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PubMed2002

Genetic structure of natural populations of the grass endophyte Epichloë festucae in semiarid grasslands.

Plants of red fescue (Festuca rubra), a commercially important turf grass, are infected by the fungal endophyte Epichloë festucae in semiarid natural grasslands, known as dehesas, in western Spain. We used amplified fragment length polymorphism (AFLP) markers to analyse the genetic polymorphism existing in two natural populations of Epichloë festucae. Linkage disequilibrium and the presence of clonal lineages indicated that nonrecombinant asexual reproduction predominates in both populations. However, most genetic variation detected was found to occur within populations, with only a moderate amount of genetic differentiation between populations (F(ST): 0.197). Overall, the study suggests that dehesa grasslands are useful reservoirs of Epichloë festucae endophytes, and provides information on population structure which is relevant to design sampling strategies.

Genetic Variation↗
PubMed1999

Contrasting levels of adolescent drug use between adjacent urban and rural communities in Scotland.

AIMS: To compare life-time prevalence of illicit drug use between adolescents resident in adjacent urban and rural localities. DESIGN: Samples of schoolchildren attending urban and rural comprehensive schools (n = 2558) were obtained using an identical questionnaire survey method. SETTING: Respondents were recruited from 10 schools in two contrasting adjacent local authorities. Five representative schools in each locality were chosen. PARTICIPANTS: All children present in each school, in the two final compulsory school years, were eligible for this study. MEASUREMENTS: Respondents were asked to provide detailed information about their place of residence and use of illegal drugs. The data obtained in schools were compared with local geographical statistics, such as levels of deprivation. FINDINGS: As expected from the demographics of their respective localities, the urban schools displayed higher levels of deprived children and lower levels of school achievement. These socio-economic differences were not reflected in reported levels of life-time drug use. This was true both between and within the urban and rural samples. CONCLUSION: These findings suggest that adolescent drug use in Scotland is not particularly concentrated in areas of urban deprivation.

Adolescent↗
PubMed2000

Ten-year survival analysis of a cohort of heroin addicts in Catalonia: the EMETYST project.

AIMS: To determine mortality rates and immediate causes of death in a cohort of heroin addicts, and to compare them with other European samples. DESIGN: Longitudinal follow-up study of a cohort for 10.5 years (March/July 1985-December 1995). SETTING: Catalonia, Spain. PARTICIPANTS: One hundred and thirty-five heroin addicts. MEASUREMENTS: (a) Number of total and annual events; (b) annual mortality rate; (c) average annual mortality rate; and (d) standardized mortality ratio (SMR). Kaplan-Meier (log rank test) was used to assess the predictive factors. FINDINGS: During this period, 41 heroin addicts died (30%), the average annual mortality rate was 3.4% and the SMR was 28.5. The most frequent causes of death fell in ICD-9 chapter III (which includes AIDS) (51%) and in chapter XVII (which includes overdose) (30%). Neither the socio-demographic characteristics nor the history of heroin consumption were predictors of survival or cause of death. CONCLUSIONS: Compared to other European studies, the cohort in the EMETYST project has the highest SMR and members have a higher chance of dying due to AIDS. The predictors of survival in the long term must be interpreted with caution, with the exceptions of being HIV positive or being diagnosed with AIDS.

Adolescent↗
PubMed2003

Improving self-reports of drug-use: numeric estimates as fuzzy sets.

AIMS: This study compared traditional crisp set to fuzzy set representations of quantitative estimates of drug use to investigate what survey respondents recall about their drug use. DESIGN: Sample survey comparing (a) responses to traditional survey questions asking for single numeric estimates to (b) responses to fuzzy set questions asking for boundary estimates of drug use. SETTING: Research facilities of a public university in a large southern California city. PARTICIPANTS: Community residents using tobacco, alcohol, marijuana or amphetamine (n = 88). MEASUREMENTS: Personal interviews in which participants reported onset, frequency and daily rate of tobacco, alcohol, marijuana and amphetamine use based on traditional survey questions and fuzzy set questions. FINDINGS: With the exception of marijuana use, fuzzy boundary estimates differed significantly from the traditional point estimates (P < 0.05). Median retest reliabilities for fuzzy boundary estimates were 0.96 (tobacco), 0.81 (alcohol), 0.96 (marijuana) and 0.95 (amphetamine). The degree of vagueness varied by behavior and drug, with estimates of daily rates showing greatest fuzziness and onset of use showing least fuzziness. CONCLUSIONS: Participants recall more about past drug use than a single numeric estimate. All numeric estimates of drug use showed fuzzy set properties. Compared to traditional self-reports of drug use, fuzzy set representations provide a more complete and detailed description of what participants recall about past drug use.

