Analysis of reproduction success, growth and milk trajectories and response to nutritional challenge in two Alpine goat lines selected on divergent longevity.

This study aims to investigate whether the variation in reproduction success, growth, and milk trajectories is associated with different adaptive strategies in the short term (response to an acute nutritional challenge), using two Alpine goat lines. A total of 382 Alpine goats (179 low longevity (low_LGV) and 203 high longevity (high_LGV)), selected for divergent functional longevity from a commercial population, were monitored for 4 years and recorded for BW, reproduction and milking performance. Every year, an average of fifty primiparous goats were exposed to a 2-d nutritional challenge in early lactation. A polynomial model was used to analyse the lifetime trajectory of lactation and BW. A piecewise model was used to analyse the individual milk yield and responses of milk components to the nutritional challenges. The statistical analysis revealed that the two lines had a similar performance for total milk yield in the first lactation, BW at birth and at first kidding, litter size and weight, kidding interval and interval from the first insemination to conception. BW trajectories revealed that low_LGV goats had a greater BW in pregnancy but then lost more weight in early lactation compared to high_LGV goats, which showed a greater BW after kidding. Milk trajectories showed that the high_LGV goats had a higher initial milk yield, an earlier but less marked lactation peak and more persistency in milk production in late lactation than low_LGV goats. Except for milk protein content, quite similar response and recovery profiles of milk yield and milk fat content were observed during the challenge for both lines. The response to the challenge was positively correlated to the initial level of milk production in early lactation but negatively correlated with milk production decline after the peak. This finding suggests that the low_LGV goats were more adapted to allocate resources to meet an expected physiological change such as gestation and lactation. However, high_LGV goats allocate more than low_LGV goats for structural mass and may better cope with an unexpected environmental change such as nutritional deficit.

Multivariate analysis of milk metabolite measures shows potential for deriving new resilience phenotypes.

In a context of growing interest in breeding more resilient animals, a noninvasive indicator of resilience would be very valuable. We hypothesized that the time-course of concentrations of several milk metabolites through a short-term underfeeding challenge could reflect the variation of resilience mechanisms to such a challenge. We submitted 138 one-year-old primiparous goats, selected for extreme functional longevity (i.e., productive longevity corrected for milk yield [60 low longevity line goats and 78 high longevity line goats]), to a 2-d underfeeding challenge during early lactation. We measured the concentration of 13 milk metabolites and the activity of 1 enzyme during prechallenge, challenge, and recovery periods. Functional principal component analysis summarized the trends of milk metabolite concentration over time efficiently without preliminary assumptions concerning the shapes of the curves. We first ran a supervised prediction of the longevity line of the goats based on the milk metabolite curves. The partial least square analysis could not predict the longevity line accurately. We thus decided to explore the large overall variability of milk metabolite curves with an unsupervised clustering. The large year × facility effect on the metabolite concentrations was precorrected for. This resulted in 3 clusters of goats defined by different metabolic responses to underfeeding. The cluster that showed higher ß-hydroxybutyrate, cholesterol, and triacylglycerols increase during the underfeeding challenge was associated with poorer survival compared with the other 2 clusters. These results suggest that multivariate analysis of noninvasive milk measures show potential for deriving new resilience phenotypes.

Selection on functional longevity in a commercial population of dairy goats translates into significant differences in longevity in a common farm environment.

