Probiotics and infective endocarditis in patients with hereditary hemorrhagic telangiectasia: a clinical case and a review of the literature.

PubMed

Boumis, Evangelo; Capone, Alessandro; Galati, Vincenzo; Venditti, Carolina; Petrosillo, Nicola

2018-02-01

In the last decades, probiotics have been widely used as food supplements because of their putative beneficial health effects. They are generally considered safe but rare reports of serious infections caused by bacteria included in the definition of probiotics raise concerns on their potential pathogenic role in patients with particular predisposing factors. Patients with hereditary hemorrhagic telangiectasia (HHT) are exposed to infections because of telangiectasias and arteriovenous malformations (AVMs). We describe what is, to our knowledge, the first case of infective endocarditis (IE) caused by Lactobacillus rhamnosus in a patient with HHT. A systematic review of the relevant medical literature is presented. A patient with HHT and an aortic bioprosthesis was admitted because of prolonged fever not responding to antibiotics. The patient had a history of repeated serious infections with hospitalizations and prolonged use of antibiotics, and used to assume large amounts of different commercial products containing probiotics. Weeks before the onset of symptoms the patient had been treated with nasal packings and with surgical closure of a nasal bleeding site because of recurrent epistaxis. A diagnosis of IE of the aortic bioprosthesis was made. All blood coltures were positive for L. rhamnosus. The patients responded to a cycle of 6 weeks of amoxicillin/clavulanate plus gentamicin. A systematic review of IE linked to consumption of probiotics, and of infective endocarditis in patients with HHT was conducted. 10 cases of IE linked to probiotics consumption and 6 cases of IE in patients with HHT were found. Consumption of probiotics can pose a risk of serious infections in patients with particular predisposing factors. Patients with HHT can be considered at risk because of their predisposition to infections. Prophylaxis with antibiotics before nasal packings in patients with HHT can be considered.

Quality of life in patients with hereditary hemorrhagic telangiectasia in Norway: a population based study.

PubMed

Geirdal, Amy Østertun; Dheyauldeen, Sinan; Bachmann-Harildstad, Gregor; Heimdal, Ketil

2012-06-01

Hereditary hemorrhagic telangiectasia (HHT) is a rare, autosomal dominant disease characterized by the presence of recurrent epistaxis and small characteristic malformations of the peripheral blood vessels near the surface of the skin or mucosal linings. Arteriovenous malformations (AVM) of the lung, liver, and CNS are also known clinical findings. The purpose of this study was to examine quality of life (QoL) in patients with HHT in Norway. Sixty-six affected patients (39 women and 27 men) were included. QoL on overall-, health-related (HR-QoL), and disease-specific levels were measured with Cantril's Ladder (CL), Short Form 36 (SF-36), and a Symptom-specific QoL question in HHT patients (SFB-HHT-Q), respectively. Comparisons were made between patients and an age and gender adjusted normative sample from the Norwegian population (N = 990). Overall, the results reflected that several HHT disease-related variables were associated with reduced QoL on all three levels; overall QoL (CL), HR-QoL (SF36) as well as disease-specific QoL (SFB-HHT-Q), while demographic variables impacted HR-QoL in HHT patients. Compared to the normative sample, all subscales of SF36, but bodily pain, were significantly poorer in the HHT patients. HHT disease variables had the strongest association with QoL compared to demographic variables. The results substantiate that disease severity is associated with poorer QoL in this patients. Pain contributed independently to all levels of QoL. Copyright © 2012 Wiley Periodicals, Inc.

Vascular deficiency of Smad4 causes arteriovenous malformations: a mouse model of Hereditary Hemorrhagic Telangiectasia.

PubMed

Crist, Angela M; Lee, Amanda R; Patel, Nehal R; Westhoff, Dawn E; Meadows, Stryder M

2018-05-01

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder that leads to abnormal connections between arteries and veins termed arteriovenous malformations (AVM). Mutations in TGFβ pathway members ALK1, ENG and SMAD4 lead to HHT. However, a Smad4 mouse model of HHT does not currently exist. We aimed to create and characterize a Smad4 endothelial cell (EC)-specific, inducible knockout mouse (Smad4 f/f ;Cdh5-Cre ERT2 ) that could be used to study AVM development in HHT. We found that postnatal ablation of Smad4 caused various vascular defects, including the formation of distinct AVMs in the neonate retina. Our analyses demonstrated that increased EC proliferation and size, altered mural cell coverage and distorted artery-vein gene expression are associated with Smad4 deficiency in the vasculature. Furthermore, we show that depletion of Smad4 leads to decreased Vegfr2 expression, and concurrent loss of endothelial Smad4 and Vegfr2 in vivo leads to AVM enlargement. Our work provides a new model in which to study HHT-associated phenotypes and links the TGFβ and VEGF signaling pathways in AVM pathogenesis.

Lifestyle and dietary influences on nosebleed severity in hereditary hemorrhagic telangiectasia.

PubMed

Silva, B Maneesha; Hosman, Anna E; Devlin, Hannah L; Shovlin, Claire L

2013-05-01

To identify factors influencing the severity of epistaxis in hereditary hemorrhagic telangiectasia (HHT). Participants with and without HHT were recruited from a specialist service and online following advertisement by the HHT Foundation International. Both groups were asked to complete a nonbiased questionnaire. The reported effects of specific treatments or lifestyle factors on epistaxis were assigned positive values if beneficial, negative values if detrimental, or zero if "no difference" and were summed to enable statistical analysis. Epistaxis affected 649 of 666 (97%) participants with HHT and was significantly more frequent than in control participants. Specialist invasive treatments were reported as beneficial, laser therapy more frequently than cauterization. Medical treatments commonly used for HHT epistaxis (female hormones, antiestrogens, tranexamic acid, aminocaproic acid, nasal creams, and bevacizumab) also had significantly positive (beneficial) scores. Lifestyle and dietary factors were generally detrimental, but room humidification, nasal lubrication, and saline treatments were all reported as beneficial (95% confidence intervals greater than zero). Multiple food items were volunteered as being detrimental to epistaxis. The most frequently reported items were alcohol (n = 45; 6.8% of participants) and spices (n = 26, 3.9% of participants). Remaining foods reported to exacerbate epistaxis were also found to be high in salicylates (including red wine, spices, chocolate, coffee, and certain fruits), natural antiplatelet activity (garlic, ginger, ginseng, ginkgo biloba, and vitamin E15), or omega-3 acids (oily fish, salmon). This study supports existing treatments and suggests lifestyle and dietary maneuvers that may also improve nosebleeds in HHT. 2c. Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.

Clinical presentation and treatment paradigms of brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia.

PubMed

Gamboa, Nicholas T; Joyce, Evan J; Eli, Ilyas; Park, Min S; Taussky, Philipp; Schmidt, Richard H; McDonald, Jamie; Whitehead, Kevin J; Kalani, M Yashar S

2018-05-01

Hereditary hemorrhagic telangiectasia (HHT) is characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectases, and multisystem arteriovenous malformations (AVMs). Brain AVMs typically present at birth and are identified in approximately 10-20% of patients with HHT. A retrospective review was undertaken of all HHT patients with known single or multiple brain AVMs treated at our institution. Thirty-nine patients with brain AVM(s) were diagnosed with HHT. Most patients presented with at least one Curaçao criterion. A total of 78 brain AVMs were identified in 39 patients. Two-thirds of patients had solitary brain AVMs, whereas 33% of patients harbored at least two lesions (range: 2-16). Brain AVMs of the supratentorial cerebral hemispheres comprised 83% of all lesions, whereas infratentorial lesions accounted for only 17%. Of the 55 brain AVMs assigned Spetzler-Martin grading, the majority of patients were Grade 1 (73%), and 23% and 4% were Grades 2 and 3, respectively. Patients were treated with surgery alone (51%), embolization alone (6%), embolization followed by surgery (9%), stereotactic radiosurgery (11%), stereotactic radiosurgery followed by surgery (3%), or observation (20%). Of patients who underwent genetic analysis, 62% possessed mutations in ENG (HHT type 1), whereas 38% had mutations in ACVRL1 (HHT type 2). This robust patient cohort of brain AVMs in 39 patients with HHT advances the collective understanding of this disease's varied presentation, diagnostic workup, genetic underpinnings, and available treatment options. Copyright © 2018. Published by Elsevier Ltd.

Relationships between epistaxis, migraines, and triggers in hereditary hemorrhagic telangiectasia.

PubMed

Elphick, Amy; Shovlin, Claire L

2014-07-01

To identify whether relationships exist between epistaxis and migraines in hereditary hemorrhagic telangiectasia (HHT), to potentially provide further preventative and therapeutic options for the debilitating nosebleeds that are often very difficult to manage in clinical practice. Study participants were recruited from a UK specialist service, and online following advertisement by the HHT Foundation International. They completed a nonbiased questionnaire in which paired questions on nosebleeds and migraines were separated by at least 17 other questions. Migraines were defined as headaches with associated autonomic and/or neurological features. The reported frequencies and precipitants of epistaxis and migraines were compared using numerical scales applied equally for each condition. The 220 HHT-affected respondents reported frequent nosebleeds, 153 (69.5%) used iron tablets, and 39 (17.7%) had received at least 10 blood transfusions. Migraines displaying typical features were reported by 51 (23.2%), and were more common with pulmonary or cerebral arteriovenous malformations. Thirty of 51 (58.8%) migraine sufferers reported that nosebleeds occurred at the same time as their migraines. More frequent migraines were reported by patients with more frequent nosebleeds (r2=15%, P=.007), or transfusions (r2=16.9%, P=.004). In menstrual, lifestyle, and dietary analyses, consistency was observed between factors having no effect, and those provoking both nosebleeds and migraines in multiple patients (premenses; activity; lack of sleep; stress; caffeine, cheese, alcohol, and chocolate). We demonstrate an unexpected and provocative association between nosebleeds and migraines in HHT patients. Evaluation of whether antimigraine approaches limit HHT nosebleeds may be appropriate. 4. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

[Paradoxical brain embolism mediated through a pulmonary arteriovenous malformation with hereditary hemorrhagic telangiectasia in a Japanese patient].

PubMed

Takeda, June; Todo, Kenichi; Yamamoto, Shiro; Yamagami, Hiroshi; Kawamoto, Michi; Kohara, Nobuo

2012-01-01

We report a case of paradoxical brain embolism mediated through a pulmonary arteriovenous malformation (PAVM) with hereditary hemorrhagic telangiectasia (HHT). A 25-year-old right handed man was admitted to our hospital after sudden headache and visual field abnormality. In neurologic examinations, he had left superior-quadrantanopsia. Laboratory findings showed iron deficiency anemia. Diffusion weighted images disclosed a high-signal-intensity area in the right occipito-temporal lobe, and intraarterial digital subtraction cerebral angiography revealed occlusion of the right posterior cerebral artery. Transesophageal echocardiography revealed continuous right-to-left shunt. We confirmed his history of spontaneous recurrent epistaxis and the first-degree relatives with epistaxis or PAVM. A contrast enhanced CT scan of the chest revealed a PAVM. The diagnosis of paradoxical brain embolism mediated through the PAVM with HHT was, thus, established. The PAVM was occluded by using embolization coils successfully. In Asian countries, the prevalence of PAVM with HHT is thought to be lower than in European countries. We should carefully take medical and family histories, especially epistaxis, in a young stroke patient.

Pulmonary arterial hypertension and portal hypertension in a patient with hereditary hemorrhagic telangiectasia.

PubMed

Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana

2015-03-15

Pulmonary arterial hypertension (PAH) is a rare disease that could be inherited with an autosomal dominant pattern. Mutations in BMPR2 gene are described in over 70% of cases, although other genes are involved in lesser extend in PAH. Hereditary hemorrhagic telangiectasia (HHT) is another rare autosomal dominant disease. PAH is a rare complication of HHT that occurs in less than 1% of cases. Liver cirrhosis with portal hypertension is also associated with the presence of PAHs in 1-2% of cases. We present here a patient with HHT who developed PAH shortly after showing portal hypertension. Some genes (BMPR2, ACVRL1, ENG) seem to play an important role in PAH pathogenesis. We analyzed these genes, detecting mutations in BMPR2 gene (c.1021G>A (V341L), c.327G>A (p.Q109Q)), ACVRL1 (c.313+20C>A, c.1502+7A>G) and ENG (c.498G>A (Q166Q)). The patient also had 3 polymorphisms in the TRPC6 gene (c.1-361A>T, c.1-254C>G, c.1-218C>T). The study of these genes will help us to identify and track individuals susceptible for developing PAH associated with other diseases. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Acoustical Applications of the HHT Method

NASA Technical Reports Server (NTRS)

Huang, Norden E.

2003-01-01

A document discusses applications of a method based on the Huang-Hilbert transform (HHT). The method was described, without the HHT name, in Analyzing Time Series Using EMD and Hilbert Spectra (GSC-13817), NASA Tech Briefs, Vol. 24, No. 10 (October 2000), page 63. To recapitulate: The method is especially suitable for analyzing time-series data that represent nonstationary and nonlinear physical phenomena. The method involves the empirical mode decomposition (EMD), in which a complicated signal is decomposed into a finite number of functions, called intrinsic mode functions (IMFs), that admit well-behaved Hilbert transforms. The HHT consists of the combination of EMD and Hilbert spectral analysis.

Functional and splicing defect analysis of 23 ACVRL1 mutations in a cohort of patients affected by Hereditary Hemorrhagic Telangiectasia

PubMed Central

Alaa el Din, Ferdos; Patri, Sylvie; Thoreau, Vincent; Rodriguez-Ballesteros, Montserrat; Hamade, Eva; Bailly, Sabine; Gilbert-Dussardier, Brigitte; Abou Merhi, Raghida; Kitzis, Alain

2015-01-01

Hereditary Hemorrhagic Telangiectasia syndrome (HHT) or Rendu-Osler-Weber (ROW) syndrome is an autosomal dominant vascular disorder. Two most common forms of HHT, HHT1 and HHT2, have been linked to mutations in the endoglin (ENG) and activin receptor-like kinase 1 (ACVRL1or ALK1) genes respectively. This work was designed to examine the pathogenicity of 23 nucleotide variations in ACVRL1 gene detected in more than 400 patients. Among them, 14 missense mutations and one intronic variant were novels, and 8 missense mutations were previously identified with questionable implication in HHT2. The functionality of missense mutations was analyzed in response to BMP9 (specific ligand of ALK1), the maturation of the protein products and their localization were analyzed by western blot and fluorescence microscopy. The splicing impairment of the intronic and of two missense mutations was examined by minigene assay. Functional analysis showed that 18 out of 22 missense mutations were defective. Splicing analysis revealed that one missense mutation (c.733A>G, p.Ile245Val) affects the splicing of the harboring exon 6. Similarly, the intronic mutation outside the consensus splicing sites (c.1048+5G>A in intron 7) was seen pathogenic by splicing study. Both mutations induce a frame shift creating a premature stop codon likely resulting in mRNA degradation by NMD surveillance mechanism. Our results confirm the haploinsufficiency model proposed for HHT2. The affected allele of ACVRL1 induces mRNA degradation or the synthesis of a protein lacking the receptor activity. Furthermore, our data demonstrate that functional and splicing analyses together, represent two robust diagnostic tools to be used by geneticists confronted with novel or conflicted ACVRL1 mutations. PMID:26176610

Topical timolol for treatment of epistaxis in hereditary haemorrhagic telangiectasia associated with bradycardia: a look at CYP2D6 metabolising variants

PubMed Central

Epperla, Narendranath; Brilliant, Murray H; Vidaillet, Humberto

2014-01-01

A 59-year-old man presented to the emergency department with lightheadedness. He had started intranasal administration of ophthalmic timolol for the prevention of epistaxis associated with hereditary haemorrhagic telangiectasia approximately 3 weeks earlier with excellent response. His heart rate was about half its normal rate, an ECG revealed sinus bradycardia, and it was determined he had significant cardiac issues in his family history. Essentially all other tests were normal. The discontinuation of the intranasal use of timolol resolved any further episodes of lightheadedness and bradycardia. It was determined through genetic testing that he is an intermediate metaboliser of CYP2D6, the main enzyme contributing to the metabolism of timolol. This explains the development of the bradycardia after intranasal timolol use. The metabolising variants of CYP2D6 need to be considered when prescribing medications metabolised by this enzyme, so possible adverse effects can be avoided. PMID:24518395

Harmonic analysis of electrified railway based on improved HHT

NASA Astrophysics Data System (ADS)

Wang, Feng

2018-04-01

In this paper, the causes and harms of the current electric locomotive electrical system harmonics are firstly studied and analyzed. Based on the characteristics of the harmonics in the electrical system, the Hilbert-Huang transform method is introduced. Based on the in-depth analysis of the empirical mode decomposition method and the Hilbert transform method, the reasons and solutions to the endpoint effect and modal aliasing problem in the HHT method are explored. For the endpoint effect of HHT, this paper uses point-symmetric extension method to extend the collected data; In allusion to the modal aliasing problem, this paper uses the high frequency harmonic assistant method to preprocess the signal and gives the empirical formula of high frequency auxiliary harmonic. Finally, combining the suppression of HHT endpoint effect and modal aliasing problem, an improved HHT method is proposed and simulated by matlab. The simulation results show that the improved HHT is effective for the electric locomotive power supply system.

Hereditary Hemorrhagic Telangiectasia - HHT

MedlinePlus

... GUIDELINES, CLINICAL TOPIC ACKNOWLEDGEMENTS MACRA MATTERS HEALTH POLICY, ECONOMICS, CODING REIMBURSEMENT AND APPEALS TOOLKITS UFE AWARENESS TOOLKIT ... GUIDELINES, CLINICAL TOPIC ACKNOWLEDGEMENTS MACRA MATTERS HEALTH POLICY, ECONOMICS, CODING REIMBURSEMENT AND APPEALS TOOLKITS UFE AWARENESS TOOLKIT ...

Medical treatment of epistaxis in hereditary hemorrhagic telangiectasia: an evidence-based review.

PubMed

Halderman, Ashleigh A; Ryan, Matthew W; Clark, Christopher; Sindwani, Raj; Reh, Douglas D; Poetker, David M; Invernizzi, Rosangela; Marple, Bradley F

2018-06-01

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant hereditary disorder resulting in vascular dysplasia and formation of arteriovenous malformations. Recurrent epistaxis is a hallmark of the disease. An array of medical therapies are used in this patient population, but robust evidence-based recommendations regarding the medical treatment of epistaxis are lacking. This systematic review was performed to look at the current literature and make meaningful evidence-based recommendations. A search of the Ovid MEDLINE, Embase, and Cochrane databases was conducted by a research librarian. Abstracts in the English language and published in a peer-review journal were reviewed for relevance and inclusion. PRISMA guidelines were followed. Eighteen studies met the inclusion criteria. In a few small studies, thalidomide was shown to consistently improve severity and frequency of epistaxis and improve hemoglobin concentrations while decreasing the need for transfusion. Tranexamic acid appeared to only impact the epistaxis severity score and not other clinical outcomes. Selective estrogen modulators (SERMs), propranolol, rose geranium oil, and N-acetylcysteine, have demonstrated promising efficacy in small trials. Appropriate medical therapies for epistaxis outcomes in HHT remain undefined, and there is no "gold standard." Many of the studies are small and the data reported are heterogeneous, and therefore the ability to make strong evidence-based recommendations is limited. However, many different medications appear to be promising options. © 2018 ARS-AAOA, LLC.

Osler-Weber-Rendu disease presenting with hepatocellular carcinoma: radiologic and genetic findings.

PubMed

Lee, Joo Ho; Lee, Yung Sang; Kim, Pyo Nyun; Lee, Beom Hee; Kim, Gu Whan; Yoo, Han Wook; Heo, Nae Yun; Lim, Young Suk; Lee, Han Chu; Chung, Young Hwa; Suh, Dong Jin

2011-12-01

This is a case report of a 68-year-old man with hepatocellular carcinoma (HCC) accompanied by hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, and hepatic vascular malformation. HHT is an autosomal dominant disorder of the fibrovascular tissue that is characterized by recurrent epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations. HHT is caused by mutation of the genes involved in the signaling pathway of transforming growth factor-β, which plays an important role in the formation of vascular endothelia. Hepatic involvement has been reported as occurring in 30-73% of patients with HHT. However, symptomatic liver involvement is quite rare, and the representative clinical presentations of HHT in hepatic involvement are high-output heart failure, portal hypertension, nodular regenerative hyperplasia, and symptoms of biliary ischemia. Some cases of HCC in association with HHT have been reported, but are very rare. We present herein the characteristic radiologic and genetic findings of HHT that was diagnosed during the evaluation and treatment of HCC.

Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14.

PubMed

Letteboer, Tom G W; Benzinou, Michael; Merrick, Christopher B; Quigley, David A; Zhau, Kechen; Kim, Il-Jin; To, Minh D; Jablons, David M; van Amstel, Johannes K P; Westermann, Cornelius J J; Giraud, Sophie; Dupuis-Girod, Sophie; Lesca, Gaetan; Berg, Jonathan H; Balmain, Allan; Akhurst, Rosemary J

2015-01-01

HHT shows clinical variability within and between families. Organ site and prevalence of arteriovenous malformations (AVMs) depend on the HHT causative gene and on environmental and genetic modifiers. We tested whether variation in the functional ENG allele, inherited from the unaffected parent, alters risk for pulmonary AVM in HHT1 mutation carriers who are ENG haploinsufficient. Genetic association was found between rs10987746 of the wild type ENG allele and presence of pulmonary AVM [relative risk = 1.3 (1.0018-1.7424)]. The rs10987746-C at-risk allele associated with lower expression of ENG RNA in a panel of human lymphoblastoid cell lines (P = 0.004). Moreover, in angiogenically active human lung adenocarcinoma tissue, but not in uninvolved quiescent lung, rs10987746-C was correlated with expression of PTPN14 (P = 0.004), another modifier of HHT. Quantitative TAQMAN expression analysis in a panel of normal lung tissues from 69 genetically heterogeneous inter-specific backcross mice, demonstrated strong correlation between expression levels of Eng, Acvrl1, and Ptpn14 (r2 = 0.75-0.9, P < 1 × 10(-12)), further suggesting a direct or indirect interaction between these three genes in lung in vivo. Our data indicate that genetic variation within the single functional ENG gene influences quantitative and/or qualitative differences in ENG expression that contribute to risk of pulmonary AVM in HHT1, and provide correlative support for PTPN14 involvement in endoglin/ALK1 lung biology in vivo. PTPN14 has been shown to be a negative regulator of Yap/Taz signaling, which is implicated in mechanotransduction, providing a possible molecular link between endoglin/ALK1 signaling and mechanical stress. EMILIN2, which showed suggestive genetic association with pulmonary AVM, is also reported to interact with Taz in angiogenesis. Elucidation of the molecular mechanisms regulating these interactions in endothelial cells may ultimately provide more rational choices for HHT therapy.

Injections of Intravenous Contrast for Computerized Tomography Scans Precipitate Migraines in Hereditary Hemorrhagic Telangiectasia Subjects at Risk of Paradoxical Emboli: Implications for Right-to-Left Shunt Risks.

PubMed

Patel, Trishan; Elphick, Amy; Jackson, James E; Shovlin, Claire L

2016-11-01

To evaluate if injection of intravenous particles may provoke migraines in subjects with right-to-left shunts due to pulmonary arteriovenous malformations (AVMs). Migraine headaches commonly affect people with hereditary hemorrhagic telangiectasia (HHT), especially those with pulmonary AVMs that provide right-to-left shunts. In our clinical practice, patients occasionally reported acute precipitation of migraine headaches following injection of technetium-labeled albumin macroaggregates for nuclear medicine scans. Self-reported migraine features and exacerbations were examined in HHT subjects with and without pulmonary AVMs, for a series of noninvasive and invasive investigations, using an unbiased online survey. One hundred and sixty-six subjects were classified as having both HHT and migraines. HHT subjects with migraines were more likely to have pulmonary AVMs (P < .0001). HHT subjects with pulmonary AVMs were more likely to report photophobia (P = .010), "flashes of light" (P = .011), or transient visual loss (P = .040). Pulse oximetry, x-rays, ultrasound, and computerized tomography (CT) scans without intravenous contrast medium rarely, if ever, provoked migraines, but unenhanced magnetic resonance imaging (MRI) was reported to exacerbate migraines by 14/124 (11.2%) subjects. One hundred and fourteen subjects had both enhanced and unenhanced CT examinations: studies with contrast media were more commonly reported to start (9/114 [7.8%]), and/or worsen migraines (18/114 [15.7%]), compared to those undertaken without contrast medium (P < .01), or after simple blood tests (P < .05). Additionally, migraine exacerbation was reported by 9/90 (10%) after contrast echocardiography, 2/44 (4.5%) after nuclear medicine scans, and 10/154 (6.5%) after blood tests. HHT subjects frequently report migraine exacerbation following blood tests, contrast echocardiograms, MRI imaging, and CT studies performed with intravenous contrast medium. Since air

Injections of Intravenous Contrast for Computerized Tomography Scans Precipitate Migraines in Hereditary Hemorrhagic Telangiectasia Subjects at Risk of Paradoxical Emboli: Implications for Right‐to‐Left Shunt Risks

PubMed Central

Patel, Trishan; Elphick, Amy; Jackson, James E.

2016-01-01

Objective To evaluate if injection of intravenous particles may provoke migraines in subjects with right‐to‐left shunts due to pulmonary arteriovenous malformations (AVMs). Background Migraine headaches commonly affect people with hereditary hemorrhagic telangiectasia (HHT), especially those with pulmonary AVMs that provide right‐to‐left shunts. In our clinical practice, patients occasionally reported acute precipitation of migraine headaches following injection of technetium‐labeled albumin macroaggregates for nuclear medicine scans. Methods Self‐reported migraine features and exacerbations were examined in HHT subjects with and without pulmonary AVMs, for a series of noninvasive and invasive investigations, using an unbiased online survey. Results One hundred and sixty‐six subjects were classified as having both HHT and migraines. HHT subjects with migraines were more likely to have pulmonary AVMs (P < .0001). HHT subjects with pulmonary AVMs were more likely to report photophobia (P = .010), “flashes of light” (P = .011), or transient visual loss (P = .040). Pulse oximetry, x‐rays, ultrasound, and computerized tomography (CT) scans without intravenous contrast medium rarely, if ever, provoked migraines, but unenhanced magnetic resonance imaging (MRI) was reported to exacerbate migraines by 14/124 (11.2%) subjects. One hundred and fourteen subjects had both enhanced and unenhanced CT examinations: studies with contrast media were more commonly reported to start (9/114 [7.8%]), and/or worsen migraines (18/114 [15.7%]), compared to those undertaken without contrast medium (P < .01), or after simple blood tests (P < .05). Additionally, migraine exacerbation was reported by 9/90 (10%) after contrast echocardiography, 2/44 (4.5%) after nuclear medicine scans, and 10/154 (6.5%) after blood tests. Conclusions HHT subjects frequently report migraine exacerbation following blood tests, contrast echocardiograms, MRI imaging, and

Real-time imaging of de novo arteriovenous malformation in a mouse model of hereditary hemorrhagic telangiectasia

PubMed Central

Park, Sung Ok; Wankhede, Mamta; Lee, Young Jae; Choi, Eun-Jung; Fliess, Naime; Choe, Se-Woon; Oh, Seh-Hoon; Walter, Glenn; Raizada, Mohan K.; Sorg, Brian S.; Oh, S. Paul

2009-01-01

Arteriovenous malformations (AVMs) are vascular anomalies where arteries and veins are directly connected through a complex, tangled web of abnormal arteries and veins instead of a normal capillary network. AVMs in the brain, lung, and visceral organs, including the liver and gastrointestinal tract, result in considerable morbidity and mortality. AVMs are the underlying cause of three major clinical symptoms of a genetic vascular dysplasia termed hereditary hemorrhagic telangiectasia (HHT), which is characterized by recurrent nosebleeds, mucocutaneous telangiectases, and visceral AVMs and caused by mutations in one of several genes, including activin receptor–like kinase 1 (ALK1). It remains unknown why and how selective blood vessels form AVMs, and there have been technical limitations to observing the initial stages of AVM formation. Here we present in vivo evidence that physiological or environmental factors such as wounds in addition to the genetic ablation are required for Alk1-deficient vessels to develop to AVMs in adult mice. Using the dorsal skinfold window chamber system, we have demonstrated for what we believe to be the first time the entire course of AVM formation in subdermal blood vessels by using intravital bright-field images, hyperspectral imaging, fluorescence recordings of direct arterial flow through the AV shunts, and vascular casting techniques. We believe our data provide novel insights into the pathogenetic mechanisms of HHT and potential therapeutic approaches. PMID:19805914

Hashimoto thyroiditis associated with ataxia telangiectasia.

PubMed

Patiroglu, Turkan; Gungor, Hatice Eke; Unal, Ekrem; Kurtoglu, Selim; Yikilmaz, Ali; Patiroglu, Tahir

2012-01-01

Ataxia telangiectasia is a rare genetic disease characterized by neurological manifestations, infections, and cancers. In addition to these cardinal features, different autoimmune diseases can be seen in patients with ataxia telangiectasia. Although there were reports of positive autoimmune thyroid antibodies associated with ataxia telangiectasia, to our knowledge, we report the first cases of nodular Hashimoto thyroiditis in two patients with ataxia telangiectasia in the English medical literature. These cases illustrate that despite the rarity of nodular Hashimoto thyroiditis associated with ataxia telangiectasia, physicians should be aware of this possibility. Furthermore, thyroid examination of patient with ataxia telangiectasia is recommended for early diagnosis.

Ataxia telangiectasia: learning from previous mistakes

PubMed Central

Kumar, Naveen; Aggarwal, Puneet; Dev, Nishanth; kumar, Gunjan

2012-01-01

Ataxia telangiectasia is an early onset neurodegenerative disorder. We report a case of childhood onset ataxia and ocular telangiectasia, presenting with pulmonary infection. The patient was diagnosed as ataxia telangiectasia. The patient succumbed to death owing to late diagnosis and sepsis. PMID:23242084

Vertical transmission of macular telangiectasia type 2.

PubMed

Delaere, Lien; Spielberg, Leigh; Leys, Anita M

2012-01-01

The purpose of this study was to report vertical transmission of macular telangiectasia type 2 and type 2 diabetes mellitus in 3 families. In this retrospective interventional case series, the charts of patients with inherited macular telangiectasia type 2 were reviewed. A large spectrum of presentations of macular telangiectasia type 2 was observed and has been studied with different techniques including best-corrected visual acuity, microperimetry, confocal blue reflectance fundus autofluorescence, fluorescein angiography, and time domain and spectral domain optical coherence tomography. Vertical transmission of macular telangiectasia type 2 and associated type 2 diabetes mellitus is described in 3 families. Symptomatic as well as asymptomatic eyes with macular telangiectasia type 2 were identified. In 2 families, a mother and son experienced visual loss and were diagnosed with macular telangiectasia type 2. All 4 patients had type 2 diabetes. Diabetic retinopathy was observed in one mother and her son. In the third family, the index patient was diagnosed macular telangiectasia type 2 after complaints of metamorphopsia. She and her family members had type 2 diabetes mellitus, and further screening of her family revealed familial macular telangiectasia type 2. None of the patients were treated for macular telangiectasia type 2. Macular telangiectasia type 2 may be more common than previously assumed, as vision can remain preserved and patients may go undiagnosed. Screening of family members is indicated, and detection of mild anomalies is possible using fundus autofluorescence and spectral domain optical coherence tomography.

Ataxia Telangiectasia

MedlinePlus

... A-T usually have normal or above normal intelligence. × Definition Ataxia-telangiectasia is a rare, childhood neurological ... A-T usually have normal or above normal intelligence. View Full Definition Treatment There is no cure ...

Ataxia - telangiectasia

MedlinePlus

... at specific symptoms. Support Groups Ataxia Telangiectasia Children's Project: www.atcp.org National Ataxia Foundation (NAF): ataxia. ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

Bioinformatic Analysis of Pathogenic Missense Mutations of Activin Receptor Like Kinase 1 Ectodomain

PubMed Central

Scotti, Claudia; Olivieri, Carla; Boeri, Laura; Canzonieri, Cecilia; Ornati, Federica; Buscarini, Elisabetta; Pagella, Fabio; Danesino, Cesare

2011-01-01

Activin A receptor, type II-like kinase 1 (also called ALK1), is a serine-threonine kinase predominantly expressed on endothelial cells surface. Mutations in its ACVRL1 encoding gene (12q11-14) cause type 2 Hereditary Haemorrhagic Telangiectasia (HHT2), an autosomal dominant multisystem vascular dysplasia. The study of the structural effects of mutations is crucial to understand their pathogenic mechanism. However, while an X-ray structure of ALK1 intracellular domain has recently become available (PDB ID: 3MY0), structure determination of ALK1 ectodomain (ALK1EC) has been elusive so far. We here describe the building of a homology model for ALK1EC, followed by an extensive bioinformatic analysis, based on a set of 38 methods, of the effect of missense mutations at the sequence and structural level. ALK1EC potential interaction mode with its ligand BMP9 was then predicted combining modelling and docking data. The calculated model of the ALK1EC allowed mapping and a preliminary characterization of HHT2 associated mutations. Major structural changes and loss of stability of the protein were predicted for several mutations, while others were found to interfere mainly with binding to BMP9 or other interactors, like Endoglin (CD105), whose encoding ENG gene (9q34) mutations are known to cause type 1 HHT. This study gives a preliminary insight into the potential structure of ALK1EC and into the structural effects of HHT2 associated mutations, which can be useful to predict the potential effect of each single mutation, to devise new biological experiments and to interpret the biological significance of new mutations, private mutations, or non-synonymous polymorphisms. PMID:22028876

Non-destructive testing of full-length bonded rock bolts based on HHT signal analysis

NASA Astrophysics Data System (ADS)

Shi, Z. M.; Liu, L.; Peng, M.; Liu, C. C.; Tao, F. J.; Liu, C. S.

2018-04-01

Full-length bonded rock bolts are commonly used in mining, tunneling and slope engineering because of their simple design and resistance to corrosion. However, the length of a rock bolt and grouting quality do not often meet the required design standards in practice because of the concealment and complexity of bolt construction. Non-destructive testing is preferred when testing a rock bolt's quality because of the convenience, low cost and wide detection range. In this paper, a signal analysis method for the non-destructive sound wave testing of full-length bonded rock bolts is presented, which is based on the Hilbert-Huang transform (HHT). First, we introduce the HHT analysis method to calculate the bolt length and identify defect locations based on sound wave reflection test signals, which includes decomposing the test signal via empirical mode decomposition (EMD), selecting the intrinsic mode functions (IMF) using the Pearson Correlation Index (PCI) and calculating the instantaneous phase and frequency via the Hilbert transform (HT). Second, six model tests are conducted using different grouting defects and bolt protruding lengths to verify the effectiveness of the HHT analysis method. Lastly, the influence of the bolt protruding length on the test signal, identification of multiple reflections from defects, bolt end and protruding end, and mode mixing from EMD are discussed. The HHT analysis method can identify the bolt length and grouting defect locations from signals that contain noise at multiple reflected interfaces. The reflection from the long protruding end creates an irregular test signal with many frequency peaks on the spectrum. The reflections from defects barely change the original signal because they are low energy, which cannot be adequately resolved using existing methods. The HHT analysis method can identify reflections from the long protruding end of the bolt and multiple reflections from grouting defects based on mutations in the instantaneous

About Ataxia-Telangiectasia

MedlinePlus

... the A-T patient usually shows another clinical hallmark of A-T: "telangiectasia," or tiny red "spider" ... children with A-T there is another clinical hallmark: immunodeficiency that usually brings recurrent respiratory infections. In ...

Variation in Telangiectasia Predisposing Genes Is Associated With Overall Radiation Toxicity

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

Tanteles, George A.; Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester; Murray, Robert J.S.

2012-11-15

Purpose: In patients receiving radiotherapy for breast cancer where the heart is within the radiation field, cutaneous telangiectasiae could be a marker of potential radiation-induced heart disease. We hypothesized that single nucleotide polymorphisms (SNPs) in genes known to cause heritable telangiectasia-associated disorders could predispose to such late, normal tissue vascular damage. Methods and Materials: The relationship between cutaneous telangiectasia as a late normal tissue radiation injury phenotype in 633 breast cancer patients treated with radiotherapy was examined. Patients were clinically assessed for the presence of cutaneous telangiectasia and genotyped at nine SNPs in three candidate genes. Candidate SNPs were withinmore » the endoglin (ENG) and activin A receptor, type II-like 1 (ACVRL1) genes, mutations in which cause hereditary hemorrhagic telangiectasia and the ataxia-telangiectasia mutated (ATM) gene associated with ataxia-telangiectasia. Results: A total of 121 (19.1%) patients exhibited a degree of cutaneous telangiectasiae on clinical examination. Regression was used to examine the associations between the presence of telangiectasiae in patients who underwent breast-conserving surgery, controlling for the effects of boost and known brassiere size (n=388), and individual geno- or haplotypes. Inheritance of ACVRL1 SNPs marginally contributed to the risk of cutaneous telangiectasiae. Haplotypic analysis revealed a stronger association between inheritance of a ATM haplotype and the presence of cutaneous telangiectasiae, fibrosis and overall toxicity. No significant association was observed between telangiectasiae and the coinheritance of the candidate ENG SNPs. Conclusions: Genetic variation in the ATM gene influences reaction to radiotherapy through both vascular damage and increased fibrosis. The predisposing variation in the ATM gene will need to be better defined to optimize it as a predictive marker for assessing radiotherapy late

Blood Disorders

MedlinePlus

... become hard, sticky, and shaped like a C. Thalassemia Red blood cell disorder. Von Willebrand Disease Blood ... Hemophilia Hereditary Hemorrhagic Telangiectasia (HHT) Sickle Cell Disease Thalassemia Vitamin K Deficiency Bleeding Von Willebrand Disease Women’s ...

Using the HHT to Search for Gravitational Waves

NASA Technical Reports Server (NTRS)

Camp, Jordan

2008-01-01

Gravitational waves are a consequence of Einstein's theory of general relativity applied to the motion of very dense and massive objects such as black holes and neutron stars. Their detection will reveal a wealth of information about these mysterious objects that cannot be obtained with electromagnetic probes. Two projects are underway to attempt the detection of gravitational waves: NASA's Laser Interferometer Space Antenna (LISA), a space based mission being designed to search for waves from supermassive black holes at the centers of galaxies, and the NSF's Laser Interferometer Gravitational Wave Observatory (LIGO), a ground based facility that is now searching for waves from supernovae. pulsars, and the coalescence of black hole and neutron star systems. Because general relativity is an inherently non-linear theory, many of the predicted source waveforms show strong frequency modulation. In addition, the LIGO and LISA detectors are highly sensitive devices that produce a variety of non-linear transient noise features. Thus the unique capabilities of the HHT. the extraction of intrawave modulation and the characterization of non-linear and non-stationary signals, have a natural application to both signal detection and experimental characterization of the detectors. In this talk I will give an overview of the status of the field. including some of the expected sources of gravitational waves, and I will also describe the LISA and LIGO detectors. Then I will describe some applications of the HHT to waveform detection and detector noise characterization.

Ionizing radiation and cell cycle progression in ataxia telangiectasia

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

Beamish, H.; Khanna, K.K.; Lavin, M.F.

1994-04-01

Exposure of mammalian cells to ionizing radiation causes delay in normal progress through the cell cycle at a number of different checkpoints. Abnormalities in these checkpoints have been described for ataxia telangiectasia cells after irradiation. In this report we show that these abnormalities occur at different phases in the cell cycle in several ataxia telangiectasia lymphoblastoid cells. Ataxia telangiectasia cells, synchronized in late G{sub 1} phase with either mimosine or aphidicolin and exposed to radiation, showed a reduced delay in entering S phase compared to irradiated control cells. Failure to exhibit G{sub 1}-phase delay in ataxia telangiectasia cells is accompaniedmore » by a reduced ability of radiation to activate the product of the tumor suppressor gene p53, a protein involved in G{sub 1}/S-phase delay. When the progress of irradiated G{sub 1}-phase cells was followed into the subsequent G{sub 2} and G{sub 1} phases ataxia telangiectasia cells showed a more pronounced accumulation in G{sub 2} phase than control cells. When cells were irradiated in S phase and extent of delay was more evident in G{sub 2} phase and ataxia telangiectasia cells were delayed to a greater extent. These results suggest that the lack of initial delay in both G{sub 1} and S phases to the radiosensitivity observed in this syndrome. 26 refs., 3 figs., 2 tabs.« less

Acute Methanol Poisoning: Prevalence and Predisposing Factors of Haemorrhagic and Non-Haemorrhagic Brain Lesions.

PubMed

Zakharov, Sergey; Kotikova, Katerina; Vaneckova, Manuela; Seidl, Zdenek; Nurieva, Olga; Navratil, Tomas; Caganova, Blazena; Pelclova, Daniela

2016-08-01

The purpose was to study the prevalence and predisposing factors of brain lesions in survivors of acute methanol poisoning. Clinical data on 106 patients with methanol poisoning were collected during the Czech mass poisoning outbreak. Of 83 survivors, in 46 (55%) patients, follow-up examinations including magnetic resonance imaging of brain (MR) were performed 3-8 and 24-28 months after discharge from the hospital. Of 46 patients with a median age of 49 (interquartile range, 35-57) years, 24 (52%) patients had a total of 40 abnormal brain findings with haemorrhagic lesions detected in 15 (33%) and non-haemorrhagic lesions found in 9 (19%) patients. The patients with haemorrhagic brain lesions were more acidemic (lower arterial blood pH, higher base deficit) and had higher glycaemia and lactacidaemia on admission than those without haemorrhages (all p < 0.05). Thirteen of 32 (41%) of patients with systemic anticoagulation and 2 of 14 (14%) of patients without it had haemorrhagic lesions (p = 0.080). Bleeding complications during the treatment occurred in 4 of 15 (27%) patients, and 5 of 15 (33%) patients had conditions predisposing to haemorrhage in the group with haemorrhagic lesions. In three cases with a series of computer tomography (CT)/MR performed during hospitalization, the necrotic lesions in the brain remained non-haemorrhagic during hospitalization and haemorrhagic lesions were detected on the follow-up MR examinations only. No association between brain haemorrhages and systemic anticoagulation during dialysis was found: brain haemorrhages might occur in severely poisoned patients treated without systemic anticoagulation, whereas treatment with high doses of heparin might not lead to brain haemorrhages. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Disorders of Upper Limb Movements in Ataxia-Telangiectasia.

PubMed

Shaikh, Aasef G; Zee, David S; Mandir, Allen S; Lederman, Howard M; Crawford, Thomas O

2013-01-01

Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task), while arms were outstretched (postural task), and at rest. Almost all ataxia-telangiectasia subjects (79/80) had abnormal involuntary movements, such as rhythmic oscillations (tremor), slow drifts (dystonia or athetosis), and isolated rapid movements (dystonic jerks or myoclonus). All patients with involuntary movements had both kinetic and postural tremor, while 48 (61%) also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia.

Disorders of Upper Limb Movements in Ataxia-Telangiectasia

PubMed Central

Shaikh, Aasef G.; Zee, David S.; Mandir, Allen S.; Lederman, Howard M.; Crawford, Thomas O.

2013-01-01

Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task), while arms were outstretched (postural task), and at rest. Almost all ataxia-telangiectasia subjects (79/80) had abnormal involuntary movements, such as rhythmic oscillations (tremor), slow drifts (dystonia or athetosis), and isolated rapid movements (dystonic jerks or myoclonus). All patients with involuntary movements had both kinetic and postural tremor, while 48 (61%) also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia. PMID:23826191

BMP9 induces EphrinB2 expression in endothelial cells through an Alk1-BMPRII/ActRII-ID1/ID3-dependent pathway: Implications for Hereditary Hemorrhagic Telangiectasia Type II

PubMed Central

Kim, Jai-Hyun; Peacock, Matthew R.; George, Steven C.; Hughes, Christopher C.W.

2012-01-01

ALK1 (ACVRL1) is a member of the TGFβ receptor family and is expressed predominantly by arterial endothelial cells (EC). Mutations in ACVRL1 are responsible for Hereditary Hemorrhagic Telangiectasia Type 2 (HHT2), a disease manifesting as fragile vessels, capillary overgrowth, and numerous arterio-venous malformations (AVMs). Arterial EC also express EphrinB2, which has multiple roles in vascular development and angiogenesis and is known to be reduced in ACVRL1 knockout mice. Using an in vitro angiogenesis model we find that the Alk1 ligand BMP9 induces EphrinB2 in EC, and this is entirely dependent on expression of Alk1 and at least one of the co-receptors BMPRII or ActRII. BMP9 induces both ID1 and ID3, and both are necessary for full induction of EphrinB2. Loss of Alk1 or EphrinB2 results in increased arterial-venous anastomosis, while loss of Alk1 but not EphrinB2 results in increased VEGFR2 expression and enhanced capillary sprouting. Conversely, BMP9 blocks EC sprouting and this is dependent on Alk1, BMPRII/ActRII and ID1/ID3. Finally, notch signaling overcomes the loss of Alk1 – restoring EphrinB2 expression in EC, and curbing excess sprouting. Thus, in an in vitro model of HHT2, loss of Alk1 blocks BMP9 signaling, resulting in reduced EphrinB2 expression, enhanced VEGFR2 expression, and misregulated EC sprouting and anastomosis. PMID:22622516

Methamphetamine-related brainstem haemorrhage.

PubMed

Chiu, Zelia K; Bennett, Iwan E; Chan, Patrick; Rosenfeld, Jeffrey V

2016-10-01

We report the case of an otherwise healthy 29-year-old woman who presented with a brainstem haemorrhage following intravenous methamphetamine use. Extensive investigation did not reveal an underlying pathology, and the development of symptoms was temporally related to methamphetamine injection. Although intracerebral haemorrhage secondary to methamphetamine use is well documented, this report describes a haemorrhage within the brainstem which is a rare location. While animal studies have demonstrated the potential of methamphetamines to produce brainstem haemorrhages, there has only been one previous report describing a haemorrhage in this location due to amphetamine use in humans. We conclude with a brief discussion of the clinical features and aetiology of methamphetamine-related stroke. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Cerebral ischemia in Rendu-Osler-Weber disease].

PubMed

Delgado Reyes, S; García de la Rocha, M L; Fernández-Armayor Ajo, V; Sierra Sierra, I; Martín Araguz, A; Moreno Martínez, J M

2000-02-01

Neurologic manifestations occur in 8-12% of the patients with Rendu-Osler-Weber disease or hereditary hemorrhagic telangiectasia (HHT), principally infectious and hemorrhagic and, less frequently, ischemic ones. More than a half of these neurologic complications are associated with pulmonary arterio-venous malformations (PAVM). The diagnosis of HHT is based on the presence of telangiectases, hemorrhagic events and a family history with an autosomal dominant pattern. We report a case of a patient diagnosed as having HHT with transient ischemic attacks and a PAVM, which was occluded by the use of embolotherapy. Cerebral ischemia in HHT is related to the existence of a PAVM and results from three mechanisms: 1) secondary poliglobulia and hyperviscosity because of the hypoxemia due to a right-left shunt; 2) communication between the airway and the pulmonary circulation during cough access, which produces gas embolism and hemoptysis; 3) and, finally, paradoxical embolism trough the PAVM, the same mechanism proposed to the infectious neurologic manifestations of the disease. When the diagnosis of HHT is suspected, early search and treatment of PAVM, with embolotherapy or surgery, are necessary in order to avoid respiratory problems (hemoptysis, exertional dyspnea, cianosis, clubbing) and neurologic complications.

Diode laser for the treatment of telangiectasias following hemangioma involution.

PubMed

Cerrati, Eric W; O, Teresa M; Chung, Hoyun; Waner, Milton

2015-02-01

Infantile hemangiomas are well known for their rapid growth during the first 6 to 9 months of life, followed by a spontaneous but slow involution. The standard of care is to treat these lesions at an early age with propranolol to expedite the involution process; however, surgery still remains an active component in the management. Medical treatment with propranolol or natural involution will often result in residual telangiectasias. We evaluated the efficacy of using a diode laser as a treatment for telangiectasias following cervicofacial infantile hemangioma involution. Case series with chart review. Tertiary care hospital and practice specializing in the care of vascular anomalies. Twenty patients, aged 4 months to 11 years (average 2.69 years), underwent treatment with a 532-nm diode laser to treat the residual telangiectasias following hemangioma involution. All procedures were performed in the operating room. To assess the efficacy, we independently evaluated pre- and posttreatment digital photographs and ranked them on a 0- to 4-point scale (0 = no change and 4 = complete response). Adverse reactions were also recorded. The telangiectasias showed considerable improvement following treatment. In more than half of the patients treated, the affected area demonstrated a complete response. No adverse reactions were noted. A 532-nm diode laser effectively treats the remaining telangiectasias following hemangioma involution. Whether used independently or in conjunction with other treatment modalities, the diode laser should be part of the surgical armamentarium when treating infantile hemangiomas. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

PubMed

Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

2014-06-01

Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic

Bilateral eyelid ecchymosis and subconjunctival haemorrhage manifesting as presenting feature in a case of dengue haemorrhagic fever.

PubMed

Jain, Sparshi; Goswami, Anup; Singh, Nidhi; Kaur, Savleen

2015-10-01

We report a case of bilateral eyelid ecchymosis and subconjunctival haemorrhage, a rare presenting feature of dengue haemorrhagic fever. A 17-year-old boy presented to the emergency department with complaints of redness in both eyes and vomiting. He had bilateral eyelid ecchymosis with subconjunctival haemorrhage. Complete blood count revealed a significantly reduced platelet count of 11000/µL suggestive of dengue haemorrhagic fever (DHF). Ocular manifestations were followed by other systemic haemorrhagic manifestations of dengue later on which violates the usual sequence of events of dengue fever. Bilateral eyelid ecchymosis is a rare clinical manifestation and a rare presenting feature of dengue fever and one has to keep high index of suspicion for presence of dengue whenever a case of fever presents with lid ecchymosis/haemorrhage. © The Author(s) 2014.

Successful Treatment of Generalized Essential Telangiectasia With 6-Mercaptopurine.

PubMed

Glazer, Alex M; Sofen, Bryan D; Rigel, Darrell S; Shupack, Jerome L

2017-03-01

Generalized essential telangiectasia (GET) is a notoriously difficult to treat disorder with no current satisfactory treatments. This case and discussion report the use of 6-mercaptopurine (6-MP) as a successful treatment for GET. Moreover, we show that GET may represent a state of increased angiogenesis, a paradigm shift from the current understanding that these telangiectasias represent dilatations of only pre-existing vessels. This new view of GET may drive others to look at novel agents for treatment.

J Drugs Dermatol. 2017;16(3):280-282.

Genetics Home Reference: hereditary hemorrhagic telangiectasia

MedlinePlus

... Central OMIM: JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic ... 10.1097/GIM.0b013e3182136d32. Review. Citation on PubMed McDonald J, Wooderchak-Donahue W, VanSant Webb C, Whitehead ...

Delayed seizures after intracerebral haemorrhage

PubMed Central

Rattani, Abbas; Anderson, Christopher D.; Ayres, Alison M.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand

2016-01-01

Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ε2/ε4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5–1

Automatic detection and quantification of pulmonary arterio-venous malformations in hereditary hemorrhagic telangiectasia

NASA Astrophysics Data System (ADS)

Fetita, Catalin; Fortemps de Loneux, Thierry; Kouvahe, Amélé Florence; El Hajjam, Mostafa

2017-03-01

Hereditary hemorrhagic telangiectasia (HHT) is an autosomic dominant disorder, which is characterized by the development of multiple arterio-venous malformations in the skin, mucous membranes, and/or visceral organs. Pulmonary Arterio-Venous Malformation (PAVM) is an abnormal connection where feeding arteries shunt directly into draining veins with no intervening capillary bed. This condition may lead to paradoxical embolism and hemorrhagic complications. PAVMs patients should systematically be screened as the spontaneous complication rate is high, reaching almost 50%. Chest enhanced contrast CT scanner is the reference screening and follow-up examination. When performed by experienced operators as the prime treatment, percutaneous embolization of PAVMs is a safe, efficient and sustained therapy. The accuracy of PAVM detection and quantification of its progression over time is the key of embolotherapy success. In this paper, we propose an automatic method for PAVM detection and quantification relying on a modeling of vessel deformation, i.e. local caliber increase, based on mathematical morphology. The pulmonary field and vessels are first segmented using geodesic operators. The vessel caliber is estimated by means of a granulometric measure and the local caliber increase is detected by using a geodesic operator, the h-maxdomes. The detection sensitivity can be tuned up according to the choice of the h value which models the irregularity of the vessel caliber along its axis and the PAVM selection is performed according to a clinical criterion of >3 mm diameter of the feeding artery of the PAVM. The developed method was tested on a 20 patient dataset. A sensitivity study allowed choosing the irregularity parameter to maximize the true positive ratio reaching 85.4% in average. A specific false positive reduction procedure targeting the vessel trunks of the arterio-venous tree near mediastinum allows a precision increase from 13% to 67% with an average number of 1

Prophylactic ethamsylate for periventricular haemorrhage.

PubMed Central

Cooke, R W; Morgan, M E

1984-01-01

Drug prophylaxis with ethamsylate for periventricular haemorrhage in very low birthweight infants significantly reduced the incidence of periventricular haemorrhage in survivors. A reduction in abnormalities at follow up and in insertion of ventriculoperitoneal shunts was also noted. PMID:6696506

Measurement of blood loss during postpartum haemorrhage.

PubMed

Lilley, G; Burkett-St-Laurent, D; Precious, E; Bruynseels, D; Kaye, A; Sanders, J; Alikhan, R; Collins, P W; Hall, J E; Collis, R E

2015-02-01

We set out to validate the accuracy of gravimetric quantification of blood loss during simulated major postpartum haemorrhage and to evaluate the technique in a consecutive cohort of women experiencing major postpartum haemorrhage. The study took part in a large UK delivery suite over a one-year period. All women who experienced major postpartum haemorrhage were eligible for inclusion. For the validation exercise, in a simulated postpartum haemorrhage scenario using known volumes of artificial blood, the accuracy of gravimetric measurement was compared with visual estimation made by delivery suite staff. In the clinical observation study, the blood volume lost during postpartum haemorrhage was measured gravimetrically according to our routine institutional protocol and was correlated with fall in haemoglobin. The main outcome measure was the accuracy of gravimetric measurement of blood loss. Validation exercise: the mean percentage error of gravimetrically measured blood volume was 4.0±2.7% compared to visually estimated blood volume with a mean percentage error of 34.7±32.1%. Clinical observation study: 356 out of 6187 deliveries were identified as having major postpartum haemorrhage. The correlation coefficient between measured blood loss and corrected fall in haemoglobin for all patients was 0.77; correlation was stronger (0.80) for postpartum haemorrhage >1500mL, and similar during routine and out-of-hours working. The accuracy of the gravimetric method was confirmed in simulated postpartum haemorrhage. The clinical study shows that gravimetric measurement of blood loss is correlated with the fall in haemoglobin in postpartum haemorrhage where blood loss exceeds 1500mL. The method is simple to perform, requires only basic equipment, and can be taught and used by all maternity services during major postpartum haemorrhage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Late post pancreatectomy haemorrhage. Risk factors and modern management.

PubMed

Sanjay, Pandanaboyana; Fawzi, Ali; Fulke, Jennifer L; Kulli, Christoph; Tait, Iain S; Zealley, Iain A; Polignano, Francesco M

2010-05-05

Current management of late post-pancreatectomy haemorrhage in a university hospital. Haemorrhage after pancreaticoduodenectomy is a serious complication. We report on risk factors and outcome following management by radiological intervention. Tertiary care centre in Scotland. Sixty-seven consecutive patients who underwent pancreaticoduodenectomy. All pancreaticoduodenectomies over a 3-year period were reviewed. International Study Group on Pancreatic Surgery (ISGPS) definition of post-pancreatectomy haemorrhage was used. Endpoints were incidence of haemorrhage, pancreaticojejunal anastomosis leak, methicillin-resistant Staphylococcus aureus (MRSA) infection and mortality. Seven patients (10.4%) developed post-pancreatectomy haemorrhage out of 67 pancreaticoduodenectomies. Median age was 71 years. All post-pancreatectomy haemorrhage were late onset (median 23 days; range: 3-35 days), extraluminal and ISGPS grade C. Post-pancreatectomy haemorrhage arose from hepatic artery (n=4), superior mesenteric artery (n=1), jejunal artery (n=1), and splenic artery (n=1). Angiographic treatment was successful in all patients by embolisation (n=5) or stent grafting (n=2). Pancreatic fistula rate was similar in post-pancreatectomy haemorrhage and "no-haemorrhage" groups (57.1% vs. 40.0%; P=0.440); MRSA infection was significantly higher in post-pancreatectomy haemorrhage group (57.1% vs. 16.7%; P=0.030). Mortality from post-pancreatectomy haemorrhage despite successful haemostasis was 42.9%. Univariate and multivariate analysis identified MRSA infection as a risk factor for post-pancreatectomy haemorrhage. CT angiogram followed by conventional catheter angiography is effective for treatment of late extraluminal post-pancreatectomy haemorrhage. MRSA infection in the abdominal drain fluid increases its risk and therefore aggressive treatment of MRSA and high index of suspicion are indicated.

Appreciating the broad clinical features of SMAD4 mutation carriers: a multi-center chart review

PubMed Central

Wain, K.E.; Ellingson, M.S.; McDonald, J.; Gammon, A.; Roberts, M.; Pichurin, P.; Winship, I.; Riegert-Johnson, D.; Weitzel, J. N.; Lindor, N.M.

2014-01-01

Heterozygous loss-of-function (LOF) SMAD4 mutations are associated with juvenile polyposis syndrome (JP) and hereditary hemorrhagic telangiectasia (HHT). Some carriers exhibit symptoms of both conditions, leading to the name JP-HHT syndrome. Three families have been reported with connective tissue abnormalities. In order to better understand the spectrum and extent of clinical findings in SMAD4 carriers, medical records of 34 patients (20 families) from five clinical practices were reviewed. Twenty-one percent (7/34) had features suggesting a connective tissue defect: enlarged aortic root (n=3), aortic and mitral insufficiency (n=2), aortic dissection (n=1), retinal detachment (n=1), brain aneurysms (n=1), lax skin and joints (n=1). JP-specific findings were almost uniformly present but variable. Ninety-seven percent had colon polyps that were generally pan-colonic and of variable histology and number. Forty-eight percent (15/31) had extensive gastric polyposis. HHT features were documented in 76% including epistaxis (19/31, 61%), mucocutaneous telangiectases (15/31, 48%), liver arteriovenous malformation (AVM) (6/16, 38%), brain AVM (1/26, 4%), pulmonary AVM (9/17, 53%), and intrapulmonary shunting (14/23, 61%). SMAD4 carriers should be managed for JP and HHT, since symptoms of both are likely yet unpredictable. Connective tissue abnormalities are an emerging component of JP-HHT syndrome, and larger studies are needed to understand these manifestations. PMID:24525918

Bevacizumab as a treatment for hereditary hemorrhagic telangiectasia in children: a case report

PubMed Central

Ospina, Fabio E; Echeverri, Alex; Posso-Osorio, Iván; Jaimes, Lina; Gutierrez, Jaiber

2017-01-01

Abstract Case description: Five-year-old female patient with hereditary hemorrhagic telangiectasia. Clinical Findings: Deterioration of cardiopulmonary function with higher oxygen requirements secondary to pulmonary arteriovenous shunts, epistaxis. Treatment and Outcome: The patient was treated with the monoclonal antibody bevacizumab, which inhibits the vascular endothelial growth factor, with good clinical outcome. Clinical Relevance: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by arteriovenous malformations in different organs, making its clinical presentations varied. Systemic therapeutic options for a generalized disease are limited. The monoclonal antibody bevacizumab, seems to be a good option in this disorder. Although reported as successful in adult population, its use in pediatric population has not yet been reported. Here we report the use of bevacizumab in a 5-year-old female patient with hereditary hemorrhagic telangiectasia, showing clinical benefits and good outcome. PMID:29021642

Atm reactivation reverses ataxia telangiectasia phenotypes in vivo.

PubMed

Di Siena, Sara; Campolo, Federica; Gimmelli, Roberto; Di Pietro, Chiara; Marazziti, Daniela; Dolci, Susanna; Lenzi, Andrea; Nussenzweig, Andre; Pellegrini, Manuela

2018-02-22

Hereditary deficiencies in DNA damage signaling are invariably associated with cancer predisposition, immunodeficiency, radiation sensitivity, gonadal abnormalities, premature aging, and tissue degeneration. ATM kinase has been established as a central player in DNA double-strand break repair and its deficiency causes ataxia telangiectasia, a rare, multi-system disease with no cure. So ATM represents a highly attractive target for the development of novel types of gene therapy or transplantation strategies. Atm tamoxifen-inducible mouse models were generated to explore whether Atm reconstitution is able to restore Atm function in an Atm-deficient background. Body weight, immunodeficiency, spermatogenesis, and radioresistance were recovered in transgenic mice within 1 month from Atm induction. Notably, life span was doubled after Atm restoration, mice were protected from thymoma and no cerebellar defects were observed. Atm signaling was functional after DNA damage in vivo and in vitro. In summary, we propose a new Atm mouse model to investigate novel therapeutic strategies for ATM activation in ataxia telangiectasia disease.

Clinical practice guidelines in intracerebral haemorrhage.

PubMed

Rodríguez-Yáñez, M; Castellanos, M; Freijo, M M; López Fernández, J C; Martí-Fàbregas, J; Nombela, F; Simal, P; Castillo, J; Díez-Tejedor, E; Fuentes, B; Alonso de Leciñana, M; Alvarez-Sabin, J; Arenillas, J; Calleja, S; Casado, I; Dávalos, A; Díaz-Otero, F; Egido, J A; Gállego, J; García Pastor, A; Gil-Núñez, A; Gilo, F; Irimia, P; Lago, A; Maestre, J; Masjuan, J; Martínez-Sánchez, P; Martínez-Vila, E; Molina, C; Morales, A; Purroy, F; Ribó, M; Roquer, J; Rubio, F; Segura, T; Serena, J; Tejada, J; Vivancos, J

2013-05-01

Intracerebral haemorrhage accounts for 10%-15% of all strokes; however it has a poor prognosis with higher rates of morbidity and mortality. Neurological deterioration is often observed during the first hours after onset and determines poor prognosis. Intracerebral haemorrhage, therefore, is a neurological emergency which must be diagnosed and treated properly as soon as possible. In this guide we review the diagnostic procedures and factors that influence the prognosis of patients with intracerebral haemorrhage and we establish recommendations for the therapeutic strategy, systematic diagnosis, acute treatment and secondary prevention for this condition. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Immunodeficiency in ataxia telangiectasia is correlated strongly with the presence of two null mutations in the ataxia telangiectasia mutated gene

PubMed Central

Staples, E R; McDermott, E M; Reiman, A; Byrd, P J; Ritchie, S; Taylor, A M R; Davies, E G

2008-01-01

Immunodeficiency affects over half of all patients with ataxia telangiectasia (A-T) and when present can contribute significantly to morbidity and mortality. A retrospective review of clinical history, immunological findings, ataxia telangiectasia mutated (ATM) enzyme activity and ATM mutation type was conducted on 80 consecutive patients attending the National Clinic for Ataxia Telangiectasia, Nottingham, UK between 1994 and 2006. The aim was to characterize the immunodeficiency in A-T and determine its relationship to the ATM mutations present. Sixty-one patients had mutations resulting in complete loss of ATM kinase activity (group A) and 19 patients had leaky splice or missense mutations resulting in residual kinase activity (group B). There was a significantly higher proportion of patients with recurrent sinopulmonary infections in group A compared with group B (31 of 61 versus four of 19 P = 0·03) and a greater need for prophylactic antibiotics (30 of 61 versus one of 19 P = 0·001). Comparing group A with group B patients, 25 of 46 had undetectable/low immunoglobulin A (IgA) levels compared with none of 19; T cell lymphopenia was found in 28 of 56 compared with one of 18 and B cell lymphopenia in 35 of 55 compared with four of 18 patients (P = 0·00004, 0·001 and 0·003 respectively). Low IgG2 subclass levels and low levels of antibodies to pneumococcal polysaccharide were more common in group A than group B (16 of 27 versus one of 11 P = 0·01; 34/43 versus six of 17 P = 0·002) patients. Ig replacement therapy was required in 10 (12·5%) of the whole cohort, all in group A. In conclusion, A-T patients with no ATM kinase activity had a markedly more severe immunological phenotype than those expressing low levels of ATM activity. PMID:18505428

Haemorrhagic Fevers, Viral

MedlinePlus

... Filoviridae (Ebola and Marburg) and Flaviviridae (yellow fever, dengue, Omsk haemorrhagic fever, Kyasanur forest disease). General information ... the Ebola vaccine trials in Guinea What is dengue and how is it treated? Fact sheets Crimean- ...

Using silicone gel sheet for the treatment of facial telangiectasias with sclerotherapy.

PubMed

Misirlioglu, Aykut; Gideroglu, Kaan; Akan, Mithat; Akoz, Tayfun

2004-03-01

Telangiectasias are superficial cutaneous vessels that are visible to human eye and are present as a dilated venule, capillary, or arteriole. They are a common cause of concern, especially when located in face. Sclerotherapy is among the treatment alternatives, but facial telangiectasias are less responsive than those located on the leg. To show the effectiveness of silicone gel sheet in improving the results obtained by sclerotherapy in facial telangiectasias. Between 1998 and 2003, 32 patients were treated with sclerotherapy and silicone gel sheet (group 1). Twenty-six patients were treated with sclerotherapy and cotton ball (group 2), and 30 patients were treated only sclerotherapy (group 3). Patients were evaluated for 12 weeks for the degree of improvement and side effects. All complications, side effects, and number of sessions were also recorded at each follow-up visit. The number of sessions is limited to six. After the final follow-up visit, the photographs taken of each treatment site at baseline and at final visit were reviewed in a double-blinded manner based on a 0 to 4 scale by two physicians. Fifty one of the 88 patients showed improvement totally. In the silicone sheet-sclerotherapy group, 22 of the 36 patients showed improvement. In the sclerotherapy-cotton ball group, 14 of the 26 patients showed improvement, and in the sclerotherapy-only group, 15 of the 30 patients showed improvement completely within the 12 weeks. The patients treated with sclerotherapy-silicone gel sheet (group 1) had more improvement than the other groups. Combining silicone gel sheeting to sclerotherapy increases the success rate in treating facial telangiectasias, especially facial subunits, which have bone support.

Subarachnoid haemorrhage with "Ecstasy" abuse in a young adult.

PubMed

Auer, J; Berent, R; Weber, T; Lassnig, E; Eber, B

2002-10-01

Abuse of the drugs like amphetamine, cocaine and "Ecstasy" may be complicated by intracerebral, subdural or subarachnoid haemorrhage. Contrary to historical opinion, drug-related intracranial haemorrhage (ICH) is frequently related to an underlying vascular malformation. We report the case of an 18-year-old man with a history of Ecstasy abuse preceding the onset of severe occipital headache. Cerebral computed tomography revealed right-sided subarachnoid haemorrhage and cerebral angiography showed right-sided middle cerebral artery aneurysm of 1 cm diameter. The patient was treated surgically with aneurysm clipping. Three weeks after onset of intracranial haemorrhage, neurological examination demonstrated normal findings. A history of severe headache immediately after using amphetamine, Ecstasy, or cocaine should alert doctors to the possibility of intracerebral haemorrhage. Arteriography should be part of the evaluation of most young patients with stroke or non-traumatic ICH.

[Pulmonary arteriovenous fistula with Rendu-Osler-Weber disease].

PubMed

Segawa, Masataka; Touge, Masayoshi; Seki, Kouji; Kusajima, Yoshinori; Saito, Katsuhiko

2012-09-01

A 36-year-old man was admitted to our hospital for examination of a nodular shadow in the left lung. Chest 3-dimensional computed tomography (3D-CT) revealed a pulmonary arteriovenous fistula (PAVF) of 21 mm in diameter composed of the feeding artery (A4) and the draining vein (V4) in the left S4. Abdominal enhanced CT revealed multiple hepatic arteriovenous fistula. Brain CT revealed a cavernous hemangioma in right occipital cerebrum. He had a family history, habitual epistaxis, and oral telangiectasia and was diagnosed as Rendu-Osler-Weber disease (hereditary hemorrhagic telangiectasia:HHT). According to his family history, PAVF was likely to be a risk factor of brain infarction and abscess, and the wedge resection of the lingual lobe was performed to remove PAVF.

Analysis of turbine-grid interaction of grid-connected wind turbine using HHT

NASA Astrophysics Data System (ADS)

Chen, A.; Wu, W.; Miao, J.; Xie, D.

2018-05-01

This paper processes the output power of the grid-connected wind turbine with the denoising and extracting method based on Hilbert Huang transform (HHT) to discuss the turbine-grid interaction. At first, the detailed Empirical Mode Decomposition (EMD) and the Hilbert Transform (HT) are introduced. Then, on the premise of decomposing the output power of the grid-connected wind turbine into a series of Intrinsic Mode Functions (IMFs), energy ratio and power volatility are calculated to detect the unessential components. Meanwhile, combined with vibration function of turbine-grid interaction, data fitting of instantaneous amplitude and phase of each IMF is implemented to extract characteristic parameters of different interactions. Finally, utilizing measured data of actual parallel-operated wind turbines in China, this work accurately obtains the characteristic parameters of turbine-grid interaction of grid-connected wind turbine.

Characterisation of ATM mutations in Slavic Ataxia telangiectasia patients.

PubMed

Soukupova, Jana; Pohlreich, Petr; Seemanova, Eva

2011-09-01

Ataxia telangiectasia (AT) is a genomic instability syndrome characterised, among others, by progressive cerebellar degeneration, oculocutaneous telangiectases, immunodeficiency, elevated serum alpha-phetoprotein level, chromosomal breakage, hypersensitivity to ionising radiation and increased cancer risk. This autosomal recessive disorder is caused by mutations in the ataxia telangiectasia mutated (ATM) gene coding for serine/threonine protein kinase with a crucial role in response to DNA double-strand breaks. We characterised genotype and phenotype of 12 Slavic AT patients from 11 families. Mutation analysis included sequencing of the entire coding sequence, adjacent intron regions, 3'UTR and 5'UTR of the ATM gene and multiplex ligation-dependent probe amplification (MLPA) for the detection of large deletions/duplications at the ATM locus. The high incidence of new and individual mutations demonstrates a marked mutational heterogeneity of AT in the Czech Republic. Our data indicate that sequence analysis of the entire coding region of ATM is sufficient for a high detection rate of mutations in ATM and that MLPA analysis for the detection of deletions/duplications seems to be redundant in the Slavic population.

Ebola haemorrhagic fever

PubMed Central

Feldmann, Heinz; Geisbert, Thomas W

2012-01-01

Ebola viruses are the causative agents of a severe form of viral haemorrhagic fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of central Africa. The exception is the species Reston Ebola virus, which has not been associated with human disease and is found in the Philippines. Ebola virus constitutes an important local public health threat in Africa, with a worldwide effect through imported infections and through the fear of misuse for biological terrorism. Ebola virus is thought to also have a detrimental effect on the great ape population in Africa. Case-fatality rates of the African species in man are as high as 90%, with no prophylaxis or treatment available. Ebola virus infections are characterised by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock. PMID:21084112

Low cerebral blood flow is a risk factor for severe intraventricular haemorrhage

PubMed Central

Meek, J.; Tyszczuk, L.; Elwell, C.; Wyatt, J

1999-01-01

AIMS—To investigate the relation between cerebral blood flow on the first day of postnatal life and the severity of any subsequent germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH).
METHODS—Cerebral blood flow was measured in 24 babies during the first 24 hours of life using near infrared spectroscopy. Repeated cerebral ultrasound examination was performed to define the maximum extent of GMH-IVH. Infants were classified as: normal scan, minor periventricular haemorrhage (haemorrhage that resolved), or severe GMH-IVH (haemorrhage distending the ventricles, that progressed to either post haemorrhagic dilatation or porencephalic cyst formation).
RESULTS—Cerebral blood flow was significantly lower in the infants with GMH-IVH (median 7.0 ml/100 g/min) than those without haemorrhage (median 12.2 ml/100 g/min), despite no difference in carbon dioxide tension and a higher mean arterial blood pressure. On subgroup analysis, those infants with severe GMH-IVH had the lowest cerebral blood flow.
CONCLUSION—A low cerebral blood flow on the first day of life is associated with the subsequent development of severe intraventricular haemorrhage.

 PMID:10375356

White-centred retinal haemorrhages (Roth spots).

PubMed

Ling, R; James, B

1998-10-01

Roth spots (white-centred retinal haemorrhages) were classically described as septic emboli lodged in the retina of patients with subacute bacterial endocarditis. Indeed many have considered Roth spots pathognomonic for this condition. More recent histological evidence suggests, however, that they are not foci of bacterial abscess. Instead, they are nonspecific and may be found in many other diseases. A review of the histology and the pathogenesis of these white-centred haemorrhages will be provided, along with the work-up of the differential diagnosis.

Macular telangiectasia type 2 (MacTel) in a 34-year-old patient

PubMed Central

Nicolai, Heleen; Wirix, Mieke; Spielberg, Leigh; Leys, Anita

2014-01-01

We report macular telangiectasia type 2 (MacTel) in a 34-year-old man, the youngest patient so far published with MacTel type 2. The patient presented with metamorphopsia and impaired reading ability. Diagnosis was based on bilateral abnormal macular autofluorescence, perifoveal telangiectasia with fluorescein angiographic hyperfluorescence without cystoid oedema, a small foveal avascular zone, asymmetric configuration of the foveal pit, disruptions in the inner segment/outer segment layer and hyper-reflective haze and spots in the outer nuclear layer. Although MacTel usually manifests with a slowly progressive decrease in visual acuity in the fifth to seventh decades of life, younger patients may occasionally be diagnosed with the disease. Awareness of subtle signs of the condition is essential for early diagnosis. PMID:25249218

[Crimean-Congo haemorrhagic fever: an enemy at the gates].

PubMed

Pittalis, Silvia; Meschi, Silvia; Castilletti, Maria Concetta; Di Caro, Antonino; Puro, Vicenzo

2009-09-01

Crimea-Congo haemorrhagic fever is a tick-borne viral zoonosis with the potential of human-to-human transmission. The disease occurs in extensive areas in Asia, South-eastern Europe and Africa. Haemorrhagic manifestations constitute a prominent symptom of the late disease stage, with case fatality rates from 9 to 50%. The recent increase in the number of cases in Eastern Europe and the potential for nosocomial outbreaks indicate the advisability of diagnosis in every patient hospitalized in Italy with haemorrhagic fever.

Excessive work and risk of haemorrhagic stroke: a nationwide case-control study.

PubMed

Kim, Beom Joon; Lee, Seung-Hoon; Ryu, Wi-Sun; Kim, Chi Kyung; Chung, Jong-Won; Kim, Dohoung; Park, Hong-Kyun; Bae, Hee-Joon; Park, Byung-Joo; Yoon, Byung-Woo

2013-10-01

Adverse effect of excessive work on health has been suggested previously, but it was not documented in cerebrovascular diseases. The authors investigated whether excessive working conditions would associate with increased risk of haemorrhagic stroke. A nationwide matched case-control study database, which contains 940 cases of incident haemorrhagic stroke (498 intracerebral haemorrhages and 442 sub-arachnoid haemorrhages) with 1880 gender- and age- (± 5-year) matched controls, was analysed. Work-related information based on the regular job situation, including type of occupation, regular working time, duration of strenuous activity during regular work and shift work, was gathered through face-to-face interviews. Conditional logistic regression analyses were used for the multivariable analyses. Compared with white-collar workers, blue-collar workers had a higher risk for haemorrhagic stroke (odds ratio, 1.33 [95% confidence interval, 1.06-1.66]). Longer regular working time was associated with increased risk of haemorrhagic stroke [odds ratio, 1.38 (95% confidence interval, 1.05-1.81) for 8-12 h/day; odds ratio, 1.95 (95% confidence interval, 1.33-2.86) for ≥ 13 h/day; compared with ≤ 4 h/day]. Exposure to ≥ 8 h/week of strenuous activity also associated haemorrhagic stroke risk [odds ratio, 1.61 (95% confidence interval, 1.26-2.05); compared with no strenuous activity]. Shift work was not associated with haemorrhagic stroke (P = 0.98). Positive associations between working condition indices and haemorrhagic stroke risk were consistent regardless of haemorrhagic stroke sub-types and current employment status. Blue-collar occupation, longer regular working time and extended duration of strenuous activity during work may relate to an increased risk of haemorrhagic stroke. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Reproducibility of oxygen saturation monitoring during six-minute walk test and exercise stress test in patients with pulmonary arteriovenous malformations associated with hereditary hemorrhagic telangiectasia.

PubMed

Li, Walter; Niu, Bolin; Henderson, Katherine; Northrup, Veronika; Pollak, Jeffery S; Trow, Terence; Fahey, John; White, Robert I

2011-06-01

Patients with pulmonary arteriovenous malformations (PAVMs) are at risk for multiple complications and require close follow-up. We investigated the reproducibility of the 6-minute walk test (6MWT) and exercise stress test (EST) for the evaluation of low oxygen saturation in patients with PAVMs. Twenty-two patients with PAVMs, most of whom had hereditary hemorrhagic telangiectasia (HHT), participated in a Human Investigations Committee-approved protocol. Patients ranged from 9 to 74 years of age (mean 28) and had a broad spectrum of anatomic subtypes of PAVMs, including focal and diffuse. Standard 6MWT and cycle ergometry EST were both performed twice with adequate rest between tests. Heart rate (HR) and oxygen saturation were measured at the beginning and end of each test. Distance walked and maximum resistance was also recorded. The intraclass correlation coefficients (r(i)) at the end of 6MWT were as follows: HR (r(i) = 0.940; 95% confidence interval [CI] 0.863-0.975), oxygen saturation (r(i) = 0.973; 95% CI 0.933-0.989), and distance (r(i) = 0.942; 95% CI 0.867-0.975). The r(i)s at the end of EST were as follows: HR (r(i) = 0.941; 95% CI 0.865-0.975), oxygen saturation (r(i) = 0.993; 95% CI 0.982-0.997), and maximum resistance (r(i) = 0.941; 95% CI 0.864-0.975). 6MWT and EST were reproducible measures of exercise capacity and oxygen saturation and are potential adjunct tests in the follow-up assessment for patients with PAVMs.

Massive retroperitoneal haemorrhage after extracorporeal shock wave lithotripsy (ESWL).

PubMed

Inoue, Hiromasa; Kamphausen, Thomas; Bajanowski, Thomas; Trübner, Kurt

2011-01-01

A 76-year-old male suffering from nephrolithiasis developed a shock syndrome 5 days after extracorporal shock wave lithotripsy (ESWL). CT scan of the abdomen showed massive haemorrhage around the right kidney. Although nephrectomy was performed immediately, the haemorrhage could not be controlled. Numerous units of erythrocytes were transfused, but the patient died. The autopsy revealed massive retroperitoneal haemorrhage around the right kidney. The kidney showed a subcapsular haematoma and a rupture of the capsule. The right renal artery was dissected. The inferior vena cava was lacerated. Accordingly, a hemorrhagic shock as the cause of death was determined, which might mainly have resulted from the laceration of the inferior vena cava due to ESWL. ESWL seems to be a relatively non-invasive modality, but one of its severe complications is perirenal hematoma. The injuries of the blood vessels might have been caused by excessive shock waves. Subsequently, anticoagulation therapy had been resumed 3 days after EWSL, which might have triggered the haemorrhage. Physicians should note that a haemorrhage after an ESWL can occur and they should pay attention to the postoperative management in aged individuals especially when they are under anticoagulation therapy.

Diagnostic laboratory for bleeding disorders ensures efficient management of haemorrhagic disorders.

PubMed

Riddell, A; Chuansumrit, A; El-Ekiaby, M; Nair, S C

2016-07-01

Haemorrhagic disorders like Postpartum haemorrhage and Dengue haemorrhagic fever are life threatening and requires an active and efficient transfusion service that could provide the most appropriate blood product which could be effective in managing them. This would essentially require prompt identification of the coagulopathy so that the best available product can be given to the bleeding patient to correct the identified haemostatic defect which will help control the bleeding. This would only be possible if the transfusion service has a laboratory to correctly detect the haemostatic defect and that too with an accuracy and precision which is ensured by a good laboratory quality assurance practices. These same processes are necessary for the transfusion services to ensure the quality of the blood products manufactured by them and that it contains adequate amounts of haemostasis factors which will be good to be effective in the management of haemorrhagic disorders. These issues are discussed in detail individually in the management of postpartum haemorrhage and Dengue haemorrhagic fever including when these can help in the use of rFVIIa in Dengue haemorrhagic fever. The requirements to ensure good-quality blood products are made available for the management of these disorders and the same have also been described. © 2016 John Wiley & Sons Ltd.

