Quantitative Backscattered Electron Imaging of Bone Using a Thermionic or a Field Emission Electron Source.

Quantitative backscattered electron imaging is an established method to map mineral content distributions in bone and to determine the bone mineralization density distribution (BMDD). The method we applied was initially validated for a scanning electron microscope (SEM) equipped with a tungsten hairpin cathode (thermionic electron emission) under strongly defined settings of SEM parameters. For several reasons, it would be interesting to migrate the technique to a SEM with a field emission electron source (FE-SEM), which, however, would require to work with different SEM parameter settings as have been validated for DSM 962. The FE-SEM has a much better spatial resolution based on an electron source size in the order of several 100 nanometers, corresponding to an about [Formula: see text] to [Formula: see text] times smaller source area compared to thermionic sources. In the present work, we compare BMDD between these two types of instruments in order to further validate the methodology. We show that a transition to higher pixel resolution (1.76, 0.88, and 0.57 µm) results in shifts of the BMDD peak and BMDD width to higher values. Further the inter-device reproducibility of the mean calcium content shows a difference of up to 1 wt% Ca, while the technical variance of each device can be reduced to [Formula: see text] wt% Ca. Bearing in mind that shifts in calcium levels due to diseases, e.g., high turnover osteoporosis, are often in the range of 1 wt% Ca, both the bone samples of the patients as well as the control samples have to be measured on the same SEM device. Therefore, we also constructed new reference BMDD curves for adults to be used for FE-SEM data comparison.

Coalignment of osteocyte canaliculi and collagen fibers in human osteonal bone.

During bone formation osteocytes get connected with each other via a dense network of canaliculi within the mineralized bone matrix. Important functions attributed to the osteocyte network include the control of bone remodeling and a contribution to mineral homeostasis. To detect structural clues of the formation and functionality of the network, this study analyzes the structure and orientation of the osteocyte lacuno-canalicular network (OLCN), specifically in relation to the concentric bone lamellae within human osteons. The network structure within 49 osteons from four samples of cortical bone from the femoral midshaft of middle-aged healthy women was determined by a combination of rhodamine staining and confocal laser scanning microscopy followed by computational image analysis. A quantitative evaluation showed that 64±1% of the canalicular length has an angle smaller than 30° to the direction towards the osteon center, while the lateral network - defined by an orientation angle larger than 60° - comprises 16±1%. With the same spatial periodicity as the bone lamellae, both radial and lateral network show variations in the network density and order. However, only the preferred orientation of the lateral network twists when crossing a lamella. This twist agrees with the preferred orientation of the fibrous collagen matrix. The chirality of the twist was found to be individual-specific. The coalignment between network and matrix extends to the orientation of the elongated osteocyte lacunae. The intimate link between OLCN and collagen matrix implies an interplay between osteocyte processes and the arrangement of the surrounding collagen fibers during osteoid formation.

Mapping dynamical mechanical properties of osteonal bone by scanning acoustic microscopy in time-of-flight mode.

An important determinant of mechanical properties of bone is Young's modulus and its variation in individual osteons of cortical bone tissue. Its mechanical behavior also depends on deformation rate owing to its visco- or poroelastic properties. We developed a method to measure dynamical mechanical properties of bulk bone tissue at osteonal level based on scanning acoustic microscopy (SAM) using time-of-flight (TOF) measurements in combination with quantitative backscattered electron imaging (qBEI). SAM-TOF yields local sound velocities and qBEI corresponding material densities together providing elastic properties. Osteons (n=55) were measured in three human femoral diaphyseal ground bone sections (∼ 30 µm in thickness). In addition, subchondral bone and mineralized articular cartilage were investigated. The mean mineral contents, the mean sound velocities, and the mean elastic modulus of the osteons ranged from 20 to 26 wt%, from 3,819 to 5,260 m/s, and from 21 to 44 GPa, respectively. There was a strong positive correlation between material density and sound velocity (Pearson's r=0.701; p<0.0001) of the osteons. Sound velocities between cartilage and bone was similar, though material density was higher in cartilage (+4.46%, p<0.0001). These results demonstrate the power of SAM-TOF to estimate dynamic mechanical properties of the bone materials at the osteonal level.

Subcanalicular Nanochannel Volume Is Inversely Correlated With Calcium Content in Human Cortical Bone.

