Autopsy Evidence Research Articles

Hypoglycaemia in hospitalised neonatal calves: Prevalence, associated conditions and impact on prognosis

Hypoglycaemia has traditionally been associated with neonatal diarrhoea and endotoxaemia in calves, but the clinical relevance of this finding in spontaneously diseased calves has not previously been evaluated. To determine the prevalence and prognostic relevance of severe hypoglycaemia (plasma glucose concentration < 2 mmol/L), data from 10,060 hospitalised calves (≤21 days of age) were retrospectively analysed. Additionally, clinical findings and diagnoses in a subset of 100 calves with severe hypoglycaemia were compared with those in 100 randomly selected calves with initial plasma glucose concentrations in the reference range (4.4–6.9 mmol/L).The prevalence of severe hypoglycaemia in the whole study sample was 6.3%. Severe hypoglycaemia was associated with a poor survival rate of 20.6% vs. 74.0% discharged animals in the group of calves with initial normoglycaemia. Review of medical records revealed that severe hypoglycaemia was significantly associated with clinical or necropsy evidence of septicaemia, hypothermia, history or clinical evidence of malnutrition, and peritonitis of varied origin, but not with the presence of neonatal diarrhoea. Only 10 of 100 calves with severe hypoglycaemia showed central nervous involvement such as seizures and opisthotonus. In conclusion, severe hypoglycaemia has a low prevalence in diseased calves in a hospital setting, but is associated with serious health problems and therefore a high risk of non-survival. Severe hypoglycaemia was not easily diagnosed based on clinical signs, but should be suspected in calves with clinical evidence of septicaemia, hypothermia, acute abdominal emergencies, and a history or clinical evidence of malnutrition.

Does Sudden Unexplained Nocturnal Death Syndrome Remain the Autopsy-Negative Disorder: A Gross, Microscopic, and Molecular Autopsy Investigation in Southern China

ObjectiveTo look for previously unrecognized cardiac structural abnormalities and address the genetic cause for sudden unexplained nocturnal death syndrome (SUNDS). MethodsData for 148 SUNDS victims and 444 controls (matched 1:3 on sex, race, and age of death within 1 year) were collected from Sun Yat-sen University from January 1, 1998, to December 31, 2014, to search morphological changes. An additional 17 patients with Brugada syndrome (BrS) collected from January 1, 2006, to December 31, 2014, served as a comparative disease cohort. Target-captured next-generation sequencing for 80 genes associated with arrhythmia/cardiomyopathy was performed in 44 SUNDS victims and 17 patients with BrS to characterize the molecular spectrum. ResultsThe SUNDS victims had slight but statistically significant increased heart weight and valve circumference compared with controls. Twelve of 44 SUNDS victims (SCN5A, SCN1B, CACNB2, CACNA1C, AKAP9, KCNQ1, KCNH2, KCNJ5, GATA4, NUP155, ABCC9) and 6 of 17 patients with BrS (SCN5A, CACNA1C; P>.05) carried rare variants in primary arrhythmia-susceptibility genes. Only 2 of 44 SUNDS cases compared with 5 of 17 patients with BrS hosted a rare variant in the most common BrS-causing gene, SCN5A (P=.01). Using the strict American College of Medical Genetics guideline-based definition, it was found that only 2 of 44 (KCNQ1) SUNDS and 3 of 17 (SCN5A) patients with BrS hosted a “(likely) pathogenic” variant. Fourteen of 44 SUNDS cases with cardiomyopathy-related variants had a subtle but significantly decreased circumference of cardiac valves, and tended to die on average 5 to 6 years younger compared with the remaining 30 cases (P=.02). ConclusionWe present the first comprehensive autopsy evidence that SUNDS victims may have concealed cardiac morphological changes. SUNDS and BrS may result from different molecular pathological underpinnings. The distinct association between cardiomyopathy-related rare variants and SUNDS warrants further investigation.

