Combined moxidectin-levamisole treatment against multidrug-resistant gastrointestinal nematodes: A four-year efficacy monitoring in lambs.

Nematicide combinations may be a valid strategy to achieve effective nematode control in the presence of drug resistance. The goal of the current trial was to evaluate the pharmaco-parasitological performance of the moxidectin (MOX) and levamisole (LEV) combination after four years of continuous use in lambs naturally parasitized with multi-resistant gastrointestinal nematodes. At the beginning of the trial, 40 lambs were divided into four groups (n = 10), which were untreated (control) or subcutaneously treated with MOX (0.2 mg/kg), LEV (8 mg/kg) or with the combination MOX + LEV (administered separately at 0.2 and 8 mg/kg, respectively). Blood samples were collected at different times post-treatment and LEV and MOX plasma concentrations were measured by HPLC. The clinical efficacy of the continuous use of MOX + LEV combination was assessed with the controlled efficacy test (CET), performed at the beginning and end of the study, and with the faecal egg count reduction (FECR) test, performed over the four-year study period. No significant adverse pharmacokinetic changes were observed either for MOX or LEV after their co-administration to infected lambs. The CET (first year) showed efficacies of 84.3 % (Haemonchus contortus), 100 % (Teladorsagia circumcincta and Trichostrongylus axei), and 97.4 % (T. colubriformis). After the repetitive use of the combined treatment for four years, those efficacies remained high (100 %) and only decreased to 58 % against T. colubriformis. The evaluation of the FECR over the study period showed fluctuations in the performance of the combined administration. The initial FECR (2014) was 99 % (MOX), 85 % (LEV) and 100 % (MOX + LEV). The co-administration of MOX + LEV during the four-year experimental period resulted in a significantly higher anthelmintic effect (87 %) than that of MOX (42 %) or LEV (69 %) given alone. The combined use of MOX + LEV to control resistant gastrointestinal nematodes appears to be a valid strategy under specific management conditions. A high initial therapeutic response to the combination would be a relevant feature for the success of this tool.

Pharmacologic interaction between oxfendazole and triclabendazole: In vitro biotransformation and systemic exposure in sheep.

The aim of the current work was to evaluate a potential pharmacokinetic interaction between the flukicide triclabendazole (TCBZ) and the broad-spectrum benzimidazole (BZD) anthelmintic oxfendazole (OFZ) in sheep. To this end, both an in vitro assay in microsomal fractions and an in vivo trial in lambs parasitized with Haemonchus contortus resistant to OFZ and its reduced derivative fenbendazole (FBZ) were carried out. Sheep microsomal fractions were incubated together with OFZ, FBZ, TCBZ, or a combination of either FBZ and TCBZ or OFZ and TCBZ. OFZ production was significantly diminished upon coincubation of FBZ and TCBZ, whereas neither FBZ nor OFZ affected the S-oxidation of TCBZ towards its sulfoxide and sulfone metabolites. For the in vivo trial, lambs were treated with OFZ (Vermox® oral drench at a single dose of 5 mg/kg PO), TCBZ (Fasinex® oral drench at a single dose of 12 mg/kg PO) or both compounds at a single dose of 5 (Vermox®) and 12 mg/kg (Fasinex®) PO. Blood samples were taken to quantify drug and metabolite concentrations, and pharmacokinetic parameters were calculated by means of non-compartmental analysis. Results showed that the pharmacokinetic parameters of active molecules and metabolites were not significantly altered upon coadministration. The sole exception was the increase in the mean residence time (MRT) of OFZ and FBZ sulfone upon coadministration, with no significant changes in the remaining pharmacokinetic parameters. This research is a further contribution to the study of metabolic drug-drug interactions that may affect anthelmintic efficacies in ruminants.

Effects of fenbendazole and triclabendazole on the expression of cytochrome P450 1A and flavin-monooxygenase isozymes in bovine precision-cut liver slices.

