bluuebunny/crossref_metadata_2025 huggingface dataset:
The withdrawal time estimation of veterinary drugs revisited
Authors: CONCORDET D. , TOUTAIN P.L.
Published: November 2003

The aim of this article is to review current issues concerning the statistical determination of a withdrawal time for a veterinary drug. Special attention has been paid to the Food and Drug Administration (FDA) approach which consists of using a regression method to estimate a 99th percentile of the population with a 95% confidence level. The different assumptions of the simple regression techniques are reviewed. It is shown, both on theoretical grounds and using Monte Carlo simulations, that the main assumptions for the correct use of linear regression do not hold when a tissue depletion curve is under investigation. Finally, it is suggested that methods other than the regression technique must be evaluated, especially a revised version of the so‐called simpler approach, which consists of using a non‐parametric strategy to estimate a withdrawal time.
Reversal of medetomidine‐induced sedation in reindeer (Rangifer tarandus tarandus) with atipamezole increases the medetomidine concentration in plasma
Authors: Ranheim B. , Horsberg T. E. , Nymoen U. , SØli N. E. , Tyler N. J. C. , Arnemo J. M.
Published: November 2003

The pharmacokinetics of two potent α2‐adrenoceptor agents that can be used for immobilization (medetomidine) and reversal (atipamezole) of the sedation in mammals, were studied in three reindeer (Rangifer tarandus tarandus) in winter and again in summer. Medetomidine (60 μg/kg) was injected intravenously (i.v.), followed by atipamezole (300 μg/kg) intravenously 60 min later. Drug concentrations in plasma were measured by HPLC. The administration of atipamezole resulted in an immediate 2.5–3.5 fold increase in the medetomidine concentration in plasma. Clearance for medetomidine (median 19.3 mL/min·kg) was lower than clearance for atipamezole (median 31.0 mL/min·kg). The median elimination half‐lives of medetomidine and atipamezole in plasma were 76.1 and 59.9 min, respectively. The animals became resedated 0.5–1 h after the reversal with atipamezole. Resedation may be explained by the longer elimination half‐life of medetomidine compared to atipamezole.
Pharmacokinetics of intravenous and intragastric cimetidine in horses I. Effects of intravenous cimetidine on pharmacokinetics of intravenous phenylbutazone
Authors: SAMS R.A. , GERKEN D.F. , DYKE T.M. , REED S.M. , ASHCRAFT S.M.
Published: November 2003

Cimetidine was administered intravenously and by the intragastric route to six mares at a dose of 4.0 mg/kg of body weight (bw). Specific and sensitive high performance liquid chromatographic methods for the determination of cimetidine in horse plasma and urine and cimetidine sulfoxide in urine are described. Plasma cimetidine concentration vs. time data were analysed by non‐linear least squares regression analysis to determine pharmacokinetic parameter estimates. The median (range) plasma clearance (Cl) was 8.20 (4.96–10.2) mL/min.kg of body weight, that of the steady‐state volume of distribution (Vdss) was 0.771 (0.521–1.15) L/kg bw, and that of the terminal elimination half‐life (t½β) was 92.4 (70.6–125) minutes. The median (range) renal clearance of cimetidine was 4.08 (2.19–6.23) mL/min.kg bw or 55.4 (36.3–81.8)% of the corresponding plasma clearance. Cimetidine sulfoxide was excreted in urine and its urinary excretion through 8 h accounted for 12.0 (9.8–16.6)% of the plasma clearance of cimetidine. The median (range) extent of intragastric bioavailability was 14.4 (6.82–21.8)% and the maximum plasma concentration after intragastric administration was 0.31 (0.24–0.50) μg/mL.

Intravenous cimetidine had no effect on the disposition of intravenous phenylbutazone or its metabolites except that the maximum plasma concentration of γ‐hydroxyphenylbutazone was less after cimetidine treatment.
Plasma pharmacokinetics of ranitidine HCl in foals
Authors: Holland P. S. , Brumbaugh G. W. , Ruoff W. W. , Brown S. A.
Published: November 2003

Plasma pharmacokinetics of ranitidine HCl were investigated after intravenous (i.v.) and oral (p.o.) administration of drug to six healthy foals. Twelve‐ to sixteen‐week‐old foals received 2.2 mg ranitidine/kg i.v. and 4.4 mg ranitidine/kg p.o. Concentrations of ranitidine were determined using normal phase high performance liquid chromatography. Plasma concentrations of ranitidine HCl declined from a mean of 3266 ng/mL at 5 min to 11 ng/mL at 720 min after administration. The profile of the plot of concentrations of ranitidine HCl vs. time was best described by a two‐exponent equation for two foals; data for the remaining four foals were best described by a three‐exponent equation. Mean values for model‐independent values were: apparent volume of distribution (Vdss) = 1.46 L/kg; area under the curve (AUC) = 16 7442 ng·min/mL; area under the moment curve (AUMC) = 18 068 221 ng·min2/mL; mean residence time (MRT) = 108.9 min; and clearance (Cl) = 13.3 mL/min.kg. Following p.o. administration, a two‐exponent equation best described data for five foals; data for the remaining foal were best described by a three‐exponent equation. Mean values of the pharmacokinetic values from the p.o. study include: AUC = 12 6413 ng·min/mL; AUMC = 18 039 825 ng·min2/mL; mean absorption time (MAT) = 32.0 min; observed time to maximum plasma concentration (Tmax) = 57.2 min; maximum observed plasma concentration (Cmax) = 635.7 ng/mL; and bioavailability (F) = 38%.
The comparative hypoxaemic effect of four α2 adrenoceptor agonists (xylazine, romifidine, detomidine and medetomidine) in sheep
Authors: CELLY C.S. , McDONELL W.N. , YOUNG S.S. , BLACK W.D.
Published: November 2003