White-centred retinal haemorrhages (Roth spots).

PubMed Central

Ling, R.; James, B.

1998-01-01

Roth spots (white-centred retinal haemorrhages) were classically described as septic emboli lodged in the retina of patients with subacute bacterial endocarditis. Indeed many have considered Roth spots pathognomonic for this condition. More recent histological evidence suggests, however, that they are not foci of bacterial abscess. Instead, they are nonspecific and may be found in many other diseases. A review of the histology and the pathogenesis of these white-centred haemorrhages will be provided, along with the work-up of the differential diagnosis. Images Figure 1 Figure 2 PMID:10211348

Consent for Brain Tissue Donation after Intracerebral Haemorrhage: A Community-Based Study.

PubMed

Samarasekera, Neshika; Lerpiniere, Christine; Fonville, Arthur F; Farrall, Andrew J; Wardlaw, Joanna M; White, Philip M; Torgersen, Antonia; Ironside, James W; Smith, Colin; Al-Shahi Salman, Rustam

2015-01-01

Spontaneous intracerebral haemorrhage is a devastating form of stroke and its incidence increases with age. Obtaining brain tissue following intracerebral haemorrhage helps to understand its cause. Given declining autopsy rates worldwide, the feasibility of establishing an autopsy-based collection and its generalisability are uncertain. We used multiple overlapping sources of case ascertainment to identify every adult diagnosed with intracerebral haemorrhage between 1st June 2010-31st May 2012, whilst resident in the Lothian region of Scotland. We sought consent from patients with intracerebral haemorrhage (or their nearest relative if the patient lacked mental capacity) to conduct a research autopsy. Of 295 adults with acute intracerebral haemorrhage, 110 (37%) could not be approached to consider donation. Of 185 adults/relatives approached, 91 (49%) consented to research autopsy. There were no differences in baseline demographic variables or markers of intracerebral haemorrhage severity between consenters and non-consenters. Adults who died and became donors (n = 46) differed from the rest of the cohort (n = 249) by being older (median age 80, IQR 76-86 vs. 75, IQR 65-83, p = 0.002) and having larger haemorrhages (median volume 23 ml, IQR 13-50 vs. 13 ml, IQR 4-40; p = 0.002). Nearly half of those approached consent to brain tissue donation after acute intracerebral haemorrhage. The characteristics of adults who gave consent were comparable to those in an entire community, although those who donate early are older and have larger haemorrhage volumes.

Macular telangiectasia type 2 (MacTel) in a 34-year-old patient.

PubMed

Nicolai, Heleen; Wirix, Mieke; Spielberg, Leigh; Leys, Anita

2014-09-23

We report macular telangiectasia type 2 (MacTel) in a 34-year-old man, the youngest patient so far published with MacTel type 2. The patient presented with metamorphopsia and impaired reading ability. Diagnosis was based on bilateral abnormal macular autofluorescence, perifoveal telangiectasia with fluorescein angiographic hyperfluorescence without cystoid oedema, a small foveal avascular zone, asymmetric configuration of the foveal pit, disruptions in the inner segment/outer segment layer and hyper-reflective haze and spots in the outer nuclear layer. Although MacTel usually manifests with a slowly progressive decrease in visual acuity in the fifth to seventh decades of life, younger patients may occasionally be diagnosed with the disease. Awareness of subtle signs of the condition is essential for early diagnosis. 2014 BMJ Publishing Group Ltd.

Treatment of facial telangiectasias with a diode-pumped Nd:YAG laser at 532 nm

NASA Astrophysics Data System (ADS)

Cassuto, Daniel A.; Ancona, Deborah M.; Emanuelli, Guglielmo

2000-06-01

Facial telangiectasias are a common cause of cosmetic concern. Current treatment modalities present various effects and limits. The pulsed dye laser has been considered the golden standard in efficacy and safety. Unfortunately it causes postoperative intracutaneous hematomata that discourage many patients form undergoing this treatment. Several other vascular lasers are disadvantaged by the risk of hypopigmented and atrophic scars. We assessed a recent powerful version of the potassium titanyl phosphate 532 nm laser, that can deliver sufficient energy in single pulses lasting 10-50 msec. Collateral damage is reduced while the heating of the vessel is slow enough to avoid explosive photothermolysis with its associated purpura. Sixty-six patients with facial telangiectasias were treated. In 62/66 patients, we achieved a 75 percent-100 percent clearance of the lesions, while two treatments were needed to reach an acceptable clearance in the remaining 4/66 patients. The overall need for more sessions was well tolerated, because the acceptable postoperative appearance allowed patients to continue normal business and social activities between treatments. No permanent complications or undesired effects were noted. The KTP/532nm laser is also being tested in combined laser-sclerotherapy of fine leg capillary telangiectasias with encouraging results.

Unilateral Nevoid Telangiectasia Associated with Ipsilateral Melorheostosis

PubMed Central

Kim, Jihyun; Cho, Sung Bin; Cho, Suhyun

2012-01-01

Melorheostosis is a rare disorder characterized by irregular, flowing hyperostosis in long bones, commonly described on radiographs as wax flowing down a candle. In addition to bony sclerosis, cutaneous manifestations overlying the involved bones have been reported including linear scleroderma, neurofibromatosis, and vascular and lymphatic malformations. Unilateral nevoid telangiectasia (UNT) is a rare primarily cutaneous condition characterized by linearly arranged small dilated blood vessels in dermatomal or Blaschkoid patterns on the skin. Here, we present the case of a nine-year-old Korean male with UNT associated with ipsilateral melorheostosis. PMID:22577274

Retinal haemorrhage in infants with pertussis.

PubMed

Raoof, Naz; Pereira, Susana; Dai, Shuan; Neutze, Jocelyn; Grant, Cameron Charles; Kelly, Patrick

2017-12-01

It has been hypothesised that paroxysmal coughing in infantile pertussis (whooping cough) could produce retinal haemorrhages identical to those seen in abusive head trauma. We aimed to test this hypothesis. This is a prospective study of infants hospitalised with pertussis in Auckland, New Zealand, from 2009 to 2014. The clinical severity of pertussis was categorised. All infants recruited had retinal examination through dilated pupils by the paediatric ophthalmology service using an indirect ophthalmoscope. Forty-eight infants with pertussis, aged 3 weeks to 7 months, were examined after a mean of 18 days of coughing. Thirty-nine had severe pertussis and nine had mild pertussis. All had paroxysmal cough, and all were still coughing at the time of examination. No retinal haemorrhages were seen. We found no evidence to support the hypothesis that pertussis may cause the pattern of retinal haemorrhages seen in abusive head trauma in infants. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[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.

Blood transfusion and the anaesthetist: management of massive haemorrhage

PubMed Central

Thomas, D; Wee, M; Clyburn, P; Walker, I; Brohi, K; Collins, P; Doughty, H; Isaac, J; Mahoney, PF; Shewry, L

2010-01-01

Hospitals must have a major haemorrhage protocol in place and this should include clinical, laboratory and logistic responses. Immediate control of obvious bleeding is of paramount importance (pressure, tourniquet, haemostatic dressings). The major haemorrhage protocol must be mobilised immediately when a massive haemorrhage situation is declared. A fibrinogen < 1 g.l−1 or a prothrombin time (PT) and activated partial thromboplastin time (aPTT) of > 1.5 times normal represents established haemostatic failure and is predictive of microvascular bleeding. Early infusion of fresh frozen plasma (FFP; 15 ml.kg−1) should be used to prevent this occurring if a senior clinician anticipates a massive haemorrhage. Established coagulopathy will require more than 15 ml.kg−1 of FFP to correct. The most effective way to achieve fibrinogen replacement rapidly is by giving fibrinogen concentrate or cryoprecipitate if fibrinogen is unavailable. 1:1:1 red cell:FFP:platelet regimens, as used by the military, are reserved for the most severely traumatised patients. A minimum target platelet count of 75 × 109.l−1 is appropriate in this clinical situation. Group-specific blood can be issued without performing an antibody screen because patients will have minimal circulating antibodies. O negative blood should only be used if blood is needed immediately. In hospitals where the need to treat massive haemorrhage is frequent, the use of locally developed shock packs may be helpful. Standard venous thromboprophylaxis should be commenced as soon as possible after haemostasis has been secured as patients develop a prothrombotic state following massive haemorrhage. PMID:20963925

UK guidelines on the management of variceal haemorrhage in cirrhotic patients

PubMed Central

Tripathi, Dhiraj; Stanley, Adrian J; Hayes, Peter C; Patch, David; Millson, Charles; Mehrzad, Homoyon; Austin, Andrew; Ferguson, James W; Olliff, Simon P; Hudson, Mark; Christie, John M

2015-01-01

These updated guidelines on the management of variceal haemorrhage have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines which this document supersedes were written in 2000 and have undergone extensive revision by 13 members of the Guidelines Development Group (GDG). The GDG comprises elected members of the BSG liver section, representation from British Association for the Study of the Liver (BASL) and Liver QuEST, a nursing representative and a patient representative. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. The nature of variceal haemorrhage in cirrhotic patients with its complex range of complications makes rigid guidelines inappropriate. These guidelines deal specifically with the management of varices in patients with cirrhosis under the following subheadings: (1) primary prophylaxis; (2) acute variceal haemorrhage; (3) secondary prophylaxis of variceal haemorrhage; and (4) gastric varices. They are not designed to deal with (1) the management of the underlying liver disease; (2) the management of variceal haemorrhage in children; or (3) variceal haemorrhage from other aetiological conditions. PMID:25887380

Intracranial haemorrhage and use of selective serotonin reuptake inhibitors

PubMed Central

de Abajo, Francisco J; Jick, Hershel; Derby, Laura; Jick, Susan; Schmitz, Stephen

2000-01-01

Aims In the past few years an increasing number of bleeding disorders have been reported in association with the use of selective serotonin reuptake inhibitors (SSRIs), including serious cases of intracranial haemorrhage, raising concerns about the safety of this class of drugs. The present study was performed to test the hypothesis of an increased risk of intracranial haemorrhage associated with the use of SSRIs. Methods We carried out a case-control study nested in a cohort of antidepressants users with the UK-based General Practice Research Database (GPRD) as the primary source of information. The study cohort encompassed subjects aged between 18 and 79 years who received a first-time prescription for any antidepressant from January, 1990 to October, 1997. Patients with presenting conditions or treatments that could be associated with an increased risk of intracranial haemorrhage were excluded from the cohort. Patients were followed-up until the occurrence of an idiopathic intracranial haemorrhage. Up to four controls per case, matched on age, sex, calendar time and practice were randomly selected from the study cohort. We estimated adjusted odds ratios and 95% confidence intervals of intracranial haemorrhage with current use of SSRIs and other antidepressants as compared with nonuse using conditional logistic regression. Results We identified 65 cases of idiopathic intracranial haemorrhage and 254 matched controls. Current exposure to SSRIs was ascertained in 7 cases (10.8%) and 24 controls (9.7%) resulting in an adjusted OR (95%CI) of 0.8 (0.3,2.3). The estimate for ‘other antidepressants’ was 0.7 (0.3,1.6). The effect measures were not modified by gender or age. No effect related to dose or treatment duration was detected. The risk estimates did not change according to the location of bleeding (intracerebral or subarachnoid). Conclusions Our results are not compatible with a major increased risk of intracranial haemorrhage among users of SSRIs or other

Epistaxis grading in Osler's disease: comparison of comprehensive scores with detailed bleeding diaries.

PubMed

Parzefall, Thomas; Wolf, Axel; Frei, Klemens; Kaider, Alexandra; Riss, Dominik

2017-03-01

Use of reliable grading scores to measure epistaxis severity in hereditary hemorrhagic telangiectasia (HHT) is essential in clinical routine and for scientific purposes. For practical reasons, visual analog scale (VAS) scoring and the Epistaxis Severity Score (ESS) are widely used. VAS scores are purely subjective, and a potential shortcoming of the ESS is that it is based on self-reported anamnestic bleeding data. The aim of this study was to validate the level of correlation between VAS scores, the ESS, and actual bleeding events, based on detailed epistaxis diaries of patients. Records from daily epistaxis diaries maintained by 16 HHT patients over 112 consecutive days were compared with the monthly ESS and daily VAS scores in the corresponding time period. The Spearman rank correlation coefficient, analysis of variance models, and multiple R 2 measures were used for statistical analysis. Although the ESS and VAS scores generally showed a high degree of correlation with actual bleeding events, mild events were underrepresented in both scores. Our results highlight the usefulness of the ESS as a standard epistaxis score in cohorts with moderate to severe degrees of epistaxis. The use of detailed epistaxis diaries should be considered when monitoring patients and cohorts with mild forms of HHT. © 2016 ARS-AAOA, LLC.

Using the ultra-long pulse width pulsed dye laser and elliptical spot to treat resistant nasal telangiectasia.

PubMed

Madan, Vishal; Ferguson, Janice

2010-01-01

Thick linear telangiectasia on the ala nasi and nasolabial crease can be resistant to treatment with the potassium-titanyl-phosphate (KTP) laser and the traditional round spot on a pulsed dye laser (PDL). We evaluated the efficacy of a 3 mm x 10 mm elliptical spot using the ultra-long pulse width on a Candela Vbeam(R) PDL for treatment of PDL- and KTP laser-resistant nasal telangiectasia. Nasal telangiectasia resistant to PDL (12 patients) and KTP laser (12 patients) in 18 patients were treated with a 3 mm x 10 mm elliptical spot on the ultra-long pulse pulsed dye laser (ULPDL) utilising long pulse width [595 nm, 40 ms, double pulse, 30:20 dynamic cooling device (DCD)]. Six patients had previously received treatment with both PDL and KTP laser prior to ULPDL (40 treatments, range1-4, mean 2.2). Complete clearance was seen in ten patients, and eight patients displayed more than 80% improvement after ULPDL treatment. Self-limiting purpura occurred with round spot PDL and erythema with KTP laser and ULPDL. Subtle linear furrows along the treatment sites were seen in three patients treated with the KTP laser. ULPDL treatment delivered using a 3 mm x 10 mm elliptical spot was non-purpuric and highly effective in the treatment of nasal telangiectasia resistant to KTP laser and PDL.

Intracerebral haemorrhage and drug abuse in young adults.

PubMed

McEvoy, A W; Kitchen, N D; Thomas, D G

2000-10-01

The epidemic of abuse of the so-called 'designer drugs' amphetamine, cocaine and ecstasy--is fast replacing traditional aetiological factors as the largest cause of intracerebral haemorrhage among young adults. Traditional teaching is that these represent hypertensive haemorrhages. Recent reports, however, have indicated that these patients may harbour underlying vascular malformations. We review 13 patients with a positive history of drug abuse preceding the onset of intracerebral haemorrhage. These patients presented to the National Hospital for Neurology and Neurosurgery in central London over a 7-month period. Of the 13 patients (eight male, five female), average age 31 years (19-43) years), 10 were well enough to undergo cerebral angiography. Intracranial aneurysms were demonstrated in six patients and arteriovenous malformations in three patients. In only one of the patients was the angiogram normal. A further patient was subsequently shown to have a middle cerebral artery aneurysm at autopsy. The epidemiology, pharmacology and systemic effects of these drugs are considered. The mechanisms by which these compounds cause intracerebral complications and their influence on prognosis are discussed. The incidence of intracerebral haemorrhage (ICH), ischaemic cerebral infarctions and subarachnoid haemorrhage (SAH) following drug abuse is increasing. Contrary to historical opinion, drug-related ICH is frequently related to an underlying vascular malformation. Arteriography should be part of the evaluation of most young patients with nontraumatic ICH. A thorough history focusing on the use of illicit substances and toxicological screening of urine and serum should be part of the evaluation of any young patient with a stroke.

Vesical Artery Embolization in Haemorrhagic Cystitis in Children

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

García-Gámez, Andrés, E-mail: agargamez@gmail.com; Bermúdez Bencerrey, Patricia, E-mail: PBERMUDE@clinic.ub.es; Brio-Sanagustin, Sonia, E-mail: sbrio@santpau.cat

Haemorrhagic cystitis is an uncommon and, in its severe form, potentially life-threatening complication of haematopoietic stem cell transplantation or cancer therapy in children. The severe form involves macroscopic haematuria with blood clots, urinary obstruction and/or renal impairment. There are many therapeutic options to treat acute haemorrhage, but only recombinant factor VII has a high level of clinical evidence in children. Supraselective vesical artery embolization (SVAE) is an increasingly used therapeutic procedure for controlling haemorrhage in adults, but is less commonly used in children. This might be due to several factors, such as the invasive nature of the procedure, lack ofmore » appropriate medical experience and possible long-term side effects. We present three cases of children successfully treated by means of effective SVAE.« less

Variant forms of ataxia telangiectasia.

PubMed Central

Taylor, A M; Flude, E; Laher, B; Stacey, M; McKay, E; Watt, J; Green, S H; Harding, A E

1987-01-01

Two ataxia telangiectasia patients with unusual clinical and cellular features are described. Cultured fibroblasts and PHA stimulated lymphocytes from these two patients showed a smaller increase of radiosensitivity than cells from other A-T patients, as measured by colony forming ability or induced chromosome damage respectively, after exposure to ionising radiation. The response of DNA synthesis to irradiation of these cells was, however, the same as for other A-T patients. Cells from a third patient with some clinical features of A-T but with a very protracted course also showed low levels of radiation induced chromosome damage, but colony forming ability and the response of DNA synthesis after irradiation were no different from cells of normal subjects. There was, however, an increased level of translocations and unstable chromosomal rearrangements in this patient's lymphocytes. Images PMID:3430541

Emergency admissions for major haemorrhage associated with direct oral anticoagulants.

PubMed

Bouget, Jacques; Oger, Emmanuel

2015-12-01

To describe the population admitted in an emergency department of a teaching hospital for severe bleeding associated with direct oral anticoagulants (DOAC). During a three-year period (2012-2014) patients older than 16 years were prospectively identified by haemorrhagic symptoms from computerised requests. At least one of the following criteria defined major haemorrhage: haemorrhagic shock, unstable haemodynamic, need for transfusion or haemostatic procedure, or a life threatening location. Fifty four patients, 23 receiving dabigatran, 30 rivaroxaban and one apixaban were included, 2 in 2012, 35 in 2013 and 17 in 2014. Median age was 84 years (range 63-99) with a sex ratio of 1.16. Haemorrhagic complications were gastrointestinal (n=27), intracranial (n=12) or miscellaneous (n=15). Indication of DOAC was stroke prevention in atrial fibrillation in 49 cases and deep vein thrombosis in 5 cases. Hospitalization was required for 45 patients (83%) with a mean length of stay of 8.5 days. Sixteen patients needed intensive care. Reversal therapy was prescribed in 11 patients. At 1 month, overall mortality was 24%, reaching 41.7% for intracranial haemorrhage. Among surviving patients, DOAC was stopped in 10 cases, continued in 17 patients and switched for other antithrombotic in 17 patients. Our study contributes to the post marketing surveillance of major haemorrhagic complications associated with DOAC. It takes part to the knowledge about the course of this severe event in emergencies. Careful awareness in risk benefit assessment, especially in elderly, is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ataxia telangiectasia presenting as dopa-responsive cervical dystonia

PubMed Central

Mohire, Mahavir D.; Schneider, Susanne A.; Stamelou, Maria; Wood, Nicholas W.; Bhatia, Kailash P.

2013-01-01

Objective: To identify the cause of cervical dopa-responsive dystonia (DRD) in a Muslim Indian family inherited in an apparently autosomal recessive fashion, as previously described in this journal. Methods: Previous testing for mutations in the genes known to cause DRD (GCH1, TH, and SPR) had been negative. Whole exome sequencing was performed on all 3 affected individuals for whom DNA was available to identify potentially pathogenic shared variants. Genotyping data obtained for all 3 affected individuals using the OmniExpress single nucleotide polymorphism chip (Illumina, San Diego, CA) were used to perform linkage analysis, autozygosity mapping, and copy number variation analysis. Sanger sequencing was used to confirm all variants. Results: After filtering of the variants, exome sequencing revealed 2 genes harboring potentially pathogenic compound heterozygous variants (ATM and LRRC16A). Of these, the variants in ATM segregated perfectly with the cervical DRD. Both mutations detected in ATM have been shown to be pathogenic, and α-fetoprotein, a marker of ataxia telangiectasia, was increased in all affected individuals. Conclusion: Biallelic mutations in ATM can cause DRD, and mutations in this gene should be considered in the differential diagnosis of unexplained DRD, particularly if the dystonia is cervical and if there is a recessive family history. ATM has previously been reported to cause isolated cervical dystonia, but never, to our knowledge, DRD. Individuals with dystonia related to ataxia telangiectasia may benefit from a trial of levodopa. PMID:23946315

Risk factors for severe post partum haemorrhage in Mulago hospital, Kampala, Uganda.

PubMed

Wandabwa, J; Doyle, P; Todd, J; Ononge, S; Kiondo, P

2008-02-01

To determine the risk factors for severe postpartum haemorrhage. A case control study. Mulago hospital labour wards, Kampala, Uganda. One hundred and six mothers with severe postpartum haemorrhage were recruited between 15th November 2001 and 30th November 2002 and were compared with 500 women who had normal delivery. The predictors for postpartum haemorrhage were co-existing hypertension (O.R 9.3, 95% CI: 1.7-51.7), chronic anaemia (OR 17.3, 95% CI: 9.5-31.7), low socio economic background (OR 5.3, 95% CI: 3.0, 9.2), past history of postpartum haemorrhage (OR 3.6, 95% CI: 1.1-11.8), previous delivery by Caesarean section (OR 7.5, 95% CI: 3.5-14.3), long birth interval of more than sixty months (OR 5.2, 95% CI: 2.1-13.0), prolonged third stage (OR 49.1, 95% CI: 8.8-342.8) and non use of oxytocics (OR 4.3%, 95% CI: 1.2-15.3). Severe postpartum haemorrhage is common in our environment and is associated with a high maternal morbidity and mortality. The determinants of postpartum haemorrhage are useful in identifying mothers at risk and together with the services of a skilled birth attendant at delivery will prevent postpartum haemorrhage and reduce the maternal morbidity and mortality associated with this condition. In our study, the following risk factors were identified: pre-existing hypertension, chronic anaemia, low socio-economic background, history of postpartum haemorrhage, previous delivery by Caesarean section, longbirth interval of more than sixty months, prolonged third stage and non use of oxytocics were found to be significant.

Retroperitoneal Haematoma in a Patient with Dengue Haemorrhagic Fever: A Rare Case Report.

PubMed

Singh, Jasminder; Singh, Harpreet; Sukhija, Gagandeep; Jagota, Ruchi; Bala, Saroj

2016-11-01

Dengue Haemorrhagic Fever (DHF) has diverse manifestations ranging from asymptomatic petechial skin haemorrhages to life threatening cerebral, pulmonary, gastrointestinal and genitourinary haemorrhages. However, the association of spontaneous retroperitoneal haematomas with DHF is not well documented in literature. We report a rare case of spontaneous retroperitoneal haematoma complicating DHF.

Treatment of facial telangiectasias with a diode-pumped Nd:YAG laser at 532 nm.

PubMed

Cassuto, D A; Ancona, D M; Emanuelli, G

2000-09-01

Facial telangiectasias are a common cause of cosmetic concern. Current treatment modalities present various untoward effects and limits. The pulsed dye laser has been considered the gold standard in efficacy and safety; unfortunately it causes postoperative intracutaneous hematomata, discouraging many patients from undergoing this treatment. Several other vascular lasers (argon, tunable dye, copper, krypton, etc.) are disadvantaged by the risk of hypopigmented and atrophic scars. We assessed a recent powerful version of the potassium titanyl phosphate (KTP) 532 nm laser, which delivers sufficient energy in single pulse lasting 10-50 msec (DioLite 532; IRIDEX, Mountain View, CA, USA). Collateral damage is reduced while the heating of the vessel is slow enough to avoid explosive photothermolysis with its associated purpura. Sixty six patients with facial telangiectasias were treated. In 62/66 patients (93.9%) we achieved a 75-100% clearance of the lesions, while two treatments were needed to reach an acceptable clearance in the remaining 4/66 patients (6.1%). The eventual need for more sessions was well tolerated because the acceptable postoperative appearance allowed patients to continue normal business and social activities between treatments. No permanent complications or undesired effects were noted. We conclude that this diode-pumped frequency-doubled Nd:YAG laser is an effective device for the treatment of facial telangiectasias, with a low profile of undesired effects that can be well tolerated by patients.

Nail haemorrhages in native highlanders of the Peruvian Andes

PubMed Central

Heath, Donald; Harris, Peter; Williams, David; Krüger, Hever

1981-01-01

Nail haemorrhages are of interest to the chest physician and cardiologist. While the common type in the distal part of the nail is produced by the minor trauma of daily life, the rarer form—scattered through the nail substance—appears to be related to hypoxaemia brought about by heart and lung disease. We thought it would be of interest to study a population which was naturally hypoxaemic because of living at high altitude. Accordingly we have studied the frequency and types of nail haemorrhage in Quechua Indians who are permanently exposed to the hypobaric hypoxia of the Andes. We found the haemorrhages to be common both in mestizos living on the coastal plain and in the native highlanders. They appeared to increase in frequency with altitude but were of the distal type and would thus seem to be the result of minor trauma as at sea level. However, just as in cases of cyanotic congenital heart disease at low altitude, those with exaggerated hypoxaemia and pronounced elevation of haematocrit—namely, subjects with Monge's disease (chronic mountain sickness)—had scattered haemorrhages in the nail substance. Images

Dermoscopy of subungual haemorrhage: its usefulness in differential diagnosis from nail-unit melanoma.

PubMed

Mun, J-H; Kim, G-W; Jwa, S-W; Song, M; Kim, H-S; Ko, H-C; Kim, B-S; Kim, M-B

2013-06-01

Subungual haemorrhages are characterized by well-circumscribed dots or blotches with a red to red-black pigmentation, but some cases can be difficult to distinguish from subungual melanoma by the naked eye alone. Dermoscopy has proven to be a useful, noninvasive tool in the diagnosis of pigmented lesions in the nail; however, few dermoscopic studies of subungual haemorrhages have been reported. To investigate characteristic dermoscopic patterns of subungual haemorrhages, and to find distinctive features that can differentiate them from nail-unit melanomas. Patients with a confirmed diagnosis of either subungual haemorrhage or nail-unit melanoma at a tertiary university hospital were included in the study. Clinical features and dermoscopic patterns were evaluated. Sixty-four patients with a total of 90 lesions of subungual haemorrhage were enrolled in the study. The majority of cases (84%) showed combinations of more than one colour, while 16% had only one colour. The most common colour of the subungual haemorrhages was purple-black, in 37% of cases. A homogeneous pattern was observed in 92% of cases, globular patterns in 42% and streaks in 39%. Peripheral fading and periungual haemorrhages were found in 54% and 22% of cases, respectively. Destruction or dystrophy of the nail plate was observed in 16% of cases. In the 16 cases of nail-unit melanomas, Hutchinson sign, longitudinal irregular bands or lines, triangular shape of bands, vascular pattern, and ulcerations were found in 100%, 81%, 25%, 6% and 81% of cases, respectively. In contrast, these features were not found in subungual haemorrhages. Dermoscopy provides valuable information for the diagnosis of subungual haemorrhage and aids in the differential diagnosis from nail-unit melanoma. © 2013 The Authors. BJD © 2013 British Association of Dermatologists.

Recognising haemorrhagic rash in children with fever: a survey of parents' knowledge.

PubMed

Aurel, M; Dubos, F; Motte, B; Pruvost, I; Leclerc, F; Martinot, A

2011-07-01

Early recognition and treatment of meningococcal disease improves its outcome. Haemorrhagic rash is one of the most specific signs that parents can learn to recognise. To determine the percentage of parents able to recognise a haemorrhagic rash and perform the tumbler test. 123 parents of children consulting for mild injuries were interviewed about the significance and recognition of haemorrhagic rash in febrile children. Although 88% of parents undressed their children when they were febrile, it was never to look specifically for a skin rash. Only 7% (95% CI 3% to 12%) were able to recognise a petechial rash and knew the tumbler test. Information campaigns about the significance of haemorrhagic rash and about the tumbler test are needed.

Preserved arterial flow secures hepatic oxygenation during haemorrhage in the pig

PubMed Central

Rasmussen, Allan; Skak, Claus; Kristensen, Michael; Ott, Peter; Kirkegaard, Preben; Secher, Niels H

1999-01-01

This study examined the extent of liver perfusion and its oxygenation during progressive haemorrhage. We examined hepatic arterial flow and hepatic oxygenation following the reduced portal flow during haemorrhage in 18 pigs. The hepatic surface oxygenation was assessed by near-infrared spectroscopy and the hepatic metabolism of oxygen, lactate and catecholamines determined the adequacy of the hepatic flow. Stepwise haemorrhage until circulatory collapse resulted in proportional reductions in cardiac output and in arterial, central venous and pulmonary wedge pressures. While heart rate increased, pulmonary arterial pressure remained stable. In addition, renal blood flow decreased, renal vascular resistance increased and there was elevated noradrenaline spill-over. Further, renal surface oxygenation was lowered from the onset of haemorrhage. Similarly, the portal blood flow was reduced in response to haemorrhage, and, as for the renal flow, the reduced splanchnic blood flow was associated with an elevated noradrenaline spill-over. In contrast, hepatic arterial blood flow was only slightly reduced by haemorrhage, and surface oxygenation did not change. The hepatic oxygen uptake was maintained until the blood loss represented more than 30 % of the estimated blood volume. At 30 % reduced blood volume, hepatic catecholamine uptake was reduced, and the lactate uptake approached zero. Subsequent reduction of cardiac output and portal blood flow elicited a selective dilatation of the hepatic arterial vascular bed. Due to this dilatation liver blood flow and hepatic cell oxygenation and metabolism were preserved prior to circulatory collapse. PMID:10087351

Pulmonary haemorrhage following renal transplantation.

PubMed Central

Khan, G. A.; Klapper, P.

1995-01-01

The case history is presented of a 32 year old black man who developed haemoptysis leading to pulmonary haemorrhage and bilateral pulmonary infiltrates. He was found to have Kaposi's sarcoma of the lung with no evidence of skin or endobronchial lesions. PMID:7886663

Spontaneous haemorrhage and rupture of third ventricular colloid cyst

PubMed Central

Ogbodo, Elisha; Kaliaperumal, Chandrasekaran; Bermingham, Niamh; O'Sullivan, Michael

2012-01-01

Acute bleeding within a colloid cyst of the third ventricle represents a rare event causing sudden increase in the cyst volume that may lead to acute hydrocephalus and rapid neurological deterioration. We report a case of spontaneous rupture of haemorrhagic third ventricular colloid cyst and its management. A 77-year-old ex-smoker presented with unsteady gait, incontinence and gradually worsening confusion over a 3-week period. Brain CT scan findings were highly suggestive of a third ventricular colloid cyst with intraventricular rupture. He underwent cyst excision and histopathology, which confirmed the radiological diagnosis with evidence of haemorrhage within the cyst. A ventriculo peritoneal shunt was performed for delayed hydrocephalus. Surgical management of these patients must include emergency ventriculostomy followed by prompt surgical removal of the haemorrhagic cyst. PMID:22949002

Neurosurgical management of L-asparaginase induced haemorrhagic stroke

PubMed Central

Ogbodo, Elisha; Kaliaperumal, Chandrasekaran; O’Sullivan, Michael

2012-01-01

The authors describe a case of L-asparaginase induced intracranial thrombosis and subsequent haemorrhage in a newly diagnosed 30-year-old man with acute lymphoblastic leukaemia who was successfully managed by surgical intervention. At presentation, he had a Glasgow Coma Score of 7/15, was aphasic and had dense right hemiplegia. Neuroimaging revealed an acute anterior left middle cerebral artery infarct with parenchymal haemorrhagic conversion, mass effect and subfalcine herniation. He subsequently underwent left frontal craniotomy and evacuation of large frontal haematoma and decompressive craniectomy for cerebral oedema. Six months postoperatively he underwent titanium cranioplasty. He had made good clinical recovery and is currently mobilising independently with mild occasional episodes of expressive dysphasia, difficulty with fine motor movement on the right side, and has remained seizure free. This is the first documented case of L-asparaginase induced haemorrhagic stroke managed by neurosurgical intervention. The authors emphasise the possible role of surgery in managing chemotherapy induced intracranial complications. PMID:22605598

Spontaneous haemothorax in Osler-Weber-Rendu disease.

PubMed Central

Karnik, A. M.; Sughayer, A.; Fenech, F. F.

1983-01-01

A case of hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu disease) is described who presented with severe, central chest pain mimicking acute myocardial infarction, a presentation which has not been described before. He was found to have developed spontaneous haemothorax which is a very rare complication of this disease. PMID:6622342

PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial.

PubMed

de Gans, Koen; de Haan, Rob J; Majoie, Charles B; Koopman, Maria M; Brand, Anneke; Dijkgraaf, Marcel G; Vermeulen, Marinus; Roos, Yvo B

2010-03-18

Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.

ALK1 Signaling Inhibits Angiogenesis by Cooperating with the Notch Pathway

PubMed Central

Larrivée, Bruno; Prahst, Claudia; Gordon, Emma; del Toro, Raquel; Mathivet, Thomas; Duarte, Antonio; Simons, Michael; Eichmann, Anne

2014-01-01

SUMMARY Activin receptor-like kinase 1 (ALK1) is an endothelial-specific member of the TGF-β/BMP receptor family that is inactivated in patients with hereditary hemorrhagic telangiectasia (HHT). How ALK1 signaling regulates angiogenesis remains incompletely understood. Here we show that ALK1 inhibits angiogenesis by cooperating with the Notch pathway. Blocking Alk1 signaling during postnatal development in mice leads to retinal hypervascularization and the appearance of arteriovenous malformations (AVMs). Combined blockade of Alk1 and Notch signaling further exacerbates hypervascularization, whereas activation of Alk1 by its high-affinity ligand BMP9 rescues hypersprouting induced by Notch inhibition. Mechanistically, ALK1-dependent SMAD signaling synergizes with activated Notch in stalk cells to induce expression of the Notch targets HEY1 and HEY2, thereby repressing VEGF signaling, tip cell formation, and endothelial sprouting. Taken together, these results uncover a direct link between ALK1 and Notch signaling during vascular morpho-genesis that may be relevant to the pathogenesis of HHT vascular lesions. PMID:22421041

ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway.

PubMed

Larrivée, Bruno; Prahst, Claudia; Gordon, Emma; del Toro, Raquel; Mathivet, Thomas; Duarte, Antonio; Simons, Michael; Eichmann, Anne

2012-03-13

Activin receptor-like kinase 1 (ALK1) is an endothelial-specific member of the TGF-β/BMP receptor family that is inactivated in patients with hereditary hemorrhagic telangiectasia (HHT). How ALK1 signaling regulates angiogenesis remains incompletely understood. Here we show that ALK1 inhibits angiogenesis by cooperating with the Notch pathway. Blocking Alk1 signaling during postnatal development in mice leads to retinal hypervascularization and the appearance of arteriovenous malformations (AVMs). Combined blockade of Alk1 and Notch signaling further exacerbates hypervascularization, whereas activation of Alk1 by its high-affinity ligand BMP9 rescues hypersprouting induced by Notch inhibition. Mechanistically, ALK1-dependent SMAD signaling synergizes with activated Notch in stalk cells to induce expression of the Notch targets HEY1 and HEY2, thereby repressing VEGF signaling, tip cell formation, and endothelial sprouting. Taken together, these results uncover a direct link between ALK1 and Notch signaling during vascular morphogenesis that may be relevant to the pathogenesis of HHT vascular lesions. Copyright © 2012 Elsevier Inc. All rights reserved.

Relationship between lunar cycle and haemorrhagic complication rate in surgery.

PubMed

Raposio, Edoardo; Caruana, Giorgia; Santi, Pierluigi; Cafiero, Ferdinando

2017-08-01

The aim of this study was to evaluate a possible relationship between lunar cycles and haemorrhagic complication rate in surgery. The possible relationship between moon phases and surgical outcome was tested by evaluating the haemorrhagic complication rate for 18,760 patients who underwent surgery between January 2001 and December 2008 at the National Institute for Cancer Research in Genoa. A total of 103 lunar phases were considered using Chi-square (χ 2 ) test analysis, and patients were allocated a surgery date. One hundred and sixty-seven haemorrhagic complications were observed. Three hundred and nine new moon phase days were analysed and 12 incidences of complications detected, with a 3.9% complication rate per day. In the waxing moon phase, 1184.5 d were analysed with 68 incidences of complications at a daily rate of 5.7%. In the full moon phase there was a 4.9% complication rate per day (15 incidences in 309 d), whereas in the waning moon phase, the 6% percentage rate per day resulted from 72 incidences in 1184.5 d. No statistically significant correlations were found between moon cycles and postoperative haemorrhagic complications (p = .50).

European research priorities for intracerebral haemorrhage.

PubMed

Steiner, Thorsten; Petersson, Jesper; Al-Shahi Salman, Rustam; Christensen, Hanne; Cordonnier, Charlotte; Csiba, Laszlo; Harnof, Sagi; Krieger, Derk; Mendelow, David; Molina, Carlos; Montaner, Joan; Overgaard, Karsten; Roine, Risto O; Schmutzhard, Erich; Tatlisumak, Turgut; Toni, Danilo; Stapf, Christian

2011-01-01

Over 2 million people are affected by intracerebral haemorrhage (ICH) worldwide every year, one third of them dying within 1 month, and many survivors being left with permanent disability. Unlike most other stroke types, the incidence, morbidity and mortality of ICH have not declined over time. No standardised diagnostic workup for the detection of the various underlying causes of ICH currently exists, and the evidence for medical or surgical therapeutic interventions remains limited. A dedicated European research programme for ICH is needed to identify ways to reduce the burden of ICH-related death and disability. The European Research Network on Intracerebral Haemorrhage EURONICH is a multidisciplinary academic research collaboration that has been established to define current research priorities and to conduct large clinical studies on all aspects of ICH. Copyright © 2011 S. Karger AG, Basel.

Streptococcus sanguinis meningitis following endoscopic ligation for oesophageal variceal haemorrhage.

PubMed

Liu, Yu-Ting; Lin, Chin-Fu; Lee, Ya-Ling

2013-05-01

We report a case of acute purulent meningitis caused by Streptococcus sanguinis after endoscopic ligation for oesophageal variceal haemorrhage in a cirrhotic patient without preceding symptoms of meningitis. Initial treatment with flomoxef failed. The patient was cured after 20 days of intravenous penicillin G. This uncommon infection due to S. sanguinis adds to the long list of infectious complications among patients with oesophageal variceal haemorrhage.

Admission blood glucose predicted haemorrhagic shock in multiple trauma patients.

PubMed

Kreutziger, Janett; Rafetseder, Andreas; Mathis, Simon; Wenzel, Volker; El Attal, René; Schmid, Stefan

2015-01-01

Admission blood glucose is known to be a predictor for outcome in several disease patterns, especially in critically ill trauma patients. The underlying mechanisms for the association of hyperglycaemia and poor outcome are still not proven. It was hypothesised that hyperglycaemia upon hospital admission is associated with haemorrhagic shock and in-hospital mortality. Data was extracted from an observational trauma database of the level 1 trauma centre at Innsbruck Medical University hospital. Trauma patients (≥18 years) with multiple injuries and an Injury Severity Score ≥17 were included and analysed. In total, 279 patients were analysed, of which 42 patients (15.1%) died. With increasing blood glucose upon hospital admission, the rate of patients with haemorrhagic shock rose significantly [from 4.4% (glucose 4.1-5.5mmol/L) to 87.5% (glucose >15mmol/L), p<0.0001]. Mortality was also associated with initial blood glucose [≤5.50mmol/L 8.3%; 5.51-7.50mmol/L 10.9%, 7.51-10mmol/L 12.4%; 10.01-15mmol/L 32.0%; ≥15.01mmol/L 12.5%, p=0.008]. Admission blood glucose was a better indicator for haemorrhagic shock (cut-off 9.4mmol/L, sensitivity 67.1%, specificity 83.9%) than haemoglobin, base excess, bicarbonate, pH, lactate, or vital parameters. Regarding haemorrhagic shock, admission blood glucose is more valuable during initial patient assessment than the second best predictive parameter, which was admission haemoglobin (cut-off value 6.5mmol/L (10.4g/dL): sensitivity 61.3%, specificity 83.9%). In multiple trauma, non-diabetic patients, admission blood glucose predicted the incidence of haemorrhagic shock. Admission blood glucose is an inexpensive, rapidly and easily available laboratory value that might help to identify patients at risk for haemorrhagic shock during initial evaluation upon hospital admission. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antiplatelet therapy for aneurysmal subarachnoid haemorrhage.

PubMed

Dorhout Mees, S M; van den Bergh, W M; Algra, A; Rinkel, G J E

2007-10-17

Secondary ischaemia is a frequent cause of poor outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). Besides vasospasm, platelet aggregation seems to play a role in the pathogenesis of secondary ischaemia. Experimental studies have suggested that antiplatelet agents can prevent secondary ischaemia. To determine whether antiplatelet agents change outcome in patients with aneurysmal SAH. We searched the Cochrane Stroke Group Trials Register (last searched August 2006), MEDLINE (1966 to August 2006) and EMBASE databases (1980 to August 2006). We also searched reference lists of identified trials. All randomised controlled trials (RCTs) comparing any antiplatelet agent with control in patients with aneurysmal SAH. Two review authors independently extracted the data and assessed trial quality. Relative risks (RR) were calculated with regard to poor outcome, case fatality, secondary ischaemia, haemorrhagic intracranial complications and aneurysmal rebleeding according to the intention-to-treat principle. In case of a statistically significant primary analysis, a worst case analysis was performed. Seven RCTs were included in the review, totalling 1385 patients. Four of these trials met the criteria for good quality studies. For any antiplatelet agent there were reductions of a poor outcome (RR 0.79, 95% confidence interval (CI) 0.62 to 1.01) and secondary brain ischaemia (RR 0.79, 95% CI 0.56 to 1.22) and more intracranial haemorrhagic complications (RR 1.36, 95% CI 0.59 to 3.12), but none of these differences were statistically significant. There was no effect on case fatality (RR 1.01, 95% CI 0.74 to 1.37) or aneurysmal rebleeding (RR 0.98, 95% CI 0.78 to 1.38). For individual antiplatelet agents, only ticlopidine was associated with statistically significant fewer occurrences of a poor outcome (RR 0.37, 95% CI 95% CI 0.14 to 0.98) but this estimate was based on only one small RCT. This review shows a trend towards better outcome in patients treated with

Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial.

PubMed

Derman, Richard J; Kodkany, Bhalchandra S; Goudar, Shivaprasad S; Geller, Stacie E; Naik, Vijaya A; Bellad, M B; Patted, Shobhana S; Patel, Ashlesha; Edlavitch, Stanley A; Hartwell, Tyler; Chakraborty, Hrishikesh; Moss, Nancy

2006-10-07

Postpartum haemorrhage is a major cause of maternal mortality in the developing world. Although effective methods for prevention and treatment of such haemorrhage exist--such as the uterotonic drug oxytocin--most are not feasible in resource-poor settings where many births occur at home. We aimed to investigate whether oral misoprostol, a potential alternative to oxytocin, could prevent postpartum haemorrhage in a community home-birth setting. In a placebo-controlled trial undertaken between September, 2002, and December, 2005, 1620 women in rural India were randomised to receive oral misoprostol (n=812) or placebo (n=808) after delivery. 25 auxiliary nurse midwives undertook the deliveries, administered the study drug, and measured blood loss. The primary outcome was the incidence of acute postpartum haemorrhage (defined as > or =500 mL bleeding) within 2 h of delivery. Analysis was by intention-to-treat. The trial was registered with the US clinical trials database (http://www. clinicaltrials.gov) as number NCT00097123. Oral misoprostol was associated with a significant reduction in the rate of acute postpartum haemorrhage (12.0% to 6.4%, p<0.0001; relative risk 0.53 [95% CI 0.39-0.74]) and acute severe postpartum haemorrhage (1.2% to 0.2%, p<0.0001; 0.20 [0.04-0.91]. One case of postpartum haemorrhage was prevented for every 18 women treated. Misoprostol was also associated with a decrease in mean postpartum blood loss (262.3 mL to 214.3 mL, p<0.0001). Postpartum haemorrhage rates fell over time in both groups but remained significantly higher in the placebo group. Women taking misoprostol had a higher rate of transitory symptoms of chills and fever than the control. Oral misoprostol was associated with significant decreases in the rate of acute postpartum haemorrhage and mean blood loss. The drug's low cost, ease of administration, stability, and a positive safety profile make it a good option in resource-poor settings.

Adolescents born prematurely with isolated grade 2 haemorrhage in the early 1990s face increased risks of learning challenges.

PubMed

Vohr, Betty R; Allan, Walter; Katz, Karol H; Schneider, Karen; Tucker, Richard; Ment, Laura R

2014-10-01

To compare the impact of low-grade haemorrhage on neurocognitive function in 16-year-old adolescents born preterm, by grade of intraventricular haemorrhage, and term controls. We evaluated 338 preterm adolescents (birth weight 600-1250 g) for intelligence, executive function and memory tasks. Eleven had grade 3-4 haemorrhage, 44 had grade 2, 31 had grade 1, and 251 had no haemorrhage. Group comparisons were made with 102 term age-matched controls, and regression models used to identify the risk that low-grade haemorrhage posed for cognitive, executive function and memory deficits. Preterm adolescents with grade 2 haemorrhage had higher deficit rates of verbal intelligence, receptive vocabulary, phonemic fluency, cognitive flexibility and phonological fluency than preterm adolescents with grade 1 or no haemorrhage, compared with term controls. After excluding preterm adolescents with both grade 2 haemorrhage and cystic periventricular leukomalacia, those with isolated grade 2 haemorrhage remained at greater risk of cognitive and executive function deficits than term controls and of cognitive deficits than preterm adolescents with no haemorrhage. Our findings suggest that preterm adolescents born in the early 1990s with isolated grade 2 haemorrhage are at increased risk of learning challenges, including cognitive and executive function deficits. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Intracranial haemorrhage possibly related to Tipranavir in an HIV-1 patient with cryptococcal meningitis.

PubMed

Chrysos, G; Gerakari, S; Stasini, F; Kokkoris, S; Kourousis, D; Velegraki, A

2008-07-01

A 55-year-old HIV-infected patient on antiretroviral treatment with Ritonavir-boosted Tipranavir as part of HAART developed intracranial haemorrhage during the acute phase of cryptococcal meningitis. CT scan and MRI confirmed the intracranial haemorrhage. Positive cryptococcal antigen and cultures of both blood and CSF confirmed the diagnosis of meningitis caused by Cryptococcus neoformans. There was no evidence of any bleeding disorder, use of aspirin or antiplatelet agents. The patient was treated with Liposomal Amphotericin B for cryptococcal meningitis. No special treatment was needed for the intracranial haemorrhage, but Tipranavir was discontinued and replaced by Kaletra and Saquinavir. Intracranial haemorrhage could be related to Tipranavir and cryptococcal meningitis was a predisposing factor. Headache stopped 3 days after starting antifungal treatment. To the best of our knowledge, this is the first reported case of intracranial haemorrhage related to Tipranavir treatment after the end of the "RESIST" studies and the only one related to meningitis.

Major haemorrhage fatalities in the Australian national coronial database.

PubMed

Gipson, Jacob S; Wood, Erica M; Cole-Sinclair, Merrole F; McQuilten, Zoe; Waters, Neil; Woodford, Noel W

2017-12-10

The aim of the study is to describe the epidemiology of major bleeding fatalities. A case series analysis of Australia's National Coronial Information System was conducted. Keywords were used to search for closed cases of major haemorrhage in the state of Victoria for the period 1 January 2009 to 31 December 2011. Coroners' findings, autopsy reports and police reports of cases were reviewed. Demographic data were extracted, and cases were assigned to a clinical bleeding context. A total of 427 cases of major bleeding causing death were identified. The cohort was predominately men (69%), with a median age of 63 years (interquartile range 45-77 years). Trauma accounted for 38%, gastrointestinal haemorrhage 28%, surgical/procedural bleeding 14%, ruptured/leaking aneurysms 12% and other 8%. Most events began in homes (46%), hospitals (22%) and at the roadside (17%). Of those whose haemorrhage began in the community, 69% did not survive to hospital. Major bleeding fatalities occurred across a diverse range of contexts, with trauma and gastrointestinal bleeding accounting for most deaths. The majority of patients did not survive to reach hospital. Major haemorrhage occurring entirely outside hospital may be underrecognised from analyses of datasets based primarily on traumatic or in-hospital bleeding. These findings have implications for management of pre-hospital resuscitation and development of clinical practice guidelines for identification and management of major bleeding in the community. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Changes in self-efficacy, collective efficacy and patient outcome following interprofessional simulation training on postpartum haemorrhage.

PubMed

Egenberg, Signe; Øian, Pål; Eggebø, Torbjørn Moe; Arsenovic, Mirjana Grujic; Bru, Lars Edvin

2017-10-01

To examine whether interprofessional simulation training on management of postpartum haemorrhage enhances self-efficacy and collective efficacy and reduces the blood transfusion rate after birth. Postpartum haemorrhage is a leading cause of maternal morbidity and mortality worldwide, although it is preventable in most cases. Interprofessional simulation training might help improve the competence of health professionals dealing with postpartum haemorrhage, and more information is needed to determine its potential. Multimethod, quasi-experimental, pre-post intervention design. Interprofessional simulation training on postpartum haemorrhage was implemented for midwives, obstetricians and auxiliary nurses in a university hospital. Training included realistic scenarios and debriefing, and a measurement scale for perceived postpartum haemorrhage-specific self-efficacy, and collective efficacy was developed and implemented. Red blood cell transfusion was used as the dependent variable for improved patient outcome pre-post intervention. Self-efficacy and collective efficacy levels were significantly increased after training. The overall red blood cell transfusion rate did not change, but there was a significant reduction in the use of ≥5 units of blood products related to severe bleeding after birth. The study contributes to new knowledge on how simulation training through mastery and vicarious experiences, verbal persuasion and psychophysiological state might enhance postpartum haemorrhage-specific self-efficacy and collective efficacy levels and thereby predict team performance. The significant reduction in severe postpartum haemorrhage after training, indicated by reduction in ≥5 units of blood transfusions, corresponds well with the improvement in collective efficacy, and might reflect the emphasis on collective efforts to counteract severe cases of postpartum haemorrhage. Interprofessional simulation training in teams may contribute to enhanced prevention and

Comparison of the cardiovascular effects of meptazinol and naloxone following haemorrhagic shock in rats and cats.

PubMed Central

Chance, E.; Paciorek, P. M.; Todd, M. H.; Waterfall, J. F.

1985-01-01

The cardiovascular effects of the opioid mixed agonist-antagonist, meptazinol, and the opioid antagonist, naloxone, have been evaluated in conscious rats, anaesthetized rats and anaesthetized cats following the induction of haemorrhagic shock. The mean arterial pressure of conscious rats decreased by 17-29 mmHg following a haemorrhage of 20% of blood volume. Meptazinol (17 mg kg-1, i.m.) administered after haemorrhage evoked a rapid and sustained increase in mean arterial pressure to pre-haemorrhage levels. Naloxone (10 mg kg-1, i.v.) also increased mean arterial pressure to a level significantly higher than post-haemorrhage values. Neither haemorrhage nor subsequent drug treatments evoked significant changes in the heart rates of conscious rats. In anaesthetized rats, 20% haemorrhage evoked decreases in mean arterial pressure, heart rate and cardiac output. Blood flow to the heart, skin, skeletal muscle, kidneys, spleen and liver (arterial) was decreased. Meptazinol and naloxone increased blood pressure and total peripheral resistance, but did not significantly alter heart rate or cardiac output. Hepatic arterial flow decreased further in both drug and vehicle treated groups. In addition meptazinol slightly reduced skeletal muscle flow. In anaesthetized cats 40% haemorrhage decreased mean arterial pressure by 46 +/- 3 mmHg. An intravenous infusion of either meptazinol or naloxone (cumulative 2 mg kg-1, i.v.) partially restored blood pressure. In experimental animal models of haemorrhagic shock, meptazinol has a similar cardiovascular profile to naloxone. The established analgesic activity of meptazinol may confer an advantage in some shock states. PMID:4052729

Predictive value of flat-panel CT for haemorrhagic transformations in patients with acute stroke treated with thrombectomy.

PubMed

Rouchaud, Aymeric; Pistocchi, Silvia; Blanc, Raphaël; Engrand, Nicolas; Bartolini, Bruno; Piotin, Michel

2014-03-01

Haemorrhagic transformations are pejorative for patients with acute ischaemic stroke (AIS). We estimated flat-panel CT performances to detect brain parenchymal hyperdense lesions immediately after mechanical thrombectomy directly on the angiography table in patients with AIS, and its ability to predict haemorrhagic transformation. We also evaluated an easy-reading protocol for post-procedure flat-panel CT evaluation by clinicians to enable them to determine the potential risk of haemorrhage. Two neuroradiologists retrospectively reviewed post-procedural flat-panel CT and 24 h follow-up imaging. We evaluated hyperdense lesions on flat-panel CT to predict the occurrence of haemorrhagic transformation within 24 h detected with conventional imaging. Of 63 patients, 60.3% presented post-procedural parenchymal hyperdensity and 54.0% had haemorrhagic transformation. Significantly more patients with hyperdense lesions on post-thrombectomy flat-panel CT presented haemorrhagic transformation (84.2% vs 8.0%; p<0.0001). No significant haemorrhagic transformations were detected for patients without parenchymal hyperdensity. Sensitivity and specificity of hyperdense lesions on flat-panel CT for the prediction of haemorrhagic transformation were 94.1% (80.3-99.3%) and 79.3% (60.3-92.0%), respectively. The positive and negative predictive values for the occurrence of haemorrhage were 84.2% (68.8-94.0%) and 92.0% (74.0-99.0%), respectively. For significant parenchymal haemorrhage type 2, sensitivity and negative predictive values were 100%. We observed good homogeneity between the different readers. Hyperdensity on post-procedural flat-panel CT was associated with a tendency for higher risk of death and lower risk of good clinical outcome. Flat-panel CT appears to be a good tool to detect brain parenchymal hyperdensities after mechanical thrombectomy in patients with AIS and to predict haemorrhagic transformation.

Renal impairment in stroke patients: A comparison between the haemorrhagic and ischemic variants.

PubMed

Shrestha, Pratyush; Thapa, Shalima; Shrestha, Shikher; Lohani, Subash; Bk, Suresh; MacCormac, Oscar; Thapa, Lekhjung; Devkota, Upendra Prasad

2017-01-01

Background: Renal impairment is regularly seen in hospitalized stroke patients, affecting the outcome of patients, as well as causing difficulties in their management. A prospective cohort study was conducted to assess the trend of renal function in hospitalized ischemic and haemorrhagic stroke patients. The incidence of renal impairment in these subgroups, the contributing factors and the need for renal replacement in renal impaired patients was evaluated. Methods: Alternate day renal function testing was performed in hospitalized stroke patients. Estimated glomerular filtration rate (e-GFR) was calculated and the trend of renal function in the two stroke subgroups (haemorrhagic and ischemic) was assessed, with renal impairment defined as e-GFR < 60mL/ minute per 1.73m 2 . Results: Among 52 patients, 25 had haemorrhagic stroke (mean age 59.81 ± 14.67) and 27 had ischemic stroke (mean age 56.12 ± 13.08). The mean e-GFR (mL/minute per 1.732m 2 ) at admission in the haemorrhagic stroke subgroup was 64.79 ± 25.85 compared to 86.04 ± 26.09 in the ischemic stroke subgroup (p=0.005). Sixteen out of 25 (64%) patients in the haemorrhagic stroke subgroup and 9 out of 27 (33.3%) patients in the ischemic subgroup developed renal impairment (p=0.027). The location of the bleed (p=0.8), volume of hematoma (p=0.966) and surgical intervention (p=0.4) did not predispose the patients to renal impairment. One out of 16 patients with haemorrhagic stroke (who eventually died), and 2 out of 9 patients with ischemic stroke required renal replacement. Conclusion : Renal impairment is commonly seen in stroke patients, more so in patients who suffered haemorrhagic strokes.  The impairment, however, is transient and rarely requires renal replacement therapy.

Losartan does not decrease renal oxygenation and norepinephrine effects in rats after resuscitated haemorrhage.

PubMed

Jönsson, Sofia; Melville, Jacqueline M; Becirovic-Agic, Mediha; Hultström, Michael

2018-04-18

Renin-angiotensin-system blockers are thought to increase the risk of acute kidney injury after surgery and haemorrhage. We found that Losartan does not cause renal cortical hypoxia after haemorrhage in rats because of decreased renal vascular resistance, but did not evaluate resuscitation. Study Losartan´s effect on renal cortical and medullary oxygenation, and norepinephrine´s vasopressor effect in a model of resuscitated haemorrhage. After seven days Losartan (60 mg/kg/day) or control treatment, male Wistar rats were haemorrhaged 20 % of the blood volume and resuscitated with Ringer's Acetate. Mean arterial pressure, renal blood flow, and kidney tissue oxygenation was measured at baseline and after resuscitation. Finally, the effect of norepinephrine on mean arterial pressure and renal blood flow was investigated. As expected, Losartan lowered mean arterial pressure but not renal blood flow. Losartan did not affect renal oxygen consumption and oxygen tension. Mean arterial pressure and renal blood flow were lower after resuscitated haemorrhage. Smaller increase of renal vascular resistance in Losartan group translated to smaller decrease in cortical oxygen tension, but no significant difference seen in medullary oxygen tension either between groups or after haemorrhage. The effect of norepinephrine on mean arterial pressure and renal blood flow was similar in controls and Losartan treated rats. Losartan does not decrease renal oxygenation after resuscitated haemorrhage because of a smaller increase in renal vascular resistance. Further, Losartan does not decrease the efficiency of norepinephrine as a vasopressor indicating that blood pressure may be managed effectively during Losartan treatment.

The use of antidepressants and the risk of haemorrhagic stroke: a nested case control study

PubMed Central

Douglas, Ian; Smeeth, Liam; Irvine, David

2011-01-01

AIM To investigate whether selective serotonin re-uptake inhibitor (SSRI) use is associated with an increased risk of haemorrhagic stroke in a cohort of antidepressant users. METHODS We conducted a case control study, nested within a cohort of antidepressant users in the United Kingdom General Practice Research Database. A cohort of 365 195 patients prescribed either an SSRI or tricyclic antidepressant between 1992 and 2006 was identified. Three hundred and fifty-seven cases of haemorrhagic stroke were observed and 1631 control patients without haemorrhagic stroke were selected. RESULTS The primary analysis showed no evidence of an association between current SSRI or TCA use and haemorrhagic stroke. Current use of an SSRI compared with no use at the time of haemorrhagic stroke was associated with an adjusted odds ratio of 1.11 (95% confidence interval (CI) 0.82, 1.50). For current tricyclic use the equivalent odds ratio was 0.73 (0.52, 1.02). There was no evidence that prior cerebrovascular events modified the effect of either SSRIs or TCAs. CONCLUSIONS We found no evidence that SSRIs are associated with an increased risk of haemorrhagic stroke, regardless of prior history of cerebrovascular events. PMID:21143507

Mortality from trauma haemorrhage and opportunities for improvement in transfusion practice.

PubMed

Stanworth, S J; Davenport, R; Curry, N; Seeney, F; Eaglestone, S; Edwards, A; Martin, K; Allard, S; Woodford, M; Lecky, F E; Brohi, K

2016-03-01

The aim of this study was to describe the prevalence, patterns of blood use and outcomes of major haemorrhage in trauma. This was a prospective observational study from 22 hospitals in the UK, including both major trauma centres and smaller trauma units. Eligible patients received at least 4 units of packed red blood cells (PRBCs) in the first 24 h of admission with activation of the massive haemorrhage protocol. Case notes, transfusion charts, blood bank records and copies of prescription/theatre charts were accessed and reviewed centrally. Study outcomes were: use of blood components, critical care during hospital stay, and mortality at 24 h, 30 days and 1 year. Data were used to estimate the national trauma haemorrhage incidence. A total of 442 patients were identified during a median enrolment interval of 20 (range 7-24) months. Based on this, the national incidence of trauma haemorrhage was estimated to be 83 per million. The median age of patients in the study cohort was 38 years and 73·8 per cent were men. The incidence of major haemorrhage increased markedly in patients aged over 65 years. Thirty-six deaths within 24 h of admission occurred within the first 3 h. At 24 h, 79 patients (17·9 per cent) had died, but mortality continued to rise even after discharge. Patients who received a cumulative ratio of fresh frozen plasma to PRBCs of at least 1 : 2 had lower rates of death than those who received a lower ratio. There were delays in administration of blood. Platelets and cryoprecipitate were either not given, or transfused well after initial resuscitation. There is a high burden of trauma haemorrhage that affects all age groups. Research is required to understand the reasons for death after the first 24 h and barriers to timely transfusion support. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Crimean-Congo haemorrhagic fever.

PubMed

Peyrefitte, C; Marianneau, P; Tordo, N; Bouloy, M

2015-08-01

Crimean-Congo haemorrhagic fever (CCHF) is one of the most widespread arboviroses in the world. It is present in Africa, south-east Europe, the Middle East and Asia. It is caused by a nairovirus (Bunyaviridae family) transmitted by several species of ticks. The geographical distribution of the disease coincides with the distribution of Hyalomma ticks. While infected livestock do not show signs of illness, humans are severely affected, with a high mortality rate. The most common symptoms are high fever, dizziness, headache, vomiting and haemorrhages. Pathogenesis studies in interferon-receptor-deficient mice indicated that the interferon response is crucial in controlling virus propagation and in protecting against the disease. Detection of the virus in biological material is currently performed by reverse-transcription polymerase chain reaction. Enzyme-linked immunosorbent assay and indirect immunofluorescence are used to detect the presence of CCHF virus-specific antibodies. In the 1970s, a formalin-inactivated vaccine prepared from suckling mouse brain was used in Eastern Europe and the former Soviet Union, but its efficacy remains to be proven. Treatment of patients with ribavirin is recommended by the World Health Organization, but it should be administered as early as possible. Although important progress has been made over the last few decades, many questions about the pathogenesis and epidemiology of the disease are still to be addressed and there is a need to develop efficient vaccines and antivirals.

Risk of cardiovascular events and death in the life after aneurysmal subarachnoid haemorrhage: a nationwide study.

PubMed

Nieuwkamp, Dennis J; Vaartjes, Ilonca; Algra, Ale; Rinkel, Gabriel J E; Bots, Michiel L

2014-12-01

The increased mortality rates of survivors of aneurysmal subarachnoid haemorrhage have been attributed to an increased risk of cardiovascular events in a registry study in Sweden. Swedish registries have however not been validated for subarachnoid haemorrhage and Scandinavian incidences of cardiovascular disease differ from that in Western European countries. We assessed risks of vascular disease and death in subarachnoid haemorrhage survivors in the Netherlands. From the Dutch hospital discharge register, we identified all patients with subarachnoid haemorrhage admission between 1997 and 2008. We determined the accuracy of coding of the diagnosis subarachnoid haemorrhage for patients admitted to our centre. Conditional on survival of three-months after the subarachnoid haemorrhage, we calculated standardized incidence and mortality ratios for fatal or nonfatal vascular diseases, vascular death, and all-cause death. Cumulative risks were estimated with survival analysis. The diagnosis of nontraumatic subarachnoid haemorrhage was correct in 95·4% of 1472 patients. Of 11,263 admitted subarachnoid haemorrhage patients, 6999 survived more than three-months. During follow-up (mean 5·1 years), 874 (12·5%) died. The risks of death were 3·3% within one-year, 11·3% within five-years, and 21·5% within 10 years. The standardized mortality ratio was 3·4 (95% confidence interval: 3·1 to 3·7) for vascular death and 2·2 (95% confidence interval: 2·1 to 2·3) for all-cause death. The standardized incidence ratio for fatal or nonfatal vascular diseases was 2·7 (95% confidence interval: 2·6 to 2·8). Dutch hospital discharge and cause of death registries are a valid source of data for subarachnoid haemorrhage, and show that the increased mortality rate in subarachnoid haemorrhage survivors is explained by increased risks for vascular diseases and death. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

A novel pathogenic variant in an Iranian Ataxia telangiectasia family revealed by next-generation sequencing followed by in silico analysis.

PubMed

Tabatabaiefar, Mohammad Amin; Alipour, Paria; Pourahmadiyan, Azam; Fattahi, Najmeh; Shariati, Laleh; Golchin, Neda; Mohammadi-Asl, Javad

2017-08-15

Ataxia telangiectasia (A-T) is a neurodegenerative autosomal recessive disorder with the main characteristics of progressive cerebellar degeneration, sensitivity to ionizing radiation, immunodeficiency, telangiectasia, premature aging, recurrent sinopulmonary infections, and increased risk of malignancy, especially of lymphoid origin. Ataxia Telangiectasia Mutated gene, ATM, as a causative gene for the A-T disorder, encodes the ATM protein, which plays an important role in the activation of cell-cycle checkpoints and initiation of DNA repair in response to DNA damage. Targeted next-generation sequencing (NGS) was performed on an Iranian 5-year-old boy presented with truncal and limb ataxia, telangiectasia of the eye, Hodgkin lymphoma, hyper pigmentation, total alopecia, hepatomegaly, and dysarthria. Sanger sequencing was used to confirm the candidate pathogenic variants. Computational docking was done using the HEX software to examine how this change affects the interactions of ATM with the upstream and downstream proteins. Three different variants were identified comprising two homozygous SNPs and one novel homozygous frameshift variant (c.80468047delTA, p.Thr2682ThrfsX5), which creates a stop codon in exon 57 leaving the protein truncated at its C-terminal portion. Therefore, the activation and phosphorylation of target proteins are lost. Moreover, the HEX software confirmed that the mutated protein lost its interaction with upstream and downstream proteins. The variant was classified as pathogenic based on the American College of Medical Genetics and Genomics guideline. This study expands the spectrum of ATM pathogenic variants in Iran and demonstrates the utility of targeted NGS in genetic diagnostics. Copyright © 2017. Published by Elsevier B.V.

Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells

PubMed Central

Coufal, Nicole G.; Garcia-Perez, Josè Luis; Peng, Grace E.; Marchetto, Maria C. N.; Muotri, Alysson R.; Mu, Yangling; Carson, Christian T.; Macia, Angela; Moran, John V.; Gage, Fred H.

2011-01-01

Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients. Here, we demonstrate an increase in the retrotransposition efficiency of engineered human L1s in cells that lack or contain severely reduced levels of ataxia telangiectasia mutated, a serine/threonine kinase involved in DNA damage signaling and neurodegenerative disease. We demonstrate that the increase in L1 retrotransposition in ataxia telangiectasia mutated-deficient cells most likely occurs by conventional target-site primed reverse transcription and generate either longer, or perhaps more, L1 retrotransposition events per cell. Finally, we provide evidence suggesting an increase in human-specific L1 DNA copy number in postmortem brain tissue derived from ataxia telangiectasia patients compared with healthy controls. Together, these data suggest that cellular proteins involved in the DNA damage response may modulate L1 retrotransposition. PMID:22159035

A survey of interventional radiology for the management of obstetric haemorrhage in the United Kingdom.

PubMed

Webster, V J; Stewart, R; Stewart, P

2010-07-01

Massive haemorrhage remains a leading cause of maternal death worldwide. Interventional radiology can be used to prevent or treat life-threatening haemorrhage, but evidence for its efficacy is limited to case series predominantly from large tertiary centres. The current availability of interventional radiology for management of obstetric haemorrhage in the UK is unknown. A postal questionnaire on the use of interventional radiology was sent to the lead clinician for obstetric anaesthesia in 226 UK maternity units. The response rate was 72%; 74 respondents (46%) had considered and 51 (31%) used interventional radiology for control of obstetric haemorrhage. Its use was primarily confined to large tertiary obstetric units and limited by availability of equipment and staff. Interventional radiology to assist in the management of obstetric haemorrhage is not uniformly available in the UK and experience remains limited. Access to this resource is subject to striking local variability and influenced by the size and nature of the hospital supporting the delivery unit. 2010 Elsevier Ltd. All rights reserved.

Tachycardic and non-tachycardic responses in trauma patients with haemorrhagic injuries.

PubMed

Reisner, Andrew T; Edla, Shwetha; Liu, Jianbo; Liu, Jiankun; Khitrov, Maxim Y; Reifman, Jaques

2018-04-30

Analyses of large databases have demonstrated that the association between heart rate (HR) and blood loss is weaker than what is taught by Advanced Trauma Life Support training. However, those studies had limited ability to generate a more descriptive paradigm, because they only examined a single HR value per patient. In a comparative, retrospective analysis, we studied the temporal characteristics of HR through time in adult trauma patients with haemorrhage, based on documented injuries and transfusion of ≥3 units of red blood cells (RBCs). We analysed archived vital-sign data of up to 60 min during either pre-hospital or emergency department care. We identified 133 trauma patients who met the inclusion criteria for major haemorrhage and 1640 control patients without haemorrhage. There were 55 haemorrhage patients with a normal median HR and 78 with tachycardia. Median ΔHR was -0.8 and +0.7 bpm per 10 min, respectively. Median time to documented hypotension was 8 and 5 min, respectively. RBCs were not significantly different; median volumes were 6 (IQR: 4-13) and 10 units (IQR: 5-16), respectively. Time-to-hypotension and mortality were not significantly different. Tachycardic patients were significantly younger (P < 0.05). Only 10 patients with normal HR developed transient/temporary tachycardia, and only 11 tachycardic patients developed a transient/temporary normal HR. The current analysis suggests that some trauma patients with haemorrhage are continuously tachycardic while others have a normal HR. For both cohorts, hypotension typically develops within 30 min, without any consistent temporal increases or trends in HR. Published by Elsevier Ltd.

The role of haemorrhage and exudate detection in automated grading of diabetic retinopathy.

PubMed

Fleming, Alan D; Goatman, Keith A; Philip, Sam; Williams, Graeme J; Prescott, Gordon J; Scotland, Graham S; McNamee, Paul; Leese, Graham P; Wykes, William N; Sharp, Peter F; Olson, John A

2010-06-01

Automated grading has the potential to improve the efficiency of diabetic retinopathy screening services. While disease/no disease grading can be performed using only microaneurysm detection and image-quality assessment, automated recognition of other types of lesions may be advantageous. This study investigated whether inclusion of automated recognition of exudates and haemorrhages improves the detection of observable/referable diabetic retinopathy. Images from 1253 patients with observable/referable retinopathy and 6333 patients with non-referable retinopathy were obtained from three grading centres. All images were reference-graded, and automated disease/no disease assessments were made based on microaneurysm detection and combined microaneurysm, exudate and haemorrhage detection. Introduction of algorithms for exudates and haemorrhages resulted in a statistically significant increase in the sensitivity for detection of observable/referable retinopathy from 94.9% (95% CI 93.5 to 96.0) to 96.6% (95.4 to 97.4) without affecting manual grading workload. Automated detection of exudates and haemorrhages improved the detection of observable/referable retinopathy.

Intracranial haemorrhage associated with ingestion of 'ecstasy'.

PubMed Central

Hughes, J C; McCabe, M; Evans, R J

1993-01-01

A case of a patient with intracranial haemorrhage thought to have been associated with ingestion of 'Ecstasy' [3-4 methylenedioxymethamphetamine (MDMA)] is presented. The case illustrates the importance of drug analysis in cases involving illicit drug use. Images Fig. 1 PMID:7906517

Minimally invasive surgery for intracerebral haemorrhage.

PubMed

Barnes, Benjamin; Hanley, Daniel F; Carhuapoma, Juan R

2014-04-01

Spontaneous intracerebral haemorrhage (ICH) imposes a significant health and economic burden on society. Despite this, ICH remains the only stroke subtype without a definitive treatment. Without a clearly identified and effective treatment for spontaneous ICH, clinical practice varies greatly from aggressive surgery to supportive care alone. This review will discuss the current modalities of treatments for ICH including preliminary experience and investigative efforts to advance the care of these patients. Open surgery (craniotomy), prothrombotic agents and other therapeutic interventions have failed to significantly improve the outcome of these stroke victims. Recently, the Surgical Trial in Intracerebral Haemorrhage (STICH) II assessed the surgical management of patients with superficial intraparenchymal haematomas with negative results. MISTIE II and other trials of minimally invasive surgery (MIS) have shown promise for improving patient outcomes and a phase III trial started in late 2013. ICH lacks a definitive primary treatment as well as a therapy targeting surrounding perihematomal oedema and associated secondary damage. An ongoing phase III trial using MIS techniques shows promise for providing treatment for these patients.

Treatment of nonneovascular idiopathic macular telangiectasia type 2 with intravitreal ranibizumab: results of a phase II clinical trial.

PubMed

Toy, Brian C; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2012-05-01

To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for nonneovascular idiopathic macular telangiectasia Type 2. Single-center, open-label Phase II clinical trial enrolling five participants with bilateral nonneovascular idiopathic macular telangiectasia Type 2. Intravitreal ranibizumab (0.5 mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in best-corrected visual acuity, area of late-phase leakage on fluorescein angiography, and retinal thickness on optical coherence tomography. The study treatment was well tolerated and associated with few adverse events. Change in best-corrected visual acuity at 12 months was not significantly different between treated study eyes (0.0 ± 7.5 letters) and control fellow eyes (+2.2 ± 1.9 letters). However, decreases in the area of late-phase fluorescein angiography leakage (-33 ± 20% for study eyes, +1 ± 8% for fellow eyes) and in optical coherence tomography central subfield retinal thickness (-11.7 ± 7.0% for study eyes and -2.9 ± 3.5% for fellow eyes) were greater in study eyes compared with fellow eyes. Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with nonneovascular idiopathic macular telangiectasia Type 2.

CT and MRI imaging at the acute phase of inaugural non-traumatic hepatic haemorrhages.

PubMed

Boulouis, G; Marmin, C; Lemaire, S; Boury, S; Sergent, G; Mordon, S; Ernst, O

2013-03-01

Although rare, non-traumatic hepatic haemorrhage is a known complication of liver tumors. In cases where the haemorrhage is the first clinical event, diagnostic work-up is critical. This retrospective study was conducted between July 2001 and March 2011. Acute phase CT-scan and MRI imaging in patients diagnosed with non-traumatic liver hematomas were interpreted with particular attention to the radio-semiotic characteristics of hematomas and liver lesions. Those findings were then confronted to the patients' final diagnoses. Twelve patients were included (mean age of 42 years). In seven of them a suspect liver lesion was discovered in the acute CT-Scan or MRI imaging. All lesions were strongly hyper vascular.The haemorrhage revealed hepatocarcinoma in four patients, liver adenoma in two and focal nodular hyperplasia in an other. It is important in spontaneous liver haemorrhage to consider the high probability of hepatocarcinoma or potentially malignant lesions even when the patient has no known hepatic disorders, and especially in young patients. The results of this study show that imaging is a key issue at the acute phase of inaugural non-traumatic hepatic haemorrhages and requires a simple but complete triphasic injected protocol. Copyright © 2012 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

On the role of vasopressin and angiotensin in the development of irreversible haemorrhagic shock

PubMed Central

Errington, M. L.; e Silva, M. Rocha

1974-01-01

1. Long-lasting haemorrhagic hypotension (4·5 hr at 35 mmHg) leading to irreversible haemorrhagic shock, has been studied in normal dogs, in dogs treated with a bradykinin potentiating nonapeptide (BPP9a), which blocks the conversion of angiotensin I to angiotensin II, and in dogs with experimental chronic diabetes insipidus (DI dogs). BPP9a was given by I.V. injection before the start of bleeding (BPP pre-treated group), 45 min after blood pressure had reached 35 mmHg (BPP early treated group) or 2 hr after blood pressure had reached 35 mmHg (BPP late-treated group). After retransfusion of blood all dogs were allowed to recover and observed for a further period of 3 days. 2. Untreated control dogs developed haemorrhagic shock with tachycardia, low cardiac output, low total peripheral conductance and low stroke volume. All died within 24 hr of retransfusion, with pathological lesions typical of irreversible haemorrhagic shock. 3. BPP pre-treated dogs developed haemorrhagic shock with bradycardia (during early shock), high cardiac output, high peripheral vascular conductance and high stroke volume when compared with the untreated controls. All pre-treated animals survived the 3 day observation period. They were then killed and on post-mortem showed no signs of irreversible haemorrhagic shock. 4. BPP early-treated animals behaved like controls before BPP, but like pre-treated animals after the drug. Only one out of eight died within the 3 day observation period. 5. BPP late-treated dogs behaved like controls before BPP. They responded to the drug with a rise in cardiac output, peripheral vascular conductance and stroke volume, and with a fall in heart rate. These responses were, however, short-lived. Four out of these eight animals died within the 3 day observation period, with lesions of irreversible haemorrhagic shock. 6. DI dogs developed haemorrhagic shock with tachycardia (like controls), but with high cardiac output and peripheral vascular conductance (like

Acute convexity subarachnoid haemorrhage and cortical superficial siderosis in probable cerebral amyloid angiopathy without lobar haemorrhage.

PubMed

Charidimou, Andreas; Boulouis, Grégoire; Fotiadis, Panagiotis; Xiong, Li; Ayres, Alison M; Schwab, Kristin M; Gurol, Mahmut Edip; Rosand, Jonathan; Greenberg, Steve M; Viswanathan, Anand

2018-04-01

Acute non-traumatic convexity subarachnoid haemorrhage (cSAH) is increasingly recognised in cerebral amyloid angiopathy (CAA). We investigated: (a) the overlap between acute cSAH and cortical superficial siderosis-a new CAA haemorrhagic imaging signature and (b) whether acute cSAH presents with particular clinical symptoms in patients with probable CAA without lobar intracerebral haemorrhage. MRI scans of 130 consecutive patients meeting modified Boston criteria for probable CAA were analysed for cortical superficial siderosis (focal, ≤3 sulci; disseminated, ≥4 sulci), and key small vessel disease markers. We compared clinical, imaging and cortical superficial siderosis topographical mapping data between subjects with versus without acute cSAH, using multivariable logistic regression. We included 33 patients with probable CAA presenting with acute cSAH and 97 without cSAH at presentation. Patients with acute cSAH were more commonly presenting with transient focal neurological episodes (76% vs 34%; p<0.0001) compared with patients with CAA without cSAH. Patients with acute cSAH were also more often clinically presenting with transient focal neurological episodes compared with cortical superficial siderosis-positive, but cSAH-negative subjects with CAA (76% vs 30%; p<0.0001). Cortical superficial siderosis prevalence (but no other CAA severity markers) was higher among patients with cSAH versus those without, especially disseminated cortical superficial siderosis (49% vs 19%; p<0.0001). In multivariable logistic regression, cortical superficial siderosis burden (OR 5.53; 95% CI 2.82 to 10.8, p<0.0001) and transient focal neurological episodes (OR 11.7; 95% CI 2.70 to 50.6, p=0.001) were independently associated with acute cSAH. This probable CAA cohort provides additional evidence for distinct disease phenotypes, determined by the presence of cSAH and cortical superficial siderosis. © Article author(s) (or their employer(s) unless otherwise stated in the

Neurodegeneration in ataxia-telangiectasia: Multiple roles of ATM kinase in cellular homeostasis.

PubMed

Choy, Kay Rui; Watters, Dianne J

2018-01-01

Ataxia-telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency, and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (ataxia-telangiectasia mutated) gene. ATM is a sensor of DNA double-strand breaks (DSBs) and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signaling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease. In proliferating cells, ATM is localized mainly in the nucleus; however, in postmitotic cells such as neurons, ATM is mostly cytoplasmic. Recent studies reveal an increasing number of roles for ATM in the cytoplasm, including activation by oxidative stress. ATM associates with organelles including mitochondria and peroxisomes, both sources of reactive oxygen species (ROS), which have been implicated in neurodegenerative diseases and aging. ATM is also associated with synaptic vesicles and has a role in regulating cellular homeostasis and autophagy. The cytoplasmic roles of ATM provide a new perspective on the neurodegenerative process in A-T. This review will examine the expanding roles of ATM in cellular homeostasis and relate these functions to the complex A-T phenotype. Developmental Dynamics 247:33-46, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

When the heart rules the head: ischaemic stroke and intracerebral haemorrhage complicating infective endocarditis.