Combinations of the anthelmintics fenbendazole (FBZ) and triclabendazole (TCBZ) have shown enhanced efficacy against the liver fluke Fasciola hepatica. This study aimed to measuring the constitutive expression of CYP1A1, CYP1A2, FMO1 and FMO3, thought to be involved in the metabolism of those compounds, by using an absolute quantitative real time (RT)-PCR approach in bovine precision-cut liver slices (PCLS). It also aimed to characterize the effects of FBZ and TCBZ (alone and in combination) on the expression and activity of the aforementioned isozymes. Both FMO1 and FMO3 were equally represented in control PCLS, whereas CYP1A2 was expressed more than CYP1A1 (P<0.05). PCLS cultured in the presence of beta naphthoflavone (ß-NF; CYP1A inducer) had higher mRNA levels of CYP1A1, CYP1A2, FMO1 and FMO3 (P<0.05). No clear-cut evidence of transcriptional effects of the anthelmintics were recorded. After incubation of PCLS with FBZ, there was a significant increase (P<0.05) vs. controls and TBCZ was observed for CYP1A1. PCLS treated with FBZ showed a higher (P<0.05) expression of CYP1A2 compared to controls, TCBZ alone, and the combination FBZ+TCBZ. The gene expression profiles of FMO1 and FMO3 were not affected by the presence of the anthelmintics; the only exception was an upregulation of FMO3 by TCBZ alone. The observed transcriptional effects of the xenobiotics were not mirrored by increased enzyme activities using prototypical substrates of the isozymes under study. Although further confirmatory studies are needed, these results suggest that PCLS represent an alternative in vitro tool for studies on the expression, regulation and function of relevant xenobiotic-metabolizing enzymes in cattle.

Assessment of the pharmacological interactions between the nematodicidal fenbendazole and the flukicidal triclabendazole: In vitro studies with bovine liver microsomes and slices.

Parasitic diseases have a significant impact on livestock production. Nematodicidal drugs, such as fenbendazole (FBZ) or its oxidized metabolite oxfendazole (OFZ), can be used along with the trematodicidal triclabendazole (TCBZ), to broaden the spectrum of anthelmintic activity. However, co-exposure to these compounds could lead to drug-drug (D-D) interactions and eventually alter the clinical profile of each active principle. The aim of this study was to assess the presence of such interactions by means of two in vitro models, namely bovine liver microsomal fractions and bovine precision-cut liver slices (PCLSs). To this end, an in vitro assessment involving incubation of FBZ and TCBZ or a combination of FBZ and TCBZ was carried out. Results with microsomal fractions showed a 78.4% reduction (p = .002) in the rate of OFZ production upon co-incubation, whereas the sulfoxide metabolite of TCBZ (TCBZSO) exhibited a decreasing tendency. With PCLS, OFZ accumulation in the incubation medium increased 1.8-fold upon co-incubation, whereas TCBZSO accumulation decreased by 28%. The accumulation of FBZ and OFZ in the liver tissue increased upon 2-hr co-incubation, from 2.1 ± 1.5 to 18.2 ± 6.1 (p = .0009) and from 0.4 ± 0.1 to 1.3 ± 0.3 nmol (p = .0005), respectively. These results confirm the presence of D-D interactions between FBZ and TCBZ. Further studies are needed to determine the extent of involvement of drug-metabolizing enzymes and membrane transporters in interactions between compounds largely used in livestock production systems.

Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows.

Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO2 ) into milk. The goal of this study was to evaluate the presence of potential in vivo drug-drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO2 was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO2 into milk was observed. The milk-to-plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO2 were not modified in the presence of OFZ. The pattern of MNPSO2 excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO2 ) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO2 ) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the in vivo pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO2 .

Factors influencing the success of aerial rabies vaccination of foxes.

Sylvatic rabies has been eradicated from most of Central Europe, but cases still occur in the Balkans. Oral rabies vaccination of foxes is an effective method for controlling the disease. The aim of this study was to evaluate the success of aerial vaccination campaigns conducted in Montenegro by identifying ecological, environmental and climatic factors that influenced the prevalence of antibodies to the rabies vaccine. To monitor the bait uptake and the serological responses to vaccination, foxes were shot by hunters. Of 175 shot foxes, 142 foxes (81.1%) had consumed baits. Of these only a total of 81 (57.0%) tested positive for rabies vaccine antibodies, possibly, due to the delayed uptake of bait in which the rabies vaccine was already inactivated. We found that low vaccination responses were associated with high fox density and bait delivery in open areas. In high fox density habitat, bait uptake might be delayed as other food and prey options for foxes are abundant. Similarly, delayed bait uptake probably occurred in open areas as such areas are less frequently used by foxes. The findings of this study suggest that efficacy of oral rabies vaccination by aerial delivery is associated with landscape features.

Hepatic biotransformation pathways and ruminal metabolic stability of the novel anthelmintic monepantel in sheep and cattle.