In the present study, the hypoxaemic potential of four α2 agonists possessing different selectivity for α2 adrenoceptors and of a saline placebo was studied in five clinically healthy sheep using a randomized Latin square design and equipotent sedative doses. Baseline values for heart rate (HR), mean arterial pressure (MAP), arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions, respiration rate and maximum change in pleural pressure (ΔPpl) were obtained, followed by the intravenous administration of either: xylazine (150 μg/kg); romifidine (50 μg/kg); detomidine (30 μg/kg); medetomidine (10 μg/kg) or placebo. Subsequent recordings were made up to 60 min after drug administration. No significant (P  0.05) alterations in any variable occurred with placebo. All the α2 agonists significantly (P  0.05) decreased PaO2 levels without a significant (P  0.05) change in PaCO2. The lowest PaO2 values were 29–42 mm Hg (3.9–5.5 kPa) with no significant difference between drugs. Respiratory rate and ΔPpl increased significantly within 2 min of drug administration; the duration of this effect varied with the α2 agonist, lasting longest with romifidine. As compared to the saline treated group, a significant increase in MAP was observed up to 10 min after administration of romifidine and detomidine, however, a significant decrease was seen at 10 and 45 min after xylazine and medetomidine, respectively. The α2 agonists studied induced a similar change in PaO2 at peak effect, despite their reported variable selectivity for α2 vs. α1 adrenoceptors.
Pharmacokinetics of enrofloxacin in newborn and one‐week‐old calves
Authors: Kaartinen L. , PyÖrÄlÄ S. , Moilanen M. , RÄisÄnen S.
Published: November 2003

The pharmacokinetic behaviour of enrofloxacin was compared in four one‐day‐old and four one‐week‐old calves in order to find out if there were any age‐related differences. Mean volume of distribution (Vd(ss)) and clearance (Cl) were significantly smaller in newborn calves: Vd(ss) was 1.8 and 2.3 L/kg, while clearance was 0.19 and 0.39 L/kg.h in newborn and one‐week‐old calves, respectively. Mean elimination half‐life (t1/2β) did not differ significantly in newborn and in one‐week‐old calves: mean t1/2β was 6.6 h and 4.9 h, respectively. Enrofloxacin was metabolized to ciprofloxacin both by newborn and one‐week‐old calves, but the maximum concentration (Cmax) of ciprofloxacin was lower and the time when maximum concentration was reached (tmax) later in newborn calves. We conclude that the dosage of enrofloxacin should be adjusted according to age when administered to very young calves.
FASTING‐INDUCED CHANGES TO THE PHARMACOKINETIC BEHAVIOUR OF ALBENDAZOLE AND ITS METABOLITES IN CALVES
Authors: SÁnchez S.F. , Alvarez L.I. , Lanusse C.E.
Published: November 2003

The influence of fasting on the bioavailability and disposition kinetics of albendazole (ABZ) and its metabolites in cattle was investigated. ABZ (10 mg/kg) was given by intraruminal (i.r.) (Experiment 1) and intravenous (i.v.) (Experiment 2) administration to Holstein calves either fed ad libitum (control) or subjected to a 48 h fasting period (fasted group) prior to treatment. The rate of passage of digesta through the gastrointestinal (GI) tract was evaluated by measurement of cobalt faecal excretion following the oral administration of the sodium‐cobalt‐ethylendiamine‐tetracetic acid complex to calves subjected to the feeding conditions above described. Jugular blood and abomasal fluid (via cannula) samples were collected over 120 h post‐treatment; samples were analysed by high performance liquid chromatography (HPLC) for ABZ, ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO2). Fasting the animals prior to the i.r. treatment resulted in pronounced modifications to the plasma and abomasal fluid disposition kinetics of ABZ and its metabolites. A greater extent of GI absorption with significantly higher Cmax (150%) and AUC (310%) values for ABZSO in plasma, was observed in fasted compared to fed animals following the i.r. administration of ABZ. Extended detection of ABZ metabolites resulting in significantly longer plasma t½el and MRT was also obtained in fasted compared to fed calves. These results correlated with the substantially enhanced availability of ABZ and its metabolites (AUCs over 200% greater) in the abomasal fluid of the fasted animals. Fasting did not induce changes to the plasma disposition of either ABZ or its metabolites after the i.v. treatment. The digesta passage rate, measured by the amount of cobalt excreted in faeces, was significantly lower in fasted compared to animals fed ad libitum. A delayed GI transit time that decreases the rate of passage of the drug down the digestive tract, may have accounted for enhanced ABZ dissolution and absorption in fasted compared to fed calves. The findings reported in this article show that fasting prior to treatment notably affects the bioavailability and disposition kinetics of ABZ and its metabolites in cattle.
Steady‐state pharmacokinetics of oral sustained‐release morphine sulphate in dogs
Authors: DOHOO S.
Published: November 2003

