Complement Factor B Mutations in Atypical Hemolytic Uremic Syndrome—Disease-Relevant or Benign?

PubMed Central

Marinozzi, Maria Chiara; Vergoz, Laura; Rybkine, Tania; Ngo, Stephanie; Bettoni, Serena; Pashov, Anastas; Cayla, Mathieu; Tabarin, Fanny; Jablonski, Mathieu; Hue, Christophe; Smith, Richard J.; Noris, Marina; Halbwachs-Mecarelli, Lise; Donadelli, Roberta; Fremeaux-Bacchi, Veronique

2014-01-01

Atypical hemolytic uremic syndrome (aHUS) is a genetic ultrarare renal disease associated with overactivation of the alternative pathway of complement. Four gain-of-function mutations that form a hyperactive or deregulated C3 convertase have been identified in Factor B (FB) ligand binding sites. Here, we studied the functional consequences of 10 FB genetic changes recently identified from different aHUS cohorts. Using several tests for alternative C3 and C5 convertase formation and regulation, we identified two gain-of-function and potentially disease-relevant mutations that formed either an overactive convertase (M433I) or a convertase resistant to decay by FH (K298Q). One mutation (R178Q) produced a partially cleaved protein with no ligand binding or functional activity. Seven genetic changes led to near-normal or only slightly reduced ligand binding and functional activity compared with the most common polymorphism at position 7, R7. Notably, none of the algorithms used to predict the disease relevance of FB mutations agreed completely with the experimental data, suggesting that in silico approaches should be undertaken with caution. These data, combined with previously published results, suggest that 9 of 15 FB genetic changes identified in patients with aHUS are unrelated to disease pathogenesis. This study highlights that functional assessment of identified nucleotide changes in FB is mandatory to confirm disease association. PMID:24652797

A novel atypical hemolytic uremic syndrome-associated hybrid CFHR1/CFH gene encoding a fusion protein that antagonizes factor H-dependent complement regulation.

PubMed

Valoti, Elisabetta; Alberti, Marta; Tortajada, Agustin; Garcia-Fernandez, Jesus; Gastoldi, Sara; Besso, Luca; Bresin, Elena; Remuzzi, Giuseppe; Rodriguez de Cordoba, Santiago; Noris, Marina

2015-01-01

Genomic aberrations affecting the genes encoding factor H (FH) and the five FH-related proteins (FHRs) have been described in patients with atypical hemolytic uremic syndrome (aHUS), a rare condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ARF. These genomic rearrangements occur through nonallelic homologous recombinations caused by the presence of repeated homologous sequences in CFH and CFHR1-R5 genes. In this study, we found heterozygous genomic rearrangements among CFH and CFHR genes in 4.5% of patients with aHUS. CFH/CFHR rearrangements were associated with poor clinical prognosis and high risk of post-transplant recurrence. Five patients carried known CFH/CFHR1 genes, but we found a duplication leading to a novel CFHR1/CFH hybrid gene in a family with two affected subjects. The resulting fusion protein contains the first four short consensus repeats of FHR1 and the terminal short consensus repeat 20 of FH. In an FH-dependent hemolysis assay, we showed that the hybrid protein causes sheep erythrocyte lysis. Functional analysis of the FHR1 fraction purified from serum of heterozygous carriers of the CFHR1/CFH hybrid gene indicated that the FHR1/FH hybrid protein acts as a competitive antagonist of FH. Furthermore, sera from carriers of the hybrid CFHR1/CFH gene induced more C5b-9 deposition on endothelial cells than control serum. These results suggest that this novel genomic hybrid mediates disease pathogenesis through dysregulation of complement at the endothelial cell surface. We recommend that genetic screening of aHUS includes analysis of CFH and CFHR rearrangements, particularly before a kidney transplant. Copyright © 2015 by the American Society of Nephrology.

Prophylactic eculizumab for kidney transplantation in a child with atypical hemolytic uremic syndrome due to complement factor H mutation.

PubMed

Ranch, Daniel; Crowther, Barrett; Arar, Mazen; Assanasen, Chatchawin

2014-09-01

We present a case of successful deceased-donor kidney transplantation in a three-yr-old child with aHUS due to complement factor H mutation, using only prophylactic eculizumab treatment prior to transplant. She developed disease exacerbation in the immediate post-operative period despite having therapeutic eculizumab concentrations and evidence for complete complement pathway blockade. The patient responded well to additional doses of eculizumab and has maintained excellent graft function and disease control in the first year post-transplantation. The optimal dosing scheme for eculizumab in the perioperative period remains to be determined. More sensitive biomarkers of early disease activity are needed to improve disease monitoring. Finally, the duration of eculizumab therapy in patients with aHUS remains to be determined. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Preservation of renal function in atypical hemolytic uremic syndrome by eculizumab: a case report.

PubMed

Giordano, Mario; Castellano, Giuseppe; Messina, Giovanni; Divella, Claretta; Bellantuono, Rosa; Puteo, Flora; Colella, Vincenzo; Depalo, Tommaso; Gesualdo, Loreto

2012-11-01

Genetic mutations in complement components are associated with the development of atypical hemolytic uremic syndrome (aHUS), a rare disease with high morbidity rate triggered by infections or unidentified factors. The uncontrolled activation of the alternative pathway of complement results in systemic endothelial damage leading to progressive development of renal failure. A previously healthy 8-month-old boy was referred to our hospital because of onset of fever, vomiting, and a single episode of nonbloody diarrhea. Acute kidney injury with preserved diuresis, hemolytic anemia, and thrombocytopenia were detected, and common protocols for management of HUS were followed without considerable improvement. The persistent low levels of complement component C3 led us to hypothesize the occurrence of aHUS. In fact, the child carried a specific mutation in complement factor H (Cfh; nonsense mutation in 3514G>T, serum levels of Cfh 138 mg/L, normal range 350-750). Given the lack of response to therapy and the occurrence of kidney failure requiring dialysis, we used eculizumab as rescue therapy, a monoclonal humanized antibody against the complement component C5. One week from the first administration, we observed a significant improvement of all clinical and laboratory parameters with complete recovery from hemodialysis, even in the presence of systemic infections. Our case report shows that complement inhibiting treatment allows the preservation of renal function and avoids disease relapses during systemic infections.

Analysis of Linear Antibody Epitopes on Factor H and CFHR1 Using Sera of Patients with Autoimmune Atypical Hemolytic Uremic Syndrome.

PubMed

Trojnár, Eszter; Józsi, Mihály; Uray, Katalin; Csuka, Dorottya; Szilágyi, Ágnes; Milosevic, Danko; Stojanović, Vesna D; Spasojević, Brankica; Rusai, Krisztina; Müller, Thomas; Arbeiter, Klaus; Kelen, Kata; Szabó, Attila J; Reusz, György S; Hyvärinen, Satu; Jokiranta, T Sakari; Prohászka, Zoltán

2017-01-01

In autoimmune atypical hemolytic uremic syndrome (aHUS), the complement regulator factor H (FH) is blocked by FH autoantibodies, while 90% of the patients carry a homozygous deletion of its homolog complement FH-related protein 1 (CFHR1). The functional consequence of FH-blockade is widely established; however, the molecular basis of autoantibody binding and the role of CFHR1 deficiency in disease pathogenesis are still unknown. We performed epitope mapping of FH to provide structural insight in the autoantibody recruitment on FH and potentially CFHR1. Eight anti-FH positive aHUS patients were enrolled in this study. With overlapping synthetic FH and CFHR1 peptides, we located the amino acids (aa) involved in binding of acute and convalescence stage autoantibodies. We confirmed the location of the mapped epitopes using recombinant FH domains 19-20 that carried single-aa substitutions at the suspected antibody binding sites in three of our patients. Location of the linear epitopes and the introduced point mutations was visualized using crystal structures of the corresponding domains of FH and CFHR1. We identified three linear epitopes on FH (aa1157-1171; aa1177-1191; and aa1207-1226) and one on CFHR1 (aa276-290) that are recognized both in the acute and convalescence stages of aHUS. We observed a similar extent of autoantibody binding to the aHUS-specific epitope aa1177-1191 on FH and aa276-290 on CFHR1, despite seven of our patients being deficient for CFHR1. Epitope mapping with the domain constructs validated the location of the linear epitopes on FH with a distinct autoantibody binding motif within aa1183-1198 in line with published observations. According to the results, the linear epitopes we identified are located close to each other on the crystal structure of FH domains 19-20. This tertiary configuration contains the amino acids reported to be involved in C3b and sialic acid binding on the regulator, which may explain the functional deficiency of FH in the presence of autoantibodies. The data we provide identify the exact structures involved in autoantibody recruitment on FH and confirm the presence of an autoantibody binding epitope on CFHR1.

Defining the genetics of thrombotic microangiopathies.

PubMed

Vieira-Martins, Paula; El Sissy, Carine; Bordereau, Pauline; Gruber, Aurelia; Rosain, Jeremie; Fremeaux-Bacchi, Veronique

2016-04-01

The spectrum of the thrombotic microangiopathies (TMA) encompasses a heterogeneous group of disorders with hereditary and acquired forms. Endothelial cell injury in the microvasculature is common to all TMAs, whatever the pathophysiological process. In this review we describe genetic mutations characteristic of certain TMAs and review their contributions to disease. Recent identification of novel pathologic mutations has been enabled by exome studies. The monogenic forms of TMA are more frequently caused by recessive alterations in von Willebrand factor cleaving protease ADAMST13, leading to congenital thrombotic thrombocytopenic purpura, or cobalamine C and DGKE genes, leading to an atypical hemolytic-uremic syndrome (aHUS)-like TMA. aHUS, whether idiopathic or linked to a known complement amplifying condition, is a TMA that primarily affects kidney function. It often results from a combination of an underlying genetic susceptibility with environmental factors activating the alternative complement pathway. Pathogenic variants in at least five complement genes coding for complement factor H (CFH) complement factor I (CFI), MCP (CD46), C3 and complement factor B (CFB) have been demonstrated to increase the risk of developing aHUS, but several more genes have been implicated. A new challenge is to separate disease-associated genetic variants from the broader background of variants or polymorphisms present in all human genomes that are rare, potentially functional, but may or may not be pathogenic. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Thrombotic Microangiopathies].

PubMed

Schubert, Jörg; Dechant, Michael

2018-06-01

Thrombotic microangiopathies are almost devastating diseases leading to death at high frequency if untreated. They consist of at least five distinct entities, TTP, HUS, aHUS, TMA due to drug interference, systemic disease or post therapy TMA. Around 10 years ago there was only one established therapeutic approach as plasmapheresis. Meanwhile, there are new drugs been licensed or within licensing process. Patients with atypical HUS can be treated successfully by the Complement inhibitor Eculizumab. In addition, there is a new inhibitor of von-Willebrand-Polymerisation available. Caplacizumab provides a significantly better remission and decrease in TMA-related death. For therapy associated TMA as VOD/SOS Defibrotide could be established within a phase III study to significantly improve outcomes. In order to select these new medical approaches individual diagnostic parameters need to be established in order to rapidly distinguish between the TMA entities and start targeted therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Prevalence in the General Population of a CFH Sequence Variant Associated with Atypical Haemolytic Uraemic Syndrome in an Extensive Family from Southwest England

PubMed Central

Hamilton, Alexander J.; Lyons, Carl B.A.; Goodship, Timothy H.J.; Bingham, Coralie

2013-01-01

Background/Aims Twenty-five members of a family from the county of Devon in England have been affected by atypical haemolytic uraemic syndrome (aHUS) associated with a CFH mutation (c.3643C>G; p.Arg1215Gly). A 65-year-old male was diagnosed with aHUS after losing a renal transplant to a thrombotic microangiopathy. Subsequent mutation screening revealed the same CFH mutation without him being knowingly related to the local kindred. We designed a study to investigate the prevalence of this mutation in the local area. In addition, we examined the diagnoses of pre-existing haemodialysis patients to determine whether other patients might unknowingly be at risk of carrying the same CFH mutation. Methods The Exeter Ten Thousand (EXTEND) study aims to recruit 10,000 healthy volunteers over the age of 18 years living within 25 miles of Exeter in Devon. We genotyped DNA from 4,000 EXTEND subjects for CFH c.3643C>G; p.Arg1215Gly. We reviewed the diagnoses of 294 haemodialysis patients in the Devon area and genotyped 7 patients with either end-stage renal disease of unknown aetiology, malignant hypertension or renovascular disease. Results CFH c.3643C>G; p.Arg1215Gly was not detected in any of the 7 haemodialysis patients or the 4,000 individuals within the EXTEND study. Conclusions We conclude that CFH c.3643C>G; p.Arg1215Gly is not endemic in Devon. This reinforces our existing practice of genotyping only patients with kidney disease and evidence of a thrombotic microangiopathy for this mutation. This is the first study looking at the prevalence of CFH mutations in the general population. PMID:24163689

Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.

PubMed

Goodship, Timothy H J; Cook, H Terence; Fakhouri, Fadi; Fervenza, Fernando C; Frémeaux-Bacchi, Véronique; Kavanagh, David; Nester, Carla M; Noris, Marina; Pickering, Matthew C; Rodríguez de Córdoba, Santiago; Roumenina, Lubka T; Sethi, Sanjeev; Smith, Richard J H

2017-03-01

In both atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) complement plays a primary role in disease pathogenesis. Herein we report the outcome of a 2015 Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference where key issues in the management of these 2 diseases were considered by a global panel of experts. Areas addressed included renal pathology, clinical phenotype and assessment, genetic drivers of disease, acquired drivers of disease, and treatment strategies. In order to help guide clinicians who are caring for such patients, recommendations for best treatment strategies were discussed at length, providing the evidence base underpinning current treatment options. Knowledge gaps were identified and a prioritized research agenda was proposed to resolve outstanding controversial issues. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Genotype-phenotype correlations of low frequency variants in the complement system in renal disease and age-related macular degeneration.

PubMed

Geerlings, M J; Volokhina, E B; de Jong, E K; van de Kar, N; Pauper, M; Hoyng, C B; van den Heuvel, L P; den Hollander, A I

2018-06-11

Genetic alterations in the complement system have been linked to a variety of diseases, including atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), and age-related macular degeneration (AMD). We performed sequence analysis of the complement genes CFH, CFI, and C3 in 866 aHUS/C3G and 697 AMD patients. In total we identified 505 low frequency alleles, representing 121 unique variants, of which 51 are novel. CFH contained the largest number of unique low frequency variants (n=64; 53%), followed by C3 (n=32; 26%) and CFI (n=25; 21%). A substantial number of variants were found in both patients groups (n=48; 40%), while 41 (34%) variants were found only in aHUS/C3G and 32 (26%) variants were AMD-specific. Genotype-phenotype correlations between the disease groups identified a higher frequency of protein-altering alleles in SCR20 of Factor H (FH), and in the serine protease domain of Factor I (FI) in aHUS/C3G patients. In AMD a higher frequency of protein-altering alleles was observed in SCR3, SCR5 and SCR7 of FH, the SRCR domain of FI, and in the MG3 domain of C3. In conclusion, we observed a substantial overlap of variants between aHUS/C3G and AMD, however, there is a distinct clustering of variants within specific domains. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Therapeutic drug monitoring of eculizumab: Rationale for an individualized dosing schedule.

PubMed

Gatault, Philippe; Brachet, Guillaume; Ternant, David; Degenne, Danielle; Récipon, Guillaume; Barbet, Christelle; Gyan, Emmanuel; Gouilleux-Gruart, Valérie; Bordes, Cécile; Farrell, Alexandra; Halimi, Jean Michel; Watier, Hervé

2015-01-01

The annual cost of eculizumab maintenance therapy in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic-uremic syndrome (aHUS) exceeds $300,000 per patient. A better understanding of eculizumab pharmacokinetics and subsequent individual dose adjustment could reduce this cost. We measured the trough eculizumab concentration in 9 patients with maintenance therapy (aHUS, n = 7; PNH, n = 2) and determined: 1) the intra- and inter-individual variability; 2) the influence of weight on eculizumab pharmacokinetics; and 3) the rate of elimination of eculizumab following discontinuation. A one-compartment model was developed to describe the pharmacokinetics of eculizumab and predicted complement activity by body weight. Trough eculizumab concentrations were >50 µg/mL in 9/9, >100 µg/mL in 8/9, and >300 µg/mL in 5/9 of patients. Intra-individual variability was low but eculizumab concentrations, closely correlated with patient weight (R(2) = 0.66, p = 0.034), varied broadly (55 ± 12 to 733 ± 164 µg/mL). Pharmacokinetic modeling showed that the elimination half-life varied greatly, with an increase from 7.8 d in a patient weighing 100 kg to 19.5 d in a 40 kg patient. We predicted that infusions of 1200 mg could be spaced every 4 or 6 weeks in patients weighing <90 and <70 kg, respectively. In this pilot study, the current recommended use of a fixed eculizumab dose for maintenance therapy is associated with excessively high trough concentrations in many patients. Further prospective larger studies are now required to support an individualized schedule adjusted for patient weight and based on the observed trough serum eculizumab concentration.

Therapeutic drug monitoring of eculizumab: Rationale for an individualized dosing schedule

PubMed Central

Gatault, Philippe; Brachet, Guillaume; Ternant, David; Degenne, Danielle; Récipon, Guillaume; Barbet, Christelle; Gyan, Emmanuel; Gouilleux-Gruart, Valérie; Bordes, Cécile; Farrell, Alexandra; Halimi, Jean Michel; Watier, Hervé

2015-01-01

The annual cost of eculizumab maintenance therapy in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic–uremic syndrome (aHUS) exceeds $300,000 per patient. A better understanding of eculizumab pharmacokinetics and subsequent individual dose adjustment could reduce this cost. We measured the trough eculizumab concentration in 9 patients with maintenance therapy (aHUS, n = 7; PNH, n = 2) and determined: 1) the intra- and inter-individual variability; 2) the influence of weight on eculizumab pharmacokinetics; and 3) the rate of elimination of eculizumab following discontinuation. A one-compartment model was developed to describe the pharmacokinetics of eculizumab and predicted complement activity by body weight. Trough eculizumab concentrations were >50 µg/mL in 9/9, >100 µg/mL in 8/9, and >300 µg/mL in 5/9 of patients. Intra-individual variability was low but eculizumab concentrations, closely correlated with patient weight (R2 = 0.66, p = 0.034), varied broadly (55 ± 12 to 733 ± 164 µg/mL). Pharmacokinetic modeling showed that the elimination half-life varied greatly, with an increase from 7.8 d in a patient weighing 100 kg to 19.5 d in a 40 kg patient. We predicted that infusions of 1200 mg could be spaced every 4 or 6 weeks in patients weighing <90 and <70 kg, respectively. In this pilot study, the current recommended use of a fixed eculizumab dose for maintenance therapy is associated with excessively high trough concentrations in many patients. Further prospective larger studies are now required to support an individualized schedule adjusted for patient weight and based on the observed trough serum eculizumab concentration. PMID:26337866

Use of eculizumab in a systemic lupus erythemathosus patient presenting thrombotic microangiopathy and heterozygous deletion in CFHR1-CFHR3. A case report and systematic review.