Monepantel (MNP) is a new amino-acetonitrile derivative anthelmintic drug used for the treatment of gastrointestinal (GI) nematodes in sheep. The present work investigated the main enzymatic pathways involved in the hepatic biotransformation of MNP in sheep and cattle. The metabolic stability in ruminal fluid of both the parent drug and its main metabolite (monepantel sulphone, MNPSO2 ) was characterized as well. Additionally, the relative distribution of both anthelmintic molecules between the fluid and particulate phases of the ruminal content was studied. Liver microsomal fractions from six (6) rams and five (5) steers were incubated with a 40 µm of MNP. Heat pretreatment (50 °C for 2 min) of liver microsomes was performed for inactivation of the flavin-monooxygenase (FMO) system. Additionally, MNP was incubated in the presence of 4, 40, and 80 µm of methimazole (MTZ), a FMO inhibitor, or equimolar concentrations of piperonyl butoxide (PBx), a well-known general cytochrome P450 (CYP) inhibitor. In both ruminant species, MNPSO2 was the main metabolite detected after MNP incubation with liver microsomes. The conversion rate of MNP into MNPSO2 was fivefold higher (P < 0.05) in sheep (0.15 ± 0.08 nmol/min·mg) compared to cattle. In sheep, the relative involvement of both FMO and CYP systems (FMO/CYP) was 36/64. Virtually, only the CYP system appeared to be involved in the production of MNPSO2 in cattle liver. Methimazole significantly reduced (41 to 79%) the rate of MNPSO2 production in sheep liver microsomes whereas it did not inhibit MNP oxidation in cattle liver microsomes. On the other hand, PBx inhibited the production of MNPSO2 in liver microsomes of both sheep (58 to 98%, in a dose-dependent manner) and cattle (almost 100%, independently of the PBx concentration added). The incubation of MNP and MNPSO2 with ruminal contents of both species showed a high chemical stability without evident metabolism and/or degradation as well as an extensive degree of adsorption (83% to 90%) to the solid phase of the ruminal content. Overall, these results are a further contribution to the understanding of the metabolic fate of this anthelmintic drug in ruminants.

Accumulation of monepantel and its sulphone derivative in tissues of nematode location in sheep: pharmacokinetic support to its excellent nematodicidal activity.

The amino-acetonitrile derivatives (AADs) are a new class of anthelmintic molecules active against a wide range of sheep gastrointestinal (GI) nematodes including those that are resistant to other anthelmintic families. The plasma disposition of monepantel (MNP) has been previously characterized in sheep. However, information on drug concentration profiles attained at tissues of parasite location is necessary to fully understand the pharmacological action of this novel compound. The current work aimed to study the relationship between the concentrations of MNP parent drug and its main metabolite monepantel sulphone (MNPSO2), measured in the bloodstream and in different GI tissues of parasite location in sheep. Twenty two (22) uninfected healthy Romney Marsh lambs received MNP (Zolvix, Novartis Animal Health) orally administered at 2.5 mg/kg. Blood samples were collected from six animals between 0 and 14 days post-treatment to characterize the drug/metabolite plasma disposition kinetics. Additionally, 16 lambs were sacrificed at 8, 24, 48 and 96 h post-administration to assess the drug concentrations in the GI fluid contents and tissues. MNP and MNPSO2 concentrations were determined by HPLC. MNP parent compound was rapidly oxidized into MNPSO2. MNP systemic availability was significantly lower than that observed for MNPSO2. The peak plasma concentrations were 15.1 (MNP) and 61.4 ng/ml (MNPSO2). The MNPSO2 to MNP plasma concentration profile ratio (values expressed in AUC) reached a value of 12. Markedly higher concentrations of MNP and MNPSO2 were measured in both abomasal and duodenal fluid contents, and mucosal tissues compared to those recovered from the bloodstream. A great MNP availability was measured in the abomasal content with concentration values ranging between 2000 and 4000 ng/g during the first 48 h post-treatment. Interestingly, the metabolite MNPSO2 was also recovered in abomasal content but its concentrations were significantly lower compared to MNP. The parent drug and its sulphone metabolite were detected in the different segments of the sheep intestine. MNPSO2 concentrations in the different intestine sections sampled were significantly higher compared to those measured in the abomasum. Although MNP is metabolized to MNPSO2 in the liver, the large concentrations of both anthelmintically active molecules recovered during the first 48 h post-treatment from the abomasum and small intestine may greatly contribute to the well-established pharmacological activity of MNP against GI nematodes.

Intestinal drug transport: ex vivo evaluation of the interactions between ABC transporters and anthelmintic molecules.

