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Histological studies were made of the conducting system and the myocardium in two cases of torsade de pointes with complex disturbances of impulse conduction and formation. A fairly similar clinicopathological pattern was seen, consisting of an unusual association of non-interruptive, widespread damage to the conducting system with the intermittent and variable electrocardiographic disorders. The inherent desynchronization of cardiac action and the bilateral, uneven, and partial disruptions of the bundle-branches have been tentatively correlated, pathophysiologically, with the re-entry circuit, or mechanism, which is held to be responsible for the cyclic fluctuation of QRS axis, peculiar to torsade de pointes. [ABSTRACT FROM PUBLISHER]

Abstract Background Iron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia. Methods Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments. Results Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells. Conclusions We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.

Abstract Background The ependyma, the lining providing a protective barrier and filtration system separating brain parenchyma from cerebrospinal fluid, is still inadequately understood in humans. In this study we aimed to define, by morphological and immunohistochemical methods, the sequence of developmental steps of the human ependyma in the brainstem (ventricular ependyma) and thoracic spinal cord (central canal ependyma) of a large sample of fetal and infant death victims, aged from 17 gestational weeks to 8 postnatal months. Additionally, we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant death and maternal smoking. Results Our results demonstrate that in early fetal life the human ependyma shows a pseudostratified cytoarchitecture including many tanycytes and ciliated cells together with numerous apoptotic and reactive astrocytes in the subependymal layer. The ependyma is fully differentiated, with a monolayer of uniform cells, after 32 to 34 gestational weeks. We observed a wide spectrum of ependymal pathological changes in sudden death victims, such as desquamation, clusters of ependymal cells in the subventricular zone, radial glial cells, and the unusual presence of neurons within and over the ependymal lining. These alterations were significantly related to maternal smoking in pregnancy. Conclusions We conclude that in smoking mothers, nicotine and its derivatives easily reach the cerebrospinal fluid in the fetus, immediately causing ependymal damage. Consequently, we suggest that the ependyma should be examined in-depth first in victims of sudden fetal or infant death with mothers who smoke.

Histological examination showed acute haemorrhage of the bifurcating His bundle and of the left bundle branch in a 35 year old man who died after being given external cardiac massage for cardiac arrest. "Hammering" of the ventricular septum crest against the central fibrous skeleton of the heart by compression of the sternum was believed to have caused the haematoma of the junctional tissue. [ABSTRACT FROM PUBLISHER]

Nicotinic acetylcholine receptors (nAChRs) are cationic channels of the neuronal cell membrane, differentially expressed in the central nervous system which, when activated by endogenous acetylcholine or exogenous nicotine, are able to enhance cholinergic transmission. The aim of this study was to investigate in human perinatal age the immunohistochemical expression of the α7-nAChR subtype, given its involvement in neuronal differentiation and its significant vulnerability to the toxic effects of nicotine. Thirty fetuses (with a gestational age between 25 and 40 weeks) and 35 infants (1-6 months old), suddenly died of known (controls) and unknown causes (unexplained deaths), with smoking and nonsmoking mothers, were included in this study. A negative or low immunoexpression of α7-nAChRs, indicative of their inactivation, was observed in the granular layers of the cerebellar cortex in 66% of the sudden unexplained perinatal deaths and 11% of the controls. A high correlation was also observed between these findings and maternal smoking. Apart from the well-known adverse effects of nicotine exposure during pregnancy, it may also cause significant alterations in cerebellar cholinergic transmission in areas of the brain involved in vital functions. These events may give us insights into the pathogenetic mechanisms leading to sudden unexplained fetal and infant death.