The spatial distribution of mineralization density is an important signature of bone growth and remodeling processes, and its alterations are often related to disease. The extracellular matrix of some vertebrate mineralized tissues is known to be perfused by a lacunocanalicular network (LCN), a fluid-filled unmineralized structure that harbors osteocytes and their fine processes and transports extracellular fluid and its constituents. The current report provides evidence for structural and compositional heterogeneity at an even smaller, subcanalicular scale. The work reveals an extensive unmineralized three-dimensional (3D) network of nanochannels (~30 nm in diameter) penetrating the mineralized extracellular matrix of human femoral cortical bone and encompassing a greater volume fraction and surface area than these same parameters of the canaliculi comprising the LCN. The present study combines high-resolution focused ion beam-scanning electron microscopy (FIB-SEM) to investigate bone ultrastructure in 3D with quantitative backscattered electron imaging (qBEI) to estimate local bone mineral content. The presence of nanochannels has been found to impact qBEI measurements fundamentally, such that volume percentage (vol%) of nanochannels correlates inversely with weight percentage (wt%) of calcium. This mathematical relationship between nanochannel vol% and calcium wt% suggests that the nanochannels could potentially provide space for ion and small molecule transport throughout the bone matrix. Collectively, these data propose a reinterpretation of qBEI measurements, accounting for nanochannel presence in human bone tissue in addition to collagen and mineral. Further, the results yield insight into bone mineralization processes at the nanometer scale and present the possibility for a potential role of the nanochannel system in permitting ion and small molecule diffusion throughout the extracellular matrix. Such a possible function could thereby lead to the sequestration or occlusion of the ions and small molecules within the extracellular matrix. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Osteocyte lacunae in transiliac bone biopsy samples across life span.

Osteocytes act as bone mechanosensors, regulators of osteoblast/osteoclast activity and mineral homeostasis, however, knowledge about their functional/morphological changes throughout life is limited. We used quantitative backscattered electron imaging (qBEI) to investigate osteocyte lacunae sections (OLS) as a 2D-surrogate characterizing the osteocytes. OLS characteristics, the density of mineralized osteocyte lacunae (i.e., micropetrotic osteocytes, md.OLS-Density in nb/mm2) and the average degree of mineralization (CaMean in weight% calcium) of cortex and spongiosa were analyzed in transiliac biopsy samples from healthy individuals under 30 (n=59) and over 30 years (n=50) (i.e., before and after the age of peak bone mass, respectively). We found several differences in OLS-characteristics: 1). Inter-individually between the age groups: OLS-Density and OLS-Porosity were reduced by about 20% in older individuals in spongiosa and in cortex versus younger probands (both, p < 0.001). 2). Intra-individually between bone compartments: OLS-Density was higher in the cortex, +18.4%, p < 0.001 for younger and +7.6%, p < 0.05 for older individuals. Strikingly, the most frequent OLS nearest-neighbor distance was about 30 µm in both age groups and at both bone sites revealing a preferential organization of osteocytes in clusters. OLS-Density was negatively correlated with CaMean in both spongiosa and cortex (both, p < 0.001). Few mineralized OLS were found in young individuals along with an increase of md.OLS-Density with age. In summary, this transiliac bone sample analysis of 200000 OLS from 109 healthy individuals throughout lifespan reveals several age-related differences in OLS characteristics. Moreover, our study provides reference data from healthy individuals for different ages to be used for diagnosis of bone abnormalities in diseases. STATEMENT OF SIGNIFICANCE: Osteocytes are bone cells embedded in lacunae within the mineralized bone matrix and have a key role in the bone metabolism and the mineral homeostasis. Not easily accessible, we used quantitative backscattered electron imaging to determine precisely number and shape descriptors of the osteocyte lacunae in 2D. We analyzed transiliac biopsy samples from 109 individuals with age distributed from 2 to 95 years. Compact cortical bone showed constantly higher lacunar density than cancellous bone but the lacunar density in both bone tissue decreased with age before the peak bone mass age at 30 years and stabilized or even increased after this age. This extensive study provides osteocyte lacunae reference data from healthy individuals usable for bone pathology diagnosis.

Assessment of chemical species of lead accumulated in tidemarks of human articular cartilage by X-ray absorption near-edge structure analysis.