The family of ATP-binding cassette (ABC) transporters is composed of several transmembrane proteins that are involved in the efflux of a large number of drugs including ivermectin, a macrocyclic lactone (ML) endectocide, widely used in human and livestock antiparasitic therapy. The aim of the work reported here was to assess the interaction between three different anthelmintic drugs with substrates of the P-glycoprotein (P-gp) and the breast cancer resistance protein (BCRP). The ability of ivermectin (IVM), moxidectin (MOX) and closantel (CST) to modulate the intestinal transport of both rhodamine 123 (Rho 123), a P-gp substrate, and danofloxacin (DFX), a BCRP substrate, across rat ileum was studied by performing the Ussing chamber technique. Compared to the controls, Rho 123 efflux was significantly reduced by IVM (69%), CST (51%) and the positive control PSC833 (65%), whereas no significant differences were observed in the presence of MOX (30%). In addition, DFX efflux was reduced between 59% and 72% by all the assayed drug molecules, showing a higher potency than that observed in the presence of the specific BCRP inhibitor pantoprazole (PTZ) (52%). An ex vivo intestinal transport approach based on the diffusion chambers technique may offer a complementary tool to study potential drug interactions with efflux transporters such as P-gp and BCRP.

Are topical oestrogens useful in faecal incontinence? Double-blind randomized trial.

BACKGROUND: Histopathological studies have shown the presence of oestrogenic receptors in the anal sphincter, which presumes a role in muscular trophism for circulating oestrogens. This could explain the increase in faecal incontinence (FI) in postmenopausal women. OBJECTIVE: To evaluate the effect of topical oestrogens (TE) in controlling symptoms of FI in postmenopausal women. Hypothesis The application of TE in postmenopausal women with FI improves continence. METHOD: We performed a prospective double-blind randomized trial applying TE to the anal mucosa in postmenopausal women with FI. STUDY PERIOD: 2005-2006. The patients were randomized into two groups: I--topical estriol, II--placebo. In both groups, the ointment was applied three times daily for a period of 6 weeks. We compared Wexner's FI score and the FI quality of life scale, before commencing and after 6 weeks of application. RESULTS: In this period we evaluated 36 patients. Average age: 67 years (48-84). Group I: 18 patients and group II: 18 patients, one patient was excluded. Wexner's FI score in group I was 11 (5-18) and 7 (0-19) with pre- and postapplication respectively (P = 0.002). Wexner's FI score in group II was 12 and 9 with pre- and postapplication respectively (P = 0.013). When we compared the results between both groups, this was not statistically significant (P = 0.521). CONCLUSION: There is improvement of continence in both groups that had the ointment applied; nonetheless this study could not show that TE improves FI more than a placebo does.

Exploring language barriers to Evidence-based Health Care (EBHC) in post-graduate medical students: a randomised trial.

BACKGROUND: Understanding the written English language might be a barrier when teaching Evidence-based Health Care (EBHC) to Spanish-speaking physicians. AIM: To quantify the magnitude of this potential barrier. METHOD: Cochrane Review abstracts in English or in Spanish were randomly distributed among first-year residents at the Pontificia Universidad Catolica of Chile. Residents answered investigator-designed questionnaires to measure their comprehension while the time needed to complete the task was recorded. RESULTS: Groups were similar at baseline. Mean score for those reading in Spanish was 11.9 +/- 2.8 (range 5 to 18) compared to 10.5 +/- 3.8 (range 1 to 17) for those reading in English (p=0.04). Low scores ( pound 9) were twice as frequent for the English group than for the Spanish group (16.7% vs 34.7%; p=0.042). The time to complete the task was also longer for the group reading in English. CONCLUSION: Language should be taken into account when teaching EBHC to Spanish-speaking physicians.

Influyen las características psicológicas y los estilos de aprendizaje en el rendimiento académico de los estudiantes de medicina? Un estudio retrospectivo / The influence of phychological features and learning styles on the academic performance of medical students

BACKGROUND: The degree of difficulty we experience while learning different concepts and skills depends, among other things, on our psychological features and learning style. This may be particularly true for medical students, whose formation involves the acquisition of multiple cognitive, affective and psychomotor skills. AIM: To assess whether the psychological features and learning styles of medical students are associated with their academic performance. SUBJECTS AND METHODS: The psychological preferences and learning styles of 66 students of the 2001-graduating cohort were determined with the Myers Briggs Type Inventory (MBTI) and the Kolb Learning Style Inventory (LSI), respectively. The academic performance was assessed by the Calificación Médica Nacional (CMN), Chile and by the marks obtained during the Basic (1st to 3rd), Preclinical (4th and 5th) and Clinical (6th and 7th) years of undergraduate training. RESULTS: The psychological features, together with the sex of students were found to be associated with the performance in the Preclinical and Clinical years, and to the CMN. In men, the interest and ability to communicate with people and the concern for harmony, and in women the tendency to function in a systematic and orderly way are the features associated to high academic performance. No associations were found between learning styles and academic performance. CONCLUSIONS: The finding that the psychological preferences of medical students are relevent to their academic performance opens a new perspective to analyze the medical education and to design programs aimed at improving learning.