The pharmacokinetics of steady‐state oral sustained‐release morphine sulphate (OSRMS) were studied in dogs. Beagles (n= 6) were randomly assigned to one of two treatment groups. Treatments included 15 mg OSRMS every 8 h for 4 days, or 15 mg OSRMS every 12 h for 4 days. Serum samples, drawn at intervals for the final 24 h of drug administration were analysed for morphine concentration using radioimmunoassay. Pharmacokinetic analysis revealed that there were no significant differences between trough serum concentrations for the concentration–time curves within either treatment group, indicating that steady‐state pharmacokinetics had been achieved. There were no significant differences in time to maximum serum concentration among the three sections of the concentration–time curve for the 8‐h group or between the two sections of the curve for the 12‐h group. Area under the concentration–time curve and maximum serum concentrations were significantly greater for the section of the curve following dosing at 7:30 h than following dosing at 19:30 h in the 12‐h treatment group. This chronopharmacokinetic variability was not present in the 8‐h treatment group. OSRMS provides sustained periods of elevated serum concentrations following administration every 8 or 12 h at a clinically applicable dosage. The clinical implications of the chronopharmacokinetic variability seen with 12‐hourly administration are not known. This formulation has potential for the treatment of chronic pain in dogs, but further studies of efficacy and safety following long‐term administration are required.
Corneal concentrations and preliminary toxicological evaluation of an itraconazole/dimethyl sulphoxide ophthalmic ointment
Authors: Ball M. A. , Rebhun W. C. , Trepanier L. , Gaarder J. , SCHWARK W. S.
Published: November 2003

The objectives of this study were to determine the concentration of itraconazole achieved in corneal tissue and aqueous humour after topical application of a 1% itraconazole ointment; to determine the effect of including dimethyl sulphoxide (DMSO) in the ointment on achievable ocular tissue itraconazole concentrations; and to assess if any gross or histopathologic ocular toxicity results from the topical application of 1% itraconazole with or without the addition of DMSO.

The experimental trial consisted of 6 horses considered to have normal eyes. Each horse had one eye treated with 0.3 mL of 1% ultra‐micronized itraconazole ointment and the fellow eye with 0.3 mL of 1% itraconazole/30% DMSO ointment. The ointment was applied every 6 h for a total of 28 treatments. Both ointments were well tolerated and no gross or histopathologic abnormalities developed during the trial.

Corneal tissue and aqueous humour concentrations of itraconazole were determined using high performance liquid chromatography. Corneal tissue concentration averaged 1.1 (± 0.4) μg/g in horses treated with the 1% ultra‐micronized itraconazole ointment and 7.9 (± 3.3) μg/g for those treated with the 1% itraconazole/30% DMSO ointment; there was a statistically significant difference between ointments (P= 0.005) No itraconazole could be detected in the aqueous humour in either treatment group.
Liver targeting of antiviral nucleoside analogues through the asialoglycoprotein receptor
Authors: Fiume L. , Stefano G. Di , Busi C. , Mattioli A. , Bonino F. , Torrani‐Cerenzia M. , Verme G. , Rapicetta M. , Bertini M. , Gervasi G. B.
Published: November 2003

Summary. In order to reduce the extrahepatic side‐effects of antiviral nucleoside analogues in the treatment of chronic viral hepatitis, these drugs are conjugated with galactosyl‐terminating macromolecules. The conjugates selectively enter hepatocytes after interaction of the carrier galactose residues with the asialoglycoprotein receptor present in large amounts and high affinity only on these cells. Within hepatocytes the conjugates are delivered to lysosomes where enzymes split the bond between the carrier and the drug, allowing the latter to become concentrated in the liver. The validity of this chemotherapeutic strategy has been endorsed by a clinical study. Adenine arabinoside monophosphate (ara‐AMP), conjugated with lactosaminated human serum albumin (L‐HSA) and administered to hepatitis B virus (HBV)‐infected patients for 28 days, exerted an antiviral activity to the same extent as the free drug without producing any clinical side‐effects, including the severe neurotoxicity caused by the free drug. Preclinical studies are now underway with conjugates obtained using lactosaminated poly‐L‐lysine (Lacpoly(Lys)) as the hepatotropic carrier. These new conjugates have some advantages over those prepared with L‐HSA: they can be administered by the intramuscular route; they are obtained entirely by chemical synthesis, thus eliminating the problems involved in the use of haemoderivatives; they have a heavy drug load, which permits administration of smaller quantities of conjugate that are more easily digested in lysosomes; and they enable higher quantities of drug to be introduced into hepatocytes. The results of the experiments with two Lac‐poly(Lys) conjugates, one with ara‐AMP and one with ribavirin, are reported in this review.
Analysis of the clinical behaviour of anaesthetists: recognition of uncertainty as a basis for practice
Authors: Klemola U‐M , Norros L
Published: November 2003