Resilience is the ability of an animal to cope with environmental disturbances, such as pathogens or negative energy balance. To improve resilience through breeding, we need resilience indicators. Functional longevity might be a good indicator of a dairy goat's lifetime resilience as it results from the ability to cope with and recover from all the challenges faced throughout its lifetime. The aim of this study was to validate the use of functional longevity as an indicator of resilience for selection. To address this question, we created 2 genetic lines of Alpine goats using hyperselected artificial insemination bucks with the most extreme estimated breeding values for functional longevity and the same milk yield performance. A total of 440 goats, 228 in the high longevity (high_LGV) and 221 in the low longevity (low_LGV) lines, were bred and monitored for 4 yr. Health treatments, serum IgG concentration as a proxy of passive immune transfer in early life, kidding, age, and reason of culling were systematically noted. Weight and body morphology were monitored. Weight and growth during the first year of life were similar in both goat lines. In contrast, the low_LGV goats had a lower weight during the beginning of first lactation than high_LGV goats. The milk fat-to-protein ratio was also significantly higher in low_LGV goats during first lactation. A multivariable Cox regression was fitted to the data to decipher survival at different stages of life in the 2 lines. The overall survival of high_LGV goats was significantly better than low_LGV goats (hazard ratio = 0.63, confidence interval = 0.47; 0.86) even after we included treatment, growth, serum IgG concentration at birth, and year effects in the model. The line effect was not constant over time; no significant effect was found during the first year, and the difference was observed after first kidding. This result suggested that survival at an early stage of life and during later productive life are under different genetic regulation. Altogether, this monitoring of the goat lines indicated that functional longevity-based selection helps to improve resilience by improving survival and mitigating some indicators of fat mobilization during early lactation.

Short- and mid-term effects on performance, health and qualitative behavioural assessment of Romane lambs in different milk feeding conditions.

The common practice of artificially rearing lambs from prolific meat breeds of sheep constitutes a welfare issue due to increased mortality rates and negative health issues. In this multidisciplinary study, we investigated the possible short- and mid-term advantages of artificially feeding fresh ewe's milk instead of commercial milk replacer on lambs' growth, health and welfare. Romane lambs were either separated from their mothers on D3 and fed with Lacaune ewes' milk (LAC, n = 13) or milk replacer (REP, n = 15), or they were reared by their mothers (MOT, n = 15). On D45, they were weaned, gathered in single-sex groups until the end of the study on D150. Lamb performance and biomarkers of overall health were assessed by measuring: growth, dirtiness of the perianal area, enteric pathogens in the faeces, total antioxidant status and redox status assessed by plasma reduced glutathione/oxidised glutathione ratio, and immune response after vaccination against chlamydiosis. As an exploratory approach, blood cell transcriptomic profiles were also investigated. Last, qualitative behaviour assessment (QBA) was performed as an integrated welfare criterion. Lacaune ewes' milk and REP never differed in their average daily gain but grew less than MOT lambs in the early suckling period and just after weaning. No effect was detected afterwards. On D30, LAC and REP lambs had lower total antioxidant and higher redox status than MOT lambs but did not differ among themselves. Lacaune ewes' milk and MOT had a cleaner perianal area than REP lambs on D21, while faecal pathogen infection did not vary between the treatment groups. After vaccination, LAC also had a stronger immune response on D90 compared to REP lambs. Transcriptome analysis performed on D150 showed differential gene expression, mainly in relation to inflammatory, immune and cell cycle response, between male lambs of the LAC group and those of the MOT and REP groups. Based on QBA, LAC lambs never differed from MOT lambs in their general activity and varied from REP only on D21; REP lambs were always more agitated than MOT lambs. In conclusion, artificial milk feeding impaired early growth rate, health and emotional state mainly during the milk feeding period and at weaning. Feeding artificially reared lambs with fresh ewe's milk partly mitigated some of the negative effects induced by milk replacer but without achieving the full benefit of being reared by the mother.

Understanding the clinical reasoning processes involved in the management of multimorbidity in an ambulatory setting: study protocol of a stimulated recall research.