The inferior colliculus is a mesencephalic structure endowed with serotonergic fibers that plays an important role in the processing of acoustic information. The implication of the neuromodulator serotonin also in the aetiology of sudden unexplained fetal and infant death syndromes and the demonstration in these pathologies of developmental alterations of the superior olivary complex (SOC), a group of pontine nuclei likewise involved in hearing, prompted us to investigate whether the inferior colliculus may somehow contribute to the pathogenetic mechanism of unexplained perinatal death. Therefore, we performed in a wide set of fetuses and infants, aged from 33 gestational weeks to 7 postnatal months and died of both known and unknown cause, an in-depth anatomopathological analysis of the brainstem, particularly of the midbrain. Peculiar neuroanatomical and functional abnormalities of the inferior colliculus, such as hypoplasia/structural disarrangement and immunonegativity or poor positivity of serotonin, were exclusively found in sudden death victims, and not in controls. In addition, these alterations were frequently related to dysgenesis of connected structures, precisely the raphé nuclei and the superior olivary complex, and to nicotine absorption in pregnancy. We propose, on the basis of these results, the involvement of the inferior colliculus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities, and then in pathological conditions underlying a sudden death in vulnerable periods of the autonomic nervous system development, particularly associated to harmful risk factors as cigarette smoking.

Experimental studies have demonstrated that the neurotrophin brain-derived neutrophic factor (BDNF) is required for the appropriate development of the central respiratory network, a neuronal complex in the brainstem of vital importance to sustaining life. The pontine Kölliker-Fuse nucleus (KFN) is a fundamental component of this circuitry with strong implications in the pre- and postnatal breathing control. This study provides detailed account for the cytoarchitecture, the physiology and the BDNF behavior of the human KFN in perinatal age. We applied immunohistochemistry in formalin-fixed and paraffin-embedded brainstem samples (from 45 fetuses and newborns died of both known and unknown causes), to analyze BDNF, gliosis and apoptosis patterns of manifestation. The KFN showed clear signs of developmental immaturity, prevalently associated to BDNF altered expression, in high percentages of sudden intrauterine unexplained death syndrome (SIUDS) and sudden infant death syndrome (SIDS) victims. Our results indicate that BDNF pathway dysfunctions can derange the normal KFN development so preventing the breathing control in the sudden perinatal death. The data presented here are also relevant to a better understanding of how the BDNF expression in the KFN can be involved in several human respiratory pathologies such as the Rett's and the congenital central hypoventilation syndromes.

Endocrine disrupting compounds (EDCs) include organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), carbamate pesticides, and plasticizers, such as bisphenol A (BPA). They persist in the environment because of their degradation resistance and bioaccumulate in the body tissues of humans and other mammals. Many studies are focused on the possible correlation between in utero exposure to EDCs and adverse health hazards in fetuses and newborns. In the last decade, environmental pollution has been considered a possible trigger for Sudden Infant Death Syndrome (SIDS) and Sudden Intrauterine Unexplained Death Syndrome (SIUDS), the most important death-causing syndromes in fetuses and newborns in developed countries. In this work, a rapid and sensitive analytical method was developed to determine the level of OCPs and OPPs, carbamates, and phenols in human fetal and newborn tissues (liver and brain) and to unveil the possible presence of non-targeted compounds. The target analytes where selected on the basis of their documented presence in the Trentino-Alto Adige region, an intensive agricultural area in northern Italy. A liquid-solid extraction procedure was applied on human and animal tissues and the extracts, after a solid phase extraction (SPE) clean-up procedure, were analyzed by gas chromatography coupled to a quadrupole mass spectrometric detector (GC-qMS). A GC-TOFMS (time-of-flight) instrument, because of its higher full-scan sensitivity, was used for a parallel detection of non-targeted compounds. Method validation included accuracy, precision, detection, and quantification limits (LODs; LOQs), and linearity response using swine liver and lamb brain spiked at different concentrations in the range of 0.4-8000.0 ng/g. The method gave good repeatability and extraction efficiency. Method LOQs ranged from 0.4-4.0 ng/g in the selected matrices. Good linearity was obtained over four orders of magnitude starting from LOQs. Isotopically labeled internal standards were used for quantitative calculations. The method was then successfully applied to the analysis of liver and brain tissues from SIUDS and SIDS victims coming from the above mentioned region.

