Autoimmune cerebellar hypermetabolism: Report of three cases and literature overview.

We report three cases of vermian cerebellar hypermetabolism in patients with autoimmune encephalitis. One of our patients was positive for anti-Ma2 antibodies and one for anti-Zic4 antibodies while the remaining patient did not present any known antibodies. The seronegative patient deteriorated after immune checkpoint inhibitor treatment for a pulmonary adenocarcinoma and improved with immunosuppressive drugs, which is in favour of an underlying autoimmune mechanism. They all presented with subacute neurological symptoms. Brain magnetic resonance imaging was normal except in one patient, where hyperintensities were present on FLAIR sequence around the third ventricle and the cerebral aqueduct. 18F-FDG brain positron emission tomography with computed tomography (18F-FDG PET-CT) demonstrated an unusual vermian cerebellar hypermetabolism in the three cases. While cerebellar hypermetabolism on 18F-FDG PET-CT has been described in various neurological diseases, such vermian - and more broadly cerebellar - hypermetabolism was seldom described in previous studies on autoimmune encephalitis. When differential diagnoses have been ruled out, this pattern may be of interest for the positive diagnosis of autoimmune encephalitis in difficult diagnostic cases.

[Flecainide acetate utilisation review among general practitioners and hospital or office-based cardiologists in France. Obepine: observational study of flecainide]. / Etude de l'usage de l'acétate de flécainide auprès des médecins généralistes et des cardiologues hospitaliers ou libéraux en France. OBEPINE: etude observationnelle des prescriptions de flécaïnide.

A pharmacoepidemiological cross-sectional observational study was performed among a representative sample of French general practitioners and cardiologists. The aim of this study was to describe the prescription modalities of flecainide acetate, an Ic class antiarrhythmic, and how these modalities match the marketing authorization and the current summary of product characteristics. A total of 941 physicians participated in the study, 496 GPs and 445 cardiologists, and 1116 patients treated with flecainide for more than one month were included. On average, the patients were 68.7-years-old and 54% of them were women. Most of the initial flecainide prescriptions came from cardiologists (96%) and the check-up included an electrocardiogram (98%), a Holter monitoring (56%) and/or an echocardiography (71%). The preferred indication was supraventricular rhythm disorders (95%) and mostly atrial fibrillation (63%). A small proportion of coronary patients (7%) and of patient suffering from cardiac insufficiency (4%) was found. Flecainide was prescribed with a median posology of 150 mg per day, mostly as LP form (64%). Overall, the indications specified in the summary of product characteristics were respected in 90% of the cases, the contraindications in 91% of the cases and the patient follow-up was appropriate in 99% of the cases. In conclusion, the study showed that the prescription's conditions of flecainide in France complied with the summary of product characteristics data for most of the prescribing physicians with a respect of the indications, contraindications and management recommendations in 84% of the cases.

Oral Beraprost sodium, a prostaglandin I(2) analogue, for intermittent claudication: a double-blind, randomized, multicenter controlled trial. Beraprost et Claudication Intermittente (BERCI) Research Group.

BACKGROUND: Beraprost sodium (BPS) is a new stable, orally active prostaglandin I(2) analogue with antiplatelet and vasodilating properties. We report the results of a phase III clinical trial of BPS in patients with intermittent claudication. METHODS AND RESULTS: Patients (n=549) with a pain-free walking distance of between 50 and 300 m were entered into a 4-week single-blind placebo run-in phase. Patients whose pain-free walking distance had changed by <25% were then randomized to receive either BPS (40 microg TID, n=209) or placebo (n=213) in a double-blind manner for 6 months. Pain-free and maximum walking distances were measured on the occasion of treadmill exercise tests performed at baseline and 1.5, 3, 4.5, and 6 months after randomization. Success was defined as an improvement of >50% in pain-free walking distance at month 6 and in > or =1 earlier treadmill exercise test in the absence of critical cardiovascular events. Success was observed more frequently in the BPS group (43.5%) than in the placebo group (33.3%, P=0.036). Pain-free walking distances increased by 81.5% and 52.5%, respectively, in the BPS and placebo groups (P=0.001) and maximum walking distances by 60.1% and 35.0%, respectively (P=0.004). The incidence of critical cardiovascular events was 4.8% in the BPS group and 8.9% in the placebo group. CONCLUSIONS: These results show that BPS is an effective symptomatic treatment of patients with intermittent claudication. The beneficial effects of BPS on critical cardiovascular events should be confirmed in appropriate clinical trials.