An analysis of deep vein thrombosis in burn patients (part II): A randomized and controlled study of thrombo-prophylaxis with low molecular weight heparin

IntroductionMorbidity and mortality from venous thrombo-embolism (VTE) remains a significant problem for trauma and medical patients and there are established guidelines for prophylaxis in these patients. However, the efficacy and safety of VTE prophylaxis in thermally injured patients continue to be elusive as it has never been studied in a prospective, randomized fashion. Selective use of VTE prophylaxis, for high risk patients, is practiced by some burn units even if objective evidence is lacking for majority of risk factors enunciated in burn patients. Differing demographics and wound management techniques are other confounding factors mandating more prospective studies to evaluate the need and role of chemoprophylaxis for deep vein thrombosis (DVT) prevention in burn patients. Ours is the first prospective, randomized, controlled study which seeks to identify risk factors for DVT in our patients, and evaluate the role of routine chemoprophylaxis and its complications. MethodsThe study design (sample size, inclusion/exclusion criteria, randomization, methodology and statistical methods) is detailed in part-1 of this two part manuscript. ResultsDoppler ultrasound (DUS) identified DVT in four out of 50 patients (8% incidence) forming the control group. DVT was not detected in any of the patients on prophylaxis (0% incidence). This difference was found to be statistically significant (p value—0.021). Patients with DVT had significantly higher %TBSA, prolonged immobility and a longer duration of stay as compared to patients without DVT in the control group. Only one patient on enoxaparin prophylaxis developed mild epistaxis which resolved spontaneously. Fifteen patients died during the study out of which two had DVT but none showed autopsy evidence of pulmonary embolism. ConclusionWith a moderate risk of developing DVT (8%) and a complication rate of only 2% with chemoprophylaxis, we feel that routine prophylaxis has the potential to decrease the incidence of VTE, without associated complications, in the moderate to high risk category.

Aphasic variant of Alzheimer disease: Clinical, anatomic, and genetic features.

To identify features of primary progressive aphasia (PPA) associated with Alzheimer disease (AD) neuropathology. A related objective was to determine whether logopenic PPA is a clinical marker for AD. A total of 139 prospectively enrolled participants with a root diagnosis of PPA constituted the reference set. Those with autopsy or biomarker evidence of AD, and who had been evaluated at mild disease stages (Aphasia Quotient ≥85), were included (n = 19). All had quantitative language testing and APOE genotyping. Fifteen had MRI morphometry. Impaired word-finding was the universal presenting complaint in the aphasic AD group. PPA clinical subtype was logopenic (n = 13) and agrammatic (n = 6). Fluency, repetition, naming, and grammaticality ranged from preserved to severely impaired. All had relative preservation of word comprehension. Eight of the 15 aphasic participants with AD showed no appreciable cortical atrophy at the individual level on MRI. As a group, atrophy was asymmetrically concentrated in the left perisylvian cortex. APOE ε4 frequency was not elevated. There is a close, but not obligatory, association between logopenic PPA and AD. No language measure, with the possible exception of word comprehension, can confirm or exclude AD in PPA. Biomarkers are therefore essential for diagnosis. Asymmetry of cortical atrophy and normal APOE ε4 prevalence constitute deviations from typical AD. These and additional neuropathologic features suggest that AD has biological subtypes, one of which causes PPA. Better appreciation of this fact should promote the inclusion of individuals with PPA and positive AD biomarkers into relevant clinical trials.

BILIRUBIN CONCENTRATIONS IN CLINICALLY HEALTHY AND DISEASED CAPTIVE WATERBUCK (KOBUS ELLIPSIPRYMNUS) AT THE SAN DIEGO ZOO SAFARI PARK.

Captive waterbuck ( Kobus ellipsiprymnus ) that appear clinically healthy have been noted to have high serum bilirubin concentrations compared with other ruminants; however, questions remain about the physiologic factors affecting bilirubin concentration and its potential association with underlying disease and icteric serum or mucous membranes. Serum bilirubin concentrations of healthy and diseased waterbuck housed at the San Diego Zoo Safari Park from 1989 to 2012 were retrospectively analyzed to determine any link between icteric serum, total bilirubin concentration (tBili), and disease entities in this species. Total bilirubin and direct (dBili) bilirubin concentrations and the prevalence of icteric serum were compared by subspecies, age group, and health status; associations with complete blood count and biochemical results and clinical diagnosis were assessed. No significant differences were found in tBili or dBili between Ellipsen (n = 32) and Defassa (n = 29) subspecies or in juveniles (n = 22) versus adults (n = 39). Clinically healthy waterbuck (n = 40) had significantly higher tBili (mean ± 2SD, 7.9 ± 1.2 mg/dl; P < 0.001) and dBili (3.7 ± 1.0 mg/dl; P < 0.001) than did diseased waterbuck (n = 21; tBili: 4.9 ± 2.56 mg/dl; dBili: 2.2 ± 0.8 mg/dl). No waterbuck had icteric tissues on physical examination. Twelve (19.7%) waterbuck (six healthy, six diseased) had icteric serum. Few minor correlations were seen between tBili or dBili and clinical, laboratory, or necropsy evidence of disease, though an inverse correlation between dBili and blood glucose was noted. Of the 40 healthy animals, reference intervals were calculated for tBili (5.5-10.3 mg/dl), dBili (1.7-5.7 mg/dl), and indirect bilirubin (2.2-6.2 mg/dl). These results suggest healthy waterbuck have relatively high tBili and dBili compared with related species. Icteric serum may be seen in up to 15% of healthy animals in the absence of icteric tissues.