PubMed

de Holanda, Maria Izabel; Pôrto, Luis Cristóvão; Wagner, Teresa; Christiani, Luis Fernando; Palma, Lilian M P

2017-12-01

The association of thrombotic microangiopathy (TMA) with systemic lupus erythematosus (SLE) has been described in 0.5 to 10% of cases, and patients present worse outcome. TMA is described as the association of microangiopathic hemolytic anemia, thrombocytopenia, and an organ injury, frequently the kidney. This study describes a successful case of use of eculizumab in a patient with SLE and TMA refractory to standard therapy, and provides a literature review. Case description and search in PubMed and MEDLINE using systemic lupus erythemathous and/or antiphospholipid syndrome (APS) and eculizumab retrieved 15 case reports. Eighteen-year-old female presented acute renal failure and TMA and was diagnosed with SLE. Steroids and IV cyclophosphamide were started together with plasma exchange. After 55 days, she still persisted with microangiopathic anemia, thrombocytopenia, and anuria, and eculizumab was introduced. She had rapid improvement in hematological parameters, and dialysis was discontinued 25 days after the first dose. Genetic analysis showed large heterozygous deletion encompassing the entire CFHR1 and CFHR3, a finding previously associated with patients presenting atypical hemolytic-uremic syndrome (aHUS). Twenty patients who received eculizumab with SLE and/or APS have been published to date: 11 were female and mean age at presentation was 31 years. Seven out of the 20 patients presented only SLE, 5 patients only APS and 8 patients both SLE and APS. Eighteen patients underwent plasma exchange, with a mean of 20 (4-120) sessions per patient. Thirteen patients received rituximab. Hematological response was evident in 100% and kidney recovery in 85% of patients. The terminal complement blockade with eculizumab is an optional treatment for patients with SLE and/or APS presenting TMA and refractory to current immunosuppression therapies. Genetic testing may help recognize patients with aHUS and SLE/APS and therefore help to determine length of treatment with eculizumab.

Arterial hypertension in children with hemolytic uremic syndrome after kidney transplantation.

PubMed

Hoenecke, Johannes; Hartmann, Hans; Melk, Anette

2015-08-01

The development of arterial hypertension after KTX is a well-known complication. HUS is a systemic disease associated with arterial hypertension during long-term follow-up. Our goal was to report on the severity of arterial hypertension after KTX in patients with typical and atypical HUS. We analyzed the course of 197 patients with HUS, of which 22 (n = 10 with typical HUS; n = 12 with atypical HUS) developed ESRF and received KTX as renal replacement therapy. We analyzed data from 1766 casual BP and 85 24-h ABPM measurements. In addition, we evaluated the used antihypertensive strategy. Comparison between the two patient groups revealed that patients with atypical HUS had significantly higher casual SBP-SDS and DBP-SDS values after KTX despite similar intensity of antihypertensive treatment. These data were supported by analysis of ABPM profiles showing comparable results for the interval 1-5 yr after KTX. Patients with atypical HUS had a greater severity of arterial hypertension despite similar treatment strategies and intensity of treatment. Our observation, even though in a small cohort, supports recent genetic studies showing arterial hypertension closely associated with HUS-causing mutations in patients with atypical HUS. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

PubMed Central

Salvadori, Maurizio; Bertoni, Elisabetta

2013-01-01

Hemolytic uremic syndrome (HUS) is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and pathogenetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the complement proteins are clearly involved in all types of thrombotic microangiopathy: typical HUS, atypical HUS and thrombotic thrombocytopenic purpura (TTP). Furthermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic aspects of this rare disease, examining both “traditional therapy” (including plasma therapy, kidney and kidney-liver transplantation) and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 monoclonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases I and II. They include anti-C5 antibodies, which are more purified, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy. PMID:24255888

[Atypical hemolytic and uremic syndrome associated with von Willebrand factor-cleaving protease (ADAMTS 13) deficiency in children].

PubMed

Ben Abdallah Chabchoub, R; Boukedi, A; Bensalah, M; Maalej, B; Gargour, L; Turk, F; Ben Halima, N; Wolf, M; Veyradier, A; Mahfoudh, A

2013-08-01

Hemolytic and uremic syndrome (HUS) is a classical form of thrombotic microangiopathies characterized by the association of hemolytic anemia with schizocytes, thrombocytopenia, and acute renal failure. Two forms of HUS have been described: the typical form that occurs after ingestion of a strain of bacteria, usually Escherichia coli types, which expresses verotoxin (also called shiga-like toxin), typically followed by bloody diarrhea, and atypical HUS, which is rare during childhood and can also be revealed by bloody diarrhea. We report a case of a 25-month-old infant who presented with hematuria and pallor after an episode of diarrhea. Biological tests revealed anemia, thrombocytopenia, and renal failure. The diagnosis of typical HUS was made, but the causal microorganism was not identified. Progression was favorable within 5 days of plasma transfusions. Two months later, the patient presented with the same symptoms and neurological impairment without any diarrhea. Von Willebrand factor-cleaving protease activity (ADAMTS 13) was low. Therefore, the diagnosis of atypical HUS by severe deficiency of ADAMTS 13 was suggested. The treatment was based on plasma transfusions resulting in remission. Atypical HUS associated with severe ADAMTS 13 deficiency rarely occurs in childhood. The prognosis, usually threatening, has been completely transformed thanks to a better understanding of the pathogenesis and to therapeutic progress. Copyright © 2013. Published by Elsevier SAS.

Disease-linked mutations in factor H reveal pivotal role of cofactor activity in self-surface-selective regulation of complement activation.

PubMed

Kerr, Heather; Wong, Edwin; Makou, Elisavet; Yang, Yi; Marchbank, Kevin; Kavanagh, David; Richards, Anna; Herbert, Andrew P; Barlow, Paul N

2017-08-11

Spontaneous activation enables the complement system to respond very rapidly to diverse threats. This activation is efficiently suppressed by complement factor H (CFH) on self-surfaces but not on foreign surfaces. The surface selectivity of CFH, a soluble protein containing 20 complement-control protein modules (CCPs 1-20), may be compromised by disease-linked mutations. However, which of the several functions of CFH drives this self-surface selectivity remains unknown. To address this, we expressed human CFH mutants in Pichia pastoris We found that recombinant I62-CFH (protective against age-related macular degeneration) and V62-CFH functioned equivalently, matching or outperforming plasma-derived CFH, whereas R53H-CFH, linked to atypical hemolytic uremic syndrome (aHUS), was defective in C3bBb decay-accelerating activity (DAA) and factor I cofactor activity (CA). The aHUS-linked CCP 19 mutant D1119G-CFH had virtually no CA on (self-like) sheep erythrocytes ( E S ) but retained DAA. The aHUS-linked CCP 20 mutant S1191L/V1197A-CFH (LA-CFH) had dramatically reduced CA on E S but was less compromised in DAA. D1119G-CFH and LA-CFH both performed poorly at preventing complement-mediated hemolysis of E S PspCN, a CFH-binding Streptococcus pneumoniae protein domain, binds CFH tightly and increases accessibility of CCPs 19 and 20. PspCN did not improve the DAA of any CFH variant on E S Conversely, PspCN boosted the CA, on E S , of I62-CFH, R53H-CFH, and LA-CFH and also enhanced hemolysis protection by I62-CFH and LA-CFH. We conclude that CCPs 19 and 20 are critical for efficient CA on self-surfaces but less important for DAA. Exposing CCPs 19 and 20 with PspCN and thus enhancing CA on self-surfaces may reverse deficiencies of some CFH variants. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[Hemolytic and uremic syndrome and maternal-fetal Escherichia coli K1 infection].

PubMed

Flandrois, M; Bessière, A; Vieira-Roth, S; Vergnaud, M; Frémeaux-Bacchi, V; Eckart, P

2011-03-01

Hemolytic uremic syndrome (HUS) is primarily a disease of infancy and early childhood. In its classic form, it is preceded by a prodrome of Escherichia coli-mediated bloody mucoid diarrhea. Typical HUS is commonly related to an infection by shiga-toxin producing E. coli. Stool cultures may detect this bacteria or its toxin, and PCRs can detect the shiga-toxin virulence genes. Atypical cases of HUS are mainly related to abnormalities of the alternative complement pathway and mutations of H, I, or B factors. Some atypical cases of HUS may also be related to von Willebrand factor or vitamin B12 metabolism abnormalities. A number of HUS cases related to invasive pneumococcal infections (pneumonia or meningitis) have been reported. We report a case of HUS associated with a bacterial E. coli K1 infection in a newborn baby, with a good clinical outcome: there was no need for dialysis and normal renal function was quickly regained. The workup did not favor a toxinic origin or an abnormality on the alternative complement pathway. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome

PubMed Central

Raghunathan, V.; Sethi, S. K.; Dragon-Durey, M. A.; Dhaliwal, M.; Raina, R.; Jha, P.; Bansal, S. B.; Kher, V.

2017-01-01

Hypertension is common in hemolytic uremic syndrome (HUS) and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV) enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency. PMID:28356668

Carboxyhemoglobin - the forgotten parameter of neonatal hyperbilirubinemia.

PubMed

Bailey, Douggl G N; Fuchs, Hans; Hentschel, Roland

2017-07-26

Neonatal hyperbilirubinemia is influenced by a wide variety of factors, one of which is hemolysis. Serious hyperbilirubinemia may lead to a kernicterus with detrimental neurologic sequelae. Patients suffering from hemolytic disease have a higher risk of developing kernicterus. Carbon monoxide (CO), a byproduct of hemolysis or heme degradation, was described by Sjöstrand in the 1960s. It is transported as carboxyhemoglobin (COHb) and exhaled through the lungs. We were interested in a potential correlation between COHb and total serum bilirubin (TSB) and the time course of both parameters. We used a point of care (POC) blood gas analyzer and did a retrospective analysis of bilirubin and COHb data collected over a 60-day period. An arbitrary cut-off point set at 2% COHb identified four patients with hemolytic disease of different origins who required phototherapy. In one patient with atypical hemolytic uremic syndrome (aHUS), COHb preceded the rise in bilirubin by about 2 days. Despite this displacement, there was a moderately good correlation of COHb with TSB levels <15 mg/dL (257 μmol/L) (r2: 0.80) and direct bilirubin (r2: 0.78) in the first patient. For all the four patients and all time points the correlation was slightly lower (r2: 0.59). COHb might be useful as a marker for high hemoglobin turnover to allow an earlier identification of newborns at risk to a rapid rise in bilirubin.

Hemolytic uremic syndrome (HUS) secondary to cobalamin C (cblC) disorder.

PubMed

Sharma, Ajay P; Greenberg, Cheryl R; Prasad, Asuri N; Prasad, Chitra

2007-12-01

Diarrhea-positive hemolytic uremic syndrome (HUS) is a common cause of acute renal failure in children. Diarrhea-negative (D-), or atypical HUS, is etiologically distinct. A Medline search identified seven previously reported D- cases of HUS secondary to cobalamin C (cblC) disease presenting in infancy. An infantile presentation is reported to be associated with a high mortality rate (6/7 cases). We describe the results of a 5-year longitudinal follow-up in a child diagnosed with D- HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene. We briefly review the published experience in cblC-associated HUS to highlight the clinical characteristics of this uncommon, but potentially treatable, condition.

Hemolytic uremic syndrome complicating Mycoplasma pneumoniae infection.

PubMed

Godron, Astrid; Pereyre, Sabine; Monet, Catherine; Llanas, Brigitte; Harambat, Jérôme

2013-10-01

Mycoplasma pneumoniae can cause various extrapulmonary manifestations but, to our knowledge, no case of Mycoplasma pneumoniae associated with hemolytic uremic syndrome (HUS) has been reported. We describe a 1-year-old boy with M. pneumoniae respiratory tract infection and associated microangiopathic hemolytic anemia, slightly decreased platelet count and mild renal impairment, suggesting a diagnosis of HUS. Assuming M. pneumoniae infection was the cause of HUS in this case, the different possible mechanisms, including an atypical HUS due to preexisting complement dysregulation, an alternative complement pathway activation induced by M. pneumoniae infection at the acute phase, an autoimmune disorder, and a direct role of the bacteria in inducing endothelial injury, are discussed. The signs of HUS resolved with treatment of the M. pneumoniae infection. Hemolytic uremic syndrome may be an unusual complication of M. pneumoniae infection.

Production of biologically active recombinant human factor H in Physcomitrella.

PubMed

Büttner-Mainik, Annette; Parsons, Juliana; Jérôme, Hanna; Hartmann, Andrea; Lamer, Stephanie; Schaaf, Andreas; Schlosser, Andreas; Zipfel, Peter F; Reski, Ralf; Decker, Eva L

2011-04-01

The human complement regulatory serum protein factor H (FH) is a promising future biopharmaceutical. Defects in the gene encoding FH are associated with human diseases like severe kidney and retinal disorders in the form of atypical haemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis II (MPGN II) or age-related macular degeneration (AMD). There is a current need to apply intact full-length FH for the therapy of patients with congenital or acquired defects of this protein. Application of purified or recombinant FH (rFH) to these patients is an important and promising approach for the treatment of these diseases. However, neither protein purified from plasma of healthy individuals nor recombinant protein is currently available on the market. Here, we report the first stable expression of the full-length human FH cDNA and the subsequent production of this glycoprotein in a plant system. The moss Physcomitrella patens perfectly suits the requirements for the production of complex biopharmaceuticals as this eukaryotic system not only offers an outstanding genetical accessibility, but moreover, proteins can be produced safely in scalable photobioreactors without the need for animal-derived medium compounds. Transgenic moss lines were created, which express the human FH cDNA and target the recombinant protein to the culture supernatant via a moss-derived secretion signal. Correct processing of the signal peptide and integrity of the moss-produced rFH were verified via peptide mapping by mass spectrometry. Ultimately, we show that the rFH displays complement regulatory activity comparable to FH purified from plasma. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

Structural and functional characterization of the product of disease-related factor H gene conversion.

PubMed

Herbert, Andrew P; Kavanagh, David; Johansson, Conny; Morgan, Hugh P; Blaum, Bärbel S; Hannan, Jonathan P; Barlow, Paul N; Uhrín, Dušan

2012-03-06

Numerous complement factor H (FH) mutations predispose patients to atypical hemolytic uremic syndrome (aHUS) and other disorders arising from inadequately regulated complement activation. No unifying structural or mechanistic consequences have been ascribed to these mutants beyond impaired self-cell protection. The S1191L and V1197A mutations toward the C-terminus of FH, which occur in patients singly or together, arose from gene conversion between CFH encoding FH and CFHR1 encoding FH-related 1. We show that neither single nor double mutations structurally perturbed recombinant proteins consisting of the FH C-terminal modules, 19 and 20 (FH19-20), although all three FH19-20 mutants were poor, compared to wild-type FH19-20, at promoting hemolysis of C3b-coated erythrocytes through competition with full-length FH. Indeed, our new crystal structure of the S1191L mutant of FH19-20 complexed with an activation-specific complement fragment, C3d, was nearly identical to that of the wild-type FH19-20:C3d complex, consistent with mutants binding to C3b with wild-type-like affinity. The S1191L mutation enhanced thermal stability of module 20, whereas the V1197A mutation dramatically decreased it. Thus, although mutant proteins were folded at 37 °C, they differ in conformational rigidity. Neither single substitutions nor double substitutions increased measurably the extent of FH19-20 self-association, nor did these mutations significantly affect the affinity of FH19-20 for three glycosaminoglycans, despite critical roles of module 20 in recognizing polyanionic self-surface markers. Unexpectedly, FH19-20 mutants containing Leu1191 self-associated on a heparin-coated surface to a higher degree than on surfaces coated with dermatan or chondroitin sulfates. Thus, potentially disease-related functional distinctions between mutants, and between FH and FH-related 1, may manifest in the presence of specific glycosaminoglycans.

Molecular Characterization of Human Atypical Sorbitol-Fermenting Enteropathogenic Escherichia coli O157 Reveals High Diversity.

PubMed

Kossow, Annelene; Zhang, Wenlan; Bielaszewska, Martina; Rhode, Sophie; Hansen, Kevin; Fruth, Angelika; Rüter, Christian; Karch, Helge; Mellmann, Alexander

2016-05-01

Alongside the well-characterized enterohemorrhagic Escherichia coli (EHEC) O157:H7, serogroup O157 comprises sorbitol-fermenting typical and atypical enteropathogenic E. coli (EPEC/aEPEC) strains that carry the intimin-encoding gene eae but not Shiga toxin-encoding genes (stx). Since little is known about these pathogens, we characterized 30 clinical isolates from patients with hemolytic uremic syndrome (HUS) or uncomplicated diarrhea with respect to their flagellin gene (fliC) type and multilocus sequence type (MLST). Moreover, we applied whole-genome sequencing (WGS) to determine the phylogenetic relationship with other eae-positive EHEC serotypes and the composition of the rfbO157 region. fliC typing resulted in five fliC types (H7, H16, H34, H39, and H45). Isolates of each fliC type shared a unique ST. In comparison to the 42 HUS-associated E. coli (HUSEC) strains, only the stx-negative isolates with fliCH7 shared their ST with EHEC O157:H7/H(-) strains. With the exception of one O157:H(-) fliCH16 isolate, HUS was exclusively associated with fliCH7. WGS corroborated the separation of the fliCH7 isolates, which were closely related to the EHEC O157:H7/H(-) isolates, and the diverse group of isolates exhibiting different fliC types, indicating independent evolution of the different serotypes. This was also supported by the heterogeneity within the rfbO157 region that exhibited extensive recombinations. The genotypic subtypes and distribution of clinical symptoms suggested that the stx-negative O157 strains with fliCH7 were originally EHEC strains that lost stx The remaining isolates form a distinct and diverse group of atypical EPEC isolates that do not possess the full spectrum of virulence genes, underlining the importance of identifying the H antigen for clinical risk assessment. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

[The revolution of monoclonal antibodies in the treatment of thrombotic microangiopathy].

PubMed

Sauvètre, G; Grange, S; Froissart, A; Veyradier, A; Coppo, P; Benhamou, Y

2015-05-01

Thrombotic microangiopathies (TMA) define a syndrome characterized by the association of microangiopathic haemolytic anaemia with schistocytes, peripheral thrombocytopenia, and organ injury of variable severity. Thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uremic syndrome (HUS) are the main forms of TMA. Recent advances in the pathophysiology of those two diseases, which include in HUS the identification of a deregulation of the alternative complement pathway, and in TTP a severe deficiency in ADAMTS-13, allowed to develop specific, pathophysiology-based therapies. Therefore, rituximab and eculizumab tends to be increasingly used, and there is an urgent need to define consensual modes of administration at the international level, as well as common definitions of response evaluation and follow-up explorations. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Acute Kidney Injury in Pregnancy.

