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Biomedical subjects

P Hartvig

Publications and source records attributed to P Hartvig.

At least 163 records · Page 9Linked to original sources
PubMed1986

A Swedish county with unexpectedly high utilization of anti-parkinsonian drugs.

This report is based on the use of L-dopa-containing drugs within 24 Swedish counties in the period 1977-1984. The mean utilization of these drugs in Sweden in 1984 was 1.46 defined daily doses (DDD)/day X 10(3) inhabitants (inh). As Parkinson's disease is virtually the only condition for which these drugs are prescribed, it seems highly probable that the determining factor for their use today is the prevalence of the disease. The exceptionally high utilization (2.34 DDD/day X 10(3) inh) of L-dopa-containing drugs in the county of Gävleborg, warranted further analyses of subareas in this particular county. The use is discussed in relation to environmental factors.

Antiparkinson Agents↗
PubMed1986

Influence of monoamine oxidase inhibitors and a dopamine uptake blocker on the distribution of 11C-N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 11C-MPTP, in the head of the rhesus monkey.

N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP, is a neurotoxic substance known to induce a parkinsonian syndrome in primates. The distribution of intravenously injected 11C-labelled MPTP (11C-MPTP) in the head of Rhesus monkeys was studied by means of positron emission tomography, PET. The influence of pretreatment with two monoamine oxidase (MAO) inhibitors, namely pargyline and clorgyline, and a dopamine uptake blocker, nomifensine, on the distribution was also evaluated. The 11C-radioactivity was taken up in all brain regions and maximum radioactivities were found 3-8 min after intravenous administration of MPTP. The 11C-MPTP-derived radioactivity showed a constant value throughout the study period in areas corresponding to the striatum and mesencephalon in monkeys not pretreated and in monkeys pretreated with clorgyline and with nomifensine. Pargyline pretreatment, however, resulted in consecutive elimination of 11C-MPTP-derived radioactivity from the different brain regions with half-lives of 40-60 min. The total radioactivity in blood was also higher after pargyline pretreatment indicating successful inhibition of metabolism. The eyes and temporal muscle each showed radioactivity values of the same order in all monkeys irrespective of pretreatment. The results support findings by other authors that MPTP was rapidly converted in the brain to a reactive metabolite which concentration remained constant in the brain during the PET study. Pargyline in the dosage used is known to be a non-selective MAO inhibitor and it prevented the metabolism of 11C-MPTP to the products retained in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Cerebrospinal fluid and plasma concentrations of clonidine in pigs after epidural, intravenous and intramuscular administration.

Epidural clonidine is an alternate way to treat severe pain in man. The cerebrospinal fluid (CSF) and plasma concentrations resulting after epidural, intravenous (i.v.) or intramuscular (i.m.) clonidine, 3 ug/kg b.w. have been determined by a sensitive gas chromatographic method. A porcine model was used, where the epidural and intrathecal spaces were cannulated via the atlanto-occipital membrane. After epidural administration of clonidine the CSF concentrations were maximal 20 minutes after the injection, 129 +/- 24 ng/ml (mean +/- S.D.). Clonidine was eliminated from CSF with an apparent half-life of 26 +/- 8.2 minutes (mean +/- S.D.). The plasma concentrations stayed below 1 ng/ml. Low plasma and undetectable CSF concentrations resulted after i.v. clonidine. Thus, epidural clonidine readily penetrates the dura mater into the CSF, and there is a marked gradient between CSF and plasma.

Animals↗
PubMed1985

Childhood psychologic environmental exposure in women with diagnosed somatoform disorders. A case-control study.

Fifty-three female patients with diagnosed somatoform disorders (having pronounced somatic symptoms without objective somatic signs) were studied regarding childhood exposure to death, divorce, serious somatic illness and prolonged pain in members of their core family. Similar registrations were made in a control group of 53 healthy women. The two groups were compared using the case-control method. The results revealed a more frequent exposure in the somatoform disorder patients regarding all four items, and for serious somatic illness and prolonged pains the difference was statistically significant. Further elaboration of the data suggested that exposure to pain in the family was the most important of the studied factors. The findings are thought to demonstrate the environmental etiologic impact on somatoform disorders occasioned by such psychologic exposure as those registered. The possibility of a genetic etiologic implication of the findings is also discussed.