Cross-sectional study of care, socio-economic status and complications in young French patients with type 1 diabetes mellitus.

OBJECTIVES: To describe the present status of type 1 diabetes care in France and study the relations between clinical and socio-economic variables on one hand and disease management and prevalence of complications on the other hand. METHODS: A random sample of 365 French specialists in diabetes care performed a cross-sectional study and included consecutively 562 children aged 10-16 and 1691 adults aged 16-45, with more than 2 years of type 1 diabetes. The main outcome measures were the prevalence of complications (retinal, renal, lower-limb, cardiovascular, ketoacidosis); disease management parameters (blood pressure, HbA1c, daily number of insulin injections, frequency of visits to a specialist in diabetes, membership of a patient association); socio-economic status as a score, and treatments received. RESULTS: Retinal complications were rare in children (0.7%) and common in adults (28.3%). 10.2% children and 15.2% adults had micro- or macro-albuminuria, 4.7% adults had plasma creatinine >or=150 micromol/L. Only 15% children and 26% adults had HbA1c<7%, 86.2% children and 62.7% adults had blood pressure<130/85 mmHg; 58% children and 80% adults had at least 3 daily insulin injections. In adults, the risk of experiencing at least one complication was linked significantly with diabetes duration, HbA1c, and socio-economic status. Age, sex, type of insulin therapy, tobacco consumption, and blood pressure control were not significant parameters. Ketoacidosis in the preceding year was only linked with HbA1C and socio-economic status. CONCLUSION: Although this sample of patients had overall a fair socio-economic status and were followed-up by specialists of diabetes care, metabolic and blood pressure control were not optimal. The care of French type 1 diabetics could probably be improved by a stricter control of glycaemia and blood pressure, and an earlier use of intensive insulin treatment, with a particular focus on adolescents and patients with the lowest socio-economic status.

Determinants of elevated urinary albumin in the 4,937 type 2 diabetic subjects recruited for the DIABHYCAR Study in Western Europe and North Africa.

OBJECTIVE: Whether ACE inhibition is useful for type 2 diabetic patients with micro- and macroalbuminuria remains unknown. The Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events and Ramipril (DIABHYCAR) Study was set up to address this issue through a multicenter double-blind parallel placebo-controlled > or = 3-year trial in Europe and North Africa. In this article, we report the characteristics of the randomized patients. RESEARCH DESIGN AND METHODS: The main selection criteria were as follows: men or women aged > or = 50 years with type 2 diabetes treated with oral antidiabetic drugs, with or without hypertension, with a plasma creatinine level < 150 mumol/l, and with persistent micro- or macroalbuminuria, as assessed centrally by two successive urine samples containing a urinary albumin concentration > or = 20 mg/l. Patient characteristics were studied by comparing patients who were randomized to those who were not, taking their geographical origin into account. RESULTS: There were 25,455 patients screened for urinary albumin (20,296 from France, 918 from Germany, 1,019 from Northwest Europe, 969 from Central Europe, 959 from Mediterranean Europe, and 1,294 from North Africa). Of these patients, 4,937 were randomized. Compared with the nonrandomized patients, the randomized patients were older, more often men, more obese, had higher systolic/diastolic blood pressure and plasma glucose, smoked more tobacco, drank more alcohol, and had complications more frequently. Using a logistic regression analysis, all the above-mentioned items appeared as independent determinants for randomization into the study, with the exception of alcohol intake. The contribution of each item varied slightly from one geographical origin to another. CONCLUSIONS: The physical, biological, and behavioral characteristics create a poor renal and cardiovascular prognosis for the type 2 diabetic patients randomized to the DIABHYCAR Study because of micro- and macroalbuminuria. Testing the usefulness of ACE inhibition for the type 2 diabetic patients with microalbuminuria seems feasible through the DIABHYCAR Study.

Efficacy of diuretics and beta-blockers in diabetic hypertensive patients. Results from a meta-analysis. The INDANA Steering Committee.