PubMed

Jim, Belinda; Garovic, Vesna D

2017-07-01

Pregnancy-related acute kidney injury (AKI) has declined in incidence in the last three decades, although it remains an important cause of maternal and fetal morbidity and mortality. Pregnancy-related causes of AKI such as preeclampsia, acute fatty liver of pregnancy, HELLP (Hemolysis, Elevated Liver function tests, Low Platelets) syndrome, and the thrombotic microangiopathies (thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome [HUS]) exhibit overlapping features and often present as diagnostic dilemmas. Differentiating among these conditions may be difficult or impossible based on clinical criteria only. In difficult and rare cases, a renal biopsy may need to be considered for the exact diagnosis and to facilitate appropriate treatment, but the risks and benefits need to be carefully weighed. The use of eculizumab for the treatment of atypical HUS has demonstrated efficacy in early case reports. Non-pregnancy related causes such as volume depletion and pyelonephritis require early and aggressive resuscitative as well as antibiotic measures respectively. We will discuss in this review the various etiologies of AKI in pregnancy, current diagnostic approaches, and the latest treatment strategies. Given the recent trends of increasing maternal age at the time of pregnancy, and the availability of modern reproductive methods increase the risks of AKI in pregnancy in the coming years. Copyright © 2017 Elsevier Inc. All rights reserved.

Mold colonization of fiberglass insulation of the air distribution system: effects on patients with hematological malignancies.

PubMed

Takuma, Takahiro; Okada, Kaoru; Yamagata, Akihiro; Shimono, Nobuyuki; Niki, Yoshihito

2011-02-01

We investigated mold colonization of air handling units (AHUs) of heating, ventilating, and air conditioning (HVAC) systems and its effects, including invasive pulmonary mycoses and febrile neutropenia, in patients with hematological malignancies. Sample collection with transparent adhesive tape and culture swabs revealed that AHUs were heavily colonized with molds, including thermotolerant, variously distributed Penicillium spp. Cases of nosocomial invasive pulmonary mycosis were not clustered in specific patient rooms but did occur frequently when the HVAC systems were not in use, prior to intervention (i.e., sealing and disuse of AHUs in private room), and during construction of a new hospital building. Multivariate logistic regression analysis of initial episodes of febrile neutropenia showed that the rate of febrile neutropenia was significantly associated with the duration of neutropenia (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.07-1.27) and with sex (OR: 0.469; CI: 0.239-0.902). An evaluation of private rooms showed that female patients also had a lower rate of fever after intervention (OR: 0.0016; 95% CI: 0.000-0.209). The reduced rate of febrile neutropenia after intervention suggests that mold colonization of AHUs had adverse effects on patients with hematological malignancies.

The Influence of Fisher Knowledge on the Susceptibility of Reef Fish Aggregations to Fishing

PubMed Central

Robinson, Jan; Cinner, Joshua E.; Graham, Nicholas A. J.

2014-01-01

Reef fishes that exhibit predictable aggregating behaviour are often considered vulnerable to overexploitation. However, fisher knowledge of this behaviour is often heterogeneous and, coupled with socioeconomic factors that constrain demand for or access to aggregated fish, will influence susceptibility to fishing. At two case study locations in Papua New Guinea, Ahus and Karkar islands, we conducted interview-based surveys to examine how local context influenced heterogeneity in knowledge of fish aggregations. We then explored the role of fisher knowledge in conferring susceptibility to fishing relative to socioeconomic drivers of fishing effort. Local heterogeneity in knowledge of aggregating behaviour differed between our case studies. At Ahus, variable access rights among fishers and genders to the main habitats were sources of heterogeneity in knowledge. By contrast, knowledge was more homogenous at Karkar and the sole source of variation was gear type. Differences between locations in the susceptibility of aggregations to fishing depended primarily on socioeconomic drivers of fishing effort rather than catchability. While Ahus fishers were knowledgeable of fish aggregations and used more selective gears, Karkar fishers were less constrained by tenure in their access to aggregation habitat. However, fishing effort was greater at Ahus and likely related to high dependency on fishing, greater access to provincial capital markets than Karkar and a weakening of customary management. Moreover, highly efficient fishing techniques have emerged at Ahus to exploit the non-reproductive aggregating behaviour of target species. Understanding how knowledge is structured within fishing communities and its relation to socioeconomic drivers of fishing effort is important if customary practices for conservation, such as tambu areas, are to be supported. The findings of this study call for a holistic approach to assessing the risks posed to reef fish aggregations by fishing, grounded in the principals of fisheries science and emerging social-ecological thinking. PMID:24646910

The influence of fisher knowledge on the susceptibility of reef fish aggregations to fishing.

PubMed

Robinson, Jan; Cinner, Joshua E; Graham, Nicholas A J

2014-01-01

Reef fishes that exhibit predictable aggregating behaviour are often considered vulnerable to overexploitation. However, fisher knowledge of this behaviour is often heterogeneous and, coupled with socioeconomic factors that constrain demand for or access to aggregated fish, will influence susceptibility to fishing. At two case study locations in Papua New Guinea, Ahus and Karkar islands, we conducted interview-based surveys to examine how local context influenced heterogeneity in knowledge of fish aggregations. We then explored the role of fisher knowledge in conferring susceptibility to fishing relative to socioeconomic drivers of fishing effort. Local heterogeneity in knowledge of aggregating behaviour differed between our case studies. At Ahus, variable access rights among fishers and genders to the main habitats were sources of heterogeneity in knowledge. By contrast, knowledge was more homogenous at Karkar and the sole source of variation was gear type. Differences between locations in the susceptibility of aggregations to fishing depended primarily on socioeconomic drivers of fishing effort rather than catchability. While Ahus fishers were knowledgeable of fish aggregations and used more selective gears, Karkar fishers were less constrained by tenure in their access to aggregation habitat. However, fishing effort was greater at Ahus and likely related to high dependency on fishing, greater access to provincial capital markets than Karkar and a weakening of customary management. Moreover, highly efficient fishing techniques have emerged at Ahus to exploit the non-reproductive aggregating behaviour of target species. Understanding how knowledge is structured within fishing communities and its relation to socioeconomic drivers of fishing effort is important if customary practices for conservation, such as tambu areas, are to be supported. The findings of this study call for a holistic approach to assessing the risks posed to reef fish aggregations by fishing, grounded in the principals of fisheries science and emerging social-ecological thinking.

[Apheresis in children: procedures and outcome].

PubMed

Tummolo, Albina; Colella, Vincenzo; Bellantuono, Rosa; Giordano, Mario; Messina, Giovanni; Puteo, Flora; Sorino, Palma; De Palo, Tommaso

2012-01-01

Apheresis procedures are used in children to treat an increasing number of conditions by removing different types of substances from the bloodstream. In a previous study we evaluated the first results of our experience in children, emphasizing the solutions adopted to overcome technical difficulties and to adapt adult apheresis procedures to a pediatric population. The aim of the present study is to present data on a larger number of patients in whom apheresis was the main treatment. Ninety-three children (50 m, 43 f) affected by renal and/or extrarenal diseases were included. They were treated with LDL apheresis, protein A immunoadsorption, or plasma exchange. Our therapeutic protocol was the same as described in the previous study. Renal diseases and immunological disorders remained the most common conditions requiring this therapeutic approach. However, hemolytic uremic syndrome (HUS) was no longer the most frequent renal condition to be treated, as apheresis is currently the first treatment option only in cases of atypical HUS. In this series we also treated small children, showing that low weight should no longer be considered a contraindication to apheresis procedures. The low rate of complications and the overall satisfactory clinical results with increasingly advanced technical procedures make a wider use of apheresis in children realistic in the years to come.

ADAMTS13 Gene Mutations in Children with Hemolytic Uremic Syndrome

PubMed Central

Choi, Hyoung Soo; Cheong, Hae Il; Kim, Nam Keun

2011-01-01

We investigated ADAMTS13 activity as well as the ADAMTS13 gene mutation in children with hemolytic uremic syndrome (HUS). Eighteen patients, including 6 diarrhea-negative (D-HUS) and 12 diarrhea-associated HUS (D+HUS) patients, were evaluated. The extent of von Willebrand factor (VWF) degradation was assayed by multimer analysis, and all exons of the ADAMTS13 gene were PCR-amplified using Taq DNA polymerase. The median and range for plasma activity of ADAMTS13 in 6 D-HUS and 12 D+HUS patients were 71.8% (22.8-94.1%) and 84.9% (37.9-119.9%), respectively, which were not statistically significantly different from the control group (86.4%, 34.2-112.3%) (p>0.05). Five ADAMTS13 gene mutations, including 2 novel mutations [1584+2T>A, 3941C>T (S1314L)] and 3 polymorphisms (Q448E, P475S, S903L), were found in 2 D-HUS and one D+HUS patients, which were not associated with deficiency of ADAMTS13 activity. Whether these mutations without reduced ADAMTS13 activity are innocent bystanders or predisposing factors in HUS remains unanswered. PMID:21488199

Habitat Evaluation Procedures Report; Carl Property - Yakama Nation.

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

Ashley, Paul; Muse, Anthony

A baseline habitat evaluation procedures (HEP) analysis was conducted on the Carl property (160 acres) in June 2007 to determine the number of habitat units to credit Bonneville Power Administration (BPA) for providing funds to acquire the property as partial mitigation for habitat losses associated with construction of McNary Dam. HEP surveys also helped assess the general ecological condition of the property. The Carl property appeared damaged from livestock grazing and exhibited a high percentage of invasive forbs. Exotic grasses, while present, did not comprise a large percentage of the available cover in most areas. Cover types were primarily grassland/shrubsteppemore » with a limited emergent vegetation component. Baseline HEP surveys generated 356.11 HUs or 2.2 HUs per acre. Habitat units were associated with the following HEP models: California quail (47.69 HUs), western meadowlark (114.78 HUs), mallard (131.93 HUs), Canada goose (60.34 HUs), and mink (1.38 HUs).« less

Angiotensinogen and interleukin-18 as markers of chronic kidney damage in children with a history of hemolytic uremic syndrome.

PubMed

Lipiec, K; Adamczyk, P; Świętochowska, E; Ziora, K; Szczepańska, M

2017-05-04

Hemolytic uremic syndrome (HUS) is a type of thrombotic microangiopathy, in the course of which some patients may develop chronic kidney disease (CKD). It is clinically important to investigate the markers of a poor prognosis. The levels of angiotensinogen (AGT) and interleukin-18 (IL-18) in serum and urine were evaluated. Study was conducted in 29 children with a history of HUS. Serum and urine AGT concentration was significantly higher in children after HUS as compared to the control group. No differences depending on the type of HUS and gender were noted. The serum concentration of IL-18 in children after HUS was significantly lower, whereas in urine did not differ significantly between the sick and healthy children. A negative correlation between the concentration of AGT in serum and albuminuria in patients after HUS was detected. The results indicate that the concentration of AGT in serum and urine in children after HUS increases, which may indicate the activation of the intrarenal renin-angiotensin-aldosterone system. The statement, that AGT may be a good biomarker of CKD after acute kidney injury due to HUS requires prospective studies with follow-up from the acute phase of the disease on a larger group of patients. Reduced IL-18 serum concentration in children after HUS with no difference in its urine concentration may indicate a loss of the protective effects of this cytokine on renal function due to previously occurred HUS.

Increased Expression of Complement Regulators CD55 and CD59 on Peripheral Blood Cells in Patients with EAHEC O104:H4 Infection

PubMed Central

Ullrich, Sebastian; Fraedrich, Katharina; Schulze zur Wiesch, Julian; Fründt, Thorben; Tiegs, Gisa; Lohse, Ansgar; Lüth, Stefan

2013-01-01

Background An outbreak of Shiga Toxin 2 (Stx-2) producing enterohemorrhagic and enteroaggregative E.coli (EAHEC) O104H4 infection in May 2011 caused enterocolitis and an unprecedented high 22% rate of hemolytic uremic syndrome (HUS). The monoclonal anti-C5 antibody Eculizumab (ECU) has been used experimentally in EAHEC patients with HUS but treatment efficacy is uncertain. ECU can effectively prevent hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) caused by a lack of complement-regulating CD55 and CD59 on blood cells. We hypothesized a low expression of CD55 and CD59, as seen in PNH, might correlate with HUS development in EAHEC patients. Methods 76 EAHEC patients (34 only gastrointestinal symptoms [GI], 23: HUS, 19: HUS and neurological symptoms [HUS/N]) and 12 healthy controls (HC) were tested for the expression of CD55 and CD59 on erythrocytes and leukocytes retrospectively. Additionally, the effect of Stx-2 on CD55 and CD59 expression on erythrocytes and leukocytes was studied ex vivo. Results CD55 expression on erythrocytes was similar in all patient groups and HC while CD59 showed a significantly higher expression in HUS and HUS/N patients compared to HC and the GI group. CD55 and CD59 expression on leukocytes and their subsets was significantly higher in all patient groups compared to HC regardless of treatment type. However, CD59 expression on erythrocytes was significantly higher in HUS and HUS/N patients treated combined with plasma separation (PS) and ECU compared to HC. Adding Stx-2 ex vivo had no effect on CD55 and CD59 expression on leukocytes from HC or patients. Conclusion HUS evolved independently from CD55 and CD59 expression on peripheral blood cells in EAHEC O104:H4 infected patients. Our data do not support a role for CD55 and CD59 in HUS development during EAHEC O104:H4 infection and point to a different mechanism within the complement system for HUS development in EAHEC patients. PMID:24086391

Increased Urine Production Due to Leg Fluid Displacement Reduces Hours of Undisturbed Sleep.

PubMed

Kiba, Keisuke; Hirayama, Akihide; Yoshikawa, Motokiyo; Yamamoto, Yutaka; Torimoto, Kazumasa; Shimizu, Nobutaka; Tanaka, Nobumichi; Fujimoto, Kiyohide; Uemura, Hirotsugu

2017-07-03

To investigate whether or not the leg fluid displacement observed when moving from the standing to recumbent position at bedtime reduces the hours of undisturbed sleep (HUS). Men aged 50 years or older who were hospitalized for urological diseases were investigated. Body water evaluation was performed three times with a bioelectric impedance method: (i) 17:00, (ii) 30 min after (short-term), and (iii) waking up (long-term). A frequency volume chart was used to evaluate the status of nocturnal urine production, and the factors affecting HUS were investigated. A total of 50 patients (mean age: 68 years) were enrolled. Short-term changes in extracellular fluid (ECF in the legs showed a significant positive correlation with urine production per unit of time at the first nocturnal voiding (UFN/HUS) (r = 0.45, P = 0.01). In the comparison between patients who had <3 HUS vs. those who had ≥3 HUS, the <3 HUS group showed significantly greater short-term changes in leg fluid volume, night-time water intake (17:00-06:00), and UFN/HUS. Multivariate analysis to assess the risk factors for <3 HUS indicated UFN/HUS as a risk factor in the overall model, and short-term changes in leg ECF and night-time water intake as risk factors in the model that only considered factors before sleep. Nocturnal leg fluid displacement may increase urine production leading up to first voiding after going to bed, and consequently, induce early awakening after falling asleep. © 2017 John Wiley & Sons Australia, Ltd.

Shiga Toxin-Producing Escherichia coli Infection, Antibiotics, and Risk of Developing Hemolytic Uremic Syndrome: A Meta-analysis.

PubMed

Freedman, Stephen B; Xie, Jianling; Neufeld, Madisen S; Hamilton, William L; Hartling, Lisa; Tarr, Phillip I; Nettel-Aguirre, Alberto; Chuck, Anderson; Lee, Bonita; Johnson, David; Currie, Gillian; Talbot, James; Jiang, Jason; Dickinson, Jim; Kellner, Jim; MacDonald, Judy; Svenson, Larry; Chui, Linda; Louie, Marie; Lavoie, Martin; Eltorki, Mohamed; Vanderkooi, Otto; Tellier, Raymond; Ali, Samina; Drews, Steven; Graham, Tim; Pang, Xiao-Li

2016-05-15

Antibiotic administration to individuals with Shiga toxin-producing Escherichia coli (STEC) infection remains controversial. We assessed if antibiotic administration to individuals with STEC infection is associated with development of hemolytic uremic syndrome (HUS). The analysis included studies published up to 29 April 2015, that provided data from patients (1) with STEC infection, (2) who received antibiotics, (3) who developed HUS, and (4) for whom data reported timing of antibiotic administration in relation to HUS. Risk of bias was assessed; strength of evidence was adjudicated. HUS was the primary outcome. Secondary outcomes restricted the analysis to low-risk-of-bias studies employing commonly used HUS criteria. Pooled estimates of the odds ratio (OR) were obtained using random-effects models. Seventeen reports and 1896 patients met eligibility; 8 (47%) studies were retrospective, 5 (29%) were prospective cohort, 3 (18%) were case-control, and 1 was a trial. The pooled OR, including all studies, associating antibiotic administration and development of HUS was 1.33 (95% confidence interval [CI], .89-1.99; I(2) = 42%). The repeat analysis including only studies with a low risk of bias and those employing an appropriate definition of HUS yielded an OR of 2.24 (95% CI, 1.45-3.46; I(2) = 0%). Overall, use of antibiotics was not associated with an increased risk of developing HUS; however, after excluding studies at high risk of bias and those that did not employ an acceptable definition of HUS, there was a significant association. Consequently, the use of antibiotics in individuals with STEC infections is not recommended. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

[Verotoxin-producing Escherichia coli: quantitative model of exposure and risk scenarios in cattle carcasses in Argentina].

PubMed

Olvera, Adib; Signorini, Marcelo; Tarabla, Héctor

2010-06-01

Quantify contamination by verotoxin-producing Escherichia coli associated with hemolytic uremic syndrome (VTEC-HUS) in cattle carcasses and generate estimates of exposure in three likely scenarios. A model was constructed of the frequency and magnitude of VTEC-HUS contamination from primary production to the removal of the carcasses from cold storage, based on the published scientific information, epidemiological data, and information from local experts. The probability distributions that best described each step in the process and scenarios were input to the @Risk program with multiple simulations using Monte Carlo analysis. Pearson s correlation test was used for the sensitivity analysis. The estimated frequency of carcasses with VTEC-HUS was 0.37 (95% CI: 0.26 to 0.58) and the final load of VTEC-HUS was 0.47 log CFU/carcass (95% CI: -2.46 to 3.62). The most closely related variables were the fattening system (r = -0.681) and the theoretical concentration of VTEC-HUS on the cattle's skin (r = 0.702). Vaccinating the animals reduced the frequency of VTEC-HUS in the carcasses by 54.1%, although there were no significant changes in the final VTEC-HUS load. Washing the carcasses reduced the final load by 0.42 log CFU/carcass compared with the baseline model, without any change in the frequency. A 50%-60% increase in the percentage of animals fattened in pens would increase the frequency of carcasses contaminated with VTEC-HUS by 15%-23%. Vaccinating the animals was the most effective scenario for reducing introduction of the bacteria in the beef production chain. Intensifying livestock production will increase the public health risk due to greater exposure to VTEC-HUS.

Relative nephroprotection during Escherichia coli O157:H7 infections: association with intravenous volume expansion.

