Intravenous thrombolysis and thrombectomy decisions in acute ischemic stroke: An interrater and intrarater agreement study.

PURPOSE: We aimed to assess agreement on intravenous tissue-plasminogen activator (IV tPA) and mechanical thrombectomy (MT) management decisions in acute ischemic stroke (AIS) patients. Secondary objectives were to assess agreement on Diffusion-Weighted-Imaging-Alberta-Stroke-Program-EArly-CT-Score (DWI-ASPECTS), and clinicians' willingness to recruit patients in a randomized controlled trial (RCT) comparing medical management with or without MT. MATERIALS AND METHODS: Studies assessing agreement of IV tPA and MT were systematically reviewed. An electronic portfolio of 41 AIS patients was sent to randomly selected providers at French stroke centers. Raters were asked 4 questions for each case: (1) What is the DWI-ASPECTS? (2) Would you perform IV tPA? (3) Would you perform MT? (4) Would you include the patient in a RCT comparing standard medical therapy with or without MT? Twenty responders were randomly selected to study intrarater agreement. Agreement was assessed using Fleiss' Kappa statistics. RESULTS: The review yielded two single center studies involving 2-5 raters, with various results. The electronic survey was answered by 86 physicians (60 vascular neurologists and 26 interventional neuroradiologists). The interrater agreement was moderate for IV tPA treatment decisions (κ=0.565 [0.420-0.680]), but only fair for MT (κ=0.383 [0.289-0.491]) and for combined treatment decisions (κ=0.399 [0.320-0.486]). The intrarater agreement was at least substantial for the majority of raters. The interrater agreement for DWI-ASPECTS was fair (κ=0.325 [0.276-0.387]). Physicians were willing to include a mean of 14±9 patients (33.1%±21.7%) in a RCT. CONCLUSION: Disagreements regarding the use of IVtPA or MT in the management of AIS patients remain frequent. Further trials are needed to resolve the numerous areas of uncertainty.

[Naso-ethmoido-maxillary protrusion (NEMP): a specific dysmorphosis]. / La pro-naso-ethmoïdo-maxillie (PNEM) : une dysmorphose spécifique.

Naso-ethmoido-maxillary protrusion (NEMP) is a rare dental and facial dysmorphosis, with excessive growth of basicranium, ethmoid, maxillary, and nasal bones. The clinical presentation includes nasal and upper lip protrusion, telecanthus, a class 2 malocclusion with maxillary protrusion and exoclusion. The craniofacial field is increased in Delaire's analysis. Contrary to isolated maxillary protrusion secondary to membranous ossification dysfunction, NEMP is a constitutional anomaly resulting from an excessive primary growth of the chondrocranium. The therapeutic management of NEMP should take into account these specificities.

Can efficient management of sheep gastro-intestinal nematodes be based on random treatment?

Targeted selective treatment has been proposed as a method to reduce gastro-intestinal nematode infections in ruminants and lower the selective pressure that leads to anthelmintic resistance. Since nematodes are highly aggregated within their host population, treating only the most heavily infected hosts offers an efficient and sustainable strategy to reduce infection within the flock and slow the spread of anthelmintic resistance. Although effective methods to correctly identify such hosts are available, their feasibility is often limited in the field conditions. Instead, treating part of the flock at random may prove to be a useful and practical alternative. This study examined whether such random treatment could be relevant in controlling nematode infections and delaying the selection of anthelmintic resistance compared to targeted selective treatment. Firstly, an individual based model was used to evaluate the sustainability of random treatment according to several parasitic distributions in the host population (negative binomial, uniform and normal distributions). Anthelmintic resistance was modelled based on benzimidazoles, as a monogenic trait. Anthelmintic treatment was done twice a year, week 23 and 41, corresponding to beginning of June and of October. The model was run over a five-year period corresponding to the minimum delay for anthelmintic resistance to be observed following its initial use. The model outputs show an increase in the proportion of treated hosts led to an increase in the frequency of the resistance allele for both treatment regimes. Random treatment was shown to be slightly less efficient than targeted selective treatment in controlling for the infection intensity regardless of the percentage of hosts treated. Random treatment was however more efficient than targeted selective treatment in counter-selecting for anthelmintic resistance in both the aggregated and uniformly distributed models. Secondly, a one grazing season experiment was conducted to compare a random treatment flock (20% of flock was treated at random monthly) against a mass treatment flock (the whole flock was treated monthly). Both treatment regimes produced similar pasture infectivity, similar mean infection intensity and similar final host live weight. This is the first time random treatment of a subset of hosts has been demonstrated to be a sustainable alternative to mass treatment.