BACKGROUND: Primary care physicians are at the very heart of managing patients suffering from multimorbidity. However, several studies have highlighted that some physicians feel ill-equipped to manage these kinds of complex clinical situations. Few studies are available on the clinical reasoning processes at play during the long-term management and follow-up of patients suffering from multimorbidity. This study aims to contribute to a better understanding on how the clinical reasoning of primary care physicians is affected during follow-up consultations with these patients. METHODS: A qualitative research project based on semi-structured interviews with primary care physicians in an ambulatory setting will be carried out, using the video stimulated recall interview method. Participants will be filmed in their work environment during a standard consultation with a patient suffering from multimorbidity using a "button camera" (small camera) which will be pinned to their white coat. The recording will be used in a following semi-structured interview with physicians and the research team to instigate a stimulated recall. Stimulated recall is a research method that allows the investigation of cognitive processes by inviting participants to recall their concurrent thinking during an event when prompted by a video sequence recall. During this interview, participants will be prompted by different video sequence and asked to discuss them; the aim will be to encourage them to make their clinical reasoning processes explicit. Fifteen to twenty interviews are planned to reach data saturation. The interviews will be transcribed verbatim and data will be analysed according to a standard content analysis, using deductive and inductive approaches. CONCLUSION: Study results will contribute to the scientific community's overall understanding of clinical reasoning. This will subsequently allow future generation of primary care physicians to have access to more adequate trainings to manage patients suffering from multimorbidity in their practice. As a result, this will improve the quality of the patient's care and treatments.

Functional Independence Measure score is associated with mortality in critically ill elderly patients admitted to an intermediate care unit.

BACKGROUND: Age alone is not a robust predictor of mortality in critically ill elderly patients. Chronic health status and functional status before admission could be better predictors. This study aimed to determine whether functional status, assessed using the Functional Independence Measure (FIM), could be an independent predictor of mortality in a geriatric population admitted to an intermediate care unit (IMCU). METHODS: A monocentric, retrospective, observational study of all patients aged ≥75 years old admitted to Geneva University Hospitals' geriatric IMCU between 01.01.2012 and 31.05.2016. The study's primary outcome metrics were one-year mortality's associations with a pre-admission FIM score and other relevant prospectively recorded prognostic variables. RESULTS: A total of 345 patients were included (56% female, mean age 85 +/- 6.5 years). Mean FIM score was 66 +/- 26. One-year mortality was 57%. Dichotomized low (≤ 63) and high FIM (> 63) scores were associated with one-year mortalities of 68 and 44%, respectively. Logistic regression calculations found an association between pre-admission FIM score and one-year mortality (p <  0.0001), including variables usually associated with mortality (e.g., age, sex, comorbidities, mini-mental health state score, renal function). Multivariate survival analysis showed a significant difference between groups, with a hazard ratio of 0.29 (95% CI: 0.13-0.65) for patients with high FIM scores. CONCLUSIONS: In the present study, higher functional status, assessed using the FIM tool before admission to an IMCU, was significantly and independently associated with lower one-year mortality. This opens up perspectives on the potential value of FIM for establishing a finer prognosis and better triage of critically ill older patients.

Lupin (Lupinus spp.) seeds exert anthelmintic activity associated with their alkaloid content.

The growing range of drug resistant parasitic nematode populations threatens the sustainability of ruminant farming worldwide. In this context, nutraceuticals, animal feed that provides necessary dietary requirements while ensuring parasite control, could contribute to increase farming sustainability in developed and low resource settings. In this study, we evaluated the anthelmintic potential of lupin seed extracts against the major ruminant trichostrongylids, Haemonchus contortus and Teladorsagia circumcincta. In vitro observations showed that seed extracts from commercially available lupin varieties could significantly but moderately inhibit larval migration. This anthelmintic effect was mediated by the seed alkaloid content and was potent against both fully susceptible and multidrug resistant H. contortus isolates as well as a susceptible T. circumcincta isolate. Analytical chemistry revealed a set of four lupanine and sparteine-derivatives with anthelmintic activity, and electrophysiology assays on recombinant nematode acetylcholine receptors suggested an antagonistic mode of action for lupin alkaloids. An in vivo trial in H. contortus infected lupin-fed ewes and goats failed to demonstrate any direct anthelmintic effect of crude lupin seeds but infected lupin-fed goats suffered significantly less parasite-mediated blood losses. Altogether, our findings suggest that the anthelmintic potential of lupin remains limited. However, the potent alkaloids identified could lead to the development of novel drugs or may be used in combination with current anthelmintics to improve their efficacy.

Divergent selection on milk somatic cell count in goats improves udder health and milk quality with no effect on nematode resistance.

