Reversibility of cardiac fibrosis in mice chronically infected with Trypanosoma cruzi, under specific chemotherapy

This investigation was performed to verify the effect of specific chemotherapy (Benznidazole or MK-346) on the inflammatory and fibrotic cardiac alterations in mice chronically infected with the strains 21 SF (Type II) and Colombian (Type III) of Trypanosoma cruzi. To obtain chronically infected mice, two groups of 100 Swiss mice each, were infected with either the 21 SF or the Colombian strain (2x 10 [raised to the power of] 4 and 5x 10 [raised to the power of] 4 blood forms respectively). The rate of morality in the acute phase was of 80% for both groups. Twenty surviving mice chronically infected with the 21 SF strain and 20 with the Colombian strain were then divided in treated and untreated groups. Excluding those that died during the course of treatment, 14 mice chronically infected with the 21 SF strain and 15 with the Colombian strain were evaluated in the present study. Chemotherapy was performed with Benznidazole (N-benzil-2-nitro-1-imidazolacetamide) in the dose of 100mg/k.b.w/day, for 60 days, or with the MK-436(3(1-methyl-5 nitroimidazol-2-yl) in two daily doses of 250 mg/k.b.w, for 20 days. Parasitological cure tests were performed (xenodiagnosis, haemoculture, subinovulation of the blood into newborn mice), and serological indirect immunofluorescence test. The treated and untreated mice as well as intact controls were killed at different periods after treatment and the heart were submitted to histopathological study with hematoxilineosin and picrosirius staining; ultrastructural study; collagen immunotyping, fibronectin and laminin identification by immunofluorescence tests. Results: the untreated controls either infected with 21 SF or Colombian strain, showed inflammatory and fibrotic alterations that were mild to moderate with the 21 SF strain and intense with the Colombian strain. Redpicrosirius staining showed bundles of collagen in the interstitial space and around cardiac fibers. Increased deposits of mitritial components and collagen fibers, macrophages and fibroblasts appeared at the ultra structural examination. Deposits of fibronectin, laminin, pro-III and IV collagens were seen, most intense in those infected with the Colombian strain. Treated nice, parasitologically cured, presented clear-cut regression of the inflammatory lesions and of the interstitial matrix thickening. Mice infected with the Colombian strain and treated with MK-436, was parasitologically cured in 5/6 cases and showed mild inflammatory infiltration and fibrosis. The mice treated with Benznidazole (Colombian strain) did not cure and showed moderate fibrosis and inflammation. Treatment of the nice infected with the 21 SF with Benznidazole determined parasitological cure of all animals, that showed mild inflammation and fibrosis of the myocardium. The cured mice of all groups and treated but uncured showed collagen degradation at electronmicroscopy and decrease of immunofluorescence pattern of the matrix.

Cardiac glycosides isolated from the Indian-snuff, Maquira sclerophylla Ducke

The hydroalcoholic extract of the powdered bark of the Indian-snuff Maquira sclerophylla Ducke was purified by column chromatography in silica-gel and the major cardenolide isolated from preparative TLC was identified by 1H-NMR, 1 2 C-NMR and IR analyses. The spectra showed that the active substance has strophanthidin as aglicone.

A web-based pilot study of inter-pathologist reproducibility using the ISHLT 2004 working formulation for biopsy diagnosis of cardiac allograft rejection: The European experience.