A highly specific accumulation of the toxic element lead was recently measured in the transition zone between non-calcified and calcified normal human articular cartilage. This transition zone, the so-called `tidemark', is considered to be an active calcification front of great clinical importance. However, little is known about the mechanisms of accumulation and the chemical form of Pb in calcified cartilage and bone. Using spatially resolved X-ray absorption near-edge structure analysis (µ-XANES) at the Pb L(3)-edge, the chemical state of Pb in the osteochondral region was investigated. The feasibility of the µ-XANES set-up at the SUL-X beamline (ANKA synchrotron light source) was tested and confirmed by comparing XANES spectra of bulk Pb-reference compounds recorded at both the XAS and the SUL-X beamline at ANKA. The µ-XANES set-up was then used to investigate the tidemark region of human bone (two patella samples and one femoral head sample). The spectra recorded at the tidemark and at the trabecular bone were found to be highly correlated with the spectra of synthetic Pb-doped carbonated hydroxyapatite, suggesting that in both of these very different tissues Pb is incorporated into the hydroxyapatite structure.

3D Interrelationship between Osteocyte Network and Forming Mineral during Human Bone Remodeling.

During bone remodeling, osteoblasts are known to deposit unmineralized collagenous tissue (osteoid), which mineralizes after some time lag. Some of the osteoblasts differentiate into osteocytes, forming a cell network within the lacunocanalicular network (LCN) of bone. To get more insight into the potential role of osteocytes in the mineralization process of osteoid, sites of bone formation are three-dimensionally imaged in nine forming human osteons using focused ion beam-scanning electron microscopy (FIB-SEM). In agreement with previous observations, the mineral concentration is found to gradually increase from the central Haversian canal toward pre-existing mineralized bone. Most interestingly, a similar feature is discovered on a length scale more than 100-times smaller, whereby mineral concentration increases from the LCN, leaving around the canaliculi a zone virtually free of mineral, the size of which decreases with progressing mineralization. This suggests that the LCN controls mineral formation but not just by diffusion of mineralization precursors, which would lead to a continuous decrease of mineral concentration from the LCN. The observation is, however, compatible with the codiffusion and reaction of precursors and inhibitors from the LCN into the bone matrix.

Newly formed and remodeled human bone exhibits differences in the mineralization process.

During human skeletal growth, bone is formed via different processes. Two of them are: new bone formation by depositing bone at the periosteal (outer) surface and bone remodeling corresponding to a local renewal of tissue. Since in remodeling formation is preceded by resorption, we hypothesize that modeling and remodeling could require radically different transport paths for ionic precursors of mineralization. While remodeling may recycle locally resorbed mineral, modeling implies the transport over large distances to the site of bone apposition. Therefore, we searched for potential differences of size, arrangement and chemical composition of mineral particles just below surfaces of modeling and remodeling sites in femur midshaft cross-sections from healthy children. These bone sites were mapped using scanning synchrotron X-ray scattering, Raman microspectroscopy, energy dispersive X-ray analysis and quantitative backscattered electron microscopy. The results show clear differences in mineral particle size and composition between the sites, which cannot be explained by a change in the rate of mineral apposition or accumulation. At periosteal modeling sites, mineral crystals are distinctly larger, display higher crystallinity and exhibit a lower calcium to phosphorus ratio and elevated Na and Mg content. The latter may originate from Mg used for phase stabilization of mineral precursors and therefore indicate different time periods for mineral transport. We conclude that the mineralization process is distinctively different between modeling and remodeling sites due to varying requirements for the transport distance and, therefore, the stability of non-crystalline ionic precursors, resulting in distinct compositions of the deposited mineral phase. STATEMENT OF SIGNIFICANCE: In growing children new bone is formed either due to apposition of bone tissue e.g. at the outer ridge of long bones to allow growth in thickness (bone modeling), or in cavities inside the mineralized matrix when replacing tissue (bone remodeling). We demonstrate that mineral crystal shape and composition are not the same between these two sites, which is indicative of differences in mineralization precursors. We suggest that this may be due to a longer mineral transport distance to sites of new bone formation as compared to remodeling where mineral can be locally recycled.

Overview of clinical forensic services in various countries of the European Union.

