Sudden infant deaths from undiagnosed ventricular septal defect - Report of two autopsy cases.

Ventricular septal defect (VSD) has a relatively non-aggressive clinical course; either spontaneous closure or causing congestive heart failure treatable with surgical intervention. We present two autopsy cases of sudden infant deaths from clinically undiagnosed VSDs. Case 1 was an 18-day-old boy. As the deceased coughed and became limp after feeding, he was carried to a hospital. Heart murmur was not auscultated there, so he was brought back to home. He presented severe dyspnea and then he was pronounced dead the next day. Case 2 was a 3-week-old boy. Any abnormality was pointed out at physical examination, although his mother felt his wheeze. He developed respiratory arrest at home in the morning and then he was confirmed dead at the hospital. Heart weights of these babies were heavier than mean weights of each normal development. There were perimembranous VSDs in both cases. Histology revealed that the pulmonary arterial walls were thickened. We diagnosed the cause of death in these cases was cardiac collapse with pulmonary hypertension due to VSD. Congenital heart diseases can be diagnosed as early as before birth, because echocardiograph and fetal echography are prevalent in these days. Most VSDs can be noticed by systolic murmur even today. We consider that the failure of initial clinical diagnosis of VSD in primary physical assessment could lead unexpected sudden death. These two cases reminded us to the importance of auscultation which is conventional but as one of the indispensable measure to find a clue for the congenital abnormality.

A hind limb tourniquet induces interleukin-6 expression in a rat dorsal root ganglion.

We investigated the mRNA levels of interleukin-6-related genes in a rat dorsal root ganglion after application of a tourniquet to a hind limb in order to identify the molecules that are induced immediately after peripheral nerve injury at the early stage. Induction of interleukin-6 and upregulation of glycoprotein 130 mRNA expressions were observed in the ipsilateral dorsal root ganglion at 4 h after tourniquet application. Interleukin-6 protein was detected in small-sized and medium-sized dorsal root ganglion cells by immunohistochemical analysis. The induction of interleukin-6 expression is likely to play a role in the protection of injured neurons perhaps related to growth of their axons. Glycoprotein 130 might also account for the inhibitory effects following nerve injury.

Medico-legal aspects of traumatic injury of the vertebrobasilar artery.

Based on our experiences with medico-legal autopsies, we analyzed traumatic injury of the vertebrobasilar artery (VBA) in traffic accident victims. VBA rupture occurred in six cases with traumatic medullary lesions, but in none with cervical cord injury. A relatively small external force applied to the head or neck can induce isolated traumatic subarachnoid hemorrhage (SAH), which accounts for approximately 11% of fatal head injuries. We examined the relationship between site of impact and site of vascular injury in 16 cases of isolated traumatic SAH. The results showed that the vertebral artery (VA) on the side of impact tended to be longitudinally injured in victims experiencing an external force equivalent to that of a fist punch to the head or face. There was no clear relationship between the site of impact and the site of vascular injury in victims who had sustained an external force greater than that of a fist punch. However, our results suggest that an external force causing rotation of the head was likely to cause tearing of the artery. In cases in which an external force equivalent to that of a fist punch was applied to the head, a raised blood alcohol level was a significant risk factor for artery rupture. Furthermore, a difference in the diameters of the left and right VAs was a risk factor for artery rupture. To determine why the VA, the most frequent site of arterial dissection, is also frequently the site of injury, we histologically examined normal and dissected VBAs. We also discuss medico-legal issues of the causal relationship between external force applied and rupture or dissection of the VA.

Nitric oxide synthase expressions in rat dorsal root ganglion after a hind limb tourniquet.

We investigated the mRNA levels of neuronal, inducible, endothelial nitric oxide synthases (nNOS, iNOS, eNOS) and tumor necrosis factor-alpha (TNF-alpha) in a rat dorsal root ganglion (DRG) after tourniquet application to a hind limb to identify molecules that trigger secondary events after peripheral nerve injury. Significantly high nNOS, iNOS mRNA and protein levels were observed in the ipsilateral DRGs 4 h after tourniquet application but not in the contralateral or control DRGs. The levels of TNF-alpha, an inducer of iNOS, were significantly increased in the ipsilateral DRGs 1 h after tourniquet application. Large amounts of NO might result in damage to the host cells and induce apotosis to eliminate damaged cells during the early stage of nerve injury.