PubMed

Ake, Julie A; Jelacic, Srdjan; Ciol, Marcia A; Watkins, Sandra L; Murray, Karen F; Christie, Dennis L; Klein, Eileen J; Tarr, Phillip I

2005-06-01

The hemolytic uremic syndrome (HUS) consists of hemolytic anemia, thrombocytopenia, and renal failure. HUS is often precipitated by gastrointestinal infection with Shiga toxin-producing Escherichia coli and is characterized by a variety of prothrombotic host abnormalities. In much of the world, E coli O157:H7 is the major cause of HUS. HUS can be categorized as either oligoanuric (which probably signifies acute tubular necrosis) or nonoligoanuric. Children with oligoanuric renal failure during HUS generally require dialysis, have more complicated courses, and are probably at increased risk for chronic sequelae than are children who experience nonoligoanuric HUS. Oligoanuric HUS should be avoided, if possible. The presentation to medical care of a child with definite or possible E coli O157:H7 infections but before HUS ensues affords a potential opportunity to ameliorate the course of the subsequent renal failure. However, it is not known whether events that occur early in E coli O157:H7 infections, particularly measures to expand circulating volume, affect the likelihood of experiencing oligoanuric HUS if renal failure develops. We attempted to assess whether pre-HUS interventions and events, especially the volume and sodium content of intravenous fluids administered early in illness, affect the risk for developing oligoanuric HUS after E coli O157:H7 infections. We performed a prospective cohort study of 29 children with HUS that was confirmed microbiologically to be caused by E coli O157:H7. Infected children were enrolled when they presented with acute bloody diarrhea or as contacts of patients who were known to be infected with E coli O157:H7, or if they had culture-confirmed infection, or if they presented with HUS. HUS was defined as hemolytic anemia (hematocrit <30%, with fragmented erythrocytes on peripheral-blood smear), thrombocytopenia (platelet count of <150000/mm3), and renal insufficiency (serum creatinine concentration that exceeded the upper limit of normal for age). A wide range of pre-HUS variables, including demographic factors, clinical history, medications given, initial laboratory values, and volume and content of parenteral fluid administered, were recorded and entered into analysis. Estimates of odds ratios were adjusted for possible confounding effects using logistic regression analysis. Twenty-nine children who were <10 years old, had HUS confirmed to be caused by E coli O157:H7, and were hospitalized at the Children's Hospital and Regional Medical Center, Seattle, were studied. The main outcome measured was development of oligoanuric renal failure. Oligoanuria was defined as a urine output <0.5 mL/kg per hour for at least 24 consecutive hours. As a group, the children with oligoanuric renal failure presented to medical attention and were evaluated with laboratory testing later than the children with nonoligoanuric renal failure. On initial assessments, the children with oligoanuric outcomes had higher white blood cell counts, lower platelet counts and hematocrits, and higher creatinine concentrations than the children with nonoligoanuric outcomes, but these determinations probably reflect later points of these initial determinations, often when HUS was already developing. Stool cultures were obtained (medians of 3 vs 2 days, respectively) and positive (medians of 7 vs 4 days, respectively) at later points in illness in the children in the oligoanuric than in the nonoligoanuric group. Intravenous volume expansion began later in illness in the children who subsequently developed oligoanuric renal failure than in those whose renal failure was nonoligoanuric (medians: 4.5 vs 3.0 days, respectively). Moreover, the 13 patients with nonoligoanuric renal failure received more intravenous fluid and sodium before HUS developed (1.7- and 2.5-fold differences, respectively, between medians) than the 16 patients with oligoanuric renal failure. These differences were even greater when the first 4 days of illness were examined, with 17.1- and 21.8-fold differences, respectively, between medians. In a multivariate analysis adjusted for age, gender, antibiotic use, and free water volume administered intravenously to these children during the first 4 days of illness, the amount of sodium infused remained associated with protection against developing oligoanuric HUS. Dialysis was used in each of the children with oligoanuric renal failure and in none of the children with nonoligoanuric renal failure. The median length of stay in hospital after the diagnosis of HUS was 12 days in the oligoanuric group and 6 days in the nonoligoanuric group. Early recognition of and parenteral volume expansion during E coli O157:H7 infections, well before HUS develops, is associated with attenuated renal injury failure. Parenteral hydration in children who are possibly infected with E coli O157:H7, at the time of presentation with bloody diarrhea and in advance of culture results, is a practice that can accelerate the start of volume expansion during the important pre-HUS interval. Rapid assessment of stools for E coli O157:H7 by microbiologists and reporting of presumptive positives immediately can alert practitioners that patients are at risk for developing HUS and can prompt volume expansion in children who are not already being so treated. Our data also suggest that isotonic intravenous solutions might be superior to hypotonic fluids for use as maintenance fluids. Children who are infected with E coli O157:H7 and are given intravenous volume expansion need careful monitoring. This monitoring should be even more assiduous as HUS evolves.

L-FABP and IL-6 as markers of chronic kidney damage in children after hemolytic uremic syndrome.

PubMed

Lipiec, Katarzyna; Adamczyk, Piotr; Świętochowska, Elżbieta; Ziora, Katarzyna; Szczepańska, Maria

2018-06-13

Hemolytic-uremic syndrome (HUS) is a form of thrombotic microangiopathy, in the course of which some patients may develop chronic kidney disease (CKD). From a clinical point of view, it is important to search for markers that allow for early identification of patients at risk of a poor prognosis. The study evaluated the serum and urine levels of liver-type fatty acid binding protein (L-FABP) and interleukin 6 (IL-6). The study was conducted in 29 children with a history of HUS. The relationship between L-FABP and IL-6 and anthropometric measurements, the value of estimated glomerular filtration rate (eGFR) and albuminuria were additionally evaluated. In children after HUS, L-FABP and IL-6 concentration in both serum and urine was significantly higher in comparison to the control group. No differences in L-FABP and IL-6 concentration in serum and urine depending on the type of HUS and gender were noted. Correlation between L-FABP and IL-6 in serum and urine with eGFR and urine albumin-creatinine ratio (ACR) in the total group of patients after HUS was not detected. In the group of children after 6 month observation after HUS, a negative correlation of L-FABP concentration with eGFR was found. The results indicate that the higher concentration of L-FABP in serum and urine of children with a history of HUS can be the result of protracted injury initiated during the acute phase of the disease. Lack of correlation of L-FABP concentration with the ACR may be associated with a short (less than 6 months) observation after acute renal failure or merely temporary renal tubular damage in the acute phase of the disease. In contrast, higher levels of IL-6 in serum and urine in children after HUS compared to healthy children and the negative correlation of L-FABP concentration and eGFR in children after 6 month observation after HUS may confirm their participation in CKD. Thus, L-FABP and IL-6 seem to be good biomarkers of chronic kidney damage in survivors of the acute phase of HUS.

Endemic Esherichia coil O157:H7 infections and hemolytic-uremic syndrome in Oklahoma, 2002-2005.

PubMed

Karpac, Charity A; Lee, Anthony; Kunnel, Binitha S; Bamgbola, Oluwatoyin F; Vesely, Sara K; George, James N

2007-11-01

Hemorrhagic enterocolitis caused by Escherichia coli O157:H7 and its complication of hemolytic-uremic syndrome (HUS) are well known from large outbreaks caused by contaminated meats and vegetables. However most cases may be endemic, not related to an outbreak. We identified cases of HUS in Oklahoma, 2002-2005, from the Inpatient Hospital Discharge Database of the Oklahoma State Department of Health (OSDH) and also the cases of HUS and E. coli O157:H7 reported to the OSDH. 110 cases of HUS were identified from the hospital discharge database; only 14 (12.7%) were reported to the OSDH; 122 cases of E. coli O157:H7 infections were reported to the OSDH. Of the 110 cases of HUS, only six (5.5%) patients in two separate clusters may have had a common source of infection. Although interpretation is limited by the few reports to OSDH, our data suggest that E. coli O157:H7 infections and HUS, presumably related to contaminated food, are endemic throughout Oklahoma.

Monocyte chemoattractant protein-1 and interleukin-8 levels in urine and serum of patents with hemolytic uremic syndrome.

PubMed

van Setten, P A; van Hinsbergh, V W; van den Heuvel, L P; Preyers, F; Dijkman, H B; Assmann, K J; van der Velden, T J; Monnens, L A

1998-06-01

The epidemic form of the hemolytic uremic syndrome (HUS) in children is hallmarked by endothelial cell damage, most predominantly displayed by the glomerular capillaries. The influx of mononuclear (MO) and polymorphonuclear cells (PMNs) into the glomeruli may be an important event in the initiation, prolongation, and progression of glomerular endothelial cell damage in HUS patients. The molecular mechanisms for the recruitment of these leukocytes into the kidney are unclear, but monocyte chemoattractant protein-1 (MCP-1) and IL-8 are suggested to be prime candidates. In this study, we analyzed the presence of both chemokines in 24-h urinary (n = 15) and serum (n = 14) samples of HUS children by specific ELISAs. Furthermore, kidney biopsies of three different HUS children were examined for MO and PMN cell infiltration by histochemical techniques and electron microscopy. Whereas the chemokines MCP-1 and IL-8 were present in only very limited amounts in urine of 17 normal control subjects, serial samples of HUS patients demonstrated significantly elevated levels of both chemokines. HUS children with anuria showed higher initial and maximum chemokine levels than their counterparts without anuria. A strong positive correlation was observed between urinary MCP-1 and IL-8 levels. Whereas initial serum IL-8 levels were significantly increased in HUS children, serum MCP-1 levels were only slightly elevated compared with serum MCP-1 in control children. No correlation was found between urinary and serum chemokine concentrations. Histologic and EM studies of HUS biopsy specimens clearly showed the presence of MOs and to a lesser extent of PMNs in the glomeruli. The present data suggest an important local role for MOs and PMNs in the process of glomerular endothelial-cell damage. The chemokines MCP-1 and IL-8 may possibly be implicated in the pathogenesis of HUS through the recruitment and activation of MOs and PMNs, respectively.

Antibody Response to Shiga Toxins in Argentinean Children with Enteropathic Hemolytic Uremic Syndrome at Acute and Long-Term Follow-Up Periods

PubMed Central

Fernández-Brando, Romina J.; Bentancor, Leticia V.; Mejías, María Pilar; Ramos, María Victoria; Exeni, Andrea; Exeni, Claudia; Laso, María del Carmen; Exeni, Ramón; Isturiz, Martín A.; Palermo, Marina S.

2011-01-01

Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is associated with a broad spectrum of clinical manifestations that include diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Systemic Stx toxemia is considered to be central to the genesis of HUS. Distinct methods have been used to evaluate anti-Stx response for immunodiagnostic or epidemiological analysis of HUS cases. The development of enzyme-linked immunosorbent assay (ELISA) and western blot (WB) assay to detect the presence of specific antibodies to Stx has introduced important advantages for serodiagnosis of HUS. However, application of these methods for seroepidemiological studies in Argentina has been limited. The aim of this work was to develop an ELISA to detect antibodies against the B subunit of Stx2, and a WB to evaluate antibodies against both subunits of Stx2 and Stx1, in order to analyze the pertinence and effectiveness of these techniques in the Argentinean population. We studied 72 normal healthy children (NHC) and 105 HUS patients of the urban pediatric population from the surrounding area of Buenos Aires city. Using the WB method we detected 67% of plasma from NHC reactive for Stx2, but only 8% for Stx1. These results are in agreement with the broad circulation of Stx2-expressing STEC in Argentina and the endemic behavior of HUS in this country. Moreover, the simultaneous evaluation by the two methods allowed us to differentiate acute HUS patients from NHC with a great specificity and accuracy, in order to confirm the HUS etiology when pathogenic bacteria were not isolated from stools. PMID:21559455

End-stage renal disease from hemolytic uremic syndrome in the United States, 1995-2010.

PubMed

Sexton, Donal J; Reule, Scott; Solid, Craig A; Chen, Shu-Cheng; Collins, Allan J; Foley, Robert N

2015-10-01

Management of hemolytic uremic syndrome (HUS) has evolved rapidly, and optimal treatment strategies are controversial. However, it is unknown whether the burden of end-stage renal disease (ESRD) from HUS has changed, and outcomes on dialysis in the United States are not well described. We retrospectively examined data for patients initiating maintenance renal replacement therapy (RRT) (n = 1,557,117), 1995-2010, to define standardized incidence ratios (SIRs) and outcomes of ESRD from HUS) (n = 2241). Overall ESRD rates from HUS in 2001-2002 were 0.5 cases/million per year and were higher for patients characterized by age 40-64 years (0.6), ≥65 years (0.7), female sex (0.6), and non-Hispanic African American race (0.7). Standardized incidence ratios remained unchanged (P ≥ 0.05) between 2001-2002 and 2009-2010 in the overall population. Compared with patients with ESRD from other causes, patients with HUS were more likely to be younger, female, white, and non-Hispanic. Over 5.4 years of follow-up, HUS patients differed from matched controls with ESRD from other causes by lower rates of death (8.3 per 100 person-years in cases vs. 10.4 in controls, P < 0.001), listing for renal transplant (7.6 vs. 8.6 per 100 person-years, P = 0.04), and undergoing transplant (6.9 vs. 9 per 100 person-years, P < 0.001). The incidence of ESRD from HUS appears not to have risen substantially in the last decade. However, given that HUS subtypes could not be determined in this study, these findings should be interpreted with caution. © 2015 International Society for Hemodialysis.

A novel strategy for hemolytic uremic syndrome: successful treatment with thrombomodulin α.

PubMed

Honda, Takashi; Ogata, Shohei; Mineo, Eri; Nagamori, Yukako; Nakamura, Shinya; Bando, Yuki; Ishii, Masahiro

2013-03-01

Hemolytic uremic syndrome (HUS) is a life-threatening infectious disease in childhood for which there is no confirmed therapeutic strategy. Endothelial inflammation leading to microthrombosis formation via complement activation is the main pathology of HUS. Thrombomodulin is an endothelial membrane protein that has anticoagulation and anti-inflammatory effects, including the suppression of complement activity. Recombinant human soluble thrombomodulin (rTM) is a novel therapeutic medicine for disseminated intravascular coagulation. We administered rTM to 3 patients with HUS for 7 days and investigated the outcomes in view of the patients' prognoses, changes in biochemical markers, complications, and adverse effects of rTM. Symptoms and laboratory data improved after initiation of rTM in all 3 patients. Abnormal activation of complements was also dramatically suppressed in 1 patient. The patients recovered without any complications or adverse effects of rTM. They were discharged having normal neurologic status and with no renal dysfunction. To our knowledge, this is the first report of rTM being used to treat HUS. These case reports show the positive effect of rTM in patients with HUS. Randomized controlled studies should be performed to assess the efficacy and safety of rTM for children with HUS.

Hemolytic-uremic syndrome in adolescents.

PubMed

Siegler, R L; Pavia, A T; Cook, J B

1997-02-01

To compare the epidemiological characteristics, clinical features, and outcome of adolescents with hemolytic-uremic syndrome (HUS) with those of children with HUS. A retrospective descriptive study using data stored in the computerized Utah HUS registry. The HUS registry contains data on postdiarrheal and nondiarrheal HUS cases since 1970 in which the patients were younger than 18 years of age at the time of diagnosis and includes virtually all Utah cases as well as those referred from surrounding states. Seventeen adolescents (age, 12-17 years) and 276 younger patients from September 30, 1970, through December 5, 1993, who met the diagnostic criteria for HUS. Age, sex, seasonality, prodromal features (eg, antecedent diarrhea), laboratory values, hospital course, outcome, and chronic sequelae. The 17 adolescent patients, who composed 5.8% of the study population, experienced a course of the disease that was similar to that of the younger patients. Diarrhea preceded HUS in approximately 90% of the patients in both groups. Laboratory values were similar in teenagers and younger patients. The hospital courses were also similar; seizures occurred in almost 20%, and hypertension and oligoanuric renal failure occurred in most. Two (12%) of the teenagers and 7 (2.4%) of the younger patients died during the acute phase of the syndrome (P = .09); almost 50% of both groups experienced 1 or more chronic renal sequelae. End-stage renal disease has occurred in 1 (5.8%) of the teenagers and 6 (2.2%) of the children. At follow-up, 1 or more years (median, 5 years) after the onset of HUS, hypertension was present in 22% of the teenagers and 6.7% of the preteens (P = .14). A below-normal glomerular filtration rate was seen in approximately 30% of both groups; proteinuria was noted in approximately 25% of both groups. Approximately 10% of both groups had a combination of proteinuria and a low glomerular filtration rate and are, therefore, at risk for eventual end-stage renal disease. In our region of the Intermountain West, HUS in adolescents closely resembles that seen in children and the outcome is more favorable than that experienced by adults.

Hemolytic Uremic Syndrome-associated Encephalopathy Successfully Treated with Corticosteroids.

PubMed

Hosaka, Takashi; Nakamagoe, Kiyotaka; Tamaoka, Akira

2017-11-01

The encephalopathy that occurs in association with hemolytic uremic syndrome (HUS), which is caused by enterohemorrhagic Escherichia coli (E. coli), has a high mortality rate and patients sometimes present sequelae. We herein describe the case of a 20-year-old woman who developed encephalopathy during the convalescent stage of HUS caused by E.coli O26. Hyperintense lesions were detected in the pons, basal ganglia, and cortex on diffusion-weighted brain MRI. From the onset of HUS encephalopathy, we treated the patient with methylprednisolone (mPSL) pulse therapy alone. Her condition improved, and she did not present sequelae. Our study shows that corticosteroids appear to be effective for the treatment of some patients with HUS encephalopathy.

West Foster Creek 2007 Follow-up Habitat Evaluation Procedures (HEP) Report.

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

Ashley, Paul R.

A follow-up habitat evaluation procedures (HEP) analysis was conducted on the West Foster Creek (Smith acquisition) wildlife mitigation site in May 2007 to determine the number of additional habitat units to credit Bonneville Power Administration (BPA) for providing funds to enhance and maintain the project site as partial mitigation for habitat losses associated with construction of Grand Coulee Dam. The West Foster Creek 2007 follow-up HEP survey generated 2,981.96 habitat units (HU) or 1.51 HUs per acre for a 34% increase (+751.34 HUs) above baseline HU credit (the 1999 baseline HEP survey generated 2,230.62 habitat units or 1.13 HUs permore » acre). The 2007 follow-up HEP analysis yielded 1,380.26 sharp-tailed grouse (Tympanuchus phasianellus) habitat units, 879.40 mule deer (Odocoileus hemionus) HUs, and 722.29 western meadowlark (Sturnella neglecta) habitat units. Mule deer and sharp-tailed grouse habitat units increased by 346.42 HUs and 470.62 HUs respectively over baseline (1999) survey results due largely to cessation of livestock grazing and subsequent passive restoration. In contrast, the western meadowlark generated slightly fewer habitat units in 2007 (-67.31) than in 1999, because of increased shrub cover, which lowers habitat suitability for that species.« less

Epidemiological and Ecological Characterization of the EHEC O104:H4 Outbreak in Hamburg, Germany, 2011

PubMed Central

Tahden, Maike; Manitz, Juliane; Baumgardt, Klaus; Fell, Gerhard; Kneib, Thomas; Hegasy, Guido

2016-01-01

In 2011, a large outbreak of entero-hemorrhagic E. coli (EHEC) and hemolytic uremic syndrome (HUS) occurred in Germany. The City of Hamburg was the first focus of the epidemic and had the highest incidences among all 16 Federal States of Germany. In this article, we present epidemiological characteristics of the Hamburg notification data. Evaluating the epicurves retrospectively, we found that the first epidemiological signal of the outbreak, which was in form of a HUS case cluster, was received by local health authorities when already 99 EHEC and 48 HUS patients had experienced their first symptoms. However, only two EHEC and seven HUS patients had been notified. Middle-aged women had the highest risk for contracting the infection in Hamburg. Furthermore, we studied timeliness of case notification in the course of the outbreak. To analyze the spatial distribution of EHEC/HUS incidences in 100 districts of Hamburg, we mapped cases' residential addresses using geographic information software. We then conducted an ecological study in order to find a statistical model identifying associations between local socio-economic factors and EHEC/HUS incidences in the epidemic. We employed a Bayesian Poisson model with covariates characterizing the Hamburg districts as well as incorporating structured and unstructured spatial effects. The Deviance Information Criterion was used for stepwise variable selection. We applied different modeling approaches by using primary data, transformed data, and preselected subsets of transformed data in order to identify socio-economic factors characterizing districts where EHEC/HUS outbreak cases had their residence. PMID:27723830

Stable and low diffusive hybrid upwind splitting methods

NASA Technical Reports Server (NTRS)

Coquel, Frederic; Liou, Meng-Sing

1992-01-01

A new concept for upwinding is introduced, named the hybrid upwind splitting (HUS), which is achieved by combining the basically distinct flux vector splitting (FVS) and the flux difference splitting (FDS) approaches. The HUS approach yields upwind methods which share the robustness of the FVS schemes in the capture of nonlinear waves and the accuracy of some of the FDS schemes. Numerical illustrations are presented proving the relevance of the HUS methods for viscous calculations.