Examination of a person who has been a victim of a physical or sexual assault may be very important for upcoming legal proceedings. In the context of a clinical forensic examination, physical findings are recorded and biological trace material is gathered and secured. Ideally, all forensic findings are documented in a detailed report combined with photographic documentation, which employs a forensic scale to depict the size of the injuries. However, the integrity of such forensic findings depends particularly on two factors. First, the examination needs to be conducted professionally to ensure that the findings are properly admissible as court evidence. Second, the examination should take place as soon as possible because the opportunity to successfully secure biological samples declines rapidly with time. Access to low-threshold clinical forensic examinations is not evenly provided in all member states of the European Union (EU); in some states, they are not available at all. As part of the JUSTeU! (Juridical standards for clinical forensic examinations of victims of violence in Europe) project, the Ludwig Boltzmann Institute for Clinical Forensic Imaging in Graz, Austria created (in cooperation with its international partner consortium) a questionnaire: the purpose was to collect information about support for victims of physical and/or sexual assault in obtaining a low-threshold clinical forensic examination in various countries of the EU. Our paper provides a summary of the responses and an overview of the current situation concerning provided clinical forensic services.

Safety, feasibility, and hemodynamic and blood flow effects of active compression-decompression of thorax and abdomen in patients with cardiac arrest.

OBJECTIVE: During closed chest compression for cardiac arrest, any increase in coronary perfusion pressure accounts for a proportional increase in myocardial blood flow and therefore the resuscitability of the patient. The objectives of this study were to evaluate the safety, feasibility, and hemodynamic effects of phased chest and abdominal compression-decompression and to compare it with mechanical chest compression during cardiopulmonary resuscitation. DESIGN: In this prospective, single-center, phase II study, we compared patients treated with the Datascope Lifestick Resuscitator with patients who had been treated with mechanical precordial compression. SETTING: Emergency department of a tertiary care university hospital. PATIENTS: We included 31 patients with cardiac arrest who had received cardiopulmonary resuscitation in the emergency department. INTERVENTIONS: The Lifestick device was used in 20 patients. In 11 patients, mechanical chest compression with the Thumper device was used as a control intervention. MEASUREMENTS AND MAIN RESULTS: We evaluated the safety, feasibility, and hemodynamic effects of both interventions and observed, with the help of echocardiography, the mechanisms through which blood flow was generated. We found no significant difference between the use of the Lifestick device and standard chest compression with the Thumper device in resuscitations. Most operators regarded the Lifestick as a feasible alternative to the Thumper. We could observe a mean increase in coronary perfusion pressure of 9.33 mm Hg (interquartile range, 1.96-14.36; p = .08) and an increase of end-tidal CO2 of 10 mm Hg (interquartile range, 5-16; p = .003) (1333Pa [interquartile range, 665-2133]) during resuscitation with the Lifestick compared with using the Thumper. CONCLUSION: In this preliminary study, resuscitation with the Lifestick was found to be safe and feasible. The design of the study and small number of patients included in it limit the conclusions about the hemodynamic effects of the Lifestick.

[Measurement of cognitive constriction in suicide notes]. / Zur Messung der kognitiven Einengung in Abschiedsbriefen.

OBJECTIVE: The target of this paper was to quantify the amount of cognitive constriction in German-language suicide notes by studying quantitative psycholinguistic parameters of texts. This should give a better understanding of presuicidal events and encourage improvement in the field of suicide prevention and crisis intervention. METHODS: The study is based on letters of the "Vienna Corpus of Suicide Notes". To prove various hypotheses a factor analysis, a number of regression analyses, and the General Linear Model were applied, apart from descriptive methods. RESULTS: The 16 parameters could be reduced to five factors of cognitive constriction, such as the writing style, the usage of words, the dichotomy, the length and the grammatical correctness of the suicide notes. Regarding the writing style the highest values of cognitive constriction were found among women (p=0.005), young persons (p< or =0.000), in short letters (p=0.027) and if psychological problems were the motive for suicide (p=0.020). The discovery site of the letters (p=0.002) was important as well. CONCLUSIONS: The construct of cognitive constriction is a multidimensional and complex phenomenon. Therefore the quantification must contain variables of the persons and the texts.

Sex and gender matters : A sex-specific analysis of original articles published in the Wiener klinische Wochenschrift between 2013 and 2015.