OBJECTIVE: To review the effectiveness of diuretic or beta-blocker-based treatment of hypertension in diabetic patients. RESEARCH DESIGN AND METHODS: A meta-analysis on individual patient data was performed on four trials of the treatment of hypertension in which diabetic patients were included and treated with first-line diuretics or beta-blockers. The main outcomes were the relative risk of death, fatal or nonfatal stroke, fatal or nonfatal coronary events, and major cardiovascular events. RESULTS: There were 92 diabetic patients who received first-line beta-blockers and 1,008 who received diuretics. In the control groups, diabetic patients had nearly twice the risk of any outcome when compared with nondiabetic patients. The same blood pressure reduction was achieved under treatment in the diabetic and nondiabetic patients, except for systolic pressure, which decreased more in the nondiabetic patients at 1 year. In the 15,843 nondiabetic patients, the risk of all four outcomes was reduced significantly in the treated group. In the 2,254 diabetic patients, the risk reduction was significant only for fatal and nonfatal stroke (36%, P = 0.011) and major cardiovascular events (20%, P = 0.032), but not for death (5%, P = 0.65) and fatal or nonfatal coronary events (15%, P = 0.23). However, no heterogeneity was detected between diabetic patients and nondiabetic patients for any outcome. The numbers of outcomes avoided for 1,000 patients treated for 5 years were higher in diabetic patients (e.g., 38 major cardiovascular events) than with nondiabetic patients (e.g., 28 major cardiovascular events). CONCLUSIONS: These results show that hypertensive diabetic patients benefit from first-line treatment with diuretics. No conclusion can be drawn for beta-blockers, owing to the small sample size.

Frequency and predictors of confirmed hypoglycaemia in type 1 and insulin-treated type 2 diabetes mellitus patients in a real-life setting: results from the DIALOG study.

AIM: DIALOG assessed the prevalence and predictors of hypoglycaemia in patients with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) in a real-life setting. METHODS: In this observational study, insulin-treated patients (n=3048) completed prospective daily questionnaires reporting the frequency and consequences of severe/confirmed non-severe hypoglycaemia over 30 days. Patients (n=3743) also retrospectively reported severe hypoglycaemia over the preceding year. RESULTS: In this prospective survey, 85.3% and 43.6% of patients with T1DM and T2DM, respectively, reported experiencing at least one confirmed hypoglycaemic event over 30 days, while 13.4% and 6.4%, respectively, reported at least one severe event. Hypoglycaemia frequency increased with longer duration of diabetes and insulin therapy. Strongly predictive factors for hypoglycaemia were previous hypoglycaemia, >2 injections/day, BMI<30kg/m(2) and duration of insulin therapy>10 years. HbA1c level was not predictive of hypoglycaemia in either T1DM or T2DM. The confirmed hypoglycaemia rate was increased in the lowest compared with the highest tertile of HbA1c in T1DM, but not T2DM. At the time of enrolment, physicians reported severe hypoglycaemia in 23.6% and 11.9% of T1DM and T2DM patients, respectively, during the preceding year; the retrospective survey yielded frequencies of 31.5% and 21.7%, respectively. Also, severe hypoglycaemia led to medical complications in 10.7% and 7.8% of events in T1DM and T2DM patients, respectively, over 30 days. CONCLUSION: Using a unique combined prospective and retrospective approach, the DIALOG study found a relatively high frequency of hypoglycaemia among insulin-treated patients. These findings emphasize the importance of a patient-centred approach for managing diabetes in which hypoglycaemia risk evaluation is critical. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01628341.

Ramipril-induced regression of left ventricular hypertrophy in treated hypertensive individuals. HYCAR Study Group.

