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We investigated the immunohistochemical expression of substance P (SP) in the brainstems of 56 subjects aged from 17 gestational weeks to 10 post natal months, who died of unknown (sudden unexplained fetal deaths and SIDS) and known causes (controls). The goals of this study were: (i) to obtain basic information about the expression of SP during the first phases of human nervous system development; (ii) to evaluate whether there are alterations of this neuromodulator in victims of sudden death; and (iii) to verify any correlation with maternal cigarette smoking. Immunohistochemistry demonstrated SP immunoreactivity in the caudal trigeminal nucleus area, with a progressive increase in the density of SP-positive fibers of the corresponding tract during normal development from fetal life to the first post natal months. Delineation of the structure of the human trigeminal nucleus, little investigated so far, provided essential data on its morphologic and functional development. Instead, a negative or low SP expression was detectable in the fibers of this tract in a wide subset of SIDS victims and, conversely, a high SP-expression in a wide subset of sudden fetal deaths. We postulate, on the basis of these results, that SP has a functional importance in the early phases of central nervous system development and in the regulation of autonomic functions. In addition, the observation of a significant correlation between sudden unexplained death, altered SP staining and maternal smoking leads us to suggest a close relation between the absorption of cigarette smoke in utero and a decreased functional activity of the trigeminal nucleus, that can trigger sudden death of the fetus during pregnancy or of the infant in the first months of life.

In order to clarify the variable behaviour of transitional cell bladder carcinomas (TCBC) with same clinico-pathologic pattern, we investigated the prognostic significance of various biomarkers (PCNA, DNA, apoptosis, karyotype).We studied 177 superficial TCBC (stage T1) undergoing transurethral resection (TUR). Analysis of biological indicators was performed on serial paraffin sections: DNA by static cytometry, karyotype by fluorescence in situ hybridisation (FISH), PCNA and apoptosis by immunohistochemistry.The most salient results are represented by prevalence of diploidy (56%), a mean PCNA labeling index (PCNA-LI) of 8.2%, nonrandom trisomies and tetrasomies of chromosome 7, and a high presence of apoptosis (in 72% of cases). These data were not related to histological grading. Multivariate analysis showed that only PCNA-LI is a an independent prognostic marker for patient survival (p = 0.01). Besides, we observed a worse prognosis in the presence of both very high PCNA indices and low or absent apoptosis.The results of this study suggest that tumor prognostic potential in TCBC should be evaluated on the basis of the association between PCNA cell kinetics and cell apoptosis information.

Atherosclerosis is the most frequent cause of death in industrialized countries. Lesions are characterized by lipid deposits, focal thickening of the arterial wall with proliferation of smooth muscle cells (SMC), mononuclear infiltrates and neoformed vessels. In this paper, we studied the proliferative characteristics and cytogenetic alterations of SMC. These cells, expressing specific muscular actin, were diploid with an increased proliferative index for PCNA. A high percentage of SMC showed intense expression of p53. There were signs of chromosomal instability, being the most frequent findings chromosome 7 trisomy and chromosome 11 monosomy. Additionally, the gene for FGF-3 showed a marked amplification. These findings strongly suggest that SMC proliferation is active, and is related to the accumulation or mutation of the p53 oncoprotein. It also presents specific chromosomal alterations in close relation with growth factors. According to these findings SMC hyperplasia in the atherosclerosis plaque may be considered as a cellular clonal expansion.

Our knowledge about the etiopathogenesis of nasal polyps (Nps) is still limited. In this study, in order to define the biological features of these neoformations, we investigated with immunohistochemistry the p53 over-expression and the proliferating cell nuclear antigen (PCNA) in 32 cases of Nps and in normal mucosa of 11 control cases. The evaluation of PCNA showed a wide range of indices (0.5-18.2%) with a mean value (6.8%) significantly higher than in normal mucosa (2.9%). Over-expression of the p53 oncoprotein, observed in 50% of Nps, was statistically related to a high PCNA-index (6.8%). Our results suggest that Nps can behave, in a high percentage of cases, like tumours.

We report the case of a 71 day-old female infant victim of SIDS. Histological observations were focused on the cardiac conduction system. We observed accessory pathways of Mahaim type with areas of resorptive degeneration. These findings, associated with particular conditions and/or neurovegetative stimuli, could cause potentially malignant arrhythmias.