BACKGROUND: The variables sex and gender are significantly related to health and disease of women and men. Aiming at quality research, biomedical publications need to account for the key variables sex and gender. METHODS: All original articles published in the Wiener klinische Wochenschrift between 2013 and 2015 were extracted into a database. As a result, the 195 published articles were selected for review led by the Sex and Gender Equity in Research Guidelines (SAGER) by the European Association of Science Editors (EASE). The slightest indications of mentioning sex and/or gender were assessed by two reviewers independently from one another. RESULTS: Of the 195 publications 4 specified sex and/or gender in the title, and 62 in the abstract. None of the authors reported whether the variables sex and/or gender may have relevance and were taken into account in the design of the study. Of the 195 publications 48 mentioned the potential implications of sex and/or gender on the study results. CONCLUSION: In the time span studied most of the selected articles of this journal did not account for the variables sex and/or gender systematically or adequately. For future research the existing guidelines can help authors and editors to overcome gender bias due to inadequate methods. Applying sex and gender-sensitive methods to biomedical and health research is necessary for high quality and as a precondition for results which are generalizable and applicable to both women and men.

Presence of pyrophosphate in bone from an atypical femoral fracture site: A case report.

Long-term antiresorptives use has been linked to atypical subtrochanteric and diaphyseal femoral fractures (AFF), the pathogenesis of which is still unknown. In the present case report we present the results of analysis of bone chips from a 74-year old female patient that had been on alendronate, ibandronate and denosumab treatment, and who sustained an atypical femoral fracture, by histology, quantitative backscattered electron imaging, and Raman spectroscopic analysis. The results indicate ongoing osteoclastic resorption, but also several abnormalities: 1) an altered arrangement of osteons; 2) impaired mineralization; 3) the presence of pyrophosphate, which might contribute to the impaired mineralization evident in the present case. Taken together, these changes may contribute to the focally reduced bone strength of this patient.

Spatial heterogeneity in the canalicular density of the osteocyte network in human osteons.

Osteocytes interconnect with each other forming an intricate cell network within the mineralized bone matrix. One important function of the osteocyte network is the mechano-regulation of bone remodeling, where a possible mechanism includes the fluid flow through the porosity housing the cell network - the osteocyte lacuno-canalicular network (OLCN). In our study the OLCN in human osteons was three-dimensionally imaged with the aim to obtain a quantitative description of the canalicular density and spatial variations of this quantity within osteons. The topology of the OLCN was determined by first staining the bone samples with rhodamine, then imaging the OLCN with confocal laser scanning microscopy and finally using image analysis to obtain a skeletonized version of the network for further analysis. In total 49 osteons were studied from the femoral cortical bone of four different middle-aged healthy women. The mean canalicular density given as length of the canaliculi in a unit volume was 0.074 ± 0.015 µm/µm3 (corresponding to 74 km/cm3). No correlation was found between the canalicular density and neither the size of the osteon nor the volume fraction occupied by osteocyte lacunae. Within osteons the canalicular density varied substantially with larger regions without any network. On average the canalicular density decreases when moving from the Haversian canal outwards towards the cement line. We hypothesize that a decrease in accessible canaliculi with tissue age as a result of micropetrosis can reduce the local mechanosensitivity of the bone. Systematic future studies on age- and disease-related changes on the topology of the OLCN have to demonstrate the diagnostic potential of the presented characterization method.

Do centenarians die healthy? An autopsy study.

BACKGROUND: Our goal was to assess the prevalence of common causes of death and the demographic variables in a selected population of centenarians. METHODS: The autopsy reports and medical histories of all individuals > or =100 years, dying unexpectedly out of hospital, were gathered from 42,398 consecutive autopsies, performed over a period of 18 years at the Institute of Forensic Medicine, Vienna. These records were evaluated with regard to age and sex, circumstances of death, season, time and the cause of death, as well as the presence of any other comorbidity. RESULTS: Forty centenarians (11 men, 29 women) were identified with a median age of 102 +/- 2.0 (range: 100-108) years. Sixty percent were described as having been healthy before death. However, an acute organic failure causing death was found in 100%, including cardiovascular diseases in 68%, respiratory illnesses in 25%, gastrointestinal disorders in 5%, and cerebrovascular disease in 2%. Additionally, centenarians suffered from several comorbidities (cardiac antecedents, neurologic disorders, liver diseases, cholecystolithiasis), which were not judged to be the cause of death. CONCLUSIONS: Centenarians, though perceived to have been healthy just prior to death, succumbed to diseases in 100% of the cases examined. They did not die merely "of old age." The 100% post mortem diagnosis of death as a result of acute organic failure justifies autopsy as a legal requirement for this clinically difficult age group.