Hybrid Upwind Splitting (HUS) by a Field-by-Field Decomposition

NASA Technical Reports Server (NTRS)

Coquel, Frederic; Liou, Meng-Sing

1995-01-01

We introduce and develop a new approach for upwind biasing: the hybrid upwind splitting (HUS) method. This original procedure is based on a suitable hybridization of current prominent flux vector splitting (FVS) and flux difference splitting (FDS) methods. The HUS method is designed to naturally combine the respective strengths of the above methods while excluding their main deficiencies. Specifically, the HUS strategy yields a family of upwind methods that exhibit the robustness of FVS schemes in the capture of nonlinear waves and the accuracy of some FDS schemes in the resolution of linear waves. We give a detailed construction of the HUS methods following a general and systematic procedure directly performed at the basic level of the field by field (i.e. waves) decomposition involved in FDS methods. For such a given decomposition, each field is endowed either with FVS or FDS numerical fluxes, depending on the nonlinear nature of the field under consideration. Such a design principle is made possible thanks to the introduction of a convenient formalism that provides us with a unified framework for upwind methods. The HUS methods we propose bring significant improvements over current methods in terms of accuracy and robustness. They yield entropy-satisfying approximate solutions as they are strongly supported in numerical experiments. Field by field hybrid numerical fluxes also achieve fairly simple and explicit expressions and hence require a computational effort between that of the FVS and FDS. Several numerical experiments ranging from stiff 1D shock-tube to high speed viscous flows problems are displayed, intending to illustrate the benefits of the present approach. We assess in particular the relevance of our HUS schemes to viscous flow calculations.

Evaluation of lymph node perfusion using continuous mode harmonic ultrasonography with a second-generation contrast agent.

PubMed

Rubaltelli, Leopoldo; Khadivi, Yeganeh; Tregnaghi, Alberto; Stramare, Roberto; Ferro, Federica; Borsato, Simonetta; Fiocco, Ugo; Adami, Fausto; Rossi, Carlo Riccardo

2004-06-01

To evaluate the contribution of continuous mode contrast-enhanced harmonic ultrasonography (CE-HUS) with a second-generation contrast agent to the characterization of superficial lymphadenopathies with respect to conventional ultrasonographic techniques (B-mode and power Doppler). Fifty-six lymph nodes from 45 patients were studied both by conventional techniques and by CE-HUS. The dimensions, intranodal architecture, margins, and location of vessels were evaluated. Subsequently, all the lymph nodes were examined by CE-HUS, and enhancement of echogenicity was evaluated. The diagnoses obtained by means of fine-needle aspiration cytologic examination, surgical biopsy, or both were compared with those obtained by ultrasonography. Of the lymph nodes examined, 30 were benign and 26 were malignant (18 metastases and 8 non-Hodgkin lymphomas). The study using CE-HUS showed intense homogeneous enhancement in 28 of 30 reactive lymph nodes; perfusion defects in 17, of which 15 were neoplastic and 2 were inflammatory; intense but inhomogeneous speckled enhancement in the early arterial phase in 5 cases of lymphoma; and, last, scarce or absent intranodal enhancement in 4 metastases. The specificity, sensitivity, and accuracy of conventional techniques in differentiation between benign and malignant lymph nodes were 76%, 80%, and 78% versus 93%, 92%, and 92.8% for CE-HUS. The increase in correct diagnoses was significant (P = .05) when conventional ultrasonography was tested against CE-HUS. Superficial lymph nodes can be characterized as being neoplastic or benign with a high degree of diagnostic accuracy on the basis of the perfusion characteristics evaluated by CE-HUS. This technique has been shown to afford a higher degree of accuracy than currently obtainable by any other ultrasonographic technique.

[Difficulties in the diagnosis of diarrhea-associated hemolytic uremic syndrome in adults].

PubMed

Malov, V A; Maleev, V V; Kozlovskaya, N L; Tsvetkova, N A; Smetanina, S V; Gorobchenko, A N; Serova, V V; Chentsov, V B; Volkov, A G; Faller, A P

Hemolytic uremic syndrome (HUS) is a rare, but menacing condition registered mainly in children. The paper gives a detailed description and analysis of a clinical case of HUS with a favorable outcome in an adult woman who developed the syndrome in the presence of bloody diarrhea. It considers an update on the etiology, pathogenesis, and clinical features of HUS associated with diarrheal syndrome and discusses differential diagnostic features, diagnostic problems, and characteristics of management tactics for patients.

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

Korhonen, Juha, E-mail: juha.p.korhonen@hus.fi; Kapanen, Mika; Department of Oncology, Helsinki University Central Hospital, POB-180, 00029 HUS

Purpose: The lack of electron density information in magnetic resonance images (MRI) poses a major challenge for MRI-based radiotherapy treatment planning (RTP). In this study the authors convert MRI intensity values into Hounsfield units (HUs) in the male pelvis and thus enable accurate MRI-based RTP for prostate cancer patients with varying tissue anatomy and body fat contents. Methods: T{sub 1}/T{sub 2}*-weighted MRI intensity values and standard computed tomography (CT) image HUs in the male pelvis were analyzed using image data of 10 prostate cancer patients. The collected data were utilized to generate a dual model HU conversion technique from MRImore » intensity values of the single image set separately within and outside of contoured pelvic bones. Within the bone segment local MRI intensity values were converted to HUs by applying a second-order polynomial model. This model was tuned for each patient by two patient-specific adjustments: MR signal normalization to correct shifts in absolute intensity level and application of a cutoff value to accurately represent low density bony tissue HUs. For soft tissues, such as fat and muscle, located outside of the bone contours, a threshold-based segmentation method without requirements for any patient-specific adjustments was introduced to convert MRI intensity values into HUs. The dual model HU conversion technique was implemented by constructing pseudo-CT images for 10 other prostate cancer patients. The feasibility of these images for RTP was evaluated by comparing HUs in the generated pseudo-CT images with those in standard CT images, and by determining deviations in MRI-based dose distributions compared to those in CT images with 7-field intensity modulated radiation therapy (IMRT) with the anisotropic analytical algorithm and 360° volumetric-modulated arc therapy (VMAT) with the Voxel Monte Carlo algorithm. Results: The average HU differences between the constructed pseudo-CT images and standard CT images of each test patient ranged from −2 to 5 HUs and from 22 to 78 HUs in soft and bony tissues, respectively. The average local absolute value differences were 11 HUs in soft tissues and 99 HUs in bones. The planning target volume doses (volumes 95%, 50%, 5%) in the pseudo-CT images were within 0.8% compared to those in CT images in all of the 20 treatment plans. The average deviation was 0.3%. With all the test patients over 94% (IMRT) and 92% (VMAT) of dose points within body (lower than 10% of maximum dose suppressed) passed the 1 mm and 1% 2D gamma index criterion. The statistical tests (t- and F-tests) showed significantly improved (p ≤ 0.05) HU and dose calculation accuracies with the soft tissue conversion method instead of homogeneous representation of these tissues in MRI-based RTP images. Conclusions: This study indicates that it is possible to construct high quality pseudo-CT images by converting the intensity values of a single MRI series into HUs in the male pelvis, and to use these images for accurate MRI-based prostate RTP dose calculations.« less

A dual model HU conversion from MRI intensity values within and outside of bone segment for MRI-based radiotherapy treatment planning of prostate cancer

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

Korhonen, Juha, E-mail: juha.p.korhonen@hus.fi; Department of Oncology, Helsinki University Central Hospital, POB-180, 00029 HUS; Kapanen, Mika

2014-01-15

Purpose: The lack of electron density information in magnetic resonance images (MRI) poses a major challenge for MRI-based radiotherapy treatment planning (RTP). In this study the authors convert MRI intensity values into Hounsfield units (HUs) in the male pelvis and thus enable accurate MRI-based RTP for prostate cancer patients with varying tissue anatomy and body fat contents. Methods: T{sub 1}/T{sub 2}*-weighted MRI intensity values and standard computed tomography (CT) image HUs in the male pelvis were analyzed using image data of 10 prostate cancer patients. The collected data were utilized to generate a dual model HU conversion technique from MRImore » intensity values of the single image set separately within and outside of contoured pelvic bones. Within the bone segment local MRI intensity values were converted to HUs by applying a second-order polynomial model. This model was tuned for each patient by two patient-specific adjustments: MR signal normalization to correct shifts in absolute intensity level and application of a cutoff value to accurately represent low density bony tissue HUs. For soft tissues, such as fat and muscle, located outside of the bone contours, a threshold-based segmentation method without requirements for any patient-specific adjustments was introduced to convert MRI intensity values into HUs. The dual model HU conversion technique was implemented by constructing pseudo-CT images for 10 other prostate cancer patients. The feasibility of these images for RTP was evaluated by comparing HUs in the generated pseudo-CT images with those in standard CT images, and by determining deviations in MRI-based dose distributions compared to those in CT images with 7-field intensity modulated radiation therapy (IMRT) with the anisotropic analytical algorithm and 360° volumetric-modulated arc therapy (VMAT) with the Voxel Monte Carlo algorithm. Results: The average HU differences between the constructed pseudo-CT images and standard CT images of each test patient ranged from −2 to 5 HUs and from 22 to 78 HUs in soft and bony tissues, respectively. The average local absolute value differences were 11 HUs in soft tissues and 99 HUs in bones. The planning target volume doses (volumes 95%, 50%, 5%) in the pseudo-CT images were within 0.8% compared to those in CT images in all of the 20 treatment plans. The average deviation was 0.3%. With all the test patients over 94% (IMRT) and 92% (VMAT) of dose points within body (lower than 10% of maximum dose suppressed) passed the 1 mm and 1% 2D gamma index criterion. The statistical tests (t- and F-tests) showed significantly improved (p ≤ 0.05) HU and dose calculation accuracies with the soft tissue conversion method instead of homogeneous representation of these tissues in MRI-based RTP images. Conclusions: This study indicates that it is possible to construct high quality pseudo-CT images by converting the intensity values of a single MRI series into HUs in the male pelvis, and to use these images for accurate MRI-based prostate RTP dose calculations.« less

Whole-Genome Characterization and Strain Comparison of VT2f-Producing Escherichia coli Causing Hemolytic Uremic Syndrome

PubMed Central

Michelacci, Valeria; Bondì, Roslen; Gigliucci, Federica; Franz, Eelco; Badouei, Mahdi Askari; Schlager, Sabine; Minelli, Fabio; Tozzoli, Rosangela; Caprioli, Alfredo; Morabito, Stefano

2016-01-01

Verotoxigenic Escherichia coli infections in humans cause disease ranging from uncomplicated intestinal illnesses to bloody diarrhea and systemic sequelae, such as hemolytic uremic syndrome (HUS). Previous research indicated that pigeons may be a reservoir for a population of verotoxigenic E. coli producing the VT2f variant. We used whole-genome sequencing to characterize a set of VT2f-producing E. coli strains from human patients with diarrhea or HUS and from healthy pigeons. We describe a phage conveying the vtx2f genes and provide evidence that the strains causing milder diarrheal disease may be transmitted to humans from pigeons. The strains causing HUS could derive from VT2f phage acquisition by E. coli strains with a virulence genes asset resembling that of typical HUS-associated verotoxigenic E. coli. PMID:27584691

Associations Between Hydration Status, Intravenous Fluid Administration, and Outcomes of Patients Infected With Shiga Toxin-Producing Escherichia coli: A Systematic Review and Meta-analysis.

PubMed

Grisaru, Silviu; Xie, Jianling; Samuel, Susan; Hartling, Lisa; Tarr, Phillip I; Schnadower, David; Freedman, Stephen B

2017-01-01

The associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin-producing Escherichia coli (STEC) remain unclear. To determine the relationship between hydration status, the development and severity of hemolytic uremic syndrome (HUS), and adverse outcomes in STEC-infected individuals. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials via the OvidSP platform, PubMed via the National Library of Medicine, CINAHL Plus with full text, Scopus, Web of Science, ClinicalTrials.gov, reference lists, and gray literature were systematically searched. Two reviewers independently identified studies that included patients with hydration status documentation, proven or presumed STEC infection, and some form of HUS that developed. No language restrictions were applied. Two reviewers independently extracted individual study data, including study characteristics, population, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale; strength of evidence was adjudicated using the Grading of Recommendations Assessment, Development, and Evaluation method. Meta-analyses were conducted using random-effects models. Development of HUS, complications (ie, oligoanuric renal failure, involvement of the central nervous system, or death), and interventions (ie, renal replacement therapy). Eight studies comprising 1511 patients (all children) met eligibility criteria. Unpublished data were provided by the authors of 7 published reports. The median risk-of-bias score was 7.5 (range, 6-9). No studies evaluated the effect of hydration during STEC infections on the risk for HUS. A hematocrit value greater than 23% as a measure of hydration status at presentation with HUS was associated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95% CI, 1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95% CI, 1.50-17.57]; I2 = 55%). Compared with putatively hydrated patients, clinically dehydrated patients had an OR of death of 3.71 (95% CI, 1.25-11.03; I2 = 0%). Intravenous fluid administration up to the day of HUS diagnosis was associated with a decreased risk of renal replacement therapy (OR, 0.26 [95% CI, 0.11-0.60]). Two predictors of poor outcomes for STEC-infected children were identified: (1) the lack of intravenous fluid administration prior to establishment of HUS and (2) a higher hematocrit value at presentation. These findings point to an association between dehydration and adverse outcomes for children with HUS.

Hemolytic-uremic syndrome

MedlinePlus

... page, please enable JavaScript. Shiga-like toxin producing E coli hemolytic-uremic syndrome (STEC-HUS) is a disorder ... HUS) often occurs after a gastrointestinal infection with E coli bacteria ( Escherichia coli O157:H7). However, the condition ...

Hemolytic Uremic Syndrome

MedlinePlus

... bleeding, or extreme fatigue. What causes HUS? Most cases of HUS occur after an E. coli infection. You can catch an E. coli infection by: Eating undercooked ground beef (for example, if the inside of a hamburger that you ...

Intermediate Follow-up of Pediatric Patients With Hemolytic Uremic Syndrome During the 2011 Outbreak Caused by E. coli O104:H4.

PubMed

Loos, Sebastian; Aulbert, Wiebke; Hoppe, Bernd; Ahlenstiel-Grunow, Thurid; Kranz, Birgitta; Wahl, Charlotte; Staude, Hagen; Humberg, Alexander; Benz, Kerstin; Krause, Martin; Pohl, Martin; Liebau, Max C; Schild, Raphael; Lemke, Johanna; Beringer, Ortraud; Müller, Dominik; Härtel, Christoph; Wigger, Marianne; Vester, Udo; Konrad, Martin; Haffner, Dieter; Pape, Lars; Oh, Jun; Kemper, Markus J

2017-06-15

In 2011 Escherichia coli O104:H4 caused an outbreak with >800 cases of hemolytic uremic syndrome (HUS) in Germany, including 90 children. Data on the intermediate outcome in children after HUS due to E. coli O104:H4 have been lacking. Follow-up data were gathered retrospectively from the medical records of patients who had been included in the German Pediatric HUS Registry during the 2011 outbreak. Seventy-two of the 89 (81%) patients were included after a median follow-up of 3.0 (0.9-4.7) years. Hypertension and proteinuria were present in 19% and 28% of these patients, respectively. Of 4 patients with chronic kidney disease (CKD) > stage 2 at short-term follow-up, 1 had a normalized estimated glomerular filtration rate, and 3 (4%) had persistent CKD > stage 2. In 1 of these patients, CKD improved from stage 4 to 3; 1 who had CKD stage 5 at presentation received kidney transplantation; and 1 patient required further hemodialysis during follow-up. One patient (1.4%) still had major neurological symptoms at the latest follow-up. Dialysis during the acute phase (P = .01), dialysis duration (P = .01), and the duration of oligo-/anuria (P = .005) were associated with the development of renal sequelae. Patients treated with eculizumab (n = 11) and/or plasmapheresis (n = 13) during the acute phase of HUS had comparable outcomes. The overall outcome of pediatric patients after HUS due to E. coli O104:H4 was equivalent to previous reports on HUS due to other types of Shiga toxin-producing E. coli (STEC). Regular follow-up visits in patients are recommended after STEC-HUS. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Estimation of community-level influenza-associated illness in a low resource rural setting in India.

PubMed

Saha, Siddhartha; Gupta, Vivek; Dawood, Fatimah S; Broor, Shobha; Lafond, Kathryn E; Chadha, Mandeep S; Rai, Sanjay K; Krishnan, Anand

2018-01-01

To estimate rates of community-level influenza-like-illness (ILI) and influenza-associated ILI in rural north India. During 2011, we conducted household-based healthcare utilization surveys (HUS) for any acute medical illness (AMI) in preceding 14days among residents of 28villages of Ballabgarh, in north India. Concurrently, we conducted clinic-based surveillance (CBS) in the area for AMI episodes with illness onset ≤3days and collected nasal and throat swabs for influenza virus testing using real-time polymerase chain reaction. Retrospectively, we applied ILI case definition (measured/reported fever and cough) to HUS and CBS data. We attributed 14days of risk-time per person surveyed in HUS and estimated community ILI rate by dividing the number of ILI cases in HUS by total risk-time. We used CBS data on influenza positivity and applied it to HUS-based community ILI rates by age, month, and clinic type, to estimate the community influenza-associated ILI rates. The HUS of 69,369 residents during the year generated risk-time of 3945 person-years (p-y) and identified 150 (5%, 95%CI: 4-6) ILI episodes (38 ILI episodes/1,000 p-y; 95% CI 32-44). Among 1,372 ILI cases enrolled from clinics, 126 (9%; 95% CI 8-11) had laboratory-confirmed influenza (A (H3N2) = 72; B = 54). After adjusting for age, month, and clinic type, overall influenza-associated ILI rate was 4.8/1,000 p-y; rates were highest among children <5 years (13; 95% CI: 4-29) and persons≥60 years (11; 95%CI: 2-30). We present a novel way to use HUS and CBS data to generate estimates of community burden of influenza. Although the confidence intervals overlapped considerably, higher point estimates for burden among young children and older adults shows the utility for exploring the value of influenza vaccination among target groups.