Background: It is well known that maternal smoking during pregnancy is very harmful to the fetus. Prenatal nicotine absorption, in particular, is associated with alterations in lung development and functions at birth and with respiratory disorders in infancy. Many of the pulmonary disorders are mediated by the interaction of nicotine with the nicotinic receptors (nAChRs), above all with the α7 nAChR subunits that are widely expressed in the developing lung. To determine whether the lung hypoplasia frequently observed in victims of sudden fetal and neonatal death with a smoker mother may result from nicotine interacting with lung nicotinic receptors, we investigated by immunohistochemistry the possible presence of the α7 nAChR subunit overexpression in these pathologies., Methods: In lung histological sections from 45 subjects who died of sudden intrauterine unexplained death syndrome (SIUDS) and 15 subjects who died of sudden infant death syndrome (SIDS), we applied the radial alveolar count (RAC) to evaluate the degree of lung maturation, and the immunohistochemical technique for nAChRs, in particular for the α7 nAChR subunit identification. In the same cases, an in-depth study of the autonomic nervous system was performed to highlight possible developmental alterations of the main vital centers located in the brainstem., Results: We diagnosed a "lung hypoplasia", on the basis of RAC values lower than the normal reference values, in 63% of SIUDS/SIDS cases and 8% of controls. In addition, we observed a significantly higher incidence of strong α7 nAChR immunostaining in lung epithelial cells and lung vessel walls in sudden fetal and infant death cases with a smoker mother than in age-matched controls. Hypoplasia of the raphe, the parafacial, the Kölliker-Fuse, the arcuate and the pre-Bötzinger nuclei was at the same time present in the brainstem of these victims., Conclusions: These findings demonstrate that when crossing the placenta, nicotine can interact with nicotinic receptors of both neuronal and non-neuronal cells, leading to lung and nervous system defective development, respectively. This work stresses the importance of implementing preventable measures to decrease the noxious potential of nicotine in pregnancy.

We present a case of sudden death of a 1-month-old male infant with heart, brainstem and genetic polymorphism involvement. Previously considered quite healthy, the child died suddenly and unexpectedly during sleep. The autopsy protocol included an in-depth anatomopathological examination of both the autonomic nervous system and the cardiac conduction system, and molecular analysis of the serotonin transporter gene promoter region, in which a specific genetic condition seems to be associated with sudden infant death. Histological examination revealed the presence of congenital cardiac alterations (hypertrophic cardiomyopathy and an accessory Mahaim fiber in the cardiac conduction system), severe hypodevelopment of all the raphe nuclei and a heterozygous genotype L/S related to the serotonin transporter gene. The sudden death of this infant was the unavoidable outcome of a complex series of congenital anomalies, each predisposing to SIDS., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3480540091031788.

A 4-month-old female infant considered to be in good health died suddenly and unexpectedly. Post- mortem examination was requested, with clinical diagnosis of sudden infant death syndrome. At autopsy the infant was described in good health. Histo- logical examination of the heart found a cardiac fibroma compressing the atrio-ventricular node and the examination of the cardiac conduction system showed an accessory fiber of Mahaim (nodo-ventricular) and cartilaginous metaplasia of the cardiac fibrous body. Probably the concomitant presence of cardiac conduction system abnormalities and a septal fibroma, compressing the atrio-ventricular node, could have an important role in causing the sudden death.

The present study was aimed at supplementing our previous investigations on the morphological features of the Purkinje cells during the autonomic nervous system development, particularly in victims of sudden perinatal death (Sudden Intrauterine Unexplained Death Syndrome and Sudden Infant Death Syndrome), given their crucial role in determining connectivity patterns in the brain as well as in the control of autonomic functions. We highlighted in these pathologies, and precisely in 21 cases of sudden foetal death and 26 cases of sudden infant death, a high percentage of developmental defects of the Purkinje cells such as heterotopia, hypoplasia, hyperplasia, mitotic and/or shrunken features and abnormal neuronal nuclear antigen expression. These alterations can be interpreted as a result of a defective maturation and/or migration of Purkinje cells in foetal cerebellum, likely consequence of exposure to injuries, particularly to maternal cigarette smoke. Interestingly, we observed in sudden perinatal deaths an association with similar developmental defects of both the dentate and the inferior olivary nuclei. This suggests the existence of a Purkinje-Olivo-Dentate network playing a fundamental role in triggering a sudden death mechanism in perinatal life in the presence of specific risk factors.