A genome scan for QTL affecting resistance to Haemonchus contortus in sheep.

Gastrointestinal nematodes are one of the main health issues in sheep breeding. To identify loci affecting the resistance to Haemonchus contortus, a genome scan was carried out using 1,275 Romane × Martinik Black Belly backcross lambs. The entire population was challenged with Haemonchus contortus in 2 consecutive experimental infections, and fecal egg counts (FEC) and packed cell volumes were measured. A subgroup of 332 lambs with extreme FEC was necropsied to determine the total worm burden, length of female worms, sex ratio in the worm population, abomasal pH, and serum and mucosal G immunoglobulins (IgG) responses. Pepsinogen concentration was measured in another subset of 229 lambs. For QTL detection, 160 microsatellite markers were used as well as the Illumina OvineSNP50 BeadChip that provided 42,469 SNP markers after quality control. Linkage, association, and joint linkage and association analyses were performed with the QTLMAP software. Linkage disequilibrium (LD) was estimated within each pure breed, and association analyses were carried out either considering or not the breed origin of the haplotypes. Four QTL regions on sheep chromosomes (OAR)5, 12, 13, and 21 were identified as key players among many other QTL with small to moderate effects. A QTL on OAR21 affecting pepsinogen concentration exactly matched the pepsinogen (PGA5) locus. A 10-Mbp region affecting FEC after the 1st and 2nd infections was found on OAR12. The SNP markers outperformed microsatellites in the linkage analysis. Taking advantage of the LD helped to refine the locations of the QTL mapped on OAR5 and 13.

Experimental and modeling approaches to evaluate different aspects of the efficacy of Targeted Selective Treatment of anthelmintics against sheep parasite nematodes.

Maintaining a refugia i.e. a proportion of the population that is not exposed to selection by treatments has been suggested as an alternative to mass treatment in the management of nematode parasites of sheep. Three refugia have been identified: nematodes in untreated hosts, encysted larvae and free-living stages on pastures. Here we tested whether Targeted Selective Treatments (TST) could be relevant in controlling nematode infections and delaying anthelmintic resistance selection. We first conducted a one grazing season experiment to compare all flock treatment (the whole flock was treated monthly) and TST based on monthly excretion eggs and daily weight gain. Nematode burden was higher in TST group, but anthelmintic susceptibility of nematodes was preserved. We then used an individual-based model to evaluate the sustainability of TST on a longer period. The simulation approach indicated that TST20% and TST30% of the flock were efficient both at maintaining resistance at a low level and controlling nematode parasite infections on a mid-term period (i.e. simulation of five grazing seasons). However for an efficient TST, these percentages of treated hosts should be adapted to flock size since the number of nematode parasites exposed to selection increases in large flocks. Our results also showed a high dependence on the timing of treatment i.e. on the size of the refugia constituted by the free-living stages on the pasture.

Contrasting genetic structures of two parasitic nematodes, determined on the basis of neutral microsatellite markers and selected anthelmintic resistance markers.