Adolescent↗
PubMed1999

Leptin levels in smokers and long-term users of nicotine gum.

BACKGROUND: The aim of this study was to examine the effects of cigarette smoking and other forms of long-term nicotine consumption on circulating leptin levels as well as the relationship between leptin levels and insulin sensitivity, measured with the euglycaemic hyperinsulinaemic clamp, in healthy middle-aged men. STUDY DESIGN: Samples from 73 subjects were analysed: 23 non-smokers, 31 smokers and 19 long-term nicotine gum chewers (NGCs) with similar ranges of age, body mass index (BMI) and per cent body fat. RESULTS: Leptin levels were higher in NGCs and smokers than in the non-smoking matched control subjects. Smoking cessation for 8 weeks further increased the leptin levels, probably due to the concomitant increase in body fat (mean +/- SD, 2.2 +/- 1.8 kg). Acute administration of one dose of nicotine nasal spray or smoking one cigarette did not significantly change the circulating leptin levels during the following 60 min. Plasma leptin concentrations were positively correlated with the proportion of body fat and negatively correlated with the degree of insulin sensitivity in each of the three subject groups. In a stepwise multiple linear regression analysis, plasma leptin concentrations were significantly correlated with the proportion of body fat, degree of insulin sensitivity and smoking status. CONCLUSION: These data show that long-term use of nicotine is associated with elevated circulating leptin levels. The increased leptin levels may be an important reason for the lower body weight in smokers. The results of this study also support the view that leptin is directly or indirectly related to insulin sensitivity in men.

Administration, Inhalation↗
PubMed2003

Psycho-spiritual well-being in patients with advanced cancer: an integrative review of the literature.

PURPOSE: An integrative literature review was undertaken to examine the research on psycho-spiritual well-being in terminally ill people, specifically patients with advanced cancer. METHOD: A comprehensive search of MEDLINE, CINAHL, CancerLit and PsycINFO using relevant keywords produced 43 primary research studies that investigated psycho-spiritual well-being in patients with advanced cancer. Each report was read, critiqued and systematically assessed for purpose statement or research questions, study design, sample size, characteristics of the subjects, measurement of independent and dependent variables, sample attrition, method of data analysis and results. Major themes and findings were identified for each of the studies. FINDINGS: Psycho-spiritual well-being is an area of interest to researchers all over the world. Retrieved studies had been conducted in 14 countries by researchers in a variety of disciplines, including nursing, medicine, psychology and theology. Six major themes repeatedly emerged as essential components of psycho-spiritual well-being: self-awareness, coping and adjusting effectively with stress, relationships and connectedness with others, sense of faith, sense of empowerment and confidence, and living with meaning and hope. CONCLUSION: Patients with an enhanced sense of psycho-spiritual well-being are able to cope more effectively with the process of terminal illness and find meaning in the experience. Prognostic awareness, family and social support, autonomy, hope and meaning in life all contribute to positive psycho-spiritual well-being. Emotional distress, anxiety, helplessness, hopelessness and fear of death all detract from psycho-spiritual well-being. The research indicated that health professionals can play an important role in enhancing psycho-spiritual well-being, but further research is needed to understand specific interventions that are effective and contribute to positive patient outcomes.

Adaptation, Psychological↗
PubMed1998

Differential effects of antihypertensive drugs on neurohormonal activation: insights from a population-based sample.