PubMed

Jiad, Estabrak; Gill, Sumanjit K; Krutikov, Maria; Turner, David; Parkinson, Michael H; Curtis, Carmel; Werring, David J

2017-01-01

Sir William Osler meticulously described the clinical manifestations of infective endocarditis in 1885, concluding that: 'few diseases present greater difficulties in the way of diagnosis … which in many cases are practically insurmountable'. Even with modern investigation techniques, diagnosing infective endocarditis can be hugely challenging, yet is critically important in patients presenting with stroke (both cerebral infarction and intracranial haemorrhage), its commonest neurological complication. In ischaemic stroke, intravenous thrombolysis carries an unacceptably high risk of intracranial haemorrhage, while in intracerebral haemorrhage, mycotic aneurysms require urgent treatment to avoid rebleeding, and in all cases, prompt treatment with antibiotics and valve surgery may be life-saving. Here, we describe typical presentations of ischaemic stroke and intracerebral haemorrhage caused by infective endocarditis. We review the diagnostic challenges, the importance of rapid diagnosis, treatment options and controversies. 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/.

Use of the TriSpan Coil to Facilitate the Transcatheter Occlusion of Pulmonary Arteriovenous Malformation

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

Cil, Barbaros E., E-mail: barbaroscil@hotmail.com, E-mail: barbaros@hacettepe.edu.tr; Erdogan, Cueneyt; Akmangit, Ilkay

Pulmonary arteriovenous malformation (PAVM) is a rare vascular malformation of the lung which may occur as an isolated entity or in association with hereditary hemorrhagic telangiectasia (HHT). Because of considerable risk of serious complications such as cerebral embolism, brain abscess and pulmonary hemorrhage, definitive treatment should be considered in most patients. Embolization with coils or detachable balloons is currently the preferred treatment. Paradoxical embolization of coils and balloons may happen, especially in patients with PAVMs with large feeding arteries. In this report we present our initial experience with the use of the TriSpan coil to lower the risk of coilmore » migration during the transcatheter occlusion of PAVMs.« less

Multimodal in vivo blood flow sensing combining particle image velocimetry and optical tweezers-based blood steering

NASA Astrophysics Data System (ADS)

Meissner, Robert; Sugden, Wade W.; Siekmann, Arndt F.; Denz, Cornelia

2018-02-01

All higher developed organisms contain complex hierarchical networks of arteries, veins and capillaries. These constitute the cardiovascular system responsible for supplying nutrients, gas and waste exchange. Diseases related to the cardiovascular system are among the main causes for death worldwide. In order to understand the processes leading to arteriovenous malformation, we studied hereditary hemorrhagic telangiectasia (HHT), which has a prevalence of 1:5000 worldwide and causes internal bleeding. In zebrafish, HHT is induced by mutation of the endoglin gene involved in HHT and observed to reduce red blood cell (RBC) flow to intersegmental vessels (ISVs) in the tail due to malformations of the dorsal aorta (DA) and posterior cardinal vein (PCV). However, these capillaries are still functional. Changes in the blood flow pattern are observed from in vivo data from zebrafish embryos through particle image velocimetry (PIV). Wall shear rates (WSRs) and blood flow velocities are obtained non-invasively with millisecond resolution. We observe significant increases of blood flow velocity in the DA for endoglin-deficient zebrafish embryos (mutants) at 3 days post fertilization. In the PCV, this increase is even more pronounced. We identified an increased similarity between the DA and the PCV of mutant fish compared to siblings, i.e., unaffected fish. To counteract the reduced RBC flow to ISVs we implement optical tweezers (OT). RBCs are steered into previously unperfused ISVs showing a significant increase of RBC count per minute. We discuss limitations with respect to biocompatibility of optical tweezers in vivo and determination of in vivo wall shear stress (WSS) connected to normal and endoglin-deficicent zebrafish embryos.

Suprasellar arachnoid cyst after subdural haemorrhage in an infant. A case based update.

PubMed

Sonnet, M-H; Joud, A; Marchal, J-C; Klein, O

2014-01-01

Brain arachnoid cysts (AC) are congenital or acquired malformations. Their prevalence in children ranges between 0.2 and 2.3% of the studied populations. Few reported studies exist where AC appears after a subdural haemorrhage. We present one case of a symptomatic suprasellar AC after post-traumatic subdural haemorrhage in an infant. After endoscopic ventriculocystostomy, the child quickly improved and the cyst reduced in size. The child was monitored for 22 months and his neurocognitive development remained normal. Our case led us to the hypothesis that the inflammatory process due to subdural haemorrhage may locally result in arachnoiditis, and thus to the creation of a neomembrane, and eventually to cyst formation. This is also the case with the development of post-traumatic spinal AC. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis.

PubMed

Whiteley, William N; Emberson, Jonathan; Lees, Kennedy R; Blackwell, Lisa; Albers, Gregory; Bluhmki, Erich; Brott, Thomas; Cohen, Geoff; Davis, Stephen; Donnan, Geoffrey; Grotta, James; Howard, George; Kaste, Markku; Koga, Masatoshi; von Kummer, Rüdiger; Lansberg, Maarten G; Lindley, Richard I; Lyden, Patrick; Olivot, Jean Marc; Parsons, Mark; Toni, Danilo; Toyoda, Kazunori; Wahlgren, Nils; Wardlaw, Joanna; Del Zoppo, Gregory J; Sandercock, Peter; Hacke, Werner; Baigent, Colin

2016-08-01

Randomised trials have shown that alteplase improves the odds of a good outcome when delivered within 4·5 h of acute ischaemic stroke. However, alteplase also increases the risk of intracerebral haemorrhage; we aimed to determine the proportional and absolute effects of alteplase on the risks of intracerebral haemorrhage, mortality, and functional impairment in different types of patients. We used individual patient data from the Stroke Thrombolysis Trialists' (STT) meta-analysis of randomised trials of alteplase versus placebo (or untreated control) in patients with acute ischaemic stroke. We prespecified assessment of three classifications of intracerebral haemorrhage: type 2 parenchymal haemorrhage within 7 days; Safe Implementation of Thrombolysis in Stroke Monitoring Study's (SITS-MOST) haemorrhage within 24-36 h (type 2 parenchymal haemorrhage with a deterioration of at least 4 points on National Institutes of Health Stroke Scale [NIHSS]); and fatal intracerebral haemorrhage within 7 days. We used logistic regression, stratified by trial, to model the log odds of intracerebral haemorrhage on allocation to alteplase, treatment delay, age, and stroke severity. We did exploratory analyses to assess mortality after intracerebral haemorrhage and examine the absolute risks of intracerebral haemorrhage in the context of functional outcome at 90-180 days. Data were available from 6756 participants in the nine trials of intravenous alteplase versus control. Alteplase increased the odds of type 2 parenchymal haemorrhage (occurring in 231 [6·8%] of 3391 patients allocated alteplase vs 44 [1·3%] of 3365 patients allocated control; odds ratio [OR] 5·55 [95% CI 4·01-7·70]; absolute excess 5·5% [4·6-6·4]); of SITS-MOST haemorrhage (124 [3·7%] of 3391 vs 19 [0·6%] of 3365; OR 6·67 [4·11-10·84]; absolute excess 3·1% [2·4-3·8]); and of fatal intracerebral haemorrhage (91 [2·7%] of 3391 vs 13 [0·4%] of 3365; OR 7·14 [3·98-12·79]; absolute excess 2·3% [1�

[Subhyaloid macular haemorrhage in Terson syndrome, treated by rupture of the posterior hyaloid using YAG laser].

PubMed

Sánchez Ferreiro, A V; Muñoz Bellido, L

2014-02-01

We present the case of a 48 year-old man who had a sudden onset of vomiting, headache and loss of consciousness. The visual acuity was severely reduced in the left eye, with a large subhyaloid haemorrhage being observed in the fundus. The combination of subarachnoid haemorrhage and a vitreous haemorrhage is called Terson syndrome. The details of the treatment of this case with YAG laser are also discussed. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Influencing the practice and outcome in acute upper gastrointestinal haemorrhage. Steering Committee of the National Audit of Acute Upper Gastrointestinal Haemorrhage.

PubMed

Rockall, T A; Logan, R F; Devlin, H B; Northfield, T C

1997-11-01

To assess changes in practice and outcome in acute upper gastrointestinal haemorrhage following the feedback of data, the reemphasis of national guidelines, and specific recommendations following an initial survey. A prospective, multicentre, audit cycle. Forty five hospitals from three health regions participated in two phases of the audit cycle. Phase I: 2332 patients with acute upper gastrointestinal haemorrhage; phase II: 1625 patients with upper gastrointestinal haemorrhage. Patients were evaluated with respect to management (with reference to the recommendations in the national guidelines), mortality, and length of hospital stay. Following the distribution of data from the first phase of the National Audit and the formulation of specific recommendations for improving practice, the proportion of hospitals with local guidelines or protocols for the management of upper gastrointestinal haemorrhage rose from 71% (32/45) to 91% (41/45); 12 of the 32 hospitals with guidelines during the first phase revised their guidelines following the initial survey. There was a small but significant increase in the proportion of all patients who underwent endoscopy (from 81% to 86%), the proportion who underwent endoscopy within 24 hours of admission (from 50% to 56%), and the use of central venous pressure monitoring in patients with organ failure requiring blood transfusion or those with profound shock (from 30% to 43%). There was, however, no change in the use of high dependency beds or joint medical/surgical management in high risk cases. There was no significant change in crude or risk standardised mortality (13.4% in the first phase and 14.4% in the second phase). Although many of the participating hospitals have made efforts to improve practice by producing or updating guidelines or protocols, there has been only a small demonstrable change in some areas of practice during the National Audit. The failure to detect any improvement in mortality may reflect this lack of

Dengue and dengue haemorrhagic fever: Indian perspective.

PubMed

Chaturvedi, U C; Nagar, Rachna

2008-11-01

The relationship of this country with dengue has been long and intense. The ?rst recorded epidemic of clinically dengue-like illness occurred at Madras in 1780 and the dengue virus was isolated for the ?rst time almost simultaneously in Japan and Calcutta in 1943-1944. After the ?rst virologically proved epidemic of dengue fever along the East Coast of India in 1963-1964, it spread to allover the country.The ?rst full-blown epidemic of the severe form of the illness,the dengue haemorrhagic fever/dengue shock syndrome occurred in North India in 1996. Aedes aegypti is the vector for transmission of the disease. Vaccines or antiviral drugs are not available for dengue viruses; the only effective way to prevent epidemic degure fever/dengue haemorrhagic fever (DF/DHF) is to control the mosquito vector, Aedes aegypti and prevent its bite. This country has few virus laboratories and some of them have done excellent work in the area of molecular epidemiology,immunopathology and vaccine development. Selected work done in this country on the problems of dengue is presented here.

Effects of the Kv7 voltage-activated potassium channel inhibitor linopirdine in rat models of haemorrhagic shock.

PubMed

Nassoiy, Sean P; Babu, Favin S; LaPorte, Heather M; Byron, Kenneth L; Majetschak, Matthias

2018-04-27

Recently, we demonstrated that Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements in short-term rat models of haemorrhagic shock. The aim of the present study was to further delineate the therapeutic potential and side effect profile of the Kv7 channel blocker linopirdine in various rat models of severe haemorrhagic shock over clinically relevant time periods. Intravenous administration of linopirdine, either before (1 or 3 mg/kg) or after (3 mg/kg) a 40% blood volume haemorrhage, did not affect blood pressure and survival in lethal haemorrhage models without fluid resuscitation. A single bolus of linopirdine (3 mg/kg) at the beginning of fluid resuscitation after haemorrhagic shock transiently reduced early fluid requirements in spontaneously breathing animals that were resuscitated for 3.5 hours. When mechanically ventilated rats were resuscitated after haemorrhagic shock with normal saline (NS) or with linopirdine-supplemented (10, 25 or 50 μg/mL) NS for 4.5 hours, linopirdine significantly and dose-dependently reduced fluid requirements by 14%, 45% and 55%, respectively. Lung and colon wet/dry weight ratios were reduced with linopirdine (25/50 μg/mL). There was no evidence for toxicity or adverse effects based on measurements of routine laboratory parameters and inflammation markers in plasma and tissue homogenates. Our findings support the concept that linopirdine-supplementation of resuscitation fluids is a safe and effective approach to reduce fluid requirements and tissue oedema formation during resuscitation from haemorrhagic shock. © 2018 John Wiley & Sons Australia, Ltd.

Retinal Crystals in Type 2 Idiopathic Macular Telangiectasia

PubMed Central

Sallo, Ferenc B; Leung, Irene; Chung, Mina; Wolf-Schnurrbusch, Ute EK; Dubra, Alfredo; Williams, David R; Clemons, Traci; Pauleikhoff, Daniel; Bird, Alan C; Peto, Tunde

2012-01-01

Purpose To characterize the phenotype and investigate the associations of intraretinal crystalline deposits in a large cohort of Type 2 Idiopathic Macular Telangiectasia (MacTel) Design Case-control study Participants Patients with and without retinal crystals from the Macular Telangiectasia Project, an international multi-centre prospective study of Type 2 MacTel. Methods Grading of stereoscopic 30° colour fundus (CF), confocal blue light reflectance (CBR), red-free (RF) and infrared (IR) images was performed according to the MacTel Natural History Study protocol and staged using the classification system devised by Gass & Blodi. SD-OCT and adaptive optics imaging were used for a finer analysis of the phenotype. Associations between crystals and other characteristics of the disease as well as potential risk factors were investigated. Main outcome measures Presence of crystals, fundus signs of MacTel, clinical characteristics, presence of potential risk factors of MacTel. Results Out of 443 probands enrolled in the MacTel study, 203 (46%) had crystalline deposits present; 60% of the cases were bilateral at baseline. Eyes with crystals had a mean letter score of 70.7 (SD=15.9) while those without crystals had a mean of 66.5 letters (SD=15.5, p<0.001). Crystals were present at all stages of the disease and showed high reflectivity within a wide wavelength range. They were located at the anterior surface of the nerve fibre layer, arranged along the nerve fibres, within an annular area centred on the fovea. Significant associations of crystalline deposits were found with a loss of retinal transparency, MPOD loss, fluorescein leakage, retinal thickness and a break in the IS/OS junction line. Associations with environmental risk factors were not found. Conclusions Intraretinal crystals are a frequent phenomenon associated with type 2 MacTel, they may appear at all stages and may aid in the early diagnosis of the disease. Their morphology further implicates Müller cells

Blood Infusion and the Risk of Haemorrhage in Patients Undergoing Cardiac Surgery with Extracorporeal Circulation.

PubMed

Luque-Oliveros, Manuel; Garcia-Carpintero, Maria Angeles; Cauli, Omar

2017-01-01

Patients undergoing cardiac surgery with extracorporeal circulation (ECC) frequently present haemorrhages as a complication associated with high morbidity and mortality. One of the factors that influences this risk is the volume of blood infused during surgery. The objective of this study was to determine the optimal volume of autologous blood that can be processed during cardiac surgery with ECC. We also determined the number of salvaged red blood cells to be reinfused into the patient in order to minimize the risk of haemorrhage in the postoperative period. This was an observational retrospective cross-sectional study performed in 162 ECC cardiac surgery patients. Data regarding the sociodemographic profiles of the patients, their pathologies and surgical treatments, and the blood volume recovered, processed, and reinfused after cell salvage were collected. We also evaluated the occurrence of postoperative haemorrhage. The volume of blood infused after cell salvage had a statistically significant effect (p < 0.01) on the risk of post-operative haemorrhage; the receiver operating characteristic sensitivity was 0.813 and the optimal blood volume cut-off was 1800 ml. The best clinical outcome (16.7% of patients presenting haemorrhages) was in patients that had received less than 1800 ml of recovered and processed autologous blood, which represented a volume of up to 580 ml reinfused red blood cells. The optimum thresholds for autologous processed blood and red blood cells reinfused into the patient were 1800 and 580 ml, respectively. Increasing these thresholds augmented the risk of haemorrhage as an immediate postoperative period complication. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dengue Haemorrhagic Encephalitis: Rare Case Report with Review of Literature.

PubMed

Kutiyal, Aditya Singh; Malik, Chetanya; Hyanki, Gitika

2017-07-01

Dengue is an endemic arboviral infection prevalent especially in tropical countries including Southern and Southeast Asia. Central Nervous System (CNS) involvement in dengue infection is uncommon. Haemorrhagic encephalitis is a rare presentation in dengue. This is a case of a 58-year-old male who presented with fever, petechial rash and altered sensorium. Dengue serology IgM was reactive and MRI brain was suggestive of haemorrhagic encephalitis. Patient was managed in Intensive Care Unit (ICU) but eventually succumbed to his illness. We report this fatal outcome of a common viral infection with unusual neurological presentation to propose an association between dengue and neurotropism and the need to look at dengue infection beyond its classical features.

Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus)

PubMed Central

Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Laws, Thomas R; Taylor, Christopher; Smith, Simon A; Salguero, Francisco J; Lever, Mark S

2013-01-01

Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50, were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals’ lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema. PMID:23441639

Influence of long-term intermittent exposures to hypoxia on decompression-induced pulmonary haemorrhage.

PubMed Central

Fang, H S; Chen, C F

1976-01-01

Healthy male rats were acclimatized by being placed in a decompression chamber at a simulated altitude of 18 000 feet (5486 m) for three hours daily for 84 days. The altitude acclimatized rats paired with unacclimatized rats were rapidly decompressed together. The range of decompression was performed from on atmospheric pressure to an ambient pressure of 30 mmHg in 0-2 seconds. It was found that in control rats, 14 of 20 lung (70%) exhibited pulmonary haemorrhage following rapid decompression. In altitude acclimatized rats, however, only 6 of 20 (30%) revealed decompression-induced haemorrhage. The difference was statistically significant. The present findings indicate that long-term intermittent exposures to hypoxia might increase the resistance of pulmonary tissue to rapid decompression, resulting in a decrease in frequency and severity of pulmonary haemorrhage. The possible mechanism of such a phenomenon is discussed. PMID:1257942

Novel bivalent vectored vaccine for control of myxomatosis and rabbit haemorrhagic disease.

PubMed

Spibey, N; McCabe, V J; Greenwood, N M; Jack, S C; Sutton, D; van der Waart, L

2012-03-24

A novel, recombinant myxoma virus-rabbit haemorrhagic disease virus (RHDV) vaccine has been developed for the prevention of myxomatosis and rabbit haemorrhagic disease (RHD). A number of laboratory studies are described illustrating the safety and efficacy of the vaccine following subcutaneous administration in laboratory rabbits from four weeks of age onwards. In these studies, both vaccinated and unvaccinated control rabbits were challenged using pathogenic strains of RHD and myxoma viruses, and 100 per cent of the vaccinated rabbits were protected against both myxomatosis and RHD.

Predominance of null mutations in ataxia-telangiectasia.

PubMed

Gilad, S; Khosravi, R; Shkedy, D; Uziel, T; Ziv, Y; Savitsky, K; Rotman, G; Smith, S; Chessa, L; Jorgensen, T J; Harnik, R; Frydman, M; Sanal, O; Portnoi, S; Goldwicz, Z; Jaspers, N G; Gatti, R A; Lenoir, G; Lavin, M F; Tatsumi, K; Wegner, R D; Shiloh, Y; Bar-Shira, A

1996-04-01

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.

Comparison of the prevalence of enteric viruses in healthy dogs and those with acute haemorrhagic diarrhoea by electron microscopy.

PubMed

Schulz, B S; Strauch, C; Mueller, R S; Eichhorn, W; Hartmann, K

2008-02-01

To evaluate prevalence of enteric viruses in healthy dogs and to compare it with prevalences in dogs with acute haemorrhagic diarrhoea. Faecal samples were collected from 200 healthy dogs and examined by electron microscopy for presence of viral particles. Data were compared with viral prevalences that had been determined retrospectively by electron microscopy for 936 dogs with acute haemorrhagic diarrhoea. There were significantly more negative faecal samples among the healthy dogs (82.0 per cent) compared with 55.8 per cent in dogs with acute haemorrhagic diarrhoea (P<0.001). With a prevalence of 17.5 per cent, significantly more healthy dogs were shedding coronavirus compared with 11.6 per cent in dogs with acute haemorrhagic diarrhoea (P=0.034). Parvovirus was only detected in one healthy dog (0.5 per cent), thus with a prevalence that was significantly lower than 16.0 per cent detected in the dogs with acute haemorrhagic diarrhoea (P<0.001). Paramyxovirus was not found in any of the healthy dogs but was found in 9.3 per cent of dogs with acute haemorrhagic diarrhoea (P<0.001). Results suggest that shedding of parvovirus and paramyxovirus is strongly associated with acute haemorrhagic diarrhoea. However, coronavirus seems to be even more prevalent among healthy dogs, raising the need for further studies to investigate the strain-associated pathogenicity of this virus.

Spontaneous subarachnoid haemorrhage and outcome--results from Tan Tock Seng Hospital, Singapore.

PubMed

Wong, S H; Yeo, T T; Seow, W T; Tan, K K; Ong, P L

1999-07-01

To ascertain the number of cases of spontaneous (aneurysmal) subarachnoid haemorrhage presenting to Tan Tock Seng Hospital, Singapore, over a one year period, the demographics of the patients involved, their treatment and their eventual outcome. A retrospective study from June 1995 to June 1996. There were 62 patients admitted over this period with an average of 5 patients per month. Their ages ranged from 9 to 85 years with a mean of 54 years. All 62 patients underwent 4-vessel cerebral angiograms. Forty-three patients (69%) underwent clipping of their aneurysms. Twelve patients (19%) had negative angiograms. Four patients (6%) underwent coiling of their aneurysms via interventional neuroradiology techniques. Patients with subarachnoid haemorrhage of Grades 1 to 3 on the WFNS (World Federation of Neurological Surgeons) grading had a favourable outcome (Glasgow Outcome Score of 4 and 5) in 85% of the cases. The overall mortality rate for the operated group (all grades) was 11%. However for the group with good WFNS grading, namely the Grade 1 to 2 groups, there were no deaths. Twenty-four percent of patients developed clinically symptomatic vasospasm. Eighteen percent of patients required ventriculo-peritoneal shunting for hydrocephalus secondary to the subarachnoid haemorrhage. The overall management mortality (operated and non-operated cases) was 14% for proven aneurysmal and angiographically-negative spontaneous subarachnoid haemorrhage. These results are comparable to that of other reputable centers reported in the literature.

Feasibility of electrical impedance tomography in haemorrhagic stroke treatment using adaptive mesh

NASA Astrophysics Data System (ADS)

Nasehi Tehrani, J.; Anderson, C.; Jin, C.; van Schaik, A.; Holder, D.; McEwan, A.

2010-04-01

EIT has been proposed for acute stroke differentiation, specifically to determine the type of stroke, either ischaemia (clot) or haemorrhage (bleed) to allow the rapid use of clot-busting drugs in the former (Romsauerova et al 2006) . This addresses an important medical need, although there is little treatment offered in the case of haemorrhage. Also the demands on EIT are high with usually no availability to take a 'before' measurement, ruling out time difference imaging. Recently a new treatment option for haemorrhage has been proposed and is being studied in international randomised controlled trial: the early reduction of elevated blood pressure to attenuate the haematoma. This has been shown via CT to reduce bleeds by up to 1mL by Anderson et al 2008. The use of EIT as a continuous measure is desirable here to monitor the effect of blood pressure reduction. A 1mL increase of haemorrhagic lesion located near scalp on the right side of head caused a boundary voltage change of less than 0.05% at 50 kHz. This could be visually observed in a time difference 3D reconstruction with no change in electrode positions, mesh, background conductivity or drift when baseline noise was less than 0.005% but not when noise was increased to 0.01%. This useful result informs us that the EIT system must have noise of less than 0.005% at 50 kHz including instrumentation, physiological and other biases.

The Response of Cerebral Cortex to Haemorrhagic Damage: Experimental Evidence from a Penetrating Injury Model

PubMed Central

Purushothuman, Sivaraman; Marotte, Lauren; Stowe, Sally; Johnstone, Daniel M.; Stone, Jonathan

2013-01-01

Understanding the response of the brain to haemorrhagic damage is important in haemorrhagic stroke and increasingly in the understanding the cerebral degeneration and dementia that follow head trauma and head-impact sports. In addition, there is growing evidence that haemorrhage from small cerebral vessels is important in the pathogenesis of age-related dementia (Alzheimer’s disease). In a penetration injury model of rat cerebral cortex, we have examined the neuropathology induced by a needlestick injury, with emphasis on features prominent in the ageing and dementing human brain, particularly plaque-like depositions and the expression of related proteins. Needlestick lesions were made in neo- and hippocampal cortex in Sprague Dawley rats aged 3–5 months. Brains were examined after 1–30 d survival, for haemorrhage, for the expression of hyperphosphorylated tau, Aβ, amyloid precursor protein (APP), for gliosis and for neuronal death. Temporal cortex from humans diagnosed with Alzheimer’s disease was examined with the same techniques. Needlestick injury induced long-lasting changes–haem deposition, cell death, plaque-like deposits and glial invasion–along the needle track. Around the track, the lesion induced more transient changes, particularly upregulation of Aβ, APP and hyperphosporylated tau in neurons and astrocytes. Reactions were similar in hippocampus and neocortex, except that neuronal death was more widespread in the hippocampus. In summary, experimental haemorrhagic injury to rat cerebral cortex induced both permanent and transient changes. The more permanent changes reproduced features of human senile plaques, including the formation of extracellular deposits in which haem and Aβ-related proteins co-localised, neuronal loss and gliosis. The transient changes, observed in tissue around the direct lesion, included the upregulation of Aβ, APP and hyperphosphorylated tau, not associated with cell death. The findings support the possibility

Haemorrhagic shock in mice--intracellular signalling and immunomodulation of peritoneal macrophages' LPS response.

PubMed

Rani, Meenakshi; Husain, Baher; Lendemans, Sven; Schade, Fritz U; Flohé, Sascha

2006-01-01

Haemorrhagic shock leads to decreased proinflammatory cytokine response which is associated with an increased susceptibility to bacterial infections. In the present study, the effect of GM-CSF on lipopolysaccharide (LPS)-induced TNF-alpha release and MAPkinase activation was analysed on the background of a possible immunostimulating activity of this substance. Male BALB/c mice were bled to a mean arterial blood pressure of 50 mmHg for 45 min followed by resuscitation. Peritoneal macrophages were isolated 20 h after haemorrhage and incubated with 10 ng/ml GM-CSF for 6h before LPS stimulation. TNF-alpha synthesis was studied in the culture supernatants using ELISA. Phosphorylation of ERK, p38MAPK and IkappaBalpha was detected by Western blotting. LPS-induced TNF-alpha production of peritoneal macrophages was significantly decreased 20 h after haemorrhage in comparison to the corresponding cells of sham-operated mice. In parallel the phosphorylation of IkappaBalpha was less in LPS-stimulated peritoneal macrophages from haemorrhagic mice. LPS-induced phosphorylation of ERK1/2 was also decreased in peritoneal macrophages isolated after haemorrhagic shock. In contrast, p38MAPK was phosphorylated more intensely after LPS-stimulation in macrophages collected from shocked mice. GM-CSF incubation elevated LPS-induced TNF-alpha response of macrophages from both sham-operated and shocked mice which was accompanied by an elevated IkappaB and ERK phosphorylation. In general, GM-CSF treatment in vitro enhanced peritoneal macrophages LPS-response both in terms of TNF-alpha synthesis and IkappaB and MAPK signalling, but the levels always stayed lower than those of GM-CSF-treated cells from sham-operated animals. In conclusion, GM-CSF preincubation could partly reactivate the depressed functions of peritoneal macrophages and may therefore exert immunostimulating properties after shock or trauma.

Sudden headache, third nerve palsy and visual deficit: thinking outside the subarachnoid haemorrhage box.

PubMed

Ní Chróinín, Danielle; Lambert, John

2013-11-01

A 75-year-old lady presented with sudden severe headache and vomiting. Examination was normal, and CT and lumbar puncture not convincing for subarachnoid haemorrhage. Shortly thereafter, she developed painless diplopia. Examination confirmed right third cranial nerve palsy plus homonymous left inferior quadrantanopia. Urgent cerebral MRI with angiography was requested to assess for a possible posterior communicating artery aneurysm, but revealed an unsuspected pituitary mass. Pituitary adenoma with pituitary apoplexy was diagnosed. Pituitary apopolexy is a syndrome comprising sudden headache, meningism, visual and/or oculomotor deficits, with an intrasellar mass. It is commonly due to haemorrhage or infarction within a pituitary adenoma. Treatment includes prompt steroid administration, and potentially surgical decompression. While subarachnoid haemorrhage is an important, well-recognised cause of sudden severe headache, other aetiologies, including pituitary apoplexy, should be considered and sought.

Development of mobile laboratory for viral haemorrhagic fever detection in Africa.

PubMed

Weidmann, Manfred; Faye, Ousmane; Faye, Oumar; Abd El Wahed, Ahmed; Patel, Pranav; Batejat, Christophe; Manugerra, Jean Claude; Adjami, Aimee; Niedrig, Matthias; Hufert, Frank T; Sall, Amadou A

2018-06-15

In order to enable local response to viral haemorrhagic fever outbreaks a mobile laboratory transportable on commercial flights was developed. The development progressed from use of mobile real time RT-PCR to mobile Recombinase Polymerase Amplification (RT-RPA). The various stages of the mobile laboratory development are described. A brief overview of its deployments, which culminated in the first on site detection of Ebola virus disease (EVD) in March 2014 and a successful use in a campaign to roll back EVD cases in Conakry in the West-Africa Ebola virus outbreak are described. The developed mobile laboratory successfully enabled local teams to perform rapid viral haemorrhagic fever disgnostics.

Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus).

PubMed

Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Laws, Thomas R; Taylor, Christopher; Smith, Simon A; Salguero, Francisco J; Lever, Mark S

2013-04-01

Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50 , were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals' lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema. © 2013 Crown copyright. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

Ischaemic Strokes in Patients with Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia: Associations with Iron Deficiency and Platelets

PubMed Central

Shovlin, Claire L.; Chamali, Basel; Santhirapala, Vatshalan; Livesey, John A.; Angus, Gillian; Manning, Richard; Laffan, Michael A.; Meek, John; Tighe, Hannah C.; Jackson, James E.

2014-01-01

Background Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke. Methodology 497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies. Principal Findings Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0

Neonatal intraventricular haemorrhage associated with maternal use of paroxetine

PubMed Central

Duijvestijn, Yvonne C M; Kalmeijer, Mathijs D; Passier, Anneke L M; Dahlem, Peter; Smiers, Frans

2003-01-01

Selective serotonin reuptake inhibitors (SSRIs) have been reported to inhibit serotonin uptake into platelets, resulting in decreased platelet function. We report a case of a large intraventricular haemorrhage in a 6-h-old boy, whose mother used paroxetine during pregnancy. PMID:14651736

Resuscitation in massive obstetric haemorrhage using an intraosseous needle.

PubMed

Chatterjee, D J; Bukunola, B; Samuels, T L; Induruwage, L; Uncles, D R

2011-04-01

A 38-year-old woman experienced a massive postpartum haemorrhage 30 minutes after emergency caesarean delivery. The patient became severely haemodynamically compromised with an unrecordable blood pressure. Rapid fluid resuscitation was limited by the capacity of the intravenous cannula in place at the time and inability to establish additional vascular access using conventional routes in a timely manner. An intraosseous needle was inserted in the proximal humerus at the first attempt and administration of resuscitation fluid by this route subsequently enabled successful placement of further intravenous lines. Blood and blood products were deployed in conjunction with intra-operative cell salvage and transoesophageal Doppler cardiac output monitoring was used to assess adequacy of volume replacement. Haemorrhage control was finally achieved with the use of recombinant factor VIIa and hysterectomy. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study.

PubMed

Rodrigues, Mark A; Samarasekera, Neshika; Lerpiniere, Christine; Humphreys, Catherine; McCarron, Mark O; White, Philip M; Nicoll, James A R; Sudlow, Cathie L M; Cordonnier, Charlotte; Wardlaw, Joanna M; Smith, Colin; Al-Shahi Salman, Rustam

2018-03-01

Identification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype. We identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort. We determined APOE genotype and radiologists rated CT imaging appearances. Radiologists were not aware of clinical, genetic, and histopathological features. A neuropathologist rated brain tissue for small vessel diseases, including CAA, and was masked to clinical, radiographic, and genetic features. We used CT and APOE genotype data in a logistic regression model, which we internally validated using bootstrapping, to predict the risk of CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and estimate diagnostic accuracy. Among 110 adults (median age 83 years [IQR 76-87], 49 [45%] men) included in the LINCHPIN study between June 1, 2010 and Feb 10, 2016, intracerebral haemorrhage was lobar in 62 (56%) participants, deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe CAA compared with 26 (42%) that were associated with absent or mild CAA, and were independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11 [42%] of 26; p=0·014), intracerebral haemorrhage with finger-like projections (14 [39%] of 36 vs 0; p=0·043), and APOE ɛ4 possession (18 [50%] of 36 vs 2 [8%] of 26; p=0·0020). A prediction model for CAA-associated lobar

Mycoplasma pneumoniae: an aetiological agent of acute haemorrhagic oedema of infancy.

PubMed

Di Lernia, Vito

2014-11-01

Acute haemorrhagic oedema of infancy (AHEI) is considered a separate clinical entity among cutaneous small vessel vasculitis of childhood. It usually occurs in children younger than 2 years of age, with spontaneous recovery occurring within a few weeks. A history of recent upper respiratory or urinary tract infections or immunisation is found in most patients. Although Mycoplasma pneumoniae has been linked to a wide array of skin eruptions or diseases, it is not recognised as a possible cause of acute haemorrhagic oedema of infancy. The authors report a child with AHEI and a concurrent M. pneumoniae infection. © 2013 The Author. Australasian Journal of Dermatology © 2013 The Australasian College of Dermatologists.

Identifying Regional Variation in the Prevalence of Postpartum Haemorrhage: A Systematic Review and Meta-Analysis

PubMed Central

Calvert, Clara; Thomas, Sara L.; Ronsmans, Carine; Wagner, Karen S.; Adler, Alma J.; Filippi, Veronique

2012-01-01

Objective To provide regional estimates of the prevalence of maternal haemorrhage and explore the effect of methodological differences between studies on any observed regional variation. Methods We conducted a systematic review of the prevalence of maternal haemorrhage, defined as blood loss greater than or equal to 1) 500 ml or 2) 1000 ml in the antepartum, intrapartum or postpartum period. We obtained regional estimates of the prevalence of maternal and severe maternal haemorrhage by conducting meta-analyses and used meta-regression to explore potential sources of between-study heterogeneity. Findings No studies reported the prevalence of antepartum haemorrhage (APH) according to our definitions. The prevalence of postpartum haemorrhage (PPH) (blood loss ≥500 ml) ranged from 7.2% in Oceania to 25.7% in Africa. The prevalence of severe PPH (blood loss ≥1000 ml) was highest in Africa at 5.1% and lowest in Asia at 1.9%. There was strong evidence of between-study heterogeneity in the prevalence of PPH and severe PPH in most regions. Meta-regression analyses suggested that region and method of measurement of blood loss influenced prevalence estimates for both PPH and severe PPH. The regional patterns changed after adjusting for the other predictors of PPH indicating that, compared with European women, Asian women have a lower prevalence of PPH. Conclusions We found evidence that Asian women have a very low prevalence of PPH compared with women in Europe. However, more reliable estimates will only be obtained with the standardisation of the measurement of PPH so that the data from different regions are comparable. PMID:22844432

Automation of CT-based haemorrhagic stroke assessment for improved clinical outcomes: study protocol and design

PubMed Central

Chinda, Betty; Medvedev, George; Siu, William; Ester, Martin; Arab, Ali; Gu, Tao; Moreno, Sylvain; D’Arcy, Ryan C N; Song, Xiaowei

2018-01-01

Introduction Haemorrhagic stroke is of significant healthcare concern due to its association with high mortality and lasting impact on the survivors’ quality of life. Treatment decisions and clinical outcomes depend strongly on the size, spread and location of the haematoma. Non-contrast CT (NCCT) is the primary neuroimaging modality for haematoma assessment in haemorrhagic stroke diagnosis. Current procedures do not allow convenient NCCT-based haemorrhage volume calculation in clinical settings, while research-based approaches are yet to be tested for clinical utility; there is a demonstrated need for developing effective solutions. The project under review investigates the development of an automatic NCCT-based haematoma computation tool in support of accurate quantification of haematoma volumes. Methods and analysis Several existing research methods for haematoma volume estimation are studied. Selected methods are tested using NCCT images of patients diagnosed with acute haemorrhagic stroke. For inter-rater and intrarater reliability evaluation, different raters will analyse haemorrhage volumes independently. The efficiency with respect to time of haematoma volume assessments will be examined to compare with the results from routine clinical evaluations and planimetry assessment that are known to be more accurate. The project will target the development of an enhanced solution by adapting existing methods and integrating machine learning algorithms. NCCT-based information of brain haemorrhage (eg, size, volume, location) and other relevant information (eg, age, sex, risk factor, comorbidities) will be used in relation to clinical outcomes with future project development. Validity and reliability of the solution will be examined for potential clinical utility. Ethics and dissemination The project including procedures for deidentification of NCCT data has been ethically approved. The study involves secondary use of existing data and does not require new consent

Sudden-onset paraplegia during pregnancy caused by haemorrhage in a spinal cord haemangioblastoma: A case report.

PubMed

Gormeli, Cemile Ayse; Sarac, Kaya; Ozdemir, Zeynep Maras; Gormeli, Gokay; Kahraman, Aysegul Sagir; Kahraman, Bayram; Oztanir, Mustafa Namik; Karadag, Nese

2016-09-01

Spinal cord haemangioblastomas are rare central nervous systems tumours, and haemorrhage.It is an uncommon occurance. We report a 28-year-old pregnant patient who presented with paraplegia due to acute haemorrhage of a spinal haemangioblastoma. Magnetic resonance imaging showed extensive syrinx cavities, an intramedullary lesion at the T4-T5 spinal cord level e, and a subarachnoid haemorrhage. Digital subtraction angiography showed the feeding artery and dilated tortuous draining vein within the dural sac. The lesion was deemed a haemangioblastoma. The histopathological examination confirmed the diagnosis. Postoperatively, the paraplegia improved and the patient was able to walk within 2 weeks. Imaging is important for early diagnosis to prevent patients persistent neurological deficits.

The ovine fetal endocrine reflex responses to haemorrhage are not mediated by cardiac nerves

PubMed Central

Wood, Charles E

2002-01-01

This study was designed to test the hypothesis that cardiac receptors tonically inhibit the secretion of renin, arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) in late-gestation fetal sheep. Eight chronically catheterised fetal sheep between 122 and 134 days gestation were subjected to injection or infusion of saline or 4 % procaine into the pericardial space. Fetal blood pressure and heart rate were monitored and fetal blood samples were drawn to measure the response to these injections. Injection of procaine into the pericardial space effectively blocked cardiac nerves, as evidenced by a reduction in the variability of fetal heart rate and by the blockade of reflex reductions in fetal heart rate after intravenous injection of phenylephrine (an α-adrenergic agonist which raises blood pressure). Injection of saline had no discernable effects on any of the measured variables. A single injection of procaine, followed by a slow infusion, produced a transient blockade of cardiac nerves. Multiple injections of procaine produced a sustained blockade of cardiac nerves and a sustained rise in fetal plasma renin activity and ACTH. In none of the experiments did procaine significantly alter fetal plasma AVP concentrations. In 11 fetuses between 121 and 134 days gestation, we combined the cardiac nerve blockade with slow haemorrhage to test the cardiac nerves as mediators of the endocrine response to haemorrhage in utero. Cardiac nerve blockade exaggerated the fetal blood gas response to haemorrhage somewhat but did not significantly alter the magnitude of the ACTH, AVP, or plasma renin activity response to haemorrhage. We conclude that cardiac nerves in the late-gestation fetal sheep have minor influences on plasma renin activity and ACTH in normovolaemic fetuses, but that changes in cardiac nerve activity do not mediate the endocrine responsiveness to haemorrhage. PMID:12042365

Incidence, trends and severity of primary postpartum haemorrhage in Australia: A population-based study using Victorian Perinatal Data Collection data for 764 244 births.

PubMed

Flood, Margaret; McDonald, Susan J; Pollock, Wendy; Cullinane, Fiona; Davey, Mary-Ann

2018-05-22

Increasing incidence and severity of postpartum haemorrhage, together with postpartum haemorrhage-associated morbidities, have been reported in many high-resource countries. In-depth analysis of such factors in Victorian births since 2002 was lacking. Our aim was to determine the incidence and trends for primary postpartum haemorrhage (World Health Organization and International Classification of Diseases 10th revision, Australian Modification definitions) for all confinements in Victoria, Australia, for the years 2003-2013 and the incidence and trends for severe postpartum haemorrhage (≥1500 mL) for 2009-2013. In this population-based cross-sectional study de-identified data from the Victorian Perinatal Data Collection were analysed for confinements (excluding terminations) from 2003 to 2013 (n = 764 244). Perinatal information for all births ≥20 weeks (or of at least 400 g birthweight if gestation was unknown) were prospectively collected. One in five women (21.8%) who gave birth between 2009 and 2013 experienced a primary postpartum haemorrhage and one in 71 women (1.4%) experienced a severe primary postpartum haemorrhage. The increasing trends in incidence of primary postpartum haemorrhage, severe primary postpartum haemorrhage, blood transfusion, admission to an intensive care or high dependency unit and peripartum hysterectomy were significant (P < 0.001). Women who had an unassisted vaginal birth had the lowest incidence of primary postpartum haemorrhage. The highest incidence was experienced by women who had an unplanned caesarean section birth. Women who had a forceps birth had the highest incidence of severe primary postpartum haemorrhage. The incidence of primary postpartum haemorrhage, severe primary postpartum haemorrhage and associated maternal morbidities have increased significantly over time in Victoria. © 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Diffuse alveolar haemorrhage secondary to propylthiouracil-induced vasculitis

PubMed Central

Ferreira, Catarina; Costa, Teresa; Marques, Ana Vieira

2015-01-01

Propylthiouracil is a drug used to treat hyperthyroidism. It can cause several side effects including pulmonary disorders that, although rare, can be severe. The authors describe the case of a woman treated with propylthiouracil who developed diffuse alveolar haemorrhage with severe respiratory failure and anaemia, which improved with discontinuation of the antithyroid drug and on starting systemic corticosteroid therapy. PMID:25661751

Ataxia-telangiectasia: founder effect among north African Jews.

PubMed

Gilad, S; Bar-Shira, A; Harnik, R; Shkedy, D; Ziv, Y; Khosravi, R; Brown, K; Vanagaite, L; Xu, G; Frydman, M; Lavin, M F; Hill, D; Tagle, D A; Shiloh, Y

1996-12-01

The ATM gene is responsible for the autosomal recessive disorder ataxia-telangiectasia (A-T), characterized by cerebellar degeneration, immunodeficiency and cancer predisposition. A-T carriers were reported to be moderately cancer-prone. A wide variety of A-T mutations, most of which are unique to single families, were identified in various ethnic groups, precluding carrier screening with mutation-specific assays. However, a single mutation was observed in 32/33 defective ATM alleles in Jewish A-T families of North African origin, coming from various regions of Morocco and Tunisia. This mutation, 103C-->T, results in a stop codon at position 35 of the ATM protein. In keeping with the nature of this mutation, various antibodies directed against the ATM protein failed to defect this protein in patient cells. A rapid carrier detection assay detected this mutation in three out of 488 ATM alleles of Jewish Moroccan or Tunisian origin. This founder effect provides a unique opportunity for population-based screening for A-T carriers in a large Jewish community.

Home therapy with continuous infusion of factor VIII after minor surgery or serious haemorrhage.

PubMed

Varon, D; Schulman, S; Bashari, D; Martinowitz, U

1996-10-01

Administration of factor VIII (F VIII) concentrates by continuous infusion is now routinely used at several haemophilia centers but almost exclusively for hospitalized patients. We evaluated various aspects of home therapy with continuous infusion of an immunoaffinity purified F VIII concentrate (Monoclate P®, Armour) in patients who would normally have been treated with high doses in bolus injections or with continuous infusion as in-patients. Twenty haemophilia A patients, eight after minor surgery and 12 for serious haemorrhage, received continuous infusion with undiluted F VIII by a minipump for a mean of 0.9 days in the hospital, followed by 3.3 days at home. Infusion bags were exchanged every 2.5 days. No haemorrhagic complications occurred, and five haemorrhages that had been resistant to treatment with bolus injections responded promptly to the continuous infusion. There were no technical problems and patient compliance and acceptance was good. We find this mode of therapy safe, efficacious and convenient for the patients as well as for the staff.

Role of T cells, cytokines and antibody in dengue fever and dengue haemorrhagic fever.

PubMed

Fink, Joshua; Gu, Feng; Vasudevan, Subhash G

2006-01-01

Dengue infections are a major cause of morbidity and mortality in the tropical and sub-tropical regions of the world. There is no vaccine for dengue and also there are no anti-viral drugs to treat the infection. Some patients, typically those experiencing a secondary infection with a different dengue serotype, may progress from an acute febrile disease to the more severe forms of disease, dengue haemorrhagic fever and dengue shock syndrome. Here we discuss the significant immunopathological component to severe disease and how T cells, cytokines and cross-reactive antibody combine to contribute to the progression to dengue haemorrhagic fever. These events are thought to lead to vascular leakage, the signature event in dengue haemorrhagic fever, and are addressed in this review by incorporating the concept of heterologous T cell immunity. The need for effective measures against dengue and dengue-related illness is clear. We propose that drugs against dengue virus, or the symptoms of severe dengue disease, are a viable goal.

Pulmonary Arteriovenous Malformations Embolized Using a Micro Vascular Plug System: Technical Note on a Preliminary Experience

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

Boatta, Emanuele, E-mail: emanuele.boatta@yahoo.it; Jahn, Christine, E-mail: christine.jahn@chru-strasbourg.fr; Canuet, Matthieu, E-mail: matthieu.canuet@chru-strasbourg.fr

AIMTo report our preliminary experience using a Micro Vascular Plug (MVP) deployed through a 2.8Fr micro-catheter for the treatment of pulmonary arteriovenous malformations (PAVMs) in a cohort of patients affected by Hereditary Haemorrhagic Telangiectasia (HHT).Materials and MethodsFour consecutive female patients (mean age 38.0 years; range 25–55 years) with PAVMs diagnosed on echocardiogram/bubble test and contrast-enhanced CT (CECT) underwent MVP embolization. One patient was symptomatic with recent transient ischaemic attack. Follow-up was undertaken at 1-month post-procedure with CECT to assess PAVMs permeability and MVP positioning and at 1-, 6-, and 12-month post-procedure, with echocardiography/bubble test and standard neurological history, to confirm absence ofmore » right-to-left shunts and recurrent symptoms.ResultsEight PAVMs were treated in 4 patients over 5 interventional sessions (mean 1.6 PAVMs per session). All PAVMs were simple, with mean feeding artery diameter of 4.25 mm. Eight 6.5 mm MVPs were deployed in total (one per lesion). Technical success was 100%. Mean procedural time and patient dose per session were 70 min (range 40–70 min) and 53418 mGy.cm{sup 2} (range 6113–101628 mGy.cm{sup 2}), respectively. No signs of reperfusion neither of MPV migration were noted at 1-month CECT follow-up. At early follow-up (mean 3.75 months; range 1–12 months), clinical success was 100% with no evidence of recurrent right-to-left shunt, and no neurological symptoms. No immediate or late complications were observed.ConclusionsMVP embolization of PAVMs appears technically feasible, safe, and effective at early follow-up. Further prospective studies are required to confirm long-term safety and efficacy of this promising technique.« less

Automation of CT-based haemorrhagic stroke assessment for improved clinical outcomes: study protocol and design.

PubMed

Chinda, Betty; Medvedev, George; Siu, William; Ester, Martin; Arab, Ali; Gu, Tao; Moreno, Sylvain; D'Arcy, Ryan C N; Song, Xiaowei

2018-04-19

Haemorrhagic stroke is of significant healthcare concern due to its association with high mortality and lasting impact on the survivors' quality of life. Treatment decisions and clinical outcomes depend strongly on the size, spread and location of the haematoma. Non-contrast CT (NCCT) is the primary neuroimaging modality for haematoma assessment in haemorrhagic stroke diagnosis. Current procedures do not allow convenient NCCT-based haemorrhage volume calculation in clinical settings, while research-based approaches are yet to be tested for clinical utility; there is a demonstrated need for developing effective solutions. The project under review investigates the development of an automatic NCCT-based haematoma computation tool in support of accurate quantification of haematoma volumes. Several existing research methods for haematoma volume estimation are studied. Selected methods are tested using NCCT images of patients diagnosed with acute haemorrhagic stroke. For inter-rater and intrarater reliability evaluation, different raters will analyse haemorrhage volumes independently. The efficiency with respect to time of haematoma volume assessments will be examined to compare with the results from routine clinical evaluations and planimetry assessment that are known to be more accurate. The project will target the development of an enhanced solution by adapting existing methods and integrating machine learning algorithms. NCCT-based information of brain haemorrhage (eg, size, volume, location) and other relevant information (eg, age, sex, risk factor, comorbidities) will be used in relation to clinical outcomes with future project development. Validity and reliability of the solution will be examined for potential clinical utility. The project including procedures for deidentification of NCCT data has been ethically approved. The study involves secondary use of existing data and does not require new consent of participation. The team consists of clinical neuroimaging

Grave prognosis on spontaneous intracerebral haemorrhage: GP on STAGE score.

PubMed

Poungvarin, Niphon; Suwanwela, Nijasri C; Venketasubramanian, Narayanaswamy; Wong, Lawrence K S; Navarro, Jose C; Bitanga, Ester; Yoon, Byung Woo; Chang, Hui M; Alam, Sardar M

2006-11-01

Spontaneous intracerebral haemorrhage (ICH) is more common in Asia than in western countries, and has a high mortality rate. A simple prognostic score for predicting grave prognosis of ICH is lacking. Our objective was to develop a simple and reliable score for most physicians. ICH patients from seven Asian countries were enrolled between May 2000 and April 2002 for a prospective study. Clinical features such as headache and vomiting, vascular risk factors, Glasgow coma scale (GCS), body temperature (BT), blood pressure on arrival, location and size of haematoma, intraventricular haemorrhage (IVH), hydrocephalus, need for surgical treatment, medical treatment, length of hospital stay and other complications were analyzed to determine the outcome using a modified Rankin scale (MRS). Grave prognosis (defined as MRS of 5-6) was judged on the discharge date. 995 patients, mean age 59.5 +/- 14.3 years were analyzed, after exclusion of incomplete data in 87 patients. 402 patients (40.4%) were in the grave prognosis group (MRS 5-6). Univariable analysis and then multivariable analysis showed only four statistically significant predictors for grave outcome of ICH. They were fever (BT > or = 37.8 degrees c), low GCS, large haematoma and IVH. The grave prognosis on spontaneous intracerebral haemorrhage (GP on STAGE) score was derived from these four factors using a multiple logistic model. A simple and pragmatic prognostic score for ICH outcome has been developed with high sensitivity (82%) and specificity (82%). Furthermore, it can be administered by most general practitioners. Validation in other populations is now required.

Breathing-Impaired Speech after Brain Haemorrhage: A Case Study

ERIC Educational Resources Information Center

Heselwood, Barry

2007-01-01

Results are presented from an auditory and acoustic analysis of the speech of an adult male with impaired prosody and articulation due to brain haemorrhage. They show marked effects on phonation, speech rate and articulator velocity, and a speech rhythm disrupted by "intrusive" stresses. These effects are discussed in relation to the speaker's…

A case series of interventional radiology in postpartum haemorrhage.

PubMed

Agarwal, N; Deinde, O; Willmott, F; Bojahr, H; MacCallum, P; Renfrew, I; Beski, S

2011-08-01

Postpartum haemorrhage (PPH) remains a significant cause of maternal morbidity and mortality in both developed and developing countries. In some instances, PPH can be anticipated and recent improvements in obstetric imaging techniques allow earlier and more reliable diagnosis of abnormalities associated with haemorrhage such as morbid placentation. However, the majority of PPH is unpredicted. Good practice notes published by the Royal College of Obstetricians and Gynaecologists state interventional radiology should be used as emergency intervention in PPH and should be considered when primary management has failed allowing arteries to be embolised to achieve haemostasis. Through collaboration between interventional radiology and maternity, appropriate guidelines need to be developed, on both emergency and elective of interventional radiology in the prevention and management of PPH. As there is mapping for neonatal services, in the future there should be consideration to develop obstetric trauma units. Maternity units which lack facilities for interventional radiology would be able to refer their cases (like placenta accreta) for safe management in units with 24 h interventional radiology services.

Pregnancy and mesenchimal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia).

PubMed

Radetskaya, L S; Makatsariya, A D; Bitsadze, V O; Khizroeva, J K

2018-07-01

The objective of this article is to attract the attention of clinical physicians to the rare but extremely relevant clinical pathology of mesenchymal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia) and especially specific characteristics of such diseases during pregnancy. Connective tissue pathology can cover different organs and systems, symptoms of the same disease can vary in different patients thus making diagnostics significantly difficult. Here clinical diagnostic criteria and methods of molecular diagnostics of diseases are described. The pathogenesis of mesenchymal dysplasias is not currently well understood. For the patients with mesenchymal dysplasias pregnancy is fraught with high risk of life-threatening complications. The preferred delivery method for such patients is caesarean section.

Severe postpartum haemorrhage after vaginal delivery: a statistical process control chart to report seven years of continuous quality improvement.

PubMed

Dupont, Corinne; Occelli, Pauline; Deneux-Tharaux, Catherine; Touzet, Sandrine; Duclos, Antoine; Bouvier-Colle, Marie-Hélène; Rudigoz, René-Charles; Huissoud, Cyril

2014-07-01

Severe postpartum haemorrhage after vaginal delivery: a statistical process control chart to report seven years of continuous quality improvement To use statistical process control charts to describe trends in the prevalence of severe postpartum haemorrhage after vaginal delivery. This assessment was performed 7 years after we initiated a continuous quality improvement programme that began with regular criteria-based audits Observational descriptive study, in a French maternity unit in the Rhône-Alpes region. Quarterly clinical audit meetings to analyse all cases of severe postpartum haemorrhage after vaginal delivery and provide feedback on quality of care with statistical process control tools. The primary outcomes were the prevalence of severe PPH after vaginal delivery and its quarterly monitoring with a control chart. The secondary outcomes included the global quality of care for women with severe postpartum haemorrhage, including the performance rate of each recommended procedure. Differences in these variables between 2005 and 2012 were tested. From 2005 to 2012, the prevalence of severe postpartum haemorrhage declined significantly, from 1.2% to 0.6% of vaginal deliveries (p<0.001). Since 2010, the quarterly rate of severe PPH has not exceeded the upper control limits, that is, been out of statistical control. The proportion of cases that were managed consistently with the guidelines increased for all of their main components. Implementation of continuous quality improvement efforts began seven years ago and used, among other tools, statistical process control charts. During this period, the prevalence of severe postpartum haemorrhage after vaginal delivery has been reduced by 50%. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Genetic ataxia telangiectasia porcine model phenocopies the multisystemic features of the human disease.

PubMed

Beraldi, Rosanna; Meyerholz, David K; Savinov, Alexei; Kovács, Attila D; Weimer, Jill M; Dykstra, Jordan A; Geraets, Ryan D; Pearce, David A

2017-11-01

Ataxia telangiectasia (AT) is a progressive multisystem autosomal recessive disorder caused by mutations in the AT-mutated (ATM) gene. Early onset AT in children is characterized by cerebellar degeneration, leading to motor impairment. Lung disease and cancer are the two most common causes of death in AT patients. Accelerated thymic involution may contribute to the cancer, and recurrent and/or chronic respiratory infections may be a contributing factor to lung disease in AT. AT patients have fertility issues, are highly sensitive to ionizing radiation and they present oculocutaneous telangiectasia. Current treatments only slightly ameliorate disease symptoms; therapy that alters or reverses the course of the disease has not yet been discovered. Previously, we have shown that ATM -/- pigs, a novel model of AT, present with a loss of Purkinje cells, altered cerebellar cytoarchitecture and motor coordination deficits. ATM -/- porcine model not only recapitulates the neurological phenotype, but also other multifaceted clinical features of the human disease. Our current study shows that ATM -/- female pigs are infertile, with anatomical and functional signs of an immature reproductive system. Both male and female ATM -/- pigs show abnormal thymus structure with decreased cell cycle and apoptosis markers in the gland. Moreover, ATM -/- pigs have an altered immune system with decreased CD8 + and increased natural killer and CD4 + CD8 + double-positive cells. Nevertheless, ATM -/- pigs manifest a deficient IgG response after a viral infection. Based on the neurological and peripheral phenotypes, the ATM -/- pig is a novel genetic model that may be used for therapeutic assessments and to identify pathomechanisms of this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

PubMed

Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

2017-07-01

Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic

Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage

PubMed Central

Wang, Jian; Doré, Sylvain

2008-01-01

Because heme oxygenase (HO) is the rate limiting enzyme in the degradation of the pro-oxidant hemin/heme from blood, here we investigated the contribution of the inducible HO-1 to early brain injury produced by intracerebral haemorrhage (ICH). We found that after induction of ICH, HO-1 proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endothelial cells. Remarkably, the injury volume was significantly smaller in HO-1 knockout (HO-1−/−) mice than in wild-type controls 24 and 72 h after ICH. Although the brain water content did not appear to be significantly different, the protection in HO-1−/− mice was associated with a marked reduction in ICH-induced leucocyte infiltration, microglia/macrophage activation and free radical levels. These data reveal a previously unrecognized role of HO-1 in early brain injury after ICH. Thus, modulation of HO-1 signalling should be assessed further in clinical settings, especially for haemorrhagic states. PMID:17525142

Haemorrhagic gastritis following Gastrografin administration for adhesive small bowel obstruction: A case report of a rare outcome.

PubMed

Guy, Stephen; Al Askari, Mohammed

2017-01-01

Adhesive small bowel obstruction (ASBO) is common after abdominal surgery. Water soluble contrast agents (WSCA) such as Gastrografin have been demonstrated to be safe and effective in predicting resolution of ASBO with conservative management while decreasing the time to resolution, decreasing the need for surgery and reducing overall length of stay. Few adverse effects have been reported. To the authors knowledge this is the first report of haemorrhagic gastritis following administration of Gastrografin for ASBO. We present a case of haemorrhagic gastritis following Gastrografin administration in a 69-year-old male with adhesive small bowel obstruction who was managed conservatively with a good outcome. The report complies with the criteria outlined in the SCARE statement (Product Information Gastrografin [Product information], 2013). The characteristics, mechanism of action, safety profile and efficacy of Gastrografin in ASBO are discussed along with the possible mechanisms underlying the haemorrhagic gastritis. This patient at high risk of gastropathy experienced haemorrhagic gastritis following administration of Gastrografin for adhesive small bowel obstruction. WSCA such as Gastrografin are usually safe and effective in ASBO however caution may be warranted in patients at high risk of gastropathy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS)

USDA-ARS?s Scientific Manuscript database

Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG, IgM and leptospiral antigens. Three ...

Identification and chromosomal localization of Atm, the mouse homolog of the ataxia-telangiectasia gene.

PubMed

Pecker, I; Avraham, K B; Gilbert, D J; Savitsky, K; Rotman, G; Harnik, R; Fukao, T; Schröck, E; Hirotsune, S; Tagle, D A; Collins, F S; Wynshaw-Boris, A; Ried, T; Copeland, N G; Jenkins, N A; Shiloh, Y; Ziv, Y

1996-07-01

Atm, the mouse homolog of the human ATM gene defective in ataxia-telangiectasia (A-T), has been identified. The entire coding sequence of the Atm transcript was cloned and found to contain an open reading frame encoding a protein of 3066 amino acids with 84% overall identity and 91% similarity to the human ATM protein. Variable levels of expression of Atm were observed in different tissues. Fluorescence in situ hybridization and linkage analysis located the Atm gene on mouse chromosome 9, band 9C, in a region homologous to the ATM region on human chromosome 11q22-q23.

Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy).

PubMed

Pezzini, Alessandro; Grassi, Mario; Iacoviello, Licia; Zedde, Marialuisa; Marcheselli, Simona; Silvestrelli, Giorgio; DeLodovici, Maria Luisa; Sessa, Maria; Zini, Andrea; Paciaroni, Maurizio; Azzini, Cristiano; Gamba, Massimo; Del Sette, Massimo; Toriello, Antonella; Gandolfo, Carlo; Bonifati, Domenico Marco; Tassi, Rossana; Cavallini, Anna; Chiti, Alberto; Calabrò, Rocco Salvatore; Musolino, Rossella; Bovi, Paolo; Tomelleri, Giampaolo; Di Castelnuovo, Augusto; Vandelli, Laura; Ritelli, Marco; Agnelli, Giancarlo; De Vito, Alessandro; Pugliese, Nicola; Martini, Giuseppe; Lanari, Alessia; Ciccone, Alfonso; Lodigiani, Corrado; Malferrari, Giovanni; Del Zotto, Elisabetta; Morotti, Andrea; Costa, Paolo; Poli, Loris; De Giuli, Valeria; Bonaiti, Silvia; La Spina, Paolo; Marcello, Norina; Micieli, Giuseppe; de Gaetano, Giovanni; Colombi, Marina; Padovani, Alessandro

2016-09-01

Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated. We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH. A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones. Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions. 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/

Severe acute haemorrhagic liver failure in a neonate with a favourable spontaneous outcome.

PubMed

Cavet, Madeleine; Balu, Marie; Garel, Catherine; Mitanchez, Delphine; Renolleau, Sylvain; Alexandre, Marie; Pariente, Danièle; Ducou le Pointe, Hubert

2008-10-01

Acute liver failure in neonates is rare and is frequently associated with an unfavourable outcome. There is no curative treatment other than liver transplantation. Screening for viral, metabolic, toxic or vascular disease is essential to assess the prognosis and to guide specific treatment. Hepatic haemorrhage in neonates is often associated with bacterial infection, trauma and coagulopathies. We present a unique case of neonatal acute liver failure and multifocal massive haemorrhagic intrahepatic lesions of traumatic origin, documented by US and MRI. The patient made a spontaneous recovery. Clinical, biological and imaging outcome was excellent despite the apparent severity of the initial features. The only possible aetiology was a difficult caesarean delivery for mild fetal macrosomia.

Childhood colon cancer in a patient with ataxia telangiectasia

PubMed Central

Jo, Kyeong Min; Park, Jong Ha; Kim, Tae Oh; Jeong, Heui Jeong; Heo, Chang Min; Jang, Ji Hoon; Hur, So Chong; Jeong, Na Ri; Jeong, Su Jin; Seol, Sang Hoon; Nam, Kyung Han

2016-01-01

Background Ataxia-telangiectasia (AT) is a rare autosomal recessive disease characterized by progressive neurologic impairment and cerebellar ataxia. In addition, patients with this disease are known to have an inherent increased susceptibility to the development of cancer, predominantly hematologic malignancies. Methods We report the case of a young boy with AT from Russia, who had abdominal pain. Laboratory tests and radiologic examinations were performed to him. Results After abdominal computed tomography (CT), colonoscopy and surgical interventions, the young boy was diagnosed with colon cancer that had signet ring cell features. Conclusions It is known that the patient with AT appeared to be predisposed to various tumors, including leukemia or lymphoma, which are more common in childhood. Even if the patient with AT could have solid tumor such as stomach cancer or breast cancer, it is less likely to have colon cancer, especially signet ring cell type. Actually, no case of colon cancer has ever been reported, especially in young patient and hence, we have focused on this point and are hereby reporting this unique case. PMID:26855947

Predicting outcome of acute non-variceal upper gastrointestinal haemorrhage without endoscopy using the clinical Rockall Score.

PubMed

Tham, T C K; James, C; Kelly, M

2006-11-01

The Rockall risk scoring system uses clinical criteria and endoscopy to identify patients at risk of adverse outcomes after acute upper gastrointestinal haemorrhage. A clinical Rockall score obtained using only the clinical criteria may be able to predict outcome without endoscopy. To validate the clinical Rockall Score in predicting outcome after acute non-variceal upper gastrointestinal haemorrhage. A retrospective observational study of consecutive patients who were admitted with non-variceal acute upper gastrointestinal haemorrhage was undertaken. Medical records were abstracted using a standardised form. 102 cases were identified (51 men and 51 women; mean age 59 years). 38 (37%) patients considered to be at low risk of adverse outcomes (clinical Rockall Score 0) had no adverse outcomes and did not require transfusion. Patients with a clinical Rockall Score of 1-3 had no adverse outcomes, although 13 of 45 (29%) patients required blood transfusions. Clinical Rockall Scores >3 (n = 19) were associated with adverse outcomes (rebleeding in 4 (21%), surgery in 1 (5%) and death in 2 (10%)). The clinical Rockall Score without endoscopy may be a useful prognostic indicator in this cohort of patients with acute non-variceal upper gastrointestinal haemorrhage. This score may reduce the need for urgent endoscopy in low-risk patients, which can instead be carried out on a more elective outpatient basis.

HAEMORRHAGIC SYNDROME IN THE CLINICAL PICTURE OF RADIATION SICKNESS IN DOGS AFFECTED BY POLONIUM (in Russian)

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

Mikhailovich, S.M.

Subcutaneous introduction of polonium to dogs brings about development of radiation sickness with appearance of haemorrhagic syndrome, which is characterized by disturbed process of blood coagulation, thrombocytopenia, decreased prothrombin value of the blood, increased permeability of capillaries. The clinical picture of the usually developed affection corresponds to the well known symptomatology, described in literature. Indicators of the haemorrhagic syndrome (blood coagulation, prothrombin value, permeabillty and stability of capillaries) appear in animals earlier than the clinical manifestations of this syndrome. (tr-auth)

Surgical Craniotomy for Intracerebral Haemorrhage.

PubMed

Mendelow, A David

2015-01-01

Craniotomy is probably indicated for patients with superficial spontaneous lobar supratentorial intracerebral haemorrhage (ICH) when the level of consciousness drops below 13 within the first 8 h of the onset of the haemorrhage. Once the level drops below 9, it is probably too late to consider craniotomy for these patients, so clinical vigilance is paramount. While this statement is only backed up by evidence that is moderately strong, meta-analysis of available data suggests that it is true in the rather limited number of patients with ICH. Meta-analyses like this can often predict the results of future prospective randomised controlled trials a decade or more before the trials are completed and published. Countless such examples exist in the literature, as is the case for thrombolysis in patients with myocardial infarction in the last millennium: meta-analysis determined the efficacy more than a decade BEFORE the last trial (ISIS-2) confirmed the benefit of thrombolysis for myocardial infarction. Careful examination of the meta-analysis' Forest plots in this chapter will demonstrate why this statement is made at the outset. Other meta-analyses of surgery for ICH have also indicated that minimal interventional techniques using topical thrombolysis or endoscopy via burrholes or even twist drill aspiration may be particularly successful for the treatment of supratentorial ICH, especially when the clot is deep seated. Ongoing clinical trials (CLEAR III and MISTIE III) should confirm this in the fullness of time. There are 2 exceptions to these generalisations. First, based on trial evidence, aneurysmal ICH is best treated with surgery. Second, cerebellar ICH represents a special case because of the development of hydrocephalus, which may require expeditious drainage as the intracranial pressure rises. The cerebellar clot will then require evacuation, usually via posterior fossa craniectomy, rather than craniotomy. Technical advances suggest that image-guided surgery

Intracerebral haemorrhage in Down syndrome: protected or predisposed?

PubMed Central

Buss, Lewis; Fisher, Elizabeth; Hardy, John; Nizetic, Dean; Groet, Jurgen; Pulford, Laura; Strydom, André

2016-01-01

Down syndrome (DS), which arises from trisomy of chromosome 21, is associated with deposition of large amounts of amyloid within the central nervous system. Amyloid accumulates in two compartments: as plaques within the brain parenchyma and in vessel walls of the cerebral microvasculature. The parenchymal plaque amyloid is thought to result in an early onset Alzheimer’s disease (AD) dementia, a phenomenon so common amongst people with DS that it could be considered a defining feature of the condition. The amyloid precursor protein ( APP) gene lies on chromosome 21 and its presence in three copies in DS is thought to largely drive the early onset AD. In contrast, intracerebral haemorrhage (ICH), the main clinical consequence of vascular amyloidosis, is a more poorly defined feature of DS. We review recent epidemiological data on stroke (including haemorrhagic stroke) in order to make comparisons with a rare form of familial AD due to duplication (i.e. having three copies) of the APP region on chromosome 21, here called ‘dup-APP’, which is associated with more frequent and severe ICH. We conclude that although people with DS are at increased risk of ICH, this is less common than in dup-APP, suggesting the presence of mechanisms that act protectively. We review these mechanisms and consider comparative research into DS and dup-APP that may yield further pathophysiological insight. PMID:27239286

Mesenchymal Stem Cell Therapy in Intracerebral Haemorrhagic Stroke.

PubMed

Bedini, Gloria; Bersano, Anna; Zanier, Elisa R; Pischiutta, Francesca; Parati, Eugenio A

2018-01-10

Spontaneous intracerebral haemorrhage (ICH) is a relatively common fatal disease, with an overall global incidence estimated at 24.6 per 100,000 person-years. Given the high degree of morbidity and mortality associated with ICH, therapies that may have neuroprotective effects are of increasing interest to clinicians. In this last context, cell therapies offer the promise of improving the disease course which cannot be addressed adequately by existing treatments. The aim of this review is to evaluate the protective effects and molecular mechanisms of mesenchymal stem cells (MSCs) on haemorrhagic brain following ICH. We also discuss possible emerging therapeutic approaches worth of further research. The available literature on the therapeutic potential of MSCs in ICH animal models clearly demonstrated that MSCs enhance the functional recovery and reduce the volume of the infarct size exerting anti-inflammatory and angiogenic properties. However, the quality of the original articles investigating the efficacy of stem cell therapies in ICH animal models is still poor and the lack of ICH clinical trial does not permit to reach any relevant conclusions. Further studies have to be implemented in order to achieve standardized methods of MSCs isolation, characterization and administration to improve ICH treatments with MSCs or MSC-derived products. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Bilateral large subconjunctival haemorrhages unmasking immune thrombocytopenic purpura during retinopathy of prematurity screening.

PubMed

Chandra, Parijat; Kumawat, Devesh; Kumar, Vinod; Tewari, Ruchir

2017-10-04

Although thrombocytopenia is known to be associated with pathogenesis of retinopathy of prematurity (ROP), immune thrombocytopenic purpura (ITP) is rare in infancy and not reported to occur with ROP. A preterm infant with aggressive posterior ROP developed bilateral massive subconjunctival haemorrhage after scleral indentation during screening. On evaluation, the infant was found to have severe ITP. Following intravenous transfusion of platelets and immunoglobulin, platelet counts improved and subconjunctival haemorrhage resolved over time. This case highlights the unusual presentation of ITP and also discusses the association of thrombocytopenia with ROP. Ophthalmologists should get prompt haematological work-up of such occurrences. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Adrenal haemorrhage due to heparin-induced thrombocytopenia.

PubMed

Ketha, Siva; Smithedajkul, Patrick; Vella, Adrian; Pruthi, Rajiv; Wysokinski, Waldemar; McBane, Robert

2013-04-01

Adrenal haemorrhage (AH) is a rare but potentially devastating complication of heparin-induced thrombocytopenia (HIT). Neither the prevalence nor the natural history of AH due to HIT are known. The objectives of this study were to identify the spectrum of AH causes, to characterise the frequency of AH due to HIT and determine the natural history of HIT-associated AH. All patients with incident adrenal haemorrhage from January 2002 through June 2012 seen at the Mayo Clinic were identified. Over this time frame, there were a total of 115 patients with AH of which 11 cases (10%; mean age 67 ± 8 years; 73% female) were associated with HIT. Of these, all but one occurred in the postoperative setting and involved both adrenal glands (89%) with acute adrenal insufficiency at the time of diagnosis. Cases were found incidentally during an evaluation for fever, shock, abdominal pain or mental status changes. All HIT patients experienced venous thrombosis at other locations including deep venous thromboses (n=14), pulmonary emboli (n= 4) and arterial thrombosis (n=2). Four patients undergoing total knee arthroplasty had "spontaneous HIT" with AH in the absence of identifiable heparin exposure. Other causes of AH included trauma (29%), sepsis (15%), antiphospholipid antibody syndrome (10%), and metastatic disease (12%). In conclusion, AH is an important but seldom recognised presumed thrombotic complication of HIT, which usually occurs in the postoperative period, especially after orthopaedic procedures. This syndrome can occur in the apparent absence of heparin exposure, especially following major joint replacement surgery.

Neutralisation of Local Haemorrhage Induced by the Saw-Scaled Viper Echis carinatus sochureki Venom Using Ethanolic Extract of Hibiscus aethiopicus L.

PubMed

Hasson, S S; Al-Balushi, M S; Said, E A; Habbal, O; Idris, M A; Mothana, R A A; Sallam, T A; Al-Jabri, A A

2012-01-01

The objective of the study is to investigate the anti-snake venom activities of a local plant, Hibiscus aethiopicus L. The H. aethiopicus was dried and extracted with ethanol. Different assays were performed according to standard techniques, to evaluate the plant's acute toxicity and its antivenom activities. The results of evaluating the systemic acute toxicity of the H. aethiopicus extract using "oral and intra-peritoneal" route were normal even at the highest dose (24 g/kg) tested. All guinea pigs (n = 3) when treated with venoms E. c. sochureki (75 μg) alone induced acute skin haemorrhage. In contrast, all guinea pigs (n = 18) treated with both venom and the plant extract at a concentration between 500 and 1000 mg/kg showed no signs of haemorrhage. Moreover, all guinea pigs (n = 18) treated with venom and the plant extract below 400 mg/kg showed acute skin haemorrhage. All guinea pigs treated with venom E. c. sochureki (75 μg) alone induced acute skin haemorrhage after both 24 and 32 hours. In contrast, all guinea pigs treated with both venom and the plant extract (administered independently) at concentrations between 500 and 1000 mg/kg showed no signs of haemorrhage after 32 hours. However, after 24 hours all tested guinea pigs showed less inhibition (<60%) compared to that obtained after 32 hours. The outcome of this study reflects that the extract of H. aethiopicus plant may contain an endogenous inhibitor of venom induced local haemorrhage.

Buccofacial apraxia and left cerebral haemorrhage.

PubMed

Maeshima, S; Truman, G; Smith, D S; Dohi, N; Itakura, T; Komai, N

1997-11-01

We examined 33 patients with left intracerebral haemorrhage to investigate the relations to buccofacial apraxia (BFA). BFA was present in 18 cases at 1 month and disappeared in 3 cases and persisted in 15 cases at 6 month from the onset. The existence of BFA seems to be partially dependent the haematoma volume which may cause the organic damage in lenticulate nucleus, insula, posterior limb or internal capsule and anterior portion of paraventricle white matter. All patients with BFA had aphasia (Broca 6, Wernicke 1, Total 10, Amnestic 1). Aphasia of the patients with transient BFA improved as well as the patients without BFA after BFA disappeared. We suspected that improvement or aphasia might be affected by BFA.

Glutamine deprivation induces interleukin-8 expression in ataxia telangiectasia fibroblasts.

PubMed

Kim, Min-Hyun; Kim, Aryung; Yu, Ji Hoon; Lim, Joo Weon; Kim, Hyeyoung

2014-05-01

To investigate whether glutamine deprivation induces expression of inflammatory cytokine interleukin-8 (IL-8) by determining NF-κB activity and levels of oxidative indices (ROS, reactive oxygen species; hydrogen peroxide; GSH, glutathione) in fibroblasts isolated from patients with ataxia telangiectasia (A-T). We used A-T fibroblasts stably transfected with empty vector (Mock) or with human full-length ataxia telangiectasia mutated (ATM) cDNA (YZ5) and mouse embryonic fibroblasts (MEFs) transiently transfected with ATM small interfering RNA (siRNA) or with non-specific control siRNA. The cells were cultured with or without glutamine or GSH. ROS levels were determined using a fluorescence reader and confocal microscopy. IL-8 or murine IL-8 homolog, keratinocyte chemoattractant (KC), and hydrogen peroxide levels in the medium were determined by enzyme-linked immunosorbent assay and colorimetric assay. GSH level was assessed by enzymatic assay, while IL-8 (KC) mRNA level was measured by reverse transcription-polymerase chain reaction (RT-PCR) and/or quantitative real-time PCR. NF-κB DNA-binding activity was determined by electrophoretic mobility shift assay. Catalase activity and ATM protein levels were determined by O2 generation and Western blotting. While glutamine deprivation induced IL-8 expression and increased NF-κB DNA-binding activity in Mock cells, both processes were decreased by treatment of cells with glutamine or GSH or both glutamine and GSH. Glutamine deprivation had no effect on IL-8 expression or NF-κB DNA-binding activity in YZ5 cells. Glutamine-deprived Mock cells had higher oxidative stress indices (increases in ROS and hydrogen peroxide, reduction in GSH) than glutamine-deprived YZ5 cells. In Mock cells, glutamine deprivation-induced oxidative stress indices were suppressed by treatment with glutamine or GSH or both glutamine and GSH. GSH levels and catalase activity were lower in Mock cells than YZ5 cells. MEFs transfected with ATM siRNA and

Telangiectasia macularis eruptiva perstans: more than skin deep

PubMed Central

Watkins, Casey E.; Bokor, Winston B.; Leicht, Stuart; Youngberg, George; Krishnaswamy, Guha

2011-01-01

Systemic mastocytosis is a rare disease involving the infiltration and accumulation of active mast cells within any organ system. By far, the most common organ affected is the skin. Cutaneous manifestations of mastocytosis, including Urticaria Pigmentosa (UP), cutaneous mastocytoma or telangiectasia macularis eruptive perstans (TMEP), may indicate a more serious and potentially life-threatening underlying disease. The presence of either UP or TMEP in a patient with anaphylactic symptoms should suggest the likelihood of systemic mastocytosis, with the caveat that systemic complications are more likely to occur in patients with UP. TMEP can usually be identified by the typical morphology, but a skin biopsy is confirmative. In patients with elevated tryptase levels or those with frequent systemic manifestations, a bone marrow biopsy is essential in order to demonstrate mast cell infiltration. Further genetic testing for mutations of c-kit gene or the FIP1L1 gene may help with disease classification and/or therapeutic approaches. Rarely, TMEP has been described with malignancy, radiation therapy, and myeloproliferative disorders. A few familial cases have also been described. In this review, we discuss the clinical features, diagnosis and management of patients with TMEP. We also discuss the possible molecular pathogenesis and the role of genetics in disease classification and treatment. PMID:25386256

In vitro analysis of platelet function in acute aneurysmal subarachnoid haemorrhage.

PubMed

von der Brelie, Christian; Subai, Alexander; Limperger, Verena; Rohde, Veit; Dempfle, Astrid; Boström, Azize

2018-04-01

Platelet function might play an essential role in the pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Thus, impaired platelet function and disturbed primary haemostasis induced by intake of acetylsalicylic acid (ASA) might influence the rate of DCI. Primary haemostasis and platelet function can be measured with in vitro diagnosis (platelet function analyser test, PFA 100). The aim of this study is to evaluate the rate of DCI, haemorrhagic complications and the neurological outcome. Two groups were compared (patients with regular platelet function versus patients with impaired platelet function). This is a retrospective observational study. An initial cohort of 787 patients with SAH has been treated from January 2005 to September 2012. Seventy-nine patients (10%) with aneurysmal SAH, a history of ASA medication and PFA testing within the first 24 h after aneurysm rupture have been included. The overall rate of DCI in the present study was 43%. In vitro platelet function testing showed pathological primary haemostasis in 69.6%. The DCI rate was higher in patients with regular tested primary haemostasis (p = 0.02, OR = 3.16, 95%CI = [1.19; 8.83]). However, outcome assessment by mGOS did not show a significant difference between the groups. Patients with impaired primary haemostasis did not display a higher rate of haemorrhagic complications. Impairment of primary haemostasis resulting from an impairment of platelet function at an early stage after SAH might lead to a lower rate of DCI. In vitro testing of platelet function might be useful to predict the occurrence of DCI in the course.

Global miRNA expression profile reveals novel molecular players in aneurysmal subarachnoid haemorrhage.