Unusual Cause of Adrenal Insufficiency

Unusual Cause of Adrenal Insufficiency

Brain arterial aging and its relationship to Alzheimer dementia.

To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD). Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models. We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002). Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD.

Histopathology Findings of Asphyxia in Lungs of Hanging and Drowning Deaths

Sometimes mysterious circumstances accompanied by inadequate external and internal findings related to ligature mark in hanging deaths as well as scarcity of classical lung features in drowning deaths makes it difficult to conclude or rule out cause of death as asphyxia. To form opinion regarding cause of death as hanging and drowning in such cases, documenting histopathology findings of lungs as supplementary autopsy evidence based on the theory that asphyxia comprises different kinds of lesions that can produce varied histopathology findings is really a meaningful exercise. Hanging and drowning being the most common prevalent asphyxia types in India, 47 hanging and 28 drowning deaths were studied to find more common histopathology findings for each group of asphyxia. Cause of deaths of the cases confirmed after meticulous post mortem examinations and police investigations. Histopathology section from lungs of every case was prepared and stained with Haematoxylin-Eosin. As compared to drowning, the histopathology findings of alveolar tissue collapse, alveolar overinsufflation, bronchiolar constriction and bronchiolar dilatations, congestion, interstitial edema and alveolar hemorrhage were more commonly observed in lungs of hanging. The only histopathology finding that was more commonly noticed in lungs of drowning was intra-alveolar edema.

Neuroleptic-induced Parkinsonism: Clinicopathological study.

ABSTRACTBackgroundDrug‐induced parkinsonism is a well‐known complication of several different drugs—the most common being neuroleptic‐induced parkinsonism. However, very few autopsies have been reported in such cases.MethodsPatients assessed at Movement Disorders Clinic Saskatchewan are offered brain autopsy. Detailed clinical records are kept.ResultsBrains were obtained from 7 drug‐induced parkinsonism patients with parkinsonian symptom onset coinciding with use of drugs known to produce parkinsonism. Six were on antipsychotics and 1 was on metoclopramide. Three cases were treated with levodopa for parkinsonism. In two cases, parkinsonian features reversed after stopping the offending agent. Both had autopsy evidence of preclinical PD. In 4 of the remaining 5, dopamine‐blocking drugs were continued until death. In 4 of those 5, brain histology revealed no cause for the parkinsonism, but 1 had mild SN neuronal loss without Lewy bodies.ConclusionThis study shows that reversal of parkinsonism after discontinuing offending drugs does not indicate absence of underlying pathology. Neuroleptics can unmask preclinical PD in patients with insufficient SN damage for the disease to manifest clinically. Though the mechanism of sustained parkinsonian features after discontinuing neuroleptics remains to be established, it is unlikely that dopamine receptor block leads to retrograde SN neuronal degeneration. Furthermore, l‐dopa does not appear to be toxic to SN. © 2015 International Parkinson and Movement Disorder Society

Association Between Necropsy Evidence of Disseminated Intravascular Coagulation and Hemostatic Variables Before Death in Horses With Colic.