Eculizumab treatment in severe pediatric STEC-HUS: a multicenter retrospective study.

PubMed

Percheron, Lucas; Gramada, Raluca; Tellier, Stéphanie; Salomon, Remi; Harambat, Jérôme; Llanas, Brigitte; Fila, Marc; Allain-Launay, Emma; Lapeyraque, Anne-Laure; Leroy, Valerie; Adra, Anne-Laure; Bérard, Etienne; Bourdat-Michel, Guylhène; Chehade, Hassid; Eckart, Philippe; Merieau, Elodie; Piètrement, Christine; Sellier-Leclerc, Anne-Laure; Frémeaux-Bacchi, Véronique; Dimeglio, Chloe; Garnier, Arnaud

2018-03-23

Hemolytic uremic syndrome related to Shiga-toxin-secreting Escherichia coli infection (STEC-HUS) remains a common cause of acute kidney injury in young children. No specific treatment has been validated for this severe disease. Recently, experimental studies highlight the potential role of complement in STEC-HUS pathophysiology. Eculizumab (EC), a monoclonal antibody against terminal complement complex, has been used in severe STEC-HUS patients, mostly during the 2011 German outbreak, with conflicting results. On behalf of the French Society of Pediatric Nephrology, we retrospectively studied 33 children from 15 centers treated with EC for severe STEC-HUS. Indication for EC was neurologic involvement in 20 patients, cardiac and neurologic involvement in 8, cardiac involvement in 2, and digestive involvement in 3. Based on medical status at last follow-up, patients were divided into two groups: favorable (n = 15) and unfavorable outcomes (n = 18). Among patients with favorable outcome, 11/14 patients (79%) displayed persistent blockade of complement activity before each EC reinjection. Conversely, in patients with unfavorable outcome, only 9/15 (53%) had persistent blockade (p = n.s.). Among 28 patients presenting neurological symptoms, 19 had favorable neurological outcome including 17 with prompt recovery following first EC injection. Only two adverse effects potentially related to EC treatment were reported. Taken together, these results may support EC use in severe STEC-HUS patients, especially those presenting severe neurological symptoms. The study, however, is limited by absence of a control group and use of multiple therapeutic interventions in treatment groups. Thus, prospective, controlled trials should be undertaken.

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

Ongoing haemolytic uraemic syndrome (HUS) outbreak caused by sorbitol-fermenting (SF) Shiga toxin-producing Escherichia coli (STEC) O157, Germany, December 2016 to May 2017.

PubMed

Vygen-Bonnet, Sabine; Rosner, Bettina; Wilking, Hendrik; Fruth, Angelika; Prager, Rita; Kossow, Annelene; Lang, Christina; Simon, Sandra; Seidel, Juliane; Faber, Mirko; Schielke, Anika; Michaelis, Kai; Holzer, Alexandra; Kamphausen, Rolf; Kalhöfer, Daniela; Thole, Sebastian; Mellmann, Alexander; Flieger, Antje; Stark, Klaus

2017-05-25

We report an ongoing, protracted and geographically dispersed outbreak of haemolytic uraemic syndrome (HUS) and gastroenteritis in Germany, involving 30 cases since December 2016. The outbreak was caused by the sorbitol-fermenting immotile variant of Shiga toxin-producing (STEC) Escherichia coli O157. Molecular typing revealed close relatedness between isolates from 14 cases. One HUS patient died. Results of a case-control study suggest packaged minced meat as the most likely food vehicle. Food safety investigations are ongoing. This article is copyright of The Authors, 2017.

Differential CT Attenuation of Metabolically Active and Inactive Adipose Tissues — Preliminary Findings

PubMed Central

Hu, Houchun H.; Chung, Sandra A.; Nayak, Krishna S.; Jackson, Hollie A.; Gilsanz, Vicente

2010-01-01

This study investigates differences in CT Hounsfield units (HUs) between metabolically active (brown fat) and inactive adipose tissues (white fat) due to variations in their densities. PET/CT data from 101 pediatric and adolescent patients were analyzed. Regions of metabolically active and inactive adipose tissues were identified and standard uptake values (SUVs) and HUs were measured. HUs of active brown fat were more positive (p<0.001) than inactive fat (−62.4±5.3 versus −86.7±7.0) and the difference was observed in both males and females. PMID:21245691

Microbiological and serological control of Escherichia coli O157: H7 in kindergarten staff in Buenos Aires city and suburban areas.

PubMed

Fernández-Brando, Romina J; Amaral, María Marta; Ciocchini, Andrés E; Bentancor, Leticia V; Trelles, Jorge A; Da Rocha, Marcelo; Landriel, Martín; Ugarte, Mariana; Briones, Gabriel; Ibarra, Cristina; Palermo, Marina S

2017-01-01

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections are implicated in the development of the life-threatening hemolytic-uremic syndrome (HUS). Despite the magnitude of the social and economic problems caused by HUS, no licensed vaccine or effective therapy is currently available for human use. Prevention of STEC infections continues being the most important measure to reduce HUS incidence. This is especially true for Argentina where HUS incidence among children is extremely high and shows an endemic pattern. The aim of this work was to investigate serologically adult staff of kindergartens in Buenos Aires city and suburban areas in order to detect possible carriers, and to educate personnel about good practices to reduce HUS transmission. We also assessed the microbiological quality of water and meal samples from the same kindergartens. We tested 67 healthy adults, 13 water supplies and 6 meals belonging to 6 public kindergartens. We analysed hand swabs for isolation of STEC and serum samples for the presence of antibodies against Stx and lipopolysaccharide (LPS) of O157 serogroup. We identified 46 Stx2-positive individuals, but only 7 for O157 LPS. No presence of STEC pathogens was detected in hands of staff, water or meal samples.

Treating TTP/HUS with plasma exchange: a single centre's 25-year experience.

PubMed

Forzley, Brian R; Sontrop, Jessica M; Macnab, Jennifer J; Chen, Salina; Clark, William F

2008-10-01

Thrombotic thrombocytopenic purpura/Haemolytic uremic syndrome (TTP/HUS) is a thrombotic microangiopathy with a 6-month mortality rate of 16-29%. The present study described the clinical features, treatment regime and 6-month all-cause mortality rate of TTP/HUS patients at the London Health Sciences Centre (LHSC), Canada. Data for this retrospective cohort study were obtained from inpatient and outpatient records for all patients referred for plasma exchange therapy at LHSC, Canada between 1981 and 2006. Patients (n = 110) were categorized as: idiopathic primary (38%) or relapsed (16%), and secondary responsive (30%) or non-responsive (16%). Mortality data were available for all but three patients. The all-cause 6-month mortality rate was 19% overall and was 12% and 26% among idiopathic and secondary TTP/HUS patients, respectively. No mortality events occurred among the 17 idiopathic patients who relapsed. Relapsed patients had the least severe presenting characteristics, the fastest response time, and experienced significant improvement in the severity of clinical features between the first and final presentation. These findings suggest an excellent outcome for relapsed TTP/HUS patients. Patient education, surveillance, and aggressive plasma exchange therapy are hypothesized to improve the likelihood of survival: these hypotheses should be tested in a randomized controlled trial.

Dehydration at admission increased the need for dialysis in hemolytic uremic syndrome children.

PubMed

Balestracci, Alejandro; Martin, Sandra Mariel; Toledo, Ismael; Alvarado, Caupolican; Wainsztein, Raquel Eva

2012-08-01

Oligoanuric forms of postdiarrheal hemolytic uremic syndrome (D+ HUS) usually have more severe acute stage and higher risk of chronic sequelae than nonoligoanuric forms. During the diarrheal phase, gastrointestinal losses could lead to dehydration with pre-renal injury enhancing the risk of oligoanuric D+ HUS. Furthermore, it had been shown that intravenous volume expansion during the prodromal phase could decrease the frequency of oligoanuric renal failure. Thus, we performed this retrospective study to determine whether dehydration on admission is associated with increased need for dialysis in D+ HUS patients. Data from 137 children was reviewed, which were divided into two groups according to their hydration status at admission: normohydrated (n = 86) and dehydrated (n = 51). Laboratory parameters of the dehydrated patients reflected expected deteriorations (higher urea, higher hematocrit and lower sodium, bicarbonate, and pH) than normohydrated ones. Likewise, the dehydrated group had a higher rate of vomiting and need for dialysis (70.6 versus 40.7 %, p = 0.0007). Our data suggests that dehydration at hospital admission might represent a concomitant factor aggravating the intrinsic renal disease in D+ HUS patients increasing the need for dialysis. Therefore, the early recognition of patients at risk of D+ HUS is encouraged to guarantee a well-hydrated status.

Serogroup-Specific Bacterial Engineered Glycoproteins as Novel Antigenic Targets for Diagnosis of Shiga Toxin-Producing-Escherichia coli-Associated Hemolytic-Uremic Syndrome

PubMed Central

Melli, Luciano J.; Ciocchini, Andrés E.; Caillava, Ana J.; Vozza, Nicolás; Chinen, Isabel; Rivas, Marta; Feldman, Mario F.

2014-01-01

Human infection with Shiga toxin-producing Escherichia coli (STEC) is a major cause of postdiarrheal hemolytic-uremic syndrome (HUS), a life-threatening condition characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. E. coli O157:H7 is the dominant STEC serotype associated with HUS worldwide, although non-O157 STEC serogroups can cause a similar disease. The detection of anti-O157 E. coli lipopolysaccharide (LPS) antibodies in combination with stool culture and detection of free fecal Shiga toxin considerably improves the diagnosis of STEC infections. In the present study, we exploited a bacterial glycoengineering technology to develop recombinant glycoproteins consisting of the O157, O145, or O121 polysaccharide attached to a carrier protein as serogroup-specific antigens for the serological diagnosis of STEC-associated HUS. Our results demonstrate that using these antigens in indirect ELISAs (glyco-iELISAs), it is possible to clearly discriminate between STEC O157-, O145-, and O121-infected patients and healthy children, as well as to confirm the diagnosis in HUS patients for whom the classical diagnostic procedures failed. Interestingly, a specific IgM response was detected in almost all the analyzed samples, indicating that it is possible to detect the infection in the early stages of the disease. Additionally, in all the culture-positive HUS patients, the serotype identified by glyco-iELISAs was in accordance with the serotype of the isolated strain, indicating that these antigens are valuable not only for diagnosing HUS caused by the O157, O145, and O121 serogroups but also for serotyping and guiding the subsequent steps to confirm diagnosis. PMID:25472487

Blood urea nitrogen to serum creatinine ratio is an accurate predictor of outcome in diarrhea-associated hemolytic uremic syndrome, a preliminary study.

PubMed

Keenswijk, Werner; Vanmassenhove, Jill; Raes, Ann; Dhont, Evelyn; Vande Walle, Johan

2017-03-01

Diarrhea-associated hemolytic uremic syndrome (D+HUS) is a common thrombotic microangiopathy during childhood and early identification of parameters predicting poor outcome could enable timely intervention. This study aims to establish the accuracy of BUN-to-serum creatinine ratio at admission, in addition to other parameters in predicting the clinical course and outcome. Records were searched for children between 1 January 2008 and 1 January 2015 admitted with D+HUS. A complicated course was defined as developing one or more of the following: neurological dysfunction, pancreatitis, cardiac or pulmonary involvement, hemodynamic instability, and hematologic complications while poor outcome was defined by death or development of chronic kidney disease. Thirty-four children were included from which 11 with a complicated disease course/poor outcome. Risk of a complicated course/poor outcome was strongly associated with oliguria (p = 0.000006) and hypertension (p = 0.00003) at presentation. In addition, higher serum creatinine (p = 0.000006) and sLDH (p = 0.02) with lower BUN-to-serum creatinine ratio (p = 0.000007) were significantly associated with development of complications. A BUN-to-sCreatinine ratio ≤40 at admission was a sensitive and highly specific predictor of a complicated disease course/poor outcome. A BUN-to-serum Creatinine ratio can accurately identify children with D+HUS at risk for a complicated course and poor outcome. What is Known: • Oliguria is a predictor of poor long-term outcome in D+HUS What is New: • BUN-to-serum Creatinine ratio at admission is an entirely novel and accurate predictor of poor outcome and complicated clinical outcome in D+HUS • Early detection of the high risk group in D+HUS enabling early treatment and adequate monitoring.

Stone Attenuation Values Measured by Average Hounsfield Units and Stone Volume as Predictors of Total Laser Energy Required During Ureteroscopic Lithotripsy Using Holmium:Yttrium-Aluminum-Garnet Lasers.

PubMed

Ofude, Mitsuo; Shima, Takashi; Yotsuyanagi, Satoshi; Ikeda, Daisuke

2017-04-01

To evaluate the predictors of the total laser energy (TLE) required during ureteroscopic lithotripsy (URS) using the holmium:yttrium-aluminum-garnet (Ho:YAG) laser for a single ureteral stone. We retrospectively analyzed the data of 93 URS procedures performed for a single ureteral stone in our institution from November 2011 to September 2015. We evaluated the association between TLE and preoperative clinical data, such as age, sex, body mass index, and noncontrast computed tomographic findings, including stone laterality, location, maximum diameter, volume, stone attenuation values measured using average Hounsfield units (HUs), and presence of secondary signs (severe hydronephrosis, tissue rim sign, and perinephric stranding). The mean maximum stone diameter, volume, and average HUs were 9.2 ± 3.8 mm, 283.2 ± 341.4 mm 3 , and 863 ± 297, respectively. The mean TLE and operative time were 2.93 ± 3.27 kJ and 59.1 ± 28.1 minutes, respectively. Maximum stone diameter, volume, average HUs, severe hydronephrosis, and tissue rim sign were significantly correlated with TLE (Spearman's rho analysis). Stepwise multiple linear regression analysis defining stone volume, average HUs, severe hydronephrosis, and tissue rim sign as explanatory variables showed that stone volume and average HUs were significant predictors of TLE (standardized coefficients of 0.565 and 0.320, respectively; adjusted R 2  = 0.55, F = 54.7, P <.001). Stone attenuation values measured by average HUs and stone volume were strong predictors of TLE during URS using Ho:YAG laser procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

An outbreak of hemolytic uremic syndrome in southern Romania during 2015-2016: Epidemiologic, clinical, laboratory, microbiologic, therapeutic and outcome characteristics.

PubMed

Balgradean, Mihaela; Croitoru, Anca; Leibovitz, Eugene

2018-05-08

To describe the epidemiologic, clinical, microbiological, therapeutic and outcome characteristics of a HUS outbreak occurring in southern Romania from 2015 to 2016. We retrospectively collected data from the medical records of all HUS cases hospitalized at the pediatric nephrology department of Marie Curie Children's Hospital of Bucharest, Romania. There were 32 HUS cases (19 girls/13 boys, 87.6% <2 years), all associated with diarrhea (bloody in 13, 40.6%). Thirteen (40.6%) and 4 (12.5%) patients had oliguria and anuria at admission. Extreme pallor, generalized edema, vomiting, dehydration, fever and seizures were found in 100%, 56.3%, 31.3%, 31.3%, 25% and 9.4% of patients, respectively. E. coli and STEC were identified in the stools of 6 and 8 patients, respectively; E. coli O 26 and O 157 infection were documented serologically in 10 and 3 children, respectively. There were 15/32 (46.9%) patients with confirmed HUS. Eighteen (56.3%) patients were hypertensive; other complications included infections, left ventricular hypertrophy, cardiopulmonary arrest, seizures and encephalopathy in 62.5%, 37.5%, 28.3%, 18.8% and 12.5%, respectively. Peritoneal dialysis and hemodialysis were performed in 23 (72%) and 2 patients, respectively. Three patients (9.4%) died early during hospitalization. A 6-12-month follow-up of 26 patients revealed that 65.4% had post-HUS sequelae (persistent hypertension and chronic renal failure in 34.6% and 30.8%, respectively). The principal STEC serotype involved was O 26 :H 11 and the number of confirmed HUS cases reached half of the patients. Compared with the medical literature, this outbreak had a higher rate of complications and renal sequelae and was associated with a high fatality rate. Copyright © 2018. Published by Elsevier B.V.

Functional compartmentalization of Rad9 and Hus1 reveals diverse assembly of the 9‐1‐1 complex components during the DNA damage response in Leishmania

PubMed Central

Damasceno, Jeziel D.; Obonaga, Ricardo; Santos, Elaine V.; Scott, Alan; McCulloch, Richard

2016-01-01

Summary The Rad9‐Rad1‐Hus1 (9‐1‐1) complex is a key component in the coordination of DNA damage sensing, cell cycle progression and DNA repair pathways in eukaryotic cells. This PCNA‐related trimer is loaded onto RPA‐coated single stranded DNA and interacts with ATR kinase to mediate effective checkpoint signaling to halt the cell cycle and to promote DNA repair. Beyond these core activities, mounting evidence suggests that a broader range of functions can be provided by 9‐1‐1 structural diversification. The protozoan parasite Leishmania is an early‐branching eukaryote with a remarkably plastic genome, which hints at peculiar genome maintenance mechanisms. Here, we investigated the existence of homologs of the 9‐1‐1 complex subunits in L. major and found that LmRad9 and LmRad1 associate with chromatin in response to replication stress and form a complex in vivo with LmHus1. Similar to LmHus1, LmRad9 participates in telomere homeostasis and in the response to both replication stress and double strand breaks. However, LmRad9 and LmHus1‐deficient cells present markedly opposite phenotypes, which suggest their functional compartmentalization. We show that some of the cellular pool of LmRad9 forms an alternative complex and that some of LmHus1 exists as a monomer. We propose that the diverse assembly of the Leishmania 9‐1‐1 subunits mediates functional compartmentalization, which has a direct impact on the response to genotoxic stress. PMID:27301589

Clinical use of a rapid collagen binding assay for von Willebrand factor cleaving protease in patients with thrombotic thrombocytopenic purpura.

PubMed

Rick, Margaret E; Moll, Stephan; Taylor, Mark A; Krizek, Dennis M; White, Gilbert C; Aronson, David L

2002-10-01

A simple collagen binding assay (CBA) for measuring activity of the von Willebrand factor cleaving protease in clinical samples is described, and results of fifty masked plasmapheresis samples rom patients with TTP/HUS and other diseases are presented. There was 97.5% concordance between the CBA and a multimer gel assay. The CBA identified low protease activity in 78% of patients who had a clinical syndrome consistent with TTP/HUS and in 2 of 10 sick controls, giving it a positive predictive value of 0.94. The heterogeneity regarding the presence or absence of vWF protease activity in patients with TTP/HUS was confirmed by finding a low negative predictive value of 0.50 with the CBA. The CBA detected inhibitors of the protease in 26 of 29 patients (90%) with TTP/HUS and low protease activity levels. The CBA is a useful clinical assay for examining von Willebrand factor protease activity and detecting inhibitors against the protease.

Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies.

PubMed

von Baeyer, Hans

2002-08-01

Current reimbursement policy of health insurance for therapeutic plasmapheresis requires proof of efficacy using the concept of evidence-based medicine. The aim of this paper is to review the outcome of plasmapheresis used to treat thrombotic microangiopathy (TMA)-associated syndromes in the last decade to provide scientific evidence to back up reimbursement applications. The strength of evidence of each reviewed study was assessed using the five levels of evidence criteria as defined by the American Society of Hematology in 1996 for assessment of the treatment of immune thrombocytopenia. The level Experimental indication was added for situations where only case reports or small series supported by pathophysiological reasoning are available. The definitions of evidence used in this paper are as follows: Level I, randomized clinical trial with low rates of error (p < 0.01); Level II, randomized clinical trial with high rates of error (p < 0.05); Level III, nonrandomized studies with concurrent control group; Level IV, nonrandomized studies with historical control group; Level V, case series without a control group or expert opinion; and Experimental, case reports and pathophysiological reasoning. The results of this analysis based on the published data is summarized as follows: The indication of plasmapheresis is assigned to Level IV evidence for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); cancer/chemotherapy-associated TTP/HUS is assigned to Level V evidence; and TTP/HUS refractory to standard plasma exchange and post-bone marrow transplantation TTP/HUS are assigned to Experimental indication. For both subsets, protein A immunoadsorption is reportedly successful. The other TMA-associated syndromes, hemolysis elevated liver enzymes low platelets and HUS in early childhood, are no indication of plasmapheresis. Two randomized clinical trials were performed in order to demonstrate the superiority of plasma exchange/fresh frozen plasma (PEX/FFP) over plasma transfusion in the management of TTP/HUS. The results prove the greater clinical success of the latter type of plasma administration. Standard PEX/FFP has reduced the mortality of TTP/HUS from 94.5% to 13%.

Shillapoo Wildlife Area 2007 Follow-up HEP Report.

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

Ashley, Paul R.

In April and May 2007 the Regional HEP Team (RHT) conducted a follow-up HEP analysis on the Egger (612 acres) and Herzog (210 acres) parcels located at the north end of the Shillapoo Wildlife Area. The Egger and Herzog parcels have been managed with Bonneville Power Administration funds since acquired in 1998 and 2001 respectively. Slightly more than 936 habitat units (936.47) or 1.14 HUs per acre was generated as an outcome of the 2007 follow-up HEP surveys. Results included 1.65 black-capped chickadee HUs, 280.57 great blue heron HUs, 581.45 Canada goose HUs, 40 mallard HUs, and 32.80 mink HUs.more » Introduction A follow-up Habitat Evaluation Procedures (HEP) (USFWS 1980) analysis was conducted by the Columbia Basin Fish and Wildlife Authority's (CBFWA) Regional HEP Team (RHT) during April and May 2007 to document changes in habitat quality and to determine the number of habitat units (HUs) to credit Bonneville Power Administration (BPA) for providing operation and maintenance (O&M) funds since WDFW acquired the parcels. The 2007 follow-up HEP evaluation was limited to Shillapoo Wildlife Area (SWA) parcels purchased with Bonneville Power Administration funds. D. Budd (pers. comm.) reported WDFW purchased the 612 acre Egger Farms parcel on November 2, 1998 for $1,737,0001 and the 210 acre Herzog acquisition on June 21, 2001 for $500,000 with Memorandum of Agreement funds (BPA and WDFW 1996) as partial fulfillment of BPA's wildlife mitigation obligation for construction of Bonneville and John Day Dams (Rasmussen and Wright 1989). Anticipating the eventual acquisition of the Egger and Herzog properties, WDFW conducted HEP surveys on these lands in 1994 to determine the potential number of habitat units to be credited to BPA. As a result, HEP surveys and habitat unit calculations were completed as much as seven years prior to acquiring the sites. The term 'Shillapoo Wildlife Area' will be used to describe only the Herzog and Egger parcels in this document. Details and results of the HEP analysis are included in this report.« less

Enterohemorrhagic Escherichia coli as Causes of Hemolytic Uremic Syndrome in the Czech Republic

PubMed Central

Marejková, Monika; Bláhová, Květa; Janda, Jan; Fruth, Angelika; Petráš, Petr

2013-01-01

Background Enterohemorrhagic Escherichia coli (EHEC) cause diarrhea-associated hemolytic uremic syndrome (D+ HUS) worldwide, but no systematic study of EHEC as the causative agents of HUS was performed in the Czech Republic. We analyzed stools of all patients with D+ HUS in the Czech Republic between 1998 and 2012 for evidence of EHEC infection. We determined virulence profiles, phenotypes, antimicrobial susceptibilities and phylogeny of the EHEC isolates. Methodology/Principal Findings Virulence loci were identified using PCR, phenotypes and antimicrobial susceptibilities were determined using standard procedures, and phylogeny was assessed using multilocus sequence typing. During the 15-year period, EHEC were isolated from stools of 39 (69.4%) of 56 patients. The strains belonged to serotypes [fliC types] O157:H7/NM[fliC H7] (50% of which were sorbitol-fermenting; SF), O26:H11/NM[fliC H11], O55:NM[fliC H7], O111:NM[fliC H8], O145:H28[fliC H28], O172:NM[fliC H25], and Orough:NM[fliC H25]. O26:H11/NM[fliC H11] was the most common serotype associated with HUS (41% isolates). Five stx genotypes were identified, the most frequent being stx 2a (71.1% isolates). Most strains contained EHEC-hlyA encoding EHEC hemolysin, and a subset (all SF O157:NM and one O157:H7) harbored cdt-V encoding cytolethal distending toxin. espPα encoding serine protease EspPα was found in EHEC O157:H7, O26:H11/NM, and O145:H28, whereas O172:NM and Orough:NM strains contained espPγ. All isolates contained eae encoding adhesin intimin, which belonged to subtypes β (O26), γ (O55, O145, O157), γ2/θ (O111), and ε (O172, Orough). Loci encoding other adhesins (efa1, lpfA O26, lpfA O157OI-141, lpfA O157OI-154, iha) were usually associated with particular serotypes. Phylogenetic analysis demonstrated nine sequence types (STs) which correlated with serotypes. Of these, two STs (ST660 and ST1595) were not found in HUS-associated EHEC before. Conclusions/Significance EHEC strains, including O157:H7 and non-O157:H7, are frequent causes of D+ HUS in the Czech Republic. Identification of unusual EHEC serotypes/STs causing HUS calls for establishment of an European collection of HUS-associated EHEC, enabling to study properties and evolution of these important pathogens. PMID:24040117

Ouabain Protects Human Renal Cells against the Cytotoxic Effects of Shiga Toxin Type 2 and Subtilase Cytotoxin.

PubMed

Amaral, María M; Girard, Magalí C; Álvarez, Romina S; Paton, Adrienne W; Paton, James C; Repetto, Horacio A; Sacerdoti, Flavia; Ibarra, Cristina A

2017-07-18

Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children. The majority of cases are associated with Shiga toxin (Stx)-producing Escherichia coli (STEC). In Argentina, HUS is endemic and presents the highest incidence rate in the world. STEC strains expressing Stx type 2 (Stx2) are responsible for the most severe cases of this pathology. Subtilase cytotoxin (SubAB) is another STEC virulence factor that may contribute to HUS pathogenesis. To date, neither a licensed vaccine nor effective therapy for HUS is available for humans. Considering that Ouabain (OUA) may prevent the apoptosis process, in this study we evaluated if OUA is able to avoid the damage caused by Stx2 and SubAB on human glomerular endothelial cells (HGEC) and the human proximal tubule epithelial cell (HK-2) line. HGEC and HK-2 were pretreated with OUA and then incubated with the toxins. OUA protected the HGEC viability from Stx2 and SubAB cytotoxic effects, and also prevented the HK-2 viability from Stx2 effects. The protective action of OUA on HGEC and HK-2 was associated with a decrease in apoptosis and an increase in cell proliferation. Our data provide evidence that OUA could be considered as a therapeutic strategy to avoid the renal damage that precedes HUS.

Ouabain Protects Human Renal Cells against the Cytotoxic Effects of Shiga Toxin Type 2 and Subtilase Cytotoxin

PubMed Central

Amaral, María M.; Girard, Magalí C.; Álvarez, Romina S.; Paton, Adrienne W.; Paton, James C.; Repetto, Horacio A.; Sacerdoti, Flavia; Ibarra, Cristina A.

2017-01-01

Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children. The majority of cases are associated with Shiga toxin (Stx)-producing Escherichia coli (STEC). In Argentina, HUS is endemic and presents the highest incidence rate in the world. STEC strains expressing Stx type 2 (Stx2) are responsible for the most severe cases of this pathology. Subtilase cytotoxin (SubAB) is another STEC virulence factor that may contribute to HUS pathogenesis. To date, neither a licensed vaccine nor effective therapy for HUS is available for humans. Considering that Ouabain (OUA) may prevent the apoptosis process, in this study we evaluated if OUA is able to avoid the damage caused by Stx2 and SubAB on human glomerular endothelial cells (HGEC) and the human proximal tubule epithelial cell (HK-2) line. HGEC and HK-2 were pretreated with OUA and then incubated with the toxins. OUA protected the HGEC viability from Stx2 and SubAB cytotoxic effects, and also prevented the HK-2 viability from Stx2 effects. The protective action of OUA on HGEC and HK-2 was associated with a decrease in apoptosis and an increase in cell proliferation. Our data provide evidence that OUA could be considered as a therapeutic strategy to avoid the renal damage that precedes HUS. PMID:28718802

Ocular involvement in paediatric haemolytic uraemic syndrome.

PubMed

Sturm, Veit; Menke, Marcel N; Landau, Klara; Laube, Guido F; Neuhaus, Thomas J

2010-11-01

The aim of this study was to estimate the frequency and severity of ocular involvement in paediatric patients with haemolytic uraemic syndrome (HUS). The study was designed as an institutional, retrospective, observational case series. Charts for all 87 paediatric patients with HUS treated at the University Children's Hospital Zurich between 1995 and 2007 were reviewed. Patients with ocular involvement were identified and clinical findings presented. Three of 69 examined patients with HUS showed ocular involvement. Ophthalmic findings in two children were consistent with bilateral Purtscher retinopathy, showing multiple haemorrhages, exudations and superficial retinal whitening. The third child presented with bilateral isolated central intraretinal haemorrhages as a milder form of ocular involvement. In one of the children with Purtscher retinopathy, laser photocoagulation was required for bilateral rubeosis irides and development of disc neovascularization. Longterm outcomes in the two severely affected children showed decreased visual acuity caused by partial atrophy of the optic nerves. In the milder case visual acuity was not impaired at any time. A minority of paediatric patients with HUS developed ocular involvement. Acute ocular findings varied in severity from isolated intraretinal haemorrhages to Purtscher-like retinopathy with retinal ischaemia. Longterm complications included the development of neovascularizations and consecutive optic nerve atrophy. Although ocular involvement in HUS seems to be rare, physicians should be aware of this complication because of its possible vision-endangering consequences. © 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.

Stable and low diffusive hybrid upwind splitting methods

NASA Technical Reports Server (NTRS)

Coquel, Frederic; Liou, Meng-Sing

1992-01-01

We introduce in this paper a new concept for upwinding: the Hybrid Upwind Splitting (HUS). This original strategy for upwinding is achieved by combining the two previous existing approaches, the Flux Vector (FVS) and Flux Difference Splittings (FDS), while retaining their own interesting features. Indeed, our approach yields upwind methods that share the robustness of FVS schemes in the capture of nonlinear waves and the accuracy of some FDS schemes in the capture of linear waves. We describe here some examples of such HUS methods obtained by hybridizing the Osher approach with FVS schemes. Numerical illustrations are displayed and will prove in particular the relevance of the HUS methods we propose for viscous calculations.

Hellsgate Big Game Winter Range Wildlife Mitigation Project : Annual Report 2008.

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

Whitney, Richard P.; Berger, Matthew T.; Rushing, Samuel

The Hellsgate Big Game Winter Range Wildlife Mitigation Project (Hellsgate Project) was proposed by the Confederated Tribes of the Colville Reservation (CTCR) as partial mitigation for hydropower's share of the wildlife losses resulting from Chief Joseph and Grand Coulee Dams. At present, the Hellsgate Project protects and manages 57,418 acres (approximately 90 miles2) for the biological requirements of managed wildlife species; most are located on or near the Columbia River (Lake Rufus Woods and Lake Roosevelt) and surrounded by Tribal land. To date we have acquired about 34,597 habitat units (HUs) towards a total 35,819 HUs lost from original inundationmore » due to hydropower development. In addition to the remaining 1,237 HUs left unmitigated, 600 HUs from the Washington Department of Fish and Wildlife that were traded to the Colville Tribes and 10 secure nesting islands are also yet to be mitigated. This annual report for 2008 describes the management activities of the Hellsgate Big Game Winter Range Wildlife Mitigation Project (Hellsgate Project) during the past year.« less

Paediatric HUS Cases Related to the Consumption of Raw Milk Sold by Vending Machines in Italy: Quantitative Risk Assessment Based on Escherichia coli O157 Official Controls over 7 years.

PubMed

Giacometti, F; Bonilauri, P; Piva, S; Scavia, G; Amatiste, S; Bianchi, D M; Losio, M N; Bilei, S; Cascone, G; Comin, D; Daminelli, P; Decastelli, L; Merialdi, G; Mioni, R; Peli, A; Petruzzelli, A; Tonucci, F; Liuzzo, G; Serraino, A

2017-11-01

A quantitative risk assessment (RA) was developed to estimate haemolytic-uremic syndrome (HUS) cases in paediatric population associated with the consumption of raw milk sold in vending machines in Italy. The historical national evolution of raw milk consumption phenomenon since 2008, when consumer interest started to grow, and after 7 years of marketing adjustment, is outlined. Exposure assessment was based on the official Shiga toxin-producing Escherichia coli O157:H7 (STEC) microbiological records of raw milk samples from vending machines monitored by the regional Veterinary Authorities from 2008 to 2014, microbial growth during storage, consumption frequency of raw milk, serving size, consumption preference and age of consumers. The differential risk considered milk handled under regulation conditions (4°C throughout all phases) and the worst time-temperature field handling conditions detected. In case of boiling milk before consumption, we assumed that the risk of HUS is fixed at zero. The model estimates clearly show that the public health significance of HUS cases due to raw milk STEC contamination depends on the current variability surrounding the risk profile of the food and the consumer behaviour has more impact than milk storage scenario. The estimated HUS cases predicted by our model are roughly in line with the effective STEC O157-associated HUS cases notified in Italy only when the proportion of consumers not boiling milk before consumption is assumed to be 1%. Raw milk consumption remains a source of E. coli O157:H7 for humans, but its overall relevance is likely to have subsided and significant caution should be exerted for temporal, geographical and consumers behaviour analysis. Health education programmes and regulatory actions are required to educate people, primarily children, on other STEC sources. © 2016 Blackwell Verlag GmbH.

Phylogenetic Clades 6 and 8 of Enterohemorrhagic Escherichia coli O157:H7 With Particular stx Subtypes are More Frequently Found in Isolates From Hemolytic Uremic Syndrome Patients Than From Asymptomatic Carriers

PubMed Central

Iyoda, Sunao; Manning, Shannon D.; Seto, Kazuko; Kimata, Keiko; Isobe, Junko; Etoh, Yoshiki; Ichihara, Sachiko; Migita, Yuji; Ogata, Kikuyo; Honda, Mikiko; Kubota, Tsutomu; Kawano, Kimiko; Matsumoto, Kazutoshi; Kudaka, Jun; Asai, Norio; Yabata, Junko; Tominaga, Kiyoshi; Terajima, Jun; Morita-Ishihara, Tomoko; Izumiya, Hidemasa; Ogura, Yoshitoshi; Saitoh, Takehito; Iguchi, Atsushi; Kobayashi, Hideki; Hara-Kudo, Yukiko; Ohnishi, Makoto; Arai, Reiko; Kawase, Masao; Asano, Yukiko; Asoshima, Nanami; Chiba, Kazuki; Furukawa, Ichiro; Kuroki, Toshiro; Hamada, Madoka; Harada, Seiya; Hatakeyama, Takashi; Hirochi, Takashi; Sakamoto, Yumiko; Hiroi, Midori; Takashi, Kanda; Horikawa, Kazumi; Iwabuchi, Kaori; Kameyama, Mitsuhiro; Kasahara, Hitomi; Kawanishi, Shinya; Kikuchi, Koji; Ueno, Hiroyuki; Kitahashi, Tomoko; Kojima, Yuka; Konishi, Noriko; Obata, Hiromi; Kai, Akemi; Kono, Tomomi; Kurazono, Takayuki; Matsumoto, Masakado; Matsumoto, Yuko; Nagai, Yuhki; Naitoh, Hideki; Nakajima, Hiroshi; Nakamura, Hiromi; Nakane, Kunihiko; Nishi, Keiko; Saitoh, Etsuko; Satoh, Hiroaki; Takamura, Mitsuteru; Shiraki, Yutaka; Tanabe, Junichi; Tanaka, Keiko; Tokoi, Yuki; Yatsuyanagi, Jun

2014-01-01

Background  Enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection causes severe diseases such as bloody diarrhea and hemolytic uremic syndrome (HUS). Although EHEC O157:H7 strains have exhibited high genetic variability, their abilities to cause human diseases have not been fully examined. Methods  Clade typing and stx subtyping of EHEC O157:H7 strains, which were isolated in Japan during 1999–2011 from 269 HUS patients and 387 asymptomatic carriers (ACs) and showed distinct pulsed-field gel electrophoresis patterns, were performed to determine relationships between specific lineages and clinical presentation. Results  Clades 6 and 8 strains were more frequently found among the isolates from HUS cases than those from ACs (P = .00062 for clade 6, P < .0001 for clade 8). All clade 6 strains isolated from HUS patients harbored stx2a and/or stx2c, whereas all clade 8 strains harbored either stx2a or stx2a/stx2c. However, clade 7 strains were predominantly found among the AC isolates but less frequently found among the HUS isolates, suggesting a significant association between clade 7 and AC (P < .0001). Logistic regression analysis revealed that 0–9 year old age is a significant predictor of the association between clade 8 and HUS. We also found an intact norV gene, which encodes for a nitric oxide reductase that inhibits Shiga toxin activity under anaerobic condition, in all clades 1–3 isolates but not in clades 4–8 isolates. Conclusions  Early detection of EHEC O157:H7 strains that belonged to clades 6/8 and harbored specific stx subtypes may be important for defining the risk of disease progression in EHEC-infected 0- to 9-year-old children. PMID:25734131

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS): a 24-year clinical experience with 178 patients

PubMed Central

Levandovsky, Mark; Harvey, Danielle; Lara, Primo; Wun, Ted

2008-01-01

Background Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTP-HUS) are related and uncommon disorders with a high fatality and complication rate if untreated. Plasma exchange therapy has been shown to produce high response rates and improve survival in patients with many forms of TTP-HUS. We performed a retrospective cohort study of 178 consecutively treated patients with TTP-HUS and analyzed whether clinical or laboratory characteristics could predict for important short- and long-term outcome measures. Results Overall 30-day mortality was 16% (n = 27). 171 patients (96%) received plasma exchange as the principal treatment, with a mean of 8 exchanges and a mean cumulative infused volume of 42 ± 71 L of fresh frozen plasma. The rate of complete response was 65% or 55% depending on whether this was defined by a platelet count of 100,000/μl or 150,000/μl, respectively. The rate of relapse was 18%. The Clinical Severity Score did not predict for 30-day mortality or relapse. The time to complete response did not predict for relapse. Renal insufficiency at presentation was associated with a decreased risk of relapse, with each unit increase in serum creatinine associated with a 40% decreased odds of relapse. 72% of our cohort had an idiopathic TTP-sporadic HUS, while 17% had an underlying cancer, received a solid organ transplant or were treated with a mitomycin-based therapy. The estimated overall 5-year survival was 55% and was significantly better in those without serious underlying conditions. Conclusion Plasma exchange therapy produced both high response and survival rates in this large cohort of patients with TTP-HUS. The Clinical Severity Score did not predict for 30-day mortality or relapse, contrary to our previous findings. Interestingly, the presence of renal insufficiency was associated with a decreased risk of relapse. The most important predictor of mortality was the presence or absence of a serious underlying disorder. PMID:19046460

Genome Sequence of the Hemolytic-Uremic Syndrome-Causing Strain Escherichia coli NCCP15647

PubMed Central

Jeong, Haeyoung; Zhao, Fumei; Igori, Davaajargal; Oh, Kyung-Hwan; Kim, Seon-Young; Kang, Sung Gyun; Kim, Byung Kwon; Kwon, Soon-Kyeong; Lee, Choong Hoon; Song, Ju Yeon; Yu, Dong Su; Park, Mi-Sun

2012-01-01

Enterohemorrhagic Escherichia coli (EHEC) causes a disease involving diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). Here we present the draft genome sequence of NCCP15647, an EHEC isolate from an HUS patient. Its genome exhibits features of EHEC, such as genes for verotoxins, a type III secretion system, and prophages. PMID:22740672

Habitat Evaluation Procedures (HEP) Report Wanaket Wildlife Area, Techical Report 2005-2006.