OBJECTIVES: The clinical course of hypertension or heart failure may be modified by the extent of concurrent neurohormonal activation. Factors that regulate neurohormones in patients with these conditions are complex. In the present study, we examined the relative contribution of antihypertensive therapy to the variability of neurohormonal levels in a well defined population based sample. DESIGN AND SETTING: Cross-sectional study of a mixed urban and rural population. SUBJECTS: Middle-aged individuals (n = 646) were analysed in order to elucidate determinants of neurohormone levels by uni- and multivariate comparisons. The assessment included anthropometric, echocardiographic and, if appropriate, genotype information. RESULTS: The intake of antihypertensive drugs was related to significant alterations of neurohormone levels that, in part, exceeded the contribution of all other variables studied. Multivariate analyses revealed that renin levels were independently related to the intake of beta blockers (n = 80; -8.4 mU L-1; P = 0.001), angiotensin-converting enzyme (ACE)-inhibitors (n = 39; +15.9 mU L-1; P = 0.0001), diuretics (n = 62; +14.3 mU L-1; P = 0.0001), and calcium channel blockers (n = 45; +5.9 mU L-1; P = 0.05). Aldosterone levels were related to ACE-inhibition (-156.5 pmol L-1; P = 0.04) and diuretic treatment (+422.4 pmol L-1; P = 0.0001) in an opposite fashion whereas beta blockers and calcium channel blockers had no significant independent effects. The levels of the atrial natriuretic peptide were significantly related to the use of beta blockers (+3.9 pmol L-1; P = 0.002) and calcium channel blockers (+3.1 pmol L-1; P = 0.05). Finally, serum angiotensinogen levels and ACE activity were not found to be significantly affected by antihypertensive medication but were rather related to gender or genotype. CONCLUSIONS: The data emphasize that antihypertensive treatment with different classes of drugs may modulate serum levels of neurohormones substantially resulting in distinct patterns of activation. These drug-related effects may require consideration when neurohormonal activation is of functional relevance or when neurohormones serve as prognostic predictors in patients with cardiovascular disorders.

Adrenergic beta-Antagonists↗
PubMed2002

The association between leptin and proinsulin is lost with central obesity.

OBJECTIVE: Hyperproinsulinaemia and hyperleptinaemia are interrelated features of the insulin resistance syndrome that are linked to the prospective risk of cardiovascular diseases. Whether the association between leptin and proinsulin is different between groups displaying different degrees of risk for cardiovascular diseases is not known. We therefore examined this association in men versus women and in pre- versus postmenopausal women from a population-based sample. DESIGN AND SUBJECTS: Healthy subjects (n = 158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease population were studied with a cross-sectional design. METHODS: Anthropometric measurements (body mass index and waist circumference) and oral glucose tolerance tests were performed. Enzyme-linked immunosorbent assays were used for the analyses of specific insulin and proinsulin, and radioimmunoassay for leptin. Insulin resistance and beta-cell function were calculated according to the homeostasis assessment model. Partial correlation coefficients adjusted for age and measures of adiposity were calculated and multiple linear regression analyses were performed with leptin as dependent variable. RESULTS: In nonobese men and premenopausal women and in obese postmenopausal women, leptin was significantly associated with proinsulin after stratification for waist circumference. Furthermore, a multivariate analyses taking age and measures of adiposity into account, showed that high fasting proinsulin was a significant predictor of high leptin in these groups. In contrast, this association was lost with increasing central obesity in men and premenopausal women. CONCLUSIONS: This study shows that both the degree of adiposity and the hormonal milieu influence the association between circulating leptin and proinsulin in a normal population. Therefore, the insulin resistance syndrome seems to be characterized by lost association between leptin and proinsulin, which may be explained by dysfunction in the adipoinsular axis.

Abdomen↗
PubMed2003

Decreasing serum concentrations of all-trans, 13-cis retinoic acids and retinol during fasting and caloric restriction.

OBJECTIVES: To investigate the effects of caloric restriction on the serum concentrations of retinoids in man. DESIGN: Samples were drawn before and during caloric restriction by fasting or 4-6 weeks after gastric surgery. SUBJECTS: The fasting group included 17 healthy subjects (11 women and six men) and 16 obese patients (10 women and six men) who underwent bariatric surgery (vertical banded gastroplasty). MAIN OUTCOME MEASURES: Serum concentrations of all-trans, 13-cis, 4-oxo-13-cis retinoic acids and retinol. RESULTS: The serum concentrations of retinol, all-trans and 13-cis retinoic acids decreased by about 20% after 5 days of fasting. After gastroplasty, the serum concentration of retinol, all-trans, 13-cis retinoic acids, retinol-binding protein and transthyretin also decreased to a similar extent after 1 month. In both groups we found a correlation between the delta values of 13-cis retinoic acid and its metabolite 4-oxo-13-cis retinoic acid. In all subjects there were also correlations between the delta values of the retinoids. However, these correlations were comparatively weak (e.g. r2 = 0.36 for retinol--all-trans retinoic acid). The change in retinoid concentrations did not correlate to the change of weight or body mass index. CONCLUSION: Our results support the hypothesis that serum retinol is one of the determinants of serum concentrations of all-trans and 13-cis retinoic acid and that the catabolism of 13-cis retinoic acid is not affected by fasting. However, in the individual case, S-Retinol is a poor predictor of S-All-trans retinoic acid.