The dynamic complexity of anaesthesia sets specific requirements for the activity of anaesthetists. By exploring the significance given by anaesthetists to their work we have demonstrated a new conceptual framework and confirmed our hypothesis that there are differences in the orientations of anaesthetists, and that these become manifest in different types of clinical behaviour. We describe methods the anaesthetists use in framing the focus of their work, the patient in anaesthesia. The patient's uniqueness and uncertainty in anaesthesia were recognized in the `realistic' orientation, which is characterized by an extensive use of situational information and an aim to construct a cumulative interpretation of a patient's physiological state. In the objectivistic orientation the patient was treated as a natural object and uncertainty was not recognized. This orientation is typified by a reactive habit of action which seemed to be based on a pre‐operative plan, and its deterministic implementation. Our results point to the need for a new strategy to cope with the uniqueness and uncertainty of actual problems. This has implications for education and practice in anaesthetic practice, since uncertainty is increasing with the ageing patient population and with implementation of new technology.
Language background, proficiency in English, and selection for language development
Authors: Chur‐Hansen A
Published: November 2003

With a diverse language background profile in an Australian medical student population, teaching interventions are necessary for students whose English language proficiency is not adequate for the study of medicine. This paper describes the screening of written and aural English language proficiency in 143 first year undergraduate students using a standardized instrument. Students identified as experiencing language difficulties were subsequently assessed by interview and allocated to faculty‐based Language Development Programme. Students with the greatest need for language support participated in a full 2 year programme. Those requiring less assistance were offered more limited support in the form of specific modules within the programme. Students allocated to the full programme were significantly weaker in language proficiency compared to those offered specific modules and those not offered a placement. The information gathered during the structured interview is valuable in establishing for medical educators specific areas in which language‐related teaching for students who require it can be directed. Future research is required to evaluate the effectiveness of faculty‐based language interventions in terms of improvement in language proficiency over time and the effect of any improvements in language proficiency on academic and clinical performance.
Can general internal medicine be taught in general practice? An evaluation of the University College London model
Authors: Murray Elizabeth , Todd Charles , Modell Michael
Published: November 2003

There is national and international interest in increasing the community‐based component of undergraduate medical education, but more research is needed on its potential, practicability and effectiveness. The objective of the study was to examine the feasibility and efficacy of general practitioners teaching basic clinical skills to first year clinical medical students in the community. The structure and methods of evaluation of the programme are described. Evaluation tools included semi‐structured interviews of general practitioner tutors; student questionnaires; assessment of student performance; and costs of the programme. The great majority of the students found the programme enjoyable (81 out of 81, 100%) and educational (79 out of 81, 97%). Students' perfomance in the end of rotation Objective Structured Clinical Examination suggested that clinical skills are acquired at least as well in the community as in hospital. Tutors identified the personal benefits of this teaching as development of their own clinical skills and the stimulation of teaching. The programme has been successfully expanded from 24 students to 230 students annually and has demonstrated that community‐based teaching can usefully contribute to undergraduate medical education in the area of clinical skills teaching. Key practical issues for schools contemplating similar initiatives are presented.
Home, training and work: mobility of British doctors
Authors: Parkhouse James , Lambert Trevor W
Published: November 2003

This study examines the locations of family homes, medical schools and places of specialist training, and work of doctors qualifying from UK medical schools in 5 calendar years between 1974 and 1993. The contribution of each UK region to the medical workforce relative to its population is assessed and trends over time are examined. The relationship between place of family home and medical school attended is examined for 14,108 doctors. Career appointment location and its relationship to medical school and family home loc‐ation are examined for over 4000 doctors. For the qualifiers of 1983, an additional analysis incorporating place of training is included. Large differences were found in the percentage of medical students from local family homes attending each regional medical school. In some cases differences reflected local populations but other cases had no obvious cause. Over all cohorts studied, 38% of respondents attended a medical school in the region of their family home (32% of 1993 qualifiers), 42% held a career post in the same region as their medical school, and 38% held a career post in the same region as their family home. Among the qualifiers of 1983, 65% had a career post in the same region as their postgraduate training, 34% also attended medical school in the same region, and 19% also came from family homes in the same region. More women than men took up a career post in the same region as their postgraduate training. The relationships to family home and medical school did not differ by gender. Consultants appeared slightly less likely than GPs to have stayed within a region, but this difference was not statistically significant.
Community hospitals and general practice: extended attachments for medical students
Authors: Grant James , Ramsay Anne , Bain John
Published: November 2003

