Subacute Sclerosing Panencephalitis in a Child with Human Immunodeficiency Virus Co-Infection.

PubMed

Maurya, Pradeep Kumar; Thakkar, Mayur Deepak; Kulshreshtha, Dinkar; Singh, Ajai Kumar; Thacker, Anup Kumar

2016-12-01

Subacute sclerosing panencephalitis is a fatal infectious disease of childhood caused by persistence of the measles virus in the brain. The effect of human immunodeficiency virus (HIV) co-infection on subacute sclerosing panencephalitis remains elusive and rare. We report a child who developed subacute sclerosing panencephalitis following a short latency period and a rapidly progressive course with HIV co-infection. © 2016 Marshfield Clinic.

Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide.

PubMed

Jacobson, Lisa A; Rane, Shruti; McReynolds, Lisa J; Steppan, Diana A; Chen, Allen R; Paz-Priel, Ido

2016-07-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare, generally progressive, and potentially fatal syndrome of unclear etiology. The syndrome is characterized by normal development followed by a sudden, rapid hyperphagic weight gain beginning during the preschool period, hypothalamic dysfunction, and central hypoventilation, and is often accompanied by personality changes and developmental regression, leading to substantial morbidity and mortality. We describe 2 children who had symptomatic and neuropsychological improvement after high-dose cyclophosphamide treatment. Our experience supports an autoimmune pathogenesis and provides the first neuropsychological profile of patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. Copyright © 2016 by the American Academy of Pediatrics.

Liver transplant in ethylmalonic encephalopathy: a new treatment for an otherwise fatal disease.

PubMed

Dionisi-Vici, Carlo; Diodato, Daria; Torre, Giuliano; Picca, Stefano; Pariante, Rosanna; Giuseppe Picardo, Sergio; Di Meo, Ivano; Rizzo, Cristiano; Tiranti, Valeria; Zeviani, Massimo; De Ville De Goyet, Jean

2016-04-01

Ethylmalonic encephalopathy is a fatal, rapidly progressive mitochondrial disorder caused by ETHE1 mutations, whose peculiar clinical and biochemical features are due to the toxic accumulation of hydrogen sulphide and of its metabolites, including thiosulphate. In mice with ethylmalonic encephalopathy, liver-targeted adeno-associated virus-mediated ETHE1 gene transfer dramatically improved both clinical course and metabolic abnormalities. Reasoning that the same achievement could be accomplished by liver transplantation, we performed living donor-liver transplantation in an infant with ethylmalonic encephalopathy. Unlike the invariably progressive deterioration of the disease, 8 months after liver transplantation, we observed striking neurological improvement with remarkable achievements in psychomotor development, along with dramatic reversion of biochemical abnormalities. These results clearly indicate that liver transplantation is a viable therapeutic option for ETHE1 disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis.

PubMed

Carlesi, Cecilia; Pasquali, Livia; Piazza, Selina; Lo Gerfo, Annalisa; Caldarazzo Ienco, Elena; Alessi, Rosaria; Fornai, Francesco; Siciliano, Gabriele

2011-03-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disorder of unknown aetiology that involves the loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Significant progress in understanding the cellular mechanisms of motor neuron degeneration in ALS has not been matched with the development of therapeutic strategies to prevent disease progression, and riluzole remains the only available therapy, with only marginal effects on disease survival. More recently alterations of mRNA processing in genetically defined forms of ALS, as those related to TDP-43 and FUS-TLS gene mutations have provided important insights into the molecular networks implicated in the disease pathogenesis. Here we review some of the recent progress in promoting therapeutic strategies for neurodegeneration.

Skin infection caused by Scedosporium apiospermum in immunocompromised patients. Report of two cases.

PubMed

Valenzuela Salas, I; Martinez Peinado, C; Fernandez Miralbell, A; Soto Diaz, Augustin; Nogueras Morillas, P; Martin Castro, A; Tercedor Sanchez, J; Garcia Mellado, V

2013-10-16

Scedosporium apiospermum is a filamentous fungus that can cause cutaneous or extracutaneous disease. A large number of cases have been published over the last decades, mainly in patients immunocompromised as a result of their disease or treatment. These kinds of infections can progress rapidly and become disseminated, leading to very serious or even fatal complications. We report two new cases of skin infection by Scedosporium apiospermum from our hospital.

Fatal hypertriglyceridaemia, acute pancreatitis and diabetic ketoacidosis possibly induced by quetiapine.

PubMed

Madsen, Kristian Roerbaek

2014-01-08

A 27-year-old man treated with quetiapine for anxiety disorder developed hypertriglyceridaemia-induced acute pancreatitis and diabetic ketoacidosis. He was otherwise physically healthy with no family history of hyperlipidaemia. Despite aggressive intensive therapy he died of multiorgan failure within 36 h from initial presentation. While second-generation antipsychotics are well known to be causally linked to diabetes and hyperlipidaemia, this is to my knowledge the first-described case of a fatal triad of extreme hypertriglyceridaemia, acute pancreatitis and diabetic ketoacidosis possibly induced by quetiapine. Clinicians should be aware of this rare clinical presentation since rapid progression to multiorgan failure can occur. Early supportive therapy should be initiated. Lactescent serum and ketoacidosis in severe acute pancreatitis should not be overlooked-initiate insulin therapy and possibly plasmapheresis in case of extreme hypertriglyceridaemia.

Fatal interstitial lung disease associated with icotinib.

PubMed

Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi; Chen, Rongchang

2014-12-01

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment.

Fatal interstitial lung disease associated with icotinib

PubMed Central

Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi

2014-01-01

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment. PMID:25590006

Fatal familial insomnia presenting with agrypnia excitata and very low atonia index level: A case report and literature review.

PubMed

Yang, Tae-Won; Park, Byeongsu; Kim, Keun Tae; Jun, Jin-Sun; Kim, Young-Soo; Lee, Soon-Tae; Jung, Keun-Hwa; Chu, Kon; Lee, Sang Kun; Jung, Ki-Young

2018-05-01

Fatal familial insomnia (FFI) is a human prion disease that is characterized by sleep-wake cycle deterioration, loss of slow-wave sleep, and motor overactivation over the daily 24-hour period. Here, we report the case of a 57-year-old man who had an irregular sleep-wake cycle and exhibited frequent movements and vocalizations during sleep. Video-polysomnography showed disrupted sleep structure, rapid alternation between sleep stages, and an absence of sleep spindles and slow-wave sleep. Moreover, body movements persisted throughout the entire sleep period, including rapid eye movement (REM) sleep. The atonia index was very low (<0.025) during REM sleep. Genetic testing revealed a prion protein gene mutation at codon 178, and the patient was diagnosed with FFI. We tried to treat with amantadine, doxycycline, and immunotherapies, but the disease progressed. Sleep disturbance is the most frequent and essential symptom of FFI. FFI is difficult to diagnose due to the low sensitivity of diagnostic tools. Diagnoses can be further supported by better knowledge of typical polysomnographic findings.

Prophylaxis and Immunization in Mice by Use of Virus-Free Defective T Particles to Protect Against Intracerebral Infection by Vesicular Stomatitis Virus

PubMed Central

Doyle, Michael; Holland, John J.

1973-01-01

Defective interfering T particles of vesicular stomatitis virus provide remarkable protection against viral disease and death when introduced intracerebrally in large numbers along with an otherwise rapidly fatal low dose of standard infectious virus. This profound prophylactic effect of defective T particles is due to homologous autointerference since it is serotype-specific and interferon is not induced. This protective effect can be demonstrated only with preparations of T particles that have been purified completely free of infectious virions. When pure T particles are injected intracerebrally along with large doses of infectious virus, they convert an otherwise rapidly fatal disease process to a slowly progressing virus infection that generally terminates in death after many days of wasting disease and paralysis. Intracerebral injection of virus-free T particles alone is apparently innocuous to mice and stimulates immunity to massive doses of homologous infectious virus. In vitro, virus-free T particles at extremely high multiplicities depress cellular RNA and protein synthesis and kill BHK21 cells in culture, but do not exhibit such effects at moderately high multiplicities. PMID:4352972

A case report for fatal Churg-Strauss syndrome complications: first reported death due to rapid progression of prominently huge hepatic capsular hematoma and multi-system organ hemorrhage

PubMed Central

Qian, Jiejing; Tong, Hongyan; Chen, Feifei; Mai, Wenyuan; Lou, Yinjun; Jin, Jie

2014-01-01

Churg-Strauss syndrome (CSS) is a rare disease that has an extremely low incidence rate. CSS prognosis is good, in general; and there are no reports of multiple-organ hemorrhage in CSS. We report a unique case of CSS, wherein, an elderly man experienced multiple organ hemorrhage -- a particularly huge hematoma under the capsule of the liver and poor prognosis. PMID:25419420

[A tamponade complicating an acute eosinophilic pericarditis due to a myeloproliferative/myelodysplastic syndrome].

PubMed

de Moreuil, C; Lieber, A; Marjanovic, Z; Bobbio, A; Alavi, Z; Blacher, J; Marie, J-P

2016-02-01

Cardiac involvement in eosinophilia is potentially fatal and requires early diagnosis and prompt treatment. We report here the case of a 71-year-old female patient with eosinophilia>10,000/mm(3) for 2 months due to a myeloproliferative/myelodysplastic syndrome, with a rapidly progressive exertional dyspnea explained by an important circumferential eosinophilic pericarditis. Due to a rapid evolution to a tamponade, an emergent surgical drainage was performed. Subsequent medical treatment combined high-dose corticosteroids (1mg/kg/day) with hydroxyurea and imatinib. The outcome was favourable with regression of the effusion, of the volume overload symptoms and decrease in eosinophilia. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Rapidly developing gas gangrene due to a simple puncture wound.

PubMed

Oncel, Selim; Arsoy, Emin Sami

2010-06-01

Gas gangrene, an infection caused by Clostridium perfringens, is a potentially fatal and physically disabling disease due to its sometimes incredibly rapid progression. An adolescent boy was referred to our university hospital with a history of nail puncture in the hand that occurred a few hours previously. The physical examination revealed a swollen and tender arm with crepitations up to the shoulder. Gas was coming out from the puncture wound with digital pressure on the forearm. The plain radiograph of the arm was typical of gas gangrene with the presence of gas under the skin and between muscular fibrils.Having received 1 dose of meropenem, the boy had surgery, in which his entire upper extremity had to be disarticulated from the shoulder. The maintenance antimicrobial therapy with intravenously administered penicillin G and clindamycin was continued for a duration of 10 days, at the end of which, the patient was discharged.The rapidly progressive character and the dramatic ending of this case made us wonder whether antimicrobial prophylaxis would play any role in the preventive management of puncture wounds.

A social change perspective on injury prevention in China.

PubMed

Ozanne-Smith, Joan; Li, Qingfeng

2018-05-05

China has undergone massive social change over the past four decades. Since national estimates became available in 1987, the overall fatal injury rate has decreased. This paper investigates targeted interventions and sociodemographic factors that may have contributed to fatal injury rate changes particularly for road traffic fatality (RTF), suicide and drowning. (1) To review the recent epidemiology of injury in China.(2)To investigate factors influencing trends in overall and specific cause injury mortality rates. Published injury mortality statistics and related literature were reviewed. Factors potentially influencing trends were investigated in the context of rapid development based on literature reviews of targeted interventions, macrolevel and microlevel contextual factors and changes specific to RTF, suicide and drowning. Overall estimated national injury mortality rates in China decreased between 1987 and 2015, despite a rapid rise in RTF. Suicide and drowning rates decreased significantly and falls displaced drowning among the leading causes. The higher female to male suicide ratio reversed. Differences were observed in frequencies and proportions of deaths by major cause by age group and over time. Economic and structural development and related social change in this period include: urbanisation, changes in demographics, life choices (eg, internal migration), education, poverty alleviation, health insurance and relevant regulations/legislation. These factors potentially explain much of the change in fatal injury rates in China. Data limitations persist. Increased investment in data and research would provide realistic opportunities for accelerated progress in implementing effective targeted interventions to further reduce China's injury burden. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

R3-R4 deletion in the PRNP gene is associated with Creutzfeldt-Jakob disease (CJD)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cervenakova, L.; Brown, P.; Nagle, J.

1994-09-01

There are conflicting reports on the association of deletions in the PRNP gene on chromosome 20 with CJD, a rapidly progressive fatal spongiform encephalopathy. We accumulated data suggesting that a deletion of R3-R4 type (parts of the third and fourth repeats are deleted from the area of four repeating 24 bp sequences in the 5{prime} region of the gene) is causing CJD. Screening of 129 unaffected control individuals demonstrated presence of a deletion of R2 type in four (1.55% of the studied chromosomes), but none of them had the R3-R4 type. Of 181 screened patients with spongiform encephalopathies, two hadmore » a deletion of R3-R4 type with no other mutations in the coding sequence. Both patients had a classical rapidly progressive dementing disease and diffuse spongiform degeneration, and both cases were apparently sporadic. The same R3-R4 type of deletion was detected in three additional neuropathologically confirmed spongiform encephalopathy patients, of which two had other known pathogenic mutations in the PRNP gene: at codon 178 on the methionine allele exhibiting the phenotype of fatal familial insomnia, and codon 200 causing CJD with severe dementia; the third was a patient with iatrogenic CJD who developed the disease after treatment with growth hormone extracted from cadaveric human pituitary glands. In all cases the deletion coincided with a variant sequence at position 129 coding for methionine.« less

Progress in reducing the burden of stroke.

PubMed

Chalmers, J; Chapman, N

2001-12-01

1. The burden of stroke worldwide is growing rapidly, driven by an ageing population and by the rapid rate of urbanization and industrialization in the developing world. There are approximately 5 million fatal and 15 million non-fatal strokes each year and over 50 million survivors of stroke alive, worldwide, today. 2. The most important determinant of stroke risk is blood pressure, with a strong, continuous relationship between the level of the systolic and diastolic pressures and the risk of initial and recurrent stroke, in both Western and Asian populations. 3. Randomized clinical trials have clearly demonstrated that blood pressure lowering reduces the risk of initial stroke by 35-40% in hypertensive patients; but, until recently, there was no conclusive evidence that blood pressure lowering was effective in the secondary prevention of stroke. 4. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) has provided definitive evidence that blood pressure lowering in patients with previous stroke or transient ischaemic attack (TIA) reduces the incidence of secondary stroke by 28%, of major vascular events by 26% and of major coronary events by 26%. These reductions were all magnified by approximately 50% in a subgroup of patients in whom the angiotensin-converting enzyme inhibitor perindopril was routinely combined with the diuretic indapamide. 5. Successful global implementation of a treatment with perindopril and indapamide in patients with a history of stroke or TIA would markedly reduce the burden of stroke and could avert between 0.5 and one million strokes each year, worldwide.

Fatal spontaneous Clostridium septicum gas gangrene: a possible association with iatrogenic gastric acid suppression.

PubMed

Wu, Yiru E; Baras, Alexander; Cornish, Toby; Riedel, Stefan; Burton, Elizabeth C

2014-06-01

The long-term use of proton pump inhibitors has been linked to an increased risk for the development of gastric polyps, hip fractures, pneumonia, and Clostridium difficile colitis. There is evidence that chronic acid suppression from long-term use of proton pump inhibitors poses some risk for the development of C difficile-associated diarrhea by decreasing the elimination of pathogenic microbes before reaching the lower gastrointestinal tract. Here we present a case of a 51-year-old woman with a recent history of abdominal pain and fever who presented to the emergency department with rapidly progressive spontaneous necrotizing fasciitis and gas gangrene and died within hours of presentation. Postmortem examination confirmed spreading tissue gas gangrene and myonecrosis. In addition, multiple intestinal ulcers containing Clostridium septicum were present at autopsy. This case illustrates a possible association between proton pump inhibitor therapy and fatal C septicum infection.

Management of a young female patient with Fournier's gangrene and Lemierre's syndrome.

PubMed

Aslanidis, Theodoros; Myrou, Athena; Giannakou-Peftoulidou, Maria

2014-01-01

Fournier's gangrene is an acute, rapidly progressive, and potentially fatal, infective necrotizing fasciitis affecting the external genitalia, perineal or perianal regions. Lemierre's syndrome is a condition characterized by thrombophlebitis of the internal jugular vein and bacteremia caused by primarily anaerobic organisms, following a recent oropharyngeal infection. Although the literature about either of them is rich, there is no report about co-appearance of the two syndromes. We present the case of a young healthy female patient who suffered concomitantly from Fournier's gangrene and Lemierre's syndrome after minor surgery.

Diagnostic criteria for selenium toxicosis in aquatic birds: histologic lesions

USGS Publications Warehouse

Green, D.E.; Albers, P.H.

1997-01-01

Chronic selenium toxicosis was induced in 1-year-old male mallard ducks (Anas platyrhynchos) by feeding selenium, as seleno-DL-methionine, in amounts of 0, 10, 20, 40, and 80 parts per million (ppm) to five groups of 21 ducks each for 16 wk during March to July 1988. All mallards in the 80 ppm group, three in the 40 ppm group, and one in the 20 ppm group died. Histologic lesions in mallards that died of selenosis were hepatocellular vacuolar degeneration progressing to centrolobular and panlobular necrosis, nephrosis, apoptosis of pancreatic exocrine cells, hypermaturity and avascularity of contour feathers of the head with atrophy of feather follicles, lymphocytic necrosis and atrophy of lymphoid organs (spleen, gut-associated lymphoid tissue, and lumbar lymph nodes), and severe atrophy and degeneration of fat. Histologic lesions in surviving mallards in the 40 ppm group, which had tissue residues of selenium comparable to mallards that died, were fewer and much milder than mallards that died; lesions consisted of atrophy of lymphoid tissue, hyalinogranular swelling of hepatocytes, atrophy of seminiferous tubules, and senescence of feathers. No significant histologic lesions were detected in euthanized mallards in the 0, 10 and 20 ppm groups. Based on tissue residues and histologic findings, primarily in the liver, there was a threshold of selenium accumulation above which pathophysiologic changes were rapid and fatal. Pathognomonic histologic lesions of fatal and nonfatal selenosis were not detected. Criteria for diagnosis of fatal selenosis in aquatic birds include consistent histologic lesions in the liver, kidneys, and organs of the immune system. Although histologic changes were present in cases of chronic non-fatal selenosis, these were inconsistent. Consistent features of fatal and non-fatal chronic selenosis were marked weight loss and elevated concentrations of selenium in organs.

Hexamethonium reverses the lethal cardiopulmonary damages in a rat model of brainstem lesions mimicking fatal enterovirus 71 encephalitis.

PubMed

Lu, Wen-Hsien; Hsieh, Kai-Sheng; Lu, Pei-Jung; Wu, Yi-Shan; Ho, Wen-Yu; Lai, Chi-Cheng; Wang, Jyh-Seng; Ger, Luo-Ping; Hsiao, Michael; Tseng, Ching-Jiunn

2013-05-01

Among enterovirus 71 infections, brainstem encephalitis progressing abruptly to cardiac dysfunction and pulmonary edema causes rapid death within several hours. However, no currently known early indicators and treatments can monitor or prevent the unexpectedly fulminant course. We investigate the possible mechanisms and treatment of fatal enterovirus 71 infections to prevent the abrupt progression to cardiac dysfunction and pulmonary edema by using an animal model. Treatment study. Research laboratory. Sprague-Dawley rats. We microinjected 6-hydroxydopamine or vitamin C into nucleus tractus solitarii of the rat and evaluated the cardiopulmonary changes after treatment with ganglionic blocker. The time course of changes in the heart and lungs of rats with brainstem lesions were investigated. Rats were administered 6-hydroxydopamine to induce brainstem lesions, causing acute hypertension in 10 minutes and acute elevations of catecholamines accompanied by acute cardiac dysfunction and increased strong expressions of connexin 43 gap junction protein in heart and lung specimens by immunohistochemical staining within 3 hours. Severe pulmonary hemorrhagic edema was produced within 6 hours, and the rats expired rapidly within 7 hours. After hexamethonium treatment, it was found that the acute hypertension induced by 6-hydroxydopamine lesions was immediately reversed and the acute high rise of catecholamine serum level was significantly attenuated within 3 hours, accompanied by preserved cardiac output and decreased expressions of connexin 43 in the heart and lungs. No pulmonary edema occurred and the rats survived for more than 14 hours. Early hexamethonium treatment attenuates acute excessive release of catecholamines to prevent cardiac dysfunction and pulmonary edema for increasing survival rate.

Epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China

PubMed Central

Liang, He; Fan, Jin-Hu; Qiao, You-Lin

2017-01-01

Esophageal cancer is one of the most fatal diseases worldwide mainly because of its rapid progression and poor prognosis. Although the incidence of esophageal adenocarcinoma has markedly risen in North America and Europe in the past several decades, esophageal squamous cell carcinoma is still the predominant subtype of esophageal cancer, especially in China. It accounts for more than 90% of all esophageal squamous cell carcinoma cases in China. Geographical differentiation is one of the most distinctive characteristics of esophageal cancer. The progression, risk factors, and prognosis of these two subtypes of esophageal cancer differ. This study reviews the epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China, thereby providing systematic references for policy-makers who will decide on issues of esophageal cancer prevention and control. PMID:28443201

Indian reservation safety improvement program : a methodology and case study.

DOT National Transportation Integrated Search

2013-10-01

The need to reduce fatal and injury crashes on Tribal lands has been recognized for years. The U.S. has : realized a decline in fatal crashes over the past several years but fatal crashes continue to increase on : Tribal lands. Little progress has be...

Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor

PubMed Central

Kim, Yunjeong; Liu, Hongwei; Galasiti Kankanamalage, Anushka C.; Weerasekara, Sahani; Hua, Duy H.; Groutas, William C.; Chang, Kyeong-Ok; Pedersen, Niels C.

2016-01-01

Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans. PMID:27027316

Fatal BK virus pneumonia following stem cell transplantation.

PubMed

Akazawa, Y; Terada, Y; Yamane, T; Tanaka, S; Aimoto, M; Koh, H; Nakane, T; Koh, K-R; Nakamae, H; Ohsawa, M; Wakasa, K; Hino, M

2012-12-01

We report the case of a 39-year-old male patient who died of severe BK virus (BKV) pneumonia 168 days after hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After suffering from BKV-associated late-onset hemorrhagic cystitis (HC) with long-term sustained BKV viremia, he died of rapidly progressive pneumonia. On autopsy, numerous viral intranuclear inclusions were seen in his lungs and bladder. An immunohistochemical examination of his lungs was positive for simian virus 40. Based on these pathological results and the high sustained BKV viral load in his blood, we reached a diagnosis of BKV pneumonia. Viral infection can occasionally become life threatening among HSCT recipients. It is widely known that BKV can cause late-onset HC, but BKV-associated pneumonia is rare. Because of its rapid progression and poor prognosis, it is difficult to make an antemortem diagnosis of BKV pneumonia. A treatment strategy for BKV pneumonia also needs to be formulated. Similar to other viral pathogens, BKV can cause pneumonia and the clinician should therefore be aware of it in immunocompromised patients. © 2012 John Wiley & Sons A/S.

Rapidly Progressive Disseminated Sporotrichosis as the First Presentation of HIV Infection in a Patient with a Very Low CD4 Cell Count

PubMed Central

de Oliveira-Esteves, Isis Cristine Morávia Ribeiro; Basílio-de-Oliveira, Rodrigo Panno; de Araujo, Luciana Ferreira; Martins, Carlos José; Neves-Motta, Rogério; Velho Mendes de Azevedo, Marcelo Costa; Signorini, Dario José Hart Pontes; Francisco da Cunha Pinto, Jorge; Moura, Lívia Machado; Laterça, Rafael Jacyntho; Pereira, Diogo Raphael Garcia de Oliveira; do Lago, Isabela Vieira; Raphael de Almeida Ferry, Fernando

2017-01-01

Sporotrichosis is a human and animal disease caused by species of the Sporothrix schenckii complex. It is classically acquired through traumatic inoculation of fungal elements. Most frequently, sporotrichosis presents as a fixed cutaneous or as a lymphocutaneous form. A much smaller number of cases occur as cutaneous disseminated and disseminated forms. These cases require immediate diagnosis and management to reduce morbidity and mortality. We present the case of a 34-year-old male patient in whom the first presentation of HIV infection was a rapidly progressive sporotrichosis with multiple cutaneous lesions, a high fungal burden in tissues, and pulmonary involvement. He had an extremely low CD4 cell count (06/mm3). Treatment with amphotericin B deoxycholate led to complete clinical resolution. Sporotrichosis remains a neglected opportunistic infection among HIV-infected patients in Rio de Janeiro state, Brazil, and awareness of this potentially fatal infection is of utmost importance if treatment is not to be delayed and if potentially devastating complications are to be avoided. PMID:29147593

Rapidly Progressive Disseminated Sporotrichosis as the First Presentation of HIV Infection in a Patient with a Very Low CD4 Cell Count.

PubMed

de Oliveira-Esteves, Isis Cristine Morávia Ribeiro; Almeida Rosa da Silva, Guilherme; Eyer-Silva, Walter de Araujo; Basílio-de-Oliveira, Rodrigo Panno; de Araujo, Luciana Ferreira; Martins, Carlos José; Neves-Motta, Rogério; Velho Mendes de Azevedo, Marcelo Costa; Signorini, Dario José Hart Pontes; Francisco da Cunha Pinto, Jorge; Moura, Lívia Machado; Laterça, Rafael Jacyntho; Pereira, Diogo Raphael Garcia de Oliveira; do Lago, Isabela Vieira; Raphael de Almeida Ferry, Fernando

2017-01-01

Sporotrichosis is a human and animal disease caused by species of the Sporothrix schenckii complex. It is classically acquired through traumatic inoculation of fungal elements. Most frequently, sporotrichosis presents as a fixed cutaneous or as a lymphocutaneous form. A much smaller number of cases occur as cutaneous disseminated and disseminated forms. These cases require immediate diagnosis and management to reduce morbidity and mortality. We present the case of a 34-year-old male patient in whom the first presentation of HIV infection was a rapidly progressive sporotrichosis with multiple cutaneous lesions, a high fungal burden in tissues, and pulmonary involvement. He had an extremely low CD4 cell count (06/mm 3 ). Treatment with amphotericin B deoxycholate led to complete clinical resolution. Sporotrichosis remains a neglected opportunistic infection among HIV-infected patients in Rio de Janeiro state, Brazil, and awareness of this potentially fatal infection is of utmost importance if treatment is not to be delayed and if potentially devastating complications are to be avoided.

Paraneoplastic subacute lower motor neuron syndrome associated with solid cancer.

PubMed

Verschueren, Annie; Gallard, Julien; Boucraut, José; Honnorat, Jerome; Pouget, Jean; Attarian, Shahram

2015-11-15

We retrospectively analyzed three patients with pure motor neuronopathy followed for more than four years in our center. The patients presented a rapidly progressive lower motor neuron syndrome (LMNS) over the course of a few weeks leading to a severe functional impairment. The neurological symptoms preceded the diagnosis of a breast adenocarcinoma and a thymoma in the first two patients, one of them with anti-CV2/CRMP5 antibodies. Cancer was not detected in the third patient who had circulating anti-Hu antibodies. A final diagnosis of paraneoplastic syndrome was made after investigations for alternative causes of lower motor neuron syndrome. Early diagnosis, combined treatment of the underlying cancer, and immunomodulatory treatment led to neurological improvement of the disease in two out of the three cases in which the cancer was diagnosed. Cases of subacute LMNS with rapid progression may occur as an expression of a paraneoplastic neurological syndrome. Identification of these syndromes is important, as the treatment of underlying malignancy along with immunomodulatory treatment may result in a favorable long-term outcome of these potentially fatal diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Research progress on combat trauma treatment in cold regions.

PubMed

Wang, Hui-Shan; Han, Jin-Song

2014-01-01

Cold regions are a special combat environment in which low temperatures have a great impact on human metabolism and other vital functions, including the nervous, motion, cardiovascular, circulatory, respiratory, and urinary systems; consequently, low temperatures often aggravate existing trauma, leading to high mortality rates if rapid and appropriate treatment is not provided. Hypothermia is an independent risk factor of fatality following combat trauma; therefore, proactive preventative measures are needed to reduce the rate of mortality. After summarizing the basic research on battlefield environments and progress in the prevention and treatment of trauma, this article concludes that current treatment and prevention measures for combat trauma in cold regions are inadequate. Future molecular biology studies are needed to elucidate the mechanisms and relevant cell factors underlying bodily injury caused by cold environment, a research goal will also allow further exploration of corresponding treatments.

Clinical characteristics of acute encephalopathy with acute brain swelling: A peculiar type of acute encephalopathy.

PubMed

Nukui, Megumi; Kawawaki, Hisashi; Inoue, Takeshi; Kuki, Ichiro; Okazaki, Shin; Amo, Kiyoko; Togawa, Masao; Ishikawa, Junichi; Rinka, Hiroshi; Shiomi, Masashi

2018-06-07

Acute encephalopathy has been observed with acute brain swelling (ABS) that is characterized by rapid progression to whole-brain swelling. The objective of this study was to describe the clinical characteristics of ABS. We encountered four patients with ABS and retrospectively investigated their clinical data with a medical chart review. Three patients had seizure clustering or status epilepticus in the clinical course. Signs of elevated intracranial pressure (ICP) appeared 3-9 h after the first convulsive attack in three patients. In all patients, signs of brainstem involvement appeared 1-8 h after signs of elevated ICP. Mild hyponatremia that progressed after signs of elevated ICP appeared was noted in three patients. Brain CT revealed mild brain swelling in the initial phase, which rapidly progressed to whole-brain swelling. No focal abnormalities were detected on brain MRI in one patient. Continuous electroencephalography was initially normal, but in two patients, high-amplitude slow waves appeared with rapid changes before signs of brainstem involvement. Although recovery was achieved without sequelae in two patients, outcome was fatal for the other two. The pathogenesis of ABS has yet to be clarified, but clinical features in our patients are not consistent with any established subtypes of acute encephalopathy. Therefore, we believe that ABS should be recognized as a new type of acute encephalopathy. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Descending necrotizing mediastinitis: report of a case following steroid neck injection.

PubMed

Harar, R P S; Cranston, C; Warwick-Brown, N

2002-10-01

Cervical necrotizing fasciitis is a rare, rapidly progressive, severe bacterial infection of the soft tissues of the neck. Uncommonly, it may descend into the mediastinum. We describe a case of descending necrotizing mediastinitis in a young man, where there was diagnostic confusion and delay, with an eventual fatal outcome. A steroid injection for neck pain is thought to be the source of infection. In this case, the signs of mediastinitis were initially masked, and the diagnosis delayed until cardiopulmonary arrest occurred. Early recognition with a low threshold for computed tomography (CT) scanning is essential. Aggressive multidisciplinary therapy with mediastinal drainage is mandatory.

Rabies: Rare Human Infection - Common Questions.

PubMed

Willoughby, Rodney E

2015-12-01

Rabies is an acute, rapidly progressive encephalitis that is almost always fatal. Prophylaxis is highly effective but economics limits disease control. The mechanism of death from rabies is unclear. It is poorly cytopathic and poorly inflammatory. Rabies behaves like an acquired metabolic disorder. There may be a continuum of disease severity. History of animal bite is rare. The diagnosis is often missed. Intermittent encephalopathy, dysphagia, hydrophobia and aerophobia, and focal paresthesias or myoclonic jerks suggest rabies. Laboratory diagnosis is cumbersome but sensitive. Treatment is controversial but survivors are increasingly reported, with good outcomes in 4 of 8 survivors. Copyright © 2015 Elsevier Inc. All rights reserved.

Pocket Guide to Transportation 2011

DOT National Transportation Integrated Search

2011-01-01

The safety of the traveling public is the number one concern of the U.S. Department of Transportation. Although progress has been made in reducing fatalities, roughly 94 percent of transportation fatalities arose from motor vehicle crashes. Injuries ...

Development of a SARS Coronavirus Vaccine from Recombinant Spike Protein Plus Delta Inulin Adjuvant.

PubMed

McPherson, Clifton; Chubet, Richard; Holtz, Kathy; Honda-Okubo, Yoshikazu; Barnard, Dale; Cox, Manon; Petrovsky, Nikolai

2016-01-01

Given periodic outbreaks of fatal human infections caused by coronaviruses, development of an optimal coronavirus vaccine platform capable of rapid production is an ongoing priority. This chapter describes the use of an insect cell expression system for rapid production of a recombinant vaccine against severe acute respiratory syndrome coronavirus (SARS). Detailed methods are presented for expression, purification, and release testing of SARS recombinant spike protein antigen, followed by adjuvant formulation and animal testing. The methods herein described for rapid development of a highly protective SARS vaccine are equally suited to rapid development of vaccines against other fatal human coronavirus infections, e.g., the MERS coronavirus.

Good outcome of brain stem progressive multifocal leukoencephalopathy in an immunosuppressed renal transplant patient: Importance of early detection and rapid immune reconstitution.

PubMed

Sauer, Roland; Gölitz, Philipp; Jacobi, Johannes; Schwab, Stefan; Linker, Ralf A; Lee, De-Hyung

2017-04-15

Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remission of symptoms with improvement of the brain stem lesion over a follow-up over 20months. In summary, early detection of PML and consequent treatment may improve neurological outcomes even in brain stem disease with a notorious bad prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Atypical cause of forearm skin ulceration in a leukaemic child: mucormycosis. A case report.

PubMed

Zirak, C; Brutus, J P; De Mey, A

2005-01-01

Primary cutaneous mucormycosis is an uncommon, deep and aggressive fungal infection occurring mainly in immunosuppressed or diabetic patients. Rapid diagnosis and therapy are necessary to prevent a fatal outcome. An eight-year-old leukaemic child presented with a dark necrotic ulcer on the volar-ulnar aspect of the left forehand. The lesion had developed over seven days, beginning as a vasculo-haemorrhagic erythematous plaque. There was no known history of trauma to the area, but skin necrosis from external compression caused by an intravenous line could not be completely ruled out. The lesion rapidly progressed to a 5 x 8 cm painful necrotic ulcer with an erythematous border. Treatment with ichthyol dressing and intra-venous antibiotherapy failed to improve the condition. Wide debridement was performed and specimens were sent for microbiology and pathology examinations. Microscopic examination demonstrated broad, irregularly walled, non-septate fungal hyphae that were consistent with Mucor. Amphotericin B was administrated intravenously (1 mg/kg/day) and hydrogel and hydrophile adhesive polyurethane foam dressings were applied. After 12 days, the soft tissue defect was covered with a split-thickness skin graft, harvested from the lateral aspect of the thigh. Diagnosis of this infection is based on complete histopathological and microbiological studies. Awareness, and a high index of suspicion are required because of the potential fulminant and fatal course.

The Syrian hamster model of hantavirus pulmonary syndrome

PubMed Central

Safronetz, David; Ebihara, Hideki; Feldmann, Heinz; Hooper, Jay W.

2012-01-01

Hantavirus pulmonary syndrome (HPS) is a relatively rare, but frequently fatal disease associated with New World hantaviruses, most commonly Sin Nombre and Andes viruses in North and South America, respectively. It is characterized by fever and the sudden, rapid onset of severe respiratory distress and cardiogenic shock, which can be fatal in up to 50% of cases. Currently there are no approved antiviral therapies or vaccines for the treatment or prevention of HPS. A major obstacle in the development of effective medical countermeasures against highly pathogenic agents like the hantaviruses is recapitulating the human disease as closely as possible in an appropriate and reliable animal model. To date, the only animal model that resembles HPS in humans is the Syrian hamster model. Following infection with Andes virus, hamsters develop HPS-like disease which faithfully mimics the human condition with respect to incubation period and pathophysiology of disease. Perhaps most importantly, the sudden and rapid onset of severe respiratory distress observed in humans also occurs in hamsters. The last several years has seen an increase in studies utilizing the Andes virus hamster model which have provided unique insight into HPS pathogenesis as well as potential therapeutic and vaccine strategies to treat and prevent HPS. The purpose of this article is to review the current understanding of HPS disease progression in Syrian hamsters and discuss the suitability of utilizing this model to evaluate potential medical countermeasures against HPS. PMID:22705798

Fatal Rocky Mountain Spotted Fever along the United States–Mexico Border, 2013–2016

PubMed Central

Yaglom, Hayley; Casal, Mariana; Fierro, Maria; Kriner, Paula; Murphy, Brian; Kjemtrup, Anne; Paddock, Christopher D.

2017-01-01

Rocky Mountain spotted fever (RMSF) is an emerging public health concern near the US–Mexico border, where it has resulted in thousands of cases and hundreds of deaths in the past decade. We identified 4 patients who had acquired RMSF in northern Mexico and subsequently died at US healthcare facilities. Two patients sought care in Mexico before being admitted to US-based hospitals. All patients initially had several nonspecific signs and symptoms, including fever, headache, nausea, vomiting, or myalgia, but deteriorated rapidly without receipt of a tetracycline-class antimicrobial drug. Each patient experienced respiratory failure late in illness. Although transborder cases are not common, early recognition and prompt initiation of appropriate treatment are vital for averting severe illness and death. Clinicians on both sides of the US–Mexico border should consider a diagnosis of RMSF for patients with rapidly progressing febrile illness and recent exposure in northern Mexico. PMID:28930006

Fatal Rocky Mountain Spotted Fever along the United States-Mexico Border, 2013-2016.

PubMed

Drexler, Naomi A; Yaglom, Hayley; Casal, Mariana; Fierro, Maria; Kriner, Paula; Murphy, Brian; Kjemtrup, Anne; Paddock, Christopher D

2017-10-01

Rocky Mountain spotted fever (RMSF) is an emerging public health concern near the US-Mexico border, where it has resulted in thousands of cases and hundreds of deaths in the past decade. We identified 4 patients who had acquired RMSF in northern Mexico and subsequently died at US healthcare facilities. Two patients sought care in Mexico before being admitted to US-based hospitals. All patients initially had several nonspecific signs and symptoms, including fever, headache, nausea, vomiting, or myalgia, but deteriorated rapidly without receipt of a tetracycline-class antimicrobial drug. Each patient experienced respiratory failure late in illness. Although transborder cases are not common, early recognition and prompt initiation of appropriate treatment are vital for averting severe illness and death. Clinicians on both sides of the US-Mexico border should consider a diagnosis of RMSF for patients with rapidly progressing febrile illness and recent exposure in northern Mexico.

Co-Infection of Rickettsia rickettsii and Streptococcus pyogenes: Is Fatal Rocky Mountain Spotted Fever Underdiagnosed?

PubMed Central

Raczniak, Gregory A.; Kato, Cecilia; Chung, Ida H.; Austin, Amy; McQuiston, Jennifer H.; Weis, Erica; Levy, Craig; Carvalho, Maria da Gloria S.; Mitchell, Audrey; Bjork, Adam; Regan, Joanna J.

2014-01-01

Rocky Mountain spotted fever, a tick-borne disease caused by Rickettsia rickettsii, is challenging to diagnose and rapidly fatal if not treated. We describe a decedent who was co-infected with group A β-hemolytic streptococcus and R. rickettsii. Fatal cases of Rocky Mountain spotted fever may be underreported because they present as difficult to diagnose co-infections. PMID:25331804

Fatal Babesia canis canis infection in a splenectomized Estonian dog.

PubMed

Tiškina, Valentina; Capligina, Valentina; Must, Külli; Berzina, Inese; Ranka, Renate; Jokelainen, Pikka

2016-01-25

A previously splenectomized dog from Estonia was presented with a sudden lack of appetite and discoloration of the urine. Despite supportive therapy, its condition deteriorated dramatically during 1 day. Severe thrombocytopenia and high numbers of protozoan hemoparasites were evident in blood smears, and the hematocrit dropped from 46 to 33 %. The dog was euthanized before specific antibabesial treatment was initiated. Blood samples from the dog and from two other dogs in the same household tested positive for Babesia using molecular methods, and the sequences of partial 18S rRNA gene confirmed the causative species as Babesia canis canis. The risk of severe, rapidly progressing babesiosis in splenectomized dogs merits awareness.

Streptococcus pneumoniae necrotizing fasciitis in systemic lupus erythematosus.

PubMed

Sánchez, A; Robaina, R; Pérez, G; Cairoli, E

2016-04-01

Necrotizing fasciitis is a rapidly progressive destructive soft tissue infection with high mortality. Streptococcus pneumoniae as etiologic agent of necrotizing fasciitis is extremely unusual. The increased susceptibility to Streptococcus pneumoniae infection in patients with systemic lupus erythematosus is probably a multifactorial phenomenon. We report a case of a patient, a 36-year-old Caucasian female with 8-year history of systemic lupus erythematosus who presented a fatal Streptococcus pneumoniae necrotizing fasciitis. The role of computed tomography and the high performance of blood cultures for isolation of the causative microorganism are emphasized. Once diagnosis is suspected, empiric antibiotic treatment must be prescribed and prompt surgical exploration is mandatory. © The Author(s) 2015.

Gasoline Prices and Their Relationship to Rising Motorcycle Fatalities, 1990–2007

PubMed Central

Stimpson, Jim P.; Hilsenrath, Peter E.

2009-01-01

Motor vehicle accidents are the leading cause of death among young adults. Although automobile fatalities have declined in recent years, motorcycle fatalities are rapidly increasing. The purpose of our research was to quantify the relationship between changing fuel prices and motorcycle fatalities. Our findings suggest that people increasingly rely on motorcycles to reduce their fuel costs in response to rising gasoline prices. We estimate that use of motorcycles and scooters instead of 4-wheeled vehicles results in over 1500 additional motorcycle fatalities annually for each dollar increase in gas prices. Motorcycle safety should receive more attention as a leading public health issue. PMID:19696374

Clinical characteristics of 26 human cases of highly pathogenic avian influenza A (H5N1) virus infection in China.

PubMed

Yu, Hongjie; Gao, Zhancheng; Feng, Zijian; Shu, Yuelong; Xiang, Nijuan; Zhou, Lei; Huai, Yang; Feng, Luzhao; Peng, Zhibin; Li, Zhongjie; Xu, Cuiling; Li, Junhua; Hu, Chengping; Li, Qun; Xu, Xiaoling; Liu, Xuecheng; Liu, Zigui; Xu, Longshan; Chen, Yusheng; Luo, Huiming; Wei, Liping; Zhang, Xianfeng; Xin, Jianbao; Guo, Junqiao; Wang, Qiuyue; Yuan, Zhengan; Zhou, Longnv; Zhang, Kunzhao; Zhang, Wei; Yang, Jinye; Zhong, Xiaoning; Xia, Shichang; Li, Lanjuan; Cheng, Jinquan; Ma, Erdang; He, Pingping; Lee, Shui Shan; Wang, Yu; Uyeki, Timothy M; Yang, Weizhong

2008-08-21

While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008. Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6-62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5 x 10(9) cells/L vs 93.0 x 10(9) cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003). The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases.

Central Nervous System Pathology Progresses Independently of KC and CXCR2 in Globoid-Cell Leukodystrophy

PubMed Central

Reddy, Adarsh S.; Patel, Jigisha R.; Vogler, Carole; Klein, Robyn S.; Sands, Mark S.

2013-01-01

Globoid-cell Leukodystrophy (GLD; Krabbe’s disease) is a rapidly progressing inherited demyelinating disease caused by a deficiency of the lysosomal enzyme Galactosylceramidase (GALC). Deficiency of GALC leads to altered catabolism of galactosylceramide and the cytotoxic lipid, galactosylsphingosine (psychosine). This leads to a rapidly progressive fatal disease with spasticity, cognitive disability and seizures. The murine model of GLD (Twitcher; GALC−/−) lacks the same enzyme and has similar clinical features. The deficiency of GALC leads to oligodendrocyte death, profound neuroinflammation, and the influx of activated macrophages into the CNS. We showed previously that keratinocyte chemoattractant factor (KC) is highly elevated in the CNS of untreated Twitcher mice and significantly decreases after receiving a relatively effective therapy (bone marrow transplantation combined with gene therapy). The action of KC is mediated through the CXCR2 receptor and is a potent chemoattractant for macrophages and microglia. KC is also involved in oligodendrocyte migration and proliferation. Based on the commonalities between the disease presentation and the functions of KC, we hypothesized that KC and/or CXCR2 contribute to the pathogenesis of GLD. Interestingly, the course of the disease is not significantly altered in KC- or CXCR2-deficient Twitcher mice. There is also no alteration in inflammation or demyelination patterns in these mice. Furthermore, transplantation of CXCR2-deficient bone marrow does not alter the progression of the disease as it does in other models of demyelination. This study highlights the role of multiple redundant cytokines and growth factors in the pathogenesis of GLD. PMID:23755134

The Syrian hamster model of hantavirus pulmonary syndrome.

PubMed

Safronetz, David; Ebihara, Hideki; Feldmann, Heinz; Hooper, Jay W

2012-09-01

Hantavirus pulmonary syndrome (HPS) is a relatively rare, but frequently fatal disease associated with New World hantaviruses, most commonly Sin Nombre and Andes viruses in North and South America, respectively. It is characterized by fever and the sudden, rapid onset of severe respiratory distress and cardiogenic shock, which can be fatal in up to 50% of cases. Currently there are no approved antiviral therapies or vaccines for the treatment or prevention of HPS. A major obstacle in the development of effective medical countermeasures against highly pathogenic agents like the hantaviruses is recapitulating the human disease as closely as possible in an appropriate and reliable animal model. To date, the only animal model that resembles HPS in humans is the Syrian hamster model. Following infection with Andes virus, hamsters develop HPS-like disease which faithfully mimics the human condition with respect to incubation period and pathophysiology of disease. Perhaps most importantly, the sudden and rapid onset of severe respiratory distress observed in humans also occurs in hamsters. The last several years has seen an increase in studies utilizing the Andes virus hamster model which have provided unique insight into HPS pathogenesis as well as potential therapeutic and vaccine strategies to treat and prevent HPS. The purpose of this article is to review the current understanding of HPS disease progression in Syrian hamsters and discuss the suitability of utilizing this model to evaluate potential medical countermeasures against HPS. Copyright © 2012 Elsevier B.V. All rights reserved.

Infection Associated Secondary Hemophagocytic Lymphohistiocytosis in Sepsis Syndromes - A Tip of an Iceberg.

PubMed

Agarwal, Arun; Agarwal, Aakanksha

2016-10-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare, underdiagnosed, fatal and devastating hyperinflammatory syndrome that has gained increasing recognition over the past decade. Patients with HLH present with clinical and laboratory evidence of uncontrolled inflammation. Delay in diagnosis and management inevitably leads to a rapidly progressive and fatal course. In this case series, we present 7 cases of secondary HLH (sHLH) in adults with their presentation, course, and outcomes. We retrospectively looked at the 7 cases of secondary HLH who were diagnosed and managed in our institute between January 2013 and august 2015. Medical records were retrieved from medical records department and data analyzed and tabulated. The median age at diagnosis was 35 years (age range 26-72 years). Diagnosis was based on HLH 2004 diagnostic criteria. We report profile of 7 adult patients with sHLH. All patients had a short history of illness (<2 weeks) and presented uniformly with prolonged fever, bi or trilineage cytopenia and multiorgan dysfunction syndrome (MODS) at admission or developed MODS during the course of their illness. None of them had prediagnosed HLH. All patients fulfilled 5 to 6 of 8 criteria as per HLH 2014 diagnostic criteria. The median length of hospital stay was 12 days (range 7-50 days) and the median time to diagnosis was 5 days (range 3 to 21 days). Mortality was 57%. HLH is a rare and under-diagnosed clinical syndrome and is rapidly fatal if not diagnosed and managed timely. The cases reported in literature probably represent a tip of an iceberg of large number of undiagnosed cases mostly labeled as sepsis with MODS in critical care units. sHLH should be suspected in any patient who present with persistent and prolonged fever, transaminitis, cytopenia, and high serum Ferritin or dramatically rising serial serum Ferritin. Early diagnosis and prompt aggressive treatment are vital for patients' survival and favorable outcome.

Infection Associated Secondary Hemophagocytic Lymphohistiocytosis in Sepsis Syndromes - A Tip of an Iceberg.

PubMed

Agarwal, Arun; Agarwal, Aakanksha

2017-10-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare, underdiagnosed, fatal and devastating hyperinflammatory syndrome that has gained increasing recognition over the past decade. Patients with HLH present with clinical and laboratory evidence of uncontrolled inflammation. Delay in diagnosis and management inevitably leads to a rapidly progressive and fatal course. In this case series, we present 7 cases of secondary HLH (sHLH) in adults with their presentation, course, and outcomes. We retrospectively looked at the 7 cases of secondary HLH who were diagnosed and managed in our institute between January 2013 and august 2015. Medical records were retrieved from medical records department and data analyzed and tabulated. The median age at diagnosis was 35 years (age range 26-72 years). Diagnosis was based on HLH 2004 diagnostic criteria. We report profile of 7 adult patients with sHLH. All patients had a short history of illness (<2 weeks) and presented uniformly with prolonged fever, bi or trilineage cytopenia and multiorgan dysfunction syndrome (MODS) at admission or developed MODS during the course of their illness. None of them had prediagnosed HLH. All patients fulfilled 5 to 6 of 8 criteria as per HLH 2014 diagnostic criteria. The median length of hospital stay was 12 days (range 7-50 days) and the median time to diagnosis was 5 days (range 3 to 21 days). Mortality was 57%. HLH is a rare and under-diagnosed clinical syndrome and is rapidly fatal if not diagnosed and managed timely. The cases reported in literature probably represent a tip of an iceberg of large number of undiagnosed cases mostly labeled as sepsis with MODS in critical care units. sHLH should be suspected in any patient who present with persistent and prolonged fever, transaminitis, cytopenia, and high serum Ferritin or dramatically rising serial serum Ferritin. Early diagnosis and prompt aggressive treatment are vital for patients' survival and favorable outcome.

Identifying countermeasure strategies to increase safety of older pedestrians : traffic tech.

DOT National Transportation Integrated Search

2013-07-01

Pedestrian deaths accounted for 13% of all traffic fatalities : in 2010. While adults 65 and older made up 13% of the U.S. : population, they accounted for 19% of all pedestrian fatalities : in 2010. This age group is rapidly expanding in size : and ...

Case report: Co-infection of Rickettsia rickettsii and Streptococcus pyogenes: is fatal Rocky Mountain spotted fever underdiagnosed?

PubMed

Raczniak, Gregory A; Kato, Cecilia; Chung, Ida H; Austin, Amy; McQuiston, Jennifer H; Weis, Erica; Levy, Craig; Carvalho, Maria da Gloria S; Mitchell, Audrey; Bjork, Adam; Regan, Joanna J

2014-12-01

Rocky Mountain spotted fever, a tick-borne disease caused by Rickettsia rickettsii, is challenging to diagnose and rapidly fatal if not treated. We describe a decedent who was co-infected with group A β-hemolytic streptococcus and R. rickettsii. Fatal cases of Rocky Mountain spotted fever may be underreported because they present as difficult to diagnose co-infections. © The American Society of Tropical Medicine and Hygiene.

Acute Promyelocytic Leukemia Presenting as Focal Neurologic Findings and Deteriorating Mental Status.

PubMed

Dolan, Matthew; Ngaruiya, Christine

2017-01-01

Acute promyelocytic leukemia (APL) is a rare but particularly malignant form of acute leukemia that is characterized by a rapid progression to fatal hemorrhage. Survival rates of patients with APL have increased with the introduction of all-trans retinoic acid (ATRA), but early deaths caused by hemorrhage still persist. A man with undiagnosed APL presenting with focal neurologic findings and deteriorating altered mental status caused by an intracranial hemorrhage is discussed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important to consider APL when diagnosing etiologies for intracranial hemorrhage. In addition to standard care, early administration of ATRA is recommended upon clinical suspicion of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Percutaneous cardiopulmonary support to treat suspected venous air embolism with cardiac arrest during open eye surgery: a case report.

PubMed

Shin, Seokyung; Nam, Bokyung; Soh, Sarah; Koo, Bon-Nyeo

2014-11-01

We report a case of possible venous air embolism (VAE) during trans pars plana vitrectomy with air-fluid exchange of the vitreous cavity. Shortly after initiation of air-fluid exchange, decreases in end-tidal CO2, oxygen saturation, and blood pressure were observed. The patient rapidly progressed to cardiac arrest unresponsive to cardiopulmonary resuscitation, and recovered after the application of percutaneous cardiopulmonary support. Prompt termination of air infusion is needed when VAE is suspected during air-fluid exchange, and extracorporeal life support should be considered in fatal cases. Although the incidence is rare the possibility of VAE during ophthalmic surgery clearly exists, and therefore awareness and vigilant monitoring seem critical.

Hypokalemic Paralysis: A Hidden Card of Several Autoimmune Diseases

PubMed Central

Velarde-Mejía, Yelitza; Gamboa-Cárdenas, Rocío; Ugarte-Gil, Manuel; Asurza, César Pastor

2017-01-01

Acute hypokalemic paralysis is a rare and potentially fatal condition, with few related causes, one of which highlights distal renal tubular acidosis (dRTA). Distal renal tubular acidosis is a rare complication of several autoimmune diseases such as systemic lupus erythematosus, Sjögren’s syndrome, and Hashimoto thyroiditis. We report a case of a lupic patient who presented rapidly progressive quadriparesis in the context of active renal disease. Research revealed severe refractory hypokalemia, metabolic acidosis, and alkaline urine suggestive of dRTA. We diagnosed Sjögren’s syndrome based on sicca symptoms, an abnormal salivary glands’ nuclear scan and the presence of anti-Ro/SSA and anti-La/SSB. In addition, the finding of thyroid peroxidase, thyroglobulin antibodies, and hypothyroidism led us to the diagnosis of Hashimoto thyroiditis. Due to the active renal involvement on the context of systemic lupus erythematosus and Sjögren’s syndrome, the patient received immunosuppression with rituximab, resulting in a progressive and complete improvement. PMID:28839447

Tyzzer's disease in foals: retrospective studies from 1969 to 2010.

PubMed

Swerczek, Thomas W

2013-09-01

Reports of 148 cases of Tyzzer's disease in foals in central Kentucky were analyzed to identify features of the disease and factors associated with it. The records indicate that Tyzzer's disease is a rapidly progressive, highly fatal hepatitis caused by Clostridium piliforme. Common clinical findings are lethargy, fever, anorexia, and icterus. Seizures, coma, and death may rapidly ensue. Laboratory findings are leukopenia, metabolic acidosis, hypoglycemia, and increased activity of hepatic enzymes. Diagnosis is primarily based on clinical signs and postmortem findings but a polymerase chain reaction (PCR) is now available to detect C. piliforme DNA in organs and feces. Disease occurred most frequently in foals between 9 and 30 days of age that were born in April to May and was associated with heavy rainfall in the spring and high protein and nitrogenous diets fed to nursing mares. The findings are consistent with the ingestion of C. piliforme in the feces of adult horses and overgrowth in the intestine of foals with a high level of nutrients in their intestine.

Reverse engineering--rapid prototyping of the skull in forensic trauma analysis.

PubMed

Kettner, Mattias; Schmidt, Peter; Potente, Stefan; Ramsthaler, Frank; Schrodt, Michael

2011-07-01

Rapid prototyping (RP) comprises a variety of automated manufacturing techniques such as selective laser sintering (SLS), stereolithography, and three-dimensional printing (3DP), which use virtual 3D data sets to fabricate solid forms in a layer-by-layer technique. Despite a growing demand for (virtual) reconstruction models in daily forensic casework, maceration of the skull is frequently assigned to ensure haptic evidence presentation in the courtroom. Owing to the progress in the field of forensic radiology, 3D data sets of relevant cases are usually available to the forensic expert. Here, we present a first application of RP in forensic medicine using computed tomography scans for the fabrication of an SLS skull model in a case of fatal hammer impacts to the head. The report is intended to show that this method fully respects the dignity of the deceased and is consistent with medical ethics but nevertheless provides an excellent 3D impression of anatomical structures and injuries. © 2011 American Academy of Forensic Sciences.

Computer Vision Malaria Diagnostic Systems-Progress and Prospects.

PubMed

Pollak, Joseph Joel; Houri-Yafin, Arnon; Salpeter, Seth J

2017-01-01

Accurate malaria diagnosis is critical to prevent malaria fatalities, curb overuse of antimalarial drugs, and promote appropriate management of other causes of fever. While several diagnostic tests exist, the need for a rapid and highly accurate malaria assay remains. Microscopy and rapid diagnostic tests are the main diagnostic modalities available, yet they can demonstrate poor performance and accuracy. Automated microscopy platforms have the potential to significantly improve and standardize malaria diagnosis. Based on image recognition and machine learning algorithms, these systems maintain the benefits of light microscopy and provide improvements such as quicker scanning time, greater scanning area, and increased consistency brought by automation. While these applications have been in development for over a decade, recently several commercial platforms have emerged. In this review, we discuss the most advanced computer vision malaria diagnostic technologies and investigate several of their features which are central to field use. Additionally, we discuss the technological and policy barriers to implementing these technologies in low-resource settings world-wide.

Fatal primary amoebic meningoencephalitis in a Norwegian tourist returning from Thailand

PubMed Central

Reiakvam, Olaug Marie; Stensvold, Christen Rune; Hermansen, Nils Olav; Holberg-Petersen, Mona; Antal, Ellen-Ann; Gaustad, Knut; Førde, Ingrid Schage; Heger, Bernt

2016-01-01

Introduction: Primary amoebic meningoencephalitis (PAM) is a rare disease caused by the free-living amoeba Naegleria fowleri. Infection occurs by insufflation of water containing amoebae into the nasal cavity, and is usually associated with bathing in freshwater. Nasal irrigation is a more rarely reported route of infection. Case presentation: A fatal case of PAM in a previously healthy Norwegian woman, acquired during a holiday trip to Thailand, is described. Clinical findings were consistent with rapidly progressing meningoencephalitis. The cause of infection was discovered by chance, owing to the unexpected detection of N. fowleri DNA by a PCR assay targeting fungi. A conclusive diagnosis was established based on sequencing of N. fowleri DNA from brain biopsies, supported by histopathological findings. Nasal irrigation using contaminated tap water is suspected as the source of infection. Conclusion: The clinical presentation of PAM is very similar to severe bacterial meningitis. This case is a reminder that when standard investigations fail to identify a cause of infection in severe meningoencephalitis, it is of crucial importance to continue a broad search for a conclusive diagnosis. PAM should be considered as a diagnosis in patients with symptoms of severe meningoencephalitis returning from endemic areas. PMID:28348761

Fatal primary amoebic meningoencephalitis in a Norwegian tourist returning from Thailand.

PubMed

Stubhaug, Tore Taksdal; Reiakvam, Olaug Marie; Stensvold, Christen Rune; Hermansen, Nils Olav; Holberg-Petersen, Mona; Antal, Ellen-Ann; Gaustad, Knut; Førde, Ingrid Schage; Heger, Bernt

2016-06-01

Primary amoebic meningoencephalitis (PAM) is a rare disease caused by the free-living amoeba Naegleria fowleri . Infection occurs by insufflation of water containing amoebae into the nasal cavity, and is usually associated with bathing in freshwater. Nasal irrigation is a more rarely reported route of infection. A fatal case of PAM in a previously healthy Norwegian woman, acquired during a holiday trip to Thailand, is described. Clinical findings were consistent with rapidly progressing meningoencephalitis. The cause of infection was discovered by chance, owing to the unexpected detection of N. fowleri DNA by a PCR assay targeting fungi. A conclusive diagnosis was established based on sequencing of N. fowleri DNA from brain biopsies, supported by histopathological findings. Nasal irrigation using contaminated tap water is suspected as the source of infection. The clinical presentation of PAM is very similar to severe bacterial meningitis. This case is a reminder that when standard investigations fail to identify a cause of infection in severe meningoencephalitis, it is of crucial importance to continue a broad search for a conclusive diagnosis. PAM should be considered as a diagnosis in patients with symptoms of severe meningoencephalitis returning from endemic areas.

Reducing health care hazards: lessons from the commercial aviation safety team.

PubMed

Pronovost, Peter J; Goeschel, Christine A; Olsen, Kyle L; Pham, Julius C; Miller, Marlene R; Berenholtz, Sean M; Sexton, J Bryan; Marsteller, Jill A; Morlock, Laura L; Wu, Albert W; Loeb, Jerod M; Clancy, Carolyn M

2009-01-01

The movement to improve quality of care and patient safety has grown, but examples of measurable and sustained progress are rare. The slow progress made in health care contrasts with the success of aviation safety. After a tragic 1995 plane crash, the aviation industry and government created the Commercial Aviation Safety Team to reduce fatal accidents. This public-private partnership of safety officials and technical experts is responsible for the decreased average rate of fatal aviation accidents. We propose a similar partnership in the health care community to coordinate national efforts and move patient safety and quality forward.

Efficacy of concurrent treatments in idiopathic pulmonary fibrosis patients with a rapid progression of respiratory failure: an analysis of a national administrative database in Japan.

PubMed

Oda, Keishi; Yatera, Kazuhiro; Fujino, Yoshihisa; Ishimoto, Hiroshi; Nakao, Hiroyuki; Hanaka, Tetsuya; Ogoshi, Takaaki; Kido, Takashi; Fushimi, Kiyohide; Matsuda, Shinya; Mukae, Hiroshi

2016-06-08

Some IPF patients show a rapid progression of respiratory failure. Most patients are treated with high-dose corticosteroids. However, no large clinical studies have investigated the prognosis or efficacy of combined treatments including high-dose corticosteroids in IPF patients with a rapid progression of respiratory failure. We enrolled IPF patients who received mechanical ventilation and high-dose corticosteroids between April 2010 and March 2013. Records were extracted from a Japanese nationwide inpatient database. We conducted a retrospective epidemiologic and prognostic analysis. Two hundred nine patients receiving an average of 12.8 days of ventilatory support were enrolled. There were 138 (66 %) fatal cases; the median survival was 21 days. The short-term (within 30 days) and long-term (within 90 days) survival rates were 44.6 and 24.6 %, respectively. The average monthly admission rate among the IPF patients with the rapid progression of respiratory failure in the winter was significantly higher than that in spring (p = 0.018). Survival did not differ to a statistically significant extent in the different geographic areas of Japan. Survivors were significantly younger (p = 0.002) with higher rates of mild dyspnea on admission (p = 0.012), they more frequently underwent bronchoscopy (p < 0.001), and received anticoagulants (p = 0.027), co-trimoxazole (p < 0.001) and macrolide (p = 0.02) more frequently than non-survivors. A multivariate logistic analysis demonstrated that two factors were significantly associated with a poor prognosis: >80 years of age (OR = 2.94, 95 % Cl 1.044-8.303; p = 0.041) and the intravenous administration of high-dose cyclophosphamide (OR = 3.17, 95 % Cl 1.101-9.148; p = 0.033). Undergoing bronchoscopy during intubation (OR = 0.25, 95 % Cl 0.079-0.798; p = 0.019) and the administration of co-trimoxazole (OR = 0.28, 95 % Cl 0.132-0.607; p = 0.001) and macrolides (OR = 0.37, 95 % Cl 0.155-0.867; p = 0.033) were significantly associated with a good prognosis. The dosage of co-trimoxazole significantly correlated with survival. Co-trimoxazole and macrolides may be a good addition to high-dose corticosteroids in the treatment of IPF patients with a rapid progression of respiratory failure.

JC Polyomavirus Attachment, Entry, and Trafficking: Unlocking the Keys to a Fatal Infection

PubMed Central

Maginnis, Melissa S.; Nelson, Christian D.S.; Atwood, Walter J.

2014-01-01

The human JC polyomavirus (JCPyV) causes a lifelong persistent infection in the reno-urinary tract in the majority of the adult population worldwide. In healthy individuals infection is asymptomatic, while in immunocompromised individuals the virus can spread to the central nervous system and cause a fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). There are currently very few treatment options for this rapidly progressing and devastating disease. Understanding the basic biology of JCPyV-host cell interactions is critical for the development of therapeutic strategies to prevent or treat PML. Research in our laboratory has focused on gaining a detailed mechanistic understanding of the initial steps in the JCPyV life cycle in order to define how JCPyV selectively targets cells in the kidney and brain. JCPyV requires sialic acids to attach to host cells and initiate infection, and JCPyV demonstrates specificity for the oligosaccharide lactoseries tetrasaccharide c (LSTc) with an α2,6-linked sialic acid. Following viral attachment, JCPyV entry is facilitated by the 5-hydroxytryptamine (5-HT)2 family of serotonin receptors via clathrin-dependent endocytosis. JCPyV then undergoes retrograde transport to the endoplasmic reticulum (ER) where viral disassembly begins. A novel retrograde transport inhibitor termed Retro-2cycl prevents trafficking of JCPyV to the ER and inhibits both initial virus infection and infectious spread in cell culture. Understanding the molecular mechanisms by which JCPyV establishes infection will open up new avenues for the prevention or treatment of virus-induced disease. PMID:25078361

Rabies - epidemiology, pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review.

PubMed

Singh, Rajendra; Singh, Karam Pal; Cherian, Susan; Saminathan, Mani; Kapoor, Sanjay; Manjunatha Reddy, G B; Panda, Shibani; Dhama, Kuldeep

2017-12-01

Rabies is a zoonotic, fatal and progressive neurological infection caused by rabies virus of the genus Lyssavirus and family Rhabdoviridae. It affects all warm-blooded animals and the disease is prevalent throughout the world and endemic in many countries except in Islands like Australia and Antarctica. Over 60,000 peoples die every year due to rabies, while approximately 15 million people receive rabies post-exposure prophylaxis (PEP) annually. Bite of rabid animals and saliva of infected host are mainly responsible for transmission and wildlife like raccoons, skunks, bats and foxes are main reservoirs for rabies. The incubation period is highly variable from 2 weeks to 6 years (avg. 2-3 months). Though severe neurologic signs and fatal outcome, neuropathological lesions are relatively mild. Rabies virus exploits various mechanisms to evade the host immune responses. Being a major zoonosis, precise and rapid diagnosis is important for early treatment and effective prevention and control measures. Traditional rapid Seller's staining and histopathological methods are still in use for diagnosis of rabies. Direct immunofluoroscent test (dFAT) is gold standard test and most commonly recommended for diagnosis of rabies in fresh brain tissues of dogs by both OIE and WHO. Mouse inoculation test (MIT) and polymerase chain reaction (PCR) are superior and used for routine diagnosis. Vaccination with live attenuated or inactivated viruses, DNA and recombinant vaccines can be done in endemic areas. This review describes in detail about epidemiology, transmission, pathogenesis, advances in diagnosis, vaccination and therapeutic approaches along with appropriate prevention and control strategies.

SARS and MERS: recent insights into emerging coronaviruses.

PubMed

de Wit, Emmie; van Doremalen, Neeltje; Falzarano, Darryl; Munster, Vincent J

2016-08-01

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses.

Fatal Human Case of Zika and Chikungunya Virus Co-Infection with Prolonged Viremia and Viruria.

PubMed

Silva, Kelly R; Bica, Blanca E R G; Pimenta, Eduardo S; Serafim, Rodrigo B; Abreu, Mirhelen M; Gonçalves, Jorge L S; Santana, Larissa de S; Cabral-Castro, Mauro J; Peralta, José M; Cavalcanti, Marta G

2018-06-21

Zika virus (ZIKV) infection usually presents as a mild and self-limited illness, but it may be associated with severe outcomes. We describe a case of a 30-year-old man with systemic erythematous lupus and common variable immunodeficiency who became infected with both Zika (ZIKV) and Chikungunya (CHIKV) virus during the 2016 outbreak in Rio de Janeiro, Brazil. The patient presented with intense wrist and right ankle arthritis, and ZIKV RNA and virus particles were detected in synovial tissue, blood and urine, and CHIKV RNA in serum sample, at the time of the diagnosis. During the follow up, ZIKV RNA persisted for 275 days post symptoms onset. The patient evolved with severe arthralgia/arthritis and progressive deterioration of renal function. Fatal outcome occurred after 310 days post ZIKV and CHIKV co-infection onset. The results show the development of severe disease and fatal outcome of ZIKV infection in an immunosuppressed adult. The data suggests a correlation between immunodeficiency and prolonged ZIKV RNA shedding in both blood and urine with progressive disease. The results also indicate a possible role for arbovirus co-infections as risk factors for severe and fatal outcomes from ZIKV infection.

[Increasing Number of Road Traffic Fatalities in Germany - Turnaround or Snap-Shot].

PubMed

Brand, S; Schmucker, U; Lob, G; Haasper, C; Juhra, C; Hell, W; Rieth, P; Matthes, G

2017-04-01

Introduction: For the first time since 20 years, the number of road accident fatalities in 2011 increased on German roads compared to earlier periods. Methods and Results: The presented paper submitted by the expert group for accident prevention investigates and discusses possible reasons for the observed increase in road traffic fatalities. Results: Climate changes as well as changes in economic environment, and technological progress in car and passenger safety are identified as possible reasons for the observed increase. Discussion: Mentioning the "Decade of Action for Road Safety" initiated by the UNO and coordinated by the WHO, the overall goal is a worldwide reduction of accident related road fatalities. But prognostic calculations predict an asymptotic approximation to a limit of road fatalities. To achieve a reduction by half until 2020 intense collaboration and disproportional expenditure are necessary. Conclusion: From the authors' point of view the current increase of traffic fatalities in Germany is rated as a snapshot rather than a turnaround. Georg Thieme Verlag KG Stuttgart · New York.

Assessing the impact of Syrian refugees on earthquake fatality estimations in southeast Turkey

NASA Astrophysics Data System (ADS)

Wilson, Bradley; Paradise, Thomas

2018-01-01

The influx of millions of Syrian refugees into Turkey has rapidly changed the population distribution along the Dead Sea Rift and East Anatolian fault zones. In contrast to other countries in the Middle East where refugees are accommodated in camp environments, the majority of displaced individuals in Turkey are integrated into local cities, towns, and villages - placing stress on urban settings and increasing potential exposure to strong earthquake shaking. Yet displaced populations are often unaccounted for in the census-based population models used in earthquake fatality estimations. This study creates a minimally modeled refugee gridded population model and analyzes its impact on semi-empirical fatality estimations across southeast Turkey. Daytime and nighttime fatality estimates were produced for five fault segments at earthquake magnitudes 5.8, 6.4, and 7.0. Baseline fatality estimates calculated from census-based population estimates for the study area varied in scale from tens to thousands of fatalities, with higher death totals in nighttime scenarios. Refugee fatality estimations were analyzed across 500 semi-random building occupancy distributions. Median fatality estimates for refugee populations added non-negligible contributions to earthquake fatalities at four of five fault locations, increasing total fatality estimates by 7-27 %. These findings communicate the necessity of incorporating refugee statistics into earthquake fatality estimations in southeast Turkey and the ongoing importance of placing environmental hazards in their appropriate regional and temporal context.