Adult↗
PubMed1998

High-pressure freezing causes structural alterations in phospholipid model membranes.

The influence of high-pressure freezing (HPF) on the lipid arrangement in phospholipid model membranes has been investigated. Liposomes consisting of pure dipalmitoyl-phosphatidylcholine (DPPC) and of DPPC mixed with a branched-chain phosphocholine (1,2-di(4-dodecyl-palmitoyl)- sn-glycero-3-phosphocholine) have been analysed by freeze-fracture electron microscopy. The liposomes were frozen either by plunging into liquid propane or by HPF. The characteristic macroripple-phase of the two-component liposome system is drastically changed in its morphology when frozen under high-pressure conditions. The influence of ethanol which acts as pressure transfer medium was ruled out by control experiments. In contrast, no high-pressure alterations of the pure DPPC bilayer membrane have been observed. We assume that the modification of the binary system is due to a pressure-induced relaxation of a stressed and unstable lipid molecule packing configuration. HPF was performed with a newly designed sample holder, for using sandwiched copper platelets with the high-pressure freezing machine Balzers HPM010. The sandwich construction turned out to be superior to the original holder system with regard to freeze-fracturing of fluid samples. By inserting a spacer between the supports samples with a thickness of 20-100 microns can be high-pressure frozen. The sandwich holder is provided with a thermocouple to monitor cooling rates and allows exact sample temperature control. Despite a two-fold mass reduction compared to the original holder no HPF cooling rate improvement has been achieved (4000 degrees Cs-1). We conclude that the cooling process in high-pressure freezing is determined mainly by cryogen velocity.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Stereological estimation of integral mixed curvature with application

This article addresses a bounded system of compact smooth surfaces in three-dimensional space. Recently, an unbiased estimator of the integral mixed curvature of the given system based on a vertical sampling design has been proposed. The aims of the present paper are: (i) to show that the proposed estimator may have an infinite variance; (ii) to suggest a modification that has better statistical properties; (iii) to extend the point estimator to a function that monitors the curvature along the gradient microstructures; (iv) to present an application of the method to real microscopic images.

Journal Article↗
PubMed2004

Population genetic structure of the sugar beet cyst nematode Heterodera schachtii: a gonochoristic and amphimictic species with highly inbred but weakly differentiated populations.

The sugar beet cyst nematode Heterodera schachtii is a soil-dwelling phytoparasitic nematode that feeds on beet roots. It is an important pest in most sugar beet growing areas, and better knowledge of its genetic variability is an important step to preserve the durability of resistant sugar beet varieties. The population genetic structure of this species in northern France was studied using five microsatellite markers. A hierarchical sampling design was used to investigate spatial structuring at the scale of the region, the field and the plant. Multilocus genotypes were obtained for single individual second-stage larvae, using only one individual per cyst in order to avoid the analysis of closely allied individuals (larvae from the same cyst share at least the same mother). A consistent trend of heterozygote deficit at all loci was observed at all spatial scales. Heterozygote deficit at the level of individual plants argues against its generation through a Wahlund effect. Inbreeding could be due to very limited active dispersal of larvae in the soil, favouring mating between siblings, such as larvae emerging from the same cyst. Such behaviour could have important consequences for the evolution of virulence in increasing the production of homozygous virulent individuals. Moreover, an analysis of molecular variance (amova) reveals that only 1.6% of the genetic variability is observed among regions, 3.7% among fields of the same region and 94.6% within fields. The very low level of genetic differentiation among fields is also indicated by low values of FST (</= 0.105) even for fields 150 km apart. We suggest that long-distance gene flows occur due to passive transport of cysts by human activities, water or wind. As such mechanisms of gene flow would involve cysts and not larvae, the strong signals of inbreeding observed at the local scale should not be disrupted. To our knowledge, this study constitutes the first investigation of the genetic structure of a phytoparasitic nematode based on neutral codominant genetic markers scored in single individuals.