This article reports a case of sudden infant death syndrome in a 1-month-old male. Some important abnormalities of the cardiac conduction system were found, consisting of persistent fetal dispersion of the atrioventricular node and His bundle, accessory atrioventricular pathways of Mahaim type and resorptive degeneration. These changes could be considered as a morphological substrate for cardiac arrhythmias.

The different clinical evolution of gastric adenocarcinomas with the same clinico-pathologic characteristics prompted the authors to investigate the prognostic significance of different biological markers.One hundred twenty-six preoperative cancer gastric biopsies, selected according the stage evaluated after following gastrectomy, were examined for DNA content by means the static cytometry, proliferating cell nuclear antigen (PCNA), p53 mutation, apoptosis by immunohistochemistry and karyotype using fluorescence in situ hybridization (FISH) techniques.The gastric cancers, ail belonging at stage III, were adenocarcinomas histologically typed as: 26 well differentiated (G1), 45 moderately differentiated (G2), 43 poorly differentiated (G3) and 12 of undifferentiated type with signet-ring cells. The tumours showed a prevalence of diploidy (68%), a mean PCNA-LI of 4.8%, trisomy of chromosome 7 in 40% of the cases, low presence of apoptosis (30%) and p53 mutation (17%). Only apoptosis was significantly correlated to histological diagnosis (p = 0.009). A multivariate analysis showed that the DNA content and PCNA-LI were the only independent prognostic markers for survival (p = 0.005 and p = 0.0002 respectively).The evaluation of these two biological variables, especially of the PCNA index, on gastric cancer biopsies may be useful in predicting the aggressiveness of each tumor and in identifying patients in need of additional perioperative therapies.

Two cell-kinetic parameters, the thymidine labeling index (T-LI) and the mitotic index (MI) were determined for a prospective series of 74 primary colorectal cancers. Dukes' stages were used to define the extent of the tumor: 10 tumors were classified as Dukes' A, 36 as Dukes' B, and 22 as Dukes' C. Of these tumors, 14 were well-differentiated, 44 moderately differentiated, and 15 poorly differentiated adenocarcinomas. The H3dT-LI values obtained varied widely, from 2.5 to 38.9% (median value: 16.8%). The MI shows a range of from 0 to 13.2% with a median value of 3.2%. The T-LI values were independent of the sex and age of the patients and of the histological grading and Dukes' stage. Conversely, the MI was related to histological grading. This study indicates that the T-LI, whose application has reached the gold standard, still represents an independent parameter and the most sensible, objective, and specific complementary method for the analysis of the S phase.

The aim of this study was to apply an easy method for the quantitative evaluation of changes in myocardial fibrocell size (area, diameter, circular shape factor, nuclear area, DNA content), and in the fibrous-interstitial area in hypertrophic cardiomyopathy (HCM) by mean of a computerized image analysis. A Vidas image analyser was employed for the morphometric study. The following parameters were assessed: area, maximum and minimum diameters, circular shape factor of myocytes; percentage of fibrosis; DNA content (integrated optical density) nuclear area of myocytes. The morphometric results in HCM compared to the ones in normal hearts, indicate an increase in the myocyte area and the transverse diameters, especially in the septum and left ventricle, altogether illustrating the hypertrophic condition of the myocytes, and increased fibrotic area was found in the left ventricular wall and septum (22.6 +/- 2.1% and 15.9 +/- 2.9% respectively). Densitometric analysis showed a significant increase in all test samples then compared with controls. The increase in the two nuclear parameters (area and DNA) also suggests hyperplasia. It is concluded that the morphometric determination of the morphologic abnormalities occurring in HCM by a rapid and less laborious approach, is an extremely useful method to describe the characteristics of this pathologic condition.

Kinetic cellular methods were used in 53 cases of various sizes of astrocytomas and glioblastomas to obtain reliable prognostic information. Kinetic analysis revealed a wide variation of proliferative activity, with a gradual increase of the mean value from the most differentiated astrocytomas to glioblastomas. DNA content was significantly correlated with the degree of histological differentiation. Chromosomic patterns, which were detected in a few cases, were generally aspecific. The sole recurrent alteration in the karyotype was a small metacentric marker. The comparison of results obtained with the follow-up of patients showed that the labeling index offers a more accurate estimate of the proliferative potential of individual tumours, and thus of the probability of survival, than histological diagnosis and the evaluation of other biological parameters such as ploidy and karyotype.