The objective of this trial was to assess the effects of 6-month daily treatment with two doses of ramipril on left ventricular mass and the dependence of this on blood pressure changes in hypertensive patients with left ventricular hypertrophy. After a selection phase of 4 to 6 weeks with patients under antihypertensive therapy with 20 mg furosemide daily, 115 patients with either controlled or uncontrolled hypertension and left ventricular hypertrophy were randomized in a double-blind manner to receive either placebo (n = 40), 1.25 mg (low dose, n = 38), or 5 mg (regular dose, n = 37) ramipril daily for 6 months. Treatment with furosemide was continued unchanged during this phase. The main outcome measured was left ventricular hypertrophy regression as assessed from central blind reading of echocardiograms recorded at randomization and after 6 months. No significant differences were observed for changes in casual or ambulatory blood pressure between the three groups. Left ventricular mass index was found to be significantly reduced in patients receiving 5 mg ramipril compared with those receiving placebo (-10.8 +/- 3.7 versus +4.1 +/- 4.0 g/m2, P = .008); in patients receiving 1.25 mg ramipril, the difference was close to borderline significance compared with placebo (-7.0 +/- 4.3 g/m2, P = .06). Similar results were observed for changes in left ventricular mass (-20.3 +/- 6.6 and -13.0 +/- 7.8 g in the 5- and 1.25-mg ramipril groups, respectively, versus +9.1 +/- 7.2 g in the placebo group; P = .004 and .04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of a rapid change of left ventricular dimensions on the echocardiographic measurement of left ventricular mass by the Penn convention.

OBJECTIVE: The purpose of this study was to test the robustness of the measurement of left ventricle mass (LVM), using Devereux's formula, in the presence of a rapid change in left ventricular volume induced by nitroglycerin. DESIGN: Forty-eight healthy volunteers with excellent echocardiographic recordings were included. The intrapatient variability of LVM measurement was assessed by two consecutive echocardiograms. The intraobserver reproducibility was assessed by the rereading of 19 echocardiograms by the same observer. The effects of nitroglycerin were compared with those of a placebo in a double-blind random manner on, the left ventricular internal dimension in diastole (LVIDd), the interventricular septum thickness, the posterior wall thickness and the LVM. RESULTS: It was shown that both the intrapatient and the intraobserver reproducibility were high. Nitroglycerin induced a significant decrease in LVIDd compared with placebo (-0.21 +/- 0.24 versus 0.01 +/- 0.21 cm, respectively, P < 0.01) and a non-significant increase in wall thickness. These variations were negatively correlated with each other (r= -0.58, P< 0.01). Despite the change of ventricular dimensions, the variation of LVM induced by nitroglycerin was not significantly different from that induced by placebo (2.0 +/- 16.0 versus 4.7 +/- 17.0 g, respectively, not significant) and close to the intrapatient variability. CONCLUSION: This experiment failed to demonstrate any influence of a rapid variation of ventricle size on the calculation of LVM with the Penn convention and strongly supports the robustness of the method in vivo.

Relationship between atrial and ventricular rates of fibrillation and cardiac contractile tissue effective refractory periods in the dog.

1 During total cardiopulmonary bypass, acetylcholine-, isoprenaline-, ouabain- and quinidine-induced variations in the atrial and ventricular rates of fibrillation were studied and compared with the variations in effective refractory periods (ERP) of atrial and ventricular contractile tissue obtained under the same experimental conditions. 2 Acetylcholine significantly shortened the ERP and accelerated the rate of fibrillation in the atrium but did not provoke any change in ventricular tissue. A parallel decrease in atrial and ventricular ERP and a parallel increase in atrial and ventricular rates of fibrillation were observed with isoprenaline. 3 Ouabain exerted a biphasic effect on the atrium, with an initial decrease in the ERP and an initial acceleration of the rate of fibrillation. It produced only a slight decrease in the ventricular ERP and no significant variation in the ventricular rate of fibrillation. 4 Quinidine induced a greater increase in the ERP and a greater slowing of the rate of fibrillation in the atrium than in the ventricle. 5 The variations in percentage change of refractoriness and rate of fibrillation were strictly correlated: r = 0.89 (P less than 0.001); the equation of the regression line was y = --0.86 x --2.98.

Outcome of atrial fibrillation after mitral valve repair.