Impact Of Rapid Incident Detection On Freeway Accident Fatalities

DOT National Transportation Integrated Search

1996-06-01

Heavily congested urban highways in the United States have spurred the development of Freeway Management Systems (FMS). Among the goals of these systems is the improvement of traffic management and the facilitation of more rapid incident detection an...

Can Progress in Reducing Alcohol-Impaired Driving Fatalities Be Resumed?

PubMed Central

Fell, James C.; Beirness, Douglas J.; Voas, Robert B.; Smith, Gordon S; Jonah, Brian; Maxwell, Jane Carlisle; Price, Jana; Hedlund, James

2016-01-01

Objective Despite successes in the 1980s and early 1990s, progress in reducing impaired driving fatalities in the United States has stagnated in recent years. Since 1997, the percentage of drivers involved in fatal crashes with illegal blood alcohol concentration (BAC) levels has remained at approximately 20% to 22%. Many experts believe that public complacency, competing social and public health issues, and the lack of political fortitude have all contributed to this stagnation. The number of alcohol-related crashes, injuries, and fatalities is still unacceptable, and most are preventable. The public needs to be aware that the problem presented by drinking drivers has not been solved. Political leaders need guidance on which measures will affect the problem, and stakeholders need to be motivated once again to implement effective strategies. Methods The National Academy of Sciences (NAS) Transportation Research Board (TRB) Alcohol, Other Drugs, and Transportation Committee (ANB50) sponsored a workshop held at the NAS facility in Woods Hole, MA, on August 24–25, 2015, to discuss the lack of progress in reducing impaired driving and to make recommendations for future progress. A total of 26 experts in research and policy related to alcohol-impaired driving participated in the workshop. The workshop began by examining the static situation in the rate of alcohol-impaired driving fatal crashes to determine what factors may be inhibiting further progress. The workshop then discussed eight effective strategies that have not been fully implemented in the United States. Workshop participants (16 of the 26) rated their top three strategies. Results Three strategies received the most support: Impose administrative sanctions for drivers with BACs = .05 to .08 g/dL.Require alcohol ignition interlocks for all alcohol-impaired driving offenders.Increase the frequency of sobriety checkpoints, including enacting legislation to allow them in the 11 states that currently prohibit them. Five other important strategies included the following: (a) increase alcohol taxes to raise the price and reduce alcohol consumption; (b) re-engage the public and raise the priority of impaired driving; (c) lower the illegal per se BAC limit to .05 for a criminal offense; (d) develop and implement in-vehicle alcohol detection systems; and (e) expand the use of screening and brief interventions in medical facilities. Conclusions Each of these strategies is proven to be effective, yet all are substantially underutilized. Each is used in some jurisdictions in the United States or Canada, but none is used extensively. Any one of the three strategies implemented on a widespread basis would decrease impaired driving crashes, injuries, and fatalities. Based on the research, all three together would have a substantial impact on the problem. PMID:26980557

Can progress in reducing alcohol-impaired driving fatalities be resumed? Results of a workshop sponsored by the Transportation Research Board, Alcohol, Other Drugs, and Transportation Committee (ANB50).

PubMed

Fell, James C; Beirness, Douglas J; Voas, Robert B; Smith, Gordon S; Jonah, Brian; Maxwell, Jane Carlisle; Price, Jana; Hedlund, James

2016-11-16

Despite successes in the 1980s and early 1990s, progress in reducing impaired driving fatalities in the United States has stagnated in recent years. Since 1997, the percentage of drivers involved in fatal crashes with illegal blood alcohol concentration (BAC) levels has remained at approximately 20 to 22%. Many experts believe that public complacency, competing social and public health issues, and the lack of political fortitude have all contributed to this stagnation. The number of alcohol-related crashes, injuries, and fatalities is still unacceptable, and most are preventable. The public needs to be aware that the problem presented by drinking drivers has not been solved. Political leaders need guidance on which measures will affect the problem, and stakeholders need to be motivated once again to implement effective strategies. The National Academy of Sciences (NAS) Transportation Research Board (TRB), Alcohol, Other Drugs, and Transportation Committee (ANB50) sponsored a workshop held at the NAS facility in Woods Hole, Massachusetts, on August 24-25, 2015, to discuss the lack of progress in reducing impaired driving and to make recommendations for future progress. A total of 26 experts in research and policy related to alcohol-impaired driving participated in the workshop. The workshop began by examining the static situation in the rate of alcohol-impaired driving fatal crashes to determine what factors may be inhibiting further progress. The workshop then discussed 8 effective strategies that have not been fully implemented in the United States. Workshop participants (16 of the 26) rated their top 3 strategies. 3 strategies received the most support: 1. Impose administrative sanctions for drivers with BACs = 0.05 to 0.08 g/dL. 2. Require alcohol ignition interlocks for all alcohol-impaired driving offenders. 3. Increase the frequency of sobriety checkpoints, including enacting legislation to allow them in the 11 states that currently prohibit them. 5 other important strategies included the following: (1) increase alcohol taxes to raise the price and reduce alcohol consumption; (2) reengage the public and raise the priority of impaired driving; (3) lower the illegal per se BAC limit to 0.05 for a criminal offense; (4) develop and implement in-vehicle alcohol detection systems; and (5) expand the use of screening and brief interventions in medical facilities. Each of these strategies is proven to be effective, yet all are substantially underutilized. Each is used in some jurisdictions in the United States or Canada, but none is used extensively. Any one of the 3 strategies implemented on a widespread basis would decrease impaired driving crashes, injuries, and fatalities. Based on the research, all 3 together would have a substantial impact on the problem.

PAGER--Rapid assessment of an earthquake?s impact

USGS Publications Warehouse

Wald, D.J.; Jaiswal, K.; Marano, K.D.; Bausch, D.; Hearne, M.

2010-01-01

PAGER (Prompt Assessment of Global Earthquakes for Response) is an automated system that produces content concerning the impact of significant earthquakes around the world, informing emergency responders, government and aid agencies, and the media of the scope of the potential disaster. PAGER rapidly assesses earthquake impacts by comparing the population exposed to each level of shaking intensity with models of economic and fatality losses based on past earthquakes in each country or region of the world. Earthquake alerts--which were formerly sent based only on event magnitude and location, or population exposure to shaking--now will also be generated based on the estimated range of fatalities and economic losses.

Estimating Casualties for Large Earthquakes Worldwide Using an Empirical Approach

USGS Publications Warehouse

Jaiswal, Kishor; Wald, David J.; Hearne, Mike

2009-01-01

We developed an empirical country- and region-specific earthquake vulnerability model to be used as a candidate for post-earthquake fatality estimation by the U.S. Geological Survey's Prompt Assessment of Global Earthquakes for Response (PAGER) system. The earthquake fatality rate is based on past fatal earthquakes (earthquakes causing one or more deaths) in individual countries where at least four fatal earthquakes occurred during the catalog period (since 1973). Because only a few dozen countries have experienced four or more fatal earthquakes since 1973, we propose a new global regionalization scheme based on idealization of countries that are expected to have similar susceptibility to future earthquake losses given the existing building stock, its vulnerability, and other socioeconomic characteristics. The fatality estimates obtained using an empirical country- or region-specific model will be used along with other selected engineering risk-based loss models for generation of automated earthquake alerts. These alerts could potentially benefit the rapid-earthquake-response agencies and governments for better response to reduce earthquake fatalities. Fatality estimates are also useful to stimulate earthquake preparedness planning and disaster mitigation. The proposed model has several advantages as compared with other candidate methods, and the country- or region-specific fatality rates can be readily updated when new data become available.

Genome-wide identification of pathogenicity factors of the free-living amoeba Naegleria fowleri.

PubMed

Zysset-Burri, Denise C; Müller, Norbert; Beuret, Christian; Heller, Manfred; Schürch, Nadia; Gottstein, Bruno; Wittwer, Matthias

2014-06-19

The free-living amoeba Naegleria fowleri is the causative agent of the rapidly progressing and typically fatal primary amoebic meningoencephalitis (PAM) in humans. Despite the devastating nature of this disease, which results in > 97% mortality, knowledge of the pathogenic mechanisms of the amoeba is incomplete. This work presents a comparative proteomic approach based on an experimental model in which the pathogenic potential of N. fowleri trophozoites is influenced by the compositions of different media. As a scaffold for proteomic analysis, we sequenced the genome and transcriptome of N. fowleri. Since the sequence similarity of the recently published genome of Naegleria gruberi was far lower than the close taxonomic relationship of these species would suggest, a de novo sequencing approach was chosen. After excluding cell regulatory mechanisms originating from different media compositions, we identified 22 proteins with a potential role in the pathogenesis of PAM. Functional annotation of these proteins revealed, that the membrane is the major location where the amoeba exerts its pathogenic potential, possibly involving actin-dependent processes such as intracellular trafficking via vesicles. This study describes for the first time the 30 Mb-genome and the transcriptome sequence of N. fowleri and provides the basis for the further definition of effective intervention strategies against the rare but highly fatal form of amoebic meningoencephalitis.

Structural and biophysical properties of metal-free pathogenic SOD1 mutants A4V and G93A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galaleldeen, Ahmad; Strange, Richard W.; Whitson, Lisa J.

2010-07-19

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease characterized by the destruction of motor neurons in the spinal cord and brain. A subset of ALS cases are linked to dominant mutations in copper-zinc superoxide dismutase (SOD1). The pathogenic SOD1 variants A4V and G93A have been the foci of multiple studies aimed at understanding the molecular basis for SOD1-linked ALS. The A4V variant is responsible for the majority of familial ALS cases in North America, causing rapidly progressing paralysis once symptoms begin and the G93A SOD1 variant is overexpressed in often studied murine models of the disease. Here wemore » report the three-dimensional structures of metal-free A4V and of metal-bound and metal-free G93A SOD1. In the metal-free structures, the metal-binding loop elements are observed to be severely disordered, suggesting that these variants may share mechanisms of aggregation proposed previously for other pathogenic SOD1 proteins.« less

Fulminant Subacute Sclerosing Panencephalitis Presenting with Acute Ataxia and Hemiparesis in a 15-Year-Old Boy

PubMed Central

Yada, Praveen; Uppin, Megha S.; Jabeen, Shaik Afshan; Cherian, Ajith; Kanikannan, Meena Angamuthu; Borgohain, Rupam; Challa, Sundaram

2014-01-01

Background Subacute sclerosing panencephalitis (SSPE) is a delayed and fatal manifestation of measles infection. Fulminant SSPE is a rare presentation in which the disease progresses to death over a period of 6 months. The clinical features are atypical and can be misleading. Case Report We report herein a teenage boy who presented with acute-onset gait ataxia followed by right hemiparesis that evolved over 1 month, with left-hemispheric, delta-range slowing on the electroencephalogram (EEG). Magnetic resonance imaging disclosed multiple white-matter hyperintensities, suggesting a diagnosis of acute disseminated encephalomyelitis. He received intravenous steroids, and within 4 days of hospital admission he developed unilateral slow myoclonic jerks. Repeat EEG revealed Rademecker complexes, pathognomonic of SSPE, and an elevated titer of IgG antimeasles antibodies was detected in his cerebrospinal fluid. The disease progressed rapidly and the patient succumbed within 15 days of hospitalization. The diagnosis of SSPE was confirmed by autopsy. Conclusions This case illustrates the difficulty of recognizing fulminant SSPE when it manifests with asymmetric clinical and EEG abnormalities. PMID:25324886

Evaluating the effectiveness of red light running camera enforcement in Cedar Rapids and developing guidelines for selection and use of red light running countermeasures.

DOT National Transportation Integrated Search

2011-11-01

Red light running (RLR) is a problem in the US that has resulted in 165,000 injuries and 907 fatalities annually. In Iowa, RLR-related crashes make up 24.5 percent of all crashes and account for 31.7 percent of fatal and major injury crashes at signa...

Flash floods, hydro-geomorphic response and risk management

NASA Astrophysics Data System (ADS)

Braud, Isabelle; Borga, Marco; Gourley, Jonathan; Hürlimann, Marcel; Zappa, Massimilano; Gallart, Francesc

2016-10-01

Each year, natural disasters are responsible for fatalities and economic losses worldwide with 101 billion USD in economic losses and 7000 fatalities reported for 2014 (SwissRE, 2015). Even if earthquakes are responsible for most of these fatalities, flash floods and landslides are recognized as a significant source of threat to human lives (SwissRE, 2015). Jonkman (2005), in a global assessment of flood-related casualties, showed that flash floods lead to the highest mortality (number of fatalities divided by the number of affected people). They are also often associated with shallow landslides and geomorphic processes that can increase threat to human lives. Analysis of a global data set of fatalities from non-seismically triggered landslides (Petley, 2012) shows that 2620 fatal landslides were recorded worldwide in the period 2004-2010, causing a total of 32,322 recorded fatalities. In addition, heavy precipitation events, at the origin of flash floods and shallow landsliding are expected to increase in the future (e.g. Scoccimarro et al., 2016 for a recent study in Europe). Progress in flash floods and landslides understanding, forecasting and warning is therefore still needed to disentangle the complex interactions between hazards, exposure and vulnerability and to increase resilience (Borga et al., 2014).

Viridans streptococcal shock syndrome during bone marrow transplantation.

PubMed

Martino, R; Manteiga, R; Sánchez, I; Brunet, S; Sureda, A; Badell, I; Argilés, B; Subirá, M; Bordes, R; Domingo-Albós, A

1995-01-01

Of 320 patients receiving a marrow transplant at the Hospital de Sant Pau between 1986 and 1992, 12% developed viridans streptococcal bacteremia during severe neutropenia. Five of these patients (13%) developed a rapidly progressive fatal shock syndrome characterized by bilateral pulmonary infiltrates, acute respiratory failure (ARDS) and septic shock early in the transplantation course (6 or 7 days posttransplantation). All patients were transplanted for acute leukemia in remission, and 2 received an allogeneic and 3 an autologous transplant. Four of these subjects were younger than 15 years of age and all had received cyclophosphamide and total body irradiation as conditioning regimen for marrow transplantation. All 5 patients died, and postmortem examinations revealed diffuse pulmonary lesions characteristic of the ARDS. These observations contribute to defining the clinical and pathologic characteristics of this serious complication of intensive anticancer treatment.

Methylation of DNA and chromatin as a mechanism of oncogenesis and therapeutic target in neuroblastoma.

PubMed

Ram Kumar, Ram Mohan; Schor, Nina Felice

2018-04-24

Neuroblastoma (NB), a developmental cancer, is often fatal, emphasizing the need to understand its pathogenesis and identify new therapeutic targets. The heterogeneous pathological and clinical phenotype of NB underscores the cryptic biological and genetic features of this tumor that result in outcomes ranging from rapid progression to spontaneous regression. Despite recent genome-wide mutation analyses, most primary NBs do not harbor driver mutations, implicating epigenetically-mediated gene regulatory mechanisms in the initiation and maintenance of NB. Aberrant epigenomic mechanisms, as demonstrated by global changes in DNA methylation signatures, acetylation, re-distribution of histone marks, and change in the chromatin architecture, are hypothesized to play a role in NB oncogenesis. This paper reviews the evidence for, putative mechanisms underlying, and prospects for therapeutic targeting of NB oncogenesis related to DNA methylation.

Advances in Merkel cell carcinoma from a pathologist's perspective.

PubMed

Barksdale, Sarah Kay

2017-10-01

Merkel cell carcinoma (MCC) is a rarely made but potentially devastating diagnosis. While local disease might be cured by surgery and radiotherapy, advanced disease is usually rapidly progressive and fatal. Until very recently, the only approach to metastatic MCC was cytotoxic chemotherapy with results so disappointing that current treatment guidelines discourage its use and recommend clinical trial as a more viable treatment option. Fortunately, recent advances in the understanding of the molecular pathogenesis of this tumour have produced a wide variety of experimental treatments for MCC, some of which are quite promising. The most current information regarding the diagnosis, staging, management of this tumour is briefly presented as well as new insights into the molecular basis of MCC and therapeutic approaches to MCC. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Effects of legislative reform to reduce drunken driving and alcohol-related traffic fatalities.

PubMed Central

Hingson, R W; Howland, J; Levenson, S

1988-01-01

From 1980 through 1985, considerable progress was made across the Nation in reducing drunken driving and fatal automobile crashes. More than 400 chapters of local citizen groups concerned with reducing drunken driving were formed. New media coverage, measured in number of stories, increased fiftyfold from 1980 to 1984. More than 500 legislative reforms were passed. All States now have adopted a legal drinking age of 21. Many also adopted criminal and administrative per se laws and instituted penalty increases for drunken driving. By 1985, the total number of fatal crashes declined to 39,168, a decrease of 6,116, or 16 percent, from the 1980 level of 45,284. Single-vehicle fatal crashes occurring at night, those most likely to involve alcohol, declined by 20 percent, with 3,674 fewer crashes in 1985 than in 1980. Among teenage drivers, declines in fatal crashes were steeper: Fatal crashes decreased 26 percent, and single-vehicle night fatal crashes were down 34 percent. After 1984, however, the number of new citizen groups established and the number of stories appearing in the media began to decline. In 1986, after decreasing for several years, the number of fatal crashes rose 5 percent, and single-vehicle night fatal crashes rose 7 percent, up 1,060 from 1985. Among teenage drivers, the increase in single-vehicle night fatal crashes was even higher, up 17 percent. In 1987, single-vehicle night fatal crashes declined slightly but still remained higher than in 1983, 1984, or 1985.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3141962

Une cryptococcose disséminée compliquant un traitement par prednisone et azathioprime d'un pemphigus vulgaire

PubMed Central

Wafa, Ammouri; Hicham, Harmouche; Yassir, Afifi; Zoubida, Tazi Mezalek; Mohamed, Adnaoui; Mohamed, Aouni; Amine, Hassani; Abdelaziz, Maaouni

2011-01-01

L'infection à cryptocoque est une complication redoutable chez les patients traités par immunosuppresseurs et dont l’évolution peut être rapidement fatal en cas de retard diagnostic. Nous rapportons le cas d'une patiente âgée de 70 ans, ayant des antécédents de pemphigus vulgaire traité par prednisone et azathioprime et admise dans le service de médecine Interne pour des nodules sous cutanés atypiques. Le diagnostic retenu était celui d'une cryptococcose disséminée. L’évolution était rapidement fatale malgré le traitement antifongique. PMID:22187617

Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID).

PubMed

Kühl, J S; Schwarz, K; Münch, A; Schmugge, M; Pekrun, A; Meisel, C; Wahn, V; Ebell, W; von Bernuth, H

2011-03-01

Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA. © Georg Thieme Verlag KG Stuttgart · New York.

A Case Report of Postmortem Radiography of Acute, Fatal Abdominal Distension After Binge Eating.

PubMed

Usui, Akihito; Kawasumi, Yusuke; Ishizuka, Yuya; Hosokai, Yoshiyuki; Ikeda, Tomoya; Saito, Haruo; Funayama, Masato

2016-12-01

This case report describes a woman who developed fatal gastric dilatation after binge eating. She called an ambulance because of stomach pain. When she arrived at the hospital, she did not look seriously ill. However, she rapidly became unconscious and collapsed immediately after she was laid on the examination table in a supine position. Postmortem chest x-ray and computed tomography showed right shift of the mediastinum and raised left diaphragm caused by massive gastric distension. Computed tomography showed no visible inferior vena cava. We think that her sudden deterioration was caused by movement of her stomach contents. Radiographic images provided some clues to the cause of her rapid collapse and death.

Rapid 3-D analysis of rockfalls

USGS Publications Warehouse

Stock, Greg M.; Guerin, A.; Avdievitch, Nikita N.; Collins, Brian D.; Jaboyedoff, Michel

2018-01-01

Recent fatal and damaging rockfalls in Yosemite National Park indicate the need for rapid response data collection methods to inform public safety and assist with management response. Here we show the use of multiple-platform remote sensing methods to rapidly capture pertinent data needed to inform management and the public following a several large rockfalls from El Capitan cliff in Yosemite Valley, California.

Uber and Metropolitan Traffic Fatalities in the United States.

PubMed

Brazil, Noli; Kirk, David S

2016-08-01

Uber and similar rideshare services are rapidly dispersing in cities across the United States and beyond. Given the convenience and low cost, Uber has been characterized as a potential countermeasure for reducing the estimated 121 million episodes of drunk driving and the 10,000 resulting traffic fatalities that occur annually in the United States. We exploited differences in the timing of the deployment of Uber in US metropolitan counties from 2005 to 2014 to test the association between the availability of Uber's rideshare services and total, drunk driving-related, and weekend- and holiday-specific traffic fatalities in the 100 most populated metropolitan areas in the United States using negative binomial and Poisson regression models. We found that the deployment of Uber services in a given metropolitan county had no association with the number of subsequent traffic fatalities, whether measured in aggregate or specific to drunk-driving fatalities or fatalities during weekends and holidays. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Next Generation Sequencing and ALS: known genes, different phenotyphes.

PubMed

Campopiano, Rosa; Ryskalin, Larisa; Giardina, Emiliano; Zampatti, Stefania; Busceti, Carla L; Biagioni, Francesca; Ferese, Rosangela; Storto, Marianna; Gambardella, Stefano; Fornai, Francesco

2017-12-01

Amyotrophic lateral sclerosis (ALS) is fatal neurodegenerative disease clinically characterized by upper and lower motor neuron dysfunction resulting in rapidly progressive paralysis and death from respiratory failure. Most cases appear to be sporadic, but 5-10 % of cases have a family history of the disease, and over the last decade, identification of mutations in about 20 genes predisposing to these disorders has provided the means to better understand their pathogenesis. Next Generation sequencing (NGS) is an advanced high-throughput DNA sequencing technology which have rapidly contributed to an acceleration in the discovery of genetic risk factors for both familial and sporadic neurological and neurodegenerative diseases. These strategies allowed to rapidly identify disease-associated variants and genetic risk factors for both familial (fALS) and sporadic ALS (sALS), strongly contributing to the knowledge of the genetic architecture of ALS. Moreover, as the number of ALS genes grows, many of the proteins they encode are in intracellular processes shared with other known diseases, suggesting an overlapping of clinical and phatological features between different diseases. To emphasize this concept, the review focuses on genes coding for Valosin-containing protein (VPC) and two Heterogeneous nuclear RNA-binding proteins (HNRNPA1 and hnRNPA2B1), recently idefied through NGS, where different mutations have been associated in both ALS and other neurological and neurodegenerative diseases.

Successful extracorporeal membrane oxygenation therapy as a bridge to sequential bilateral lung transplantation for a patient after severe paraquat poisoning.

PubMed

Tang, Xiao; Sun, Bing; He, Hangyong; Li, Hui; Hu, Bin; Qiu, Zewu; Li, Jie; Zhang, Chunyan; Hou, Shengcai; Tong, Zhaohui; Dai, Huaping

2015-11-01

Paraquat is a widely used herbicide that can cause severe to fatal poisoning in humans. The irreversible and rapid progression of pulmonary fibrosis associated with respiratory failure is the main cause of death in the later stages of poisoning. There are infrequent reports of successful lung transplants for cases of severe paraquat poisoning. We expect that this successful case will provide a reference for other patients in similar circumstances. A 24-year-old female was sent to the hospital approximately 2 hours after ingesting 50 ml of paraquat. She experienced rapidly aggravated pulmonary fibrosis and severe respiratory failure. On the 34th day after ingestion, she underwent intubation and invasive mechanical ventilation. The patient was evaluated for lung transplantation, and veno-venous extracorporeal membrane oxygenation (ECMO) was established as a bridge to lung transplantation on the 44th day. On the 56th day, she successfully underwent a bilateral sequential lung transplantation. Through respiratory and physical rehabilitation and nutrition support, the patient was weaned from mechanical ventilation and extubated on the 66th day. On the 80th day, she was discharged. During the 1-year follow-up, the patient was found to be in good condition, and her pulmonary function improved gradually. We suggest that lung transplantation may be an effective treatment in the end stages of paraquat-induced pulmonary fibrosis and consequential respiratory failure. For patients experiencing a rapid progression to a critical condition in whom lung transplantation cannot be performed immediately (e.g., while awaiting a viable donor or toxicant clearance), ECMO should be a viable bridge to lung transplantation.

Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.

PubMed

Lindow, Janet C; Wunder, Elsio A; Popper, Stephen J; Min, Jin-Na; Mannam, Praveen; Srivastava, Anup; Yao, Yi; Hacker, Kathryn P; Raddassi, Khadir; Lee, Patty J; Montgomery, Ruth R; Shaw, Albert C; Hagan, Jose E; Araújo, Guilherme C; Nery, Nivison; Relman, David A; Kim, Charles C; Reis, Mitermayer G; Ko, Albert I

2016-11-01

Leptospirosis causes significant morbidity and mortality worldwide; however, the role of the host immune response in disease progression and high case fatality (>10-50%) is poorly understood. We conducted a multi-parameter investigation of patients with acute leptospirosis to identify mechanisms associated with case fatality. Whole blood transcriptional profiling of 16 hospitalized Brazilian patients with acute leptospirosis (13 survivors, 3 deceased) revealed fatal cases had lower expression of the antimicrobial peptide, cathelicidin, and chemokines, but more abundant pro-inflammatory cytokine receptors. In contrast, survivors generated strong adaptive immune signatures, including transcripts relevant to antigen presentation and immunoglobulin production. In an independent cohort (23 survivors, 22 deceased), fatal cases had higher bacterial loads (P = 0.0004) and lower anti-Leptospira antibody titers (P = 0.02) at the time of hospitalization, independent of the duration of illness. Low serum cathelicidin and RANTES levels during acute illness were independent risk factors for higher bacterial loads (P = 0.005) and death (P = 0.04), respectively. To investigate the mechanism of cathelicidin in patients surviving acute disease, we administered LL-37, the active peptide of cathelicidin, in a hamster model of lethal leptospirosis and found it significantly decreased bacterial loads and increased survival. Our findings indicate that the host immune response plays a central role in severe leptospirosis disease progression. While drawn from a limited study size, significant conclusions include that poor clinical outcomes are associated with high systemic bacterial loads, and a decreased antibody response. Furthermore, our data identified a key role for the antimicrobial peptide, cathelicidin, in mounting an effective bactericidal response against the pathogen, which represents a valuable new therapeutic approach for leptospirosis.

[Clinical polymorphism of amyotrophic lateral sclerosis].

PubMed

Kovrazhkina, E A; Razinskaya, O D; Gubsky, L V

To clarify clinical polymorphism of amyotrophic lateral sclerosis (ALS). The study was based on records of a hospital personalized register. Ninety-four patients, aged from 25 to 81 years, diagnosed with ALS according to El Escorial criteria were included. Electromyography and, if necessary, transcranial magnetic stimulation and magnetic-resonance tomography were used to confirm the diagnosis. Disease progression was assessed with the ARSFRS. Age at disease onset, progression rate and duration of survival of patients, rare symptoms of ALS ('extramotor'), time for palliative care (gastrostomy, non-invasive and invasive lung ventilation) and provision of the care to the patient, family history were recorded in a specially designed questionnaire. Most of the patients had sporadic ALS, only two familial cases were identified. Spinal onset ALS was found in 66.0% of the patients, bulbar onset in 29.8%, diffuse onset (spinal and bulbar motor neurons were affected simultaneously) in 4.2%. Moderate ALS progression was observed in 42.6% of the patients, mean time till death was 3.0±1.2 years. A slow progression was found in patients with cervical, low back and bulbar onset. A rapid and even 'momentary' type of progression was in diffuse and breast onset. An extremely slow progression with the long-term hospital treatment and survival >5 years was found in 9.7%. Rare ALS symptoms were represented by specific cognitive and psychological impairments, a type of frontal/temporal dysfunction, but only 5 (5.3%) patients were diagnosed with ALS-dementia. Signs of pathological muscle fatigue (myasthenic syndrome) were identified in 18 (19.1%), extrapyramidal disorders in 5 (5.3%), coordination disorders in 4 (4.3%), pain in 12 (12.8%), sensory symptoms in 5 (5.3%) of the patients. ALS is a multisystemic neurodegeneration disease though the progressive motor neuron death determines the fatal outcome.

Preventing fatalities in building bombings: what can we learn from the Oklahoma City bombing?

PubMed

Glenshaw, Mary T; Vernick, Jon S; Li, Guohua; Sorock, Gary S; Brown, Sheryll; Mallonee, Sue

2007-07-01

Bombings are an increasing threat to the public's health. Descriptive studies of blast injuries have been published, but these injuries have not been studied using analytical epidemiological methods. This study assesses factors associated with fatality risk among individuals exposed to the 1995 Oklahoma City bombing. Retrospective case-control analysis using multivariable logistic regression. Odds ratios (OR) of fatality are calculated among occupants of the Alfred P. Murrah Federal Building on April 19, 1995. Of the 348 occupants exposed, 163 (46.8%) were fatally injured. Fatality risk was greatest in the collapsed region of the building (adjusted OR 176.7, 95% confidence interval [CI] 65.9-474.2). Age > or =40 was also associated with a significantly increased risk of fatality (OR 3.7, 95% CI 1.4-9.8). Among people found in the noncollapsed region of the building, employees' status compared to a visitor's or child's status was protective (OR 0.13, 95% CI 0.01-1.3). Structural collapse is the most important risk factor for fatality in a building bombing. Progressive collapse may be prevented through more supportive building design. Protection of vulnerable building occupants can be improved by placement of relevant facilities in more structurally reinforced areas. Regular evacuation training of personnel and clear egress routes may also reduce fatality in a building bombing.

[Fatal acute pancreatitis caused by severe hypertriglyceridaemia].

PubMed

Abed, Osama Karim; Lindberg, Mats; Andos, Shadi

2014-04-14

We report a case of fatal acute pancreatitis caused by severe hypertriglyceridaemia in a 27-year-old male who was treated with quetiapine. The blood samples were milk-like with markedly elevated triglycerides (> 55 mmol/l). Computer tomography revealed a severe pancreatitis without bile stones or cholestasis. In spite of treatment the patient's condition rapidly worsened and he died 48 hours after admission. We discuss the option of treating hypertriglyceridaemia-induced pancreatitis with apheresis.

[Morphological findings in fatal cases of hantavirus cardiopulmonary syndrome. Report of 7 autopsies].

PubMed

Guzmán G, Pablo; Tapia E, Oscar; Villaseca H, Miguel; Araya O, Juan; Antonio P, Lilia; Lee O, Bolívar; Roa S, Juan

2010-10-01

Hantavirus cardiopulmonary syndrome (HCPS) is an acute infectious disease characterized by sudden cardiorespiratory failure and high mortality, caused by a RNA virus of the genus Hantavirus, family Bunyaviridae, 15% of Chilean cases have been detected in the Araucania Region. To determine in fatal cases of HCPS, clinical and morphological characteristics. Descriptive-retrospective analysis of seven fatal cases with postmortem study of HCPS, attended between 1997 and 2009 at the Hospital of Temuco, Chile. Cases were young patients from rural areas, and presented as an illness of progressive respiratory failure, with leukocytosis, thrombocytopenia and bilateral interstitial pulmonary infiltrates. Main morphological findings were marked intersticial and intraalveolar pulmonary edema, with minimal epithelial injury and mononuclear cell intersticial infiltrate and mild edematous intersticial inflamatory process. Epidemiological, clinical and laboratory background allow to suspect HCPS. In fatal cases, the autopsy makes possible to discard other similar pathologies and provide tissue for confirmation of the disease.

Lassa fever or lassa hemorrhagic fever risk to humans from rodent-borne zoonoses.

PubMed

El-Bahnasawy, Mamdouh M; Megahed, Laila Abdel-Mawla; Abdalla Saleh, Hala Ahmed; Morsy, Tosson A

2015-04-01

Viral hemorrhagic fevers (VHFs) typically manifest as rapidly progressing acute febrile syndromes with profound hemorrhagic manifestations and very high fatality rates. Lassa fever, an acute hemorrhagic fever characterized by fever, muscle aches, sore throat, nausea, vomiting, diarrhea and chest and abdominal pain. Rodents are important reservoirs of rodent-borne zoonosis worldwide. Transmission rodents to humans occur by aerosol spread, either from the genus Mastomys rodents' excreta (multimammate rat) or through the close contact with infected patients (nosocomial infection). Other rodents of the genera Rattus, Mus, Lemniscomys, and Praomys are incriminated rodents hosts. Now one may ask do the rodents' ectoparasites play a role in Lassa virus zoonotic transmission. This paper summarized the update knowledge on LHV; hopping it might be useful to the clinicians, nursing staff, laboratories' personals as well as those concerned zoonoses from rodents and rodent control.

[GENETIC AND METABOLIC URGENCIES IN THE NEONATAL INTENSIVE CARE UNIT: MAPLE SYRUP URINE DISEASE].

PubMed

Páez Rojas, Paola Liliana; Suarez Obando, Fernando

2015-07-01

Maple syrup urine disease (MSUD) is a hereditary disorder of branched chain amino/keto acid metabolism, caused by a decreased activity of the branched-chain alpha- ketoacid dehydrogenase complex (BCKAD), which leads to abnormal elevated plasma concentrations of branched-chain amino acids (BCAAs) clinically manifested as a heavy burden for Central Nervous system. The toxic accumulation of substrates promotes the development of a severe and rapidly progressive neonatal encephalopathy if treatment is not immediately given. This disorder has a specific medical management in acute phase in order to minimize mortality and morbidity. For all those reasons, it is important to include the MSUD as a possible diagnosis in a encephalopathic newborn. We present a colombian newborn with classical MSUD with fatal outcome as an example of metabolic emergency and a differential diagnosis in the encephalopathic newborn. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Gas gangrene in orthopaedic patients.

PubMed

Ying, Zhimin; Zhang, Min; Yan, Shigui; Zhu, Zhong

2013-01-01

Clostridial myonecrosis is most often seen in settings of trauma, surgery, malignancy, and other underlying immunocompromised conditions. Since 1953 cases of gas gangrene have been reported in orthopaedic patients including open fractures, closed fractures, and orthopaedic surgeries. We present a case of 55-year-old obese woman who developed rapidly progressive gas gangrene in her right leg accompanied by tibial plateau fracture without skin lacerations. She was diagnosed with clostridial myonecrosis and above-the-knee amputation was carried out. This patient made full recovery within three weeks of the initial episode. We identified a total of 50 cases of gas gangrene in orthopaedic patients. Several factors, if available, were analyzed for each case: age, cause of injury, fracture location, pathogen, and outcome. Based on our case report and the literature review, emergency clinicians should be aware of this severe and potentially fatal infectious disease and should not delay treatment or prompt orthopedic surgery consultation.

Fournier's Gangrene: Current Practices

PubMed Central

Mallikarjuna, M. N.; Vijayakumar, Abhishek; Patil, Vijayraj S.; Shivswamy, B. S.

2012-01-01

Fournier's gangrene is an acute, rapidly progressive, and potentially fatal, infective necrotizing fasciitis affecting the external genitalia, perineal or perianal regions, which commonly affects men, but can also occur in women and children. There has been an increase in number of cases in recent times. Despite advanced management mortality is still high and averages 20–30%. Early diagnosis using Laboratory Risk Indicator for Necrotizing Fasciitis score and stratification of patients into high risk category using Fournier's Gangrene Severity Index score help in early initiation of treatment. Triple antibiotic combined with radical debridement is the mainstay of treatment. There have been many advances in management of Fournier gangrene including use of vaccum assisted closure and hyperbaric oxygen therapy. With introduction of newer devices like Flexi-Seal, fecal diversion can be done, avoiding colostomy. Reconstruction of perineal defects using skin grafts, flaps, and urethral reconstruction using gracilis flaps can reduce the morbidity associated with FG and provide acceptable functional and aesthetic outcomes. PMID:23251819

Gas Gangrene in Orthopaedic Patients

PubMed Central

Ying, Zhimin; Zhang, Min; Yan, Shigui; Zhu, Zhong

2013-01-01

Clostridial myonecrosis is most often seen in settings of trauma, surgery, malignancy, and other underlying immunocompromised conditions. Since 1953 cases of gas gangrene have been reported in orthopaedic patients including open fractures, closed fractures, and orthopaedic surgeries. We present a case of 55-year-old obese woman who developed rapidly progressive gas gangrene in her right leg accompanied by tibial plateau fracture without skin lacerations. She was diagnosed with clostridial myonecrosis and above-the-knee amputation was carried out. This patient made full recovery within three weeks of the initial episode. We identified a total of 50 cases of gas gangrene in orthopaedic patients. Several factors, if available, were analyzed for each case: age, cause of injury, fracture location, pathogen, and outcome. Based on our case report and the literature review, emergency clinicians should be aware of this severe and potentially fatal infectious disease and should not delay treatment or prompt orthopedic surgery consultation. PMID:24288638

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis

PubMed Central

Patten, Shunmoogum A.; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary A.B.; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J. Alexander

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease. PMID:29202456

Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B. mallei–like Variation in the bimA Motility Gene, Australia

PubMed Central

Fane, Anne; Sarovich, Derek S.; Price, Erin P.; Rush, Catherine M.; Govan, Brenda L.; Parker, Elizabeth; Mayo, Mark; Currie, Bart J.; Ketheesan, Natkunam

2017-01-01

Neurologic melioidosis is a serious, potentially fatal form of Burkholderia pseudomallei infection. Recently, we reported that a subset of clinical isolates of B. pseudomallei from Australia have heightened virulence and potential for dissemination to the central nervous system. In this study, we demonstrate that this subset has a B. mallei–like sequence variation of the actin-based motility gene, bimA. Compared with B. pseudomallei isolates having typical bimA alleles, isolates that contain the B. mallei–like variation demonstrate increased persistence in phagocytic cells and increased virulence with rapid systemic dissemination and replication within multiple tissues, including the brain and spinal cord, in an experimental model. These findings highlight the implications of bimA variation on disease progression of B. pseudomallei infection and have considerable clinical and public health implications with respect to the degree of neurotropic threat posed to human health. PMID:28418830

Quadriplegia due to pachymeningitis, vasculitis and sepsis in a patient with rheumatoid arthritis: a case report.

PubMed

Mari, E; Maraldi, C; Grandi, E; Gallerani, M

2011-05-01

We report the case of a 84-year-old man, with history of rheumatoid arthritis, admitted the Hospital for a fall and complaining of dysaesthesia and pain located to the cervical spine and arms. Within a few hours after admission, fever and acute, progressive, ascendant quadriplegia became evident. Magnetic resonance imaging (MRI) of cervical spine showed spinal canal stenosis between C4-C6 with spinal cord compression. Hemocultures resulted positive for Staphylococcus aureus. The clinical picture rapidly evolved to sepsis with a fatal multi-organ failure. An autopsy found a osteosclerosis narrowing the neurocanal at the level of C3-C6, and recent cervical medulla infarction. A histological exam revealed the presence of a suppurative pachymeningitis with local phenomenas of periradiculitis, vasculitis and thrombosis of the anterior medullar artery, associated with coagulative necrosis of the neural tissue.

Averting a malaria disaster: will insecticide resistance derail malaria control?

PubMed

Hemingway, Janet; Ranson, Hilary; Magill, Alan; Kolaczinski, Jan; Fornadel, Christen; Gimnig, John; Coetzee, Maureen; Simard, Frederic; Roch, Dabiré K; Hinzoumbe, Clément Kerah; Pickett, John; Schellenberg, David; Gething, Peter; Hoppé, Mark; Hamon, Nicholas

2016-04-23

World Malaria Day 2015 highlighted the progress made in the development of new methods of prevention (vaccines and insecticides) and treatment (single dose drugs) of the disease. However, increasing drug and insecticide resistance threatens the successes made with existing methods. Insecticide resistance has decreased the efficacy of the most commonly used insecticide class of pyrethroids. This decreased efficacy has increased mosquito survival, which is a prelude to rising incidence of malaria and fatalities. Despite intensive research efforts, new insecticides will not reach the market for at least 5 years. Elimination of malaria is not possible without effective mosquito control. Therefore, to combat the threat of resistance, key stakeholders need to rapidly embrace a multifaceted approach including a reduction in the cost of bringing new resistance management methods to market and the streamlining of associated development, policy, and implementation pathways to counter this looming public health catastrophe. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

PubMed

Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

2017-11-16

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B. mallei-like Variation in the bimA Motility Gene, Australia.

PubMed

Morris, Jodie L; Fane, Anne; Sarovich, Derek S; Price, Erin P; Rush, Catherine M; Govan, Brenda L; Parker, Elizabeth; Mayo, Mark; Currie, Bart J; Ketheesan, Natkunam

2017-05-01

Neurologic melioidosis is a serious, potentially fatal form of Burkholderia pseudomallei infection. Recently, we reported that a subset of clinical isolates of B. pseudomallei from Australia have heightened virulence and potential for dissemination to the central nervous system. In this study, we demonstrate that this subset has a B. mallei-like sequence variation of the actin-based motility gene, bimA. Compared with B. pseudomallei isolates having typical bimA alleles, isolates that contain the B. mallei-like variation demonstrate increased persistence in phagocytic cells and increased virulence with rapid systemic dissemination and replication within multiple tissues, including the brain and spinal cord, in an experimental model. These findings highlight the implications of bimA variation on disease progression of B. pseudomallei infection and have considerable clinical and public health implications with respect to the degree of neurotropic threat posed to human health.

Do failures in non-technical skills contribute to fatal medical accidents in Japan? A review of the 2010–2013 national accident reports

PubMed Central

Uramatsu, Masashi; Fujisawa, Yoshikazu; Mizuno, Shinya; Souma, Takahiro; Komatsubara, Akinori; Miki, Tamotsu

2017-01-01

Objectives We sought to clarify how large a proportion of fatal medical accidents can be considered to be caused by poor non-technical skills, and to support development of a policy to reduce number of such accidents by making recommendations about possible training requirements. Design Summaries of reports of fatal medical accidents, published by the Japan Medical Safety Research Organization, were reviewed individually. Three experienced clinicians and one patient safety expert conducted the reviews to determine the cause of death. Views of the patient safety expert were given additional weight in the overall determination. Setting A total of 73 summary reports of fatal medical accidents were reviewed. These reports had been submitted by healthcare organisations across Japan to the Japan Medical Safety Research Organization between April 2010 and March 2013. Primary and secondary outcome measures The cause of death in fatal medical accidents, categorised into technical skills, non-technical skills and inevitable progress of disease were evaluated. Non-technical skills were further subdivided into situation awareness, decision making, communication, team working, leadership, managing stress and coping with fatigue. Results Overall, the cause of death was identified as non-technical skills in 34 cases (46.6%), disease progression in 33 cases (45.2%) and technical skills in two cases (5.5%). In two cases, no consensual determination could be achieved. Further categorisation of cases of non-technical skills were identified as 14 cases (41.2%) of problems with situation awareness, eight (23.5%) with team working and three (8.8%) with decision making. These three subcategories, or combinations of them, were identified as the cause of death in 33 cases (97.1%). Conclusions Poor non-technical skills were considered to be a significant cause of adverse events in nearly half of the fatal medical accidents examined. Improving non-technical skills may be effective for reducing accidents, and training in particular subcategories of non-technical skills may be especially relevant. PMID:28209605

Serological Evidence of Hantavirus Infection in Apparently Healthy People from Rural and Slum Communities in Southern Chile

PubMed Central

Muñoz-Zanzi, Claudia; Saavedra, Farides; Otth, Carola; Domancich, Ljubica; Hott, Melissa; Padula, Paula

2015-01-01

Hantavirus disease in America has been recognizable because of its rapid progression in clinical cases, occurrence in previously healthy young adults, and high case fatality rate. Hantavirus disease has been proposed now to define the diversity of clinical manifestations. Since 1995, a total of 902 cases of hantavirus pulmonary syndrome have been reported in Chile, caused by Andes virus (ANDV), with overall fatality of 32%. This report describes the sero-epidemiology of hantavirus in apparently healthy people in rural and urban slum communities from southern Chile. Ten of 934 samples yielded a positive result resulting in a seroprevalence of 1.07% (95% confidence intervals: 0.05%–2.0%). A higher proportion of positive samples was found among individuals from rural villages (1.3%) and slums (1.5%) compared with farms (0.5%). Seropositivity was associated with age (p = 0.011), low education level (p = 0.006) and occupations linked to the household (homemaker, retired, or student) (p = 0.016). No evidence of infection was found in 38 sigmodontinae rodents trapped in the peri-domestic environment. Our findings highlight that exposure risk was associated with less documented risk factors, such as women in slum and rural villages, and the occurrence of infection that may have presented as flu-like illness that did not require medical attention or was misdiagnosed. PMID:25912713

Disseminated hyperkeratotic and granulomatous nodules in a child with fatal Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis.

PubMed

Brinkmeier, Thomas; Reuter, Thomas; Metze, Dieter; Frosch, Peter J; Herbst, Rudolf A

2006-01-01

Hemophagocytic lymphohistiocytosis is a rare and potentially fatal syndrome associated with a variety of genetic, malignant, autoimmune, or infectious conditions. The importance of cutaneous presentations of this syndrome has only recently been brought forward. We report the first case of Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis presenting with papulonodular and granulomatous skin lesions. A girl of African origin developed several umbilicated papules on her extremities and face at the age of 18 months. She was born in Germany, had never visited Africa, and was otherwise healthy. Over the next 5 months the lesions progressed in size and number and became hyperkeratotic. Histopathologic analysis of early lesions revealed a superficial lympho- and plasmacellular dermatitis with some features of panniculitis. Later biopsy specimens from nodular lesions showed the formation of tuberculoid granulomas in the deep dermis. At the age of 23 months she became severely ill, rapidly developing high fever, hepatosplenomegaly, icterus, pancytopenia, and ascites. On the basis of bone marrow and lymph node biopsies, the diagnosis of hemophagocytic lymphohistiocytosis was established. However, this phenomenon could not be detected in any of the skin specimens. An active Epstein-Barr virus infection was diagnosed by polymerase chain reaction in blood, lymphoid tissue, and skin. Despite chemotherapy with etoposide and cortisone, the girl expired 14 days after clinical onset of her systemic disease.

The Effects of a Rectangular Rapid-Flashing Beacon on Vehicle Speed

ERIC Educational Resources Information Center

VanWagner, Michelle; Van Houten, Ron; Betts, Brian

2011-01-01

In 2008, nearly 31% of vehicle fatalities were related to failure to adhere to safe vehicle speeds (National Highway Traffic Safety Administration [NHTSA], 2009). The current study evaluated the effect of a rectangular rapid-flashing beacon (RRFB) triggered by excessive speed on vehicle speed using a combined alternating treatments and reversal…

Comparison of G protein sequences of South African street rabies viruses showing distinct progression of the disease in a mouse model of experimental rabies.

PubMed

Seo, Wonhyo; Servat, Alexandre; Cliquet, Florence; Akinbowale, Jenkins; Prehaud, Christophe; Lafon, Monique; Sabeta, Claude

Rabies is a fatal zoonotic disease and infections generally lead to a fatal encephalomyelitis in both humans and animals. In South Africa, domestic (dogs) and the wildlife (yellow mongoose) host species maintain the canid and mongoose rabies variants respectively. In this study, pathogenicity differences of South African canid and mongoose rabies viruses were investigated in a murine model, by assessing the progression of clinical signs and survivorship. Comparison of glycoprotein gene sequences revealed amino acid differences that may underpin the observed pathogenicity differences. Cumulatively, our results suggest that the canid rabies virus may be more neurovirulent in mice than the mongoose rabies variant. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Identification of Sildenafil (Viagra) and Its Metabolite (UK 103,320) in Six Aviation Fatalities

DTIC Science & Technology

2006-02-01

Identification of Sildenafil ( Viagra ®) and Its Metabolite (UK-103,320) in Six Aviation Fatalities Robert D. Johnson Russell J. Lewis Civil...DOT/FAA/AM-06/3 4. Title and Subtitle 5. Report Date February 2006 Identification of Sildenafil ( Viagra ®) and Its Metabolite (UK-103,320...report presents a rapid and reliable method for the identification and quantitation of sildenafil ( Viagra ®) and its active metabolite, UK-103,320. This

Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis.

PubMed

Reis, Eliana A G; Hagan, José E; Ribeiro, Guilherme S; Teixeira-Carvalho, Andrea; Martins-Filho, Olindo A; Montgomery, Ruth R; Shaw, Albert C; Ko, Albert I; Reis, Mitermayer G

2013-01-01

The role of the immune response in influencing leptospirosis clinical outcomes is not yet well understood. We hypothesized that acute-phase serum cytokine responses may play a role in disease progression, risk for death, and severe pulmonary hemorrhage syndrome (SPHS). We performed a case-control study design to compare cytokine profiles in patients with mild and severe forms of leptospirosis. Among patients hospitalized with severe disease, we compared those with fatal and nonfatal outcomes. During active outpatient and hospital-based surveillance we prospectively enrolled 172 patients, 23 with mild disease (outpatient) and 149 with severe leptospirosis (hospitalized). Circulating concentrations of pro- and anti-inflammatory cytokines at the time of patient presentation were measured using a multiplex bead array assay. Concentrations of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, and TNF-α were significantly higher (P<0.05) in severe disease compared to mild disease. Among severe patients, levels of IL-6 (P<0.001), IL-8 (P = 0.0049) and IL-10 (P<0.001), were higher in fatal compared to non-fatal cases. High levels of IL-6 and IL-10 were independently associated (P<0.05) with case fatality after adjustment for age and days of symptoms. IL-6 levels were higher (P = 0.0519) among fatal cases who developed SPHS than among who did not. This study shows that severe cases of leptospirosis are differentiated from mild disease by a "cytokine storm" process, and that IL-6 and IL-10 may play an immunopathogenic role in the development of life-threatening outcomes in human leptospirosis.

Veno-arterial extracorporeal membrane oxygenation for Streptococcus pyogenes toxic shock syndrome in pregnancy.

PubMed

Imaeda, Taro; Nakada, Taka-Aki; Abe, Ryuzo; Tateishi, Yoshihisa; Oda, Shigeto

2016-06-01

Streptococcal toxic shock syndrome (STSS), an invasive Streptococcus pyogenes (Group A streptococcus) infection with hypotension and multiple organ failure, is quite rare in pregnancy but is characterized by rapid disease progression and high fatality rates. We present a case of STSS with infection-induced cardiac dysfunction in a pregnant woman who was treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A 24-year-old multiparous woman in the third trimester had early symptoms of high fever and diarrhea 1 day prior to admission to the hospital emergency department. On admission, she had multiple organ failure including circulatory failure. Due to fetal distress, emergency Cesarean section was carried out and transferred to intensive care units. She had refractory circulatory failure with depressed myocardial contractility with progressive multiple organ failure, despite receiving significant hemodynamic supports including high-dose catecholamine. Thus, VA-ECMO was initiated 18 h after intensive care unit admission. Consequently, ECMO provided extra time to recover from infection and myocardial depression. She was successfully weaned from VA-ECMO on day 7 and was discharged home on day 53. VA-ECMO can be a therapeutic option for refractory circulatory failure with significant myocardial depression in STSS.

Progression of Pancreatic Adenocarcinoma Is Significantly Impeded with a Combination of Vaccine and COX-2 Inhibition1

PubMed Central

Mukherjee, Pinku; Basu, Gargi D.; Tinder, Teresa L.; Subramani, Durai B.; Bradley, Judy M.; Arefayene, Million; Skaar, Todd; De Petris, Giovanni

2013-01-01

With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly fatal malignancies. Current protocols for the treatment of pancreas cancer are not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)-based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and low-dose chemotherapy (gemcitabine) was effective in preventing the progression of preneoplastic intraepithelial lesions to invasive pancreatic ductal adenocarcinomas. The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRASG12D mutation and that expresses human MUC1 as a self molecule. The combination treatment elicited robust antitumor cellular and humoral immune responses and was associated with increased apoptosis in the tumor. The mechanism for the increased immune response was attributed to the down-regulation of circulating prostaglandin E2 and indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of T regulatory and myeloid suppressor cells within the tumor microenvironment. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer. PMID:19109152

Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition.

PubMed

Mukherjee, Pinku; Basu, Gargi D; Tinder, Teresa L; Subramani, Durai B; Bradley, Judy M; Arefayene, Million; Skaar, Todd; De Petris, Giovanni

2009-01-01

With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly fatal malignancies. Current protocols for the treatment of pancreas cancer are not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)-based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and low-dose chemotherapy (gemcitabine) was effective in preventing the progression of preneoplastic intraepithelial lesions to invasive pancreatic ductal adenocarcinomas. The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRAS(G12D) mutation and that expresses human MUC1 as a self molecule. The combination treatment elicited robust antitumor cellular and humoral immune responses and was associated with increased apoptosis in the tumor. The mechanism for the increased immune response was attributed to the down-regulation of circulating prostaglandin E(2) and indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of T regulatory and myeloid suppressor cells within the tumor microenvironment. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer.

The history of antiretroviral therapy and of its implementation in resource-limited areas of the world.

PubMed

Vella, Stefano; Schwartländer, Bernard; Sow, Salif Papa; Eholie, Serge Paul; Murphy, Robert L

2012-06-19

HIV/AIDS not only represents the most severe epidemic in modern times, but also the greatest public health challenge in history. The response of the scientific community has been impressive and in just a few years, turned an inevitably fatal disease into a chronic manageable although not yet curable condition. The development of antiretroviral therapy is not only the history of scientific advancements: it is the result of the passionate 'alliance' towards a common goal between researchers, doctors and nurses, pharmaceutical industries, regulators, public health officials and the community of HIV-infected patients, which is rather unique in the history of medicine. In addition, the rapid and progressive development of antiretroviral therapy has not only proven to be life-saving for many millions but has been instrumental in unveiling the inequities in access to health between rich and poor countries of the world. Optimal benefits indeed, are not accessible to all people living with HIV, with challenges to coverage and sustainability in low and middle income countries. This paper will review the progress made, starting from the initial despairing times, till the current battle towards universal access to treatment and care for all people living with HIV.

Development of a proto-typology of opiate overdose onset.

PubMed

Neale, Joanne; Bradford, Julia; Strang, John

2017-01-01

The time available to act is a crucial factor affecting the probable success of interventions to manage opiate overdose. We analyse opiate users' accounts of non-fatal overdose incidents to (i) construct a proto-typology of non-fatal opiate overdose onset and (ii) assess the implications for overdose management and prevention of fatalities. Re-analysis of a subset of data from a large qualitative study of non-fatal opiate overdose conducted from 1997 to 1999. Data were generated from semi-structured interviews undertaken with opiate users who had experienced a non-fatal overdose in the previous 24 hours. Forty-four participants (30 men; 14 women; aged 16-47 years) provided sufficient information for in-depth analysis. Data relating to 'memory of the moment of overdose', 'time to loss of consciousness' and 'subjective description of the overdose experience' were scrutinised using iterative categorization. Four types of overdose onset were identified: type A 'amnesic' (n = 8), characterized by no memory, rapid loss of consciousness and no description of the overdose experience; type B 'conscious' (n = 17), characterized by some memory, sustained consciousness and a description of the overdose in terms of feeling unwell and symptomatic; type C 'instant' (n = 14), characterized by some memory, immediate loss of consciousness and no description of the overdose experience; and type D 'enjoyable' (n = 5), characterized by some memory, rapid loss of consciousness and a description of the overdose experience as pleasant or positive. The identification of different types of overdose onset highlights the complexity of overdose events, the need for a range of interventions and the challenges faced in managing incidents and preventing fatalities. Opiate overdose victims who retain consciousness for a sustained period and recognize the negative signs and symptoms of overdosing could summon help or self-administer naloxone, thus indicating that opiate overdose training should incorporate self-management strategies. © 2016 Society for the Study of Addiction.

Community acquired methicillin resistant Staphylococcus aureus pneumonia: an update for the emergency and intensive care physician.

PubMed

Karampela, I; Poulakou, G; Dimopoulos, G

2012-08-01

Pneumonia caused by community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) among individuals without healthcare-associated (HA) risk factors was first recognized a decade ago. CA-MRSA has now been established as a pathogen responsible for rapidly progressive, frequently fatal disease manifesting as necrotizing pneumonia, severe sepsis and necrotizing fasciitis. The frequency of occurrence, risk factors, and optimal treatment of CA-MRSA pneumonia remain unclear and vary significantly across countries. CA-MRSA is resistant to β-lactam antimicrobials due to the acquisition of novel methicillin resistance genetic cassettes. Additionally many CA-MRSA strains produce Panton-Valentine leukocidin (PVL), due to which they probably exceed the virulence of hospital-acquired MRSA isolates (HA-MRSA). CA-MRSA pneumonia requires early suspicion -especially in young otherwise healthy individuals with rapidly evolving clinical picture presenting with cavitary consolidation, bilateral infiltrates, pleural effusion and hemoptysis. Prompt hospitalization and aggressive treatment with intravenous antibiotics is warranted to improve outcomes. Therapeutic approach for severe CA-MRSA infections and particularly pneumonia is generally the same as that for invasive HA-MRSA infections. New anti-MRSA agents and possible combinations are of great importance to be evaluated in the future.

Necrotizing streptococcal myositis of the upper extremity: a case report.

PubMed

Reichert, Johannes C; Habild, Götz; Simon, Paul; Nöth, Ulrich; Krümpelmann, Jan B

2017-08-15

Necrotizing myositis is a rare but life-threatening soft-tissue infection characterized by rapidly spreading inflammation and subsequent necrosis of the affected tissue. The myositis is often caused by toxin-producing, virulent bacteria such as group A β-hemolytic streptococcus and associated with severe systemic toxicity. It is rapidly fatal unless diagnosed promptly and treated aggressively. However, necrotizing myositis is often initially misdiagnosed as a more benign soft-tissue infection as such fulminant, invasive muscle infections are rare with no more than 30 cases reported over the last century. We illustrate the case of a 74-year-old male Caucasian initially presenting with a progressing swelling and gradually oncoming pain of the upper right extremity. Rapidly, livid discolorations of the skin, blisters, hypoesthesia and severe pain resistant to analgesics treatment developed accompanied by disruption of the arterial blood flow. Due to a manifest compartment syndrome the patient was admitted to theater for fasciotomy of the arm. After multiple revision surgeries wound closure was achieved using a pedicled, fasciocutaneous parascapular flap and a free, ipsilateral anterolateral thigh flap. Microbiological analysis revealed group A β-hemolytic streptococcus, histology a bacterial interstitial myositis with necrotic muscular fibers. A high degree of clinical suspicion is necessary to avert potentially disastrous consequences of necrotizing myositis. Timely diagnosis, broad-spectrum antibiotic therapy, and aggressive surgical debridement of affected tissue are keys to the treatment of this serious, often life-threatening infection.

Neurocognitive features distinguishing primary central nervous system lymphoma from other possible causes of rapidly progressive dementia.

PubMed

Deutsch, Mariel B; Mendez, Mario F

2015-03-01

Define the neurocognitive features of primary central nervous system lymphoma (PCNSL) presenting with dementia, and compare with other causes of rapidly progressive dementia (RPD). PCNSL can present as an RPD. Differentiating PCNSL from other RPDs is critical because lymphomatous dementia may be reversible, and untreated PCNSL is fatal. We performed a meta-analysis of case reports of dementia from PCNSL (between 1950 and 2013); 20 patients (14 with lymphomatosis cerebri) met our criteria. We compared these patients to a case series of patients with RPD from Creutzfeldt-Jakob disease and other non-PCNSL etiologies (Sala et al, 2012. Alzheimer Dis Assoc Disord. 26:267-271). Median age was 66 years (range 41 to 81); 70% were men. Time from symptom onset to evaluation was <6 months in 65%. No patients had seizures; 5% had headaches; 45% had non-aphasic speech difficulty. There was significantly more memory impairment in patients with PCNSL than other RPDs and significantly less myoclonus and parkinsonism. Behavioral changes and cerebellar signs were not significantly different. Significantly more patients with PCNSL than other RPDs had white matter changes; significantly fewer had atrophy. Elevated CSF protein and pleocytosis were more frequent in PCNSL; patients with other RPDs tended to have normal CSF±14-3-3 protein. Unlike patients with RPD from other causes, those with PCNSL commonly present with impaired memory, apathy, and abnormal speech and gait, without headache, seizure, or myoclonus. White matter changes and CSF abnormalities predominate. Improved clinical awareness of PCNSL can prompt earlier diagnosis and treatment.

Clostridium Sordellii as an Uncommon Cause of Fatal Toxic Shock Syndrome in a Postpartum 33-Year-Old Asian Woman, and the Need for Antepartum Screening for This Clostridia Species in the General Female Population.

PubMed

Guzzetta, Melissa; Williamson, Alex; Duong, Scott

2016-08-01

Clostridium sordellii (C. sordellii) is an anaerobic gram-positive rod most commonly found in the soil and sewage but also as part of the normal flora of the gastrointestinal tract and vagina of a small percentage of healthy individuals. C. sordellii infection is considered to result from childbirth, abortion, and/or gynecological procedures. Although many strains of C. sordellii are nonpathogenic, virulent toxin-producing strains exist. Infection with this organism typically manifests as a patient experiencing septic shock rapidly followed by end-organ failure. Identification of C. sordelli has been successful by traditional culture, mass spectrometry methods, and via molecular methods. Herein, we present a fatal case of C. sordellii infection of a postpartum 33-year-old Asian woman. The organism was isolated by culture and identified using matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) technology. With the advent of rapid detection methods, antepartum screening for the fatal Clostridium species should be implemented in the general female population. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Scrapie

USDA-ARS?s Scientific Manuscript database

Prion diseases are a heterogeneous group of transmissible spongiform encephalopathies (TSEs) that affect a variety of mammals, causing a slowly progressive and ultimately fatal, degenerative disease of the brain. Classical scrapie, commonly just referred to as ‘scrapie’, is a naturally transmissibl...

Twenty-one-year experience with land mine injuries.

PubMed

Adams, D B; Schwab, C W

1988-01-01

Land mines produce devastating injuries which are usually fatal. In Guantanamo Bay, there have been no survivors from close range, functioning antipersonnel mines of the M-16 series. All 15 antipersonnel mine fatalities suffered extremity amputation. Seven of the 15 patients suffered immediately fatal head, neck, or truncal injuries (Type I injury). The three patients who underwent hospital resuscitation had extremity amputation but were spared major head, neck, or truncal injury. It is in this group of injured that potentially salvageable patients can be identified; for them aggressive rescue and resuscitation must be performed. Those with Type II injuries are the highest priority in any triage plan. In a mass casualty or combat casualty scenario, Type II patients, in particular those with high bilateral above-the-knee amputations, may be reassigned to an expectant treatment category so as to allow the main focus on more salvageable patients. The prehospital management plan emphasizes rapid assessment and triage of patients, use of tourniquets to control extremity hemorrhage, supplemental oxygen or endotracheal intubation if possible, neck immobilization, use of the extremity section of the pneumatic antishock garment if applicable, and rapid transport to a hospital. Hospital management of these patients emphasizes aggressive resuscitation, early endotracheal intubation, and rapid volume replacement with simultaneous balanced salt solution and blood. Operative debridement with broad-spectrum antibiotic coverage and tetanus prophylaxis is performed; wounds are managed in an open fashion and frequently examined at subsequent dates in the operating room.

Can we reduce workplace fatalities by half?

PubMed

Koh, David Soo Quee

2012-06-01

Singapore, an island republic of over 5 million inhabitants, has 3.1 million workers. Most are employed in the service, finance and tourist/transport industry. Significant numbers work in manufacturing, construction and heavy industry. Following a series of construction and shipyard accidents with multiple deaths in 2004, the government announced its intention to reduce workplace fatalities from 4.9 to 2.5 per 100,000 by 2015. There was strong political will to achieve this target. The strategic approaches were to build workplace safety and health (WSH) capabilities; implement legislative changes with enforcement; promote benefits of WSH and recognize best practices, and enhance partnership with stakeholders. The anticipated outcomes were to reduce workplace fatality and injury rates; have WSH as an integral part of business; and establish a progressive and pervasive WSH culture. With these measures, the workplace fatality rate declined from 4.9/100,000 in 2004, to 2.2/100,000 in 2010. However, other confounding factors could also account for this decline, and have to be considered. The next target, announced by Singapore's Prime Minister in 2008, is to further reduce the workplace fatality rate to 1.8/100,000 by 2018, and to have "one of the best workplace safety records in the world".

Discontinuation of penicillamine in the absence of alternative orphan drugs (trientine-zinc): a case of decompensated liver cirrhosis in Wilson's disease.

PubMed

Ping, C C; Hassan, Y; Aziz, N A; Ghazali, R; Awaisu, A

2007-02-01

To report a case of early-decompensated liver cirrhosis secondary to discontinuation of penicillamine therapy in a patient with Wilson's disease. A 33-year-old Chinese female patient was diagnosed with Wilson's disease, for which penicillamine 250 mg p.o. once daily was prescribed. However, the patient developed intolerance and penicillamine was discontinued without alternative treatment. Five months later, she developed decompensated liver cirrhosis with hepatic encephalopathy. Eventually, the patient died because of the complications of sepsis and decompensated liver failure. Chelating agent is the mainstay of treatment in Wilson's disease, which is an inherited disorder of hepatic copper metabolism. Therapy must be instituted and continued for life once diagnosis is confirmed. Interruption of therapy can be fatal or cause irreversible relapse. Penicillamine given orally is the chelating agent of first choice. However, its unfavourable side-effects profile leads to discontinuation of therapy in 20-30% of patients. In most case reports, cessation of penicillamine without replacement treatment causes rapid progression to fulminant hepatitis, which is fatal unless liver transplantation is performed. In this, we highlight a case of discontinuation of penicillamine in a patient with Wilson's disease without substitution with alternative regimen. This was caused by unavailability of the alternative agents such as trientine in our country. Consequently, the patient progressed to decompensated liver cirrhosis with encephalopathy and eventually passed-away within 5 months. One recent study supports a combination of trientine and zinc in treating patient with decompensated liver cirrhosis. This combination is capable of reversing liver failure and prevents the need of liver transplantation. Both trientine and zinc are not registered in Malaysia. Therefore, liver transplantation was probably the only treatment option for this patient. Hence, non-availability of orphan drugs in clinical practice is certainly a subject of serious concern. Systems for better management of patients with rare diseases need to be instituted by all the institutions concerned.

A method for the generation of ectromelia virus (ECTV) recombinants: in vivo analysis of ECTV vCD30 deletion mutants.

PubMed

Alejo, Ali; Saraiva, Margarida; Ruiz-Argüello, Maria Begoña; Viejo-Borbolla, Abel; de Marco, Mar Fernández; Salguero, Francisco Javier; Alcami, Antonio

2009-01-01

Ectromelia virus (ECTV) is the causative agent of mousepox, a lethal disease of mice with similarities to human smallpox. Mousepox progression involves replication at the initial site of infection, usually the skin, followed by a rapid spread to the secondary replicative organs, spleen and liver, and finally a dissemination to the skin, where the typical rash associated with this and other orthopoxviral induced diseases appears. Case fatality rate is genetically determined and reaches up to 100% in susceptible mice strains. Like other poxviruses, ECTV encodes a number of proteins with immunomodulatory potential, whose role in mousepox progression remains largely undescribed. Amongst these is a secreted homologue of the cellular tumour necrosis factor receptor superfamily member CD30 which has been proposed to modulate a Th1 immune response in vivo. To evaluate the contribution of viral CD30 (vCD30) to virus pathogenesis in the infected host, we have adapted a novel transient dominant method for the selection of recombinant ECTVs. Using this method, we have generated an ECTV vCD30 deletion mutant, its corresponding revertant control virus as well as a virus encoding the extracellular domain of murine CD30. These viruses contain no exogenous marker DNA sequences in their genomes, as opposed to other ECTVs reported up to date. We show that the vCD30 is expressed as a secreted disulfide linked trimer and that the absence of vCD30 does not impair mousepox induced fatality in vivo. Replacement of vCD30 by a secreted version of mouse CD30 caused limited attenuation of ECTV. The recombinant viruses generated may be of use in the study of the role of the cellular CD30-CD30L interaction in the development of the immune response. The method developed might be useful for the construction of ECTV mutants for the study of additional genes.

[Abortion using a bicycle pump on the mistress and unusual suicide of a blind man].

PubMed

Holzer, F J

1973-01-01

In Tyrol a case of fatal air embolism after an abortion attempt with a bicycle pump, performed by a blind man who later committed suicide, is described. The bicycle tube was inserted into the vagina and air and a soapy solution were pumped in. Autopsies revealed internal bleeding, gas embolisms in the veins of the ovaries and heart, a bloody foamy liquid in the lungs, and an intact 14 cm male fetus. 3 similar cases of fatal air embolisms after abortion attempts with bicycle pumps are described. In 1 case a soapy solution had been injected. Abortion attempts with a pipe and a rubber catheter, reported here, also resulted in rapidly fatal air embolisms. In 1 case death occurred a few seconds after a partner blew air with his mouth into his pregnant mistress' vagina. It is concluded that under some conditions filling the vagina with air (tightly) can cause fatal air embolisms.

T cells play an essential role in anti-F1 mediated rapid protection against bubonic plague.