Milk somatic cell count (SCC) is commonly higher in goats than in cattle and sheep. Furthermore, the ability of milk SCC to predict mastitis is considered lower in goats than in cattle and sheep, and the relevance of somatic cell score (SCS)-based selection in this species has been questioned. To address this issue, we created 2 divergent lines of Alpine goats using artificially inseminated bucks with extreme estimated breeding values for SCS. A total of 287 goats, 158 in high- and 129 in low-SCS lines, were scrutinized for mastitis infections. We subjected 2,688 milk samples to conventional bacteriological analyses on agarose and bacterial counts were estimated for positive samples. The SCS, milk yield, fat content, and protein content were recorded every 3 wk. Clinical mastitis was systematically noted. A subset of 40 goats (20 from each line) was subsequently challenged with Haemonchus contortus and monitored for anemia (blood packed cell volume) and fecal egg counts to see if SCS-based selection had an indirect effect on resistance to gastrointestinal nematodes. Milk production traits, including milk quantity, fat content, and protein content, were similar in both goat lines. In contrast, the raw milk SCC almost doubled between the lines, with 1,542,000 versus 855,000 cells/mL in the high- and low-SCS lines, respectively. The difference in breeding value for SCS between lines was 1.65 genetic standard deviation equivalents. The Staphylococcus spp. most frequently isolated from milk were S. xylosus, S. caprae, S. epidermidis, and S. aureus. The frequency of positive bacteriology samples was significantly higher in the high-SCS line (49%) than in the low-SCS line (33%). The highest odds ratio was 3.49 (95% confidence interval: 11.95-6.25) for S. aureus. The distribution of bacterial species in positive samples between lines was comparable. The average quantity of bacteria in positive samples was also significantly higher in high-SCS goats (69 ± 80 growing colonies) than in low-SCS goats (38 ± 62 growing colonies). Clinical cases were rare and equally distributed between high- (n = 4; 2.5%) and low-SCS (n = 3; 2.3%) lines. Furthermore, the larger the amounts of bacteria in milk the higher the SCS level. Conversely, goats with repeatedly culture-negative udders exhibited the lowest SCC levels, with an average of below 300,000 cells/mL. We therefore confirmed that SCS is a relevant predictor of intramammary infection and hygienic quality of milk in goats and can be used for prophylactic purposes. After challenge with H. contortus, goats were anemic with high fecal egg counts but we found no difference between the genetic lines. This result provides initial evidence that resistance to mastitis or to gastrointestinal nematodes infections is under independent genetic regulation. Altogether, this monitoring of the goat lines indicated that SCS-based selection helps to improve udder health by decreasing milk cell counts and reducing the incidence of infection and related bacterial shedding in milk. Selection for low SCC should not affect a goat's ability to cope with gastrointestinal nematodes.

Melioidosis in patients with suspected tuberculosis in Cambodia: a single-center cross-sectional study.

SETTING: Melioidosis-Burkholderia pseudomallei infection-is increasingly recognized in Cambodia, a country with a high incidence of tuberculosis (TB). Melioidosis and TB can be clinically indistinguishable. OBJECTIVE: To quantify the proportion of patients with clinically suspected TB who had melioidosis by testing sputum for B. pseudomallei. DESIGN: This was a prospective, 6-month cross-sectional single-center study at a Cambodian provincial referral hospital among patients with suspicion of TB who provided sputum specimens for testing. TB was diagnosed using sputum Xpert® MTB/RIF molecular assay or culture; melioidosis was diagnosed using sputum culture for B. pseudomallei. RESULTS: Of 404 patients evaluated for possible TB, 52 (12.9%, 95%CI 9.8-16.5) had TB. Four patients (1.0%, 95%CI 0.3-2.5) had melioidosis; none had concurrent TB or an existing medical risk factor for melioidosis, although two were farmers, an occupational risk factor. CONCLUSION: One per cent of patients being evaluated for TB at a Cambodian provincial referral hospital had culture-proven respiratory melioidosis, a highly lethal infection. None had previously recognized medical conditions that would increase their risk of melioidosis. Testing for melioidosis should be considered in patients presenting with suspected TB in Cambodia.