This study expands our understanding of the organization of the human caudal pons, providing a morphologic characterization of the medial superior olivary nucleus (MSO), component of the superior olivary complex (SOC) that plays an important role in the processing of acoustic information. We examined victims of sudden unexplained fetal and infant death and controls (n = 75), from 25 gestational weeks to 8 months of postnatal age, by complete autopsy and in-depth autonomic nervous system histological examination, particularly of the MSO nucleus, the focus of this study. Peculiar cytoarchitectural features of the MSO nucleus were found in sudden death cases, such as hypoplasia/agenesis and immature hypercellularity, frequently related to dysgenesis of contiguous structures involved in respiratory rhythm-generating circuit, in particular to hypoplasia of the retrotrapezoid and the facial nuclei. We propose the involvement of this nucleus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities. Besides, we highlight the fundamental role of the maternal smoking in pregnancy as etiological factor in the dysmorphic neuroanatomical development of the MSO nucleus.

Background: Iron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia., Methods: Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments., Results: Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells., Conclusions: We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.

Background: The ependyma, the lining providing a protective barrier and filtration system separating brain parenchyma from cerebrospinal fluid, is still inadequately understood in humans. In this study we aimed to define, by morphological and immunohistochemical methods, the sequence of developmental steps of the human ependyma in the brainstem (ventricular ependyma) and thoracic spinal cord (central canal ependyma) of a large sample of fetal and infant death victims, aged from 17 gestational weeks to 8 postnatal months. Additionally, we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant death and maternal smoking., Results: Our results demonstrate that in early fetal life the human ependyma shows a pseudostratified cytoarchitecture including many tanycytes and ciliated cells together with numerous apoptotic and reactive astrocytes in the subependymal layer. The ependyma is fully differentiated, with a monolayer of uniform cells, after 32 to 34 gestational weeks. We observed a wide spectrum of ependymal pathological changes in sudden death victims, such as desquamation, clusters of ependymal cells in the subventricular zone, radial glial cells, and the unusual presence of neurons within and over the ependymal lining. These alterations were significantly related to maternal smoking in pregnancy., Conclusions: We conclude that in smoking mothers, nicotine and its derivatives easily reach the cerebrospinal fluid in the fetus, immediately causing ependymal damage. Consequently, we suggest that the ependyma should be examined in-depth first in victims of sudden fetal or infant death with mothers who smoke.

This study, besides to delineate the cytoarchitecture and the localization in the brainstem of the human raphé nuclei, aims to evaluate the correlation between neuropathological raphé defects and serotonin transporter gene (5-HTT) promoter region polymorphisms in a cohort of 28 SIDS victims, 12 sudden intrauterine unexplained deaths (SIUD), and 17 controls. Hypoplasia of one or more nuclei of both the rostral and caudal raphé groups was found in 57% of SIDS, in 67% of SIUD, and only in 12% of controls. Furthermore, a significant correlation among 5-HTT Long (L) allele, hypoplasia of the raphé nuclei, and maternal smoking in pregnancy was observed in sudden fetal and infant deaths. The presence of the L allele represents a predisposing factor for sudden fetal and infant death in association with morphologic developmental defects of the raphé nuclei and prenatal smoke exposure. A further consideration of the authors is that SIUD should not be regarded as a separate entity from SIDS, given the potentially shared neuropathological and genetic bases.

The present study was undertaken to evaluate the possible alterations of the triangle of Guillain and Mollaret (G-Mt), a neuronal brainstem/cerebellum network (from the dentate nucleus to red nucleus and inferior olivary nucleus) already known for its involvement in the pathogenesis of the palatal myoclonus, in sudden unexplained perinatal and infant death. In 44 cases of perinatal and infant death victims, aged from 26 gestational weeks to 10 months of life, we investigated, besides the histological morphology of the three nuclei, the c-fos and apoptotic expression, as well as the possible effects elicited by maternal cigarette smoking.A significant increase of lesions (hypoplasia and/or increased c-fos and apoptotic neuronal immunopositivity) of the three nuclei was found in unexplained death victims, compared with age-matched controls. These alterations were related to maternal cigarette smoking habit.We postulated that the G-Mt is an important network involved in the pathogenesis of a wide spectrum of pathological manifestations and that maternal smoking during pregnancy can exert an adverse influence on this complex, even leading to sudden death in vulnerable periods of perinatal or infant development.