BackgroundDisseminated intravascular coagulation (DIC) is frequent in horses with severe gastrointestinal disorders. Postmortem studies have found fibrin microthrombi in tissues of these horses, but studies relating these histopathological findings with antemortem hemostatic data are lacking.HypothesisAntemortem classification of coagulopathy is related to the presence and severity of fibrin deposits observed postmortem in horses with severe gastrointestinal disorders.AnimalsAntemortem hemostatic profile data and postmortem tissue samples (kidney, lung, liver) from 48 horses with colic.MethodsTissue samples were stained with phosphotungstic acid hematoxylin and immunohistochemical methods for histological examination. A fibrin score (grades 0–4) was assigned for each technique, tissue and horse, as well as the presence or absence of DIC at postmortem examination. D‐dimer concentration, prothrombin time (PT), activated partial thromboplastin time (aPTT), and antithrombin (AT) activity, as well as the clinicopathological evidence of coagulopathy, were determined from plasma samples collected 0–24 hours before death or euthanasia. Histologic and clinicopathologic data from the same horses were compared retrospectively.ResultsNo association was found between antemortem classification of coagulopathy and postmortem diagnosis of DIC based on tissue fibrin deposition. None of the hemostatic parameters was significantly different between horses with or without postmortem diagnosis of DIC. There was no association between horses with fibrin in tissues or different cut‐offs for D‐dimer concentration and postmortem evidence of DIC.Conclusions and Clinical ImportanceAbnormalities of the routine clotting profile, including D‐dimer concentration, were not useful in predicting histologic evidence of DIC at necropsy in horses with severe gastrointestinal disorders.

Neuromelanin marks the spot: identifying a locus coeruleus biomarker of cognitive reserve in healthy aging

Leading a mentally stimulating life may build up a reserve of neural and mental resources that preserve cognitive abilities in late life. Recent autopsy evidence links neuronal density in the locus coeruleus (LC), the brain's main source of norepinephrine, to slower cognitive decline before death, inspiring the idea that the noradrenergic system is a key component of reserve (Robertson, I. H. 2013. A noradrenergic theory of cognitive reserve: implications for Alzheimer's disease. Neurobiol. Aging. 34, 298–308). Here, we tested this hypothesis using neuromelanin-sensitive magnetic resonance imaging to visualize and measure LC signal intensity in healthy younger and older adults. Established proxies of reserve, including education, occupational attainment, and verbal intelligence, were linearly correlated with LC signal intensity in both age groups. Results indicated that LC signal intensity was significantly higher in older than younger adults and significantly lower in women than in men. Consistent with the LC-reserve hypothesis, both verbal intelligence and a composite reserve score were positively associated with LC signal intensity in older adults. LC signal intensity was also more strongly associated with attentional shifting ability in older adults with lower cognitive reserve. Together these findings link in vivo estimates of LC neuromelanin signal intensity to cognitive reserve in normal aging.

John Hunter (1728-1793) and his legacy to science.

John Hunter was born in 1728 in Kilbride East, Lanarkshire, Scotland, as the youngest child of a family of ten children. John’s father died in 1741 and he was thus left to care for his mother. When John was about 17, young John moved to London to study under William Hunter (1718–1783), his 10-yearelder brother and was already an anatomist and obstetrician [24]. He studied as a dissector in William’s Anatomy School in Covent Garden in 1748 and showed his abilities on cadaver dissections. In 1749, he became a lecturer and demonstrator in anatomy [11]. His brother obtained permission for him to attend the Chelsea Hospital under the supervision of Dr. William Cheselden (1688–1752), Hunter’s first master in surgery and the most celebrated surgeon of his time. On the retirement of Dr. William Cheselden from Chelsea Hospital, Hunter entered as surgeon’s pupil at St. Bartholomew’s Hospital and became a pupil of Percivall Pott (1714–1788) [17]. During his studies under the aforementioned scientists, John made a great progress on dissection. In 1753, as an award of his progress and an honor bestowed upon his mentor Percivall Pott, Hunter was elected Master of Anatomy at Surgeon’s Hall [3]. During the Seven Years’ War (1756–1763) with France, Hunter was commissioned as an army surgeon in Belle Isle and Portugal. He acquired surgical skills and experienced on gunshot wounds and inflammation [11]. He began to collect materials on those issues which published posthumously in 1794 [15]. On his return to England in 1763, he began to build up his private practice. In 1767, he was elected as a Fellow of the Royal Society [22]. He published the first part of his Treatise on the teeth in May 1771 [12, 19]. Two months later, he married Anne Home (1742–1821), a daughter of an old Scottish family [8]. In 1768, he was elected Surgeon to St. George’s Hospital and he was appointed as SurgeonExtraordinary to King George III in 1776. In 1786, he won the Copley Medal, the highest award of the Royal Society [24]. While meeting of the Board of Governors of St. George’s Hospital, he collapsed and died on 16 October 1793. There are some conflicts on the reason of his death. The autopsy demonstrated lesions in his aorta compatible with his self-induced syphilis [22]. Others argued that there was no autopsy evidence of syphilis but evidence only of advanced arteriosclerotic vascular disease [6, 10]. He was initially buried in a crypt of the Church of St. Martin-in-the-Field. His remains were transferred to Westminster Abbey in February 1859 [24].