In recent years the abnormal DNA content of cancer cells and the ploidy model have played an important role in biological and medical research aimed at achieving a more accurate diagnostic and prognostic assessment. Static cytometry was studied in histological sections using an image analyser which enabled the DNA content of cancer cells coloured using Feulgen's method, the elective method for nucleic acids, to be evaluated. A high percentage of aneuploidy in human gastric tumours was found to be correlated with a low degree of histological differentiation (G3), with tumoral invasion of the lowest tissue strata and neighbouring lymph nodes, and with a negative prognosis. The practical clinical application of DNA evaluation therefore allows cases which evolve more rapidly since they possess a greater tumoral aggressiveness to be identified (aneuploid tumours).

A 4-month-old infant dying suddenly is diagnosed as sudden infant death syndrome (SIDS). Important modifications of the cardiac conduction system were found, consisting of conspicuous accessory atrioventricular (AV) pathways of Mahaim and Kent type, which can be regarded as arrhythmogenic in nature.

Four cases of myocarditis from toxoplasma gondii were observed at autopsy among 18 consecutive cases of acquired immunodeficiency syndrome (AIDS). All cases showed spotty inflammatory myocardial infiltration, consisting mainly of T lymphocytes and, to a lesser extent, of B lymphocytes, histiocytes, mastocytes and eosinophilic granulocytes, with presence of toxoplasma gondii in the cytoplasm of a few myocardial cells. The incidence of toxoplasmic myocarditis in heart involvement in AIDS was 22% in our cases, manifold higher than in preceding reports from the literature. This suggests that cardiac toxoplasmosis is far from rare in patients with AIDS.

The potential proliferative activity, expressed as labelling index, has been studied in 24 cases of bladder transitional cell carcinomas. The data showed a wide range of values, varying between 0.4 and 36%. The average proliferative activity was 3.2%. An analysis of the connection between the labelling index and the histological grading has also brought out the existence of a gradient of proliferative activity; average values of 1.6-2.53% and 3.49%, respectively, were found for grades I-II and grade III.

One question which still remains unanswered concerning expansion of human skin is whether expansion simply stretches the skin or whether it induces a real neo-production of epithelium. To evaluate the proliferative activity of the human skin before and after expansion, we performed an autoradiographic study and a densitometric analysis on sections of skin biopsy from 11 patients. The results of the cellular kinetic study showed that expansion induces an increase in the epidermal proliferative activity. On the contrary, the densitometric analysis did not show a parallel increase of the proliferating cells after expansion. This discrepancy is discussed in terms of the modified morphology of the tissue. The proliferative activity of skin in the back region increases more than in that of the neck. Preliminary results have shown that the proliferative activity increases with time of expansion in days. The presence of a low percentage of cells with altered DNA content indicates, at least over the short term, the absence of dysplastic processes in expanded skins.

The aim of this study was to determine whether cell proliferation and/or apoptotic cell death occur in hyperacute and acute infarction. Proliferating cell nuclear antigen (PCNA) and apoptosis were investigated in ten autoptic hearts within a few hours of infarction and in three normal hearts as controls. The PCNA Labeling Index (PCNA-LI) ranged from 0 to 3.1 in hyperacute infarction (mean 1.38), from 0.3 to 4 in acute infarction (mean 2.04) and from 0 to 1.2 in controls (mean 0.7). Although the results were not statistically significant, PCNA-LI was higher in acute than in hyperacute myocardial infarctions; and it was higher in hyperacute infarctions than in controls. Regarding apoptosis, the Apoptotic Index (AI) in hyperacute infarctions ranged from 0.7 to 3 (mean 1.78), in acute infarctions from 0.9 to 5 (mean 3.24) and in controls from 0 to 0.4 (mean 0.1). The AI was significantly higher in hyperacute and acute infarctions than in controls (p0.05).

We studied 18 patients who underwent skin expansion. In 3 patients the prostheses had been inserted in anatomical areas previously expanded: in 3 other patients scarring tissue had been involved in the expansion. The DNA content of sections of epidermis, before and after the implantation of expanders, were analysed using an image analyzer (IBAS 2000). The preliminary data demonstrate that, at the end of the expansion, epidermis enters a phase of quiescency and is not affected by dysplastic processes.