Background: Carotid barochemoreceptor pathological lesions have been studied in animals, but few human necropsies have been performed. Therefore, data rely on case patients following surgery, radiotherapy and carotid endarterectomy. Almost no data are available regarding whether the effect of aging prevails over pathological conditions, despite the classic description that glomic fibrosis increases with age., Objective: To morphometrically characterize the alterations of the carotid barochemoreceptors and their supplying arteries., Methods: Patients (n=23) who had suffered and died from stroke, with and without complicated internal carotid atheromatosis, were divided by age (group 1: older than 80 years; group 2: 65 to 80 years; and group 3: younger than 65 years). Carotid segments were obtained at autopsy. The specimens were stained for light microscopy and immunohistochemistry., Results: Carotid glomus presented from moderate-to-severe atrophy and fibrosis. A focal decrease in vascularization (CD34-positive) of the glomus (greater than 50%) was observed in areas of atrophy and fibrosis. Damaged nerve endings (S100 protein-positive) were observed at the media of the carotid sinus. Morphometric data showed no differences between groups for glomus area, number of type 1 and 2 cells, and the wall to lumen arteriole ratio. No statistical differences were demonstrated in the pathological findings of the carotid glomus when comparing complicated with noncomplicated plaques or age groups., Conclusion: Severe carotid chemoreceptor damage exists in patients who have died from stroke and suffered from carotid atheromatosis. These findings were independent from aging and plaque type. However, damage was correlated with a marked narrowing of the supplying arterioles as a consequence of hemodynamic and/or metabolic alterations (dyslipidemia, diabetes).

Genotypes and allelic frequencies of TPH2, 5-HTTLPR, the 5-HTT (SLC6A4) intron 2 variable-number tandem repeat (VNTR) region, and the MAOA VNTR region were determined in brain-stem samples of 20 "genuine" SIDS cases and compared with results obtained from 150 healthy controls. The SNP G1463A responsible for 80% functionality loss of TPH2 (tryptophan hydroxylase 2) was not detected, neither in SIDS infants nor in the controls. In contrast, a strict relation was found between the 5-HTTLPR genotype and its allelic frequencies with SIDS cases. The L/L genotype and the long allele (L) of the promoter region of the serotonin transporter were significantly associated (likelihood ratio (LR) test, p<0.001) with the syndrome (L/L, 60% SIDS vs 14% controls; L, 80% SIDS vs 42.6% controls). Polymorphisms of the intron 2 VNTR of the same gene showed a trend for significant differences between genotypes 10/10 and 12/12 (LR test, p=0.068), with the L-12 haplotype being almost twofold in SIDS (44.5%) with respect to controls (23.4%). Differences were even higher considering the genotype combination L/L-12/12 (20% SIDS vs 2.6%), and variations among categories were statistically highly significant (p<0.001). Although additional differences were observed in the frequency of the MAOA (monoamine oxidase A) VNTR genotype 3R/3R between SIDS and controls (respectively 15% vs 26%), the results were not supported by statistical significance. Molecular polymorphisms are discussed considering their functional role in regulating serotonin synthesis (TPH2), neuronal reuptake (5-HTTLPR and 5-HTT intron 2), and catabolism (MAOA) in the nervous system of Italian SIDS infants. Comparisons are made with previous data obtained in different ethnic groups.

Objective: Because the fetal origin of coronary artery lesions is controversial, early atherosclerotic coronary artery lesions in late fetal stillborns and infants, as well as the possible atherogenic role of maternal cigarette smoking, were studied., Methods: Twenty-two fetal death and 36 sudden infant death syndrome victims were examined by autopsy. In 28 of 58 cases, the mothers were smokers. Serially cut sections of coronary arteries were stained for light microscopy and immunotypified for CD68, CD34, alpha-smooth muscle actin, proliferating cell nuclear antigen, c-fos and apoptosis., Results: Multifocal coronary lesions were detected in 10 of 12 fetuses and in 15 of 16 infants whose mothers smoked. Arterial lesions in infants with nonsmoking mothers were observed in only five cases (two of 10 fetuses and three of 20 infants) (P<0.001). Alterations ranged from focal areas with mild myointimal thickening in prenatal life to early soft plaques in infants. Smooth muscle cells infiltrated into the subendothelium. These early lesions demonstrated c-fos gene activation in the smooth muscle cells of the media, and in some of these, positivity for apoptosis was observed, suggesting that c-fos overexpression may promote proliferation, as evidenced by proliferating cell nuclear antigen-positive cells., Conclusions: Early intimal alterations of the coronary arteries are detectable in the prenatal and infancy period, and may be significantly associated with maternal smoking.