PubMed

Levy, Yinon; Flashner, Yehuda; Tidhar, Avital; Zauberman, Ayelet; Aftalion, Moshe; Lazar, Shirley; Gur, David; Shafferman, Avigdor; Mamroud, Emanuelle

2011-09-16

Plague, which is initiated by Yersinia pestis infection, is a fatal disease that progresses rapidly and leads to high mortality rates if not treated. Antibiotics are an effective plague therapy, but antibiotic-resistant Y. pestis strains have been reported and therefore alternative countermeasures are needed. In the present study, we assessed the potential of an F1 plus LcrV-based vaccine to provide protection shortly pre- or post-exposure to a lethal Y. pestis infection. Mice vaccinated up to one day before or even several hours after subcutaneous challenge were effectively protected. Mice immunized one or three days pre-challenge were protected even though their anti-F1 and anti-LcrV titers were below detection levels at the day of challenge. Moreover, using B-cell deficient μMT mice, we found that rapidly induced protective immunity requires the integrity of the humoral immune system. Analysis of the individual contributions of vaccine components to protection revealed that rF1 is responsible for the observed rapid antibody-mediated immunity. Applying anti-F1 passive therapy in the mouse model of bubonic plague demonstrated that anti-F1 F(ab')(2) can delay mortality, but it cannot provide long-lasting protection, as do intact anti-F1 molecules. Fc-dependent immune components, such as the complement system and (to a lesser extent) neutrophils, were found to contribute to mouse survival. Interestingly, T cells but not B cells were found to be essential for the recovery of infected animals following passive anti-F1 mediated therapy. These data extend our understanding of the immune mechanisms required for the development of a rapid and effective post-exposure therapy against plague. Copyright © 2011 Elsevier Ltd. All rights reserved.

Do failures in non-technical skills contribute to fatal medical accidents in Japan? A review of the 2010-2013 national accident reports.

PubMed

Uramatsu, Masashi; Fujisawa, Yoshikazu; Mizuno, Shinya; Souma, Takahiro; Komatsubara, Akinori; Miki, Tamotsu

2017-02-16

We sought to clarify how large a proportion of fatal medical accidents can be considered to be caused by poor non-technical skills, and to support development of a policy to reduce number of such accidents by making recommendations about possible training requirements. Summaries of reports of fatal medical accidents, published by the Japan Medical Safety Research Organization, were reviewed individually. Three experienced clinicians and one patient safety expert conducted the reviews to determine the cause of death. Views of the patient safety expert were given additional weight in the overall determination. A total of 73 summary reports of fatal medical accidents were reviewed. These reports had been submitted by healthcare organisations across Japan to the Japan Medical Safety Research Organization between April 2010 and March 2013. The cause of death in fatal medical accidents, categorised into technical skills, non-technical skills and inevitable progress of disease were evaluated. Non-technical skills were further subdivided into situation awareness, decision making, communication, team working, leadership, managing stress and coping with fatigue. Overall, the cause of death was identified as non-technical skills in 34 cases (46.6%), disease progression in 33 cases (45.2%) and technical skills in two cases (5.5%). In two cases, no consensual determination could be achieved. Further categorisation of cases of non-technical skills were identified as 14 cases (41.2%) of problems with situation awareness, eight (23.5%) with team working and three (8.8%) with decision making. These three subcategories, or combinations of them, were identified as the cause of death in 33 cases (97.1%). Poor non-technical skills were considered to be a significant cause of adverse events in nearly half of the fatal medical accidents examined. Improving non-technical skills may be effective for reducing accidents, and training in particular subcategories of non-technical skills may be especially relevant. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Allergic sinusitis and severe asthma caused by occupational exposure to locust bean gum: Case report

PubMed Central

Hawley, Brie; Cummings, Kristin J.; Mohammed, Mohammed; Dimmock, Anne E.; Bascom, Rebecca

2017-01-01

We present a case that highlights the difficulties with diagnosis and the dangers of occupational allergic sinusitis and asthma left unrecognized. We describe the case history of a man who experienced work-related symptoms 1 year after beginning work as a cheesemaker at a creamery, and whose respiratory symptoms progressively worsened over 16 years before an occupational cause of his asthma was identified. His initial discrete episodes of sinusitis and acute bronchitis evolved into persistent asthma of increasing severity with exacerbations requiring repeated emergency room treatment. The case described in our report emphasizes the importance of clinician diagnosis of OA, and subsequent removal from exposure, such that asthma severity does not progress to near-fatal or fatal asthma in the sensitized worker. As demonstrated by this case report, identification of an occupational cause of asthma relies on a high degree of suspicion and excellent detective work by the clinician. PMID:28497854

[Smallpox virus as biological weapon].

PubMed

Kondrusik, Maciej; Hermanowska-Szpakowicz, Teresa

2003-02-01

Smallpox, because of its high case-fatality rate, easy transmission from human to human, lack of specific treatment represents nowadays one of the main threats in bioterrorist attacks. Over the centuries, naturally occurring smallpox with its case-fatality over 30 percent and its ability to spread in any climate and season has been treated as the most dangerous infectious disease. But it is now, 25 years after the last documented case of smallpox and cessation of routine vaccination in present mobile and susceptible population, smallpox virus spread might be rapid and devastating.

The Ebola virus matrix protein penetrates into the plasma membrane: a key step in viral protein 40 (VP40) oligomerization and viral egress.

PubMed

Adu-Gyamfi, Emmanuel; Soni, Smita P; Xue, Yi; Digman, Michelle A; Gratton, Enrico; Stahelin, Robert V

2013-02-22

Ebola, a fatal virus in humans and non-human primates, has no Food and Drug Administration-approved vaccines or therapeutics. The virus from the Filoviridae family causes hemorrhagic fever, which rapidly progresses and in some cases has a fatality rate near 90%. The Ebola genome encodes seven genes, the most abundantly expressed of which is viral protein 40 (VP40), the major Ebola matrix protein that regulates assembly and egress of the virus. It is well established that VP40 assembles on the inner leaflet of the plasma membrane; however, the mechanistic details of plasma membrane association by VP40 are not well understood. In this study, we used an array of biophysical experiments and cellular assays along with mutagenesis of VP40 to investigate the role of membrane penetration in VP40 assembly and egress. Here we demonstrate that VP40 is able to penetrate specifically into the plasma membrane through an interface enriched in hydrophobic residues in its C-terminal domain. Mutagenesis of this hydrophobic region consisting of Leu(213), Ile(293), Leu(295), and Val(298) demonstrated that membrane penetration is critical to plasma membrane localization, VP40 oligomerization, and viral particle egress. Taken together, VP40 membrane penetration is an important step in the plasma membrane localization of the matrix protein where oligomerization and budding are defective in the absence of key hydrophobic interactions with the membrane.

Rift valley Fever virus encephalitis is associated with an ineffective systemic immune response and activated T cell infiltration into the CNS in an immunocompetent mouse model.

PubMed

Dodd, Kimberly A; McElroy, Anita K; Jones, Tara L; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

2014-06-01

Rift Valley fever virus (RVFV) causes outbreaks of severe disease in livestock and humans throughout Africa and the Arabian Peninsula. In people, RVFV generally causes a self-limiting febrile illness but in a subset of individuals, it progresses to more serious disease. One manifestation is a delayed-onset encephalitis that can be fatal or leave the afflicted with long-term neurologic sequelae. In order to design targeted interventions, the basic pathogenesis of RVFV encephalitis must be better understood. To characterize the host immune responses and viral kinetics associated with fatal and nonfatal infections, mice were infected with an attenuated RVFV lacking NSs (ΔNSs) that causes lethal disease only when administered intranasally (IN). Following IN infection, C57BL/6 mice developed severe neurologic disease and succumbed 7-9 days post-infection. In contrast, inoculation of ΔNSs virus subcutaneously in the footpad (FP) resulted in a subclinical infection characterized by a robust immune response with rapid antibody production and strong T cell responses. IN-inoculated mice had delayed antibody responses and failed to clear virus from the periphery. Severe neurological signs and obtundation characterized end stage-disease in IN-inoculated mice, and within the CNS, the development of peak virus RNA loads coincided with strong proinflammatory responses and infiltration of activated T cells. Interestingly, depletion of T cells did not significantly alter survival, suggesting that neurologic disease is not a by-product of an aberrant immune response. Comparison of fatal (IN-inoculated) and nonfatal (FP-inoculated) ΔNSs RVFV infections in the mouse model highlighted the role of the host immune response in controlling viral replication and therefore determining clinical outcome. There was no evidence to suggest that neurologic disease is immune-mediated in RVFV infection. These results provide important insights for the future design of vaccines and therapeutic options.

Atmosphere-fire simulation of effects of low-level jets on pyro-convective plume dynamics

Treesearch

Colin C. Simpson; Marwan Katurji; Michael T. Kiefer; Shiyuan Zhong; Joseph J. Charney; Warren E. Heilman; Xindi Bian

2013-01-01

Blow-up fire behaviour can be broadly defined as a rapid escalation in the intensity or forward rate of spread of a wildland fire, and is often accompanied by extreme pyro-convection associated with rapid smoke release and dispersion. Blow-up fire behaviour is difficult to predict and has been linked to firefighter fatalities, making it an important fire management...

Emmonsia helica Infection in HIV-Infected Man, California, USA.

PubMed

Rofael, Martin; Schwartz, Ilan S; Sigler, Lynne; Kong, Li K; Nelson, Nicholas

2018-01-01

Emmonsia-like fungi have rarely been reported from North America. We report a fatal case of E. helica infection in a man with advanced HIV infection from California, USA, who had progressive respiratory failure and a brain abscess.

Early prognostic markers for fatal fulminant hepatic failure cases with viral hepatitis: proton nuclear magnetic resonance spectroscopic studies of serum.

PubMed

Bala, Lakshmi; Mehrotra, Mayank; Mohindra, Samir; Saxena, Rajan; Khetrapal, Chunni Lal

2013-02-01

Fulminant hepatic failure is associated with liver metabolic derangements which could have fatal consequences. The aim of the present study is to identify serum markers for early prediction of the outcome. Proton nuclear magnetic resonance spectroscopic studies of serum of fulminant hepatic failure patients due to viral hepatitis with grade II/III of encephalopathy (twenty-four: ten prospective and fourteen retrospective) and twenty-five controls were undertaken. Of the twenty-four patients, fifteen survived with medical management alone while nine had fatal outcome. The results demonstrated significantly elevated indices of amino acids (alanine, lysine, glutamine, histidine, tyrosine, phenylalanine and 1,2-propanediol) in fatal cases compared to survivors and controls. Principal component analysis showed clear separation of fatal and surviving cases. Liver function parameters were significantly deranged in patients but they failed to provide early significant differences between surviving and fatal cases. Compared to model for end-stage liver disease scores, principal component analysis appear to be better as an early prognostic indicator. Biochemical mapping of pathways suggested interruptions in amino acid metabolism and urea cycle. Proton nuclear magnetic resonance studies of serum have the potential of rapidly identifying patients with irreversible fulminant hepatic failure requiring liver transplantation as life saving option. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Rapidly Fatal Silicosis Among Jewellery Workers Attending a District Medical College of West Bengal, India.

PubMed

Panchadhyayee, Prabodh; Saha, Kaushik; Saha, Indranil; Ta, Rupam Kumar; Ghosh, Santanu; Saha, Arnab; Barma, Pratik; Mitra, Mrinmoy

2015-01-01

Silicosis is a slowly progressive chronic occupational lung disease, developed after a prolong period of exposure to high concentration of silica dust. In this longitudinal study, we enrolled old and new silicosis patients (n=19; 8 jewellery polishers, 11 from other occupations) seen at our Pulmonary Medicine Department from June 2009 to December 2012 to document the course of illness as per their occupational exposure. Six of the eight jewellery polishing workers had developed silicosis within five years of exposure, while six of the 11 other workers with other occupational exposure had developed silicosis after exposure of 10 years or more. Mean duration of exposure was significantly less among jewellery polishing workers compared to other workers (3.4 +/- 1.7 versus 9.3 +/- 4.1; p=0.001). Mean duration of illness (months) (14.9 +/- 5.8 versus 28.5 +/- 16.5; p=0.040) were significantly less among the jewellery polishing workers compared to other workers. At the end of the study period, all eight jewellery polishing workers with silicosis had died while four of the 11 patients with other occupational exposure had died. Silicosis among jewellery polishing workers was found to be more severe and progressive compared to silicosis due to other occupational exposures, in our study.

Morphology and Morphometry of the Lung in Corn Snakes (Pantherophis guttatus) Infected with Three Different Strains of Ferlavirus.

PubMed

Starck, J M; Neul, A; Schmidt, V; Kolb, T; Franz-Guess, S; Balcecean, D; Pees, M

2017-05-01

Ophidian paramyxovirus (ferlavirus) is a global threat to reptilian sauropsids in herpetological collections, with occasional but fatal effects. This study characterizes the effects of three different genetic strains of ferlavirus on the dynamic changes of histology and morphometry of the lung of corn snakes (Pantherophis guttatus). Lungs from 42 corn snakes were either sham-infected or infected experimentally under standardized conditions. From 4 to 49 days after intratracheal inoculation, the lungs were examined qualitatively and quantitatively. Progressive microscopical changes were seen in the lung. Initially, increased numbers of heterophils were observed in the interstitium followed by proliferation and vacuolation of epithelial cells lining faveoli. Electron microscopy revealed loss of type-I pneumocytes, hyperplasia of type-II pneumocytes, and interstitial infiltrates of heterophils and mononuclear cells. With progression of disease the respiratory epithelium was initially overgrown by transformed type-II pneumocytes and later became multilayered. The results of the study suggest that the respiratory capacity of the lungs declines with disease development. The dynamics of disease development and histopathology differed in snakes infected with different ferlavirus genogroups. Animals infected with virus genogroup B developed histopathological changes and morphometric changes more rapidly and of greater intensity than snakes infected with viruses from genogroups A or C. Copyright © 2017 Elsevier Ltd. All rights reserved.

Histamine and H1-antihistamines: celebrating a century of progress.

PubMed

Simons, F Estelle R; Simons, Keith J

2011-12-01

In this review we celebrate a century of progress since the initial description of the physiologic and pathologic roles of histamine and 70 years of progress since the introduction of H(1)-antihistamines for clinical use. We discuss histamine and clinically relevant information about the molecular mechanisms of action of H(1)-antihistamines as inverse agonists (not antagonists or blockers) with immunoregulatory effects. Unlike first (old)-generation H(1)-antihistamines introduced from 1942 to the mid-1980s, most of the second (new)-generation H(1)-antihistamines introduced subsequently have been investigated extensively with regard to clinical pharmacology, efficacy, and safety; moreover, they are relatively free from adverse effects and not causally linked with fatalities after overdose. Important advances include improved nasal and ophthalmic H(1)-antihistamines with rapid onset of action (in minutes) for allergic rhinitis and allergic conjunctivitis treatment, respectively, and effective and safe use of high (up to 4-fold) doses of oral second-generation H(1)-antihistamines for chronic urticaria treatment. New H(1)-antihistamines introduced for clinical use include oral formulations (bilastine and rupatadine), and ophthalmic formulations (alcaftadine and bepotastine). Clinical studies of H(3)-antihistamines with enhanced decongestant effects have been conducted in patients with allergic rhinitis. Additional novel compounds being studied include H(4)-antihistamines with anti-inflammatory effects in allergic rhinitis, atopic dermatitis, and other diseases. Antihistamines have a storied past and a promising future. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Fibrin facilitates both innate and T cell-mediated defense against Yersinia pestis.1

PubMed Central

Luo, Deyan; Lin, Shiuan; Parent, Michelle A.; Kanevsky, Isis Mullarky; Szaba, Frank M.; Kummer, Lawrence W.; Duso, Debra K.; Tighe, Michael; Hill, Jim; Gruber, Andras; Mackman, Nigel; Gailani, David; Smiley, Stephen T.

2013-01-01

The gram-negative bacterium Yersinia pestis causes plague, a rapidly progressing and often fatal disease. The formation of fibrin at sites of Y. pestis infection supports innate host defense against plague, perhaps by providing a non-diffusible spatial cue that promotes the accumulation of inflammatory cells expressing fibrin-binding integrins. This report demonstrates that fibrin is an essential component of T cell-mediated defense against plague but can be dispensable for antibody-mediated defense. Genetic or pharmacologic depletion of fibrin abrogated innate and T cell-mediated defense in mice challenged intranasally with Y. pestis. The fibrin-deficient mice displayed reduced survival, increased bacterial burden, and exacerbated hemorrhagic pathology. They also showed fewer neutrophils within infected lung tissue and reduced neutrophil viability at sites of liver infection. Depletion of neutrophils from wild type mice weakened T cell-mediated defense against plague. The data suggest that T cells combat plague in conjunction with neutrophils, which require help from fibrin in order to withstand Y. pestis encounters and effectively clear bacteria. PMID:23487423

Suppurative bite wound by repetitive aggression of dominance hierarchy during group housing in rhesus monkeys.

PubMed

Choi, Yunjung; Ahn, Kyung-Ha; Lee, Jae-Il

2014-12-01

Group formation of rhesus monkeys, often leads to victims of repeated attacks by the high ranking animal. We reported a case of an injured middle ranking monkey from repetitive and persistent aggression. 4-male rhesus group was formed by a rapid group formation strategy 2 years ago. One monkey in the group suddenly showed depressive and reluctant movement. Physical examination revealed multiple bite wounds and scars in the dorsal skin. Overall increased opacity of the dorsal soft tissue and some free air was observed on radiographic examination. An unidentified anaerobic gram negative bacillus was isolated from the bacterial culture. Reconstructive surgery was performed and in consequence, the wound was clearly reconstructed one week later. Eventually, the afflicted monkey was separated and housed apart from the hierarchical group. This case report indicate that group formation in rhesus monkeys is essentially required sufficient time and stages, as well as more attention and a progressive contact program to reduce animal stress and fatal accidents.

Action and function of Chromobacterium violaceum in health and disease: Violacein as a promising metabolite to counteract gastroenterological diseases.

PubMed

Justo, Giselle Zenker; Durán, Nelson

2017-12-01

Chromobacterium violaceum is a Gram negative, β-proteobacterium found in the microbiota of tropical and subtropical environments. Although considered an opportunistic pathogen, infection rapidly progress to fatal sepsis, with metastatic abscesses. It is noteworthy the multidrug resistant phenotype of C. violaceum and the possibility of relapse. Recently, an influence of global climate in the incidence of cases beyond the previous areas has been observed. Furthermore, chronic granulomatous disease has been considered a risk factor to infection. Despite the increase in C. violaceum infection incidence and high mortality, most clinicians are not familiar with it. This review pointed out important features of this life threatening microorganism, including its pathogenicity, mechanistic aspects, genetic and drug resistance associated factors, and the clinical association with chronic granulomatous disease. In addition, its main metabolite violacein may be a promising agent to counteract gastroenterological diseases, such as colorectal cancer and inflammatory gastric lesions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical and Psychosocial Factors Influencing Retinal Screening Uptake Among Young Adults with Type 2 Diabetes.

PubMed

Lake, A J; Rees, G; Speight, J

2018-05-24

Young adults with type 2 diabetes (T2D, 18-39 years) experience early-onset and rapid progression of diabetic retinopathy (DR), the leading cause of vision loss for working age adults. Despite this, uptake of retinal screening, the crucial first step in preventing vision loss from DR, is low. The aim of this review is to summarize the clinical and psychosocial factors affecting uptake of retinal screening. Barriers include lack of diabetes-related symptoms, low personal DR risk perception, high rates of depression and diabetes-related distress, fatalism about inevitability of complications, time and financial constraints, disengagement with existing diabetes self-management services, and perceived stigma due to having a condition associated with older adults. Young adults with T2D are an under-researched population who face an accumulation of barriers to retinal screening. Tailored interventions that address the needs, characteristics, and priorities of young adults with T2D are warranted.

Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague.

PubMed

Sebbane, Florent; Jarrett, Clayton O; Gardner, Donald; Long, Daniel; Hinnebusch, B Joseph

2006-04-04

Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread.

Delayed anaphylaxis involving IgE to galactose-alpha-1,3-galactose

PubMed Central

Platts-Mills, Thomas A E; Schuyler, Alexander J; Hoyt, Alice E W; Commins, Scott P

2015-01-01

Hypersensitivity in the allergic setting refers to immune reactions, stimulated by soluble antigens that can be rapidly progressing and, in the case of anaphylaxis, are occasionally fatal. As the number of known exposures associated with anaphylaxis is limited, identification of novel causative agents is important in facilitating both education and other allergen-specific approaches that are crucial to long-term risk management. Within the last 10 years several seemingly separate observations were recognized to be related, all of which resulted from the development of antibodies to a carbohydrate moiety on proteins where exposure differed from airborne allergens but which were nevertheless capable of producing anaphylactic and hypersensitivity reactions. Our recent work has identified these responses as being due to a novel IgE antibody directed against a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal). This review will present the history and biology of alpha-gal and discuss our current approach to management of the mammalian meat allergy and delayed anaphylaxis. PMID:26130470

Yellow fever 17-D vaccine is neurotropic and produces encephalitis in immunosuppressed hamsters.

PubMed

Mateo, Rosa I; Xiao, Shu-Yuan; Travassos da Rosa, Amelia P A; Lei, Hao; Guzman, Hilda; Lu, Liang; Tesh, Robert B

2007-11-01

Immunosuppressed (cyclophosphamide) adult golden hamsters inoculated intraperitoneally (i.p.) with wild-type Asibi yellow fever virus (YFV) developed a rapidly fatal illness. Histopathologic and immunohistochemical studies of tissues from these animals showed typical hepatic changes of severe yellow fever (inflammation, hepatocyte necrosis, and steatosis) without brain involvement. In contrast, 50% of immunosuppressed hamsters receiving the YFV-17D-attenuated vaccine developed a slowly progressive encephalitic-type illness. Brain tissue from these latter animals revealed focal neuronal changes, inflammation, and YFV antigen-positive neurons; however, the liver and spleen appeared normal. YFV was isolated from brain cultures of many of these animals. Immunocompetent (non-immunosuppressed) hamsters inoculated with both viruses developed a subclinical infection. Results of this study indicate that wild-type YFV is hepatotropic in immunosuppressed hamsters, whereas the attenuated YFV-17 is primarily neurotropic. These findings support current recommendations against yellow fever vaccination of immunosuppressed/immunocompromised people and suggest that this hamster model might be useful for monitoring the safety of other live-attenuated YFV vaccines.

Therapeutic progress in amyotrophic lateral sclerosis-beginning to learning.

PubMed

Kumar, Vijay; Islam, Asimul; Hassan, Md Imtaiyaz; Ahmad, Faizan

2016-10-04

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle weakness, paralysis and finally death. The proposed mechanisms of ALS include glutamate excitotoxicity, oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and proteasomal dysfunction. Although numerous pathological mechanisms have been explained, ALS remains incurable disease because of failure of clinical trials and lack of any effective therapy. The rapid advancement in genetic discoveries in ALS emphasizes the point that ALS is a multi-subtype syndrome rather than a single disease. This can be argued as one of the single reason why many previous therapeutic drug trials have failed. Efforts to develop novel ALS treatments which target specific pathomechanisms are currently being pursued. Herein, we review the recent discovery and preclinical characterization of neuroprotective compounds and compare their effects on disease onset, duration and survival. Furthermore, the structure-activity relationships of these agents are analyzed with the overall goal of developing a screening strategy for future clinical applications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

First report of two rapid-onset fatal infections caused by a newly emerging hypervirulent K. Pneumonia ST86 strain of serotype K2 in China.

PubMed

Zhang, Yibo; Sun, Jingyong; Mi, Chenrong; Li, Wenhui; Zhao, Shengyuan; Wang, Qun; Shi, Dake; Liu, Luo; Ding, Bingyu; Chang, Yung-Fu; Guo, Hongxiong; Guo, XiaoKui; Li, Qingtian; Zhu, Yongzhang

2015-01-01

Here, we present the first report of one suspected dead case and two confirmed rapid-onset fatal infections caused by a newly emerging hypervirulent Klebsiella pneumoniae ST86 strain of serotype K2. The three cases occurred in a surgery ward during 2013 in Shanghai, China. A combination of multilocus sequence typing, pulsed-field gel electrophoresis, phenotypic and PCR tests for detecting virulence factors (VFs) was used to identify the isolates as K2 ST86 strains with common VFs, including Aerobactin and rmpA. Furthermore, the two K2 ST86 strains additionally harbored a distinct VF kfu (responsible for iron uptake system), which commonly existed in invasive K1 strains only. Thus, the unusual presence of both K1 and K2 VFs in the lethal ST86 strain might further enhance its hypervirulence and cause rapid onset of a life-threatening infection. Nevertheless, despite the administration of a combined antibiotic treatment, these three patients all died within 24 h of acute onset, thereby highlighting that the importance of early diagnosis to determine whether the ST86 strains harbor key K2 VF and unusual K1 kfu and whether patients should receive a timely and targeted antibiotic therapy to prevent ST86 induced fatal pneumonia. Finally, even though these patients are clinically improved, keeping on with oral antibiotic treatment for additional 2-3 weeks will be also vital for successfully preventing hvKP reinfection or relapse.

Estimating alcohol involvement in fatal crashes in light of increases in restraint use

DOT National Transportation Integrated Search

1998-03-01

This report investigates several extreme examples of the long-term effect of : ignoring the alcohol involvement-restraint use interaction using data for : calendar year 1995. By studying the interaction, the study attempts to : determine the progress...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Shannon L.; Daligault, Hajnalka E.; Davenport, Karen W.

Francisella tularensis is a highly infectious bacterium that has the potential of causing high fatality rates if infections are untreated. To aid in the development of rapid and accurate detection assays, we have sequenced and annotated the genomes of 18 F. tularensis and Francisella philomiragia strains.

MOLD SPECIFIC QUANTITATIVE PCR FOR RAPID IDENTIFICATION AND ENUMERATION

EPA Science Inventory

There is growing awareness that indoor molds/fungi may be connected to such conditions as asthma, allergies, hemorrhaging, chronic rhinosinusitis, memory loss, and a symptom complex called sick-building-syndrome. In addition, molds cause frequently fatal nosocomical infections. ...

Citalopram Overdose: a Fatal Case.

PubMed

Kraai, Erik P; Seifert, Steven A

2015-06-01

Citalopram is a selective serotonin reuptake inhibitor (SSRI) with cardiac and neurologic toxicities as well as the potential for serotonin syndrome. In most instances, patients recover fully from toxic ingestions of SSRIs. We describe a fatal case of a citalopram overdose. A 35-year-old woman presented to the emergency department after having witnessed seizures at home. An empty citalopram prescription bottle was located, and an intentional overdose was suspected. At the scene, she was found to be in cardiac arrest with pulseless electrical activity and underwent cardiopulmonary resuscitation, including intravenous epinephrine and bicarbonate. In the emergency department, her physical exam was notable for cough and gag reflexes and movement in all extremities with increased muscle tone and tachycardia. Her initial postresuscitation ECG showed sinus rhythm with QRS 92 ms and QTc 502 ms. Her temperature was initially normal, but she rapidly became febrile to 41.8 °C shortly after admission. She was treated symptomatically and with cyproheptadine for suspected serotonin syndrome (SS) but became increasingly hemodynamically unstable over the next 6 h and then developed torsades des pointes (TdP) progressing to pulseless, wide complex tachycardia. She underwent cardiopulmonary resuscitation (CPR) for approximately 50 min but ultimately expired. Postmortem serum analysis revealed a citalopram concentration of 7300 ng/mL (therapeutic range 9-200 ng/mL) and THC, but no other non-resuscitation drugs or substances. Citalopram overdoses often have only mild to moderate symptoms, particularly with ingestions under 600 mg in adults. However, with higher doses, severe manifestations have been described, including QTc prolongation, TdP, and seizures. Serotonin syndrome has also been described in SSRI overdose, and our patient exhibited signs consistent with SS, including increased muscle tone and autonomic dysregulation. Our patient's serum concentration suggests a massive overdose, with major clinical effects, possible SS, and death. Although most patients recover from citalopram overdose, high-dose ingestions can produce severe effects and fatalities may occur. In this case, it is likely that the patient's delayed presentation also contributed significantly to her death. The clinician must be aware of the potential for large ingestions of citalopram to produce life-threatening effects and monitor closely for the neurologic, cardiovascular, and other manifestations that, in rare cases, can be fatal.

Camouflage and misdirection: the full-on assault of ebola virus disease.

PubMed

Misasi, John; Sullivan, Nancy J

2014-10-23

Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and nonhuman primates. Ebola protein interactions with host cellular proteins disrupt type I and type II interferon responses, RNAi antiviral responses, antigen presentation, T-cell-dependent B cell responses, humoral antibodies, and cell-mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and "cytokine storm" that is characteristic of fatal ebolavirus infection. Here, we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade antiviral defenses.

A comparison of clinical and epidemiological characteristics of fatal human infections with H5N1 and human influenza viruses in Thailand, 2004-2006.

PubMed

Shinde, Vivek; Hanshaoworakul, Wanna; Simmerman, James M; Narueponjirakul, Ubolrat; Sanasuttipun, Wiwan; Kaewchana, Suchada; Areechokechai, Darin; Ungchusak, Kumnuan; Fry, Alicia M

2011-04-29

The National Avian Influenza Surveillance (NAIS) system detected human H5N1 cases in Thailand from 2004-2006. Using NAIS data, we identified risk factors for death among H5N1 cases and described differences between H5N1 and human (seasonal) influenza cases. NAIS identified 11,641 suspect H5N1 cases (e.g. persons with fever and respiratory symptoms or pneumonia, and exposure to sick or dead poultry). All suspect H5N1 cases were tested with polymerase chain reaction (PCR) assays for influenza A(H5N1) and human influenza viruses. NAIS detected 25 H5N1 and 2074 human influenza cases; 17 (68%) and 22 (1%) were fatal, respectively. We collected detailed information from medical records on all H5N1 cases, all fatal human influenza cases, and a sampled subset of 230 hospitalized non-fatal human influenza cases drawn from provinces with ≥1 H5N1 case or human influenza fatality. Fatal versus non-fatal H5N1 cases were more likely to present with low white blood cell (p = 0.05), lymphocyte (p<0.02), and platelet counts (p<0.01); have elevated liver enzymes (p = 0.05); and progress to circulatory (p<0.001) and respiratory failure (p<0.001). There were no differences in age, medical conditions, or antiviral treatment between fatal and non-fatal H5N1 cases. Compared to a sample of human influenza cases, all H5N1 cases had direct exposure to sick or dead birds (60% vs. 100%, p<0.05). Fatal H5N1 and fatal human influenza cases were similar clinically except that fatal H5N1 cases more commonly: had fever (p<0.001), vomiting (p<0.01), low white blood cell counts (p<0.01), received oseltamivir (71% vs. 23%, p<.001), but less often had ≥1 chronic medical conditions (p<0.001). In the absence of diagnostic testing during an influenza A(H5N1) epizootic, a few epidemiologic, clinical, and laboratory findings might provide clues to help target H5N1 control efforts. Severe human influenza and H5N1 cases were clinically similar, and both would benefit from early antiviral treatment.

Porcine models of muscular dystrophy

USDA-ARS?s Scientific Manuscript database

Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein, dystrophin. This disease is modeled by a variety of animal models including several fish models, mice, rats, and dogs. While these models have contributed substantially t...

Effect of Ebola progression on transmission and control in Liberia.

PubMed

Yamin, Dan; Gertler, Shai; Ndeffo-Mbah, Martial L; Skrip, Laura A; Fallah, Mosoka; Nyenswah, Tolbert G; Altice, Frederick L; Galvani, Alison P

2015-01-06

The Ebola outbreak that is sweeping across West Africa is the largest, most volatile, and deadliest Ebola epidemic ever recorded. Liberia is the most profoundly affected country, with more than 3500 infections and 2000 deaths recorded in the past 3 months. To evaluate the contribution of disease progression and case fatality on transmission and to examine the potential for targeted interventions to eliminate the disease. Stochastic transmission model that integrates epidemiologic and clinical data on incidence and case fatality, daily viral load among survivors and nonsurvivors evaluated on the basis of the 2000-2001 outbreak in Uganda, and primary data on contacts of patients with Ebola in Liberia. Montserrado County, Liberia, July to September 2014. Ebola incidence and case-fatality records from 2014 Liberian Ministry of Health and Social Welfare. The average number of secondary infections generated throughout the entire infectious period of a single infected case, R, was estimated as 1.73 (95% CI, 1.66 to 1.83). There was substantial stratification between survivors (RSurvivors), for whom the estimate was 0.66 (CI, 0.10 to 1.69), and nonsurvivors (RNonsurvivors), for whom the estimate was 2.36 (CI, 1.72 to 2.80). The nonsurvivors had the highest risk for transmitting the virus later in the course of disease progression. Consequently, the isolation of 75% of infected individuals in critical condition within 4 days from symptom onset has a high chance of eliminating the disease. Projections are based on the initial dynamics of the epidemic, which may change as the outbreak and interventions evolve. These results underscore the importance of isolating the most severely ill patients with Ebola within the first few days of their symptomatic phase. National Institutes of Health.

Effect of Ebola Progression on Transmission and Control in Liberia

PubMed Central

Yamin, Dan; Gertler, Shai; Ndeffo-Mbah, Martial L.; Skrip, Laura A.; Fallah, Mosoka; Nyenswah, Tolbert G.; Altice, Frederick L.; Galvani, Alison P.

2015-01-01

Background The Ebola outbreak that is sweeping across West Africa is the largest, most volatile, and deadliest Ebola epidemic ever recorded. Liberia is the most profoundly affected country, with more than 3500 infections and 2000 deaths recorded in the past 3 months. Objective To evaluate the contribution of disease progression and case fatality on transmission and to examine the potential for targeted interventions to eliminate the disease. Design Stochastic transmission model that integrates epidemiologic and clinical data on incidence and case fatality, daily viral load among survivors and nonsurvivors evaluated on the basis of the 2000–2001 outbreak in Uganda, and primary data on contacts of patients with Ebola in Liberia. Setting Montserrado County, Liberia, July to September 2014. Measurements Ebola incidence and case-fatality records from 2014 Liberian Ministry of Health and Social Welfare. Results The average number of secondary infections generated throughout the entire infectious period of a single infected case, R, was estimated as 1.73 (95% CI, 1.66 to 1.83). There was substantial stratification between survivors (RSurvivors), for whom the estimate was 0.66 (CI, 0.10 to 1.69), and nonsurvivors (RNonsurvivors), for whom the estimate was 2.36 (CI, 1.72 to 2.80). The nonsurvivors had the highest risk for transmitting the virus later in the course of disease progression. Consequently, the isolation of 75% of infected individuals in critical condition within 4 days from symptom onset has a high chance of eliminating the disease. Limitation Projections are based on the initial dynamics of the epidemic, which may change as the outbreak and interventions evolve. Conclusion These results underscore the importance of isolating the most severely ill patients with Ebola within the first few days of their symptomatic phase. Primary Funding Source National Institutes of Health. PMID:25347321

Rescue therapeutic strategy combining ultra-protective mechanical ventilation with extracorporeal CO2 removal membrane in near-fatal asthma with severe pulmonary barotraumas: A case report.

PubMed

Pavot, Arthur; Mallat, Jihad; Vangrunderbeeck, Nicolas; Thevenin, Didier; Lemyze, Malcolm

2017-10-01

Mechanical ventilation of severe acute asthma is still considered a challenging issue, mainly because of the gas trapping phenomenon with the potential for life-threatening barotraumatic pulmonary complications. Herein, we describe 2 consecutive cases of near-fatal asthma for whom the recommended protective mechanical ventilation approach using low tidal volume of 6 mL/kg and small levels of PEEP was rapidly compromised by giant pneumomediastinum with extensive subcutaneousemphysema. Near fatal asthma. A rescue therapeutic strategy combining extracorporeal CO2 removal membrane with ultra-protective extremely low tidal volume (3 mL/kg) ventilation was applied. Both patients survived hospital discharge. These 2 cases indicate that ECCO2R associated with ultra-protective ventilation could be an alternative to surgery in case of life-threatening barotrauma occurring under mechanical ventilation.

Occupational Exposures in the Oil and Gas Extraction Industry: State of the Science and Research Recommendations

PubMed Central

Witter, Roxana Z.; Tenney, Liliana; Clark, Suzanne; Newman, Lee S.

2015-01-01

The oil and gas extraction industry is rapidly growing due to horizontal drilling and high volume hydraulic fracturing (HVHF). This growth has provided new jobs and economic stimulus. The industry occupational fatality rate is 2.5 times higher than the construction industry and 7 times higher than general industry; however injury rates are lower than the construction industry, suggesting injuries are not being reported. Some workers are exposed to crystalline silica at hazardous levels, above occupational health standards. Other hazards (particulate, benzene, noise, radiation) exist. In this article, we review occupational fatality and injury rate data; discuss research looking at root causes of fatal injuries and hazardous exposures; review interventions aimed at improving occupational health and safety; and discuss information gaps and areas of needed research. We also describe Wyoming efforts to improve occupational safety in this industry, as a case example. PMID:24634090

A case of osmotic demyelination syndrome occurred after the correction of severe hyponatraemia in hyperemesis gravidarum

PubMed Central

2014-01-01

Background Osmotic demyelination syndrome (ODS) may be observed as a result of a rapid change in serum osmolarity, such as that induced by an overly rapid correction of serum sodium levels in hyponatraemic patients. Case presentation We describe the case of a 21-year-old woman who was hospitalized at week 10 of gestation because of severe hyperemesis. At admission the patient appeared restless and confused and severe hyponatraemia (serum sodium 107 mmol/L) and hypokalemia (serum potassium 1.1 mmol/L) were detected. Active and simultaneous correction of these imbalances led to an overly rapid increase of serum sodium levels (17 mmol/L in the first 24 hours). Isotonic saline solution was stopped and replaced by 5% dextrose solution infusion. However, the neurological alterations worsened and the radiological features were consistent with the diagnosis of extra-pontine ODS. Steroids were administered intravenously with progressive improvement of biochemical and clinical abnormalities. At the time of discharge, 20 days later, the patient was able to walk and eat autonomously with only minimal external support. Conclusions This report illustrates an unusual case of ODS, occurred after an excessive rate of correction of hyponatraemia obtained with isotonic saline infusion. Hypokaliemia and its active correction very likely played a crucial role in facilitating the onset of ODS. This interesting aspect will be explained in detail in the article. A more cautious and thoughtful correction of electrolyte alterations, would have probably prevented the onset of ODS in this patient. Physicians should be aware of the possibly fatal consequences that an exceedingly rapid change of serum osmolarity may have and should strictly follow the known safety measures in order to prevent it to occur. PMID:24725751

Progressive alveolar echinococcosis after discontinuation of anthelmintic therapy

PubMed Central

2013-01-01

We report a case of a female patient with alveolar echinococcosis (AE) who presented with progressive pulmonary and hepatic lesions and had a fatal outcome. AE affecting the liver, the lungs and the brain had been diagnosed 20 years ago and treated successfully with albendazole and stereotactic gamma knife therapy. Due to severe hair loss albendazole was stopped 14 years before presentation. Lesions had remained stable in imaging studies for at least 11 years, but then had started to progress. Lifelong anthelmintic maintenance therapy and regular follow-up may therefore be crucial in order to prevent such a dramatic clinical course. PMID:24289745

Decoding ALS: From Genes to Mechanism

PubMed Central

Taylor, J. Paul; Brown, Robert H.; Cleveland, Don W.

2017-01-01

Preface Amyotrophic lateral sclerosis (ALS) is a progressive and uniformly fatal neurodegenerative disease. A plethora of genetic factors underlying ALS have now been identified that drive motor neuron degeneration, increase susceptibility to the disease, or influence the rate of progression. Emerging themes include dysfunction in RNA metabolism and protein homeostasis, with specific defects in nucleocytoplasmic trafficking, induction of endoplasmic reticulum stress, and impaired dynamics of ribonucleoprotein bodies such as RNA granules that assemble through the process of liquid-liquid phase separation. Extraordinary recent progress in understanding the biology of ALS provides new grounds for optimism that meaningful therapies for ALS will be identified. PMID:27830784

Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival

PubMed Central

Henkel, Jenny S; Beers, David R; Wen, Shixiang; Rivera, Andreana L; Toennis, Karen M; Appel, Joan E; Zhao, Weihua; Moore, Dan H; Powell, Suzanne Z; Appel, Stanley H

2013-01-01

In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are neuroprotective, slowing disease progression. To address whether Tregs and FoxP3, a transcription factor required for Treg function, similarly influence progression rates of ALS patients, T-lymphocytes from patients were assessed by flow cytometry. Both numbers of Tregs and their FoxP3 protein expressions were reduced in rapidly progressing ALS patients and inversely correlated with progression rates. The mRNA levels of FoxP3, TGF-β, IL4 and Gata3, a Th2 transcription factor, were reduced in rapidly progressing patients and inversely correlated with progression rates. Both FoxP3 and Gata3 were accurate indicators of progression rates. No differences in IL10, Tbx21, a Th1 transcription factor or IFN-γ expression were found between slow and rapidly progressing patients. A 3.5-year prospective study with a second larger cohort revealed that early reduced FoxP3 levels were indicative of progression rates at collection and predictive of future rapid progression and attenuated survival. Collectively, these data suggest that Tregs and Th2 lymphocytes influence disease progression rates. Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients. PMID:23143995

Progress towards zero, an international comparison: Improvements in traffic fatality from 1990 to 2010 for different age groups in the USA and 15 of its peers.

PubMed

Ahangari, Hamed; Atkinson-Palombo, Carol; Garrick, Norman W

2016-06-01

In January 2015, the United States Department of Transportation (USDOT) announced that the official target of the federal government transportation safety policy was zero deaths. Having a better understanding of traffic fatality trends of various age cohorts-and to what extent the US is lagging other countries-is a crucial first step to identifying policies that may help the USDOT achieve its goal. In this paper we analyze fatality rates for different age cohorts in developed countries to better understand how road traffic fatality patterns vary across countries by age cohort. Using benchmarking analysis and comparative index analysis based on panel data modelling and data for selected years between 1990 and 2010, we compare changes in the rate of road traffic fatality over time, as well as the absolute level of road traffic fatality for six age groups in the US, with 15 other developed countries. Our findings illustrate tremendous variations in road fatality rates (both in terms of the absolute values and the rates of improvement over time) among different age cohorts in all of the 16 countries. Looking specifically at the US, our analysis shows that safety improvements for Youngsters (15-17 years old) was much better than for other age groups, and closely tracked peer countries. In sharp contrast, Children (0-14 years old) and Seniors (+65 years old) in the US, fare very poorly when compared to peer countries. For example, in 2010, Children in the US were a stunning five times more likely to experience a road traffic fatality than Children in the UK. This startling statistic suggests an immediate need to explore further the causes and potential solutions to these disparities. This is especially important if countries, including the US, are to achieve the ambitious goals set out in Zero Vision initiatives. Copyright © 2016 Elsevier Ltd and National Safety Council. All rights reserved.

Methemoglobinemia and benzocaine.

PubMed

Moos, Daniel D; Cuddeford, James D

2007-01-01

Benzocaine administration to facilitate upper endoscopic procedures can result in the relatively uncommon but potentially fatal complication known as methemoglobinemia. For this reason, the Veterans Health Administration (VA) announced on February 8, 2006, that they would stop using benzocaine-containing sprays for procedures involving the mouth and throat. Methemoglobinemia should be considered in any patient who demonstrates cyanosis, respiratory distress, headache, lightheadedness, and a dark, chocolate-colored blood after receiving pharyngeal anesthesia. Prompt recognition of this rare (but potentially fatal) condition is important. Once identified, treatment is generally rapid with methylene blue. The patient should be monitored in the intensive care setting for recurrence. Knowledge of this adverse medication reaction is essential for all gastroenterology nurses.

Camouflage and Misdirection: The Full-On Assault of Ebola Virus Disease

PubMed Central

Misasi, John; Sullivan, Nancy J.

2014-01-01

Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and non-human primates. Ebola protein interactions with host cellular proteins disrupt Type I and Type II interferon responses, RNAi anti-viral responses, antigen presentation, T-cell mediated antibody responses, humoral antibodies and cell mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and “cytokine storm” that is characteristic of fatal ebolavirus infection. Here we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade anti-viral defenses. PMID:25417101

Seat belt, DWI, and other traffic violations among recent immigrants in Florida and Tennessee : traffic tech.

DOT National Transportation Integrated Search

2013-05-01

The rapidly changing racial and ethnic composition of the : U.S. population is important to traffic safety specialists : because involvement in fatal traffic crashes varies across : racial and ethnic groups. Some research suggests that certain : mino...

Assessing flight safety differences between the United States regional and major airlines

NASA Astrophysics Data System (ADS)

Sharp, Broderick H.

During 2008, the U.S. domestic airline departures exceeded 28,000 flights per day. Thirty-nine or less than 0.2 of 1% of these flights resulted in operational incidents or accidents. However, even a low percentage of airline accidents and incidents continue to cause human suffering and property loss. The charge of this study was the comparison of U.S. major and regional airline safety histories. The study spans safety events from January 1982 through December 2008. In this quantitative analysis, domestic major and regional airlines were statistically tested for their flight safety differences. Four major airlines and thirty-seven regional airlines qualified for the safety study which compared the airline groups' fatal accidents, incidents, non-fatal accidents, pilot errors, and the remaining six safety event probable cause types. The six other probable cause types are mechanical failure, weather, air traffic control, maintenance, other, and unknown causes. The National Transportation Safety Board investigated each airline safety event, and assigned a probable cause to each event. A sample of 500 events was randomly selected from the 1,391 airlines' accident and incident population. The airline groups' safety event probabilities were estimated using the least squares linear regression. A probability significance level of 5% was chosen to conclude the appropriate research question hypothesis. The airline fatal accidents and incidents probability levels were 1.2% and 0.05% respectively. These two research questions did not reach the 5% significance level threshold. Therefore, the airline groups' fatal accidents and non-destructive incidents probabilities favored the airline groups' safety differences hypothesis. The linear progression estimates for the remaining three research questions were 71.5% for non-fatal accidents, 21.8% for the pilot errors, and 7.4% significance level for the six probable causes. These research questions' linear regressions are greater than the 5% level. Consequently, these three research questions favored airline groups' safety similarities hypothesis. The study indicates the U.S. domestic major airlines were safer than the regional airlines. Ideas for potential airline safety progress can examine pilot fatigue, the airline groups' hiring policies, the government's airline oversight personnel, or the comparison of individual airline's operational policies.

Altered Splicing of the BIN1 Muscle-Specific Exon in Humans and Dogs with Highly Progressive Centronuclear Myopathy

PubMed Central

Böhm, Johann; Vasli, Nasim; Maurer, Marie; Cowling, Belinda; Shelton, G. Diane; Kress, Wolfram; Toussaint, Anne; Prokic, Ivana; Schara, Ulrike; Anderson, Thomas James; Weis, Joachim; Tiret, Laurent; Laporte, Jocelyn

2013-01-01

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies. PMID:23754947

A Comparison of Clinical and Epidemiological Characteristics of Fatal Human Infections with H5N1 and Human Influenza Viruses in Thailand, 2004–2006

PubMed Central

Shinde, Vivek; Hanshaoworakul, Wanna; Simmerman, James M.; Narueponjirakul, Ubolrat; Sanasuttipun, Wiwan; Kaewchana, Suchada; Areechokechai, Darin; Ungchusak, Kumnuan; Fry, Alicia M.

2011-01-01

Background The National Avian Influenza Surveillance (NAIS) system detected human H5N1 cases in Thailand from 2004–2006. Using NAIS data, we identified risk factors for death among H5N1 cases and described differences between H5N1 and human (seasonal) influenza cases. Methods and Findings NAIS identified 11,641 suspect H5N1 cases (e.g. persons with fever and respiratory symptoms or pneumonia, and exposure to sick or dead poultry). All suspect H5N1 cases were tested with polymerase chain reaction (PCR) assays for influenza A(H5N1) and human influenza viruses. NAIS detected 25 H5N1 and 2074 human influenza cases; 17 (68%) and 22 (1%) were fatal, respectively. We collected detailed information from medical records on all H5N1 cases, all fatal human influenza cases, and a sampled subset of 230 hospitalized non-fatal human influenza cases drawn from provinces with ≥1 H5N1 case or human influenza fatality. Fatal versus non-fatal H5N1 cases were more likely to present with low white blood cell (p = 0.05), lymphocyte (p<0.02), and platelet counts (p<0.01); have elevated liver enzymes (p = 0.05); and progress to circulatory (p<0.001) and respiratory failure (p<0.001). There were no differences in age, medical conditions, or antiviral treatment between fatal and non-fatal H5N1 cases. Compared to a sample of human influenza cases, all H5N1 cases had direct exposure to sick or dead birds (60% vs. 100%, p<0.05). Fatal H5N1 and fatal human influenza cases were similar clinically except that fatal H5N1 cases more commonly: had fever (p<0.001), vomiting (p<0.01), low white blood cell counts (p<0.01), received oseltamivir (71% vs. 23%, p<.001), but less often had ≥1 chronic medical conditions (p<0.001). Conclusions In the absence of diagnostic testing during an influenza A(H5N1) epizootic, a few epidemiologic, clinical, and laboratory findings might provide clues to help target H5N1 control efforts. Severe human influenza and H5N1 cases were clinically similar, and both would benefit from early antiviral treatment. PMID:21559080

Fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery for a pituitary tumor: A case report.

PubMed

Li, Chiao-Zhu; Li, Chiao-Ching; Hsieh, Chih-Chuan; Lin, Meng-Chi; Hueng, Dueng-Yuan; Liu, Feng-Chen; Chen, Yuan-Hao

2017-01-01

The fatal type of antiphospholipid syndrome is a rare but life-threating condition. It may be triggered by surgery or infection. Endoscopic transnasal-transsphenoidal surgery is a common procedure for pituitary tumor. We report a catastrophic case of a young woman died of fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery. A 31-year-old woman of a history of stroke received endoscopic transnasal-transsphenoidal surgery for a pituitary tumor. The whole procedure was smooth. However, the patient suffered from acute delirium on postoperative day 4. Then, her consciousness became comatose state rapidly with dilatation of pupils. Urgent magnetic resonance imaging of brain demonstrated multiple acute lacunar infarcts. The positive antiphosphoipid antibody and severe thrombocytopenia were also noted. Fatal antiphospholipid syndrome was diagnosed. Plasma exchange, corticosteroids, anticoagulant agent were prescribed. The hemodynamic condition was gradually stable. However, the consciousness was still in deep coma. The patient died of organ donation 2 months later. If patients have a history of cerebral stroke in their early life, such as a young stroke, the APS and higher risk of developing fatal APS after major surgery should be considered. The optimal management of APS remains controversial. The best treatment strategies are only early diagnosis and aggressive therapies combing of anticoagulant, corticosteroid, and plasma exchange. The intravenous immunoglobulin is prescribed for patients with refractory APS.

A Comparative Analysis of State Traffic Safety Countermeasures and Implications for Progress “Toward Zero Deaths” in the United States : Traffic Safety Facts - Research Note

DOT National Transportation Integrated Search

2017-10-01

States use a variety of countermeasures to reduce traffic crashes, injuries, and fatalities within their jurisdictions. These countermeasures focus primarily on engineering, law enforcement, and public education (NHTSA, 2006). NHTSA's bi-annual publi...

AIR POLLUTION AND CASE FATALITY OF SARS IN THE PEOPLE'S REPUBLIC OF CHINA: AN ECOLOGIC STUDY. (R827352)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Seat-Belt Use In US Counties: Limited Progress Toward Healthy People 2020 Objectives.

PubMed

Sunshine, Jacob; Dwyer-Lindgren, Laura; Chen, Alan; Mokdad, Ali H

2017-04-01

Spikes in automobile fatalities in 2015 and 2016 have renewed discussions about automobile safety. We measured the prevalence of reported seat-belt compliance in every US county from 2002 to 2012 and found considerable variation. Project HOPE—The People-to-People Health Foundation, Inc.

A novel risk assessment method for landfill slope failure: Case study application for Bhalswa Dumpsite, India.

PubMed

Jahanfar, Ali; Amirmojahedi, Mohsen; Gharabaghi, Bahram; Dubey, Brajesh; McBean, Edward; Kumar, Dinesh

2017-03-01

Rapid population growth of major urban centres in many developing countries has created massive landfills with extraordinary heights and steep side-slopes, which are frequently surrounded by illegal low-income residential settlements developed too close to landfills. These extraordinary landfills are facing high risks of catastrophic failure with potentially large numbers of fatalities. This study presents a novel method for risk assessment of landfill slope failure, using probabilistic analysis of potential failure scenarios and associated fatalities. The conceptual framework of the method includes selecting appropriate statistical distributions for the municipal solid waste (MSW) material shear strength and rheological properties for potential failure scenario analysis. The MSW material properties for a given scenario is then used to analyse the probability of slope failure and the resulting run-out length to calculate the potential risk of fatalities. In comparison with existing methods, which are solely based on the probability of slope failure, this method provides a more accurate estimate of the risk of fatalities associated with a given landfill slope failure. The application of the new risk assessment method is demonstrated with a case study for a landfill located within a heavily populated area of New Delhi, India.

Identification of pulmonary edema in forensic autopsy cases of fatal anaphylactic shock using Fourier transform infrared microspectroscopy.

PubMed

Lin, Hancheng; Luo, Yiwen; Wang, Lei; Deng, Kaifei; Sun, Qiran; Fang, Ruoxi; Wei, Xin; Zha, Shuai; Wang, Zhenyuan; Huang, Ping

2018-03-01

Anaphylaxis is a rapid allergic reaction that may cause sudden death. Currently, postmortem diagnosis of anaphylactic shock is sometimes difficult and often achieved through exclusion. The aim of our study was to investigate whether Fourier transform infrared (FTIR) microspectroscopy combined with pattern recognition methods would be complementary to traditional methods and provide a more accurate postmortem diagnosis of fatal anaphylactic shock. First, the results of spectral peak area analysis showed that the pulmonary edema fluid of the fatal anaphylactic shock group was richer in protein components than the control group, which included mechanical asphyxia, brain injury, and acute cardiac death. Subsequently, principle component analysis (PCA) was performed and showed that the anaphylactic shock group contained more turn and α-helix protein structures as well as less tyrosine-rich proteins than the control group. Ultimately, a partial least-square discriminant analysis (PLS-DA) model combined with a variables selection method called the genetic algorithm (GA) was built and demonstrated good separation between these two groups. This pilot study demonstrates that FTIR microspectroscopy has the potential to be an effective aid for postmortem diagnosis of fatal anaphylactic shock.

Assessment of the 2010 global measles mortality reduction goal: results from a model of surveillance data.

PubMed

Simons, Emily; Ferrari, Matthew; Fricks, John; Wannemuehler, Kathleen; Anand, Abhijeet; Burton, Anthony; Strebel, Peter

2012-06-09

In 2008 all WHO member states endorsed a target of 90% reduction in measles mortality by 2010 over 2000 levels. We developed a model to estimate progress made towards this goal. We constructed a state-space model with population and immunisation coverage estimates and reported surveillance data to estimate annual national measles cases, distributed across age classes. We estimated deaths by applying age-specific and country-specific case-fatality ratios to estimated cases in each age-country class. Estimated global measles mortality decreased 74% from 535,300 deaths (95% CI 347,200-976,400) in 2000 to 139,300 (71,200-447,800) in 2010. Measles mortality was reduced by more than three-quarters in all WHO regions except the WHO southeast Asia region. India accounted for 47% of estimated measles mortality in 2010, and the WHO African region accounted for 36%. Despite rapid progress in measles control from 2000 to 2007, delayed implementation of accelerated disease control in India and continued outbreaks in Africa stalled momentum towards the 2010 global measles mortality reduction goal. Intensified control measures and renewed political and financial commitment are needed to achieve mortality reduction targets and lay the foundation for future global eradication of measles. US Centers for Disease Control and Prevention (PMS 5U66/IP000161). Copyright © 2012 Elsevier Ltd. All rights reserved.

False negative PCR despite high levels of JC virus DNA in spinal fluid: Implications for diagnostic testing

PubMed Central

Landry, Marie L.; Eid, Tore; Bannykh, Serguei; Major, Eugene

2009-01-01

Genome amplification methods such as polymerase chain reaction (PCR) have revolutionized our ability to detect viruses in spinal fluids of patients with neurologic diseases. It is not as well appreciated among clinicians that PCR protocols, quality assurance, and technical expertise vary significantly among laboratories. In a multi-laboratory blinded study of herpes simplex virus PCR, the most widely used and best validated CSF PCR assay, low-level positives were often missed and false positives were not uncommon [Schloss L, van Loon AM, Cinque P, Cleator G, Echevarria JM, Falk KI, et al. An international external quality assessment of nucleic acid amplification of herpes simplex virus. J Clin Virol 2003;28(2):175–85]. In addition, genome variability and mutations, which are increasingly recognized for a number of different viruses, can lead to falsely low or negative results. Both clinicians and laboratories must recognize the limitations of PCR, since misleading results may have serious consequences. We present here a case of a rapidly progressive, fatal neurologic illness in a young mother, whose CSF JCV DNA PCR at a reference laboratory was falsely negative. Ultimately, brain biopsy established the diagnosis of progressive multifocal leukoencephalopathy (PML). Repeat PCR testing of the same CSF targeting a different region of the genome yielded a high positive result. PMID:18701345

Traffic tech: Examination of changes to the motorcycle law in Puerto Rico.

DOT National Transportation Integrated Search

2017-04-01

Puerto Rico enacted a comprehensive motorcycle safety law in 2007 to address the rise in fatal motorcycle crashes. Prior to the enactment of the law, the popularity of motorcycle riding increased rapidly from 47,920 registrations in 2000, to 89,379 i...

Fatal Enterococcus durans aortic valve endocarditis: a case report and review of the literature

PubMed Central

Vijayakrishnan, Rajakrishnan; Rapose, Alwyn

2012-01-01

Most enterococcal endocarditis is caused by Enterococcus faecalis and Enterococcus faecium. Enterococcus durans is a rare member of non-faecalis, non-faecium enterococcal species and is found in the intestines of animals. E durans endocarditis is a very rare infection—only two cases of endocarditis in humans have been reported in the literature—and usually associated with good outcomes when treated with appropriate antibiotics. We report the first case of fatal E durans endocarditis. This patient had end-stage liver disease with associated compromised immune status that likely contributed to the progression of disease in spite of appropriate antibiotic coverage and clearance of bacteraemia. PMID:22684831

Rapid death of duck cells infected with influenza: a potential mechanism for host resistance to H5N1.

PubMed

Kuchipudi, Suresh V; Dunham, Stephen P; Nelli, Rahul; White, Gavin A; Coward, Vivien J; Slomka, Marek J; Brown, Ian H; Chang, Kin Chow

2012-01-01

Aquatic birds are the natural reservoir for most subtypes of influenza A, and a source of novel viruses with the potential to cause human pandemics, fatal zoonotic disease or devastating epizootics in poultry. It is well recognised that waterfowl typically show few clinical signs following influenza A infection, in contrast, terrestrial poultry such as chickens may develop severe disease with rapid death following infection with highly pathogenic avian influenza. This study examined the cellular response to influenza infection in primary cells derived from resistant (duck) and susceptible (chicken) avian hosts. Paradoxically, we observed that duck cells underwent rapid cell death following infection with low pathogenic avian H2N3, classical swine H1N1 and 'classical' highly pathogenic H5N1 viruses. Dying cells showed morphological features of apoptosis, increased DNA fragmentation and activation of caspase 3/7. Following infection of chicken cells, cell death occurred less rapidly, accompanied by reduced DNA fragmentation and caspase activation. Duck cells produced similar levels of viral RNA but less infectious virus, in comparison with chicken cells. Such rapid cell death was not observed in duck cells infected with a contemporary Eurasian lineage H5N1 fatal to ducks. The induction of rapid death in duck cells may be part of a mechanism of host resistance to influenza A, with the loss of this response leading to increased susceptibility to emergent strains of H5N1. These studies provide novel insights that should help resolve the long-standing enigma of host-pathogen relationships for highly pathogenic and zoonotic avian influenza.

Enterovirus 71 Outbreak, Brunei

PubMed Central

Sam, I-Ching; Yusof, Jaliha; Lim, Meng Keang; Misbah, Suzana; Hooi, Poh-Sim

2009-01-01

Enterovirus 71 (EV71) outbreaks occur periodically in the Asia-Pacific region. In 2006, Brunei reported its first major outbreak of EV71 infections, associated with fatalities from neurologic complications. Isolated EV71 strains formed a distinct lineage with low diversity within subgenogroup B5, suggesting recent introduction and rapid spread within Brunei. PMID:19116058

Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014.

PubMed

Nyakarahuka, Luke; Ojwang, Joseph; Tumusiime, Alex; Balinandi, Stephen; Whitmer, Shannon; Kyazze, Simon; Kasozi, Sam; Wetaka, Milton; Makumbi, Issa; Dahlke, Melissa; Borchert, Jeff; Lutwama, Julius; Ströher, Ute; Rollin, Pierre E; Nichol, Stuart T; Shoemaker, Trevor R

2017-06-01

In September 2014, a single fatal case of Marburg virus was identified in a healthcare worker in Kampala, Uganda. The source of infection was not identified, and no secondary cases were identified. We describe the rapid identification, laboratory diagnosis, and case investigation of the third Marburg virus outbreak in Uganda.

Techniques for Efficient Detection of Rapid Weather Change and Analysis of their Impacts on a Highway Network

DOT National Transportation Integrated Search

2017-10-06

Adverse weather conditions have a significant impact on the safety, mobility, and efficiency of highway networks. Annually, 24 percent of all crashes, more than 7,400 roadway fatalities, and over 673,000 crash related injuries were caused by adverse ...

Genome Sequencing of 18 Francisella Strains To Aid in Assay Development and Testing

DOE PAGES

Johnson, Shannon L.; Daligault, Hajnalka E.; Davenport, Karen W.; ...

2015-04-30

Francisella tularensis is a highly infectious bacterium that has the potential of causing high fatality rates if infections are untreated. To aid in the development of rapid and accurate detection assays, we have sequenced and annotated the genomes of 18 F. tularensis and Francisella philomiragia strains.

Rapidly fatal nasal natural killer/T-cell lymphoma: orbital and ocular adnexal presentations.

PubMed

Yousuf, Salman J; Kumar, Nitin; Kidwell, Earl D; Copeland, Robert A

2011-03-01

Nasal natural killer/T-cell lymphoma (NKTL) is an aggressive malignancy that may initially present with orbital and/or ocular adnexal symptoms. We describe the case of a 27-year-old female with nasal NKTL, who initially presented with epiphora and died 4 months thereafter.

Chlorogenic Acid Attenuates High Mobility Group Box 1 (HMGB1) and Enhances Host Defense Mechanisms in Murine Sepsis

PubMed Central

Lee, Chan-Ho; Yoon, Seong-Jin; Lee, Sun-Mee

2012-01-01

Sepsis is a complex, multifactorial, rapidly progressive disease characterized by an overwhelming activation of the immune system and the countervailing antiinflammatory response. In the current study in murine peritoneal macrophages, chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1) release in a concentration-dependent manner. Administration of chlorogenic acid also attenuated systemic HMGB1 accumulation in vivo and prevented mortality induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)-4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, which are critical for cytokine release. The protection conferred by chlorogenic acid was achieved through modulation of cytokine and chemokine release, suppression of immune cell apoptosis and augmentation of bacterial elimination. Chlorogenic acid warrants further evaluation as a potential therapeutic agent for the treatment of sepsis and other potentially fatal systemic inflammatory disorders. PMID:23168580

Current Understanding of Acute Bovine Liver Disease in Australia.

PubMed

Read, Elizabeth; Edwards, Jacqueline; Deseo, Myrna; Rawlin, Grant; Rochfort, Simone

2016-12-26

Acute bovine liver disease (ABLD) is a hepatotoxicity principally of cattle which occurs in southern regions of Australia. Severely affected animals undergo rapid clinical progression with mortalities often occurring prior to the recognition of clinical signs. Less severely affected animals develop photosensitization and a proportion can develop liver failure. The characteristic histopathological lesion in acute fatal cases is severe, with acute necrosis of periportal hepatocytes with hemorrhage into the necrotic areas. Currently there are a small number of toxins that are known to cause periportal necrosis in cattle, although none of these have so far been linked to ABLD. Furthermore, ABLD has frequently been associated with the presence of rough dog's tail grass ( Cynosurus echinatus ) and Drechslera spp. fungi in the pasture system, but it is currently unknown if these are etiological factors. Much of the knowledge about ABLD is contained within case reports, with very little experimental research investigating the specific cause(s). This review provides an overview of the current and most recently published knowledge of ABLD. It also draws on wider research and unpublished reports to suggest possible fungi and mycotoxins that may give rise to ABLD.

Clinical and pathological aspects of human African trypanosomiasis (T. b. gambiense) with particular reference to reactive arsenical encephalopathy.

PubMed

Haller, L; Adams, H; Merouze, F; Dago, A

1986-01-01

Fourteen of 330 patients treated with melarsoprol (Mel B) for human African trypanosomiasis (HAT) developed a severe reactive arsenical encephalopathy (RAE). Six of these cases were fatal and postmortem examination was performed on 5 patients. Symptoms of "sleeping sickness" were compared with symptoms after treatment with arsenicals and the subsequent onset of RAE. There are 3 characteristic syndromes of RAE: convulsive status associated with acute cerebral edema, rapidly progressive coma without convulsions, and acute nonlethal mental disturbances without neurological signs. Three subjects revealed hypoxic brain damage with acute cerebral edema, and multiple hemorrhages of brain stem in those comatose. The pathology of the underlying HAT (chronic perivascular inflammation and plasma cytic infiltration of the brain) and the pathology of the RAE (characterized by acute vasculitis) are distinct. RAE occurs in the first as well as in the second stage (CNS involvement) of trypanosomiasis but the reason for this is unclear; an exclusive toxicity of the drug, or a Herxheimer reaction are possible but seem unlikely. Both clinical and laboratory findings point rather to a drug-related, delayed immune response.

Chronic liver disease and consumption of raw oysters: a potentially lethal combination--a review of Vibrio vulnificus septicemia.

PubMed

Haq, Samir M; Dayal, Hari H

2005-05-01

Vibrio vulnificus septicemia is the most common cause of fatality related to seafood consumption in the United States. It occurs predominantly in patients with chronic liver disease following consumption of raw oysters. V. vulnificus is a highly virulent human pathogen, normally found in warm estuarine and marine environment. It lodges in filter feeders like oysters. The onset of this illness is abrupt, rapidly progressing to septic shock with a high mortality. Clinicians managing patients with chronic liver disease need to educate their patients of the risk associated with the consumption of raw seafood, especially oysters. A high index of suspicion is necessary for appropriate treatments, as doxycycline, the antibiotic of choice, is not usually a part of the empiric therapy for septicemia. The high mortality associated with this septicemia demands aggressive preventive measures: susceptible individuals must be forewarned by signs displayed in restaurants; physicians must educate patients with chronic liver disease about the risk of raw oyster consumption; and harvesting methods which reduce contamination by V. vulnificus must be utilized.

Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague

PubMed Central

Sebbane, Florent; Jarrett, Clayton O.; Gardner, Donald; Long, Daniel; Hinnebusch, B. Joseph

2006-01-01

Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread. PMID:16567636

Spinal Cord Ventral Horns and Lymphoid Organ Involvement in Powassan Virus Infection in a Mouse Model

PubMed Central

Santos, Rodrigo I.; Hermance, Meghan E.; Gelman, Benjamin B.; Thangamani, Saravanan

2016-01-01

Powassan virus (POWV) belongs to the family Flaviviridae and is a member of the tick-borne encephalitis serogroup. Transmission of POWV from infected ticks to humans has been documented in the USA, Canada, and Russia, causing fatal encephalitis in 10% of human cases and significant neurological sequelae in survivors. We used C57BL/6 mice to investigate POWV infection and pathogenesis. After footpad inoculation, infected animals exhibited rapid disease progression and 100% mortality. Immunohistochemistry and immunofluorescence revealed a very strong neuronal tropism of POWV infection. The central nervous system infection appeared as a meningoencephalitis with perivascular mononuclear infiltration and microglial activation in the brain, and a poliomyelitis-like syndrome with high level of POWV antigen at the ventral horn of the spinal cord. Pathological studies also revealed substantial infection of splenic macrophages by POWV, which suggests that the spleen plays a more important role in pathogenesis than previously realized. This report provides a detailed description of the neuroanatomical distribution of the lesions produced by POWV infection in C57BL/6 mice. PMID:27529273

Spinal Cord Ventral Horns and Lymphoid Organ Involvement in Powassan Virus Infection in a Mouse Model.

PubMed

Santos, Rodrigo I; Hermance, Meghan E; Gelman, Benjamin B; Thangamani, Saravanan

2016-08-12

Powassan virus (POWV) belongs to the family Flaviviridae and is a member of the tick-borne encephalitis serogroup. Transmission of POWV from infected ticks to humans has been documented in the USA, Canada, and Russia, causing fatal encephalitis in 10% of human cases and significant neurological sequelae in survivors. We used C57BL/6 mice to investigate POWV infection and pathogenesis. After footpad inoculation, infected animals exhibited rapid disease progression and 100% mortality. Immunohistochemistry and immunofluorescence revealed a very strong neuronal tropism of POWV infection. The central nervous system infection appeared as a meningoencephalitis with perivascular mononuclear infiltration and microglial activation in the brain, and a poliomyelitis-like syndrome with high level of POWV antigen at the ventral horn of the spinal cord. Pathological studies also revealed substantial infection of splenic macrophages by POWV, which suggests that the spleen plays a more important role in pathogenesis than previously realized. This report provides a detailed description of the neuroanatomical distribution of the lesions produced by POWV infection in C57BL/6 mice.

Laboratory Diagnosis of Human Rabies: Recent Advances

PubMed Central

Mani, Reeta Subramaniam; Madhusudana, Shampur Narayan

2013-01-01

Rabies, an acute progressive, fatal encephalomyelitis, transmitted most commonly through the bite of a rabid animal, is responsible for an estimated 61,000 human deaths worldwide. The true disease burden and public health impact due to rabies remain underestimated due to lack of sensitive laboratory diagnostic methods. Rapid diagnosis of rabies can help initiate prompt infection control and public health measures, obviate the need for unnecessary treatment/medical tests, and assist in timely administration of pre- or postexposure prophylactic vaccination to family members and medical staff. Antemortem diagnosis of human rabies provides an impetus for clinicians to attempt experimental therapeutic approaches in some patients, especially after the reported survival of a few cases of human rabies. Traditional methods for antemortem and postmortem rabies diagnosis have several limitations. Recent advances in technology have led to the improvement or development of several diagnostic assays which include methods for rabies viral antigen and antibody detection and assays for viral nucleic acid detection and identification of specific biomarkers. These assays which complement traditional methods have the potential to revolutionize rabies diagnosis in future. PMID:24348170

Fatal CNS vasculopathy in a patient with refractory celiac disease and lymph node cavitation.