Adolescent↗
PubMed1985

Positron emission tomography in experimental perinatology.

Positron emission tomography (PET) is a new tracer technique by which short-lived radionuclides, such as 11C are used for labeling drugs, amino acids and other compounds. The concentration in the various organs is determined non-invasively after I.V. injection. Positrons, emitted by 11C attract an electron, and the two masses are annihilated by emitting photons. These can be registered by external detectors. Measurement of the radioactivity per volume of tissue as a function of time is accomplished by computerized processing of the data. The PET technique may be used for studies of the kinetics of the injected compound in different organs of the body. However, PET registers only the total radioactivity meaning that the measured 11C-radioactivity represents the sum of the parent compound and the radiolabelled metabolites. Chemical and radiochemical analyses in various body fluids may then help to interpret the PET images.

Animals↗
PubMed1984

Steady state pharmacokinetics of trimethoprim 300 mg once daily in healthy volunteers assessed by two independent methods.

The steady state pharmacokinetics of trimethoprim was determined after 300 mg orally once daily to 6 healthy volunteers for 9 days. The microbiological assay of plasma level was unreliable at trimethoprim concentrations greater than 4 micrograms/ml, so results from an HPLC-assay are given. Steady state was present after 3 days. The plasma concentration peaked 1 to 4 h (mean 2.0 h) after the dose at a mean of 6.0 micrograms/ml (range 3.1-9.5 micrograms/ml); the minimum value was 1.5 micrograms/ml (range 0.6-2.9 micrograms/ml). The mean AUCss was 77 micrograms/ml X h and the mean plasma clearances was 67 and 74 ml/min on Days 8 and 9. Renal clearance was about 60% of the plasma clearance. The average plasma half life was 10.6 h (range 8.7-15.3 h). Thus, there was considerable interindividual variation in all pharmacokinetic parameters. 72 h after the last dose trimethoprim was detectable in plasma in only 1 of the 6 subjects. The minimum urinary concentration of trimethoprim during treatment was always well above (range 22 to 220 micrograms/ml) the MIC values for most urinary tract pathogens. Therefore, a daily dose of 300 mg trimethoprim results in a therapeutic concentration in urine at steady state that lasts throughout the dosing interval and in most subjects probably lasts also for a further 24 h. Trimethoprim administration raised mean serum creatinine from 67 to 97 mumol/l, probably due to competitive inhibition of the tubular secretion of creatinine.

Adult↗
PubMed1984

Two-phase derivatization of pentazocine with chloroformate esters and determination by gas chromatography.

Two-phase derivatization with chloroformate esters of tertiary amines that contain a phenol group has been studied. The derivatives were analysed by gas chromatography with sensitive and selective detectors. The N,O-bis derivative of pentazocine was formed using an aqueous phase at pH 9.8, with tetrabutylammonium ion for extraction of the phenolate ion as an ion-pair. The organic phase comprised methylene chloride with trichloroethyl chloroformate or ethyl chloroformate. At pH 10.7 the derivative was hydrolysed by hydroxide ions extracted into the organic phase. Hydrolysis also occurred when more lipophilic counter-ions such as tetrapentyl-ammonium ions were used. Two-phase derivatization could also be achieved with toluene or ethyl acetate as the organic phase, although the reaction rate was considerably slower. The method was also applied to the assay of pentazocine in plasma. The best results were achieved after selective extraction of pentazocine from plasma, two-phase derivatization with ethyl chloroformate and determination by mass spectrometry or thermionic detection. The minimum detectable concentration of pentazocine was 10 ng/ml in a 1-ml plasma sample.

Journal Article↗
PubMed1984

Chemical principles of chelate therapy in neurotoxicology.

