Reinhard Dettmeyer

Role of Virus-Induced Myocardial Affections in Sudden Infant Death Syndrome: A Prospective Postmortem Study

The cause of sudden infant death syndrome (SIDS) is an unresolved problem of high relevance. Previous studies indicate a role of infections. In our prospective study, we investigated the frequency of virus-induced myocardial affections in SIDS. Postmortem samples from SIDS victims and control subjects were investigated prospectively. Pediatric cases of unnatural death served as controls. Samples were studied for enteroviruses, adenoviruses, parvovirus B19, and Epstein-Barr virus applying PCR. Immunohistochemical investigations for inflammatory cells, the necrosis marker C5b-9(m) complement complex, and the enteroviral capsid protein VP1 were performed. Overall, 62 SIDS victims were studied. As controls, 11 infants were enrolled. Enteroviruses were detected in 14 (22.5%), adenoviruses in 2 (3.2%), Epstein-Barr viruses in 3 (4.8%), and parvovirus B19 in 7 (11.2%) cases of SIDS. Control group samples were completely virus negative. Compared with controls, immunohistochemical investigations partially revealed a significant increase in the number of T lymphocytes in SIDS myocardial samples (p < 0.05). Furthermore, cases with elevated numbers of leukocytes and + necroses, and enteroviral VP1 macrophages, microfocal C5b-9(m) capsid protein within the myocardium were detected. Applying a comprehensive combination of molecular and immunohistochemical techniques, our results demonstrate a clearly higher prevalence of viral myocardial affections in SIDS. Our results emphasize the importance of PCR-based diagnosis of viral myocardial affections. We suggest preliminary criteria for cellular immunohistochemical diagnosis of viral myocardial affections derived from our findings. For future investigations in SIDS, we suggest a comprehensive approach that includes PCR and immunohistochemistry. Our results offer novel strategies for diagnosis of pediatric myocardial viral affections.

Fatal myeloencephalopathy due to accidental intrathecal vincristin administration : a report of two cases

We report on two fatal cases of accidental intrathecal vincristine instillation in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks after intrathecal injection of vincristine. Clinically, the onset was characterized by the signs of opistothonus, sensory and motor dysfunction and ascending paralysis. Histological and immunohistochemical investigations (HE-LFB, CD-68, Neurofilament) revealed degeneration of myelin and axons as well as pseudocystic transformation in areas exposed to vincristine, accompanied by secondary changes with numerous prominent macrophages. The clinical course and histopathological results of the two cases are presented. A review of all reported cases in the literature is given. A better controlled regimen for administering vincristine and intrathecal chemotherapy is recommended.

Coxsackie B3 Myocarditis in 4 Cases of Suspected Sudden Infant Death Syndrome: Diagnosis by Immunohistochemical and Molecular-Pathologic Investigations

Immunohistochemical and molecular-pathologic techniques have improved the diagnosis of myocarditis as compared with conventional histologic staining methods done according to the Dallas criteria. Most investigations were carried out on adults, and only a few authors investigating childhood deaths applied these modern methods, used for diagnosing myocarditis. We report on four children under one year of age, who suddenly died without prodromal symptoms. Their deaths were attributed to SIDS (sudden infant death syndrome). Immunohistochemical (LCA, CD68, CD45R0, MHC-class-II-molecules, VP1-capsid-protein of enteroviruses) and molecular-pathologic (RT-PCR) investigations, however, suggested that death was caused by a coxsackie-B3-myocarditis. In the future, these methods should be used for investigating cases with suspicion of SIDS.

Fatal parvovirus B19 myocarditis in an 8-year-old boy.

A report is given on an 8-year-old boy who suddenly and unexpected died. Autopsy findings point to acute heart failure. Microscopic examination of the heart showed increased interstitial and perivasal fibrosis and myocarditis with macrophage infiltration. Polymerase chain reaction (PCR) analysis for parvovirus B19 was positive in heart samples and in the spleen. Immunostaining for parvoviral surface antigens was negative. Although the virus does not appear to have infected the cardiomyocytes, we speculate that myocarditis arose from immunological cross-reaction to epitopes shared between the virus and the myocardium.

Immunohistochemical techniques improve the diagnosis of myocarditis in cases of suspected sudden infant death syndrome (SIDS)

Immunohistochemical techniques have improved the diagnosis of myocarditis. In a post mortem study, eight specimens in each case of the formalin-fixed and paraffin-embedded hearts of 20 suspected cases of sudden infant death syndrome (SIDS) were investigated with traditional hematoxylin-eosin staining and immunohistochemical methods. The hematoxylin-eosin stained specimens were examined for myocarditis according to the Dallas criteria; only in one case was a myocarditis diagnosed. The subsequent definition of the major histocompatibility complex class II antigens (HLA-DP,DQ,DR and HLA-DR), known to be enhanced in cases of myocarditis, the quantification of leucocytes with leucocyte common antigen (LCA) and characterization and quantification of T-lymphocytes using a specific marker (CD-3) allowed the definite diagnosis of myocarditis in three additional cases, six cases were found with moderate changes and ten cases without signs of inflammation.