PubMed

Keller, Christian E; Gamboa, Eugenia T; Hays, Arthur P; Karlitz, Jordan; Lowe, Gina; Green, Peter H R; Bhagat, Govind

2006-02-01

Celiac disease is an enteropathy occurring in genetically predisposed individuals due to a dietary intolerance to gluten. Patients with celiac disease may develop a neurological disorder of unknown cause, although autoimmune mechanisms are suspected. We report on a 56-year-old man with celiac disease, who became refractory to a gluten-free diet and died of a rapidly progressive encephalopathy. Magnetic resonance imaging indicated focal lesions of the cerebellum and brainstem, and electrodiagnostic studies suggested an axonal neuropathy. Autopsy revealed a flattened small-bowel mucosa with intraepithelial lymphocytosis, a spectrum of degenerative changes of the intra-abdominal and mediastinal lymph nodes, including cavitary degeneration, and splenomegaly. Histologically, the lymph nodes showed pseudocyst formation and lymphocytic vasculitis with fibrinoid necrosis, and sections of the brain exhibited fibrinoid degeneration of small blood vessels, sparse perivascular lymphocytic infiltrates, and perivascular ischemic lesions. Identical T-cell clones were identified in the duodenum, stomach, lymph nodes, and spleen. This patient had an unusual neurological disorder related to a vasculopathy, probably mediated by a circulating neoplastic clone of activated T cells.

Infections and systemic lupus erythematosus.

PubMed

Esposito, S; Bosis, S; Semino, M; Rigante, D

2014-09-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that presents a protean spectrum of clinical manifestations, and may affect any organ. The typical course of SLE is insidious, slow, and progressive, with potential exacerbations and remissions, and even dramatically acute and rapidly fatal outcomes. Recently, infections have been shown to be highly associated with the onset and/or exacerbations of SLE, and their possible causative and/or protective role has been largely emphasized in the medical literature. However, the etiopathogenesis of SLE is still obscure and far from being completely elucidated. Among infections, particularly Epstein-Barr virus (EBV), parvovirus B19, retrovirus, and cytomegalovirus (CMV) infections might play a pivotal pathogenetic role. The multifaceted interactions between infections and autoimmunity reveal many possibilities for either causative or protective associations. Indeed, some infections, primarily protozoan infections, might confer protection from autoimmune processes, depending on the unique interaction between the microorganism and host. Further studies are needed in order to demonstrate that infectious agents might, indeed, be causative of SLE, and to address the potential clinical sequelae of infections in the field of autoimmunity.

Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

PubMed

Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

2015-01-01

Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

Accidental and experimentally induced 5-fluorouracil toxicity in dogs.

PubMed

Sayre, Rebecca S; Barr, James W; Bailey, E Murl

2012-10-01

To summarize the literature involving 5-fluorouracil (5-FU) toxicosis in dogs. 5-Fluorouracil's mechanism of action revolves around the metabolism of 5-FU into fluorouridine triphosphate which then interferes with RNA synthesis and function as well as the inhibition of thymidylate synthase which ultimately impairs DNA stability. Toxicity of 5-FU is the most pronounced on rapidly dividing cells. Toxicity manifests itself mainly in the neurologic, gastrointestinal, respiratory, or hematopoietic systems. History of accidental exposure to 5-FU-containing products. Therapy for 5-FU toxicosis involves typical decontamination procedures and symptomatic therapy for the subsequent toxicity. Seizure control and treatment of the severe gastrointestinal signs that follow are the primary goals in the acute setting. As the disease progresses, management of the sequelae to bone marrow suppression and pulmonary complications are essential. The prognosis for dogs with ingestion of 5-FU is dependent on the amount consumed, with severe intoxication carrying a poor prognosis. Toxic doses can be as little as 5 mg/kg, and doses ≥40 mg/kg are reported to be uniformly fatal. © Veterinary Emergency and Critical Care Society 2012.

Factors associated with pilot fatalities in work-related aircraft crashes--Alaska, 1990-1999.

PubMed

2002-04-26

Despite its large geographic area, Alaska has only 12,200 miles of public roads, and 90% of the state's communities are not connected to a highway system. Commuter and air-taxi flights are essential for transportation of passengers and delivery of goods, services, and mail to outlying communities (Figure 1). Because of the substantial progress in decreasing fatalities in the fishing and logging industries, aviation crashes are the leading cause of occupational death in Alaska. During 1990-1999, aircraft crashes in Alaska caused 107 deaths among workers classified as civilian pilots. This is equivalent to 410 fatalities per 100,000 pilots each year, approximately five times the death rate for all U.S. pilots and approximately 100 times the death rate for all U.S. workers. As part of a collaborative aviation safety initiative that CDC's National Institute for Occupational Safety and Health (NIOSH) is implementing with the Federal Aviation Administration (FAA), the National Transportation Safety Board (NTSB), and the National Weather Service, CDC analyzed data from NTSB crash reports to determine factors associated with pilot fatalities in work-related aviation crashes in Alaska. This report summarizes the result of this analysis, which found that the following factors were associated with pilot fatalities: crashes involving a post-crash fire, flights in darkness or weather conditions requiring instrument use, crashes occurring away from an airport, and crashes in which the pilot was not using a shoulder restraint. Additional pilot training, improved fuel systems that are less likely to ignite in crashes, and company policies that discourage flying in poor weather conditions might help decrease pilot fatalities. More detailed analyses of crash data, collaborations with aircraft operators to improve safety, and evaluation of new technologies are needed.

Ten-year fatal and non-fatal myocardial infarction incidence in elderly populations in Spain: the EPICARDIAN cohort study

PubMed Central

Gabriel, Rafael; Alonso, Margarita; Reviriego, Blanca; Muñiz, Javier; Vega, Saturio; López, Isidro; Novella, Blanca; Suárez, Carmen; Rodríguez-Salvanés, Francisco

2009-01-01

Background In Spain, more than 85% of coronary heart disease deaths occur in adults older than 65 years. However, coronary heart disease incidence and mortality in the Spanish elderly have been poorly described. The aim of this study is to estimate the ten-year incidence and mortality rates of myocardial infarction in a population-based large cohort of Spanish elders. Methods A population-based cohort of 3729 people older than 64 years old, free of previous myocardial infarction, was established in 1995 in three geographical areas of Spain. Any case of fatal and non-fatal myocardial infarction was investigated until December 2004 using the "cold pursuit method", previously used and validated by the the WHO-MONICA project. Results Men showed a significantly (p < 0.001) higher cumulative incidence of myocardial infarction (7.2%; 95%CI: 5.94-8.54) than women (3.8%; 95%CI: 3.06-4.74). Although cumulative incidence increased with age (p < 0.05), gender-differences tended to narrow. Adjusted incidence rates were higher in men (957 per 100 000 person-years) than in women (546 per 100 000 person-years) (p < 0.001) and increased with age (p < 0.001). The increase was progressive in women but not in men. Adjusted mortality rates were also higher in men than in women (p < 0.001), being three times higher in the age group of ≥ 85 years old than in the age group of 65-74 years old (p < 0.001). Conclusion Incidence of fatal and non-fatal myocardial infarction is high in the Spanish elderly population. Men show higher rates than women, but gender differences diminish with age. PMID:19778417

An Analysis of 332 Fatalities Infected with Pandemic 2009 Influenza A (H1N1) in Argentina

PubMed Central

Balanzat, Ana M.; Hertlein, Christian; Apezteguia, Carlos; Bonvehi, Pablo; Cámera, Luis; Gentile, Angela; Rizzo, Oscar; Gómez-Carrillo, Manuel; Coronado, Fatima; Azziz-Baumgartner, Eduardo; Chávez, Pollyanna R.; Widdowson, Marc-Alain

2012-01-01

Background The apparent high number of deaths in Argentina during the 2009 pandemic led to concern that the influenza A H1N1pdm disease was different there. We report the characteristics and risk factors for influenza A H1N1pdm fatalities. Methods We identified laboratory-confirmed influenza A H1N1pdm fatalities occurring during June-July 2009. Physicians abstracted data on age, sex, time of onset of illness, medical history, clinical presentation at admission, laboratory, treatment, and outcomes using standardize questionnaires. We explored the characteristics of fatalities according to their age and risk group. Results Of 332 influenza A H1N1pdm fatalities, 226 (68%) were among persons aged <50 years. Acute respiratory failure was the leading cause of death. Of all cases, 249 (75%) had at least one comorbidity as defined by Advisory Committee on Immunization Practices. Obesity was reported in 32% with data and chronic pulmonary disease in 28%. Among the 40 deaths in children aged <5 years, chronic pulmonary disease (42%) and neonatal pathologies (35%) were the most common co-morbidities. Twenty (6%) fatalities were among pregnant or postpartum women of which only 47% had diagnosed co-morbidities. Only 13% of patients received antiviral treatment within 48 hours of symptom onset. None of children aged <5 years or the pregnant women received antivirals within 48 h of symptom onset. As the pandemic progressed, the time from symptom-onset to medical care and to antiviral treatment decreased significantly among case-patients who subsequently died (p<0.001). Conclusion Persons with co-morbidities, pregnant and who received antivirals late were over-represented among influenza A H1N1pdm deaths in Argentina, though timeliness of antiviral treatment improved during the pandemic. PMID:22506006

Accidental poisoning in childhood: five year urban population study with 15 year analysis of fatality.

PubMed Central

Pearn, J; Nixon, J; Ansford, A; Corcoran, A

1984-01-01

Patterns of accidental poisoning in children are changing dramatically. A five year population study (1977-81) was undertaken in urban children from Brisbane (population 1 000 000). A total of 2098 children were poisoned during this period with only one fatality, which represents a dramatic reduction in mortality. Over the past 15 years (1968-82) 13 children have died from accidental poisoning from this population, and two were murdered with drugs. A study of secular trends has indicated that peak incidence occurred in 1979, and the rate has been falling progressively since. The current age corrected rate of poisoning is 393 per 100 000 children per year (0-5 year olds). The rank order of poisons, drugs, and chemicals causing hospital admission and death is: petroleum distillates 13%; antihistamines 9%; benzodiazepines 9%; bleach and detergents 7%; and aspirin 6%. The ratio of fatalities to ingestions requiring hospital admission was calculated to give an index of a practical danger of noxious agents to which children are currently exposed and the rank order is: cardiotoxic drugs, one fatality to 25 ingestions; tricyclic antidepressants, one to 44; sympathomimetic drugs, one to 54; caustic soda, one to 68; aspirin, one fatality to 350 ingestions. Accidental poisoning of children leading to death has been reduced because patterns of drug prescriptions have changed, packaging of dangerous drugs has been made safer, and substances such as kerosene have been coloured blue. PMID:6140065

Bibliography of Literature for Avian Issues in Solar and Wind Energy and Other Activities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walston, Leroy J.; White, Ellen M.; Meyers, Stephanie A.

2015-04-01

Utility-scale solar energy has been a rapidly expanding energy sector in the United States in recent years and is expected to continue to grow. In 2014, concerns were raised over the risk of avian fatalities associated with utility-scale solar plants. With funding from the U.S. Department of Energy SunShot Program, Argonne National Laboratory and the National Renewable Energy Laboratory studied the issue and released A Review of Avian Monitoring and Mitigation Information at Existing Utility-Scale Solar Facilities (ANL/EVS-15/2, March 2015). A comprehensive literature review included peer-reviewed journal articles on avian fatalities from solar energy facilities and other sources (e.g., windmore » energy, building collisions, etc.), project-specific technical reports on avian monitoring and fatality at solar facilities, information on mitigation measures and best management practices, and literature pertaining to avian behavioral patterns and habitat use. The source citations are listed in this bibliography; they are current through December 2014.« less

[Postoperative necrotizing fasciitis: a rare and fatal complication].

PubMed

Ghezala, Hassen Ben; Feriani, Najla

2016-01-01

Postoperative parietal complications can be exceptionally severe and serious threatening vital prognosis. Necrotizing fasciitis is a rare infection of the skin and deep subcutaneous tissues, spreading along fascia and adipose tissue. It is mainly caused by group A streptococcus (streptococcus pyogenes) but also by other bacteria such as Vibrio vulnificus, Clostridium perfringens or Bacteroides fragilis. Necrotizing fasciitis is a real surgical and medical emergency. We report, in this study, a very rare case of abdominal parietal gangrene occurring in a 75-year-old woman on the fifth day after surgery for an ovarian cyst. Evolution was marked by occurrence of a refractory septic shock with a rapidly fatal course on the third day of management.

From Diagnosis, to Life Saving Therapy, to Hollywood: The Journey of John Crowley

ERIC Educational Resources Information Center

Apel, Laura

2010-01-01

In February of 2000, "Exceptional Parent" introduced readers to the Crowley family. The author profiled John, Aileen, and their three children: Megan, Patrick, and John Jr. They told "Exceptional Parent" that in 1998 both Megan and Patrick were diagnosed with Pompe disease, a progressive, multisystemic, debilitating, and often fatal muscular…

Scrapie resistant goats: Keep your herd healthy and help your business with a new gene test

USDA-ARS?s Scientific Manuscript database

Classical scrapie is an infectious disease of goats and sheep that causes slowly progressive but ultimately fatal degeneration of the brain, with advanced cases often hindering their ability to move properly. Currently, a single diagnosis of classical scrapie results in permanent quarantine or eutha...

Elevated PGC-1α activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS.

PubMed

Da Cruz, Sandrine; Parone, Philippe A; Lopes, Vanda S; Lillo, Concepción; McAlonis-Downes, Melissa; Lee, Sandra K; Vetto, Anne P; Petrosyan, Susanna; Marsala, Martin; Murphy, Anne N; Williams, David S; Spiegelman, Bruce M; Cleveland, Don W

2012-05-02

The transcriptional coactivator PGC-1α induces multiple effects on muscle, including increased mitochondrial mass and activity. Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, adult-onset neurodegenerative disorder characterized by selective loss of motor neurons and skeletal muscle degeneration. An early event is thought to be denervation-induced muscle atrophy accompanied by alterations in mitochondrial activity and morphology within muscle. We now report that elevation of PGC-1α levels in muscles of mice that develop fatal paralysis from an ALS-causing SOD1 mutant elevates PGC-1α-dependent pathways throughout disease course. Mitochondrial biogenesis and activity are maintained through end-stage disease, accompanied by retention of muscle function, delayed muscle atrophy, and significantly improved muscle endurance even at late disease stages. However, survival was not extended. Therefore, muscle is not a primary target of mutant SOD1-mediated toxicity, but drugs increasing PGC-1α activity in muscle represent an attractive therapy for maintaining muscle function during progression of ALS. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification and Molecular Typing of Naegleria fowleri from a Patient of Primary Amebic Meningoencephalitis (PAM) in China.

PubMed

Zhang, Ling-Ling; Wu, Mao; Hu, Bang-Chuan; Chen, Hua-Liang; Pan, Jin-Ren; Ruan, Wei; Yao, Li-Nong

2018-05-08

Naegleria fowleri (N. fowleri) is the only Naegleria spp. known to cause an acute, fulminant, and rapidly fatal central nervous system infection called primary amebic meningoencephalitis (PAM) in human. In 2016, a suspected PAM patient was found in Zhejiang Province of China. The pathogen was identified by microscopic examination and PCR. The positive PCR products were sequenced and the sequences were aligned using NCBI BLAST programme. The homologous and phylogenetic analysis was conducted using the MEGA 6 programme. Under the microscopy, the motile cells with pseudopodia were observed in the direct smear, the motion characteristics of pseudopodia as well as the cell morphology suggested that the pathogen were amoeba trophozoites. The smears stained with Wright-Giemsa showed amoeba trophozoites with various sharps, which were measured of 10-25μm and characterized by the prominent, centrally placed nucleolus and the vacuolated cytoplasm. The PCR showed negative for E. histolytica and E. dispar, while positive for Naegleria spp.and N. fowleri. The nucleotide sequences acquired from this study were submitted to the Genbank with accession numbers of KX909928 and KX909927, respectively. The Blast analysis revealed that the sequences of KX909928 and KX909927 have 100% similarity with the sequence of N. fowleri gene (KT375442.1). Sequence alignment and phylogenetic tree reavealed that N. fowleri collected from this study was classified as genotype 2 and had a closest relative with N. lovaniensis. This study confirms N. fowleri as the agent responsible for this patient, however, PAM normally progresses fast and universally fatal within a week, so the patient still died at two weeks after the onset of symptoms. Copyright © 2018. Published by Elsevier Ltd.

Fatal outbreak from consuming Xanthium strumarium seedlings during time of food scarcity in northeastern Bangladesh.

PubMed

Gurley, Emily S; Rahman, Mahmudur; Hossain, M Jahangir; Nahar, Nazmun; Faiz, M Abul; Islam, Nazrul; Sultana, Rebeca; Khatun, Selina; Uddin, Mohammad Zashim; Haider, M Sabbir; Islam, M Saiful; Ahmed, Be-Nazir; Rahman, Muhammad Waliur; Mondal, Utpal Kumar; Luby, Stephen P

2010-03-18

An outbreak characterized by vomiting and rapid progression to unconsciousness and death was reported in Sylhet Distrct in northeastern Bangladesh following destructive monsoon floods in November 2007. We identified cases presenting to local hospitals and described their clinical signs and symptoms. We interviewed patients and their families to collect illness histories and generate hypotheses about exposures associated with disease. An epidemiological study was conducted in two outbreak villages to investigate risk factors for developing illness. 76 patients were identified from 9 villages; 25% (19/76) died. Common presenting symptoms included vomiting, elevated liver enzymes, and altered mental status. In-depth interviews with 33 cases revealed that 31 (94%) had consumed ghagra shak, an uncultivated plant, in the hours before illness onset. Ghagra shak was consumed as a main meal by villagers due to inaccessibility of other foods following destructive monsoon flooding and rises in global food prices. Persons who ate this plant were 34.2 times more likely (95% CI 10.2 to 115.8, p-value<0.000) than others to develop vomiting and unconsciousness during the outbreak in our multivariate model. Ghagra shak is the local name for Xanthium strumarium, or common cocklebur. The consumption of Xanthium strumarium seedlings in large quantities, due to inaccessibility of other foods, caused this outbreak. The toxic chemical in the plant, carboxyatratyloside, has been previously described and eating X. strumarium seeds and seedlings has been associated with fatalities in humans and livestock. Unless people are able to meet their nutritional requirements with safe foods, they will continue to be at risk for poor health outcomes beyond undernutrition.

Fatal Outbreak from Consuming Xanthium strumarium Seedlings during Time of Food Scarcity in Northeastern Bangladesh

PubMed Central

Gurley, Emily S.; Rahman, Mahmudur; Hossain, M. Jahangir; Nahar, Nazmun; Faiz, M. Abul; Islam, Nazrul; Sultana, Rebeca; Khatun, Selina; Uddin, Mohammad Zashim; Haider, M. Sabbir; Islam, M. Saiful; Ahmed, Be-Nazir; Rahman, Muhammad Waliur; Mondal, Utpal Kumar; Luby, Stephen P.

2010-01-01

Background An outbreak characterized by vomiting and rapid progression to unconsciousness and death was reported in Sylhet Distrct in northeastern Bangladesh following destructive monsoon floods in November 2007. Methods and Findings We identified cases presenting to local hospitals and described their clinical signs and symptoms. We interviewed patients and their families to collect illness histories and generate hypotheses about exposures associated with disease. An epidemiological study was conducted in two outbreak villages to investigate risk factors for developing illness. 76 patients were identified from 9 villages; 25% (19/76) died. Common presenting symptoms included vomiting, elevated liver enzymes, and altered mental status. In-depth interviews with 33 cases revealed that 31 (94%) had consumed ghagra shak, an uncultivated plant, in the hours before illness onset. Ghagra shak was consumed as a main meal by villagers due to inaccessibility of other foods following destructive monsoon flooding and rises in global food prices. Persons who ate this plant were 34.2 times more likely (95% CI 10.2 to 115.8, p-value<0.000) than others to develop vomiting and unconsciousness during the outbreak in our multivariate model. Ghagra shak is the local name for Xanthium strumarium, or common cocklebur. Conclusions The consumption of Xanthium strumarium seedlings in large quantities, due to inaccessibility of other foods, caused this outbreak. The toxic chemical in the plant, carboxyatratyloside, has been previously described and eating X. strumarium seeds and seedlings has been associated with fatalities in humans and livestock. Unless people are able to meet their nutritional requirements with safe foods, they will continue to be at risk for poor health outcomes beyond undernutrition. PMID:20305785

Improvement of a Clinical Score for Necrotizing Fasciitis: ‘Pain Out of Proportion’ and High CRP Levels Aid the Diagnosis

PubMed Central

Siegel, Ekkehard; Hanke, Eric; von Stebut, Esther

2015-01-01

Necrotizing fasciitis (NF) is a rare mono-/polymicrobial skin infection that spreads to underlying tissues. NF is quickly progressing and leads to life threatening situations. Immediate surgical debridement together with i.v. antibiotic administration is required to avoid fatal outcome. Early diagnosis is often delayed due to underestimation or confusion with cellulitis. We now compared the initial clinical and laboratory presentation of NF and cellulitis in detail to assess if a typical pattern can be identified that aids timely diagnosis of NF and avoidance of fatal outcome. 138 different clinical and laboratory features of 29 NF patients were compared to those of 59 age- and gender matched patients with severe erysipelas requiring a subsequent hospitalization time of ≥10 days. Differences in clinical presentation were not obvious; however, NF patients suffered significantly more often from strong pain. NF patients exhibited dramatically elevated CRP levels (5-fold, p>0.001). The overall laboratory risk indicator for necrotizing fasciitis (LRINEC) score was significantly higher in NF patients as compared to cellulitis. However, a modification of the score (alteration of laboratory parameters, addition of clinical parameters) led to a clear improvement of the score with a higher positive predictive value without losing specificity. In summary, clinical differentiation of NF from cellulitis appears to be hard. ‘Pain out of proportion’ may be an early sign for NF. An improvement of the LRINEC score emphasizing only relevant laboratory and clinical findings as suggested may aid the early diagnosis of NF in the future leading to improvement of disease outcome by enabling rapid adequate therapy. PMID:26196941

Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice.

PubMed

Li, Kun; Wohlford-Lenane, Christine L; Channappanavar, Rudragouda; Park, Jung-Eun; Earnest, James T; Bair, Thomas B; Bates, Amber M; Brogden, Kim A; Flaherty, Heather A; Gallagher, Tom; Meyerholz, David K; Perlman, Stanley; McCray, Paul B

2017-04-11

The Middle East respiratory syndrome (MERS) emerged in Saudi Arabia in 2012, caused by a zoonotically transmitted coronavirus (CoV). Over 1,900 cases have been reported to date, with ∼36% fatality rate. Lack of autopsies from MERS cases has hindered understanding of MERS-CoV pathogenesis. A small animal model that develops progressive pulmonary manifestations when infected with MERS-CoV would advance the field. As mice are restricted to infection at the level of DPP4, the MERS-CoV receptor, we generated mice with humanized exons 10-12 of the mouse Dpp4 locus. Upon inoculation with MERS-CoV, human DPP4 knockin (KI) mice supported virus replication in the lungs, but developed no illness. After 30 serial passages through the lungs of KI mice, a mouse-adapted virus emerged (MERS MA ) that grew in lungs to over 100 times higher titers than the starting virus. A plaque-purified MERS MA clone caused weight loss and fatal infection. Virus antigen was observed in airway epithelia, pneumocytes, and macrophages. Pathologic findings included diffuse alveolar damage with pulmonary edema and hyaline membrane formation associated with accumulation of activated inflammatory monocyte-macrophages and neutrophils in the lungs. Relative to the parental MERS-CoV, MERS MA viruses contained 13-22 mutations, including several within the spike (S) glycoprotein gene. S-protein mutations sensitized viruses to entry-activating serine proteases and conferred more rapid entry kinetics. Recombinant MERS MA bearing mutant S proteins were more virulent than the parental virus in hDPP4 KI mice. The hDPP4 KI mouse and the MERS MA provide tools to investigate disease causes and develop new therapies.

Severe Hemorrhagic Fever in Strain 13/N Guinea Pigs Infected with Lujo Virus

PubMed Central

Bird, Brian H.; Dodd, Kimberly A.; Erickson, Bobbie R.; Albariño, César G.; Chakrabarti, Ayan K.; McMullan, Laura K.; Bergeron, Eric; Ströeher, Ute; Cannon, Deborah; Martin, Brock; Coleman-McCray, JoAnn D.; Nichol, Stuart T.; Spiropoulou, Christina F.

2012-01-01

Lujo virus (LUJV) is a novel member of the Arenaviridae family that was first identified in 2008 after an outbreak of severe hemorrhagic fever (HF). In what was a small but rapidly progressing outbreak, this previously unknown virus was transmitted from the critically ill index patient to 4 attending healthcare workers. Four persons died during this outbreak, for a total case fatality of 80% (4/5). The suspected rodent source of the initial exposure to LUJV remains a mystery. Because of the ease of transmission, high case fatality, and novel nature of LUJV, we sought to establish an animal model of LUJV HF. Initial attempts in mice failed, but infection of inbred strain 13/N guinea pigs resulted in lethal disease. A total of 41 adult strain 13/N guinea pigs were infected with either wild-type LUJV or a full-length recombinant LUJV. Results demonstrated that strain 13/N guinea pigs provide an excellent model of severe and lethal LUJV HF that closely resembles what is known of the human disease. All infected animals experienced consistent weight loss (3–5% per day) and clinical illness characterized by ocular discharge, ruffled fur, hunched posture, and lethargy. Uniform lethality occurred by 11–16 days post-infection. All animals developed disseminated LUJV infection in various organs (liver, spleen, lung, and kidney), and leukopenia, lymphopenia, thrombocytopenia, coagulopathy, and elevated transaminase levels. Serial euthanasia studies revealed a temporal pattern of virus dissemination and increasing severity of disease, primarily targeting the liver, spleen, lungs, and lower gastrointestinal tract. Establishing an animal LUJV model is an important first step towards understanding the high pathogenicity of LUJV and developing vaccines and antiviral therapeutic drugs for this highly transmissible and lethal emerging pathogen. PMID:22953019

Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

DTIC Science & Technology

2015-11-01

systemic therapy to prevent breast cancer bone colony progression. Figure 6. Colocalization of Ac-PhscNGGK-Bio with DiI in lung– extravasated SUM149PT cells...breast cancer progression that are ultimately fatal. Hence, prevention of extravasation which leads to colony formation would increase life...1 Award Number: W81XWH-12-1-0097 TITLE: “Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site

Evaluating the Effectiveness of an Ultrasonic Acoustic Deterrent for Reducing Bat Fatalities at Wind Turbines.

PubMed

Arnett, Edward B; Hein, Cris D; Schirmacher, Michael R; Huso, Manuela M P; Szewczak, Joseph M

2013-01-01

Large numbers of bats are killed by wind turbines worldwide and minimizing fatalities is critically important to bat conservation and acceptance of wind energy development. We implemented a 2-year study testing the effectiveness of an ultrasonic acoustic deterrent for reducing bat fatalities at a wind energy facility in Pennsylvania. We randomly selected control and treatment turbines that were searched daily in summer and fall 2009 and 2010. Estimates of fatality, corrected for field biases, were compared between treatment and control turbines. In 2009, we estimated 21-51% fewer bats were killed per treatment turbine than per control turbine. In 2010, we determined an approximate 9% inherent difference between treatment and control turbines and when factored into our analysis, variation increased and between 2% more and 64% fewer bats were killed per treatment turbine relative to control turbines. We estimated twice as many hoary bats were killed per control turbine than treatment turbine, and nearly twice as many silver-haired bats in 2009. In 2010, although we estimated nearly twice as many hoary bats and nearly 4 times as many silver-haired bats killed per control turbine than at treatment turbines during the treatment period, these only represented an approximate 20% increase in fatality relative to the pre-treatment period for these species when accounting for inherent differences between turbine sets. Our findings suggest broadband ultrasound broadcasts may reduce bat fatalities by discouraging bats from approaching sound sources. However, effectiveness of ultrasonic deterrents is limited by distance and area ultrasound can be broadcast, in part due to rapid attenuation in humid conditions. We caution that an operational deterrent device is not yet available and further modifications and experimentation are needed. Future efforts must also evaluate cost-effectiveness of deterrents in relation to curtailment strategies to allow a cost-benefit analysis for mitigating bat fatalities.

Evaluating the Effectiveness of an Ultrasonic Acoustic Deterrent for Reducing Bat Fatalities at Wind Turbines

PubMed Central

Arnett, Edward B.; Hein, Cris D.; Schirmacher, Michael R.; Huso, Manuela M. P.; Szewczak, Joseph M.

2013-01-01

Large numbers of bats are killed by wind turbines worldwide and minimizing fatalities is critically important to bat conservation and acceptance of wind energy development. We implemented a 2-year study testing the effectiveness of an ultrasonic acoustic deterrent for reducing bat fatalities at a wind energy facility in Pennsylvania. We randomly selected control and treatment turbines that were searched daily in summer and fall 2009 and 2010. Estimates of fatality, corrected for field biases, were compared between treatment and control turbines. In 2009, we estimated 21–51% fewer bats were killed per treatment turbine than per control turbine. In 2010, we determined an approximate 9% inherent difference between treatment and control turbines and when factored into our analysis, variation increased and between 2% more and 64% fewer bats were killed per treatment turbine relative to control turbines. We estimated twice as many hoary bats were killed per control turbine than treatment turbine, and nearly twice as many silver-haired bats in 2009. In 2010, although we estimated nearly twice as many hoary bats and nearly 4 times as many silver-haired bats killed per control turbine than at treatment turbines during the treatment period, these only represented an approximate 20% increase in fatality relative to the pre-treatment period for these species when accounting for inherent differences between turbine sets. Our findings suggest broadband ultrasound broadcasts may reduce bat fatalities by discouraging bats from approaching sound sources. However, effectiveness of ultrasonic deterrents is limited by distance and area ultrasound can be broadcast, in part due to rapid attenuation in humid conditions. We caution that an operational deterrent device is not yet available and further modifications and experimentation are needed. Future efforts must also evaluate cost-effectiveness of deterrents in relation to curtailment strategies to allow a cost-benefit analysis for mitigating bat fatalities. PMID:23840369

Forecasting Japan's Physician Shortage in 2035 as the First Full-Fledged Aged Society

PubMed Central

Yamaguchi, Rui; Matsumura, Tomoko; Murashige, Naoko; Kodama, Yuko; Minayo, Satoru; Imai, Kohzoh; Kami, Masahiro

2012-01-01

Introduction Japan is rapidly becoming a full-fledged aged society, and physician shortage is a significant concern. The Japanese government has increased the number of medical school enrollments since 2008, but some researchers warn that this increase could lead to physician surplus in the future. It is unknown how many physicians will be required to accommodate future healthcare needs. Materials and Methods We simulated changes in age/sex composition of the population, fatalities (the number of fatalities for the consecutive five years), and number of physicians from 2010 to 2035. Two indicators were defined: fatalities per physician and fatalities by physician working hour, based on the data of the working hours of physicians for each tuple of sex and age groups. We estimated the necessary number of physicians in 2035 and the number of new physicians to maintain the indicator levels in 2010. Results The number of physicians per 1,000 population is predicted to rise from 2·00 in 2010 to 3·14 in 2035. The number of physicians aged 60 years or older is expected to increase from 55,375 (20% of physicians) to 141,711 (36%). In 2010 and 2035, fatalities per physician were 23·1 and 24·0 for the total population, and 13·9 and 19·2 for 75 years or older, respectively. Fatalities per physician working hour are predicted to rise from 0·128 to 0·138. If working hours are limited to 48 hours per week in 2035, the number of fatalities per physician working hour is expected to be 0·196, and the number of new physicians must be increased by 53% over the current pace. Discussion The number of physicians per population continues to rise, but the estimated supply will not fulfill the demand for healthcare in the aging society. Strategies to increase the number of physicians and improve working conditions are urgently needed. PMID:23233868

Evaluating the effectiveness of an ultrasonic acoustic deterrent for reducing bat fatalities at wind turbines

USGS Publications Warehouse

Arnett, Edward B.; Hein, Cris D.; Schirmacher, Michael R.; Huso, Manuela M.P.; Szewczak, Joseph M.

2013-01-01

Large numbers of bats are killed by wind turbines worldwide and minimizing fatalities is critically important to bat conservation and acceptance of wind energy development. We implemented a 2-year study testing the effectiveness of an ultrasonic acoustic deterrent for reducing bat fatalities at a wind energy facility in Pennsylvania. We randomly selected control and treatment turbines that were searched daily in summer and fall 2009 and 2010. Estimates of fatality, corrected for field biases, were compared between treatment and control turbines. In 2009, we estimated 21–51% fewer bats were killed per treatment turbine than per control turbine. In 2010, we determined an approximate 9% inherent difference between treatment and control turbines and when factored into our analysis, variation increased and between 2% more and 64% fewer bats were killed per treatment turbine relative to control turbines. We estimated twice as many hoary bats were killed per control turbine than treatment turbine, and nearly twice as many silver-haired bats in 2009. In 2010, although we estimated nearly twice as many hoary bats and nearly 4 times as many silver-haired bats killed per control turbine than at treatment turbines during the treatment period, these only represented an approximate 20% increase in fatality relative to the pre-treatment period for these species when accounting for inherent differences between turbine sets. Our findings suggest broadband ultrasound broadcasts may reduce bat fatalities by discouraging bats from approaching sound sources. However, effectiveness of ultrasonic deterrents is limited by distance and area ultrasound can be broadcast, in part due to rapid attenuation in humid conditions. We caution that an operational deterrent device is not yet available and further modifications and experimentation are needed. Future efforts must also evaluate cost-effectiveness of deterrents in relation to curtailment strategies to allow a cost-benefit analysis for mitigating bat fatalities.

A matter of life and death: substance-caused and substance-related fatalities in Ibiza in 2015.

PubMed

Santacroce, Rita; Ruiz Bennasar, Claudia; Sancho Jaraiz, Juan Ramon; Fiori, Federica; Sarchione, Fabiola; Angelini, Federica; Catalano, Gabriella; Carenti, Maria Luisa; Corkery, John Martin; Schifano, Fabrizio; Di Giannantonio, Massimo; Martinotti, Giovanni

2017-05-01

In the framework of the EU-funded project "EU-Madness," we collected and analysed all the reports of fatalities directly or indirectly related to substances of abuse registered in Ibiza from January to September 2015, in order to analyse the characteristics of the sample, the identified substances, and the nature of deaths associated with their consumption. A significant increase of substance-caused deaths with respect to the previous 4 years has been highlighted. Most of the subjects were young males, more than half were not Spanish. Males prevailed also amongst the victims of traffic accidents and suicides. The most commonly involved substances included MDMA, alcohol, cocaine, THC, opiates and prescription drugs. Although the use of NPS is rapidly increasing in Europe, according to the results from our sample, alcohol and well-known stimulants (MDMA and cocaine) are still the substances of abuse mainly involved in the cases of substance-caused and substance-related fatalities. The significant increase of fatalities in Ibiza in the last 5 years is an issue that must be taken into account and should be better investigated, as other theories besides NPS-increased diffusion should be proposed, and therefore, targeted prevention strategies should be designed. Copyright © 2017 John Wiley & Sons, Ltd.

Outbreak of henipavirus infection, Philippines, 2014.

PubMed

Ching, Paola Katrina G; de los Reyes, Vikki Carr; Sucaldito, Maria Nemia; Tayag, Enrique; Columna-Vingno, Alah Baby; Malbas, Fedelino F; Bolo, Gilbert C; Sejvar, James J; Eagles, Debbie; Playford, Geoffrey; Dueger, Erica; Kaku, Yoshihiro; Morikawa, Shigeru; Kuroda, Makoto; Marsh, Glenn A; McCullough, Sam; Foxwell, A Ruth

2015-02-01

During 2014, henipavirus infection caused severe illness among humans and horses in southern Philippines; fatality rates among humans were high. Horse-to-human and human-to-human transmission occurred. The most likely source of horse infection was fruit bats. Ongoing surveillance is needed for rapid diagnosis, risk factor investigation, control measure implementation, and further virus characterization.

Thyroidectomy: post-operative care and common complications.

PubMed

Furtado, L

Any surgical procedure involves risks. Thyroid surgery can cause potentially fatal complications during the early post-operative phase. It is essential that nurses have the knowledge and skills to detect early signs and symptoms of potential complications and take appropriate action. Early detection and rapid response are key to maintaining patient safety and minimising harm.

Rapid microfluidic assay for the detection of botulinum neurotoxin in animal sera

USDA-ARS?s Scientific Manuscript database

The potent botulinum neurotoxins (BoNTs) represent a threat to public health and safety. Botulism is a disease caused by BoNT intoxication that results in muscle paralysis that can be fatal. Sensitive assays capable of detecting BoNTs from different substrates and settings are essential to limit f...

Strategies in Ebola virus disease (EVD) diagnostics at the point of care.

PubMed

Coarsey, Chad T; Esiobu, Nwadiuto; Narayanan, Ramswamy; Pavlovic, Mirjana; Shafiee, Hadi; Asghar, Waseem

2017-11-01

Ebola virus disease (EVD) is a devastating, highly infectious illness with a high mortality rate. The disease is endemic to regions of Central and West Africa, where there is limited laboratory infrastructure and trained staff. The recent 2014 West African EVD outbreak has been unprecedented in case numbers and fatalities, and has proven that such regional outbreaks can become a potential threat to global public health, as it became the source for the subsequent transmission events in Spain and the USA. The urgent need for rapid and affordable means of detecting Ebola is crucial to control the spread of EVD and prevent devastating fatalities. Current diagnostic techniques include molecular diagnostics and other serological and antigen detection assays; which can be time-consuming, laboratory-based, often require trained personnel and specialized equipment. In this review, we discuss the various Ebola detection techniques currently in use, and highlight the potential future directions pertinent to the development and adoption of novel point-of-care diagnostic tools. Finally, a case is made for the need to develop novel microfluidic technologies and versatile rapid detection platforms for early detection of EVD.

A large Legionnaires' disease outbreak in Pamplona, Spain: early detection, rapid control and no case fatality

PubMed Central

CASTILLA, J.; BARRICARTE, A.; ALDAZ, J.; GARCÍA CENOZ, M.; FERRER, T.; PELAZ, C.; PINEDA, S.; BALADRÓN, B.; MARTÍN, I.; GOÑI, B.; ARATAJO, P.; CHAMORRO, J.; LAMEIRO, F.; TORROBA, L.; DORRONSORO, I.; MARTÍNEZ-ARTOLA, V.; ESPARZA, M. J.; GASTAMINZA, M. A.; FRAILE, P.; ALDAZ, P.

2008-01-01

SUMMARY An outbreak of Legionnaire's disease was detected in Pamplona, Spain, on 1 June 2006. Patients with pneumonia were tested to detect Legionella pneumophila antigen in urine (Binax Now; Binax Inc., Scarborough, ME, USA), and all 146 confirmed cases were interviewed. The outbreak was related to district 2 (22 012 inhabitants), where 45% of the cases lived and 50% had visited; 5% lived in neighbouring districts. The highest incidence was found in the resident population of district 2 (3/1000 inhabitants), section 2 (14/1000). All 31 cooling towers of district 2 were analysed. L. pneumophila antigen (Binax Now) was detected in four towers, which were closed on 2 June. Only the strain isolated in a tower situated in section 2 of district 2 matched all five clinical isolates, as assessed by mAb and two genotyping methods, AFLP and PFGE. Eight days after closing the towers, new cases ceased appearing. Early detection and rapid coordinated medical and environmental actions permitted immediate control of the outbreak and probably contributed to the null case fatality. PMID:17662166

A large Legionnaires' disease outbreak in Pamplona, Spain: early detection, rapid control and no case fatality.

PubMed

Castilla, J; Barricarte, A; Aldaz, J; García Cenoz, M; Ferrer, T; Pelaz, C; Pineda, S; Baladrón, B; Martín, I; Goñi, B; Aratajo, P; Chamorro, J; Lameiro, F; Torroba, L; Dorronsoro, I; Martínez-Artola, V; Esparza, M J; Gastaminza, M A; Fraile, P; Aldaz, P

2008-06-01

An outbreak of Legionnaire's disease was detected in Pamplona, Spain, on 1 June 2006. Patients with pneumonia were tested to detect Legionella pneumophila antigen in urine (Binax Now; Binax Inc., Scarborough, ME, USA), and all 146 confirmed cases were interviewed. The outbreak was related to district 2 (22 012 inhabitants), where 45% of the cases lived and 50% had visited; 5% lived in neighbouring districts. The highest incidence was found in the resident population of district 2 (3/1000 inhabitants), section 2 (14/1000). All 31 cooling towers of district 2 were analysed. L. pneumophila antigen (Binax Now) was detected in four towers, which were closed on 2 June. Only the strain isolated in a tower situated in section 2 of district 2 matched all five clinical isolates, as assessed by mAb and two genotyping methods, AFLP and PFGE. Eight days after closing the towers, new cases ceased appearing. Early detection and rapid coordinated medical and environmental actions permitted immediate control of the outbreak and probably contributed to the null case fatality.

BK virus-associated fatal renal failure following late-onset hemorrhagic cystitis in an unrelated bone marrow transplantation.

PubMed

Iwamoto, Shotaro; Azuma, Eiichi; Hori, Hiroki; Hirayama, Masahiro; Kobayashi, Michihiro; Komada, Yoshihiro; Nishimori, Hisashi; Miyahara, Masazumi

2002-06-01

The human polyomavirus BK (BKV)-associated hemorrhagic cystitis (HC) has been a frequent and, seldom life-threatening complication after bone marrow transplantation (BMT). The authors report a male with melodysplastic syndrome, who developed BKV-associated late-onset HC 12 days after HLA-matched unrelated BMT. His urine contained epithelial cells with intranuclear inclusion bodies suggestive of BKV infection and was positive for BKV in polymerase chain reaction. He did not respond to any treatment for HC. In addition, he developed BKV-associated acute renal failure on day 26, followed by hepatic veno-occlusive disease on day 42. This is the first case in which BKV may be associated with fatal progressive renal failure.

[Fatal female genital mutilation in a 10-year-old girl].

PubMed

Sow, A; Diagne, G; Keita, Y; Sow, O; Ndiath, A; Ouattara, A; Sarr, M-L; Sylla, A; Moreira, C

2017-10-01

Female genital mutilation (FGM) comprises all procedures involving partial or total removal of the external genitalia and/or any other procedures affecting the female genitalia, for cultural or religious reasons or for nontherapeutic purposes in general. FGM is responsible for a number of short-, medium-, and long-term complications that can engage the vital and functional prognosis, especially in African countries. We report on a case in a 10-year-old girl who underwent genital mutilation, a traditional type of total excision during the neonatal period. She was followed for urethral meatus stenosis, which then was complicated by obstructive chronic kidney failure and urinary sepsis, whose progression was fatal. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Rapid estimation of the economic consequences of global earthquakes

USGS Publications Warehouse

Jaiswal, Kishor; Wald, David J.

2011-01-01

The U.S. Geological Survey's (USGS) Prompt Assessment of Global Earthquakes for Response (PAGER) system, operational since mid 2007, rapidly estimates the most affected locations and the population exposure at different levels of shaking intensities. The PAGER system has significantly improved the way aid agencies determine the scale of response needed in the aftermath of an earthquake. For example, the PAGER exposure estimates provided reasonably accurate assessments of the scale and spatial extent of the damage and losses following the 2008 Wenchuan earthquake (Mw 7.9) in China, the 2009 L'Aquila earthquake (Mw 6.3) in Italy, the 2010 Haiti earthquake (Mw 7.0), and the 2010 Chile earthquake (Mw 8.8). Nevertheless, some engineering and seismological expertise is often required to digest PAGER's exposure estimate and turn it into estimated fatalities and economic losses. This has been the focus of PAGER's most recent development. With the new loss-estimation component of the PAGER system it is now possible to produce rapid estimation of expected fatalities for global earthquakes (Jaiswal and others, 2009). While an estimate of earthquake fatalities is a fundamental indicator of potential human consequences in developing countries (for example, Iran, Pakistan, Haiti, Peru, and many others), economic consequences often drive the responses in much of the developed world (for example, New Zealand, the United States, and Chile), where the improved structural behavior of seismically resistant buildings significantly reduces earthquake casualties. Rapid availability of estimates of both fatalities and economic losses can be a valuable resource. The total time needed to determine the actual scope of an earthquake disaster and to respond effectively varies from country to country. It can take days or sometimes weeks before the damage and consequences of a disaster can be understood both socially and economically. The objective of the U.S. Geological Survey's PAGER system is to reduce this time gap to more rapidly and effectively mobilize response. We present here a procedure to rapidly and approximately ascertain the economic impact immediately following a large earthquake anywhere in the world. In principle, the approach presented is similar to the empirical fatality estimation methodology proposed and implemented by Jaiswal and others (2009). In order to estimate economic losses, we need an assessment of the economic exposure at various levels of shaking intensity. The economic value of all the physical assets exposed at different locations in a given area is generally not known and extremely difficult to compile at a global scale. In the absence of such a dataset, we first estimate the total Gross Domestic Product (GDP) exposed at each shaking intensity by multiplying the per-capita GDP of the country by the total population exposed at that shaking intensity level. We then scale the total GDP estimated at each intensity by an exposure correction factor, which is a multiplying factor to account for the disparity between wealth and/or economic assets to the annual GDP. The economic exposure obtained using this procedure is thus a proxy estimate for the economic value of the actual inventory that is exposed to the earthquake. The economic loss ratio, defined in terms of a country-specific lognormal cumulative distribution function of shaking intensity, is derived and calibrated against the losses from past earthquakes. This report describes the development of a country or region-specific economic loss ratio model using economic loss data available for global earthquakes from 1980 to 2007. The proposed model is a potential candidate for directly estimating economic losses within the currently-operating PAGER system. PAGER's other loss models use indirect methods that require substantially more data (such as building/asset inventories, vulnerabilities, and the asset values exposed at the time of earthquake) to implement on a global basis and will thus take more time to develop and implement within the PAGER system.

Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

PubMed

Banelli, Barbara; Merlo, Domenico Franco; Allemanni, Giorgio; Forlani, Alessandra; Romani, Massimo

2013-01-01

Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma) that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months). Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

Dissecting dysfunctional crosstalk pathways regulated by miRNAs during glioma progression

PubMed Central

Li, Feng; Li, Xiang; Feng, Li; Shi, Xinrui; Wang, Lihua; Li, Xia

2016-01-01

Glioma is a malignant nervous system tumor with a high fatality rate and poor prognosis. MicroRNAs (miRNAs) are important post-transcriptional modulators of glioma initiation and progression. Tumor progression often results from dysfunctional co-operation between pathways regulated by miRNAs. We therefore constructed a glioma progression-related miRNA-pathway crosstalk network that not only revealed some key miRNA-pathway patterns, but also helped characterize the functional roles of miRNAs during glioma progression. Our data indicate that crosstalk between cell cycle and p53 pathways is associated with grade II to grade III progression, while cell communications-related pathways involving regulation of actin cytoskeleton and adherens junctions are associated with grade IV glioblastoma progression. Furthermore, miRNAs and their crosstalk pathways may be useful for stratifying glioma and glioblastoma patients into groups with short or long survival times. Our data indicate that a combination of miRNA and pathway crosstalk information can be used for survival prediction. PMID:27013589

Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

PubMed

Roede, James R; Uppal, Karan; Park, Youngja; Lee, Kichun; Tran, Vilinh; Walker, Douglas; Strobel, Frederick H; Rhodes, Shannon L; Ritz, Beate; Jones, Dean P

2013-01-01

Progression of Parkinson's disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.

Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome.

PubMed

Chen, Byron; Hui, Jessica; Montgomery, Kelsey S; Gella, Alejandro; Bolea, Irene; Sanz, Elisenda; Palmiter, Richard D; Quintana, Albert

2017-01-01

Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS) is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established. Here, we used a mouse model of LS lacking Ndufs4 , a mitochondrial complex I subunit, to confirm that loss of complex I, but not complex II, alters respiration in the striatum. To assess the role of striatal dysfunction in the pathology, we selectively inactivated Ndufs4 in the striatal medium spiny neurons (MSNs), which account for over 95% of striatal neurons. Our results show that lack of Ndufs4 in MSNs causes a non-fatal progressive motor impairment without affecting the cognitive function of mice. Furthermore, no inflammatory responses or neuronal loss were observed up to 6 months of age. Hence, complex I deficiency in MSNs contributes to the motor deficits observed in LS, but not to the neural degeneration, suggesting that other neuronal populations drive the plethora of clinical signs in LS.

Deployable, Field-Sustainable, Reverse Transcription-Polymerase Chain Reaction Assays for Rapid Screening and Serotype Identification of Dengue Virus in Mosquitoes

DTIC Science & Technology

2007-03-01

C, Gottig S, Schiiiing S, et ai: Rapid detection and quantiilcation of RNA of Eboia and Marburg viruses, L.assa virus, Crimean - Congo hemorrhagic fever ...the past two decades, dengue fever (DF) and the poten- tially fatal forms ofthe disease, dengue hemorrhagic fever (DHF) and dengue shock syndrome, have...Viroi 2003; 77: i 1436-47. 5. Gubler DJ: Dengue and dengue hemorrhagic fever . Ciin Microbiol Rev 1998; 11: 480-96. 6. Fonseca BA, Fonseca SN: Dengue virus

The Rose Report [Continued]: "The Invisible Worm"

ERIC Educational Resources Information Center

Drummond, Mary Jane

2009-01-01

While Colin Richards' article is a trenchant analysis of the big themes and missed opportunities of the Rose Report, this response examines some of the small print. It concludes that the document is disfigured by many minor blemishes, and is also fatally flawed by a crude misapprehension of the nature of progress and the purpose of education.

Mesothelial Cell Autoantibodies Induce Collagen Deposition in vitro & Using a Case Study to Introduce Undergraduates to Bioinformatics

ERIC Educational Resources Information Center

Serve, Kinta M.

2013-01-01

Part I. Pleural fibrosis, a non-malignant, asbestos-related respiratory disease characterized by excessive collagen deposition, is progressive, debilitating, and potentially fatal. Disease severity may be influenced by the type of asbestos fiber inhaled, with Libby amphibole (LA) a seemingly more potent mediator of pleural fibrosis than chrysotile…

Trends in alcohol-impaired driving in Canada.

PubMed

Vanlaar, Ward; Robertson, Robyn; Marcoux, Kyla; Mayhew, Daniel; Brown, Steve; Boase, Paul

2012-09-01

While a general decreasing trend in the number of persons killed in a traffic crash involving a drinking driver has occurred in Canada since the 1980s, it is evident that much of this decrease occurred in the 1990s. Since 2002, less progress has been made as the number of persons killed in crashes involving drinking drivers remains high. To better understand the current situation, this paper describes trends in drinking and driving in Canada from 1998 to 2011 using multiple indicators based on data collected for the Traffic Injury Research Foundation's (TIRF) Road Safety Monitor (RSM), the National Opinion Poll on Drinking and Driving, and trends in alcohol-related crashes based on data collected for TIRF's national Fatality Database in Canada. There has been a continued and consistent decrease in the number of fatalities involving a drinking driver in Canada. This remains true when looking at the number of fatalities involving a drinking driver per 100,000 population and per 100,000 licensed drivers. This decreasing trend is also still apparent when considering the percentage of persons killed in a traffic crash in Canada involving a drinking driver although less pronounced. Data from the RSM further show that the percentage of those who reported driving after they thought they were over the legal limit has also declined. However, regardless of the apparent decreasing trend in drinking driving fatalities and behaviour, reductions have been relatively modest, and fatalities in crashes involving drivers who have consumed alcohol remain high at unacceptable levels. Copyright © 2012 Elsevier Ltd. All rights reserved.

Coccidioidomycosis and other endemic mycoses in Mexico.

PubMed

Laniado-Laborín, Rafael

2007-12-31

The endemic mycoses traditionally include coccidioidomycosis, histoplasmosis, blastomycosis and paracoccidioidomycosis. Although sporotrichosis and chromomycosis are technically not included among the endemic mycoses, they are frequently diagnosed in Mexico. Most systemic endemic mycoses are a consequence of inhaling the fungi, while subcutaneous mycoses are acquired through the inoculation of vegetable matter or soil containing the organism. Coccidioidomycosis is caused by Coccidioides spp., a dimorphic pathogenic fungus. Approximately 60% of exposures result in asymptomatic infection; in the rest there are protean manifestations that range from a benign syndrome also known as "Valley Fever" to progressive pulmonary or extrapulmonary disease. Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic to the Americas. Pulmonary histoplasmosis manifestations are protean, ranging from a brief period of malaise to a severe, prolonged illness. The spectrum of illness in disseminated histoplasmosis ranges from a chronic, intermittent course to an acute and rapidly fatal infection. Paracoccidioidomycosis is a chronic, granulomatous systemic disease caused by Paracoccidioides brasiliensis that characteristically produces a primary pulmonary infection, often asymptomatic, and then disseminates to form ulcerative granulomata of the oral, nasal and occasionally the gastrointestinal mucosa. Sporotrichosis, caused by Sporothrix schenckii, has diverse clinical manifestations; the most frequent is the lymphocutaneous form. Generally, infection results from inoculation of the fungus through thorns, splinters, scratches and small traumas. Chromomycosis (Chromoblastomycosis) is a slowly progressive cutaneous and subcutaneous mycosis attributed to various saprophyte Hypomycetes fungi. The primary lesion is also thought to develop as a result of percutaneous traumatic inoculation.

Alleviation of Psychological Distress and the Improvement of Quality of Life in Patients With Amyotrophic Lateral Sclerosis: Adaptation of a Short-Term Psychotherapeutic Intervention.

PubMed

Oberstadt, Moritz Caspar Franz; Esser, Peter; Classen, Joseph; Mehnert, Anja

2018-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is inevitably fatal. To be diagnosed with a terminal illness such as ALS deeply affects one's personal existence and goes along with significant changes regarding the physical, emotional, and social domains of the patients' life. ALS patients have to face a rapidly debilitating physical decline which restrains mobility and impairs all activities of daily living. This progressive loss of autonomy may lead to a sense of hopelessness and loss of quality of life, which in turn may even result in thoughts about physician-assisted suicide. Here, we would like to propose a psychotherapeutic manualized, individual, semi-structured intervention to relieve distress and promote psychological well-being in ALS patients. This short-term intervention was originally developed for advanced cancer patients. "Managing Cancer and Living Meaningfully (CALM)" focuses on the four dimensions: (i) symptom management and communication with healthcare providers, (ii) changes in self and relations with close others, (iii) spirituality, sense of meaning and purpose and (iv) thinking of the future, hope, and mortality. We suggest to supplement the concept by two additional dimensions which take into account specific issues of ALS patients: (v) communication skills, and (vi) emotional expression and control. This therapeutic concept named " M anag I ng B urden in A LS and L iving M eaningfully (mi-BALM)" may be a further treatment option to help improving quality of life of ALS patients.

Hypoventilation improvement in an adult non-invasively ventilated patient with Rapid-onset Obesity with Hypothalamic Dysfunction Hypoventilation and Autonomic Dysregulation (ROHHAD).

PubMed

Graziani, Alessandro; Casalini, Pierpaolo; Mirici-Cappa, Federica; Pezzi, Giuseppe; Giuseppe Stefanini, Francesco

2016-01-01

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare disease of unknown etiology, characterized by rapid-onset obesity in young children, hypoventilation, hypothalamic and autonomic dysfunction. Patients between the ages of 2 and 4 present with hyperphagia and weight gain, followed by neuro-hormonal dysfunction and central hypoventilation months or years later. Cardiac arrest may represent the fatal complication of alveolar hypoventilation and early mechanical ventilation is essential for the patient's life. In this paper, we describe a 22-year-old patient with ROHHAD syndrome who had an acute respiratory failure during nocturnal non-invasive ventilation (NIV).

Application of an in vitro drug screening assay based on the release of phosphoglucose isomerase to determine the structure-activity relationship of thiazolides against Echinococcus multilocularis metacestodes.

PubMed

Stadelmann, Britta; Scholl, Sabrina; Müller, Joachim; Hemphill, Andrew

2010-03-01

The disease alveolar echinococcosis (AE), caused by the larval stage of the cestode Echinococcus multilocularis, is fatal if treatment is unsuccessful. Current treatment options are, at best, parasitostatic, and involve taking benzimidazoles (albendazole, mebendazole) for the whole of a patient's life. In conjunction with the recent development of optimized procedures for E. multilocularis metacestode cultivation, we aimed to develop a rapid and reliable drug screening test, which enables efficient screening of a large number of compounds in a relatively short time frame. Metacestodes were treated in vitro with albendazole, the nitro-thiazole nitazoxanide and 29 nitazoxanide derivatives. The resulting leakage of phosphoglucose isomerase (PGI) activity into the medium supernatant was measured and provided an indication of compound efficacy. We show that upon in vitro culture of E. multilocularis metacestodes in the presence of active drugs such as albendazole, the nitro-thiazole nitazoxanide and 30 different nitazoxanide derivatives, the activity of PGI in culture supernatants increased. The increase in PGI activity correlated with the progressive degeneration and destruction of metacestode tissue in a time- and concentration-dependent manner, which allowed us to perform a structure-activity relationship analysis on the thiazolide compounds used in this study. The assay presented here is inexpensive, rapid, can be used in 24- and 96-well formats and will serve as an ideal tool for first-round in vitro tests on the efficacy of large numbers of antiparasitic compounds.

Combination of neurofilament heavy chain and complement c3 as CSF biomarkers for ALS

PubMed Central

Ganesalingam, Jeban; An, Jiyan; Shaw, Christopher E; Shaw, Gerry; Lacomis, David; Bowser, Robert

2011-01-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease with an average survival of 3 years from symptom onset. Rapid and conclusive early diagnosis is essential if interventions with disease-modifying therapies are to be successful. Cytoskeletal modification and inflammation are known to occur during the pathogenesis of ALS. We measured levels of cytoskeletal proteins and inflammatory markers in the cerebrospinal fluid (CSF) of ALS, disease controls and healthy subjects. We determined threshold values for each protein that provided the optimal sensitivity and specificity for ALS within a training set, as determined by receiver operating characteristic (ROC) analysis. Interestingly, the optimal assay was a ratio of the levels for phosphorylated neurofilament heavy chain and complement C3 (pNFH/C3). We next applied this assay to a separate test set of CSF samples to verify our results. Overall, the predictive pNFH/C3 ratio identified ALS with 87.3% sensitivity and 94.6% specificity in a total of 71 ALS subjects, 52 disease control subjects and 40 healthy subjects. In addition, the level of CSF pNFH correlated with survival of ALS patients. We also detected increased pNFH in the plasma of ALS patients and observed a correlation between CSF and plasma pNFH levels within the same subjects. These findings support large-scale prospective biomarker studies to determine the clinical utility of diagnostic and prognostic signatures in ALS. PMID:21418221

Naegleria fowleri after 50 years: is it a neglected pathogen?

PubMed

Martínez-Castillo, Moisés; Cárdenas-Zúñiga, Roberto; Coronado-Velázquez, Daniel; Debnath, Anjan; Serrano-Luna, Jesús; Shibayama, Mineko

2016-09-01

It has been 50 years since the first case of primary amoebic meningoencephalitis (PAM), an acute and rapidly fatal disease of the central nervous system (CNS), was reported in Australia. It is now known that the aetiological agent of PAM is Naegleria fowleri, an amoeba that is commonly known as 'the brain-eating amoeba'. N. fowleri infects humans of different ages who are in contact with water contaminated with this micro-organism. N. fowleri is distributed worldwide and is found growing in bodies of freshwater in tropical and subtropical environments. The number of PAM cases has recently increased, and the rate of recovery from PAM has been estimated at only 5 %. Amphotericin B has been used to treat patients with PAM. However, it is important to note that there is no specific treatment for PAM. Moreover, this amoeba is considered a neglected micro-organism. Researchers have exerted great effort to design effective drugs to treat PAM and to understand the pathogenesis of PAM over the past 50 years, such as its pathology, molecular and cellular biology, diagnosis and prevention, and its biological implications, including its pathogenic genotypes, its distribution and its ecology. Given the rapid progression of PAM and its high mortality rate, it is important that investigations continue and that researchers collaborate to gain better understanding of the pathogenesis of this disease and, consequently, to improve the diagnosis and treatment of this devastating infection of the CNS.

Accounting for unsearched areas in estimating wind turbine-caused fatality

USGS Publications Warehouse

Huso, Manuela M.P.; Dalthorp, Dan

2014-01-01

With wind energy production expanding rapidly, concerns about turbine-induced bird and bat fatality have grown and the demand for accurate estimation of fatality is increasing. Estimation typically involves counting carcasses observed below turbines and adjusting counts by estimated detection probabilities. Three primary sources of imperfect detection are 1) carcasses fall into unsearched areas, 2) carcasses are removed or destroyed before sampling, and 3) carcasses present in the searched area are missed by observers. Search plots large enough to comprise 100% of turbine-induced fatality are expensive to search and may nonetheless contain areas unsearchable because of dangerous terrain or impenetrable brush. We evaluated models relating carcass density to distance from the turbine to estimate the proportion of carcasses expected to fall in searched areas and evaluated the statistical cost of restricting searches to areas near turbines where carcass density is highest and search conditions optimal. We compared 5 estimators differing in assumptions about the relationship of carcass density to distance from the turbine. We tested them on 6 different carcass dispersion scenarios at each of 3 sites under 2 different search regimes. We found that even simple distance-based carcass-density models were more effective at reducing bias than was a 5-fold expansion of the search area. Estimators incorporating fitted rather than assumed models were least biased, even under restricted searches. Accurate estimates of fatality at wind-power facilities will allow critical comparisons of rates among turbines, sites, and regions and contribute to our understanding of the potential environmental impact of this technology.

Migration of bats past a remote island offers clues toward the problem of bat fatalities at wind turbines

USGS Publications Warehouse

Cryan, P.M.; Brown, A.C.

2007-01-01

Wind energy is rapidly becoming a viable source of alternative energy, but wind turbines are killing bats in many areas of North America. Most of the bats killed by turbines thus far have been migratory species that roost in trees throughout the year, and the highest fatality events appear to coincide with autumn migration. Hoary bats (Lasiurus cinereus) are highly migratory and one of the most frequently killed species at wind turbines. We analyzed a long-term data set to investigate how weather and moonlight influenced the occurrence of hoary bats at an island stopover point along their migration route. We then related our results to the problem of bat fatalities at wind turbines. We found that relatively low wind speeds, low moon illumination, and relatively high degrees of cloud cover were important predictors of bat arrivals and departures, and that low barometric pressure was an additional variable that helped predict arrivals. Slight differences in the conditions under which bats arrived and departed from the island suggest that hoary bats may be more likely to arrive on the island with passing storm fronts in autumn. These results also indicate that fatalities of hoary bats at wind turbines may be predictable events, that the species may be drawn to prominent landmarks that they see during migration, and that they regularly migrate over the ocean. Additional observations from this and other studies suggest that the problem of bat fatalities at wind turbines may be associated with flocking and autumn mating behaviors.

Development of a rapid DNA extraction method and one-step nested PCR for the detection of Naegleria fowleri from the environment.

PubMed

Ahmad, Arine Fadzlun; Lonnen, James; Andrew, Peter W; Kilvington, Simon

2011-10-15

Naegleria fowleri is a small free-living amoebo-flagellate found in natural and manmade thermal aquatic habitats worldwide. The organism is pathogenic to man causing fatal primary amoebic meningoencephalitis (PAM). Infection typically results from bathing in contaminated water and is usually fatal. It is, therefore, important to identify sites containing N. fowleri in the interests of preventive public health microbiology. Culture of environmental material is the conventional method for the isolation of N. fowleri but requires several days incubation and subsequent biochemical or molecular tests to confirm identification. Here, a nested one-step PCR test, in conjunction with a direct DNA extraction from water or sediment material, was developed for the rapid and reliable detection of N. fowleri from the environment. Here, the assay detected N, fowleri in 18/109 river water samples associated with a nuclear power plant in South West France and 0/10 from a similar site in the UK. Although culture of samples yielded numerous thermophilic free-living amoebae, none were N. fowleri or other thermophilic Naegleria spp. The availability of a rapid, reliable and sensitive one-step nested PCR method for the direct detection of N. fowleri from the environment may aid ecological studies and enable intervention to prevent PAM cases. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

76 FR 71348 - Role of Naloxone in Opioid Overdose Fatality Prevention; Public Workshop; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-17

... discussion about the potential value of making naloxone more widely available outside of conventional medical... registration on the day of the public workshop will be based on space availability. If registration reaches..., is an injectable medicine that can rapidly reverse the overdose of either prescription (e.g., Oxy...

The Risk of Progressive Multifocal Leukoencephalopathy in the Biologic Era: Prevention and Management.

PubMed

Molloy, Eamonn S; Calabrese, Cassandra M; Calabrese, Leonard H

2017-02-01

Progressive multifocal leukoencephalopathy (PML) is a rare, typically fatal, demyelinating central nervous system infection caused by reactivation of the John Cunningham virus that generally occurs in immunosuppressed patients. With an evolving understanding of a greater clinical heterogeneity of PML and significant implications for therapy, PML should be considered in the differential diagnosis of neurologic presentations of rheumatic diseases. Increased awareness of PML among rheumatologists is required, as earlier diagnosis and restoration of immune function may improve the otherwise grim prognosis associated with PML. Copyright © 2016 Elsevier Inc. All rights reserved.

Completed suicide in a case of clinically diagnosed progressive supranuclear palsy.

PubMed

Wiener, Jennifer; Moran, Maria T; Haut, Marc W

2015-08-01

We present the clinical history and the cognitive and behavioral presentations of a male patient with suspected progressive supranuclear palsy (PSP) who fatally shot himself in the head. We believe his act of suicide was the consequence of impulsivity, rather than primary depression or mood disturbance. In cases of suspected PSP and other atypical parkinsonisms, health professionals must be aware of neurobehavioral risk factors for suicide attempts and completions to promote patient safety; however, the literature on this topic is sparse. Our case highlights the potentially lethal consequences of impulsivity and other neuropsychiatric symptoms in PSP and related syndromes.

Role of levetiracetam in refractory seizures due to a rare progressive myoclonic epilepsy: Lafora body disease

PubMed Central

Hashmi, Mubashira; Saleem, Feroza; Mustafa, Muhammad Shahid; Sheerani, Mughis; Ehtesham, Zeeshan; Siddiqui, Khurram

2010-01-01

Lafora disease is one of the rare, most fatal progressive myoclonic epilepsies reported. We present a case of a teenager with intractable seizures and progressive mental decline, diagnosed as Lafora body disease on axillary skin biopsy. He was admitted with status epilepticus with refractory myoclonic and generalised tonic clonic seizures. Despite on maximum doses of multiple antiepileptic drugs and infusions of propofol and midazolam, his seizures were refractory to all forms of medical therapy tried. Levetiracetam (LEV), a pyrrolidine derivative, was introduced; he showed a prompt response and was weaned off successfully from infusions of anticonvulsants and mechanical ventilation within 48 h of introduction of LEV, followed by an almost seizure-free status. PMID:22791845

Ashwagandha supplementation enhances ovarian tumoricidal activity of NK cells | Division of Cancer Prevention

Cancer.gov

Ovarian cancer (OVCA) is a fatal malignancy of women with highest case to death ratio among gynecological cancers. OVCA differs from other malignancies that it mainly disseminates locally in the peritoneal and abdominal cavity. Thus, factors in tumor microenvironment play critical roles in tumor progression as well as prevention of OVCA metastasis. Innate immune cells are

Ebolavirus Vaccines for Humans and Apes

PubMed Central

Fausther-Bovendo, Hugues; Mulangu, Sabue

2012-01-01

Due to high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes. PMID:22560007

Effect of Job Satisfaction and Motivation towards Employee's Performance in XYZ Shipping Company

ERIC Educational Resources Information Center

Octaviannand, Ramona; Pandjaitan, Nurmala K.; Kuswanto, Sadikin

2017-01-01

In the digital and globalization era which are demanding for tech progress. Human resources need to work more closely and concentration. Small errors can lead to fatal errors that result in high costs for the company. The loss of motivation at work influences employee satisfaction and have a negative impact on employee performance. Research was…

Fatal coinfection with Legionella pneumophila serogroup 8 and Aspergillus fumigatus.

PubMed

Guillouzouic, Aurélie; Bemer, Pascale; Gay-Andrieu, Françoise; Bretonnière, Cédric; Lepelletier, Didier; Mahé, Pierre-Joachim; Villers, Daniel; Jarraud, Sophie; Reynaud, Alain; Corvec, Stéphane

2008-02-01

Legionella pneumophila is an important cause of community-acquired and nosocomial pneumonia. We report on a patient who simultaneously developed L. pneumophila serogroup 8 pneumonia and Aspergillus fumigatus lung abscesses. Despite appropriate treatments, Aspergillus disease progressed with metastasis. Coinfections caused by L. pneumophila and A. fumigatus remain exceptional. In apparently immunocompetent patients, corticosteroid therapy is a key risk factor for aspergillosis.

Temporal trends in motor vehicle fatalities in the United States, 1968 to 2010 - a joinpoint regression analysis.

PubMed

Bandi, Priti; Silver, Diana; Mijanovich, Tod; Macinko, James

2015-12-01

In the past 40 years, a variety of factors might have impacted motor vehicle (MV) fatality trends in the US, including public health policies, engineering innovations, trauma care improvements, etc. These factors varied in their timing across states/localities, and many were targeted at particular population subgroups. In order to identify and quantify differential rates of change over time and differences in trend patterns between population subgroups, this study employed a novel analytic method to assess temporal trends in MV fatalities between 1968 and 2010, by age group and sex. Cause-specific MV fatality data from traffic injuries between 1968 and 2010, based on death certificates filed in the 50 states, and DC were obtained from Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). Long-term (1968 to 2010) and short-term (log-linear piecewise segments) trends in fatality rates were compared for males and females overall and in four separate age groups using joinpoint regression. MV fatalities declined on average by 2.4% per year in males and 2.2% per year in females between 1968 and 2010, with significant declines observed in all age groups and in both sexes. In males overall and those 25 to 64 years, sharp declines between 1968 and mid-to-late 1990s were followed by a stalling until the mid-2000s, but rates in females experienced a long-term steady decline of a lesser magnitude than males during this time. Trends in those aged <1 to 14 years and 15 to 24 years were mostly steady over time, but males had a larger decline than females in the latter age group between 1968 and the mid-2000s. In ages 65+, short-term trends were similar between sexes. Despite significant long-term declines in MV fatalities, the application of Joinpoint Regression found that progress in young adult and middle-aged adult males stalled in recent decades and rates in males declined relatively more than in females in certain age groups. Future research is needed to establish the causes of these observed trends, including the potential role of contemporaneous MV-related policies and their repeal. Such research is needed in order to better inform the design and evaluation of future population interventions addressing MV fatalities nationally.