For the first time, the neutral genetic relatedness of natural populations of Trichostrongylid nematodes was investigated in relation to polymorphism of the beta-tubulin gene, which is selected for anthelminthic treatments. The aim of the study was to assess the contribution of several evolutionary processes: migration and genetic drift by neutral genetic markers and selection by anthelminthic treatments on the presence of resistance alleles at beta-tubulin. We studied two nematode species (Teladorsagia circumcincta and Haemonchus contortus) common in temperate climatic zones; these species are characterized by contrasting life history traits. We studied 10 isolated populations of goat nematode parasites: no infected adult goat had been exchanged after the herds were established. Beta-tubulin polymorphism was similar in these two species. One and two beta-tubulin alleles from T. circumcincta and H. contortus respectively were shared by several populations. Most of the beta-tubulin alleles were 'private' alleles. No recombination between alleles was detected in BZ-resistant alleles from T. circumcincta and H. contortus. The T. circumcincta populations have not diverged much since their isolation (F(ST) <0.08), whereas H. contortus displayed marked local genetic differentiation (F(ST) ranging from 0.08 to 0.18). These findings suggest that there are severe bottlenecks in the H. contortus populations, possibly because of their reduced abundance during unfavourable periods and their high reproductive rate, which allows the species to persist even after severe population reduction. Overall, the data reported contradict the hypothesis of the origin of beta-tubulin resistance alleles in these populations from a single mutational event, but two other hypotheses (recurrent mutation generating new alleles in isolated populations and the introduction of existing alleles) emerge as equally likely.

Resistance of trichostrongyles to benzimidazoles in Italy: a first report in a goat farm with multiple and repeated introductions.

Anthelmintic resistance is widely distributed in small ruminants throughout the world. The extension of resistance seems lower in southern European countries and has not been reported previously in Italy. In the present study, resistance to benzimidazoles, levamisole and ivermectin was evaluated in a multi-breed goat farm of southern Italy. The farm had a history of repeated goat introductions from other flocks and a moderate regimen of anthelmintic treatments using alternatively the three above-mentioned drugs. Resistance of gastrointestinal strongyles was studied on the basis of faecal egg counts, egg hatch assay and necropsies. Resistance to anthelmintics was evidenced for benzimidazoles only, and Trichostrongylus colubriformis was the only resistant strongyle species. Single drug and single species resistance suggest that resistance is on its beginning and that measures for reducing the spread of resistance are of interest and should be promoted.

Substitution of benzimidazole-resistant nematodes for susceptible nematodes in grazing lambs.

Multi-drug-resistant gastrointestinal nematode parasite populations are becoming more and more prevalent. Since anthelmintic treatments are of limited effectiveness, one solution could be to replace the anthelmintic-resistant population by a susceptible population, in order to re-establish the possibility of drug-based anthelmintic control. We investigated this substitution strategy in 4 paddocks of 0.7 ha, each of which was seeded with a benzimidazole-resistant Teladorsagia circumcincta population. The proportion of benzimidazole-resistant worms in these paddocks ranged from 20% to 89%. A 2-step replacement was performed: first, the paddocks were not grazed for 6 months (from December to July), and then the grass was cut to eliminate any residual infective larvae, before contaminating each of the paddocks with 10 seeder lambs experimentally infected with a benzimidazole-susceptible strain of T. circumcincta (from July to November). At the end of the experiment, all the populations on the 4 paddocks were phenotypically benzimidazole-susceptible, but genotyping indicated that 2 populations harboured 1% and 3% resistant worms respectively. This study demonstrates that nematode replacement is feasible in temperate areas, using semi-intensive stock management, even when the initial levels of benzimidazole-resistance are very high. Further research should next assess replacing the whole community to cope with the species diversity observed under field conditions.

Estimation of abomasum strongyle nematode infections in sheep at necropsy: tentative proposals for a simplified technique.