Foreign body asphyxia: a preventable cause of death in the elderly.

BACKGROUND: To assess the prevalence of food/foreign body asphyxia in the elderly Viennese population in order to reduce the incidence of these fatal events. METHODS: This is an autopsy-based, retrospective study in Vienna, Austria. Participants included all nonhospitalized (n =200) cases of choking in 1984 to 2001, from a total 42,745 consecutive autopsies performed at the Institute of Forensic Medicine. In addition, data from hospitalized adult cases of fatal choking (n =73) in 1984 to 2001, from the mortality registrar of Vienna, were included. RESULTS: The nonhospitalized choking victims were analyzed according to age (18 to 64 vs >/=65 years), sex, circumstances of death, and predisposing factors. Hospitalized cases were analyzed according to age, sex, and whether an autopsy was already performed by pathologists at the institution where they died. In the study period, 273 adults died of food/foreign body asphyxia, 73% of them out of the hospital and 27% in hospitals. Food/foreign body asphyxia in the elderly was characterized by a significantly higher asphyxiation of soft/slick foods (p <0.007) with agomphiasis (p <0.002), occurring most frequently during lunch (49%), and in 2.5% during feeding of neurologically impaired. In contrast, younger individuals choked significantly more often on large pieces of foreign material (p <0.002) and showed a significantly higher rate of blood alcohol concentration (p <0.001). CONCLUSIONS: This study demonstrates that semisolid foods are the cause of a large number of asphyxiations, especially among the elderly. Knowledge of the fact that semisolid foods are a high-risk factor in elderly individuals should be distributed in public and private healthcare systems, and awareness could be a first step in reducing the incidence of food/foreign body asphyxia.

Injury pattern in correlation with the height of fatal falls.

BACKGROUND: Death due to blunt trauma as a sequel of falls, as a cause of an increased life span is expected. The aim of this retrospective study was to examine the correlation between the height of fall and the frequency, the extensiveness, and the type of injuries of certain body regions and organs. METHODS: The study included 201 cases of fatal falls, which consisted 118 male and 83 female cases. All subjects were assessed in a standard autopsy for height of fall, cause of death, and injury pattern. RESULTS: Concerning the height of fall, 111 (55.2 %) cases involved falls on a plane level, 72 (35.8 %) from one level to another lower level, less than 5 meters, and 18 (9 %) cases from one level to another lower level, more than 5 meters. Mean age at the time of death was 66.7-years-old (range 22-98). The immediate cause of death was in 94 cases blunt head trauma, in 40 cases cardiovascular diseases, in 56 cases bronchopulmonal diseases, in 3 patients Polytrauma, in 5 patients multi organ failure, and in 3 patients other causes were identified. At the autopsy, 66 patients showed fractures of the skeletal system. The most common cause of death independent from the height of fall was head trauma with 46.7 %. CONCLUSION: Both post-mortem findings and medical and psychiatric history, in conjunction with the findings at the death scene and toxicology results have to be considered to obtain the clearest possible picture of the circumstance of death.

Unexpected out-of-hospital deaths in persons aged 85 years or older: an autopsy study of 1886 patients.

PURPOSE: The aim of this study was to determine the causes of death in the very elderly. METHODS: We reviewed 24,081 consecutive autopsies performed over 10 years (1989 to 1998) at the Institute of Forensic Medicine, Vienna, Austria. We focused on autopsies of people aged 85 years or older who died unexpectedly out of hospital. RESULTS: The mean age of the 1886 patients (561 men and 1325 women) at the time of death was 88 +/- 3 years (range, 85 to 108 years). Thirty-one percent (n = 588) of those who died were described as having been previously healthy. Cardiovascular disease was the most common cause of death (n = 1465 [77%]). Thirteen percent (n = 246) died of respiratory illness, 5% (n = 94) of gastrointestinal disorders, and 3% (n = 53) of diseases of the central nervous system. Genitourinary and metabolic diseases were uncommon. CONCLUSION: Although this out-of-hospital sample is not representative of the entire elderly population, postmortem examinations emphasize the importance of cardiovascular diseases in causing unexpected deaths in older persons.