OBJECTIVE: The aim of the study was to evaluate the prognostic factors for return to sinus rhythm after mitral valve repair. METHOD: One hundred ninety-one patients underwent surgery for mitral valve repair, including 142 procedures for valve repair only (74%). The patients with preoperative atrial fibrillation (50.5%) were older, clinically more symptomatic, and had a greater degree of left atrial dilation than the patients who had sinus rhythm. RESULTS: Preoperative cardiac rhythm, the duration of preoperative atrial fibrillation, and a lesser degree of left atrial hypertrophy are significant prognostic factors independent of the maintenance of sinus rhythm. The probability of return to stable sinus rhythm was 93.7% when sinus rhythm was already present before the operation and 80% when atrial fibrillation was intermittent or of less than 1 year's duration; probability declined abruptly for durations over 1 year. No significant difference in patient survival was noted between those who had sinus rhythm (99% +/- 0.9% at 1 year and 86% +/- 6.6% at 5 years) and those who had atrial fibrillation in the preoperative period (95% +/- 3.1% at 1 year and 86% +/- 8.4% at 5 years). In contrast, the postoperative return to sinus rhythm was associated with 99% +/- 0.9% and 94% +/- 4.8% survivals at 1 and 4 years versus 97% +/- 1.5% and 77% +/- 13% in the event of postoperative atrial fibrillation. CONCLUSION: The aim of restoring postoperative sinus rhythm after mitral valve repair should lead to surgery being conducted on patients who have sinus rhythm or recent-onset atrial fibrillation. Surgery for atrial fibrillation may be of value in patients with a long history of atrial fibrillation, providing that it does not induce prohibitive excess mortality.

In vivo measurement of myocardial oxidative metabolism and blood flow does not show changes in cancer patients undergoing doxorubicin therapy.

PURPOSE: The aim was to investigate in patients receiving doxorubicin whether any alteration in myocardial oxidative metabolism or blood flow as assessed by positron emission tomography (PET) could be observed either after the first dose of the drug, or during its chronic administration. METHODS: Six female non-heart-failure cancer patients treated with doxorubicin were included in a longitudinal study. Resting radionuclide cineangiography and PET scanning with carbon-11 acetate were performed the day before the initiation of doxorubicin treatment at a dosage of 50 mg/m2 every 3 weeks, and 3 weeks after the cumulative administration of 300 mg/m2 (chronic toxicity). In addition, PET was performed 24 h after the first administration of doxorubicin (evaluation of acute toxicity). Myocardial oxidative metabolism and blood flow were assessed by PET (acute and chronic toxicity), and left ventricular ejection fraction was measured by radionuclide angiography (chronic toxicity). RESULTS: Using PET for both acute and chronic toxicity evaluations, no significant effect of doxorubicin was observed either on the flux through the tricarboxylic acid (TCA) cycle or on myocardial blood flow. However, systolic left ventricular function showed a small but significant impairment after the administration of 300 mg/m2 of doxorubicin. CONCLUSIONS: Other hypotheses should be explored to better explain the predominant mechanisms of the cardiotoxicity of anthracyclines in humans.

Centrally mediated cardiovascular effects of nicergoline in the dog compared to those of clonidine.

The intracisternal administration of nicergoline (5 micrograms/kg) or clonidine (4 micrograms/kg) in chloralose-anesthetized dogs induced significant decreases in blood pressure and heart rate. The same dose of nicergoline induced similar effects on atropine-pretreated dogs. Guanethidine pretreatment (30 mg/kg i.v. the day before) prevented the hypotension but not the bradycardia induced by clonidine. Guanethidine prevented both the hypotension and the bradycardia induced by nicergoline. Thus, nicergoline, unlike clonidine, does not increase cardiac parasympathetic activity. When administered by the same route at the same doses, nicergoline did not change the slope and reduced the amplitude whereas clonidine increased both the slope and the amplitude of the heart period vs. blood pressure curve obtained by intravenous administration of phenylephrine. Taken together, these results suggest that nicergoline and clonidine probably act on different structures within the central nervous system.

Effects of mild hyperkalemia on conduction velocity and effective refractory period in various parts of the dog heart in situ.