Several necropsy techniques are available for estimating the abundance of gastro-intestinal nematodes in abomasum of ruminants. Standardization of techniques is needed to allow accurate comparisons between laboratories. Here we propose a standardized technique for estimating the abundance of worms. We intend to compare the worms' number estimations in lambs and ewes based on contents and washings, to determine the uniformity of worm counts in aliquots, and to estimate the total worm number from washings. The digesta (or "contents") and the washings of the abomasum are treated separately. The worms of each subsample are diluted with water and the total number of worms is estimated on a small volume (aliquots) of these subsamples. The use of aliquots assumes that the worms are uniformly distributed in the whole volume of each subsample. We first confirmed that the use of aliquots is appropriate in most cases. We then show that the use of the washings alone allows a faster and a suitable estimation of the total worm burden for all strongyle species of the abomasum in both ewes and lambs. The evaluation of our necropsy procedure is a first step to a standardized technique which should be improved by validation in other laboratories.

Evolution of nematode community in grazing sheep selected for resistance and susceptibility to Teladorsagia circumcincta and Trichostrongylus colubriformis: a 4-year experiment.

Field trials were undertaken to compare nematode population dynamics in two experimental flocks of rams selected for high and for low faecal egg counts (FECs) following two doses with 20000 infective larvae, 12000 Teladorsagia circumcincta (Tcirc) and 8000 Trichostrongylus colubriformis (Tcol) separated by a treatment. The selection was done by dosing 200 ram lambs (INRA 401 breed) and FECs proceeded with egg identification on days 28 and 35 post-each-infection. The 30 lambs with the lowest FECs constituted the group of permanent resistant rams (R), the 30 with the highest values the group of susceptible ones (S). Each group grazed separated pastures from April to November, this during 4 consecutive years. The contamination (number of eggs deposited) was estimated every 3 weeks on each pasture. The larval populations was measured by successive groups of tracer lambs. The infection of the permanent rams was done by slaughtering eight R and S rams on mid and end of each grazing season. Each autumn, new R and S ram lambs were selected to complete the R and S groups before turning out in spring. On third year, a third species (Haemonchus contortus, Hcon) was added to compare its behaviour with the two others. The regulation of parasite populations were studied by comparing what happens in R rams and pasture to S ones. The selected R ram lambs had a FEC of Tcirc 50% lower than S ones. This induced a similar lowered pasture contamination, a 25% decrease of infective larval population in years 2 and 3, and the worm burdens in R rams were the half of that in S rams after 2 years. The FEC of Tcol was 75% lower at the selection and induced similar difference in pasture contamination, but 65 and 96% reduction in L3 population, respectively, after 1 and 2 years. The worm burden was reduced by 99%. Adding Hcon species during the third year, in year 4, the L3 population was half in R pasture compared with S one, and R rams had 60% less worms of this species than S ones. This selection without any drench prevent outbreaks observed in young tracer lambs on S pasture. The comparison of selected resistant rams to selected susceptible ones and not to unselected controls gave more rapid information about the tendency of the regulation of the communities of nematode parasites.

Rapid efficacy of highly active antiretroviral therapy in a case of HIV myelitis.

An HIV-seropositive patient with severe immunodepression was diagnosed as having HIV myelitis. Plasma and cerebrospinal fluid (CSF) HIV-RNA PCR were, respectively, 4.11 and 5.19log(10). After 1 month of treatment with highly active antiretroviral therapy (HAART), there was clinical recovery and both plasma and CSF HIV viral load had decreased considerably. This dramatic improvement was associated with a high concentration of antiviral drugs in the CSF, suggestive of the direct efficacy of HAART on HIV myelitis.

Acute pericarditis with transient constriction.

Transient constrictive pericarditis is a rare entity. It is characterized by clinical and echocardiographic features similar to constrictive pericarditis, but is distinguished by its transient nature. This feature is important to recognize for avoiding unnecessary pericardectomy. The case of a patient who presented with acute myopericarditis and typical echocardiographic features of constriction is described. Within weeks, all signs of constriction disappeared spontaneously.