Excited delirium: A psychiatric review.

The term 'excited delirium' (ED) is used to explain sudden and unexpected restraint-related deaths. Since the 1990s, ED has often been identified as the principal cause of death in restrained individuals, rather than the restraint procedure itself. Forensic pathologists and psychiatrists attach different meanings to the term delirium. For psychiatrists, delirium is a specific technical term, which implies a grave and potentially life-threatening underlying physical illness. If a patient dies during a bout of delirium, psychiatrists assume that there will be autopsy evidence to demonstrate the primary underlying organic cause. Conversely, pathologists appear to be using the term ED to refer to restraint-related deaths in either highly disturbed cocaine users or psychiatric patients in a state of extreme agitation. In these cases, there is no underlying physical disorder other than a terminal cardiac arrhythmia. As the term ED has different meanings for psychiatrists and for pathologists, it would be helpful for these two professional groups to develop a mutually agreed terminology.

Forensic relevance of post-mortem CT imaging of the haemopericardium in determining the cause of death.

The post-mortem diagnosis of pericardial tamponade is associated with several medical legal problems. Thus, we explored whether post-mortem computed tomography might provide useful and reliable information for the diagnosis of this relevant disease in combination with autopsy data. We retrospectively reviewed the post-mortem computed tomography and autopsy reports of 15 autopsy cases with haemopericardium detected at the Institute of Forensic Medicine in Berne from July 2005 to February 2010. Two computer tomography findings were examined in combination with autopsy results. The first was the "hyperdense armoured heart," which has been previously described as post-mortem evidence of heart beating for a time after the initiation of intrapericardial bleeding. The second was the "flattening of the anterior surface" of the heart which has been previously observed in vivo as a sign of the compression effect of the haemopericardium on the heart. Our retrospective analysis showed the combined presence of both of these findings in all cases of autopsy evidence of pericardial tamponade with the exception of one case. In contrast, the concomitance of both of them was never observed in cases of autopsy death due to haemorrhage in which neither the flattening of the anterior surface of the heart was detected except for one case. In conclusion, these results should be considered a first step toward the potentially using post-mortem computed tomography in combination with autopsy data in the diagnosis of pericardial tamponade especially considering the possibility to detect sign as the flattened heart signal which cannot be assessed after opening the pericardium at autopsy.

Pathology of tuberculosis in maternal mortality: an autopsy study

Tuberculosis is a leading cause of death among women in the reproductive period. Studies suggest that immunobiologic changes in pregnancy influence tuberculosis. However there is a dearth of data on pathomorphology of tuberculosis in pregnancy. <h3>Aim</h3> To characterize pathomorphologic patterns, co-existing lesions and obstetric complications in maternal deaths associated with tuberculosis. <h3>Methods</h3> We performed a two-year retrospective study of all autopsies of maternal mortality associated with tuberculosis. <h3>Results</h3> Among 151 autopsies of maternal deaths a current clinical history or autopsy evidence of tuberculosis was noted in 14 patients. Six among these had died post-partum and four following spontaneous abortions. Multi-organ tuberculosis and isolated pulmonary tuberculosis was observed in ten and three patients respectively. One patient with on-going anti-tuberculosis treatment had massive hepatic necrosis but no tuberculosis at autopsy. Six patients had a poorly reactive tuberculosis pattern. Diffuse alveolar damage was noted in three, two patients each had intracardiac mural thrombi and brain infarcts, one had perforative peritonitis while another revealed features suggestive of aortitis. Fetal outcome was poor with only two live births. <h3>Discussion</h3> The study suggests that maternal mortality associated with tuberculosis commonly has a florid multi-organ involvement, is often poorly reactive and has a poor fetal outcome.

