Evidence of Renal Infection in Fatal Cases of 2009 Pandemic Influenza A (HI NI)

The 2009 pandemic influenza A (H1N1) caused significant morbidity and mortality. Acute lung injury is the hallmark of the disease, but multiple organ system dysfunction can develop and lead to death. Therefore, we sought to investigate whether there was postmortem evidence of H1N1 presence and virus-induced organ injury in autopsy specimens. Five cases in which patients died of influenza A (H1N1) virus infection were studied. The lungs of all patients showed macroscopic and microscopic findings already described for H1N1 (consolidation, edema, hemorrhage, alveolar damage, hyaline membrane, and inflammation), and H1N1 viruses were present in alveolar cells in immunochemical studies. Acute tubular necrosis was present in all cases, but there was no evidence of direct virus-induced kidney injury. Nevertheless, H1N1 viruses were found in the cytoplasm of glomerular macrophages in the kidneys of 4 patients. Therefore, our data provide strong evidence that H1N1 presence is not restricted to the lungs.

Pediatric epidemiological aspects of scorpionism and report on fatal cases from Tityus stigmurus stings (Scorpiones: Buthidae) in State of Pernambuco, Brazil

Introduction Envenomation by scorpion stings is a major public health problem in numerous tropical countries because of its frequent incidence and potential severity. Approximately 1,900 species of scorpions are known in the world, and at least 130 of these have been described in Brazil. Methods This work reports on 3 child deaths caused by Tityus stigmurus stings and characterizes epidemiological and clinical surveys on pediatric cases of scorpionism recorded in the Centro de Assistência Toxicológica de Pernambuco (Ceatox-PE). Results Scorpion stings accounted for more than 60% of all cases recorded for venomous animals. The children were from 37 cities of the Pernambuco state and accounted for 28.8% of the victims treated for scorpion stings, with the highest incidence in the metropolitan area of Recife. Stings occurred throughout the year and slightly increased during the rainy season. Independent of the elapsed time for a prognosis, most cases showed mild symptoms. Three moderate cases that resulted in death featured cardiogenic shock and/or pulmonary edema or severe neurological symptoms. For the first time, death attributed to T. stigmurus was confirmed by the presence of the scorpion. Conclusions These results suggest that scorpionism in Pernambuco is a public health problem that needs to be monitored carefully throughout the year by the government.

Risk Factors in Fatal Cases of Anaphylaxis due to Contrast Media: A Forensic Evaluation.

BACKGROUND: Fatalities following contrast medium exposure are extremely rare in clinical routine, though they may occur as an exception. Some may fall under the purview of the inquiring authorities and forensic pathologists due to their in-hospital occurrence. The purpose of this study was to assess the risk factors for anaphylaxis due to contrast medium administration that can be identified in fatal cases. METHODS: Fatalities occurred during the course of clinical investigations with contrast media described in the literature and fatal reactions to contrast agents that had undergone forensic investigations in our medicolegal center were reviewed with respect to patient characteristics, administered contrast medium, performed biochemical investigations and potential risk factors identified based on clinical history and medical records. RESULTS: Biochemical investigations into the fatal cases examined in our facility revealed increased mast cell tryptase, total IgE and activated mast cells in all subjects. Data obtained from the literature and our own investigations indicated that in only a minority of the fatal cases had there been previous exposure to contrast compounds, while most cases of severe anaphylaxis involved patients who apparently reacted on initial exposure. CONCLUSIONS: Most fatal cases failed to present any identifiable predisposing conditions out of those traditionally considered as risk factors for an anaphylactic reaction to contrast compounds in the medical histories of the patients. Comprehensive clinical histories and thorough reviews of medical data, along with exhaustive forensic investigations, provide information that is relevant in order to better appreciate the interwoven relationships linking all factors potentially involved in the pathogenesis of fatal anaphylaxis to contrast media. © 2014 S. Karger AG, Basel.

Brazilian spotted fever: Real-time PCR for diagnosis of fatal cases

Suspicion of Brazilian spotted fever (BSF) should occur in endemic regions upon surveillance of the acute febrile icteric hemorrhagic syndrome (AFIHS). However, limitations associated with currently available laboratory tests pose a challenge to early diagnosis, especially in fatal cases. Two real-time PCR (qPCR) protocols were evaluated to diagnose BSF in 110 fatal AFIHS cases, collected in BSF-endemic regions in 2009-2010. Of these, 24 were positive and 86 negative by indirect immunofluorescence (IFA) assay (cutoff IgG and/or IgM >= 128). DNA from these samples was used in the qPCR protocols: one to detect Rickettsia spp. (Citrate synthase gene) and another to determine spotted fever group (SFG) Rickettsia species (OmpA gene). Of the 24 IFA-positive samples, 5 (21%) were positive for OmpA and 9 (38%) for citrate synthase. In the IFA-negative group (n = 86), OmpA and citrate synthase were positive in 23 (27%) and 27 (31%), respectively. These results showed that the 2 qPCR protocols were about twice as sensitive as the IFA test alone (93% concordance). In conclusion, qPCR is a sensitive method for the diagnosis of fatal BSF cases and should be considered for routine surveillance of AFIHS in places like Brazil, where spotted fever-related lethality is high and other endemic diseases like dengue and leptospirosis can mislead diagnosis. (C) 2012 Elsevier GmbH. All rights reserved.

