The vicious spiral in Sudden Infant Death Syndrome.

Sudden Infant Death Syndrome (SIDS) is the sudden and unexpected death of an otherwise healthy infant less than 1 year of age where the cause of death remains unexplained after a thorough post-mortem investigation and evaluation of the circumstances. Epidemiological, clinical, biochemical, immunological and pathological evidence indicates that three factors must coincide for SIDS to occur: a vulnerable developmental stage of the immune system and central nervous system in the infant, predisposing factors, and external trigger events. This model is referred to as the fatal triangle or triple risk hypothesis.

Toxic effects of mineral oil saturated hydrocarbons (MOSH) and relation to accumulation in rat liver.

Humans are daily exposed to mineral oil saturated hydrocarbons (MOSH) from the diet. We exposed female Fischer 344 rats to a broad mixture and sub-fractions of MOSH. Chemical characterization of the MOSH mixture used and material accumulated in rat tissues were previously reported (Barp et al.

Death-scene investigations contribute to legal protection in unexpected child deaths in Norway.

Aim: This study reviewed cases of sudden unexpected child deaths in Norway to determine the significance of death-scene investigations (DSIs) in establishing cause and manner of death, and thereby it is relevance to legal protection.

Methods: Data from forensic autopsy reports and DSIs were collected and analysed for cases of unexpected deaths in children below 4 years of age in Norway during 2010-2016.

Results: Out of 141 cases, the death scene was investigated as a voluntary procedure in 75 cases and by the police in 41 cases.

Toxic effects of mineral oil saturated hydrocarbons (MOSH) and relation to accumulation in rat liver.

Humans are daily exposed to mineral oil saturated hydrocarbons (MOSH) from the diet. We exposed female Fischer 344 rats to a broad mixture and sub-fractions of MOSH. Chemical characterization of the MOSH mixture used and material accumulated in rat tissues were previously reported.

Traceability and distribution of DNA in archived post mortem tissue samples from patients with systemic meningococcal disease.

Background: The pathophysiology and outcome of meningococcal septic shock is closely associated with the plasma level of lipopolysaccharides (LPS, endotoxin) and the circulating level of meningococcal DNA. The aim of the present study was to quantify the number of in different formalin-fixed, paraffin-embedded (FFPE) tissue samples and fresh frozen (FF) tissue samples from patients with systemic meningococcal disease (SMD), to explore the distribution of in the body.

Methods: DNA in FFPE and FF tissue samples from heart, lungs, liver, kidneys, spleen and brain from patients with meningococcal shock and controls (lethal pneumococcal infection) stored at variable times, were isolated.

The gene encoding the inwardly rectifying potassium channel Kir4.1 may be involved in sudden infant death syndrome.

Aim: Disturbances in brain function and development may play a role in sudden infant death syndrome (SIDS). This Norwegian study aimed to test the hypothesis that specific variants of genes involved in water transport and potassium homeostasis would be predisposing factors for SIDS.

Methods: Genetic variation in the genes encoding aquaporin-4 (AQP4), Kir4.

Altered gene expression and possible immunodeficiency in cases of sudden infant death syndrome.

Background: A large number of studies have tried to uncover a genetic predisposition for sudden infant death syndrome (SIDS), but there is still uncertainty concerning the pathogenesis of these deaths. The purpose of this study was to investigate mRNA gene expression in SIDS cases and controls, in order to uncover genes that are differentially expressed in the two groups.

Methods: Tissue from brain, heart, and liver from 15 SIDS cases and 15 controls were included in the study, and mRNA expression was determined using the Illumina whole genome gene expression DASL HT assay.

Massive Organ Inflammation in Experimental and in Clinical Meningococcal Septic Shock.

Fulminant meningococcal sepsis is characterized by a massive growth of bacteria in the circulation, regarded as the primary inflammatory site, with no specific solid organ focus. Here we aimed to study the local inflammatory response in organs using a porcine model of fulminant meningococcal septic shock challenged with exponentially increasing doses of heat inactivated Neisseria meningitidis. The results were compared with those obtained in organs post mortem from three patients with lethal meningococcal septic shock.

Forensic autopsies in a naturalistic setting in Norway: autopsy rates and toxicological findings.

Autopsies can give valuable information about the cause of death, and represent an important tool for obtaining valid cause of death statistics. In particular, they may shed light on the circumstances of death in ambiguous and criminal cases. To address the need for information on current autopsy practices, forensic autopsy rates in two counties in Central Norway over the period 2007-2009 were assessed.

Aquaporin-4 gene variation and sudden infant death syndrome.

The purpose of this study was to investigate the aquaporin-4 (AQP4) gene in cases of sudden infant death syndrome (SIDS) and controls and to elucidate the hypothesis that a genetically determined disturbed water homeostasis in the brain is involved as a predisposing factor in SIDS. The single nucleotide polymorphisms (SNPs) rs2075575, rs4800773, rs162004, and rs3763043 in the AQP4 gene were investigated in 141 SIDS cases and 179 controls. For each SIDS case, a brain/body weight ratio was calculated.

IL-1 gene cluster polymorphisms and sudden infant death syndrome.