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Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation. The clinical phenotype of HLH-induced multiple organ failure (MOF) is very similar to other phenotypes of MOF in critically ill children such as thrombocytopenia-associated MOF (TAMOF) syndrome and immune paralysis/lymphoid depletion syndrome. Methods: We reviewed consecutive autopsy reports of children who died with a diagnosis of HLH between 2005-2012 in a tertiary care university-based pediatric hospital. Two autopsies were limited - one with liver/spleen/bone marrow, and the other with chest/abdomen. Results: Twelve autopsy reports were analyzed. All patients had received treatment with dexamethosone and etoposide. 83.3% (10/12) of patients met criteria for TAMOF at death: platelet count < 100K/mm3 and at least 3 failing organs. 60% (6/10) of patients who met criteria for TAMOF had evidence of microvascular thrombosis on autopsy, 50% (3/6) had evidence of microvascular thrombosis in more than one organ: 2/6 brain, 2/6 heart, 1/6 in lungs, 1/6 in liver, 3/6 in kidneys, 1/6 in pancreas and 2/6 in spleen. Two thirds (4/6) patients also had hypocellular bone marrow. Of the 4 patients who met criteria for TAMOF without microvascular thrombosis on autopsy, 3 had hypocellular bone marrow and one had occlusive aggregates of septated hyphae in blood vessels and no bone marrow was obtained at autopsy. 83% (10/12) of patients had evidence of infection at time of autopsy, categorized as: bacterial (58%), viral (50%), fungal (42%), and 42% of patients had infections in more than one category. 50% (6/12) of patients had lymphocyte depletion in spleen, thymus or bone marrow, and 66% (4/6) of whom were chronically lymphopenic (>7 days absolute lymphocyte count <1000/microliter), and 83% (5/6) with infection on autopsy. Conclusions: Many patients who died with HLH have 1) clinical evidence of TAMOF syndrome and autopsy evidence of disseminated microvascular thrombosis and 2) clinical lymphopenia and autopsy evidence of lymphoid depletion and unresolved infection. These autopsy findings suggest that MOF in patients with HLH is complex with overlapping MOF phenotypes. Further studies are warranted.

The Meniere attack: An ischemia/reperfusion disorder of inner ear sensory tissues

We believe Meniere attacks arise as a chance association of endolymphatic hydrops and vascular risk factors for intracerebral ischemia. Hydrops acts as a variable Starling resistor upon the inner ear vasculature that is capable of inducing ischemic attacks only in people with reduced perfusion pressure in the ear. The unique characteristics of the attacks (loss of vestibular response and hearing acutely followed by a return to apparent normalcy over hours) are explained by the differential sensitivity of the inner ear tissues to transient ischemia, with the sensory tissues (dendrites, hair cells) vulnerable to hours-long ischemia/reperfusion injury, and the stria vulnerable to ischemia due to its high metabolic rate. Permanent hearing loss and vestibular damage after many attacks would result when small areas of irreversible sensory cell damage accumulate and become confluent.This theory is supported by the strong correlation of hydrops with Meniere attacks, the finding that autoregulation of cochlear blood flow is impaired in the hydropic ear, and studies demonstrating that symptoms and signs in people and in animal models vary with conditions that alter perfusion pressure in the inner ear. Induction of Meniere attacks in animal models requires both hydrops and a mechanism that reduces perfusion pressure, such as epinephrine injection or head dependency. There is a strong clinical association between Meniere attacks and disorders that increase the risk for cerebrovascular ischemia, such as migraine. The excitable tissues in the sensory structures have long been known to be more vulnerable to ischemia than the remaining aural tissues, and are now known to be vulnerable to excitotoxicity induced by ischemia/reperfusion. This correlates well with autopsy evidence of damage to dendrites and hair cells and with strial atrophy in late Meniere disease cases.If this hypothesis is confirmed, treatment of vascular risk factors may allow control of symptoms and result in a decreased need for ablative procedures in this disorder. If attacks are controlled, the previously inevitable progression to severe hearing loss may be preventable in some cases.

Serum-cholesterol, diet, and coronary heart-disease in Africans and Asians in Uganda*