Effects of mild hyperkalemia on conduction velocity, effective refractory periods (ERPs) and sinus rate were studied on 16 anesthetized dogs, using endocavitary His bundle recordings, the extrastimulus method and standard electrocardiogram. Six dogs were placed under acetylcholine infusion (300 micrograms/kg/min) (ACh group), 10 received atropine sulfate 0.2 mg/kg intravenously (atropine group). Intraventricular conduction time, ventricular ERP and QRS duration of the EKG were studied on 7 other open-chested dogs (ventricular group). During a 60 min potassium chloride infusion (0.025 mmol/kg/min, 30 min, then 0.05 mmol/kg/min, 30 min), following observations were made: - In the ACh group, AV node conduction time (A-H interval) decreased by 20% and AV node ERP by 17%, whereas, in the atropine group, the former parameter was not affected and atrial ERP increased by 29%. - At the same time, sinus rate increased in the ACh group and was unaffected in the atropine group. - Conduction times in atrial contractile tissue (S-A interval), His-Purkinje system (H-V interval) and ventricular contractile tissue, like ventricular ERP, exhibited no variation or very slight, occasionally biphasic variations under both conditions. These results can be accounted for by an "anticholinergic" effect of mild hyperkalemia which is discussed.

Inhibition of subintimal hyperplasia of autologous vein bypass grafts by nimodipine in rats: a placebo-controlled study.

An arterial bypass may be required for the management of neoplastic or cerebrovascular disease. When an arterial graft is not suitable, autologous vein grafts are the most commonly used conduits; however, as many as 20% of the vein grafts used in vascular surgery may occlude as a result of subintimal hyperplasia. Although the mechanism initiating subintimal hyperplasia remains unclear, it is known that subintimal hyperplasia is dependent upon smooth muscle cell proliferation and migration from the media to the intimal layer. The present study focused on the prevention of smooth muscle cell proliferation using a calcium antagonist. Forty rats received an autologous vein bypass graft from the jugular vein to reconstruct the abdominal aorta. They were randomly divided into two groups of 20 rats each. Animals in the treated group received a calcium antagonist (nimodipine), and those in the control group received a placebo. Nine months after grafting, the group receiving the calcium antagonist presented no or only slight sub intimal hyperplasia as compared with the placebo-treated group (P less than 0.001). These data suggest that a calcium antagonist could be used for the prevention of venous graft disease.

Treatment with growth hormone-releasing hormone (GHRH) 1-44 in children with idiopathic growth hormone deficiency: a randomized double-blind dose-effect study. The GHRH European Multicenter Study (GEMS) Group.

One hundred and eleven pre-pubertal children (70 boys, 41 girls, aged 2.5 to 14.3 years) with growth failure (height 2 SD below the mean for chronological age (CA) and height velocity (HV) below the 10th percentile for bone age) due to idiopathic growth hormone deficiency (peak plasma GH < 20 mUI/1 to two standard provocative tests) were treated with GHRH 1-44 NH2. Patient stratification in two classes was performed according to body weight; in each class, patients were randomly allocated to one of seven GHRH doses, from 30 to 300 micrograms/day. GHRH was injected subcutaneously, every evening, for six months in a double-blind fashion. No relationship was found between the absolute or incremental HV during treatment and the dose (range from 1.3-23.1 micrograms/kg/day) of GHRH. However, HV (cm/year) increased from 3.8 +/- 0.1 (mean +/- SEM) before treatment to 6 +/- 0.2 during six months treatment and 47 patients (42%) increased their HV up to at least the mean normal HV for bone age (catch-up growth). Low titer antibodies to GHRH were found in 19 patients (17.1%) at six months; no adverse effect was observed. Our results suggest that patients showing catch-up growth were older, had a height closer to the mean for chronological age and a slower pre-treatment height velocity. Failure to demonstrate a relationship between GHRH dose and changes in growth velocity might be explained by the combination of a placebo effect, insufficient frequency of GHRH administration and heterogeneity of the population.

Experimental assessment of new stent technologies: validation of a comparative paired rabbit iliac artery study model.