The first year experience of an innovative experiment in undergraduate medical education is described. The study investigated the educational effectiveness of prolonged clinical attachments for medical undergraduates in community hospital‐based general practice. It has also assessed the ability of students to take some responsibility for their own learning in a clinically challenging environment. A retrospective evaluation of the experience obtained during the 3 month attachments for a self‐selected group of fourth year Dundee medical school undergraduates was made. These undergraduates were placed in 10 mainly rural Scottish general practices with attached community hospitals providing a wide spectrum of inpatient and outpatient medical and surgical care. Students were assessed on the satisfactory completion of a portfolio of learning experiences and a practical clinical skills list. They were also required to submit a clinical project based on some aspect of their work during the attachment. The initial results showed a high degree of student and tutor satisfaction with the attachments. The assessment of all 10 of the students' educational achievements in their attachment were regarded as satisfactory and two were assessed as outstanding. Tutor assessment confirmed the validity of the initiative. Prolonged attachments in community hospital‐based general practice for medical undergraduates have proved educationally valid and popular with both students and tutors. The development and dissemination of this model on a wider scale has resource issues which require to be addressed.
Medical problem‐solving: a five stage approach in primary medical care
Authors: Erasmus R J E , Coetzer P W W , Hay I T
Published: November 2003

A methodology for a five stage or pentagonal problem‐based approach to solve individual or family health‐related problems is described. The model can be applied in health worker learning, student teaching or problem solving in the real world of the patient and his/her family within the context of community health. The model stresses interdisciplinary co‐operation, the consideration of ethical factors in each case, and a logical transition from individual patient care to community diagnosis and intervention. The model is applicable to any disease process, all levels of care, all levels of intervention and all clinical disciplines.
Problem‐based medical education: development of a theoretical foundation and a science‐based professional attitude
Authors: Dahle L O , Forsberg P , Svanberg‐Hård H , Wyon Y , Hammar M
Published: November 2003

Problem‐based learning, combined with early patient contact, integration between different subject areas, elements of multiprofessional education, and special emphasis on the development of communications skills has become the basis for the medical curriculum at the Faculty of Health Sciences in Linköping. Critics have questioned the depth of the scientific and theoretical aspects of the curriculum. Through a series of specific measures in the organization of the curriculum and examinations, and due to the pedagogical principles involved per se, our claim is that students graduating at Linköping do possess the required theoretical knowledge and a scientific attitude to the practice of medicine, at least equivalent to that obtained in a more conventional medical curriculum. One such specific measure is that all students perform one field study and two scientific studies during the course of the curriculum. An investigation of student opinions regarding the value of performing scientific projects of their own have shown that these projects have had a positive impact on the students' general scientific attitude and their willingness to engage in future scientific work. The specific skills acquired, as confirmed by oral examinations, were largely determined by the scientific nature of the chosen field of study. Our graduates have not yet progressed far enough in their careers for comparisons to be made on the basis of the Swedish Licensing Board Internship Examinations, but continuing evaluations of students, graduates and licensed doctors emerging from the curriculum will provide future evi‐dence as to whether our present evaluation is correct.
Medical students' professional identity: self‐reflection during the preclinical years
Authors: Niemi P M
Published: November 2003

Critical thinking, readiness for self‐reflection and professional development have recently been emphasized as important goals of medical education. However, little is known about the developmental processes through which a medical student elaborates his or her personal experiences during the training, and about the way he or she gradually develops a professional identity. How does the student identify the opportunities and alternatives offered by the profession and finally commit to the professional values and goals he or she finds personally important? In order to grasp the essential characteristics of the personal development process in depth, qualitative, process‐oriented and individually tailored methods are warranted. In this paper, the quality of professional self‐reflection and identity formation during the preclinical training are described on the basis of two qualitative materials – learning logs and identity status interviews. Four types of learning log reports on the early patient contact course could be identified: `committed reflection', `emotional exploration', `objective reporting' and `diffuse reporting'. At the end of the preclinical training, the identity status of several students could still be characterized as diffuse or giving rise to only very tentative professional considerations.
A medical school for rural areas
Authors: Inoue K , Hirayama Y , Igarashi M
Published: November 2003

Jichi Medical School (JMS) was established in 1972 to supply graduates to rural areas where medical resources are scarce. JMS has several unique characteristics aimed at motivating graduates to work in a rural practice. These include financial aid for students, a home prefecture recruiting scheme, location in a non‐urban area, management by prefectures and support from the national government. The achievements of JMS over the 24‐year period since its foundation have been evaluated. A questionnaire has been mailed to all JMS graduates since the first year of graduation. Using a pro‐active approach to follow‐up, the return rate has been virtually 100%. The authors investigated annual changes in the distribution of the graduates as well as the present status of the graduates in 1995. At that time, JMS graduates were distributed all over Japan. Among the 1871 graduates, 792 (42%) were working in rural areas in 1995. Nine‐hundred and twenty‐four graduated in the period from the first to the ninth output of graduates. Among these, 858 (93%) completed the requisite 9 years of work contracted between JMS and the graduates, 620 (67%) had practised in the same prefecture, and 305 (33%) were still practising in a rural area. Although there are still improvements to be made, JMS has succeeded in achieving its aim of supplying doctors to rural areas. The recruiting system of JMS is an effective approach to overcoming the shortage of rural doctors, which has continued to be an unresolved global problem.
Learning in a problem‐based medical curriculum: students' conceptions
Authors: Hughes Caplow Julie A , Donaldson Joe F , Kardash CarolAnne , Hosokawa Micheal
Published: November 2003