The prognostic value of proliferative activity was determined in 48 cases of squamous cell carcinoma of the larynx. Tumor samples were obtained during surgery: DNA content was determined by static cytometry with an image analysis program, and cell kinetics were analyzed by the in vitro thymidine labeling index (T-LI). The DNA content analysis visualized a diploid cellular population in 32 cases and an aneuploid cellular population in 16 cases. The DNA content was not significantly related to the sex and the age of the patients or the TN stage of the tumors, but to histological grade (p = 0.03). Similarly significant correlation was found between T-LI and age of the patients, indeed the median value was higher in patients older than 59 (p = 0.024). T-LI was not related to the sex of the patients, or to the histological grade or the TN stage of the tumors. In multivariate analysis, using the Cox model, T-LI was the most important prognostic parameter (p = 0.015), superior to DNA content (p = 0.021) and to TN stage (p = 0.047; p = 0.043). From the data obtained in this study it can be concluded that evaluation of DNA content and thymidine labeling index in squamous cell carcinoma of the larynx may be new independent parameters of prognosis and may contribute to optimal and individualized therapy.

To investigate cell death via apoptosis in non-small cell lung carcinoma (NSCLC) and its correlation with proliferative indices and follow-up.In 38 cases of NSCLC (21 squamous cell carcinomas and 17 adenocarcinomas) we analyzed apoptosis by nuclear morphology and in situ DNA fragmentation end labeling and the cell kinetics by an autoradiographic method with tritiated thymidine and by immunohistochemistry with anti-proliferating cell nuclear antigen (anti-PCNA) antibodies. We also evaluated mitotic frequency. Apoptotic index (AI) was correlated with the thymidine and PCNA labeling indices (T-LI and PCNA-LI, respectively) and with the mitotic index.The percentage of proliferating cells (T-LI range, 0.1-20.1%; PCNA-LI range, 0-14.7%) was generally considerably higher than that of apoptotic cells (range, 0-8%) and of mitotic cells (range, 0.1-1%). Survival at six years was significantly higher in patients with high levels of apoptosis and low T-LI values.AI and T-LI are independent and very useful prognostic factors in NSCLC. A high percentage of proliferating cells in terms of T-LI correlates with poor prognosis, whereas a high AI indicates a favorable outcome.

Aim of this study is to determine the expression of apoptosis and Proliferating Cell Nuclear Antigen (PCNA) in the cardiac conduction system in crib death and explained death (ED) cases. Postnatal morphogenesis of the conducting tissue is an important part of its normal development. In the atrio-ventricular node (AVN) and His bundle (HB) it consists of degeneration, cell death and replacing in an orderly programmed way. However, its nature and its relation to crib death is not yet fully explained. Apoptosis and PCNA were investigated in 8 heart conduction systems of infants dying of crib death and in 3 conduction systems of infants dying of ED as controls. The cardiac conduction system was removed in two blocks: the first included the sino-atrial node (SAN) and the crista terminalis, the second contained the atrio-ventricular node (AVN), His bundle (HB), bifurcation, and bundle branches. In the conduction systems as well as in the common myocardium the PCNA Labeling Index (PCNA-LI) was found to be negative in all cases. The apoptotic indices (AI) in SIDS and in ED were found to have no statistically significant differences (p0.05). The SAN, in both groups, showed an AI similar to the one detected in common myocardium. In almost all cases, TUNEL labeling was detected in peripheral region of the AVN, close to the atrial myocardium. The AI was higher in the AVN, HB and the initial tract of bundle branches than in the common myocardium (p0.05; Student's t test).

Cell kinetics in transitional cancer of the bladder was studied in 35 patients by using the in vitro 3H-thymidine labeling index. The proliferative activity was remarkably lower than that observed for other human histotypes. Analysis of the relation between cell kinetics and histologic grading showed a value for grade III tumors two-fold that of grade I and grade II tumors. Cytogenetic analysis was possible in 15 cases, and different chromosome numbers from 40 to 120 and the presence of various structural aberrations were observed. When cytogenetic features were analyzed in relation to cell kinetics, higher proliferative activities were always associated with a loss of chromosome 13 and, except for one case, with a loss of chromosome 22.