Preventing coronary in-stent restenosis is a major challenge for physicians and industry. To assess new stent technologies, a comparative paired iliac artery model in rabbits is proposed. One tubular stent was implanted in each external iliac artery in 12 rabbits (i.e., 24 stents). An artery overdilatation level of 20% was strictly observed. Restenosis was examined at 30 days by angiography, intravascular ultrasound (IVUS) examination, and histomorphometry. On quantitative angiography, the mean loss of angiographic diameter was 9.8 +/- 4.4% in the right as compared to 9.3 +/- 55% in the left artery (p = 0.75). On IVUS, the volume of intrastent neointimal proliferation was 26.6 +/- 4.9 mm(3) in the right and 25.8 +/- 3.5 mm(3) in the left artery (p = 0.58). In histomorphometry, the neointimal proliferation area was 0.78 +/- 17 mm(2) in the right and 0.76 +/- 0.17 mm(2) in the left artery (p = 0.87). Intrastent neointimal proliferation was comparable between the left and right arteries of all rabbits. The model has three main advantages: (1) arterial dilatation and thus arterial wall aggression are controlled, (2) pairing makes each animal its own control subject, and (3) the statistical power for comparative testing is maximized. The model enables the effect of a new drug-delivery device to be assessed.

Use of IgG Avidity test in case definitions of toxoplasmosis in pregnancy.

A survey network for congenital toxoplasmosis (TOXO-NET) was set up in December 1996 in Piedmont (Italy). Participants were asked to classify the infections in pregnant mothers and newborns by the criteria of the European Network on Congenital Toxoplasmosis published by Lebech in 1996. Because the IgG Avidity test is largely employed as a 2nd level test in toxoplasmosis diagnosis and it could be helpful to date infection, the co-ordinators of TOXO-NET suggested including it in the "case definition" of "probable" infection and "unlikely" infection. 117 cases of toxoplasmosis in pregnancy divided into the risk categories under Lebech's criteria were re-examined using the "new" case definitions. 77 out of 117 (65.8%) Toxoplasma gondii infections during pregnancy could be defined with only one serum sample using the IgG Avidity test. The IgG Avidity test proved a useful method to classify the Toxoplasma gondii infections in pregnancy, especially when we had only one serum sample.

[Calcium channel antagonists and myocardial ischemia or ischemia/reperfusion]. / Antagonistes calciques et ischémie ou ischémie/reperfusion myocardiques.

Many theoretical and experimental studies suggest that calcium antagonists drugs should be useful in pathological situations of myocardial ischemia or ischemia/reperfusion. This therapeutic model was tested in controlled trials of angina, post-infarction and cardiac surgery. The authors undertook a meta-analysis of these trials using the occurrence of myocardial infarction or death as criteria of judgement. No long-term benefits seem to be associated with the dihydropyridines such as nifedipine and nicardipine in anginal patients. In unstable angina, betablockers seem to be more effective but the difference is not statistically significant. In the post-infarction period, nifedipine does not reduce the risk of recurrence of myocardial infarction and may even increase the mortality by 15%, though this was not significant in the 9,055 patients studied (p = 0.08). Verapamil and diltiazem globally reduce the risk of recurrent infarction by 21% (p = 0.009) but not mortality (p = 0.52). Because of the small numbers of patients and the low prevalence of observed events, no useful conclusions can be drawn from studies of calcium antagonists in cardiac surgery. The results of the validation of the therapeutic model "calcium antagonists in pathological situation of myocardial ischemia or ischemia/reperfusion" does not justify the labels "anti-ischemics" or "cardio protectors" often applied to the calcium antagonists.

[Intermediary and substitution criteria in the development of anti-arrhythmia agents]. / Critères intermédiaires et critères de substitution dans le développement des antiarythmiques.

The traditional view that the suppression of arrhythmias (risk factor) after myocardial infarction can only be beneficial, has been queried by the results of the Cardiac Arrhythmia Suppression Trial (CAST) which showed increased mortality in two treatment groups. The methodology of trials of secondary prevention of myocardial infarction by antiarrhythmic agents partially explains why the reduction of anti-arrhythmias has come to be considered as a substitute for mortality in the assessment of drug efficacy. The authors define substitutive criteria and describe their three advantages (facility, correspondence, estimation). A meta-analysis of 6 trials of secondary prevention of myocardial infarction by Class I antiarrhythmics, in which the antiarrhythmic effect was evaluated (Holter monitoring) in parallel with mortality, shows that anti-arrhythmias were significantly reduced by nearly 60% (p = 10-8) whereas mortality remained unchanged (p = 0.41). A special graphic presentation of the results of these 6 trials shows that, even before the results of the CAST, it was clear that the suppression of antiarrhythmics was not a suitable substitutive end point for mortality.