Analysis of Variance↗
PubMed2002

Ageing of substantia nigra in humans: cell loss may be compensated by hypertrophy.

In a stereological study of the human substantia nigra (SN), the total number of melanin-positive and melanin-negative neurones from 28 male subjects aged 19-92 years was estimated using a uniform sampling design and optical disectors. There was a significant decrease in the total number of melanin-positive neurones as a function of age (r(2)=0.18, residual-CV=0.35, 2P=0.032). Using the rotator method, the size distribution of the melanin-positive neurones was estimated and showed a significant difference in mean cell volume of melanin-positive neurones between the seven youngest (21,077 microm(3)) and the seven oldest individuals (32,011 microm(3)), 2P=0.022. Using a combination of the total number of melanin-positive neurones and their size distribution, the total perikaryon volume of melanin-positive neurones could be estimated and showed no decrease with increasing age (r(2)=0.01, residual-CV=0.41, 2P=0.62). Age-related decline in dopamine-transporter neurones within the SN might explain the occurrence of extrapyramidal symptoms in many elderly individuals. Although age-related cell hypertrophy is usually considered to be an indication of cell degeneration or necrosis, this might not always be the case. The fact that motor symptoms, although present in many of the elderly, are of a limited nature despite the high percentage of lost neurones could be due to a compensatory increase in the cell body of dopamine-producing SN neurones. Thus, the total amount of cell substance capable of producing the essential transmitters might not be reduced to a critically low level as a result of ageing.

Adaptation, Physiological↗
PubMed2000

Cytodiagnosis of cutaneous basal and squamous cell carcinoma.

OBJECTIVE: We performed a prospective study to evaluate the diagnostic accuracy of cytologic examination in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), in order to assess its clinical value. Study design Samples were taken by the "scraping" technique which involves scraping with a scalpel blade directly over the skin tumor surface, smearing the cells onto several glass slides, and fixing them with "citospray." The specimens were stained with the Papanicolaou stain. Punch biopsies were taken to confirm the clinical and cytologic impression. RESULTS: We collected 45 skin tumors in total, clinically presumed to be either BCC (n = 15) or SCC (n = 30). Imprint cytology demonstrated to be of help in the rapid diagnosis of skin tumors. CONCLUSIONS: Cytologic examination is easy to perform, saves time, provides a rapid diagnosis, and can be considered, under experienced hands, reliable in the confirmation of malignant skin tumors. Cytology does not give much information about tumor patterns or subtypes which can be related to aggressive behavior and can be very important in further therapeutic decisions. Therefore, histopathologic confirmation is mandatory before any therapeutic maneuver.

Adult↗
PubMed1999

Factors affecting disability in patients attending the internal medicine departments of general hospitals.

The aim of this study was to investigate the effect of sociodemographic factors, physical factors and mental factors on the physical and social disability of patients attending outpatient clinics of general hospitals. Physical and psychiatric morbidity in 1580 consecutive patients attending the internal medicine department of general hospitals was assessed using a stratified two-stage sampling design method. Of the total, 336 patients completed the second stage interview composed of Primary Care Version of Composite International Diagnostic Interview and Groningen Social Disability Schedule to assess sociodemographic, physical and mental factors. In this study, restricted activity days, disability days and Brief Disability Questionnaire were used for the assessment of physical disability, and Groningen Social Disability Schedule was used for social disability. Sociodemographic, physical and mental factors were all related to disability. Among sociodemographic factors, unemployment was associated with physical disability and social disability mildly. Among physical factors, the severity of physical disease was not associated with disability and medically explained somatic symptoms were associated with disability. Furthermore, the mental factor was more strongly associated with physical and social disability. It could be said that the mental factor is more strongly associated with physical and social disability than sociodemographic or physical factors. In addition, even mild mental symptoms not leading to ICD-10 mental disorders affected disability. From the viewpoint of the patients' burden, it is important to assess the mental symptoms as well as physical status in outpatient clinics of internal medicine or primary care.

Adolescent↗
PubMed2004

Host specificity in marine sponge-associated bacteria, and potential implications for marine microbial diversity.