The mechanism underlying the occurrence of traumatic brainstem lesions in victims of traffic accidents.

Autopsy records and photographs of traffic accident deaths from 1985 to 2000 as well as police reports were reviewed to determine the morbidity and pathological features of traumatic brainstem lesions and to determine the relationship between lesions and forces applied. Of 156 autopsied traffic accident cases, 26 (16.7%) of the victims had gross primary brainstem injury. The 26 victims included 19 pedestrians, five cyclists, one driver and one passenger. There were four cases of upper face impact and two cases of lower face impact in which the direct forces to the head had caused hyperextension of the neck. However, eight of the pedestrians and two of the cyclists had medullary lesions for which the cause could not be explained by the direct impact to the head, suggesting that indirect forces, i.e. the inertia of the head, had caused neck hyperextension at the moment of impact with the car. Based on the findings in this study, it was concluded that when a pedestrian or cyclist is hit by a vehicle travelling at high speed, the traction force due to the inertia of the head is one of the causes of violent hyperextension of the head that result in traumatic brainstem lesions.

Expression of cytokines, neurotrophins, neurotrophin receptors and NOS mRNA in dorsal root ganglion of a rat tourniquet model.

We studied temporal changes in mRNA expression patterns for nitric oxide synthase (NOS), cytokines, neurotrophins and neurotrophin receptors in the dorsal root ganglion (DRG) of the rat, after application of a tourniquet to the hind limb. Collapsed myelin and degenerated axons were observed in the tourniquet segment of the sciatic nerve. Gene expression level of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) was significantly increased in ipsilateral DRG samples at 4h after application of the tourniquet but not in the contralateral or control DRG samples. Upregulation of tumor necrosis factor (TNF)-alpha, activating transcription factor (ATF)-3 and neurotrophin-3 (NT3) expressions began at 1h after application of the tourniquet in ipsilateral DRGs. It is likely that transient expression of these molecules triggers secondary events that may be beneficial to wound repair and regeneration.

Changes in mRNA expression patterns for cytokines in blood leukocytes of a rat tourniquet model.

We examined changes in mRNA expression patterns for proinflammatory cytokines and growth factors in blood samples after application of a tourniquet to the rat hind limb. Slight upregulations of interferon (IFN)-gamma, macrophage colony-stimulating factor (M-CSF) and transforming growth factor (TGF)-beta1 mRNA began at 2h after tourniquet application and were short-lived. The levels of activating transcription factor (ATF)-3, a stress-inducible gene, had increased at 1h after tourniquet application. No significant expression of interleukin (IL)-6 mRNA was observed in most samples. There were no significant temporal changes in the levels of IL-1beta, cardiotrophin (CT)-1 mRNA compared to the control levels, but, downregulation of gp130, a receptor of the IL-6 family, began at 1h after tourniquet application. Nerve growth factor (NGF) mRNA gradually increased and reached a significantly high level at 4h after application of the tourniquet. Gene expression induction in blood leukocytes occurred soon after application of the tourniquet and was short-lived. The transient mRNA expressions probably trigger secondary events that may be beneficial to wound repair and regeneration.

Induction of nerve growth factor mRNA in a rat dorsal root ganglion after application of a tourniquet.

We investigated the mRNA levels of neurotrophins and neurotrophin receptors in a rat dorsal root ganglion (DRG), after tourniquet application to a hind limb, to identify the nerve-protective molecules that are induced immediately after peripheral nerve crush and play a part in the process leading to secondary events. No significant expression of nerve growth factor (NGF) mRNA or protein was observed in the control or contralateral DRG. NGF mRNA expression started within 2 h and NGF protein expression was observed in Schwann cells at 4 h after application of the tourniquet, due to termination of the neurotrophin supply from peripheral nerves. The levels of neurotrophin 3 mRNA were significantly increased in the DRGs on both sides at 1 and 2 h after tourniquet application, but no significant changes in brain-derived neurotrophic factor and neurotrophin 4/5 expression levels were observed in either the contralateral or ipsilateral DRG. The expression levels of neurotrophin receptors in the DRGs on both the contralateral and ipsilateral sides had decreased at 1 to 2 h after application of the tourniquet and had returned to the control levels at 4 h after tourniquet application.