The thymidine labeling index (T-LI) evaluated with the autoradiographic technique on fresh specimens is the most objective and specific marker of tumor proliferative cell fraction. In this study we investigated T-LI and PCNA expression in 68 cases of transitional cell bladder carcinomas in order to evaluate whether PCNA immunostaining in paraffin sections could be a valid alternative to autoradiographic methods for cell kinetic detection. Immunohistochemistry was applied after different fixatives: usual formalin, neutral 4% buffered formalin and Bouin. The results revealed that only in buffered formalin-fixed tumor specimens, considering the most darkly stained cells, the PCNA-LI in all cases overlapped with T-LI. Higher values than those observed with autoradiography were detected in PCNA values obtained after usual formalin fixation whereas no or faint PCNA staining was seen in material fixed in Bouin. Thus, only cells with strong PCNA staining can be considered as significant in evaluating the proliferative activity in transitional cell bladder carcinoma. By using immunohistochemical methods it should thus be possible to overcome many of the inherent difficulties of autoradiography and likewise to obtain accurate and significant information on the biological aggressiveness of bladder tumors and consequently of patient prognosis.

To obtain basic information about the expression of somatostatin in the human central nervous system and, in particular, to evaluate its possible involvement in unexplained perinatal and in sudden infant death syndrome.Sixty-seven brainstems from subjects aged from 30 gestational weeks to 12 postnatal months, dying of both known and unknown causes, were selected for this study. The unexplained deaths included 17 sudden intrauterine deaths, 5 sudden neonatal deaths and 28 sudden infant deaths.All brainstems were fixed in 10% phosphate-buffered formalin, processed and embedded in paraffin, according to our protocol available on the web site: http://users.unimi.it/-pathol/sids/riscontro_diagnostico_e.html. The distribution of the somatostatin in the brainstem was studied by immunohistochemistry on serial sections.We observed an intense somatostatin positivity in many brainstem nuclei prevalently involved in the respiratory activity (parabrachial/Kölliker-Fuse complex, locus coeruleus, hypoglossus nucleus, dorsal vagus motor nucleus, tractus solitarii nucleus, ambiguus nucleus, reticular formation) in stillbirths. In 10 fetuses with unexplained death the neurons of the hypoglossus nucleus were somatostatin-negative. In the postnatal deaths, we observed immunopositivity in the ventrolateral and ventral subnuclei of the tractus solitarii nucleus. Besides, in 15 sudden infant death victims and in 1 control case, somatostatin-positive neurons were also present in the hypoglossus nucleus. In 10 of these 15 cases, a high apoptotic index was also reported.We suggest that abnormalities in the distribution of SS in the hypoglossus nucleus before and after birth may contribute to the induction of both fatal breathing in prenatal life and abnormal ventilatory control after birth leading to irreversible apnea.

In this study, the Authors search for morphologic alterations in the aorticopulmonary paraganglia (APP) of sudden infant death syndrome (SIDS) victims when compared with age-matched controls. Morphometric studies on serial sections of the APP were performed with an image analyzer in combination with a standard microscope attached to a video camera. APP hyperplasia, characterized by an increase in some parameters such as number, mean lobule diameter and total glomic tissue volume when compared with age-matched controls, was observed in 23.8% of SIDS victims. Similar alterations have been reported in peripheral chemoreceptors of animals and human beings who are chronically hypoxemic. In SIDS, it could reflect an abnormal chemoreceptor function, contributing to an altered respiration control.

We report a noteworthy case of a 7-month-old infant who suddenly and unexpectedly died during her sleep. After a complete postmortem examination, review of the clinical history, and detailed death scene investigation, the death remained unexplained, leading to a diagnosis of sudden infant death syndrome. However, an extensive review of the brainstem neuropathology revealed a severe alteration in the area postrema (a highly vascular structure lying at the base of the fourth ventricle outside of the blood-brain barrier). The alteration was likely due to massive and repeated to a common household insecticide in the last few weeks of life. These results provide an explanation for this sudden infant death, allowing a differential diagnosis from sudden infant death syndrome.