Genotype by environment interactions for behavioral reactivity in sheep.

In sheep, social reactivity and reactivity to humans are relevant behavioral responses that are used to investigate the behavioral adaptation of farm animals to various rearing conditions. Such traits were previously reported as heritable and associated with several QTLs. However, few behavior-related genotype by environment (G × E) interactions have been reported to date. The experiment was performed on 2,989 male and female lambs issued from 30 sires. Every sire had progeny reared under both intensive and extensive conditions. After weaning, all lambs were individually exposed to two standardized behavioral tests. A broad range of behaviors including vocalizations, locomotion, localization, vigilance, and flight distance were assessed. Two complementary statistic approaches, with and without assumptions on the biological significance of behaviors, were performed to investigate social reactivity and reactivity to humans. G × E interactions were investigated based on the genetic correlations estimated for each factor or trait between farming conditions; those significantly different from 1 indicating a G × E. Environmental effects showed that social reactivity and reactivity to humans were higher in intensively reared lambs. The heritability of factors or traits used to measure social reactivity and reactivity to humans was similar in both rearing conditions. Estimated heritabilities were high for vocalizations in response to social isolation, moderate for locomotion and vigilance in response to social isolation, and low for both flight distance to an approaching human and proximity to a motionless human. No significant G × E interaction was found for vocalizations. G × E interactions were found for locomotion, vigilance and flight distance. Genetic correlations between both environments were low to moderate for vigilance, locomotion and flight distance. Vocalization in response to social isolation with or without human presence was identified as a robust trait and could be used to improve sheep sociability, independently of the environment. A G × E interaction was observed for behavioral reactivity to humans. Although moderate, the genetic correlation for this trait between intensive and extensive conditions could be used to select sires in the same environment by taking into account the G × E and to produce in different environments progenies that are less reactive to humans.

[Exercise-induced muscle pain due to phosphofrutokinase deficiency: Diagnostic contribution of metabolic explorations (exercise tests, 31P-nuclear magnetic resonance spectroscopy)]. / Intolérance musculaire à l'effort par déficit en phosphofructokinase : apport au diagnostic du bilan métabolique musculaire (tests d'effort, spectroscopie RMN du P31).

INTRODUCTION: Muscle phosphofructokinase deficiency, the seventh member of the glycogen storage diseases family, is also called Tarui's disease (GSD VII). METHODS: We studied two patients in two unrelated families with Tarui's disease, analyzing clinical features, CK level, EMG, muscle biopsy findings and molecular genetics features. Metabolic muscle explorations (forearm ischemic exercise test [FIET]; bicycle ergometer exercise test [EE]; 31P-nuclear magnetic resonance spectroscopy of calf muscle [31P-NMR-S]) are performed as appropriate. RESULTS: Two patients, a 47-year-old man and a 38-year-old woman, complained of exercise-induced fatigue since childhood. The neurological examination was normal or showed light weakness. Laboratory studies showed increased CPK, serum uric acid and reticulocyte count without anemia. There was no increase in the blood lactate level during the FIET or the EE although there was a light increase in the respiratory exchange ratio during the EE. 31P-NMR-S revealed no intracellular acidification or accumulated intermediates such as phosphorylated monoesters (PME) known to be pathognomic for GSD VII. Two new mutations were identified. DISCUSSION: FIET and EE were non-contributive to diagnosis, but 31P-NMR provided a characteristic spectra of Tarui's disease, in agreement with phosphofructokinase activity level in erythrocytes. Muscle biopsy does not always provide useful information for diagnosis. In these two cases, genetic studies failed to establish a genotype-phenotype correlation. CONCLUSION: The search for phosphofructokinase deficiency should be continued throughout life in adults experiencing fatigability or weakness because of the severe disability for daily life activities caused by the late onset form.

Impact of double-blind vs. open study design on the observed treatment effects of new oral anticoagulants in atrial fibrillation: a meta-analysis.