Hair morphine concentrations of fatal heroin overdose cases and living heroin users

Aims To compare heroin and other opiate use of heroin overdose fatalities, current street heroin users and drug-free therapeutic community clients. Design Hair morphine concentrations that assess heroin use and other opiate use in the 2 months preceding interview or death were compared between heroin overdose fatalities diagnosed by forensic pathologists (fOD) (n = 42), current street heroin users (CU) (n = 100) and presumably abstinent heroin users in a drug-free therapeutic community (TC) (n = 50). Setting Sydney, Australia. Findings The mean age and gender breakdown of the three samples were 32.3 years, 83% male (FOD), 28.7 years, 58% male (CU) and 28.6 years, 60% male (TC). The median blood morphine concentration among the FOD cases was 0.35 mg/l, and 82% also had other drugs detected. There were large differences between the three groups in hair morphine concentrations, with the CU group (2.10 ng/mg) having concentration approximately four times that of the FOD group (0.53 ng/mg), which in turn had a concentration approximately six times that of the TC group (0.09 ng/mg). There were no significant differences between males and females in hair concentrations within any of the groups. Hair morphine concentrations were correlated significantly with blood morphine concentrations among FOD cases (r = 0.54), and self-reported heroin use among living participants (r = 0.57). Conclusions The results indicate that fatal cases had a lower degree of chronic opiate intake than the active street users, but they were not abstinent during this period.

Infective endocarditis (IE) first diagnosed at autopsy: analysis of 31 cases in Ribeirão Preto, Brazil

Thirty one infective endocarditis (IE) fatal cases whose diagnosis was first obtained at autopsy were studied. The clinical data of these patients (Group 1) showed significant differences compared to other 141 IE cases (Group 2). The average age of 53 years in Group 1 patients was 18 years higher than that of Group 2. The Group 1 patients had a low frequency of IE predisposing heart disease. Both patient groups presented fever (about 87%), but a significant low frequency of cardiac murmur (25.8%) was observed in Group 1 patients and echocardiography tests were performed in only 16.1%, suggesting that IE diagnosis was not suspected. Likewise, although most Group 1 patients appeared with severe acute illness, they did not present the classic IE clinical presentation. Blood cultures were performed in only 64.5% of the Group 1 patients. However, bacteria were isolated in 70% of these blood cultures and Staphylococcus aureus was isolated in 71.4%. The bacteria attacked mitral and aortic valves. Complications such as embolizations and cardiac failure occurred in almost half of the cases and they also presented with infections of the lungs, urinary tract, and central nervous system. Medical procedures were performed in practically all fatal cases whose diagnosis was first obtained at autopsy. Sepsis occurred in about half of the patients and it was followed by shock in more than 25%. This form of IE must be suspected in mature and in old febrile hospitalized patients having infection predisposing diseases, embolization, and suffering medical procedures.

A study of infectious endocarditis in Ribeirão Preto, SP - Brazil. Analysis of cases occurring between 1992 and 1997

OBJECTIVE: To analyze the epidemiology, diagnosis, clinical aspects causes and evolution of infectious endocarditis. METHODS: The patients analyzed were treated at the University Hospital of the Faculdade de Medicina of Ribeirão Preto-USP and had a diagnosis of infectious endocarditis defined by Duke's criteria, which classifies infectious endocarditis as native, prosthetic valve or that occurring in intravenous drug users. RESULTS: One hundred and eighty episodes of infectious endocarditis in 168 patients were observed. Echocardiograms in 132 (73.3%) provided a diagnosis of infectious endocarditis in 111 (84%) patients; mitral valves were affected in 55 (30.5%), tricuspid valves in 30 (16.6%) and the aortic valve in 28 (15.5%) patients. Hemocultures were performed in 148 (93.8%) episodes of IE. The most commonly isolated infectious organisms were Staphylococcus aureus in 46 (27.2%) patients and Streptococcus viridans in 27 (15.9%). Complications occurred in 116 (64.4%) patients and 73 (40.5%) of the patients died. CONCLUSION: The general profile of the observed infectious endocarditis was similar to that reported in studies performed in other countries and included users of intravenous drugs. The high degree of mortality observed is not compatible with progress in diagnosis and treatment of infectious endocarditis and is probably due to the absence of diagnostic suspicion. The high frequency of fatal cases of septicemia (45.1% of deaths) in the patients studied indicates that unnoticed cases of infectious endocarditis had only been diagnosed at necropsy.