BACKGROUND: The aim of this study was to assess, at the European level and using digital technology, the inter-pathologist reproducibility of the ISHLT 2004 system and to compare it with the 1990 system We also assessed the reproducibility of the morphologic criteria for diagnosis of antibody-mediated rejection detailed in the 2004 grading system. METHODS: The hematoxylin-eosin-stained sections of 20 sets of endomyocardial biopsies were pre-selected and graded by two pathologists (A.A. and M.B.) and digitized using a telepathology digital pathology system (Aperio ImageScope System; for details refer to http://aperio.com/). Their diagnoses were considered the index diagnoses, which covered all grades of acute cellular rejection (ACR), early ischemic lesions, Quilty lesions, late ischemic lesions and (in the 2005 system) antibody-mediated rejection (AMR). Eighteen pathologists from 16 heart transplant centers in 7 European countries participated in the study. Inter-observer reproducibility was assessed using Fleiss's kappa and Krippendorff's alpha statistics. RESULTS: The combined kappa value of all grades diagnosed by all 18 pathologists was 0.31 for the 1990 grading system and 0.39 for the 2005 grading system, with alpha statistics at 0.57 and 0.55, respectively. Kappa values by grade for 1990/2005, respectively, were: 0 = 0.52/0.51; 1A/1R = 0.24/0.36; 1B = 0.15; 2 = 0.13; 3A/2R = 0.29/0.29; 3B/3R = 0.13/0.23; and 4 = 0.18. For the 2 cases of AMR, 6 of 18 pathologists correctly suspected AMR on the hematoxylin-eosin slides, whereas, in each of 17 of the 18 AMR-negative cases a small percentage of pathologists (range 5% to 33%) overinterpreted the findings as suggestive for AMR. CONCLUSIONS: Reproducibility studies of cardiac biopsies by pathologists in different centers at the international level were feasible using digitized slides rather than conventional histology glass slides. There was a small improvement in interobserver agreement between pathologists of different European centers when moving from the 1990 ISHLT classification to the "new" 2005 ISHLT classification. Morphologic suspicion of AMR in the 2004 system on hematoxylin-eosin-stained slides only was poor, highlighting the need for better standardization of morphologic criteria for AMR. Ongoing educational programs are needed to ensure standardization of diagnosis of both acute cellular and antibody-mediated rejection.

Use of levosimendan as rescue therapy in children with low cardiac output syndrome.

Objective: Aim of post operative treatments after cardiac surgery is to avoid low cardiac output syndrome (LCOS). Levosimendan, a new inotrope agent, has been demonstrated in adult patient to be an effective treatment for this purpose when classical therapy is not effective. It shows a positive effect on cardiac output, with fewer adverse effects and lower mortality than with dopamine. There is very few data on its benefit in the paediatric population. The aim of this study is to evaluate the effect of levosimendan in cardiac children with LCOS.Methods: Retrospective analysis of 25 children hospitalised in our PICU after cardiac surgery that demonstrated LCOS not responding to classical catecholamine therapy and who received levosimendan as rescue. LCOS parameters like urine output, mixed venous oxygen saturation (SvO2), arterio-venous differences in CO2 (AVCO2) and plasmatic lactate were compared before therapy and at 12, 24, 48 and 72 hours after the beginning of the levosimendan infusion. We also analyzed the effect on the utilisation of amines (amine score), adverse events and mortality.Results: After the beginning of levosimendan infusion, urine output (3.1 vs 5.3ml/kg/h, p=0.003) and SVO2 (56 vs 64mmHg, p=0.001) increase significantly during first 72 hours and at the same time plasmatic lactate (2.6 vs 1.4 mmole/l, p<0.001), AVCO2 (11 vs 8 mmHg, p=0.002) and amine score (63 vs 39, p=0.007) decrease significantly. No side effects were noted during administration of levosimendan. In this group of patients, mortality was 0%.Conclusion: Levosimendan is an effective treatment in children after congenital heart surgery. Our study, with a greater sample of patient than other studies, confirms the improvement of cardiac output already shown in other paediatric studies.

Cost evaluation of cardiac magnetic resonance imaging versus coronary angiography for the work-up of coronary artery disease

Background: CMR has recently emerged as a robust and reliable technique to assess coronary artery disease (CAD). A negative perfusion CMR test predicts low event rates of 0.3-0.5%/year. Invasive coronary angiography (CA) remains the "gold standard" for the evaluation of CAD in many countries.Objective: Assessing the costs of the two strategies in the European CMR registry for the work-up of known or suspected CAD from a health care payer perspective. Strategy 1) a CA to all patients or 2) a CA only to patients who are diagnosed positive for ischemia in a prior CMR.Method and results: Using data of the European CMR registry (20 hospitals, 11'040 consecutive patients) we calculated the proportion of patients who were diagnosed positive (20.6%), uncertain (6.5%), and negative (72.9%) after the CMR test in patients with known or suspected CAD (n=2'717). No other medical test was performed to patients who were negative for ischemia. Positive diagnosed patients had a coronary angiography. Those with uncertain diagnosis had additional tests (84.7%: stress echocardiography, 13.1%: CCT, 2.3% SPECT), these costs were added to the CMR strategy costs. Information from costs for tests in Germany and Switzerland were used. A sensibility analysis was performed for inpatient CA. For costs see figure. Results - costs.Discussion: The CMR strategy costs less than the CA strategy for the health insurance systems both, in Germany and Switzerland. While lower in costs, the CMR strategy is a non-invasive one, does not expose to radiation, and yields additional information on cardiac function, viability, valves, and great vessels. Developing the use of CMR instead of CA might imply some reduction in costs together with superior patient safety and comfort, and a better utilization of resources at the hospital level. Document introduit le : 01.12.2011