The purpose of this study was to examine students' conception of their learning in a problem‐based learning medical curriculum. A multiple case study design was used with two units of analyses: two PBL lab groups; and 15 individual students within each lab group. Data collected included weekly journals by students, video‐tapes of PBL sessions, focus group interviews with students, two open‐ended questionnaires completed by students, and interviews with the PBL tutors. Three thematic categories of students' conceptions of their learning emerged: (1) awareness of PBL goals and expectations; (2) efficiency and expertise; and (3) the role of the tutor.
Population genetic structure of the butterfly Melitaea didyma (Nymphalidae) along a northern distribution range border
Authors: JOHANNESEN J. , VEITH M. , SEITZ A.
Published: November 2003

The population genetic structure of the butterfly Melitaea didyma was studied along the northern distribution range border in Central Germany by means of allozyme electrophoresis. Individuals were sampled from a total of 21 habitat patches from four regions, and two provinces. Sampling was designed to estimate local vs. regional differentiation. High levels of variability were found, He= 0.14‐0.21. The mean expected sample heterozygosity from one region, Mosel, was significantly lower than from the Hammelburg region, He= 0.17 and 0.19, respectively. Two hierarchical levels of genetic differentiation were found. Within regions individuals sampled from different patches behaved as belonging to one population with high levels of gene flow (Hammelburg FST= 0.015, Mosel FST= 0.044), though local isolation barriers did create a substructuring of these populations. The inbreeding coefficients, FIS, were constant over all sample levels, suggesting a similar distribution of habitat patches within regions. Between regions gene flow was limited. An isolation by distance analysis indicated that the hierarchical structure, at the provincial level, may be breaking down due to isolation of regional populations. A more general observation was that the sampling design may greatly have influenced the estimation of genetic differentiation. Depending on which samples were included, overall FST estimates ranged from 0.059‐0.090.
Low genetic variability of the koala Phascolarctos cinereus in south‐eastern Australia following a severe population bottleneck
Authors: HOULDEN B. A. , ENGLAND P. R. , TAYLOR A. C. , GREVILLE W. D. , SHERWIN W. B.
Published: November 2003

Genotyping of koalas at CA‐repeat microsatellite loci has revealed significant differences in the levels of allelic diversity (A) and expected heterozygosity (HE) between populations from north‐eastern and south‐eastern Australia. In the 10 populations studied, allelic diversity ranged from 8.0 in the Nowendoc population to 1.7 in the Kangaroo Is. population, and values of HE ranged from 0.831 in the Nowendoc population to 0.331 in the Kangaroo Is. population. Data from pooled populations revealed koalas from the northeastern region had significantly higher levels of allelic diversity (A= 11.5 ± 1.4) than those from south‐eastern Australia (A= 5.3 ± 1.0). Furthermore significantly higher heterozygosity levels were found in the north‐eastern (HE= 0.851) vs. the south‐eastern (HE= 0.436) regions of Australia. Following a near‐extinction bottleneck in the 1920s, mainland Victorian and Kangaroo Is. koalas have been involved in an extensive program of relocations. The source populations of the relocated animals were islands in Westernport Bay, which were founded by very few individuals in the late 1800s and early 1900s. The significantly lower levels of variation between south‐eastern Australian populations suggests that human intervention has had a severe effect on levels of genetic diversity in this region, and this may have long‐term genetic consequences.
The evolution of growth‐forms in the Macaronesian genus Aeonium (Crassulaceae) inferred from chloroplast DNA RFLPs and morphology
Authors: MES T. H. M. , HART H. T.
Published: November 2003

Phylogenetic relationships among species of Aeonium were studied using morphological characters and chloroplast DNA RFLPs. Cladistic analysis of weighted morphological data indicates that the small, herbaceous and least woody species are basal in the genus. Chloroplast DNA data gave similar results, supporting the separation of the herbaceous or small, woody species from the large, hapaxanth rosettes, rosette trees, and branched subshrubs with yellow, white or red flowers as well as the only (herbaceous) species with axillary inflorescences. The relationships among the species descending from a polytomy that comprises all species of the genus as well as a polytomy which comprises 18 of the 26 species studied, are only very incompletely resolved, except for two monophyletic clades that contain the branched subshrubs with yellow flowers (A. sect. Aeonium) and the branched subshrubs and rosette trees with white or red flowers (A. sect. Leuconium), respectively. Cladistic analysis of the combined morphological and chloroplast DNA data improved resolution considerably. Four monophyletic clades are distinguished, each of which, except for three species, comprises only one of the five main growth‐form types. Although Aeonium is generally regarded as an outstanding example of adaptive radiation, this mode of speciation seems to have been of minor significance in the evolution of the genus, because each growth‐form apparently evolved only once. Instead, island speciation in the absence of major ecological shifts, is probably more important in the evolution of the genus.
Genetic introgression between native and introduced brown trout Salmo trutta L. populations in the Rhone River Basin
Authors: LARGIADER C. R. , SCHOLL A.
Published: November 2003