Fatal metformin overdose: case report and postmortem biochemistry contribution.

Metformin is an oral antihyperglycemic agent used in the management of type 2 diabetes mellitus. Lactic acidosis from metformin overdose is a rare complication of metformin therapy and occurs infrequently with therapeutic use. Fatal cases, both accidental and intentional, are extremely rare in clinical practice. Metformin is eliminated by the kidneys, and impaired renal function can result in an increased plasma concentration of the drug. In this report, we describe an autopsy case involving a 70-year-old woman suffering from diabetes mellitus and impaired renal function who received metformin treatment. Metformin concentrations in the peripheral blood collected during hospitalization and femoral blood collected during autopsy were 42 and 47.3 µg/ml, respectively. Lactic acidosis (29.10 mmol/l) was objectified during hospitalization. Furthermore, postmortem biochemistry allowed ketoacidosis to be diagnosed (blood β-hydroxybutyrate, 10,500 µmol/l). Death was attributed to lactic acidosis due to metformin intoxication. Increased plasma concentrations of the drug were attributed to severely impaired renal function. The case emphasizes the usefulness of performing exhaustive toxicology and postmortem biochemistry towards the more complete understanding of the pathophysiological mechanisms that may be involved in the death process.

Radiopaque stomach contents in postmortem CT in suicidal oral medication intoxication: report of three cases

In clinical medicine, plane radiography is used for detecting the remains of medications in the stomach in oral medication intoxication cases. Since postmortem computed tomography (CT), performed prior to autopsy, is currently intensively entering the forensic routine, the technique was applied to three fatal cases of oral medication intoxication. Here we report CT and autopsy findings for these cases. In all three cases, hyperdense areas within the stomach content were documented. The measurement of Hounsfield Units (HU) beyond 74HU showed mean values of 338, 88 and 98HU. Postmortem CT also showed brain edema and pulmonary aspiration in one case. At autopsy, tablet remains in the stomach were detected microscopically in all three cases. The ex vivo CT scans of the ingested medicaments showed similar HU values. Despite the fact that further case studies are necessary beyond this one, and in spite of its limitations, postmortem CT was found to be a useful screening and documentation method for stomach contents in oral medication intoxication.

Clinical Consequences Of Tityus Bahiensis And Tityus Serrulatus Scorpion Stings In The Region Of Campinas, Southeastern Brazil.

Scorpion stings account for most envenomations by venomous animals in Brazil. A retrospective study (1994-2011) of the clinical consequences of Tityus scorpion stings in 1327 patients treated at a university hospital in Campinas, southeastern Brazil, is reported. The clinical classification, based on outcome, was: dry sting (no envenoming), class I (only local manifestations), class II (systemic manifestations), class III (life-threatening manifestations, such as shock and/or cardiac failure requiring inotropic/vasopressor agents, and/or respiratory failure), and fatal. The median patient age was 27 years (interquartile interval = 15-42 years). Scorpions were brought for identification in 47.2% of cases (Tityus bahiensis 27.7%; Tityus serrulatus 19.5%). Sting severity was classified and each accounted for the following percentage of cases: dry stings - 3.4%, class I - 79.6%, class II - 15.1%, class III - 1.8% and fatal - 0.1%. Pain was the primary local manifestation (95.5%). Systemic manifestations such as vomiting, agitation, sweating, dyspnea, bradycardia, tachycardia, tachypnea, somnolence/lethargy, cutaneous paleness, hypothermia and hypotension were detected in class II or class III + fatal groups, but were significantly more frequent in the latter group. Class III and fatal cases occurred only in children <15 years old, with scorpions being identified in 13/25 cases (T. serrulatus, n = 12; T. bahiensis, n = 1). Laboratory blood abnormalities (hyperglycemia, hypokalemia, leukocytosis, elevations in serum total CK, CK-MB and troponin T, bicarbonate consumption and an increase in base deficit and blood lactate), electrocardiographic changes (ST segment) and echocardiographic alterations (ventricular ejected fraction <54%) were frequently detected in class III patients. Seventeen patients developed pulmonary edema, 16 had cardiac failure and seven had cardiogenic shock. These results indicate that most scorpion stings involved only local manifestations, mainly pain; the greatest severity was associated with stings by T. serrulatus and in children <15 years old.

Antibody Recognition Of Plasmodium Falciparum Infected Red Blood Cells By Symptomatic And Asymptomatic Individuals In The Brazilian Amazon.

In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms.

The Real-life Experience With Cardiovascular Complications In The First Dose Of Fingolimod For Multiple Sclerosis.

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.