BACKGROUND: The prospective, randomized, open, blinded endpoint evaluation (PROBE) design has been proposed as a valid alternative to the double-blind (DB) design for trials comparing new oral anticoagulants (NOAs) with INR-adjusted vitamin K antagonists in patients with non-valvular atrial fibrillation (NVAF). OBJECTIVES: To determine whether the observed treatment effects of NOAs in patients with NVAF differ between PROBE/open-label trials and DB trials. METHODS: All phase II or III trials were eligible. The main efficacy and safety outcomes were stroke/systemic embolism (SSE) and major bleeding, respectively. Other outcomes included ischemic SSE, hemorrhagic stroke, intracranial and extracranial bleeding, myocardial infarction, and all-cause and cardiovascular mortality. Interaction (Cochran's chi-squared test) between PROBE and DB designs was tested. RESULTS: Thirteen studies (61 620 patients) were included. For SSE, a greater treatment effect of NOAs vs. INR-adjusted warfarin was observed in PROBE trials (RR 0.76, CI 0.65-0.89) compared with DB trials (RR 0.88, CI 0.78-0.98), but the interaction test was non-significant (P = 0.16). A significant 67% enhancement of treatment effect was found with PROBE/open-label trials compared with DB trials (interaction test, P = 0.05) for hemorrhagic stroke. No other interaction was significant. A non-significant interaction (P = 0.07) between oral direct thrombin inhibitors (RR 0.33; 0.22-0.51) and factor Xa inhibitors (RR 0.54; 0.40-0.72) was seen. No heterogeneity was found for any outcome. CONCLUSIONS: Our meta-analysis showed no significant interaction of study design for the main efficacy and safety outcomes. However, the non-significantly exaggerated reduction in SSE suggests interdependence of treatment effect and PROBE design, especially for hemorrhagic stroke.

[Unexplained, subclinical chronically elevated transaminases]. / Élévation modérée, persistante et inexpliquée des transaminases.

Unexplained, subclinical chronically elevated transaminases is mainly a marker of non-alcoholic fatty liver disease, metabolic syndrome, alcoholism and diabetes, which are very common situations but viral hepatitis and iatrogenic origin must also be considered. Before looking for hepatic or genetic rare diseases, it is worth considering hypertransaminasemia as a clue for muscular disease, particularly in paediatric settings, and creatine phosphokinase is a specific marker. Then, patient history, examination and appropriate biologic requests can permit the identification of less frequent disorders where isolated hypertransaminasemia is possibly the unique marker of the disease for a long while: hemochromatosis, celiac disease, autoimmune hepatitis, Wilson's disease, α1-anti-trypsine deficiency, thyroid dysfunctions, Addison's disease. Liver biopsy should be performed only in patients with aspartate aminotransferases upper the normal range or alanine aminotransferases higher than twice the normal range after 6 months delay with dietetic corrections.

[How to assess the impact of morbimortality conferences on healthcare quality and safety in ICU ?]. / Comment évaluer l'impact des revues de morbi-mortalité sur la qualité et la sécurité des soins en réanimation ?

OBJECTIVE: To estimate the morbidity and mortality conferences (MMC) impact in intensive care unit (ICU) setting on quality of care and patients' safety. DATA SOURCES: A review of English and French articles in Medline database (1990-2011) related to MMC in the ICU. Keywords used: "morbidity (and) mortality conference(s)", "intensive care unit", "intensive/critical care medicine". Additional studies identified by hand search in French national guidelines about MMCs and in the Annales Françaises d'Anesthésie Réanimation and Réanimation journals index. Identification and preliminary analysis performed using title and abstract, for every study related to MMC in the ICU. STUDY SELECTION: Only original studies about MMC in the ICU setting that reported an assessment were included. Papers reporting guidelines and methods for MMC implementation were excluded. DATA EXTRACTION: Extraction used predefined data fields, including study design, MMC characteristics, assessment methods and results. DATA SYNTHESIS: Studies about MMC in the ICU are recent and scarce. Results comparison and synthesis are impaired by discrepancies in study designs. Although the effectiveness of MMC is not evidence-based, data are consistent for their positive impact on quality of care and patient safety in the ICU. CONCLUSION: Further studies are required to assess the impact of MMC in the ICU. Based on this literature review, a 4-level evaluation scheme can be suggested: 1) evaluation of MMC implementation in care units and facilities; 2) evaluation of MMC organization; 3) evaluation of MMC on quality of care; 4) evaluation of MMC impact on patients' mortality and morbidity.