Tipos psicológicos y estilos de aprendizaje de los estudiantes que ingresan a medicina en la Pontificia Universidad Católica de Chile / Psychological types and learning styles of students entering medical school at the Pontificia Universidad Católica de Chile

BACKGROUND: Psychological type and learning style influence the way students perceive and process information. However, research in medical education in Chile still does not put enough emphasis in the study of these variables. AIM: To characterize the psychological types and learning styles of the students admitted to a Medical School. SUBJECTS AND METHODS: The Myers Briggs Type Indicator (MBTI) and the Kolb's Learning Styles Inventory (IEA) were administered to the 270 students admitted from 2000 to 2002 to the medical school of the Pontificia Universidad Católica de Chile. RESULTS: Fifty five percent of our students are concentrated in 4 of the 16 psychological types described. These students are characterized by the ability to base their decisions upon logical and objective reasoning (Thinking [T]) and to face life in a structured and decided way (Judging [J]). Only 10 per cent of the students have preferences opposite to T and J. These students base their decisions on the preservation of harmony and teamwork (Feeling [F]) and have a flexible attitude towards life (Perceiving [P]). The remaining 35 per cent have types with pairs of preferences TP and FJ. With regard to learning styles, more than two thirds of our students are Assimilators or Convergers. These learners tend to assimilate large amounts of information and abstract the main concepts, rather than to pay attention to concrete details. In general, our students are more reflective than active; they evaluate thoroughly all alternatives before making a decision. CONCLUSIONS: The psychological types and learning styles of medical students cluster around specific patterns whose features may either favor or hamper a specific learning. Knowledge of the differences in psychological types and learning styles of students may provide teachers with a new and valuable tool for improving learning and contributing to the academic success of students.

Neumonía adquirida en la comunidad en el adulto hospitalizado. Cuadro clínico y factores pronósticos / Community-acquired pneumonia in hospitalized adult patients. Clinical presentation and prognostic factors

BACKGROUND: Community-acquired pneumonia (CAP) is a serious health problem in Chile. AIM: To study prognostic factors on admission and outcome of CAP, in immune competent adult patients, hospitalized in the Catholic University Clinical Hospital. PATIENTS AND METHODS: All adult patients admitted with a CAP in a period of 2 years were prospectively studied. Patients with immunodeficiency, solid tumors or receiving oral adrenal steroids were excluded from the study. RESULTS: In the study period, 463 patients (69 +/- 19 years, 55 per cent male) were evaluated. Ninety four percent were treated with 2nd or 3rd generation cephalosporins. Mean hospital length of stay was 10 days. Mortality during hospital stay was 8 per cent and in the ensuing 30 days, it was 12 per cent. Bacterial etiology was established in 25 per cent of cases. The most frequent pathogens isolated were Streptococcus pneumoniae (10.2 per cent), Haemophilus influenzae (3.7 per cent), Staphylococcus aureus (2.8 per cent) and Gram negative bacilli (5.2 per cent). Admission prognostic factors associated with hospital mortality were an age over 65 years, presence of comorbidity, chronic neurological and hepatic disease, suspicion of aspiration, duration of symptoms for less than 3 days, presence of dyspnea and altered mental status, absence of cough, fever and chills; low blood pressure, tachypnea, metabolic acidosis, hypoxemia, high blood urea nitrogen, hypernatremia, hyperkalemia, hyperphosphatemia, hypoalbuminemia, multilobar radiographic pulmonary infiltrates, bacteremia, high risk categories of the Fine Index (IV and V), and admission to Intermediate Care Unit or ICU. CONCLUSIONS: The features of community acquired pneumonia of these patients are similar to those reported abroad.

Colour, form, and movement are not perceived simultaneously.