PubMed

Lopes, Katia de Paiva; Vinasco-Sandoval, Tatiana; Vialle, Ricardo Assunção; Paschoal, Fernando Mendes; Bastos, Vanessa Albuquerque P Aviz; Bor-Seng-Shu, Edson; Teixeira, Manoel Jacobsen; Yamada, Elizabeth Sumi; Pinto, Pablo; Vidal, Amanda Ferreira; Ribeiro-Dos-Santos, Arthur; Moreira, Fabiano; Santos, Sidney; Paschoal, Eric Homero Albuquerque; Ribeiro-Dos-Santos, Ândrea

2018-06-08

The molecular mechanisms behind aneurysmal subarachnoid haemorrhage (aSAH) are still poorly understood. Expression patterns of miRNAs may help elucidate the post-transcriptional gene expression in aSAH. Here, we evaluate the global miRNAs expression profile (miRnome) of patients with aSAH to identify potential biomarkers. We collected 33 peripheral blood samples (27 patients with cerebral aneurysm, collected 7 to 10 days after the haemorrhage, when usually is the cerebral vasospasm risk peak, and six controls). Then, were performed small RNA sequencing using an Illumina Next Generation Sequencing (NGS) platform. Differential expression analysis identified eight differentially expressed miRNAs. Among them, three were identified being up-regulated, and five down-regulated. miR-486-5p was the most abundant expressed and is associated with poor neurological admission status. In silico miRNA gene target prediction showed 148 genes associated with at least two differentially expressed miRNAs. Among these, THBS1 and VEGFA, known to be related to thrombospondin and vascular endothelial growth factor. Moreover, MYC gene was found to be regulated by four miRNAs, suggesting an important role in aneurysmal subarachnoid haemorrhage. Additionally, 15 novel miRNAs were predicted being expressed only in aSAH, suggesting possible involvement in aneurysm pathogenesis. These findings may help the identification of novel biomarkers of clinical interest.

Leptospirosis pulmonary haemorrhage syndrome is associated with linear deposition of immunoglobulin and complement on the alveolar surface.

PubMed

Croda, J; Neto, A N D; Brasil, R A; Pagliari, C; Nicodemo, A C; Duarte, M I S

2010-06-01

Leptospirosis is a zoonotic infection associated with severe diseases such as leptospirosis pulmonary haemorrhage syndrome (LPHS). The cause of pulmonary haemorrhage is unclear. Understanding which mechanisms and processes are involved in LPHS will be important in treatment regimens under development for this life-threatening syndrome. In the present study, we evaluated 30 lung specimens from LPHS patients and seven controls using histology and immunohistochemistry (detection of IgM, IgG, IgA and C3) in order to describe the pathological features associated with this syndrome. Immunoglobulin deposits were detected on the alveolar surface in 18/30 LPHS patients. Three staining patterns were observed for the immunoglobulins and C3 in the lung tissues of LPHS patients: AS, delicate linear staining adjacent to the alveolar surface, which was indicative of a membrane covering the luminal surface of type I and II pneumocyte cells; S, heterogeneous staining which was sporadically distributed along the alveolar septum; and IA, weak, focal intra-alveolar granular staining. Human LPHS is associated with individual and unique histological patterns that differ from those of other causes of pulmonary haemorrhage. In the present study, it was found that the linear deposition of immunoglobulins (IgA, IgG and IgM) and complement on the alveolar surface may play a role in the pathogenesis of pulmonary haemorrhage in human leptospirosis.

Design and Experimental Evaluation of a Non-Invasive Microwave Head Imaging System for Intracranial Haemorrhage Detection

PubMed Central

Mobashsher, A. T.; Bialkowski, K. S.; Abbosh, A. M.; Crozier, S.

2016-01-01

An intracranial haemorrhage is a life threatening medical emergency, yet only a fraction of the patients receive treatment in time, primarily due to the transport delay in accessing diagnostic equipment in hospitals such as Magnetic Resonance Imaging or Computed Tomography. A mono-static microwave head imaging system that can be carried in an ambulance for the detection and localization of intracranial haemorrhage is presented. The system employs a single ultra-wideband antenna as sensing element to transmit signals in low microwave frequencies towards the head and capture backscattered signals. The compact and low-profile antenna provides stable directional radiation patterns over the operating bandwidth in both near and far-fields. Numerical analysis of the head imaging system with a realistic head model in various situations is performed to realize the scattering mechanism of haemorrhage. A modified delay-and-summation back-projection algorithm, which includes effects of surface waves and a distance-dependent effective permittivity model, is proposed for signal and image post-processing. The efficacy of the automated head imaging system is evaluated using a 3D-printed human head phantom with frequency dispersive dielectric properties including emulated haemorrhages with different sizes located at different depths. Scattered signals are acquired with a compact transceiver in a mono-static circular scanning profile. The reconstructed images demonstrate that the system is capable of detecting haemorrhages as small as 1 cm3. While quantitative analyses reveal that the quality of images gradually degrades with the increase of the haemorrhage’s depth due to the reduction of signal penetration inside the head; rigorous statistical analysis suggests that substantial improvement in image quality can be obtained by increasing the data samples collected around the head. The proposed head imaging prototype along with the processing algorithm demonstrates its feasibility

Osteogenesis imperfecta presenting as aneurysmal subarachnoid haemorrhage in a 53-year-old man

PubMed Central

Kaliaperumal, Chandrasekaran; Walsh, Tom; Balasubramanian, Chandramouli; Wyse, Gerry; Fanning, Noel; Kaar, George

2011-01-01

The authors describe a case of aneurysmal subarachnoid haemorrhage in a 53-year-old man with background of osteogenesis imperfecta (OI). CT brain revealed diffuse subarachnoid haemorrhage (SAH) and cerebral angiogram subsequently confirmed vertebral artery aneurysm rupture leading to SAH. To the authors knowledge this is the first case of vertebral artery aneurysmal SAH described in OI. A previously undiagnosed OI was confirmed by genetic analysis (COL1A1 gene mutation). This aneurysm was successfully treated by endovascular route. Post interventional treatment patient developed stroke secondary to vasospasm. Communicating hydrocephalus, which developed in the process of management, was successfully treated with ventriculo-peritoneal shunt. The aetio-pathogenesis and management of this condition is described. The authors have reviewed the literature and genetic basis of this disease. PMID:22674700

Acute haemorrhagic diarrhoea syndrome in dogs: 108 cases.

PubMed

Mortier, F; Strohmeyer, K; Hartmann, K; Unterer, S

2015-06-13

No prospective studies including large numbers of dogs with acute haemorrhagic diarrhoea syndrome (AHDS) are published so far. The aim of this case-control study was to describe signalment, history, clinical signs, laboratory values and course of disease in dogs with AHDS. Dogs (108) with idiopathic acute haemorrhagic diarrhoea (<3 days) were prospectively enrolled. Clinical assessment was performed by calculation of the 'AHDS index' (0-18). The hospital population and 21 healthy dogs served as control groups. Dogs with AHDS had a significantly lower body weight (median 9.8 kg) and age (median five years) than other dogs of the hospital population (20 kg; 10 years) (P<0.001). Predisposed breeds were Yorkshire terrier, miniature pinscher, miniature schnauzer and Maltese. The syndrome was more likely to occur during winter. Vomiting preceded the onset of bloody diarrhoea in 80 per cent of dogs and haematemesis was observed in half of those cases. Median AHDS index at presentation was 12 (range 3-17). Haematocrit was generally high (median 57.1 per cent; range 33-76 per cent), but exceeded 60 per cent only in 31.4 per cent of dogs. Haematocrit of 48.1 per cent of dogs was above reference range, as was monocyte (50.0 per cent), segmented (59.6 per cent) and band neutrophil count (45.2 per cent). A rapid clinical improvement occurred during the first 48 hours. British Veterinary Association.

Germline Mutations of the Ataxia-Telangiectasia Gene, ATM, as a Risk Factor for Radiation-Associated Breast Cancer

DTIC Science & Technology

1999-07-01

Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R...Human Molecular Genetics 1996;5(4): 433-439. 33. Gilad S, Bar-Shira A, Harnik R, et. al. Ataxia-Telangiectasia: Founder Effect Among North African Jews...1998:62:86-97. 39. Gilad S, Khosravi R, Harnik R, Ziv Y, Shkedy D,Galanty Y, Frydman M, Levi J, et al. Identification of mutations using extended RT

Small Arteriovenous Malformation of the Common Bile Duct Causing Hemobilia in a Patient with Hereditary Hemorrhagic Telangiectasia

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

Hayashi, Sadao, E-mail: hayashi@m.kufm.kagoshima-u.ac.jp; Baba, Yasutaka; Ueno, Kazuto

We report a 54-year-old male patient with arteriovenous malformation located at the common bile duct and hereditary hemorrhagic telangiectasia. The patient was treated as gallstone pancreatitis at first. Three days after endoscopic nasobiliary drainage (ENBD) for biliary drainage to subside gallstone pancreatitis, hemobilia was drained from the ENBD tube and the serum hemoglobin level gradually decreased. Cholangioscopy and angiography revealed that hemobilia was due to a small arteriovenous malformation located at the common bile duct. Subsequently, the patient was successfully treated by endovascular intervention.

Remote cerebellar haemorrhage after placement of an external ventricular drainage for acute hydrocephalus: A case report.

PubMed

Caldeira, I; Lavrador, J; Basílio, G; Sousa, R; Reimão, S

2017-03-01

Remote cerebellar haemorrhage (RCH) is a rare complication following a craniotomy. This generally benign phenomenon is an identifiable complication of supratentorial craniotomies and should not be mistaken with other pathologies. The most common presenting symptom is a decrease in the level of consciousness but in some cases the RCH may be asymptomatic and accidentally discovered in follow-up CT scans. A 70-year-old man was admitted to our emergency department with sudden mental status deterioration. A head CT scan was carried out and an acute hydrocephalus was diagnosed. The patient was transferred to the operating room for external ventricular drainage (EVD) placement via a frontal burr-hole. At 24hours, the patient made a complete neurological recovery. On third postoperative day, a follow-up CT scan showed an asymptomatic right remote cerebellar haemorrhage. The MRI assessment confirmed the diagnosis. The EVD was removed on the 6th postoperative day and the patient was discharged after one week with no further symptoms. This case report is the first documented case, to our knowledge, of a remote cerebellar haemorrhage after placement of external ventricular drainage via a frontal burr-hole. The precise aetiology of remote cerebellar haemorrhage remains unclear. One of the most accepted theories is the "cerebellar sag" explanation, which defends hypothesis that peri-operative over drainage of cerebrospinal fluid (CSF) is the main mechanism involved. Further investigation is required to understand the pathogenesis and risk factors for the occurrence of this phenomenon. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Acute variceal haemorrhage in the United Kingdom: patient characteristics, management and outcomes in a nationwide audit.

PubMed

Jairath, Vipul; Rehal, Sunita; Logan, Richard; Kahan, Brennan; Hearnshaw, Sarah; Stanworth, Simon; Travis, Simon; Murphy, Michael; Palmer, Kelvin; Burroughs, Andrew

2014-05-01

Despite advances in treatment, acute variceal haemorrhage remains life-threatening. To describe contemporary characteristics, management and outcomes of patients with cirrhosis and acute variceal haemorrhage and risk factors for rebleeding and mortality. Multi-centre clinical audit conducted in 212 UK hospitals. In 526 cases of acute variceal haemorrhage, 66% underwent endoscopy within 24h with 64% (n=339) receiving endoscopic therapy. Prior to endoscopy, 57% (n=299) received proton pump inhibitors, 44% (n=232) vasopressors and 27% (n=144) antibiotics. 73% (n=386) received red cell transfusion, 35% (n=184) fresh frozen plasma and 14% (n=76) platelets, with widely varying transfusion thresholds. 26% (n=135) experienced further bleeding and 15% (n=80) died by day 30. The Model for End Stage Liver Disease score was the best predictor of mortality (area under the receiver operating curve=0.74, P<0.001). Neither the clinical nor full Rockall scores were useful predictors of outcome. Coagulopathy was strongly associated with rebleeding (odds ratio 2.23, 95% CI 1.22-4.07, P=0.01, up to day 30) and mortality (odds ratio 3.06, 95% CI 1.29-7.26, P=0.01). Although mortality has improved following acute variceal haemorrhage, rebleeding rates remain appreciably high. There are notable deficiencies in the use of vasopressors and endoscopic therapy. More work is needed to understand the optimum transfusion strategies. Better risk stratification tools are required to identify patients needing more intensive support. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Ebolavirus and Haemorrhagic Syndrome

PubMed Central

Matua, Gerald A.; Van der Wal, Dirk M.; Locsin, Rozzano C.

2015-01-01

The Ebola virus is a highly virulent, single-stranded ribonucleic acid virus which affects both humans and apes and has fast become one of the world’s most feared pathogens. The virus induces acute fever and death, with haemorrhagic syndrome occurring in up to 90% of patients. The known species within the genus Ebolavirus are Bundibugyo, Sudan, Zaïre, Reston and Taï Forest. Although endemic in Africa, Ebola has caused worldwide anxiety due to media hype and concerns about its international spread, including through bioterrorism. The high fatality rate is attributed to unavailability of a standard treatment regimen or vaccine. The disease is frightening since it is characterised by rapid immune suppression and systemic inflammatory response, causing multi-organ and system failure, shock and often death. Currently, disease management is largely supportive, with containment efforts geared towards mitigating the spread of the virus. This review describes the classification, morphology, infective process, natural ecology, transmission, epidemic patterns, diagnosis, clinical features and immunology of Ebola, including management and epidemic containment strategies. PMID:26052448

Ebolavirus and Haemorrhagic Syndrome.

PubMed

Matua, Gerald A; Van der Wal, Dirk M; Locsin, Rozzano C

2015-05-01

The Ebola virus is a highly virulent, single-stranded ribonucleic acid virus which affects both humans and apes and has fast become one of the world's most feared pathogens. The virus induces acute fever and death, with haemorrhagic syndrome occurring in up to 90% of patients. The known species within the genus Ebolavirus are Bundibugyo, Sudan, Zaïre, Reston and Taï Forest. Although endemic in Africa, Ebola has caused worldwide anxiety due to media hype and concerns about its international spread, including through bioterrorism. The high fatality rate is attributed to unavailability of a standard treatment regimen or vaccine. The disease is frightening since it is characterised by rapid immune suppression and systemic inflammatory response, causing multi-organ and system failure, shock and often death. Currently, disease management is largely supportive, with containment efforts geared towards mitigating the spread of the virus. This review describes the classification, morphology, infective process, natural ecology, transmission, epidemic patterns, diagnosis, clinical features and immunology of Ebola, including management and epidemic containment strategies.

Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia

PubMed Central

Devgan, S S; Sanal, O; Doil, C; Nakamura, K; Nahas, S A; Pettijohn, K; Bartek, J; Lukas, C; Lukas, J; Gatti, R A

2011-01-01

Maintaining genomic integrity is critical to avoid life-threatening disorders, such as premature aging, neurodegeneration and cancer. A multiprotein cascade operates at sites of DNA double-strand breaks (DSBs) to recognize, signal and repair damage. RNF168 (ring-finger nuclear factor) contributes to this emerging pathway of several E3 ubiquitin ligases that perform sequential ubiquitylations on damaged chromosomes, chromatin modifications essential for aggregation of repair complexes at the DSB sites. Here, we report the clinical and cellular phenotypes associated with a newly identified homozygous nonsense mutation in the RNF168 gene of a patient with a syndrome mimicking ataxia-telangiectasia. The mutation eliminated both of RNF168's ubiquitin-binding motifs, thus blocking progression of the ubiquitylation cascade and retention of repair proteins including tumor suppressors 53BP1 and BRCA1 at DSB sites, consistent with the observed defective DNA damage checkpoints/repair and pronounced radiosensitivity. Rapid screening for RNF168 pathway deficiency was achieved by scoring patients' lymphoblastoid cells for irradiation-induced nuclear foci containing 53BP1, a robust assay we propose for future diagnostic applications. The formation of radiation-induced DSB repair foci was rescued by ectopic expression of wild-type RNF168 in patient's cells, further causally linking the RNF168 mutation with the pathology. Clinically, this novel syndrome featured ataxia, telangiectasia, elevated alphafetoprotein, immunodeficiency, microcephaly and pulmonary failure and has implications for the differential diagnosis of autosomal recessive ataxias. PMID:21394101

Regulation of oxidative stress responses by ataxia-telangiectasia mutated is required for T cell proliferation.

PubMed

Bagley, Jessamyn; Singh, Gyanesh; Iacomini, John

2007-04-15

Mutations in the gene encoding ataxia-telangiectasia (A-T) mutated (Atm) cause the disease A-T, characterized by immunodeficiency, the molecular basis of which is not known. Following stimulation through the TCR, Atm-deficient T cells and normal T cells in which Atm is inhibited undergo apoptosis rather than proliferation. Apoptosis is prevented by scavenging reactive oxygen species (ROS) during activation. Atm therefore plays a critical role in T cell proliferation by regulating responses to ROS generated following T cell activation. The inability of Atm-deficient T cells to control responses to ROS is therefore the molecular basis of immunodeficiency associated with A-T.

Christmas disease: diagnosis and management of a haemorrhagic diathesis following dentofacial trauma

PubMed Central

Tamagond, Sridevi B; Hugar, Santosh I; Patil, Anil; Huddar, SandhyaRani

2015-01-01

Haemorrhagic diathesis has been of much concern to health professionals including dentists. It is not infrequent that a dentist becomes the first person to diagnose a bleeding disorder while performing dental treatment. Haemophilia is an X linked disorder with a frequency of about 1:10 000 births. Haemophilia B is much less common than haemophilia A, and affects only 1:300 000 males born alive. The clinical features of haemophilia B are very similar to those of haemophilia A with a prolongation of activated partial thromboplastin time. This case report describes the dental management of a patient with an uncommon haematological disorder, namely, factor IX deficiency, which remained undiagnosed until the patient had to undergo dentofacial trauma with unexpected severe haemorrhage. Preventive dentistry remains vital to young haemophiliacs. Surgical dental procedures may be performed for haemophiliacs but they must be judiciously coordinated by dental and medical health professionals. PMID:25568261

Ribavirin for treating Crimean Congo haemorrhagic fever.

PubMed

Johnson, Samuel; Henschke, Nicholas; Maayan, Nicola; Mills, Inga; Buckley, Brian S; Kakourou, Artemisia; Marshall, Rachel

2018-06-05

Crimean Congo haemorrhagic fever (CCHF) is a tick-borne disease that occurs in parts of Asia, Europe and Africa. Since 2000 the infection has caused epidemics in Turkey, Iran, Russia, Uganda and Pakistan. Good-quality general supportive medical care helps reduce mortality. There is uncertainty and controversy about treating CCHF with the antiviral drug ribavirin. To assess the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever. We searched the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (OVID); Science Citation Index-Expanded, Social Sciences Citation index, conference proceedings (Web of Science); and CINAHL (EBSCOHost). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for trials in progress. We conducted all searches up to 16 October 2017. We also contacted experts in the field and obtained further studies from these sources. We evaluated studies assessing the use of ribavirin in people with suspected or confirmed Crimean Congo haemorrhagic fever. We included randomised control trials (RCTs); non-randomised studies (NRSs) that included more than 10 participants designed as cohort studies with comparators; and case-control studies. Two review authors assessed eligibility, risk of bias, and extracted data. For non-randomized studies we used the ROBINS-I tool to assess risk of bias. The main effects analysis included all studies where we judged the risk of bias to be low, moderate or high. We summarized dichotomous outcomes using risk ratios (RRs) and continuous outcomes using mean differences (MDs), and used meta-analyses where appropriate. We carried out a subsidiary appraisal and analysis of studies with critical risk of bias for the primary outcome, as these are often cited to support using ribavirin. For the main effects analysis, five studies met our inclusion criteria: one RCT with 136

Procedure-related haemorrhage in embolisation of intracranial aneurysms with Guglielmi detachable coils.

PubMed

Kwon, B J; Han, M H; Oh, C W; Kim, K H; Chang, K H

2003-08-01

We reviewed the haemorrhagic complications of the endovascular treatment of intracranial aneurysms, in terms of frequency, pre-embolisation clinical status, clinical and radiological manifestations, management and prognosis. In 275 patients treated for 303 aneurysms over 7 years we had seven (one man and six women--2.3%) with haemorrhage during or immediately after endovascular treatment. All procedures were performed with a standardised protocol of heparinisation and anaesthesia. Four had ruptured aneurysms, two at the tip of the basilar artery, and one ach on the internal carotid and posterior cerebral artery, treated after 12, 5, 14, and 2 days, respectively, three were in Hunt and Hess grade 2 and one in grade 1. Bleeding occurred during coiling in three, after placement of at least four coils, and during manipulation of the guidewire to enter the aneurysm in the fourth. Haemorrhage was manifest as extravasation of contrast medium, with a sudden rise in systolic blood pressure in three patients. The other three patients had unruptured aneurysms; they had stable blood pressure and angiographic findings during the procedure, but one, under sedation, had seizures immediately after insertion of four coils, and the other two had seizures, headache and vomiting on the day following the procedure. Heparin reversal with protamine sulphate was started promptly started when bleeding was detected in four patients, and the embolisation was completed with additional coils in three. Emergency ventricular drainage was performed in the two patients with ruptured aneurysm and one with an unruptured aneurysm who had abnormal neurological responses or hydrocephalus. The bleeding caused a third nerve palsy in one patient, which might have been due to ischaemia and progressively improved.

Pulmonary function in adolescents with ataxia telangiectasia.

PubMed

McGrath-Morrow, Sharon; Lefton-Greif, Maureen; Rosquist, Karen; Crawford, Thomas; Kelly, Amber; Zeitlin, Pamela; Carson, Kathryn A; Lederman, Howard M

2008-01-01

Pulmonary complications are common in adolescents with ataxia telangiectasia (A-T), however objective measurements of lung function may be difficult to obtain because of underlying bulbar weakness, tremors, and difficulty coordinating voluntary respiratory maneuvers. To increase the reliability of pulmonary testing, minor adjustments were made to stabilize the head and to minimize leaks in the system. Fifteen A-T adolescents completed lung volume measurements by helium dilution. To assess for reproducibility of spirometry testing, 10 A-T adolescents performed spirometry on three separate occasions. Total lung capacity (TLC) was normal or just mildly decreased in 12/15 adolescents tested. TLC correlated positively with functional residual capacity (FRC), a measurement independent of patient effort (R2=0.71). The majority of individuals had residual volumes (RV) greater than 120% predicted (10/15) and slow vital capacities (VC) less than 70% predicted (9/15). By spirometry, force vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) values were reproducible in the 10 individuals who underwent testing on three separate occasions (R=0.97 and 0.96 respectively). Seven of the 10 adolescents had FEV1/FVC ratios>90%. Lung volume measurements from A-T adolescents revealed near normal TLC values with increased RV and decreased VC values. These findings indicate a decreased ability to expire to residual volume rather then a restrictive defect. Spirometry was also found to be reproducible in A-T adolescents suggesting that spirometry testing may be useful for tracking changes in pulmonary function over time in this population. Copyright (c) 2007 Wiley-Liss, Inc.

Dietary fibre intake and risk of ischaemic and haemorrhagic stroke in the UK Women's Cohort Study.

PubMed

Threapleton, D E; Burley, V J; Greenwood, D C; Cade, J E

2015-04-01

Stroke risk is modifiable through many risk factors, one being healthy dietary habits. Fibre intake was associated with a reduced stroke risk in recent meta-analyses; however, data were contributed by relatively few studies, and few examined different stroke types. A total of 27,373 disease-free women were followed up for 14.4 years. Diet was assessed with a 217-item food frequency questionnaire and stroke cases were identified using English Hospital Episode Statistics and mortality records. Survival analysis was applied to assess the risk of total, ischaemic or haemorrhagic stroke in relation to fibre intake. A total of 135 haemorrhagic and 184 ischaemic stroke cases were identified in addition to 138 cases where the stroke type was unknown or not recorded. Greater intake of total fibre, higher fibre density and greater soluble fibre, insoluble fibre and fibre from cereals were associated with a significantly lower risk for total stroke. For total stroke, the hazard ratio per 6 g/day total fibre intake was 0.89 (95% confidence intervals: 0.81-0.99). Different findings were observed for haemorrhagic and ischaemic stroke in healthy-weight or overweight women. Total fibre, insoluble fibre and cereal fibre were inversely associated with haemorrhagic stroke risk in overweight/obese participants, and in healthy-weight women greater cereal fibre was associated with a lower ischaemic stroke risk. In non-hypertensive women, higher fibre density was associated with lower ischaemic stroke risk. Greater total fibre and fibre from cereals are associated with a lower stroke risk, and associations were more consistent with ischaemic stroke. The different observations by stroke type, body mass index group or hypertensive status indicates potentially different mechanisms.

Inherited neurovascular diseases affecting cerebral blood vessels and smooth muscle.

PubMed

Sam, Christine; Li, Fei-Feng; Liu, Shu-Lin

2015-10-01

Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment.

Viral haemorrhagic fever and vascular alterations.

PubMed

Aleksandrowicz, P; Wolf, K; Falzarano, D; Feldmann, H; Seebach, J; Schnittler, H

2008-02-01

Pathogenesis of viral haemorrhagic fever (VHF) is closely associated with alterations of the vascular system. Among the virus families causing VHF, filoviruses (Marburg and Ebola) are the most fatal, and will be focused on here. After entering the body, Ebola primarily targets monocytes/macrophages and dendritic cells. Infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. Monocytes/macrophages, however, immediately activate after viral contact and release reasonable amounts of cytokines that target the vascular system, particularly the endothelial cells. Some underlying molecular mechanisms such as alteration of the vascular endothelial cadherin/catenin complex, tyrosine phosphorylation, expression of cell adhesion molecules, tissue factor and the effect of soluble viral proteins released from infected cells to the blood stream will be discussed.

Major obstetric haemorrhage of 2000 ml or greater: a clinical audit.

PubMed

O'Sullivan, J; Mansfield, R; Talbot, R; Cairns, A E

2018-05-04

Haemorrhage remains a leading cause of maternal death. We conducted an audit to identify strategies to improve the management at our local NHS Trust. A data collection form was based on our local guideline. A coded database search was conducted for all deliveries where the estimated blood loss was ≥2000 ml (from June 1 2015 to December 31 2015), returning 68 search results (13.7/1000 births). Fifty-six records were included. Poor compliance (<75%) was seen in some key areas including the major obstetric haemorrhage (MOH) call activation (52%), the presence of an anaesthetic consultant (63%) and tranexamic acid administration (46%). Thirty out of 56 cases (54%) were acutely transfused. Women, who were not transfused acutely, appeared to be more likely to need a secondary transfusion if no MOH call had been activated (9/27 (33%) versus 3/29 (10%), p = .052). A key area for improvement was the activation of MOH calls. Following this audit, we adjusted our guideline to make it more clinically useful and staff training sessions were held, including simulation training. Impact statement What is already known on this subject? A postpartum haemorrhage (PPH) is an obstetric emergency. A structured approach is important to optimise the care of the mothers during this dangerous time, and has been shown to reduce the transfusion requirements. However, clinical practice may not adhere to the guideline recommendations. What the results of this study add? With the objective evidence of increased rates of PPH ≥2000 ml at our institution, our work identifying the flaws in management was a critical component of the work to improve the outcomes. This study gives impetus to find innovative ways to improve adherence to guidelines, and inspired an update of our local guideline to improve the applicability and utility. This project suggests a new marker for the adequacy of an acute management (a requirement for secondary blood transfusion without having received an acute

Anti-fibrinolytic treatment in the pre-operative management of subarachnoid haemorrhage caused by ruptured intracranial aneurysm.

PubMed Central

Ameen, A A; Illingworth, R

1981-01-01

One hundred consecutive patients treated with epsilon aminocaproic acid 24 grams daily prior to surgery for ruptured intracranial aneurysms have been compared with the previous 100 patients managed similarly but without anti-fibrinolytic drugs. No other alterations in management were made and the two series are closely comparable in all other respects. Fewer episodes of recurrent haemorrhage and deaths from this cause occurred in the treated patients, but more cases of cerebral ischaemia occurred. Neither difference is statistically significant and overall more deaths occurred in the patients treated with antifibrinolytic drugs. The value of this method of treatment in the management of aneurysmal subarachnoid haemorrhage is questioned. PMID:7229645

Role of canine circovirus in dogs with acute haemorrhagic diarrhoea.

PubMed

Anderson, A; Hartmann, K; Leutenegger, C M; Proksch, A L; Mueller, R S; Unterer, S

2017-06-03

Canine circovirus (CanineCV) has been detected in some dogs with severe haemorrhagic diarrhoea, but its pathogenic role is unclear. This study evaluated a suspected association between the presence of CanineCV and acute haemorrhagic diarrhoea syndrome (AHDS) in dogs. The prevalence of CanineCV in dogs with AHDS was compared with that in healthy dogs and those infected with canine parvovirus (CPV). Additionally, time to recovery and mortality rate were compared between CanineCV-positive and CanineCV-negative dogs. Faecal samples of dogs with AHDS (n=55), healthy dogs (n=66) and dogs infected with CPV (n=54) were examined by two real-time TaqMan PCR assays targeting the replicase and capsid genes of CanineCV. CanineCV was detected in faecal samples of two dogs with AHDS, three healthy controls and seven dogs infected with CPV. Among the three groups, there was no significant difference in prevalence of CanineCV. CPV-infected animals that were coinfected with CanineCV had a significantly higher mortality rate compared with those negative for CanineCV. CanineCV does not appear to be the primary causative agent of AHDS in dogs, but might play a role as a negative co-factor in disease outcome in dogs with CPV infection. British Veterinary Association.

Rediscovering the wound haematoma as a site of haemostasis during major arterial haemorrhage

PubMed Central

White, N.J.; Mehic, E.; Wang, X.; Chien, D.; Lim, E.; St. John, A.E.; Stern, S.A.; Mourad, P.D.; Rieger, M.; Fries, D.; Martinowitz, U.

2015-01-01

Background Treatments for major internal bleeding after injury include permissive hypotension to decrease the rate of blood loss, intravenous infusion of plasma or clotting factors to improve clot formation, and rapid surgical haemostasis or arterial embolization to control bleeding vessels. Yet, little is known regarding major internal arterial haemostasis, or how these commonly-used treatments might influence haemostasis. Objectives (1) Use a swine model of femoral artery bleeding to understand the perivascular haemostatic response to contained arterial haemorrhage. (2) Directly confirm the association between hemodynamics and bleeding velocity. (3) Observe the feasibility of delivering an activated clotting factor directly to internal sites of bleeding using a simplified angiographic approach. Methods Ultrasound was used to measure bleeding velocity and in vivo clot formation by elastography in a swine model of contained femoral artery bleeding with fluid resuscitation. A swine model of internal pelvic and axillary artery haemorrhage was also used to demonstrate feasibility of local delivery of an activated clotting factor. Results In this model, clots formed slowly within the peri-wound hematoma , but eventually containing the bleeding. Central hemodynamics correlated positively with bleeding velocity. Infusion of recombinant human activated Factor VII into the injured artery nearby the site of major internal haemorrhage in the pelvis and axillae was feasible. Conclusions We rediscover that clot formation within the peri-wound haematoma is an integral component of haemostasis and a feasible target for treatment of major internal bleeding using activated clotting factors delivered using a simplified angiographic approach. PMID:26414624

Impact of NICE guidance on rates of haemorrhage after tonsillectomy: an evaluation of guidance issued during an ongoing national tonsillectomy audit.

PubMed

Audit, National Prospective Tonsillectomy

2008-08-01

The National Institute for Health and Clinical Excellence (NICE) issued guidance on surgical techniques for tonsillectomy during a national audit of surgical practice and postoperative complications. To assess the impact of the guidance on tonsillectomy practice and outcomes. An interrupted time-series analysis of routinely collected Hospital Episodes Statistics data, and an analysis of longitudinal trends in surgical technique using data from the National Prospective Tonsillectomy Audit. Patients undergoing tonsillectomy in English NHS hospitals between January 2002 and December 2004. Postoperative haemorrhage within 28 days. The rate of haemorrhage increased by 0.5% per year from 2002, reaching 6.4% when the guidance was published. After publication, the rate of haemorrhage fell immediately to 5.7% (difference 0.7%: 95% CI -1.3% to 0.0%) and the rate of increase appeared to have stopped. Data from the National Prospective Tonsillectomy Audit showed that the fall coincided with a shift in surgical techniques, which was consistent with the guidance. NICE guidance influenced surgical tonsillectomy technique and in turn produced an immediate fall in postoperative haemorrhage. The ongoing national audit and strong support from the surgical specialist association may have aided its implementation.

Guideline for the management of terminal haemorrhage in palliative care patients with advanced cancer discharged home for end-of-life care.

PubMed

Ubogagu, Edith; Harris, Dylan G

2012-12-01

Terminal haemorrhage is a rare and distressing emergency in palliative oncology. We present an algorithm for the management of terminal haemorrhage in patients likely to receive end-of-life care at home, based on a literature review of the management of terminal haemorrhage for patients with advanced cancer, where a DNAR (do not attempt resuscitation) order is in place and the patient wishes to die at home. A literature review was conducted to identify literature on the management of terminal haemorrhage in patients with advanced cancer who are no longer amenable to active interventional/invasive procedures. Electronic databases, the grey literature, local guidelines from hospitals and hospices, and online web portals were all searched systematically. The literature review was used to formulate a management algorithm. The evidence base is very limited. A three-step practical algorithm is suggested: preparing for the event, managing the event ('ABC') and 'aftercare'. Step 1 involves the identification and optimisation of risk factors. Step 2 (the event) consists of A (assure and re-assure the patient), B (be there - above all stay with the patient) and C (comfort, calm, consider dark towels and anxiolytics if possible). Step 3 (the aftercare) involves the provision of practical and psychological support to those involved including relatives and professionals. Terminal haemorrhage is a rare yet highly feared complication of advanced cancer, for which there is a limited evidence base to guide management. The suggested three-step approach to managing this situation gives professionals a logical framework within which to work.

Viral haemorrhagic fevers imported into non-endemic countries: risk assessment and management.

PubMed

Bannister, Barbara

2010-01-01

Viral haemorrhagic fevers (VHFs) are severe infections capable of causing haemorrhagic disease and fatal multi-organ failure. Crimean-Congo, Marburg, Ebola and Lassa viruses cause both sporadic cases and large epidemics over wide endemic areas. Original articles and reviews identified by PubMed search and personal reading; European and United States national guidance and legislation. World Health Organization information, documents and reports. VHFs cause significant morbidity and mortality in their endemic areas; they can cause healthcare-related infections, and their broad diversity and range are increasingly recognized. There is uncertainty about the risks presented by VHFs in non-endemic countries, particularly in healthcare environments. Consensus on the best modes of care and infection control are only slowly emerging. With increasing commerce in rural and low-income areas, VHF outbreaks increasingly expand, causing social and economic damage. New ecologies, viral strains and clinical syndromes are being discovered. There is a great need for rapid diagnostic tests and effective antiviral treatments. Vaccine development programmes are challenged by multiple viral strains and the need for trials in rural communities.

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial.

PubMed

Hanley, Daniel F; Lane, Karen; McBee, Nichol; Ziai, Wendy; Tuhrim, Stanley; Lees, Kennedy R; Dawson, Jesse; Gandhi, Dheeraj; Ullman, Natalie; Mould, W Andrew; Mayo, Steven W; Mendelow, A David; Gregson, Barbara; Butcher, Kenneth; Vespa, Paul; Wright, David W; Kase, Carlos S; Carhuapoma, J Ricardo; Keyl, Penelope M; Diener-West, Marie; Muschelli, John; Betz, Joshua F; Thompson, Carol B; Sugar, Elizabeth A; Yenokyan, Gayane; Janis, Scott; John, Sayona; Harnof, Sagi; Lopez, George A; Aldrich, E Francois; Harrigan, Mark R; Ansari, Safdar; Jallo, Jack; Caron, Jean-Louis; LeDoux, David; Adeoye, Opeolu; Zuccarello, Mario; Adams, Harold P; Rosenblum, Michael; Thompson, Richard E; Awad, Issam A

2017-02-11

Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9

Postoperative haemorrhage following transurethral resection of the prostate (TURP) and photoselective vaporisation of the prostate (PVP)

PubMed Central

Lynch, Mark; Sriprasad, Seshadri; Subramonian, Kesavapillai; Thompson, Peter

2010-01-01

INTRODUCTION Intractable haemorrhage after endoscopic surgery, including transurethral resection of the prostate (TURP) and photoselective vaporisation of the prostate (PVP), is uncommon but a significant and life-threatening problem. The knowledge and technical experience to deal with this complication may not be wide-spread among urologists and trainees. We describe our series of TURPs and PVPs and the incidence of postoperative bleeding requiring intervention. PATIENTS AND METHODS We retrospectively reviewed 437 TURPs and 590 PVPs over 3 years in our institution. We describe the conservative, endoscopic and open prostatic packing techniques used for patients who experienced postoperative bleeding. RESULTS Of 437 TURPs, 19 required endoscopic intervention for postoperative bleeding. Of 590 PVPs, two patients were successfully managed endoscopically for delayed haemorrhage at 7 and 13 days post-surgery, respectively. In one TURP and one PVP patient, endoscopic management was insufficient to control postoperative haemorrhage and open exploration and packing of the prostatic cavity was performed. CONCLUSIONS Significant bleeding after endoscopic prostatic surgery is still a potentially life-threatening complication. Prophylactic measures have been employed to reduce peri-operative bleeding but persistent bleeding post-endoscopic prostatic surgery should be treated promptly to prevent the risk of rapid deterioration. We demonstrated that the technique of open prostate packing may be life-saving. PMID:20522311

Aneurysmal subarachnoid haemorrhage in Parry–Rhomberg syndrome

PubMed Central

Kuechler, Derek; Kaliaperumal, Chandrasekaran; Hassan, Alfrazdaq; Fanning, Noel; Wyse, Gerry; O’Sullivan, Michael

2011-01-01

Parry–Romberg syndrome (PRS) or progressive hemi facial atrophy syndrome is a rare condition of unknown aetiology that is characterised by progressive unilateral facial and cranial atrophic changes of skin, subcutaneous tissues and bone. The authors describe a 37-year-old female with a history of PRS, who presented with a subarachnoid haemorrhage secondary to rupture of a 9 mm fusiform aneurysm of the posterior cerebral artery. There was an associated external carotid arterio-venous fistula noted with this aneurysm. The aneurysm was treated by endovascular route and was successfully coiled. Follow-up angiogram revealed spontaneous resolution of the fistula with good occlusion of the aneurysm. The aetio-pathogenesis of this rare occurrence, literature review and its management is discussed. PMID:22674607

Skin rash, headache and abnormal behaviour: unusual presentation of intracranial haemorrhage in dengue fever

PubMed Central

Wani, Abdul Majid; Mejally, Mousa Ali Al; Hussain, Waleed Mohd; Maimani, Wail Al; Hanif, Sadia; Khoujah, Amer Mohd; Siddiqi, Ahmad; Akhtar, Mubeena; Bafaraj, Mazen G; Fareed, Khurram

2010-01-01

Dengue viral infections are one of the most important mosquito borne diseases in the world. The dengue virus is a single stranded RNA virus belonging to the Flaviviridae family. There are four serotypes (DEN 1–4) classified according to biological and immunological criteria. Patients may be asymptomatic or their condition may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide and 2.5 billion people are at risk. At present, dengue is endemic in 112 countries. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. We present an interesting case of dengue fever with headache, skin rash and abnormal behaviour who had a massive intracranial haemorrhage with fatal outcome. PMID:22242067

Haemoglobin scavenging after subarachnoid haemorrhage.

PubMed

Durnford, A; Dunbar, J; Galea, J; Bulters, D; Nicoll, J A R; Boche, D; Galea, I

2015-01-01

Rapid and effective clearance of cell-free haemoglobin after subarachnoid haemorrhage (SAH) is important to prevent vasospasm and neurotoxicity and improve long-term outcome. Haemoglobin is avidly bound by haptoglobin, and the complex is cleared by CD163 expressed on the membrane surface of macrophages. We studied the kinetics of haemoglobin and haptoglobin in cerebrospinal fluid after SAH. We show that haemoglobin levels rise gradually after SAH. Haptoglobin levels rise acutely with aneurysmal rupture as a result of injection of blood into the subarachnoid space. Although levels decline as haemoglobin scavenging occurs, complete depletion of haptoglobin does not occur and levels start rising again, indicating saturation of CD163 sites available for haptoglobin-haemoglobin clearance. In a preliminary neuropathological study we demonstrate that meningeal CD163 expression is upregulated after SAH, in keeping with a proinflammatory state. However, loss of CD163 occurs in meningeal areas with overlying blood compared with areas without overlying blood. Becauses ADAM17 is the enzyme responsible for shedding membrane-bound CD163, its inhibition may be a potential therapeutic strategy after SAH.

Amplatzer Vascular Plugs Versus Coils for Embolization of Pulmonary Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia.

PubMed

Tau, Noam; Atar, Eliyahu; Mei-Zahav, Meir; Bachar, Gil N; Dagan, Tamir; Birk, Einat; Bruckheimer, Elchanan

2016-08-01

Coil embolization of pulmonary arteriovenous malformations (PAVMs) has a high re-canalization/re-perfusion rate. Embolization with Amplatzer plugs has been previously described, but the long-term efficacy is not established. This study reports the experience of a referral medical center with the use of coils and Amplatzer plugs for treating PAVMs in patients with hereditary hemorrhagic telangiectasia. The study was approved by the Institutional Review Board with waiver of informed consent. The cohort included all patients who underwent PAVM embolization in 2004-2014 for whom follow-up imaging scans were available. The medical files were retrospectively reviewed for background data, embolization method (coils, Amplatzer plugs, both), and complications. Re-canalization of treated PAVMs was assessed from intrapulmonary angiograms (following percutaneous procedures) or computed tomography angiograms. Fisher's exact test and Pearson Chi-squared test or t test were used for statistical analysis, with significance at p < 0.05. 16 patients met the study criteria. Imaging scans were available for 63 of the total 110 PAVMs treated in 41 procedures. Coils were used for embolization in 37 PAVMs, Amplatzer plugs in 21, and both in five. Median follow-up time was 7.7 years (range 1.4-18.9). Re-canalization was detected in seven vessels, all treated with coils; there were no cases of re-canalization in plug-occluded vessels (p = 0.0413). The use of Amplatzer plugs for the embolization of PAVMs in patients with hemorrhagic telangiectasia is associated with a significantly lower rate of re-canalization of feeding vessels than coils. Long-term prospective studies are required to confirm these findings.

Pathogenesis of arteriovenous malformations in the absence of endoglin.

PubMed

Mahmoud, Marwa; Allinson, Kathleen R; Zhai, Zhenhua; Oakenfull, Rachael; Ghandi, Pranita; Adams, Ralf H; Fruttiger, Marcus; Arthur, Helen M

2010-04-30

Arteriovenous malformations (AVMs) result in anomalous direct blood flow between arteries and veins, bypassing the normal capillary bed. Depending on size and location, AVMs may lead to severe clinical effects including systemic cyanosis (pulmonary AVMs), hemorrhagic stroke (cerebral AVMs) and high output cardiac failure (hepatic AVMs). The factors leading to AVM formation are poorly understood, but patients with the familial disease hereditary hemorrhagic telangiectasia (HHT) develop AVMs at high frequency. As most HHT patients have mutations in ENG (endoglin) or ACVRL1 (activin receptor-like kinase 1), a better understanding of the role of these genes in vascular development is likely to reveal the etiology of AVM formation. Using a mouse with a conditional mutation in the Eng gene, we investigated the sequence of abnormal cellular events occurring during development of an AVM. In the absence of endoglin, subcutaneous Matrigel implants in adult mice were populated by reduced numbers of new blood vessels compared with controls, and resulted in local venous enlargement (venomegaly). To investigate abnormal vascular responses in more detail, we turned to the more readily accessible vasculature of the neonatal retina. Endoglin-deficient retinas exhibited delayed remodeling of the capillary plexus, increased proliferation of endothelial cells and localized AVMs. Muscularization of the resulting arteriovenous shunts appeared to be a secondary response to increased blood flow. AVMs develop when an angiogenic stimulus is combined with endoglin depletion. Moreover, AVM formation appears to result from the combination of delayed vascular remodeling and an inappropriate endothelial cell proliferation response in the absence of endoglin.

Crystallization and preliminary X-ray studies of a non-haemorrhagic fibrin(ogen)olytic metalloproteinase from the venom of Agkistrodon acutus

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

Hou, Jing; Li, Ming; Chen, Jiashu

Crystals of a non-haemorrhagic fibrin(ogen)olytic metalloproteinase from the venom of A. acutus have been obtained and characterized by X-ray diffraction. A non-haemorrhagic fibrin(ogen)olytic metalloproteinase from the venom of Agkistrodon acutus has been crystallized by the hanging-drop method. The crystals belong to space group P3{sub 1}21, with unit-cell parameters a = b = 80.57, c = 66.77 Å and one molecule in the asymmetric unit. X-ray diffraction data were collected to 1.86 Å resolution.

Blood, sweat and tears: androgenic-anabolic steroid misuse and recurrent primary post-tonsillectomy haemorrhage

PubMed Central

Fox, Richard; Varadharajan, Kiran; Patel, Bhavesh; Beegun, Issa

2014-01-01

A 30-year-old male body builder and androgenic-anabolic steroid and insulin abuser was admitted for day case elective tonsillectomy (bipolar). He returned with primary post-tonsillectomy haemorrhage 18 h after the operation and required bipolar cautery to the multiple small bleeding points in the right and left tonsillar fossa. Thorough coagulation screen was normal. Recurrent primary haemorrhage occurred 3 h post-operatively requiring immediate surgical intervention, removal of the inferior poles, precautionary throat packs, intubation and observation on the intensive treatment unit (ITU). Re-examination in theatre revealed a bleeding left superior pole that was under-run to achieve haemostasis and the patient returned to ITU. Hypertensive episodes were noted in the emergency department and intraoperatively including one recording >200 mm Hg. Haemostasis was eventually achieved once the blood pressure was adequately controlled. A slow wean of steroids was also instigated and the patient was managed on a surgical ward for 2 weeks post-tonsillectomy. PMID:25398921

Blood, sweat and tears: androgenic-anabolic steroid misuse and recurrent primary post-tonsillectomy haemorrhage.

PubMed

Fox, Richard; Varadharajan, Kiran; Patel, Bhavesh; Beegun, Issa

2014-11-14

A 30-year-old male body builder and androgenic-anabolic steroid and insulin abuser was admitted for day case elective tonsillectomy (bipolar). He returned with primary post-tonsillectomy haemorrhage 18 h after the operation and required bipolar cautery to the multiple small bleeding points in the right and left tonsillar fossa. Thorough coagulation screen was normal. Recurrent primary haemorrhage occurred 3 h post-operatively requiring immediate surgical intervention, removal of the inferior poles, precautionary throat packs, intubation and observation on the intensive treatment unit (ITU). Re-examination in theatre revealed a bleeding left superior pole that was under-run to achieve haemostasis and the patient returned to ITU. Hypertensive episodes were noted in the emergency department and intraoperatively including one recording >200 mm Hg. Haemostasis was eventually achieved once the blood pressure was adequately controlled. A slow wean of steroids was also instigated and the patient was managed on a surgical ward for 2 weeks post-tonsillectomy. 2014 BMJ Publishing Group Ltd.

Prehospital antiplatelet use and functional status on admission of patients with non-haemorrhagic moyamoya disease: a nationwide retrospective cohort study (J-ASPECT study)

PubMed Central

Onozuka, Daisuke; Hagihara, Akihito; Nishimura, Kunihiro; Kada, Akiko; Nakagawara, Jyoji; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Toyoda, Kazunori; Matsuda, Shinya; Suzuki, Akifumi; Kataoka, Hiroharu; Nakamura, Fumiaki; Kamitani, Satoru; Nishimura, Ataru; Kurogi, Ryota; Sayama, Tetsuro; Iihara, Koji

2016-01-01

Objectives To elucidate the association between antiplatelet use in patients with non-haemorrhagic moyamoya disease before hospital admission and good functional status on admission in Japan. Design Retrospective, multicentre, non-randomised, observational study. Setting Nationwide registry data in Japan. Participants A total of 1925 patients with non-haemorrhagic moyamoya disease admitted between 1 April 2012 and 31 March 2014 in Japan. Main outcome measure We performed propensity score-matched analysis to examine the association between prehospital antiplatelet use and no significant disability on hospital admission, as defined by a modified Rankin Scale score of 0 or 1. Results Propensity-matched patients who received prehospital antiplatelet drugs were associated with a good outcome on hospital admission (OR adjusted for all covariates, 3.82; 95% CI 1.22 to 11.99) compared with those who did not receive antiplatelet drugs prior to hospital admission. Conclusions Prehospital antiplatelet use was significantly associated with good functional status on hospital admission among patients with non-haemorrhagic moyamoya disease in Japan. Our results suggest that prehospital antiplatelet use should be considered when evaluating outcomes of patients with non-haemorrhagic moyamoya disease. PMID:27008684

Automatic telangiectasia analysis in dermoscopy images using adaptive critic design.

PubMed

Cheng, B; Stanley, R J; Stoecker, W V; Hinton, K

2012-11-01

Telangiectasia, tiny skin vessels, are important dermoscopy structures used to discriminate basal cell carcinoma (BCC) from benign skin lesions. This research builds off of previously developed image analysis techniques to identify vessels automatically to discriminate benign lesions from BCCs. A biologically inspired reinforcement learning approach is investigated in an adaptive critic design framework to apply action-dependent heuristic dynamic programming (ADHDP) for discrimination based on computed features using different skin lesion contrast variations to promote the discrimination process. Lesion discrimination results for ADHDP are compared with multilayer perception backpropagation artificial neural networks. This study uses a data set of 498 dermoscopy skin lesion images of 263 BCCs and 226 competitive benign images as the input sets. This data set is extended from previous research [Cheng et al., Skin Research and Technology, 2011, 17: 278]. Experimental results yielded a diagnostic accuracy as high as 84.6% using the ADHDP approach, providing an 8.03% improvement over a standard multilayer perception method. We have chosen BCC detection rather than vessel detection as the endpoint. Although vessel detection is inherently easier, BCC detection has potential direct clinical applications. Small BCCs are detectable early by dermoscopy and potentially detectable by the automated methods described in this research. © 2011 John Wiley & Sons A/S.

A single ataxia telangiectasia gene with a product similar to PI-3 kinase.

PubMed

Savitsky, K; Bar-Shira, A; Gilad, S; Rotman, G; Ziv, Y; Vanagaite, L; Tagle, D A; Smith, S; Uziel, T; Sfez, S; Ashkenazi, M; Pecker, I; Frydman, M; Harnik, R; Patanjali, S R; Simmons, A; Clines, G A; Sartiel, A; Gatti, R A; Chessa, L; Sanal, O; Lavin, M F; Jaspers, N G; Taylor, A M; Arlett, C F; Miki, T; Weissman, S M; Lovett, M; Collins, F S; Shiloh, Y

1995-06-23

A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer.

Control of cell respiration by nitric oxide in Ataxia Telangiectasia lymphoblastoid cells.

PubMed

Masci, Alessandra; Mastronicola, Daniela; Arese, Marzia; Piane, Maria; De Amicis, Andrea; Blanck, Thomas J J; Chessa, Luciana; Sarti, Paolo

2008-01-01

Ataxia Telangiectasia (AT) patients are particularly sensitive to oxidative-nitrosative stress. Nitric oxide (NO) controls mitochondrial respiration via the reversible inhibition of complex IV. The mitochondrial response to NO of AT lymphoblastoid cells was investigated. Cells isolated from three patients and three intrafamilial healthy controls were selected showing within each group a normal diploid karyotype and homogeneous telomere length. Different complex IV NO-inhibition patterns were induced by varying the electron flux through the respiratory chain, using exogenous cell membrane permeable electron donors. Under conditions of high electron flux the mitochondrial NO inhibition of respiration was greater in AT than in control cells (P< or =0.05). This property appears peculiar to AT, and correlates well to the higher concentration of cytochrome c detected in the AT cells. This finding is discussed on the basis of the proposed mechanism of reaction of NO with complex IV. It is suggested that the peculiar response of AT mitochondria to NO stress may be relevant to the mitochondrial metabolism of AT patients.

Acute post-stroke blood pressure relative to premorbid levels in intracerebral haemorrhage versus major ischaemic stroke: a population-based study

PubMed Central

Fischer, Urs; Cooney, Marie Therese; Bull, Linda M; Silver, Louise E; Chalmers, John; Anderson, Craig S; Mehta, Ziyah; Rothwell, Peter M

2014-01-01

Summary Background It is often assumed that blood pressure increases acutely after major stroke, resulting in so-called post-stroke hypertension. In view of evidence that the risks and benefits of blood pressure-lowering treatment in acute stroke might differ between patients with major ischaemic stroke and those with primary intracerebral haemorrhage, we compared acute-phase and premorbid blood pressure levels in these two disorders. Methods In a population-based study in Oxfordshire, UK, we recruited all patients presenting with stroke between April 1, 2002, and March 31, 2012. We compared all acute-phase post-event blood pressure readings with premorbid readings from 10-year primary care records in all patients with acute major ischaemic stroke (National Institutes of Health Stroke Scale >3) versus those with acute intracerebral haemorrhage. Findings Of 653 consecutive eligible patients, premorbid and acute-phase blood pressure readings were available for 636 (97%) individuals. Premorbid blood pressure (total readings 13 244) had been measured on a median of 17 separate occasions per patient (IQR 8–31). In patients with ischaemic stroke, the first acute-phase systolic blood pressure was much lower than after intracerebral haemorrhage (158·5 mm Hg [SD 30·1] vs 189·8 mm Hg [38·5], p<0·0001; for patients not on antihypertensive treatment 159·2 mm Hg [27·8] vs 193·4 mm Hg [37·4], p<0·0001), was little higher than premorbid levels (increase of 10·6 mm Hg vs 10-year mean premorbid level), and decreased only slightly during the first 24 h (mean decrease from <90 min to 24 h 13·6 mm Hg). By contrast with findings in ischaemic stroke, the mean first systolic blood pressure after intracerebral haemorrhage was substantially higher than premorbid levels (mean increase of 40·7 mm Hg, p<0·0001) and fell substantially in the first 24 h (mean decrease of 41·1 mm Hg; p=0·0007 for difference from decrease in ischaemic stroke). Mean systolic blood pressure also

Acute retrobulbar haemorrhage: An ophthalmologic emergency for the emergency physician.

PubMed

Pamukcu, Can; Odabaşı, Mahmut

2015-07-01

Acute retrobulbar haemorrhage (ARBH) is a rare ophthalmic emergency observed following blunt eye trauma. Multiple trauma and loss of consciousness can hide symptoms of ARBH. Rapid diagnosis and immediate lateral canthotomy and cantholysis must be performed to prevent permanent visual loss in patients. Medical treatment can be added to surgical therapy. Lateral canthotomy and cantholysis are simple procedures that can be performed by emergency physicians. In this report, it was aimed to present a case with post-traumatic ARBH and provide general knowledge about the diagnosis, follow-up and treatment of ARBH.

The effect of tranexamic acid on the risk of death and hysterectomy in women with post-partum haemorrhage: statistical analysis plan for the WOMAN trial.

PubMed

Shakur, Haleema; Roberts, Ian; Edwards, Philip; Elbourne, Diana; Alfirevic, Zarko; Ronsmans, Carine

2016-05-17

Severe haemorrhage is a leading cause of maternal death worldwide. Most haemorrhage deaths occur soon after childbirth. Severe post-partum bleeding is sometimes managed by the surgical removal of the uterus (hysterectomy). Death and hysterectomy are important health consequences of post-partum haemorrhage, and clinical trials of interventions aimed at preventing these outcomes are needed. The World Maternal Antifibrinolytic trial aims to determine the effect of tranexamic acid on death, hysterectomy and other health outcomes in women with post-partum haemorrhage. It is an international, multicentre, randomised trial. Approximately 20,000 women with post-partum haemorrhage will be randomly allocated to receive an intravenous injection of either tranexamic acid or matching placebo in addition to usual care. The primary outcome measure is a composite of death in hospital or hysterectomy within 42 days of delivery. The cause of death will be described. Secondary outcomes include death, death due to bleeding, hysterectomy, thromboembolic events, blood transfusion, surgical and radiological interventions, complications, adverse events and quality of life. The health status and occurrence of thromboembolic events in breastfed babies will also be reported. We will conduct subgroup analyses for the primary outcome by time to treatment, type of delivery and cause of haemorrhage. We will conduct an analysis of treatment effect adjusted for baseline risk. The World Maternal Antifibrinolytic trial should provide reliable evidence for the efficacy of tranexamic acid in the prevention of death, hysterectomy and other outcomes that are important to patients. We present a protocol update and the statistical analysis plan for the trial. Current Controlled Trials ISRCTN76912190 (Registration date 08 December 2008), Clinicaltrials.gov NCT00872469 (Registration date 30 March 2009) and Pan African Clinical Trials Registry: PACTR201007000192283 (Registration date 02 September 2010).

Amplatzer Vascular Plugs Versus Coils for Embolization of Pulmonary Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia

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

Tau, Noam, E-mail: taunoam@gmail.com; Atar, Eliyahu; Mei-Zahav, Meir

PurposeCoil embolization of pulmonary arteriovenous malformations (PAVMs) has a high re-canalization/re-perfusion rate. Embolization with Amplatzer plugs has been previously described, but the long-term efficacy is not established. This study reports the experience of a referral medical center with the use of coils and Amplatzer plugs for treating PAVMs in patients with hereditary hemorrhagic telangiectasia.MethodsThe study was approved by the Institutional Review Board with waiver of informed consent. The cohort included all patients who underwent PAVM embolization in 2004–2014 for whom follow-up imaging scans were available. The medical files were retrospectively reviewed for background data, embolization method (coils, Amplatzer plugs, both),more » and complications. Re-canalization of treated PAVMs was assessed from intrapulmonary angiograms (following percutaneous procedures) or computed tomography angiograms. Fisher’s exact test and Pearson Chi-squared test or t test were used for statistical analysis, with significance at p < 0.05.Results16 patients met the study criteria. Imaging scans were available for 63 of the total 110 PAVMs treated in 41 procedures. Coils were used for embolization in 37 PAVMs, Amplatzer plugs in 21, and both in five. Median follow-up time was 7.7 years (range 1.4–18.9). Re-canalization was detected in seven vessels, all treated with coils; there were no cases of re-canalization in plug-occluded vessels (p = 0.0413).ConclusionThe use of Amplatzer plugs for the embolization of PAVMs in patients with hemorrhagic telangiectasia is associated with a significantly lower rate of re-canalization of feeding vessels than coils. Long-term prospective studies are required to confirm these findings.« less

Ataxia Telangiectasia in Siblings: Oral Motor and Swallowing Characterization.

PubMed

Rondon-Melo, Silmara; de Almeida, Isabel Junqueira; Andrade, Claudia Regina Furquim de; Sassi, Fernanda Chiarion; Molini-Avejonas, Daniela Regina

2017-07-12

BACKGROUND The body of literature on oral motor and swallowing disorders in patients with ataxia telangiectasia (AT) is limited. CASE REPORT The purpose of this study was to characterize oral motor and swallowing disorders in two siblings with AT, based on oral motor and swallowing assessments. Specific procedures were applied for oral motor and swallowing assessments and both patients underwent videofluoroscopy (VFS). Case 1 presented vocal instability, change in postural control during feeding; food retention in oral cavity; slower oral transit time; and multiple swallowing (signs for solid and liquid). Case 2 presented parted lips at rest and reduced muscle strength; reduced strength and mobility of the tongue; vocal weakness and instability; reduced speech precision and intelligibility; decreased intonation pattern; food retention in oral cavity during feeding; slower oral transit time; multiple swallowing (signs for solid and liquid); poor bolus ejection; incoordination and difficulty in controlling the sips of water taken from the cup; altered cervical auscultation after swallowing and respiratory distress (liquid and puree). For both patients VFS results revealed laryngeal penetration for liquid. CONCLUSIONS Although the literature describes the occurrence of dysarthria and swallowing disorders in patients with AT, little attention has been given to describing which oral motor deficits are responsible for these disorders. Early identification of swallowing alterations and rehabilitation could decrease the risk of aspiration pneumonia. Future studies are necessary in order to investigate the deterioration process of swallowing in AT and the influence of rehabilitation in maintaining functional health.

Subarachnoid Haemorrhage and Sports

PubMed Central

Sousa Nanji, Liliana; Melo, Teresa P.; Canhão, Patrícia; Fonseca, Ana Catarina; Ferro, José Manuel

2015-01-01

Background Some cases of subarachnoid haemorrhage (SAH) have been associated with vigorous physical activity, including sports. Our research aimed to describe the association between SAH and sports and to identify the types of sports that were more frequently found as precipitating factors in a tertiary single-centre SAH register. Methods We retrieved information from a prospectively collected SAH registry and reviewed discharge notes of acute SAH patients admitted to the Stroke Unit of Hospital de Santa Maria, Lisbon, between 1995 and 2014. Results Out of 738 patients included in the analysis, 424 (57.5%) cases of SAH were preceded by physical activity. Nine cases (1.2%) were associated with sports, namely running (2 cases), aerobics (2 cases), cycling, body balance, dance, surf and windsurf. Patients with SAH while practicing sports were younger than controls (average age 43.1 vs. 57.0 years; p = 0.007). In 1 patient, there was a report of trauma to the neck. Patients in the sports group only had Hunt and Hess scale grades 1 (11.1%) or 2 (88.9%) at admission, while patients in the control group had a wider distribution in severity. Conclusions Our findings indicate that SAH precipitated by sports is not very frequent and is uncommonly related to trauma. Patients who suffered SAH associated with sports were younger and apparently had a milder clinical presentation. PMID:26648972

Subarachnoid Haemorrhage and Sports.

PubMed

Sousa Nanji, Liliana; Melo, Teresa P; Canhão, Patrícia; Fonseca, Ana Catarina; Ferro, José Manuel

2015-01-01

Some cases of subarachnoid haemorrhage (SAH) have been associated with vigorous physical activity, including sports. Our research aimed to describe the association between SAH and sports and to identify the types of sports that were more frequently found as precipitating factors in a tertiary single-centre SAH register. We retrieved information from a prospectively collected SAH registry and reviewed discharge notes of acute SAH patients admitted to the Stroke Unit of Hospital de Santa Maria, Lisbon, between 1995 and 2014. Out of 738 patients included in the analysis, 424 (57.5%) cases of SAH were preceded by physical activity. Nine cases (1.2%) were associated with sports, namely running (2 cases), aerobics (2 cases), cycling, body balance, dance, surf and windsurf. Patients with SAH while practicing sports were younger than controls (average age 43.1 vs. 57.0 years; p = 0.007). In 1 patient, there was a report of trauma to the neck. Patients in the sports group only had Hunt and Hess scale grades 1 (11.1%) or 2 (88.9%) at admission, while patients in the control group had a wider distribution in severity. Our findings indicate that SAH precipitated by sports is not very frequent and is uncommonly related to trauma. Patients who suffered SAH associated with sports were younger and apparently had a milder clinical presentation.

Pulmonary artery haemorrhage in newborn calves following bluetongue virus serotype 8 experimental infections of pregnant heifers.

PubMed

Martinelle, Ludovic; Dal Pozzo, Fabiana; Sarradin, Pierre; De Leeuw, Ilse; De Clercq, Kris; Thys, Christine; Thiry, Etienne; Saegerman, Claude

2013-12-27

The emergence of bluetongue disease (BT) among livestock in Europe in 2006 raised many questions including the occurrence and epidemiological significance of foetal infections in cattle. To clarify these aspects, vaccinated and unvaccinated pregnant heifers were sequentially infected twice in an isolation facility (biosafety level 3) with a northern European outbreak strain of Bluetongue virus serotype 8 (BTV-8). The study was terminated 2 months after calving with necropsy of the dams and their offspring. The cattle were monitored throughout the study by clinical scoring and for the presence of circulating neutralising antibodies, and after calving for the presence of infectious virus and viral RNA in blood and milk. Four calves, one born from a vaccinated dam and three from non-vaccinated ones, that were infected at 120 days of gestation had obvious haemorrhage of the pulmonary artery at necropsy. Although haemorrhage of the pulmonary artery is highly characteristic of BT, viral RNA was not detected in any of these calves. Furthermore, although none of the calves born from heifers infected prior to mid-gestation had teratogenic BTV typical brain lesions, some had lesions at birth suggestive of in utero BTV infection. Despite the lack of viral RNA detection, the presence of haemorrhage of the pulmonary artery deserves to be reported as a new observation in the context of the multiple investigations having as main subject the BTV placental crossing in cattle. Copyright © 2013 Elsevier B.V. All rights reserved.

Postpartum haemorrhage and eclampsia: differences in knowledge and care-seeking behaviour in two districts of Bangladesh.

PubMed

Kalim, Nahid; Anwar, Iqbal; Khan, Jasmin; Blum, Lauren S; Moran, Allisyn C; Botlero, Roslin; Koblinsky, Marge

2009-04-01

In high- and low-performing districts of Bangladesh, the study explored the demand-side of maternal healthcare by looking at differences in perceived knowledge and care-seeking behaviours of women in relation to postpartum haemorrhage or eclampsia. Haemorrhage and eclampsia are two major causes of maternal mortality in Bangladesh. The study was conducted during July 2006-December 2007. Both postpartum bleeding and eclampsia were recognized by women of different age-groups as severe and life-threatening obstetric complications. However, a gap existed between perception and actual care-seeking behaviours which could contribute to the high rate of maternal deaths associated with these conditions. There were differences in care-seeking practices among women in the two different areas of Bangladesh, which may reflect sociocultural differences, disparities in economic and educational opportunities, and a discrimination in the availability of care.

Pathogenetic mechanisms in dengue haemorrhagic fever: Report of an international collaborative study*

PubMed Central

1973-01-01

In a study of 55 persons with dengue haemorrhagic fever—36 of whom showed the dengue shock syndrome—clinical, haematological, virological, and serological changes were correlated with serial measurements of complement components and immunopathological studies. Viruses dengue-1 or dengue-2 were isolated from the sera of 9 patients. Serological responses indicative of secondary dengue virus infections were observed in 53 patients; 2 (infants) had primary infections. During the acute phase of the disease, dengue antibody titres rose logarithmically. Marked depression of complement components, especially C3, was observed. Activation of both the classical and alternative complement pathways was demonstrated, with depression of both C4 and C3 proactivator levels in most instances, although in some cases it appeared that one mechanism was involved to a greater extent than the other. The level of depression of C3 was correlated with the severity of the disease. Relatively stable transferrin levels indicated that depletion of complement proteins was not primarily due to extravasation. Fibrinogen levels were depressed and fibrinogen split products were found in the plasma. The accumulated data provide further evidence of the central role that activated complement components play in the pathogenesis of dengue haemorrhagic fever. PMID:4575523

Evaluation of an In-house indirect ELISA for detection of antibody against haemorrhagic septicemia in Asian elephants.

PubMed

Tankaew, Pallop; Singh-La, Thawatchai; Titaram, Chatchote; Punyapornwittaya, Veerasak; Vongchan, Preeyanat; Sawada, Takuo; Sthitmatee, Nattawooti

2017-03-01

Pasteurella multocida causes haemorrhagic septicemia in livestock and wild animals, including elephants. The disease has been reported in Asian elephants in India and Sri Lanka, but to date there have been no reported cases in Thailand. ELISA or indirect hemagglutination assays (IHA) have been demonstrated to be able to detect the antibody against the disease in cattle, but no data are available for elephants. The present study reports a novel in-house indirect ELISA for antibody detection of haemorrhagic septicemia in Asian elephants, and evaluates the sensitivity and specificity of the method using a Bayesian approach. The characteristics of ELISA and IHA were analyzed using a one population Bayesian model assuming conditional dependence between these two diagnostic tests. The IHA was performed as recommended by the World Organization for Animal Health (OIE) manual for haemorrhagic septicemia. An in-house indirect ELISA was developed with a heat extract antigen of P. multocida strain M-1404 (serovar B:2) as a coating antigen and rabbit anti-immunoglobulin G conjugated with horseradish peroxidase (eIgG-HRP). The checkerboard titration method was done using elephant sera immunized with P. multocida bacterin and negative sera from colostrum-deprived elephant calves. The concentrations of heat extract antigen (160μg/ml), sample serum (1:100), and eIgG-HRP (1:1000) were optimal for the assay. The calculated cut-off value was 0.103. Of the elephant sera, 50.59% (43/85) were considered seropositive by ELISA. The sensitivity of the ELISA test was higher than that of the IHA test [median=86.5%, 95% posterior probability interval (PPI)=52.5-98.9%] while the specificity was lower (median=54.1%, PPI=43.6-64.7%). The median sensitivity and specificity of IHA were 80.5% (PPI=43.8-98.0%) and 78.4% (PPI=69.0-87.0%), respectively. These findings suggest that our in-house indirect ELISA can be used as a tool to detect the antibody against haemorrhagic septicemia in Asian

Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the Global Burden of Disease Study 2010

PubMed Central

Krishnamurthi, Rita V; Feigin, Valery L; Forouzanfar, Mohammad H; Mensah, George A; Connor, Myles; Bennett, Derrick A; Moran, Andrew E; Sacco, Ralph L; Anderson, Laurie M; Truelsen, Thomas; O’Donnell, Martin; Venketasubramanian, Narayanaswamy; Barker-Collo, Suzanne; Lawes, Carlene M M; Wang, Wenzhi; Shinohara, Yukito; Witt, Emma; Ezzati, Majid; Naghavi, Mohsen; Murray, Christopher

2014-01-01

Summary Background The burden of ischaemic and haemorrhagic stroke varies between regions and over time. With differences in prognosis, prevalence of risk factors, and treatment strategies, knowledge of stroke pathological type is important for targeted region-specific health-care planning for stroke and could inform priorities for type-specific prevention strategies. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010. Methods We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR) to calculate regional and country-specific estimates for ischaemic and haemorrhagic stroke incidence, mortality, mortality-to-incidence ratio, and disability-adjusted life-years (DALYs) lost, by age group (aged <75 years, ≥75 years, and in total) and country income level (high-income and low-income and middle-income) for 1990, 2005, and 2010. Findings We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). Worldwide, the burden of ischaemic and haemorrhagic stroke increased significantly between 1990 and 2010 in terms of the absolute number of people with incident ischaemic and haemorrhagic stroke (37% and 47% increase, respectively), number of deaths (21% and 20% increase), and DALYs lost (18% and 14% increase). In the past two decades in high-income countries, incidence of ischaemic stroke reduced significantly by 13% (95% CI 6–18), mortality by 37% (19–39), DALYs lost by 34% (16–36), and mortality-to-incidence ratios by 21% (10–27). For haemorrhagic stroke, incidence reduced significantly by 19% (1–15), mortality by 38% (32–43), DALYs lost by 39% (32–44

Selective melanocortin MC4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage

PubMed Central

Giuliani, D; Mioni, C; Bazzani, C; Zaffe, D; Botticelli, A R; Capolongo, S; Sabba, A; Galantucci, M; Iannone, A; Grieco, P; Novellino, E; Colombo, G; Tomasi, A; Catania, A; Guarini, S

2007-01-01

Background and purpose: In circulatory shock, melanocortins have life-saving effects likely to be mediated by MC4 receptors. To gain direct insight into the role of melanocortin MC4 receptors in haemorrhagic shock, we investigated the effects of two novel selective MC4 receptor agonists. Experimental approach: Severe haemorrhagic shock was produced in rats under general anaesthesia. Rats were then treated with either the non-selective agonist [Nle4, D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH) or with the selective MC4 agonists RO27-3225 and PG-931. Cardiovascular and respiratory functions were continuously monitored for 2 h; survival rate was recorded up to 24 h. Free radicals in blood were measured using electron spin resonance spectrometry; tissue damage was evaluated histologically 25 min or 24 h after treatment. Key results: All shocked rats treated with saline died within 30-35 min. Treatment with NDP-α-MSH, RO27-3225 and PG-931 produced a dose-dependent (13-108 nmol kg-1 i.v.) restoration of cardiovascular and respiratory functions, and improved survival. The three melanocortin agonists also markedly reduced circulating free radicals relative to saline-treated shocked rats. All these effects were prevented by i.p. pretreatment with the selective MC4 receptor antagonist HS024. Moreover, treatment with RO27-3225 prevented morphological and immunocytochemical changes in heart, lung, liver, and kidney, at both early (25 min) and late (24 h) intervals. Conclusions and Implications: Stimulation of MC4 receptors reversed haemorrhagic shock, reduced multiple organ damage and improved survival. Our findings suggest that selective MC4 receptor agonists could have a protective role against multiple organ failure following circulatory shock. PMID:17245369

First dengue haemorrhagic fever epidemic in the Americas, 1981: insights into the causative agent.

PubMed

Rodriguez-Roche, Rosmari; Hinojosa, Yoandri; Guzman, Maria G

2014-12-01

Historical records describe a disease in North America that clinically resembled dengue haemorrhagic fever during the latter part of the slave-trading period. However, the dengue epidemic that occurred in Cuba in 1981 was the first laboratory-confirmed and clinically diagnosed outbreak of dengue haemorrhagic fever in the Americas. At that time, the presumed source of the dengue type 2 strain isolated during this epidemic was considered controversial, partly because of the limited sequence data and partly because the origin of the virus appeared to be southern Asia. Here, we present a molecular characterisation at the whole-genome level of the original strains isolated at different time points during the epidemic. Phylogenetic trees constructed using Bayesian methods indicated that 1981 Cuban strains group within the Asian 2 genotype. In addition, the study revealed that viral evolution occurred during the epidemic - a fact that could be related to the increasing severity from month to month. Moreover, the Cuban strains exhibited particular amino acid substitutions that differentiate them from the New Guinea C prototype strain as well as from dengue type 2 strains isolated globally.

Getting an evidence-based post-partum haemorrhage policy into practice.

PubMed

Cameron, Carolyn A; Roberts, Christine L; Bell, Jane; Fischer, Wendy

2007-06-01

Post-partum haemorrhage (PPH) is a potentially life-threatening complication of childbirth occurring in up to 10% of births. The NSW Department of Health (DoH) issued a new evidence-based policy (Framework for Prevention, Early Recognition and Management of Post-partum Haemorrhage) in November 2002. Feedback from maternity units indicated that there were deficiencies in the skills and experience is needed to develop the written protocols and local plans of action required by the Framework. All 96 hospitals in NSW that provide care for childbirth were surveyed. A senior midwife completed a semistructured telephone interview. Ninety four per cent of hospitals had PPH policies. Among hospitals that provided a copy of their policy, 83% were dated after the release of the DoH's Framework, but 22% contained an incorrect definition of PPH. Only 71% of respondents in small rural and urban district hospitals recalled receiving a copy of the Framework. There was considerable variation in the frequency of postnatal observations. Key factors that impede local policy development were resources, entrenched practices and centralised policy development. Enabling factors were effective relationships, the DoH policy directive (Framework), education and organisational issues/time. Greater assistance is needed to ensure that hospitals have the capacity to develop a policy applicable to local needs. Maternity hospitals throughout the state provide different levels of care and NSW DoH policy directives should not be 'one size fits all' documents. Earlier recognition of PPH may be facilitated by routine post-partum monitoring of all women and should be consistent throughout the state, regardless of hospital level.

Infrastructure and clinical practice for the detection and management of trauma-associated haemorrhage and coagulopathy.

PubMed

Driessen, A; Schäfer, N; Albrecht, V; Schenk, M; Fröhlich, M; Stürmer, E K; Maegele, M

2015-08-01

Early detection and management of post-traumatic haemorrhage and coagulopathy have been associated with improved outcomes, but local infrastructures, logistics and clinical strategies may differ. To assess local differences in infrastructure, logistics and clinical management of trauma-associated haemorrhage and coagulopathy, we have conducted a web-based survey amongst the delegates to the 15th European Congress of Trauma and Emergency Surgery (ECTES) and the 2nd World Trauma (WT) Congress held in Frankfurt, Germany, 25-27 May 2014. 446/1,540 delegates completed the questionnaire yielding a response rate of 29%. The majority specified to work as consultants/senior physicians (47.3%) in general (36.1%) or trauma/orthopaedic surgery (44.5%) of level I (70%) or level II (19%) trauma centres. Clinical assessment (>80%) and standard coagulation assays (74.6%) are the most frequently used strategies for early detection and monitoring of bleeding trauma patients with coagulopathy. Only 30% of the respondents declared to use extended coagulation assays to better characterise the bleeding and coagulopathy prompted by more individualised treatment concepts. Most trauma centres (69%) have implemented local protocols based on international and national guidelines using conventional blood products, e.g. packed red blood cell concentrates (93.3%), fresh frozen plasma concentrates (93.3%) and platelet concentrates (83%), and antifibrinolytics (100%). 89% considered the continuous intake of anticoagulants including "new oral anticoagulants" and platelet inhibitors as an increasing threat to bleeding trauma patients. This study confirms differences in infrastructure, logistics and clinical practice for the detection and management of trauma-haemorrhage and trauma-associated coagulopathy amongst international centres. Ongoing work will focus on geographical differences.

Policies for management of postpartum haemorrhage: the HERA cross-sectional study in France.

PubMed

Vendittelli, Françoise; Barasinski, Chloé; Pereira, Bruno; Dreyfus, Michel; Lémery, Didier; Bouvier-Colle, Marie-Hélène

2016-10-01

The principal objective of this study was to describe the policies reported by French maternity units for the prevention and early management of postpartum haemorrhage (PPH). The second objective was to assess their variation according to hospital level and status. Cross-sectional observational study of French maternity units, from January 2010 to April 2011. The medical supervisor (obstetrician or midwife) of participating maternity wards completed a questionnaire designed to ascertain the unit's protocol for preventing and managing PPH after both vaginal and caesarean deliveries at a gestational age >22 weeks (or a birth weight >500g). The main outcome measure was the percentage of units reporting protocols adhering to the principal criteria for adequate management defined by the 2004 French guidelines for PPH. 252 maternity units participated in the survey. Almost all units had a written protocol for PPH (97.2%). For vaginal deliveries, 82.5% of units had a definition of PPH (>500ml) and 92.8% had a policy of preventive oxytocin use. For caesareans, only 23.8% defined PPH (as >1000ml), 68.8% used manual delivery of the placenta, and 76.9% recommended oxytocin injection immediately after the birth. The first-line medication for PPH was oxytocin (96.3%) and the second-line treatment a prostaglandin (97.5%). Level III maternity units had a definition of haemorrhage for vaginal deliveries more often than did other levels of care (P=0.04). Manual removal of the placenta after caesareans was significantly more frequent in level I than level III units (P=0.008) and in private than other types of maternity units. Medical management of haemorrhage did not differ according to level of care or maternity status. The responses by maternity unit supervisors showed significant improvement in the management of PPH accordingly to the 2004 French guidelines, especially for the third stage of labour. This improvement did not differ between hospitals by levels of care or legal

A risk scoring system for prediction of haemorrhagic stroke.

PubMed

Zodpey, S P; Tiwari, R R

2005-01-01

The present pair-matched case control study was carried out at Government Medical College Hospital, Nagpur, India, a tertiary care hospital with the objective to devise and validate a risk scoring system for prediction of hemorrhagic stroke. The study consisted of 166 hospitalized CT scan proved cases of hemorrhagic stroke (ICD 9, 431-432), and a age and sex matched control per case. The controls were selected from patients who attended the study hospital for conditions other than stroke. On conditional multiple logistic regression five risk factors- hypertension (OR = 1.9. 95% Cl = 1.5-2.5). raised scrum total cholesterol (OR = 2.3, 95% Cl = 1.1-4.9). use of anticoagulants and antiplatelet agents (OR = 3.4, 95% Cl =1.1-10.4). past history of transient ischaemic attack (OR = 8.4, 95% Cl = 2.1- 33.6) and alcohol intake (OR = 2.1, 95% Cl = 1.3-3.6) were significant. These factors were ascribed statistical weights (based on regression coefficients) of 6, 8, 12, 21 and 8 respectively. The nonsignificant factors (diabetes mellitus, physical inactivity, obesity, smoking, type A personality, history of claudication, family history of stroke, history of cardiac diseases and oral contraceptive use in females) were not included in the development of scoring system. ROC curve suggested a total score of 21 to be the best cut-off for predicting haemorrhag stroke. At this cut-off the sensitivity, specificity, positive predictivity and Cohen's kappa were 0.74, 0.74, 0.74 and 0.48 respectively. The overall predictive accuracy of this additive risk scoring system (area under ROC curve by Wilcoxon statistic) was 0.79 (95% Cl = 0.73-0.84). Thus to conclude, if substantiated by further validation, this scorincy system can be used to predict haemorrhagic stroke, thereby helping to devise effective risk factor intervention strategy.