Rôle de l'IRM cardiaque dans le dépistage des cardiomyopathies de l'adulte [Cardiomyopathy and cardiac magnetic resonance].

Cardiovascular magnetic resonance (CMR) is a rapidly emerging non-invasive imaging technique free of X-Ray and offers higher spatial resolution than alternative forms of cardiac imaging for the assessment of left ventricular (LV) anatomy, function, and viability due to the unique capability of myocardial tissue characterization after gadolinium-chelates contrast administration. This imaging technique has clinical utility over a broad spectrum of heart diseases: ranging from ischaemic to non ischaemic aetiologies. Cardiomyopathies (CMP) are a heterogeneous group of diseases of the myocardium associated with architectural abnormalities and mechanical dysfunction. CMR can help excluding coronary artery disease and can provide positive diagnostic features for several CMP resulted in better diagnosis and management, Leading to improvements in mortality.

Involvement of amphetamines in sudden and unexpected death.

In the present study, the effects of amphetamine-class drugs were examined in cases reported to the Victorian coroner from 2001 to 2005 to determine if death can occur from the use of amphetamine-class drugs alone. A total of 169 cases were reviewed where a forensic autopsy detected amphetamine(s) in the blood. Pathology, toxicology, and police reports were analyzed in all cases to ascertain the involvement of amphetamine-class drugs in these deaths. In Victoria, methamphetamine (MA) is the principal abused amphetamine-class followed by methylenedioxymethamphetamine (MDMA). There were six cases in which a cerebral hemorrhage caused death and three cases in which serotonin syndrome was established as being caused by the interaction of MDMA and moclobemide. There were 19 cases in which long-term use of amphetamines was associated with heart disease. There were three cases where amphetamine-class drugs alone were regarded as the cause of death, of which two cases exhibited high levels of MDMA and lesser amounts of MA and/or amphetamine. There were no cases in which significant natural disease was absent and death was regarded as caused by the use of MA. There was no correlation between blood concentration of drug and outcome.

IRM cardiaque dans le suivi des cardiopathies congénitales à l'âge adulte [Cardiac MRI in the follow-up of adult congenital cardiomyopathy patients].

Magnetic resonance imaging is a rapidly developing modality in cardiology. It offers an excellent image definition and a large field of view, allowing a more accurate morphological assessment of cardiac malformations. Due to its unique versatility and its ability to provide myocardial tissue characterization, cardiac magnetic resonance (CMR) is now recognized as a central imaging modality for a wide range of congenital heart diseases, including assessment of post-surgical cardiac anatomy, quantification of valvular disease and detection of myocardial ischemia. CMR provides useful diagnostic information without any radiation exposure, and improves the global management of patients with congenital heart disease.

Two Unusual Cases of Sudden Death in Children

We report two unusual cases of sudden unexpected death in children. Histopathologic examination showed intimal fibroplasias, a variant of fibromuscular dysplasia of the right coronary artery associated in both cases with fatty infiltration of the right ventricular myocardium. The significance of this particular combination of two lesions known to induce a sudden death in young people is discussed.

Evaluation cardiologique préopératoire avant chirurgie non cardiaque: stratification du risque cardiovasculaire [Preoperative cardiac assessment before non-cardiac surgery: cardiac risk stratification].