Relationship between helminth species diversity, intensity of infection and breeding management in dairy goats.

Helminth infection, species diversity (proportion of each species in the community), species number, intensity of infection and anthelmintic resistance were investigated in 16 dairy-goat farms of south-western France. The aim of the study was to estimate which breeding management factors may affect diversity and intensity of infection. Anthelmintic resistance was investigated because this factor may modify composition of nematode communities. Farm history and breeding management were recorded by means of a questionnaire. Natural and experimental infections were compared to determine which strategy was the best to estimate diversity index and number of species from nematode community of a whole herd. A total of 17 species of helminths, among which 14 nematodes, one cestode (Moniezia spp.) and two trematodes (Paramphistomum daubneyi and Dicrocoelium lanceolatum) were recovered in the 26 necropsied culled goats. One culled goat worm burden represented conveniently species number but not species diversity (Shannon index) of parasite community harboured in the whole herd. Experimental sheep infection with larvae from pooled faeces of 15 goats was the best strategy to estimate species diversity in farms. Diversity could be predicted from the number of farms from which goats originated at constitution of the herd, the duration of goat winter withdrawal from pastures, and intensity of infection. Anthelmintic resistance was correlated with the number of farms of origin, area of permanent pastures and intensity of infection. The strategy adopted for the herd constitution was a critical step as species diversity and risk of anthelmintic resistance increased with the number of farms of origin. Intensity of infection was negatively correlated with species diversity. This suggested that more diverse communities were better controlled by the host, in agreement with the widespread statement that diversity would beget stability.

[Venous thromboembolism and cancer]. / Maladie thromboembolique veineuse et cancer.

INTRODUCTION: Thromboembolic venous disease, which includes both peripheral venous thrombosis and pulmonary embolism, is a frequent disorder in patients with cancer. Although thromboembolic manifestations may precede the diagnosis of cancer, the value of extensive clinical search for potential underlying cancer when faced with venous thromboembolic manifestations has not been demonstrated. CURRENT KNOWLEDGE AND KEY POINTS: Clinical and biological studies have demonstrated that acquired abnormalities in blood hemostasis, especially procoagulant factors, account for the onset of thromboembolic manifestations in patients with cancer. Classical anticoagulant therapy is associated with low efficacy and tolerance in patience with cancer who are at high risk for hemorrhagic complications and recurrence of thromboembolic disease. FUTURE PROSPECTS AND PROJECTS: Recent data suggest the value of anticoagulant therapy using either low molecular weight heparin or warfarin at low doses (INR < 2) according to the specific surgical or medical context.

Segmental myocardial contractility versus perfusion in Kawasaki disease with coronary arterial aneurysm.

The impact of Kawasaki-related coronary injury on the myocardium was evaluated in 13 patients with persistent coronary aneurysm after a follow-up period of 7.92+/-3.97 years (range 1.8 to 14.3). Myocardial segmental perfusion and contractility integrity were assessed by resting and exercise echocardiography and technetium-99 (Tc-99m) sestamibi scan. Eight patients (61.5%) had giant aneurysms (> or = 8 mm) and 9 had multivessel involvement; the mean diameter of the largest aneurysm was 8.6+/-2.5 mm (range 5 to 14). During the acute phase, myocardial infarction occurred in 1 patient and coronary thrombosis in another. At the latest echocardiographic evaluation, the mean aneurysm diameter was 6.8+/-2.4 mm (range 4.5 to 12), there was persistent giant aneurysms in 5 of 8 patients, and 3 of 9 patients had multivessel involvement. Coronary angiography demonstrated stenosis in 7 of 10 patients, with multiple levels in 2. At sestamibi scan, all 13 patients had perfusion anomalies at rest, whereas only 7 had detectable hypokinesia on echocardiography. With exercise, perfusion returned to near normal in 3 patients, improved in 3, remained unchanged in 4, and worsened in 3 patients. Segmental contractility similarly deteriorated in the latter 3 patients but also in 2 patients whose perfusion scan had improved with exercise. Three patients, normal at rest, developed segmental hypokinesia during exercise. When present, the location of observed changes in contractility on stress echocardiography corresponded to that of perfusion defect. In conclusion, abnormal myocardial perfusion is present long term after complicated Kawasaki disease, the worst anomalies accompanying persistent giant aneurysms. Unfavorable perfusion response was coupled with abnormal contractility; however, enhanced perfusion with exercise correlated poorly with segmental contractility response.