Lsa21, a novel leptospiral protein binding adhesive matrix molecules and present during human infection

Background: It has been well documented over past decades that interaction of pathogens with the extracellular matrix (ECM) plays a primary role in host cell attachment and invasion. Adherence to host tissues is mediated by surface-exposed proteins expressed by the microorganisms during infection. The mechanisms by which pathogenic leptospires invade and colonize the host remain poorly understood since few virulence factors contributing to the pathogenesis of the disease have been identified. Whole-genome sequencing analysis of L. interrogans allowed identification of a repertoire of putative leptospiral surface proteins. Results: Here, we report the identification and characterization of a new leptospiral protein that exhibits extracellular matrix-binding properties, called as Lsa21 (leptospiral surface adhesin, 21 kDa). Compatible with its role in adhesion, the protein was shown to be surface-exposed by indirect immunofluorescence. Attachment of Lsa21 to laminin, collagen IV, and plasma fibronectin was specific and dose dependent. Laminin oxidation by sodium metaperiodate reduced the protein-laminin interaction in a concentration-dependent manner, indicating that laminin sugar moieties are crucial for this interaction. The gene coding for Lsa21 is present in pathogenic strains belonging to the L. interrogans species but was not found in the saprophytic L. biflexa serovar Patoc strain Patoc 1. Loss of gene expression occurs upon culture attenuation of pathogenic strains. Environmental factors such as osmolarity and temperature affect Lsa21 expression at the transcriptional level. Moreover, anti-Lsa21 serum labeled liver and kidney tissues of human fatal cases of leptospirosis. Conclusion: Our data suggest a role of Lsa21 in the pathogenesis of leptospirosis.

Association between intratumoral lymphatic microvessel density (LMVD) and clinicopathologic features in endometrial cancer: a retrospective cohort study

Background: Lymph node metastasis in endometrial cancer significantly decreases survival rate. Few data on the influence of intratumoral lymphatic microvessel density (LMVD) on survival in endometrial cancer are available. Our aim was to assess the intratumoral LMVD of endometrial carcinomas and to investigate its association with classical pathological factors, lymph node metastasis and survival. Methods: Fifty-seven patients with endometrial carcinoma diagnosed between 2000 and 2008 underwent complete surgical staging and evaluation of intratumoral LMVD and other histologic variables. Lymphatic microvessels were identified by immunohistochemical staining using monoclonal antibody against human podoplanin (clone D2-40) and evaluated by counting the number of immunostained lymphatic vessels in 10 hot spot areas at 400x magnification. The LMVD was expressed by the mean number of vessels in these 10 hot spot microscopic fields. We next investigated the association of LMVD with the clinicopathologic findings and prognosis. Results: The mean number of lymphatic vessels counted in all cases ranged between 0 and 4.7. The median value of mean LMVD was 0.5, and defined the cut-off for low and high LMVD. We identified low intratumoral LMVD in 27 (47.4%) patients and high LMVD in 30 (52.6%) patients. High intratumoral LMVD was associated with lesser miometrial and adnaexal infiltration, lesser cervical and peritoneal involvement, and fewer fatal cases. Although there was lower lymph node involvement among cases with high LMVD, the difference did not reach significance. No association was seen between LMVD and FIGO staging, histological type, or vascular invasion. On the other hand, low intratumoral LMVD was associated with poor outcome. Seventy-five percent of deaths occurred in patients with low intratumoral LMVD. Conclusion: Our results show association of high intratumoral LMVD with features related to more localized disease and better outcome. We discuss the role of lymphangiogenesis as an early event in the endometrial carcinogenesis.

Airway smooth muscle thickness in asthma is related to severity but not duration of asthma

Asthma is characterised by an increased airway smooth muscle (ASM) area (ASMarea) within the airway wall. The present study examined the relationship of factors including severity and duration of asthma to ASMarea. The perimeter of the basement membrane (PBM) and ASMarea were measured on transverse sections of large and small airways from post mortem cases of fatal (n=107) and nonfatal asthma (n=37) and from control subjects (n=69). The thickness of ASM (ASMarea/PBM) was compared between asthma groups using multivariate linear regression. When all airways were considered together, ASMarea/PBM (in millimetres) was increased in nonfatal (median 0.04; interquartile range 0.013-0.051; p=0.034) and fatal cases of asthma (0.048; 0.025-0.078; p<0.001) compared with controls (0.036; 0.024-0.042). Compared with cases of nonfatal asthma, ASMarea/PBM was greater in cases of fatal asthma in large (p<0.001) and medium (p<0.001), but not small, airways. ASMarea/PBM was not related to duration of asthma, age of onset of asthma, sex or smoking. No effect due to study centre, other than that due to sampling strategy, was found. The thickness of the ASM layer is increased in asthma and is related to the severity of asthma but not its duration.