Modelling gastrointestinal parasitism infection in a sheep flock over two reproductive seasons: in silico exploration and sensitivity analysis.

In reproducing ewes, a periparturient breakdown of immunity is often observed to result in increased fecal egg excretion, making them the main source of infection for their immunologically naive lambs. In this study, we expanded a simulation model previously developed for growing lambs to explore the impact of the genotype (performance and resistance traits) and host nutrition on the performance and parasitism of both growing lambs and reproducing ewes naturally infected with Teladorsagia circumcincta. Our model accounted for nutrient-demanding phases, such as gestation and lactation, and included a supplementary module to manage the age structure of the ewe flock. The model was validated by comparison with published data. Because model parameters were unknown or poorly estimated, detailed sensitivity analysis of the model was performed for the sheep mortality and the level of infection, following a preliminary screening step. The parameters with the greatest effect on parasite-related outputs were those driving animal growth and milk yield. Our model enables different parasite-control strategies (host nutrition, breeding for resistance and anthelmintic treatments) to be assessed on the long term in a sheep flock. To optimize in silico exploration, the parameters highlighted by the sensitivity analysis should be refined with real data.

[Evaluation of management of infarction in the Franche Comté province by the use of the Franche Comté Cardiology Registry, May 2005-May 2006]. / L'évaluation des pratiques professionnelles pour la prise en charge des infarctus en Franche-Comté. Expérience d'une évaluation à l'échelle régionale par l'utilisation des données du registre franc-comtois de cardiologie, mai 2005-mai 2006.

RATIONALE: The management of acute infarction often necessitates a network of organisation between different centres, thus making it the object of an evaluation of professional practices (EPP). We report the experience in the Franche Comté province of an EPP at a regional level in the management of infarction. METHODS: All of the patients admitted to 10 of the 11 centres in the region were included in a prospective survey. Quality indicators for acute and chronic care were defined, as well as scores, on the basis of use of treatments specified in guidelines. RESULTS: Between May 2005 and May 2006, 1,170 patients were admitted. The patients' risk levels and quality scores were calculated. The rate of use of the quality indicators was higher in our survey than that observed in all of the published studies, except for the use of betablockers. The quality of care could therefore be considered as highly satisfactory. Comparison between the centres revealed some differences. Even after adjustment for the risk score on admission, the quality score for acute care was related to mortality at 1 month. CONCLUSIONS: An EPP is possible for the management of infarction, on a regional scale such as in the province of Franche Comté. The acute quality score turned out to be an independent factor for mortality. The indicators showed that the quality of care was highly satisfactory, even though more progress could be made in the prescription of betablockers.

Randomised comparison of Micro Stent I with Palmaz-Schatz stent placement for the elective treatment of short coronary stenoses.

This randomised trial compared the Micro Stent I and the Palmaz-Schatz stent for the elective treatment of short (<8 mm long), new-onset coronary stenoses. The primary endpoints were restenosis rate and minimal luminal diameter at 6 mo angiographic follow-up. The secondary endpoints were angiographic and procedural success of stenting and a composite clinical endpoint at 6 mo (death, myocardial infarction, and target site revascularisation). A total of 93 patients were randomised. Clinical and angiographic characteristics of the two groups were comparable. Angiographic success of stenting was 96% in both groups, and there were no complications so that the procedural success was also 96% in both groups. The restenosis rate was 29% for Micro Stent I and 27% for the Palmaz-Schatz stent (P = NS). The minimal luminal diameter at 6 mo was 1.75 +/- 0.72 mm in the Micro Stent I group and 1.84 +/- 0.59 in the Palmaz-Schatz group (P = NS). At 6 mo, a clinical endpoint was reached by 21% of the patients in the Micro Stent I group and by 11% in the Palmaz-Schatz group (P = NS). In conclusion, the elective treatment of short coronary stenosis with the Micro Stent I or the Palmaz-Schatz stent resulted in similar early and late outcomes. In particular, the late angiographic results were very similar.

A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group.

BACKGROUND: The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate. METHODS: Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years. RESULTS: At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). CONCLUSIONS: In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.

Comparison of 6F with 7F and 8F guiding catheters for elective coronary angioplasty: results of a prospective, multicenter, randomized trial.

A group of 460 patients was considered in our prospective study of assessment of the efficiency and safety of 6F (internal diameter 0.062 inches) guiding catheters to perform elective percutaneous coronary angioplasty by the femoral approach by using conventional balloon systems. The patients were randomly assigned either a 6F guiding catheter (first group, n = 231; 247 coronary lesions), or a 7F or 8F guiding catheter (second group, n = 229; 252 coronary lesions). The exclusion criteria were the ongoing myocardial infarction, the marked reduction of left ventricular function, and the decision to treat the lesion with a device not fitting the 6F guiding catheter. The angioplasty success rates (87% in the 6F group vs 88% in the 7F or 8F group) and the stent implantation rates (21% vs 25%) were similar in both groups. The ischemic complication rates (death, 2 vs 1 ) were also similar. The incidence of the femoral complications was significantly less important in the 6F group than in the 7/8F group (13.8% vs 23.5%; p < 0.01). Significant differences also were noted for the procedural time (36 +/- 22 vs 41 +/- 28 min; p < 0.01), the fluoroscopy time (11 +/- 10 vs 14 +/- 4 min; p < 0.05), the volume of contrast injected (136 +/- 68 ml vs 168 +/- 95 ml; p < 0.0001), and the time of femoral compression after the introducer sheath removal (11.7 +/- 9 vs 14.1 +/- 12 min; p < 0.01). Our data suggest that 6F guiding catheters for elective coronary angioplasty are more effective than are the larger diameter catheters. Besides a significant decrease of vascular complications, angioplasty with a 6F guiding catheter reduces the procedural time and the amount of contrast.