Biodiversity is fundamental to both eukaryote and prokaryote ecology, yet investigations of diversity often differ markedly between the two disciplines. Host specificity - the association of organisms with only a few (specialism) or many (generalism) host species - is recognized within eukaryote ecology as a key determinant of diversity. In contrast, its implications for microbial diversity have received relatively little attention. Here we explore the relationship between microbial diversity and host specificity using marine sponge-bacteria associations. We used a replicated, hierarchical sampling design and both 16S rDNA- and rpoB-based denaturing gradient gel electrophoresis (DGGE) to examine whether three co-occurring sponges from temperate Australia -Cymbastela concentrica, Callyspongia sp. and Stylinos sp. - contained unique, specialized communities of microbes. Microbial communities varied little within each species of sponge, but variability among species was substantial. Over five seasons, the microbial community in C. concentrica differed significantly from other sponges, which were more similar to seawater. Overall, three types of sponge-associated bacteria were identified via 16S rDNA sequencing of excised DGGE bands: 'specialists'- found on only one host species, 'sponge associates'- found on multiple hosts but not in seawater, and 'generalists' from multiple hosts and seawater. Analogous to other high diversity systems, the degree of specificity of prokaryotes to host eukaryotes could have a potentially significant effect on estimates of marine microbial diversity.

Animals↗
PubMed2002

The effectiveness of spinal manipulation for the treatment of headache disorders: a systematic review of randomized clinical trials.

To carry out a systematic review of the literature examining the effectiveness of spinal manipulation for the treatment of headache disorders, computerized literature searches were carried out in Medline, Embase, Amed and CISCOM. Studies were included only if they were randomized trials of (any type of) spinal manipulation for (any type of) headache in human patients in which spinal manipulation was compared either to no treatment, usual medical care, a 'sham' intervention, or to some other active treatment. Two investigators independently extracted data on study design, sample size and characteristics, type of intervention, type of control/comparison, direction and nature of the outcome(s). Methodological quality of the trials was also assessed using the Jadad scale. Eight trials were identified that met our inclusion criteria. Three examined tension-type headaches, three migraine, one 'cervicogenic' headache, and one 'spondylogenic' chronic headache. In two studies, patients receiving spinal manipulation showed comparable improvements in migraine and tension headaches compared to drug treatment. In the 4 studies employing some 'sham' interventions (e.g. laser light therapy), results were less conclusive with 2 studies showing a benefit for manipulation and 2 studies failing to find such an effect. Considerable methodological limitations were observed in most trials, the principal one being inadequate control for nonspecific (placebo) effects. Despite claims that spinal manipulation is an effective treatment for headache, the data available to date do not support such definitive conclusions. It is unclear to what extent the observed treatment effects can be explained by manipulation or by nonspecific factors (e.g. of personal attention, patient expectation). Whether manipulation produces any long-term changes in these conditions is also uncertain. Future studies should address these two crucial questions and overcome the methodological limitations of previous trials.

Headache Disorders↗
PubMed2001

Vanadium pharmacokinetics and oral bioavailability upon single-dose administration of vanadyl sulfate to rats.

Vanadium pharmacokinetic parameters and oral bioavailability were determined after administration of vanadyl sulfate, an antidiabetic agent, to male Wistar rats. An optimal sampling design was used over a 21-day period; vanadium was measured in blood by atomic absorption spectrophotometry (AAS). After i.v. bolus injection (3.025 mg V/kg body weight), a three-compartment model was fitted to the data. Mean (+/- SD) half-lives were 0.90 +/- 0.56 hours, 24.8 +/- 14.5 h and 201 +/- 74 h, respectively, for the three phases observed. Vanadium clearance averaged 37.6 +/- 15.8 mL/h. Initial volume of distribution was 2.43 +/- 1.22 L/kg whereas total volume of distribution was 25.4 +/- 3.9 L/kg; these values largely exceeded body weight (i.e. 300 g), in agreement with a great uptake and retention of vanadium in tissues. After oral gavage administration (15.12 and 7.56 mg V/kg body weight), vanadium disposition was best described by a three-compartment model, with absorption appearing to occur by a zero-order rate. This process lasted 10.3 +/- 1.3 h and 10.9 +/- 1.1 h for the two dosage levels, respectively. Half-lives corresponding to the terminal log-linear part of the curve were 173.5 +/- 1.6 h and 172 +/- 6 h (Bayesian estimates). No dose-dependency was observed for any of the parameters determined. Absolute bioavailabilities, with reference to the i.v. administration, were 12.5% and 16.8% when determined from AUCmod. Bioavailability appeared to be higher than generally stated in the literature.

Administration, Oral↗