PCR-Based Diagnosis of Enterovirus and Parvovirus B19 in Paraffin-Embedded Heart Tissue of Children with Suspected Sudden Infant Death Syndrome

The diagnosis of viral myocarditis remains difficult and generally depends on clinical and histologic criteria. Viral cultures and serology are often unrewarding with low yields. The purpose of this study was to analyze the usefulness of PCR in the rapid diagnosis of myocarditis in children. PCR was used to analyze 120 myocardial tissue samples from 60 cases of sudden infant death syndrome (SIDS) and 56 myocardial tissue samples from 36 cases with well-known causes of sudden death (11 children younger than 1 year and 25 children 1–10 years old). The myocardial tissue samples were evaluated for the presence of enteroviruses and parvovirus B19 using PCR primers designed to consensus and unique sequences of these viral genomes. Enteroviruses could be detected in 14 cases of SIDS, whereas the detection of enteroviral nucleic acid within the control group was negative. Seven cases with myocardial infection caused by parvovirus B19 were found in the SIDS group. The detection of parvoviruses in the control group of the 11 children younger than 1 year was negative, whereas 3 positive cases of parvoviruses could be detected in the control group of children from 1 to 10 years old. In the myocardial sample of one SIDS case, both enteroviruses and parvovirus B19 could be detected. Our results emphasize the importance of modern molecular biologic methods in cases of sudden infant death even when conventional histologic examination revealed no serious findings in heart muscle tissue.

Child abuse and neglect: Diagnosis and Management

BACKGROUND The findings of studies on the frequency of violence against children imply that many cases go undetected. METHODS Selective literature review based on a search of different databases for publications on all types of violence against children, except sexual abuse. RESULTS The physical abuse of children can involve blunt trauma, thermal injury, and the so-called shaking trauma syndrome (STS). Physical and psychological child neglect have very serious long-term effects. It can be difficult to draw a clear distinction of child abuse and neglect on the one hand, and acceptable behavior on the other, because of the varying social acceptance of certain child-raising practices. Münchhausens syndrome by proxy (MSbP) is a rare, special type of child abuse. CONCLUSION At the beginning of the 21(st) century, well-established normative structures are in place to protect children against abuse and neglect, and the available help from social organizations can also have a preventive effect. Further improvements will depend on interdisciplinary coordination and better training of specialists in all of the involved disciplines.

Heroin-associated nephropathy

Since the first reports in the late 1960s and early 1970s there have been numerous studies describing the clinical and pathological features of renal diseases associated with chronic parenteral abuse of heroin, cocaine, morphine, amphetamine, and other narcotic and hallucinogenic drugs, including several adulterants. The past 35years have witnessed an explosive growth in illicit drug use in many parts of the world. Meanwhile, drug addict nephropathy constitutes an important cause of end-stage renal disease. The term ´heroin-associated nephropathy’ includes different morphological findings following chronic drug abuse. Up to now it still remains ambiguous as to whether or not heroin/morphine itself, adulterants, other diseases like hepatitis B and C infection, or HIV, lead to a spectrum of morphologically described ´heroin-associated’ findings in the kidneys. As a measure of prevention it appears that the purity of heroin plays an important role.

Pulmonary edema in fatal heroin overdose: immunohistological investigations with IgE, collagen IV and laminin — no increase of defects of alveolar-capillary membranes

Pulmonary edema complicating heroin overdosage is a well recognized entity and regarded as the major mechanism contributing to death in heroin addicts. Its pathogenesis is unknown, several mechanisms are discussed: hypoxia-induced increase of pulmonary capillary permeability, depressed myocardial contractility, centrally induced respiratory depression, primary toxic effects on the alveolar capillaries and acute anaphylactic shock. The present study included opiate-related deaths (n=23) and a control group of sudden cardiovascular deaths (n=12) to verify the hypothesis, that defects of the alveolar capillary membranes and/or an acute anaphylactic reaction leads to pulmonary congestion, edema and hemorrhages. Lung specimens were obtained from these 35 autopsies of persons autopsied in the Institute of Forensic Medicine, University of Bonn, in 1997 and 1998. All specimens were examined with hematoxylin-eosin, prussian blue and investigated with immunohistological methods using primary antibodies against collagen IV, laminin and IgE. Defects of the basal laminae of the alveoli were found, demonstrated by laminin and collagen IV, and the number of IgE-positive cells was counted in both groups. There was an increased but not significant number of IgE-positive cells in the heroin-group and defects of the epithelial and endothelial basal laminae were found in both groups without significant differences.

Sudden death in cases with anomalous origin of the left coronary artery

UNLABELLED Ectopic origin of the left coronary artery from the right sinus of valsalva with anterior and posterior courses are thought to be benign anomalies. CASE REPORTS a 58-year-old woman died suddenly after a car accident without having sustained any injuries. The only abnormal finding was an ectopic origin of the left coronary artery from the right sinus with anterior free wall course. The anomaly was complicated by the absence of a left descending branch and a hypoplastic circumflex artery. A 38-year-old male died suddenly during work. Beside the ostium of the right coronary artery originated the normal calibered circumflex branch of the left coronary artery which passed behind the aorta. The left anterior descending branch had a normal origin. There was a 2 cm in diameter transmural infarct observed microscopically.