OCT Angiography Helps Distinguish Between Proliferative Macular Telangiectasia Type 2 and Neovascular Age-Related Macular Degeneration.

PubMed

Zheng, Fang; Motulsky, Elie H; de Oliveira Dias, João Rafael; de López, Edith Pérez; Gregori, Giovanni; Rosenfeld, Philip J

2018-05-01

To demonstrate the advantage of optical coherence tomography angiography (OCTA) for the diagnosis and management of proliferative macular telangiectasia type 2 (MacTel2) masquerading as neovascular age-related macular degeneration (AMD). This is an observational cases series. Three patients referred with the diagnosis of neovascular AMD were identified in this retrospective study. In addition to color fundus, fluorescein angiography, and spectral-domain OCT (SD-OCT) imaging, SD-OCTA (AngioPlex; Carl Zeiss Meditec, Dublin, CA) was performed. SD-OCTA revealed bilateral parafoveal retinal microvascular changes in three patients and unambiguously confirmed the diagnosis of MacTel2. OCTA is an important tool for the correct diagnosis of MacTel2 in older patients with the concomitant or masquerading diagnosis of AMD. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:303-312.]. Copyright 2018, SLACK Incorporated.

Progress towards the treatment of Ebola haemorrhagic fever.

PubMed

Ströher, Ute; Feldmann, Heinz

2006-12-01

Being highly pathogenic for human and nonhuman primates and the subject of former weapon programmes makes Ebola virus one of the most feared pathogens worldwide today. Due to a lack of licensed pre- and postexposure intervention, the current response depends on rapid diagnostics, proper isolation procedures and supportive care of case patients. Consequently, the development of more specific countermeasures is of high priority for the preparedness of many nations. Over the past years, enhanced research efforts directed to better understand virus replication and pathogenesis have identified potential new targets for intervention strategies. The authors discuss the most promising therapeutic approaches for Ebola haemorrhagic fever as judged by their efficacy in animal models. The current development in this field encourages discussions on how to move some of the experimental approaches towards clinical application.

A Rare Case of Fatal Haemorrhage After Tracheostomy

PubMed Central

Praveen, CV; Martin, A

2007-01-01

Tracheo-arterial fistula after tracheostomy causing massive haemorrhage is fortunately rare, but can be serious and often fatal. Brachiocephalic trunk is commonly at risk of erosion because of its close relation with the trachea. Factors responsible for fistula are pressure from tube rubbing on the trachea and adjacent vessel, infection, malignant neoplastic invasion of a vessel near the trachea and low tracheostomy. We present a rare case of massive arterial bleeding which happened on the second day and recurred on fifth day, because of slippage of the ligature from the thyroid artery, causing aspiration and death. A low tracheostomy below the third ring should be avoided. If there is bleeding, as a first-aid measure the cuff should be over inflated without removing the tracheostomy tube. PMID:17999811

A rare case of Weil's disease with alveolar haemorrhage.

PubMed

Chakrabarti, Abhiram; Nandy, Manab; Pal, Dipankar; Mallik, Sudesna

2014-05-01

Leptospirosis, a disease of protean manifestations occurs sporadically throughout the year with a peak seasonal incidence during the rainy season mimicking other febrile viral illness. In the rare case, the disease leads to renal and hepatic involvement with hemorrhage which may be associated with multisystem organ dysfunction in form of pulmonary, cardiac and central nervous system, when it is known as Weil's disease. Rarely haemorrhagic manifestations are assosciated. Early diagnosis is important as sometimes the disease may be life threatening. Proper antibiotics results in dramatic improvement. We hereby presented a case that had clinical features of Weil's disease with cough, dyspnoea and haemoptysis. Leptospirosis was detected on ELISA testing. Patient was cured rapidly with antibiotics.

The Bulgarian vaccine Crimean-Congo haemorrhagic fever virus strain.

PubMed

Papa, Anna; Papadimitriou, Evangelia; Christova, Iva

2011-03-01

The Crimean-Congo haemorrhagic fever virus (CCHFV) is a 3-segmented RNA virus, which causes disease with a high fatality rate in humans. An inactivated suckling mouse brain-derived vaccine is used in Bulgaria for protection against CCHF. Strain V42/81 is currently used for the vaccine preparation. As the M-RNA segment plays a major role in the immune response, the full-length M segment sequence of the V42/81 strain was characterized. A great genetic diversity was observed among CCHFV strains. In order to gain an insight into the topology of the strain in the CCHFV phylogenetic trees, the full-length S and partial L segments were additionally sequenced and analyzed.

The influence of the platelet count on the incidence of thrombotic and haemorrhagic complications in polycythaemia vera

PubMed Central

Dawson, Audrey A.; Ogston, D.

1970-01-01

In polycythaemia vera, those patients who have an elevated platelet count develop more thrombotic and more haemorrhagic complications than those with a normal count, even when the haematocrit is maintained by therapy within the normal range. PMID:5416508

On the Hilbert-Huang Transform Theoretical Foundation

NASA Technical Reports Server (NTRS)

Kizhner, Semion; Blank, Karin; Huang, Norden E.

2004-01-01

The Hilbert-Huang Transform [HHT] is a novel empirical method for spectrum analysis of non-linear and non-stationary signals. The HHT is a recent development and much remains to be done to establish the theoretical foundation of the HHT algorithms. This paper develops the theoretical foundation for the convergence of the HHT sifting algorithm and it proves that the finest spectrum scale will always be the first generated by the HHT Empirical Mode Decomposition (EMD) algorithm. The theoretical foundation for cutting an extrema data points set into two parts is also developed. This then allows parallel signal processing for the HHT computationally complex sifting algorithm and its optimization in hardware.

Radiation Dose-effects on Cell Cycle, Apoptosis, and Marker Expression of Ataxia Telangiectasia-Heterozygous Human Breast Epithelial Cells

NASA Technical Reports Server (NTRS)

Cruz, A.; Bors, K.; Jansen, H.; Richmond, R.

2003-01-01

Ataxia-telangiectasia (A-T) is a radiation-sensitive genetic condition. AT-heterozygous human mammary epithelial cells (HMEC) were irradiated using a Cs137 source in order to compare cell cycle, apoptosis, and marker expression responses across 3 radiation doses. No differences in cell cycle and apoptosis were found with any of the radiation doses used (30, 60, and 90 rads) compared with the unirradiated control (0 rad). At the same doses, however, differences were found in marker expression, such as keratin 18 (kl8), keratin 14 (k14), insulin-like growth factor I receptor (IGF-IR), and connexin 43 (cx43). This may indicate that radiation sensitivity in the heterozygous state may be initiated through signal transduction responses.

Cell and Molecular Biology of Ataxia Telangiectasia Heterozygous Human Mammary Epithelial Cells Irradiated in Culture

NASA Technical Reports Server (NTRS)

Richmond, Robert C.

2001-01-01

Autologous isolates of cell types from obligate heterozygotes with the autosomal disorder ataxia-telangiectasia (A-T)were used to begin a tissue culture model for assessing pathways of radiation-induced cancer formation in this target tissue. This was done by establishing cultures of stromal fibroblasts and long-term growth human mammary epithelial cells (HMEC) in standard 2-dimensional tissue culture in order to establish expression of markers detailing early steps of carcinogenesis. The presumptive breast cancer susceptibility of A-T heterozygotes as a sequel to damage caused by ionizing radiation provided reason to study expression of markers in irradiated HMEC. Findings from our study with HMEC have included determination of differences in specific protein expression amongst growth phase (e.g., log vs stationary) and growth progression (e.g., pass 7 vs pass 9), as well as differences in morphologic markers within populations of irradiated HMEC (e.g., development of multinucleated cells).

Haemorrhage from varicose veins and varicose ulceration: A systematic review.

PubMed

Serra, Raffaele; Ielapi, Nicola; Bevacqua, Egidio; Rizzuto, Antonia; De Caridi, Giovanni; Massara, Mafalda; Casella, Filomena; Di Mizio, Giulio; de Franciscis, Stefano

2018-05-28

Varicose veins (VVs) and varicose ulceration (VU) are usually considered non-life-threatening conditions, but in some cases they can lead to major complications such as fatal bleeding. The aim of this systematic review is to evidence the most updated information on bleeding from VV and VU. As evidence acquisition, we planned to include all the studies dealing with "Haemorrhage/Bleeding" and "VVs/VU". We excluded all the studies, which did not properly fit our research question, and with insufficient data. As evidence synthesis, of the 172 records found, after removing of duplicates, and after records excluded in title and abstract, 85 matched our inclusion criteria. After reading the full-text articles, we decided to exclude 68 articles because of the following reasons: (1) not responding properly to our research questions; (2) insufficient data; the final set included 17 articles. From literature searching, we identify the following main issues to be discussed in the review: epidemiology and predisposing factors, pathophysiology and forensic aspects, first aid. It has been estimated that deaths for bleeding due to peripheral venous problems account up to 0.01% of autopsy cases. From a pathological point of view, venous bleeding may arise from either acute or chronic perforation of an enlarged vein segment through the weakened skin. From a forensic point of view, in cases of fatal haemorrhage the death scene can even simulate non-natural events, due to crime or suicide. In most cases, incorrect first aid led to fatal complications. Further investigation on epidemiology and prevention measures are needed. © 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Detecting active pelvic arterial haemorrhage on admission following serious pelvic fracture in multiple trauma patients.

PubMed

Brun, Julien; Guillot, Stéphanie; Bouzat, Pierre; Broux, Christophe; Thony, Frédéric; Genty, Céline; Heylbroeck, Christophe; Albaladejo, Pierre; Arvieux, Catherine; Tonetti, Jérôme; Payen, Jean-Francois

2014-01-01

The early diagnosis of pelvic arterial haemorrhage is challenging for initiating treatment by transcatheter arterial embolization (TAE) in multiple trauma patients. We use an institutional algorithm focusing on haemodynamic status on admission and on a whole-body CT scan in stabilized patients to screen patients requiring TAE. This study aimed to assess the effectiveness of this approach. This retrospective cohort study included 106 multiple trauma patients admitted to the emergency room with serious pelvic fracture [pelvic abbreviated injury scale (AIS) score of 3 or more]. Of the 106 patients, 27 (25%) underwent pelvic angiography leading to TAE for active arterial haemorrhage in 24. The TAE procedure was successful within 3h of arrival in 18 patients. In accordance with the algorithm, 10 patients were directly admitted to the angiography unit (n=8) and/or operating room (n=2) for uncontrolled haemorrhagic shock on admission. Of the remaining 96 stabilized patients, 20 had contrast media extravasation on pelvic CT scan that prompted pelvic angiography in 16 patients leading to TAE in 14. One patient underwent a pelvic angiography despite showing no contrast media extravasation on pelvic CT scan. All 17 stabilized patients who underwent pelvic angiography presented a more severely compromised haemodynamic status on admission, and they required more blood products during their initial management than the 79 patients who did not undergo pelvic angiography. The incidence of unstable pelvic fractures was however comparable between the two groups. Overall, haemodynamic instability and contrast media extravasation on the CT-scan identified 26 out of the 27 patients who required subsequent pelvic angiography leading to TAE in 24. An algorithm focusing on haemodynamic status on arrival and on the whole-body CT scan in stabilized patients may be effective at triaging multiple trauma patients with serious pelvic fractures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Emerging rabbit haemorrhagic disease virus 2 (RHDV2) at the gates of the African continent.

PubMed

Martin-Alonso, Aarón; Martin-Carrillo, Natalia; Garcia-Livia, Katherine; Valladares, Basilio; Foronda, Pilar

2016-10-01

Until the beginning of this decade, the genetic characterization of rabbit haemorrhagic disease virus (RHDV) from Iberian Peninsula had revealed the existence of two genogroups, G1 and sporadically G6. In 2010, the new emerging rabbit haemorrhagic disease variant, RHDV2 or RHDVb, was described in France, from where it has rapidly spread throughout Europe, including Iberian Peninsula countries. Nevertheless, although cases of rabbit haemorrhagic disease (RHD) have been reported in the Canary Islands, a Spanish archipelago located 100km off the coast of Morocco, no genetic characterization of RHDV had been carried out. Consequently, in order to identify the circulating RHDV strains in this archipelago, liver samples of six farm rabbits and fifteen wild rabbits were collected from several areas of the largest island, Tenerife, and analyzed for the presence of RHDV by antigen capture double antibody sandwich ELISA. In case of positive ELISA result, we amplified and sequenced two fragments of the vp60 gene, which were concatenated for phylogenetic purposes. The sequences analysis revealed the presence of RHDV2 in both farm and wild rabbits from several areas of Tenerife. This result constitutes the first finding of RHDV2 in the Canary Islands. These RHDV2 strains found in Tenerife shared two exclusive SNPs that have not been observed in the rest of RHDV2 strains. The identification of RHDV2 and the absence of classic RHDV strains in this study suggest that RHDV2 may be replacing classic strains in Tenerife, as has been also proposed in Iberian Peninsula, France and Azores. Given the proximity of the Canary Islands to the African continent, this result should raise awareness about a possible dispersal of RHDV2 from the Canary Islands to the North of Africa. Copyright © 2016 Elsevier B.V. All rights reserved.

Case definition for Ebola and Marburg haemorrhagic fevers: a complex challenge for epidemiologists and clinicians.

PubMed

Pittalis, Silvia; Fusco, Francesco Maria; Lanini, Simone; Nisii, Carla; Puro, Vincenzo; Lauria, Francesco Nicola; Ippolito, Giuseppe

2009-10-01

Viral haemorrhagic fevers (VHFs) represent a challenge for public health because of their epidemic potential, and their possible use as bioterrorism agents poses particular concern. In 1999 the World Health Organization (WHO) proposed a case definition for VHFs, subsequently adopted by other international institutions with the aim of early detection of initial cases/outbreaks in western countries. We applied this case definition to reports of Ebola and Marburg virus infections to estimate its sensitivity to detect cases of the disease. We analyzed clinical descriptions of 795 reported cases of Ebola haemorrhagic fever: only 58.5% of patients met the proposed case definition. A similar figure was obtained reviewing 169 cases of Marburg diseases, of which only 64.5% were in accordance with the case definition. In conclusion, the WHO case definition for hemorrhagic fevers is too specific and has poor sensitivity both for case finding during Ebola or Marburg outbreaks, and for early detection of suspected cases in western countries. It can lead to a hazardous number of false negatives and its use should be discouraged for early detection of cases.

Purkinje cell-specific males absent on the first (mMof) gene deletion results in an ataxia-telangiectasia-like neurological phenotype and backward walking in mice

PubMed Central

Kumar, Rakesh; Hunt, Clayton R.; Gupta, Arun; Nannepaga, Suraj; Pandita, Raj K.; Shay, Jerry W.; Bachoo, Robert; Ludwig, Thomas; Burns, Dennis K.; Pandita, Tej K.

2011-01-01

The brains of ataxia telangiectasia (AT) patients display an aberrant loss of Purkinje cells (PCs) that is postulated to contribute to the observed deficits in motor coordination as well as in learning and cognitive function. AT patients have mutations in the ataxia telangiectasia mutated (ATM) gene [Savitsky et al. (1995) Science 268:1749–1753]. However, in Atm-deficient mice, the neurological defects are limited, and the PCs are not deformed or lost as observed in AT patients [Barlow et al. (1996) Cell 86:159–171]. Here we report that PC-specific deletion of the mouse males absent on the first (mMof) gene (Cre−), which encodes a protein that specifically acetylates histone H4 at lysine 16 (H4K16ac) and influences ATM function, is critical for PC longevity. Mice deficient for PC-specific Mof display impaired motor coordination, ataxia, a backward-walking phenotype, and a reduced life span. Treatment of MofF/F/Pcp2-Cre+ mice with histone deacetylase inhibitors modestly prolongs PC survival and delays death. Therefore, Mof expression and H4K16 acetylation are essential for PC survival and function, and their absence leads to PC loss and cerebellar dysfunction similar to that observed in AT patients. PMID:21321203

Gastrointestinal haemorrhage due to lymphangiectasia caused by protein-losing enteropathy in the Fontan circulation.

PubMed

Gras, Pauline; Gottrand, Frédéric; Godart, François

2017-10-01

We report the case of a 14-year-old boy with severe protein-losing enteropathy after Fontan surgery that led to lymphangiectasia, which caused gastrointestinal haemorrhage and required invasive treatment to stop the bleeding. Through this case and a review of the literature on protein-losing enteropathy after Fontan surgery, we highlight a rare and serious presentation of the disease and the difficulties of diagnosis and management.

[Hantavirus infection as the cause of haemorrhagic fever with renal syndrome].

PubMed

Redal-Baigorri, Belén; Chen Nielsen, Xiaohui; Martin-Iguacel, Raquel

2012-10-29

Hantavirus is an RNA virus that can cause potentially fatal pulmonary and renal diseases in humans. Infections with Hantaviruses occur through inhalation of aerosol from rodent faeces, urine or saliva. The predominant virus type in Denmark is the Puumala virus, which causes the mildest form of haemorrhagic fever with renal syndrome, the so-called nephropathia epidemica (NE) with good prognosis (mortality 0.1-0.4%). The incidence of Hantavirus-infection in Denmark is about ten cases a year. The diagnosis of Hantavirus-infection is based on serology and/or polymerase chain reaction in blood or urine.

High-Power Single- and Dual-Wavelength Nd:GdVO4 Lasers with Potential Application for the Treatment of Telangiectasia

NASA Astrophysics Data System (ADS)

Chen, Lijuan; Wang, Zhengping; Yu, Haohai; Zhuang, Shidong; Han, Shuo; Zhao, Yongguang; Xu, Xinguang

2012-11-01

Diode-end-pumped high-power Nd:GdVO4 lasers at 1083 nm are presented. The maximum continuous-wave output power was 10.1 W with an optical conversion efficiency of 31.3%. For acoustooptic (AO) Q-switched operation, the largest pulse energy, shortest pulse width, and highest peak power were 111 µJ, 77 ns, and 1.44 kW, respectively. By decreasing the 1063 nm transmission of the output coupler, we also achieved efficient CW dual-wavelength operation at 1083 and 1063 nm. Their total output power reached 6.7 W, and the optical conversion efficiency reached 31.6%. These lasers have special requirements in the treatment of facial telangiectasia.

Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial.

PubMed

Kim, Bum Joon; Lee, Eun-Jae; Kwon, Sun U; Park, Jong-Ho; Kim, Yong-Jae; Hong, Keun-Sik; Wong, Lawrence K S; Yu, Sungwook; Hwang, Yang-Ha; Lee, Ji Sung; Lee, Juneyoung; Rha, Joung-Ho; Heo, Sung Hyuk; Ahn, Sung Hwan; Seo, Woo-Keun; Park, Jong-Moo; Lee, Ju-Hun; Kwon, Jee-Hyun; Sohn, Sung-Il; Jung, Jin-Man; Navarro, Jose C; Kang, Dong-Wha

2018-06-01

The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients. In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532. Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0-3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57-1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20-1·27; superiority

Development and validation of a pre-hospital "Red Flag" alert for activation of intra-hospital haemorrhage control response in blunt trauma.

PubMed

Hamada, Sophie Rym; Rosa, Anne; Gauss, Tobias; Desclefs, Jean-Philippe; Raux, Mathieu; Harrois, Anatole; Follin, Arnaud; Cook, Fabrice; Boutonnet, Mathieu; Attias, Arie; Ausset, Sylvain; Boutonnet, Mathieu; Dhonneur, Gilles; Duranteau, Jacques; Langeron, Olivier; Paugam-Burtz, Catherine; Pirracchio, Romain; de St Maurice, Guillaume; Vigué, Bernard; Rouquette, Alexandra; Duranteau, Jacques

2018-05-05

Haemorrhagic shock is the leading cause of early preventable death in severe trauma. Delayed treatment is a recognized prognostic factor that can be prevented by efficient organization of care. This study aimed to develop and validate Red Flag, a binary alert identifying blunt trauma patients with high risk of severe haemorrhage (SH), to be used by the pre-hospital trauma team in order to trigger an adequate intra-hospital standardized haemorrhage control response: massive transfusion protocol and/or immediate haemostatic procedures. A multicentre retrospective study of prospectively collected data from a trauma registry (Traumabase®) was performed. SH was defined as: packed red blood cell (RBC) transfusion in the trauma room, or transfusion ≥ 4 RBC in the first 6 h, or lactate ≥ 5 mmol/L, or immediate haemostatic surgery, or interventional radiology and/or death of haemorrhagic shock. Pre-hospital characteristics were selected using a multiple logistic regression model in a derivation cohort to develop a Red Flag binary alert whose performances were confirmed in a validation cohort. Among the 3675 patients of the derivation cohort, 672 (18%) had SH. The final prediction model included five pre-hospital variables: Shock Index ≥ 1, mean arterial blood pressure ≤ 70 mmHg, point of care haemoglobin ≤ 13 g/dl, unstable pelvis and pre-hospital intubation. The Red Flag alert was triggered by the presence of any combination of at least two criteria. Its predictive performances were sensitivity 75% (72-79%), specificity 79% (77-80%) and area under the receiver operating characteristic curve 0.83 (0.81-0.84) in the derivation cohort, and were not significantly different in the independent validation cohort of 2999 patients. The Red Flag alert developed and validated in this study has high performance to accurately predict or exclude SH.

Severe acute pulmonary haemorrhage and haemoptysis in ten dogs following eastern brown snake (Pseudonaja textilis) envenomation: Clinical signs, treatment and outcomes.

PubMed

Leong, Oriana S; Padula, Andrew M; Leister, Ellie

2018-05-29

This report describes a series of ten cases of fulminant pulmonary haemorrhage in dogs following envenomation by the eastern brown snake (Pseudonaja textilis) in south eastern Queensland, Australia. All cases were presented for veterinary treatment during 2011-2018 at a specialist veterinary emergency centre. Each case received prompt antivenom treatment and supportive care. Pulmonary haemorrhage was diagnosed based on clinical examination; overt haemoptysis; thoracic radiographic demonstration of a diffuse alveolar pattern; and, the presence of venom induced consumptive coagulopathy. The median elapsed time from hospital admission to onset of haemoptysis was 2 h (range 0-18 h). In 80% (8/10) of cases endotracheal intubation was required, whilst 20% (2/10) were successfully treated with mask oxygen supplementation alone, and 40% (4/10) received mechanical ventilation; but only 25% (1/4) of these survived to hospital discharge. Fresh frozen canine plasma was administered to 70% (7/10) of cases and 43% (3/7) of these survived. Of the total number of cases presented for treatment, 30% (3/10) survived to hospital discharge, 60% (6/10) were euthanised due to poor prognosis and 10% (1/10) died from cardiac arrest. Initial serum brown snake venom antigen levels were retrospectively measured from frozen serum samples by venom specific sandwich ELISA in two dogs at 154 ng/mL (survived) and 3607 ng/mL (euthanised); no free venom was detected post-antivenom. Dogs that survived were discharged from hospital without apparent complications. Pulmonary haemorrhage is an uncommon event following envenomation by P. textilis in dogs and has not been described in similarly envenomed humans. This case series highlights the potential for fulminant and fatal pulmonary haemorrhage in dogs following eastern brown snake envenomation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ultrastructural and clinical evidence of subretinal debris accumulation in type 2 macular telangiectasia.

PubMed

Cherepanoff, Svetlana; Killingsworth, Murray C; Zhu, Meidong; Nolan, Timothy; Hunyor, Alex P; Young, Stephanie H; Hageman, Gregory S; Gillies, Mark C

2012-11-01

To describe subretinal debris found on ultrastructural examination in an eye with macular telangiectasia (MacTel) type 2 and on optical coherence tomography (OCT) in a subset of patients with MacTel type 2. Blocks from the mid-periphery and temporal perifovea of an eye with clinically documented MacTel type 2 were examined with electron microscopy (EM). Cases came from the Sydney centre of the MacTel project and the practices of the authors. On EM examination, subretinal debris was found in the perifovea with accumulation of degenerate photoreceptor elements in the subretinal space. Despite the substantial subretinal debris, there was minimal retinal pigment epithelial (RPE) reaction. Focal defects were seen in the inner limiting membrane in the perifovea. Of the 65 Sydney MacTel project participants, three (5%) had prominent yellow material at the fovea. OCT revealed smooth mounds between the RPE and the ellipsoid region. The material was hyperautofluorescent. This study suggests that subretinal accumulation of photoreceptor debris may be a feature of MacTel type 2. Ultrastructural and OCT evidence of disease beyond the vasculature, involving photoreceptors and Muller cells, is presented.

EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia

PubMed Central

Li, Jiali; Hart, Ronald P.; Mallimo, Elyse M.; Swerdel, Mavis R.; Kusnecov, Alexander; Herrup, Karl

2014-01-01

The symptoms of ataxia-telangiectasia (A-T) include a progressive neurodegeneration caused by ATM protein deficiency. We previously found that nuclear accumulation of histone deacetylase-4, HDAC4, contributes to this degeneration; we now report that increased histone H3K27 trimethylation (H3K27me3) mediated by polycomb repressive complex 2 (PRC2) also plays an important role in the A-T phenotype. Enhancer of zeste homolog 2 (EZH2), a core catalytic component of PRC2, is a new ATM kinase target, and ATM-mediated S734 phosphorylation of EZH2 reduces protein stability. Thus, PRC2 formation is elevated along with H3K27me3in ATM deficiency. ChIP-sequencing shows a significant increase in H3K27me3 ‘marks’ and a dramatic shift in their location. The change of H3K27me3 chromatin-binding pattern is directly related to cell cycle re-entry and cell death of ATM-deficient neurons. Lentiviral knockdown of EZH2 rescues Purkinje cell degeneration and behavioral abnormalities in Atm−/− mice, demonstrating that EZH2 hyperactivity is another key factor in A-T neurodegeneration. PMID:24162653

Outcome of infants shunted for post-haemorrhagic ventricular dilatation.

PubMed

Hislop, J E; Dubowitz, L M; Kaiser, A M; Singh, M P; Whitelaw, A G

1988-08-01

Between April 1980 and March 1986, 19 infants underwent cerebrospinal fluid (CSF) shunting procedures for post-haemorrhagic ventricular dilatation at the Hammersmith Hospital, London. A total of 58 shunt-related procedures have been performed on these children. The major perioperative complication was seizure activity (eight children). Postoperative complications included infection (12 shunts) and blockage (29 shunts). Prophylactic antibiotics failed to prevent shunt infection. The likelihood of the first shunt failing was significantly reduced by greater weight of the infant and lower CSF protein at surgery. Long-term outcome was poor: three have died and another four are quadriplegic with severe mental retardation. Only four children are developmentally normal. These outcomes cannot be related to the shunt surgery or its complications, but correlate best with pre-operative parenchymal brain-lesions, as shown on ultrasound scans.

On Hilbert-Huang Transform Based Synthesis of a Signal Contaminated by Radio Frequency Interference or Fringes

NASA Technical Reports Server (NTRS)

Kizhner, Semion; Shiri, Ron S.; Vootukuru, Meg; Coletti, Alessandro

2015-01-01

Norden E. Huang et al. had proposed and published the Hilbert-Huang Transform (HHT) concept correspondently in 1996, 1998. The HHT is a novel method for adaptive spectral analysis of non-linear and non-stationary signals. The HHT comprises two components: - the Huang Empirical Mode Decomposition (EMD), resulting in an adaptive data-derived basis of Intrinsic Mode functions (IMFs), and the Hilbert Spectral Analysis (HSA1) based on the Hilbert Transform for 1-dimension (1D) applied to the EMD IMF's outcome. Although paper describes the HHT concept in great depth, it does not contain all needed methodology to implement the HHT computer code. In 2004, Semion Kizhner and Karin Blank implemented the reference digital HHT real-time data processing system for 1D (HHT-DPS Version 1.4). The case for 2-Dimension (2D) (HHT2) proved to be difficult due to the computational complexity of EMD for 2D (EMD2) and absence of a suitable Hilbert Transform for 2D spectral analysis (HSA2). The real-time EMD2 and HSA2 comprise the real-time HHT2. Kizhner completed the real-time EMD2 and the HSA2 reference digital implementations respectively in 2013 & 2014. Still, the HHT2 outcome synthesis remains an active research area. This paper presents the initial concepts and preliminary results of HHT2-based synthesis and its application to processing of signals contaminated by Radio-Frequency Interference (RFI), as well as optical systems' fringe detection and mitigation at design stage. The Soil Moisture Active Passive (SMAP mission (SMAP) carries a radiometer instrument that measures Earth soil moisture at L1 frequency (1.4 GHz polarimetric - H, V, 3rd and 4th Stokes parameters). There is abundant RFI at L1 and because soil moisture is a strategic parameter, it is important to be able to recover the RFI-contaminated measurement samples (15% of telemetry). State-of-the-art only allows RFI detection and removes RFI-contaminated measurements. The HHT-based analysis and synthesis facilitates

Long-lived CD8+ T cell responses following Crimean-Congo haemorrhagic fever virus infection

PubMed Central

Goedhals, Dominique; Paweska, Janusz T.

2017-01-01

Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the Orthonairovirus genus of the Nairoviridae family and is associated with haemorrhagic fever in humans. Although T lymphocyte responses are known to play a role in protection from and clearance of viral infections, specific T cell epitopes have yet to be identified for CCHFV following infection. A panel of overlapping peptides covering the CCHFV nucleoprotein and the structural glycoproteins, GN and GC, were screened by ELISpot assay to detect interferon gamma (IFN-γ) production in vitro by peripheral blood mononuclear cells from eleven survivors with previous laboratory confirmed CCHFV infection. Reactive peptides were located predominantly on the nucleoprotein, with only one survivor reacting to two peptides from the glycoprotein GC. No single epitope was immunodominant, however all but one survivor showed reactivity to at least one T cell epitope. The responses were present at high frequency and detectable several years after the acute infection despite the absence of continued antigenic stimulation. T cell depletion studies confirmed that IFN-γ production as detected using the ELISpot assay was mediated chiefly by CD8+ T cells. This is the first description of CD8+ T cell epitopic regions for CCHFV and provides confirmation of long-lived T cell responses in survivors of CCHFV infection. PMID:29261651

A recombinase polymerase amplification assay for rapid detection of Crimean-Congo Haemorrhagic fever Virus infection

PubMed Central

Afrough, Babak; Mullojonova, Manija; Dzhuraeva, Viktoriya; Tishkova, Farida; Hewson, Roger

2017-01-01

Background Crimean-Congo Haemorrhagic fever Virus (CCHFV) is a rapidly emerging vector-borne pathogen and the cause of a virulent haemorrhagic fever affecting large parts of Europe, Africa, the Middle East and Asia. Methodology/principle findings An isothermal recombinase polymerase amplification (RPA) assay was successfully developed for molecular detection of CCHFV. The assay showed rapid (under 10 minutes) detection of viral extracts/synthetic virus RNA of all 7 S-segment clades of CCHFV, with high target specificity. The assay was shown to tolerate the presence of inhibitors in crude preparations of mock field samples, indicating that this assay may be suitable for use in the field with minimal sample preparation. The CCHFV RPA was successfully used to screen and detect CCHFV positives from a panel of clinical samples from Tajikistan. Conclusions/significance The assay is a rapid, isothermal, simple-to-perform molecular diagnostic, which can be performed on a light, portable real-time detection device. It is ideally placed therefore for use as a field-diagnostic or in-low resource laboratories, for monitoring of CCHF outbreaks at the point-of-need, such as in remote rural regions in affected countries. PMID:29028804

A recombinase polymerase amplification assay for rapid detection of Crimean-Congo Haemorrhagic fever Virus infection.

PubMed

Bonney, Laura C; Watson, Robert J; Afrough, Babak; Mullojonova, Manija; Dzhuraeva, Viktoriya; Tishkova, Farida; Hewson, Roger

2017-10-01

Crimean-Congo Haemorrhagic fever Virus (CCHFV) is a rapidly emerging vector-borne pathogen and the cause of a virulent haemorrhagic fever affecting large parts of Europe, Africa, the Middle East and Asia. An isothermal recombinase polymerase amplification (RPA) assay was successfully developed for molecular detection of CCHFV. The assay showed rapid (under 10 minutes) detection of viral extracts/synthetic virus RNA of all 7 S-segment clades of CCHFV, with high target specificity. The assay was shown to tolerate the presence of inhibitors in crude preparations of mock field samples, indicating that this assay may be suitable for use in the field with minimal sample preparation. The CCHFV RPA was successfully used to screen and detect CCHFV positives from a panel of clinical samples from Tajikistan. The assay is a rapid, isothermal, simple-to-perform molecular diagnostic, which can be performed on a light, portable real-time detection device. It is ideally placed therefore for use as a field-diagnostic or in-low resource laboratories, for monitoring of CCHF outbreaks at the point-of-need, such as in remote rural regions in affected countries.

Efficacy and safety of recombinant tissue plasminogen activator and gas versus bevacizumab and gas for subretinal haemorrhage.

PubMed

Mayer, Wolfgang J; Hakim, Imad; Haritoglou, Christos; Gandorfer, Arnd; Ulbig, Michael; Kampik, Anselm; Wolf, Armin

2013-05-01

To report the 12 months efficacy of initial intravitreal bevacizumab or intravitreal recombinant tissue plasminogen activator (rtPA) combined with expansile gas in patients with subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD). Forty-five eyes of 45 patients with subretinal haemorrhage (1-5 disc diameters) involving the fovea secondary to neovascular AMD were evaluated retrospectively consecutively. Thirty-two eyes underwent treatment with rtPA (50 μg/0.05 ml) combined with intravitreal sulphur hexafluoride (SF6). The other 13 eyes were treated with bevacizumab (1.25 mg/0.05 ml) and SF6. Thereafter, all patients received Vascular Endothelial Growth Factor (anti-VEGF) treatment according to modified PrONTO criteria. Main outcome was change of best-corrected visual acuity (VA) at 12 months as determined by Early Treatment Diabetic Retinopathy (ETDRS). There was more improvement in patients initially treated with rtPA and gas (14 letters; bevacizumab and gas eight letters) and not suffering from adverse events. The incidence of vitreous haemorrhages was significantly higher in the rtPA group (nine of 32 versus one of 13, p < 0.01). In both groups, an average of 3.5 anti-VEGF injections were performed per patient during 12 months (no difference between both groups). Both initial treatment regimen lead to improved functional results after 1 year. However, patients, not suffering from adverse events, who underwent initial treatment with rtPA and gas showed better results. To maintain VA, controlling neovascular AMD by anti-VEGF treatment regime after initial treatment with rtPA+gas is important for all cases. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Fatal haemorrhage and neoplastic thrombosis in a captive African lion (Panthera leo) with metastatic testicular sex cord-stromal tumour.

PubMed

Gonzales-Viera, Omar Antonio; Sánchez-Sarmiento, Angélica María; Fernandes, Natália Coelho Couto de Azevedo; Guerra, Juliana Mariotti; Ressio, Rodrigo Albergaria; Catão-Dias, José Luiz

2017-10-13

The study of neoplasia in wildlife species contributes to the understanding of cancer biology, management practices, and comparative pathology. Higher frequencies of neoplasms among captive non-domestic felids have been reported most commonly in aging individuals. However, testicular tumours have rarely been reported. This report describes a metastatic testicular sex cord-stromal tumour leading to fatal haemorrhage and thrombosis in a captive African lion (Panthera leo). During necropsy of a 16-year-old male African lion, the left testicle and spermatic cord were found to be intra-abdominal (cryptorchid), semi-hard and grossly enlarged with multiple pale-yellow masses. Encapsulated haemorrhage was present in the retroperitoneum around the kidneys. Neoplastic thrombosis was found at the renal veins opening into the caudal vena cava. Metastases were observed in the lungs and mediastinal lymph nodes. Histology revealed a poorly differentiated pleomorphic neoplasm comprised of round to polygonal cells and scattered spindle cells with eosinophilic cytoplasm. An immunohistochemistry panel of inhibin-α, Ki-67, human placental alkaline phosphatase, cytokeratin AE1/AE3, cKit, vimentin and S100 was conducted. Positive cytoplasmic immunolabeling was obtained for vimentin and S100. The gross, microscopic and immunohistochemical findings of the neoplasm were compatible with a poorly differentiated pleomorphic sex cord-stromal tumour. Cause of death was hypovolemic shock from extensive retroperitoneal haemorrhage and neoplastic thrombosis may have contributed to the fatal outcome. To our knowledge, this is the first report of sex cord-stromal tumour in non-domestic felids.

Ataxia Telangiectasia in Siblings: Oral Motor and Swallowing Characterization

PubMed Central

Rondon-Melo, Silmara; de Almeida, Isabel Junqueira; de Andrade, Claudia Regina Furquim; Sassi, Fernanda Chiarion; Molini-Avejonas, Daniela Regina

2017-01-01

Case series Patient: Male, 23 • Female, 20 Final Diagnosis: Ataxia telnagiectasia Symptoms: Gagging • coughing • hoarseness • articulatory inaccuracy Medication: — Clinical Procedure: Oral motor and swallowing assessment Specialty: Neurology Objective: Rare disease Background: The body of literature on oral motor and swallowing disorders in patients with ataxia telangiectasia (AT) is limited. Case Report: The purpose of this study was to characterize oral motor and swallowing disorders in two siblings with AT, based on oral motor and swallowing assessments. Specific procedures were applied for oral motor and swallowing assessments and both patients underwent videofluoroscopy (VFS). Case 1 presented vocal instability, change in postural control during feeding; food retention in oral cavity; slower oral transit time; and multiple swallowing (signs for solid and liquid). Case 2 presented parted lips at rest and reduced muscle strength; reduced strength and mobility of the tongue; vocal weakness and instability; reduced speech precision and intelligibility; decreased intonation pattern; food retention in oral cavity during feeding; slower oral transit time; multiple swallowing (signs for solid and liquid); poor bolus ejection; incoordination and difficulty in controlling the sips of water taken from the cup; altered cervical auscultation after swallowing and respiratory distress (liquid and puree). For both patients VFS results revealed laryngeal penetration for liquid. Conclusions: Although the literature describes the occurrence of dysarthria and swallowing disorders in patients with AT, little attention has been given to describing which oral motor deficits are responsible for these disorders. Early identification of swallowing alterations and rehabilitation could decrease the risk of aspiration pneumonia. Future studies are necessary in order to investigate the deterioration process of swallowing in AT and the influence of rehabilitation in maintaining

Evaluating the effect of metronidazole plus amoxicillin-clavulanate versus amoxicillin-clavulanate alone in canine haemorrhagic diarrhoea: a randomised controlled trial in primary care practice.

PubMed

Ortiz, V; Klein, L; Channell, S; Simpson, B; Wright, B; Edwards, C; Gilbert, R; Day, R; Caddy, S L

2018-06-07

To investigate the benefit of supplementing amoxicillin-clavulanic acid therapy with metronidazole in dogs presenting to a primary care veterinary practice with severe haemorrhagic diarrhoea. Prospective randomised blinded trial on dogs presenting with haemorrhagic diarrhoea of less than 3 days duration to a primary care veterinary hospital and also requiring intravenous fluid therapy. Cases were randomised to receive either metronidazole or saline, in addition to standard supportive therapy consisting of amoxicillin-clavulanic acid, intravenous fluid therapy, buprenorphine and omeprazole. Treatment efficacy was measured by duration of hospitalisation and daily scoring of disease severity. Thirty-four cases successfully completed the trial. There was no significant difference in hospitalisation time between treatment groups (mean for dogs receiving metronidazole was 29.6 hours and for controls was 26.3 hours) nor in daily clinical scores. This study strongly suggests that addition of metronidazole is not an essential addition to amoxicillin-clavulanic acid therapy for treatment of severe cases of haemorrhagic diarrhoea in dogs. © 2018 British Small Animal Veterinary Association.

Endothelial Depletion of Acvrl1 in Mice Leads to Arteriovenous Malformations Associated with Reduced Endoglin Expression

PubMed Central

Allinson, Kathleen R.; Redgrave, Rachael E.; Zhai, Zhenhua; Oh, S. Paul; Fruttiger, Marcus; Arthur, Helen M.

2014-01-01

Rare inherited cardiovascular diseases are frequently caused by mutations in genes that are essential for the formation and/or function of the cardiovasculature. Hereditary Haemorrhagic Telangiectasia is a familial disease of this type. The majority of patients carry mutations in either Endoglin (ENG) or ACVRL1 (also known as ALK1) genes, and the disease is characterized by arteriovenous malformations and persistent haemorrhage. ENG and ACVRL1 encode receptors for the TGFβ superfamily of ligands, that are essential for angiogenesis in early development but their roles are not fully understood. Our goal was to examine the role of Acvrl1 in vascular endothelial cells during vascular development and to determine whether loss of endothelial Acvrl1 leads to arteriovenous malformations. Acvrl1 was depleted in endothelial cells either in early postnatal life or in adult mice. Using the neonatal retinal plexus to examine angiogenesis, we observed that loss of endothelial Acvrl1 led to venous enlargement, vascular hyperbranching and arteriovenous malformations. These phenotypes were associated with loss of arterial Jag1 expression, decreased pSmad1/5/8 activity and increased endothelial cell proliferation. We found that Endoglin was markedly down-regulated in Acvrl1-depleted ECs showing endoglin expression to be downstream of Acvrl1 signalling in vivo. Endothelial-specific depletion of Acvrl1 in pups also led to pulmonary haemorrhage, but in adult mice resulted in caecal haemorrhage and fatal anaemia. We conclude that during development, endothelial Acvrl1 plays an essential role to regulate endothelial cell proliferation and arterial identity during angiogenesis, whilst in adult life endothelial Acvrl1 is required to maintain vascular integrity. PMID:24896812

Potentiation by caffeine of x-ray damage to cultured human skin fibroblasts from normal subjects and ataxia-telangiectasia patients

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

Furcinitti, P.S.

1983-07-01

Caffeine was found to potentiate x-ray-induced killing of human diploid fibroblasts from a normal subject and an ataxia-telangiectasia (AT) patient when it was present at 2 mM concentration for 30 to 66 h postirradiation. The dose-modifying factor for caffeine-treated normal cells had an average value of 1.26 +- 0.13 which did not vary significantly with treatment time or x-ray dose. The dose-modifying factor for caffeine-treated AT cells was 1.12 +- 0.12 at 30 h, rose to 1.66 +- 0.17 at 41 h, and decreased to 1.31 +- 0.13 at 66 h. Thus no clear difference was observed between these twomore » cell strains' susceptibility to postirradiation caffeine treatment.« less

[Haemorrhagic proctocolitis as primary manifestation of lymphogranuloma venereum in an HIV-positive male].

PubMed

Gormsen, Andreas Brandt; Diernæs, Jon Erik-Fraes; Jensen, Jørgen Skov; Koppelhus, Uffe

2018-03-12

This is a case report of lymphogranuloma venereum (LGV) manifesting as haemorrhagic proctocolitis in a homosexual HIV-positive male. The primary symptom was a rectal abscess, which was initially surgically treated and subsequently insufficiently treated with single-dose tablet azithromycin. The patient's symptoms were successfully treated after a 21-day doxycycline regime. LGV is a sexually transmitted infection with a rising incidence among persons with risk behaviour. This case report underlines the importance, that all positive rectal screenings for Chlamydia trachomatis should be routinely serotyped.

[Haemorrhagic proctocolitis as primary manifestation of lymphogranuloma venereum in an HIV-positive male].

PubMed

Gormsen, Andreas Brandt; Fraes Diernæs, Jon Erik; Jensen, Jørgen Skov; Koppelhus, Uffe

2018-05-14

This is a case report of lymphogranuloma venereum (LGV) manifesting as haemorrhagic proctocolitis in a homosexual HIV-positive male. The primary symptom was a rectal abscess, which was initially surgically treated and subsequently insufficiently treated with single-dose tablet azithromycin. The patient's symptoms were successfully treated after a 21-day doxycycline regime. LGV is a se xually transmitted infection with a rising incidence among persons with risk behaviour. This case report underlines the importance, that all positive rectal screenings for Chlamydia trachomatis should be routinely serotyped.

Endovascular Treatment of Epistaxis: Indications, Management, and Outcome

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

Strach, Katharina; Schroeck, Andreas; Wilhelm, Kai

2011-12-15

Objective: Epistaxis is a common clinical problem, and the majority of bleedings can be managed conservatively. However, due to extensive and sometimes life-threatening bleeding, further treatment, such as superselective embolization, may be required. We report our experience with endovascular treatment of life-threatening epistaxis. Methods: All patients presenting with excessive epistaxis, which received endovascular treatment at a German tertiary care facility between January 2001 and December 2009, were retrospectively identified. Demographic data, etiology, origin and clinical relevance of bleeding, interventional approach, therapy-associated complications, and outcome were assessed. Results: A total of 48 patients required 53 embolizations. Depending on the etiology ofmore » bleeding, patients were assigned to three groups: 1) idiopathic epistaxis (31/48), 2) traumatic or iatrogenic epistaxis (12/48), and 3) hereditary hemorrhagic telangiectasia (HHT) (5/48). Eleven of 48 patients required blood transfusions, and 9 of these 11 patients (82%) were termed clinically unstable. The sphenopalatine artery was embolized unilaterally in 10 of 53 (18.9%) and bilaterally in 41 of 53 (77.4%) procedures. During the same procedure, additional vessels were embolized in three patients (3/53; 5.7%). In 2 of 53(3.8%) cases, the internal carotid artery (ICA) was occluded. Long-term success rates of embolization were 29 of 31 (93.5%) for group 1 and 11 of 12 (91.7%) for group 2 patients. Embolization of patients with HHT offered at least a temporary relief in three of five (60%) cases. Two major complications (necrosis of nasal tip and transient hemiparesis) occurred after embolization. Conclusions: Endovascular treatment proves to be effective for prolonged and life-threatening epistaxis. It is easily repeatable if the first procedure is not successful and offers a good risk-benefit profile.« less

Safety evaluation of a recombinant myxoma-RHDV virus inducing horizontal transmissible protection against myxomatosis and rabbit haemorrhagic disease.

PubMed

Torres, J M; Ramírez, M A; Morales, M; Bárcena, J; Vázquez, B; Espuña, E; Pagès-Manté, A; Sánchez-Vizcaíno, J M

2000-09-15

We have recently developed a transmissible vaccine to immunize rabbits against myxomatosis and rabbit haemorrhagic disease based on a recombinant myxoma virus (MV) expressing the rabbit haemorrhagic disease virus (RHDV) capsid protein [Bárcena et al. Horizontal transmissible protection against myxomatosis and rabbit haemorragic disease using a recombinant myxoma virus. J. Virol. 2000;74:1114-23]. Administration of the recombinant virus protects rabbits against lethal RHDV and MV challenges. Furthermore, the recombinant virus is capable of horizontal spreading promoting protection of contact animals, thus providing the opportunity to immunize wild rabbit populations. However, potential risks must be extensively evaluated before considering its field use. In this study several safety issues concerning the proposed vaccine have been evaluated under laboratory conditions. Results indicated that vaccine administration is safe even at a 100-fold overdose. No undesirable effects were detected upon administration to immunosuppressed or pregnant rabbits. The recombinant virus maintained its attenuated phenotype after 10 passages in vivo.

Tranexamic acid for treatment of women with post-partum haemorrhage in Nigeria and Pakistan: a cost-effectiveness analysis of data from the WOMAN trial.

PubMed

Li, Bernadette; Miners, Alec; Shakur, Haleema; Roberts, Ian

2018-02-01

Sub-Saharan Africa and southern Asia account for almost 85% of global maternal deaths from post-partum haemorrhage. Early administration of tranexamic acid, within 3 h of giving birth, was shown to reduce the risk of death due to bleeding in women with post-partum haemorrhage in the World Maternal Antifibrinolytic (WOMAN) trial. We aimed to assess the cost-effectiveness of early administration of tranexamic acid for treatment of post-partum haemorrhage. For this economic evaluation we developed a decision model to assess the cost-effectiveness of the addition of tranexamic acid to usual care for treatment of women with post-partum haemorrhage in Nigeria and Pakistan. We used data from the WOMAN trial to inform model parameters, supplemented by estimates from the literature. We estimated costs (calculated in 2016 US$), life-years, and quality-adjusted life-years (QALYs) with and without tranexamic acid, calculated incremental cost-effectiveness ratios (ICERs), and compared these to threshold values in each country. Costs were assessed from the health-care provider perspective and discounted at 3% per year in the base case analysis. We did a series of one-way sensitivity analyses and probabilistic sensitivity analysis to assess the robustness of the results to parameter uncertainty. Early treatment of post-partum haemorrhage with tranexamic acid generated an average gain of 0·18 QALYs at an additional cost of $37·12 per patient in Nigeria and an average gain of 0·08 QALYs at an additional cost of $6·55 per patient in Pakistan. The base case ICER results were $208 per QALY in Nigeria and $83 per QALY in Pakistan. These ICERs were below the lower bound of the cost-effectiveness threshold range in both countries. The ICERs were most sensitive to uncertainty in parameter inputs for the relative risk of death due to bleeding with tranexamic acid, the discount rate, the cost of the drug, and the baseline probability of death due to bleeding. Early treatment of post

Crimean-Congo haemorrhagic fever virus infection in birds: field investigations in Senegal.

PubMed

Zeller, H G; Cornet, J P; Camicas, J L

1994-01-01

In Senegal, wild ground-feeding birds are frequently infested with immature ticks. In two areas where numerous Crimean-Congo haemorrhagic fever (CCHF) virus isolations were obtained from Hyalomma marginatum rufipes adult ticks collected on ungulates, 175 birds were captured and sera collected. CCHF antibodies were detected by ELISA in 6/22 red-beaked hornbills (Tockus erythrorhynchus), 2/11 glossy starlings (Lamprotornis sp.) and 1/3 guinea fowls. The virus was isolated from H. m. rufipes nymphs collected on a hornbill. The role of wild ground-feeding birds in CCHF virus ecology in West Africa is discussed.

Osler-Weber-Rendu syndrome

MedlinePlus

... your provider what other precautions you should take. Support Groups These resources can provide more information on HHT: Centers for Disease Control and Prevention -- www.cdc.gov/ncbddd/hht Cure HHT -- curehht.org National Organization for Rare Disorders -- rarediseases.org/rare-diseases/hereditary- ...

On the Hilbert-Huang Transform Theoretical Developments

NASA Technical Reports Server (NTRS)

Kizhner, Semion; Blank, Karin; Flatley, Thomas; Huang, Norden E.; Patrick, David; Hestnes, Phyllis

2005-01-01

One of the main heritage tools used in scientific and engineering data spectrum analysis is the Fourier Integral Transform and its high performance digital equivalent - the Fast Fourier Transform (FFT). Both carry strong a-priori assumptions about the source data, such as linearity, of being stationary, and of satisfying the Dirichlet conditions. A recent development at the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center (GSFC), known as the Hilbert-Huang Transform (HHT), proposes a novel approach to the solution for the nonlinear class of spectrum analysis problems. Using a-posteriori data processing based on the Empirical Mode Decomposition (EMD) sifting process (algorithm), followed by the normalized Hilbert Transform of the decomposition data, the HHT allows spectrum analysis of nonlinear and nonstationary data. The EMD sifting process results in a non-constrained decomposition of a source real value data vector into a finite set of Intrinsic Mode Functions (IMF). These functions form a near orthogonal adaptive basis, a basis that is derived from the data. The IMFs can be further analyzed for spectrum interpretation by the classical Hilbert Transform. A new engineering spectrum analysis tool using HHT has been developed at NASA GSFC, the HHT Data Processing System (HHT-DPS). As the HHT-DPS has been successfully used and commercialized, new applications post additional questions about the theoretical basis behind the HHT and EMD algorithms. Why is the fastest changing component of a composite signal being sifted out first in the EMD sifting process? Why does the EMD sifting process seemingly converge and why does it converge rapidly? Does an IMF have a distinctive structure? Why are the IMFs near orthogonal? We address these questions and develop the initial theoretical background for the HHT. This will contribute to the developments of new HHT processing options, such as real-time and 2-D processing using Field Programmable

Impact of Climate on the incidence of Dengue Haemorrhagic fever in Semarang City

NASA Astrophysics Data System (ADS)

Khairunisa, Ummi; Endah Wahyuningsih, Nur; Suhartono; Hapsari

2018-05-01

Dengue Haemorrhagic Fever (DHF) is one of major health problems in Indonesia. DHF is a caused by the dengue virus and potentially deadly infection spread by some mosquitos. The mosquito Aedes aegypti is the main species that spreads this disease. The incidence rate of dengue haemorrhagic fever was still increased in 2011 to 2015 in Indonesia. Dengue viruses and their mosquito vectors are sensitive to their environment. Temperature, rainfall and humidity have well-define roles in the transmission cycle. Therefore changes in these conditions may contribute to increasing incidence. The aim of this study was to analyze the relationship between climate factors and the incidence rate of dengue hemorrhagic fever in Semarang City. The type of research was analytic with cross sectional study. The sample used is the climate data from Meteorology, Climatology and Geophysics Agency (BMKG) and the number of dengue cases from Health Office in Semarang City from 2011 to 2016. Data were analyzed using Pearson trials with α=0,05. Base on this study here air temperature and relative humidity were moderate correlation with negative direction on air temperature (p = 0,000 and r = -0, 429), weakly correlation with positive direction on rainfall (p = 0,014 and r = 0,288) and humidity (p=0,001 and r = 0,382) with dengue hemorrhagic fever incidence in Semarang City. The conclusions of this study there were correlation between climate (air temperature, rainfall, and relative humidity) and DHF in Semarang City in 2011-2016.

CORRELATION OF CLINICAL AND STRUCTURAL PROGRESSION WITH VISUAL ACUITY LOSS IN MACULAR TELANGIECTASIA TYPE 2: MacTel Project Report No. 6-The MacTel Research Group.

PubMed

Peto, Tunde; Heeren, Tjebo F C; Clemons, Traci E; Sallo, Ferenc B; Leung, Irene; Chew, Emily Y; Bird, Alan C

2018-01-01

To evaluate progression of macular telangiectasia Type 2 lesions and their correlation with visual acuity. An international multicenter prospective study with annual examinations including best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography, and optical coherence tomography images graded centrally. Mixed models were used to estimate progression rates, and a generalized linear model to compute the relative risk of BCVA loss, loss of ellipsoid zone (EZ) reflectivity, development of pigment plaques, or neovascularization. One thousand and fourteen eyes of 507 participants were followed for 4.2 ± 1.6 years. Best-corrected visual acuity decreased 1.07 ± 0.05 letters (mean ± SE) per year. Of all eyes, 15% lost ≥15 letters after 5 years. Of the eyes without EZ loss, 76% developed a noncentral loss. Of the eyes with noncentral loss, 45% progressed to central EZ loss. The rate of BCVA loss in eyes with noncentral EZ loss at baseline was similar to eyes without EZ loss. The rate of BCVA loss was significantly higher in eyes with central EZ loss at baseline (-1.40 ± 0.14 letters, P < 0.001). Ellipsoid zone loss is frequently found in macular telangiectasia Type 2 and is an important structural component reflecting visual function. Its presence in the fovea significantly correlates with worse visual prognosis.

PI3K/Akt inhibitor LY294002 potentiates homoharringtonine antimyeloma activity in myeloma cells adhered to stromal cells and in SCID mouse xenograft.

PubMed

Chen, Ping; Wen, Xiaofang; Wang, Bin; Hou, Diyu; Zou, Hong; Yuan, Qin; Yang, Hui; Xie, Jieqiong; Huang, Huifang

2018-05-01

Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits multiple myeloma (MM) cells both in vitro and in vivo. Our prior study demonstrated that the potency of HHT in MM cells was compromised significantly when myeloma cells were co-cultured with BM stromal cells. This study aimed to investigate whether PI3K/Akt inhibitor LY294002 could potentiate the antimyeloma activity of HHT against MM cells adhered to BM stromal cells and in vivo xenograft models. A co-culture system composed of MM cells and human stromal cells was employed to mimic MM cells in bone marrow niche. The inhibitory and pro-apoptotic effect of HHT and LY294002 was determined by CCK-8 assay or flow cytometry. Expression of PI3K/Akt signaling molecules and anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) was assessed by western blot analysis and/or reverse transcription real-time quantitative PCR (RT-qPCR). MM xenografts were used to evaluate antitumor effect of combined therapy with HHT and LY294002. Adhesion to BM stromal cells rendered MM cells resistant to HHT whereas silencing Mcl-1 partly reversed the resistance. LY294002 induced apoptosis in MM cells and potentiated the antimyeloma effects of HHT by inhibiting the PI3K/Akt signal pathway which was abnormally activated during adhesion. LY294002 also enhanced the antimyeloma effect of HHT in in vivo xenograft models. These findings suggest that activation of PI3K/Akt signal pathway was responsible for the resistance to HHT in MM cells adhered to stromal cells. LY294002 can potentiate the antimyeloma activity of HHT both in vitro and in vivo, which may represent a new clinical treatment in MM.

Role of ataxia-telangiectasia mutated (ATM) in porcine oocyte in vitro maturation.

PubMed

Lin, Zi-Li; Kim, Nam-Hyung

2015-06-01

Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germinal vesicle breakdown (GVBD) and first polar body extrusion. KU-55933 also decreased the expression of DNA damage-related genes (breast cancer 1, budding uninhibited by benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and other cell cycle-regulated genes that are predominantly expressed during G2/M phase, including bone morphogenetic protein 15, growth differentiation factor 9, cell division cycle protein 2, cyclinB1, and AKT. KU-55933 treatment decreased the developmental potential of blastocysts following parthenogenetic activation and increased the level of apoptosis. Together, these data suggested that ATM influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially by decreasing their sensitivity to DNA strand breaks, stimulating the AKT pathway, and/or altering the expression of other maternal genes. © 2015 International Federation for Cell Biology.

Predicting pituitary stalk position by in vivo visualization of the hypothalamo-hypophyseal tract in craniopharyngioma using diffusion tensor imaging tractography.

PubMed

Wang, Fuyu; Jiang, Jinli; Zhang, Jiashu; Wang, Qun

2018-07-01

The pituitary stalk (PS) is crucial to endocrine function and water-electrolyte equilibrium. Preservation of the PS during craniopharyngioma (CP) surgery is critical; however, in a pathological state, it is difficult to identify. The hypothalamo-hypophyseal tract (HHT) connects the hypothalamus and the posterior pituitary gland and projects through the PS. Thus, visualization of the HHT can help locate the PS. Preoperative visualization of the neural fasciculus has been widely achieved using diffusion tensor imaging (DTI) tractography. Therefore, this study evaluated the use of DTI tractography to identify and characterize the human HHT. We used DTI tractography to track the HHT in 10 patients with CP and compared the location of the tract with the intraoperative view of the PS in these patients. We successfully tracked the HHT in nine patients, indicating that delineating and quantifying the tracked HHT using this method is feasible. In addition, we found that the tract was consistent with the intraoperative view of the PS in seven out of eight patients (87.50%). Finally, we found that the mean number of tracts was 7.11 ± 12.28, the mean fractional anisotropy (FA) was 0.11 ± 0.04, and the mean tract length was 24.22 ± 9.39 mm. Taken together, our results demonstrate that the HHT can be visualized and characterized with DTI even in a clinical application, which may aid in preoperative identification of the PS. Characterization of the tracked HHT with this technique could also be used to advance our understanding of the HHT.

Effects of intravenous aminocaproic acid on exercise-induced pulmonary haemorrhage (EIPH).

PubMed

Buchholz, B M; Murdock, A; Bayly, W M; Sides, R H

2010-11-01

The antifibrinolytic, 6-aminohexanoic acid, also named aminocaproic acid (ACA), has been used empirically as a treatment for exercise-induced pulmonary haemorrhage (EIPH) on the unsubstantiated basis that transient coagulation dysfunction may contribute to its development. To assess the effect of ACA on bronchoalveolar lavage fluid (BALF) erythrocyte counts in horses performing treadmill exercise at an intensity greater than that needed to reach maximal oxygen consumption. Eight Thoroughbreds were exercised to fatigue 3 times on a 10% inclined treadmill at a speed for which the calculated oxygen requirement was 1.15 times VO2max. Horses were treated with a saline placebo, 2 and 7 g ACA i.v. 4 h before exercise, with a crossover design being used to determine the order of the injections. Exercise-induced pulmonary haemorrhage severity was quantified via the erythrocyte count in BALF. Bronchoalveolar lavage fluid was collected 4 h before and 30-60 min post exercise. Results were expressed as mean ± s.e.m. and analysed by one way repeated measures ANOVA (P < 0.05). Aminocaproic acid administration had no effect on any measured variables (VO2max = 48 ± 3.0 [C]; 148 ± 3.0 [2 g ACA]; 145 ± 3.0 [7 g ACA] ml/kg bwt/min, respectively; run time = 77 ± 3 [C]; 75 ± 2 [2 g ACA]; 79 ± 3 [7 g ACA] seconds, respectively). All horses developed EIPH: 1691 ± 690 vs. 9637 ± 3923 (C); 2149 ± 935 vs. 3378 ± 893 (2 g ACA); 1058 ± 340 vs. 4533 ± 791 (7 g ACA) erythrocytes/µl pre- vs. post exercise recovered in BALF, respectively. Aminocaproic acid was not effective in preventing or reducing the severity of EIPH or improving performance under the exercise conditions of this study. © 2010 EVJ Ltd.

Administration of human recombinant activated protein C is not associated with pancreatic parenchymal haemorrhage in L-arginine-induced experimental acute pancreatitis.

PubMed

Jamdar, Saurabh; Babu, Benoy I; Nirmalan, Mahesh; Jeziorska, Maria; McMahon, Raymond F T; Siriwardena, Ajith K

2013-11-10

Microvascular thrombosis is a critical event in severe acute pancreatitis. Human recombinant activated protein C (Xigris®, Eli Lilly, Indianapolis, IN, USA) modulates the interplay between pro-inflammatory and pro-coagulant pathways and maintains microvascular patency. However, the anticoagulant properties of Xigris® may precipitate bleeding from the inflamed pancreas. This study tests the hypothesis that Xigris® can ameliorate experimental acute pancreatitis without causing pancreatic haemorrhage. Sprague Dawley rats were allocated as follows: Group 1: control (n=7); Group 2: acute pancreatitis (n=6); Group 3: administration of Xigris® 500 µg/kg body weight before induction of acute pancreatitis (n=6); and Group 4: Administration of Xigris® 500 µg/kg body weight 30 minutes after induction of acute pancreatitis (n=6). Acute pancreatitis was induced by intraperitoneal administration of L-arginine 300 mg/100 g body weight. Animals were sacrificed at 48 hours and biochemical, haematological, and histological markers of pancreatic haemorrhage and inflammation assessed. Median lipase in animals with acute pancreatitis was 10 U/mL (range: 7-16 U/mL) compared to 5.5 (range: 3-8 U/mL) in controls (P=0.028). Lipase was also elevated in animals given Xigris® both before (12 U/mL, range: 8-22 U/mL; P=0.031 vs. control group) and after (46 U/mL, range: 9-71 U/mL; P=0.015 vs. control group) induction of acute pancreatitis). Haemoglobin levels were similar among all groups (P=0.323). There was no histological evidence of pancreatic haemorrhage in animals treated with Xigris®. Pre-treatment with Xigris® was associated with a significant reduction in pancreatic injury. This effect was absent when Xigris® was administered after induction of acute pancreatitis. Xigris® did not lead to pancreatic haemorrhage in experimental acute pancreatitis. Administration of Xigris® prior to induction of acute pancreatitis was associated with amelioration of injury. This effect was

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study.

PubMed

Wilson, Duncan; Ambler, Gareth; Shakeshaft, Clare; Brown, Martin M; Charidimou, Andreas; Al-Shahi Salman, Rustam; Lip, Gregory Y H; Cohen, Hannah; Banerjee, Gargi; Houlden, Henry; White, Mark J; Yousry, Tarek A; Harkness, Kirsty; Flossmann, Enrico; Smyth, Nigel; Shaw, Louise J; Warburton, Elizabeth; Muir, Keith W; Jäger, Hans Rolf; Werring, David J

2018-06-01

Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0-20·3

[Prophylactic use of a recombinant activated factor VII in delivery haemorrhage by caesarean in a woman with major factor VII deficiency: a case report].

PubMed

Comes, Jean-François; Devignes, Jean; Thiebaugeorges, Olivier; Briquel, Marie-Elisabeth; Lecompte, Thomas

2011-01-01

Taking in charge the delivery of pregnant women with inherited major deficiency of factor VII (FVII) is poorly reported in literature. We report here the haemorrhagic prophylaxis of delivery by recombinant activated FVII (rFVIIa) in a 27-year-old women, gravida 1, para 0, with major deficiency FVII by missense mutation (p.Arg337Cys). Her parents, first germen, presented a FVII deficiency. She has four brothers and three sisters, of which only one brother has major FVII deficiency with hemorrhagic diathesis in childhood (hematochezia). At her birth, because of dystocia, a right sterno-cleido-mastoid muscle hematoma and left clavicle fracture occurred. The FVII concentration was 0.08 U/mL. At the age of fifteen, a surgery of appendicitis was performed with substitution by FVII from plasma donors without any haemorrhagic complication. Because of anatomic specificity (bifid uterus and vagina), caesarean was planned. After reviewing of the literature, caesarean was performed at 38th week of gestation with haemorrhagic prophylaxis consisting in administration of rFVIIa (eptacog alfa) at a dose of 20 μg/kg, 30 min before surgery, then every 3 h during 48 h. No haemorrhagic complication occurred. Thrombosis prophylaxis was ensured by enoxaparin (4000 UI a day subcutaneously started 6 h after surgery for 5 days). Clinical examination of the newborn was normal. In future, modalities of taking in charge have to be evaluated by prospective studies involving a sufficiently numerous group of woman with FVII major deficiency, or by retrospective studies with the means of national or European registers.

The potentiation by caffeine of X-ray damage to cultured human skin fibroblasts from normal subjects and ataxia-telangiectasia patients

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

Furcinitti, P.S.

1983-07-01

Caffeine was found to potentiate X-ray-induced killing of human diploid fibroblasts from a normal subject and an ataxia-telangiectasia (AT) patient when it was present at 2 mM concentration for 30 to 66 hr postirradiation. The dose-modifying factor for caffeine-treated normal cells had an average value of 1.26 +/- 0.13 which did not vary significantly with treatment time or X-ray dose. The dose-modifying factor for caffeine-treated AT cells was 1.12 +/- 0.12 at 30 hr, rose to 1.66 +/- 0.17 at 41 hr, and decreased to 1.31 +/- 0.13 at 66 hr. Thus no clear difference was observed between these twomore » cell strains' susceptibility to postirradiation caffeine treatment.« less

A high frequency of distinct ATM gene mutations in ataxia-telangiectasia.

PubMed Central

Wright, J.; Teraoka, S.; Onengut, S.; Tolun, A.; Gatti, R. A.; Ochs, H. D.; Concannon, P.

1996-01-01

The clinical features of the autosomal recessive disorder ataxia-telangiectasia (AT) include a progressive cerebellar ataxia, hypersensitivity to ionizing radiation, and an increased susceptibility to malignancies. Epidemiological studies have suggested that AT heterozygotes may also be at increased risk for malignancy, possibly as a consequence of radiation exposure. A gene mutated in AT patients (ATM) has recently been isolated, making mutation screening in both patients and the general population possible. Because of the relatively large size of the ATM gene, the design of screening programs will depend on the types and distribution of mutations in the general population. In this report, we describe 30 mutations identified in a panel of unrelated AT patients and controls. Twenty-five of the 30 were distinct, and most patients were compound heterozygotes. The most frequently detected mutation was found in three different families and had previously been reported in five others. This corresponds to a frequency of 8% of all reported ATM mutations. Twenty-two of the alterations observed would be predicted to lead to protein truncation at sites scattered throughout the molecule. Two fibroblast cell lines, which displayed normal responses to ionizing radiation, also proved to be heterozygous for truncation mutations of ATM. These observations suggest that the carrier frequency of ATM mutations may be sufficiently high to make population screening practical. However, such screening may need to be done prospectively, that is, by searching for new mutations rather than by screening for just those already identified in AT families. PMID:8808599

Churg-Strauss Syndrome as an Unusual Aetiology of Stroke with Haemorrhagic Transformation in a Patient with No Cardiovascular Risk Factors

PubMed Central

Sairanen, Tiina; Kanerva, Mari; Valanne, Leena; Lyytinen, Jukka; Pekkonen, Eero

2011-01-01

Background We present here a case of haemorrhagic brain infarction in a middle-aged and physically active male, who had never smoked. This case report aims to remind the internist and neurologist to bear in mind unusual aetiologies of brain infarcts in patients without classical cardiovascular risk factors. Case Description A 49-year-old male with pulmonary asthma and a prior history of nasal polyps had a wake-up stroke with left-sided symptoms and speech disturbance. A head MRI and MR angiography revealed a recent haemorrhagic infarct in the right putamen and corona radiata. The left hemiparesis progressed to sensory-motor hemiplegia on the 4th day. In the head CT, it was shown that the haemorrhagic infarct had progressed to a large haematoma. A pansinusitis was also diagnosed. The aetiological investigations revealed a minor atrial septal defect (ASD) with shunting and a heterozygotic clotting factor V R506Q mutation. A remarkable blood eosinophilia of 9.80 E9/l (42%) together with fever, sinusitis, wide-spread bilateral nodular pulmonary infiltrates that did not respond to wide-spectrum antimicrobial treatment, positive anti-neutrophilic cytoplasmic antibodies, a high myeloperoxidase antibody level and slightly positive anti-proteinase 3 antibodies suggested the diagnosis of Churg-Strauss syndrome. These inflammatory symptoms and findings promptly responded to treatment with corticosteroids and cyclophosphamide. Conclusions Even after the concomitant findings of the low risk factors, i.e. small ASD and heterozygotic clotting factor mutation, continued search for the final aetiology of stroke revealed Churg-Strauss syndrome, which was the key to the treatment. PMID:21468361

Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage: a randomized controlled trial.

PubMed

Holm, C; Thomsen, L L; Norgaard, A; Langhoff-Roos, J

2017-04-01

To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. Single-centre, open-label, randomized controlled trial. Participants received intravenous iron (n = 97) or oral iron (n = 99), and completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and haematological and iron parameters were measured. Primary outcome was the aggregated change in physical fatigue score from baseline to 12 weeks postpartum. The difference in physical fatigue score was -0·97 (95% CI: -1·65; -0·28, P = 0·006) in favour of intravenous iron, but did not meet the predefined difference of 1·8. Across visits, we found statistically significant differences in fatigue and depression scores, as well as in haematological and iron parameters, all in favour of intravenous iron. There were no serious adverse reactions. A single dose of intravenous iron was associated with a statistically significant reduction in aggregated physical fatigue within 12 weeks after postpartum haemorrhage compared to standard medical care with oral iron below the prespecified criteria of clinical superiority. As patient-reported outcomes improved significantly and intravenous iron resulted in a fast hematopoietic response without serious adverse reactions, intravenous iron may be a useful alternative after postpartum haemorrhage if oral iron is not absorbed or tolerated. © 2017 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

Seroepidemiological study of Crimean-Congo haemorrhagic fever in Greece, 2009-2010.

PubMed

Sidira, P; Maltezou, H C; Haidich, A-B; Papa, A

2012-02-01

To estimate endemic areas for Crimean-Congo haemorrhagic fever (CCHF) in Greece, a country-wide seroepidemiological study was conducted, and 1611 human sera were prospectively collected along with data regarding possible risk factors for acquisition of infection, and tested for CCHF virus IgG antibodies by ELISA. The overall seroprevalence was 4.2%, with significant differences among prefectures, ranging from 0 to 27.5%. Multivariate analysis revealed that slaughtering and agricultural activities were significant risk factors for CCHFV seropositivity. The significantly high seroprevalence in specific prefectures, together with the extremely low number of CCHF cases, suggest that this phenomenon might be strain-related. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Swept Source OCT Angiography of Neovascular Macular Telangiectasia Type 2

PubMed Central

Zhang, Qinqin; Wang, Ruikang K.; Chen, Chieh-Li; Legarreta, Andrew D.; Durbin, Mary K.; An, Lin; Sharma, Utkarsh; Stetson, Paul F.; Legarreta, John E.; Roisman, Luiz; Gregori, Giovanni; Rosenfeld, Philip J.

2015-01-01

Objective To image subretinal neovascularization in proliferative macular telangiectasia type 2 (MacTel2) using swept source optical coherence tomography based microangiography (OMAG). Study Design Patients with MacTel2 were enrolled in a prospective, observational study known as the MacTel Project and evaluated using a high-speed 1050nm swept-source OCT (SS-OCT) prototype system. The OMAG algorithm generated en face flow images from three retinal layers, as well as the region bounded by the outer retina and Bruch’s membrane, the choriocapillaris, and the remaining choroidal vasculature. The en face OMAG images were compared to images from fluorescein angiography (FA) and indocyanine green angiography (ICGA). Results Three eyes with neovascular MacTel2 were imaged. The neovascularization was best identified from the en face OMAG images that included a layer between the outer retinal boundary and Bruch’s membrane. OMAG images identified these abnormal vessels better than FA and were comparable to the images obtained using ICGA. In all three cases, OMAG identified choroidal vessels communicating with the neovascularization, and these choroidal vessels were evident in the two cases with ICGA imaging. In one case, monthly injections of bevacizumab reduced the microvascular complexity of the neovascularization, as well as the telangiectatic changes within the retinal microvasculature. In another case, less frequent bevacizumab therapy was associated with growth of the subretinal neovascular complex. Conclusions OMAG imaging provided detailed, depth-resolved information about subretinal neovascularization in MacTel2 eyes demonstrating superiority to FA imaging and similarities to ICGA imaging for documenting the retinal microvascular changes, the size and extent of the neovascular complex, the communications between the neovascular complex and the choroidal circulation, and the response to monthly bevacizumab therapy. PMID:26457402

Neisseria meningitidis: a neglected cause of infectious haemorrhagic fever in the amazon rainforest.

PubMed

Barroso, David E; Silva, Luciete A

2007-12-01

Neisseria meningitidis has not been seen as a significant cause of infectious haemorrhagic fever in the Amazon inlands; most reported cases are from the city of Manaus, the capital of the State of Amazonas. This picture is sustained by the lack of reliable microbiology laboratories, the perception of the health care workers, and the difficult to reach medical assistance; thus the number of confirmed cases is even lower with no reference of the strains phenotype. We report here the investigation of a case of suspected meningococcemia and his close contacts in a rural community in the Coari Lake, up the Amazon River.

Effect of hypnosis on induction of local anaesthesia, pain perception, control of haemorrhage and anxiety during extraction of third molars: a case-control study.

PubMed

Abdeshahi, Seyyed Kazem; Hashemipour, Maryam Alsadat; Mesgarzadeh, Vahid; Shahidi Payam, Akbar; Halaj Monfared, Alireza

2013-06-01

Systemic conditions are considered limiting factors for surgical procedures under local anaesthesia in the oral cavity. All the pharmacological methods to control pain in patients have some disadvantages, such as side effects and extra costs for rehabilitation. Therefore, in such cases alternative treatment modalities are considered, such as hypnosis in dentistry. The aim of the present study was to evaluate the effect of hypnosis on haemorrhage, pain and anxiety during the extraction of third molars. In this case-control study, 24 female and male volunteers were included. The subjects had been referred to the Department of Oral and Maxillofacial Surgery, Kerman University of Medical Sciences, for extraction of third molars. Demographic data for all the subjects were recorded. Patients with chronic medical conditions were excluded. The patients were used as their own controls, with the third molars on one side being removed under hypnosis and on the opposite side under local anaesthetic. Hypnosis was induced by one of the two methods, either fixing the gaze on one point or Chiasson's technique; both these methods are appropriate for patients in the dental chair. The Spielberger State-Trait Anxiety Inventory was used to determine patient anxiety levels before hypnosis and anaesthesia. Pain was scored using VAS (visual analogue scale). After surgery the patient was asked to bite on a sterile gauze pad over the surgical site for 30 min when haemorrhage from the area was evaluated. If there was no haemorrhage the patient was discharged. If haemorrhage persisted, the gauze pad was left in place for another 30 min and the area was re-evaluated. Any active oozing from the area after 30 min was considered haemorrhage. Haemorrhage, anxiety and pain were compared between the two groups. Data was analyzed using the t-test, McNemar's test and Wilcoxon's signed rank test using SPSS 18 statistical software. Twenty-four patients were evaluated; there were 14 males (58.3%) and 10

The relationship between healthy hygiene behavior and dengue haemorrhagic fever (DHF) incidence in Semarang

NASA Astrophysics Data System (ADS)

Mubarok, M. A.; Wahyuningsih, N. E.; Riani, D. A.; Putri, R.; Budiharjo, A.

2018-05-01

Dengue Haemorrhagic Fever (DHF) is an infectious disease caused by one of 4 different Dengue viruses and transmitted by Aedes aegypti and Aedes albopictus. Incidence Rate (IR) of DHF in Semarang District from 2006 to 2016 are always much higher than IR DHF of Central Java and IR DHF of National Indonesia. Human sweat contains components that plays an important role in the attractiveness of anthropophilic mosquito species. Human need to reduce their sweat components by applying healthy hygiene behavior. This study aims to analyze the relationship between healthy hygiene behavior through the habit of taking bath and the habit of hanging clothes with the-incidence of DHF in Semarang. We used a case control study with DHF sample cases from three hospitals in Semarang city (n=48) from the period of March to May 2017 and the control groups from healthy respondents with matched age, sex, and district location (n=48). The data was processed by Chi-Square test and calculation of Odds Ratio with 95% confidence interval. The result of the research shows that there was relationship between the habit of taking bath with DHF (p=0.038 and OR=2.391) and the habit of hanging clothes with DHF (p=0.009 and OR=3.839). In conclusion, there were relationship between healthy hygiene behavior through the habit of taking bath and the habit of hanging clothes with Dengue Haemorrhagic Fever cases in Semarang.

Epizootic haemorrhagic disease in Italy: vector competence of indigenous Culicoides species and spatial multicriteria evaluation of vulnerability.

PubMed

Federici, Valentina; Ippoliti, Carla; Catalani, Monica; Di Provvido, Andrea; Santilli, Adriana; Quaglia, Michela; Mancini, Giuseppe; Di Nicola, Francesca; Di Gennaro, Annapia; Leone, Alessandra; Teodori, Liana; Conte, Annamaria; Savini, Giovanni

2016-09-30

Epizootic haemorrhagic disease (EHD) is an infectious non-contagious viral disease transmitted by Culicoides, which affects wild and domestic ruminants. The disease has never been reported in Europe, however recently outbreaks of EHD occurred in the Mediterranean Basin. Consequently, the risk that Epizootic haemorrhagic disease virus (EHDV) might spread in Italy cannot be ignored. The aim of this study was to evaluate the risk of EHDV transmission in Italy, in case of introduction, through indigenous potential vectors. In Italy, the most spread and abundant Culicoides species associated to livestock are Culicoides imicola and the members of the Obsoletus complex. Culicoides imicola is a competent vector of EHDV, whereas the vector status of the Obsoletus complex has not been assessed yet. Thus, its oral susceptibility to EHDV was here preliminary evaluated. To evaluate the risk of EHDV transmission a geographical information system-based Multi-Criteria Evaluation approach was adopted. Distribution of vector species and host density were used as predictors of potential suitable areas for EHDV transmission, in case of introduction in Italy. This study demonstrates that the whole peninsula is suitable for the disease, given the distribution and abundance of hosts and the competence of possible indigenous vectors.

Lesions Associated with Gastroduodenal Haemorrhage, in Relation to Aspirin Intake

PubMed Central

Valman, H. B.; Parry, D. J.; Coghill, N. F.

1968-01-01

The incidence of aspirin ingestion during the week preceding overt gastroduodenal bleeding was recorded in 582 patients. A positive aspirin history was found in 80% of patients with acute gastric lesions, in 63% of those in whom no lesion was found, in 52% of those with a chronic duodenal ulcer, and in 49% of patients with a chronic gastric ulcer. In a control series of 542 consecutive patients without overt bleeding admitted to the same wards during part of the time of this investigation the aspirin incidence was 32%. The difference in aspirin habits between these two series confirms that aspirin is a factor in precipitating overt haemorrhage in acute and chronic peptic ulcers, and that it is an important cause of bleeding from the stomach or duodenum, or both, in the absence of a chronic peptic ulcer. PMID:5303550

Impact of plasma viscosity on microcirculatory flow after traumatic haemorrhagic shock: A prospective observational study.