Several studies indicate that interleukin gene polymorphisms are of importance to sudden infant death syndrome (SIDS), and so far it has been reported that associations between SIDS and polymorphism in the genes encoding tumor necrosis factor alpha, IL (interleukin)-6, and IL-10. IL-1 are important for the synthesis of acute phase proteins, and it is a pyrogen cytokine that may cause fever. The purpose of the present study was to investigate two polymorphisms in the IL-1alpha gene; a variable number of tandem repeat (VNTR) in intron 6 and a single nucleotide polymorphism in +4845G/T, as well as the -511C/T polymorphism in the gene encoding IL-1beta, and a VNTR in intron 2 of the competitive antagonist IL-1Ra, in SIDS cases, cases of infectious death, and controls.

Interleukin-6 and the serotonergic system of the medulla oblongata in the sudden infant death syndrome.

Mild infection may trigger sudden death in the vulnerable infant by cytokine interactions with a compromised medullary serotonergic (5-HT) system, leading to disrupted cardiorespiratory regulation and sleep-related sudden death. The cytokine interleukin (IL)-6 is elevated in the cerebrospinal fluid in SIDS. We tested the hypothesis that the expression of IL-6 receptors (IL-6R) and/or gp130 (involved in IL-6R signaling) is altered in the medullary 5-HT system in SIDS.

Surfactant protein A and D gene polymorphisms and protein expression in victims of sudden infant death.

Aim: To investigate the innate immune components surfactant protein A (SP-A) and D (SP-D) in victims of sudden infant death syndrome (SIDS).

Methods: Ten common single nucleotide polymorphisms (SNPs) in the exons of SP-A1, SP-A2 and SP-D genes were analysed in 42 cases of SIDS and 46 explained sudden infant deaths. SP-A and SP-D protein expression in tissue from the aerodigestive tract was semi-quantitatively evaluated by immunohistochemistry.

TNF-alpha promoter polymorphisms in sudden infant death.

Several studies indicate that the immune system is stimulated in sudden infant death syndrome (SIDS). Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that strongly affects the cytokine cascade. A genetic variant associated with high production of TNF-alpha may thus be of significance in the pathogenesis of SIDS.

Helicobacter pylori antigen in stool is associated with SIDS and sudden infant deaths due to infectious disease.

Infection with Helicobacter pylori has been proposed to be a common cause of Sudden Infant Death Syndrome (SIDS). We investigated the frequency of H. pylori infection in 160 infant deaths and 156 live controls by means of the Helicobacter pylori stool antigen (HpSA) immunoassay.

Serotonin transporter gene variation in sudden infant death syndrome.

Aim: To investigate polymorphisms in the serotonin transporter (5-HTT) gene in cases of sudden infant death syndrome (SIDS) and controls, and further to elucidate a possible relationship between 5-HTT genotypes and external risk factors for SIDS.

Method: The subjects investigated consist of 163 SIDS cases and 243 controls. Polymorphisms in both the promoter and intron 2 of the 5-HTT gene were investigated, and the genotypes were determined using polymerase chain reaction (PCR) and gel electrophoresis.

Cardiac potassium channel dysfunction in sudden infant death syndrome.

Life-threatening arrhythmias have been suspected as one cause of the sudden infant death syndrome (SIDS), and this hypothesis is supported by the observation that mutations in arrhythmia susceptibility genes occur in 5-10% of cases. However, the functional consequences of cardiac potassium channel gene mutations associated with SIDS and how these alleles might mechanistically predispose to sudden death are unknown. To address these questions, we studied four missense KCNH2 (encoding HERG) variants, one compound KCNH2 genotype, and a missense KCNQ1 mutation all previously identified in Norwegian SIDS cases.

Post-neonatal drop in alveolar SP-A expression: biological significance for increased vulnerability to SIDS?

Background: Surfactant protein A (SP-A) is synthesized in the lung and is a part of the innate immune system. The aim of this study was to evaluate the expression of SP-A in lung tissue from fetuses, infants, children and adults with special regard to sudden infant death syndrome (SIDS).

Methods: A total of 160 cases were studied; 19 fetuses and neonates, 59 SIDS and 49 explained infant deaths below 1 year of age, 19 toddlers and 14 adults.

A mitochondrial DNA polymorphism associated with cardiac arrhythmia investigated in sudden infant death syndrome.

Aim: Long QT syndrome (LQTS) has been shown to be the cause of death in some cases originally diagnosed as sudden infant death syndrome (SIDS). Such cardiac arrhythmias have also been noted in families with mitochondrial disease, and studies indicate that mitochondrial disease could be involved in SIDS. This makes the mtDNA polymorphism T3394C interesting, as a previous study has shown it to be associated with electrocardiographic (ECG) changes after exercise in a family with LQTS, where some members harboured a KCNH2 mutation.

Cardiac sodium channel dysfunction in sudden infant death syndrome.

Background: Mutations in genes responsible for the congenital long-QT syndrome, especially SCN5A, have been identified in some cases of sudden infant death syndrome. In a large-scale collaborative genetic screen, several SCN5A variants were identified in a Norwegian sudden infant death syndrome cohort (n=201). We present functional characterization of 7 missense variants (S216L, R680H, T1304M, F1486L, V1951L, F2004L, and P2006A) and 1 in-frame deletion allele (delAL586-587) identified by these efforts.