In the African population of Uganda coronary heart disease is almost non-existent. This statement is confirmed by adequate necropsy evidence. In the Asian community, on the other hand, coronary heart disease is a major problem. During the three years 1956–58 the Kampala health department registered 102 male and 45 female deaths over 30 years of age among Asians and of these 48 (44 male and 4 females) were certified as due to coronary heart disease (‘‘myocardial infarction’’, ‘‘coronary thrombosis’’). Though the errors inherent in certification must be borne in mind, it is noteworthy that 43% of male deaths and 9% female deaths over 30 years of age were attributed to coronary heart disease. While the significance of a high-serum-cholesterol level in the pathogenesis of coronary atherosclerosis cannot yet be taken as proven, it is supported by much indirect evidence. In a survey of a multiracial community in Cape Town Bronte-Stewart et al. have shown that wide differences in the incidence of coronary heart disease in different races may be associated with a parallel difference in the mean serum-cholesterol levels. Moreover the report of a prospective study, in which blood-lipid measurements were made in healthy men who were then observed for two years, establishes clearly that elevation of blood-lipids precedes clinical coronary disease and that mean serumcholesterol concentrations appear to have a high predictive value for populations; although this cannot be applied to the clinical prediction of coronary heart-disease in the individual. In view of the radically different incidences of coronary heart disease in the two communities in Kampala and their marked differences in social, economic, and dietary backgrounds, we decided to measure serum-cholesterol concentrations in African and Asian males at three age-levels – viz., 12 years, 20 years, and over 40 years.

Unifying the definitions of sudden unexpected death in epilepsy

Sudden unexpected death in epilepsy (SUDEP) is a category of death in people with epilepsy occurring in the absence of a known structural cause of death and is most likely heterogeneous with regard to mechanisms and circumstances. SUDEP is particularly difficult to investigate in research studies for several reasons, including its relatively low incidence, its unpredictable occurrence often in unwitnessed settings, and its low rate of complete autopsy examinations. Over the past two decades, two complementary definitions have been used in most SUDEP studies, but often with variations. We propose here a unified SUDEP definition and classification to resolve current ambiguities and to retrieve cases that would not have been further studied if the previous definitions were used. The proposed Unified SUDEP Definition and Classification contains, in addition to concepts inherent in the previous definitions, nine main recommendations. (1) The word "unexpected," and not the word "unexplained," should be uniformly used in the term SUDEP. (2) The SUDEP category should be applied when appropriate, whether or not a terminal seizure is known to have occurred. (3) The "Possible SUDEP" category should be used only for cases with competing causes of death, with cases left unclassified when data are insufficient to reasonably permit their classification. (4) Cases that would otherwise fulfill the definition of SUDEP should be designated as "SUDEP Plus" when evidence indicates that a preexisting condition, known before or after autopsy, could have contributed to the death, which otherwise is classified as SUDEP (e.g., coronary insufficiency with no evidence of myocardial infarction or long-QT syndrome with no documented primary ventricular arrhythmia leading to death). (5) To be considered SUDEP, the death should have occurred within 1 h from the onset of a known terminal event. (6) For status epilepticus as an exclusion criterion for SUDEP, the duration of seizure activity should be 30 min or more. (7) A specific category of SUDEP due to asphyxia should not be designated, the distinction being largely impractical on circumstantial or autopsy evidence, with more than one mechanism likely to be contributory in many cases. (8) Death occurring in water but without circumstantial or autopsy evidence of submersion should be classified as "Possible SUDEP." If any evidence of submersion is present, the death should not be classified as SUDEP. (9) A category of "Near-SUDEP" should be agreed to include cases in which cardiorespiratory arrest was reversed by resuscitation efforts with subsequent survival for more than 1 h. Scenarios that demonstrate the basis for each SUDEP category are described. If disagreement exists about which category fits a particular case, we suggest the use of consensus decision by a panel of informed reviewers to adjudicate the classification of the case.

The prevalence of pulmonary embolism in chronically paralyzed subjects: a review of available evidence

Qualitative systematic review. To examine the validity of the prevailing notion that pulmonary embolism (PE) is rare in the chronic spinal cord injury (SCI) population. USA. Review surveys of adult SCI subjects >2 months after injury in which PE has been looked for and its prevalence estimated. A total of 16 surveys of chronic SCI subjects published between 1956 and 2009 offered data on PE prevalence. Two autopsy surveys, 178 subjects paralyzed >2 months, revealed no PE. Eleven surveys of the cause of death, 3193 subjects paralyzed 1-25 years, revealed PE in 2.1%. Two surveys of survivors of SCI, 5761 subjects paralyzed 1-25 years, revealed PE in 0.4%. Our survey of 112 subjects paralyzed 1-50 years before death, revealed PE in 21 (18.7%), based on autopsy, imaging, clinical and electrocardiographic evidence. In 7 (33%) of the 21 subjects with PE, pulmonary hypertension by transthoracic echocardiography was detected, indicating recurrent and/or unresolved PE. PE is not infrequent in the chronic SCI subject; but its presentation may be subclinical; and its apparent recurrence may lead to pulmonary hypertension.