Perioperative cardiac events occurring in patients undergoing non-cardiac surgery are a common cause of morbidity and mortality. Current guidelines recommend an individualized approach to preoperative cardiac risk stratification prior to non-cardiac surgery, integrating risk factors both for the patient (active cardiac conditions, clinical risk factors, functional capacity) and for the planned surgery. Preoperative cardiac investigations are currently limited to high-risk patients in whom they may contribute to modify the perioperative management. A multidisciplinary approach to such patients, integrating the general practitioner, is recommended in order to define an individualized peri-operative strategy.

A human MYBPC3 mutation appearing about 10 centuries ago results in a hypertrophic cardiomyopathy with delayed onset, moderate evolution but with a risk of sudden death.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a genetically heterogeneous disease. One specific mutation in the MYBPC3 gene is highly prevalent in center east of France giving an opportunity to define the clinical profile of this specific mutation. METHODS: HCM probands were screened for mutation in the MYH7, MYBPC3, TNNT2 and TNNI3 genes. Carriers of the MYBPC3 IVS20-2A>G mutation were genotyped with 8 microsatellites flanking this gene. The age of this MYBPC3 mutation was inferred with the software ESTIAGE. The age at first symptom, diagnosis, first complication, first severe complication and the rate of sudden death were compared between carriers of the IVS20-2 mutation (group A) and carriers of all other mutations (group B) using time to event curves and log rank test. RESULTS: Out of 107 HCM probands, 45 had a single heterozygous mutation in one of the 4 tested sarcomeric genes including 9 patients with the MYBPC3 IVS20-2A>G mutation. The IVS20-2 mutation in these 9 patients and their 25 mutation carrier relatives was embedded in a common haplotype defined after genotyping 4 polymorphic markers on each side of the MYBPC3 gene. This result supports the hypothesis of a common ancestor. Furthermore, we evaluated that the mutation occurred about 47 generations ago, approximately at the 10th century.We then compared the clinical profile of the IVS20-2 mutation carriers (group A) and the carriers of all other mutations (group B). Age at onset of symptoms was similar in the 34 group A cases and the 73 group B cases but group A cases were diagnosed on average 15 years later (log rank test p = 0.022). Age of first complication and first severe complication was delayed in group A vs group B cases but the prevalence of sudden death and age at death was similar in both groups. CONCLUSION: A founder mutation arising at about the 10th century in the MYBPC3 gene accounts for 8.4% of all HCM in center east France and results in a cardiomyopathy starting late and evolving slowly but with an apparent risk of sudden death similar to other sarcomeric mutations.

Risk of death due to chronic chagasic cardiopathy

In this longitudinal study 5,710 people were included. The inclusion criteria were two positive serological results for Trypanosoma cruzi infection, 15 and 50 years old and no other demostrable diesease at the time of study. In the five year follow up 1,117 patients were lost. The follow up involved yearly evaluation of serology, clinical examination, X-ray of torax, and ECG, for 4,593 patients and 263 were contacted at home because they did not assist for their clinical consultant. Time average of follow up was 5.3 years. Eighty nine (1.5%) of the 4,593 patients died during the follow-up period, 63 (71%) by cardiac insufiency (CI) and 26 (29%) by severe ventricular arrithmias. Diagnosis of cardiomegaly was present in all the patients with diagnosis of CI and in 15 (5%) of the patients with diagnosis of arrithmias.The ECG alterations of these pacients show 61 right bundle brunch block (RBBB), associated or not with left anterior hemiblock (LAHB), 47 pathological Q wave and 70 primary repolarization alterations; 61 had polyfocal ventricular arrithmia. The death rate was similar in the sexes and was more frequent between 40 and 50 years of age. Information on 1,380 recuperated patients shows that 15 died with no previous symptoms and without medical assistance and were interpretate as sudden death. The latest ECG in three follow-up of these pacients indicates (before death) that only one had normal study and 14 presented 12 RBBB; 9 LAHB; 7 isolated ventricular arrithmia; 10 repolariz alterations; 2 patological Q wave, 10 patients of them with RBBB and repolariz alterations. In all the cases we had people between 35 and 43 years old, 9 men and 6 women. This study shows that in Chagas disease is possible to differenciate two risk groups. A low risk death group that have normal ECG and clinical evaluation during the follow up, and a high risk group associate ECG with RBBB and primary alterations of repolarization and/or inactivation zones with not anual clinical evaluation.