Objective: To evaluate the involvement of alterations of the central autonomic nervous system, particularly of the brainstem and cerebellum, in a wide set of victims of sudden and unexplained perinatal and infant death., Material and Methods: The study population consisted of 63 stillbirths, 28 neonatal deaths and 140 suspected SIDS. The victims were subjected to in-depth anatomopathological examination following appropriate guidelines. The protocol included, in particular, the histological evaluation on serial sections of the cardiorespiratory autonomic nervous system., Results: A diagnosis of "unexplained death" was established for 217 of the 231 victims (59 stillbirths, 28 newborns and 130 SIDS). In a very high percentage of these deaths (84%) we observed one or more anomalies of the nuclei and/or structures of the brainstem and cerebellum related to vital functions., Conclusion: Unexpected perinatal loss should not be regarded as a separate entity from SIDS, given the common neuropathological substrates.

In this study, we wanted to evaluate whether the engrailed EN-2 gene, a homeobox gene with an essential role in the development of the rhombic lip derivatives in different species, is (1) expressed also in man in the differentiation process of the medullary arcuate nucleus (ArcN) and (2) involved in sudden unexplained perinatal and infant death, frequently related to developmental defects of the ArcN. We evaluated by means of the monoclonal antibody 4D9, exclusively recognizing engrailed-2 protein, the expression of the EN-2 gene in the ArcN on histological sections of the brainstems of 30 subjects aged from 17 gestational weeks to 10 postnatal months, who had died of known (17 cases) and unknown causes (13 cases). We observed in the greater number of the cases that the expression of the EN-2 gene is very high in the ArcN neurons from the 17th to the 22nd gestational week, then decreases up to the first days after birth and later disappears. Moreover, in eight of the 13 sudden deaths (61%), a hypoplasia of the ArcN was present. In almost all of these cases, EN-2 expression was negative. In conclusion, we support the role of the EN-2 gene in the normal neuronal development and in the anatomic organization of the human ArcN as well as the possible existence of EN-2 mutations related to hypoplasia of this nucleus.

Cot death is the commonest form of death among babies in the first year of life. The authors report the unusual case of a 2-month-old female infant dying suddenly and unexpectedly in whom a postmortem histological examination demonstrated a cardiac multifocal Purkinje cell tumor. Necroscopy studies of sudden infant death should always include an accurate histological examination of the cardiac conduction system and brainstem using serial sections.

Objective: Previously we failed to demonstrate a correlation between plaque type and symptoms in 165 carotid endarterectomy specimens. The purpose of this study was to analyze the relation between the anatomy of the carotid plaques and the presence of symptoms in 281 carotid endarterectomy specimens., Methods: The patients were 213 men (mean age, 68 years) and 68 women (mean age, 68.7 years), with symptomatic disease (n = 133) or asymptomatic disease (n = 148). Specimens were processed for histologic analysis and immunohistochemistry., Results: Plaques were categorized as complicated or noncomplicated, and ruptured or nonruptured. Risk factors could not be correlated with any pathologic or immunohistochemical findings or between plaque type and clinical symptoms., Conclusions: Almost 70% of plaque specimens demonstrated thrombus, intraplaque hemorrhage, or both. Thrombosis was observed in one fourth of specimens, and intraplaque hemorrhage in almost two thirds of specimens. Sixty four percent of plaques demonstrated neovascularization. It was not possible to demonstrate that complicated plaques (plaque rupture, thrombosis, intraplaque hemorrhage) are associated with symptoms, and it appears that such plaques may occur at any time, irrespective of symptoms.