Causes and circumstances of damage to people in Calabria (Italy) due to hydrogeological events in the period 1980-2014

NASA Astrophysics Data System (ADS)

Aceto, Luigi; Pasqua, A. Aurora; Petrucci, Olga

2017-04-01

Damaging Hydrogeological Events (DHE) can be defined as rainy periods during which landslides and floods can damage people. We investigates the effects of DHE on people in Calabria (southern Italy) ,in the period 1980-2014, using data coming from the systematic survey of regional daily newspapers. Data about "fatalities", people "injured" and people "involved" (not killed neither hurt) are stored in the database named PEOPLE, made of five sections: 1) event identification, 2) victim identification, 3) type of victim's involvement, 4) victim-event interaction, and 5) effects on victim. The outcomes highlight vulnerability factors related to gender and age: males were killed more frequently (75%) than females (25%), and fatalities were older (average age 49 years) than injured (40.1 years) and involved people (40.5 years). The average age of females killed (67.5 years), injured (43.4 years) and involved (44.6 years) were higher than the same values assessed for males, maybe indicating that younger females tend to be more cautious than coetaneous males, while older females show an intrinsic greater vulnerability. Involved people were younger than injured and fatalities, perhaps because younger people showed greater promptness to react in dangerous situations. In the study region, floods caused more fatalities (67.9%), injured (55%) and involved people (55.3%) than landslides. Fatalities and injured mainly occurred outdoor, especially along roads, and the most dangerous dynamic seems to be dragged by flood, causing the majority of fatalities. The present work is the progression of the described research, and it has been carried out by enlarging the database to a 34-year period, from 1980 to 2014. The aim is to validate the conclusions drawn for the 2000-2014 period and to investigate if and how the gender and age vulnerability factors of Calabrian people have been changing throughout the study period.

Liver histopathology of fatal phosphine poisoning.

PubMed

Saleki, Sepideh; Ardalan, Farid Azmoudeh; Javidan-Nejad, Abdullah

2007-03-02

Two commonly used pesticides in agriculture are phosphides of aluminium and zinc. Both of these metal phosphides act through elaboration of toxic phosphine gas. The poisoning in Iran is mostly oral and suicidal. Phosphine is rapidly absorbed throughout the gastrointestinal tract after ingestion and it is partly carried to the liver by the portal vein. In this study the liver histopathology of fatal poisoning is scrutinized. A descriptive, retrospective study was performed on 38 fatal phosphine poisonings. The slides of liver specimens of the cases were retrieved and studied separately by two pathologists. The poisoning was suicidal in 33 (86.5%) of cases. Portal inflammation was negligible in 37 cases and only in one of the cases, a moderate degree of chronic inflammation accompanied by granuloma formation was observed. Major histopathologic findings were as follows: mild sinusoidal congestion; 12 cases (31.6%), severe sinusoidal congestion; 25 cases (45.8%), central vein congestion; 23 cases (60.5%), centrilobular necrosis; 3 cases (7.9%), hepatocytes nuclear fragmentation; 6 cases (15.8%), sinusoidal clusters of polymorphonuclear leukocytes; 12 cases (31.6%), and mild macrovesicular steatosis; 5 cases (13.2%). Fine isomorphic cytoplasmic vacuoles were observed in 36 cases (94.7%). These vacuoles were distributed uniformly in all hepatic zones in the majority (75%) of cases. This study reveals that the main histopathologic findings of fatal phosphine poisoning in the liver are fine cytoplasmic vacuolization of hepatocytes and sinusoidal congestion.

Urban Earthquakes - Reducing Building Collapse Through Education

NASA Astrophysics Data System (ADS)

Bilham, R.

2004-12-01

Fatalities from earthquakes rose from 6000k to 9000k/year in the past decade, yet the ratio of numbers of earthquake fatalities to instantaneous population continues to fall. Since 1950 the ratio declined worldwide by a factor of three, but in some countries the ratio has changed little. E.g in Iran, 1 in 3000 people can expect to die in an earthquake, a percentage that has not changed significantly since 1890. Fatalities from earthquakes remain high in those countries that have traditionally suffered from frequent large earthquakes (Turkey, Iran, Japan, and China), suggesting that the exposure time of recently increased urban populations in other countries may be too short to have interacted with earthquakes with long recurrence intervals. This in turn, suggests that disasters of unprecendented size will occur (more than 1 million fatalities) when future large earthquakes occur close to megacities. However, population growth is most rapid in cities of less than 1 million people in the developing nations, where the financial ability to implement earthquake resistant construction methods is limited. In that structural collapse can often be traced to ignorance about the forces at work in an earthquake, the future collapse of buildings presently under construction could be much reduced were contractors, builders and occupants educated in the principles of earthquake resistant assembly. Education of builders who are tempted to cut assembly costs is likely to be more cost effective than material aid.

Could chest wall rigidity be a factor in rapid death from illicit fentanyl abuse?

PubMed

Burns, Glenn; DeRienz, Rebecca T; Baker, Daniel D; Casavant, Marcel; Spiller, Henry A

2016-06-01

There has been a significant spike in fentanyl-related deaths from illicit fentanyl supplied via the heroin trade. Past fentanyl access was primarily oral or dermal via prescription fentanyl patch diversion. One factor potentially driving this increase in fatalities is the change in route of administration. Rapid intravenous (IV) fentanyl can produce chest wall rigidity. We evaluated post-mortem fentanyl and norfentanyl concentrations in a recent surge of lethal fentanyl intoxications. Fentanyl related deaths from the Franklin County coroner's office from January to September 2015 were identified. Presumptive positive fentanyl results were confirmed by quantitative analysis using liquid chromatography tandem mass spectrometry (LC/MS/MS) and were able to quantify fentanyl, norfentanyl, alfentanyl, and sufentanyl. 48 fentanyl deaths were identified. Mean fentanyl concentrations were 12.5 ng/ml, (range 0.5 ng/ml to >40 ng/ml). Mean norfentanyl concentrations were 1.9 ng/ml (range none detected to 8.3 ng/ml). No appreciable concentrations of norfentanyl could be detected in 20 of 48 cases (42%) and were less than 1 ng/ml in 25 cases (52%). Elevated fentanyl concentrations did not correlate with rises in norfentanyl levels. In several cases fentanyl concentrations were strikingly high (22 ng/ml and 20 ng/ml) with no norfentanyl detected. The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity. An alternate explanation could be a dose-related rapid onset of respiratory arrest. Deaths occurred with low levels of fentanyl in the therapeutic range (1-2 ng/ml) in apparent non-naïve opiate abusers. Acute chest wall rigidity is a well-recognized complication in the medical community but unknown within the drug abuse community. The average abuser of illicit opioids may be unaware of the increasing fentanyl content of their illicit opioid purchase. In summary we believe sudden onset chest wall rigidity may be a significant and previously unreported factor leading to an increased mortality, from illicit IV fentanyl use. Fentanyl and norfentanyl ratios and concentrations suggest a more rapid onset of death given the finding of fentanyl without norfentanyl in many of the fatalities. Chest wall rigidity may help explain the cause of death in these instances, in contrast to the typical opioid-related overdose deaths. Intravenous heroin users should be educated regarding this potentially fatal complication given the increasingly common substitution and combination with heroin of fentanyl.

When dementia progresses quickly: a practical approach to the diagnosis and management of rapidly progressive dementia.

PubMed

Day, Gregory S; Tang-Wai, David F

2014-01-01

Making a diagnosis of rapidly progressive dementia requires practical adaptation of the skills used to assess patients with chronic causes of cognitive impairment. An expedited assessment, commensurate with the accelerated pace of the disease, is required to identify the cause of symptoms amidst a myriad of possibilities. Features upon history, physical examination and cognitive assessment that support specific diagnoses are reviewed, and a stratified approach to testing is presented. The use of readily-accessible investigations is prioritized, acknowledging the implications and applications of novel diagnostic tests. The coordinated use of clinical and laboratory measures are promoted as a means of facilitating rapid evaluation, with the ultimate goal of identifying patients with potentially reversible causes of rapidly progressive dementia.

NON-FATAL INFECTION OF MICE FOLLOWING INTRACEREBRAL INOCULATION OF YELLOW FEVER VIRUS

PubMed Central

Fox, John P.

1943-01-01

Observations have been reported which indicate that mice inoculated intracerebrally with active yellow fever virus may develop an infection which is not only non-fatal but may also be completely inapparent. The most extensive observations were made on mice which showed signs of infection but were still alive 22 days after inoculation with virus of one or another of several 17D substrains. In such cases, the infection usually progressed no further and partial or complete recovery often ensued. Agents other than yellow fever virus were excluded as a significant cause of such nonfatal infections by the failure of repeated attempts to isolate other infective agents, by the demonstration of antibodies against yellow fever virus in the sera of the mice, and by the demonstration of a high degree of resistance on the part of such surviving mice to reinoculation with large doses of neurotropic yellow fever virus. Completely inapparent infections with 17D virus were also shown to occur. Studies of apparently normal survivors of 17D virus titrations revealed a small but significant number of animals resistant to intracerebral challenge with neurotropic yellow fever virus. Further, pooled sera from such mice were shown to contain specific protective antibodies. The occurrence of non-fatal infections with 17D virus was found related to virus dose and substrain. Small doses of virus provoked a significantly higher proportion of non-fatal infections than large doses; while different 17D substrains, tested over equivalent ranges of virus dose, varied greatly with respect to the proportion of infections which did not terminate with death. In the case of two substrains (17DD low and 17D3), non-fatal infections (as demonstrated by resistance to intracerebral challenge with neurotropic virus) were sufficiently frequent to cause an increase, when included in the computation of the infective titers, of 25 per cent above the figures based on deaths alone. The demonstration of non-fatal infections, thus, may be important to the accuracy of quantitative determinations of infectivity. Limited observations with virus of the French neurotropic and the pantropic Asibi strains revealed that non-fatal infections do occur, but only rarely. Somewhat more extensive observations with unmodified virus of strains isolated from Brazilian cases of jungle yellow fever, in contrast, revealed an occurrence of non-fatal infections much greater than that observed with the most productive 17D substrains. With these jungle strains, the demonstration of non-fatal infections proved indispensable to any measure of the level of infectivity of virus preparations. The demonstration of the proportional occurrence in mice of non-fatal infections with yellow fever virus provides an additional means by which different virus strains and substrains may be characterized. PMID:19871300

Fatal toxic shock syndrome from an intrauterine device.

PubMed

Klug, Cameron D; Keay, C Ryan; Ginde, Adit A

2009-11-01

Toxic shock syndrome is a rare toxin-mediated condition that can rapidly produce multiorgan failure and severe shock. Toxic shock syndrome has been previously recognized in various clinical situations relating to surgery, nasal packing, abscesses, burns, and most notably menstrual-related cases. This case report describes a previously healthy 33-year-old woman presenting to the emergency department with complaints of nausea, vomiting, and diarrhea; vital signs at triage were normal. Within hours, she developed shock and cardiopulmonary arrest. The patient met all 6 of the Centers for Disease Control and Prevention diagnostic criteria for toxic shock syndrome, and her intrauterine device grew out Staphylococcus aureus. To our knowledge, this is the first reported case in the medical literature of fatal toxic shock syndrome related to an intrauterine device.

Automobile-dependency as a barrier to vision zero, evidence from the states in the USA.

PubMed

Ahangari, Hamed; Atkinson-Palombo, Carol; Garrick, Norman W

2017-10-01

With a traffic fatality rate of 10.6 per 100,000 as of 2013-more than triple that in the UK, the Netherlands, and Sweden-the United States has the worst traffic safety performance of all developed countries. Statewide variations are even more pronounced. North Dakota registers more than twice the national average and five times the rate of Massachusetts. We used panel models and annual data from 1997 to 2013 to capture the effect of seven separate sets of factors that influence traffic safety: exposure, travel behavior, socioeconomics, macroeconomics, safety policies, and mitigating factors such as health care. The results of our panel models and supplementary analysis of state effects show that two variables - Vehicle Miles Traveled and Vehicles per Capita-have the strongest impact on traffic fatality rates. This is closely followed by Infant Mortality Rates, the proxy that we used to represent the quality of health care. Policy levers such as Graduated Driver's Licenses (GDL) have improved safety, but to a limited extent. We also found that states with higher urban density and more walking are associated with lower traffic fatality rates. Taken as a whole, our findings suggest that if additional progress is to be made in reducing traffic fatalities, emphasis needs to move beyond simply focusing on policies such as GDL and seat belt laws, which have already been adopted by almost all jurisdictions across the United States. We need to also consider factors that focus on the type of urban form that we are creating to ensure that we are fostering environments that encourage multi-modal transportation such as walking to reduce the VMT and Vehicles per Capita, the two strongest predictors of traffic fatalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling.

PubMed

Kido, Masahiro; Watanabe, Norihiko; Okazaki, Taku; Akamatsu, Takuji; Tanaka, Junya; Saga, Kazuyuki; Nishio, Akiyoshi; Honjo, Tasuku; Chiba, Tsutomu

2008-10-01

Because of the lack of animal models developing spontaneous autoimmune hepatitis (AIH), the molecular mechanisms involved in the development of AIH are still unclear. This study aims to examine the regulatory roles of naturally arising CD4(+)CD25(+) regulatory T (Treg) cells and programmed cell death 1 (PD-1)-mediated signaling in the development of AIH. To induce a concurrent loss of Treg cells and PD-1-mediated signaling, neonatal thymectomy (NTx), which severely reduces the number of Treg cells, was performed on PD-1(-/-) mice. After the NTx, we performed histologic examination, assessed autoantibody production and infiltrating cells in the liver, and conducted adoptive transfer experiments. In contrast to NTx mice and PD-1(-/-) mice, NTx-PD-1(-/-) mice produced antinuclear antibodies and developed fatal hepatitis characterized by a CD4(+) and CD8(+) T-cell infiltration invading the parenchyma with massive lobular necrosis. Induction of AIH in NTx-PD-1(-/-) mice was suppressed by transfer of Treg cells, even derived from PD-1(-/-) mice. Transfer of total but not CD4(+) T-cell-depleted splenocytes from NTx-PD-1(-/-) mice into RAG2(-/-) mice induced the development of severe hepatitis. In contrast, the transfer of CD8(+) T-cell-depleted splenocytes triggered only mononuclear infiltrates without massive necrosis of the parenchyma. NTx-PD-1(-/-) mice are the first mouse model of spontaneous fatal AIH. The concurrent loss of Treg cells and PD-1-mediated signaling can induce the development of fatal AIH. Autoreactive CD4(+) T cells are essential for induction of AIH, whereas CD8(+) T cells play an important role in progression to fatal hepatic damage.

CD8+ T Cells Induce Fatal Brainstem Pathology during Cerebral Malaria via Luminal Antigen-Specific Engagement of Brain Vasculature

PubMed Central

Swanson, Phillip A.; Hart, Geoffrey T.; Russo, Matthew V.; Nayak, Debasis; Yazew, Takele; Peña, Mirna; Khan, Shahid M.; Pierce, Susan K.; McGavern, Dorian B.

2016-01-01

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death. At the peak of ECM, we revealed using intravital two-photon microscopy that myelomonocytic cells and parasite-specific CD8+ T cells associated primarily with the luminal surface of CNS blood vessels. Myelomonocytic cells participated in the removal of parasitized red blood cells (pRBCs) from cerebral blood vessels, but were not required for the disease. Interestingly, the majority of disease-inducing parasite-specific CD8+ T cells interacted with the lumen of brain vascular endothelial cells (ECs), where they were observed surveying, dividing, and arresting in a cognate peptide-MHC I dependent manner. These activities were critically dependent on IFN-γ, which was responsible for activating cerebrovascular ECs to upregulate adhesion and antigen-presenting molecules. Importantly, parasite-specific CD8+ T cell interactions with cerebral vessels were impaired in chimeric mice rendered unable to present EC antigens on MHC I, and these mice were in turn resistant to fatal brainstem pathology. Moreover, anti-adhesion molecule (LFA-1 / VLA-4) therapy prevented fatal disease by rapidly displacing luminal CD8+ T cells from cerebrovascular ECs without affecting extravascular T cells. These in vivo data demonstrate that parasite-specific CD8+ T cell-induced fatal vascular breakdown and subsequent neuronal death during ECM is associated with luminal, antigen-dependent interactions with cerebrovasculature. PMID:27907215

Postexposure prevention of progressive vaccinia in SCID mice treated with vaccinia immune globulin.

PubMed

Fisher, R W; Reed, J L; Snoy, P J; Mikolajczyk, M G; Bray, M; Scott, D E; Kennedy, M C

2011-01-01

A recently reported case of progressive vaccinia (PV) in an immunocompromised patient has refocused attention on this condition. Uniformly fatal prior to the licensure of vaccinia immune globulin (VIG) in 1978, PV was still fatal in about half of VIG-treated patients overall, with a greater mortality rate in infants and children. Additional therapies would be needed in the setting of a smallpox bioterror event, since mass vaccination following any variola virus release would inevitably result in exposure of immunocompromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support the licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia virus-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia virus-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if left untreated. Postexposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most of the mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most of the animals, even when initiated 7 days postinfection. These results support the possibility that combination treatments may be effective in humans and support using this SCID model of PV to test new antibody therapies and combination therapies and to provide further insights into the pathogenesis and treatment of PV.

Earthquake impact scale

USGS Publications Warehouse

Wald, D.J.; Jaiswal, K.S.; Marano, K.D.; Bausch, D.

2011-01-01

With the advent of the USGS prompt assessment of global earthquakes for response (PAGER) system, which rapidly assesses earthquake impacts, U.S. and international earthquake responders are reconsidering their automatic alert and activation levels and response procedures. To help facilitate rapid and appropriate earthquake response, an Earthquake Impact Scale (EIS) is proposed on the basis of two complementary criteria. On the basis of the estimated cost of damage, one is most suitable for domestic events; the other, on the basis of estimated ranges of fatalities, is generally more appropriate for global events, particularly in developing countries. Simple thresholds, derived from the systematic analysis of past earthquake impact and associated response levels, are quite effective in communicating predicted impact and response needed after an event through alerts of green (little or no impact), yellow (regional impact and response), orange (national-scale impact and response), and red (international response). Corresponding fatality thresholds for yellow, orange, and red alert levels are 1, 100, and 1,000, respectively. For damage impact, yellow, orange, and red thresholds are triggered by estimated losses reaching $1M, $100M, and $1B, respectively. The rationale for a dual approach to earthquake alerting stems from the recognition that relatively high fatalities, injuries, and homelessness predominate in countries in which local building practices typically lend themselves to high collapse and casualty rates, and these impacts lend to prioritization for international response. In contrast, financial and overall societal impacts often trigger the level of response in regions or countries in which prevalent earthquake resistant construction practices greatly reduce building collapse and resulting fatalities. Any newly devised alert, whether economic- or casualty-based, should be intuitive and consistent with established lexicons and procedures. Useful alerts should also be both specific (although allowably uncertain) and actionable. In this analysis, an attempt is made at both simple and intuitive color-coded alerting criteria; yet the necessary uncertainty measures by which one can gauge the likelihood for the alert to be over- or underestimated are preserved. The essence of the proposed impact scale and alerting is that actionable loss information is now available in the immediate aftermath of significant earthquakes worldwide on the basis of quantifiable loss estimates. Utilizing EIS, PAGER's rapid loss estimates can adequately recommend alert levels and suggest appropriate response protocols, despite the uncertainties; demanding or awaiting observations or loss estimates with a high level of accuracy may increase the losses. ?? 2011 American Society of Civil Engineers.

[Current diagnosis of classic mastitis carcinomatosa].

PubMed

Borojević, N; Trbojević, P; Zamurović, J

1990-01-01

Mastitis carcinomatosa (inflammatory carcinoma) is a very rare form of breast cancer, with a rapid progress, generalisation and dissemination into the vital organs, and lethal issue. Inflammatory carcinoma of the breast (ICB) accounts for 1 to 4 per cent of all breast carcinomas. Only 3 to 6 per cent of patients survive for 5 years, and a great number of patients die within 1 to 2 years, with disseminated metastases. Undefined diagnostical criteria of the desease are responsible of undefined therapeutical procedures. There are still contra-many diction which are well documented in the literature. In this paper we tried to give our contribution to the solution of some of these problems. Today it is clear that tumour embolism in dermal lymphatics of the involved breast skin is a pathohistologic basis of this fatal desease. Accordingly consequences are visible in all clinical signs, which have a very poor prognosis. There is a very large group of local advanced breast carcinomas that are similar to the ICB, but that are not really ICB. In fact, although all these malignant deseases are very similar, their differentiation is very important esspecialy because of their evaluation. A great number of other benignant deseases have very similar signs. Therefore ICB is a interdisciplinary problem.

Necrotizing fasciitis: case series and review of the literature on clinical and medico-legal diagnostic challenges.

PubMed

Fais, Paolo; Viero, Alessia; Viel, Guido; Giordano, Renzo; Raniero, Dario; Kusstatscher, Stefano; Giraudo, Chiara; Cecchetto, Giovanni; Montisci, Massimo

2018-04-07

Necrotizing fasciitis (NF) is a life-threatening infection of soft tissues spreading along the fasciae to the surrounding musculature, subcutaneous fat and overlying skin areas that can rapidly lead to septic shock and death. Due to the pandemic increase of medical malpractice lawsuits, above all in Western countries, the forensic pathologist is frequently asked to investigate post-mortem cases of NF in order to determine the cause of death and to identify any related negligence and/or medical error. Herein, we review the medical literature dealing with cases of NF in a post-mortem setting, present a case series of seven NF fatalities and discuss the main ante-mortem and post-mortem diagnostic challenges of both clinical and forensic interests. In particular, we address the following issues: (1) origin of soft tissue infections, (2) micro-organisms involved, (3) time of progression of the infection to NF, (4) clinical and histological staging of NF and (5) pros and cons of clinical and laboratory scores, specific forensic issues related to the reconstruction of the ideal medical conduct and the evaluation of the causal value/link of any eventual medical error.

Current Understanding of Acute Bovine Liver Disease in Australia

PubMed Central

Read, Elizabeth; Edwards, Jacqueline; Deseo, Myrna; Rawlin, Grant; Rochfort, Simone

2016-01-01

Acute bovine liver disease (ABLD) is a hepatotoxicity principally of cattle which occurs in southern regions of Australia. Severely affected animals undergo rapid clinical progression with mortalities often occurring prior to the recognition of clinical signs. Less severely affected animals develop photosensitization and a proportion can develop liver failure. The characteristic histopathological lesion in acute fatal cases is severe, with acute necrosis of periportal hepatocytes with hemorrhage into the necrotic areas. Currently there are a small number of toxins that are known to cause periportal necrosis in cattle, although none of these have so far been linked to ABLD. Furthermore, ABLD has frequently been associated with the presence of rough dog’s tail grass (Cynosurus echinatus) and Drechslera spp. fungi in the pasture system, but it is currently unknown if these are etiological factors. Much of the knowledge about ABLD is contained within case reports, with very little experimental research investigating the specific cause(s). This review provides an overview of the current and most recently published knowledge of ABLD. It also draws on wider research and unpublished reports to suggest possible fungi and mycotoxins that may give rise to ABLD. PMID:28035972

[Ehlers-Danlos syndromes: we are all concerned].

PubMed

de Wazières, B; Plauchu, H; Boucand, M H

1998-10-17

EHLERS-DANLOS SYNDROMES (EDS): A heterogeneous group of hereditary conditions having in common a molecular anomaly of the extracellular matrix comprise EDS. Clinical and genetic features are used for classification and in some cases the molecular anomaly can be demonstrated. Six main types are recognized and termed classic, hypermobile, vascular, cyphoscoliotic, arthrochalasic and dermatosparaxis. Skin and joint signs predominate, visceral disease is fortunately rare. The skin is hyperelastic and heals poorly. Joint involvement may lead to luxations and early-onset osteoarthritis causing chronic pain. The prognosis is severe in certain types such as vascular EDS where arterial ruptures may be life-threatening. Patients with cyphoscoliotic EDS may become bedridden due to the scoliosis and muscular hypotrophy. Minor forms as well as rapidly fatal major forms often go undiagnosed or are identified late after a complication which could have been avoided. A multidisciplinary approach is needed as certain interventions, technical procedures or explorations may have catastrophic consequences. The creation of an EDS association would be helpful in federating specialists and allow global management. The gravity of certain forms, the poorly understood epidemiology and the progressive nature of EDS point to the need for a national registry.

Delayed anaphylaxis to alpha-gal, an oligosaccharide in mammalian meat

PubMed Central

Commins, Scott P.; Jerath, Maya R.; Cox, Kelly; Erickson, Loren D.; Platts-Mills, Thomas

2016-01-01

IgE-mediated hypersensitivity refers to immune reactions that can be rapidly progressing and, in the case of anaphylaxis, are occasionally fatal. To that end, identification of the associated allergen is important for facilitating both education and allergen avoidance that are essential to long-term risk reduction. As the number of known exposures associated with anaphylaxis is limited, discovery of novel causative agents is crucial to evaluation and management of patients with idiopathic anaphylaxis. Within the last 10 years several apparently separate observations were recognized to be related, all of which resulted from the development of antibodies to a carbohydrate moiety on proteins. Interestingly, the exposure differed from airborne allergens but was nevertheless capable of producing anaphylactic and hypersensitivity reactions. Our recent work has identified these responses as being due to a novel IgE antibody directed against a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (“alpha-gal”). This review will present the historical summary of the identification of cetuximab hypersensitivity due to alpha-gal IgE and discuss the non-primate mammalian meat food allergy as well as current goals and directions of our research programs. PMID:26666477

Exogenous Variables and Value-Added Assessments: A Fatal Flaw

ERIC Educational Resources Information Center

Berliner, David C.

2014-01-01

Background: There has been rapid growth in value-added assessment of teachers to meet the widely supported policy goal of identifying the most effective and the most ineffective teachers in a school system. The former group is to be rewarded while the latter group is to be helped or fired for their poor performance. But, value-added approaches to…

Arterial Gas Embolism Induced Ageusia (Case Report)

DTIC Science & Technology

2011-07-01

Pulmonary barotraumas are also reported in tbe literature; one case report described delayed onset pul- monary barotrauma in a diver which resolved...be rapidly fatal; it includes shock, pulmonary "chokes", and neurolog ic sequelae resembling cere- brovascular accidents due to nitrogen bubbles...pressures and may cause pneumothoraces. Air may evolve into the mediastinum (mediastinal emphysema ) or the skin (subcutaneous emphysema ). Lastly

Genetic Detection and Isolation of Crimean-Congo hemorrhagic fever virus, Kosovo, Yugoslavia

PubMed Central

Boźović, Bojana; Pavlidou, Vassiliki; Papadimitriou, Evangelia; Pelemis, Mijomir; Antoniadis, Aantonis

2002-01-01

Crimean-Congo hemorrhagic fever virus (C-CHFV) strains were isolated from a fatal case and the attending physician in Kosovo, Yugoslavia. Early, rapid diagnosis of the disease was achieved by reverse transcription-polymerase chain reaction. The physician was successfully treated with oral ribavirin. These cases yielded the first genetically studied C-CHFV human isolates in the Balkans. PMID:12141973

Strategies in Ebola virus disease (EVD) diagnostics at the point of care

PubMed Central

Coarsey, Chad T.; Esiobu, Nwadiuto; Narayanan, Ramswamy; Pavlovic, Mirjana; Shafiee, Hadi; Asghar, Waseem

2017-01-01

Ebola virus disease (EVD) is a devastating, highly infectious illness with a high mortality rate. The disease is endemic to regions of Central and West Africa, where there is limited laboratory infrastructure and trained staff. The recent 2014 West African EVD outbreak has been unprecedented in case numbers and fatalities, and has proven that such regional outbreaks can become a potential threat to global public health, as it became the source for the subsequent transmission events in Spain and the USA. The urgent need for rapid and affordable means of detecting Ebola is crucial to control the spread of EVD and prevent devastating fatalities. Current diagnostic techniques include molecular diagnostics and other serological and antigen detection assays; which can be time-consuming, laboratory-based, often require trained personnel and specialized equipment. In this review, we discuss the various Ebola detection techniques currently in use, and highlight the potential future directions pertinent to the development and adoption of novel point-of-care diagnostic tools. Finally, a case is made for the need to develop novel microfluidic technologies and versatile rapid detection platforms for early detection of EVD. PMID:28440096

Civilian helicopter accidents into water: analysis of 46 cases, 1979-2006.

PubMed

Brooks, Christopher James; MacDonald, Conor Vaughan; Donati, Leo; Taber, Michael John

2008-10-01

When a helicopter crashes or ditches into water the crew and passengers must often make an escape from underwater and a number of the occupants do not survive. This paper examined fatality rates, human factors problems with escape, and causes of death in Canadian civilian registered helicopter accidents in water (1979-2006). Data obtained from the Transportation Safety Board of Canada was reviewed. Key issues such as fatalities, injuries, warning time, sinking, and inversion were examined. There were 46 helicopters that ditched into water. There were 124 crew and passengers involved. Of those, 27 (23%) crew and passengers died. Lack of warning time (55%), rapid sinking (72%), and inversion (35%) were the most common issues in the accidents. Survival rates for Canadian registered helicopter accidents into water (78%) show little change from previously reported worldwide data. Lack of warning time, rapid sinking, and inversion were the significant factors in the survival rate. The practical implication is that crew and passengers involved in planned flights over water must wear all the life support equipment on strap-in and not have it stowed on the back of the seat or in the cabin.

Spatial patterns monitoring of road traffic injuries in Karachi metropolis.

PubMed

Lateef, Muhammad U

2011-06-01

This article aims to assess the pattern of road traffic injuries (RTIs) and fatalities in Karachi metropolis. Assessing the pattern of RTIs in Karachi at this juncture is important for many reasons. The rapid motorisation in the recent years due to the availability of credit has significantly increased the traffic volume of the city. Since then, the roads of Karachi have continuously developed at a rapid pace. This development has come with a high human loss, because the construction of multilevel flyovers, signal-free corridors and the resulting high-speed traffic ultimately increase the severity of injuries. The reasons for this high proportion are inadequate infrastructure, poor enforcement of safety regulations, high crash severity index and greater population of vulnerable road user groups (riders and pedestrians). This research is the first of its kind in the country to have a geocoded database of fatalities and injuries in a geographical information system for the entire city of Karachi. In fact, road crashes are both predictable and preventable. Developing countries should learn from the experience of highly motorised nations to avoid the high burden of RTIs by adopting road safety and prevention measures.

Cytophagic histiocytic panniculitis and hemophagocytic lymphohistiocytosis: an overview.

PubMed

Aronson, Iris K; Worobec, Sophie M

2010-01-01

Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis that is associated with systemic features including fevers, hepatosplenomegaly, lymphadenopathy, pancytopenia, hepatic abnormalities, hypertriglyceridemia, and coagulopathy without an elevated erythrocyte sedimentation rate. The panniculitis lesions show adipose tissue lymphocytic and histiocytic infiltration along with hemophagocytosis, which may also appear in bone marrow, spleen, lymph nodes, and liver. Patients may have a rapidly fatal disease course, a longer disease course with intermittent remissions and exacerbations for many years prior to death, or a nonfatal acute or intermittent course responsive to treatment. The cytophagocytic disorder in these patients is a hemophagocytic lymphohistiocytosis (HLH), similar to the infection-activated reaction associated with perforin mutations found in familial hemophagocytic lymphohistiocytosis. HLH is a group of autoinflammatory disorders, which include macrophage activation syndrome and infection-associated hemophagocytic syndrome, which if not treated rapidly, can be fatal. The relationship of CHP and HLH is discussed. CHP associated diseases include: subcutaneous panniculitis-like T cell lymphomas; infections, connective tissue diseases, other malignancies, and the molecular disorders that cause HLH. Treatment of CHP includes: glucocorticoids in combination with cyclosporine, combined chemotherapeutic medications and most recently, anakinra, an Interleukin-1 receptor antagonist; along with supportive care, search for underlying malignancies and treatment thereof, and control of associated infections.

Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure

PubMed Central

Mease, P; Deodhar, A; Fleischmann, R; Wollenhaupt, J; Gladman, D; Leszczyński, P; Vitek, P; Turkiewicz, A; Khraishi, M; FitzGerald, O; Landewé, R; de Longueville, M; Hoepken, B; Peterson, L; van der Heijde, D

2015-01-01

Objective Previous reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF) therapy. We report efficacy and safety data from a 96-week data cut of RAPID-PsA. Methods RAPID-PsA was placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. We present efficacy data including American College of Rheumatology (ACR)/Psoriasis Area and Severity Index (PASI) responses, HAQ-DI, pain, minimal disease activity (MDA), modified total Sharp score (mTSS) and ACR responses in patients with/without prior anti-TNF exposure, in addition to safety data. Results Of 409 patients randomised, 273 received CZP from week 0. 54 (19.8%) CZP patients had prior anti-TNF exposure. Of patients randomised to CZP, 91% completed week 24, 87% week 48 and 80% week 96. ACR responses were maintained to week 96: 60% of patients achieved ACR20 at week 24, and 64% at week 96. Improvements were observed with both CZP dose regimens. ACR20 responses were similar in patients with (week 24: 59%; week 96: 63%) and without (week 24: 60%; week 96: 64%) prior anti-TNF exposure. Placebo patients switching to CZP displayed rapid clinical improvements, maintained to week 96. In patients with ≥3% baseline skin involvement (60.8% week 0 CZP patients), PASI responses were maintained to week 96. No progression of structural damage was observed over the 96-week period. In the Safety Set (n=393), adverse events occurred in 345 patients (87.8%) and serious adverse events in 67 (17.0%), including 6 fatal events. Conclusions CZP efficacy was maintained to week 96 with both dose regimens and in patients with/without prior anti-TNF exposure. The safety profile was in line with that previously reported from RAPID-PsA, with no new safety signals observed with increased exposure. Trial registration number NCT01087788. PMID:26509074

American football and fatal exertional heat stroke: a case study of Korey Stringer.

PubMed

Grundstein, Andrew; Knox, John A; Vanos, Jennifer; Cooper, Earl R; Casa, Douglas J

2017-08-01

On August 1, 2001, Korey Stringer, a Pro Bowl offensive tackle for the Minnesota Vikings, became the first and to date the only professional American football player to die from exertional heat stroke (EHS). The death helped raise awareness of the dangers of exertional heat illnesses in athletes and prompted the development of heat safety policies at the professional, collegiate, and interscholastic levels. Despite the public awareness of this death, no published study has examined in detail the circumstances surrounding Stringer's fatal EHS. Using the well-documented details of the case, our study shows that Stringer's fatal EHS was the result of a combination of physiological limitations, organizational and treatment failings, and extreme environmental conditions. The COMfort FormulA (COMFA) energy budget model was used to assess the relative importance of several extrinsic factors on Stringer's EHS, including weather conditions, clothing insulation, and activity levels. We found that Stringer's high-intensity training in relation to the oppressive environmental conditions was the most prominent factor in producing dangerous, uncompensable heat stress conditions and that the full football uniform played a smaller role in influencing Stringer's energy budget. The extreme energy budget levels that led to the fatal EHS would have been avoided according to our modeling through a combination of reduced intensity and lower clothing insulation. Finally, a long delay in providing medical treatment made the EHS fatal. These results highlight the importance of modern heat safety guidelines that provide controls on extrinsic factors, such as the adjustment of duration and intensity of training along with protective equipment modifications based on environmental conditions and the presence of an emergency action plan focused on rapid recognition and immediate on-site aggressive cooling of EHS cases.

American football and fatal exertional heat stroke: a case study of Korey Stringer

NASA Astrophysics Data System (ADS)

Grundstein, Andrew; Knox, John A.; Vanos, Jennifer; Cooper, Earl R.; Casa, Douglas J.

2017-08-01

On August 1, 2001, Korey Stringer, a Pro Bowl offensive tackle for the Minnesota Vikings, became the first and to date the only professional American football player to die from exertional heat stroke (EHS). The death helped raise awareness of the dangers of exertional heat illnesses in athletes and prompted the development of heat safety policies at the professional, collegiate, and interscholastic levels. Despite the public awareness of this death, no published study has examined in detail the circumstances surrounding Stringer's fatal EHS. Using the well-documented details of the case, our study shows that Stringer's fatal EHS was the result of a combination of physiological limitations, organizational and treatment failings, and extreme environmental conditions. The COMfort FormulA (COMFA) energy budget model was used to assess the relative importance of several extrinsic factors on Stringer's EHS, including weather conditions, clothing insulation, and activity levels. We found that Stringer's high-intensity training in relation to the oppressive environmental conditions was the most prominent factor in producing dangerous, uncompensable heat stress conditions and that the full football uniform played a smaller role in influencing Stringer's energy budget. The extreme energy budget levels that led to the fatal EHS would have been avoided according to our modeling through a combination of reduced intensity and lower clothing insulation. Finally, a long delay in providing medical treatment made the EHS fatal. These results highlight the importance of modern heat safety guidelines that provide controls on extrinsic factors, such as the adjustment of duration and intensity of training along with protective equipment modifications based on environmental conditions and the presence of an emergency action plan focused on rapid recognition and immediate on-site aggressive cooling of EHS cases.

Cerebral aneurysms: Formation, progression and developmental chronology

PubMed Central

Etminan, Nima; Buchholz, Bruce A.; Dreier, Rita; Bruckner, Peter; Torner, James C.; Steiger, Hans-Jakob; Hänggi, Daniel; Macdonald, R. Loch

2015-01-01

The prevalence of unruptured intracranial aneurysms (UAIs) in the general population is up to 3%. Existing epidemiological data suggests that only a small fraction of UIAs progress towards rupture over the lifetime of an individual, but the surrogates for subsequent rupture and the natural history of UIAs are discussed very controversially at present. In case of rupture of an UIA, the case-fatality is up to 50%, which therefore continues to stimulate interest in the pathogenesis of cerebral aneurysm formation and progression. Actual data on the chronological development of cerebral aneurysm has been especially difficult to obtain and, until recently, the existing knowledge in this respect is mainly derived from animal or mathematical models or short-term observational studies. Here, we highlight the current data on cerebral aneurysm formation and progression as well as a novel approach to investigate the developmental chronology of cerebral aneurysms. PMID:24323717

Ebolavirus vaccines for humans and apes.

PubMed

Fausther-Bovendo, Hugues; Mulangu, Sabue; Sullivan, Nancy J

2012-06-01

Because of high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes. Published by Elsevier B.V.

[Fatal toxic leukoencephalopathy associated with consumption of pasta base of cocaine: Report of three cases].

PubMed

Cartier R, Luis; González L, Daniela; Harán D, Jorge

2015-11-01

The prevalence of drug-associated toxic encephalopathy is unknown, but it is an uncommon condition. Toxic leukoencephalopathy was described associated with heroin consumption, it has been less commonly described with the use of cocaine and there are no reports of its association with consumption pasta base of cocaine (PBC). We report two females aged 31 years and a male aged 19 years, consumers of PBC who developed a fatal toxic leukoencephalopathy. They initiated their disease with severe and persistent headache, sequential focal neurologic deficits and a progressive impairment of consciousness that culminated with their death. Laboratory parameters such as blood count, cerebrospinal fluid analyses or infectious biological indices were normal. MRI showed multifocal lesions in brain white matter of both hemispheres confirming the leukoencephalopathy. There was no response to the use of methylprednisolone.

Spontaneous bilateral chylothorax with fatal outcome in a patient with melorheostosis.

PubMed

Leuenberger, Michèle; Braunwalder, Jan; Schmid, Ralph A; Stanga, Zeno

2008-11-01

We report a case of progressive, multifocal melorheostosis in a 28-year-old woman, with involvement of the left arm, chest, spine, and impressive soft tissue involvement. In the past, she had undergone multiple vascular interventions. She presented with spontaneous massive bilateral chylothorax. After conservative treatment without success, we conducted bilateral pleurodesis. This resulted in a clear reduction of pleural effusions, but her medical condition subsequently worsened due to progressive parenchymatous infiltrates, and increased interlobal pleural effusions. She ultimately died of global respiratory insufficiency. In patients with melorheostosis, involvement of the soft tissue can result in distinctive morbidity, and whenever possible, treatment should be conservative.

Progress in translational research on intracerebral hemorrhage: Is there an end in sight?

PubMed Central

Xi, Guohua; Strahle, Jennifer; Hua, Ya; Keep, Richard F.

2013-01-01

Intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype for which specific therapies and treatments remain elusive. To address this, many recent experimental and translational studies of ICH have been conducted, and these have led to several ongoing clinical trials. This review focuses on the progress of translational studies of ICH including those of the underlying causes and natural history of ICH, animal models of the condition, and effects of ICH on the immune and cardiac systems, among others. Current and potential clinical trials also are discussed for both ICH alone and with intraventricular extension. PMID:24139872

The likelihood of achieving quantified road safety targets: a binary logistic regression model for possible factors.

PubMed

Sze, N N; Wong, S C; Lee, C Y

2014-12-01

In past several decades, many countries have set quantified road safety targets to motivate transport authorities to develop systematic road safety strategies and measures and facilitate the achievement of continuous road safety improvement. Studies have been conducted to evaluate the association between the setting of quantified road safety targets and road fatality reduction, in both the short and long run, by comparing road fatalities before and after the implementation of a quantified road safety target. However, not much work has been done to evaluate whether the quantified road safety targets are actually achieved. In this study, we used a binary logistic regression model to examine the factors - including vehicle ownership, fatality rate, and national income, in addition to level of ambition and duration of target - that contribute to a target's success. We analyzed 55 quantified road safety targets set by 29 countries from 1981 to 2009, and the results indicate that targets that are in progress and with lower level of ambitions had a higher likelihood of eventually being achieved. Moreover, possible interaction effects on the association between level of ambition and the likelihood of success are also revealed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Radiological and Pathological Correlation in Anti-MDA5 Antibody-positive Interstitial Lung Disease: Rapidly Progressive Perilobular Opacities and Diffuse Alveolar Damage.

PubMed

Chino, Haruka; Sekine, Akimasa; Baba, Tomohisa; Iwasawa, Tae; Okudela, Koji; Takemura, Tamiko; Itoh, Harumi; Sato, Shinji; Suzuki, Yasuo; Ogura, Takashi

2016-01-01

We herein present the first case of rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody evaluated by surgical lung biopsy (SLB). High-resolution CT scan revealed perilobular opacities, which rapidly became thicker and formed consolidation, resulting in remarkable loss of lung volume. Specimens taken from SLB revealed membranous organization with alveolar occlusion, dilation of alveolar ducts, and sacs with collapsed alveoli, which are typical features of diffuse alveolar damage (DAD). Rapidly progressive perilobular opacities may be characteristic of RP-ILD with anti-MDA5 antibody and DAD.

Hemopericardium Following Acupuncture

PubMed Central

Kim, Jung Heon; Lee, Yong Jik; Hong, Jung Seok; Ahn, Ryeok; Hong, Eun Seog

2011-01-01

Acupuncture-related hemopericardium is a rare but potentially fatal complication. We describe a hemopericardium that occurred shortly after acupuncture in a 55-year-old woman. A chest CT scan and echocardiography revealed a hemopericardium, and pericardiocentesis was then immediately and successfully performed. Subsequently, her clinical course improved. This case increases the attention of emergency physicians for acupuncture-related complications, especially hemopericardium, and the necessity of rapid diagnosis and management. PMID:21155058

Preclinical Mouse Models of Neurofibromatosis

DTIC Science & Technology

2006-10-01

Patients. Persons with NF1 are predisposed to benign neurofibromas, optic nerve gliomas, and to specific malignant neoplasms . Individuals with NF1...malignant neoplasms seen in NF1 patients include astrocytoma, malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, and juvenile...Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proc Natl Acad Sci U S A 2004;101(2):597-602. 14. Chan IT, Kutok JL

The Impact of In-Vehicle Cell-Phone Use on Accidents or Near-Accidents among College Students.

ERIC Educational Resources Information Center

Seo, Dong-Chul; Torabi, Mohammad R.

2004-01-01

With in-vehicle use of cell phones rapidly increasing, the safety of young drivers, who represent 14% of licensed drivers but 26% of drivers involved in fatal crashes, may be disproportionately threatened. The authors used a questionnaire to examine the association between in-vehicle cell-phone use and accidents or near-accidents among 1,291…

A Fatal Spontaneous Gas Gangrene due to Clostridium perfringens during Neutropenia of Allogeneic Stem Cell Transplantation: Case Report and Literature Review.

PubMed

Lee, Hae-Lim; Cho, Sung-Yeon; Lee, Dong-Gun; Ko, Yumi; Hyun, Ji In; Kim, Bo Kyoung; Seo, Jae Hyun; Lee, Jung Woo; Lee, Seok

2014-09-01

Most cases of gas gangrene caused by Clostridium species begin with trauma-related injuries but in rare cases, spontaneous gas gangrene (SGG) can occur when patients have conditions such as advanced malignancy, diabetes, or immunosuppression. Clostridium perfringens, a rare cause of SGG, exists as normal flora of skin and intestines of human. Adequate antibiotics with surgical debridement of infected tissue is the only curative therapeutic management. Mortality rate among adults is reported range of 67-100% and majority of deaths are occurred within 24 hours of onset. We experienced a case of SGG on the trunk, buttock and thigh in a neutropenic patient with acute lymphoblastic leukemia. His clinical course was rapid and fatal during pre-engraftment neutropenic period of allogeneic stem cell transplantation.

A Fatal Spontaneous Gas Gangrene due to Clostridium perfringens during Neutropenia of Allogeneic Stem Cell Transplantation: Case Report and Literature Review

PubMed Central

Lee, Hae-Lim; Cho, Sung-Yeon; Ko, Yumi; Hyun, Ji In; Kim, Bo Kyoung; Seo, Jae Hyun; Lee, Jung Woo; Lee, Seok

2014-01-01

Most cases of gas gangrene caused by Clostridium species begin with trauma-related injuries but in rare cases, spontaneous gas gangrene (SGG) can occur when patients have conditions such as advanced malignancy, diabetes, or immunosuppression. Clostridium perfringens, a rare cause of SGG, exists as normal flora of skin and intestines of human. Adequate antibiotics with surgical debridement of infected tissue is the only curative therapeutic management. Mortality rate among adults is reported range of 67-100% and majority of deaths are occurred within 24 hours of onset. We experienced a case of SGG on the trunk, buttock and thigh in a neutropenic patient with acute lymphoblastic leukemia. His clinical course was rapid and fatal during pre-engraftment neutropenic period of allogeneic stem cell transplantation. PMID:25298910

A 2,4-dichlorophenoxyacetic acid induced fatality.

PubMed

Jorens, P G; Heytens, L; De Paep, R J; Bossaert, L; Selala, M I; Schepens, P J

1995-03-01

This paper reports on a fatal intoxication by oral ingestion of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). At admission, the victim was unconscious. His condition deteroriated rapidly with blood loss from his mouth and nose. Since the cause of this condition was not known, gastroscopy was performed and haemorrhagic mucosa was observed in the mouth, oesophagus and stomach. Gastric contents (removed by lavage), urine and blood were submitted for toxicological analysis. Unfortunately, within 3 h of admission (about 5 h following ingestion of the toxin) profound cardiogenic shock developed and the patient died. The identity of the toxic xenobiotic was revealed by gas chromatography-mass spectrometry. Analytical quantification of the herbicide was performed by acid extraction prior to gas chromatographic examination using electron capture detection. His blood level of 2,4-D was 192 mg l-1.

Case Series of Fatal Leptospira spp./Dengue Virus Co-Infections—Puerto Rico, 2010–2012

PubMed Central

Pérez Rodríguez, Nicole M.; Galloway, Renee; Blau, Dianna M.; Traxler, Rita; Bhatnagar, Julu; Zaki, Sherif R.; Rivera, Aidsa; Torres, Jose V.; Noyd, David; Santiago-Albizu, Xavier E.; García, Brenda Rivera; Tomashek, Kay M.; Bower, William A.; Sharp, Tyler M.

2014-01-01

Co-infection with pathogens that cause acute febrile illness creates a diagnostic challenge as a result of overlapping clinical manifestations. Here, we describe four fatal cases of Leptospira species/dengue virus co-infection in Puerto Rico. Although all patients sought care early, antibiotic administration was delayed for most. Steroids were administered to all patients, in most cases before antibiotics. These cases show the need for clinicians evaluating patients in or recently returned from the tropics with acute febrile illness to consider both dengue and leptospirosis. Furthermore, they illustrate the need for nucleic acid- or antigen-based rapid diagnostic tests to enable timely patient diagnosis and management. In particular, antibiotic therapy should be initiated early for patients with suspected leptospirosis, and steroids should not be administered to patients with suspected dengue. PMID:25092820

A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma[S

PubMed Central

Jiang, Xuntian; Sidhu, Rohini; Porter, Forbes D.; Yanjanin, Nicole M.; Speak, Anneliese O.; te Vruchte, Danielle Taylor; Platt, Frances M.; Fujiwara, Hideji; Scherrer, David E.; Zhang, Jessie; Dietzen, Dennis J.; Schaffer, Jean E.; Ory, Daniel S.

2011-01-01

Niemann-Pick type C1 (NPC1) disease is a rare, progressively fatal neurodegenerative disease for which there are no FDA-approved therapies. A major barrier to developing new therapies for this disorder has been the lack of a sensitive and noninvasive diagnostic test. Recently, we demonstrated that two cholesterol oxidation products, specifically cholestane-3β,5α,6β-triol (3β,5α,6β-triol) and 7-ketocholesterol (7-KC), were markedly increased in the plasma of human NPC1 subjects, suggesting a role for these oxysterols in diagnosis of NPC1 disease and evaluation of therapeutics in clinical trials. In the present study, we describe the development of a sensitive and specific LC-MS/MS method for quantifying 3β,5α,6β-triol and 7-KC human plasma after derivatization with N,N-dimethylglycine. We show that dimethylglycine derivatization successfully enhanced the ionization and fragmentation of 3β,5α,6β-triol and 7-KC for mass spectrometric detection of the oxysterol species in human plasma. The oxysterol dimethylglycinates were resolved with high sensitivity and selectivity, and enabled accurate quantification of 3β,5α,6β-triol and 7-KC concentrations in human plasma. The LC-MS/MS assay was able to discriminate with high sensitivity and specificity between control and NPC1 subjects, and offers for the first time a noninvasive, rapid, and highly sensitive method for diagnosis of NPC1 disease. PMID:21518695

Development of Technologies for Early Detection and Stratification of Breast Cancer

DTIC Science & Technology

2015-10-01

fatal disease progression, or in the cases of over-treatment, unnecessary physical and emotional trauma.4 ELISA, the most common immunoassay for...laboratory to discover new biomarkers that meet these requirements within serum so that a simple blood test can be implemented. We are also working to...microspheres and tested first on standard samples. Assay performance characteristics will be determined to ascertain that they will address

Pharmacological intervention for dengue virus infection.

PubMed

Lai, Jenn-Haung; Lin, Yi-Ling; Hsieh, Shie-Liang

2017-04-01

Dengue virus (DENV) infection has a considerable health impact in tropical and subtropical countries worldwide. Escalation of infection rates greatly increases morbidity and mortality, most commonly from deaths due to dengue hemorrhagic fever and dengue shock syndrome. Although the development of an effective, long-lasting vaccine has been a major aim for control and prevention of DENV infection, the currently licensed vaccine has limitations and is less than satisfactory. Thus, there remains an important need to identify effective and tolerable medications for treatment of DENV-infected patients both in the early phase, to prevent progression to fatal outcomes, and to minimize deaths after patients develop severe complications. This review will address several specific points, including (1) approaches to identify anti-DENV medications, (2) recent advances in the development of potential compounds targeting DENV infection, (3) experience with clinical trials of regimens for DENV infection, (4) some available medications of potential for clinical trials against DENV infection, (5) reasons for unsuccessful outcomes and challenges of anti-DENV treatments, and (6) directions for developing or selecting better anti-DENV strategies. This review provides useful guidance for clinicians selecting drugs for DENV-infected patients with severe manifestations or potential fatal disease progression, and for basic researchers seeking to develop effective anti-DENV regimens. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterisation of rapid progressors to type 1 diabetes among children with HLA-conferred disease susceptibility.

PubMed

Pöllänen, Petra M; Lempainen, Johanna; Laine, Antti-Pekka; Toppari, Jorma; Veijola, Riitta; Vähäsalo, Paula; Ilonen, Jorma; Siljander, Heli; Knip, Mikael

2017-07-01

In this study, we aimed to characterise rapid progressors to type 1 diabetes among children recruited from the general population, on the basis of HLA-conferred disease susceptibility. We monitored 7410 HLA-predisposed children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study for the development of beta cell autoimmunity and type 1 diabetes from birth over a median follow-up time of 16.2 years (range 0.9-21.1 years). Islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD (GADA) and islet antigen 2 (IA-2A) were assessed as markers of beta cell autoimmunity. Rapid progression was defined as progression to clinical type 1 diabetes within 1.5 years of autoantibody seroconversion. We analysed the association between rapid progression and demographic and autoantibody characteristics as well as genetic markers, including 25 non-HLA SNPs predisposing to type 1 diabetes. Altogether, 1550 children (21%) tested positive for at least one diabetes-associated autoantibody in at least two samples, and 248 (16%) of seroconverters progressed to type 1 diabetes by the end of 2015. The median time from seroconversion to diagnosis was 0.51 years in rapid progressors (n = 42, 17%) and 5.4 years in slower progressors. Rapid progression was observed both among young (<5 years) and early pubertal children (>7 years), resulting in a double-peak distribution of seroconversion age. Compared with slower progressors, rapid progressors had a higher frequency of positivity for multiple (≥2) autoantibodies and had higher titres of ICA, IAA and IA-2A at seroconversion, and there was a higher prevalence of the secretor genotype in the FUT2 gene among those carrying the high-risk HLA genotype. Compared with autoantibody-positive non-progressors, rapid progressors were younger, were more likely to carry the high-risk HLA genotype and a predisposing SNP in the PTPN22 gene, had higher frequency of ICA, IAA, GADA and IA-2A positivity and multipositivity, and had higher titres of all four autoantibodies at seroconversion. At seroconversion, individuals with rapid progression to type 1 diabetes were characterised by a younger age, higher autoantibody titres, positivity for multiple autoantibodies and higher prevalence of a FUT2 SNP. The double-peak profile for seroconversion age among the rapid progressors demonstrates for the first time that rapid progression may take place not only in young children but also in children in early puberty. Rapid progressors might benefit from careful clinical follow-up and early preventive measures.

Melioidosis: evolving concepts in epidemiology, pathogenesis, and treatment.

PubMed

Currie, Bart J

2015-02-01

Infection with Burkholderia pseudomallei can result in asymptomatic seroconversion, a single skin lesion that may or may not heal spontaneously, a pneumonia which can be subacute or chronic and mimic tuberculosis or rapidly progressive resulting in fatal overwhelming sepsis. Latency with subsequent activation of disease is well recognized, but very uncommon. Melioidosis also has a myriad of other clinical presentations and diagnosis is often delayed because of this and because of difficulties with laboratory diagnosis and lack of recognition outside melioidosis-endemic regions. The perception of B. pseudomallei as a top tier biothreat agent has driven large funding for research, yet resources for diagnosis and therapy of melioidosis in many endemic locations remain extremely limited, with mortality as high as 50% in comparison to around 10% in regions where state-of-the-art intensive care therapy for sepsis is available. Fatal melioidosis is extremely unlikely from natural infection in a healthy person, provided the diagnosis is made early, ceftazidime or meropenem is commenced and intensive care therapy is available. While biothreat research is directed toward potential aerosol exposure to B. pseudomallei, the overall proportion of melioidosis cases resulting from inhalation rather than from percutaneous inoculation remains entirely uncertain, although the epidemiology supports a shift to inhalation during severe weather events such as cyclones and typhoons. What makes B. pseudomallei such a dangerous organism for patients with diabetes and other selective risk factors remains unclear, but microbial genome-wide association studies linking clinical aspects of melioidosis cases to nonubiquitous or polymorphic B. pseudomallei genes or genomic islands are beginning to uncover specific virulence signatures. Finally, what also remains uncertain is the global phylogeography of B. pseudomallei and whether melioidosis is spreading beyond historical locations or is just being unmasked in Africa and the Americas by better recognition and increased surveillance. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Leadership, infrastructure and capacity to support child injury prevention: can these concepts help explain differences in injury mortality rankings between 18 countries in Europe?

PubMed

MacKay, J Morag; Vincenten, Joanne A

2012-02-01

Mortality and morbidity rates, traditionally used indicators for child injury, are limited in their ability to explain differences in child injury between countries, are inadequate in capturing actions to address the problem of child injury and do not adequately identify progress made within countries. There is a need for a broader set of indicators to help better understand the success of countries with low rates of child injury, provide guidance and benchmarks for policy makers looking to make investments to reduce their rates of fatal and non-fatal child injury and allow monitoring of progress towards achieving these goals. This article describes an assessment of national leadership, infrastructure and capacity in the context of child injury prevention in 18 countries in Europe and explores the potential of these to be used as additional indicators to support child injury prevention practice. Partners in 18 countries coordinated data collection on 21 items relating to leadership, infrastructure and capacity. Responses were coded into an overall score and scores for each of the three areas and were compared with child injury mortality rankings using Spearman's rank correlation. Overall score and scores for leadership and capacity were significantly negatively correlated to child injury mortality ranking. Findings of this preliminary work suggest that these three policy areas may provide important guidance for the types of commitments that are needed in the policy arena to support advances in child safety and their assessment a way to measure progress.

Symptomatic Cushing's syndrome and hyperandrogenemia in a steroid cell ovarian neoplasm: a case report.

PubMed

Sedhom, Ramy; Hu, Sophia; Ohri, Anupam; Infantino, Dorian; Lubitz, Sara

2016-10-12

Malignant steroid cell tumors of the ovary are rare and frequently associated with hormonal abnormalities. There are no guidelines on how to treat rapidly progressive Cushing's syndrome, a medical emergency. A 67-year-old white woman presented to our hospital with rapidly developing signs and symptoms of Cushing's syndrome secondary to a steroid-secreting tumor. Her physical and biochemical manifestations of Cushing's syndrome progressed, and she was not amenable to undergoing conventional chemotherapy secondary to the debilitating effects of high cortisol. Her rapidly progressive Cushing's syndrome ultimately led to her death, despite aggressive medical management with spironolactone, ketoconazole, mitotane, and mifepristone. We report an unusual and rare case of Cushing's syndrome secondary to a malignant steroid cell tumor of the ovary. The case is highlighted to discuss the complications of rapidly progressive Cushing's syndrome, an underreported and often unrecognized endocrine emergency, and the best available evidence for treatment.

The Vulnerability of People to Damaging Hydrogeological Events in the Calabria Region (Southern Italy)

PubMed Central

Salvati, Paola; Aceto, Luigi; Bianchi, Cinzia; Pasqua, Angela Aurora; Guzzetti, Fausto

2017-01-01

Background: Damaging Hydrogeological Events (DHEs) are severe weather periods during which floods, landslides, lightning, windstorms, hail or storm surges can harm people. Climate change is expected to increase the frequency/intensity of DHEs and, consequently, the potential harm to people. Method: We investigated the impacts of DHEs on people in Calabria (Italy) over 37 years (1980–2016). Data on 7288 people physically affected by DHEs were gathered from the systematic analysis of regional newspapers and collected in the database named PEOPLE. The damage was codified in three severity levels as follows: fatalities (people who were killed), injured (people who suffered physical harm) and involved (people who were present at the place where an accident occurred but survived and were not harmed). During the study period, we recorded 68 fatalities, 566 injured and 6654 people involved in the events. Results: Males were more frequently killed, injured and involved than females, and females who suffered fatalities were older than males who suffered fatalities, perhaps indicating that younger females tended to be more cautious than same-aged males, while older females showed an intrinsic greater vulnerability. Involved people were younger than injured people and fatalities, suggesting that younger people show greater promptness in reacting to dangerous situations. Floods caused the majority of the fatalities, injured and involved people, followed by landslides. Lightning was the most dangerous phenomenon, and it affected a relatively low number of people, killing 11.63% of them and causing injuries to 37.2%. Fatalities and injuries mainly occurred outdoors, largely along roads. In contrast, people indoors, essentially in public or private buildings, were more frequently involved without suffering harm. Being “dragged by water/mud” and “surrounded by water/mud”, respectively, represented the two extremes of dynamic dangerousness. The dragging effect of rapid-flowing water totally or partially obstructed the attempts of people to save their lives. In contrast, people surrounded by steady water/mud encountered difficulties but ultimately could survive. Conclusions: The study outcomes can be used in informational campaigns to increase risk awareness among both administrators and citizens and to improve community resilience, particularly in promoting self-protective behaviors and avoiding the underestimation of hazardous situations. PMID:29286338

Ifosfamide-induced Fanconi syndrome with diabetes insipidus.

PubMed

Leem, Ah Young; Kim, Han Sang; Yoo, Byung Woo; Kang, Beo Deul; Kim, Min Hwan; Rha, Sun Young; Kim, Hyo Song

2014-03-01

Ifosfamide-induced Fanconi syndrome is a rare complication that typically occurs in young patients due to a cumulative dose of ifosfamide > 40-60 g/m(2), a reduction in kidney mass, or concurrent cisplatin treatment. It is usually characterized by severe and fatal progression accompanied by type II proximal renal tubular dysfunction, as evidenced by glycosuria, proteinuria, electrolyte loss, and metabolic acidosis. Diabetes insipidus is also a rare complication of ifosfamide-induced renal disease. We herein describe a case involving a 61-year-old man who developed ifosfamide-induced Fanconi syndrome accompanied by diabetes insipidus only a few days after the first round of chemotherapy. He had no known risk factors. In addition, we briefly review the mechanisms and possible therapeutic options for this condition based on other cases in the literature. Patients who receive ifosfamide must be closely monitored for renal impairment to avoid this rare but fatal complication.

Ifosfamide-induced Fanconi syndrome with diabetes insipidus

PubMed Central

Leem, Ah Young; Kim, Han Sang; Yoo, Byung Woo; Kang, Beo Deul; Kim, Min Hwan; Rha, Sun Young

2014-01-01

Ifosfamide-induced Fanconi syndrome is a rare complication that typically occurs in young patients due to a cumulative dose of ifosfamide > 40-60 g/m2, a reduction in kidney mass, or concurrent cisplatin treatment. It is usually characterized by severe and fatal progression accompanied by type II proximal renal tubular dysfunction, as evidenced by glycosuria, proteinuria, electrolyte loss, and metabolic acidosis. Diabetes insipidus is also a rare complication of ifosfamide-induced renal disease. We herein describe a case involving a 61-year-old man who developed ifosfamide-induced Fanconi syndrome accompanied by diabetes insipidus only a few days after the first round of chemotherapy. He had no known risk factors. In addition, we briefly review the mechanisms and possible therapeutic options for this condition based on other cases in the literature. Patients who receive ifosfamide must be closely monitored for renal impairment to avoid this rare but fatal complication. PMID:24648810

Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques.

PubMed

Sugimoto, Chie; Merino, Kristen M; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A; Wakao, Hiroshi; Mori, Kazuyasu; Kim, Woong-Ki; Veazey, Ronald S; Didier, Elizabeth S; Kuroda, Marcelo J

2017-09-01

Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4 + T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU + ] CD163 + ), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants. IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model, this work was performed to address why infants infected with SIV progress more quickly to AIDS than do adults. Earlier we reported that in adult rhesus macaques, increasing monocyte turnover reflected tissue macrophage damage by SIV and was predictive of terminal disease progression to AIDS. Here we report that uninfected infant rhesus macaques exhibited a higher physiological baseline monocyte turnover rate than adults. Furthermore, once infected with SIV, infants displayed further increased monocyte turnover that may have facilitated the accelerated progression to AIDS. These results support a role for monocytes and macrophages in the pathogenesis of SIV/HIV and begin to explain why infants are more prone to rapid disease progression. Copyright © 2017 American Society for Microbiology.

Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques

PubMed Central

Sugimoto, Chie; Merino, Kristen M.; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A.; Wakao, Hiroshi; Kim, Woong-Ki; Veazey, Ronald S.; Didier, Elizabeth S.

2017-01-01

ABSTRACT Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4+ T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU+] CD163+), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants. IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model, this work was performed to address why infants infected with SIV progress more quickly to AIDS than do adults. Earlier we reported that in adult rhesus macaques, increasing monocyte turnover reflected tissue macrophage damage by SIV and was predictive of terminal disease progression to AIDS. Here we report that uninfected infant rhesus macaques exhibited a higher physiological baseline monocyte turnover rate than adults. Furthermore, once infected with SIV, infants displayed further increased monocyte turnover that may have facilitated the accelerated progression to AIDS. These results support a role for monocytes and macrophages in the pathogenesis of SIV/HIV and begin to explain why infants are more prone to rapid disease progression. PMID:28566378

Isolation and molecular typing of Naegleria fowleri from the brain of a cow that died of primary amebic meningoencephalitis.

PubMed

Visvesvara, Govinda S; De Jonckheere, Johan F; Sriram, Rama; Daft, Barbara

2005-08-01

Naegleria fowleri causes an acute and rapidly fatal central nervous system infection called primary amebic meningoencephalitis (PAM) in healthy children and young adults. We describe here the identification of N. fowleri isolated from the brain of one of several cows that died of PAM based on sequencing of the internal transcribed spacers, including the 5.8S rRNA genes.

Hypercaloric enteral nutrition in Amyotrophic Lateral Sclerosis: a randomized double-blind placebo-controlled trial

PubMed Central

Wills, Anne-Marie; Hubbard, Jane; Macklin, Eric A.; Glass, Jonathan; Tandan, Rup; Simpson, Ericka P; Brooks, Benjamin; Gelinas, Deborah; Mitsumoto, Hiroshi; Mozaffar, Tahseen; Hanes, Gregory P.; Ladha, Shafeeq S.; Heiman-Patterson, Terry; Katz, Jonathan; Lou, Jau-Shin; Mahoney, Katy; Grasso, Daniela; Lawson, Robert; Yu, Hong; Cudkowicz, Merit

2014-01-01

Background Amyotrophic Lateral Sclerosis (ALS) is a rapidly fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in ALS patients and calorie-dense diets increase survival in an ALS mouse model. We therefore hypothesized that hypercaloric diets might lead to weight gain and slow ALS disease progression. Methods In this double-blind, placebo-controlled, multi-center clinical trial, we enrolled adults with ALS without a history of diabetes, significant liver or cardiovascular disease, who were already receiving percutaneous enteral nutrition. We randomly assigned participants to one of three dietary interventions: replacement calories using an isocaloric diet (controls) vs. a high-carbohydrate hypercaloric diet (HC/HC), vs. a high-fat hypercaloric diet (HF/HC). Participants received the intervention diets for four months and were followed for five months. The primary outcomes were safety and tolerability. Secondary outcomes included measures of disease progression, survival, and metabolism. This trial is registered with Clinicaltrials.gov, number NCT00983983. Findings A total of 24 participants were enrolled of whom 20 initiated study diet (six control, eight HC/HC, six HF/HC). Baseline demographics were similar among the three study arms. The HC/HC diet was better tolerated with fewer serious adverse events than the control diet (zero vs. nine, p<0·001) and fewer dose discontinuations due to adverse events (0% vs. 50%). There were no deaths in the HC/HC arm vs. three deaths (43%) in the control arm (logrank p = 0·03). The HF/HC arm was not statistically different from the controls in adverse events, tolerability, deaths or disease progression. Interpretation Our results suggest that hypercaloric enteral nutrition is safe and tolerable in ALS and support the study of nutritional interventions at earlier stages of the disease. Funding The Muscular Dystrophy Association with additional support from the National Center for Research Resources, the National Institutes of Health, and the Harvard NeuroDiscovery Center. PMID:24582471

GM2 Gangliosidosis Variant 0 (Sandhoff Disease) in a Mixed-Breed Dog.

PubMed

Kohyama, Moeko; Yabuki, Akira; Kawasaki, Yasuaki; Kawaguchi, Hiroaki; Miura, Naoki; Kitano, Yoshiaki; Onitsuka, Toshinori; Rahman, Mohammad Mahbubur; Miyoshi, Noriaki; Yamato, Osamu

2015-01-01

GM2 gangliosidosis variant 0 (Sandhoff disease, SD) is a fatal, progressive, neurodegenerative lysosomal storage disease caused by simultaneous deficiencies of acid β-hexosaminidases A and B. Canine SD has so far been identified only in two purebreeds. In this article, we present the case of a 10 mo old, male dog of mixed breed that developed progressive neurological signs including ataxia, postural deficit, and visual deficits and finally died at the age of 21 mo. The dog was diagnosed with SD on the basis of the results of biochemical and histopathological analyses. This is the third report of canine SD and the first time it has been identified in a mixed breed.

Influenza-associated intensive-care unit admissions and deaths - California, September 29, 2013-January 18, 2014.