Behavioural, neuro-anatomical and clinical evidence suggests that different aspects of the visual scene are processed separately, but the extent to which the processing is carried out along segregated and independent parallel pathways is still debated. Moreover, it is also unclear whether these aspects are processed at the same rate, and their neural correlates reach consciousness at the same time. An experiment investigated this issue in the case of three attributes of 2D displays: colour, form, and movement. There were three conditions, one for each possible pairing of these attributes. Stimuli were combinations of two values for each attribute (red/green, circle/square, fixed/moving). In each condition the stimuli changed twice in close temporal succession, each attribute switching asynchronously between the two possible values. The observer's task was to report which change had occurred first. Response probabilities were computed for 13 values of the asynchrony, and transformed into estimates of perception time with the help of a psychophysical model. The results showed that colour and form are processed almost simultaneously. By contrast, movement perception is delayed by about 50 ms. The implications of these findings vis à vis the so-called perceptual binding problem are discussed.

[Determination of opiates in urine: interpretation of comparison between the EIA and FPIA and confirmation of data with GC/MS]. / Determinazione degli oppiacei nelle urine: interpretazione del confronto tra EIA e FPIA e conferma dei dati con GC/MS.

BACKGROUND: The aim of this study was to evaluate some urine samples and to analyse them using two immunochemical screening methods. METHODS: A more reliable method has been used to obtain a critical analysis of the validity of the first analysis methods used. A total of 147 urine samples were examined using both the FPIA technique (Adx, Abbott) and the EIA technique (Random 120, Bracco); confirmation was obtained using GC/MS. RESULTS: When the threshold was altered from 200 to 300 ng/ml the EIA technique is more severely affected by changes in reference values compared to FPIA. In different values between two techniques, confirmation with GC/MS was possible only 5 cases. CONCLUSIONS: The study of data processing with immunochemical tests and after confirmation showed that the results with GC/MS are closer to Adx. The FPIA results are in agreement with the GC/MS technique both at 200 and 300 ng/ml with a percentage of 80.0%. The EIA technique has a different result, at 200 ng/ml it is in agreement for 40.0%, but at 300 ng/ml there is only 20.0%.

Proprioception does not quickly drift during visual occlusion.

Several perceptual studies have shown that the ability to estimate the location of the arm degrades quickly during visual occlusion. To account for this effect, it has been suggested that proprioception drifts when not continuously calibrated by vision. In the present study, we re-evaluated this hypothesis by isolating the proprioceptive component of position sense (i.e., the subjects were forced to rely exclusively on proprioception to locate their hand, which was not the case in earlier studies). Three experiments were conducted. In experiment 1, subjects were required to estimate the location of their unseen right hand, at rest, using a visual spot controlled by the left hand through a joystick. Results showed that the mean accuracy was identical whether the localization task was performed immediately after the positioning of the hand or after a 10-s delay. In experiments 2 and 3, subjects were required to point, without vision of their limb, to visual targets. These two experiments relied on the demonstration that biases in the perception of the initial hand location induced systematic variations of the movement characteristics (initial direction, final accuracy, end-point variability). For these motor tasks, the subjects did not pay attention to the initial hand location, which removed the possible occurrence of confounding cognitive strategies. Results indicated that movement characteristics were, on average, not affected when a 15-s or 20-s delay was introduced between the positioning of the arm at the starting point and the presentation of the target. When considered together, our results suggest that proprioception does not quickly drift in the absence of visual information. The potential origin of the discrepancy between our results and earlier studies is discussed.

Perceptual anticipation in handwriting: the role of implicit motor competence.

In two experiments, perceptual anticipation--that is, the observer's ability to predict the course of dynamic visual events--in the case of handwriting traces was investigated. Observers were shown the dynamic display of the middle letter l excerpted from two cursive trigrams (lll or lln) handwritten by one individual. The experimental factor was the distribution of the velocity along the trace, which was controlled by a single parameter, beta. Only for one value of this parameter (beta = 2/3) did the display comply with the two-thirds power law, which describes how tangential velocity depends on curvature in writing movements. The task was to indicate the trigram from which the trace was excerpted--that is, to guess the letter that followed the specific instance of the l that had been displayed. In Experiment 1, the no answer option was available. Experiment 2 adopted a forced-choice response rule. Responses were never reinforced. When beta = 2/3, the rate of correct guesses was high (Experiment 1, P¿correct¿ = .69; Experiment 2, P¿correct¿ = .78). The probability of a correct answer decreased significantly for both smaller and larger values of beta, with wrong answers becoming predominant at the extremes of the range of variation of this parameter. The results are consistent with the hypothesis that perceptual anticipation of human movements involves comparing the perceptual stimulus with an internal dynamic representation of the ongoing event.