In the Doubs River (Rhone drainage) two distinct brown trout (S. trutta) phenotypes are observed. One phenotype is locally called Doubs trout and is characterized by four black stripes on the sides, similar to perch (Perca fluviatilis L.) and the other is the common phenotype of the fluviatile ecotype of brown trout, Salmo trutta f. fario. Protein data for three samples from the Doubs show that the Doubs trout belongs to the Mediterranean population group of brown trout, whereas the fario phenotype originates from stocking with hatchery strains of Atlantic basin origin. The two forms, however, do not hybridize freely. This is indicated by considerable gametic phase disequilibrium between alleles of hatchery and Doubs trout at one sampling site, and by lack of intermediate genotypes and phenotypes at another sampling site. The introgression patterns observed at the two sites suggest that differences in local habitat conditions can affect the degree of hybridization and introgression.
Low mitochondrial DNA variation and recent colonization of Scandinavia by the wood lemming Myopus schisticolor
Authors: Fedorov V. , Jaarola M. , Fredga K.
Published: November 2003

The population genetic structure of wood lemmings (Myopus schisticolor) from Scandinavia, Finland and western Siberia was examined by restriction fragment length polymorphism of mitochondrial DNA (mtDNA) in 45 individuals from six localities. The 12 observed mtDNA haplotypes demonstrated a distinct phylogeographic pattern, suggesting that the postglacial colonization of Scandinavia by wood lemmings occurred from north‐east. However, a very low level of haplotype and nucleotide diversity and a lack of geographical structure were found within Scandinavia. The limited mtDNA diversity in the Scandinavian populations probably reflects recent divergence in situ after colonization by a limited number of founders. Allozyme data support this scenario.
Identification of a hybrid zone between distinctive colour variants of the alpine weta Hemideina maori (Orthoptera: Stenopelmatidae) on the Rock and Pillar range, southern New Zealand
Authors: King T. M. , Wallis G. P. , Hamilton S. A. , Fraser J. R.
Published: November 2003

The weta Hemideina maori occurs as yellow (to the north), black (to the south) and intermediate colour variants on the Rock and Pillar range in New Zealand. Isozyme electrophoresis revealed little genetic variation, whereas RFLP analysis of an amplified mtDNA sequence uncovered two haplotypes correlating completely with colour in allopatry and nearly so in sympatry. Intermediates had one or other haplotype. The observed distribution of colour variation and mtDNA genotypes is characteristic of a hybrid zone, perhaps formed by secondary contact. Work is continuing to locate nuclear DNA markers and to study the genetic interactions of the colour variants.
Micro‐evolution in the weevil genus Larinus: the formation of host biotypes and speciation
Authors: Briese D. T. , Espiau C. , Pouchot‐Lermans A.
Published: November 2003

Data are presented on allozyme variation between 15 populations of the stenophagous capitulum weevil, Larinus cynarae, and three populations of its congener, L. latus, that had been collected throughout the northern mediterranean range of these species. A phenetic analysis of these data revealed no direct relationship between genetic variation and host‐plant association within L. cynarae, but there was a strong geographical structuring of allozyme patterns. Most of the genetic variation was due to differences between geographical regions and variation within these was small. Wright's FST values showed that Italian and Greek populations of L. cynarae were most distinct from L. latus, with southern Iberian, northern Spanish and French populations increasingly less so. This pattern was associated with a cline in the frequencies of certain alleles along this geographical arc from France to Greece. A phenogram of Nei's genetic distances indicated the close genetic relationship between the two species of Larinus and separated the populations of L. cynarae into three allopatric groups. These groups have different host‐plant spectra ‐ dominated by Cynara cardunculus in Italy and Greece, Cynara humilis/Onopordum in southern Iberia and Onopordum spp. in France/Northern Spain ‐ and can be considered to be host biotypes of L. cynarae. L. latus, which occurs in Greece and further east is also an Onopordum specialist. An analysis of the phylogeny of this group of Larinus indicates a primary separation into eastern (L. latus) and western (L. cynarae) taxa, with further branching of the L. cynarae lineage into the putative host‐biotypes. An hypothesis for the evolution of these taxa is given, based on the evolutionary history of host‐plant taxa and geographical constraints.
A hierarchical analysis of population genetic structure in Rhizobium leguminosarum bv. trifolii
Authors: HAGEN M. J. , HAMRICK J. L.
Published: November 2003

Little is known about the population processes that shape the genetic diversity in natural populations of rhizobia. A sample of 912 Rhizobium leguminosarum biovar trifolii isolates were collected from naturalized red clover populations (Trifolium pratense) and analysed for 15 allozyme loci to determine the levels and distribution of genetic diversity. Hierarchical analyses compared different sampling levels, geographical separation, and temporal separation. Total genetic diversity across all isolates was H= 0.426, with 57.6% of the total diversity found among isolates obtained from individual red clover plants. Relatively low genetic differentiation among populations and high differentiation among plants within populations was observed; this suggests that gene flow and founder effect act differently at geographical and local scales. Significant differences were observed in (i) allele frequencies among populations and among plants within populations, and (ii) the frequency distribution of the most widespread and the most abundant strains. When multilocus linkage disequilibrium was calculated, significant levels of disequilibrium were observed in the total sample and in three of the eight populations.
A suite of falcon single‐locus minisatellite probes: a powerful alternative to DNA fingerprinting
Authors: Wetton J. H. , Parkin D. T.
Published: November 2003