PubMed

Ayscue, Patrick; Murray, Erin; Uyeki, Timothy; Zipprich, Jennifer; Harriman, Kathleen; Salibay, Catheryn; Kang, Monica; Luu, Annie; Glenn-Finer, Rose; Watt, James; Glaser, Carol; Louie, Janice

2014-02-21

The California Department of Public Health (CDPH) conducts surveillance on severe influenza illness among California residents aged <65 years. Severe cases are defined as those resulting in admission to an intensive care unit (ICU) or death; reporting of ICU cases is voluntary, and reporting of fatal cases is mandatory. This report describes the epidemiologic, laboratory, and clinical characteristics of ICU and fatal influenza cases with symptom onset on or after September 29, 2013, and reported by January 18, 2014 of the 2013-14 influenza season. At the time of this report, local health jurisdictions (LHJs) in California had reported 94 deaths and 311 ICU admissions of patients with a positive influenza test result. The 405 reports of severe cases (i.e., fatal and ICU cases combined) were more than in any season since the 2009 pandemic caused by the influenza A (H1N1)pdm09 (pH1N1) virus. The pH1N1 virus is the predominant circulating influenza virus this season. Of 405 ICU and fatal influenza cases, 266 (66%) occurred among patients aged 41-64 years; 39 (10%) severe influenza illnesses occurred among children aged <18 years. Only six (21%) of 28 patients with fatal illness whose vaccination status was known had received 2013-14 seasonal influenza vaccine ≥2 weeks before symptom onset. Of 80 patients who died for whom sufficient information was available, 74 (93%) had underlying medical conditions known to increase the risk for severe influenza, as defined by the Advisory Committee on Immunization Practices (ACIP). Of 47 hospitalized patients with fatal illness and known symptom onset and antiviral therapy dates, only eight (17%) received neuraminidase inhibitors within 48 hours of symptom onset. This report supports previous recommendations that vaccination is important to prevent influenza virus infections that can result in ICU admission or death, particularly in high-risk populations, and that empiric antiviral treatment should be promptly initiated when influenza virus infection is suspected in hospitalized patients, despite negative results from rapid diagnostic tests.

Deaths from pesticide poisoning in England and Wales: 1945-1989.

PubMed

Casey, P; Vale, J A

1994-02-01

1. Data on deaths from pesticide poisoning occurring in England and Wales between 1945 and 1989 (no data are available for 1954) have been collated; pesticides were responsible for only 1012 (1.1%) of the 87,385 deaths from poisoning (excluding those due to carbon monoxide) occurring over this 44 year period. At least 73% of all pesticide fatalities were due to suicide and overall there was a predominance of males (male:female ratio 2.4:1). No deaths from pesticide poisoning in children under 10 years have been reported since 1974 although almost 50% of suspected pesticide poisoning incidents involve this age group. 2. Herbicides were responsible for 787 (78%) fatal poisonings, 110 (11%) were caused by insecticides, 69 (6.8%) by rodenticides, 30 (3.0%) by wood preservatives and 16 (1.6%) by other pesticides. 3. The herbicide, paraquat, was responsible for 570 of 1012 (56%) deaths and, although there has been a progressive decline in the annual number of deaths from paraquat poisoning since 1982, paraquat remains the most common cause of fatal pesticide poisoning in England and Wales. 4. Sodium chlorate caused 113 (11.2%) deaths, most of these fatalities occurring between 1965 and 1983; only one death has been recorded since 1984. The phenoxyacetate herbicides resulted in 50 deaths; 2,4-D was implicated most commonly. Sixty-eight deaths were due to organophosphorus insecticides; demeton-S-methyl, malathion and mevinphos were involved most frequently. Only eight deaths resulted from organochlorine insecticides and two of these also involved an organophosphorus insecticide.(ABSTRACT TRUNCATED AT 250 WORDS)

Causes of bat fatalities at wind turbines: Hypotheses and predictions

USGS Publications Warehouse

Cryan, P.M.; Barclay, R.M.R.

2009-01-01

Thousands of industrial-scale wind turbines are being built across the world each year to meet the growing demand for sustainable energy. Bats of certain species are dying at wind turbines in unprecedented numbers. Species of bats consistently affected by turbines tend to be those that rely on trees as roosts and most migrate long distances. Although considerable progress has been made in recent years toward better understanding the problem, the causes of bat fatalities at turbines remain unclear. In this synthesis, we review hypothesized causes of bat fatalities at turbines. Hypotheses of cause fall into 2 general categoriesproximate and ultimate. Proximate causes explain the direct means by which bats die at turbines and include collision with towers and rotating blades, and barotrauma. Ultimate causes explain why bats come close to turbines and include 3 general types: random collisions, coincidental collisions, and collisions that result from attraction of bats to turbines. The random collision hypothesis posits that interactions between bats and turbines are random events and that fatalities are representative of the bats present at a site. Coincidental hypotheses posit that certain aspects of bat distribution or behavior put them at risk of collision and include aggregation during migration and seasonal increases in flight activity associated with feeding or mating. A surprising number of attraction hypotheses suggest that bats might be attracted to turbines out of curiosity, misperception, or as potential feeding, roosting, flocking, and mating opportunities. Identifying, prioritizing, and testing hypothesized causes of bat collisions with wind turbines are vital steps toward developing practical solutions to the problem. ?? 2009 American Society of Mammalogists.

A new methodology for estimating nuclear casualties as a function of time.

PubMed

Zirkle, Robert A; Walsh, Terri J; Disraelly, Deena S; Curling, Carl A

2011-09-01

The Human Response Injury Profile (HRIP) nuclear methodology provides an estimate of casualties occurring as a consequence of nuclear attacks against military targets for planning purposes. The approach develops user-defined, time-based casualty and fatality estimates based on progressions of underlying symptoms and their severity changes over time. This paper provides a description of the HRIP nuclear methodology and its development, including inputs, human response and the casualty estimation process.

Fatal pneumonia and empyema thoracis caused by imipenem-resistant Nocardia abscessus in a cancer patient.

PubMed

Lai, Chih-Cheng; Tsai, Hsih-Yeh; Ruan, Sheng-Yuan; Liao, Chun-Hsing; Hsueh, Po-Ren

2015-12-01

We describe a case of pneumonia and empyema thoracis caused by trimethoprim-sulfamethoxazole-susceptible, but imipenem-resistant Nocardia abscessus in a cancer patient. The isolate was confirmed to the species level by 16S rRNA sequencing analysis. The patient did not respond to antibiotic therapy, including ceftriaxone and imipenem, and died of progressing pneumonia and multiple organ failure. Copyright © 2013. Published by Elsevier B.V.

Fatal Balamuthia mandrillaris infection in a gorilla - first case of balamuthiasis in Germany.

PubMed

Mätz-Rensing, Kerstin; Kunze, Marius; Zöller, Martina; Roos, Christian; Kiderlen, Albrecht F; Ludwig, Carsten; Kaup, Franz-Josef

2011-12-01

A 12-year-old female western lowland gorilla died in a zoological garden in Germany after exhibiting general neurological signs. Balamuthia mandrillaris was identified as causative agent by indirect immunofluorescent staining of brain sections and confirmed by PCR and respective sequencing. The animal suffered from a chronic progressive necrotizing amebic meningoencephalitis. This is the first case of Balamuthia amebic encephalitis in Germany. © 2011 John Wiley & Sons A/S.

[Fatal outcome of an hydrogen sulfide poisoning].

PubMed

Querellou, E; Jaffrelot, M; Savary, D; Savry, C; Perfus, J-P

2005-10-01

We report a case of fatal outcome poisoning by massive exposure to hydrogen sulfide of a sewer worker. This rare event was associated with a moderate intoxication of two members of the rescue team. The death was due to asystole and massive lung oedema. Autopsy analysis showed diffuse necrotic lesions in lungs. Hydrogen sulfide is a direct and systemic poison, produced by organic matter decomposition. The direct toxicity mechanism is still unclear. The systemic toxicity is due to an acute toxicity by oxygen depletion at cellular level. It is highly diffusable and potentially very dangerous. At low concentration, rotten egg smell must trigger hydrogen sulfide suspicion since at higher concentration it is undetectable, making intoxication possible. In case of acute intoxication, there is an almost instantaneous cardiovascular failure and a rapid death. Hydrogen sulfide exposure requires prevention measures and more specifically the use of respiratory equipment for members of the rescue team.

Engineers Attack the "No. One Killer" in Coal Mining: The Bureau of Mines and the Promotion of Roof Bolting, 1947-1969.

PubMed

Aldrich, Mark

In 1948 roof falls were the number one killer of coal miners in America. While the Bureau of Mines had been formed in 1910 to improve coalmine safety, it had largely focused on explosions, for which technological solutions appeared to exist. Roof falls, by contrast, were not amenable to a technical fix. Beginning in 1948, however, the Bureau discovered roof bolting, which it promoted as a safer technology that might yield dramatic benefits. The new approach spread rapidly, yet fatality rates from roof falls failed to decline for nearly two decades. This lag reflected the need for organizational learning, while companies also traded safety for productivity. Finally, only larger mines employed bolting and its impact was masked by a growth in the employment share of small companies. After 1965, as the expansion of small mines ended and organizational learning continued, fatality rates began a long decline.

Hemolysis in a patient with alkaptonuria and chronic kidney failure.

PubMed

Heng, Anne-Elisabeth; Courbebaisse, Marie; Kemeny, Jean Louis; Matesan, Raluca; Bonniol, Claude; Deteix, Patrice; Souweine, Bertrand

2010-07-01

In alkaptonuria, the absence of homogentisic acid oxidase results in the accumulation of homogentisic acid (HGA) in the body. Fatal disease cases are infrequent, and death often results from kidney or cardiac complications. We report a 24-year-old alkaptonuric man with severe decreased kidney function who developed fatal metabolic acidosis and intravascular hemolysis. Hemolysis may have been caused by rapid and extensive accumulation of HGA and subsequent accumulation of plasma soluble melanins. Toxic effects of plasma soluble melanins, their intermediates, and reactive oxygen side products are increased when antioxidant mechanisms are overwhelmed. A decrease in serum antioxidative activity has been reported in patients with chronic decreased kidney function. However, despite administration of large doses of an antioxidant agent and ascorbic acid and intensive kidney support, hemolysis and acidosis could not be brought under control and hemolysis led to the death of the patient.

Seven cases of fatal aconite poisoning: forensic experience in China.

PubMed

Liu, Qian; Zhuo, Luo; Liu, Liang; Zhu, Shaohua; Sunnassee, Ananda; Liang, Man; Zhou, Lan; Liu, Yan

2011-10-10

This paper presents seven fatal cases of aconite poisoning encountered in the Tongji Center for Medicolegal Expertise in Hubei (TCMEH), China, from 1999 to 2008 retrospectively. In six of the cases, deaths occurred after drinking homemade medicated liquor containing aconite, and in one case death was due to ingestion of traditional Chinese medication containing aconite. Forensic autopsy and pathological examinations ruled out the presence of physical trauma or life-threatening diseases. Diagnosis of aconite poisoning was made after postmortem toxicological analysis. Animal experiment was performed in one case demonstrating that the medicated liquor could cause death rapidly. We present the autopsy and histopathological findings, toxicological analysis, and results of animal experiment done on samples from those seven cases. As an important herbal Chinese medicine, Aconitum species deserve special attention, especially because it contains poisonous alkaloids. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

High-altitude cerebral oedema mimicking stroke.

PubMed

Yanamandra, Uday; Gupta, Amul; Patyal, Sagarika; Varma, Prem Prakash

2014-03-26

High-altitude cerebral oedema (HACO) is the most fatal high-altitude illness seen by rural physicians practising in high-altitude areas. HACO presents clinically with cerebellar ataxia, features of raised intracranial pressure (ICP) and coma. Early identification is important as delay in diagnosis can be fatal. We present two cases of HACO presenting with focal deficits mimicking stroke. The first patient presented with left-sided hemiplegia associated with the rapid deterioration in the sensorium. Neuroimaging revealed features suggestive of vasogenic oedema. The second patient presented with monoplegia of the lower limb. Neuroimaging revealed perfusion deficit in anterior cerebral artery territory. Both patients were managed with dexamethasone and they improved dramatically. Clinical picture and neuroimaging closely resembled acute ischaemic stroke in both cases. Thrombolysis in these patients would have been disastrous. Recent travel to high altitude, young age, absence of atherosclerotic risk factors and features of raised ICP concomitantly directed the diagnosis to HACO.

Subacute sclerosing panencephalitis presenting as rapidly progressive young-onset dementia.

PubMed

Chakor, Rahul Tryambak; Santosh, Nandanavana Subbareddy

2013-07-01

Onset of dementia before 65 years of age is termed as young-onset dementia (YOD). Very little literature exists regarding the clinical features and diagnoses of dementia in younger individuals. We present a case series of four patients of age 10 to 23 years with severe dementia within 18 months of clinical onset (rapidly progressive dementia). Three patients had generalised periodic complexes typical of subacute sclerosing panencephalitis (SSPE) on electroencephalogram (EEG). All patients had elevated cerebrospinal fluid (CSF) IgG measles antibodies. Our case series highlights that SSPE is an important cause of rapidly progressive YOD in developing countries like India.

TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia.

PubMed

Wegert, Jenny; Vokuhl, Christian; Ziegler, Barbara; Ernestus, Karen; Leuschner, Ivo; Furtwängler, Rhoikos; Graf, Norbert; Gessler, Manfred

2017-10-01

TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We identified TP53 alterations in at least 90% of fatal cases of anaplastic Wilms tumour, and even more when diffuse anaplasia was present, indicating a very strong if not absolute coupling between anaplasia and deregulation of p53 function. Unfortunately, TP53 mutations do not provide additional predictive value in anaplastic tumours since the same mutation rate was found in a cohort of non-fatal anaplastic tumours. When classified according to tumour stage, patients with stage I diffuse anaplastic tumours still had a high chance of survival (87%), but this rate dropped to 26% for stages II-IV. Thus, volume of anaplasia or possible spread may turn out to be critical parameters. Importantly, among non-anaplastic fatal tumours, 26% had TP53 alterations, indicating that TP53 screening may identify additional cases at risk. Several of these non-anaplastic tumours fulfilled some criteria for anaplasia, for example nuclear unrest, suggesting that such partial phenotypes should be under special scrutiny to enhance detection of high-risk tumours via TP53 screening. A major drawback is that these alterations are secondary changes that occur only later in tumour development, leading to striking intratumour heterogeneity that requires multiple biopsies and analysis guided by histological criteria. In conclusion, we found a very close correlation between histological signs of anaplasia and TP53 alterations. The latter may precede development of anaplasia and thereby provide diagnostic value pointing towards aggressive disease.

TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia

PubMed Central

Wegert, Jenny; Vokuhl, Christian; Ziegler, Barbara; Ernestus, Karen; Leuschner, Ivo; Furtwängler, Rhoikos; Graf, Norbert

2017-01-01

Abstract TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We identified TP53 alterations in at least 90% of fatal cases of anaplastic Wilms tumour, and even more when diffuse anaplasia was present, indicating a very strong if not absolute coupling between anaplasia and deregulation of p53 function. Unfortunately, TP53 mutations do not provide additional predictive value in anaplastic tumours since the same mutation rate was found in a cohort of non‐fatal anaplastic tumours. When classified according to tumour stage, patients with stage I diffuse anaplastic tumours still had a high chance of survival (87%), but this rate dropped to 26% for stages II–IV. Thus, volume of anaplasia or possible spread may turn out to be critical parameters. Importantly, among non‐anaplastic fatal tumours, 26% had TP53 alterations, indicating that TP53 screening may identify additional cases at risk. Several of these non‐anaplastic tumours fulfilled some criteria for anaplasia, for example nuclear unrest, suggesting that such partial phenotypes should be under special scrutiny to enhance detection of high‐risk tumours via TP53 screening. A major drawback is that these alterations are secondary changes that occur only later in tumour development, leading to striking intratumour heterogeneity that requires multiple biopsies and analysis guided by histological criteria. In conclusion, we found a very close correlation between histological signs of anaplasia and TP53 alterations. The latter may precede development of anaplasia and thereby provide diagnostic value pointing towards aggressive disease. PMID:29085664

Contributing factors of crash injury severity at public highway-railroad grade crossings in the U.S.

PubMed

Haleem, Kirolos; Gan, Albert

2015-06-01

The Moving Ahead for Progress in the 21st Century (MAP-21) includes a separate program that supports safety improvements to reduce the number of fatalities and injuries at public highway-railroad grade crossings (HRGCs). This study identifies the significant factors affecting crash injury severity at public HRGCs in the United States. Crashes from 2009 through 2013 on 5,528 public HRGCs, extracted from the Federal Railroad Administration database, were used in the analysis. A comprehensive list of risk factors was explored. Examples include predictors related to geographic region of crash, geometry (e.g., area type and pavement marking type), railroad (e.g., warning device type and railroad class), traffic (e.g., train speed and vehicles annual average daily traffic "AADT"), highway user (e.g., driver age and gender), and environment (e.g., lighting and weather conditions). The study used the mixed logit model to better capture the complex highway user behavior at HRGCs. Female highway users were at higher risk of involvement in injuries and fatalities compared to males. Higher train speeds, very old drivers, open areas, concrete road surface types, and railroad equipment striking highway users before crash, were all found to increase the injury likelihood. On the other hand, young and middle-age drivers, non-passing of standing vehicles at HRGCs, industrial areas, and presence of warning bells were found to reduce injuries and fatalities. The mixed logit model succeeded in identifying contributing factors of crash severity at public HRGCs and potential countermeasures to reduce both fatalities and injuries are suggested. It is important to install warning bells at public HRGCs, especially at those with high number of injury and fatality crashes. Enforcement of traffic nearby HRGCs is necessary to prevent vehicles from overtaking of standing vehicles. Copyright © 2015 Elsevier Ltd. and National Safety Council. Published by Elsevier Ltd. All rights reserved.

[Experimental research on individual-specific rapid potassium supplementation strategy for fatal severe hypokalemia].

PubMed

Du, Yu; Mou, Yi; Liu, Jin

2018-05-01

To explore the effectiveness and safety of the individual-specific rapid potassium supplementation strategy, and to provide experimental basis for treating fatal severe hypokalemia. An acute fatal severe hypokalemia model was reproduced in 20 healthy adult Japanese big ear white rabbits with half lethal dose (LD50) of barium chloride (BaCl 2 ) solution 168 mg×5 mL -1 ×kg -1 . The rabbits were divided into conventional potassium supplementation group and individual-specific rapid potassium supplementation group according to random number table method with 10 rabbits in each group. All the animals were injected with 3% KCl through the auricular marginal veins by a micro-injection pump, and the target plasma potassium concentration was 4 mmol/L. The rabbits in conventional potassium supplementation group were administered continuously potassium infusion at the standard infusion rate of 0.4 mmol×kg -1 ×h -1 . And those in the individual-specific rapid potassium supplementation group were treated in two steps: first, a loading dose of potassium was rapidly injected within 5 minutes, and this step was repeated until the plasma potassium concentration increased to 3.5 mmol/L; second, a sustaining dose of potassium infusion was continued at the rate of 0.4 mmol×kg -1 ×h -1 after the increase in plasma potassium concentration. The changes in electrocardiogram, blood pressure, respiratory rate (RR), plasma potassium concentration, urine potassium concentration, urine volume, potassium content in extracellular fluid (ECF) and other parameters were monitored. The potassium supplementation, potassium excretion and potassium cross cell status were recorded. Adverse reactions and 7-day death were observed. Since the BaCl 2 administration, the plasma potassium concentration of all experimental rabbits were significantly lower than baseline at 0.5 hour, which was decreased below 2.5 mmol/L at 2.0 hours when the ventricular arrhythmias appeared, indicating the reproduction of fatal severe hypokalemia model was successful. There was no significant difference in gender, weight, baseline heart rate (HR), RR, mean arterial pressure (MAP), blood gas analysis or K + , Na + , Cl - levels between the two groups. Compared with baseline levels, MAP was significantly decreased and RR was significantly increased before potassium supplementation in both groups, but the parameters were improved significantly and restored to the baseline after potassium supplementation. There was no significant difference in MAP or RR during potassium supplementation between the two groups. The amount of potassium supplementation in two groups showed no significant differences. However, compared with the conventional potassium supplementation group, in the individual-specific rapid potassium supplementation group, the increase in plasma potassium concentration, urine potassium concentration, and the increase in potassium content in ECF were significantly increased [the increase in plasma potassium concentration (mmol/L): 2.40±0.33 vs. 1.51±0.75, urine potassium concentration (mmol/L): 164.94±18.07 vs. 108.35±19.67, the increase in potassium content in ECF (mmol): 1.17±0.16 vs. 0.73±0.35], the duration of potassium infusion was shortened (hours: 2.1±0.7 vs. 4.7±1.4), the total urine volume, renal excretion of potassium, and the amount of transcellular potassium shift were significantly decreased [total urine volume (mL): 6.40±1.78 vs. 13.60±4.69, renal excretion of potassium (mmol): 1.04±0.26 vs. 1.46±0.51, amount of transcellular potassium shift (mmol): 1.39±0.21 vs. 1.84±0.62], the duration of arrhythmia was shortened (minutes: 19.60±8.92 vs. 71.80±9.84), with statistically significant differences (all P < 0.05). Hyperkalemia did not occur in both groups. The rabbits of the individual-specific rapid potassium supplementation group were all alive, while 4 died in the conventional potassium supplementation group, and statistically significant difference was found between the two groups (P < 0.01). These data demonstrate that the individual-specific rapid potassium supplementation strategy can shorten the time for correcting hypokalemia, which is a better option to reverse life-threatening arrhythmia caused by severe hypokalemia, with a high rescue success rate. The process of potassium supplement is safe and effective.

Subgaleal hemorrhage in the newborn infant associated with silicone elastomer vacuum extractor.

PubMed

Florentino-Pineda, I; Ezhuthachan, S G; Sineni, L G; Kumar, S P

1994-01-01

Subgaleal hemorrhage in the newborn infant has been reported worldwide, but despite the efforts of previous authors, this entity has not received the necessary attention in pediatric literature, and continues to represent a potentially fatal problem. Although the association of subgaleal hemorrhage with the use of the metal cup vacuum extractor has clearly been documented, its association with the silicone elastomer version has not been previously reported. We describe two cases in newborn infants where silicone elastomer cup vacuum extractor was used. The diagnosis of subgaleal hemorrhage must be considered in any infant with a scalp swelling and a falling hematocrit, and coagulation studies should be performed in all infants with a diagnosis of subgaleal hemorrhage. Complications include shock and death if subgaleal hemorrhage is massive and acute, and anemia and hyperbilirubinemia if it is slowly progressive. The familiarity with and ability of care givers to recognize the signs and symptoms of subgaleal hemorrhage are essential in preventing fatalities. A systematic approach to diagnosis with close monitoring of vital signs, hematocrit, blood gases, head circumference, and signs of tissue hypoperfusion is recommended for infants after instrument deliveries. Pathogenesis of this lesion needs to be emphasized in pediatric literature so that early recognition and prompt treatment may avoid a fatal outcome.

Analysis of horse race videos to identify intra-race risk factors for fatal distal limb fracture.

PubMed

Parkin, T D H; Clegg, P D; French, N P; Proudman, C J; Riggs, C M; Singer, E R; Webbon, P M; Morgan, K L

2006-04-17

The objective of this study was to identify risk factors, during racing, associated with imminent fatal distal limb fracture in Thoroughbreds. One hundred and nine cases of fatal distal limb fracture were identified from all 59 UK racecourses over a 2-year period (February 1999-January 2001). Three uninjured control horses were randomly selected from the same race as the case horse. Videos of races in which fractures occurred were viewed using a defined protocol. Fractures in flat races occurred at any time during the race, whereas 74% (45/61) of cases in national hunt type races occurred in the second half of races. More than 75% (79/103) of cases were spontaneous, i.e. there was no obvious external influence such as a fall at a fence or collision with another horse. Sixty-six percent (44/67) of horses, sustaining a forelimb fracture, fractured the forelimb they were using as lead leg at the time of fracture. When case and control horses were compared, horses that were: (a) making good progress through the race, (b) reluctant to start and (c) received encouragement in the final 10s before the time of fracture, were more likely to sustain a fracture.

Integrated database for rapid mass movements in Norway

NASA Astrophysics Data System (ADS)

Jaedicke, C.; Lied, K.; Kronholm, K.

2009-03-01

Rapid gravitational slope mass movements include all kinds of short term relocation of geological material, snow or ice. Traditionally, information about such events is collected separately in different databases covering selected geographical regions and types of movement. In Norway the terrain is susceptible to all types of rapid gravitational slope mass movements ranging from single rocks hitting roads and houses to large snow avalanches and rock slides where entire mountainsides collapse into fjords creating flood waves and endangering large areas. In addition, quick clay slides occur in desalinated marine sediments in South Eastern and Mid Norway. For the authorities and inhabitants of endangered areas, the type of threat is of minor importance and mitigation measures have to consider several types of rapid mass movements simultaneously. An integrated national database for all types of rapid mass movements built around individual events has been established. Only three data entries are mandatory: time, location and type of movement. The remaining optional parameters enable recording of detailed information about the terrain, materials involved and damages caused. Pictures, movies and other documentation can be uploaded into the database. A web-based graphical user interface has been developed allowing new events to be entered, as well as editing and querying for all events. An integration of the database into a GIS system is currently under development. Datasets from various national sources like the road authorities and the Geological Survey of Norway were imported into the database. Today, the database contains 33 000 rapid mass movement events from the last five hundred years covering the entire country. A first analysis of the data shows that the most frequent type of recorded rapid mass movement is rock slides and snow avalanches followed by debris slides in third place. Most events are recorded in the steep fjord terrain of the Norwegian west coast, but major events are recorded all over the country. Snow avalanches account for most fatalities, while large rock slides causing flood waves and huge quick clay slides are the most damaging individual events in terms of damage to infrastructure and property and for causing multiple fatalities. The quality of the data is strongly influenced by the personal engagement of local observers and varying observation routines. This database is a unique source for statistical analysis including, risk analysis and the relation between rapid mass movements and climate. The database of rapid mass movement events will also facilitate validation of national hazard and risk maps.

Effects of disulfiram on apoptosis in PANC-1 human pancreatic cancer cell line.

PubMed

Dastjerdi, M Nikbakht; Babazadeh, Z; Rabbani, M; Gharagozloo, M; Esmaeili, A; Narimani, M

2014-01-01

Pancreatic carcinoma is currently considered as a rapidly progressive and fatal disease, and is typically diagnosed late in its natural course. It is characterized by a poor diagnosis and lack of response to conventional therapy. Recent studies have suggested that disulfiram (DSF), a member of the dithiocarbamate family, may have antitumor activity. This study aimed to evaluate the in vitro effect of DSF on apoptosis in human pancreatic cancerous cell line (PANC-1). PANC-1 cells were cultured and treated with DSF at doses of 5, 10, 13 μM for 24 h and apoptosis was measured. Methylation specific PCR (MS-PCR) and real-time quantitative PCR were carried out to detect the methylation pattern and to estimate the mRNA expression levels of RASSF1A, p21 and Bax. MS-PCR analysis demonstrated that no unmethylated band was apeared in PANC-1 cell line after DSF treatments. The real-time quantitative PCR results showed no significant mRNA expression for RASSF1A (p>0.05); whereas p21 and Bax expression were significantly (p<0.01) enhanced after treatment with DSF. The results of the current study indicated that DSF can induce appoptosis in PANC-1 through p21 and Bax pathway but not through RASSF1A.

Detection and Control of Prion Diseases in Food Animals

PubMed Central

Hedlin, Peter; Taschuk, Ryan; Potter, Andrew; Griebel, Philip; Napper, Scott

2012-01-01

Transmissible spongiform encephalopathies (TSEs), or prion diseases, represent a unique form of infectious disease based on misfolding of a self-protein (PrPC) into a pathological, infectious conformation (PrPSc). Prion diseases of food animals gained notoriety during the bovine spongiform encephalopathy (BSE) outbreak of the 1980s. In particular, disease transmission to humans, to the generation of a fatal, untreatable disease, elevated the perspective on livestock prion diseases from food production to food safety. While the immediate threat posed by BSE has been successfully addressed through surveillance and improved management practices, another prion disease is rapidly spreading. Chronic wasting disease (CWD), a prion disease of cervids, has been confirmed in wild and captive populations with devastating impact on the farmed cervid industries. Furthermore, the unabated spread of this disease through wild populations threatens a natural resource that is a source of considerable economic benefit and national pride. In a worst-case scenario, CWD may represent a zoonotic threat either through direct transmission via consumption of infected cervids or through a secondary food animal, such as cattle. This has energized efforts to understand prion diseases as well as to develop tools for disease detection, prevention, and management. Progress in each of these areas is discussed. PMID:23738120

Toxin-neutralizing antibodies protect against Clostridium perfringens-induced necrosis in an intestinal loop model for bovine necrohemorrhagic enteritis.

PubMed

Goossens, Evy; Verherstraeten, Stefanie; Valgaeren, Bonnie R; Pardon, Bart; Timbermont, Leen; Schauvliege, Stijn; Rodrigo-Mocholí, Diego; Haesebrouck, Freddy; Ducatelle, Richard; Deprez, Piet R; Van Immerseel, Filip

2016-06-13

Bovine necrohemorrhagic enteritis is caused by Clostridium perfringens type A. Due to the rapid progress and fatal outcome of the disease, vaccination would be of high value. In this study, C. perfringens toxins, either as native toxins or after formaldehyde inactivation, were evaluated as possible vaccine antigens. We determined whether antisera raised in calves against these toxins were able to protect against C. perfringens challenge in an intestinal loop model for bovine necrohemorrhagic enteritis. Alpha toxin and perfringolysin O were identified as the most immunogenic proteins in the vaccine preparations. All vaccines evoked a high antibody response against the causative toxins, alpha toxin and perfringolysin O, as detected by ELISA. All antibodies were able to inhibit the activity of alpha toxin and perfringolysin O in vitro. However, the antibodies raised against the native toxins were more inhibitory to the C. perfringens-induced cytotoxicity (as tested on bovine endothelial cells) and only these antibodies protected against C. perfringens challenge in the intestinal loop model. Although immunization of calves with both native and formaldehyde inactivated toxins resulted in high antibody titers against alpha toxin and perfringolysin O, only antibodies raised against native toxins protect against C. perfringens challenge in an intestinal loop model for bovine necrohemorrhagic enteritis.

Adaptive response of Yersinia pestis to extracellular effectors of innate immunity during bubonic plague.

PubMed

Sebbane, Florent; Lemaître, Nadine; Sturdevant, Daniel E; Rebeil, Roberto; Virtaneva, Kimmo; Porcella, Stephen F; Hinnebusch, B Joseph

2006-08-01

Yersinia pestis causes bubonic plague, characterized by an enlarged, painful lymph node, termed a bubo, that develops after bacterial dissemination from a fleabite site. In susceptible animals, the bacteria rapidly escape containment in the lymph node, spread systemically through the blood, and produce fatal sepsis. The fulminant progression of disease has been largely ascribed to the ability of Y. pestis to avoid phagocytosis and exposure to antimicrobial effectors of innate immunity. In vivo microarray analysis of Y. pestis gene expression, however, revealed an adaptive response to nitric oxide (NO)-derived reactive nitrogen species and to iron limitation in the extracellular environment of the bubo. Polymorphonuclear neutrophils recruited to the infected lymph node expressed abundant inducible NO synthase, and several Y. pestis homologs of genes involved in the protective response to reactive nitrogen species were up-regulated in the bubo. Mutation of one of these genes, which encodes the Hmp flavohemoglobin that detoxifies NO, attenuated virulence. Thus, the ability of Y. pestis to destroy immune cells and remain extracellular in the bubo appears to limit exposure to some but not all innate immune effectors. High NO levels induced during plague may also influence the developing adaptive immune response and contribute to septic shock.

A study of finite element modeling for simulation of vehicle rollover

NASA Astrophysics Data System (ADS)

Lin, Zhigui; Liu, Changye; Lv, Juncheng; Jia, Ligang; Sun, Haichao; Chen, Tao

2017-04-01

At present, the automobile ownership has been a very large figure, and growing rapidly with the social progress and development. Automobile has been one of the most important transportation in people's life. Accordingly, there are a large number of fatalities and serious injuries in traffic accident every year. Vehicle safety has been paid more and more attentions in recent years. There are several kinds of traffic accidents including frontal crash, side crash, etc., while rollover crash is a special kind. The vehicle rollover has the lowest incidence in the all kinds of traffic accidents but has the highest rate of seriously injuries, most of which lead to death. For these reasons, it is very necessary to study the vehicle rollover crash. However, it's so hard that there are a small amount of literatures studying rollover due to its variety, large degree of freedom, and difficulty to repeat and control. The method to investigate rollover crash contains experiment, the finite element method and rigid-body-based models. The finite element method contains many advantages such as low cost, repeatability, detailed data and so on, but the limitation is obvious. A test and simulation has been accomplished to study the FEM for vehicle rollover crash particularly in this paper.

Fulminant encephalitis associated with a vaccine strain of rubella virus.

PubMed

Gualberto, Felipe Augusto Souza; de Oliveira, Maria Isabel; Alves, Venancio A F; Kanamura, Cristina T; Rosemberg, Sérgio; Sato, Helena Keico; Arantes, Benedito A F; Curti, Suely Pires; Figueiredo, Cristina Adelaide

2013-12-01

Involvement of the central nervous system is common in measles, but rare in rubella. However, rubella virus (RV) can cause a variety of central nervous system syndromes, including meningitis, encephalitis, Guillain-Barré syndrome and sub acute sclerosing panencephalitis. We report the occurrence of one fatal case of the encephalitis associated with measles-rubella (MR) vaccine during an immunization campaign in São Paulo, Brazil. A 31 year-old-man, previously in good health, was admitted at emergency room, with confusion, agitation, inability to stand and hold his head up. Ten days prior to admission, he was vaccinated with combined MR vaccine (Serum Institute of India) and three days later he developed 'flu-like' illness with fever, myalgia and headache. Results of clinical and laboratory exams were consistent with a pattern of viral encephalitis. During hospitalization, his condition deteriorated rapidly with tetraplegia and progression to coma. On the 3rd day of hospitalization he died. Histopathology confirmed encephalitis and immunohistochemistry was positive for RV on brain tissue. RV was also detected by qPCR and virus isolation in cerebrospinal fluid, brain and other clinical samples. The sequence obtained from the isolated virus was identical to that of the RA 27/3 vaccine strain. Copyright © 2013 Elsevier B.V. All rights reserved.

NAXE Mutations Disrupt the Cellular NAD(P)HX Repair System and Cause a Lethal Neurometabolic Disorder of Early Childhood.

PubMed

Kremer, Laura S; Danhauser, Katharina; Herebian, Diran; Petkovic Ramadža, Danijela; Piekutowska-Abramczuk, Dorota; Seibt, Annette; Müller-Felber, Wolfgang; Haack, Tobias B; Płoski, Rafał; Lohmeier, Klaus; Schneider, Dominik; Klee, Dirk; Rokicki, Dariusz; Mayatepek, Ertan; Strom, Tim M; Meitinger, Thomas; Klopstock, Thomas; Pronicka, Ewa; Mayr, Johannes A; Baric, Ivo; Distelmaier, Felix; Prokisch, Holger

2016-10-06

To safeguard the cell from the accumulation of potentially harmful metabolic intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding the accumulation of toxic metabolites. The clinical importance of the NAD(P)HX repair system has been unknown. Exome sequencing revealed pathogenic biallelic mutations in NAXE in children from four families with (sub-) acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions. Lactate was elevated in cerebrospinal fluid of all affected individuals. Disease onset was during the second year of life and clinical signs as well as episodes of deterioration were triggered by febrile infections. Disease course was rapidly progressive, leading to coma, global brain atrophy, and finally to death in all affected individuals. NAXE levels were undetectable in fibroblasts from affected individuals of two families. In these fibroblasts we measured highly elevated concentrations of the toxic metabolite cyclic-NADHX, confirming a deficiency of the mitochondrial NAD(P)HX repair system. Finally, NAD or nicotinic acid (vitamin B3) supplementation might have therapeutic implications for this fatal disorder. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The 2008 Cholera Epidemic in Zimbabwe: Experience of the icddr,b Team in the Field

PubMed Central

Bardhan, Pradip Kumar; Iqbal, Anwarul; Mazumder, Ramendra Nath; Khan, Azharul Islam; Islam, Md. Sirajul; Siddique, Abul Kasem; Cravioto, Alejandro

2011-01-01

During August 2008–June 2009, an estimated 95,531 suspected cases of cholera and 4,282 deaths due to cholera were reported during the 2008 cholera outbreak in Zimbabwe. Despite the efforts by local and international organizations supported by the Zimbabwean Ministry of Health and Child Welfare in the establishment of cholera treatment centres throughout the country, the case-fatality rate (CFR) was much higher than expected. Over two-thirds of the deaths occurred in areas without access to treatment facilities, with the highest CFRs (>5%) reported from Masvingo, Manicaland, Mashonaland West, Mashonaland East, Midland, and Matabeleland North provinces. Some factors attributing to this high CFR included inappropriate cholera case management with inadequate use of oral rehydration therapy, inappropriate use of antibiotics, and a shortage of experienced healthcare professionals. The breakdown of both potable water and sanitation systems and the widespread contamination of available drinking-water sources were also considered responsible for the rapid and widespread distribution of the epidemic throughout the country. Training of healthcare professionals on appropriate cholera case management and implementation of recommended strategies to reduce the environmental contamination of drinking-water sources could have contributed to the progressive reduction in number of cases and deaths as observed at the end of February 2009. PMID:22106761

Hypertensive crisis.

PubMed

Rodriguez, Maria Alexandra; Kumar, Siva K; De Caro, Matthew

2010-01-01

Hypertension is a common chronic medical condition affecting over 65 million Americans. Uncontrolled hypertension can progress to a hypertensive crisis defined as a systolic blood pressure >180 mm Hg or a diastolic blood pressure >120 mm Hg. Hypertensive crisis can be further classified as a hypertensive urgency or hypertensive emergency depending on end-organ involvement including cardiac, renal, and neurologic injury. The prompt recognition of a hypertensive emergency with the appropriate diagnostic tests and triage will lead to the adequate reduction of blood pressure, ameliorating the incidence of fatal outcomes. Severely hypertensive patients with acute end-organ damage (hypertensive emergencies) warrant admission to an intensive care unit for immediate reduction of blood pressure with a short-acting titratable intravenous antihypertensive medication. Hypertensive urgencies (severe hypertension with no or minimal end-organ damage) may in general be treated with oral antihypertensives as an outpatient. Rapid and short-lived intravenous medications commonly used are labetalol, esmolol, fenoldopam, nicardipine, sodium nitroprusside, and clevidipine. Medications such as hydralazine, immediate release nifedipine, and nitroglycerin should be avoided. Sodium nitroprusside should be used with caution because of its toxicity. The risk factors and prognosticators of a hypertensive crisis are still under recognized. Physicians should perform complete evaluations in patients who present with a hypertensive crisis to effectively reverse, intervene, and correct the underlying trigger, as well as improve long-term outcomes after the episode.

Fatal asbestosis 50 years after brief high intensity exposure in a vermiculite expansion plant.

PubMed

Wright, Robert S; Abraham, Jerrold L; Harber, Philip; Burnett, Bryan R; Morris, Peter; West, Phil

2002-04-15

The authors report the case of a 65-year-old accountant whose only asbestos exposure was during a summer job 50 years earlier in a California vermiculite expansion plant. Vermiculite is a silicate material that is useful in building and agriculture as a filler and insulating agent. He developed extensive fibrocalcific pleural plaques and end-stage pulmonary fibrosis, with rapidly progressive respiratory failure. Careful occupational and environmental history revealed no other source of asbestos exposure, and the initial clinical diagnosis was idiopathic pulmonary fibrosis; open lung biopsy shortly before his death confirmed asbestosis. Electron microscopic lung fiber burden analysis revealed over 8,000,000 asbestos fibers per gram dry lung, 68% of which were tremolite asbestos. Additional asbestiform fibers of composition not matching any of the standard asbestos varieties were also present at over 5,000,000 fibers per gram dry lung. Comparison analysis of a sample of Libby, Montana, vermiculite showed a similar mix of asbestiform fibers including tremolite asbestos. This case analysis raises several concerns: risks of vermiculite induced disease among former workers of the more than 200 expansion plants throughout the United States; health effects of brief but very high-intensity exposures to asbestos; and possible health effects in end-users of consumer products containing vermiculite.

Mass Fatality Management following the South Asian Tsunami Disaster: Case Studies in Thailand, Indonesia, and Sri Lanka

PubMed Central

Morgan, Oliver W; Sribanditmongkol, Pongruk; Perera, Clifford; Sulasmi, Yeddi; Van Alphen, Dana; Sondorp, Egbert

2006-01-01

Background Following natural disasters, mismanagement of the dead has consequences for the psychological well-being of survivors. However, no technical guidelines currently exist for managing mass fatalities following large natural disasters. Existing methods of mass fatality management are not directly transferable as they are designed for transport accidents and acts of terrorism. Furthermore, no information is currently available about post-disaster management of the dead following previous large natural disasters. Methods and Findings After the tsunami disaster on 26 December 2004, we conducted three descriptive case studies to systematically document how the dead were managed in Thailand, Indonesia, and Sri Lanka. We considered the following parameters: body recovery and storage, identification, disposal of human remains, and health risks from dead bodies. We used participant observations as members of post-tsunami response teams, conducted semi-structured interviews with key informants, and collected information from published and unpublished documents. Refrigeration for preserving human remains was not available soon enough after the disaster, necessitating the use of other methods such as dry ice or temporary burial. No country had sufficient forensic capacity to identify thousands of victims. Rapid decomposition made visual identification almost impossible after 24–48 h. In Thailand, most forensic identification was made using dental and fingerprint data. Few victims were identified from DNA. Lack of national or local mass fatality plans further limited the quality and timeliness of response, a problem which was exacerbated by the absence of practical field guidelines or an international agency providing technical support. Conclusions Emergency response should not add to the distress of affected communities by inappropriately disposing of the victims. The rights of survivors to see their dead treated with dignity and respect requires practical guidelines and technical support. Mass fatality management following natural disasters needs to be informed by further field research and supported by a network of regional and international forensic institutes and agencies. PMID:16737348

Administrative license suspension: Does length of suspension matter?

PubMed

Fell, James C; Scherer, Michael

2017-08-18

Administrative license revocation (ALR) laws, which provide that the license of a driver with a blood alcohol concentration at or over the illegal limit is subject to an immediate suspension by the state department of motor vehicles, are an example of a traffic law in which the sanction rapidly follows the offense. The power of ALR laws has been attributed to how swiftly the sanction is applied, but does the length of suspension matter? Our objectives were to (a) determine the relationship of the ALR suspension length to the prevalence of drinking drivers relative to sober drivers in fatal crashes and (b) estimate the extent to which the relationship is associated to the general deterrent effect compared to the specific deterrent effect of the law. Data comparing the impact of ALR law implementation and ALR law suspension periods were analyzed using structural equation modeling techniques on the ratio of drinking drivers to nondrinking drivers in fatal crashes from the Fatality Analysis Reporting System (FARS). States with an ALR law with a short suspension period (1-30 days) had a significantly lower drinking driver ratio than states with no ALR law. States with a suspension period of 91-180 days had significantly lower ratios than states with shorter suspension periods, while the three states with suspension lengths of 181 days or longer had significantly lower ratios than states with shorter suspension periods. The implementation of any ALR law was associated with a 13.1% decrease in the drinking/nondrinking driver fatal crash ratio but only a 1.8% decrease in the intoxicated/nonintoxicated fatal crash ratio. The ALR laws and suspension lengths had a significant general deterrent effect, but no specific deterrent effect. States might want to keep (or adopt) ALR laws for their general deterrent effects and pursue alternatives for specific deterrent effects. States with short ALR suspension periods should consider lengthening them to 91 days or longer.

Mass fatality management following the South Asian tsunami disaster: case studies in Thailand, Indonesia, and Sri Lanka.

PubMed

Morgan, Oliver W; Sribanditmongkol, Pongruk; Perera, Clifford; Sulasmi, Yeddi; Van Alphen, Dana; Sondorp, Egbert

2006-06-01

Following natural disasters, mismanagement of the dead has consequences for the psychological well-being of survivors. However, no technical guidelines currently exist for managing mass fatalities following large natural disasters. Existing methods of mass fatality management are not directly transferable as they are designed for transport accidents and acts of terrorism. Furthermore, no information is currently available about post-disaster management of the dead following previous large natural disasters. After the tsunami disaster on 26 December 2004, we conducted three descriptive case studies to systematically document how the dead were managed in Thailand, Indonesia, and Sri Lanka. We considered the following parameters: body recovery and storage, identification, disposal of human remains, and health risks from dead bodies. We used participant observations as members of post-tsunami response teams, conducted semi-structured interviews with key informants, and collected information from published and unpublished documents. Refrigeration for preserving human remains was not available soon enough after the disaster, necessitating the use of other methods such as dry ice or temporary burial. No country had sufficient forensic capacity to identify thousands of victims. Rapid decomposition made visual identification almost impossible after 24-48 h. In Thailand, most forensic identification was made using dental and fingerprint data. Few victims were identified from DNA. Lack of national or local mass fatality plans further limited the quality and timeliness of response, a problem which was exacerbated by the absence of practical field guidelines or an international agency providing technical support. Emergency response should not add to the distress of affected communities by inappropriately disposing of the victims. The rights of survivors to see their dead treated with dignity and respect requires practical guidelines and technical support. Mass fatality management following natural disasters needs to be informed by further field research and supported by a network of regional and international forensic institutes and agencies.

Maintenance of Epithelial Stem Cells by Cbl Proteins

DTIC Science & Technology

2013-09-01

our research findings during the entire grant period (Sept. 2010 – Aug. 2013). 1. Analysis of Cbl functions in progenitor-type mammary epithelial...catenin pathway, but further investigation is required to establish this. 2. Analysis of Cbl functions in vivo using gene mutant mouse models We...Nandwani N, Gu H, Band V, Band H. Rapidly fatal myeloproliferative disorders in mice with deletion of Casitas B-cell lymphoma (Cbl) and Cbl-b in

Saturday night blue--a case of near fatal poisoning from the abuse of amyl nitrite.

PubMed Central

Stambach, T; Haire, K; Soni, N; Booth, J

1997-01-01

A case of severe methaemoglobinaemia caused by the abuse of volatile nitrites is reported. The agents are commonly abused, but this complication is rare. The clinical presentation can make diagnosis difficult; however, the subsequent treatment needs to be rapid to avoid serious morbidity or mortality. This report presents the clinical picture and the background information leading to the detection and treatment of this unusual problem. PMID:9315944

Refractory Coronary Artery Spasm after Minimally Invasive Direct Coronary Artery Bypass Grafting

PubMed Central

Ju, Min Ho; Kim, Joon-Bum; Kim, Hee Jung

2011-01-01

Postoperative coronary arterial spasm is a rare but potentially fatal complication. A 51-year-old male patient with a history of a reactive ergonovine stress test coronary angiogram developed refractory coronary artery spasm after undergoing minimally invasive direct coronary artery bypass grafting of the left anterior descending coronary artery. The patient was successfully managed with rapid implementation of intra-aortic balloon-pump counter pulsation and extracorporeal membrane oxygenation. PMID:22263171

Isolation and Molecular Typing of Naegleria fowleri from the Brain of a Cow That Died of Primary Amebic Meningoencephalitis

PubMed Central

Visvesvara, Govinda S.; De Jonckheere, Johan F.; Sriram, Rama; Daft, Barbara

2005-01-01

Naegleria fowleri causes an acute and rapidly fatal central nervous system infection called primary amebic meningoencephalitis (PAM) in healthy children and young adults. We describe here the identification of N. fowleri isolated from the brain of one of several cows that died of PAM based on sequencing of the internal transcribed spacers, including the 5.8S rRNA genes. PMID:16081978

Peripheral Organs of Dengue Fatal Cases Present Strong Pro-Inflammatory Response with Participation of IFN-Gamma-, TNF-Alpha- and RANTES-Producing Cells.

PubMed

Póvoa, Tiago F; Oliveira, Edson R A; Basílio-de-Oliveira, Carlos A; Nuovo, Gerard J; Chagas, Vera L A; Salomão, Natália G; Mota, Ester M; Paes, Marciano V

2016-01-01

Dengue disease is an acute viral illness caused by dengue virus (DENV) that can progress to hemorrhagic stages leading to about 20000 deaths every year worldwide. Despite many clinical investigations regarding dengue, the immunopathogenic process by which infected patients evolve to the severe forms is not fully understood. Apart from differences in virulence and the antibody cross reactivity that can potentially augment virus replication, imbalanced cellular immunity is also seen as a major concern in the establishment of severe dengue. In this context, the investigation of cellular immunity and its products in dengue fatal cases may provide valuable data to help revealing dengue immunopathogenesis. Here, based in four dengue fatal cases infected by the serotype 3 in Brazil, different peripheral organs (livers, lungs and kidneys) were studied to evaluate the presence of cell infiltrates and the patterns of local cytokine response. The overall scenario of the studied cases revealed a considerable systemic involvement of infection with mononuclear cells targeted to all of the evaluated organs, as measured by immunohistochemistry (IHC). Quantification of cytokine-expressing cells in peripheral tissues was also performed to characterize the ongoing inflammatory process by the severe stage of the disease. Increased levels of IFN-γ- and TNF-α-expressing cells in liver, lung and kidney samples of post-mortem subjects evidenced a strong pro-inflammatory induction in these tissues. The presence of increased RANTES-producing cell numbers in all analyzed organs suggested a possible link between the clinical status and altered vascular permeability. Co-staining of DENV RNA and IFN-γ or TNF-α using in situ hibridization and IHC confirmed the virus-specific trigger of the pro-inflammatory response. Taken together, this work provided additional evidences that corroborated with the traditional theories regarding the "cytokine storm" and the occurrence of uneven cellular immunity in response to DENV as major reasons for progress to severe disease.

Road crash injuries and fatalities in Isfahan, Iran from March 2006 to March 2009.

PubMed

Mohammadi, Ghorbanali

2014-01-01

With rapid development of social economies, road traffic accidents have continued to increase, and have become the primary public hazard to humans. The main goal of the present study was to investigate road traffic crash (RTC) fatalities and injuries in the city of Isfahan, Iran. A sample of 150,940 accident cases was considered from Isfahan Police Safety Driving Department, involving drivers and passengers of all ages, and covering a 3-year period. The record linkage identified 24,608 drivers and passengers injured or died as a result of RTC in the city of Isfahan over the 3-year period. The finding of this study shows that the highest rate of RTC fatality was 40% and 58%, which comprises the male drivers and female passengers within the age classes 25-34 and 35-44, respectively. On average, there were one death every 3 days and every hour, someone was injured and taken to an emergency department for RTCs in the city of Isfahan. The highest men to women death and injured ratios were 4:1 and 2:1, respectively. The use of seat belt devices in our population was worrisome. The article ends with a number of recommended measures for the improvement of road safety.

Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses.

PubMed

Martines, Roosecelis Brasil; Ng, Dianna L; Greer, Patricia W; Rollin, Pierre E; Zaki, Sherif R

2015-01-01

Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Age, period, and cohort effects in motor vehicle mortality in the United States, 1980-2010: the role of sex, alcohol involvement, and position in vehicle.

PubMed

Macinko, James; Silver, Diana; Bae, Jin Yung

2015-02-01

Although substantive declines in motor vehicle fatalities in 1980-2010 have been observed, declines by position in the vehicle and alcohol involvement have not been well elucidated. Analyses of FARS data use the Intrinsic Estimator (IE) to produce estimates of all age, period, and cohort effects simultaneously by position in the car and by alcohol involvement. Declines in MVC deaths by position in the car vary for men and women by age and cohort over time. Cohorts born before 1970 had higher risks than those born later. Analyses using proxy indicators of alcohol involvement found the highest risks for those aged 16-24. By period, these risks declined more rapidly than non- alcohol related traffic fatalities. Changes in risk patterns are consistent with evidence regarding the contributions of new technologies and public policy efforts to reduce fatalities, but gains have not been shared evenly by sex or position in the car. Greater attention is needed in reducing deaths among older drivers and pedestrians. Gender differences should be addressed in prevention efforts aimed at reducing MVCs due to alcohol involvement. Copyright © 2014 Elsevier Ltd and National Safety Council. All rights reserved.

Spinning the wheels and rolling the dice: life-cycle risks and benefits of bicycle commuting in the U.S.

PubMed

Edwards, Ryan D; Mason, Carl N

2014-07-01

To assess the net impact on U.S. longevity of the decision to commute by bicycle rather than automobile. We construct fatality rates per distance traveled using official statistics and denominators from the 2009 National Household Travel Survey. We model the life-table impact of switching from auto to bicycle commuting. Key factors are increased risks from road accidents and reduced risks from enhanced cardiovascular health. Bicycling fatality rates in the U.S. are an order of magnitude higher than in Western Europe. Risks punish both young and old, while the health benefits guard against causes of mortality that rise rapidly with age. Although the protective effects of bicycling appear significant, it may be optimal to wait until later ages to initiate regular bicycle commuting in the current U.S. risk environment, especially if individuals discount future life years. The lifetime health benefits of bicycle commuting appear to outweigh the risks in the U.S., but individuals who sufficiently discount or disbelieve the health benefits may delay or avoid bicycling. Bicycling in middle age avoids much fatality risk while capturing health benefits. Significant cross-state variations in bicycling mortality suggest that improvements in the built environment might spur changes in transit mode. Copyright © 2014 Elsevier Inc. All rights reserved.

Friedrich Nietzsche's mental illness--general paralysis of the insane vs. frontotemporal dementia.

PubMed

Orth, M; Trimble, M R

2006-12-01

For a long time it was thought that Nietzsche suffered from general paralysis of the insane (GPI). However, this diagnosis has been questioned recently, and alternative diagnoses have been proposed. We have charted Friedrich Nietzsche's final fatal illness, and viewed the differential diagnosis in the light of recent neurological understandings of dementia syndromes. It is unclear that Nietzsche ever had syphilis. He lacked progressive motor and other neurological features of a progressive syphilitic central nervous system (CNS) infection and lived at least 12 years following the onset of his CNS signs, which would be extremely rare for patients with untreated GPI. Finally, his flourish of productivity in 1888 would be quite uncharacteristic of GPI, but in keeping with reports of burgeoning creativity at some point in the progression of frontotemporal dementia (FTD). We suggest that Nietzsche did not have GPI, but died from a chronic dementia, namely FTD.

Ebola hemorrhagic Fever.

PubMed

Burnett, Mark W

2014-01-01

Ebola hemorrhagic fever is an often-fatal disease caused by a virus of the Filoviridae family, genus Ebolavirus. Initial signs and symptoms of the disease are nonspecific, often progressing on to a severe hemorrhagic illness. Special Operations Forces Medical Providers should be aware of this disease, which occurs in sporadic outbreaks throughout Africa. Treatment at the present time is mainly supportive. Special care should be taken to prevent contact with bodily fluids of those infected, which can transmit the virus to caregivers. 2014.

Neuropsychiatric Symptoms of Dementia: Consent, Quality of Life, and Dignity

PubMed Central

Passmore, Michael J.

2013-01-01

Degenerative forms of dementia are progressive, incurable, fatal, and likely to cause suffering in conjunction with personal incapacity. Timely diagnostic disclosure and counseling can facilitate important advance care planning. The risk of harm associated with neuropsychiatric symptoms (NPS) of dementia often has to be balanced against the risk of harm associated with medication management of NPS. A palliative care framework can help preserve autonomy, quality of life, comfort, and dignity for patients with NPS. PMID:23853768

Treatment and recovery.

PubMed

Raia, Susan

2005-01-01

Addiction is a chronic, progressive, fatal disease. It is a primary disease, not caused by any other disease process. It has recognizable symptoms that if left untreated, can lead to premature death, deterioration of physical conditions, social withdrawal and disintegration of all support systems. The family and co-workers are affected as well. There is no cure, but we know that treatment works! Don't stand by while someone you care about needs help. Nurses helping nurses, let's take care of our own.

Twenty years of hantavirus pulmonary syndrome in Brazil: a review of epidemiological and clinical aspects.

PubMed

Pinto Junior, Vitor Laerte; Hamidad, Amani Moura; Albuquerque Filho, Dalcy de Oliveira; dos Santos, Vitorino Modesto

2014-02-13

Hantavirus infection is transmitted to humans by wild rodents and the most common clinical form in Brazil is the Hantavirus Pulmonary Syndrome (HPS). The first serological evidence of the disease was identified in 1990, in Recife, Pernambuco State, and later in 1993 in Juquitiba, State of São Paulo. Since then there has been a progressive increase in case notification in all regions of the country. The clinical aspects of the disease in Brazil are characterized by a prodromal phase, with nonspecific signs and symptoms of an acute febrile illness. After about three days, respiratory distress develops, accompanied by dry cough that turns progressively productive, evolving to dyspnea and respiratory failure with cardiogenic shock. Although the majority of patients receive hospital care in intensive care therapy units, case-fatality rate in Brazil ranges from 33% to 100% depending on the region. Besides it has to be added the problem of differential diagnosis with other prevalent diseases in the country, like dengue and leptospirosis. Questions about the impact of uncontrolled urbanization and other environmental changes caused by human action have been raised. Due to increasing incidence and high case-fatality, there is an urge to respond to such questions to recommend preventative measures. This article aims to review the main acquisitions in clinical and epidemiological knowledge about HPS in Brazil in the last twenty years.

Consensus clinical management guidelines for Niemann-Pick disease type C.

PubMed

Geberhiwot, Tarekegn; Moro, Alessandro; Dardis, Andrea; Ramaswami, Uma; Sirrs, Sandra; Marfa, Mercedes Pineda; Vanier, Marie T; Walterfang, Mark; Bolton, Shaun; Dawson, Charlotte; Héron, Bénédicte; Stampfer, Miriam; Imrie, Jackie; Hendriksz, Christian; Gissen, Paul; Crushell, Ellen; Coll, Maria J; Nadjar, Yann; Klünemann, Hans; Mengel, Eugen; Hrebicek, Martin; Jones, Simon A; Ory, Daniel; Bembi, Bruno; Patterson, Marc

2018-04-06

Niemann-Pick Type C (NPC) is a progressive and life limiting autosomal recessive disorder caused by mutations in either the NPC1 or NPC2 gene. Mutations in these genes are associated with abnormal endosomal-lysosomal trafficking, resulting in the accumulation of multiple tissue specific lipids in the lysosomes. The clinical spectrum of NPC disease ranges from a neonatal rapidly progressive fatal disorder to an adult-onset chronic neurodegenerative disease. The age of onset of the first (beyond 3 months of life) neurological symptom may predict the severity of the disease and determines life expectancy.NPC has an estimated incidence of ~ 1: 100,000 and the rarity of the disease translate into misdiagnosis, delayed diagnosis and barriers to good care. For these reasons, we have developed clinical guidelines that define standard of care for NPC patients, foster shared care arrangements between expert centres and family physicians, and empower patients. The information contained in these guidelines was obtained through a systematic review of the literature and the experiences of the authors in their care of patients with NPC. We adopted the Appraisal of Guidelines for Research & Evaluation (AGREE II) system as method of choice for the guideline development process. We made a series of conclusive statements and scored them according to level of evidence, strengths of recommendations and expert opinions. These guidelines can inform care providers, care funders, patients and their carers of best practice of care for patients with NPC. In addition, these guidelines have identified gaps in the knowledge that must be filled by future research. It is anticipated that the implementation of these guidelines will lead to a step change in the quality of care for patients with NPC irrespective of their geographical location.

The variable presentations of glycogen storage disease type IV: a review of clinical, enzymatic and molecular studies.

PubMed

Moses, Shimon W; Parvari, Ruti

2002-03-01

Glycogen storage disease type IV (GSD-IV), also known as Andersen disease or amylopectinosis (MIM 23250), is a rare autosomal recessive disorder caused by a deficiency of glycogen branching enzyme (GBE) leading to the accumulation of amylopectin-like structures in affected tissues. The disease is extremely heterogeneous in terms of tissue involvement, age of onset and clinical manifestations. The human GBE cDNA is approximately 3-kb in length and encodes a 702-amino acid protein. The GBE amino acid sequence shows a high degree of conservation throughout species. The human GBE gene is located on chromosome 3p14 and consists of 16 exons spanning at least 118 kb of chromosomal DNA. Clinically the classic Andersen disease is a rapidly progressive disorder leading to terminal liver failure unless liver transplantation is performed. Several mutations have been reported in the GBE gene in patients with classic phenotype. Mutations in the GBE gene have also been identified in patients with the milder non-progressive hepatic form of the disease. Several other variants of GSD-IV have been reported: a variant with multi-system involvement including skeletal and cardiac muscle, nerve and liver; a juvenile polysaccharidosis with multi-system involvement but normal GBE activity; and the fatal neonatal neuromuscular form associated with a splice site mutation in the GBE gene. Other presentations include cardiomyopathy, arthrogryposis and even hydrops fetalis. Polyglucosan body disease, characterized by widespread upper and lower motor neuron lesions, can present with or without GBE deficiency indicating that different biochemical defects could result in an identical phenotype. It is evident that this disease exists in multiple forms with enzymatic and molecular heterogeneity unparalleled in the other types of glycogen storage diseases.

A Serious Complication of Illicit Silicone Injections: Latent Silicone Embolization Syndrome after Incision and Drainage of Local Injection Site.

PubMed

Purdy-Payne, Erin K; Green, Jillian; Zenoni, Scott; Evans, Alexander N; Bilski, Tracy R

2015-08-01

Silicone embolization syndrome, a serious adverse effect of illicit silicone injections by laypersons, occurs when silicone particles enter the circulation and shower the lungs and other vital organs. We review the literature on silicone embolization syndrome and describe a unique case of the syndrome that developed after a latent period of several months, upon surgical debridement of an injection site abscess. In the scientific literature, silicone embolization syndrome has been well described and multiple presentations have been delineated. Immediate presentation with a rapidly fatal course occurs in cases of erroneous intra-vascular injection, in which large volumes of silicone occlude pulmonary arteries and cause cor pulmonale. Insidious presentation of progressive respiratory distress and systemic inflammatory response syndrome occurs in cases of peri-vascular injection, caused by gradual vascular infiltration by smaller silicone emboli that shower pulmonary capillaries diffusely, causing alveolar hemorrhage and inflammation. Rarely, latent cases have presented months to years later upon trauma to the original site, which disrupts the sequestered siliconoma, allowing re-exposure to the immune system and the opportunity for vascular infiltration. To the best of our knowledge, this is the first description of silicone embolization syndrome that occurred after surgical manipulation of the site. It has important management implications for patients with a history of prior silicone injections at a site being considered for surgical intervention. Strategies for managing this potential complication include adding a regimen of daily debridement, aggressive ventilator support, and maintaining close observation in an intensive care unit (ICU) or progressive care unit (PCU) during the high-risk post-operative period. Alternatively, when possible, surgeons may avoid disruption of the siliconoma by trialing medical management of localized inflammation or using alternative procedures such as image-guided wide local excision or liposuction with fat transfer.

Immune checkpoint inhibitor-related myocarditis.

PubMed

Tajiri, Kazuko; Aonuma, Kazutaka; Sekine, Ikuo

2018-01-01

Immune checkpoint inhibitors have demonstrated significant clinical benefit in many cancers. The clinical benefit afforded by these treatments can be accompanied by a unique and distinct spectrum of adverse events. Recently, several fatal cases of immune checkpoint inhibitor-related myocarditis were reported. Although its frequency is comparatively lower than that of other immune-related adverse events, myocarditis can lead to circulatory collapse and lethal ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in establishing peripheral tolerance to the heart. Evidence from studies using genetically engineered mouse models suggests that CTLA-4 signaling terminates proliferation and promotes anergy during the primary response to cardiac self-peptide recognition. PD-1 signaling restrains autoreactive T cells that enter the peripheral tissues and recognize cardiac-peptide, maintaining them in an anergic state. Patients affected by immune checkpoint inhibitor-related myocarditis often experience rapid onset of profound hemodynamic compromise progressing to cardiogenic shock. Early diagnosis is mandatory to address specific therapy and correct the timing of circulatory support. However, the diagnosis of myocarditis is challenging due to the heterogeneity of clinical presentations. Owing to its early onset, nonspecific symptomatology and fulminant progression, especially when these drugs are used in combination, oncologists should be vigilant for immune checkpoint inhibitor-related myocarditis. With many questions yet to be answered, from basic immune biology to clinical management, future research should aim to optimize the use of these drugs by identifying predictive biomarkers of either a response to therapy or the risks of myocarditis development. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Resection of primary tumor at diagnosis in stage IV-S neuroblastoma: does it affect the clinical course?

PubMed

Guglielmi, M; De Bernardi, B; Rizzo, A; Federici, S; Boglino, C; Siracusa, F; Leggio, A; Cozzi, F; Cecchetto, G; Musi, L; Bardini, T; Fagnani, A M; Bartoli, G C; Pampaloni, A; Rogers, D; Conte, M; Milanaccio, C; Bruzzi, P

1996-05-01

To determine whether resection of primary tumor has a favorable influence on outcome of infants (age 0 to 11 months) with stage IV-S neuroblastoma. Between March 1976 and December 1993, 97 infants with previously untreated neuroblastoma diagnosed in 21 Italian institutions were classified as having stage IV-S disease. Seventy percent were younger than 4 months. Adrenal was the primary tumor site in 64 of 85 patients with a recognizable primary tumor. Liver was the organ most often infiltrated by the tumor (82 patients), followed by bone marrow and skin. The overall survival (OS) rate at 5 years in 80% and event-free survival (EFS) rate 68%. In 24 infants, the effect of resection of primary tumor could not be evaluated because of rapidly fatal disease progression (n = 8), absence of a primary tumor (n = 12), or partial resection (n = 4). Of 73 assessable patients, 26 underwent primary tumor resection at diagnosis: one died of surgical complications, one relapsed locally and died, and two others relapsed (one of these two locally) and survived, for a 5-year OS rate of 92% and EFS rate of 84%. Of the remaining 47 patients who did not undergo primary tumor resection at diagnosis 11 suffered unfavorable events, of whom five died, for an OS rate of 89% and EFS rate of 75% (no significant difference from previous group). Disease recurred at the primary tumor site in only one five who died, and in only one of six survivors of progression or relapse; in these patients, the primary tumor, located in the mediastinum, was successfully resected. Infants who underwent resection of the primary tumor at diagnosis had no better outcome than those in whom the decision was made not to operate.

Recreational nitrous oxide use: Prevalence and risks.

PubMed

van Amsterdam, Jan; Nabben, Ton; van den Brink, Wim

2015-12-01

Nitrous oxide (N2O; laughing gas) is clinically used as a safe anesthetic (dentistry, ambulance, childbirth) and appreciated for its anti-anxiety effect. Since five years, recreational use of N2O is rapidly increasing especially in the dance and festival scene. In the UK, N2O is the second most popular recreational drug after cannabis. In most countries, nitrous oxide is a legal drug that is widely available and cheap. Last month prevalence of use among clubbers and ravers ranges between 40 and almost 80 percent. Following one inhalation, mostly from a balloon, a euphoric, pleasant, joyful, empathogenic and sometimes hallucinogenic effect is rapidly induced (within 10 s) and disappears within some minutes. Recreational N2O use is generally moderate with most users taking less than 10 balloons of N2O per episode and about 80% of the users having less than 10 episodes per year. Side effects of N2O include transient dizziness, dissociation, disorientation, loss of balance, impaired memory and cognition, and weakness in the legs. When intoxicated accidents like tripping and falling may occur. Some fatal accidents have been reported due to due to asphyxia (hypoxia). Heavy or sustained use of N2O inactivates vitamin B12, resulting in a functional vitamin B12 deficiency and initially causing numbness in fingers, which may further progress to peripheral neuropathy and megaloblastic anemia. N2O use does not seem to result in dependence. Considering the generally modest use of N2O and its relative safety, it is not necessary to take legal measures. However, (potential) users should be informed about the risk of vitamin B12-deficiency related neurological and hematological effects associated with heavy use. Copyright © 2015 Elsevier Inc. All rights reserved.

Rapid evidence assessment of approaches to community neurological nursing care for people with neurological conditions post-discharge from acute care hospital.

PubMed

Pugh, Judith Dianne; McCoy, Kathleen; Williams, Anne M; Bentley, Brenda; Monterosso, Leanne

2018-04-16

Neurological conditions represent leading causes of non-fatal burden of disease that will consume a large proportion of projected healthcare expenditure. Inconsistent access to integrated healthcare and other services for people with long-term neurological conditions stresses acute care services. The purpose of this rapid evidence assessment, conducted February-June 2016, was to review the evidence supporting community neurological nursing approaches for patients with neurological conditions post-discharge from acute care hospitals. CINAHL Plus with Full Text and MEDLINE were searched for English-language studies published January 2000 to June 2016. Data were extracted using a purpose-designed protocol. Studies describing community neurological nursing care services post-discharge for adults with stroke, dementia, Alzheimer's disease, Parkinson's disease, multiple sclerosis or motor neurone disease were included and their quality was assessed. Two qualitative and three quantitative studies were reviewed. Two themes were identified in the narrative summary of findings: (i) continuity of care and self-management and (ii) variable impact on clinical or impairment outcomes. There was low quality evidence of patient satisfaction, improved patient social activity, depression scores, stroke knowledge and lifestyle modification associated with post-discharge care by neurological nurses as an intervention. There were few studies and weak evidence supporting the use of neurology-generalist nurses to promote continuity of care for people with long-term or progressive, long-term neurological conditions post-discharge from acute care hospital. Further research is needed to provide role clarity to facilitate comparative studies and evaluations of the effectiveness of community neurological nursing models of care. © 2018 John Wiley & Sons Ltd.

Emotional and cognitive changes during and post a near fatal heart attack and one-year after: a case study.

PubMed

Lane, Andrew M; Godfrey, Richard

2010-01-01

This case study reports on changes in emotions before and during an unexpected heart rate in a young, apparently healthy male with a life-long history of exercise in the absence of family history of heart problems. He completed the Brunel Mood Scale (Terry et al. , 2003) to assess emotions before, during, and after the heart attack, and also describing his thoughts during these periods. Results indicate he experienced unpleasant emotions in the build up to the heart attack, feelings he attributed at the time to frustration to achieve fitness goals. He maintained an exercise regime prior to having a heart attack, a finding consistent with previous research suggesting that early diagnosis, although vital for survival, is not likely to be identified among seemingly healthy individuals. During the heart attack, he experienced a rapid emotional change characterised by a rapid increase in anger coupled with thoughts of needing to survive. The intensity of emotions and regulation strategies employed before and during the heart attack provide insight this experience, and we suggest future research should investigate emotional change during adverse conditions. Key pointsThe present case study details emotions experienced and attempts to regulate these emotions before, during and post a heart attack. Unpleasant emotions experienced before the heart were attributed to lack of progress toward fitness goals, a perception that is plausible as he was a regular exerciser.Early identification of heart attack is critical as "Time is Muscle" (Whyte et al., 2009) and therefore even people perceived to be at low risk should consider the possibility of such an eventuality, and seek medical treatment early in the process.