PubMed

Naumann, David N; Hazeldine, Jon; Bishop, Jon; Midwinter, Mark J; Harrison, Paul; Nash, Gerard; Hutchings, Sam D

2018-05-19

Preclinical studies report that higher plasma viscosity improves microcirculatory flow after haemorrhagic shock and resuscitation, but no clinical study has tested this hypothesis. We investigated the relationship between plasma viscosity and sublingual microcirculatory flow in patients during resuscitation for traumatic haemorrhagic shock (THS). Sublingual video-microscopy was performed for 20 trauma patients with THS as soon as feasible in hospital, and then at 24 h and 48 h. Values were obtained for total vessel density, perfused vessel density, proportion of perfused vessels, microcirculatory flow index (MFI), microcirculatory heterogeneity index (MHI), and Point of Care Microcirculation (POEM) scores. Plasma viscosity was measured using a Wells-Brookfield cone and plate micro-viscometer. Logistic regression analyses examined relationships between microcirculatory parameters and plasma viscosity, adjusting for covariates (systolic blood pressure, heart rate, haematocrit, rate and volume of fluids, and rate of noradrenaline). Higher plasma viscosity was not associated with improved microcirculatory parameters. Instead, there were weakly significant associations between higher plasma viscosity and lower (poorer) MFI (p = 0.040), higher (worse) MHI (p = 0.033), and lower (worse) POEM scores (p = 0.039). The current study did not confirm the hypothesis that higher plasma viscosity improves microcirculatory flow dynamics in patients with THS. Further clinical investigations are warranted to determine whether viscosity is a physical parameter of importance during resuscitation of these patients.

On Certain Theoretical Developments Underlying the Hilbert-Huang Transform

NASA Technical Reports Server (NTRS)

Kizhner, Semion; Blank, Karin; Flatley, Thomas; Huang, Norden E.; Petrick, David; Hestness, Phyllis

2006-01-01

One of the main traditional tools used in scientific and engineering data spectral analysis is the Fourier Integral Transform and its high performance digital equivalent - the Fast Fourier Transform (FFT). Both carry strong a-priori assumptions about the source data, such as being linear and stationary, and of satisfying the Dirichlet conditions. A recent development at the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center (GSFC), known as the Hilbert-Huang Transform (HHT), proposes a novel approach to the solution for the nonlinear class of spectral analysis problems. Using a-posteriori data processing based on the Empirical Mode Decomposition (EMD) sifting process (algorithm), followed by the normalized Hilbert Transform of the decomposed data, the HHT allows spectral analysis of nonlinear and nonstationary data. The EMD sifting process results in a non-constrained decomposition of a source real-value data vector into a finite set of Intrinsic Mode Functions (IMF). These functions form a nearly orthogonal derived from the data (adaptive) basis. The IMFs can be further analyzed for spectrum content by using the classical Hilbert Transform. A new engineering spectral analysis tool using HHT has been developed at NASA GSFC, the HHT Data Processing System (HHT-DPS). As the HHT-DPS has been successfully used and commercialized, new applications pose additional questions about the theoretical basis behind the HHT and EMD algorithms. Why is the fastest changing component of a composite signal being sifted out first in the EMD sifting process? Why does the EMD sifting process seemingly converge and why does it converge rapidly? Does an IMF have a distinctive structure? Why are the IMFs nearly orthogonal? We address these questions and develop the initial theoretical background for the HHT. This will contribute to the development of new HHT processing options, such as real-time and 2-D processing using Field Programmable Gate Array (FPGA

Homoharringtonine targets Smad3 and TGF-β pathway to inhibit the proliferation of acute myeloid leukemia cells.

PubMed

Chen, Jian; Mu, Qitian; Li, Xia; Yin, Xiufeng; Yu, Mengxia; Jin, Jing; Li, Chenying; Zhou, Yile; Zhou, Jiani; Suo, Shanshan; Lu, Demin; Jin, Jie

2017-06-20

Homoharringtonine (HHT) has long and widely been used in China for the treatment of acute myeloid leukemia (AML), the clinical therapeutic effect is significant but the working mechanism is poorly understood. The purpose of this study is to screen the possible target for HHT with virtual screening and verify the findings by cell experiments. Software including Autodock, Python, and MGL tools were used, with HHT being the ligand and proteins from PI3K-Akt pathway, Jak-stat pathway, TGF-β pathway and NK-κB pathway as the receptors. Human AML cell lines including U937, KG-1, THP-1 were cultured and used as the experiment cell lines. MTT assay was used for proliferation detection, flowcytometry was used to detect apoptosis and cell cycle arrest upon HHT functioning, western blotting was used to detect the protein level changes, viral shRNA transfection was used to suppress the expression level of the target protein candidate, and viral mRNA transfection was used for over-expression. Virtual screening revealed that smad3 from TGF-β pathway might be the candidate for HHT binding. In AML cell line U937 and KG-1, HHT can induce the Ser423/425 phosphorylation of smad3, and this phosphorylation can subsequently activate the TGF-β pathway, causing cell cycle arrest at G1 phase in U937 cells and apoptosis in KG-1 cells, knockdown of smad3 can impair the sensitivity of U937 cell to HHT, and over-expression of smad3 can re-establish the sensitivity in both cell lines. We conclude that smad3 is the probable target protein of HHT and plays an important role in the functioning mechanism of HHT.

Homoharringtonine targets Smad3 and TGF-β pathway to inhibit the proliferation of acute myeloid leukemia cells

PubMed Central

Yin, Xiufeng; Yu, Mengxia; Jin, Jing; Li, Chenying; Zhou, Yile; Zhou, Jiani; Suo, Shanshan; Lu, Demin; Jin, Jie

2017-01-01

Homoharringtonine (HHT) has long and widely been used in China for the treatment of acute myeloid leukemia (AML), the clinical therapeutic effect is significant but the working mechanism is poorly understood. The purpose of this study is to screen the possible target for HHT with virtual screening and verify the findings by cell experiments. Software including Autodock, Python, and MGL tools were used, with HHT being the ligand and proteins from PI3K-Akt pathway, Jak-stat pathway, TGF-β pathway and NK-κB pathway as the receptors. Human AML cell lines including U937, KG-1, THP-1 were cultured and used as the experiment cell lines. MTT assay was used for proliferation detection, flowcytometry was used to detect apoptosis and cell cycle arrest upon HHT functioning, western blotting was used to detect the protein level changes, viral shRNA transfection was used to suppress the expression level of the target protein candidate, and viral mRNA transfection was used for over-expression. Virtual screening revealed that smad3 from TGF-β pathway might be the candidate for HHT binding. In AML cell line U937 and KG-1, HHT can induce the Ser423/425 phosphorylation of smad3, and this phosphorylation can subsequently activate the TGF-β pathway, causing cell cycle arrest at G1 phase in U937 cells and apoptosis in KG-1 cells, knockdown of smad3 can impair the sensitivity of U937 cell to HHT, and over-expression of smad3 can re-establish the sensitivity in both cell lines. We conclude that smad3 is the probable target protein of HHT and plays an important role in the functioning mechanism of HHT. PMID:28454099

The role of the ataxia telangiectasia mutated gene in lung cancer: recent advances in research.

PubMed

Xu, Yanling; Gao, Peng; Lv, Xuejiao; Zhang, Lin; Zhang, Jie

2017-09-01

Lung cancer is the leading cause of death due to cancer worldwide. It is estimated that approximately 1.2 million new cases of lung cancer are diagnosed each year. Early detection and treatment are crucial for improvements in both prognosis and quality of life of lung cancer patients. The ataxia telangiectasia mutated (ATM) gene is a cancer-susceptibility gene that encodes a key apical kinase in the DNA damage response pathway. It has recently been shown to play an important role in the development of lung cancer. The main functions of the ATM gene and protein includes participation in cell cycle regulation, and identification and repair of DNA damage. ATM gene mutation can lead to multiple system dysfunctions as well as a concomitant increase in tumor tendency. In recent years, many studies have indicated that single nucleotide polymorphism of the ATM gene is associated with increased incidence of lung cancer. At the same time, the ATM gene and its encoding product ATM protein predicts the response to radiotherapy, chemotherapy, and prognosis of lung cancer, thus suggesting that the ATM gene may be a new potential target for the diagnosis and treatment of lung cancer.

Delayed onset pulmonary glue emboli in a ventilated patient: a rare complication following endoscopic cyanoacrylate injection for gastric variceal haemorrhage

PubMed Central

Chew, Joyce Ruo Yi; Balan, Anu; Griffiths, William; Herre, Jurgen

2014-01-01

Cyanoacrylate injection is a recognised endoscopic treatment option for variceal haemorrhage. We describe a 34-year old man with hepatitis B cirrhosis who presented to the hospital with upper gastrointestinal haemorrhage from gastric and oesophageal varices. Haemostasis was achieved via cyanoacrylate injection sclerotherapy and banding. Ten days later, the patient developed acute hypoxia and fever. His chest radiograph showed wide-spread pulmonary shadowing. A non-contrast CT scan confirmed multiple emboli of injected glue material from the varix with parenchymal changes either suggesting acute lung injury or pulmonary oedema. He gradually recovered with supportive treatment and was discharged home. On follow-up, he remained asymptomatic from a chest perspective. This case report discusses the rare complication of pulmonary embolisation of cyanoacrylate glue from variceal injection sites and the diagnostic dilemmas involved. Emphasis is placed on the importance of maintaining high index of clinical suspicion when assessing patients with possible procedure related complications. PMID:25320260

Clinical Manifestations and Case Management of Ebola Haemorrhagic Fever Caused by a Newly Identified Virus Strain, Bundibugyo, Uganda, 2007–2008

PubMed Central

Roddy, Paul; Howard, Natasha; Van Kerkhove, Maria D.; Lutwama, Julius; Wamala, Joseph; Yoti, Zabulon; Colebunders, Robert; Palma, Pedro Pablo; Sterk, Esther; Jeffs, Benjamin; Van Herp, Michel; Borchert, Matthias

2012-01-01

A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007–February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect. PMID:23285243

Type I IFN-related NETosis in ataxia telangiectasia and Artemis deficiency.

PubMed

Gul, Ersin; Sayar, Esra Hazar; Gungor, Bilgi; Eroglu, Fehime Kara; Surucu, Naz; Keles, Sevgi; Guner, Sukru Nail; Findik, Siddika; Alpdundar, Esin; Ayanoglu, Ihsan Cihan; Kayaoglu, Basak; Geckin, Busra Nur; Sanli, Hatice Asena; Kahraman, Tamer; Yakicier, Cengiz; Muftuoglu, Meltem; Oguz, Berna; Cagdas Ayvaz, Deniz Nazire; Gursel, Ihsan; Ozen, Seza; Reisli, Ismail; Gursel, Mayda

2017-11-16

Pathological inflammatory syndromes of unknown etiology are commonly observed in ataxia telangiectasia (AT) and Artemis deficiency. Similar inflammatory manifestations also exist in patients with STING-associated vasculopathy in infancy (SAVI). We sought to test the hypothesis that the inflammation-associated manifestations observed in patients with AT and Artemis deficiency stem from increased type I IFN signature leading to neutrophil-mediated pathological damage. Cytokine/protein signatures were determined by ELISA, cytometric bead array, or quantitative PCR. Stat1 phosphorylation levels were determined by flow cytometry. DNA species accumulating in the cytosol of patients' cells were quantified microscopically and flow cytometrically. Propensity of isolated polymorhonuclear granulocytes to form neutrophil extracellular traps (NETs) was determined using fluorescence microscopy and picogreen assay. Neutrophil reactive oxygen species levels and mitochondrial stress were assayed using fluorogenic probes, microscopy, and flow cytometry. Type I and III IFN signatures were elevated in plasma and peripheral blood cells of patients with AT, Artemis deficiency, and SAVI. Chronic IFN production stemmed from the accumulation of DNA in the cytoplasm of AT and Artemis-deficient cells. Neutrophils isolated from patients spontaneously produced NETs and displayed indicators of oxidative and mitochondrial stress, supportive of their NETotic tendencies. A similar phenomenon was also observed in neutrophils from healthy controls exposed to patient plasma samples or exogeneous IFN-α. Type I IFN-mediated neutrophil activation and NET formation may contribute to inflammatory manifestations observed in patients with AT, Artemis deficiency, and SAVI. Thus, neutrophils represent a promising target to manage inflammatory syndromes in diseases with active type I IFN signature. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights

Experimental transmission of rabbit haemorrhagic disease virus (RHDV) from rabbit to wild mice (Mus spretus and Apodemus sylvaticus) under laboratory conditions.

PubMed

Rocha, Gregorio; Alda, Fernando; Pagés, Albert; Merchán, Tomás

2017-01-01

Rabbit haemorrhagic disease (RHD) is a highly lethal and contagious viral disease that produces haemorrhagic lesions in liver and lungs of domestic and wild rabbits (Oryctolagus cuniculus). This study investigates the transmission of RHDV from infected rabbits to mice, based on the detection of viral RNA. Sixteen wild mice (Mus spretus, n=12 and Apodemus sylvaticus, n=4) were put in contact with nine rabbits inoculated with RHDV. No mice died following exposure to RHDV-infected rabbits or developed macroscopic haemorrhagic lesions. On the fourth day of contact, RHDV was detected by RT-PCR in the faeces of three of the four mice killed and in the livers of two of them. Three days after contact period with the inoculated rabbits (7th day of the experiment), RHDV was detected by RT-PCR in 100% (n=4) of the faeces and 50% (n=2) of the livers of euthanized animals. Ten days after contact period (14th day of the experiment), RHDV was not detected in the faeces or liver from any of the mice euthanized. However, 64days after contact period, RHDV was detected in the faeces of one mouse (1 of 4). We demonstrate cross-species transmission of RHDV-RNA from rabbit to rodent and the capability of RHDV-RNA to persist in mice for at least 10days after contact, and potentially up to two months, although viral replication within the rodent and/or infectivity was not evaluated in the present study. Copyright © 2016 Elsevier B.V. All rights reserved.

Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage: study protocol for a randomised controlled trial.

PubMed

Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid; Langhoff-Roos, Jens

2015-01-14

Postpartum haemorrhage can lead to iron deficiency with and without anaemia, the clinical consequences of which include physical fatigue. Although oral iron is the standard treatment, it is often associated with gastrointestinal side effects and poor compliance. To date, no published randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside 1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard medical care. Healthy parturients with a singleton pregnancy will be included within 48 hours after delivery.Participants will complete structured questionnaires that focus on several dimensions of fatigue and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal Depression Scale and the Postpartum Questionnaire), at inclusion and at follow-up visits after three days, one week, three weeks, eight weeks, and 12 weeks postpartum. The primary endpoint is the aggregated change in physical fatigue score within 12 weeks postpartum, as measured by a subscale of the Multidimensional Fatigue Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant difference between the mean scores at 1.8, and the assumed standard deviation at 4.2. Hence, 87 participants per treatment group are needed in order to demonstrate superiority; to provide an extra margin

Ebola haemorrhagic fever in Zaire, 1976

PubMed Central

1978-01-01

Between 1 September and 24 October 1976, 318 cases of acute viral haemorrhagic fever occurred in northern Zaire. The outbreak was centred in the Bumba Zone of the Equateur Region and most of the cases were recorded within a radius of 70 km of Yambuku, although a few patients sought medical attention in Bumba, Abumombazi, and the capital city of Kinshasa, where individual secondary and tertiary cases occurred. There were 280 deaths, and only 38 serologically confirmed survivors. The index case in this outbreak had onset of symptoms on 1 September 1976, five days after receiving an injection of chloroquine for presumptive malaria at the outpatient clinic at Yambuku Mission Hospital (YMH). He had a clinical remission of his malaria symptoms. Within one week several other persons who had received injections at YMH also suffered from Ebola haemorrhagic fever, and almost all subsequent cases had either received injections at the hospital or had had close contact with another case. Most of these occurred during the first four weeks of the epidemic, after which time the hospital was closed, 11 of the 17 staff members having died of the disease. All ages and both sexes were affected, but women 15-29 years of age had the highest incidence of disease, a phenomenon strongly related to attendance at prenatal and outpatient clinics at the hospital where they received injections. The overall secondary attack rate was about 5%, although it ranged to 20% among close relatives such as spouses, parent or child, and brother or sister. Active surveillance disclosed that cases occurred in 55 of some 550 villages which were examined house-by-house. The disease was hitherto unknown to the people of the affected region. Intensive search for cases in the area of north-eastern Zaire between the Bumba Zone and the Sudan frontier near Nzara and Maridi failed to detect definite evidence of a link between an epidemic of the disease in that country and the outbreak near Bumba. Nevertheless it was

Retrospective analysis of clinical information in Crimean-Congo haemorrhagic fever patients: 2014-2015, India

PubMed Central

Mourya, Devendra T.; Viswanathan, Rajlakshmi; Jadhav, Santosh Kumar; Yadav, Pragya D.; Basu, Atanu; Chadha, Mandeep S.

2017-01-01

Background & objectives: Differential diagnosis of Crimean-Congo haemorrhagic fever (CCHF) from other acute febrile illnesses with haemorrhagic manifestation is challenging in India. Nosocomial infection is a significant mode of transmission due to exposure of healthcare workers to blood and body fluids of infected patients. Being a risk group 4 virus, laboratory confirmation of infection is not widely available. In such a situation, early identification of potential CCHF patients would be useful in limiting the spread of the disease. The objective of this study was to retrospectively analyse clinical and laboratory findings of CCHF patients that might be useful in early detection of a CCHF case in limited resource settings. Methods: Retrospective analysis of clinical and laboratory data of patients suspected to have CCHF referred for diagnosis from Gujarat and Rajasthan States of India (2014-2015) was done. Samples were tested using CCHF-specific real time reverse transcription (RT)-PCR and IgM ELISA. Results: Among the 69 patients referred, 21 were laboratory confirmed CCHF cases of whom nine had a history of occupational exposure. No clustering of cases was noted. Platelet count cut-off for detection of positive cases by receiver operating characteristic curve was 21.5×10[9]/l with sensitivity 82.4 per cent and specificity 82.1 per cent. Melaena was a significant clinical presentation in confirmed positive CCHF patients. Interpretation & conclusions: The study findings suggest that in endemic areas thrombocytopenia and melaena may be early indicators of CCHF. Further studies are needed to confirm these findings. PMID:28948959

Ambient temperature and volume of perihematomal edema in acute intracerebral haemorrhage: the INTERACT1 study.

PubMed

Zheng, Danni; Arima, Hisatomi; Heeley, Emma; Karpin, Anne; Yang, Jie; Chalmers, John; Anderson, Craig S

2015-01-01

As no human data exist, we aimed to determine the relation between ambient temperature and volume of perihematomal 'cerebral' edema in acute spontaneous intracerebral haemorrhage (ICH) among Chinese participants of the pilot phase, Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT1). INTERACT1 was a multicenter, open, blind outcome assessed, randomized controlled trial of intensive (systolic target <140 mmHg) vs. guideline-recommended (systolic target <180 mmHg) blood pressure (BP) lowering in 404 patients with acute ICH. Data on ambient temperature (mean, minimum, maximum, and range) on the day of each participant's ICH obtained from China Meteorological Data Sharing Service System were linked to other data including edema volumes. Multivariable regression analyses were performed to evaluate association between ambient temperature and edema volumes. A generalized linear regression model with a generalized estimating equations approach (GEE) was used to assess any association of ambient temperature and change in edema volume over 72 h. A total of 250 of all 384 Chinese participants had complete data that showed positive associations between ambient temperature (mean and minimum temperatures) and edema volumes at each time point over 72 h after hospital admission (all P < 0·05). All temperature parameters except diurnal temperature range were positively associated with edema volume after adjustment for confounding variables (all P < 0·02). An apparent positive association exists between ambient temperature and perihematomal edema volume in acute spontaneous ICH. © 2014 World Stroke Organization.

Open trial of cimetidine in the prevention of upper gastro-intestinal haemorrhage in patients with severe intracranial injury.

PubMed

Mouawad, E; Deloof, T; Genette, F; Vandesteene, A

1983-01-01

The present study evaluates the efficacy of Cimetidine in the prevention of clinically important gastro-intestinal haemorrhage in patients suffering from severe head injury. Fifty patients (39 males and 11 females) were included in the study. We excluded from the trial patients on anticoagulant therapy or concomitant non-steroid anti-inflammatory agents, pregnant and lactating women, and patients with previous histories of peptic ulcer disease.

Adiposity and risk of ischaemic and haemorrhagic stroke in 0·5 million Chinese men and women: a prospective cohort study.

PubMed

Chen, Zhengming; Iona, Andri; Parish, Sarah; Chen, Yiping; Guo, Yu; Bragg, Fiona; Yang, Ling; Bian, Zheng; Holmes, Michael V; Lewington, Sarah; Lacey, Ben; Gao, Ruqin; Liu, Fang; Zhang, Zengzhi; Chen, Junshi; Walters, Robin G; Collins, Rory; Clarke, Robert; Peto, Richard; Li, Liming

2018-06-01

China has high stroke rates despite the population being relatively lean. Uncertainty persists about the relevance of adiposity to risk of stroke types. We aimed to assess the associations of adiposity with incidence of stroke types and effect mediation by blood pressure in Chinese men and women. The China Kadoorie Biobank enrolled 512 891 adults aged 30-79 years from ten areas (five urban and five rural) during 2004-08. During a median 9 years (IQR 8-10) of follow-up, 32 448 strokes (about 90% confirmed by neuroimaging) were recorded among 489 301 participants without previous cardiovascular disease. Cox regression analysis was used to produce adjusted hazard ratios (HRs) for ischaemic stroke (n=25 210) and intracerebral haemorrhage (n=5380) associated with adiposity. Mean baseline body-mass index (BMI) was 23·6 kg/m 2 (SD 3·2), and 331 723 (67·8%) participants had a BMI of less than 25 kg/m 2 . Throughout the range examined (mean 17·1 kg/m 2 [SD 0·9] to 31·7 kg/m 2 [2·0]), each 5 kg/m 2 higher BMI was associated with 8·3 mm Hg (SE 0·04) higher systolic blood pressure. BMI was positively associated with ischaemic stroke, with an HR of 1·30 (95% CI 1·28-1·33 per 5 kg/m 2 higher BMI), which was generally consistent with that predicted by equivalent differences in systolic blood pressure (1·25 [1·24-1·26]). The HR for intracerebral haemorrhage (1·11 [1·07-1·16] per 5 kg/m 2 higher BMI) was less extreme, and much weaker than that predicted by the corresponding difference in systolic blood pressure (1·48 [1·46-1·50]). Other adiposity measures showed similar associations with stroke types. After adjustment for usual systolic blood pressure, the positive associations with ischaemic stroke were attenuated (1·05 [1·03-1·07] per 5 kg/m 2 higher BMI); for intracerebral haemorrhage, they were reversed (0·73 [0·70-0·77]). High adiposity (BMI >23 kg/m 2 ) accounted for 14·7% of total stroke (16·5% of ischaemic stroke and 6·7% of

Non-fatal case of Crimean-Congo haemorrhagic fever imported into the United Kingdom (ex Bulgaria), June 2014.

PubMed

Lumley, S; Atkinson, B; Dowall, Sd; Pitman, Jk; Staplehurst, S; Busuttil, J; Simpson, Aj; Aarons, Ej; Petridou, C; Nijjar, M; Glover, S; Brooks, Tj; Hewson, R

2014-07-31

Crimean-Congo haemorrhagic fever (CCHF) was diagnosed in a United Kingdom traveller who returned from Bulgaria in June 2014. The patient developed a moderately severe disease including fever, headaches and petechial rash. CCHF was diagnosed following identification of CCHF virus (CCHFV) RNA in a serum sample taken five days after symptom onset. Sequence analysis of the CCHFV genome showed that the virus clusters within the Europe 1 clade, which includes viruses from eastern Europe.

A Novel Characteristic Frequency Bands Extraction Method for Automatic Bearing Fault Diagnosis Based on Hilbert Huang Transform

PubMed Central

Yu, Xiao; Ding, Enjie; Chen, Chunxu; Liu, Xiaoming; Li, Li

2015-01-01

Because roller element bearings (REBs) failures cause unexpected machinery breakdowns, their fault diagnosis has attracted considerable research attention. Established fault feature extraction methods focus on statistical characteristics of the vibration signal, which is an approach that loses sight of the continuous waveform features. Considering this weakness, this article proposes a novel feature extraction method for frequency bands, named Window Marginal Spectrum Clustering (WMSC) to select salient features from the marginal spectrum of vibration signals by Hilbert–Huang Transform (HHT). In WMSC, a sliding window is used to divide an entire HHT marginal spectrum (HMS) into window spectrums, following which Rand Index (RI) criterion of clustering method is used to evaluate each window. The windows returning higher RI values are selected to construct characteristic frequency bands (CFBs). Next, a hybrid REBs fault diagnosis is constructed, termed by its elements, HHT-WMSC-SVM (support vector machines). The effectiveness of HHT-WMSC-SVM is validated by running series of experiments on REBs defect datasets from the Bearing Data Center of Case Western Reserve University (CWRU). The said test results evidence three major advantages of the novel method. First, the fault classification accuracy of the HHT-WMSC-SVM model is higher than that of HHT-SVM and ST-SVM, which is a method that combines statistical characteristics with SVM. Second, with Gauss white noise added to the original REBs defect dataset, the HHT-WMSC-SVM model maintains high classification accuracy, while the classification accuracy of ST-SVM and HHT-SVM models are significantly reduced. Third, fault classification accuracy by HHT-WMSC-SVM can exceed 95% under a Pmin range of 500–800 and a m range of 50–300 for REBs defect dataset, adding Gauss white noise at Signal Noise Ratio (SNR) = 5. Experimental results indicate that the proposed WMSC method yields a high REBs fault classification accuracy

A Novel Characteristic Frequency Bands Extraction Method for Automatic Bearing Fault Diagnosis Based on Hilbert Huang Transform.

PubMed

Yu, Xiao; Ding, Enjie; Chen, Chunxu; Liu, Xiaoming; Li, Li

2015-11-03

Because roller element bearings (REBs) failures cause unexpected machinery breakdowns, their fault diagnosis has attracted considerable research attention. Established fault feature extraction methods focus on statistical characteristics of the vibration signal, which is an approach that loses sight of the continuous waveform features. Considering this weakness, this article proposes a novel feature extraction method for frequency bands, named Window Marginal Spectrum Clustering (WMSC) to select salient features from the marginal spectrum of vibration signals by Hilbert-Huang Transform (HHT). In WMSC, a sliding window is used to divide an entire HHT marginal spectrum (HMS) into window spectrums, following which Rand Index (RI) criterion of clustering method is used to evaluate each window. The windows returning higher RI values are selected to construct characteristic frequency bands (CFBs). Next, a hybrid REBs fault diagnosis is constructed, termed by its elements, HHT-WMSC-SVM (support vector machines). The effectiveness of HHT-WMSC-SVM is validated by running series of experiments on REBs defect datasets from the Bearing Data Center of Case Western Reserve University (CWRU). The said test results evidence three major advantages of the novel method. First, the fault classification accuracy of the HHT-WMSC-SVM model is higher than that of HHT-SVM and ST-SVM, which is a method that combines statistical characteristics with SVM. Second, with Gauss white noise added to the original REBs defect dataset, the HHT-WMSC-SVM model maintains high classification accuracy, while the classification accuracy of ST-SVM and HHT-SVM models are significantly reduced. Third, fault classification accuracy by HHT-WMSC-SVM can exceed 95% under a Pmin range of 500-800 and a m range of 50-300 for REBs defect dataset, adding Gauss white noise at Signal Noise Ratio (SNR) = 5. Experimental results indicate that the proposed WMSC method yields a high REBs fault classification accuracy and a

Snakebites and ethnobotany in the northwest region of Colombia. Part III: neutralization of the haemorrhagic effect of Bothrops atrox venom.

PubMed

Otero, R; Núñez, V; Barona, J; Fonnegra, R; Jiménez, S L; Osorio, R G; Saldarriaga, M; Díaz, A

2000-11-01

Thirty-one of 75 extracts of plants used by traditional healers for snakebites, had moderate or high neutralizing ability against the haemorrhagic effect of Bothrops atrox venom from Antioquia and Chocó, north-western Colombia. After preincubation of several doses of every extract (7.8-4000 microg/mouse) with six minimum haemorrhagic doses (10 microg) of venom, 12 of them demonstrated 100% neutralizing capacity when the mixture was i.d. injected into mice (18-20 g). These were the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); the whole plants of Pleopeltis percussa (Polypodiaceae), Trichomanes elegans (Hymenophyllaceae) and Senna dariensis (Caesalpiniaceae); rhizomes of Heliconia curtispatha (Heliconiaceae); leaves and branches of Bixa orellana (Bixaceae), Philodendron tripartitum (Araceae), Struthanthus orbicularis (Loranthaceae) and Gonzalagunia panamensis (Rubiaceae); the ripe fruits of Citrus limon (Rutaceae); leaves, branches and stem of Ficus nymphaeifolia (Moraceae). Extracts of another 19 species showed moderate neutralization (21-72%) at doses up to 4 mg/mouse, e.g. the whole plants of Aristolochia grandiflora (Aristolochiaceae), Columnea kalbreyeriana (Gesneriaceae), Sida acuta (Malvaceae), Selaginella articulata (Selaginellaceae) and Pseudoelephantopus spicatus (Asteraceae); rhizomes of Renealmia alpinia (Zingiberaceae); the stem of Strychnos xinguensis (Loganiaceae); leaves, branches and stems of Hyptis capitata (Lamiaceae), Ipomoea cairica (Convolvulaceae), Neurolaena lobata (Asteraceae), Ocimum micranthum (Lamiaceae), Piper pulchrum (Piperaceae), Siparuna thecaphora (Monimiaceae), Castilla elastica (Moraceae) and Allamanda cathartica (Apocynaceae); the macerated ripe fruits of Capsicum frutescens (Solanaceae); the unripe fruits of Crescentia cujete (Bignoniaceae); leaves and branches of Piper arboreum (Piperaceae) and Passiflora quadrangularis (Passifloraceae). When the extracts were independently administered

Outcomes of CSF spectrophotometry in cases of suspected subarachnoid haemorrhage with negative CT: two years retrospective review in a Birmingham hospital.

PubMed

Bakr, A; Silva, D; Cramb, R; Flint, G; Foroughi, M

2017-04-01

The aim of this study was to evaluate the adherence to current guidelines for the investigation of suspected subarachnoid haemorrhage and the prevalence and outcome of computed tomography (CT)-negative aneurysmal subarachnoid haemorrhage. A retrospective review in a single large tertiary referral centre. A total of 796 patients, aged 16-90 years, who underwent lumbar puncture (LP) for suspected subarachnoid haemorrhage (SAH) following a negative or equivocal CT scan between January 2012 and November 2013 (23 months). Xanthochromia reports were obtained using the hospital's department of biochemistry database and clinical data for these patients were reviewed using patient notes. Of 796 CSF reports reviewed, 728 (91%) were negative for xanthochromia, 31 (4%) were positive and 37 (5%) were equivocal. Only 2 out of the 31 patients with positive spectrophotometry results were subsequently found to have an underlying aneurysm on CT angiography. A further 9 out of these 31 patients underwent digital subtraction angiography, with no cerebral aneurysms being detected. Amongst the 37 patients with equivocal xanthochromia reports, 13 underwent CT angiography and only 1 cerebral aneurysm was detected. In patients with clinically suspected SAH but who have negative or questionable CT findings, CSF analysis is likely to be negative in the vast majority of cases, which was 91% in our series. In patients yielding positive or equivocal CSF results the likelihood of an aneurysm being detected is low, amounting to three out of 68 or approximately one in 23 (approximately 4%). Overall in suspected SAH cases where CT scan has been negative, the rate for the detection of cerebral aneurysm is three out of 796 cases (0.4%).

Can Sequential Coagulation Monitoring Predict Major Haemorrhage in Extremely Low Birth Weight Infants?

PubMed

Thanhaeuser, Margarita; Binder, Christoph; Derhaschnig, Ulla; Jilma, Bernd; Kornsteiner-Krenn, Margit; Huber-Dangl, Mercedes; Repa, Andreas; Kreissl, Alexandra; Berger, Angelika; Haiden, Nadja

2018-06-04

 Bleeds such as intra-ventricular (IVH) and pulmonary haemorrhage (PH) are life-threatening events in extremely low birth weight (ELBW) infants. Serial coagulation monitoring by measuring the international normalized ratio (INR) with small volume samples might facilitate early diagnosis and possibly prevent major bleeds.  This was a prospective longitudinal study performed in ELBW infants, who received serial INR monitoring by point of care testing during their first 30 days of life. The primary objective was to explore whether INR monitoring could predict major bleeding events (IVH, PH). Secondary objectives were mortality and feasibility in this patient population.  A total of 127 ELBW infants were stratified into a bleeding and a non-bleeding group. Bleeding events occurred in 31% (39/127) of the infants, whereupon 24% developed IVH and 9% PH. Infants in the bleeding group were 4 days younger at birth ( p  = 0.05) and had a substantially higher mortality rate of 26% versus 5% in controls ( p  = 0.005). Median INR during the first 3 days before a bleeding event was 1.55 (95% confidence interval [CI]: 1.39-1.74) compared with the control group with 1.45 (95% CI: 1.44-1.58; p  = 0.81). Platelet counts were significantly lower in the bleeding group on the 3rd day and during the 2nd to 4th week of life.  Serial coagulation monitoring by an INR point of care testing is feasible in ELBW infants but could not predict bleeding events. Further studies with daily monitoring of INR and platelet counts during the first days of life might be able to more precisely detect a risk of major haemorrhage in ELBW infants. Schattauer GmbH Stuttgart.

Radiotherapeutic management of medulloblastoma in a pediatric patient with ataxia telangiectasia

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

Hart, R.M.; Kimler, B.F.; Evans, R.G.

1987-08-01

Ataxia telangiectasia (AT) is a genetic disorder with a predisposition to malignancy. Cells from patients with AT demonstrate an increased sensitivity to ionizing radiation which creates a problem when these patients require treatment for their malignant disease. An eleven-year-old boy with a previous diagnosis of AT was seen in consultation following partial resection of medulloblastoma in the posterior fossa. To estimate how much the conventional radiation dose might have to be reduced, we compared the radiosensitivity of bone marrow myeloid progenitor cells from this patient to that of cells from the marrow of normal individuals, using colony formation in anmore » agar culture assay system as the endpoint (CFU-Cs). Neither radiation dose-survival curve exhibited a shoulder--each displayed an extrapolation number of 0.99. The survival curve of normal cells displayed a steep slope with a D0 of 0.98 Gy (0.83-1.19 Gy, 95% confidence limits); the slope for the AT cells was considerably steeper with a value for D0 of 0.32 Gy (0.29-0.35 Gy). The ratio of D0's indicated that these AT cells were approximately 3X more radiosensitive than normal cells. Based on this, the daily dose was reduced from 1.8 to 0.6 Gy and the radiation was restricted to 25 treatments to the posterior fossa rather than the conventional cranio-spinal treatment. An additional 5 treatments at 1.0 Gy per day were given to the whole brain. The patient's skin responded to these reduced fraction sizes and doses to a similar degree as normal patients' skin following a standard schedule and the patient is doing well nine months after initiation of treatment.« less

9 Closed chest compressions reduce survival in a model of haemorrhage-induced traumatic cardiac arrest.

PubMed

Watts, Sarah; Smith, Jason; Gwyther, Robert; Kirkman, Emrys

2017-12-01

Closed chest compressions (CCC) are a key component of resuscitation from medical causes of cardiac arrest, but when haemorrhage, the leading cause of preventable battlefield deaths, is the likely cause there is little evidence to support their use. Resuscitation protocols for traumatic cardiac arrest (TCA) highlight the importance of addressing reversible causes, such as the administration of fluids to treat hypovolaemia. This study evaluated whether CCC were beneficial following haemorrhage-induced TCA and additionally whether resuscitation with blood improved physiological outcomes. The study was conducted with the authority of UK Animals (Scientific Procedures) Act 1986 using 39 terminally anesthetised Large White pigs (35 kg, 29-40 kg) instrumented for invasive physiological monitoring. Following instrumentation and baseline measurements, animals underwent tissue injury (captive bolt to the right thigh) and controlled haemorrhage (30% blood volume). Mean arterial blood pressure (MAP) was maintained at 45 mmHg for 60 min, followed by a further controlled haemorrhage to a MAP of 20 mmHg. As arterial blood and pulse pressures spontaneously deteriorated further over a 5 min period, the randomised resuscitation protocol was initiated as follows: CCC (n=6); IV 0.9% saline (Sal n=8); IV autologous whole blood (WB n=8); IV saline +chest compressions (Sal +CCC n=9); and IV whole blood +chest compressions (WB +CCC n=8). 3×10 ml/kg fluid boluses were administered using the Belmont Rapid Infuser (200 ml/min). CCC were performed using the LUCAS II Chest Compression System.Outcome was attainment of return of spontaneous circulation (ROSC) 15 min post-resuscitation. ROSC was categorised by MAP (MAP ≥50 mmHg=ROSC; MAP >20 <50 mmHg=partial ROSC; MAP ≤20 mmHg=dead).emermed;34/12/A866-a/F1F1F1Figure 1 RESULTS: Outcome was significantly worse in the group that received CCC compared to WB and Sal groups (6/6 dead versus 0/8 and 0/8 respectively) (p<0.0001).A

Analysis of the nucleoprotein gene identifies three distinct lineages of viral haemorrhagic septicemia virus (VHSV) within the European marine environment

USGS Publications Warehouse

Snow, M.; Cunningham, C.O.; Melvin, W.T.; Kurath, G.

1999-01-01

A ribonuclease (RNase) protection assay (RPA) has been used to detect nucleotide sequence variation within the nucleoprotein gene of 39 viral haemorrhagic septicaemia virus (VHSV) isolates of European marine origin. The classification of VHSV isolates based on RPA cleavage patterns permitted the identification of ten distinct groups of viruses based on differences at the molecular level. The nucleotide sequence of representatives of each of these groupings was determined and subjected to phylogenetic analysis. This revealed grouping of the European marine isolates of VHSV into three genotypes circulating within distinct geographic areas. A fourth genotype was identified comprising isolates originating from North America. Phylogenetic analyses indicated that VHSV isolates recovered from wild caught fish around the British Isles were genetically related to isolates responsible for losses in farmed turbot. Furthermore, a relationship between naturally occurring marine isolates and VHSV isolates causing mortality among rainbow trout in continental Europe was demonstrated. Analysis of the nucleoprotein gene identifies distinct lineages of viral haemorrhagic septicaemia virus within the European marine environment. Virus Res. 63, 35-44. Available from: 

Between life and death: women's experiences of coming close to death, and surviving a severe postpartum haemorrhage and emergency hysterectomy.

PubMed

Elmir, Rakime; Schmied, Virginia; Jackson, Debra; Wilkes, Lesley

2012-04-01

to describe women's experiences of having an emergency hysterectomy following a severe postpartum haemorrhage. a qualitative research approach was used to guide this study. Data were collected through semi-structured, tape recorded face to face, email internet and telephone interviews. three States in Australia: New South Wales, Victoria and Western Australia. twenty-one Australian women who experienced a severe post partum followed by an emergency hysterectomy participated in the study. The median age of participants at time of interview was 42 years and the median time since having the hysterectomy was four years. a process of inductive analysis revealed the major theme, 'between life and death' and three sub-themes, 'being close to death: bleeding and fear', 'having a hysterectomy: devastation and realisation' and 'reliving the trauma: flashbacks and memories'. formulating a plan of care for women identifiably at risk of PPH and ensuring appropriate follow-up counselling is made, is key to help reduce the emotional and psychological symptoms experienced by these women in the aftermath of severe postpartum haemorrhage and hysterectomy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reducing Mitochondrial ROS Improves Disease-related Pathology in a Mouse Model of Ataxia-telangiectasia

PubMed Central

D'Souza, Anthony D; Parish, Ian A; Krause, Diane S; Kaech, Susan M; Shadel, Gerald S

2013-01-01

The disease ataxia-telangiectasia (A-T) has no cure and few treatment options. It is caused by mutations in the ATM kinase, which functions in the DNA-damage response and redox sensing. In addition to severe cerebellar degeneration, A-T pathology includes cancer predisposition, sterility, immune system dysfunction, and bone marrow abnormalities. These latter phenotypes are recapitulated in the ATM null (ATM−/−) mouse model of the disease. Since oxidative stress and mitochondrial dysfunction are implicated in A-T, we determined whether reducing mitochondrial reactive oxygen species (ROS) via overexpression of catalase targeted to mitochondria (mCAT) alleviates A-T–related pathology in ATM−/− mice. We found that mCAT has many beneficial effects in this context, including reduced propensity to develop thymic lymphoma, improved bone marrow hematopoiesis and macrophage differentiation in vitro, and partial rescue of memory T-cell developmental defects. Our results suggest that positive effects observed on cancer development may be linked to mCAT reducing mitochondrial ROS, lactate production, and TORC1 signaling in transforming double-positive cells, whereas beneficial effects in memory T cells appear to be TORC1-independent. Altogether, this study provides proof-of-principle that reducing mitochondrial ROS production per se may be therapeutic for the disease, which may have advantages compared with more general antioxidant strategies. PMID:23011031

An alternative approach to characterize nonlinear site effects

USGS Publications Warehouse

Zhang, R.R.; Hartzell, S.; Liang, J.; Hu, Y.

2005-01-01

This paper examines the rationale of a method of nonstationary processing and analysis, referred to as the Hilbert-Huang transform (HHT), for its application to a recording-based approach in quantifying influences of soil nonlinearity in site response. In particular, this paper first summarizes symptoms of soil nonlinearity shown in earthquake recordings, reviews the Fourier-based approach to characterizing nonlinearity, and offers justifications for the HHT in addressing nonlinearity issues. This study then uses the HHT method to analyze synthetic data and recordings from the 1964 Niigata and 2001 Nisqually earthquakes. In doing so, the HHT-based site response is defined as the ratio of marginal Hilbert amplitude spectra, alternative to the Fourier-based response that is the ratio of Fourier amplitude spectra. With the Fourier-based approach in studies of site response as a reference, this study shows that the alternative HHT-based approach is effective in characterizing soil nonlinearity and nonlinear site response.

Sublocalization of an Ataxia-Telangiectasia Gene Distal to D11S384 by Ancestral Haplotyping In Costa Rican Families

PubMed Central

Uhrhammer, Nancy; Lange, Ethan; Porras, Oscar; Naeim, Arash; Chen, Xiaoguang; Sheikhavandi, Sepideh; Chiplunkar, Sujata; Yang, Lan; Dandekar, Sugandha; Liang, Teresa; Patel, Nima; Teraoka, Sharon; Udar, Nitin; Calvo, Nidia; Concannon, Patrick; Lange, Kenneth; Gatti, Richard A.

1995-01-01

In an effort to localize a gene for ataxia-telangiectasia (A-T), we have genotyped 27 affected Costa Rican families, with 13 markers, in the chromosome 11q22-23 region. Significant linkage disequilibrium was detected for 9/13 markers between D11S1816 and D11S1391. Recombination events observed in these pedigrees places A-T between D11S1819 and D11S1960. One ancestral haplotype is common to 24/54 affected chromosomes and roughly two-thirds of the families. Inferred (ancestral) recombination events involving this common haplotype in earlier generations suggest that A-T is distal to D11S384 and proximal to D11S1960. Several other common haplotypes were identified, consistent with multiple mutations in a single gene. When considered together with all other evidence, this study further sublocalizes the major A-T locus to ≈200 kb, between markers S384 and S535. ImagesFigure 5 PMID:7611278

Global nursing in an Ebola viral haemorrhagic fever outbreak: before, during and after deployment

PubMed Central

von Strauss, Eva; Paillard-Borg, Stéphanie; Holmgren, Jessica; Saaristo, Panu

2017-01-01

ABSTRACT Background: Nurses are on the forefront and play a key role in global disaster responses. Nevertheless, they are often not prepared for the challenges they are facing and research is scarce regarding the nursing skills required for first responders during a disaster situation. Objectives: To investigate how returnee nursing staff experienced deployment before, during and after having worked for the Red Cross at an Ebola Treatment Center in Kenema, West Africa, and to supply knowledge on how to better prepare and support staff for viral haemorrhagic fever outbreaks. Methods: A descriptive, cross-sectional approach. Questionnaires were administered to nurses having worked with patients suffering from Ebola in 2014 and 2015. Data collection covered aspects of pre-, during and post-deployment on clinical training, personal health, stress management, leadership styles, socio-cultural exposure and knowledge transfer, as well as attitudes from others. Data was analysed using both quantitative and qualitative methods. Results: Response-rate was 88%: forty-four nurses from 15 different countries outside West Africa answered the questionnaire. The respondents identified the following needs for improvement: increased mental health and psychosocial support and hands-on coping strategies with focus on pre- and post-deployment; more pre-deployment task-oriented clinical training; and workload reduction, as exhaustion is a risk for safety. Conclusions: This study supplies knowledge on how to better prepare health care staff for future viral haemorrhagic fever outbreaks and other disasters. Participants were satisfied with their pre-deployment physical health preparation, whereas they stressed the importance of mental health support combined with psychosocial support after deployment. Furthermore, additional pre-clinical training was requested. PMID:29017025

Cubic spline interpolation with overlapped window and data reuse for on-line Hilbert Huang transform biomedical microprocessor.

PubMed

Chang, Nai-Fu; Chiang, Cheng-Yi; Chen, Tung-Chien; Chen, Liang-Gee

2011-01-01

On-chip implementation of Hilbert-Huang transform (HHT) has great impact to analyze the non-linear and non-stationary biomedical signals on wearable or implantable sensors for the real-time applications. Cubic spline interpolation (CSI) consumes the most computation in HHT, and is the key component for the HHT processor. In tradition, CSI in HHT is usually performed after the collection of a large window of signals, and the long latency violates the realtime requirement of the applications. In this work, we propose to keep processing the incoming signals on-line with small and overlapped data windows without sacrificing the interpolation accuracy. 58% multiplication and 73% division of CSI are saved after the data reuse between the data windows.

Production and characterization of streptomycin dependent mutants of Pasteurella multocida from bovine haemorrhagic septicaemia.

PubMed Central

de Alwis, M C; Carter, G R; Chengappa, M M

1980-01-01

A large number of streptomycin dependent mutants were produced from bovine haemorrhagic septicaemia strains of Pasteurella multocida. The mutants required a minimum concentration of 25-50 microgram/mL streptomycin for growth and tolerated a concentration of 200 mg/mL. These mutants were avirulent to mice, when inoculated alone, but some mutants killed mice when inoculated with streptomycin. Biochemically all mutants were uniform and similar to the wild type. Most mutants were stable, but a few produced streptomycin independent revertants. The rate of reversion varied with each mutant. Most revertants were highly virulent for mice, some totally avirulant and a few relatively avirulent. PMID:6778598

Hilbert-Huang transform analysis of dynamic and earthquake motion recordings

USGS Publications Warehouse

Zhang, R.R.; Ma, S.; Safak, E.; Hartzell, S.

2003-01-01

This study examines the rationale of Hilbert-Huang transform (HHT) for analyzing dynamic and earthquake motion recordings in studies of seismology and engineering. In particular, this paper first provides the fundamentals of the HHT method, which consist of the empirical mode decomposition (EMD) and the Hilbert spectral analysis. It then uses the HHT to analyze recordings of hypothetical and real wave motion, the results of which are compared with the results obtained by the Fourier data processing technique. The analysis of the two recordings indicates that the HHT method is able to extract some motion characteristics useful in studies of seismology and engineering, which might not be exposed effectively and efficiently by Fourier data processing technique. Specifically, the study indicates that the decomposed components in EMD of HHT, namely, the intrinsic mode function (IMF) components, contain observable, physical information inherent to the original data. It also shows that the grouped IMF components, namely, the EMD-based low- and high-frequency components, can faithfully capture low-frequency pulse-like as well as high-frequency wave signals. Finally, the study illustrates that the HHT-based Hilbert spectra are able to reveal the temporal-frequency energy distribution for motion recordings precisely and clearly.

Evaluation of a vector-control strategy of haemorrhagic thelohanellosis in carp, caused by Thelohanellus hovorkai (Myxozoa).

PubMed

Liyanage, Yasoja S; Yokoyama, Hiroshi; Wakabayashi, Hisatsugu

2003-06-20

The life cycle of Thelohanellus hovorkai (Myxozoa), the causative agent of haemorrhagic thelohanellosis of carp Cyprinus carpio, involves the alternate oligochaete host Branchiura sowerbyi, which plays the role of vector in the parasite's transmission. Field investigations in carp farms suggested that oligochaete fauna were closely associated with the substrate type of the pond. The pond bottom in the enzootic farm consisted of clay soil and soft sediments comprised of organic mud, in which B. sowerbyi dominated in high densities, with a maximum of 5.6 ind. kg(-1) soil. In another case, in a carp farm with no previous history of the disease, the pond bottom was sandy soil, in which small-sized oligochaetes, composed mainly of Limnodrilus socialis, dominated. Laboratory studies on the substrate preference of oligochaetes proved that B. sowerbyi prefers mud to sand, whereas L. socialis has no tendency to substrate tropism. The delicate body surface of B. sowerbyi was subject to damage by rugged-edged sand particles, which inflicted severe injuries to the worms. Transmission experiments showed that L. socialis, which are non-susceptible to T. hovorkai, suppressed the production of T. hovorkai actinospores in B. sowerbyi in a mixed assemblage of oligochaetes. Field and experimental evidence in this study imply that substrate replacement in culture ponds might regulate the benthic oligochaete communities, resulting in minimization of the impact of haemorrhagic thelohanellosis. We propose that ecological control of oligochaete fauna by environmental management is a promising strategy against myxozoan diseases.

Protection of cerebral microcirculation, mitochondrial function, and electrocortical activity by small-volume resuscitation with terlipressin in a rat model of haemorrhagic shock.

PubMed

Ida, K K; Chisholm, K I; Malbouisson, L M S; Papkovsky, D B; Dyson, A; Singer, M; Duchen, M R; Smith, K J

2018-06-01

During early treatment of haemorrhagic shock, cerebral perfusion pressure can be restored by small-volume resuscitation with vasopressors. Whether this therapy is improved with additional fluid remains unknown. We assessed the value of terlipressin and lactated Ringer's solution (LR) on early recovery of microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex. Animals treated with LR replacing three times (3LR) the volume bled (n=26), terlipressin (n=27), terlipressin plus 1LR (n=26), 2LR (n=16), or 3LR (n=15) were compared with untreated (n=36) and sham-operated rats (n=17). In vivo confocal microscopy was used to assess cortical capillary perfusion, changes in tissue oxygen concentration, and mitochondrial membrane potential and redox state. Electrophysiological function was assessed by cortical somatosensory evoked potentials, spinal cord dorsum potential, and peripheral electromyography. Compared with sham treatment, haemorrhagic shock reduced the mean (SD) area of perfused vessels [82% (sd 10%) vs 38% (12%); P<0.001] and impaired oxygen concentration, mitochondrial redox state [99% (4%) vs 59% (15%) of baseline; P<0.001], and somatosensory evoked potentials [97% (13%) vs 27% (19%) of baseline]. Administration of terlipressin plus 1LR or 2LR was able to recover these measures, but terlipressin plus 3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function. Resuscitation from haemorrhagic shock using terlipressin with small-volume LR was superior to high-volume LR, with regard to cerebral microcirculation, and mitochondrial and electrophysiological functions. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Interleukin 6 trigged ataxia-telangiectasia mutated activation facilitates lung cancer metastasis via MMP-3/MMP-13 up-regulation.

PubMed

Jiang, Yi Na; Yan, Hong Qiong; Huang, Xiao Bo; Wang, Yi Nan; Li, Qing; Gao, Feng Guang

2015-12-01

Our previous studies show that the phosphorylation of ataxia-telangiectasia mutated (ATM) induced by interleukin 6 (IL-6) treatment contributes to multidrug resistance formation in lung cancer cells, but the exact role of ATM activation in IL-6 increased metastasis is still elusive. In the present study, matrix metalloproteinase-3 (MMP-3) and MMP-13 were firstly demonstrated to be involved in IL-6 correlated cell migration. Secondly, IL-6 treatment not only increased MMP-3/MMP-13 expression but also augmented its activities. Thirdly, the inhibition of ATM phosphorylation efficiently abolished IL-6 up-regulating MMP-3/MMP-13 expression and increasing abilities of cell migration. Most importantly, the in vivo test showed that the inhibition of ATM abrogate the effect of IL-6 on lung cancer metastasis via MMP-3/MMP-13 down-regulation. Taken together, these findings demonstrate that IL-6 inducing ATM phosphorylation increases the expression of MMP-3/MMP-13, augments the abilities of cell migration, and promotes lung cancer metastasis, indicating that ATM is a potential target molecule to overcome IL-6 correlated lung cancer metastasis.

Comparison of an automatic analysis and a manual analysis of conjunctival microcirculation in a sheep model of haemorrhagic shock.

PubMed

Arnemann, Philip-Helge; Hessler, Michael; Kampmeier, Tim; Morelli, Andrea; Van Aken, Hugo Karel; Westphal, Martin; Rehberg, Sebastian; Ertmer, Christian

2016-12-01

Life-threatening diseases of critically ill patients are known to derange microcirculation. Automatic analysis of microcirculation would provide a bedside diagnostic tool for microcirculatory disorders and allow immediate therapeutic decisions based upon microcirculation analysis. After induction of general anaesthesia and instrumentation for haemodynamic monitoring, haemorrhagic shock was induced in ten female sheep by stepwise blood withdrawal of 3 × 10 mL per kilogram body weight. Before and after the induction of haemorrhagic shock, haemodynamic variables, samples for blood gas analysis, and videos of conjunctival microcirculation were obtained by incident dark field illumination microscopy. Microcirculatory videos were analysed (1) manually with AVA software version 3.2 by an experienced user and (2) automatically by AVA software version 4.2 for total vessel density (TVD), perfused vessel density (PVD) and proportion of perfused vessels (PPV). Correlation between the two analysis methods was examined by intraclass correlation coefficient and Bland-Altman analysis. The induction of haemorrhagic shock decreased the mean arterial pressure (from 87 ± 11 to 40 ± 7 mmHg; p < 0.001); stroke volume index (from 38 ± 14 to 20 ± 5 ml·m -2 ; p = 0.001) and cardiac index (from 2.9 ± 0.9 to 1.8 ± 0.5 L·min -1 ·m -2 ; p < 0.001) and increased the heart rate (from 72 ± 9 to 87 ± 11 bpm; p < 0.001) and lactate concentration (from 0.9 ± 0.3 to 2.0 ± 0.6 mmol·L -1 ; p = 0.001). Manual analysis showed no change in TVD (17.8 ± 4.2 to 17.8 ± 3.8 mm*mm -2 ; p = 0.993), whereas PVD (from 15.6 ± 4.6 to 11.5 ± 6.5 mm*mm -2 ; p = 0.041) and PPV (from 85.9 ± 11.8 to 62.7 ± 29.6%; p = 0.017) decreased significantly. Automatic analysis was not able to identify these changes. Correlation analysis showed a poor correlation between the analysis methods and a wide

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial.

PubMed

Sprigg, Nikola; Flaherty, Katie; Appleton, Jason P; Al-Shahi Salman, Rustam; Bereczki, Daniel; Beridze, Maia; Christensen, Hanne; Ciccone, Alfonso; Collins, Ronan; Czlonkowska, Anna; Dineen, Robert A; Duley, Lelia; Egea-Guerrero, Juan Jose; England, Timothy J; Krishnan, Kailash; Laska, Ann Charlotte; Law, Zhe Kang; Ozturk, Serefnur; Pocock, Stuart J; Roberts, Ian; Robinson, Thompson G; Roffe, Christine; Seiffge, David; Scutt, Polly; Thanabalan, Jegan; Werring, David; Whynes, David; Bath, Philip M

2018-05-26

Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral haemorrhage. We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214. We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio [aOR] 0·88, 95% CI 0·76-1·03, p=0·11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0·73, 0·53-0·99, p=0·0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0·92, 95% CI 0·77-1·10, p=0·37). Fewer patients had serious adverse events after tranexamic

Imaging cerebral haemorrhage with magnetic induction tomography: numerical modelling.

PubMed

Zolgharni, M; Ledger, P D; Armitage, D W; Holder, D S; Griffiths, H

2009-06-01

Magnetic induction tomography (MIT) is a new electromagnetic imaging modality which has the potential to image changes in the electrical conductivity of the brain due to different pathologies. In this study the feasibility of detecting haemorrhagic cerebral stroke with a 16-channel MIT system operating at 10 MHz was investigated. The finite-element method combined with a realistic, multi-layer, head model comprising 12 different tissues, was used for the simulations in the commercial FE package, Comsol Multiphysics. The eddy-current problem was solved and the MIT signals computed for strokes of different volumes occurring at different locations in the brain. The results revealed that a large, peripheral stroke (volume 49 cm(3)) produced phase changes that would be detectable with our currently achievable instrumentation phase noise level (17 m degrees ) in 70 (27%) of the 256 exciter/sensor channel combinations. However, reconstructed images showed that a lower noise level than this, of 1 m degrees , was necessary to obtain good visualization of the strokes. The simulated MIT measurements were compared with those from an independent transmission-line-matrix model in order to give confidence in the results.

S phase entry causes homocysteine-induced death while ataxia telangiectasia and Rad3 related protein functions anti-apoptotically to protect neurons.

PubMed

Ye, Weizhen; Blain, Stacy W

2010-08-01

A major phenotype seen in neurodegenerative disorders is the selective loss of neurons due to apoptotic death and evidence suggests that inappropriate re-activation of cell cycle proteins in post-mitotic neurons may be responsible. To investigate whether reactivation of the G1 cell cycle proteins and S phase entry was linked with apoptosis, we examined homocysteine-induced neuronal cell death in a rat cortical neuron tissue culture system. Hyperhomocysteinaemia is a physiological risk factor for a variety of neurodegenerative diseases, including Alzheimer's disease. We found that in response to homocysteine treatment, cyclin D1, and cyclin-dependent kinases 4 and 2 translocated to the nucleus, and p27 levels decreased. Both cyclin-dependent kinases 4 and 2 regained catalytic activity, the G1 gatekeeper retinoblastoma protein was phosphorylated and DNA synthesis was detected, suggesting transit into S phase. Double-labelling immunofluorescence showed a 95% co-localization of anti-bromodeoxyuridine labelling with apoptotic markers, demonstrating that those cells that entered S phase eventually died. Neurons could be protected from homocysteine-induced death by methods that inhibited G1 phase progression, including down-regulation of cyclin D1 expression, inhibition of cyclin-dependent kinases 4 or 2 activity by small molecule inhibitors, or use of the c-Abl kinase inhibitor, Gleevec, which blocked cyclin D and cyclin-dependent kinase 4 nuclear translocation. However, blocking cell cycle progression post G1, using DNA replication inhibitors, did not prevent apoptosis, suggesting that death was not preventable post the G1-S phase checkpoint. While homocysteine treatment caused DNA damage and activated the DNA damage response, its mechanism of action was distinct from that of more traditional DNA damaging agents, such as camptothecin, as it was p53-independent. Likewise, inhibition of the DNA damage sensors, ataxia-telangiectasia mutant and ataxia telangiectasia and Rad

Case control study of thermal environment preceding haemorrhagic shock encephalopathy syndrome

PubMed Central

Bacon, C; Bell, S; Gaventa, J; Greenwood, D

1999-01-01

The purpose of the study was to investigate whether the thermal environment in which babies slept before developing haemorrhagic shock encephalopathy syndrome (HSES) differed from that of other babies. Data were collected by standardised interview from parents of 31 babies who had had HSES before the age of 7 months and compared with equivalent data for 124 control babies, with matching for outside temperature on the relevant night and for age. Multivariate analysis showed a strong association between HSES and covering of the baby's head by bedding, the odds ratio being 30.7 (95% confidence interval, 2.5 to 384). There were weaker associations with other aspects of the thermal environment. This suggests a link between HSES and some cases of cot death, supports the suggestion that HSES may be caused by overheating, and reinforces advice that babies should be placed to sleep in such a way that they are less likely to become totally covered.

 PMID:10490526

Neurosarcoidosis associated with intracerebral haemorrhage: a challenge in diagnosis and management.

PubMed

Maskery, Mark Peter; Cooper, Paul N; Pace, Adrian

2018-06-01

Sarcoidosis is an idiopathic multisystem granulomatous disorder of unknown cause. Nervous system involvement (central and/or peripheral) is uncommon, developing in 5%-10%. The presenting symptoms are variable, reflecting the level of involvement, and frequently fluctuate and progress. Diagnosing neurosarcoidosis in people with previously confirmed systemic disease may be relatively straightforward, but diagnosing primary neurosarcoidosis is challenging. Managing neurosarcoidosis is primarily consensus based; corticosteroid is its mainstay, alongside corticosteroid-sparing agents and emerging novel therapies. We describe a 39-year-old woman who presented with cranial neuropathy. Serial imaging, cerebrospinal fluid sampling and tissue biopsy gave a diagnosis of probable neurosarcoidosis. Her clinical course was complicated by intracerebral haemorrhage following intravenous corticosteroids for neurological relapse. This is a very rare complication of neurosarcoidosis; we discuss its possible causes and suggest ways to reduce its risk. © 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.

Emergence of a new lagovirus related to Rabbit Haemorrhagic Disease Virus

PubMed Central

2013-01-01

Since summer 2010, numerous cases of Rabbit Haemorrhagic Disease (RHD) have been reported in north-western France both in rabbitries, affecting RHD-vaccinated rabbits, and in wild populations. We demonstrate that the aetiological agent was a lagovirus phylogenetically distinct from other lagoviruses and which presents a unique antigenic profile. Experimental results show that the disease differs from RHD in terms of disease duration, mortality rates, higher occurrence of subacute/chronic forms and that partial cross-protection occurs between RHDV and the new RHDV variant, designated RHDV2. These data support the hypothesis that RHDV2 is a new member of the Lagovirus genus. A molecular epidemiology study detected RHDV2 in France a few months before the first recorded cases and revealed that one year after its discovery it had spread throughout the country and had almost replaced RHDV strains. RHDV2 was detected in continental Italy in June 2011, then four months later in Sardinia. PMID:24011218

Clinical and epidemiological patterns of Argentine haemorrhagic fever

PubMed Central

Maiztegui, J. I.

1975-01-01

The epidemiology of Argentine haemorrhagic fever (AHF) is closely related to cricetine rodents acting as natural hosts of Junin virus. The endemo-epidemic area, which has increased 5 times since the disease was first recognized 15-20 years ago, is located in a densely populated region of Argentina. It has been shown that the virus of LCM is active in humans and rodents of the AHF endemic area; this demonstrates the simultaneous presence of two arenaviruses pathogenic for man in a given geographic location. The disease is characterized by haematological, renal, neurological and cardiovascular changes. Electron microscopy and immunohistochemical studies have shown cytopathic changes, characteristic intracellular virus-like particles, and antigenic determinants of Junin virus in different organs from 9 cases of AHF. No deposits of immunoglobulins or C3 were found in the kidneys; in addition, an absence of fibrinogen and C3 in the hepatocytes and of immunoglobulins in the spleen was observed. These findings suggest a direct viral pathogenic action in the human disease. Ultrastructural and immunofluorescence studies in tissues of guinea-pigs inoculated with two strains of Junin virus revealed the presence of the same types of virus-like particles and antigenic determinants of Junin virus as were encountered in the human subjects with AHF. ImagesFig. 2Fig. 3 PMID:1085212

Gastroprotective effects of Hwanglyeonhaedok-tang against Helicobacter pylori-induced gastric cell injury.

PubMed

Park, Hee-Seon; Wijerathne, Charith U B; Jeong, Hye-Yun; Seo, Chang-Seob; Ha, Hyekyung; Kwun, Hyo-Jung

2018-04-24

Helicobacter pylori, which is found in the stomachs of approximately half of the world's population, has been associated with the development of chronic gastritis and gastric cancer. Hwanglyeonhaedok-tang (HHT) is a popular traditional medicine for the therapies of gastric ulcers and gastritis. The emerging resistance of H. pylori to antibiotics arouses requirement on alternative nonantibiotic-based therapies. In the present study, we investigated the anti-inflammatory activity and anti-microbial activity of HHT against H. pylori in vitro and in an H. pylori-infected mouse model. H. pylori were treated with various concentrations of HHT and then incubated with human gastric carcinoma AGS cells. For the in vivo study, mice were orally infected with H. pylori three times over the course of 1 week, and then subjected to daily administration of HHT (120 or 600 mg/kg) for 4 weeks or standard triple therapy for 1 week. At the scheduled termination of the experiment, all mice were killed and their stomachs were collected for histological examination, quantitative real-time PCR, and Western blot analysis. Our in vitro studies showed that HHT treatment inhibited the adhesion of H. pylori to AGS cells and suppressed the H. pylori-induced increases of inflammatory regulators, such as interleukin (IL)-8, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). In the mouse model, HHT treatment significantly reduced H. pylori colonization, inflammation, and the levels of IL-1β, IL-6, C-X-C motif chemokine ligand 1 (CXCL1), tumor necrosis factor alpha (TNF-α), COX-2, and iNOS in gastric mucosa. Further investigation showed that HHT treatment reduced the H. pylori-induced phosphorylations of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and nuclear factor-kappa B (NF-κB). Our findings collectively suggest that HHT has anti-inflammatory activity and antibacterial activity

The effectiveness and safety of antifibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis.

PubMed

Ker, Katharine; Prieto-Merino, David; Sprigg, Nikola; Mahmood, Abda; Bath, Philip; Kang Law, Zhe; Flaherty, Katie; Roberts, Ian

2017-01-01

Introduction : The Antifibrinolytic Trialists Collaboration aims to increase knowledge about the effectiveness and safety of antifibrinolytic treatment by conducting individual patient data (IPD) meta-analyses of randomised trials. This article presents the statistical analysis plan for an IPD meta-analysis of the effects of antifibrinolytics for acute intracranial haemorrhage. Methods : The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42016052155). We will conduct an individual patient data meta-analysis of randomised controlled trials with 1000 patients or more assessing the effects of antifibrinolytics in acute intracranial haemorrhage. We will assess the effect on two co-primary outcomes: 1) death in hospital at end of trial follow-up, and 2) death in hospital or dependency at end of trial follow-up. The co-primary outcomes will be limited to patients treated within three hours of injury or stroke onset. We will report treatment effects using odds ratios and 95% confidence intervals. We use logistic regression models to examine how the effect of antifibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of antifibrinolytics on secondary outcomes including death, dependency, vascular occlusive events, seizures, and neurological outcomes. Secondary outcomes will be assessed in all patients irrespective of time of treatment. All analyses will be conducted on an intention-to-treat basis. Conclusions : This IPD meta-analysis will examine important clinical questions about the effects of antifibrinolytic treatment in patients with intracranial haemorrhage that cannot be answered using aggregate data. With IPD we can examine how effects vary by time to treatment, bleeding severity, and age, to gain better understanding of the balance of benefit and harms on which to base recommendations for practice.

A clinical analysis of 32 brainstem haemorrhages; with special reference to surviving but severely disabled cases.

PubMed

Komiyama, M; Boo, Y E; Yagura, H; Yasui, T; Baba, M; Hakuba, A; Nishimura, S

1989-01-01

Thirty-two patients with CT-documented primary brainstem haemorrhage were reviewed retrospectively to obtain a clearer overall clinical picture, especially of the severely disabled survivors. They were divided into 3 groups according to outcome: eleven cases (Group 1) died within 1 month following haemorrhage, 11 cases (Group 2) survived but became bedridden, necessitating full living support, and 10 cases (Group 3) showed minimal neurological deficits and resumed normal activities. Owing to CT and improved critical care, the survival rate was 66% for the whole series. Group 2 comprised 34% of all cases. These patients were mostly alert, quadruplegic, and communicated only with great difficulty. The most common initial symptoms and CT finding in each group were as follows; Group 1: unconsciousness, respiratory disturbance, negative light reflex, tachycardia, and haematoma greater than 3.0 cm; Group 2: disturbance of consciousness, respiratory disturbance, positive light reflex, normal heart rate, and 2.0 greater than haematoma less than 3.5 cm; and Group 3: alertness or only slight disturbance of consciousness, normal respiration, positive light reflex, normal heart rate, haematoma less than 2.5 cm. Although there is an overlap among them, these findings will be useful to distinguish the three groups from each other. Patients with disturbance of consciousness, respiratory disturbance, positive light reflex, normal heart rate, and 2.0 greater than haematoma less than 3.5 cm, have a chance to survive, but in severely disabled condition, if they were treated with vigorous intensive care in the acute stage.

Improving non-technical skills (teamwork) in post-partum haemorrhage: A grouped randomised trial.

PubMed

Letchworth, Pippa M; Duffy, Shane P; Phillips, Dan

2017-10-01

To determine the effect of a decision support technology on teamwork and associated non-technical (NTS) and technical skills when teams manage post-partum haemorrhage (PPH) in the simulated environment. Multidisciplinary (MDT) maternity teams were taught how to manage post partum haemorrhage. They were randomised to the intervention: using a decision support mobile digital platform or a control group. Each team managed a post-partum simulation, which was recorded and reviewed by assessors. Primary outcome measures to assess teams NTS were the validated Global Assessment of Obstetric Team Performance (GAOTP) and Clinical Teamwork Scale (CTS). Secondary outcome measures were the 'friends and family test', technical skills, and the System Usability Scale (SUS). Sample size estimation was calculated by using 80% power 5% significance two tailed test (p1=85% p2=40%) n=34. 38 teams from August 2014-February 2016, were recruited, technical issues with failure of recording equipment meant 4 teams were excluded from teamwork analysis (1 intervention 3 control). Teamwork improved across all domains with the intervention (using a decision support mobile digital platform) p <0.01. CTS improved between 6.7-16.8% (average 14.2%) and GAOTP between 8.6-17.1% (average 13.5%) for all domains. Using the control group as baseline, the intervention improved teamwork by 25% using CTS and 22% using GAOTP. Fewer technical skills were missed with the intervention (p<0.01). There was no statistical difference in the time technical skills were achieved. Assessors were more likely to recommend intervention teams 87.5% (77/88) than control teams 63.6% (56/88) p<0.01 to their friends or family. The SUS was 'Good' (69) becoming excellently 'Usable' (81.6) over the study period. We report a decision support system, which improved NTS when managing PPH. Lack of teamwork is often cited as the cause of failures in care and we report a usable technology that assists with and improves teamwork during

The model of response to viral haemorrhagic fevers of the National Institute for Infectious Diseases "Lazzaro Spallanzani".

PubMed

Armignacco, O; Lauria, F N; Puro, V; Macrì, G; Petrecchia, A; Ippolito, G

2001-01-01

Viral haemorrhagic fevers (VHF) are severe and life-threatening diseases caused by a range of viruses. However, only four agents of VHF are known to be readily capable of person-to-person spread: Lassa virus, Crimean/Congo haemorrhagic fever virus, Ebola and Marburg viruses. Diseases caused by these viruses are endemic only in few areas in the world, most notably Africa and some rural parts of the Middle East and Eastern Europe. Nonetheless, the increasing volume of international travel presents a greater likelihood for the importation of these infections or of suspected cases in non endemic countries. Four conditions can lead to the importation and to the subsequent recognition of VHF within Europe: 1) patients arriving as a result of a planned medical evacuation; 2) persons who became sick on route to their destination; 3) persons discovered ill when entering a country, for example during routine clinical examination at the airport; 4) persons becoming sick after their arrival. Public health implications and the risk of secondary spread of pathogens in the above reported circumstances are very different. Similarly, preparedness and response should vary. This paper summarizes the present knowledge on the four VHF capable of person-to-person spread, describes the high isolation area constructed at the Italian National Institute for Infectious Diseases Lazzaro Spallanzani in Rome to respond to the occurrence of VHF. A brief overview of procedures and equipment adopted is provided.

Cerebrospinal fluid from subarachnoid haemorrhage patients causes excessive oxidative metabolism compared to vascular smooth muscle force generation.

PubMed

Pyne, G J; Cadoux-Hudson, T A; Clark, J F

2001-01-01

Cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH) patients can stimulate vascular smooth muscle to generate force in vitro. CSF from SAH patients suffering from delayed ischaemic neurological deficits due to cerebral vasospasm can generate near maximal force in vitro and previous experiments have ascribed this generation of force to be a calcium mediated event. The intracellular calcium concentration has been demonstrated to rise during the vasospastic process. Calcium also stimulates oxidative metabolism as does adenosine diphosphate (ADP), the product of adenosine triphosphate (ATP) hydrolysis. Significant alteration in high energy metabolites such as ATP, ADP and phosphocreatine have also been demonstrated in various models of SAH mediated vasospasm. Vascular smooth muscle predominantly uses oxidative metabolism for force generation and reserves glycolytic metabolism for ion homeostasis. A decrease in oxidative metabolism during force generation would imply failing mitochondria and increased glycolytic high-energy phosphate supply. Increased oxidative metabolism would imply a decreased efficiency of the contractile apparatus or mitochondria. The aim of this study was to see if SAH CSF stimulation of porcine carotid artery oxidative metabolism was altered during force generation when compared with incremental calcium stimulation with potassium chloride depolarisation. CSF from patients (n = 10) who had subarachnoid haemorrhage stimulated force generation but with a significant 'right shift' in oxygen consumption. This 'right shift' is indicative of an increased energy cost for contractile work. These results suggest that vascular smooth muscle contractile apparatus, when stimulated by subarachnoid cerebrospinal fluid, is consuming excess adenosine triphosphate during force generation.

Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia.

PubMed

Shaikh, Aasef G; Marti, Sarah; Tarnutzer, Alexander A; Palla, Antonella; Crawford, Thomas O; Zee, David S; Straumann, Dominik

2013-11-01

Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder with prominent eye movement deficits localizing to the cerebellum. We sought to determine if 4-aminopyridine (4-AP), which putatively enhances the precision of Purkinje neurons, could improve the disorders of eye movements and vestibular function in A-T. The influence of 4-AP on disorders of eye movements and vestibular function was studied in four A-T patients. The effects on the cerebellar control of vestibulo-ocular reflex (VOR) was quantitatively assessed by the decay time constant of per- and post-rotational nystagmus during constant velocity en bloc rotations. The length of the VOR time constant determines the fidelity of the vestibular velocity storage, a neural mechanism that increases the bandwidth of VOR under cerebellar control. The VOR time constant was not increased in A-T patients. The latter is explained by the extent of cerebellar lesion as previously described in A-T and other cerebellar disorders. Nevertheless, 4-AP shortened the VOR time constant during horizontal rotations. Severe disinhibition of velocity storage in subjects with putatively profound cerebellar degeneration manifest periodic alternating nystagmus (PAN). Among two A-T subjects who manifested PAN, 4-AP reduced the peak slow phase velocity of the more severely affected individual and abrogated the PAN in the other. Two A-T subjects manifested horizontal and vertical spontaneous nystagmus (SN) in primary gaze, 4-AP reduced its slow phase velocity. We conclude that in subjects with A-T 4-AP has a prominent effect on the ocular motor and vestibular deficits that are ascribed to the loss of cerebellar Purkinje neurons.

Associations with health-related quality of life after intracerebral haemorrhage: pooled analysis of INTERACT studies.

PubMed

Delcourt, Candice; Zheng, Danni; Chen, Xiaoying; Hackett, Maree; Arima, Hisatomi; Hata, Jun; Heeley, Emma; Al-Shahi Salman, Rustam; Woodward, Mark; Huang, Yining; Robinson, Thompson; Lavados, Pablo M; Lindley, Richard I; Stapf, Christian; Davies, Leo; Chalmers, John; Anderson, Craig S; Sato, Shoichiro

2017-01-01

Limited data exist on health-related quality of life (HRQoL) after intracerebral haemorrhage (ICH). We aimed to determine baseline factors associated with HRQoL among participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). The INTERACT studies were randomised controlled trials of early intensive blood pressure (BP) lowering in patients with ICH (<6 hours) and elevated systolic BP (150-220 mm Hg). HRQoL was determined using the European Quality of Life Scale (EQ-5D) at 90 days, completed by patients or proxy responders. Binary logistic regression analyses were performed to identify factors associated with poor overall HRQoL. 2756 patients were included. Demographic, clinical and radiological factors associated with lower EQ-5D utility score were age, randomisation outside of China, antithrombotic use, high baseline National Institutes of Health Stroke Scale (NIHSS) score, larger ICH, presence of intraventricular extension and use of proxy responders. High (≥14) NIHSS score, larger ICH and proxy responders were associated with low scores in all five dimensions of the EQ-5D. The NIHSS score had a strong association with poor HRQoL (p<0.001). Female gender and antithrombotic use were associated with decreased scores in dimensions of pain/discomfort and usual activity, respectively. Poor HRQoL was associated with age, comorbidities, proxy source of assessment, clinical severity and ICH characteristics. The strongest association was with initial clinical severity defined by high NIHSS score. NCT00226096 and NCT00716079; Post-results. 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/.

The impact of glutamine supplementation on the symptoms of ataxia-telangiectasia: a preclinical assessment.

PubMed

Chen, Jianmin; Chen, Yanping; Vail, Graham; Chow, Heiman; Zhang, Yang; Louie, Lauren; Li, Jiali; Hart, Ronald P; Plummer, Mark R; Herrup, Karl

2016-08-18

Our previous studies of Alzheimer's disease (AD) suggested that glutamine broadly improves cellular readiness to respond to stress and acts as a neuroprotectant both in vitro and in AD mouse models. We now expand our studies to a second neurodegenerative disease, ataxia-telangiectasia (A-T). Unlike AD, where clinically significant cognitive decline does not typically occur before age 65, A-T symptoms appear in early childhood and are caused exclusively by mutations in the ATM (A-T mutated) gene. Genetically ATM-deficient mice and wild type littermates were maintained with or without 4 % glutamine in their drinking water for several weeks. In ATM mutants, glutamine supplementation restored serum glutamine and glucose levels and reduced body weight loss. Lost neurophysiological function assessed through the magnitude of hippocampal long term potentiation was significantly restored. Glutamine supplemented mice also showed reduced thymus pathology and, remarkably, a full one-third extension of lifespan. In vitro assays revealed that ATM-deficient cells are more sensitive to glutamine deprivation, while supra-molar glutamine (8 mM) partially rescued the reduction of BDNF expression and HDAC4 nuclear translocation of genetically mutant Atm(-/-) neurons. Analysis of microarray data suggested that glutamine metabolism is significantly altered in human A-T brains as well. Glutamine is a powerful part of an organism's internal environment. Changes in its concentrations can have a huge impact on the function of all organ systems, especially the brain. Glutamine supplementation thus bears consideration as a therapeutic strategy for the treatment of human A-T and perhaps other neurodegenerative diseases.

Extraction of microseismic waveforms characteristics prior to rock burst using Hilbert-Huang transform

NASA Astrophysics Data System (ADS)

Li, Xuelong; Li, Zhonghui; Wang, Enyuan; Feng, Junjun; Chen, Liang; Li, Nan; Kong, Xiangguo

2016-09-01

This study provides a new research idea concerning rock burst prediction. The characteristics of microseismic (MS) waveforms prior to and during the rock burst were studied through the Hilbert-Huang transform (HHT). In order to demonstrate the advantage of the MS features extraction based on HHT, the conventional analysis method (Fourier transform) was also used to make a comparison. The results show that HHT is simple and reliable, and could extract in-depth information about the characteristics of MS waveforms. About 10 days prior to the rock burst, the main frequency of MS waveforms transforms from the high-frequency to low-frequency. What's more, the waveforms energy also presents accumulation characteristic. Based on our study results, it can be concluded that the MS signals analysis through HHT could provide valuable information about the coal or rock deformation and fracture.

Air pollution and the incidence of ischaemic and haemorrhagic stroke in the South London Stroke Register: a case-cross-over analysis.

PubMed

Butland, B K; Atkinson, R W; Crichton, S; Barratt, B; Beevers, S; Spiridou, A; Hoang, U; Kelly, F J; Wolfe, C D

2017-07-01

Few European studies investigating associations between short-term exposure to air pollution and incident stroke have considered stroke subtypes. Using information from the South London Stroke Register for 2005-2012, we investigated associations between daily concentrations of gaseous and particulate air pollutants and incident stroke subtypes in an ethnically diverse area of London, UK. Modelled daily pollutant concentrations based on a combination of measurements and dispersion modelling were linked at postcode level to incident stroke events stratified by haemorrhagic and ischaemic subtypes. The data were analysed using a time-stratified case-cross-over approach. Conditional logistic regression models included natural cubic splines for daily mean temperature and daily mean relative humidity, a binary term for public holidays and a sine-cosine annual cycle. Of primary interest were same day mean concentrations of particulate matter <2.5 and <10 µm in diameter (PM 2.5 , PM 10 ), ozone (O 3 ), nitrogen dioxide (NO 2 ) and NO 2 +nitrogen oxide (NO X ). Our analysis was based on 1758 incident strokes (1311 were ischaemic and 256 were haemorrhagic). We found no evidence of an association between all stroke or ischaemic stroke and same day exposure to PM 2.5 , PM 10 , O 3 , NO 2 or NO X . For haemorrhagic stroke, we found a negative association with PM 10 suggestive of a 14.6% (95% CI 0.7% to 26.5%) fall in risk per 10 µg/m 3 increase in pollutant. Using data from the South London Stroke Register, we found no evidence of a positive association between outdoor air pollution and incident stroke or its subtypes. These results, though in contrast to recent meta-analyses, are not inconsistent with the mixed findings of other UK studies. 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/.