The chemical significance of heavy metals in biology arises from their ability to form bonds with metal-binding substances. These bonds are tighter than ordinary ionic bonds and partly of a covalent nature. Metal-binding substances, many of which act by complex formation, play an important role in the regulation of uptake into cells of trace heavy metals. In biology metal-binding substances predominantly act by: Removal of metal ions from cells, i.e. antidotes to mask or remove toxic metal ions that have accidentally been ingested. Imposition of the metal ion into cells in a concentration above normal, e.g. the mechanism of action of many bactericides and fungicides. The fundamental requirements concerning the complex formation capacity of the complexing agent, as well as the toxicity and pharmacokinetics of the complexing agent and complex must be considered before use in medicine as e.g. antidotes. Easily obtained excretion of the complexing agent as well as of the complex is essential to avoid unwanted side effects. The importance of this requirement is demonstrated by alternative treatment regimens in thallotoxicosis.

Chelating Agents↗
PubMed1984

Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard.

The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4-7.1) under fasting and 3.3 (range 1.3-7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.

Adult↗
PubMed1984

Kinetics of 11C-labeled opiates in the brain of rhesus monkeys.

The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appeared 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity.

Animals↗
PubMed1983

Simultaneous determination of ketobemidone and its N-demethylated metabolite in patient plasma samples by gas chromatography mass spectrometry with selected ion monitoring.

An analytical procedure has been developed for the simultaneous determination of ketobemidone and its N-demethylated metabolite, norketobemidone. After isolation from plasma and re-extraction to acidic aqueous phase, the two aminophenols were extracted as ions pairs with tetrabutylammonium to dichloromethane, where derivatization with ethyl chloroformate took place. Determination was performed by gas chromatography mass spectrometry with selected ion monitoring. Ketobemidone and norketobemidone could be detected in plasma in a concentration of 1 ng ml-1 and 3 ng ml-1, respectively. Determinations were performed down to 5 ng ml-1. The relative standard deviation of the method in the analysis of 10 ng ml-1 of ketobemidone and norketobemidone, respectively, was 8% and 9% (n=10). The absolute recovery of unconjugated ketobemidone and norketobemidone through the method at the 100 ng ml-1 level was 91% and 85%, respectively. The method was applied to the determination of ketobemidone and norketobemidone in plasma from patients given ketobemidone. The concentrations of unconjugated norketobemidone was too small to be detected.

Analgesics, Opioid↗
PubMed1983

Occupational handling of cytostatic drugs.

The bacterial fluctuation test and measurement of the frequency of sister chromatid exchanges were used for evaluation of the exposure of different groups of hospital personnel to cytostatic drugs. Increased mutagenic activity in the urine was detected only in personnel working with inadequate safety precautions, e.g., lack of a ventilated safety cabin for preparation of parenteral solutions. Although such a safety cabin was used within the hospital pharmacy, increased mutagenic activity was detected in the urine of prescriptionists preparing parenteral cytostatic drugs. After a change of glove material and improvement of ventilation in the safety cabin, no work-related increase in urinary mutagenic activity was seen. None of the different groups tested, showed any increase in the frequency of sister chromatid exchanges. It is therefore concluded that handling of cytostatic drugs according to the issued safety recommendations including working in a well ventilated safety cabin, will not result in any enhancement of mutagenic activity in the urine related to work.

Adult↗
PubMed1983

Coronary heart disease risk factors in bus and truck drivers. A controlled cohort study.

Fifty-two bus and truck drivers and a control group of 52 male industrial workers were studied with regard to risk factors for coronary heart disease (CHD) as well as some psycho-social and occupational indicators. The main results were: higher mean values for serum cholesterol, serum triglycerides and blood pressure in the driver group, indicating a markedly higher risk of CHD in the driver group. The two groups were matched for age, socio-economic status, dietary habits, smoking habits and alcohol consumption. In the study the groups were found to be equal as regards CHD-inheritance, physical activity in leisure time, and relative body weight, W/H2. No CO could be traced in the vehicles. The psycho-social and occupational indicators showed considerable differences. The average score for the exposure factor "tempo/time-limit/urgency in job" was 50% higher, and the number of persons with the characteristic "type-A coronary-prone behaviour" was 30% higher in the driver group than in the control group. The difference in blood lipids and blood pressure increased with age. It is suggested that the higher CHD-risk in the driver group is associated with two factors: (1) greater psychic pressure in the working situation; (2) the selection of more type-A persons to driver occupations. A probable, but not commonly accepted theory, is that these psychosocial indicators may influence the traditional risk factors in a harmful way.

Adult↗