Potent Innate Immune Response to Pathogenic Leptospira in Human Whole Blood

PubMed Central

Hartskeerl, Rudy A.; van Gorp, Eric C. M.; Schuller, Simone; Monahan, Avril M.; Nally, Jarlath E.; van der Poll, Tom; van 't Veer, Cornelis

2011-01-01

Background Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. The bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. In general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. Not much is known about the innate immune response to leptospires during haematogenous dissemination. Previous work showed that a human THP-1 cell line recognized heat-killed leptospires and leptospiral LPS through TLR2 instead of TLR4. The LPS of virulent leptospires displayed a lower potency to trigger TNF production by THP-1 cells compared to LPS of non-virulent leptospires. Methodology/Principal Findings We investigated the host response and killing of virulent and non-virulent Leptospira of different serovars by human THP-1 cells, human PBMC's and human whole blood. Virulence of each leptospiral strain was tested in a well accepted standard guinea pig model. Virulent leptospires displayed complement resistance in human serum and whole blood while in-vitro attenuated non-virulent leptospires were rapidly killed in a complement dependent manner. In vitro stimulation of THP-1 and PBMC's with heat-killed and living leptospires showed differential serovar and cell type dependence of cytokine induction. However, at low, physiological, leptospiral dose, living virulent complement resistant strains were consistently more potent in whole blood stimulations than the corresponding non-virulent complement sensitive strains. At higher dose living virulent and non-virulent leptospires were equipotent in whole blood. Inhibition of different TLRs indicated that both TLR2 and TLR4 as well as TLR5 play a role in the whole blood cytokine response to living leptospires. Conclusions/Significance Thus, in a minimally altered system as human whole blood, highly virulent Leptospira are potent inducers of the cytokine response. PMID:21483834

Potent innate immune response to pathogenic leptospira in human whole blood.

PubMed

Goris, Marga G A; Wagenaar, Jiri F P; Hartskeerl, Rudy A; van Gorp, Eric C M; Schuller, Simone; Monahan, Avril M; Nally, Jarlath E; van der Poll, Tom; van 't Veer, Cornelis

2011-03-31

Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. The bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. In general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. Not much is known about the innate immune response to leptospires during haematogenous dissemination. Previous work showed that a human THP-1 cell line recognized heat-killed leptospires and leptospiral LPS through TLR2 instead of TLR4. The LPS of virulent leptospires displayed a lower potency to trigger TNF production by THP-1 cells compared to LPS of non-virulent leptospires. We investigated the host response and killing of virulent and non-virulent Leptospira of different serovars by human THP-1 cells, human PBMC's and human whole blood. Virulence of each leptospiral strain was tested in a well accepted standard guinea pig model. Virulent leptospires displayed complement resistance in human serum and whole blood while in-vitro attenuated non-virulent leptospires were rapidly killed in a complement dependent manner. In vitro stimulation of THP-1 and PBMC's with heat-killed and living leptospires showed differential serovar and cell type dependence of cytokine induction. However, at low, physiological, leptospiral dose, living virulent complement resistant strains were consistently more potent in whole blood stimulations than the corresponding non-virulent complement sensitive strains. At higher dose living virulent and non-virulent leptospires were equipotent in whole blood. Inhibition of different TLRs indicated that both TLR2 and TLR4 as well as TLR5 play a role in the whole blood cytokine response to living leptospires. Thus, in a minimally altered system as human whole blood, highly virulent Leptospira are potent inducers of the cytokine response.

Guideline of transthyretin-related hereditary amyloidosis for clinicians

PubMed Central

2013-01-01

Transthyretin amyloidosis is a progressive and eventually fatal disease primarily characterized by sensory, motor, and autonomic neuropathy and/or cardiomyopathy. Given its phenotypic unpredictability and variability, transthyretin amyloidosis can be difficult to recognize and manage. Misdiagnosis is common, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. This article aims to help physicians better understand transthyretin amyloidosis—and, specifically, familial amyloidotic polyneuropathy—so they can recognize and manage the disease more easily and discuss it with their patients. We provide guidance on making a definitive diagnosis, explain methods for disease staging and evaluation of disease progression, and discuss symptom mitigation and treatment strategies, including liver transplant and several pharmacotherapies that have shown promise in clinical trials. PMID:23425518

[Infant botulism: case report and review].

PubMed

Arriagada S, Daniela; Wilhelm B, Jan; Donoso F, Alejandro

2009-04-01

Botulism is a rare disease in Chile and of the known clinical presentation, infant botulism is the most common. We report the case of a previously healthy seven month old male infant with a two weeks history of rinorrea, cough, fatigue, constipation and progressive weakness after the consumption of honey. Stool cultures were positive for Clostridium botulinum group 1 type A and electromyography was compatible with the diagnosis. The patient evolved with arterial hypertension, interpreted as secondary to autonomic dysfunction, which responded to calcium channel blockers. Muscle tone improved progressively during the following four weeks. Infant botulism is a potentially fatal disease; diagnosis can be difficult given the broad clinical manifestations. Prevention should focus on education of parents of infants as well as medical personnel.

[Clinical end-points and surrogate markers of pulmonary arterial hypertension in the light of evidence-based treatment].

PubMed

Can, Mehmet Mustafa; Kaymaz, Cihangir

2010-08-01

Pulmonary arterial hypertension (PAH) is a rare, fatal and progressive disease. There is an acceleration in the advent of new therapies in parallel to the development of the knowledge about etiogenesis and pathogenesis of PAH. Therefore, to optimize the goals of PAH-specific treatment and to determine the time to shift from monotherapy to combination therapy, simple, objective and reproducible end-points, which may predict the disease severity, progression rate and life expectancy are needed. The adventure of end points in PAH has started with six minute walk distance and functional capacity, and continues with new parameters (biochemical marker, time to clinical worsening, echocardiography and magnetic resonance imaging etc.), which can better reflect the clinical outcome.

A case of fulminant subacute sclerosing panencephalitis presenting with acute myoclonic-astatic epilepsy.

PubMed

Magurano, Fabio; Marella, Gian Luca; Marchi, Antonella; Filia, Antonietta; Marsella, Luigi Tonino; Potenza, Saverio; Massa, Roberto; Bucci, Paola; Baggieri, Melissa; Nicoletti, Loredana

2017-01-01

The neurologic sequelae post-measles are less common than other complications measles-related and can lead to severe disability or death: primary measles encephalitis (PME), acute post-infectious measles encephalomyelitis (APME), measles inclusion body encephalitis (MIBE), and subacute sclerosing panencephalitis (SSPE). SSPE syndrome can affect people years from the acute measles virus infection, as result of the persistence of defective viral particles in brain cells. Clinical onset typically manifests with progressive intellectual deterioration, behavioral changes, and myoclonic jerks. The course of SSPE in the majority of affected children is that of a progressive worsening with fatal outcome within two years. This report described an Italian case of fulminant SSPE syndrome that led to death within few months from the initial onset.

Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults.

PubMed

Olar, Adriana; Raghunathan, Aditya; Albarracin, Constance T; Aldape, Kenneth D; Cahill, Daniel P; Powell, Suzanne Z; Goodman, J Clay; Fuller, Gregory N

2012-06-01

Advanced age and contrast enhancement portend a poor prognosis in diffuse glioma (DG). Diffuse glioma may present as nonenhancing tumors that rapidly progress in weeks to months to a pattern of ring enhancement, characteristic of glioblastoma (GBM). Mutations involving isocitrate dehydrogenase 1 (IDH1) have recently emerged as important diagnostic and prognostic markers in DG. R132H is the most common mutation, expressed in more than 80% of DG and secondary GBM but in less than 10% of primary GBM. Adults older than 50 years with nonenhancing, rapidly progressing DG were identified. A comparison group comprised randomly selected, age-matched patients with nonenhancing, nonprogressing DG. Isocitrate dehydrogenase 1 status was evaluated using anti-IDH1-R132H antibodies (Dianova, Hamburg, Germany). The results were correlated with the clinical outcomes. We identified 4 patients who presented with nonenhancing DG that rapidly progressed to ring-enhancing lesions that were subsequently diagnosed on surgical resection as GBM. This group showed absent IDH1-R132H expression, which is characteristic of primary GBM. The comparison group of 5 patients presented with nonenhancing, nonprogressing DG, and all 5 tumors showed IDH1-R132H expression. In conclusion, negative IDH1-R132H mutation status in nonenhancing DG of older adults is a poor prognostic factor associated with rapid progression to ring-enhancing GBM. The shorter interval of progression and negative IDH1-R132H mutation status suggest a similar molecular pathway as seen in primary GBM. Copyright © 2012 Elsevier Inc. All rights reserved.

Whole milk intake is associated with prostate cancer-specific mortality among U.S. male physicians.

PubMed

Song, Yan; Chavarro, Jorge E; Cao, Yin; Qiu, Weiliang; Mucci, Lorelei; Sesso, Howard D; Stampfer, Meir J; Giovannucci, Edward; Pollak, Michael; Liu, Simin; Ma, Jing

2013-02-01

Previous studies have associated higher milk intake with greater prostate cancer (PCa) incidence, but little data are available concerning milk types and the relation between milk intake and risk of fatal PCa. We investigated the association between intake of dairy products and the incidence and survival of PCa during a 28-y follow-up. We conducted a cohort study in the Physicians' Health Study (n = 21,660) and a survival analysis among the incident PCa cases (n = 2806). Information on dairy product consumption was collected at baseline. PCa cases and deaths (n = 305) were confirmed during follow-up. The intake of total dairy products was associated with increased PCa incidence [HR = 1.12 (95% CI: 0.93, 1.35); >2.5 servings/d vs. ≤0.5 servings/d]. Skim/low-fat milk intake was positively associated with risk of low-grade, early stage, and screen-detected cancers, whereas whole milk intake was associated only with fatal PCa [HR = 1.49 (95% CI: 0.97, 2.28); ≥237 mL/d (1 serving/d) vs. rarely consumed]. In the survival analysis, whole milk intake remained associated with risk of progression to fatal disease after diagnosis [HR = 2.17 (95% CI: 1.34, 3.51)]. In this prospective cohort, higher intake of skim/low-fat milk was associated with a greater risk of nonaggressive PCa. Most importantly, only whole milk was consistently associated with higher incidence of fatal PCa in the entire cohort and higher PCa-specific mortality among cases. These findings add further evidence to suggest the potential role of dairy products in the development and prognosis of PCa.

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis

PubMed Central

Farci, Patrizia; Wollenberg, Kurt; Diaz, Giacomo; Engle, Ronald E.; Lai, Maria Eliana; Klenerman, Paul; Purcell, Robert H.; Pybus, Oliver G.; Alter, Harvey J.

2012-01-01

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis. PMID:22829669

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis.

PubMed

Farci, Patrizia; Wollenberg, Kurt; Diaz, Giacomo; Engle, Ronald E; Lai, Maria Eliana; Klenerman, Paul; Purcell, Robert H; Pybus, Oliver G; Alter, Harvey J

2012-09-04

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis.

Factors Implicated in Safety-related Firefighter Fatalities.

PubMed

Kahn, Steven A; Palmieri, Tina L; Sen, Soman; Woods, Jason; Gunter, Oliver L

Firefighting is wrought with risk, as 80-100 firefighters (FFs) die on the job each year in the United States. Many of the fatalities have been analyzed by the National Institute for Occupational Safety and Health (NIOSH) to determine contributing factors. The purpose of this study is to determine variables that put FFs at risk for potentially preventable workplace mortality such as use of personal protective equipment (PPE), seat belts, and appropriate training/fitness/clearance for duty. The NIOSH FF Fatality Database reports from 2009 to 2014 were analyzed. Data including age, gender, years on the job, weather, other calls on the same shift, and department type were compared between FFs who employed PPE, seat belts, or wellness/fitness and those who did not. A second group of FFs was determined by NIOSH to have inexperience, lack of training, or inappropriate clearance for duty implicated in their fatalities. Comparisons for the second group were between those whose department used training and safety-related standard operating protocols and those who did not. In 84/176 deaths, PPE/seat belts/fitness was implicated in the fatality. Lack of PPE was more likely on clear days (P = .03) but less likely on cloudy and windy days (P < .001). These FFs dying with lack of PPE had more time on the job in a single department, 18 vs 13 years (P = .03), and more time in a volunteer department, 17 vs 8 years (P < .01). Being deployed on another call during the same shift was associated with lack of PPE-34 vs 16% of those who had not been on another call (P = .005). Lack of training, experience, or medical clearance was implicated in fatalities for 100/176 FFs. FFs who worked in departments that lacked standard operating protocols for respirator fit testing, PPE, fitness testing, rapid intervention, medical clearance, safety/distress alarms, vehicle maintenance, or incident command were statistically more likely to have lack of experience/training/clearance implicated in the fatality. Good weather during a call and more years on the job, particularly in a volunteer department, are associated with FF mortality related to unsafe practices. These factors might create an air of complacency that puts FFs at risk for safety-related omissions. Having been on a recent call may create distraction or fatigue that puts FF at risk during subsequent calls. Lack of key safety-related protocols appears to put FFs at risk of mortality, and the risk may be increasing over time. Further study and prevention efforts from multidisciplinary groups are needed to better understand and combat this problem.

Studies of Genetic Variation in the Aids Virus: Relevance to Disease Pathogenesis, Anti-viral Therapy, and Vaccine Development

DTIC Science & Technology

1988-03-15

variation among independent isolates of Human Immunodeficiency Virus Type 1 (HIV-1) is a widely recognized property of the virus ’- . The molecular...other lentiviral systems including eauine infectious anemia virus (EIAV), visna virus, and simian immunodeficiency virus (SIV)’ " 9. For EIAV, it is clear...tailed macaque that possesses altered biologic and antigenic properties leading to a broader host-range and a rapid, fatal immunodeficiency syndrome

[Staphylococcal toxic shock syndrome at a chronic hemodialysis].

PubMed

Alaoui, Hassan; Belhadj, Ayoub; Aissaoui, Younes; Seddiki, Rachid; Zoubir, Mohamed; Bougalem, Mohamed

2017-01-01

Staphylococcal toxic shock syndrome is an acute and systemic infectious syndrome associated with the super-antigenic activity of staphylococcal toxins. It is a pathology that is rather rare but remains burdened with a considerable mortality despite the therapeutic management. The gateway is usually cutaneous with secondary bacteremic spread could be subject to preventive measures. We report the case of a rapidly fatal staphylococcal toxic shock, developed in a chronic hemodialysis whose entry from the arteriovenous fistula was suspected.

Estimating shaking-induced casualties and building damage for global earthquake events: a proposed modelling approach

USGS Publications Warehouse

So, Emily; Spence, Robin

2013-01-01

Recent earthquakes such as the Haiti earthquake of 12 January 2010 and the Qinghai earthquake on 14 April 2010 have highlighted the importance of rapid estimation of casualties after the event for humanitarian response. Both of these events resulted in surprisingly high death tolls, casualties and survivors made homeless. In the Mw = 7.0 Haiti earthquake, over 200,000 people perished with more than 300,000 reported injuries and 2 million made homeless. The Mw = 6.9 earthquake in Qinghai resulted in over 2,000 deaths with a further 11,000 people with serious or moderate injuries and 100,000 people have been left homeless in this mountainous region of China. In such events relief efforts can be significantly benefitted by the availability of rapid estimation and mapping of expected casualties. This paper contributes to ongoing global efforts to estimate probable earthquake casualties very rapidly after an earthquake has taken place. The analysis uses the assembled empirical damage and casualty data in the Cambridge Earthquake Impacts Database (CEQID) and explores data by event and across events to test the relationships of building and fatality distributions to the main explanatory variables of building type, building damage level and earthquake intensity. The prototype global casualty estimation model described here uses a semi-empirical approach that estimates damage rates for different classes of buildings present in the local building stock, and then relates fatality rates to the damage rates of each class of buildings. This approach accounts for the effect of the very different types of buildings (by climatic zone, urban or rural location, culture, income level etc), on casualties. The resulting casualty parameters were tested against the overall casualty data from several historical earthquakes in CEQID; a reasonable fit was found.

[Rapidly progressive glomerulonephritis: a diagnostic and therapeutic emergency].

PubMed

Halfon, Matthieu; Teta, Daniel; Rotman, Samuel; Pruijm, Menno; Humbert, Antoine

2014-02-26

Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome characterized by kidney damage that can lead to irreversible kidney failure. RPG can be caused by primary glomerular disease or can be part of a systemic autoimmune disorder. All RPG have a similar pathophysiology (proliferation of cells in Bowman's capsule and formation of crescents) and clinical evolution (rapidly progressive kidney failure with proteinuria and an active urine sediment). Immunosuppressive therapy and sometimes plasma exchanges are required. Overall- and kidney survival are closely linked to the blood creatinine level at presentation, the percentage of damaged glomeruli, and to the underlying cause. RPG is therefore a diagnostic and therapeutic emergency that needs quick referral to a nephrologist.

Fatality rates of the M w ~8.2, 1934, Bihar-Nepal earthquake and comparison with the April 2015 Gorkha earthquake

NASA Astrophysics Data System (ADS)

Sapkota, Soma Nath; Bollinger, Laurent; Perrier, Frédéric

2016-03-01

Large Himalayan earthquakes expose rapidly growing populations of millions of people to high levels of seismic hazards, in particular in northeast India and Nepal. Calibrating vulnerability models specific to this region of the world is therefore crucial to the development of reliable mitigation measures. Here, we reevaluate the >15,700 casualties (8500 in Nepal and 7200 in India) from the M w ~8.2, 1934, Bihar-Nepal earthquake and calculate the fatality rates for this earthquake using an estimation of the population derived from two census held in 1921 and 1942. Values reach 0.7-1 % in the epicentral region, located in eastern Nepal, and 2-5 % in the urban areas of the Kathmandu valley. Assuming a constant vulnerability, we obtain, if the same earthquake would have repeated in 2011, fatalities of 33,000 in Nepal and 50,000 in India. Fast-growing population in India indeed must unavoidably lead to increased levels of casualty compared with Nepal, where the population growth is smaller. Aside from that probably robust fact, extrapolations have to be taken with great caution. Among other effects, building and life vulnerability could depend on population concentration and evolution of construction methods. Indeed, fatalities of the April 25, 2015, M w 7.8 Gorkha earthquake indicated on average a reduction in building vulnerability in urban areas, while rural areas remained highly vulnerable. While effective scaling laws, function of the building stock, seem to describe these differences adequately, vulnerability in the case of an M w >8.2 earthquake remains largely unknown. Further research should be carried out urgently so that better prevention strategies can be implemented and building codes reevaluated on, adequately combining detailed ancient and modern data.

Maternal death from stroke: a thirty year national retrospective review.

PubMed

Foo, Lin; Bewley, Susan; Rudd, Anthony

2013-12-01

In the United Kingdom (UK), the maternal mortality rate from stroke is reported at 0.3/100,000 deliveries, but only antenatal data have previously been reviewed. We hypothesise that the true rate is much higher due to a propensity for stroke occurring in the post-partum period, and that the rate will rise in parallel with trends of increasing maternal age and medical co-morbidities. Our objectives are to investigate the UK stroke mortality rate in pregnancy and the puerperium, and to examine temporal changes in fatal maternal strokes over a 30 year period. Retrospective review of stroke-related maternal deaths reported to the UK confidential enquiries into maternal death between 1979 and 2008, encompassing 21,514,457 maternities. In accordance with the ICD.10 classification, cases were divided into direct or indirect deaths. Late and coincidental deaths were not included in analyses. Lessons from sub-standard care associated with maternal death from stroke were collated. In 1979-2008 there were 347 maternal deaths from stroke: 139 cases were direct deaths, i.e. the fatal stroke was a direct result of pregnancy. The incidence of fatal stroke is relatively constant at 1.61/100,000 maternities, with a 13.9% (95% CI 12.6-15.3) proportional mortality rate. Intracranial haemorrhage was the single greatest cause of maternal death from stroke. This is the largest UK study examining the incidence of fatal maternal stroke in pregnancy and the puerperium. Our results highlight the high proportion of women who die from stroke in the puerperium. Sub-standard care featured especially in regard to management of dangerously high systolic blood pressure levels. These deaths highlight the importance of education in managing rapid-onset hypertension and superimposed coagulopathies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

DTIC Science & Technology

2015-11-01

increased PhScN potency as a result of preventing endoproteolytic degradation. Finally, the in vivo lung extravasation and colonization data, as well as...successful colonization are late stages in breast cancer progression that are ultimately fatal. Hence, prevention of extravasation which leads to colony...Award Number: TITLE: “Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma

The Role of ERG and CXCR4 in Prostate Cancer Progression

DTIC Science & Technology

2010-06-01

Attard, G., Clark, J., Ambroisine, L., Fisher, G., Kovacs, G., Flohr, P., Berney , D., Foster, C. S., Fletcher, A., Gerald, W. L., Moller, H., Reuter...Parker, M. D., Foster, C. S., Berney , D., Kovacs, G., and Cooper, C. S. Complex patterns of ETS gene alteration arise during cancer development in...Kovacs G, Flohr P, Berney D, Foster CS, Fletcher A, Gerald WL, et al. (2008). Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal

Fatal extraintestinal toxoplasmosis in a young male cat with enlarged mesenteric lymph nodes

PubMed Central

Cohen, Tamara M.; Blois, Shauna; Vince, Andrew R.

2016-01-01

A 22-month-old indoor/outdoor neutered male domestic short-haired cat had a history of progressive lethargy, vomiting, and decreased appetite. Abdominal ultrasound revealed an irregular hyperechoic mass in the mid-abdomen. He was unresponsive to symptomatic medical management and was euthanized after 3 days of hospitalization. A diagnosis of disseminated extraintestinal toxoplasmosis was made based on the finding of intracytoplasmic protozoan parasites on histopathological examination of mesenteric lymph nodes, hepatic and intestinal samples, and on immunohistochemistry. PMID:27152033

Fatal extraintestinal toxoplasmosis in a young male cat with enlarged mesenteric lymph nodes.

PubMed

Cohen, Tamara M; Blois, Shauna; Vince, Andrew R

2016-05-01

A 22-month-old indoor/outdoor neutered male domestic short-haired cat had a history of progressive lethargy, vomiting, and decreased appetite. Abdominal ultrasound revealed an irregular hyperechoic mass in the mid-abdomen. He was unresponsive to symptomatic medical management and was euthanized after 3 days of hospitalization. A diagnosis of disseminated extraintestinal toxoplasmosis was made based on the finding of intracytoplasmic protozoan parasites on histopathological examination of mesenteric lymph nodes, hepatic and intestinal samples, and on immunohistochemistry.

MRI and MR spectroscopy findings of a case of subacute sclerosing panencephalitis affecting the corpus callosum

PubMed Central

Öztürk, Mehmet; Sığırcı, Ahmet; Yakıncı, Cengiz

2015-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressive, fatal, inflammatory and neurodegenerative disease that is seen mostly in children and young adolescents, and primarily affects the parieto-occipital lobes. The corpus callosum, cerebellum and basal ganglia are less frequently involved. MR spectroscopy (MRS) may illustrate the pathophysiological features of SSPE. To the best of our knowledge, this is the second report of MRS findings of corpus callosum involvement in a stage 3 SSPE case. PMID:26163552

A dose-responsive model of smoke inhalation injury. Severity-related alteration in cardiopulmonary function.

PubMed Central

Shimazu, T; Yukioka, T; Hubbard, G B; Langlinais, P C; Mason, A D; Pruitt, B A

1987-01-01

The dose responsiveness of selected physiologic indices was studied in a sheep model of smoke inhalation injury. In this model, graded severity of injury was achieved by changing the contact time with smoke (defined by "unit"), whereas other variables were kept constant. Blood gas and cardiopulmonary indices were measured in 70 sheep, including 12 controls, either 24 or 72 hours after exposure to 3, 6, 9, 12, 15, or 18 units of smoke. A 12-unit dose of smoke was fatal within 72 hours and an 18-unit dose was fatal within 24 hours. The best correlation between smoke dose and response was observed in arterial oxygen tension 24 hours after exposure. At 24 hours, most of the cardiopulmonary indices showed significant change only after a 12-unit exposure. Although the exact shape of the dose-response curve could not be defined, sigmoid or curved linear shape was suggested, reflecting the progressive deterioration. Images Fig. 3. Fig. 4A. Fig. 4B. PMID:3606236

Fatal course of takotsubo cardiomyopathy in a female with recurrent Clostridium difficile infection.

PubMed

Elikowski, Waldemar; Małek-Elikowska, Małgorzata; Lisiecka, Monika; Mozer-Lisewska, Iwona

2017-06-23

Among diverse triggering factors of stress-induced takotsubo cardiomyopathy (TC), a viral or bacterial infection is rarely observed. Sepsis is an exception, regardless of the etiologic pathogen, in which case an excess of catecholamines may result in acute left ventricular dysfunction. TC precipitated by Clostridium difficile infection (CDI) has been reported only in two patients so far. The authors describe another case of TC triggered this time by recurrent C. difficile colitis which occurred in a 72-yearold female. Severe heart failure developed on the second day of a new episode of diarrhea. Echocardiography revealed apical ballooning, a typical form of TC, while the coronary arteries in coronary angiography were normal. Despite proper treatment of CDI, the course of the disease was fatal due to heart failure progression. In considerations of TC pathogenesis in the case presented, the impact of C. difficile toxins should be taken into account. One should remember about the potential extraintestinal complications of CDI, including sudden myocardial depression.

Hypertensive chronic kidney disease in African Americans: Strategies for improving care

PubMed Central

MARTINS, DAVID; AGODOA, LAWRENCE; NORRIS, KEITH C.

2013-01-01

African Americans have a disproportionate burden of chronic kidney disease (CKD), which tends to have an earlier onset and a more rapid progression in this population. Many of the factors responsible for the rapid progression of CKD in African Americans are detectable by screening and are modifiable with prompt therapy. PMID:23027732

Significant air embolism: A possibility even with collapsible intravenous fluid containers when used with rapid infuser system

PubMed Central

Pant, Deepanjali; Narani, Krishan Kumar; Sood, Jayashree

2010-01-01

Significant venous air embolism may develop acutely during the perioperative period due to a number of causes such as during head and neck surgery, spinal surgery, improper central venous and haemodialysis catheter handling, etc. The current trend of using self collapsible intravenous (IV) infusion bags instead of the conventional glass or plastic bottles has several advantages, one of thaem being protection against air embolism. We present a 56-year-old man undergoing kidney transplantation, who developed a near fatal venous air embolism during volume resuscitation with normal saline in collapsible IV bags used with rapid infuser system. To our knowledge, this problem with collapsible infusion bags has not been reported earlier. PMID:20532073

[Fatal alveolar haemorrhage following a "bang" of cannabis].

PubMed

Grassin, F; André, M; Rallec, B; Combes, E; Vinsonneau, U; Paleiron, N

2011-09-01

The new methods of cannabis consumption (home made water pipe or "bang") may be responsible for fatal respiratory complications. We present a case, with fatal outcome, of a man of 19 years with no previous history other than an addiction to cannabis using "bang". He was admitted to intensive care with acute dyspnoea. A CT scan showed bilateral, diffuse alveolar shadowing. He was anaemic with an Hb of 9.3g/l. Bronchoalveolar lavage revealed massive alveolar haemorrhage. Investigations for infection and immunological disorder were negative and toxicology was negative except for cannabis. Antibiotic treatment was given and favourable progress allowed early discharge. Death occurred 15 days later due to alveolar haemorrhage following a further "bang" of cannabis. Autopsy showed toxic alveolar haemorrhage. The probable mechanism is pulmonary damage due to acid anhydrides released by the incomplete combustion of cannabis in contact with plastic. These acids have a double effect on the lungs: a direct toxicity with severe inflammation of the mucosa leading to alveolar haemorrhage and subsequently the acid anhydrides may lead to the syndrome of intra-alveolar haemorrhage and anaemia described in occupational lung diseases by Herbert in Oxford in 1979. It manifests itself by haemoptysis and intravascular haemolysis. We draw attention to the extremely serious potential consequences of new methods of using cannabis, particularly the use of "bang" in homemade plastic materials. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Severe hypertriglyceridemia with pancreatitis: thirteen years' treatment with lomitapide.

PubMed

Sacks, Frank M; Stanesa, Maxine; Hegele, Robert A

2014-03-01

Recurrent pancreatitis is a potentially fatal complication of severe hypertriglyceridemia. Genetic defects and lifestyle risk factors may render this condition unresponsive to current treatments. We report this first case of long-term management of intractable near-fatal recurrent pancreatitis secondary to severe hypertriglyceridemia by a novel use of lomitapide, an inhibitor of microsomal triglyceride transfer protein, recently approved for treatment of familial homozygous hypercholesterolemia. The patient had been hospitalized many times for pancreatitis since age 15 years. Her serum triglyceride level averaged 3900 mg/dL while she received therapy with approved lipid drugs. She is homozygous for a coding mutation (P234L) in lipoprotein lipase, leaving her unable to metabolize triglycerides in chylomicrons and very low density lipoproteins (VLDL). Lomitapide reduces the secretion of chylomicrons and VLDL. Lomitapide, which was started when she was 44 years old after near-fatal pancreatitis, lowered her fasting triglyceride level from greater than 3000 mg/dL to a mean (SD) of 903 (870) mg/dL while she received 30 mg/d and to 524 (265) mg/dL while she received 40 mg/d; eliminated chronic abdominal pain; and prevented pancreatitis. However, fatty liver, present before treatment, progressed to steatohepatitis and fibrosis after 12 to 13 years. Lomitapide prevented pancreatitis in severe intractable hypertriglyceridemia but at a potential long-term cost of hepatotoxicity.

Rapidly Progressive Quadriplegia and Encephalopathy.

PubMed

Wynn, DonRaphael; McCorquodale, Donald; Peters, Angela; Juster-Switlyk, Kelsey; Smith, Gordon; Ansari, Safdar

2016-11-01

A woman aged 77 years was transferred to our neurocritical care unit for evaluation and treatment of rapidly progressive motor weakness and encephalopathy. Examination revealed an ability to follow simple commands only and abnormal movements, including myoclonus, tongue and orofacial dyskinesias, and opsoclonus. Imaging study findings were initially unremarkable, but when repeated, they demonstrated enhancement of the cauda equina nerve roots, trigeminal nerve, and pachymeninges. Cerebrospinal fluid examination revealed mildly elevated white blood cell count and protein levels. Serial electrodiagnostic testing demonstrated a rapidly progressive diffuse sensory motor axonopathy, and electroencephalogram findings progressed from generalized slowing to bilateral periodic lateralized epileptiform discharges. Critical details of her recent history prompted a diagnostic biopsy. Over time, the patient became completely unresponsive with no further abnormal movements and ultimately died. The differential diagnosis, pathological findings, and diagnosis are discussed with a brief review of a well-known yet rare diagnosis.

Progressive Ischemic Stroke due to Thyroid Storm-Associated Cerebral Venous Thrombosis.

PubMed

Tanabe, Natsumi; Hiraoka, Eiji; Hoshino, Masataka; Deshpande, Gautam A; Sawada, Kana; Norisue, Yasuhiro; Tsukuda, Jumpei; Suzuki, Toshihiko

2017-02-23

BACKGROUND Cerebral venous thrombosis (CVT) is a rare but fatal complication of hyperthyroidism that is induced by the hypercoagulable state of thyrotoxicosis. Although it is frequently difficult to diagnose CVT promptly, it is important to consider it in the differential diagnosis when a hyperthyroid patient presents with atypical neurologic symptoms. CASE REPORT A 49-year-old Japanese female with unremarkable medical history came in with thyroid storm and multiple progressive ischemic stroke identified at another hospital. Treatment for thyroid storm with beta-blocker, glucocorticoid, and potassium iodide-iodine was started and MR venography was performed on hospital day 3 for further evaluation of her progressive ischemic stroke. The MRI showed CVT, and anticoagulation therapy, in addition to the anti-thyroid agents, was initiated. The patient's thyroid function was successfully stabilized by hospital day 10 and further progression of CVT was prevented. CONCLUSIONS Physicians should consider CVT when a patient presents with atypical course of stroke or with atypical MRI findings such as high intensity area in apparent diffusion coefficient (ADC) mapping. Not only is an early diagnosis and initiation of anticoagulation important, but identifying and treating the underlying disease is essential to avoid the progression of CVT.

A new method for the production of social fragility functions and the result of its use in worldwide fatality loss estimation for earthquakes

NASA Astrophysics Data System (ADS)

Daniell, James; Wenzel, Friedemann

2014-05-01

A review of over 200 fatality models over the past 50 years for earthquake loss estimation from various authors has identified key parameters that influence fatality estimation in each of these models. These are often very specific and cannot be readily adapted globally. In the doctoral dissertation of the author, a new method is used for regression of fatalities to intensity using loss functions based not only on fatalities, but also using population models and other socioeconomic parameters created through time for every country worldwide for the period 1900-2013. A calibration of functions was undertaken from 1900-2008, and each individual quake analysed from 2009-2013 in real-time, in conjunction with www.earthquake-report.com. Using the CATDAT Damaging Earthquakes Database containing socioeconomic loss information for 7208 damaging earthquake events from 1900-2013 including disaggregation of secondary effects, fatality estimates for over 2035 events have been re-examined from 1900-2013. In addition, 99 of these events have detailed data for the individual cities and towns or have been reconstructed to create a death rate as a percentage of population. Many historical isoseismal maps and macroseismic intensity datapoint surveys collected globally, have been digitised and modelled covering around 1353 of these 2035 fatal events, to include an estimate of population, occupancy and socioeconomic climate at the time of the event at each intensity bracket. In addition, 1651 events without fatalities but causing damage have also been examined in this way. The production of socioeconomic and engineering indices such as HDI and building vulnerability has been undertaken on a country-level and state/province-level leading to a dataset allowing regressions not only using a static view of risk, but also allowing for the change in the socioeconomic climate between the earthquake events to be undertaken. This means that a year 1920 event in a country, will not simply be regressed against a year 2000 event, but normalised. A global human development index (HDI) (life expectancy, education and income) was developed and collected for the first time from 1900-2013 globally on a country and province level allowing for a very useful parameter in the regression. In addition, the occupancy rate from the time of day that the event occurred, as well as population density and individual earthquake attributes like the existence of a foreshock were also examined for the 3004 events in the regression analysis. Where an event has not occurred in a country previously, a regionalisation strategy based on building typologies, seismic code index, building practice, climate, earthquake history and socioeconomic climate is proposed. The result is a set of "social fragility functions" calculating fatalities for use in any country worldwide using the parameters of macroseismic intensity, population, HDI, time of day and occupancy, that provide a robust accurate method, which has not only been calibrated to country level data but to town and city data through time. The estimates will continue to be used in conjunction with Earthquake Report, a non-profit worldwide earthquake reporting website and has shown very promising results from 2010-2013 for rapid estimates of fatalities globally.

Identifying the superior measure of rapid fibrosis for predicting premature cirrhosis after liver transplantation for hepatitis C.

PubMed

Howell, J; Sawhney, R; Angus, P; Fink, M; Jones, R; Wang, B Z; Visvanathan, K; Crowley, P; Gow, P

2013-12-01

Hepatitis C virus (HCV) recurrence post liver transplant is universal, with a subgroup of patients developing rapid hepatic fibrosis. Various clinical definitions of rapid fibrosis (RF) have been used to identify risks for rapid progression, but their comparability and efficacy at predicting adverse outcomes has not been determined. Retrospective data analysis was conducted on 100 adult patients with HCV who underwent liver transplantation at a single center. We measured year 1 fibrosis progression (RF defined as METAVIR F score ≥ 1 at 1-year liver biopsy), time to METAVIR F2-stage fibrosis, and fibrosis rate (calculated using liver biopsies graded by METAVIR scoring F0-4; fibrosis rate = fibrosis stage/year post transplant). RF was defined as ≥ 0.5 units/year. Multivariate analysis revealed that donor age and peak HCV viral load were significant risks for RF, when fibrosis rate was used to define RF. Advanced donor age was a risk for rapid progression to F2-stage fibrosis, whereas genotype 2 or 3 HCV infection was protective. Fibrosis rate had the strongest correlation with time to cirrhosis development (P < 0.0001, r = -0.76) and was the most accurate predictor of rapid graft cirrhosis (P < 0.0001, area under the curve 0.979, sensitivity 100%, specificity 94%). Different measures of RF progression identify different risks for RF and are not directly comparable. Fibrosis rate was the most accurate predictor of rapid graft cirrhosis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Urban occupational health in the Mexican and Latino/Latina immigrant population: A literature review

PubMed Central

Gany, Francesca; Novo, Patricia; Dobslaw, Rebecca; Leng, Jennifer

2017-01-01

Mexican and Latino/Latina immigrants represent a rapidly growing population within the United States. The majority settle in urban areas. As a group, Mexican immigrants typically have low educational attainment and socioeconomic status, and limited English proficiency. These immigrants often find work in hazardous jobs, with high injury and fatality rates. They often have inadequate or no safety training, no personal protective equipment, limited understanding of workers’ rights, job insecurity, fear of report of undocumented status and lack health care benefits. This review includes what has been published on the urban occupational health of this population. The findings suggest that Mexican and Latino/Latina immigrants experience higher rates of workrelated fatalities and injuries compared to other populations, and may be less likely to report such incidents to employers or to apply for workers’ compensation. There is a strong need to develop effective programs to address the health and safety of this vulnerable population. PMID:23468371

Is air pollution causing landslides in China?

NASA Astrophysics Data System (ADS)

Zhang, Ming; McSaveney, Mauri J.

2018-01-01

Air pollution in China often exceeds "unhealthy" levels, but Chinese air is not only a threat from being breathed: the pollutants may also be causing fatal landslides. Very acid rain from severe air pollution falls widely in southwest China, where coal is a major energy source. We discuss where acid rain may provide an unsuspected link between mining and the fatal 2009 Jiweishan landslide in southwest China; it may have reduced the strength of a thin, calcareous, black sapropelic shale in Jiweishan Mountain by removing cementing carbonate minerals and sapropel matrix. Mining beneath the potential slide mass may not have directly triggered the landslide, but collapse of abandoned adits drained a perched aquifer above a regional black-shale aquiclude. Inflow of acid, oxygenated water and nutrients into the aquiclude may have accelerated the reduction of strength of the weakest rocks and consequently led to rapid sliding of a large rock mass on a layer of weathered shale left composed largely of soft, and slippery talc.

Golden Eagle fatalities and the continental-scale consequences of local wind-energy generation

USGS Publications Warehouse

Katzner, Todd E.; Nelson, David M.; Braham, Melissa A.; Doyle, Jacqueline M.; Fernandez, Nadia B.; Duerr, Adam E.; Bloom, Peter H.; Fitzpatrick, Matthew C.; Miller, Tricia A.; Culver, Renee C. E.; Braswell, Loan; DeWoody, J. Andrew

2017-01-01

Renewable energy production is expanding rapidly despite mostly unknown environmental effects on wildlife and habitats. We used genetic and stable isotope data collected from Golden Eagles (Aquila chrysaetos) killed at the Altamont Pass Wind Resource Area (APWRA) in California in demographic models to test hypotheses about the geographic extent and demographic consequences of fatalities caused by renewable energy facilities. Geospatial analyses of δ2H values obtained from feathers showed that ≥25% of these APWRA-killed eagles were recent immigrants to the population, most from long distances away (>100 km). Data from nuclear genes indicated this subset of immigrant eagles was genetically similar to birds identified as locals from the δ2H data. Demographic models implied that in the face of this mortality, the apparent stability of the local Golden Eagle population was maintained by continental-scale immigration. These analyses demonstrate that ecosystem management decisions concerning the effects of local-scale renewable energy can have continental-scale consequences.

Golden Eagle fatalities and the continental-scale consequences of local wind-energy generation.

PubMed

Katzner, Todd E; Nelson, David M; Braham, Melissa A; Doyle, Jacqueline M; Fernandez, Nadia B; Duerr, Adam E; Bloom, Peter H; Fitzpatrick, Matthew C; Miller, Tricia A; Culver, Renee C E; Braswell, Loan; DeWoody, J Andrew

2017-04-01

Renewable energy production is expanding rapidly despite mostly unknown environmental effects on wildlife and habitats. We used genetic and stable isotope data collected from Golden Eagles (Aquila chrysaetos) killed at the Altamont Pass Wind Resource Area (APWRA) in California in demographic models to test hypotheses about the geographic extent and demographic consequences of fatalities caused by renewable energy facilities. Geospatial analyses of δ 2 H values obtained from feathers showed that ≥25% of these APWRA-killed eagles were recent immigrants to the population, most from long distances away (>100 km). Data from nuclear genes indicated this subset of immigrant eagles was genetically similar to birds identified as locals from the δ 2 H data. Demographic models implied that in the face of this mortality, the apparent stability of the local Golden Eagle population was maintained by continental-scale immigration. These analyses demonstrate that ecosystem management decisions concerning the effects of local-scale renewable energy can have continental-scale consequences. © 2016 Society for Conservation Biology.

PubMed

Remmert, Hermann

1970-06-01

Limosina brachystoma can be reared even when the food and substratum (dry leaves of Urtica or almost any other plant) are moistened with 15‰ NaCl p.a. or with 15‰ NaCl plus KCl. Orchestia lives about three weeks if kept on a substratum moistened with a solution of 15‰ NaCl (Food: Fucus).H 2 SO 4 , on the other hand, is fatal especially, for Orchestia.Burning oil gives off pollutants into the surrounding water. These pollutants are fatal for all the animals studied even at very low concentrations. But in air (not in water) these pollutants disappear within one week and the substratum may be colonized again.Crude oil which has floated in the sea for a long time is not any longer poisonous to the animals studied. It does not hinder rapid propagation of all species Larvae of the flies and - to a lesser extent - of the amphipodes rummage in their substratum and disperse a big piece of old crude oil into fine parts throughout the petri dish.

Speed enforcement in China: National, provincial and city initiatives and their success.

PubMed

He, Jie; King, Mark; Watson, Barry; Rakotonirainy, Andry; Fleiter, Judy

2013-01-01

China is motorizing rapidly, with associated urban road development and extensive construction of motorways. Speeding accounts for about 10% of fatalities, which represents a large decrease from a peak of 17.2% in 2004. Speeding has been addressed at a national level through the introduction of laws and procedural requirements in 2004, in provinces either across all road types or on motorways, and at city level. Typically, documentation of speed enforcement programmes has taken place when new technology (i.e. speed cameras) is introduced, and it is likely that many programmes have not been documented or widely reported. In particular, the national legislation of 2004 and its implementation was associated with a large reduction in fatalities attributed to speeding. In Guangdong Province, after using speed detection equipment, motorway fatalities due to speeding in 2005 decreased by 32.5% comparing with 2004. In Beijing, the number of traffic monitoring units which were used to photograph illegal traffic activities such as traffic light violations, speeding and using bus lanes illegally increased to 1958 by April 1, 2009, and in the future such automated enforcement will become the main means of enforcement, expected to account for 60% of all traffic enforcement in Beijing. This paper provides a brief overview of the speeding enforcement programmes in China which have been documented and their successes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fatal acute hepatic failure in a family infected with the hepatitis A virus subgenotype IB

PubMed Central

Yoshida, Yuichi; Okada, Yohei; Suzuki, Akiko; Kakisaka, Keisuke; Miyamoto, Yasuhiro; Miyasaka, Akio; Takikawa, Yasuhiro; Nishizawa, Tsutomu; Okamoto, Hiroaki

2017-01-01

Abstract Rationale: Hepatitis A viral infection is a well-known cause of subclinical or acute self-limited hepatitis. Few cases of hepatitis A virus (HAV)–associated acute liver failure (ALF) have been reported in low HAV endemic countries annually. Patients concerns: To investigate the possible factors that affected the severity of HAV infection, a family cluster infected with the HAV subgenotype IB strain, which is not common in Japan, was described. Diagnoses: This family consisted of five members who all were infected with HAV. Interventions: Four of the five patients hospitalized except for an asymptomatic patient. Outcomes: Two of the five patients, men in their 50s and 60s, developed ALF, and one patient died. Various host factors, including sex (male), age, and a high bilirubin level, may affect the outcomes. Based on viral factors, HAV RNA was higher in the fatal case compared with others, and it decreased within a short period of time. The similarity of the nucleotide sequences was 99.9% among the HAV isolates based on an entire genomic sequence. Deletions and/or insertions on the HAV protein-coding sequences that caused a frameshift were found in surviving cases but not in the fatal case. Lessons: The rapid clearance of increased HAV and the absence of defective HAV might be closely associated with the onset of liver failure. PMID:28858094

Fatal acute hepatic failure in a family infected with the hepatitis A virus subgenotype IB: A case report.

PubMed

Yoshida, Yuichi; Okada, Yohei; Suzuki, Akiko; Kakisaka, Keisuke; Miyamoto, Yasuhiro; Miyasaka, Akio; Takikawa, Yasuhiro; Nishizawa, Tsutomu; Okamoto, Hiroaki

2017-09-01

Hepatitis A viral infection is a well-known cause of subclinical or acute self-limited hepatitis. Few cases of hepatitis A virus (HAV)-associated acute liver failure (ALF) have been reported in low HAV endemic countries annually. To investigate the possible factors that affected the severity of HAV infection, a family cluster infected with the HAV subgenotype IB strain, which is not common in Japan, was described. This family consisted of five members who all were infected with HAV. Four of the five patients hospitalized except for an asymptomatic patient. Two of the five patients, men in their 50s and 60s, developed ALF, and one patient died. Various host factors, including sex (male), age, and a high bilirubin level, may affect the outcomes. Based on viral factors, HAV RNA was higher in the fatal case compared with others, and it decreased within a short period of time. The similarity of the nucleotide sequences was 99.9% among the HAV isolates based on an entire genomic sequence. Deletions and/or insertions on the HAV protein-coding sequences that caused a frameshift were found in surviving cases but not in the fatal case. The rapid clearance of increased HAV and the absence of defective HAV might be closely associated with the onset of liver failure.

Aircraft Research and Technology for Antimisting Kerosene Conference, February 18-19, 1981.

DTIC Science & Technology

1981-06-01

carrier turbine aircraft fatal accidents from 1964 through 1976. Since antimisting fuel is intended to inhibit ignition and flame propagation when fuel is...been shown to be possible and rapid, although costly and complex. One item that should be added at this point is in the event turbine engine power...port side with 0.28 percent FM-9 fuel was ignited by the rocket motors. When the turbine engine separated from the wing, localized fire remained with

Partial deletion of long arm of chromosome 17

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golomb, H.M.; Rowley, J.; Vardiman, J.

Two patients with acute promyelocytic leukemia had an identical chromosomal abnormality detected by fluorescence banding. In each case, the clinical course was rapidly fatal, and was characterized by a lack of response to chemotherapy with cytarabine and thioguanine, and was complicated by disseminated intravascular coagulation. Bone marrow cells from each patient contained 46 chromosomes; in each instance, however, one chromosome 17 had a deletion of almost one half of the proximal portion of the long arm (del(17)(q11q21 or 22)).

Studies of Genetic Variation in the AIDS Virus: Relevance to Disease Pathogenesis Anti-Viral Therapy, and Vaccine Development

DTIC Science & Technology

1990-06-30

lentiviral systems including equine infectious anemia virus (EIAV), visna virus, and simian immunodeficiency virus (SIV) (119,120,154). For EIAV, it is clear...a pig-tailed macaque that possesses altered biologic and antigenic properties leading to a broader host-range and a rapid, fatal immunodeficiency ...envelope/LTR region of a replication-defective variant of feline leukemia virus (FeLV), when introduced into a replication competent construct of FeLV, was

[Prevention of the refeeding syndrome].

PubMed

Martínez Núñez, Maria E; Hernández Muniesa, B

2010-01-01

The refeeding syndrome can be defined as the metabolic alterations developed by the rapid nutrition repletion (oral, enteral as well as parenteral feeding) of severaly malnourished patients. Refeeding syndrome is a potentially fatal clinical condition and it is often underdiagnosed on non-specialized nutrition units. The most important key for its prevention is to identify patients at high risk for developing refeeding syndrome, before nutrition repletion. The present case describes the steps to prevent the refeeding syndrome as well as the clinical recommendations to restart nutrition support.

Clinical Neurogenetics: Amyotrophic Lateral Sclerosis

PubMed Central

Harms, Matthew B.; Baloh, Robert H.

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, about which our understanding is expanding rapidly as its genetic causes are uncovered. The pace of new gene discovery over the last 5 years has accelerated, providing new insights into the pathogenesis of disease and highlighting biological pathways for target for therapeutic development. This article reviews our current understanding of the heritability of ALS, provides an overview of each of the major ALS genes, highlighting their phenotypic characteristics and frequencies as a guide for clinicians evaluating patients with ALS. PMID:24176417

A case report: anti-NMDA receptor encephalitis

PubMed Central

Bhat, Pavan; Ahmed, Ameer; Jolepalem, Preetam; Sittambalam, Charmian

2018-01-01

ABSTRACT N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis is a potentially fatal autoimmune syndrome in which there is antibody production against the NMDAR causing profound dysregulation of neurotransmission. The syndrome is frequently associated with ovarian teratomas and women are disproportionately affected. Patients most often present with a constellation of neuropsychiatric signs and symptoms, including memory loss, hallucinations, and decreased level of consciousness. This condition is lethal if left untreated. Immunotherapy and surgical resection of the culprit malignancy often results in the rapid resolution of symptoms. PMID:29915659

The Effect of an Experimental Missile Wound to the Brain on Brain Electrolytes, Regional Cerebral Blood Flow and Blood Brain Barrier Permeability.

DTIC Science & Technology

1987-02-10

lung: 2 of 76 missile-wounded cats died from fulminant lung failure - C and probable neurogenic pulmonary edema. Phenomena affecting lung function w...have observed at least 3 mild cases of pulmonary decompensation plus 2 fulminating , fatal instances of neurogenic pulmonary edema. These findings suggest...can be artificially elevated owing to their rapid synthesis following decapitation and before freezing. This process itself subjects brain cells to

Developing an Inclusive System in a Rapidly Changing European Society

ERIC Educational Resources Information Center

Drudy, Sheelagh; Kinsella, William

2009-01-01

This paper uses Ireland--one of Europe's most rapidly changing societies--as a case study and examines progress towards an inclusive education system. It explores policy and progress on developing an inclusive system under a number of key headings: social class, ethnicity, gender and disability. On the basis of analysis of official statistics and…

Non-fatal suicidal behaviour in rural Ethiopia: a cross-sectional facility- and population-based study.

PubMed

Fekadu, Abebaw; Medhin, Girmay; Selamu, Medhin; Shiferaw, Tsion; Hailemariam, Maji; Rathod, Sujit D; Jordans, Mark; Teferra, Solomon; Lund, Crick; Breuer, Erica; Prince, Martin; Giorgis, Tedla W; Alem, Atalay; Hanlon, Charlotte

2016-03-22

Injury related to self-harm is one of the leading causes of global disease burden. As a formative work for a programme to implement comprehensive mental healthcare in a rural district in Ethiopia, we determined the 12-month prevalence of non-fatal suicidal behaviour as well as factors associated with this behaviour to understand the potential burden of the behaviour in the district. Population-based (n = 1485) and facility-based (n = 1014) cross-sectional surveys of adults, using standardised, interview-based measures for suicidality (items on suicide from the Composite International Diagnostic Interview), depressive symptoms (the Patient Health Questionnaire) and alcohol use disorders (Alcohol Use Disorder Investigation Test; AUDIT). The overall 12-month prevalence of non-fatal suicidal behaviour, consisting of suicidal ideation, plan and attempt, was 7.9 % (95 % Confidence Interval (CI) = 6.8 % to 8.9 %). The prevalence was significantly higher in the facility sample (10.3 %) compared with the community sample (6.3 %). The 12-month prevalence of suicide attempt was 4.4 % (95 % CI = 3.6 % to 5.3 %), non-significantly higher among the facility sample (5.4 %) compared with the community sample (3.8 %). Over half of those with suicidal ideation (56.4 %) transitioned from suicidal ideation to suicide attempt. Younger age, harmful use of alcohol and higher depression scores were associated significantly with increased non-fatal suicidal behaviours. The only factor associated with transition from suicidal ideation to suicide attempt was high depression score. Only 10.5 % of the sample with suicidal ideation had received any treatment for their suicidal behaviour: 10.8 % of the community sample and 10.2 % of the facility sample. Although help seeking increased with progression from ideation to attempt, there was no statistically significant difference between the groups. Non-fatal suicidal behaviour is an important public health problem in this rural district. A more in-depth understanding of the context of the occurrence of the behaviour, improving access to care and targeting depression and alcohol use disorder are important next steps. The role of other psychosocial factors should also be explored to assist the provision of holistic care.

Maternal and neonatal tetanus

PubMed Central

Thwaites, C Louise; Beeching, Nicholas J; Newton, Charles R

2017-01-01

Maternal and neonatal tetanus is still a substantial but preventable cause of mortality in many developing countries. Case fatality from these diseases remains high and treatment is limited by scarcity of resources and effective drug treatments. The Maternal and Neonatal Tetanus Elimination Initiative, launched by WHO and its partners, has made substantial progress in eliminating maternal and neonatal tetanus. Sustained emphasis on improvement of vaccination coverage, birth hygiene, and surveillance, with specific approaches in high-risk areas, has meant that the incidence of the disease continues to fall. Despite this progress, an estimated 58 000 neonates and an unknown number of mothers die every year from tetanus. As of June, 2014, 24 countries are still to eliminate the disease. Maintenance of elimination needs ongoing vaccination programmes and improved public health infrastructure. PMID:25149223

Could Sirtuin Activities Modify ALS Onset and Progression?

PubMed

Tang, Bor Luen

2017-10-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a complex etiology. Sirtuins have been implicated as disease-modifying factors in several neurological disorders, and in the past decade, attempts have been made to check if manipulating Sirtuin activities and levels could confer benefit in terms of neuroprotection and survival in ALS models. The efforts have largely focused on mutant SOD1, and while limited in scope, the results were largely positive. Here, the body of work linking Sirtuins with ALS is reviewed, with discussions on how Sirtuins and their activities may impact on the major etiological mechanisms of ALS. Moving forward, it is important that the potentially beneficial effect of Sirtuins in ALS disease onset and progression are assessed in ALS models with TDP-43, FUS, and C9orf72 mutations.

Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

PubMed Central

Pandya, Rachna S.; Zhu, Haining; Li, Wei; Bowser, Robert; Friedlander, Robert M.

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression. PMID:23864030

[Subacute sclerosing panencephalitis (SSPE)].

PubMed

Hosoya, Mitsuaki

2011-11-01

Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal central nervous system disorder that results from a persistent SSPE virus infection. The efficacy of inosine pranobex, an antiviral/immunomodulator agent, remains controversial. Intraventricular interferon-alpha combined with oral inosine pranobex slows the progressive course of SSPE, but does not cure the disease. We examined a wide variety of antiviral compounds for their inhibitory effects on SSPE virus strains in vitro and in vivo, and found that ribavirin had potent inhibitory activity against SSPE. We tried to treat SSPE patients first with high-dose intravenous ribavirin therapy, and then with intraventricular ribavirin therapy. Ribavirin therapy seemed to have a certain effect on clinical courses of patients with SSPE. To reach the conclusion that ribavirin therapy is clinically effective, clinical trials on many cases will be required.

Lenalidomide maintenance after first-line therapy for high-risk chronic lymphocytic leukaemia (CLLM1): final results from a randomised, double-blind, phase 3 study.

PubMed

Fink, Anna Maria; Bahlo, Jasmin; Robrecht, Sandra; Al-Sawaf, Othman; Aldaoud, Ali; Hebart, Holger; Jentsch-Ullrich, Kathleen; Dörfel, Steffen; Fischer, Kirsten; Wendtner, Clemens-Martin; Nösslinger, Thomas; Ghia, Paolo; Bosch, Francesc; Kater, Arnon P; Döhner, Hartmut; Kneba, Michael; Kreuzer, Karl-Anton; Tausch, Eugen; Stilgenbauer, Stephan; Ritgen, Matthias; Böttcher, Sebastian; Eichhorst, Barbara; Hallek, Michael

2017-10-01

The combined use of genetic markers and detectable minimal residual disease identifies patients with chronic lymphocytic leukaemia with poor outcome after first-line chemoimmunotherapy. We aimed to assess lenalidomide maintenance therapy in these high-risk patients. In this randomised, double-blind, phase 3 study (CLLM1; CLL Maintenance 1 of the German CLL Study Group), patients older than 18 years and diagnosed with immunophenotypically confirmed chronic lymphocytic leukaemia with active disease, who responded to chemoimmunotherapy 2-5 months after completion of first-line therapy and who were assessed as having a high risk for an early progression with at least a partial response after four or more cycles of first-line chemoimmunotherapy, were eligible if they had high minimal residual disease levels or intermediate levels combined with an unmutated IGHV gene status or TP53 alterations. Patients were randomly assigned (2:1) to receive either lenalidomide (5 mg) or placebo. Randomisation was done with a fixed block size of three, and was stratified according to the minimal residual disease level achieved after first-line therapy. Maintenance was started with 5 mg daily, and was escalated to the target dose of 15 mg. If tolerated, medication was administered until disease progression. The primary endpoint was progression-free survival according to an independent review. The pre-planned interim analysis done by intention to treat was done after 20% of the calculated progression-free survival events. This study is registered with ClinicalTrials.gov, number NCT01556776; treatment in the lenalidomide group is still ongoing. Between July 5, 2012, and March 15, 2016, 468 previously untreated patients with chronic lymphocytic leukaemia were screened for the study; 379 (81%) were not eligible. Recruitment was closed prematurely due to poor accrual after 89 of 200 planned patients were randomly assigned: 60 (67%) enrolled patients were assigned to the lenalidomide group and 29 (33%) to the placebo group, of whom 56 (63%) received lenalidomide and 29 (33%) placebo, with a median of 11·0 (IQR 4·5-20·5) treatment cycles at data cutoff. After a median observation time of 17·9 months (IQR 9·1-28·1), the hazard ratio for progression-free survival assessed by an independent review was 0·168 (95% CI 0·074-0·379). Median progression-free survival was 13·3 months (95% CI 9·9-19·7) in the placebo group and not reached (95% CI 32·3-not evaluable) in the lenalidomide group. The most frequent adverse events were skin disorders (35 patients [63%] in the lenalidomide group vs eight patients [28%] in the placebo group), gastrointestinal disorders (34 [61%] vs eight [28%]), infections (30 [54%] vs 19 [66%]), haematological toxicity (28 [50%] vs five [17%]), and general disorders (28 [50%] vs nine [31%]). One fatal adverse event was reported in each of the treatment groups (one [2%] patient with fatal acute lymphocytic leukaemia in the lenalidomide group and one patient (3%) with fatal multifocal leukoencephalopathy in the placebo group). Lenalidomide is an efficacious maintenance therapy reducing the relative risk of progression in first-line patients with chronic lymphocytic leukaemia who do not achieve minimal residual disease negative disease state following chemoimmunotherapy approaches. The toxicity seems to be acceptable considering the poor prognosis of the eligible patients. The trial independently confirms the clinical significance of a novel, minimal residual disease-based algorithm to predict short progression-free survival, which might be incorporated in future clinical trials to identify candidates for additional maintenance treatment. Celgene Corporation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Is toxicity of PMMA (paramethoxymethamphetamine) associated with cytochrome P450 pharmacogenetics?

PubMed

Vevelstad, Merete; Øiestad, Elisabeth Leere; Bremer, Sara; Bogen, Inger Lise; Zackrisson, Anna-Lena; Arnestad, Marianne

2016-04-01

In 2010-2013, 29 fatal intoxications related to the designer drug paramethoxymethamphetamine (PMMA, 4-methoxymethamphetamine) occurred in Norway. The current knowledge about metabolism and toxicity of PMMA in humans is limited. Metabolism by the polymorphic cytochrome P450 (CYP) 2D6 enzyme to the psychoactive metabolite 4-hydroxymethamphetamine (OH-MA), and possibly by additional enzymes, is suggested to be involved in its toxicity. The aim of this work was to study the association between CYP genetics, PMMA metabolism and risk of fatal PMMA toxicity in humans. The frequency distribution of clinically relevant gene variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A5, and the phenotypic blood CYP2D6 metabolic ratio (OH-MA/PMMA) in particular, were compared in fatal PMMA intoxications (n=17) and nonfatal PMMA abuse controls (n=30), using non-abusers (n=305) as references for the expected genotype frequencies in the Norwegian population. Our study demonstrated that the CYP2D6 enzyme and genotype are important in the metabolism of PMMA to OH-MA in humans, but that other enzymes are also involved in this biotransformation. In the fatal PMMA intoxications, the blood concentrations of PMMA were higher and the CYP2D6 metabolic ratios were lower, than in the nonfatal PMMA abuse controls (median (range) 2.1 (0.03-5.0) vs 0.3 (0.1-0.9) mg/L, and ratio 0.6 (0.0-4.6) vs 2.1 (0.2-7.4) p=0.021, respectively). Overall, our findings indicated that, in most cases, PMMA death occurred rapidly and at an early stage of PMMA metabolism, following the ingestion of large and toxic PMMA doses. We could not identify any genetic CYP2D6, CYP2C9, CYP2C19 or CYP3A5 predictive marker on fatal toxicity of PMMA in humans. The overrepresentation of the CYP2D6 poor metabolizer (PM) genotype found in the nonfatal PMMA abuse controls warrants further investigations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Fatal and non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone.

PubMed

Kelty, Erin; Hulse, Gary

2017-08-01

Illicit opioid use is associated with high rates of fatal and non-fatal opioid overdose. This study aims to compare rates of fatal and serious but non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone, and to identify risk factors for fatal opioid overdose. Opioid dependent patients treated with methadone (n=3515), buprenorphine (n=3250) or implant naltrexone (n=1461) in Western Australia for the first time between 2001 and 2010, were matched against state mortality and hospital data. Rates of fatal and non-fatal serious opioid overdoses were calculated and compared for the three treatments. Risk factors associated with fatal opioid overdose were examined using multivariate cox proportional hazard models. No significant difference was observed between the three groups in terms of crude rates of fatal or non-fatal opioid overdoses. During the first 28days of treatment, rates of non-fatal opioid overdose were high in all three groups, as were fatal opioid overdoses in patients treated with methadone. However, no fatal opioid overdoses were observed in buprenorphine or naltrexone patients during this period. Following the first 28 days, buprenorphine was shown to be protective, particularly in terms of non-fatal opioid overdoses. After the cessation of treatment, rates of fatal and non-fatal opioid overdoses were similar between the groups, with the exception of lower rates of non-fatal opioid overdose in the naltrexone treated patients compared with the methadone treated patients. After the commencement of treatment, gender, and hospitalisations with a diagnosis of opioid poisoning, cardiovascular or mental health problems were significant predictors of subsequent fatal opioid overdose. Rates of fatal and non-fatal opioid overdose were not significantly different in patients treated with methadone, buprenorphine or implant naltrexone. Gender and prior cause-specific hospitalisations can be used to identify patients at a high risk of fatal opioid overdose. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma.

PubMed

Biankin, Andrew V; Kench, James G; Dijkman, Floriaan P; Biankin, Sandra A; Henshall, Susan M

2003-02-01

Precursor lesions are assuming greater importance in the study of pancreatic ductal adenocarcinoma. As pancreatic cancer is almost universally fatal due to late clinical presentation and biological aggressiveness, characterisation of its precursor lesions may create scope for early diagnosis and improved outcome with conventional therapies as well as the development of novel therapeutic and preventative strategies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous tumours (IPMTs) are thought to be precursor lesions of ductal adenocarcinoma of the pancreas. Recent work has focused on the molecular aberrations associated with these lesions leading to the formulation of a progression model for pancreatic cancer. Progressive histopathological changes along the progression model are associated with aberrations of cell cycle regulatory and growth factor signalling molecules that occur in pancreatic cancer at high frequency and are common to many cancers. Characterisation of these molecular aberrations provides scope for the development of novel diagnostic and treatment strategies that will ultimately impact on the outcome for people who develop pancreatic cancer.

Progressive thalamocortical neuron loss in Cln5 deficient mice: distinct effects in Finnish variant late infantile NCL

PubMed Central

von Schantz, Carina; Kielar, Catherine; Hansen, Stine N; Pontikis, Charlie C; Alexander, Noreen A; Kopra, Outi; Jalanko, Anu; Cooper, Jonathan D

2009-01-01

Finnish variant LINCL (vLINCLFin) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCLFin, these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL. PMID:19385065

Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL.

PubMed

von Schantz, Carina; Kielar, Catherine; Hansen, Stine N; Pontikis, Charlie C; Alexander, Noreen A; Kopra, Outi; Jalanko, Anu; Cooper, Jonathan D

2009-05-01

Finnish variant LINCL (vLINCL(Fin)) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCL(Fin), these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL.

Short-term in situ shading effectively mitigates linear progression of coral-killing sponge Terpios hoshinota.

PubMed

Thinesh, Thangadurai; Meenatchi, Ramu; Pasiyappazham, Ramasamy; Jose, Polpass Arul; Selvan, Muthamizh; Kiran, George Seghal; Selvin, Joseph

2017-01-01

The coral-killing sponge, Terpios hoshinota is a global invasive species that has conquered coral patches within a short span of time, which has led to a significant decline in living coral cover at various geographical locations. In this study, we surveyed the linear progression and impact of the Terpios invasion on live coral patches along Palk Bay, Indian Ocean, from August 2013 to August 2015. The field inventory revealed an extensive fatality rate of 76% as a result of Terpios outbreak. Experimental findings showed that symbiotic cyanobacteria act as a nutritional factory for the aggressive growth of Terpios. Shading hypothetically impairs the nutritional symbiont of the invasive species: the effect of sunlight on cyanobacterial biomass and its influence on Terpios progression over live coral patches was tested through in situ shading experiments. This study showed that artificial shading with cotton fabric could effectively mitigate sponge growth on live coral without affecting coral homeostasis.

Efficacy of superficial temporal artery-middle cerebral artery double anastomoses in a patient with rapidly progressive moyamoya disease: case report.

PubMed

Yokosawa, Michiko; Hayashi, Toshiaki; Shirane, Reizo; Tominaga, Teiji

2014-01-01

Moyamoya disease can be associated with a rapidly progressive course in young patients. This report describes a patient with moyamoya disease who experienced rapid disease progression, resulting in cerebral infarction and a wide area of diminished cerebral perfusion. Double superficial temporal artery (STA)-middle cerebral artery (MCA) anastomoses were utilized to immediately increase cerebral perfusion in the affected area. This case involved a 5-year-old girl who had been diagnosed with moyamoya disease and had undergone STA-MCA anastomosis with indirect bypass in the right hemisphere at the age of 3. At the time of presentation, magnetic resonance (MR) imaging showed cerebral infarction at the left frontal lobe, and MR angiography showed rapidly progressive narrowing of the left MCA that had not been present 3 months prior. N-isopropyl-p-[I123] iodoamphetamine single-photon emission computed tomography (IMP-SPECT) showed markedly decreased uptake in the left hemisphere. She underwent emergent STA-MCA double anastomoses with indirect bypass on the left side. IMP-SPECT showed marked increase in uptake in the left hemisphere. The anterior cerebral artery (ACA) territory adjacent to the cerebral infarction also showed increased uptake on the SPECT. Postoperatively, there were no clinical or radiographic indications of ischemic or hemorrhagic complications. Double anastomoses are effective in quickly and significantly increasing blood flow. The postoperative course in this case was uneventful. Double anastomoses are a surgical option for patients with moyamoya disease who show rapid disease progression, even in those in the acute phase of cerebral infarction.

Efficacy of Superficial Temporal Artery-Middle Cerebral Artery Double Anastomoses in a Patient with Rapidly Progressive Moyamoya Disease: Case Report

PubMed Central

YOKOSAWA, Michiko; HAYASHI, Toshiaki; SHIRANE, Reizo; TOMINAGA, Teiji

2014-01-01

Moyamoya disease can be associated with a rapidly progressive course in young patients. This report describes a patient with moyamoya disease who experienced rapid disease progression, resulting in cerebral infarction and a wide area of diminished cerebral perfusion. Double superficial temporal artery (STA)-middle cerebral artery (MCA) anastomoses were utilized to immediately increase cerebral perfusion in the affected area. This case involved a 5-year-old girl who had been diagnosed with moyamoya disease and had undergone STA-MCA anastomosis with indirect bypass in the right hemisphere at the age of 3. At the time of presentation, magnetic resonance (MR) imaging showed cerebral infarction at the left frontal lobe, and MR angiography showed rapidly progressive narrowing of the left MCA that had not been present 3 months prior. N-isopropyl-p-[I123] iodoamphetamine single-photon emission computed tomography (IMP-SPECT) showed markedly decreased uptake in the left hemisphere. She underwent emergent STA-MCA double anastomoses with indirect bypass on the left side. IMP-SPECT showed marked increase in uptake in the left hemisphere. The anterior cerebral artery (ACA) territory adjacent to the cerebral infarction also showed increased uptake on the SPECT. Postoperatively, there were no clinical or radiographic indications of ischemic or hemorrhagic complications. Double anastomoses are effective in quickly and significantly increasing blood flow. The postoperative course in this case was uneventful. Double anastomoses are a surgical option for patients with moyamoya disease who show rapid disease progression, even in those in the acute phase of cerebral infarction. PMID:24584280

Can We Leapfrog? The Potential of Education Innovations to Rapidly Accelerate Progress. Skills for a Changing World

ERIC Educational Resources Information Center

Winthrop, Rebecca; McGivney, Eileen

2017-01-01

Today, examples of rapid, non-linear progress--sometimes called leapfrogging--are evident in a number of sectors. Often, these instances are most obvious in the developing world, where in telecommunications or banking, for example, whole phases of infrastructure and institution-building that other countries had to go through have been by-passed by…

Disseminated necrotic mediastinitis spread from odontogenic abscess: our experience

PubMed Central

Filiaci, Fabio; Riccardi, Emiliano; Mitro, Valeria; Piombino, Pasquale; Rinna, Claudio; Agrillo, Alessandro; Ungari, Claudio

2015-01-01

Summary Aims Deep neck infections are rare but potentially fatal complication of pulpal abscess of the teeth. If an infection can progress rapidly from a toothache to a life threatening infection, then it is critical that dentists be able to recognize the danger signs and identify the patients who are at risk. Mediastinitis is a severe inflammatory process involving the connective tissues that fills the intracellular spaces and surrounds the organs in the middle of the chest. This pathology has both an acute and a chronic form and, in most cases, it has an infectious etiology. This study want to expose the experience acquired in the Oral and Maxillo-facial Sciences Department, Policlinico Umberto I, “Sapienza” University of Rome, regarding two clinical cases of disseminated necrotizing mediastinitis starting from an odontogenic abscess. Methods We report two clinical cases of disseminated necrotic mediastinitis with two different medical and surgical approaches. The radiographic and photographic documentation of the patients was collected in the pre-and post-operatively. All patients underwent a CT scan and MRI. Results Mediastinitis can result from a serious odontogenic abscess, and the extent of its inflammation process must be never underestimated. Dental surgeons play a key role as a correct diagnosis can prevent further increasing of the inflammation process. Conclusions A late diagnosis and an inadequate draining represent the major causes of the elevated mortality rate of disseminated necrotizing mediastinitis. PMID:26330907

A Proposed Physiopathological Pathway to Hyperammonemic Encephalopathy in a Non-Cirrhotic Patient with Fibrolamellar Hepatocellular Carcinoma without Ornithine Transcarbamylase (OTC) Mutation.