Dengue fever and dengue haemorrhagic fever in adolescents and adults

PubMed Central

Tantawichien, Terapong

2012-01-01

Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a paediatric disease, the age distribution of dengue has been rising and more cases have been observed in adolescents and adults. Furthermore, the development of tourism in the tropics has led to an increase in the number of tourists who become infected, most of whom are adults. Symptoms and risk factors for dengue haemorrhagic fever (DHF) and severe dengue differ between children and adults, with co-morbidities and incidence in more elderly patients associated with greater risk of mortality. Treatment options for DF and DHF in adults, as for children, centre round fluid replacement (either orally or intravenously, depending on severity) and antipyretics. Further data are needed on the optimal treatment of adult patients. PMID:22668446

The Kinase Activity of Ataxia-Telangiectasia Mutated Interferes with Adenovirus E4 Mutant DNA Replication

PubMed Central

Gautam, Dipendra

2013-01-01

Adenovirus (Ad) mutants that lack early region 4 (E4) are unable to produce the early regulatory proteins that normally inactivate the Mre11/Rad50/Nbs1 (MRN) sensor complex, which is a critical component for the ability of cells to respond to DNA damage. E4 mutant infection therefore activates a DNA damage response, which in turn interferes with a productive viral infection. MRN complex proteins localize to viral DNA replication centers in E4 mutant-infected cells, and this complex is critical for activating the kinases ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR), which phosphorylate numerous substrates important for DNA repair, cell cycle checkpoint activation, and apoptosis. E4 mutant growth defects are substantially rescued in cells lacking an intact MRN complex. We have assessed the role of the downstream ATM and ATR kinases in several MRN-dependent E4 mutant phenotypes. We did not identify a role for either ATM or ATR in “repair” of E4 mutant genomes to form concatemers. ATR was also not observed to contribute to E4 mutant defects in late protein production. In contrast, the kinase activity of ATM was important for preventing efficient E4 mutant DNA replication and late gene expression. Our results suggest that the MRN complex interferes with E4 mutant DNA replication at least in part through its ability to activate ATM. PMID:23740981

The face of Ebola: changing frequency of haemorrhage in the West African compared with Eastern-Central African outbreaks.

PubMed

Petti, Stefano; Messano, Giuseppe Alessio; Vingolo, Enzo Maria; Marsella, Luigi Tonino; Scully, Crispian

2015-12-11

The West-African (WA) Zaire Ebolavirus disease (EVD) outbreak was characterized by an exceptionally high number of cases and deaths as compared with the Eastern-Central African (ECA) outbreaks. Despite the Zaire Ebolavirus being the most lethal for humans, case-fatality rate, close to 80 % in ECA outbreaks, almost halved to 47 % in Guinea-Liberia-Sierra Leone (WA). Such an improvement was due to the remarkable implementation of international humanitarian aids. Some studies also suggested that the long human-to-human transmission cycle occurred in WA, gave rise to human adaptation and consequent immune escape. Haemorrhage, the main feature in seriously infected EVD patients, is due to the immune system that triggers the infected endothelial cells which expose the spike-like glycoprotein (GP) of the virion on their surface. If the human adaptation hypothesis holds true, the proportion of EVD patients with haemorrhage in the WA outbreak should be lower than in the ECA outbreaks due to immune escape. Therefore, the aim of this meta-analysis was to compare the relative frequencies of three typical haemorrhagic symptoms (conjunctival -CB, nasal -NB, gingival -GB- bleedings) in the ECA and WA outbreaks. Literature searches were performed through PubMed and Scopus using generic keywords; surveys including at least ten patients reporting CB, NB, GB relative frequencies were extracted and split into ECA and WA. The meta-analytical methods chosen were based on the levels of between-study heterogeneity and publication bias. Pooled CB, NB, GB relative frequencies in ECA and WA were estimated and compared. Subgroup analysis including only studies on Zaire Ebolavirus also was performed. Fifteen studies (10 ECA, 5 WA) were located with 4,867 (CB), 3,859 (NB), 4,278 (GB) EVD patients overall. GB pooled relative frequency was 45.3 % (95 % confidence interval -95 CI, 34.7-56.1 %) and 18.0 % (95 CI, 6.0-34.5 %), in ECA and WA; NB was 10.6 % (95 CI, 5.7-16.8 %) and 1.3 % (1

Two novel cases of cerebral haemorrhages at the neonatal period associated with inherited factor VII deficiency, one of them revealing a new nonsense mutation (Ser52Stop).

PubMed

Giansily-Blaizot, Muriel; Aguilar-Martinez, Patricia; Briquel, Marie-Elisabeth; d'Oiron, Roseline; De Maistre, Emmanuel; Epelbaum, Serge; Schved, Jean-François

2003-02-01

Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.

Acute Aneurismal Bilateral Subdural Haematoma without Subarachnoid Haemorrhage: A Case Report and Review of the Literature

PubMed Central

Mansour, Ossama; Hassen, Tamer; Fathy, Sameh

2014-01-01

Spontaneous pure acute bilateral subdural haematoma (ASDH) without intraparenchymal or subarachnoid haemorrhage caused by a ruptured cerebral aneurysm is extremely rare. It can follow rupture of different aneurysms specially located in anterior incisural space; the most frequently encountered location is the PcoA aneurysms as demonstrated in the present case. We present a case report of a PcoA aneurysm presenting as pure bilateral ASDH. A high level of suspicion for bleeding of arterial origin should be maintained in all cases of acute subdural haematoma without history of trauma. The neurological status on admission dictates the appropriate timing and methodology of the neuroradiological investigations. PMID:25045554

Crystals seen on CSF microscopy in a case of suspected subarachnoid haemorrhage

PubMed Central

Weiand, Daniel; Hanning, Ian; Mouhamadou, Moussa; Wearmouth, Debbie

2015-01-01

Although crystals are rarely identified on cerebrospinal fluid (CSF) microscopy, their presence can be of significant diagnostic value. We report a case of oxalate crystals seen on CSF microscopy of a 43-year-old woman. The patient presented with headaches, nausea and vomiting. CT of the head showed a small focus of hyper-density, suspicious of haemorrhage, in the right side of the pontine cistern. CSF cell count was within the normal range. Although no organisms were seen on microscopy, copious oxalate crystals were seen. The same crystals were seen on microscopy of CSF collected in a fluoride oxalate container used for glucose analysis. A follow-up contrast-enhanced CT angiogram did not demonstrate any abnormalities. It transpired that excess CSF had been collected into a fluoride oxalate container. This had subsequently been decanted into a plain container for microbiological analysis. Correct specimen collection should be emphasised when teaching lumbar puncture technique. PMID:26139652

Acute tracheal oedema and haemorrhage with fibrinonecrotic tracheitis in pigs--a porcine counterpart of bovine honker syndrome?

PubMed

Szeredi, L; Dán, Á; Makrai, L; Takács, N; Biksi, I

2015-01-01

Cases of acute tracheal oedema and haemorrhage with fibrinonecrotic tracheitis have been described in Hungarian pig herds. Clinical signs and gross and microscopical tracheal lesions bore resemblance to those of bovine 'honker syndrome'. Diagnostic examination of affected tracheas and corresponding lungs revealed the presence of a variety of agents; however, in some cases tracheal lesions developed without detectable pathogens or associated pulmonary pathology. In line with the bovine condition, this suggests the possibility of cough-induced tracheal damage as an initiating factor for this tracheal change in swine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antidepressant use in late gestation and risk of postpartum haemorrhage: a retrospective cohort study.

PubMed

Grzeskowiak, L E; McBain, R; Dekker, G A; Clifton, V L

2016-11-01

To investigate the association between antidepressant use in late gestation and postpartum haemorrhage (PPH). Retrospective cohort study. Tertiary teaching hospital in Adelaide, Australia. A total of 30 198 women delivering between 2002 and 2008. Relative risks adjusted for maternal sociodemographics and comorbidities (aRRs) were calculated for PPH, comparing women with late-gestation exposure to antidepressants (n = 558), women with a psychiatric illness but no antidepressant use (n = 1292), and women with neither antenatal exposures (n = 28 348). Additional sensitivity analyses were undertaken, examining associations with severe PPH and postpartum anaemia. The primary outcome was PPH, defined as a recorded blood loss of ≥500 mL for vaginal deliveries and ≥1000 mL for caesarean sections. Secondary outcomes included severe PPH (≥1000 mL blood loss, irrespective of method of delivery), and the presence of postpartum anaemia (identified from hospital medical records). Compared with unexposed controls, women exposed to antidepressants had an increased risk of PPH (aRR 1.53; 95% confidence interval, 95% CI 1.25-1.86), whereas no increased risk was observed for women with a psychiatric illness but no antidepressant use (aRR 1.04; 95% CI 0.89-1.23). In sensitivity analyses, late gestation antidepressant exposure was associated with an increased risk of severe PPH (aRR 1.84; 95% CI 1.39-2.44), as well as postpartum anaemia (aRR 1.80; 95% CI 1.46-2.22). Exposure to antidepressants in late gestation was associated with a significantly increased risk of PPH. Although potential confounding by unmeasured factors cannot be ruled out, these findings suggest a direct effect of antidepressant exposure on PPH. Late gestation antidepressant exposure is associated with a significantly increased risk of postpartum haemorrhage. © 2015 Royal College of Obstetricians and Gynaecologists.

Characterization of large-scale fluctuations and short-term variability of Seine river daily streamflow (France) over the period 1950-2008 by empirical mode decomposition and the Hilbert-Huang transform

NASA Astrophysics Data System (ADS)

Massei, N.; Fournier, M.

2010-12-01

Daily Seine river flow from 1950 to 2008 was analyzed using Hilbert-Huang Tranform (HHT). For the last ten years, this method which combines the so-called Empirical Mode Decomposition (EMD) multiresolution analysis and the Hilbert transform has proven its efficiency for the analysis of transient oscillatory signals, although the mathematical definition of the EMD is not totally established yet. HHT also provides an interesting alternative to other time-frequency or time-scale analysis of non-stationary signals, the most famous of which being wavelet-based approaches. In this application of HHT to the analysis of the hydrological variability of the Seine river, we seek to characterize the interannual patterns of daily flow, differenciate them from the short-term dynamics and eventually interpret them in the context of regional climate regime fluctuations. In this aim, HHT is also applied to the North-Atlantic Oscillation (NAO) through the annual winter-months NAO index time series. For both hydrological and climatic signals, dominant variability scales are extracted and their temporal variations analyzed by determination of the intantaneous frequency of each component. When compared to previous ones obtained from continuous wavelet transform (CWT) on the same data, HHT results highlighted the same scales and somewhat the same internal components for each signal. However, HHT allowed the identification and extraction of much more similar features during the 1950-2008 period (e.g., around 7-yr, between NAO and Seine flow than what was obtained from CWT, which comes to say that variability scales in flow likely to originate from climatic regime fluctuations were much properly identified in river flow. In addition, a more accurate determination of singularities in the natural processes analyzed were authorized by HHT compared to CWT, in which case the time-frequency resolution partly depends on the basic properties of the filter (i.e., the reference wavelet chosen

Crimean-Congo haemorrhagic fever virus replication in adult Hyalomma truncatum and Amblyomma variegatum ticks.

PubMed

Gonzalez, J P; Cornet, J P; Wilson, M L; Camicas, J L

1991-01-01

The kinetics of the replication of the Crimean-Congo haemorrhagic fever virus (CCHFV) was studied in intra-anally inoculated adult Hyalomma truncatum and Amblyomma variegatum ticks. The virus was re-isolated by suckling mouse inoculation and revealed by antigen capture with ground ticks and indirect immunofluorescence of haemolymph. The virus was detected in ticks in the first hours post-inoculation (p.i.) and its replication was observed from 36 h p.i. onwards. Virus titre reached a maximum within 3-5 days then decreased slowly to a level of at 2 log LD50/ml for several months until the end of observations. Several specific, non-identified factors seem to favour CCHFV replication in H. truncatum. Long-term virus persistence seems to occur in CCHFV-infected adult ticks.

Mortality and rebleeding following variceal haemorrhage in liver cirrhosis and periportal fibrosis.

PubMed

Mohammed, Sara Elfadil Abbas; Abdo, Abdelmunem Eltayeb; Mudawi, Hatim Mohamed Yousif

2016-11-08

To investigate mortality and rebleeding rate and identify associated risk factors at 6 wk and 5 d following acute variceal haemorrhage in patients with liver cirrhosis and schistosomal periportal fibrosis. This is a prospective study conducted during the period from March to December 2014. Patients with portal hypertension presenting with acute variceal haemorrhage secondary to either liver cirrhosis (group A) or schistosomal periportal fibroses (group B) presenting within 24 h of the onset of the bleeding were enrolled in the study and followed for a period of 6 wk. Analysis of data was done by Microsoft Excel and comparison between groups was done by Statistical Package of Social Sciences version 20 to calculate means and find the levels of statistical differences and define the mortality rates, the P value of < 0.05 was considered to be significant. A total of 94 patients were enrolled in the study. Thirty-two patients (34%) had liver cirrhosis (group A) and 62 (66%) patients had periportal fibrosis (group B). Mortality: The 6-wk and 5-d mortality were 53% and 16% respectively in group A compared to 10% and 0% in group B ( P value < 0.000 and < 0.004). In group A; a Child-Turcotte-Pugh class C and rebleeding within 5 d were significantly associated with 5-d mortality ( P value < 0.029 and < 0.049 respectively) and Child- Turcotte-Pugh class C was also a significant risk factor for 6-wk mortality ( P value < 0.018). In group B; mortality was significantly associated with rebleeding within the 6-wk follow-up period and requirement for blood transfusion on admission ( P value < 0.005 and < 0.049). Rebleeding: The 6-wk and 5-d rebleeding rate in group A were 56% and 25% respectively compared to 32% and 3% in group B ( P value < 0.015 and < 0.002). Clinical presentation with encephalopathy was a significant risk factor for 5 d rebleeding in group A ( P value < 0.005) while grade III periportal fibrosis and requirement for blood transfusion on admission were

Telomere length, ATM mutation status and cancer risk in Ataxia-Telangiectasia families.

PubMed

Renault, Anne-Laure; Mebirouk, Noura; Cavaciuti, Eve; Le Gal, Dorothée; Lecarpentier, Julie; d'Enghien, Catherine Dubois; Laugé, Anthony; Dondon, Marie-Gabrielle; Labbé, Martine; Lesca, Gaetan; Leroux, Dominique; Gladieff, Laurence; Adenis, Claude; Faivre, Laurence; Gilbert-Dussardier, Brigitte; Lortholary, Alain; Fricker, Jean-Pierre; Dahan, Karin; Bay, Jacques-Olivier; Longy, Michel; Buecher, Bruno; Janin, Nicolas; Zattara, Hélène; Berthet, Pascaline; Combès, Audrey; Coupier, Isabelle; Hall, Janet; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Lesueur, Fabienne

2017-10-01

Recent studies have linked constitutive telomere length (TL) to aging-related diseases including cancer at different sites. ATM participates in the signaling of telomere erosion, and inherited mutations in ATM have been associated with increased risk of cancer, particularly breast cancer. The goal of this study was to investigate whether carriage of an ATM mutation and TL interplay to modify cancer risk in ataxia-telangiectasia (A-T) families.The study population consisted of 284 heterozygous ATM mutation carriers (HetAT) and 174 non-carriers (non-HetAT) from 103 A-T families. Forty-eight HetAT and 14 non-HetAT individuals had cancer, among them 25 HetAT and 6 non-HetAT were diagnosed after blood sample collection. We measured mean TL using a quantitative PCR assay and genotyped seven single-nucleotide polymorphisms (SNPs) recurrently associated with TL in large population-based studies.HetAT individuals were at increased risk of cancer (OR = 2.3, 95%CI = 1.2-4.4, P = 0.01), and particularly of breast cancer for women (OR = 2.9, 95%CI = 1.2-7.1, P = 0.02), in comparison to their non-HetAT relatives. HetAT individuals had longer telomeres than non-HetAT individuals (P = 0.0008) but TL was not associated with cancer risk, and no significant interaction was observed between ATM mutation status and TL. Furthermore, rs9257445 (ZNF311) was associated with TL in HetAT subjects and rs6060627 (BCL2L1) modified cancer risk in HetAT and non-HetAT women.Our findings suggest that carriage of an ATM mutation impacts on the age-related TL shortening and that TL per se is not related to cancer risk in ATM carriers. TL measurement alone is not a good marker for predicting cancer risk in A-T families. © The Author 2017. Published by Oxford University Press.

Disorders of B cells and helper T cells in the pathogenesis of the immunoglobulin deficiency of patients with ataxia telangiectasia.

PubMed Central

Waldmann, T A; Broder, S; Goldman, C K; Frost, K; Korsmeyer, S J; Medici, M A

1983-01-01

The pathogenesis of the immunoglobulin deficiency of 20 patients with ataxia telangiectasia was studied using an in vitro immunoglobulin biosynthesis system. 10 patients had no detectable IgA in their serum as assessed by radial diffusion in agar and 3 had a reduced serum IgA concentration. The peripheral blood mononuclear cells of 17 of the patients and 17 normal controls were cultured with pokeweed mitogen for 12 d and the immunoglobulin in the supernatants measured. The immunoglobulin synthesis was below the lower limit of the normal 95% confidence interval for IgM in 5 patients, for IgG in 8, and for IgA in 14. The mononuclear cells from 9 of the 10 patients with a serum IgA concentration less than 0.1 mg/ml failed to synthesize IgA in vitro. None of the patients manifested excessive suppressor cell activity. All patients had reduced but measurable helper T cell activity for immunoglobulin synthesis by co-cultured normal pokeweed mitogen-stimulated B cells (geometric mean 22% of normal). Furthermore, the addition of normal irradiated T cells to patient peripheral blood mononuclear cells led to an augmentation of IgM synthesis in 15 of 17 and to increased IgG synthesis in 9 of the 17 patients studied, including 9 of the 12 patients who had synthesized IgG before the addition of the irradiated T cells. In addition, IgA synthesis was increased in all eight patients examined that had serum IgA concentrations greater than 0.1 mg/ml. These studies suggest that a helper T cell defect contributes to the diminished immunoglobulin synthesis. However, a helper T cell defect does not appear to be the sole cause since there was no IgA synthesis by the peripheral blood mononuclear cells of 9 of the 10 patients with a profoundly reduced serum IgA even when co-cultured with normal T cells. Furthermore, the cells of the nine patients with profoundly reduced IgA levels examined also failed to produce IgA when stimulated with the relatively helper T cell-independent polyclonal

Computed tomography-guided aspiration versus key-hole craniotomy for spontaneous putaminal haemorrhage: a prospective comparison of minimally invasive procedures.

PubMed

Zhao, J Z; Zhou, L F; Zhou, D B; Wang, R Z; Wang, M; Wang, D J; Wang, S; Yuan, G; Kang, S; Ji, N; Zhao, Y L; Ye, X

2009-08-01

To compare the effectiveness of two minimally invasive procedures, namely computed tomography-guided aspiration and the key-hole approach, in the neurosurgical management for spontaneous putaminal haemorrhage, and to explore the indications for the two approaches. A multicentre, single-blinded controlled trial. Hospitals taking part in this trial and the sources for patients were from China. Among others, the hospitals involved in the interventions included: the Beijing Tiantan Hospital (of the Capital University of Medical Sciences), the General Hospital of People's Liberation Army, the Peking Union Hospital, and the Shanghai Huashan Hospital (of the Fudan University medical school). From September 2001 to November 2003, data were available for analysis from a total of 841 patients with spontaneous putaminal haemorrhage from 135 hospitals all over China (except Tibet, Hong Kong, Taiwan, and Macao). All follow-up data were for at least 3 months. Mortality, Glasgow Coma Scale score, postoperative complications, Kanofsky Performance Scale score, and Barthel Index. There were 563 patients who underwent computed tomography-guided aspiration, and 165 were treated by the key-hole approach. Respective mortality rates 1 month after the operation were 17.9% and 18.3%; at 3 months they were 19.4% and 19.4%. In those undergoing computed tomography-guided aspiration, mortality rates at 3 months after the operation were 28.2% in patients with Glasgow Coma Scale scores of 8 or below, as opposed to 8.2% in those with higher scores. This amounted to a 3.4-fold difference. In those treated by the key-hole approach, the corresponding rates were 30.2% and 7.6%, which amounted to a 4-fold difference. The corresponding mortality at 3 months in patients with complications was 3.9 times as great as in those without complications. In those with haematoma volumes of 70 mL or greater, it was 2.7 times as much as in those in whom the volumes below 30 mL. The postoperative complication rate

Substantial numerical decline in South Australian rabbit populations following the detection of rabbit haemorrhagic disease virus 2.

PubMed

Mutze, Greg; De Preu, Nicki; Mooney, Trish; Koerner, Dylan; McKenzie, Darren; Sinclair, Ron; Kovaliskli, John; Peacock, David

2018-05-19

Lagovirus europaeus GI.2, also commonly known as rabbit haemorrhagic disease virus 2, was first detected at two long-term monitoring sites for European rabbits, Oryctolagus cuniculus , in South Australia, in mid-2016. Numbers of rabbits in the following 12-18 months were reduced to approximately 20 per cent of average numbers in the preceding 10 years. The impact recorded at the two South Australian sites, if widespread in Australia and persistent for several years, is likely to be of enormous economic and environmental benefit. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Acute haemorrhagic oedema of infancy in a 5-week-old boy referred to the Child Protection Unit.

PubMed

Hawkrigg, Sharon; Johnson, Alice; Flynn, James; Thom, Graham; Wright, Helen

2014-06-01

We describe the case of a 5-week-old infant boy presenting with purpura and oedema to both hands and torso. He was otherwise well, with no antecedent history of illness or trauma. Laboratory investigations were within normal limits. A review by the Child Protection Unit was organised during his admission for consideration of inflicted trauma as a cause of the lesions; this was felt most unlikely. A clinical diagnosis, following a dermatology consultation, of acute haemorrhagic oedema of infancy (AHO) was made. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Hyberbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis

PubMed Central

Dellis, Athanasios; Papatsoris, Athanasios; Kalentzos, Vasileios; Deliveliotis, Charalambos; Skolarikos, Andreas

2017-01-01

ABSTRACT Purpose To examine the safety and efficacy of hyperbaric oxygen as the primary and sole treatment for severe radiation-induced haemorrhagic cystitis. Materials and methods Hyperbaric oxygen was prospectively applied as primary treatment in 38 patients with severe radiation cystitis. Our primary endpoint was the incidence of complete and partial response to treatment, while the secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. Results All patients completed therapy without complications with a mean follow-up of 29.33 months. Median number of sessions needed was 33. Complete and partial response rate was 86.8% and 13.2%, respectively. All 33 patients with complete response received therapy within 6 months of the haematuria onset. One patient needed cystectomy, while 33 patients were alive at the end of follow-up. Conclusions Our study suggests the early primary use of hyperbaric oxygen for radiation-induced severe cystitis as an effective and safe treatment option. PMID:28338304

Factors associated with poor outcome for aneurysmal subarachnoid haemorrhage in a series of 334 patients.

PubMed

Rivero Rodríguez, D; Scherle Matamoros, C; Fernández Cúe, L; Miranda Hernández, J L; Pernas Sánchez, Y; Pérez Nellar, J

This study evaluates care-related sociodemographic, clinical, and imaging factors and influences associated with outcome at discharge in patients with aneurismal subarachnoid haemorrhage. Retrospective cohort study in 334 patients treated at Hospital Hermanos Ameijeiras in Havana, Cuba between October 2005 and June 2014. Logistic regression analysis determined that the following factors were associated with higher risk of poor outcome: age older than 65 years (OR 3.51, 95% CI 1.79-5.7, P=.031), female sex (OR 2.17, 95% CI 1.22-3.84, P=.0067), systolic hypertension (OR 4.82, 95% CI 2.27-9.8, P=.0001), and hyperglycaemia at admission (OR 3.93, 95% CI 2.10-7.53, P=.0003). Certain complications were also associated with poor prognosis, including respiratory infection (OR 2.73, 95% CI 1.27-5.85, P=.0085), electrolyte disturbances (OR 3.33, 95% CI 1.33-8.28, P=.0073), hydrocephalus (OR 2.21, 95% CI 1.05-4.63, P=.0039), rebleeding (OR 16.50, 95% CI 8.24-41.24, P=.0000), symptomatic vasospasm (OR 19.00, 95% CI 8.86-41.24, P=.0000), cerebral ischaemia (OR 3.82, 95% CI 1.87-7.80, P=.000) and multiplex rebleeding (OR 6.69, 95% CI 1.35-36.39, P=.0019). Grades of iii and iv on the World Federation of Neurological Surgeons (OR 2.09, 95% CI 1.12-3.91, P=.0021) and Fisher scales (OR 5.18, 95% CI 2.65-10.29, P=.0008) were also related to poor outcome. Outcome of aneurysmal subarachnoid haemorrhage was related to age, sex, clinical status at admission to the stroke unit, imaging findings according to the Fisher scale, blood pressure, glycaemia and such complications as electrolyte disturbances, hydrocephalus, rebleeding, and multiplex rebleeding. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Rare problems with RhD immunoglobulin for postnatal prophylaxis after large fetomaternal haemorrhage

PubMed Central

Kidson-Gerber, Giselle

2015-01-01

We report a case of unusually large fetomaternal haemorrhage in a RhD- patient; of symptomatic non-sustained haemolysis of fetal red cells in the maternal circulation with infusion of intravenous high-dose RhD immunoglobulin; and of a failure to prevent RhD alloimmunisation. The haemolytic reaction is not previously reported in this patient group and we suggest would be limited to patients where the number of fetal red cells in the circulation is high. We advocate caution in treatment and spaced dosing of RhD immunoglobulin where the required dose is high, and refer readers to the WinRhoSDF™ RhD immunoglobulin product information for their updated dosing recommendations. There is a need for better understanding of pathophysiology and RhD immunoglobulin effects, to further reduce alloimmunisation rates, and we support the reporting of prophylaxis failures to haemovigilance programmes as is in place in the United Kingdom. PMID:27512480

Coxsackievirus A24 Variant Associated with Acute Haemorrhagic Conjunctivitis Cases, French Guiana, 2017.

PubMed

Enfissi, Antoine; Joffret, Marie-Line; Delaune, Déborah; Delpeyroux, Francis; Rousset, Dominique; Bessaud, Maël

2018-06-13

In 2017, numerous cases of acute haemorrhagic conjunctivitis (AHC) were reported in the Caribbean and in South America. Preliminary reports identified adenoviruses and enteroviruses in some patient samples but, until now, none of the etiologic agents have been fully characterized. We report the full-length genomic sequences of 4 coxsackievirus A24 (CV-A24) isolates collected from AHC patients in French Guiana during this outbreak (May and June 2017). These isolates are very closely related and belong to the genotype IV of CV-A24 variant, which consists of strains sampled worldwide during AHC outbreaks in the 2000s and 2010s. No recombination events were detected within the genomic sequences, indicating that members of this genotype have continuously circulated worldwide for more than 10 years without undergoing recombination with other enteroviruses. This unusual trait could be due to their ocular tropism that could impede genetic exchanges between these viruses and other enteroviruses, which replicate mainly in the gut. © 2018 S. Karger AG, Basel.

Cerebral venous thrombosis in a gentleman presenting with fever, convulsion and frontotemporal haemorrhages.

PubMed

Chan, K H; Cheung, R T F; Liu, W M; Mak, W; Ho, S L

2005-02-01

Cerebral venous thrombosis (CVT) is an uncommon but serious type of stroke. Thrombosis may involve the cortical or deep veins or the venous sinuses. The presenting clinical features are non-specific. We report a 48-year-old man with CVT who presented with fever, bitemporal throbbing headache, and generalised convulsion. Computed tomography (CT) of the brain revealed acute haemorrhages over right anterior frontal and posterior temporal regions with surrounding oedema and right anterior temporal subcortical oedema. The initial diagnosis was herpes simplex encephalitis. Absence of venous flow over the right transverse and sigmoid sinuses during the venous phase of digital subtraction angiography (DSA) revealed CVT. He was anti-coagulated for 6 months. An underlying cause of CVT was not detected. A high index of suspicion is required when risk factors of CVT are present. CT brain may be normal or showing non-specific findings. Magnetic resonance imaging plus venography, CT venography, or DSA is diagnostic.

Haemostatic monitoring during postpartum haemorrhage and implications for management

PubMed Central

Solomon, C.; Collis, R. E.; Collins, P. W.

2012-01-01

Summary Postpartum haemorrhage (PPH) is a major risk factor for maternal morbidity and mortality. PPH has numerous causative factors, which makes its occurrence and severity difficult to predict. Underlying haemostatic imbalances such as consumptive and dilutional coagulopathies may develop during PPH, and can exacerbate bleeding and lead to progression to severe PPH. Monitoring coagulation status in patients with PPH may be crucial for effective haemostatic management, goal-directed therapy, and improved outcomes. However, current PPH management guidelines do not account for the altered baseline coagulation status observed in pregnant patients, and the appropriate transfusion triggers to use in PPH are unknown, due to a lack of high-quality studies specific to this area. In this review, we consider the evidence for the use of standard laboratory-based coagulation tests and point-of-care viscoelastic coagulation monitoring in PPH. Many laboratory-based tests are unsuitable for emergency use due to their long turnaround times, so have limited value for the management of PPH. Emerging evidence suggests that viscoelastic monitoring, using thrombelastography- or thromboelastometry-based tests, may be useful for rapid assessment and for guiding haemostatic therapy during PPH. However, further studies are needed to define the ranges of reference values that should be considered ‘normal’ in this setting. Improving awareness of the correct application and interpretation of viscoelastic coagulation monitoring techniques may be critical in realizing their emergency diagnostic potential. PMID:23075633

Development of vaccines against Crimean-Congo haemorrhagic fever virus.

PubMed

Dowall, Stuart D; Carroll, Miles W; Hewson, Roger

2017-10-20

Crimean-Congo haemorrhagic fever virus (CCHFV) is a deadly human pathogen of the utmost seriousness being highly lethal causing devastating disease symptoms that result in intense and prolonged suffering to those infected. During the past 40years, this virus has repeatedly caused sporadic outbreaks responsible for relatively low numbers of human casualties, but with an alarming fatality rate of up to 80% in clinically infected patients. CCHFV is transmitted to humans by Hyalomma ticks and contact with the blood of viremic livestock, additionally cases of human-to-human transmission are not uncommon in nosocomial settings. The incidence of CCHF closely matches the geographical range of permissive ticks, which are widespread throughout Africa, Asia, the Middle East and Europe. As such, CCHFV is the most widespread tick-borne virus on earth. It is a concern that recent data shows the geographic distribution of Hyalomma ticks is expanding. Migratory birds are also disseminating Hyalomma ticks into more northerly parts of Europe thus potentially exposing naïve human populations to CCHFV. The virus has been imported into the UK on two occasions in the last five years with the first fatal case being confirmed in 2012. A licensed vaccine to CCHF is not available. In this review, we discuss the background and complications surrounding this limitation and examine the current status and recent advances in the development of vaccines against CCHFV. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Comparing the odds of postpartum haemorrhage in planned home birth against planned hospital birth: results of an observational study of over 500,000 maternities in the UK

PubMed Central

2012-01-01

Background The aim of this study is to compare the odds of postpartum haemorrhage among women who opt for home birth against the odds of postpartum haemorrhage for those who plan a hospital birth. It is an observational study involving secondary analysis of maternity records, using binary logistic regression modelling. The data relate to pregnancies that received maternity care from one of fifteen hospitals in the former North West Thames Regional Health Authority Area in England, and which resulted in a live or stillbirth in the years 1988–2000 inclusive, excluding ‘high-risk’ pregnancies, unplanned home births, pre-term births, elective Caesareans and medical inductions. Results Even after adjustment for known confounders such as parity, the odds of postpartum haemorrhage (≥1000ml of blood lost) are significantly higher if a hospital birth is intended than if a home birth is intended (odds ratio 2.5, 95% confidence interval 1.7 to 3.8). The ‘home birth’ group included women who were transferred to hospital during labour or shortly after birth. Conclusions Women and their partners should be advised that the risk of PPH is higher among births planned to take place in hospital compared to births planned to take place at home, but that further research is needed to understand (a) whether the same pattern applies to the more life-threatening categories of PPH, and (b) why hospital birth is associated with increased odds of PPH. If it is due to the way in which labour is managed in hospital, changes should be made to practices which compromise the safety of labouring women. PMID:23157856

Staging of Macular Telangiectasia: Power-Doppler Optical Coherence Tomography and Macular Pigment Optical Density

PubMed Central

Chin, Eric K.; Kim, Dae Yu; Hunter, Allan A.; Pilli, Suman; Wilson, Machelle; Zawadzki, Robert J.; Werner, John S.; Park, Susanna S.

2013-01-01

Purpose. Two methods were used to study the stages of macular telangiectasia (MacTel): Power-Doppler optical coherence tomography (PD-OCT), which allows imaging of the retinal circulation in three dimensions, and macular pigment optical density (MPOD), which quantifies the distribution of macular carotenoids. Methods. Among 49 patients with MacTel identified, 12 eyes (6 patients) with MacTel and 7 age-matched control eyes (7 patients) were imaged with a custom-built Fourier-domain OCT instrument to acquire PD-OCT images. MPOD was measured using heterochromatic flicker photometry in 10 eyes (5 patients) with MacTel and compared with 44 age-matched control eyes (44 patients). Clinical staging of MacTel was based on best-corrected visual acuity, fundus biomicroscopy, fluorescein angiography, and OCT. Results. Stage 1 eyes (n = 2) had subtle punctate vascular signal confined to the inner portion of the outer plexiform layer (OPL) on PD-OCT. Stage 2 (n = 2) showed larger oblique vascular signal extending into deeper OPL. Stage 3 (n = 5) had disruption of outer retinal layers with abnormal vasculature extending into the outer nuclear layer. Stage 4 (n = 3) showed diffuse blurring of the retinal layers with vascular channels extending the full thickness of the retina. MPOD values in four eyes with stage 1 or 2 MacTel correlated well with age-matched controls. Six eyes with stage 3 or 4 MacTel had loss of MPOD especially at the fovea. Conclusions. PD-OCT shows penetration of the retinal capillaries into the deeper retinal layers in early stages of MacTel, with full thickness vascular proliferation in advanced disease. MPOD is commonly depleted but may appear normal in early stage MacTel. PMID:23716628

Evaluation of a metal artifact reduction algorithm applied to post-interventional flat detector CT in comparison to pre-treatment CT in patients with acute subarachnoid haemorrhage.

PubMed

Mennecke, Angelika; Svergun, Stanislav; Scholz, Bernhard; Royalty, Kevin; Dörfler, Arnd; Struffert, Tobias

2017-01-01

Metal artefacts can impair accurate diagnosis of haemorrhage using flat detector CT (FD-CT), especially after aneurysm coiling. Within this work we evaluate a prototype metal artefact reduction algorithm by comparison of the artefact-reduced and the non-artefact-reduced FD-CT images to pre-treatment FD-CT and multi-slice CT images. Twenty-five patients with acute aneurysmal subarachnoid haemorrhage (SAH) were selected retrospectively. FD-CT and multi-slice CT before endovascular treatment as well as FD-CT data sets after treatment were available for all patients. The algorithm was applied to post-treatment FD-CT. The effect of the algorithm was evaluated utilizing the pre-post concordance of a modified Fisher score, a subjective image quality assessment, the range of the Hounsfield units within three ROIs, and the pre-post slice-wise Pearson correlation. The pre-post concordance of the modified Fisher score, the subjective image quality, and the pre-post correlation of the ranges of the Hounsfield units were significantly higher for artefact-reduced than for non-artefact-reduced images. Within the metal-affected slices, the pre-post slice-wise Pearson correlation coefficient was higher for artefact-reduced than for non-artefact-reduced images. The overall diagnostic quality of the artefact-reduced images was improved and reached the level of the pre-interventional FD-CT images. The metal-unaffected parts of the image were not modified. • After coiling subarachnoid haemorrhage, metal artefacts seriously reduce FD-CT image quality. • This new metal artefact reduction algorithm is feasible for flat-detector CT. • After coiling, MAR is necessary for diagnostic quality of affected slices. • Slice-wise Pearson correlation is introduced to evaluate improvement of MAR in future studies. • Metal-unaffected parts of image are not modified by this MAR algorithm.

Prevention of haematoma progression by tranexamic acid in intracerebral haemorrhage patients with and without spot sign on admission scan: a statistical analysis plan of a pre-specified sub-study of the TICH-2 trial.

PubMed

Ovesen, Christian; Jakobsen, Janus Christian; Gluud, Christian; Steiner, Thorsten; Law, Zhe; Flaherty, Katie; Dineen, Rob A; Bath, Philip M; Sprigg, Nikola; Christensen, Hanne

2018-06-13

We present the statistical analysis plan of a prespecified Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 sub-study aiming to investigate, if tranexamic acid has a different effect in intracerebral haemorrhage patients with the spot sign on admission compared to spot sign negative patients. The TICH-2 trial recruited above 2000 participants with intracerebral haemorrhage arriving in hospital within 8 h after symptom onset. They were included irrespective of radiological signs of on-going haematoma expansion. Participants were randomised to tranexamic acid versus matching placebo. In this subgroup analysis, we will include all participants in TICH-2 with a computed tomography angiography on admission allowing adjudication of the participants' spot sign status. Primary outcome will be the ability of tranexamic acid to limit absolute haematoma volume on computed tomography at 24 h (± 12 h) after randomisation among spot sign positive and spot sign negative participants, respectively. Within all outcome measures, the effect of tranexamic acid in spot sign positive/negative participants will be compared using tests of interaction. This sub-study will investigate the important clinical hypothesis that spot sign positive patients might benefit more from administration of tranexamic acid compared to spot sign negative patients. Trial registration ISRCTN93732214 ( http://www.isrctn.com ).

Audit of CT reporting standards in cases of intracerebral haemorrhage at a comprehensive stroke centre in Australia.

PubMed

Barras, Christen D; Asadi, Hamed; Phal, Pramit M; Tress, Brian M; Davis, Stephen M; Desmond, Patricia M

2016-12-01

Multiple CT-derived biomarkers that are predictive of intracerebral haemorrhage (ICH) growth and outcome have been described in the literature, but the extent to which these appear in imaging reports of ICH is unknown. The aim of this retrospective process audit was to determine which of the known predictors of ICH outcome was recorded in reports of the disease, with a view to providing reporting recommendations, as appropriate. We examined the initial CT report of patients diagnosed with ICH presenting to a metropolitan comprehensive stroke centre and meeting inclusion criteria during the audit period between 1 March 2013 and 28 February 2014. Each report was assessed for the inclusion of the following ICH characteristics: the number of measurement dimensions; volume; location; hydrocephalus; shape; density; 'CTA spot sign' (where CTA was performed). A total of 100 patients met audit inclusion criteria. At least one ICH dimension was recorded in 90% of reports; however, 39% did not include the measurements in three dimensions and volume was reported in just 6%. No ICH dimension was recorded in 10% of reports. With the exception of density and shape, reporting of other CT features exceeded 95%. Where CTA was performed (58%), 14 (24%) of 58 reported the 'CTA spot sign' status. In this audit, volume was the most under-reported of the established ICH characteristics predictive of ICH outcome. Readily calculated from multiplanar reformats using the ABC/2 technique, the routine reporting of ICH volume is recommended. More reporting attention to ICH density heterogeneity and shape irregularity is encouraged, given their emerging importance. Where acute CTA is performed, the presence of any dynamic haemorrhage (CTA spot sign) should be reported. © 2016 The Royal Australian and New Zealand College of Radiologists.

Haemorrhagic Complications and Symptomatic Venous Thromboembolism in Interventional Tumour Ablations: The Impact of Peri-interventional Thrombosis Prophylaxis

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

Mohnike, Konrad, E-mail: konrad.mohnike@med.ovgu.de; Sauerland, Hanna; Seidensticker, Max

AimThe aim of this study was to assess the rates of haemorrhagic and thrombotic complications in patients undergoing interventional tumour ablation with and without peri-interventional low-molecular-weight heparin (LMWH) thrombosis prophylaxis.MethodsPatients presented with primary and secondary neoplastic lesions in the liver, lung, kidney, lymph nodes and other locations. A total of 781 tumour ablations (radiofrequency ablation, n = 112; interstitial brachytherapy, n = 669) were performed in 446 patients over 22 months; 260 were conducted under peri-interventional thrombosis prophylaxis with LMWH (H-group;) and 521 without this (NH-group, in 143 of these, LMWH was given post-interventionally).ResultsSixty-three bleeding events occurred. There were significantly more bleedings in the H-groupmore » than in the NH-group (all interventions, 11.66 and 6.26 %, p = 0.0127; liver ablations, 12.73 and 7.1 %, p = 0.0416). The rate of bleeding events Grade ≥ III in all procedures was greater by a factor of >2.6 in the H-group than in the NH-group (4.64 and 1.73 %, p = 0.0243). In liver tumour ablations, the corresponding factor was about 3.3 (5.23 and 1.54 %, p = 0.028). In uni- and multivariate analyses including covariates, the only factor constantly and significantly associated with the rate of haemorrhage events was peri-interventional LMWH prophylaxis. Only one symptomatic lung embolism occurred in the entire cohort (NH-group). The 30- and 90-day mortalities were significantly greater in the H-group than in the NH-group.ConclusionsPeri-interventional LMWH thrombosis prophylaxis should be considered with caution. The rate of clinically relevant thrombotic events was extremely low.« less

Deafness due to haemorrhagic labyrinthitis and a review of relapses in Streptococcus suis meningitis.

PubMed

Tan, J H; Yeh, B I; Seet, C S R

2010-02-01

Deafness is a common and often permanent neurological sequel of Streptococcus (S.) suis meningitis. Suppurative labyrinthitis, rather than direct auditory nerve infection, has been found to be the site responsible for deafness. Neuroimaging is important to localise the site involved in hearing loss and to assess the feasibility of a cochlear implantation. S. suis is very sensitive to penicillin. Although a relapse of S. suis meningitis is uncommon, it can occur despite an adequate duration of appropriate antibiotic therapy. We describe a patient with S. suis meningitis, who developed permanent deafness from haemorrhagic labyrinthitis, as shown on magnetic resonance imaging. She suffered a relapse despite a seven-week course of intravenous antibiotics. A review on six cases of relapse reported in the literature shows that relapses occurred despite two to four weeks of antibiotics being administered to the patients. The clinical implications and treatment of relapse are discussed.

Frequency-difference MIT imaging of cerebral haemorrhage with a hemispherical coil array: numerical modelling.

PubMed

Zolgharni, M; Griffiths, H; Ledger, P D

2010-08-01

The feasibility of detecting a cerebral haemorrhage with a hemispherical MIT coil array consisting of 56 exciter/sensor coils of 10 mm radius and operating at 1 and 10 MHz was investigated. A finite difference method combined with an anatomically realistic head model comprising 12 tissue types was used to simulate the strokes. Frequency-difference images were reconstructed from the modelled data with different levels of the added phase noise and two types of a priori boundary errors: a displacement of the head and a size scaling error. The results revealed that a noise level of 3 m degrees (standard deviation) was adequate for obtaining good visualization of a peripheral stroke (volume approximately 49 ml). The simulations further showed that the displacement error had to be within 3-4 mm and the scaling error within 3-4% so as not to cause unacceptably large artefacts on the images.

A large pulmonary arteriovenous malformation causing cerebrovascular accidents.

PubMed

Sladden, David; Casha, Aaron; Azzopardi, Conrad; Manche', Alexander

2015-04-16

The incidence of pulmonary arteriovenous malformations (PAVMs) is 2.5 in 100,000. 80% are associated with Osler-Weber-Rendu syndrome or hereditary haemorrhagic telangiectasia. We report the case of a 70-year-old man with a 6 cm spherical mass incidentally found on chest X-ray. There was a localised systolic bruit over the right lower zone posteriorly; however, he was asymptomatic. He had suffered a stroke, affecting his right hand and his speech, from which he recovered. He experienced regular transient ischaemic attacks, on an average of every 2 months. He underwent a right lower lobectomy and on ligating the right lower lobe pulmonary artery the saturations of oxygen rose from 92% to 97%, demonstrating a significant right to left extracardiac shunt. Postoperative recovery was excellent and 1 year later the patient reports no further neurological symptoms. 40% of such lesions exhibit symptoms, however, only one-third are neurological. Treatment should be by percutaneous embolisation. 2015 BMJ Publishing Group Ltd.

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial.

PubMed

2017-05-27

Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10

Prostaglandins for preventing postpartum haemorrhage.

PubMed

Tunçalp, Özge; Hofmeyr, G Justus; Gülmezoglu, A Metin

2012-08-15

Prostaglandins have mainly been used for postpartum haemorrhage (PPH) when other measures fail. Misoprostol, a new and inexpensive prostaglandin E1 analogue, has been suggested as an alternative for routine management of the third stage of labour. To assess the effects of prophylactic prostaglandin use in the third stage of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 January 2011). We updated this search on 25 May 2012 and added the results to the awaiting classification section. Randomised trials comparing a prostaglandin agent with another uterotonic or no prophylactic uterotonic (nothing or placebo) as part of management of the third stage of labour. The primary outcomes were blood loss 1000 mL or more and the use of additional uterotonics. Two review authors independently assessed eligibility and trial quality and extracted data. We included 72 trials (52,678 women). Oral or sublingual misoprostol compared with placebo is effective in reducing severe PPH (oral: seven trials, 6225 women, not totalled due to significant heterogeneity; sublingual: risk ratio (RR) 0.66; 95% confidence interval (CI) 0.45 to 0.98; one trial, 661 women) and blood transfusion (oral: RR 0.31; 95% CI 0.10 to 0.94; four trials, 3519 women).Compared with conventional injectable uterotonics, oral misoprostol was associated with higher risk of severe PPH (RR 1.33; 95% CI 1.16 to 1.52; 17 trials, 29,797 women) and use of additional uterotonics, but with a trend to fewer blood transfusions (RR 0.84; 95% CI 0.66 to 1.06; 15 trials; 28,213 women). Additional uterotonic data were not totalled due to heterogeneity. Misoprostol use is associated with significant increases in shivering and a temperature of 38º Celsius compared with both placebo and other uterotonics. Oral or sublingual misoprostol shows promising results when compared with placebo in reducing blood loss after delivery. The margin of benefit may be affected by whether other components of the

Genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV).

PubMed

Snow, M; Bain, N; Black, J; Taupin, V; Cunningham, C O; King, J A; Skall, H F; Raynard, R S

2004-10-21

The nucleotide sequences of a specific region of the nucleoprotein gene were compared in order to investigate the genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV). Analysis of the sequence from 128 isolates of diverse geographic and host origin renders this the most comprehensive molecular epidemiological study of marine VHSV conducted to date. Phylogenetic analysis of nucleoprotein gene sequences confirmed the existence of the 4 major genotypes previously identified based on N- and subsequent G-gene based analyses. The range of Genotype I included subgroups of isolates associated with rainbow trout aquaculture (Genotype Ia) and those from the Baltic marine environment (Genotype Ib) to emphasise the relatively close genetic relationship between these isolates. The existence of an additional genotype circulating within the Baltic Sea (Genotype II) was also confirmed. Genotype III included marine isolates from around the British Isles in addition to those associated with turbot mariculture, highlighting a continued risk to the development of this industry. Genotype IV consisted of isolates from the marine environment in North America. Taken together, these findings suggest a marine origin of VHSV in rainbow trout aquaculture. The implications of these findings with respect to the future control of VHSV are discussed. The capacity for molecular phylogenetic analysis to resolve complex epidemiological problems is also demonstrated and its likely future importance to disease management issues highlighted.

Inhibition of Transforming Growth Factor-Beta1 SignalingAttenuates Ataxia Telangiectasia Mutated Activity in Response toGenotoxic Stress

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

Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose

2006-01-01

Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta} (TGF{beta})-1, which is activated by radiation, is a potent and pleiotropic mediator of physiologic and pathologic processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}I null murine epithelial cells or human epithelial cells treated with a small-molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17, and p53; reduced H2AX radiation-induced foci; and increased radiosensitivity compared with TGF{beta} competent cells.more » We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM, which directs epithelial cell stress responses, cell fate, and tissue integrity. Thus, Tgf{beta}I, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.« less

Influence of signals length and noise in power spectral densities computation using Hilbert-Huang Transform in synthetic HRV

NASA Astrophysics Data System (ADS)

Rodríguez, María. G.; Altuve, Miguel; Lollett, Carlos; Wong, Sara

2013-11-01

Among non-invasive techniques, heart rate variability (HRV) analysis has become widely used for assessing the balance of the autonomic nervous system. Research in this area has not stopped and alternative tools for the study and interpretation of HRV, are still being proposed. Nevertheless, frequency-domain analysis of HRV is controversial when the heartbeat sequence is non-stationary. The Hilbert-Huang Transform (HHT) is a relative new technique for timefrequency analyses of non-linear and non-stationary signals. The main purpose of this work is to investigate the influence of time serieś length and noise in HRV from synthetic signals, using HHT and to compare it with Welch method. Synthetic heartbeat time series with different sizes and levels of signal to noise ratio (SNR) were investigated. Results shows i) sequencés length did not affect the estimation of HRV spectral parameter, ii) favorable performance for HHT for different SNR. Additionally, HHT can be applied to non-stationary signals from nonlinear systems and it will be useful to HRV analysis to interpret autonomic activity when acute and transient phenomena are assessed.

Chromosome Aberrations in Normal and Ataxia-Telangiectasia Cells Exposed to Heavy Ions

NASA Technical Reports Server (NTRS)

Kawata, T.; Ito, H.; Liu, C.; Shigematsu, N.; George, K.; Cucinotta, F. A.

2007-01-01

Although cells derived from Ataxia Telangiectasia (AT) patients are known to exhibit abnormal responses to ionizing radiations, its underlying mechanism still remains unclear. Previously, the authors reported that at the same gamma-irradiation dose AT cells show higher frequencies of misrepair and deletions compared to normal human fibroblast cells. In this study, we investigated the effects of heavy ions beams on chromosomal aberrations in normal and AT cells. Normal and AT fibroblast cells arrested at G0/G1 phase were irradiated with 2 Gy of X-rays, 490 MeV/u Silicon (LET 55 keV/m), 500 MeV/u Iron (LET 185 keV/m) and 200 MeV/u Iron (LET 440 keV/m) particles, and then cells were allowed to repair for 24 hours at 37 degrees before subculture. Calyculin-A induced PCC method was employed to collect G2/M chromosomes and whole DNA probes 1 and 3 were used to analyze chromosomal aberrations such as color-junctions, deletions, simple exchanges (incomplete and reciprocal exanges) and complex-type exchanges. The percentages of aberrant cells were higher when normal and AT cells were exposed to heavy ions compared to X-rays, and had a tendency to increase with increasing LET up to 185 keV/m and then decreased at 440 keV/m. When the frequency of color-junctions per cell was compared after X-ray exposure, AT cells had around three times higher frequency of color-junctions (mis-rejoining) than normal cells. However, at 185 keV/m there was no difference in the frequency of color-junctions between two cell lines. It was also found that the frequency of simple exchanges per cell was almost constant in AT cells regardless LET levels, but it was LET dependent for normal cells. Interestingly, the frequency of simple exchanges was higher for AT cells when it was compared at 185 keV/m but AT cells had more complex-type exchanges at the same LET levels. Heavy ions are more efficient in inducing chromosome aberrations in normal and AT cells compared to X-rays, and the aberration types

Analysis of glutathione S-transferase Pi isoform (GSTP1) single-nucleotide polymorphisms and macular telangiectasia type 2.

PubMed

Szental, Joshua A; Baird, Paul N; Richardson, Andrea J; Islam, F M Amirul; Scholl, Hendrik P N; Charbel Issa, Peter; Holz, Frank G; Gillies, Mark; Guymer, Robyn H

2010-12-01

Recent imaging studies have suggested that macular pigment is decreased centrally in macular telangiectasia type 2 (MT2). The uptake of xanthophyll pigment into the macula is thought to be facilitated by a xanthophyll-binding protein (XBP). The Pi isoform of glutathione S-transferase (GSTP1) represents one such XBP with high binding affinity. This case-control study aimed to determine whether two common single-nucleotide polymorphisms (SNPs) of GSTP1 were associated with MT2. DNA samples from 39 cases and 21 controls were collected. Two polymorphic sites of Ile105Val and Ala114Val in exons 5 and 6 respectively, of the GSTP1 gene were analysed. Comparison of alleles and genotypes between cases and controls indicated that there were no statistically significant differences for either the Ile105Val SNP (P=0.43) or the Ala114Val SNP (P=0.85), or for any combinations; however, the homozygous at-risk genotype (GG) of the Ile105Val SNP was present in 8% of cases but absent in controls. This study found no statistically significant association between two common GSTP1 SNPs and MT2; however, a trend towards a greater frequency of the GG genotype of the Ile105Val SNP in cases is of great interest. The biological plausibility of disturbed macular pigment uptake in MT2 makes GSTP1 an excellent candidate gene. Further investigation is warranted in future studies of MT2.

Possible interaction between myxomatosis and calicivirosis related to rabbit haemorrhagic disease affecting the European rabbit.

PubMed

Marchandeau, S; Bertagnoli, S; Peralta, B; Boucraut-Baralon, C; Letty, J; Reitz, F

2004-11-06

Serological data on myxoma virus, rabbit haemorrhagic disease (RHD) virus and RHD-like viruses in juvenile rabbits (Oryctolagus cuniculus) trapped in 1995, 1996 and 1997 in two areas of France were analysed. For each disease, the effects of bodyweight, year, month and seropositivity for the other disease were modelled by using logistic regressions. In one area, a model including RHD seropositivity was selected to explain the myxoma virus seropositivity. Models including myxoma virus seropositivity were selected to explain the RHD seropositivity in both areas, and the odds of a rabbit being seropositive to both viruses were 5.1 and 8.4 times higher than the odds of a rabbit being seronegative to myxoma virus and seropositive to RHD. The year and bodyweight had significant effects for myxomatosis in one area and for RHD in both areas.

A clinical characteristic analysis of pregnancy-associated intracranial haemorrhage in China.

PubMed

Liang, Zhu-Wei; Lin, Li; Gao, Wan-Li; Feng, Li-Min

2015-03-30

Intracerebral haemorrhage (ICH) occurring during pregnancy and the puerperium is an infrequent but severe complication with a high mortality and poor prognosis. Until recently, previous studies have mainly focused on the effect of different treatments on prognosis. However, few studies have provided solid evidence to clarify the key predisposing factors affecting the prognosis of ICH. In the present study, based on a unique sample with a high ICH incidence and mortality rate, we described the main clinical characteristics of ICH patients and found that the prognosis of patients who underwent surgical intervention was not better than that of patients who received other treatment modalities. However, pre-eclampsia patients had higher maternal and neonatal mortality rates than other aetiology groups. Furthermore, univariate regression analysis identified onset to diagnosis time (O-D time) and pre-eclampsia as the only factors showing independent correlation with poor maternal outcomes (modified Rankin Scale, mRS ≥ 3), and only O-D time was identified as a predictor of maternal mortality. These results revealed that the aetiology of ICH and O-D time might be crucial predisposing factors to prognosis, especially for patients with pre-eclampsia. The study highlighted a novel direction to effectively improve the prognosis of pregnancy-associated ICH.

Localization of an Ataxia-Telangiectasia Gene to an −500-kb Interval on Chromosome 11q23.1: Linkage Analysis of 176 Families by an International Consortium

PubMed Central

Lange, Ethan; Borresen, Anna-Lise; Chen, Xiaoguang; Chessa, Luciana; Chiplunkar, Sujata; Concannon, Patrick; Dandekar, Sugandha; Gerken, Steven; Lange, Kenneth; Liang, Teresa; McConville, Carmel; Polakow, Jeff; Porras, Oscar; Rotman, Galit; Sanal, Ozden; Sheikhavandi, Sepideh; Shiloh, Yosef; Sobel, Eric; Taylor, Malcolm; Telatar, Milhan; Teraoka, Sharon; Tolun, Aslihan; Udar, Nitin; Uhrhammer, Nancy; Vanagaite, Lina; Wang, Zhijun; Wapelhorst, Beth; Wright, Jocyndra; Yang, Huan-Ming; Yang, Lan; Ziv, Yael; Gatti, Richard A.

1995-01-01

We describe a 20-point linkage analysis map of chromosome 11q22-23 that is based on genotyping 249 families (59 CEPH and 190 A-T). Monte Carlo linkage analyses of 176 ataxia-telangiectasia (A-T) families localizes the major A-T locus to the region between S1819(A4) and S1818(A2). When seven nonlinking families were excluded from subsequent analyses, a 2-lod support interval of ∼500 kb was identified between S1819(A4) and S1294. No recombinants were observed between A-T and markers S384, B7, S535, or S1294. Only 17 of the international consortium families have been assigned to complementation groups. The available evidence favors either a cluster of A-T genes on chromosome 11 or intragenic defects in a single gene. PMID:7611279

Progressive DNA and RNA damage from oxidation after aneurysmal subarachnoid haemorrhage in humans.

PubMed

Jorgensen, Anders; Staalsoe, Jonatan M; Simonsen, Anja H; Hasselbalch, Steen G; Høgh, Peter; Weimann, Allan; Poulsen, Henrik E; Olsen, Neils V

2018-01-01

Free radical toxicity is considered as a key mechanism in the neuronal damage occurring after aneurysmal subarachnoid haemorrhage (SAH). We measured markers of DNA and RNA damage from oxidation (8-oxodG and 8-oxoGuo, respectively) in cerebrospinal fluid from 45 patients with SAH on day 1-14 after ictus and 45 age-matched healthy control subjects. At baseline, both markers were significantly increased in patients compared to controls (p values < .001), and exhibited a progressive further increase (to >20-fold above control levels) from day 5-14. None of the markers predicted the occurrence of vasospasms or mortality, although there was a trend that the 8-oxoGuo marker was more strongly associated with mortality than the 8-oxodG marker. We conclude that SAH leads to a massive increase in damage to nucleic acids from oxidative stress, which is likely to play a role in neuronal dysfunction and death. As only patients in need of a ventriculostomy catheter were included in the study, the findings cannot necessarily be extrapolated to all patients with SAH.

A major haemorrhage protocol improves the delivery of blood component therapy and reduces waste in trauma massive transfusion.

PubMed

Khan, Sirat; Allard, Shubha; Weaver, Anne; Barber, Colin; Davenport, Ross; Brohi, Karim

2013-05-01

Major haemorrhage protocols (MHP) are required as part of damage control resuscitation regimens in modern trauma care. The primary objectives of this study were to ascertain whether a MHP improved blood product administration and reduced waste compared to traditional massive transfusion protocols (MTP). Datasets on adult trauma admissions 1 year prior and 1 year post implementation of a MHP at a Level 1 trauma centre were obtained from the trauma registry. Demographic and clinical data were collected prospectively including mechanism of injury, physiological observations, ICU admission and length of stay. The volume of blood components (packed red blood cells, platelets, cryoprecipitate and fresh frozen plasma) issued, transfused, returned to stock and wasted within the first 24h was gathered retrospectively. Over the 2-year study period 2986 patient records were available for analysis. 40 patients required a 10+ Units of packed red blood ells transfusion in the MTP group vs. 56 patients post MHP implementation. The administration of blood component therapy improved significantly post MHP implementation. FFP:PRBC transfusion improved from 1:3 to 1:2 (p<0.01) and CRYO:PRBC improved from 1:10 to 1:7 (p<0.05). We reported a significant reduction in the waste of platelets from 14% to 2% (p<0.01). Outcomes had improved: Median hospital length of stay was reduced from 54 days to 26 days (p<0.05). Implementation of a MHP results in improved delivery of blood components and a reduction in the waste of blood products compared to the older model of MTP. In combination with educational programmes MHP can significantly improve blood product administration and patient outcomes in trauma haemorrhage. Level III diagnostic test study. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Effects of vaccination against viral haemorrhagic disease and myxomatosis on long-term mortality rates of European wild rabbits.

PubMed

Calvete, C; Estrada, R; Lucientes, J; Osacar, J J; Villafuerte, R

2004-09-25

The effects of vaccination against myxomatosis and viral haemorrhagic disease (VHD) on long-term mortality rates in European rabbits (Oryctolagus cuniculus) were studied from 1993 to 1996 by radiotracking a free-living population of wild rabbits. During the three months after immunisation, unvaccinated young rabbits weighing between 180 and 600 g were 13.6 times more likely to die than vaccinated young rabbits. In adult rabbits, vaccination did not significantly decrease mortality, mainly owing to the high proportion of rabbits which had previously been exposed to the antigens of both diseases. Compared with adult rabbits with natural antibodies to VHD, rabbits without these antibodies were 5.2 times more likely to die of VHD during annual outbreaks.

Ataxia telangiectasia mutated (ATM) interacts with p400 ATPase for an efficient DNA damage response.

PubMed

Smith, Rebecca J; Savoian, Matthew S; Weber, Lauren E; Park, Jeong Hyeon

2016-11-04

Ataxia telangiectasia mutated (ATM) and TRRAP proteins belong to the phosphatidylinositol 3-kinase-related kinase family and are involved in DNA damage repair and chromatin remodeling. ATM is a checkpoint kinase that is recruited to sites of DNA double-strand breaks where it phosphorylates a diverse range of proteins that are part of the chromatin and DNA repair machinery. As an integral subunit of the TRRAP-TIP60 complexes, p400 ATPase is a chromatin remodeler that is also targeted to DNA double-strand break sites. While it is understood that DNA binding transcriptional activators recruit p400 ATPase into a regulatory region of the promoter, how p400 recognises and moves to DNA double-strand break sites is far less clear. Here we investigate a possibility whether ATM serves as a shuttle to deliver p400 to break sites. Our data indicate that p400 co-immunoprecipitates with ATM independently of DNA damage state and that the N-terminal domain of p400 is vital for this interaction. Heterologous expression studies using Sf9 cells revealed that the ATM-p400 complex can be reconstituted without other mammalian bridging proteins. Overexpression of ATM-interacting p400 regions in U2OS cells induced dominant negative effects including the inhibition of both DNA damage repair and cell proliferation. Consistent with the dominant negative effect, the stable expression of an N-terminal p400 fragment showed a decrease in the association of p400 with ATM, but did not alter the association of p400 with TRRAP. Taken together, our findings suggest that a protein-protein interaction between ATM and p400 ATPase occurs independently of DNA damage and contributes to efficient DNA damage response and repair.

Identification of defective illegitimate recombinational repair of oxidatively-induced DNA double-strand breaks in ataxia-telangiectasia cells

NASA Technical Reports Server (NTRS)

Dar, M. E.; Winters, T. A.; Jorgensen, T. J.

1997-01-01

Ataxia-telangiectasia (A-T) is an autosomal-recessive lethal human disease. Homozygotes suffer from a number of neurological disorders, as well as very high cancer incidence. Heterozygotes may also have a higher than normal risk of cancer, particularly for the breast. The gene responsible for the disease (ATM) has been cloned, but its role in mechanisms of the disease remain unknown. Cellular A-T phenotypes, such as radiosensitivity and genomic instability, suggest that a deficiency in the repair of DNA double-strand breaks (DSBs) may be the primary defect; however, overall levels of DSB rejoining appear normal. We used the shuttle vector, pZ189, containing an oxidatively-induced DSB, to compare the integrity of DSB rejoining in one normal and two A-T fibroblast cells lines. Mutation frequencies were two-fold higher in A-T cells, and the mutational spectrum was different. The majority of the mutations found in all three cell lines were deletions (44-63%). The DNA sequence analysis indicated that 17 of the 17 plasmids with deletion mutations in normal cells occurred between short direct-repeat sequences (removing one of the repeats plus the intervening sequences), implicating illegitimate recombination in DSB rejoining. The combined data from both A-T cell lines showed that 21 of 24 deletions did not involve direct-repeats sequences, implicating a defect in the illegitimate recombination pathway. These findings suggest that the A-T gene product may either directly participate in illegitimate recombination or modulate the pathway. Regardless, this defect is likely to be important to a mechanistic understanding of this lethal disease.

SD-OCT stages of progression of type 2 macular telangiectasia in a patient followed for 3 years.

PubMed

Coscas, Gabriel; Coscas, Florence; Zucchiatti, Ilaria; Bandello, Francesco; Soubrane, Gisele; SouÏed, Eric

2013-01-01

To describe the natural course of type 2 idiopathic macular telangiectasia (MT) using spectral-domain optical coherence tomography (SD-OCT). Analysis of the different stages of progression of type 2 MT during a period of 3 years using multimodal imaging, including SD-OCT correlated with angiographic and autofluorescence images. The analysis of the different steps was obtained initially from the first eye, then successively from the fellow eye when progressive changes appeared. The earliest visible alteration at SD-OCT was the interruption of the interface between inner segment and ellipsoid (IS/EL) (stage 1). The second stage was characterized by the complete interruption of both IS/EL interface and external limiting membrane (stage 2). At the next step, a wide disruption of the outer nuclear layer was noted (stage 3). The fourth stage showed a complete disorganization of the inner layers with aspect of fusion of the inner retinal layers associated with progressive atrophy of the outer layers (stage 4). Hyper-reflective deposits were found in both the internal and external retinal layers (stage 5). Small intraretinal cystoid spaces appeared in the different retinal layers (stage 6). This last feature was an earlier manifestation of the typical intraretinal cysts that are the well-known OCT appearance of type 2 MT. We describe the 6 steps of progression from earlier SD-OCT findings that led to a complete disorganization and fusion of the inner layers (probably due to changes in the Müller cells) to the typical intraretinal cysts.

Ataxia-telangiectasia mutated (ATM) deficiency decreases reprogramming efficiency and leads to genomic instability in iPS cells

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

Kinoshita, Taisuke; Nagamatsu, Go, E-mail: gonag@sc.itc.keio.ac.jp; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012

2011-04-08

Highlights: {yields} iPS cells were induced with a fluorescence monitoring system. {yields} ATM-deficient tail-tip fibroblasts exhibited quite a low reprogramming efficiency. {yields} iPS cells obtained from ATM-deficient cells had pluripotent cell characteristics. {yields} ATM-deficient iPS cells had abnormal chromosomes, which were accumulated in culture. -- Abstract: During cell division, one of the major features of somatic cell reprogramming by defined factors, cells are potentially exposed to DNA damage. Inactivation of the tumor suppressor gene p53 raised reprogramming efficiency but resulted in an increased number of abnormal chromosomes in established iPS cells. Ataxia-telangiectasia mutated (ATM), which is critical in the cellularmore » response to DNA double-strand breaks, may also play an important role during reprogramming. To clarify the function of ATM in somatic cell reprogramming, we investigated reprogramming in ATM-deficient (ATM-KO) tail-tip fibroblasts (TTFs). Although reprogramming efficiency was greatly reduced in ATM-KO TTFs, ATM-KO iPS cells were successfully generated and showed the same proliferation activity as WT iPS cells. ATM-KO iPS cells had a gene expression profile similar to ES cells and WT iPS cells, and had the capacity to differentiate into all three germ layers. On the other hand, ATM-KO iPS cells accumulated abnormal genome structures upon continuous passages. Even with the abnormal karyotype, ATM-KO iPS cells retained pluripotent cell characteristics for at least 20 passages. These data indicate that ATM does participate in the reprogramming process, although its role is not essential.« less

Application of the Hilbert-Huang Transform to Financial Data

NASA Technical Reports Server (NTRS)

Huang, Norden

2005-01-01

A paper discusses the application of the Hilbert-Huang transform (HHT) method to time-series financial-market data. The method was described, variously without and with the HHT name, in several prior NASA Tech Briefs articles and supporting documents. To recapitulate: The method is especially suitable for analyzing time-series data that represent nonstationary and nonlinear phenomena including physical phenomena and, in the present case, financial-market processes. The method involves the empirical mode decomposition (EMD), in which a complicated signal is decomposed into a finite number of functions, called "intrinsic mode functions" (IMFs), that admit well-behaved Hilbert transforms. The HHT consists of the combination of EMD and Hilbert spectral analysis. The local energies and the instantaneous frequencies derived from the IMFs through Hilbert transforms can be used to construct an energy-frequency-time distribution, denoted a Hilbert spectrum. The instant paper begins with a discussion of prior approaches to quantification of market volatility, summarizes the HHT method, then describes the application of the method in performing time-frequency analysis of mortgage-market data from the years 1972 through 2000. Filtering by use of the EMD is shown to be useful for quantifying market volatility.

The impact of early outcome events on the effect of tranexamic acid in post-partum haemorrhage: an exploratory subgroup analysis of the WOMAN trial.

PubMed

Brenner, Amy; Shakur-Still, Haleema; Chaudhri, Rizwana; Fawole, Bukola; Arulkumaran, Sabaratnam; Roberts, Ian

2018-06-07

In severe post-partum haemorrhage, death can occur within hours of bleeding onset so interventions to control the bleeding must be given immediately. In clinical trials of treatments for life-threatening bleeding, established treatments are given priority and the trial treatment is usually given last. However, enrolling patients in whom severe maternal morbidity or death is imminent or inevitable at the time of randomisation may dilute the effects of a trial treatment. We conducted an exploratory analysis of data from the WOMAN trial, an international, randomised placebo-controlled trial of the effects of tranexamic acid on death and surgical intervention in 20,060 women with post-partum haemorrhage. We assessed the impact of early maternal death or hysterectomy due to exsanguination on the effect of tranexamic acid on each of these respective outcomes. We conducted repeated analyses excluding patients with these outcomes at increasing intervals from the time of randomisation. We quantified treatment effects using risk ratios (RR) and 99% confidence intervals (CI) and prepared cumulative failure plots. Among 14,923 women randomised within 3 h of delivery (7518 tranexamic acid and 7405 placebo), there were 216 bleeding deaths (1.5%) and 383 hysterectomies due to bleeding (2.8%). After excluding deaths from exsanguination at increasing time intervals following randomization, there was a significant reduction in the risk of death due to bleeding with tranexamic acid (RR = 0.41; 99% CI 0.19-0.89). However, after excluding hysterectomies at increasing time intervals post-randomization, there was no reduction in the risk of hysterectomy due to bleeding with tranexamic acid (RR = 0.79; 99% CI 0.33-1.86). Findings from this analysis provide further evidence that tranexamic acid reduces the risk of death from exsanguination in women who experience postpartum haemorrhage. It is uncertain whether tranexamic acid reduces the risk of hysterectomy for bleeding after

Efficacy of a glycoprotein DNA vaccine against viral haemorrhagic septicaemia (VHS) in Pacific herring, Clupea pallasii Valenciennes

USGS Publications Warehouse

Hart, L.M.; Lorenzen, Niels; LaPatra, S.E.; Grady, C.A.; Roon, S.E.; O’Reilly, J.; Gregg, J.L.; Hershberger, P.K.

2012-01-01

Viral haemorrhagic septicaemia virus (VHSV) and its associated disease state, viral haemorrhagic septicaemia (VHS), is hypothesized to be a proximate factor accounting for the decline and failed recovery of Pacific herring populations in Prince William Sound, AK (Marty et al. 1998, 2003, 2010). Survivors of laboratory-induced VHSV epizootics develop resistance to subsequent viral exposure (Kocan et al. 2001; Hershberger et al. 2007, 2010), which is likely the result of immune system recognition of the viral glycoprotein (G) (Lecocq-Xhonneux et al. 1994), a surface antigen that contains neutralizing epitopes (Lorenzen, Olesen & Jorgensen 1990; Jørgensen et al. 1995) and cell attachment domains (Lecocq-Xhonneux et al. 1994; Estepa & Coll 1996). These properties have proven useful in the development of G-gene-based DNA vaccines for VHSV and a related rhabdovirus, infectious haematopoietic necrosis virus (IHNV) (Anderson et al. 1996; Heppell et al. 1998; Corbeil et al. 1999; Einer-Jensen et al. 2009). Rainbow trout fingerlings, Oncorhynchus mykiss (Walbaum), vaccinated with 1 µg of either the VHS or IHN vaccine are protected from VHS when exposed to virus as early as 4 days (44 degree days) post-vaccination (p.v.) (Lorenzen et al. 2002). At later time points (80 days p.v.; 880 degree days), the level of cross-protection against VHS by IHN vaccination is either completely lost (60 days p.v.; 660 degree days) (3 g rainbow trout; 1 µg vaccine dose) (Lorenzen et al. 2002) or present at intermediate levels (6.5 g rainbow trout; 1 µg vaccine dose) (Einer-Jensen et al. 2009). Comparatively, VHS vaccination remains effective as long as 9 months (2520 degree days) p.v. (100 g rainbow trout; 0.5 µg vaccine dose) (McLauchlan et al. 2003). These results suggest that IHN and VHS vaccination activate a rapid transitory innate immune response against VHSV that is followed by long-term adaptive immunity in VHS-vaccinated trout (Lorenzen et al. 2002).

Prospective study of bacteraemia in acute haemorrhagic diarrhoea syndrome in dogs.

PubMed

Unterer, S; Lechner, E; Mueller, R S; Wolf, G; Straubinger, R K; Schulz, B S; Hartmann, K

2015-03-21

In dogs with idiopathic acute haemorrhagic diarrhoea syndrome (AHDS), a serious loss of intestinal mucosal barrier integrity occurs. However, the incidence of bacterial translocation in dogs with idiopathic AHDS is not known. Thus, the objectives of this prospective study were to identify the incidence of bacteraemia, to evaluate the frequency of septic events and the influence of bacteraemia on various clinical and laboratory parameters, duration of hospitalisation and survival of dogs with idiopathic AHDS. The study included 87 dogs with idiopathic AHDS. Twenty-one healthy dogs served as control group. To evaluate clinical significance of bacterial translocation, blood culture results were compared between patients and controls. Clinical and laboratory parameters were compared between patients with positive and negative blood cultures. There was no significant difference in either incidence of bacteraemia between patients with idiopathic AHDS (11 per cent) and controls (14 per cent) or in severity of clinical signs, laboratory parameters, duration of hospitalisation or mortality between blood culture-positive and culture-negative dogs with idiopathic AHDS. The results of this study suggest that the incidence of bacteraemia in dogs with idiopathic AHDS is low and not different from that of healthy control dogs. Bacteraemia does not influence the clinical course or survival and thus antibiotic treatment is not indicated to prevent sepsis. British Veterinary Association.

Simple and validated UHPLC-MS/MS analysis of nimodipine in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage.

PubMed

Mohamed, Susan; Riva, Roberto; Contin, Manuela

2016-08-15

We present a simple, fast and validated method for the determination of nimodipine in plasma and cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Plasma or CSF 250μL aliquots were pretreated with acetonitrile spiked with lacosamide as internal standard. The chromatographic separation was performed on a Fusion (3μm) 50×2.0mm I.D. column with gradient elution of 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in acetonitrile at a flow rate of 0.35mL/min. The MS/MS ion transitions were 419.1→343 for nimodipine and 251.1→91 for the internal standard. The linearity was determined from 2.0 to 40.0ng/mL in plasma and 40.0-800.0pg/mL in CSF. The lower limit of quantitation (LLOQ) of nimodipine was 0.4ng/mL in plasma and 40pg/mL in CSF. The mean recovery for nimodipine was ≥75% in plasma and ≥90% in CSF at all three considered concentrations. Intra- and interassay precision and accuracy were ≤15% at all quality control concentrations in plasma and CSF. The method was applied to measure plasma and CSF concentrations of nimodipine in a series of patients with subarachnoid haemorrhage treated with intravenous nimodipine. The present procedure, omitting time-consuming liquid-liquid extraction and drying steps, is faster, simpler and cheaper than published LC-MS/MS analytical methods for nimodipine in plasma and the first validated one for nimodipine in CSF. Copyright © 2016 Elsevier B.V. All rights reserved.

A serosurvey of bluetongue and epizootic haemorrhagic disease in a convenience sample of sheep and cattle herds in Zimbabwe.

PubMed

Gordon, Stuart J G; Bolwell, Charlotte; Rogers, Chris W; Musuka, Godfrey; Kelly, Patrick; Guthrie, Alan; Mellor, Philip S; Hamblin, Chris

2017-11-14

A convenience sample of sheep and cattle herds around the cities of Harare, Kwekwe and Bulawayo, located in the Highveld region of Zimbabwe, was used to estimate the seroprevalence and sero-incidence of bluetongue virus (BTV) and epizootic haemorrhagic disease virus (EHDV) antibodies. A competitive enzyme-linked immunosorbent assay was used to identify serum antibodies against BTV and EHDV across three rainy seasons. The median sero-prevalence of BTV and EHDV antibodies in cattle was 62% (interquartile range [IQR]: 30-89) and 56% (IQR: 5-77), respectively. In sheep, the median sero-prevalence of BTV and EHDV was 41% (IQR: 19-63) and 0% (IQR: 0-21), respectively. Median sero-incidences of BTV and EHDV antibodies in cattle of 43% (IQR: 22-67) and 27% (IQR: 9-57) respectively were recorded. The median sero-incidence of BTV in sheep was 14% (IQR: 6-23). Based on these preliminary findings, animal health workers in Zimbabwe should continue to monitor the exposure rates of cattle and sheep to BTV and consider the possibility of strains emerging with increased pathogenicity. There are no previous published reports of antibodies against EHDV in Zimbabwe so the possibility of epizootic haemorrhagic disease existing in domestic livestock should now be considered by Zimbabwean animal health officials. Seroconversions to BTV and EHDV occurred predominantly at the end of each rainy season (March and April), which generally corresponds to high numbers of the Culicoides vectors. BTV isolations were made from three individual cows in two of the sentinel herds and all three were identified as serotype 3. This is the first time BTV serotype 3 has been recorded in Zimbabwe, although its presence in neighbouring South Africa is well documented.

Hilbert-Huang transform based instrumental assessment of intention tremor in multiple sclerosis

NASA Astrophysics Data System (ADS)

Carpinella, Ilaria; Cattaneo, Davide; Ferrarin, Maurizio

2015-08-01

Objective. This paper describes a method to extract upper limb intention tremor from gyroscope data, through the Hilbert-Huang transform (HHT), a technique suitable for the study of nonlinear and non-stationary processes. The aims of the study were to: (i) evaluate the method’s ability to discriminate between healthy controls and MS subjects; (ii) validate the proposed procedure against clinical tremor scores assigned using Fahn’s tremor rating scale (FTRS); and (iii) compare the performance of the HHT-based method with that of linear band-pass filters. Approach. HHT was applied on gyroscope data collected on 20 MS subjects and 13 healthy controls (CO) during finger-to-nose tests (FNTs) instrumented with an inertial sensor placed on the hand. The results were compared to those obtained after traditional linear filtering. The tremor amplitude was quantified with instrumental indexes (TIs) and clinical FTRS ratings. Main results. The TIs computed after HHT-based filtering discriminated between CO and MS subjects with clinically-detected intention tremor (MS_T). In particular, TIs were significantly higher in the final part of the movement (TI2) with respect to the first part (TI1), and, for all components (X, Y, Z), MST showed a TI2 significantly higher than in CO subjects. Moreover, the HHT detected subtle alterations not visible from clinical ratings, as TI2 (Z-component) was significantly increased in MS subjects without clinically-detected tremor (MS_NT). The method’s validity was demonstrated by significant correlations between clinical FTRS scores and TI2 related to X (rs = 0.587, p = 0.006) and Y (rs = 0.682, p < 0.001) components. Contrarily, fewer differences among the groups and no correlation between instrumental and clinical indexes emerged after traditional filtering. Significance. The present results supported the use of the HHT-based procedure for a fully-automated quantitative and objective measure of intention tremor in MS, which can overcome

Oxytocin via Uniject (a prefilled single-use injection) versus oral misoprostol for prevention of postpartum haemorrhage at the community level: a cluster-randomised controlled trial.

