unconjugated pholcodine. Morphine was detected to be a metabolite of pholcodine and 0.5-1% of the pholcodine dose was excreted as morphine glucuronide. The identity of morphine was confirmed by capillary gas chromatography-mass spectroscopy (GC-MS).

Adult↗
PubMed1990

Determination of pholcodine and its metabolites in urine by capillary gas chromatography.

A sensitive and selective method for the determination of pholcodine and its metabolites in urine using capillary gas chromatography with nitrogen detection is described. The procedure includes enzymatic hydrolysis of urine by beta-glucuronidase and sample pretreatment on C2 solid-phase extraction columns. Validation of the method showed good sensitivity, precision and reproducibility. The method was useful for the study of pholcodine metabolism in man. Pholcodine was found to conjugate with glucuronic acid. Morphine was identified as a metabolite and another unidentified metabolite was also detected.

Chromatography, Gas↗
PubMed1990

[Perichondritis of the ear caused by acupuncture].

A case of perichondritis and necrosis of the cartilage of the outer ear after acupuncture of the ear is presented. Repeated cultures showed growth of Pseudomonas aeruginosa. Despite intensive antibiotic treatment and extensive surgical toilet, the patient developed a severely deformed outer ear.

Acupuncture Therapy↗
PubMed1989

High-performance size-exclusion chromatographic procedure for the determination of fluoresceinyl isothiocyanate dextrans of various molecular masses in biological media.

A high-performance size-exclusion chromatographic procedure, using Nucleosil Diol, for the quantitative analysis of fluoresceinyl isothiocyanate dextrans of various molecular masses (10,000-150,000) in biological media was developed. The influence of the molecular mass and the degree of substitution of the conjugates on the chromatographic behaviour are discussed. In addition to quantitation, the molecular mass of the conjugates with degree of substitution below 1.6 could be estimated from the chromatograms. Linear standard calibration curves were obtained at concentrations down to 0.050 micrograms ml-1 in rabbit plasma and urine and homogenates of rabbit liver, lymph node and muscle when the derivative (degree of substitution 0.85) was monitored by fluorescence detection (lambda ex = 493 nm, lambda em = 520 mm). The fluoresceinyl isothiocyanate dextrans were found to be stable for more than three days at 37 degrees in all biological media under investigation. A pH-rate profile for the alkaline hydrolysis of fluoresceinyl isothiocyanate dextrans was constructed. The applicability of the method to pharmacokinetic studies was demonstrated by recording the plasma concentration-time profile of a fluoresceinyl isothiocyanate dextran T-70 conjugate following intravenous injection to a rabbit. In relation to future pharmacokinetic investigations on dextran conjugates, the results reported indicate that labelling of the parent dextran with fluoresceinyl isothiocyanate and monitoring of the fluoresceinyl isothiocyanate dextran conjugate throughout the organism using the described method is a promising development.

Animals↗
PubMed1989

Macromolecular prodrugs. XVI. Colon-targeted delivery--comparison of the rate of release of naproxen from dextran ester prodrugs in homogenates of various segments of the pig gastrointestinal (GI) tract.

We have determined initial rates of naproxen formation from dextran-naproxen ester prodrugs incubated in homogenates of various segments of the pig GI tract. Drug liberation proceeded 15-17 times faster in cecum and colon homogenates than in aqueous pH 7.4 buffer or homogenates of the small intestine. The degree of conjugate substitution did not affect the liberation rates, whereas enhanced drug activation was observed with decreasing molecular size of the carrier dextran. During incubation in colon homogenates the average molecular weight of the dextran prodrugs decreased. The mechanism of drug activation from the prodrugs may therefore involve an initial depolymerization step of the dextran chains by dextranases secreted from bacteria in the pig colon. The generated small fragments then serve as substrates for esterases and other hydrolases.

Animals↗
PubMed1989

Macromolecular prodrugs. XV. Colon-targeted delivery--bioavailability of naproxen from orally administered dextran-naproxen ester prodrugs varying in molecular size in the pig.

The bioavailability of naproxen after oral administration of aqueous solutions of various dextran-naproxen ester prodrugs in pigs was determined. The dextran prodrugs employed ranged in molecular weight from 10,000 to 500,000. As calculated relative to an equivalent oral dose of parent naproxen, the absorption fractions of all the derivatives were close to 100%. Only small interindividual variation of naproxen bioavailability was observed. The naproxen plasma profiles for all the administered prodrugs exhibited a characteristic lag time of naproxen appearance in the blood (2-3 hr). Compared to administration of the prodrugs alone, coadministration of excess of the parent dextran further delayed the absorption of naproxen from the GI tract. The results of the present study demonstrate the potential of dextran prodrugs for colon site-specific delivery of drugs containing a carboxylic acid functional group.

Administration, Oral↗
PubMed1987

Macromolecular prodrugs. V. Simultaneous determination of high-molecular-weight dextran metronidazole monosuccinate ester prodrugs and the hydrolysis products metronidazole and the corresponding monosuccinate ester on nucleosil diol.

A high-performance size-exclusion chromatography procedure using Nucleosil Diol has been developed which provides the simultaneous determination of macromolecular dextran metronidazole monosuccinate ester prodrugs and the hydrolysis products metronidazole and metronidazole monosuccinate. Various factors influencing the chromatographic behaviour of the compounds are discussed. Baseline separation of the three substances was achieved within 8 min by using a 0.05 M phosphate buffer pH 7.5 eluent at a flow-rate of 2 ml min-1. The detection limit at 320 nm for a conjugate with a degree of substitution of 4.61 was found to be 3.5 micrograms ml-1.

Chromatography, Gel↗
PubMed1983

Prodrugs as drug delivery systems XXV: Hydrolysis of oxazolidines--a potential new prodrug type.

The hydrolysis kinetics of several oxazolidines derived from (-)-ephedrine and various aldehydes and ketones were studied to assess their suitability as prodrug forms for beta-amino alcohols and/or carbonyl-containing compounds. The oxazolidines were found to undergo a facile and complete hydrolysis in the pH range of 1-11 at 37 degrees. The hydrolysis rates were subject to general acid-base catalysis by buffer substances and depended strongly on pH. Most oxazolidines showed sigmoidal pH-rate profiles with maximum rates at pH greater than 7-7.5. At pH 7.40 and 37 degrees the following half-lives of hydrolysis for the various ephedrine oxazolidines were found: 5 sec (formaldehyde), 18 sec (propionaldehyde), 5 min (benzaldehyde), 5 sec (salicylaldehyde), 30 min (pivalaldehyde), 4 min (acetone), and 6 min (cyclohexanone). The reaction rates in neutral and basic solutions were shown to decrease with increasing steric effects of the substituents derived from the carbonyl component and to decrease with increasing basicity of the oxazolidines. The oxazolidines are weaker bases (pKa 5.2-6.9) than the parent beta-amino alcohol and more lipophilic at physiological pH. It is suggested that oxazolidines can be considered as potentially useful prodrug candidates for drugs containing a beta-amino alcohol moiety or carbonyl groups.

Buffers↗