PubMed

Surjan, Rodrigo C; Dos Santos, Elizabeth S; Basseres, Tiago; Makdissi, Fabio F; Machado, Marcel A

2017-03-08

BACKGROUND Hyperammonemic encephalopathy is a potentially fatal condition that may progress to irreversible neuronal damage and is usually associated with liver failure or portosystemic shunting. However, other less common conditions can lead to hyperammonemia in adults, such as fibrolamellar hepatocellular carcinoma. Clinical awareness of hyperammonemic encephalopathy in patients with normal liver function is paramount to timely diagnosis, but understanding the underlying physiopathology is decisive to initiate adequate treatment for complete recovery. CASE REPORT A 31-year-old male with fibrolamellar carcinoma and peritoneal carcinomatosis presented with rapid onset hyperammonemic encephalopathy. Despite usual treatment for hepatic encephalopathy, his hyperammonemia was aggravated. A physiopathological pathway to encephalopathy resulting from hepatocellular dysfunction or portosystemic shunting was suspected and proper treatment was initiated, which resulted in complete remission of encephalopathy. Thus, we propose there is a physiopathology path to hyperammonemic encephalopathy in non-cirrhotic patients with fibrolamellar carcinoma independent of ornithine transcarbamylase (OTC) mutation. An ornithine metabolism imbalance resulting from overexpression of Aurora Kinase A as a result of a single, recurrent heterozygous deletion on chromosome 19, common to all fibrolamellar carcinomas, can lead to a c-Myc and ornithine decarboxylase overexpression that results in ornithine transcarboxylase dysfunction with urea cycle disorder and subsequent hyperammonemia. CONCLUSIONS The identification of a physiopathological pathway allowed adequate medical treatment and full patient recovery from severe hyperammonemic encephalopathy.

Combined therapy with gas gangrene antitoxin and recombinant human soluble thrombomodulin for Clostridium perfringens sepsis in a rat model.

PubMed

Hifumi, Toru; Nakano, Daisuke; Chiba, Joe; Takahashi, Motohide; Yamamoto, Akihiko; Fujisawa, Yoshihide; Kawakita, Kenya; Kuroda, Yasuhiro; Nishiyama, Akira

2018-01-01

Cases of Clostridium perfringens septicemia, such as liver abscess, often develop a rapidly progressive intravascular hemolysis and coagulation; the mortality rate with current standard care including antibiotics and surgery is high. Herein, we firstly investigated the effects of gas gangrene antitoxin (GGA) (antitoxin against C. perfringens) and recombinant human soluble thrombomodulin (rTM) on the hemolysis, coagulation status, inflammatory process, and mortality in α-toxin-treated rats. Male 11-week-old Sprague Dawley rats were randomly divided into five groups: control group, α-toxin group, GGA group, rTM group, and combined GGA and rTM (combination group). After α-toxin injection, mortality and platelet counts, and hemolysis were observed for 6 h. The fibrin/fibrinogen degradation products (FDP), and plasma high-mobility group box 1 (HMGB1) were also measured at 6 h. The combination group demonstrated 100% survival compared with 50% survival in the α-toxin group and demonstrated significantly improved hemolysis, platelet counts, and lactate levels compared with those in the α-toxin group (p < .01). The FDP and HMGB1 levels in the combination therapy group were significantly lower than those in the α-toxin group (p < .05). Combination therapy with GGA and rTM administration is applicable as adjunct therapy for fatal C. perfringens sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

PubMed

Marzi, Andrea; Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Igarashi, Manabu; Nakayama, Eri; Kuroda, Makoto; Saijo, Masayuki; Feldmann, Friederike; Brining, Douglas; Feldmann, Heinz; Takada, Ayato

2012-01-01

Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

Recurrently Mutated Genes Differ between Leptomeningeal and Solid Lung Cancer Brain Metastases.

PubMed

Li, Yingmei; Liu, Boxiang; Connolly, Ian David; Kakusa, Bina Wasunga; Pan, Wenying; Nagpal, Seema; Montgomery, Stephen B; Hayden Gephart, Melanie

2018-03-29

When compared with solid brain metastases from NSCLC, leptomeningeal disease (LMD) has unique growth patterns and is rapidly fatal. Patients with LMD do not undergo surgical resection, limiting the tissue available for scientific research. In this study we performed whole exome sequencing on eight samples of LMD to identify somatic mutations and compared the results with those for 26 solid brain metastases. We found that taste 2 receptor member 31 gene (TAS2R31) and phosphodiesterase 4D interacting protein gene (PDE4DIP) were recurrently mutated among LMD samples, suggesting involvement in LMD progression. Together with a retrospective review of the charts of an additional 44 patients with NSCLC LMD, we discovered a surprisingly low number of KRAS mutations (n = 4 [7.7%]) but a high number of EGFR mutations (n = 33 [63.5%]). The median interval for development of LMD from NSCLC was shorter in patients with mutant EGFR (16.3 months) than in patients with wild-type EGFR (23.9 months) (p = 0.017). Targeted analysis of recurrent mutations thus presents a useful complement to the existing diagnostic tool kit, and correlations of EGFR in LMD and KRAS in solid metastases suggest that molecular distinctions or systemic treatment pressure underpin the differences in growth patterns within the brain. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Assessing idiopathic pulmonary fibrosis (IPF) with bronchoscopic OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hariri, Lida P.; Adams, David C.; Colby, Thomas V.; Tager, Andrew M.; Suter, Melissa J.

2016-03-01

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal form of fibrotic lung disease, with a 3 year survival rate of 50%. Diagnostic certainty of IPF is essential to determine the most effective therapy for patients, but often requires surgery to resect lung tissue and look for microscopic honeycombing not seen on chest computed tomography (CT). Unfortunately, surgical lung resection has high risks of associated morbidity and mortality in this patient population. We aim to determine whether bronchoscopic optical coherence tomography (OCT) can serve as a novel, low-risk paradigm for in vivo IPF diagnosis without surgery or tissue removal. OCT provides rapid 3D visualization of large tissue volumes with microscopic resolutions well beyond the capabilities of CT. We have designed bronchoscopic OCT catheters to effectively and safely access the peripheral lung, and conducted in vivo peripheral lung imaging in patients, including those with pulmonary fibrosis. We utilized these OCT catheters to perform bronchoscopic imaging in lung tissue from patients with pulmonary fibrosis to determine if bronchoscopic OCT could successfully visualize features of IPF through the peripheral airways. OCT was able to visualize characteristic features of IPF through the airway, including microscopic honeycombing (< 1 mm diameter) not visible by CT, dense peripheral fibrosis, and spatial disease heterogeneity. These findings support the potential of bronchoscopic OCT as a minimally-invasive method for in vivo IPF diagnosis. However, future clinical studies are needed to validate these findings.

Rapidly Progressive Maxillary Atelectasis.

PubMed

Elkhatib, Ahmad; McMullen, Kyle; Hachem, Ralph Abi; Carrau, Ricardo L; Mastros, Nicholas

2017-07-01

Report of a patient with rapidly progressive maxillary atelectasis documented by sequential imaging. A 51-year-old man, presented with left periorbital and retro-orbital pain associated with left nasal obstruction. An initial computed tomographic (CT) scan of the paranasal sinuses failed to reveal any significant abnormality. A subsequent CT scan, indicated for recurrence of symptoms 11 months later, showed significant maxillary atelectasis. An uncinectomy, maxillary antrostomy, and anterior ethmoidectomy resulted in a complete resolution of the symptoms. Chronic maxillary atelectasis is most commonly a consequence of chronic rhinosinusitis. All previous reports have indicated a chronic process but lacked documentation of the course of the disease. This report documents a patient of rapidly progressive chronic maxillary atelectasis with CT scans that demonstrate changes in the maxillary sinus (from normal to atelectatic) within 11 months.

Infection of hamsters with historical and epidemic BI types of Clostridium difficile.

PubMed

Razaq, Nadia; Sambol, Susan; Nagaro, Kristin; Zukowski, Walter; Cheknis, Adam; Johnson, Stuart; Gerding, Dale N

2007-12-15

North American and European hospitals have reported outbreaks of Clostridium difficile-associated disease with unexpectedly high mortality caused by a newly recognized group of C. difficile strains, group BI. Our objective was to compare, in hamsters, the virulence of a historical nonepidemic BI type, BI1, with that of 2 recent epidemic BI types, BI6 and BI17, and with that of 2 standard toxigenic strains, K14 and 630. For each strain, 10 hamsters were given 1 dose of clindamycin, followed 5 days later with 100 C. difficile spores administered by gastric inoculation. Outcomes were recorded. The hamster model demonstrated variations in mean times from inoculation to death (for BI6, 40 h; for BI1, 48 h; for K14, 49 h; for BI17, 69 h; for 630, 102 h; for BI6, BI1, and K14 vs. 630, P< .01; for BI17 vs. 630, P< .05) and from colonization to death (for BI1, 7 h; for BI17, 13 h; for BI6, 16 h; for K14, 17 h; for 630, 52 h; for BI1, BI17, BI6, and K14 vs. 630, P< .01). Group BI strains were not more rapidly fatal than the standard toxinotype 0 strain K14 but were more rapidly fatal than the standard toxinotype 0 strain 630. BI6, the most common BI type in our collection, was particularly virulent in hamsters, consistently causing death within 48 h of inoculation.

Global earthquake casualties due to secondary effects: A quantitative analysis for improving rapid loss analyses

USGS Publications Warehouse

Marano, K.D.; Wald, D.J.; Allen, T.I.

2010-01-01

This study presents a quantitative and geospatial description of global losses due to earthquake-induced secondary effects, including landslide, liquefaction, tsunami, and fire for events during the past 40 years. These processes are of great importance to the US Geological Survey's (USGS) Prompt Assessment of Global Earthquakes for Response (PAGER) system, which is currently being developed to deliver rapid earthquake impact and loss assessments following large/significant global earthquakes. An important question is how dominant are losses due to secondary effects (and under what conditions, and in which regions)? Thus, which of these effects should receive higher priority research efforts in order to enhance PAGER's overall assessment of earthquakes losses and alerting for the likelihood of secondary impacts? We find that while 21.5% of fatal earthquakes have deaths due to secondary (non-shaking) causes, only rarely are secondary effects the main cause of fatalities. The recent 2004 Great Sumatra-Andaman Islands earthquake is a notable exception, with extraordinary losses due to tsunami. The potential for secondary hazards varies greatly, and systematically, due to regional geologic and geomorphic conditions. Based on our findings, we have built country-specific disclaimers for PAGER that address potential for each hazard (Earle et al., Proceedings of the 14th World Conference of the Earthquake Engineering, Beijing, China, 2008). We will now focus on ways to model casualties from secondary effects based on their relative importance as well as their general predictability. ?? Springer Science+Business Media B.V. 2009.

Fatal fall into a volcanic fumarole.

PubMed

Cantrell, Lee; Young, Michael

2009-01-01

Fatalities secondary to inhalation of volcanic gases in the United States have rarely been reported. We report the deaths of 3 ski patrol members at a popular California ski resort. After a snowstorm, ski patrol members were fencing off a well-known volcanic fumarole when the snow around the vent collapsed. Two members slid into the deep hole and rapidly lost consciousness. A third member carrying oxygen descended into the hole and also lost consciousness. A fourth member affixed an oxygen mask, but still lost consciousness upon descent. The 3 initial victims expired at the scene, while the fourth victim survived. Autopsy results for all 3 were consistent with a suffocation/asphyxiation death. In the case described, the involved fumarole is a well-known source of toxic gases. Atmospheric sampling data dating back decades demonstrate that carbon dioxide levels typically range from 97% to 99%, nitrogen gas from 1% to 3%, and hydrogen sulfide from .004% to .07%. Other gases in smaller concentrations include oxygen, hydrogen, and carbon monoxide. Given the rapidity with which our victims lost consciousness and the historical data available on the Mammoth Mountain Fumarole (MMF), it is plausible that our patients suffered from acute asphyxiation, although the contribution of the directly toxic effects of the gases involved cannot be ruled out. During winter months, snow can build up and disguise volcanic vents and potentially trap toxic fumes to form dangerous, gas-filled pits. Recognition of such potential hazards is essential when working in or venturing into volcanically active areas during the winter.

Genetic Insights in Barrett’s Esophagus and Esophageal Adenocarcinoma

PubMed Central

Reid, Brian J.; Paulson, Thomas G.; Li, Xiaohong

2015-01-01

Beginning in the 1980s, an alarming rise in the incidence of esophageal adenocarcinoma (EA) led to screening of patients with reflux to detect Barrett’s esophagus (BE) and surveillance of BE to detect early EA. This strategy, based on linear progression disease models, resulted in selective detection of BE that does not progress to EA over a lifetime (overdiagnosis) and missed BE that rapidly progresses to EA (underdiagnosis). Here we review the historical thought processes that resulted in this undesired outcome and the transformation in our understanding of genetic and evolutionary principles governing neoplastic progression that has come from application of modern genomic technologies to cancers and their precursors. This new synthesis provides improved strategies for prevention and early detection of EA by addressing the environmental and mutational processes that can determine “windows of opportunity” in time to detect rapidly progressing BE and distinguish it from slowly or non-progressing BE. PMID:26208895

Rapidly progressive internal root resorption: a case report.

PubMed

Keinan, David; Heling, Ilana; Stabholtz, Adam; Moshonov, Joshua

2008-10-01

The etiology of internal root resorption is not fully understandable, trauma and chronic pulpitis are considered the main risk factors. Usually the process is asymptomatic and diagnosed upon routine radiographic examination. This case report presents a rapid progression of internal resorption related directly to traumatic injury. A 16-year-old female arrived at the emergency room after a mild extrusion of the mandibular incisors. The initial treatment included repositioning and splinting of the teeth. Radiographs performed at repositioning and splinting demonstrated normal configuration of the incisor's roots. Ten months later progressive internal resorption of the left mandibular first incisor was diagnosed. While treating this tooth similar process was detected in the right mandibular second incisor and in the mandibular left second incisor. The lower right first incisor reacted inconsistently to vitality test. As a result of the severe and rapidly progressive nature of the process, root canal treatments were performed in all lower incisors. The follow-up radiographs demonstrate arrest of the internal resorption process.

Uremic Solutes in Chronic Kidney Disease and Their Role in Progression.

PubMed

van den Brand, Jan A J G; Mutsaers, Henricus A M; van Zuilen, Arjan D; Blankestijn, Peter J; van den Broek, Petra H; Russel, Frans G M; Masereeuw, Rosalinde; Wetzels, Jack F M

2016-01-01

To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated. Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year) or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated. In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time. Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated.

Low CD1c + myeloid dendritic cell counts correlated with a high risk of rapid disease progression during early HIV-1 infection.

PubMed

Diao, Yingying; Geng, Wenqing; Fan, Xuejie; Cui, Hualu; Sun, Hong; Jiang, Yongjun; Wang, Yanan; Sun, Amy; Shang, Hong

2015-08-19

During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined. EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients. When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/μL) had a 4-fold higher risk of rapid disease progression than those with high CD1c + mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression. During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts.

[Myxedema coma in a patient with type 1 neurofibromatosis: rare association].

PubMed

Sasazawa, Denise Tieko; Tsukumo, Daniela Miti; Lalli, Cristina Alba

2013-12-01

Myxedema coma, a rare but fatal emergency, is an extreme expression of hypothyroidism. We describe a 51-year-old male patient who has discontinued hypothyroidism treatment 10 months earlier and developed lethargy, edema, and cold intolerance symptoms. He also had a previous diagnosis of neurofibromatosis. After admission, he progressed to respiratory insufficiency and coma. The prompt recognition of the condition, thyroid hormone replacement, and management of the complications (hypoventilation, cardiogenic shock associated with swinging heart, adrenal and renal insufficiency and sepsis), resulted in a favorable evolution.

Fatal bilateral dioctophymatosis.

PubMed

Li, Gang; Liu, Caigang; Li, Fang; Zhou, Maoyi; Liu, Xiangyong; Niu, Yuanjie

2010-12-01

Dioctophyma renale is a parasite that frequently occurs in animals but rarely in humans. The present report describes the clinical observations of a D. renale infection in a 51-yr-old woman. Its clinical signs and diagnostic findings were unspecific until giant worms were observed in the urine and histological findings confirmed it was a D. renale infection. She refused treatment and died of bilateral renal function failure. This is the first confirmed report to follow the natural progression of D. renale infection in a human. Here, we discuss a conservative therapeutic approach and features associated with this parasitic infection.

Modeling bladder cancer in mice: opportunities and challenges

PubMed Central

Kobayashi, Takashi; Owczarek, Tomasz B.; McKiernan, James M.; Abate-Shen, Cory

2015-01-01

The prognosis and treatment of bladder cancer have hardly improved in the last 20 years. Bladder cancer remains a debilitating and often fatal disease, and among the most costly cancers to treat. The generation of informative mouse models has the potential to improve our understanding of bladder cancer progression, as well as impact its diagnosis and treatment. However, relatively few mouse models of bladder cancer have been described and particularly few that develop invasive cancer phenotypes. This review focuses on opportunities for improving the landscape of mouse models of bladder cancer. PMID:25533675

MRI and MR spectroscopy findings of a case of subacute sclerosing panencephalitis affecting the corpus callosum.

PubMed

Öztürk, Mehmet; Sığırcı, Ahmet; Yakıncı, Cengiz

2015-07-10

Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressive, fatal, inflammatory and neurodegenerative disease that is seen mostly in children and young adolescents, and primarily affects the parieto-occipital lobes. The corpus callosum, cerebellum and basal ganglia are less frequently involved. MR spectroscopy (MRS) may illustrate the pathophysiological features of SSPE. To the best of our knowledge, this is the second report of MRS findings of corpus callosum involvement in a stage 3 SSPE case. 2015 BMJ Publishing Group Ltd.

Role of the dental team in mass fatality incidents.

PubMed

Fixott, R H; Arendt, D; Chrz, B; Filippi, J; McGivney, J; Warnick, A

2001-04-01

The process of dental identification for a mass fatality incident has unique aspects in comparison with that of a routine dental identification, outside of the obvious increase in the number of victims and responders. The dental team is a small part of a large effort to resolve the incident. Incident command structure applies to the dental team as a unit as well as to the entire organization of the response. Teamwork and planning are essential on all levels. Discussing the casework is limited to the public information officer; only the public information officer is authorized to talk to anyone outside the medical examiner's office. For the team, communication is essential between the team members and between the team and other morgue sections. Daily meetings not only update progress, but also identify and solve problems as they arise. Redundancy and cross-checking occur each step in each section. A core team of trained individuals provides a framework for the use of less experienced members. Use of a dental identification computer program is extremely beneficial, especially as the amount of fragmentation or number of victims increases. Because of the magnitude of the response, the physical and mental stresses require critical incident stress debriefing for all responders, regardless of their experience. The past and future service of the dental profession to the victims of mass fatality incidents and their families is an excellent example of the ideal of service on which the profession is based.

Adverse weather conditions and fatal motor vehicle crashes in the United States, 1994-2012.

PubMed

Saha, Shubhayu; Schramm, Paul; Nolan, Amanda; Hess, Jeremy

2016-11-08

Motor vehicle crashes are a leading cause of injury mortality. Adverse weather and road conditions have the potential to affect the likelihood of motor vehicle fatalities through several pathways. However, there remains a dearth of assessments associating adverse weather conditions to fatal crashes in the United States. We assessed trends in motor vehicle fatalities associated with adverse weather and present spatial variation in fatality rates by state. We analyzed the Fatality Analysis Reporting System (FARS) datasets from 1994 to 2012 produced by the National Highway Traffic Safety Administration (NHTSA) that contains reported weather information for each fatal crash. For each year, we estimated the fatal crashes that were associated with adverse weather conditions. We stratified these fatalities by months to examine seasonal patterns. We calculated state-specific rates using annual vehicle miles traveled data for all fatalities and for those related to adverse weather to examine spatial variations in fatality rates. To investigate the role of adverse weather as an independent risk factor for fatal crashes, we calculated odds ratios for known risk factors (e.g., alcohol and drug use, no restraint use, poor driving records, poor light conditions, highway driving) to be reported along with adverse weather. Total and adverse weather-related fatalities decreased over 1994-2012. Adverse weather-related fatalities constituted about 16 % of total fatalities on average over the study period. On average, 65 % of adverse weather-related fatalities happened between November and April, with rain/wet conditions more frequently reported than snow/icy conditions. The spatial distribution of fatalities associated with adverse weather by state was different than the distribution of total fatalities. Involvement of alcohol or drugs, no restraint use, and speeding were less likely to co-occur with fatalities during adverse weather conditions. While adverse weather is reported for a large number of motor vehicle fatalities for the US, the type of adverse weather and the rate of associated fatality vary geographically. These fatalities may be addressed and potentially prevented by modifying speed limits during inclement weather, improving road surfacing, ice and snow removal, and providing transit alternatives, but the impact of potential interventions requires further research.

Unusual Presentation of Melioidosis in a Case of Pseudoaneurysm of Descending Thoracic Aorta: Review of Two Case Reports

PubMed Central

Padmaja, Kanne; Lakshmi, Vemu; Sudhaharan, Sukanya; Venkata Surya Malladi, Subbalaxmi; Gopal, Palanki; Venkata Ravinuthala, Kumar

2015-01-01

Introduction: Melioidosis is a rapidly fatal infectious disease caused by Burkholderia pseudomallei, an agent of potential biothreat, endemic in several parts of India. Most melioidosis-induced infected aneurysms are located in the abdominal or thoracic aorta. Case Presentation: We reported two unusual cases of melioidosis resulting in pseudoaneurysm of the descending thoracic aorta. In both cases, blood cultures yielded B. pseudomallei. The first patient was managed with resection of aneurysm and reconstruction with Dacron graft followed by medical treatment and was discharged uneventfully. The second patient died within one week of admission before the infecting etiological agent was identified and aneurysmal repair was planned. Conclusions: A high clinical index of suspicion, especially in areas of endemicity is essential for timely management of intracavitary infected pseudoaneurysms caused by B. pseudomallei and use of rapid microbiological techniques, such as bact/alert 3D system, which enables rapid and early recovery of the etiological agent. PMID:26380820

A self-pumping lab-on-a-chip for rapid detection of botulinum toxin.

PubMed

Lillehoj, Peter B; Wei, Fang; Ho, Chih-Ming

2010-09-07

A robust poly(dimethylsiloxane) (PDMS) surface treatment was utilized for the development of a self-pumping lab-on-a-chip (LOC) to rapidly detect minute quantities of toxic substances. One such toxin, botulinum neurotoxin (BoNT), is an extremely lethal substance, which has the potential to cause hundreds of thousands of fatalities if as little as a few grams are released into the environment. To prevent such an outcome, a quick (<45 min) and sensitive detection format is needed. We have developed a self-pumping LOC that can sense down to 1 pg of BoNT type A (in a 1 microL sample) within 15 min in an autonomous manner. The key technologies enabling for such a device are a sensitive electrochemical sensor, an optimized fluidic network and a robust hydrophilic PDMS coating, thereby facilitating autonomous delivery of liquid samples for rapid detection. The stability, simplicity and portability of this device make possible for a storable and distributable system for monitoring bioterrorist attacks.

Complicated acute appendicitis presenting as a rapidly progressive soft tissue infection of the abdominal wall: a case report.

PubMed

Beerle, Corinne; Gelpke, Hans; Breitenstein, Stefan; Staerkle, Ralph F

2016-12-01

We report a case of a rare complication of acute appendicitis with perforation through the abdominal wall. The case points out that an intraabdominal origin should be considered in patients presenting with rapidly spreading soft tissue infections of the trunk. A 58-year-old European woman presented to our hospital with a 1-week history of severe abdominal pain accompanied by rapidly spreading erythema and emphysema of the lower abdomen. On admission, the patient was in septic shock with leukocytosis and elevation of C-reactive protein. Among other diagnoses, necrotizing fasciitis was suspected. Computed tomography showed a large soft tissue infection with air-fluid levels spreading through the lower abdominal wall. During the operation, we found a perforated appendicitis breaking through the fascia and causing a rapidly progressive soft tissue infection of the abdominal wall. Appendicitis was the origin of the soft tissue infection. The abdominal wall was only secondarily involved. Even though perforated appendicitis as an etiology of a rapidly progressive soft tissue infection of the abdominal wall is very rare, it should be considered in the differential diagnosis of abdominal wall cellulitis. The distinction between rapidly spreading subcutaneous infection with abscess formation and early onset of necrotizing fasciitis is often difficult and can be confirmed only by surgical intervention.

The strength of graduated drivers license programs and fatalities among teen drivers and passengers.

PubMed

Morrisey, Michael A; Grabowski, David C; Dee, Thomas S; Campbell, Christine

2006-01-01

The purpose of this study is to investigate the effects of differentially stringent graduated drivers license programs on teen driver fatalities, day-time and night-time teen driver fatalities, fatalities of teen drivers with passengers present, and fatalities among teen passengers. The study uses 1992-2002 data on motor vehicle fatalities among 15-17-year-old drivers from the Fatality Analysis Reporting System to identify the effects of "good", "fair", and "marginal" GDL programs based upon designations by the Insurance Institute for Highway Safety. Analysis is conducted using conditional negative binomial regressions with fixed effects. "Good" programs reduce total fatalities among young drivers by 19.4% (c.i. -33.0%, -5.9%). "Fair" programs reduce night-time young driver fatalities by 12.6% (c.i. -23.9%, -1.2%), but have no effect on day-time fatalities. "Marginal" programs had no statistically meaningful effect on driver fatalities. All three types of programs reduced teen passenger fatalities, but the effects of limitations on the number of passengers appear to have had only minimal effects in reducing fatalities among young drivers themselves. Stronger GDL programs are more effective than weaker programs in reducing teenage motor vehicle fatalities.

Continuous passive motion and its effects on knee flexion after total knee arthroplasty in patients with knee osteoarthritis.

PubMed

Liao, Chun-De; Huang, Yi-Ching; Lin, Li-Fong; Chiu, Yen-Shuo; Tsai, Jui-Chen; Chen, Chun-Lung; Liou, Tsan-Hon

2016-08-01

This study evaluated the effects of continuous passive motion (CPM) on accelerated flexion after total knee arthroplasty (TKA) and whether CPM application measures (i.e. initial angle and daily increment) are associated with functional outcomes. A retrospective investigation was conducted at the rehabilitation centre of a university-based teaching hospital. Patients who received CPM therapy immediately after TKA surgery were categorized into rapid-, normal-, and slow-progress groups according to their response to CPM during their acute inpatient stay. Knee pain, passive knee flexion, and knee function-measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-were assessed preoperatively at discharge and at 3- and 6-month outpatient follow-up visits. A total of 354 patients were followed for 6 months after inpatient-stay discharge. The patients in the rapid-progress group (n = 119) exhibited significantly greater knee flexions than those in the slow-progress group did (n = 103) at the 3-month follow-up [mean difference (MD) = 10.3°, 95 % confidence interval (CI) 4.3°-16.3°, p < 0.001] and 6-month follow-up (MD = 10.9°, 95 % CI 6.3°-15.6°, p < 0.001). Significant WOMAC score differences between the rapid- and slow-progress groups were observed at the 3-month follow-up (MD = 7.2, 95 % CI 5.4-9.1, p < 0.001) and 6-month follow-up (MD = 16.1, 95 % CI 13.4-18.7, p < 0.001). CPM initial angles and rapid progress significantly predicted short- and long-term outcomes in knee flexion and WOMAC scores (p < 0.001). When CPM is used, early application with initial high flexion and rapid progress benefits knee function up to 6 months after TKA. II.

Operational research in malawi: making a difference with cotrimoxazole preventive therapy in patients with tuberculosis and HIV

PubMed Central

2011-01-01

Background In Malawi, high case fatality rates in patients with tuberculosis, who were also co-infected with HIV, and high early death rates in people living with HIV during the initiation of antiretroviral treatment (ART) adversely impacted on treatment outcomes for the national tuberculosis and ART programmes respectively. This article i) discusses the operational research that was conducted in the country on cotrimoxazole preventive therapy, ii) outlines the steps that were taken to translate these findings into national policy and practice, iii) shows how the implementation of cotrimoxazole preventive therapy for both TB patients and HIV-infected patients starting ART was associated with reduced death rates, and iv) highlights lessons that can be learnt for other settings and interventions. Discussion District and facility-based operational research was undertaken between 1999 and 2005 to assess the effectiveness of cotrimoxazole preventive therapy in reducing death rates in TB patients and subsequently in patients starting ART under routine programme conditions. Studies demonstrated significant reductions in case fatality in HIV-infected TB patients receiving cotrimoxazole and in HIV-infected patients about to start ART. Following the completion of research, the findings were rapidly disseminated nationally at stakeholder meetings convened by the Ministry of Health and internationally through conferences and peer-reviewed scientific publications. The Ministry of Health made policy changes based on the available evidence, following which there was countrywide distribution of the updated policy and guidelines. Policy was rapidly moved to practice with the development of monitoring tools, drug procurement and training packages. National programme performance improved which showed a significant decrease in case fatality rates in TB patients as well as a reduction in early death in people with HIV starting ART. Summary Key lessons for moving this research endeavour through to policy and practice were the importance of placing operational research within the programme, defining relevant questions, obtaining "buy-in" from national programme staff at the beginning of projects and having key actors or "policy entrepreneurs" to push forward the policy-making process. Ultimately, any change in policy and practice has to benefit patients, and the ultimate judge of success is whether treatment outcomes improve or not. PMID:21794154

Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia with Novel Targeted Agents.

PubMed

Cheson, Bruce D; Heitner Enschede, Sari; Cerri, Elisa; Desai, Monali; Potluri, Jalaja; Lamanna, Nicole; Tam, Constantine

2017-11-01

Tumor lysis syndrome (TLS) is an uncommon but potentially life-threatening complication associated with the treatment of some cancers. If left untreated, TLS may result in acute renal failure, cardiac dysrhythmia, neurologic complications, seizures, or death. Tumor lysis syndrome is most commonly observed in patients with hematologic malignancies with a high proliferation rate undergoing treatment with very effective therapies. In chronic lymphocytic leukemia (CLL), historically, TLS has been observed less often, owing to a low proliferation rate and slow response to chemotherapy. New targeted therapies have recently been approved in the treatment of CLL, including the oral kinase inhibitors, idelalisib and ibrutinib, and the B-cell lymphoma-2 protein inhibitor, venetoclax. Several others are also under development, and combination strategies of these agents are being explored. This review examines the diagnosis, prevention, and management of TLS and summarizes the TLS experience in CLL clinical trials with newer targeted agents. Overall, the risk of TLS is small, but the consequences may be fatal; therefore, patients should be monitored carefully. Therapies capable of eliciting rapid response and combination regimens are increasingly being evaluated for treatment of CLL, which may pose a higher risk of TLS. For optimal management, patients at risk for TLS require prophylaxis and close monitoring with appropriate tests and appropriate management to correct laboratory abnormalities, which allows for safe and effective disease control. Tumor lysis syndrome (TLS) is a potentially fatal condition observed with hematologic malignancies, caused by release of cellular components in the bloodstream from rapidly dying tumor cells. The frequency and severity of TLS is partly dependent upon the biology of the disease and type of therapy administered. Novel targeted agents highly effective at inducing rapid cell death in chronic lymphocytic leukemia (CLL) may pose a risk for TLS in patients with tumors characterized by rapid growth, high tumor burden, and/or high sensitivity to treatment. In this review, prevention strategies and management of patients with CLL who develop TLS are described. © 2017 The Authors The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity.

PubMed

Beers, David R; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R; Alsuliman, Abdullah S; Shpall, Elizabeth J; Rezvani, Katy; Appel, Stanley H

2017-03-09

Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression.

Multidistrict Outbreak of Marburg Virus Disease-Uganda, 2012.

PubMed

Knust, Barbara; Schafer, Ilana J; Wamala, Joseph; Nyakarahuka, Luke; Okot, Charles; Shoemaker, Trevor; Dodd, Kimberly; Gibbons, Aridth; Balinandi, Stephen; Tumusiime, Alex; Campbell, Shelley; Newman, Edmund; Lasry, Estrella; DeClerck, Hilde; Boum, Yap; Makumbi, Issa; Bosa, Henry Kyobe; Mbonye, Anthony; Aceng, Jane Ruth; Nichol, Stuart T; Ströher, Ute; Rollin, Pierre E

2015-10-01

In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription-polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. Average RT-PCR cycle threshold values for fatal cases during the acute phase of illness were significantly lower than those for nonfatal cases. Following the institution of contact tracing, active case surveillance, care of patients with isolation precautions, community mobilization, and rapid diagnostic testing, the outbreak was successfully contained 14 days after its initial detection. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Predictive Factors for Fatal Tick-Borne Spotted Fever in Brazil.

PubMed

de Oliveira, S V; Willemann, M C A; Gazeta, G S; Angerami, R N; Gurgel-Gonçalves, R

2017-11-01

In Brazil, two pathogenic Rickettsia species have been identified causing tick-borne spotted fever (SF). The aetiological agent Rickettsia rickettsii causes serious illness, particularly in the south-eastern region of the country. Moreover, the Rickettsia sp. strain Atlantic Rainforest cause milder clinical manifestations in south-eastern, south and north-east regions. This study has sought to analyse predictive factors for fatal SF. A case-control study was performed using disease notification records in Brazil. The cases included were individuals with laboratory confirmation and fatal progression of SF, while the controls included individuals with SF who were cured. A total of 386 cases and 415 controls were identified (1 : 1.1), and the cases and controls were similar in age. The factors identified as being protective against death were reported presence of ticks (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.41-0.88), residing in urban areas (OR, 0.47, 95% CI, 0.31-0.74) and presenting lymphadenopathy (OR, 0.43; 95% CI, 0.23-0.82). Males exhibited a greater chance of death (OR, 1.57; 95% CI, 1.13-2.18), as did patients who were hospitalized (OR, 10.82; 95% CI, 6.38-18.35) and who presented hypotension or shock (OR, 10.80; 95% CI, 7.33-15.93), seizures (OR, 11.24; 95% CI, 6.49-19.45) and coma (OR of 15.16; 95% CI, 8.51-27.02). The study demonstrates the severity profile of the SF cases, defined either as the frequency of hospitalization (even in cases that were cured) or as the increased frequency of the clinical complications typically found in critical patients. Opportune clinical diagnosis, a careful evaluation of the epidemiological aspects of the disease and adequate care for patients are determining factors for reducing SF fatality rates. © 2017 Blackwell Verlag GmbH.

Clinical review of two fatal equine cases of infection with the insectivorous bat strain of Australian bat lyssavirus.

PubMed

Annand, E J; Reid, P A

2014-09-01

The first two confirmed cases of Australian bat lyssavirus (ABLV) infection in horses are presented. Both cases occurred in the same week in May 2013 in paddock mates in south-east Queensland. Australia has been one of only a few countries considered free from rabies-like viruses in domestic animal species. ABLV infection had previously only been confirmed in bats and humans. All three confirmed human cases were fatal, the latest in February 2013. An additional human case of possible abortive infection in 1996 has also been reported. Both equine cases reported here resulted in euthanasia. The risks of infection across other mammalian species are still to be determined. These two equine cases highlight that ABLV should be considered as a differential diagnosis in animals with similar clinical presentations in Australia. There is a need for greater awareness regarding the zoonotic risk, use of personal protective equipment, pre- and post-exposure prophylactic measures and laboratory diagnostic options. The authors recommend ABLV testing for all Australian cases of progressive equine neurological disease. © 2014 Australian Veterinary Association.

[Severe Legionella micdadei pneumonia effectively treated with hemofiltration therapy].

PubMed

Matsubara, S; Akashi, S; Naitoh, K; Nakahara, Y; Hayashi, S

1998-10-01

A 42-year-old man was admitted because of fever, productive cough, and progressive dyspnea. Chest x-ray films and computed tomographic scans disclosed dense consolidation in the left and right lung fields. No pathogenic agent was found despite extensive bacteriological examinations. Based on serological findings, the patient was given a diagnosis of acute pneumonia caused by Legionella micdadei. It has been reported that Legionnaire's disease is easily complicated by fatal systemic illnesses such as disseminated intravascular coagulation (DIC) and multiple organ failure. In fact, the patient suffered from severe hypotension and DIC on admission. Treatments against systemic complications were started together with intravenous administration of antibiotics including erythromycin. Continuous intravenous cathecolamin, however, failed to alleviate the patient's shock. We therefore applied endotoxin eliminating therapy using a polymyxin-B-column (PMX) and continuous hemofiltration (CHF). The patient recovered from critical shock immediately after the start of PMX, which together with CHF, alleviated his systemic complications. Although the factors responsible for fatal systemic complications in Legionnare's disease are not well-documented, our findings suggested that some substances removable by PMX and CHF play an important role in pathogenesis.

Experience matters: neurologists' perspectives on ALS patients' well-being.

PubMed

Aho-Özhan, Helena E A; Böhm, Sarah; Keller, Jürgen; Dorst, Johannes; Uttner, Ingo; Ludolph, Albert C; Lulé, Dorothée

2017-04-01

Despite the fatal outcome and progressive loss of physical functioning in amyotrophic lateral sclerosis (ALS), many patients maintain contentment in life. It has been shown that non-professionals tend to underestimate the well-being of patients with ALS, but professionals' perspective is yet to be studied. In total, 105 neurologists with varying degrees of experience with ALS were included in an anonymous survey. They were asked to estimate the quality of life and depressiveness of ALS patients with artificial ventilation and nutrition. Physicians' estimations were compared with previously reported subjective ratings of ALS patients with life-prolonging measures. Neurologists with significant experience on ALS and palliative care were able to accurately estimate depressiveness and quality of life of ALS patients with life-prolonging measures. Less experienced neurologists' estimation differed more from patients' reports. Of all life-prolonging measures neurologists regarded invasive ventilation as the measure associated with lowest quality of life and highest depressiveness of the patients. Experienced neurologists as well as neurologists with experience in palliative care are able to better empathize with patients with a fatal illness such as ALS and support important decision processes.

Varicella infection in a neonate with subsequent staphylococcal scalded skin syndrome and fatal shock.

PubMed

Singh, Shakal Narayan; Tahazzul, Mohammad; Singh, Anita; Chandra, Surabhi

2012-08-01

A male term neonate, at day 23 of life, presented with vesicular lesions over the trunk, which spread to allover the body on the next day. Five days later, he started developing blistering of the skin over the trunk and extremities, which subsequently ruptured, leaving erythematous, tender raw areas with peeling of the skin. The mother had vesicular eruptions, which started on the second day of delivery and progressed over the next 3 days. Subsequently, similar eruptions were noticed in two of the siblings before affecting the neonate. On the basis of the exposure history and clinical picture, a diagnosis was made of varicella infection with staphylococcal scalded skin syndrome (SSSS). The blood culture and the wound surface culture grew Staphylococcus aureus. Treatment included intravenous fluid, antibiotics, acyclovir and wound care. However, after 72 h of hospitalisation, the neonate first developed shock, refractory to fluid boluses, vasopressors and catecholamine along with other supports; and he then succumbed. In all neonates, staphylococcal infection with varicella can be fatal due to SSSS, the toxic shock syndrome or septicaemia.

Respiratory failure in a patient with antecedent poliomyelitis: amyotrophic lateral sclerosis or post-polio syndrome?

PubMed

Terao, Shin-ichi; Miura, Naofumi; Noda, Aiji; Yoshida, Mari; Hashizume, Yoshio; Ikeda, Hiroshi; Sobue, Gen

2006-10-01

We report a 69-year-old man who developed paralytic poliomyelitis in childhood and then decades later suffered from fatal respiratory failure. Six months before this event, he had progressive weight loss and shortness of breath. He had severe muscular atrophy of the entire right leg as a sequela of the paralytic poliomyelitis. He showed mild weakness of the facial muscle and tongue, dysarthria, and severe muscle atrophy from the neck to proximal upper extremities and trunk, but no obvious pyramidal signs. Electromyogram revealed neurogenic changes in the right leg, and in the paraspinal, sternocleidomastoid, and lingual muscles. There was a slight increase in central motor conduction time from the motor cortex to the lumbar anterior horn. Pulmonary function showed restrictive ventilation dysfunction, which was the eventual cause of death. Some neuropathological features were suggestive of amyotrophic lateral sclerosis (ALS), namely Bunina bodies. In patients with a history of paralytic poliomyelitis who present after a long stable period with advanced fatal respiratory failure, one may consider not only respiratory impairment from post-polio syndrome but also the onset of ALS.

Distance matters: Effect of geographic trauma system resource organization on fatal motor vehicle collisions.

PubMed

Brown, Joshua B; Rosengart, Matthew R; Billiar, Timothy R; Peitzman, Andrew B; Sperry, Jason L

2017-07-01

Trauma systems improve outcome; however, it is unclear how geographic organization of trauma system resources (TSR) affects outcome. Our objective was to evaluate the relationship of fatal motor vehicle collision (MVC) rates and the distance from individual MVC locations to the nearest TSR as a measure of the geographical organization of trauma systems, as well as how theoretical changes in the distribution of TSR may affect fatal MVC rates. All fatal MVC in Pennsylvania 2013-2014 were mapped from the Fatality Analysis Reporting System database. Deaths on scene were excluded. TSR including trauma centers and helicopter bases were mapped. Distance between each fatal MVC and nearest TSR was calculated. The primary outcome was fatal MVC rate per 100 million vehicle miles traveled (VMT). Empiric Bayes kriging and hot spot analysis were performed to evaluate geographic patterns in fatal MVC rates. Association between fatal MVC rate and distance to the nearest TSR was evaluated with linear regression. Spatial lag regression evaluated this association while controlling for MVC and county-level characteristics. We identified 886 fatalities from 863 fatal MVC. Median fatal MVC rate was 0.187 per 100 million VMT. Higher fatal MVC rates and fatality hot spots occur in locations farther from TSR. The fatal MVC rate increased 0.141 per 100 million VMT for every 10 miles farther from the nearest TSR (p < 0.01). When controlling for confounders, the fatal MVC rate increased by 0.089 per 100 million VMT for every 10 miles farther from the nearest TSR (p < 0.01). If two helicopters stationed at trauma centers were relocated into the highest fatality regions, our model predicts a 12.3% relative reduction in the overall MVC fatality rate. Increasing distance to the nearest TSR is associated with increasing fatal MVC rate. The geographic organization of trauma systems may impact outcome, and geospatial analysis can allow data-driven changes to potentially improve outcome. Prognostic/Epidemiologic, level III; Case management, level III.

Postoperative fatal hypothermia in hydranencephaly with pre-operative hypothermia and a nerve palsy: a case report and review of the literature.

PubMed

Musara, A; Kalangu, K K N

2010-01-01

Hydranencephaly is a rare condition characterised by complete or near complete absence of the cerebral hemispheres within relatively normal sized meninges and skull, the resulting cavity being filled with cerebrospinal fluid. The following is a case report of a five month old hydranencephalic child with right upper motor facial nerve palsy who presented with signs of hydrocephalus who developed intractable hypothermia rapidly post ventriculo-peritoneal shunt insertion and demised. Her preoperative condition was associated with hypothermia.

Thailand's Work and Health Transition.

PubMed

Kelly, Matthew; Strazdins, Lyndall; Dellora, Tarie; Khamman, Suwanee; Seubsman, Sam-Ang; Sleigh, Adrian C

2010-09-01

Thailand has experienced a rapid economic transition from agriculture to industry and services, and from informal to formal employment. It has much less state regulation and worker representation relative to developed nations, who underwent these transitions more slowly and sequentially, decades earlier. We examine the strengthening of Thai government policy and legislation affecting worker's health, responding to international norms, a new democratic constitution, fear of foreign importer embargos and several fatal workplace disasters. We identify key challenges remaining for Thai policy makers, including legislation enforcement and the measurement of impacts on worker's mental and physical health.

Fatalities and fatality rates in alcohol-impaired crashes by state, 2005-2006

DOT National Transportation Integrated Search

2008-02-01

In 2006, as compared to 2005, while the overall fatality rate declined from 1.46 to 1.41 fatalities per 100 million vehicle miles of travel (VMT), the alcohol-impaired fatality rate remained flat at 0.45 fatalities per 100 million VMT. In 2006, the a...

Rapidly progressive idiopathic lenticular astigmatism.

PubMed

Tint, Naing L; Jayaswal, Rakesh; Masood, Imran; Maharajan, V Senthil

2007-02-01

A myopic 43-year-old woman with early nuclear sclerotic cataract developed more than 11.0 diopters (D) of astigmatism over a 6-month period. This was found to be lenticular in origin. Phacoemulsification with intraocular lens implantation was performed, resulting in residual astigmatism of 0.75 D. To our knowledge, this is the first case of rapidly progressive lenticular astigmatism in an otherwise healthy eye with early nuclear sclerotic cataract.

Proteomic Analysis of Cerebrospinal Fluid in a Fulminant Case of Multiple Sclerosis

PubMed Central

Füvesi, Judit; Hanrieder, Jörg; Bencsik, Krisztina; Rajda, Cecilia; Kovács, S. Krisztián; Kaizer, László; Beniczky, Sándor; Vécsei, László; Bergquist, Jonas

2012-01-01

Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient’s death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject. PMID:22837721

Comprehensive analysis of the functional microRNA–mRNA regulatory network identifies miRNA signatures associated with glioma malignant progression

PubMed Central

Li, Yongsheng; Xu, Juan; Chen, Hong; Bai, Jing; Li, Shengli; Zhao, Zheng; Shao, Tingting; Jiang, Tao; Ren, Huan; Kang, Chunsheng; Li, Xia

2013-01-01

Glioma is the most common and fatal primary brain tumour with poor prognosis; however, the functional roles of miRNAs in glioma malignant progression are insufficiently understood. Here, we used an integrated approach to identify miRNA functional targets during glioma malignant progression by combining the paired expression profiles of miRNAs and mRNAs across 160 Chinese glioma patients, and further constructed the functional miRNA–mRNA regulatory network. As a result, most tumour-suppressive miRNAs in glioma progression were newly discovered, whose functions were widely involved in gliomagenesis. Moreover, three miRNA signatures, with different combinations of hub miRNAs (regulations≥30) were constructed, which could independently predict the survival of patients with all gliomas, high-grade glioma and glioblastoma. Our network-based method increased the ability to identify the prognostic biomarkers, when compared with the traditional method and random conditions. Hsa-miR-524-5p and hsa-miR-628-5p, shared by these three signatures, acted as protective factors and their expression decreased gradually during glioma progression. Functional analysis of these miRNA signatures highlighted their critical roles in cell cycle and cell proliferation in glioblastoma malignant progression, especially hsa-miR-524-5p and hsa-miR-628-5p exhibited dominant regulatory activities. Therefore, network-based biomarkers are expected to be more effective and provide deep insights into the molecular mechanism of glioma malignant progression. PMID:24194606

Prion protein gene analysis in three kindreds with fatal familial insomnia (FFI): Codon 178 mutation and codon 129 polymorphism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medori, R.; Tritschler, H.J.

1993-10-01

Fatal familial insomnia (FFI) is a disease linked to a GAC(Asp) [yields] AAC(Asn) mutation in codon 178 of the prion protein (PrP) gene. FFI is characterized clinically by untreatable progressive insomnia, dysautonomia, and motor dysfunctions and is characterized pathologically by selective thalamic atrophy. The authors confirmed the 178[sup Asn] mutation in the PrP gene of a third FFI family of French ancestry. Three family members who are under 40 years of age and who inherited the mutation showed only reduced perfusion in the basal ganglia on single photon emission computerized tomography. Some FFI features differ from the clinical and neuropathologicmore » findings associated with 178[sup Asn] reported elsewhere. However, additional intragenic mutations accounting for the phenotypic differences were not observed in two affected individuals. In other sporadic and familial forms of Creutzfeldt-Jakob disease and Gerstmann-Straeussler syndrome, Met or Val homozygosity at polymorphic codon 129 is associated with a more severe phenotype, younger age at onset, and faster progression. In FFI, young and old individuals at disease onset had 129[sup Met/Val]. Moreover, of five 178[sup Asn] individuals who are above age-at-onset range and who are well, two have 129[sup Met] and three have 129[sup Met/Val], suggesting that polymorphic site 129 does not modulate FFI phenotypic expression. Genetic heterogeneity and environment may play an important role in inter- and intrafamilial variability of the 178[sup Asn] mutation. 32 refs., 5 figs., 1 tab.« less

Nonfatal and fatal intoxications with pure caffeine - report of three different cases.

PubMed

Magdalan, Jan; Zawadzki, Marcin; Skowronek, Rafał; Czuba, Magdalena; Porębska, Barbara; Sozański, Tomasz; Szpot, Paweł

2017-09-01

Caffeine is not usually perceived as a drug by most people because it is found in many foods and drinks, including caffeinated energy drinks, as well as in over the counter analgesics and cold preparations. Recently in Poland it has become increasingly common to take pure caffeine, bought through online stores, as a psychoanaleptic. This creates a much higher risk of severe and even fatal poisoning in comparison with the risk associated with the abuse of food products and non-prescription medicines containing low doses of caffeine. This paper presents three different cases of poisoning that occurred when pure caffeine was taken as psychostimulant; in cases 1 and 2 poisoning was the result of a single overdose, while in the case 3 poisoning resulted from a cumulative overdose. In the case 1 there was a severe intoxication (persistent vomiting, hypotension, tremor), and the concentration of caffeine in the blood was found to be 80.16 μg/mL. The patient was treated using hemodialysis, which caused a rapid decrease in blood levels of caffeine and relief of the clinical symptoms of poisoning. Cases 2 and 3 were fatal poisonings, and recorded levels of caffeine in post mortem blood samples were 140.64 μg/mL and 613.0 μg/mL. In case 2 the patient died 10 min after admission to hospital as a result of sudden cardiac arrest, which was preceded by an attack of convulsions, and in case 3 death occurred in home and was also sudden in nature. Taking pure caffeine as a stimulant is associated with a high risk of overdose and the development of serious and even fatal poisoning, and those using pure caffeine are generally completely unaware of these risks. In such cases, death is usually sudden due to functional mechanisms.

Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea

PubMed Central

Vernet, Marie-Astrid; Reynard, Stéphanie; Fizet, Alexandra; Schaeffer, Justine; Pannetier, Delphine; Rives, Max; Georges, Nadia; Garcia-Bonnet, Nathalie; Sylla, Aboubacar I.; Grovogui, Péma; Kerherve, Jean-Yves; Savio, Christophe; Savio-Coste, Sylvie; de Séverac, Marie-Laure; Linares, Sandrine; Harouna, Souley; Abdoul, Bing M’Lebing; Petitjean, Frederic; Samake, Nenefing; Kinda, Moumouni; Koundouno, Fara Roger; Mateo, Mathieu; Lecine, Patrick; Page, Audrey; Tchamdja, Tang Maleki; Schoenhals, Matthieu; Barbe, Solenne; Simon, Bernard; Tran-Minh, Tuan; L’Hériteau, François

2017-01-01

BACKGROUND. The pathogenesis of Ebola virus (EBOV) disease (EVD) is poorly characterized. The establishment of well-equipped diagnostic laboratories close to Ebola treatment centers (ETCs) has made it possible to obtain relevant virological and biological data during the course of EVD and to assess their association with the clinical course and different outcomes of the disease. METHODS. We were responsible for diagnosing EBOV infection in patients admitted to two ETCs in forested areas of Guinea. The pattern of clinical signs was recorded, and an etiological diagnosis was established by RT-PCR for EBOV infection or a rapid test for malaria and typhoid fever. Biochemical analyses were also performed. RESULTS. We handled samples from 168 patients between November 29, 2014, and January 31, 2015; 97 patients were found to be infected with EBOV, with Plasmodium falciparum coinfection in 18%. Overall mortality for EVD cases was 58%, rising to 86% if P. falciparum was also present. Viral load was higher in fatal cases of EVD than in survivors, and fatal cases were associated with higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT), C-reactive protein (CRP), and IL-6 levels. Furthermore, regardless of outcome, EVD was characterized by higher creatine kinase (CPK), amylase, and creatinine levels than in febrile patients without EVD, with higher blood urea nitrogen (BUN) levels in fatal cases of EVD only. CONCLUSION. These findings suggest that a high viral load at admission is a marker of poor EVD prognosis. In addition, high AST, ALT, CRP, and IL-6 levels are associated with a fatal outcome of EVD. Damage to the liver and other tissues, with massive rhabdomyolysis and, probably, acute pancreatitis, is associated with EVD and correlated with disease severity. Finally, biochemical analyses provide substantial added value at ETCs, making it possible to improve supportive rehydration and symptomatic care for patients. FUNDING. The French Ministry of Foreign Affairs, the Agence Française de Développement, and Institut Pasteur. PMID:28352651

Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea.

PubMed

Vernet, Marie-Astrid; Reynard, Stéphanie; Fizet, Alexandra; Schaeffer, Justine; Pannetier, Delphine; Guedj, Jeremie; Rives, Max; Georges, Nadia; Garcia-Bonnet, Nathalie; Sylla, Aboubacar I; Grovogui, Péma; Kerherve, Jean-Yves; Savio, Christophe; Savio-Coste, Sylvie; de Séverac, Marie-Laure; Zloczewski, Philippe; Linares, Sandrine; Harouna, Souley; Abdoul, Bing M'Lebing; Petitjean, Frederic; Samake, Nenefing; Shepherd, Susan; Kinda, Moumouni; Koundouno, Fara Roger; Joxe, Ludovic; Mateo, Mathieu; Lecine, Patrick; Page, Audrey; Tchamdja, Tang Maleki; Schoenhals, Matthieu; Barbe, Solenne; Simon, Bernard; Tran-Minh, Tuan; Longuet, Christophe; L'Hériteau, François; Baize, Sylvain

2017-03-23

BACKGROUND. The pathogenesis of Ebola virus (EBOV) disease (EVD) is poorly characterized. The establishment of well-equipped diagnostic laboratories close to Ebola treatment centers (ETCs) has made it possible to obtain relevant virological and biological data during the course of EVD and to assess their association with the clinical course and different outcomes of the disease. METHODS. We were responsible for diagnosing EBOV infection in patients admitted to two ETCs in forested areas of Guinea. The pattern of clinical signs was recorded, and an etiological diagnosis was established by RT-PCR for EBOV infection or a rapid test for malaria and typhoid fever. Biochemical analyses were also performed. RESULTS. We handled samples from 168 patients between November 29, 2014, and January 31, 2015; 97 patients were found to be infected with EBOV, with Plasmodium falciparum coinfection in 18%. Overall mortality for EVD cases was 58%, rising to 86% if P . falciparum was also present. Viral load was higher in fatal cases of EVD than in survivors, and fatal cases were associated with higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT), C-reactive protein (CRP), and IL-6 levels. Furthermore, regardless of outcome, EVD was characterized by higher creatine kinase (CPK), amylase, and creatinine levels than in febrile patients without EVD, with higher blood urea nitrogen (BUN) levels in fatal cases of EVD only. CONCLUSION. These findings suggest that a high viral load at admission is a marker of poor EVD prognosis. In addition, high AST, ALT, CRP, and IL-6 levels are associated with a fatal outcome of EVD. Damage to the liver and other tissues, with massive rhabdomyolysis and, probably, acute pancreatitis, is associated with EVD and correlated with disease severity. Finally, biochemical analyses provide substantial added value at ETCs, making it possible to improve supportive rehydration and symptomatic care for patients. FUNDING. The French Ministry of Foreign Affairs, the Agence Française de Développement, and Institut Pasteur.

Development of an Earthquake Impact Scale

NASA Astrophysics Data System (ADS)

Wald, D. J.; Marano, K. D.; Jaiswal, K. S.

2009-12-01

With the advent of the USGS Prompt Assessment of Global Earthquakes for Response (PAGER) system, domestic (U.S.) and international earthquake responders are reconsidering their automatic alert and activation levels as well as their response procedures. To help facilitate rapid and proportionate earthquake response, we propose and describe an Earthquake Impact Scale (EIS) founded on two alerting criteria. One, based on the estimated cost of damage, is most suitable for domestic events; the other, based on estimated ranges of fatalities, is more appropriate for most global events. Simple thresholds, derived from the systematic analysis of past earthquake impact and response levels, turn out to be quite effective in communicating predicted impact and response level of an event, characterized by alerts of green (little or no impact), yellow (regional impact and response), orange (national-scale impact and response), and red (major disaster, necessitating international response). Corresponding fatality thresholds for yellow, orange, and red alert levels are 1, 100, and 1000, respectively. For damage impact, yellow, orange, and red thresholds are triggered by estimated losses exceeding 1M, 10M, and $1B, respectively. The rationale for a dual approach to earthquake alerting stems from the recognition that relatively high fatalities, injuries, and homelessness dominate in countries where vernacular building practices typically lend themselves to high collapse and casualty rates, and it is these impacts that set prioritization for international response. In contrast, it is often financial and overall societal impacts that trigger the level of response in regions or countries where prevalent earthquake resistant construction practices greatly reduce building collapse and associated fatalities. Any newly devised alert protocols, whether financial or casualty based, must be intuitive and consistent with established lexicons and procedures. In this analysis, we make an attempt at both simple and intuitive color-coded alerting criterion; yet, we preserve the necessary uncertainty measures by which one can gauge the likelihood for the alert to be over- or underestimated.

The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.

PubMed

Woodward, M; Zhang, X; Barzi, F; Pan, W; Ueshima, H; Rodgers, A; MacMahon, S

2003-02-01

To provide reliable age- and region-specific estimates of the associations between diabetes and major cardiovascular diseases and death in populations from the Asia-Pacific region. Twenty-four cohort studies from Asia, Australia, and New Zealand (median follow-up, 5.4 years) provided individual participant data from 161,214 people (58% from Asia) of whom 4,873 had a history of diabetes at baseline. The associations of diabetes with the risks of coronary heart disease, stroke, and cause-specific mortality during follow-up were estimated using time-dependent Cox models, stratified by study cohort and sex and adjusted for age at risk. In all, 9,277 deaths occurred (3,635 from cardiovascular disease). The hazard ratio (95% CI) associated with diabetes was 1.97 (1.72-2.25) for fatal cardiovascular disease; there were similar hazard ratios for fatal coronary heart disease, fatal stroke, and composites of fatal and nonfatal outcomes. For all cardiovascular outcomes, hazard ratios were similar in Asian and non-Asian populations and in men and women, but were greater in younger than older individuals. For noncardiovascular death, the hazard ratio was 1.56 (1.38-1.77), with separately significant increases in the risks of death from renal disease, cancer, respiratory infections, and other infective causes. The hazard ratio for all-causes mortality was 1.68 (1.55-1.84), with similar ratios in Asian and non-Asian populations, but with significantly higher ratios in younger than older individuals. The relative effect of diabetes on the risks of cardiovascular disease and death in Asian populations is much the same as that in the largely Caucasian populations of Australia and New Zealand. Hazard ratios were severalfold greater in younger people than older people. The rapidly growing prevalence of diabetes in Asia heralds a large increase in the incidence of diabetes-related death in the coming decades.

Rapid Development and Use of a Nationwide Training Program for Cholera Management, Haiti, 2010

PubMed Central

Lynch, Michael; Lambert, Yves; Sobel, Jeremy; Domerçant, Jean W.; Khan, Azharul

2011-01-01

When epidemic cholera appeared in Haiti in October 2010, the medical community there had virtually no experience with the disease and needed rapid training as the epidemic spread throughout the country. We developed a set of training materials specific to Haiti and launched a cascading training effort. Through a training-of-trainers course in November 14–15, 2010, and department-level training conducted in French and Creole over the following 3 weeks, 521 persons were trained and equipped to further train staff at the institutions where they worked. After the training, the hospitalized cholera patients’ case-fatality rate dropped from 4% to <2% by mid-December and was <1% by January 2011. Continuing in-service training, monitoring and evaluation, and integration of cholera management into regular clinical training will help sustain this success. PMID:22099112

Large-Scale Phenotype-Based Antiepileptic Drug Screening in a Zebrafish Model of Dravet Syndrome1,2,3

PubMed Central

Dinday, Matthew T.

2015-01-01

Abstract Mutations in a voltage-gated sodium channel (SCN1A) result in Dravet Syndrome (DS), a catastrophic childhood epilepsy. Zebrafish with a mutation in scn1Lab recapitulate salient phenotypes associated with DS, including seizures, early fatality, and resistance to antiepileptic drugs. To discover new drug candidates for the treatment of DS, we screened a chemical library of ∼1000 compounds and identified 4 compounds that rescued the behavioral seizure component, including 1 compound (dimethadione) that suppressed associated electrographic seizure activity. Fenfluramine, but not huperzine A, also showed antiepileptic activity in our zebrafish assays. The effectiveness of compounds that block neuronal calcium current (dimethadione) or enhance serotonin signaling (fenfluramine) in our zebrafish model suggests that these may be important therapeutic targets in patients with DS. Over 150 compounds resulting in fatality were also identified. We conclude that the combination of behavioral and electrophysiological assays provide a convenient, sensitive, and rapid basis for phenotype-based drug screening in zebrafish mimicking a genetic form of epilepsy. PMID:26465006

Laguna Negra Virus Infection Causes Hantavirus Pulmonary Syndrome in Turkish Hamsters (Mesocricetus brandti).

PubMed

Hardcastle, K; Scott, D; Safronetz, D; Brining, D L; Ebihara, H; Feldmann, H; LaCasse, R A

2016-01-01

Laguna Negra virus (LNV) is a New World hantavirus associated with severe and often fatal cardiopulmonary disease in humans, known as hantavirus pulmonary syndrome (HPS). Five hamster species were evaluated for clinical and serologic responses following inoculation with 4 hantaviruses. Of the 5 hamster species, only Turkish hamsters infected with LNV demonstrated signs consistent with HPS and a fatality rate of 43%. Clinical manifestations in infected animals that succumbed to disease included severe and rapid onset of dyspnea, weight loss, leukopenia, and reduced thrombocyte numbers as compared to uninfected controls. Histopathologic examination revealed lung lesions that resemble the hallmarks of HPS in humans, including interstitial pneumonia and pulmonary edema, as well as generalized infection of endothelial cells and macrophages in major organ tissues. Histologic lesions corresponded to the presence of viral antigen in affected tissues. To date, there have been no small animal models available to study LNV infection and pathogenesis. The Turkish hamster model of LNV infection may be important in the study of LNV-induced HPS pathogenesis and development of disease treatment and prevention strategies. © The Author(s) 2015.

Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection.

PubMed

Zhang, Jie; Liu, Huan; Wei, Bin

Herpes simplex virus type 1 (HSV-1), a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life including fatal disseminated disease in newborns, cold sores, eye disease, and fatal encephalitis in adults. HSV-1 infection can trigger rapid immune responses, and efficient inhibition and clearance of HSV-1 infection rely on both the innate and adaptive immune responses of the host. Multiple strategies have been used to restrict host innate immune responses by HSV-1 to facilitate its infection in host cells. The adaptive immunity of the host plays an important role in inhibiting HSV-1 infections. The activation and regulation of T cells are the important aspects of the adaptive immunity. They play a crucial role in host-mediated immunity and are important for clearing HSV-1. In this review, we examine the findings on T cell immune responses during HSV-1 infection, which hold promise in the design of new vaccine candidates for HSV-1.

Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection*

PubMed Central

Zhang, Jie; Liu, Huan; Wei, Bin

2017-01-01

Herpes simplex virus type 1 (HSV-1), a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life including fatal disseminated disease in newborns, cold sores, eye disease, and fatal encephalitis in adults. HSV-1 infection can trigger rapid immune responses, and efficient inhibition and clearance of HSV-1 infection rely on both the innate and adaptive immune responses of the host. Multiple strategies have been used to restrict host innate immune responses by HSV-1 to facilitate its infection in host cells. The adaptive immunity of the host plays an important role in inhibiting HSV-1 infections. The activation and regulation of T cells are the important aspects of the adaptive immunity. They play a crucial role in host-mediated immunity and are important for clearing HSV-1. In this review, we examine the findings on T cell immune responses during HSV-1 infection, which hold promise in the design of new vaccine candidates for HSV-1. PMID:28378566

Resetting the transcription factor network reverses terminal chronic hepatic failure

PubMed Central

Nishikawa, Taichiro; Bell, Aaron; Brooks, Jenna M.; Setoyama, Kentaro; Melis, Marta; Han, Bing; Fukumitsu, Ken; Handa, Kan; Tian, Jianmin; Kaestner, Klaus H.; Vodovotz, Yoram; Locker, Joseph; Soto-Gutierrez, Alejandro; Fox, Ira J.

2015-01-01

The cause of organ failure is enigmatic for many degenerative diseases, including end-stage liver disease. Here, using a CCl4-induced rat model of irreversible and fatal hepatic failure, which also exhibits terminal changes in the extracellular matrix, we demonstrated that chronic injury stably reprograms the critical balance of transcription factors and that diseased and dedifferentiated cells can be returned to normal function by re-expression of critical transcription factors, a process similar to the type of reprogramming that induces somatic cells to become pluripotent or to change their cell lineage. Forced re-expression of the transcription factor HNF4α induced expression of the other hepatocyte-expressed transcription factors; restored functionality in terminally diseased hepatocytes isolated from CCl4-treated rats; and rapidly reversed fatal liver failure in CCl4-treated animals by restoring diseased hepatocytes rather than replacing them with new hepatocytes or stem cells. Together, the results of our study indicate that disruption of the transcription factor network and cellular dedifferentiation likely mediate terminal liver failure and suggest reinstatement of this network has therapeutic potential for correcting organ failure without cell replacement. PMID:25774505

Rapid Laboratory Identification of Neisseria meningitidis Serogroup C as the Cause of an Outbreak - Liberia, 2017.

PubMed

Patel, Jaymin C; George, Josiah; Vuong, Jeni; Potts, Caelin C; Bozio, Catherine; Clark, Thomas A; Thomas, Jerry; Schier, Joshua; Chang, Arthur; Waller, Jessica L; Diaz, Maureen H; Whaley, Melissa; Jenkins, Laurel T; Fuller, Serena; Williams, Desmond E; Redd, John T; Arthur, Ray R; Taweh, Fahn; Vera Walker, Yatta; Hardy, Patrick; Freeman, Maxwell; Katawera, Victoria; Gwesa, Gulu; Gbanya, Miatta Z; Clement, Peter; Kohar, Henry; Stone, Mardia; Fallah, Mosoka; Nyenswah, Tolbert; Winchell, Jonas M; Wang, Xin; McNamara, Lucy A; Dokubo, E Kainne; Fox, LeAnne M

2017-10-27

On April 25, 2017, a cluster of unexplained illness and deaths among persons who had attended a funeral during April 21-22 was reported in Sinoe County, Liberia (1). Using a broad initial case definition, 31 cases were identified, including 13 (42%) deaths. Twenty-seven cases were from Sinoe County (1), and two cases each were from Grand Bassa and Monsterrado counties, respectively. On May 5, 2017, initial multipathogen testing of specimens from four fatal cases using the Taqman Array Card (TAC) assay identified Neisseria meningitidis in all specimens. Subsequent testing using direct real-time polymerase chain reaction (PCR) confirmed N. meningitidis in 14 (58%) of 24 patients with available specimens and identified N. meningitidis serogroup C (NmC) in 13 (54%) patients. N. meningitidis was detected in specimens from 11 of the 13 patients who died; no specimens were available from the other two fatal cases. On May 16, 2017, the National Public Health Institute of Liberia and the Ministry of Health of Liberia issued a press release confirming serogroup C meningococcal disease as the cause of this outbreak in Liberia.

Vibrio vulnificus: death on the half shell. A personal journey with the pathogen and its ecology.

PubMed

Oliver, James D

2013-05-01

Vibrio vulnificus is an estuarine bacterium which occurs in high numbers in filter-feeding molluscan shellfish, such as oysters. In individuals with certain underlying diseases, ingestion of the bacterium, e.g., in raw or undercooked oysters, can lead to a rapid and extremely fatal infection. Indeed, this one bacterium is responsible for 95 % of all seafood-borne deaths. In addition, the bacterium is capable of entering a preexisting lesion or cut obtained during coastal recreational activities, resulting in potentially fatal wound infections. This brief review, which comprised a presentation made at the Gordon Research Conference on "Oceans and Human Health," reflects over 35 years of research on this bacterium in the author's laboratory. It describes some of the known virulence factors and why males account for ca 85 % of all V. vulnificus cases. It notes the two genotypes now known to exist and how this pathogen enters a dormant, "viable but nonculturable" state during the winter months. Finally, the review discusses how global warming may be causing worldwide increases in the frequency and geographical extent of Vibrio infections.