PubMed

Diop, Ayisha; Daff, Bocar; Sow, Maimouna; Blum, Jennifer; Diagne, Mamadou; Sloan, Nancy L; Winikoff, Beverly

2016-01-01

Access to injectable uterotonics for management of postpartum haemorrhage remains limited in Senegal outside health facilities, and misoprostol and oxytocin delivered via Uniject have been deemed viable alternatives in community settings. We aimed to compare the efficacy of these drugs when delivered by auxiliary midwives at maternity huts. We did an unmasked cluster-randomised controlled trial at maternity huts in three districts in Senegal. Maternity huts with auxiliary midwives located 3-21 km from the closest referral centre were randomly assigned (1:1; via a computer-generated random allocation overseen by Gynuity Health Projects) to either 600 μg oral misoprostol or 10 IU oxytocin in Uniject (intramuscular), stratified by reported previous year clinic volume (deliveries) and geographical location (inland or coastal). Maternity huts that had been included in a previous study of misoprostol for prevention of postpartum haemorrhage were excluded to prevent contamination. Pregnant women in their third trimester were screened for eligibility either during community outreach or at home-based prenatal visits. Only women delivered by the auxiliary midwives in the maternity huts were eligible for the study. Women with known allergies to prostaglandins or pregnancy complications were excluded. The primary outcome was mean change in haemoglobin concentration measured during the third trimester and after delivery. This study was registered with ClinicalTrials.gov, number NCT01713153. 28 maternity hut clusters were randomly assigned-14 to the misoprostol group and 14 to the oxytocin group. Between June 6, 2012, and Sept 21, 2013, 1820 women were recruited. 647 women in the misoprostol group and 402 in the oxytocin group received study drug and had recorded pre-delivery and post-delivery haemoglobin concentrations, and overall 1412 women delivered in the study maternity huts. The mean change in haemoglobin concentrations was 3·5 g/L (SD 16·1) in the misoprostol group

Identifying the risk: a prospective cohort study examining postpartum haemorrhage in a regional Australian health service.

PubMed

Kearney, Lauren; Kynn, Mary; Reed, Rachel; Davenport, Lisa; Young, Jeanine; Schafer, Keppel

2018-06-07

In industrialised countries the incidence of postpartum haemorrhage (PPH) is increasing, for which exact etiology is not well understood. Studies have relied upon retrospective data with estimated blood loss as the primary outcome, known to be underestimated by clinicians. This study aimed to explore variables associated with PPH in a cohort of women birthing vaginally in coastal Queensland, Australia, using the gravimetric method to measure blood loss. Women were prospectively recruited to participate using an opt-out consent process. Maternal demographics; pregnancy history; model of care; mode of birth; third stage management practices; antenatal, intrapartum and immediate postpartum complications; gravimetric and estimated blood loss; and haematological laboratory data, were collected via a pre-designed data collection instrument. Descriptive statistics were used for demographic, intrapartum and birthing practices. A General Linear Model was used for multivariate analysis to examine relationship between gravimetric blood loss and demographic, birthing practices and intrapartum variables. The primary outcome was a postpartum haemorrhage (blood loss > 500 ml). 522 singleton births were included in the analysis. Maternal mean age was 29 years; 58% were multiparous. Most participants received active (291, 55.7%) or modified active management of third stage (191, 36.6%). Of 451 births with valid gravimetric blood loss recorded, 35% (n = 159) recorded a loss of 500 ml or more and 111 (70%) of these were recorded as PPH. Gravimetric blood loss was strongly correlated with estimated blood loss (r = 0.88; p < 0.001). On average, the estimated blood loss was lower than the gravimetric blood loss, about 78% of the measured value. High neonatal weight, perineal injury, complications during labour, separation of mother and baby, and observation of a gush of blood were associated with PPH. Nulliparity, labour induction and augmentation, syntocinon use were not

Impact of dexamethasone in patients with aneurysmal subarachnoid haemorrhage.

PubMed

Czorlich, P; Sauvigny, T; Ricklefs, F; Abboud, T; Nierhaus, A; Vettorazzi, E; Reuter, D A; Regelsberger, J; Westphal, M; Schmidt, N O

2017-04-01

The role of corticosteroids in the treatment of patients with aneurysmal subarachnoid haemorrhage (SAH) has remained controversial for decades. Recent studies have suggested that the administration of corticosteroids in SAH patients is associated with favourable outcomes. Given their significant adverse effects, it is essential to identify those patients who will benefit from treatment with corticosteroids. A retrospective analysis of a prospectively collected cohort (n = 306) with SAH who were treated by microsurgical clipping or endovascular intervention was performed. The role of dexamethasone administration was analysed with regard to clinical conditions and SAH-related complications. Outcome was assessed at discharge and during follow-up using the Glasgow Outcome Scale (GOS). Patients treated with dexamethasone presented with more episodes of hyperglycaemia (P < 0.001), more overall infections (P < 0.001) and more ventriculostomy-related infections (P = 0.004). Multivariate analysis demonstrated that treatment with dexamethasone was associated with an unfavourable outcome at discharge (GOS 1-3) [odds ratio (OR) 2.814, 95% confidence interval (CI) 1.440-5.497, P = 0.002]. In the subgroup of microsurgically treated patients, dexamethasone administration was associated with a favourable outcome at follow-up (OR 0.193, 95% CI 0.06-0.621, P = 0.006). A higher risk for unfavourable outcome (OR 3.382, 95% CI 1.67-6.849, P = 0.001) at discharge was observed in endovascularly treated patients who received dexamethasone but this had no impact on the outcome at follow-up. Treatment with dexamethasone seems to be associated with a risk reduction for an unfavourable outcome in those patients who underwent microsurgical clipping. Despite an increased frequency of adverse effects, glucocorticoids may have a potential benefit in this specific surgical subgroup compared to endovascularly treated SAH patients. © 2017 EAN.

Lifetime risks for aneurysmal subarachnoid haemorrhage: multivariable risk stratification.

PubMed

Vlak, Monique H M; Rinkel, Gabriel J E; Greebe, Paut; Greving, Jacoba P; Algra, Ale

2013-06-01

The overall incidence of aneurysmal subarachnoid haemorrhage (aSAH) in western populations is around 9 per 100 000 person-years, which confers to a lifetime risk of around half per cent. Risk factors for aSAH are usually expressed as relative risks and suggest that absolute risks vary considerably according to risk factor profiles, but such estimates are lacking. We aimed to estimate incidence and lifetime risks of aSAH according to risk factor profiles. We used data from 250 patients admitted with aSAH and 574 sex-matched and age-matched controls, who were randomly retrieved from general practitioners files. We determined independent prognostic factors with multivariable logistic regression analyses and assessed discriminatory performance using the area under the receiver operating characteristic curve. Based on the prognostic model we predicted incidences and lifetime risks of aSAH for different risk factor profiles. The four strongest independent predictors for aSAH, namely current smoking (OR 6.0; 95% CI 4.1 to 8.6), a positive family history for aSAH (4.0; 95% CI 2.3 to 7.0), hypertension (2.4; 95% CI 1.5 to 3.8) and hypercholesterolaemia (0.2; 95% CI 0.1 to 0.4), were used in the final prediction model. This model had an area under the receiver operating characteristic curve of 0.73 (95% CI 0.69 to 0.76). Depending on sex, age and the four predictors, the incidence of aSAH ranged from 0.4/100 000 to 298/100 000 person-years and lifetime risk between 0.02% and 7.2%. The incidence and lifetime risk of aSAH in the general population varies widely according to risk factor profiles. Whether persons with high risks benefit from screening should be assessed in cost-effectiveness studies.

A crimean - congo haemorrhagic Fever outbreak in northern balochistan.

PubMed

Ali, Nadir; Chotani, Rashid A; Anwar, Masood; Nadeem, Mansoor; Karamat, Karamat Ahmed; Tariq, Waheed Uz Zaman

2007-08-01

To describe the clinical characteristics, epidemiology, predictors of fatal outcome (PFO), and management effects of Crimean-Congo haemorrhagic fever (CCHF) patients during an outbreak in Northern Balochistan. Descriptive study. Fatima Jinnah Hospital and Combined Military Hospital, Quetta, from June to October, 2001. Patients presenting with a fever of less than 2 weeks duration and bleeding manifestations were included. Clinical history was recorded and patients were placed on oral ribavirin, and hematological support. Diagnosis was established by PCR for CCHF or detection of CCHF specific IgM and IgG. Eighty-four patients were received, 34 (40.5%) were suspected of suffering from classical CCHF. All 34 (100%) patients presented with a history of fever and bleeding (epistaxis, gum bleeding, melena or haematuria). Mean platelet count was 30 x 109/L and mean ALT (alanine transferase) was 288 U/L. Among fatal cases, the mean platelet count was 18.4 x 109/L and ALT was 781 units/L. PCR for CCHF viral RNA performed on 10 patients was positive in 3 (30%) patients. CCHF specific IgM and IgG was positive in 17.6% (6/34). Four patients were brought in moribund condition and expired before treatment could be started, 4 patients expired during treatment and 76.5% (26/34) were cured. The overall mortality was 23.5% (8/34). Main predictors of fatal outcome were ALT Z 150 units/L, activated partial thromboplastin time(aPT) Z 60 seconds, prothrombin time (PT) Z 34 seconds, aspartate transferase (AST) Z 200 units/L, platelets 20 x 109/L, and fibrinogen 110 mg/dL. In this series of CCHF occurring in Northern parts of Balochistan, gastrointestinal tract bleeding was the worst prognostic factor associated with fatal outcome. Providing education to healthcare workers and at risk populations, hematological support, anti-viral drugs, and barrier nursing may help reduce mortality.

Comparative susceptibility among three stocks of yellow perch, Perca flavescens (Mitchill), to viral haemorrhagic septicaemia virus strain IVb from the Great Lakes

USGS Publications Warehouse

Olson, W.; Emmenegger, E.; Glenn, J.; Winton, J.; Goetz, F.

2013-01-01

The Great Lakes strain of viral haemorrhagic septicaemia virus IVb (VHSV-IVb) is capable of infecting a wide number of naive species and has been associated with large fish kills in the Midwestern United States since its discovery in 2005. The yellow perch, Perca flavescens (Mitchill), a freshwater species commonly found throughout inland waters of the United States and prized for its high value in sport and commercial fisheries, is a species documented in several fish kills affiliated with VHS. In the present study, differences in survival after infection with VHSV IVb were observed among juvenile fish from three yellow perch broodstocks that were originally derived from distinct wild populations, suggesting innate differences in susceptibility due to genetic variance. While all three stocks were susceptible upon waterborne exposure to VHS virus infection, fish derived from the Midwest (Lake Winnebago, WI) showed significantly lower cumulative % survival compared with two perch stocks derived from the East Coast (Perquimans River, NC and Choptank River, MD) of the United States. However, despite differences in apparent susceptibility, clinical signs did not vary between stocks and included moderate-to-severe haemorrhages at the pelvic and pectoral fin bases and exophthalmia. After the 28-day challenge was complete, VHS virus was analysed in subsets of whole fish that had either survived or succumbed to the infection using both plaque assay and quantitative PCR methodologies. A direct correlation was identified between the two methods, suggesting the potential for both methods to be used to detect virus in a research setting.

Environmental variability and the transmission of haemorrhagic fever with renal syndrome in Changsha, People's Republic of China.

PubMed

Xiao, H; Gao, L D; Li, X J; Lin, X L; Dai, X Y; Zhu, P J; Chen, B Y; Zhang, X X; Zhao, J; Tian, H Y

2013-09-01

The transmission of haemorrhagic fever with renal syndrome (HFRS) is influenced by climatic, reservoir and environmental variables. The epidemiology of the disease was studied over a 6-year period in Changsha. Variables relating to climate, environment, rodent host distribution and disease occurrence were collected monthly and analysed using a time-series adjusted Poisson regression model. It was found that the density of the rodent host and multivariate El Niño Southern Oscillation index had the greatest effect on the transmission of HFRS with lags of 2–6 months. However, a number of climatic and environmental factors played important roles in affecting the density and transmission potential of the rodent host population. It was concluded that the measurement of a number of these variables could be used in disease surveillance to give useful advance warning of potential disease epidemics.

Treatment of Non-neovascular Idiopathic Macular Telangiectasia Type 2 with Intravitreal Ranibizumab: Results of a Phase II Clinical Trial

PubMed Central

Toy, Brian C.; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

2015-01-01

Purpose To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for non-neovascular idiopathic macular telangiectasia, type 2 (IMT2). Methods Single-center, open-label phase II clinical trial enrolling 5 participants with bilateral non-neovascular IMT2. Intravitreal ranibizumab (0.5mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in: best corrected visual acuity (BCVA), area of late-phase leakage on fluorescein angiography (FA), and retinal thickness on optical coherence tomography (OCT). Results The study treatment was well-tolerated and associated with few adverse events. Change in BCVA at 12 months was not significantly different between treated study eyes (0.0±7.5 letters) and control fellow eyes (+2.2±1.9 letters). However, decreases in the area of late-phase FA leakage (−33±20% for study eyes, +1±8% for fellow eyes) and in OCT central subfield retinal thickness (−11.7±7.0% for study eyes and −2.9±3.5% for fellow eyes) were greater in study eyes compared to fellow eyes. Conclusions Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with non-neovascular IMT2. PMID:22266930

The clinical value of MRA at 3.0 T for the diagnosis and therapeutic planning of patients with subarachnoid haemorrhage.

PubMed

Chen, Yuan-Chang; Sun, Zhen-Kui; Li, Ming-Hua; Li, Yong-Dong; Wang, Wu; Tan, Hua-Qiao; Gu, Bin-Xian; Chen, Shi-Wen

2012-07-01

To evaluate the clinical value of unenhanced magnetic resonance angiography (MRA) at 3.0 T for the diagnosis and therapeutic planning of patients with subarachnoid haemorrhage (SAH). A total of 165 patients with SAH were referred for three-dimensional time-of-flight MRA (3D-TOF-MRA) before digital subtraction angiography (DSA). For each aneurysm, 3D-TOF-MRA was used to determine whether the aneurysm was suitable for coil placement with or without balloon/stent-assisted coiling, surgical clipping or conservative treatment. Treatment planning with 3D-TOF-MRA was compared with actual treatment decisions or treatment that had been carried out in each aneurysm decided using DSA. The aneurysm-based evaluation yielded accuracy of 96.9%, sensitivity of 97.6%, specificity of 93.1%, positive predictive value (PPV) of 98.8% and negative predictive value (NPV) of 87.1%, in the detection of intracranial aneurysms. Treatment planning could be correctly made on the basis of aneurysm anatomy and working view by volume rendering (VR) 3D-TOF-MRA with accuracy, sensitivity, specificity, PPV and NPV of 94.9%, 94.0%, 100%, 100% and 74.4%, respectively, on a per aneurysm-based evaluation. VR 3D-TOF-MRA offers high diagnostic accuracy in the detection of ruptured intracranial aneurysms, and appears to be an effective treatment planning tool for most patients with SAH. VR 3D-TOF-MRA offers high diagnostic accuracy for detecting ruptured intracranial aneurysms. • VR 3D-TOF-MRA helps treatment planning for patients with subarachnoid haemorrhage. • 3D-TOF-MRA is non-invasive and avoids using ionising radiation or contrast agents.

Risk of transmission of viral haemorrhagic fevers and the insecticide susceptibilitystatus of aedes aegypti (linnaeus) in some sites in Accra, Ghana.

PubMed

Suzuki, Takashi; Osei, Joseph H; Sasaki, Akihiro; Adimazoya, Michelle; Appawu, Maxwell; Boakye, Daniel; Ohta, Nobuo; Dadzie, Samuel

2016-09-01

Dengue is one of the emerging diseases that can mostly only be controlled by vector control since there is no vaccine for the disease. Although, Dengue has not been reported in Ghana, movement of people from neighbouring countries where the disease has been reported can facilitate transmission of the disease. This study was carried on the University of Ghana campus to determine the risk of transmission of viral haemorrhagic fevers and the insecticide susceptibility status of Ae. aegypti in some sites in Accra, Ghana. Larval surveys were carried to inspect containers within households and estimate larval indices and adult Aedes mosquitoes were collected using human landing collection technique. WHO tube assays was used to assess the insecticide susceptibility status of Aedes mosquitoes. Ae. aegypti were the most prevalent species, 75.5% and followed by Ae. vittatus , 23.9 %. Ae. albopictus and Ae. granti were in smaller numbers. Household index (HI), Breteau index (BI), and container index were calculated as 8.2%, 11.2% and 10.3% respectively with man-vector contact rate of 0.67 bites/man-hour estimated for the area. The mortalities recorded for Ae. aegypti from WHO tube assays was 88%, 94%, 80% and 99% for DDT (4%), deltamethrin (0.05%), lambdacyhalothrin (0.05%) and permethrin (0.75%) respectively. The survey results indicated that the density of Aedes mosquitoes was considered to be sufficient to promote an outbreak of viral haemorrhagic fevers on Legon Campus. Aedes mosquitoes were found to be resistant to DDT, deltamethrin and lamdacyhalothrin, but susceptible to permethrin. This study was supported in part by Japan Initiative for Global Research Network on Infectious Diseases (J-Grid).

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial.

PubMed

Al-Shahi Salman, Rustam; Dennis, Martin S; Murray, Gordon D; Innes, Karen; Drever, Jonathan; Dinsmore, Lynn; Williams, Carol; White, Philip M; Whiteley, William N; Sandercock, Peter A G; Sudlow, Cathie L M; Newby, David E; Sprigg, Nikola; Werring, David J

2018-03-05

For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Final results of RESTART will be analysed and disseminated in 2019. ISRCTN71907627 ( www.isrctn.com/ISRCTN71907627 ). Prospectively registered on 25 April 2013.

[Association between oxytocin augmentation intervals and the risk of postpartum haemorrhage].

PubMed

Loscul, C; Chantry, A-A; Caubit, L; Deneux-Tharaux, C; Goffinet, F; Le Ray, C

2016-09-01

To study the association between the duration of oxytocin augmentation intervals and the risk of postpartum haemorrhage (PPH) among primiparous women in spontaneous labour. Retrospective cohort including primiparous women in spontaneous labour who received oxytocin during labour (n=454). Oxytocin augmentation intervals were dichotomized in intervals<20minutes and≥20minutes. Obstetrical and neonatal issues were analyzed according to the duration oxytocin augmentation intervals. The association between oxytocin augmentation intervals and PPH was analyzed using univariate and multivariate analysis. Oxytocin augmentation intervals were shorter than 20minutes for 43.8% of the study population. The rate of PPH was higher (9.1% vs 3.5%; P=0.014), and the use of sulprostone was more frequent (6.5% vs 3.5%; P=0.013) if oxytocin augmentation intervals were shorter than 20minutes in comparison with intervals≥20minutes. The association between oxytocin augmentation intervals and PPH remains significant after adjustment on other PPH risk factors (adjusted OR=3.48, 95% CI [1.45-8.34]). The rate of adverse neonatal issue, defined by arterial pH at birth≤7.10 and/or 5minutes score d'Apgar≤7, was higher if oxytocin augmentation intervals were<20minutes (12.1% vs 4.3%; P=0.002). Our study demonstrated an increased risk of PPH for primiparous women in spontaneous labour who received oxytocin with augmentation intervals shorter than 20minutes. Copyright © 2016. Published by Elsevier Masson SAS.

Prevention of postpartum haemorrhage by community-based auxiliary midwives in hard-to-reach areas of Myanmar: a qualitative inquiry into acceptability and feasibility of task shifting.

PubMed

Than, Kyu Kyu; Mohamed, Yasmin; Oliver, Victoria; Myint, Theingi; La, Thazin; Beeson, James G; Luchters, Stanley

2017-05-17

In Myanmar, postpartum haemorrhage is the leading cause of maternal mortality and contributes to around 30% of all maternal deaths. The World Health Organization recommends training and supporting auxiliary midwives to administer oral misoprostol for prevention of postpartum haemorrhage in resource-limited settings. However, use of misoprostol by auxiliary midwives has not formally been approved in Myanmar. Our study aimed to explore community and provider perspectives on the roles of auxiliary midwives and community-level provision of oral misoprostol by auxiliary midwives. A qualitative inquiry was conducted in Ngape Township, Myanmar. A total of 15 focus group discussions with midwives, auxiliary midwives, community members and mothers with children under the age of three were conducted. Ten key informant interviews were performed with national, district and township level health planners and implementers of maternal and child health services. All audio recordings were transcribed verbatim in Myanmar language. Transcripts of focus group discussions were fully translated into English before coding, while key informants' data were coded in Myanmar language. Thematic analysis was done using ATLAS.ti software. Home births are common and auxiliary midwives were perceived as an essential care provider during childbirth in hard-to-reach areas. Main reasons provided were that auxiliary midwives are more accessible than midwives, live in the hard-to-reach areas, and are integrated in the community and well connected with midwives. Auxiliary midwives generally reported that their training involved instruction on active management of the third stage of labour, including use of misoprostol, but not all auxiliary midwives reported using misoprostol in practice. Supportive reasons for task-shifting administration of oral misoprostol to auxiliary midwives included discussions around the good relationship and trust between auxiliary midwives and midwives, whereby midwives felt

Real-time imaging and detection of intracranial haemorrhage by electrical impedance tomography in a piglet model.

PubMed

Xu, C H; Wang, L; Shi, X T; You, F S; Fu, F; Liu, R G; Dai, M; Zhao, Z W; Gao, G D; Dong, X Z

2010-01-01

The aim of this study was to use electrical impedance tomography (EIT) to detect and image acute intracranial haemorrhage (ICH) in an animal model. Blood was infused into the frontal lobe of the brains of anaesthetized piglets and impedance was measured using 16 electrodes placed in a circle on the scalp. The EIT images were constructed using a filtered back-projection algorithm. The mean of all the pixel intensities within a region of interest--the mean resistivity value (MRV)--was used to evaluate the relative impedance changes in the target region. A symmetrical index (SI), reflecting the relative impedance on both sides of the brain, was also calculated. Changes in MRV and SI were associated with the injection of blood, demonstrating that EIT can successfully detect ICH in this animal model. The unique features of EIT may be beneficial for diagnosing ICH early in patients after cranial surgery, thereby reducing the risk of complications and mortality.

Delayed postpartum haemorrhage secondary to a ruptured uterine artery pseudo-aneurysm, successfully treated by transarterial embolisation

PubMed Central

Moatti, Zoe; Nisner, Tamar; Saini, Ashish; Karoshi, Mahantesh

2011-01-01

A 29-year-old woman (gravida 1, para 1) had an uneventful first pregnancy and a delivery by emergency caesarean section at term. The caesarean section was complicated by a massive obstetric haemorrhage of 5000 ml. After closure, an immediate re-laparotomy was indicated due to heavy vaginal bleeding. The site of bleeding was identified as an extension of the uterine incision, and was sutured. She was stabilised by transfusion of blood and blood products in the intensive therapy unit, and discharged 5 days later. The patient was re-admitted 6 weeks later with brisk, painless vaginal bleeding, passing large clots from a well-contracted uterus. Her haemoglobin decreased from 11.8 to 7.8 g/dl overnight. In view of her history, an urgent CT angiogram was performed, which revealed the presence of a pseudo-aneurysm arising from the left uterine artery. This was successfully occluded by transarterial embolisation, obviating the need for further surgical exploration. PMID:22674937

Delayed postpartum haemorrhage secondary to a ruptured uterine artery pseudo-aneurysm, successfully treated by transarterial embolisation.

PubMed

Moatti, Zoe; Nisner, Tamar; Saini, Ashish; Karoshi, Mahantesh

2011-12-01

A 29-year-old woman (gravida 1, para 1) had an uneventful first pregnancy and a delivery by emergency caesarean section at term. The caesarean section was complicated by a massive obstetric haemorrhage of 5000 ml. After closure, an immediate re-laparotomy was indicated due to heavy vaginal bleeding. The site of bleeding was identified as an extension of the uterine incision, and was sutured. She was stabilised by transfusion of blood and blood products in the intensive therapy unit, and discharged 5 days later. The patient was re-admitted 6 weeks later with brisk, painless vaginal bleeding, passing large clots from a well-contracted uterus. Her haemoglobin decreased from 11.8 to 7.8 g/dl overnight. In view of her history, an urgent CT angiogram was performed, which revealed the presence of a pseudo-aneurysm arising from the left uterine artery. This was successfully occluded by transarterial embolisation, obviating the need for further surgical exploration.

Hilbert–Huang transform in detecting and analyzing the uterine contraction activities

PubMed Central

Aydın, Kemal; Demirer, Murat; Bayrak, Coşkun

2015-01-01

Objective The diagnosis of labor is currently one of the most difficult problems encountered by obstetrical healthcare providers. A major health problem is the increase in the rate of preterm delivery, which is responsible for 75% of all deaths in newborns. In addition, preterm delivery is associated with several cognitive and health problems in later life and enormous costs for the health system. A better understanding of myometrial activities could help to reduce preterm deliveries and the costs associated with prematurity in the following years. Therefore, the objective of this study was to determine whether using the Hilbert–Huang transform (HHT) to analyze the uterine contraction data would help us gain a better insight of the myometrial activities of the human uterus during pregnancy. Material and Methods Uterine magnetomyographic (MMG) signals were recorded from pregnant patients at gestational ages of 32–38 weeks. The study was approved by the Human Research Advisory Board of the University of Arkansas for Medical Sciences (UAMS) and performed after obtaining written consent from each patient. The recording of transabdominal MMG signals was conducted with the SQUID Array for Reproductive Assessment (SARA, VSM MedTech Inc; Coquitlam, BC, Canada) system, which has 151 primary magnetic sensors allocated approximately 3 cm apart over an area of 850 cm2. The arrangement of sensors is concave in nature and, in a similar lateral distance, spans the maternal abdomen longitudinally from the symphysis pubis to the uterine fundus. The recording times ranged from 12 to 28 min, and the sampling rate was 250 Hz. The data were down-sampled to 25 Hz to reduce the computational complexity and post-processed with a bandpass filter (0.05–1 Hz) because the uterine contraction activity is a band-limited process (0.05–1 Hz). The recordings of one intrauterine pressure catheter (IUPC) dataset and two mother-perceived contraction datasets were compared with the HHT results

Diagnosis of subarachnoid haemorrhage: a survey of Australasian emergency physicians and trainees.

PubMed

Rogers, Andrew; Furyk, Jeremy; Banks, Colin; Chu, Kevin

2014-10-01

This study aims to establish current practice among Australasian emergency physicians and trainees on several aspects of the investigation of suspected subarachnoid haemorrhage (SAH). An electronic questionnaire (SurveyMonkey™) was distributed to emergency physicians and trainees by email through the ACEM. Survey recipients were asked about demographics, followed by a series of questions relating to the investigation of SAH. There were 878 survey respondents (response rate 24%). Our data showed that 47.3% of respondents agreed or strongly agreed that a CT brain within 6 h of headache onset is sufficient to exclude a diagnosis of SAH. For a CT performed within 12 h of ictus, 14.4% were satisfied that SAH could be excluded. After a negative CT scan, for further investigation of SAH, 88% of respondents preferred lumbar puncture to CT angiography. For detection of xanthochromia in the cerebrospinal fluid, 57.7% of respondents felt that spectrophotometry (vs visual inspection) is necessary to accurately diagnose SAH. A range of information was collected regarding the investigation of suspected SAH. We report significant differences in the diagnostic approach of Australasian emergency physicians and trainees to this condition, in particular the utility of CT within 6 h for exclusion of SAH. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants.

PubMed

Smit, Elisa; Odd, David; Whitelaw, Andrew

2013-08-13

Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. Phenobarbital has been suggested as a safe treatment that stabilises blood pressure and may protect against free radicals. To determine the effect of postnatal administration of phenobarbital on the risk of IVH, neurodevelopmental impairment or death in preterm infants. We used the search strategy of the Neonatal Collaborative Review Group. The original review author (A Whitelaw) was an active trialist in this area and had personal contact with many groups in this field. He handsearched journals from 1976 (when cranial computed tomography (CT) scanning started) to October 2000; these included: Pediatrics, Journal of Pediatrics, Archives of Disease in Childhood, Pediatric Research, Developmental Medicine and Child Neurology, Acta Paediatrica, European Journal of Pediatrics, Neuropediatrics, New England Journal of Medicine, Lancet and British Medical Journal. We searched the National Library of Medicine (USA) database (via PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL, 2012, Issue 10) through to 31 October 2012. We did not limit the searches to the English language, as long as the article included an English abstract. We read identified articles in the original language or translated. We included randomised or quasi-randomised controlled trials in which phenobarbital was given to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birthweight below 1500 g or respiratory failure. Adequate determination of IVH by ultrasound or CT was also required. In addition to details of patient selection and control of bias, we extracted the details of the administration of phenobarbital. We

Clinical decision-making: midwifery students' recognition of, and response to, post partum haemorrhage in the simulation environment.

PubMed

Scholes, Julie; Endacott, Ruth; Biro, MaryAnne; Bulle, Bree; Cooper, Simon; Miles, Maureen; Gilmour, Carole; Buykx, Penny; Kinsman, Leigh; Boland, Rosemarie; Jones, Jan; Zaidi, Fawzia

2012-03-23

This paper reports the findings of a study of how midwifery students responded to a simulated post partum haemorrhage (PPH). Internationally, 25% of maternal deaths are attributed to severe haemorrhage. Although this figure is far higher in developing countries, the risk to maternal wellbeing and child health problem means that all midwives need to remain vigilant and respond appropriately to early signs of maternal deterioration. Simulation using a patient actress enabled the research team to investigate the way in which 35 midwifery students made decisions in a dynamic high fidelity PPH scenario. The actress wore a birthing suit that simulated blood loss and a flaccid uterus on palpation. The scenario provided low levels of uncertainty and high levels of relevant information. The student's response to the scenario was videoed. Immediately after, they were invited to review the video, reflect on their performance and give a commentary as to what affected their decisions. The data were analysed using Dimensional Analysis. The students' clinical management of the situation varied considerably. Students struggled to prioritize their actions where more than one response was required to a clinical cue and did not necessarily use mnemonics as heuristic devices to guide their actions. Driven by a response to single cues they also showed a reluctance to formulate a diagnosis based on inductive and deductive reasoning cycles. This meant they did not necessarily introduce new hypothetical ideas against which they might refute or confirm a diagnosis and thereby eliminate fixation error. The students response demonstrated that a number of clinical skills require updating on a regular basis including: fundal massage technique, the use of emergency standing order drugs, communication and delegation of tasks to others in an emergency and working independently until help arrives. Heuristic devices helped the students to evaluate their interventions to illuminate what else could

Clinical decision-making: midwifery students' recognition of, and response to, post partum haemorrhage in the simulation environment

PubMed Central

2012-01-01

Background This paper reports the findings of a study of how midwifery students responded to a simulated post partum haemorrhage (PPH). Internationally, 25% of maternal deaths are attributed to severe haemorrhage. Although this figure is far higher in developing countries, the risk to maternal wellbeing and child health problem means that all midwives need to remain vigilant and respond appropriately to early signs of maternal deterioration. Methods Simulation using a patient actress enabled the research team to investigate the way in which 35 midwifery students made decisions in a dynamic high fidelity PPH scenario. The actress wore a birthing suit that simulated blood loss and a flaccid uterus on palpation. The scenario provided low levels of uncertainty and high levels of relevant information. The student's response to the scenario was videoed. Immediately after, they were invited to review the video, reflect on their performance and give a commentary as to what affected their decisions. The data were analysed using Dimensional Analysis. Results The students' clinical management of the situation varied considerably. Students struggled to prioritise their actions where more than one response was required to a clinical cue and did not necessarily use mnemonics as heuristic devices to guide their actions. Driven by a response to single cues they also showed a reluctance to formulate a diagnosis based on inductive and deductive reasoning cycles. This meant they did not necessarily introduce new hypothetical ideas against which they might refute or confirm a diagnosis and thereby eliminate fixation error. Conclusions The students response demonstrated that a number of clinical skills require updating on a regular basis including: fundal massage technique, the use of emergency standing order drugs, communication and delegation of tasks to others in an emergency and working independently until help arrives. Heuristic devices helped the students to evaluate their

Localization of an ataxia-telangiectasia gene by linkage disequilibrium in the Costa Rican population

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

Uhrhammer, N.A.; Lange, E.; Gatti, R.A.

1994-09-01

Linkage disequilibrium (LD) was studied in 27 Costa Rican families with ataxia-telangiectasia. Previous studies indicate that the ATA and ATC gene(s) are on chromosome 11q22.3, between D11S1819 and D11S927. We studied the ordered loci D11-S1816, S1817, S1343, S1819, S384, S535, S1295, S1818, S927, S1300 and S1004 by PCR and Southern blotting. We noted moderate LD at the more distant markers S1816, S1300, and S1004. LD was higher at markers closer to A-T, and also where A-T was associated with rarer alleles. This broad region of disequilibrium did not by itself contribute to further localization of the A-T gene(s). We analyzedmore » 54 affected chromosomal haplotypes. The most common haplotype occurred 34 times, including some that had recombined outside the known A-T region. Other haplotypes occurred seven times, five times, two occurred twice, and the four remaining were unique. The most common haplotype had `broken` at S927 in five different patients, placing A-T proximal to this marker. We looked for recombination events in 15 of the families to further localize A-T. We observed one family with a recombination event placing A-T distal to S1819. A second family appears to either not link to 11q22.3 or to have a double-crossover between the markers S384 and S927; two affected sibs share haplotypes for the entire region studied, and a normal sib shared the same two haplotypes. Since all or part of this A-T haplotype occurs in 32 other, unrelated, Costa Rican patients, we anticipate a double-crossover in the 1600 kb between the informative flanking markers. All other families show segregation patterns consistent with placing A-T at 11q22.3. These results demonstrate that the major A-T gene in the Costa Rican population is located between S1819 and S927 at 11q22.3.« less

Potential distribution of the viral haemorrhagic septicaemia virus in the Great Lakes region

USGS Publications Warehouse

Escobar, Luis E.; Kurath, Gael; Escobar-Dodero, Joaquim; Craft, Meggan E.; Phelps, Nicholas B.D.

2017-01-01

Viral haemorrhagic septicaemia virus (VHSV) genotype IVb has been responsible for large-scale fish mortality events in the Great Lakes of North America. Anticipating the areas of potential VHSV occurrence is key to designing epidemiological surveillance and disease prevention strategies in the Great Lakes basin. We explored the environmental features that could shape the distribution of VHSV, based on remote sensing and climate data via ecological niche modelling. Variables included temperature measured during the day and night, precipitation, vegetation, bathymetry, solar radiation and topographic wetness. VHSV occurrences were obtained from available reports of virus confirmation in laboratory facilities. We fit a Maxent model using VHSV-IVb reports and environmental variables under different parameterizations to identify the best model to determine potential VHSV occurrence based on environmental suitability. VHSV reports were generated from both passive and active surveillance. VHSV occurrences were most abundant near shore sites. We were, however, able to capture the environmental signature of VHSV based on the environmental variables employed in our model, allowing us to identify patterns of VHSV potential occurrence. Our findings suggest that VHSV is not at an ecological equilibrium and more areas could be affected, including areas not in close geographic proximity to past VHSV reports.

Bluetongue and epizootic haemorrhagic disease virus in local breeds of cattle in Kenya.

PubMed

Toye, P G; Batten, C A; Kiara, H; Henstock, M R; Edwards, L; Thumbi, S; Poole, E J; Handel, I G; Bronsvoort, B M deC; Hanotte, O; Coetzer, J A W; Woolhouse, M E J; Oura, C A L

2013-06-01

The presence of bluetongue virus (BTV) and Epizootic Haemorrhagic Disease virus (EHDV) in indigenous calves in western Kenya was investigated. Serum was analysed for BTV and EHDV antibodies. The population seroprevalences for BTV and EHDV for calves at 51 weeks of age were estimated to be 0.942 (95% CI 0.902-0.970) and 0.637 (95% CI 0.562-0.710), respectively, indicating high levels of circulating BTV and EHDV. The odds ratio of being positive for BTV if EHDV positive was estimated to be 2.57 (95% CI 1.37-4.76). When 99 calves were tested for BTV and EHDV RNA by real-time RT-PCR, 88.9% and 63.6% were positive, respectively. Comparison of the serology and real-time RT-PCR results revealed an unexpectedly large number of calves that were negative by serology but positive by real-time RT-PCR for EHDV. Eight samples positive for BTV RNA were serotyped using 24 serotype-specific real-time RT-PCR assays. Nine BTV serotypes were detected, indicating that the cattle were infected with a heterogeneous population of BTVs. The results show that BTV and EHDV are highly prevalent, with cattle being infected from an early age. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bluetongue and Epizootic Haemorrhagic Disease virus in local breeds of cattle in Kenya

PubMed Central

Toye, P.G.; Batten, C.A.; Kiara, H.; Henstock, M.R.; Edwards, L.; Thumbi, S.; Poole, E.J.; Handel, I.G.; Bronsvoort, B.M.deC.; Hanotte, O.; Coetzer, J.A.W.; Woolhouse, M.E.J.; Oura, C.A.L.

2013-01-01

The presence of bluetongue virus (BTV) and Epizootic Haemorrhagic Disease virus (EHDV) in indigenous calves in western Kenya was investigated. Serum was analysed for BTV and EHDV antibodies. The population seroprevalences for BTV and EHDV for calves at 51 weeks of age were estimated to be 0.942 (95% CI 0.902–0.970) and 0.637 (95% CI 0.562–0.710), respectively, indicating high levels of circulating BTV and EHDV. The odds ratio of being positive for BTV if EHDV positive was estimated to be 2.57 (95% CI 1.37–4.76). When 99 calves were tested for BTV and EHDV RNA by real-time RT-PCR, 88.9% and 63.6% were positive, respectively. Comparison of the serology and real-time RT-PCR results revealed an unexpectedly large number of calves that were negative by serology but positive by real-time RT-PCR for EHDV. Eight samples positive for BTV RNA were serotyped using 24 serotype-specific real-time RT-PCR assays. Nine BTV serotypes were detected, indicating that the cattle were infected with a heterogeneous population of BTVs. The results show that BTV and EHDV are highly prevalent, with cattle being infected from an early age. PMID:23261160

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

PubMed

Mahmood, Abda; Roberts, Ian; Shakur, Haleema

2017-07-17

Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage

The importance of ERCP for the surgical tactic in haemorrhagic necrotizing pancreatitis (preliminary report).

PubMed

Gebhardt, C; Riemann, J F; Lux, G

1983-03-01

In patients with haemorrhagic necrotizing pancreatitis who are scheduled for surgery, we have been carrying out a preoperative retrograde investigation of the pancreatic duct system for the past 3 months. The results in, to date, ten patients, all of whom survived their severe illness, revealed four different morphological findings of importance for the surgical tactic. 1. A normal pancreatic duct system with no signs of fistulae: only peripancreatic necrosectomy is required. 2. Contrast medium leaks via a ductal fistula: left resection, including the removal of the fistulous area, must be done. 3. Normal duct system with complete segmental parenchymal staining, representing total necrosis in this region: left resection of the pancreas. 4. Duodenoscopically demonstrable perforation into the duodenum of a necrotic cavity in the head of the pancreas: conservative management only, no surgery, since this lesions, resulting in drainage of the necrotic cavity into the bowel, permits self-healing, while the site of the perforation within the necrotic wall cannot be dealt with by surgery. The experience gained so far indicates that the surgical tactic can be determined with greater selectivity by the use of ERCP.

Vector prevalence and detection of Crimean-Congo haemorrhagic fever virus in Golestan Province, Iran.

PubMed

Sedaghat, Mohammad Mehdi; Sarani, Moslem; Chinikar, Sadegh; Telmadarraiy, Zakiye; Moghaddam, Abdolreza Salahi; Azam, Kamal; Nowotny, Norbert; Fooks, Anthony R; Shahhosseini, Nariman

2017-01-01

Crimean-Congo haemorrhagic fever virus (CCHFV) causes severe disease with fatality rate of 30%. The virus is transmitted to humans through the bite of an infected tick, direct contact with the products of infected livestock as well as nosocomially. The disease occurs sporadically throughout many of African, Asian and European countries. Different species of ticks serve either as vector or reservoir for CCHFV. This study was aimed to determine the prevalence of CCHFV in hard ticks (Ixodidae) in the Golestan Province of Iran. A molecular survey was conducted on hard ticks (Ixodidae) isolated from six counties in Golestan Province, north of Iran during 2014-15. The ticks were identified using morphological characteristics and presence of CCHFV RNA was detected using RT-PCR. Data revealed the presence of CCHFV in 5.3% of the ticks selected for screening. The infected ticks belonged to Hyalomma dromedarii, Hy. anatolicum, Hy. marginatum and Rhipicephalus sanguineus species. The study demonstrated that Hyalomma ticks are the main vectors of CCHFV in Golestan Province. Thus, preventive strategies such as using acaricides and repellents in order to avoid contact with Hyalomma ticks are proposed.

Vasomodulatory effects of the angiotensin II type 1 receptor antagonist losartan on experimentally induced cerebral vasospasm after subarachnoid haemorrhage.

PubMed

Wanderer, Stefan; Mrosek, Jan; Gessler, Florian; Seifert, Volker; Konczalla, Juergen

2018-02-01

Cerebral vasospasm following subarachnoid haemorrhage (SAH) remains one of the major factors contributing to poor overall patient outcome. Prostaglandin F2-alpha (PGF2a) induces vasoconstriction. After SAH, PGF2a leads to cerebral inflammation and enhanced vasoconstriction, resulting in cerebral vasospasm. Losartan is already known to have beneficial effects in stroke models and also on several cerebral inflammatory processes. Therefore, the aim of the study was to analyse the effect of losartan on PGF2a-enhanced vasoconstriction after SAH. To investigate the effect of losartan on PGF2a-enhanced vasoconstriction after SAH, cerebral vasospasm was induced by a double-haemorrhage model. Rats were killed on day 3 and 5 after SAH followed by measurement of the isometric force of basilar artery ring segments in an organ bath. PGF2a induced a dose-dependent contraction. After pre-incubation with losartan, the maximum contraction (E max ) for sham-operated animals was significantly lowered [E max 6% in losartan 3 × 10 -4  molar (M) vs. 56% without losartan]. Also, after induced SAH, PGF2a induced no vasoconstriction in pre-incubated vessels with losartan 3 × 10 -4  M on day 3 (d3) as well as on day 5 (d5). For the vasorelaxative investigations, vessel segments were pre-incubated with PFG2a. Cumulative application of losartan completely resolved the pre-contraction in sham-operated animals (non SAH: 95% relaxation). After SAH, losartan not only resolved the pre-contraction (d5: 103%), but also exceeded the pre-contraction (d3: 119%). Therefore, a statistically significantly increased and earlier relaxation was calculated for all losartan concentrations [E max (d3/d5) and pD 2 (d3/d5)] compared with the solvent control group. In a physiological and pathophysiological setup, losartan reduces a PGF2-induced vasoconstriction and reverses a PGF2a-precontraction completely. This fact can be integrated in pushing forward further concepts trying to antagonise

Nutritional status of patients with ataxia-telangiectasia: A case for early and ongoing nutrition support and intervention.

PubMed

Ross, Lynda J; Capra, Sandra; Baguley, Brenton; Sinclair, Kate; Munro, Kate; Lewindon, Peter; Lavin, Martin

2015-08-01

Ataxia-telangiectasia (A-T) is a rare genomic syndrome resulting in severe disability. Chronic childhood disorders can profoundly influence growth and development. Nutrition-related issues in A-T are not well described, and there are no nutritional guidelines. This study investigated the nutrition-related characteristics and behaviours of Australian A-T patients attending a national clinic. A cross-sectional analysis of 13 A-T patients (nine females; aged: 4-23 years): nutritional status was assessed by anthropometric and body cell mass (BCM) calculations. Parents reported their child's diet history and physical and behavioural factors that affect nutrition including fatigue and need for assistance. Ten (77%) had short stature (height for age z scores <-1), and seven (54%) were underweight for height (weight/height z scores <-1). Significant malnutrition (BCM z scores <-2) was detected in nine (69%) including the one adult who was severely malnourished. Malnutrition increased significantly with age (BCM for height z scores and age, r = -0.937, P < 0.001). Eight (62%) patients ate poorly compared with estimated energy requirement for weight. Poor diet quality was characterised by high fat and sugar choices. Parents reported significant nutritional barriers as chronic tiredness and the need for care giver assistance with meals. This study confirms profound malnutrition in Australian A-T patients. Poor intakes and diet quality suggest the need for early nutrition intervention. Ongoing support for families and early discussions on tube feeding are required to address changing needs in childhood and likely nutritional decline into adulthood. A prospective study is required to assess feasibility and effectiveness of nutrition interventions in young people with A-T. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Novel serotype of bluetongue virus in South America and first report of epizootic haemorrhagic disease virus in Ecuador.

PubMed

Verdezoto, J; Breard, E; Viarouge, C; Quenault, H; Lucas, P; Sailleau, C; Zientara, S; Augot, D; Zapata, S

2018-02-01

Bluetongue virus (BTV) and Epizootic haemorrhagic disease virus (EHDV) are closely related Orbiviruses that affect domestic and wild ruminants. In Ecuador previous serological studies reported the presence of BTV; however, no data are available about the presence of EHDV. In this study, 295 cattle without symptoms of infection were sampled from two farms located in Andean and Amazonian regions and from a slaughterhouse in the coastal region. ELISA analyses showed high prevalence of BTV (98.9%) and EHDV (81.3%) antibodies, and RT-qPCRs revealed the presence of EHDV (24.1%) and BTV (10.2%) genomes in cattle blood samples. Viral isolation allowed to identify EHDV serotype 1 (EHDV1) and BTV serotypes 9 (BTV9), 13 and 18. These findings suggest that BTV and EHDV are enzootic diseases in Ecuador. © 2017 Blackwell Verlag GmbH.

First report on the seroprevalence of the Crimean-Congo haemorrhagic fever virus, a tick-borne virus, in Malaysia's Orang Asli population.

PubMed

Lani, R; Mohd Rahim, N F; Hassan, H; Yaghoobi, R; Chang, L-Y; AbuBakar, S; Zandi, K

2015-01-01

The Crimean-Congo haemorrhagic fever virus (CCHFV), which is transmitted by the ticks of Hyalomma spp. in general and H. marginatumin particular, can cause severe disease in humans, with mortality rates of 3-30%. Other than from the bites of infected ticks, CCHFV can also be transmitted through contact with patients with the acute phase of infection or contact with blood or tissues from viraemic livestock.  Outbreaks of human cases of haemorrhagic manifestations have been documented since 1945 and described in parts of Africa, Asia, Eastern Europe and the Middle East and most recently India in 2011. In addition, serological evidence of the disease has been reported in some countries where no human cases were reported. As regional neighbours China and India have been affected by this virus, this study was conducted to determine the seroprevalence of CCHFV among Orang Asli population of Malaysia as the most at risk people who residing in the deep forests. A total of 682 serum samples were collected from the Orang Asli population residing in eight states in peninsular Malaysia and analysed for the presence of anti-CCHFV immunoglobulin G (IgG) using a commercial enzyme-linked immunosorbent assay kit. The study subjects comprised 277 (40.6%) men and 405 (59.4%) women. However, anti-CCHFV IgG was detected in only one female serum sample (0.1%). The presence of anti-CCHFV IgG could not be correlated to age or sex from these findings. The results of this screening survey showed that the seroprevalence of the anti-CCHFV IgG among Malaysia's Orang Asli population is too low for detection or totally negative compared with that in neighbouring countries, such as India and China.

Disease severity in a mouse model of ataxia telangiectasia is modulated by the DNA damage checkpoint gene Hus1

PubMed Central

Balmus, Gabriel; Zhu, Min; Mukherjee, Sucheta; Lyndaker, Amy M.; Hume, Kelly R.; Lee, Jaesung; Riccio, Mark L.; Reeves, Anthony P.; Sutter, Nathan B.; Noden, Drew M.; Peters, Rachel M.; Weiss, Robert S.

2012-01-01

The human genomic instability syndrome ataxia telangiectasia (A-T), caused by mutations in the gene encoding the DNA damage checkpoint kinase ATM, is characterized by multisystem defects including neurodegeneration, immunodeficiency and increased cancer predisposition. ATM is central to a pathway that responds to double-strand DNA breaks, whereas the related kinase ATR leads a parallel signaling cascade that is activated by replication stress. To dissect the physiological relationship between the ATM and ATR pathways, we generated mice defective for both. Because complete ATR pathway inactivation causes embryonic lethality, we weakened the ATR mechanism to different degrees by impairing HUS1, a member of the 911 complex that is required for efficient ATR signaling. Notably, simultaneous ATM and HUS1 defects caused synthetic lethality. Atm/Hus1 double-mutant embryos showed widespread apoptosis and died mid-gestationally. Despite the underlying DNA damage checkpoint defects, increased DNA damage signaling was observed, as evidenced by H2AX phosphorylation and p53 accumulation. A less severe Hus1 defect together with Atm loss resulted in partial embryonic lethality, with the surviving double-mutant mice showing synergistic increases in genomic instability and specific developmental defects, including dwarfism, craniofacial abnormalities and brachymesophalangy, phenotypes that are observed in several human genomic instability disorders. In addition to identifying tissue-specific consequences of checkpoint dysfunction, these data highlight a robust, cooperative configuration for the mammalian DNA damage response network and further suggest HUS1 and related genes in the ATR pathway as candidate modifiers of disease severity in A-T patients. PMID:22575700

Telangiectasia

MedlinePlus

... Klippel-Trenaunay-Weber syndrome (disease that causes port-wine stain, varicose veins, and soft tissue problems) Nevus flammeus such as port-wine stain Rosacea (skin condition that causes redness of ...

Findings and differential diagnosis of fetal intracranial haemorrhage and fetal ischaemic brain injury: what is the role of fetal MRI?

PubMed Central

Kennedy, Anne

2017-01-01

Ventriculomegaly (VM) is a non-specific finding on fetal imaging. Identification of the specific aetiology is important, as it affects prognosis and may even change the course of current or future pregnancies. In this review, we will focus on the application of fetal MRI to demonstrate intracranial haemorrhage and ischaemic brain injury as opposed to other causes of VM. MRI is able to identify the specific aetiology of VM with much more sensitivity and specificity than ultrasound and should be considered whenever VM is identified on obstetric ultrasound. Advances in both fetal and neonatal MRI have the potential to shed further light on mechanisms of brain injury and the impact of chronic hypoxia; such information may guide future interventions. PMID:27734711

Human-to-human transmission of Brucella - a systematic review.

PubMed

Tuon, Felipe F; Gondolfo, Regina B; Cerchiari, Natacha

2017-05-01

The most common form of transmitting human brucellosis is through contaminated food or direct contact with infected animals. Human-to-human transmission (HHT) has been described as isolated case reports. The aim of this systematic review was to describe all cases of HHT of human brucellosis reported in the medical literature. A literature search was conducted using PubMed, Scopus and Scielo databases using specific search terms published until March 2016. Two investigators independently determined study eligibility. All clinical data were evaluated to construct a table comprising the most important clinical aspects, age, gender, confirmed infection and detection method, transmission method and HHT confirmation and potential source of infection for human transmission. No statistical method was employed in this study. The initial search resulted in 615 publications, but only 35 were included. 45 brucellosis HHT cases were identified. 61% of patients who acquired brucellosis from another human were <1 year old (newborn and breastfeeding). Other cases include sexual transmission, blood transfusion, bone marrow transplantation and aerosol from an infected patient. Most patients (40/45) presented symptoms upon diagnosis. Diagnostic tests included culture, molecular methods and serum testing. Human brucellosis is a disease liable to transmission between humans by placental barrier, lactation, sexual and tissues such as blood and bone marrow. The indication for screening in tissue banks, transplants, blood and pregnancy is not yet established. © 2017 John Wiley & Sons Ltd.

Fibrinogen concentrate as a treatment for postpartum haemorrhage-induced coagulopathy: A study protocol for a randomised multicentre controlled trial. The fibrinogen in haemorrhage of DELivery (FIDEL) trial.

PubMed

Ducloy-Bouthors, Anne-Sophie; Mignon, Alexandre; Huissoud, Cyril; Grouin, Jean-Marie; Mercier, Frédéric J

2016-08-01

Postpartum haemorrhage (PPH) remains the leading cause for maternal mortality worldwide. Hypofibrinogenaemia has been identified as a major risk factor for progress towards severe PPH. The efficacy of fibrinogen concentrate supplementation in PPH has been shown in various clinical settings but the level of evidence is not sufficient to prove the benefit, evaluate the risks, and determine the value, timing and dose of fibrinogen supplementation in PPH. The FIDEL trial objective is to evaluate the impact of a therapeutic strategy based on the early administration of human fibrinogen concentrate compared to the current practice based on late administration in severe PPH patients requiring second line uterotonics. This is a prospective multicentre, randomised, double-blind, placebo-controlled trial. A total of 412 patients will be randomised if they meet the following criteria: female patients≥18 years old, vaginal delivery, PPH requiring IV administration of prostaglandins (sulprostone) after 20 to 30minutes of oxytocin failure. The participants are assigned to receive either fibrinogen 3g or placebo infusions. The primary endpoint is a composite endpoint defined as the percentage of patients losing at least 4g/dL of Hb, and/or requiring a transfusion of at least 2 units of packed red blood cells, within the 48hours following fibrinogen administration. The purpose of this study is to demonstrate the efficacy and safety of an early fibrinogen concentrate infusion in uncontrolled active PPH. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Chronic hypopituitarism is uncommon in survivors of aneurysmal subarachnoid haemorrhage.

PubMed

Hannon, M J; Behan, L A; O'Brien, M M; Tormey, W; Javadpour, M; Sherlock, M; Thompson, C J

2015-01-01

The incidence of hypopituitarism after aneurysmal subarachnoid haemorrhage (SAH) is unclear from the conflicting reports in the literature. As routine neuroendocrine screening for hypopituitarism for all patients would be costly and logistically difficult, there is a need for precise data on the frequency of hypopituitarism and on factors which might predict the later development of pituitary dysfunction. We aimed to: (i) Establish the incidence of long-term hypopituitarism in patients with aneurysmal SAH. (ii) Determine whether data from patients' acute admission with SAH could predict the occurrence of long-term hypopituitarism. One hundred patients were studied prospectively from the time of presentation with acute SAH. Plasma cortisol, plasma sodium and a variety of clinical and haemodynamic parameters were sequentially measured for the first 12 days of their acute admission. Forty-one patients then underwent dynamic pituitary testing at median 15 months following SAH (range 7-30 months), with insulin tolerance test (ITT) or, if contraindicated, a glucagon stimulation test (GST) plus short synacthen test (SST). If symptoms of cranial diabetes insipidus (CDI) were present, a water deprivation test was also performed. Forty-one patients attended for follow-up dynamic pituitary testing. Although 14 of 100 had acute glucocorticoid deficiency immediately following SAH, only two of 41 had long-term adrenocorticotrophic hormone (ACTH) deficiency and four of 41 had growth hormone (GH) deficiency. None were hypothyroid or gonadotrophin deficient. None had chronic CDI or hyponatraemia. There was no association between acute glucocorticoid deficiency, acute CDI or acute hyponatraemia and long-term pituitary dysfunction. Both anterior and posterior hypopituitarism are very uncommon following SAH and are not predicted by acute clinical, haemodynamic or endocrinological parameters. Routine neuroendocrine screening is not justified in SAH patients. © 2014 John Wiley & Sons

Increased virulence of Rabbit Haemorrhagic Disease Virus associated with genetic resistance in wild Australian rabbits (Oryctolagus cuniculus)

PubMed Central

Elsworth, Peter; Cooke, Brian D.; Kovaliski, John; Sinclair, Ronald; Holmes, Edward C.; Strive, Tanja

2015-01-01

The release of myxoma virus (MYXV) and Rabbit Haemorrhagic Disease Virus (RHDV) in Australia with the aim of controlling overabundant rabbits has provided a unique opportunity to study the initial spread and establishment of emerging pathogens, as well as their co-evolution with their mammalian hosts. In contrast to MYXV, which attenuated shortly after its introduction, rapid attenuation of RHDV has not been observed. By studying the change in virulence of recent field isolates at a single field site we show, for the first time, that RHDV virulence has increased through time, likely because of selection to overcome developing genetic resistance in Australian wild rabbits. High virulence also appears to be favoured as rabbit carcasses, rather than diseased animals, are the likely source of mechanical insect transmission. These findings not only help elucidate the co-evolutionary interaction between rabbits and RHDV, but reveal some of the key factors shaping virulence evolution. PMID:25146599

Comparison of endoscopic evacuation, stereotactic aspiration and craniotomy for the treatment of supratentorial hypertensive intracerebral haemorrhage: study protocol for a randomised controlled trial.

PubMed

Xu, Xinghua; Zheng, Yi; Chen, Xiaolei; Li, Fangye; Zhang, Huaping; Ge, Xin

2017-06-28

Hypertensive intracerebral haemorrhage (HICH) is the most common form of haemorrhagic stroke with the highest morbidity and mortality of all stroke types. The choice of surgical or conservative treatment for patients with HICH remains controversial. In recent years, minimally invasive surgeries, such as endoscopic evacuation and stereotactic aspiration, have been attempted for haematoma removal and offer promise. However, research evidence on the benefits of endoscopic evacuation or stereotactic aspiration is still insufficient. A multicentre, randomised controlled trial will be conducted to compare the efficacy of endoscopic evacuation, stereotactic aspiration and craniotomy in the treatment of supratentorial HICH. About 1350 eligible patients from 10 neurosurgical centres will be randomly assigned to an endoscopic group, a stereotactic group and a craniotomy group at a 1:1:1 ratio. Randomisation is undertaken using a 24-h randomisation service accessed by telephone or the Internet. All patients will receive the corresponding surgery based on their grouping. They will be followed-up at 1, 3 and 6 months after surgery. The primary outcome is the modified Rankin Scale at 6-month follow-up. Secondary outcomes include: haematoma clearance rate; Glasgow Coma Scale 7 days after surgery; rebleeding rate; intracranial infection rate; hospitalisation time; mortality at 1 month and 3 months after surgery; the Barthel Index and the WHO quality of life at 3 months and 6 months after surgery. The trial aims to investigate whether endoscopic evacuation and stereotactic aspiration could improve the outcome of supratentorial HICH compared with craniotomy. The trial will help to determine the best surgical method for the treatment of supratentorial HICH. ClinicalTrials.gov, ID: NCT02811614 . Registered on 20 June 2016.

Nailfold videocapillaroscopy micro-haemorrhage and giant capillary counting as an accurate approach for a steady state definition of disease activity in systemic sclerosis.

PubMed

Sambataro, Domenico; Sambataro, Gianluca; Zaccara, Eleonora; Maglione, Wanda; Polosa, Riccardo; Afeltra, Antonella M V; Vitali, Claudio; Del Papa, Nicoletta

2014-10-09

Nailfold videocapillaroscopy (NVC) in systemic sclerosis (SSc) is a procedure commonly used for patient classification and subsetting, but not to define disease activity (DA). This study aimed to evaluate whether the number of micro-haemorrhages (MHE), micro-thrombosis (MT), giant capillaries (GC), and normal/dilated capillaries (Cs) in NVC could predict DA in SSc. Eight-finger NVC was performed in 107 patients with SSc, and the total number of MHE/MT, GC, and the mean number of Cs were counted and defined as number of micro-haemorrhages (NEMO), GC and Cs scores, respectively. The European Scleroderma Study Group (ESSG) index constituted the gold standard for DA assessment, and scores ≥ 3.5 and = 3 were considered indicative of high and moderate activity, respectively. NEMO and GC scores were positively correlated with ESSG index (R = 0.65, P < 0.0001, and R = 0.47, P <0.0001, respectively), whilst Cs score showed a negative correlation with that DA index (R = -0.30, P <0.001). The area under the curve (AUC) of receiver operating characteristic plots, obtained by NEMO score sensitivity and specificity values in classifying patients with ESSG index ≥ 3.5, was significantly higher than the corresponding AUC derived from either GC or Cs scores (P <0.03 and P <0.0006, respectively). A modified score, defined by the presence of a given number of MHE/MT and GC, had a good performance in classifying active patients (ESSG index ≥ 3, sensitivity 95.1%, specificity 84.8%, accuracy 88.7%). MHE/MT and GC appear to be good indicators of DA in SSc, and enhances the role of NVC as an easy technique to identify active patients.

Drug interactions with phenprocoumon and the risk of serious haemorrhage: a nested case-control study in a large population-based German database.

PubMed

Jobski, Kathrin; Behr, Sigrid; Garbe, Edeltraut

2011-09-01

Phenprocoumon is the most frequently used vitamin K antagonist in Germany. The aim of this study was to estimate the risk of serious bleeding as a result of the use of drugs with potential interaction with phenprocoumon. We conducted a nested case-control study in a cohort of 246,220 phenprocoumon users in the German Pharmacoepidemiological Research Database. Cases were patients hospitalised for haemorrhage of different kinds. Ten controls were matched to each case by health insurance, birth year and sex using incidence density sampling. Odds ratios (OR) with 95% confidence intervals (CI) of the risk of serious bleeding associated with combined use of phenprocoumon and potentially interacting drugs versus phenprocoumon alone were estimated using conditional logistic regression analysis. Our analyses considered multiple risk factors, such as bleeding history, other comorbidities or co-medication. Our study included 2,553 cases and 25,348 matched controls. An increased risk of bleeding was observed for the combined use of phenprocoumon and clopidogrel vs phenprocoumon use alone (OR: 1.83, 95% CI: 1.41-2.36). Antibiotic drugs associated with an increased risk of haemorrhage in the population of phenprocoumon users included the group of quinolones with ORs ranging from 2.74 (95% CI: 1.80-4.18) for ciprofloxacin to 4.40 (95% CI: 2.45-7.89) for levofloxacin, amoxicillin plus clavulanic acid (OR: 2.99, 95% CI: 1.39-6.42) and cotrimoxazole (OR 3.57, 95% CI: 2.36-5.40). Among non-steroidal anti-inflammatory drugs (NSAIDs), ketoprofen and naproxen were associated with the highest risks. Significantly elevated risks of major bleeding were mainly observed for drugs with known pharmacodynamic interaction with phenprocoumon, and less for drugs with possible pharmacokinetic interaction.

The impact of the implementation of the postpartum haemorrhage management guidelines at the first regional perinatal centre in Southern Kazakhstan.

PubMed

Nadisauskiene, Ruta J; Dobozinskas, Paulius; Kacerauskiene, Justina; Kliucinskas, Mindaugas; Zhumagali, Ismailov; Kokenova, Madina; Bekeshov, Jesengeldy; Dzabagijeva, Saltanat; Sapargalijeva, Aigul; Glazebnaja, Inna; Konyrbajeva, Gulmyra; Uteshova, Zijas; Tasbulatova, Aina

2016-08-19

Postpartum haemorrhage (PPH) remains one of the most common causes of maternal morbidity and mortality. Therefore, clearly written PPH management guidelines should be used in clinical practice. The aim of this study was to evaluate the effectiveness of the implementation of PPH management guidelines at the First Regional Perinatal Centre of Southern Kazakhstan (FRPC). Between 2012 and 2013 an interventional study was performed whereby the PPH management guidelines were implemented at the FRPC. All of the deliveries that were complicated by PPH 8 months before and 8 months after the intervention were analysed. Prevalence and severity of PPH, and the change in prevention, diagnostics and management of PPH was evaluated and statistical analysis using the SPSS 22.0 was performed. There were in total 5404 and 5956 deliveries in the pre- and post-intervention periods, respectively. The rates of PPH and severe PPH decreased from 1.17 to 1.02 % (p = 0.94) and from 0.24 to 0.22 % (p = 0.94), respectively. Blood loss on average increased from 1055 to 1170 ml in the post-intervention period. The pharmacological treatment of postpartum haemorrhage with uterotonics was administered most frequently during both periods. After the implementation of the guidelines, the number of transfused units of packed red blood cells decreased from 4.76 to 2.48 units/case. In addition, the amount of transfused fresh frozen plasma decreased by 20 %. The number of conservative interventions and conservative operations increased from 7.9 to 52.7 % and from 3.9 to 48.6 %, respectively. The number of hysterectomies decreased from 23.7 % in pre-intervention to 8.1 % in the post-intervention period. The implementation of the PPH management guidelines had a positive effect on PPH prevention, diagnostics and management. It led to a more conservative aproach to the treatment of PPH. Therefore, clearly written PPH management guidelines, adapted for a particular hospital, should be

Cerebral haemodynamics in patients with hydrocephalus after subarachnoid haemorrhage due to ruptured aneurysm.

PubMed

Chang, Chia-Cheng; Kuwana, Nobumasa; Ito, Susumu; Yokoyama, Takaakira; Kanno, Hiroshi; Yamamoto, Isao

2003-01-01

Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) may be reduced in patients with normal pressure hydrocephalus (NPH) after subarachnoid haemorrhage (SAH). However, little is known about brain circulation in asymptomatic patients with ventriculomegaly after SAH. This study investigated CBF and CVR in symptomatic and asymptomatic patients with ventriculomegaly to clarify the mechanism of NPH. CBF and CVR were investigated in 48 patients with ventriculomegaly after SAH due to ruptured aneurysm. Mean CBF of the whole brain was measured by first-pass radionuclide angiography using technetium-99m hexamethylpropylene amine oxime. CVR was measured as the percentage change from the baseline mean CBF value after administration of 500 mg acetazolamide. Thirty patients with NPH who responded to shunting had significantly ( P<0.01) reduced mean CBF and CVR compared with normal controls. Fourteen asymptomatic patients with ventriculomegaly showed significant ( P<0.01) reduction in CVR but no difference in mean CBF. Four symptomatic patients who did not respond to shunting showed significantly ( P<0.01) reduced mean CBF but had preserved CVR. Postoperative mean CBF and CVR increased significantly ( P<0.01) in 21 patients who responded to shunting, but showed no significant change in four symptomatic patients who did not respond to shunting. Reduction of CBF superimposed on pre-existing impairment of CVR may be an essential step in the mechanism responsible for the manifestation of symptoms of NPH.

Emergence of rabbit haemorrhagic disease virus 2 in the archipelago of Madeira, Portugal (2016-2017).

PubMed

Carvalho, Carina Luísa; Silva, Sara; Gouveia, Paz; Costa, Margarida; Duarte, Elsa Leclerc; Henriques, Ana Margarida; Barros, Sílvia Santos; Luís, Tiago; Ramos, Fernanda; Fagulha, Teresa; Fevereiro, Miguel; Duarte, Margarida Dias

2017-12-01

We report the detection of rabbit haemorrhagic disease virus 2 (RHDV2) in the Madeira archipelago, Portugal. Viral circulation was confirmed by RT-qPCR and vp60 sequencing. Epidemiological data revealed the outbreak initiated in October 2016 in Porto Santo affecting wild and domestic rabbits. It was then detected three months later on the island of Madeira. Five haplotypes were identified and a genetic overall similarity of 99.54 to 99.89% was observed between the two viral populations. Unique single nucleotide polymorphisms were recognised in the Madeira archipelago strains, two of which resulting in amino acid substitutions at positions 480 and 570 in the VP60 protein. Phylogenetic investigation by Maximum Likelihood showed all the vp60 sequences from the Madeira archipelago group together with high bootstraps. The analysis also showed that the Madeira archipelago strains are closely related to the strains detected in the south of mainland Portugal in 2016, suggesting a possible introduction from the mainland. The epidemiological data and high genetic similarity indicate a common source for the Porto Santo and Madeira RHDV2 outbreaks. Human activity related to hunting was most probably at the origin of the Madeira outbreak.

Co-circulation of bluetongue and epizootic haemorrhagic disease viruses in cattle in Reunion Island.

PubMed

Sailleau, Corinne; Zanella, Gina; Breard, Emmanuel; Viarouge, Cyril; Desprat, Alexandra; Vitour, Damien; Adam, Micheline; Lasne, Laurent; Martrenchar, Arnaud; Bakkali-Kassimi, Labib; Costes, Laura; Zientara, Stéphan

2012-03-23

Bluetongue virus (BTV) and epizootic haemorrhagic disease virus (EHDV) in deer have already been isolated in Reunion Island and have caused more or less severe clinical signs in cattle (EHDV) or in sheep (BTV), as observed in 2003. In January 2009, cattle in Reunion Island showed clinical signs suggesting infection by one or the other of these arboviral diseases. A study was set up to determine the etiology of the disease. Analysis by reverse transcriptase-polymerase chain reaction (RT-PCR) performed on blood samples from 116 cattle from different districts of the island detected the presence of the EHDV genome in 106 samples and, in 5 of them, the simultaneous occurrence of BTV and EHDV. One strain of EHDV (7 isolates) and one of BTV were isolated in embryonated eggs and a BHK-21 cell culture. Group and subgroup primer-pairs were designed on the segment 2 sequences available in GenBank to identify and type the EHDV strains. Phylogenetic analysis of the genomic segment 2 (encoding the VP2 serotype-specific protein) of the isolates confirmed the serotypes of these two orbiviruses as BTV-2 and EHDV-6 and allowed them to be compared with previously isolated strains. Copyright © 2011 Elsevier B.V. All rights reserved.

Sexual and transovarian transmission of Crimean-Congo haemorrhagic fever virus in Hyalomma truncatum ticks.

PubMed

Gonzalez, J P; Camicas, J L; Cornet, J P; Faye, O; Wilson, M L

1992-01-01

Male Hyalomma truncatum ticks were inoculated with Crimean-Congo haemorrhagic fever (CCHF) virus, hypostomectomized and then allowed to mate with uninfected females feeding on a naive rabbit. After mating, CCHF virus was reisolated from 2 out of 3 males tested and from 4 of 6 mated, engorged females (titre greater than or equal to 2.2 log LD50/ml). Vertical transmission was then demonstrated by virus reisolation from a portion of 2 of the 6 batches of eggs laid by the positive females. From these 2 positive egg batches, 6 larvae pools were tested with successful virus reisolation from one. Attempts to reisolate CCHF virus from 15 nymph pools of this positive batch of larvae were unsuccessful. Virus reisolation from gonopore-closed female H. truncatum which cofed with preinfected males demonstrated transmission in the absence of copulation. Rabbits that served as bloodmeal sources seroconverted after infestation by infected male ticks. However, CCHF virus was not reisolated from 3 gonopore-closed, engorged females, nor from their eggs, after feeding with hypostomectomized preinfected males. Transmission of CCHF virus during mating or cofeeding of adult H. truncatum, and subsequent transovarial transmission, appear to represent additional mechanisms of infection in the tick population, and may contribute to the maintenance of transmission in nature.

Protective effects of a Modified Vaccinia Ankara-based vaccine candidate against Crimean-Congo Haemorrhagic Fever virus require both cellular and humoral responses.

PubMed

Dowall, Stuart D; Graham, Victoria A; Rayner, Emma; Hunter, Laura; Watson, Robert; Taylor, Irene; Rule, Antony; Carroll, Miles W; Hewson, Roger

2016-01-01

Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. There is no approved vaccine currently available against CCHF. The most promising candidate, which has previously been shown to confer protection in the small animal model, is a modified Vaccinia Ankara virus vector expressing the CCHF viral glycoprotein (MVA-GP). It has been shown that MVA-GP induces both humoral and cellular immunogenicity. In the present study, sera and T-lymphocytes were passively and adoptively transferred into recipient mice prior to challenge with CCHF virus. Results demonstrated that mediators from both arms of the immune system were required to demonstrate protective effects against lethal challenge.

Antenatal testing to predict outcome in pregnancies with unexplained antepartum haemorrhage.

PubMed

Ajayi, R A; Soothill, P W; Campbell, S; Nicolaides, K H

1992-02-01

To investigate whether Doppler studies of placental perfusion and antenatal tests for fetal hypoxia can identify reduced placental functional reserve in women with unexplained antepartum haemorrhage (APH). A prospective, longitudinal study. Fetal Surveillance Unit, King's College Hospital, London. 48 women with bleeding from the genital tract after 26 weeks gestation without a clinical diagnosis of abruption or ultrasound evidence of placenta praevia. Fetal surveillance by Doppler measurements of the umbilical and uterine arteries, biophysical profile scoring and computerized measurement of the mean minute range of FHR variation. A poor outcome was defined by one or more of the following: (i) birthweight greater than 2SD below the normal mean for gestational age and sex, (ii) abnormal FHR pattern in labour resulting in operative delivery, (iii) umbilical vein blood pH at delivery less than 7.15, (iv) a 5-min Apgar score less than 7. Fifteen of the 48 pregnancies had a poor outcome; seven occurred in the 10 women delivered preterm (less than 37 weeks) and eight in the 36 women delivered between 37 and 42 weeks. Two women were delivered after 42 weeks and both infants had a good outcome. The results of Doppler studies of uterine and umbilical arteries, fetal biophysical profile or FHR variation were not significantly different between the two outcome groups. The 36 pregnancies delivered between 37 and 42 weeks were matched retrospectively for maternal age, parity and race with 36 pregnancies without APH; there was no significant difference in outcome between the women with unexplained APH and the matched comparison group. Morbidity related to unexplained APH is associated with preterm delivery rather than with damage to utero-placental function.

International Roughness Index (IRI) measurement using Hilbert-Huang transform

NASA Astrophysics Data System (ADS)

Zhang, Wenjin; Wang, Ming L.

2018-03-01

International Roughness Index (IRI) is an important metric to measure condition of roadways. This index is usually used to justify the maintenance priority and scheduling for roadways. Various inspection methods and algorithms are used to assess this index through the use of road profiles. This study proposes to calculate IRI values using Hilbert-Huang Transform (HHT) algorithm. In particular, road profile data is provided using surface radar attached to a vehicle driving at highway speed. Hilbert-Huang transform (HHT) is used in this study because of its superior properties for nonstationary and nonlinear data. Empirical mode decomposition (EMD) processes the raw data into a set of intrinsic mode functions (IMFs), representing various dominating frequencies. These various frequencies represent noises from the body of the vehicle, sensor location, and the excitation induced by nature frequency of the vehicle, etc. IRI calculation can be achieved by eliminating noises that are not associated with the road profile including vehicle inertia effect. The resulting IRI values are compared favorably to the field IRI values, where the filtered IMFs captures the most characteristics of road profile while eliminating noises from the vehicle and the vehicle inertia effect. Therefore, HHT is an effect method for road profile analysis and for IRI measurement. Furthermore, the application of HHT method has the potential to eliminate the use of accelerometers attached to the vehicle as part of the displacement measurement used to offset the inertia effect.

Pipe leak diagnostic using high frequency piezoelectric pressure sensor and automatic selection of intrinsic mode function

NASA Astrophysics Data System (ADS)

Yusop, Hanafi M.; Ghazali, M. F.; Yusof, M. F. M.; Remli, M. A. Pi; Kamarulzaman, M. H.

2017-10-01

In a recent study, the analysis of pressure transient signals could be seen as an accurate and low-cost method for leak and feature detection in water distribution systems. Transient phenomena occurs due to sudden changes in the fluid’s propagation in pipelines system caused by rapid pressure and flow fluctuation due to events such as closing and opening valves rapidly or through pump failure. In this paper, the feasibility of the Hilbert-Huang transform (HHT) method/technique in analysing the pressure transient signals in presented and discussed. HHT is a way to decompose a signal into intrinsic mode functions (IMF). However, the advantage of HHT is its difficulty in selecting the suitable IMF for the next data postprocessing method which is Hilbert Transform (HT). This paper reveals that utilizing the application of an integrated kurtosis-based algorithm for a z-filter technique (I-Kaz) to kurtosis ratio (I-Kaz-Kurtosis) allows/contributes to/leads to automatic selection of the IMF that should be used. This technique is demonstrated on a 57.90-meter medium high-density polyethylene (MDPE) pipe installed with a single artificial leak. The analysis results using the I-Kaz-kurtosis ratio revealed/confirmed that the method can be used as an automatic selection of the IMF although the noise level ratio of the signal is low. Therefore, the I-Kaz-kurtosis ratio method is recommended as a means to implement an automatic selection technique of the IMF for HHT analysis.

Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa.

PubMed

Leroy, E M; Gonzalez, J-P; Baize, S

2011-07-01

Ebola and Marburg viruses are the only members of the Filoviridae family (order Mononegavirales), a group of viruses characterized by a linear, non-segmented, single-strand negative RNA genome. They are among the most virulent pathogens for humans and great apes, causing acute haemorrhagic fever and death within a matter of days. Since their discovery 50 years ago, filoviruses have caused only a few outbreaks, with 2317 clinical cases and 1671 confirmed deaths, which is negligible compared with the devastation caused by malnutrition and other infectious diseases prevalent in Africa (malaria, cholera, AIDS, dengue, tuberculosis …). Yet considerable human and financial resourses have been devoted to research on these viruses during the past two decades, partly because of their potential use as bioweapons. As a result, our understanding of the ecology, host interactions, and control of these viruses has improved considerably. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Emerging vector-borne diseases in dromedaries in Tunisia: West Nile, bluetongue, epizootic haemorrhagic disease and Rift Valley fever.

PubMed

Hassine, Thameur B; Amdouni, Jihane; Monaco, Federica; Savini, Giovanni; Sghaier, Soufien; Selimen, Imed B; Chandoul, Walid; Hamida, Khaled B; Hammami, Salah

2017-03-31

A total of 118 sera were collected during 2016 from two groups of dromedaries from Kebili and Medenine governorates in the south of Tunisia. The aim of this study was to provide the first serological investigation of four emerging vector-borne diseases in two groups of dromedaries in Tunisia. Sera were tested by ELISA and serum neutralisation test to identify West Nile virus (WNV), bluetongue virus (BTV), epizootic haemorrhagic disease virus (EHDV) and Rift Valley fever virus (RVFV). In the first group, the seroprevalence for BTV was 4.6%, while in the second group, it was 25.8% for WNV and 9.7% for BTV. Only serotype 1 was detected for BTV in the two groups. No evidence for circulation of RVF and EHD viruses was revealed. Results indicated that dromedaries can be infected with BTV and WNV, suggesting that this species might play a significant role in the epizootiology of these viral diseases in Tunisia and neighbouring countries.

Transmission of haemorrhagic fever with renal syndrome in china and the role of climate factors: a review.

PubMed

Hansen, Alana; Cameron, Scott; Liu, Qiyong; Sun, Yehuan; Weinstein, Philip; Williams, Craig; Han, Gil-Soo; Bi, Peng

2015-04-01

Haemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease that poses a serious public health threat in China. HFRS is caused by hantaviruses, mainly Seoul virus in urban areas and Hantaan virus in agricultural areas. Although preventive measures including vaccination programs and rodent control measures have resulted in a decline in cases in recent years, there has been an increase in incidence in some areas and new endemic areas have emerged. This review summarises the recent literature relating to the effects of climatic factors on the incidence of HFRS in China and discusses future research directions. Temperature, precipitation and humidity affect crop yields, rodent breeding patterns and disease transmission, and these can be influenced by a changing climate. Detailed surveillance of infections caused by Hantaan and Seoul viruses and further research on the viral agents will aid in interpretation of spatiotemporal patterns and a better understanding of the environmental and ecological drivers of HFRS amid China's rapidly urbanising landscape and changing climate. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Protective effects of a Modified Vaccinia Ankara-based vaccine candidate against Crimean-Congo Haemorrhagic Fever virus require both cellular and humoral responses

PubMed Central

Dowall, Stuart D.; Graham, Victoria A.; Rayner, Emma; Hunter, Laura; Watson, Robert; Taylor, Irene; Rule, Antony; Carroll, Miles W.; Hewson, Roger

2016-01-01

Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. There is no approved vaccine currently available against CCHF. The most promising candidate, which has previously been shown to confer protection in the small animal model, is a modified Vaccinia Ankara virus vector expressing the CCHF viral glycoprotein (MVA-GP). It has been shown that MVA-GP induces both humoral and cellular immunogenicity. In the present study, sera and T-lymphocytes were passively and adoptively transferred into recipient mice prior to challenge with CCHF virus. Results demonstrated that mediators from both arms of the immune system were required to demonstrate protective effects against lethal challenge. PMID:27272940

COL5A1: Genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberous sclerosis 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II

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

Greenspan, D.S.; Northrup, H.; Au, K.S.

1995-02-10

COL5A1, the gene for the {alpha}1 chain of type V collagen, has been considered a candidate gene for certain diseases based on chromosomal location and/or disease phenotype. We have employed 3{prime}-untranslated region RFLPs to exclude COL5A1 as a candidate gene in families with tuberous sclerosis 1, Ehlers-Danlos syndrome type H, and nail-patella syndrome. In addition, we describe a polymorphic simple sequence repeat (SSR) within a COL5A1 intron. This SSR is used to exclude COL5A1 as a candidate gene in hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber disease) and to add COL5A1 to the existing map of {open_quotes}index{close_quotes} markers of chromosome 9 by evaluationmore » of the COL5A1 locus on the CEPH 40-family reference pedigree set. This genetic mapping places COL5A1 between markers D9S66 and D9S67. 14 refs., 1 fig., 2 tabs.« less