Intracoronary stenting without coumadin: one month results of a French multicenter study.

In order to simplify post-coronary stenting treatment and to obtain a lower rate of complications, especially in bailout situations, seven French institutions treated 246 stented patients with 0.25 g/day of ticlopidine, 0.1 g/day of IV aspirin, and 2 days of heparin followed by low-molecular-weight heparin for 1 month. Fifty percent of patients had a planned stenting procedure, and 50% had an unplanned procedure, including 29 (11.8%) in bailout situations. Subacute occlusion occurred in three (1.2%) patients (one death, two non-Q-wave infarctions). During the 1 month follow-up period, another death was reported (non-stent-related), two elective coronary artery bypass grafts were performed, and three additional patients presented with non-Q-wave myocardial infarctions. Nine (3.7%) patients had a groin complication that required blood transfusion or surgical repair. These results suggest that while waiting for the technological advancements of stents, postprocedural treatment that includes a low dosage of ticlopidine, aspirin, and low-molecular-weight heparin is a very effective alternative to conventional poststenting therapy.

HIV1 quantitation in infected patients: a comparison of cell viraemia, plasma viraemia and R-HEV.

Anti-HIV1 trials require sensitive, reproducible and reliable parameters which measure virus load and virus production. The aim of the present study of 14 patients at different CDC stages was to compare results provided by three techniques which evaluate, respectively, cell-associated HIV1 infectivity (cell viraemia), plasma-associated HIV1 infectivity (plasma viraemia) and radiation-resistant expression ex vivo (R-HEV). For each patient, TCD4 lymphocytes were numbered and an HIV1 antigenaemia determination was carried out. We found no correlation between cellular viraemia and R-HEV; on the contrary, data concerning plasma viraemia and R-HEV were significantly correlated. While cellular viraemia and R-HEV were not correlated with TCD4 levels, plasma viraemia exhibited a significant negative correlation with TCD4 counts. Despite theoretical and practical differences, plasma viraemia and R-HEV may measure events in the viral replication cycle which bear a close resemblance; however, as designed, R-HEV seems to be far less discriminative than plasma viraemia.

[Anatomical and coronary angiography data on coronary anastomosis]. / Anastomoses coronariennes données anatomiques et coronarographiques.

Beyond two series of heart studies (anatomical with 150 hearts treated by injection-corosion method, and angiographic with 211 coronarography 3 days after a heart attack) the authors have noticed 92 coronary anastomosis with: 28 right homolateral 22 left homolateral 42 contralateral The existence of these anastomosis has been confirmed by coronarography of 30 out of 173 patients having a significant lesion of the artery responsible for the heart attack. The authors noticed also that these anastomosis are effective when the coronary system is deficient and the supplies are ensured by the other artery. The study permits to distinguish two groups of functional collateral: the functional collateral spontaneously observed during coronarography recruitable collaterals which are ready to be functional in case of main coronary artery obstruction.

Evaluation of the inhibition by heparin and hirudin of coagulation activation during r-tPA-induced thrombolysis.

Thrombin bound to a fibrin clot remains active and poorly accessible to heparin-AT III complex. During fibrinolysis, thrombin is released as thrombin-FDP complex and is inactivated by heparin-AT III. However, as successive fibrin layers are removed, inaccessible molecules of thrombin are exposed at the surface of the residual clot, possibly contributing to the occurrence during thrombolytic therapy of coagulation that is poorly controlled by heparin. We have investigated the accessibility of fibrin-bound thrombin to hirudin. The results clearly show that two recombinant hirudin variants neutralize thrombin both in solution and fibrin bound. Furthermore, we have found that in in vitro models, hirudin present in the surrounding medium of a clot under lysis is more efficient than heparin in preventing the activation of coagulation. This observation suggests that hirudin may be effective in the prevention of the rethrombotic process frequently encountered during thrombolytic therapy.

Changes in plasma fibrin degradation products as a marker of thrombus evolution in patients with deep vein thrombosis.