article This study indicates the impact of nicotine and pesticides (organochlorine and organophosphate insecticides used in agriculture) on neuronal α7-nicotinic acetylcholine receptor expression in brainstem regions receiving cholinergic projections in human perinatal life. An in-depth anatomopathological examination of the autonomic nervous system and immunohistochemistry to analyze the α7-nicotinic acetylcholine receptor expression in the brainstem from 44 fetuses and newborns were performed. In addition, the presence of selected agricultural pesticides in cerebral cortex samples of the victims was determined by specific analytical procedures. Hypodevelopment of brainstem structures checking the vital functions, frequently associated with α7-nicotinic acetylcholine receptor immunopositivity and smoke absorption in pregnancy, was observed in high percentages of victims of sudden unexpected perinatal death. In nearly 30% of cases however the mothers never smoked, but lived in rural areas. The search for pesticides highlighted in many of these cases traces of both organochlorine and organophosphate pesticides. We detain that exposition to pesticides in pregnancy produces homologous actions to those of nicotine on neuronal α7-nicotinic acetylcholine receptor, allowing to developmental alterations of brainstem vital centers in victims of sudden unexplained death.

Physiopathology of barochemoreception is hindered by the scarce information on its morphology in disease. The baroreflex is of major importance for the maintenance of arterial pressure during orthostatic stress. The purpose of this paper was to characterize the morphological alterations of carotid glomus in old patients who died from stroke and suffering obstructive carotid atheromatosis.Bilateral carotid segments were obtained at autopsy from 17 patients (51-89 years old). Specimens were stained with hematoxylin and eosin; Azan trichrome, Grimelius silver stain for catecholamine detection, and were immunophenotyped for CD34 and S-100. Similar segments of both carotid arteries of six patients (62-77 years old) who died by accidents were used as controls.The carotid glomus of patients who died from stroke presented atrophy and fibrosis (2.59+/-0.5 vs. 1.17+/-0.39 in the control group; p0.0001). There was a loss of chief cells and of the argyrophilic staining granules. A focal diminution of glomus vascularization was observed in the areas of atrophy and fibrosis (2.73+/-0.45 vs. 1.5+/-0.52 in the control group; p0.0001). The arterioles to glomus showed severe fibrointimal proliferation, disruption of internal elastic lamina and luminal narrowing, and luminal thrombi.A severe carotid glomic damage does exist in old patients who died from stroke and suffering from carotid atheromatosis, independent from aging, of note, a "culprit" marked narrowing of the corresponding arterioles was observed.

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.

We examined a large number of sudden infant death syndrome victims in order to point out a possible causal relationship between a previous hexavalent vaccination and the sudden infant death. We selected 110 cases submitted to in-depth histological examination of the autonomic nervous system and provided with detailed clinical and environmental information. In 13 cases (11.8%) the death occurred in temporal association with administration of the hexavalent vaccine (from 1 to 7 days). In none of these victims congenital developmental alterations of the main nervous structures regulating the vital functions were observed. Only the hypoplasia of the arcuate nucleus was present in 5 cases. In one case in particular an acquired hyperacute encephalitis of the tractus solitarii nucleus was diagnosed in the brainstem. This study does not prove a causal relationship between the hexavalent vaccination and SIDS. However, we hypothesize that vaccine components could have a direct role in sparking off a lethal outcome in vulnerable babies. In conclusion, we sustain the need that deaths occurring in a short space of time after hexavalent vaccination are appropriately investigated and submitted to a post-mortem examination particularly of the autonomic nervous system by an expert pathologist to objectively evaluate the possible causative role of the vaccine in SIDS. We examined a large number of sudden infant death syndrome victims in order to point out a possible causal relationship between a previous hexavalent vaccination and the sudden infant death. We selected 110 cases submitted to in-depth histological examination of the autonomic nervous system and provided with detailed clinical and environmental information. In 13 cases (11.8%) the death occurred in temporal association with administration of the hexavalent vaccine (from 1 to 7 days). In none of these victims congenital developmental alterations of the main nervous structures regulating the vital functions were observed. Only the hypoplasia of the arcuate nucleus was present in 5 cases. In one case in particular an acquired hyperacute encephalitis of the tractus solitarii nucleus was diagnosed in the brainstem. This study does not prove a causal relationship between the hexavalent vaccination and SIDS. However, we hypothesize that vaccine components could have a direct role in sparking off a lethal outcome in vulnerable babies. In conclusion, we sustain the need that deaths occurring in a short space of time after hexavalent vaccination are appropriately investigated and submitted to a post-mortem examination particularly of the autonomic nervous system by an expert pathologist to objectively evaluate the possible causative role of the vaccine in SIDS. © 2014 Bentham Science Publishers.