[Assessment of mortality morbidity conference in obstetrics: literature review]. / Évaluation de l'impact des revues de morbi-mortalité en obstétrique: revue de la littérature.

OBJECTIVES: To assess this effectiveness of morbi-mortality conference (MMC) in improving quality of care. MATERIALS AND METHODS: A review was carried out by searching Medline, Pascal and Cochrane databases, Google scholar and websites of French obstetrics professional societies, until July 2011. Search terms included morbidity, mortality, conference, and obstetrics. The eligible reports of assessment of MMC in obstetrics have been analysed by four reviewers with a standardized form. RESULTS: Among 319 records identified, four observational studies published between 2009 and 2011 were included. The objective of these MMC was students' training (n=2), quality of care improvement (n=1), or both (n=1). The MMC organization was heterogeneous. The impact of MMC was assessed using qualitative (n=2), semi-quantitative (n=1) or quantitative (n=1) method. None of these studies showed a significant impact of MMC on students' training or quality of care. CONCLUSION: Available evidence is insufficient to evaluate the effectiveness of MMC in improving quality of obstetrics care.

New insights into the influence of breed and time of the year on the response of ewes to the 'ram effect'.

Exposure of anoestrous ewes to rams induces an increase in LH secretion, eventually leading to ovulation. This technique therefore is an effective, low-cost and hormone-free way of mating sheep outside the breeding season. However, the use of this technique is limited by the variability of the ewes' responses. In this study, our objective was to understand more completely the origins of this variability and to determine the relative roles of breed, the point in time during anoestrus and the depth of anoestrus on the response to the 'ram effect'. In the first experiment, the pattern of anoestrus on the basis of the concentration of progesterone determined weekly, was determined in four breeds including two less seasonal (Mérinos d'Arles and Romane), one highly seasonal (Mouton Vendéen) and one intermediate (Île-de-France) breeds. Anoestrus was longer and deeper in Mouton Vendéen and Île-de-France than in Romane or Mérinos d'Arles. In the second experiment, we used the same four breeds and tested their hypophyseal response to a challenge with a single dose of 75 ng gonadotrophin-releasing hormone (GnRH) in early, mid and late anoestrus, and then we examined their endocrine and ovarian responses to the 'ram effect'. Most (97%) ewes responded to GnRH and most (93%) showed a short-term increase in LH pulsatility following the 'ram effect'. The responses in both cases were higher in females that went on to ovulate, suggesting that the magnitude of the hypophyseal response to a GnRH challenge could be a predictor of the response to the 'ram effect'. As previously observed, the best ovarian response was in Mérinos d'Arles at the end of anoestrus. However, there was no relationship between the proportion of females in the flock showing spontaneous ovulation and the response to the 'ram effect' of anoestrous ewes from the same flock.

[Recurrent aseptic meningitis secondary to nonsteroidal anti-inflammatory drugs in a patient with lupus]. / Méningite aseptique récidivante due aux anti-inflammatoires non stéroïdiens chez une patiente lupique.

We report a 39-year-old woman with systemic lupus who presented with recurrent aseptic meningitis secondary to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). She presented two episodes following ibuprofen administration that were characterized by aseptic meningitis with high protein level in cerebrospinal fluid, and increased serum acute phase reactants. No evidence of an infection or vasculitis was documented. Clinical manifestation resolved rapidly with ibuprofen discontinuation, and corticosteroids therapy was unnecessary. Aseptic meningitis related to NSAIDs reported in lupus patients should be considered because of their specific modality of care and their favourable outcome.