The level of fibrin degradation products (fdp) as a marker of fibrin clot dissolution was studied prospectively in 51 patients with phlebographically identified deep vein thrombosis (DVT). For this purpose a highly sensitive fdp assay using an anti D neo monoclonal antibody (McAb) was used. At the onset of the hospitalization, in 47 (92%) of the 51 patients tested, the plasma fdp level performed was high, but does not reflect the size of the thrombus, demonstrating that spontaneous thrombus lysis varies from one patient to another. During 10 days of standard heparin or low molecular weight heparin treatment, two different patterns of fdp evolution could be identified in these patients, independent of the type of heparin used. The first was characterized by a gradual decrease in fdp level and a corresponding reduction in the thrombus size. The second pattern showed a persistence of high levels of fdp after 10 days of therapy although the phlebographic score reveals a poor or partial response indicating that fibrinolysis or the balance of thrombus formation/fibrinolysis did not insure total thrombus dissolution. The 4 patients whose initial plasma fdp levels were only slightly increased during the 10 days, seem to have poor thrombolysis, as was shown by the unmodified phlebographic score after 10 days of treatment. Consequently, we conclude that the investigation of plasma fdp levels with a highly sensitive assay should contribute to the evaluation of thrombus evolution in DVT.

[Exertion-induced parameters of left ventricular function in patients with chronic cardiac insufficiency. An isotope study]. / Evolution à l'effort des paramètres de fonction ventriculaire gauche chez des patients atteints d'une insuffisance cardiaque chronique. Etude isotopique.

Exercise-induced changes in haemodynamic values were studied by radionuclide ventriculography in 21 patients with permanent systolic dysfunction (15 with non-obstructive cardiomyopathy and 6 with ischaemic heart disease). The results were compared with those obtained in 8 control subjects with normal heart. In healthy subjects, during exercise the ejection fraction increased due to constant diminution of the end-systolic volume; the end-diastolic volume and the systolic ejection volume did not significantly vary; the cardiac output augmented only because of the accelerated heart rate. In patients with permanent left ventricular dysfunction, the ejection fraction remained unchanged during exercise, whereas the end-systolic volume increased significantly. Yet the systolic ejection volume increased due to a rise in end-diastolic volume. Heart rate and cardiac index increased, but not as much as in normal subjects. There was a close correlation between changes in end-diastolic and end-systolic volumes. It was the relative importance of changes in these two ventricular volumes that determined the direction and amplitude of variations in ejection fraction. It is concluded that in patients with permanent left ventricular dysfunction: (1) the end-systolic volume increases during exercise, thus betraying a worsening of the systolic dysfunction; (2) however, the systolic ejection volume is maintained or increases due to an increase in end-diastolic volume; (3) the changes in ejection fraction observed during exercise are of little value to characterize the modifications that occur in left ventricular work performance.

Adaptation of the left ventricular function parameters to dynamic exercise in aortic stenosis.

The left ventricular volumes, the left ventricular ejection fraction, the stroke volume index and the cardiac index were non-invasively determined in 47 patients suffering from moderate to severe pure aortic stenosis using radionuclide angiography at rest and at peak supine exercise. Each patient was previously submitted to right and left heart catheterization and to selective coronary angiography. The left ventricular ejection fraction decreased significantly during exercise (0.62 +/- 0.09 to 0.59 +/- 0.09, P less than 0.01). End-systolic volume, end-diastolic volume, stroke volume index and cardiac index increased significantly. The stroke volume variations were linked to the end-diastolic volume variations by a strong relationship (r = 0.84, P less than 0.001) and to left ventricular mass by a weak, but significant, inverse relationship (r = -0.42, P less than 0.05). No relation existed between stroke volume index variations and any other variables, particularly systolic gradient, aortic valve area and resting left ventricular ejection fraction. The results suggest that, in aortic stenosis, the adaptation of the left ventricular pump function during exercise is mostly dependent upon the diastolic properties of the left ventricular wall and is limited by the progression of left ventricular hypertrophy, i.e. diastolic stiffness. By contrast, the role of the basal systolic pump function and of the severity of the valvular obstruction seems of limited importance.

[A new treatment of deep venous thrombosis: low molecular weight heparin fractions. Randomized study]. / Un nouveau traitement des thromboses veineuses profondes: les fractions d'héparine de bas poids moléculaire. Etude randomisée.

Sixty-eight patients with acute deep vein thrombosis were allocated at random to two treatment groups. One group (n = 33) received a fixed dose of 750 anti-Xa units of a low molecular weight heparin (CY 222 Choay Institute); the other group (n = 35) received standard heparin in doses of 500 IU/kg/24 h. Both treatments were given for 10 days in two daily subcutaneous injections. A second phlebography was performed on the last day of treatment. No haemorrhagic complication was observed in the group treated with CY 222, as opposed to three cases of haemorrhage in the group treated with standard heparin. The initial phlebographic score and the location of deep vein thrombotic lesions were the same in both groups. Angiographic improvement, with more than 30% thrombolysis, was obtained at the end of treatment in 64% of patients in the CY 222 group and in 65% of patients in the standard heparin group (NS). In 2 patients treated with standard heparin the second phlebography showed extension of the thrombosis. The initial score remained unchanged in 1/3 of patients in both groups. The activated partial thromboplastin time was prolonged (2 or 3 fold the normal value) in the standard heparin group and unchanged in the CY 222 group. Anti-Xa activity was significantly higher in the CY 222 group than in the standard heparin group. It is concluded that CY 222 and standard heparin were equally effective in patients with deep vein thrombosis. However, haemorrhagic complications were more frequent with standard heparin that with CY 222.