Mitral valve repair: Intermediate to long-term echocardiographic follow-up.

OBJECTIVE: To review intermediate to long term echocardiographic follow-up after mitral valve repair for mitral regurgitation. DESIGN: Nonrandomized, retrospective and prospective observational study. SETTING: Sacré-Coeur Hospital, University of Montreal, Montreal, Quebec. PATIENTS: Echocardiographic findings in 37 patients (mean age 62.1 +/- 10 years) three to 197 months (median 45) after mitral valve repair were reviewed. INTERVENTIONS: Preoperative data were collated from hospital records. Between October 1994 and March 1995, all patients had a clinical evaluation and a complete transthoracic echocardiogram done by a cardiologist. RESULT: There was a significant reduction in the dimensions of the left-sided cavities compared with preoperative data. Left atrial diameter decreased from from 50.9 +/- 7.7 to 46.3 +/- 8.1 mm (P = 0.01), left ventricular end-diastolic diameter from 59.6 +/- 7.1 to 51.2 +/- 6.3 mm (P < 0.001) and left ventricular end-systolic diameter from 35.3 +/- 7.9 to 32.8 +/- 7.8 mm (P = 0.07). On colour Doppler echocardiography, nine patients had no mitral regurgitation, 25 had mitral regurgitation grade I to II/IV, and three had grade III/IV. The mean mitral valve gradient was 4.2 +/- 1.8 mmHg and the pressure half-time 121.9 +/- 48 ms. There was no difference in gradient, mitral valve area and mitral regurgitation in patients with degenerative (29) compared with rheumatic (five) mitral valve disease. CONCLUSIONS: Mitral valve repair is highly effective in reducing mitral regurgitation in the long term and is associated with a reduction in the dimensions of the left atrium and the left ventricle. However, it leaves a mild degree of mitral valve obstruction.

Fitness of benzimidazole-resistant and -susceptible worms of Teladorsagia circumcincta, a nematode parasite of small ruminants.

We compared, some fitness-related traits of benzimidazole resistant (rr) and susceptible (rS, SS) worms of Teladorsagia circumcincta, a gastrointestinal parasite of the small ruminants, under laboratory conditions. PCR was used to determine the genotypes (rr, SS, rS) and the fitness of each was compared within the same strain. There was no significant difference in egg production, development rate from egg to infective larvae stage, establishment of these larvae in the host or the survival of adult worms and infective larvae for the 3 genotypes. The same results were obtained for the establishment rate of larvae in the host and the production of infective larvae under conditions of strong competition between resistant and susceptible worms. The fact that there were no differences in fitness suggests that the installation of benzimidazole resistance in a worm population is irreversible. This agrees with field observations.

Salmonella endocarditis of a ventricular aneurysm: a case report and review of the literature.

A 63-year-old man with salmonella endocarditis of a ventricular aneurysm is presented. The patient had a documented apical aneurysm with mural thrombus and left ventricular dysfunction following a previous myocardial infarction. His condition was unresponsive to maximal medical therapy and was cured by surgery. A review of the English-language literature revealed that only two other published cases of nonvalvular salmonella endocarditis resulted in patient survival. This report underscores the importance of suspecting a cardiovascular origin in cases of salmonella bacteremia to avoid delay in diagnosis and surgical intervention in this deadly condition.