Nine falcon single‐locus minisatellite probes have been cloned, characterized and shown to provide a powerful alternative to multilocus DNA fingerprinting for determining the parentage of broods of young. Eight clones derived from size‐selected peregrine Falco peregrinus and merlin F. columbarius charomid libraries were found to detect single minisatellite loci in all tested members of the genus Falco. A further clone (cFti1) randomly selected from a kestrel F. tinnunculus library identified a single locus in other members of the genus and certain species of the Accipitridae. The nine loci display a mean heterozygosity of 88% and considerable allelic diversity in the peregrine and merlin. Pedigree analysis provides evidence consistent with the clustering of minisatellites in linkage groups that are conserved between species. Mutations were observed at five loci among families of peregrines and kestrels. Composite profiles produced with this suite of probes provide an excellent means of confirming identity and parentage. The use of profiling for investigating familial relationships, population dynamics and combating the illegal trade in wild falcons is discussed.
Planarian mitochondria sequence heterogeneity: relationships between the type of cytochrome c oxidase subunit I gene sequence, karyotype and genital organ
Authors: Bessho Y. , Tamura S. , Hori H. , Tanaka H. , Ohama T. , Osawa S.
Published: November 2003

Freshwater planarians Dugesia japonica from three localities were examined for cytochrome c oxidase subunit I (COI) gene sequence, karyotype and the presence of genital organ. The planarians from Mt Fujiwara in Japan were composed of two different groups; one revealed inter‐ and intraindividual COI gene heterogeneity, while another revealed no sequence heterogeneity. The sequence in planarians from Mt Alishan in Taiwan was homogeneous, while that from the Kenting National Park in Taiwan revealed a considerable heterogeneity. All the planarians having the homogeneous gene sequences carry the 2X karyotype and many of them had genital organs. These are assumed to belong to the sexual lineage. In contrast, almost all planarians having heterogeneous sequences carry the karyotype of either 3X plus 2X (mixoploid) or 3X, and all of them lack genital organs. These lineages are assumed to be asexual. The heterogeneity of COI gene sequences in the presumed asexual lineages would have resulted from an accumulation of mutations by repeated asexual reproduction.
Does polyploidy lead to fewer and shorter microsatellites in Barbus (Teleostei: Cyprinidae)?
Authors: Chenuil A. , Desmarais E. , Pouyaud L. , Berrebi P.
Published: November 2003

Screening of a hybrid Barbus barbus‐B. meridionalis genome was performed for CA, GA, TAT, TCT, TAG, TGT, TATT, TACT, ATCT motifs, and simultaneously on another fish species, tilapia S. melanotheron. Sequences of positive clones were obtained for Barbus and revealed that repetitive structure significantly depends on the motif: most TAT and TATT repeats contain small numbers of repeats, and these repeats are highly heterogeneous, whereas other motifs (we mainly obtained CA and GATA repeats) form longer and much more homogeneous arrays. Polymorphism data from five loci in two different species of barbel show that perfectly repetitive loci are much more variable than imperfect loci (TAT and TATT). We compared the frequency of positive clones for different repeat motifs between barbel and tilapia. For dinucleotide repeats (CA and GA), the comparison was extended to additional fish species, trout and sea bass, which were screened in nearly identical conditions for these motifs. The most salient feature of these comparisons reveals that arrays of dinucleotide motifs are significantly under‐represented and shorter in Barbus than in other fish species. We propose an explanation that can account for most features of microsatellites characterizing the genome of barbel. A bias toward deletion affecting slipped‐strand mispairing events would lead to shortening and loss of microsatellite loci. Such a bias would represent an efficient way of eliminating useless DNA from polyploidized species with an excessive amount of DNA.
Molecular scatology: the use of molecular genetic analysis to assign species, sex and individual identity to seal faeces
Authors: Reed J. Z. , Tollit D. J. , Thompson P. M. , Amos W.
Published: November 2003

Seals and commercial fisheries are potential competitors for fish and cephalopods. Research into the diet of British seal species has been based on conventional dietary analyses, but these methods often do not allow assignment of species identity to scat samples. We present a protocol for obtaining DNA from seal scat (faecal) samples which can be used in polymerase chain reactions to amplify both nuclear and mitochondrial DNA. This can provide a method of identifying the species, sex and individual identity of the seal, from a particular scat sample. Combined with conventional dietary analyses these techniques will allow us to assess sources of variation in seal diet composition.

Scat samples have been collected from intertidal haul‐out sites around the inner Moray Firth, north‐east Scotland. We have assessed methods to extract and purify faecal DNA, a combination of DNA from the individual seal, prey items, and gut bacteria, for use in PCR. Controls using faecal and blood samples from the same individual have enabled microsatellite primer sets from four pinniped species to be tested. Approximately 200 scat samples have been examined for species identity and individual matches. This study will provide essential information for the assessment of interactions between seals and commercial or recreational fisheries.