Camille Boulagnon

Viral causes of human myocarditis

The diagnosis of acute myocarditis is complex and challenging. The use of the Dallas criteria in the diagnosis of myocarditis is associated with poor sensitivity and specificity because of the sampling error related to the often focal distribution of the specific histological lesions in cardiac tissue and the variability in pathological interpretation. To improve histological diagnosis, additional virological evaluation of cardiac tissues is required, with immunohistochemical and polymerase chain reaction (PCR) techniques allowing identification and quantification of viral infection markers. The diagnostic gold standard is endomyocardial biopsy (EMB) with the histological Dallas criteria, in association with new immunohistochemical and PCR analyses of cardiac tissues. Using real-time PCR and reverse transcription PCR assays, parvovirus B19, Coxsackie B virus, human herpesvirus 6 (HHV-6) type B and adenovirus have been detected in 37, 33, 11 and 8% of EMB, respectively, from young adults (aged<35 years) with histologically proven acute myocarditis. Viral co-infections have also been found in 12% of acute myocarditis cases, generally parvovirus B19 plus HHV-6. Moreover, herpesviruses such as the Epstein-Barr virus or cytomegalovirus can also be associated with myocarditis after heart transplantation. During the clinical course of myocarditis, the immunohistochemical detection of enterovirus, adenovirus or parvovirus B19 capsid proteins or herpesvirus late proteins is necessary to differentiate a viral cardiac infection with replication activities from a persistent or latent cardiac infection. These new viral diagnostic approaches can lead to better identification of the aetiology of myocarditis and may therefore enable the development and evaluation of specific aetiology-directed treatment strategies.

Post-mortem biochemistry of vitreous humor and glucose metabolism: an update.

Abstract Post-mortem biochemistry, also called thanatochemistry, has proved useful in forensics for estimating the time since death and assessing the cause of death. Ketoacidosis is a frequent complication of diabetes mellitus which can be lethal, with possible medicolegal implications. However, interpretation of biochemical analyses is difficult because of post-mortem blood alterations involving glucose metabolic pathways. Vitreous humor is better preserved than blood after death, and therefore is preferentially used in thanatochemistry. However, both the lack of experience of most biochemists with this matrix in clinical practice, and the paucity of post-mortem studies make interpretation of post-mortem analyses difficult. This review examines the recent advances in the knowledge of glucose metabolism in vitreous humor, and the methods used for the post-mortem diagnosis of diabetic complications.

Quantitative Genomic and Antigenomic Enterovirus RNA Detection in Explanted Heart Tissue Samples from Patients with End-Stage Idiopathic Dilated Cardiomyopathy

ABSTRACT Standardized one-step real-time RT-PCR assay detected enterovirus RNA in cardiac biopsy samples from 4 of 20 patients suffering from idiopathic dilated cardiomyopathy (IDCM). The median viral load was 287 copies per microgram of total extracted nucleic acids, with positive- to negative-strand RNA ratios ranging from 2 to 20. These results demonstrate enterovirus persistence in the heart of IDCM patients, characterized by low viral loads and low positive- to negative-RNA ratios.

Post-mortem diagnosis, of cytomegalovirus and varicella zoster virus co-infection by combined histology and tissue molecular biology, in a sudden unexplained infant death

Abstract Background An autopsy case of a two-month-old male infant who suddenly and unexpectedly died during his sleep, eight days after the onset of benign varicella. Objectives To describe post-mortem combined histological and tissue molecular biological techniques for the diagnosis of cytomegalovirus and varicella zoster virus co-infection as a cause of death. Study design Real-time quantitative PCR and RT-PCR assays for Herpesviruses, respiratory viruses, Adenovirus, Enterovirus and Parvovirus B19 were performed on multi-organ frozen samples and paraffin-embedded tissues in combination with histology. Results Cytomegalovirus and varicella zoster virus were detected by molecular biology with highest viral loads detected in the lungs (4.6×107 and 1.9×105 genome copies per million of cells, respectively). Pulmonary extensive necrotizing inflammation and immunohistochemistry correlated to virological data. Virological molecular biology was negative on paraffin-embedded tissues. Conclusions This case shows that thorough quantitative virological investigations on frozen tissues must be performed in combination with histology and immunohistochemistry for the determination of the cause of a sudden unexplained infant death.

Influenza A/H1N1 (2009) Infection as a Cause of Unexpected Out-of-Hospital Death in the Young*

Abstract:  In March 2009, a new strain of influenza A/H1N1 virus was identified in Mexico, responsible for a pandemic. Worldwide, more than 13,500 patients died, most often from acute respiratory distress syndrome. Because sudden death cases were rare, involving mostly young apparently healthy persons, influenza A/H1N1 (2009)‐related deaths may be misdiagnosed, which can raise medico‐legal issues. Case history: we report on an unexpected out‐of‐hospital death involving a young male with no past medical history and no vaccination. Fever was his only symptom. Laboratory tests: histology showed patchy necrotic foci with mononuclear inflammation in the lungs. The heart was histologically normal, but virological analyses using molecular biology on frozen myocardial samples showed high virus load. In conclusion, this case report shows that influenza A/H1N1 (2009) virus can be a cause of sudden cardiac death in the young and demonstrates the importance of quantitative virological analyses for the diagnosis of myocarditis.

[Investigation of the sudden infant death syndrome: a multidisciplinary approach is required].

The concept of sudden infant death syndrome (SIDS) is defined as the sudden, unexpected death of an infant less than a year old which remains unexplained after in-depth investigations comprising a complete autopsy, biological analyses, and a clinical examination of the circumstances surrounding the death. This definition underlines the importance of finding the cause of this disease in order to improve preventative measures to reduce the number of deaths due to sudden infant death syndrome. Among the causes of SIDS, pediatric infectious diseases may be neglected and must be systematically sought after. We report upon a SIDS death case of a four and a half month-old that occurred during his sleep. Following the absence of an evident cause of death a scientific autopsy was performed. The histological examination of pulmonary tissue revealed broncolitic lesions associated with numerous micro-abscesses. The post mortem microbiological analyses revealed evidence of an infection by the respiratory syncytial virus complicated by a bacterial infection due to Haemophilus influenzae. The case underlines the necessity of a multidisciplinary approach to researching SIDS, involving both clinicians and biologists, in order to determine the causes of these deaths.

Cas anatomocliniqueUne cause de nécrose palatine à ne pas méconnaîtreA cause of palatal necrosis not to ignore

We report a case of pseudotumoral nasal septum and hard palate perforation in a 42-years-old man. The diagnosis retained after differential diagnosis exclusion was necrotic midfacial lesion due to chronic inhalation of cocaine. This condition can mimic vasculitis, primary tumors and granulomatous infections. Differential diagnosis and pathophysiology of this condition will be discussed in this anatomo-clinical case.

Une cause de nécrose palatine à ne pas méconnaître

We report a case of pseudotumoral nasal septum and hard palate perforation in a 42-years-old man. The diagnosis retained after differential diagnosis exclusion was necrotic midfacial lesion due to chronic inhalation of cocaine. This condition can mimic vasculitis, primary tumors and granulomatous infections. Differential diagnosis and pathophysiology of this condition will be discussed in this anatomo-clinical case.