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

Ashley, Paul

2006-02-01

The Regional HEP Team (RHT) and Confederated Tribes of the Umatilla Indian Reservation (CTUIR) Wildlife Program staff conducted a follow-up habitat evaluation procedures (HEP) analysis on the Wanaket Wildlife Management Area in June 2005. The 2005 HEP investigation generated 3,084.48 habitat units (HUs) for a net increase of 752.18 HUs above 1990/1995 baseline survey results. The HU to acre ratio also increased from 0.84:1.0 to 1.16:1.0. The largest increase in habitat units occurred in the shrubsteppe/grassland cover type (California quail and western meadowlark models), which increased from 1,544 HUs to 2,777 HUs (+43%), while agriculture cover type HUs were eliminatedmore » because agricultural lands (managed pasture) were converted to shrubsteppe/grassland. In addition to the agriculture cover type, major changes in habitat structure occurred in the shrubsteppe/grassland cover type due to the 2001 wildfire which removed the shrub component from well over 95% of its former range. The number of acres of all other cover types remained relatively stable; however, habitat quality improved in the riparian herb and riparian shrub cover types. The number and type of HEP species models used during the 2005 HEP analysis were identical to those used in the 1990/1995 baseline HEP surveys. The number of species models employed to evaluate the shrubsteppe/grassland, sand/gravel/mud/cobble, and riparian herb cover types, however, were fewer than reported in the McNary Dam Loss Assessment (Rassmussen and Wright 1989) for the same cover types.« less

Associations of age and sex with the clinical outcome and incubation period of Shiga toxin-producing Escherichia coli O104:H4 infections, 2011.

PubMed

Werber, Dirk; King, Lisa A; Müller, Luise; Follin, Per; Buchholz, Udo; Bernard, Helen; Rosner, Bettina; Ethelberg, Steen; de Valk, Henriette; Höhle, Michael

2013-09-15

We pooled data on adults who reported diarrhea or developed life-threatening hemolytic uremic syndrome (HUS) in any of 6 closed cohorts from 4 countries (1 cohort each in Denmark, France, and Sweden and 3 in Germany) that were investigated during a large outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in 2011. Logistic regression and Weibull regression for interval censored data were used to assess the relation of age and sex with clinical outcome and with incubation period. Information on the latter was used in a nonparametric back-projection context to estimate when adult cases reported in Germany were exposed to STEC O104:H4. Overall, data from 119 persons (median age, 49 years; 80 women) were analyzed. Bloody diarrhea and HUS were recorded as the most severe outcome for 44 and 26 individuals, respectively. Older age was significantly associated with bloody diarrhea but not with HUS. Woman had nonsignificantly higher odds for bloody diarrhea (odds ratio = 1.81) and developing HUS (odds ratio = 1.83) than did men. Older participants had a statistically significantly reduced incubation period. The shortest interval that included 75% of exposures in adults spanned only 12 days and preceded outbreak detection. In conclusion, the frequency of bloody diarrhea but not of HUS and the length of the incubation period depended on the age of individuals infected with STEC O104:H4. A large number of people were exposed to STEC O104:H4 for a short period of time.

Commentary: The Observed Association between Autistic Severity Measured by the Social Responsiveness Scale (SRS) and General Psychopathology-- A Response to Hus et al.()

ERIC Educational Resources Information Center

Constantino, John N.; Frazier, Thomas W.

2013-01-01

In their analysis of the accumulated data from the clinically ascertained Simons Simplex Collection (SSC), Hus et al. (2013) provide a large-scale clinical replication of previously reported associations (see Constantino, Hudziak & Todd, 2003) between quantitative autistic traits [as measured by the Social Responsiveness Scale (SRS)] and…

West Foster Creek Expansion Project 2007 HEP Report.

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

Ashley, Paul R.

During April and May 2007, the Columbia Basin Fish and Wildlife Authority's (CBFWA) Regional HEP Team (RHT) conducted baseline Habitat Evaluation Procedures (HEP) (USFWS 1980, 1980a) analyses on five parcels collectively designated the West Foster Creek Expansion Project (3,756.48 acres). The purpose of the HEP analyses was to document extant habitat conditions and to determine how many baseline/protection habitat units (HUs) to credit Bonneville Power Administration (BPA) for funding maintenance and enhancement activities on project lands as partial mitigation for habitat losses associated with construction of Grand Coulee and Chief Joseph Dams. HEP evaluation models included mule deer (Odocoileus hemionus),more » western meadowlark (Sturnella neglecta), sharp-tailed grouse, (Tympanuchus phasianellus), Bobcat (Lynx rufus), mink (Neovison vison), mallard (Anas platyrhynchos), and black-capped chickadee (Parus atricapillus). Combined 2007 baseline HEP results show that 4,946.44 habitat units were generated on 3,756.48 acres (1.32 HUs per acre). HEP results/habitat conditions were generally similar for like cover types at all sites. Unlike crediting of habitat units (HUs) on other WDFW owned lands, Bonneville Power Administration received full credit for HUs generated on these sites.« less

Acoustic properties of a short-finned pilot whale head with insight into temperature influence on tissues' sound velocity.

PubMed

Dong, Jianchen; Song, Zhongchang; Li, Songhai; Gong, Zining; Li, Kuan; Zhang, Peijun; Zhang, Yu; Zhang, Meng

2017-10-01

Acoustic properties of odontocete head tissues, including sound velocity, density, and acoustic impedance, are important parameters to understand dynamics of its echolocation. In this paper, acoustic properties of head tissues from a freshly dead short-finned pilot whale (Globicephala macrorhynchus) were reconstructed using computed tomography (CT) and ultrasound. The animal's forehead soft tissues were cut into 188 ordered samples. Sound velocity, density, and acoustic impedance of each sample were either directly measured or calculated by formula, and Hounsfield Unit values (HUs) were obtained from CT scanning. According to relationships between HUs and sound velocity, HUs and density, as well as HUs and acoustic impedance, distributions of acoustic properties in the head were reconstructed. The inner core in the melon with low-sound velocity and low-density is an evidence for its potential function of sound focusing. The increase in acoustic impedance of forehead tissues from inner core to outer layer may be important for the acoustic impedance matching between the outer layer tissue and seawater. In addition, temperature dependence of sound velocity in soft tissues was also examined. The results provide a guide to the simulation of the sound emission of the short-finned pilot whale.

Genomic Comparisons and Shiga Toxin Production among Escherichia coli O157:H7 Isolates from a Day Care Center Outbreak and Sporadic Cases in Southeastern Wisconsin

PubMed Central

Gouveia, S.; Proctor, M. E.; Lee, M.-S.; Luchansky, J. B.; Kaspar, C. W.

1998-01-01

Contour-clamped homogeneous electric field pulsed-field gel electrophoresis (CHEF-PFGE) was used to compare Wisconsin isolates of Escherichia coli O157:H7, including 39 isolates from a 1994 day care center outbreak, 28 isolates from 18 individuals from the surrounding geographic area with sporadic cases occurring during the 3 months before the outbreak, and 3 isolates, collected in 1995, from patients with hemolytic-uremic syndrome (HUS) who were from eastern Wisconsin counties other than those inhabited by the day care center and sporadic-case individuals. The technique of CHEF-PFGE using XbaI identified seven highly related restriction endonuclease digestion profiles (REDPs) (93 to 98% similarity) among the 39 day care center isolates and nine XbaI REDPs (63 to 93% similarity) among the 28 isolates from sporadic-case individuals, including REDP 33, which was exhibited by both day care and sporadic-case isolates. PFGE analyses of sequential E. coli O157:H7 isolates from symptomatic day care center attendees revealed that the REDPs of 25 isolates from eight patients were indistinguishable whereas the REDPs of 2 of 6 isolates from two patients differed slightly (93 to 95% similarity). The REDPs of the three isolates from 1995 HUS patients were 78 to 83% similar, with REDP 26 being exhibited by one HUS-associated isolate and an isolate from one day care attendee who did not develop HUS. The genes for both Shiga toxins I and II (stx1 and stx2, respectively) were detected in all but one isolate (sporadic case), and Shiga toxin production by the day care center isolates was not significantly different from that of the other isolates, including the three HUS-associated isolates. Analyses of E. coli O157:H7 isolates from both the day care center outbreak and sporadic cases by CHEF-PFGE permitted us to define the REDP variability of an outbreak and geographic region and demonstrated that the day care center outbreak and a HUS case in 1995 were caused by E. coli O157:H7 strains endemic to eastern Wisconsin. PMID:9508303

Stone size limits the use of Hounsfield units for prediction of calcium oxalate stone composition.

PubMed

Stewart, Gregory; Johnson, Lewis; Ganesh, Halemane; Davenport, Daniel; Smelser, Woodson; Crispen, Paul; Venkatesh, Ramakrishna

2015-02-01

To evaluate the role of stone size in predicting urinary calculus composition using Hounsfield units on noncontrasted computed tomography (CT) scan. A retrospective review was performed for all patients who underwent ureteroscopy or percutaneous nephrolithotomy during a 1-year period, had a stone analysis performed, and had CT imaging available for review. All CT scans were reviewed by a board-certified radiologist. Variables evaluated included age, sex, body mass index, stone size, stone location, Hounsfield units (HUs), and stone composition. We identified a total of 91 patients (41 men and 50 women) with CT imaging and stone analysis available for review. Stone analysis showed 41 calcium oxalate monohydrate (CaOxMH), 13 calcium oxalate dihydrate, 29 calcium phosphate, 5 uric acid, 2 struvite, and 1 cystine stone. Average age was 46 years, and average body mass index was 32 kg/m2. Measured HUs varied significantly with size for CaOxMH and calcium oxalate dihydrate stones (P values <.05), but not for calcium phosphate stones (P = .126). Using a CaOxMH identification value of 700-1000 HUs, 28 of 41 stone compositions (68%) would not have been correctly identified, including all 10 (100%) small (<5 mm) stones, 13 of 22 (59%) medium (5-10 mm) stones, and 5 of 9 large (>10 mm) stones (55%). For calcium stones, the ability of CT HUs to predict stone composition was limited, likely due to the mixed stone composition. Within a cohort of CaOxMH stone formers, measured HUs varied linearly with stone size. All stones <5 mm were below thresholds for CaOxMH composition. Copyright © 2015 Elsevier Inc. All rights reserved.

ASP archiving solution of regional HUSpacs.

PubMed

Pohjonen, Hanna; Kauppinen, Tomi; Ahovuo, Juhani

2004-09-01

The application service provider (ASP) model is not novel, but widely used in several non-health care-related business areas. In this article, ASP is described as a potential solution for long-term and back-up archiving of the picture archiving and communication system (PACS) of the Hospital District of Helsinki and Uusimaa (HUS). HUSpacs is a regional PACS for 21 HUS hospitals serving altogether 1.4 million citizens. The ultimate goal of this study was to define the specifications for the ASP archiving service and to compare different commercial options for archiving solutions (costs derived by unofficial requests for proposal): in-house PACS components, the regional ASP concept and the hospital-based ASP concept. In conclusion, the large scale of the HUS installation enables a cost-effective regional ASP archiving, resulting in a four to five times more economical solution than hospital-based ASP.

Therapeutic use of a receptor mimic probiotic reduces intestinal Shiga toxin levels in a piglet model of hemolytic uremic syndrome

PubMed Central

2014-01-01

Background Hemolytic uremic syndrome (HUS) is a systemic and potentially fatal complication of gastroenteritis secondary to Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) infection characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal damage. Shiga toxin (Stx), the toxin principle in HUS, is produced locally within the gut following EHEC colonization and is disseminated via the vasculature. Clinical development of HUS currently has no effective treatment and is a leading cause of renal failure in children. Novel post-exposure therapies are currently needed for HUS; therefore, the purpose of this study was to investigate the efficacy of a Stx receptor mimic probiotic in a porcine model of HUS. Edema disease, an infection of swine caused by host adapted Shiga toxin-producing Escherichia coli (STEC) and mediated by Shiga toxin 2e (Stx2e), shares many pathogenic similarities to HUS. In this study, three-week old piglets were inoculated with STEC and 24 hours later treated twice daily with a probiotic expressing an oligosaccharide receptor mimic for Stx2e to determine if the probiotic could reduce intestinal toxin levels. Methods Piglets were orally inoculated with 1010 CFU of STEC strain S1191 eight days after weaning. Beginning day 1 post-inoculation, piglets were treated orally twice daily with 5 × 1011 CFU of either the receptor mimic probiotic or a sham probiotic for 10 days. Intestinal Stx2e levels were assessed daily via Vero cell assay. The efficacy of the probiotic at reducing intestinal Stx2e, vascular lesions, and clinical disease was evaluated with repeated measures ANOVA and Fisher’s exact test as appropriate. Results The probiotic significantly reduced intestinal Stx2e, as reflected by decreased fecal toxin titers on days 3–8 post-inoculation (p < 0.01). Despite this reduction in intestinal toxin levels, however, the probiotic failed to reduce the incidence of vascular necrosis in target organs and had no effect on clinical disease. Conclusions The data suggest that post-exposure treatment with a Stx-binding probiotic is effective in reducing intestinal toxin burden. Future studies could target this approach for possible development of post-exposure interventions. PMID:24890228

Interventions for preventing diarrhea-associated hemolytic uremic syndrome: systematic review

PubMed Central

2013-01-01

Background Hemolytic Uremic Syndrome (HUS) may follow infection with Shiga-toxin-producing organisms, principally E. coli O157: H7 (STEC), causing high morbidity and mortality. Our aim was to identify interventions to prevent diarrhea-associated HUS. Methods Systematic search of the literature for relevant systematic reviews (SRs), randomised controlled trials (RCTs) and public health guidelines. Results Of 1097 animal and 762 human studies, 18 animal studies (2 SRs, 2 reviews, plus 14 RCTs) and 6 human studies (3 SRs, plus 3 RCTs) met inclusion criteria. E. coli O157: H7 Type III secreted protein vaccination decreased fecal E. coli O157 shedding in cattle (P = 0.002). E. coli O157: H7 siderophore receptor and porin proteins (SRP) vaccines reduced fecal shedding in cows (OR 0.42 (95% CI 0.25 to 0.73) and increased anti-E. coli 0157: H7 SRP antibodies in their calves (P < 0.001). Bacterin vaccines had no effect. Probiotic or sodium chlorate additives in feeds reduced fecal E. coli O157 load as did improved farm hygiene (P < 0.05). Solarization of soil reduced E. coli O157: H7 contamination in the soil (P < 0.05). In an RCT examining the role of antibiotic treatment of E. coli O157: H7 diarrhea, HUS rates were similar in children treated with Trimethoprim-sulfamethoxazole and controls (RR 0.57; 95% CI 0.11 to 2.81). In another RCT, HUS rates were similar in children receiving Synsorb-Pk and placebo (RR 0.93; 95% CI 0.39 to 2.22). In one SR, hand washing reduced diarrhea by 39% in institutions (IRR 0.61; 95% CI 0.40 to 0.92) and 32% in community settings (IRR 0.68; 95% CI 0.52 to 0.90) compared to controls. Guidelines contained recommendations to prevent STEC transmission from animals and environments to humans, including appropriate food preparation, personal hygiene, community education, and control of environmental contamination, food and water quality. Conclusions Animal carriage of STEC is decreased by vaccination and improved farm practices. Treatment of STEC diarrhea with antibiotics and toxin-binders did not prevent HUS. Public health interventions are the key to preventing STEC-associated diarrhea and HUS. PMID:24007265

Community-wide outbreak of haemolytic uraemic syndrome associated with Shiga toxin 2-producing Escherichia coli O26:H11 in southern Italy, summer 2013

PubMed Central

Germinario, Cinzia; Caprioli, Alfredo; Giordano, Mario; Chironna, Maria; Gallone, Maria Serena; Tafuri, Silvio; Minelli, Fabio; Maugliani, Antonella; Michelacci, Valeria; Santangelo, Luisa; Mongelli, Onofrio; Montagna, Cosimo; Scavia, Gaia

2016-01-01

In summer 2013, an excess of paediatric cases of haemolytic uraemic syndrome (HUS) in a southern region of Italy prompted the investigation of a community-wide outbreak of Shiga toxin 2-producing Escherichia coli (STEC) O26:H11 infections. Case finding was based on testing patients with HUS or bloody diarrhoea for STEC infection by microbiological and serological methods. A case–control study was conducted to identify the source of the outbreak. STEC O26 infection was identified in 20 children (median age 17 months) with HUS, two of whom reported severe neurological sequelae. No cases in adults were detected. Molecular typing showed that two distinct STEC O26:H11 strains were involved. The case–control study showed an association between STEC O26 infection and consumption of dairy products from two local plants, but not with specific ready-to-eat products. E.coli O26:H11 strains lacking the stx genes were isolated from bulk milk and curd samples, but their PFGE profiles did not match those of the outbreak isolates. This outbreak supports the view that infections with Stx2-producing E. coli O26 in children have a high probability of progressing to HUS and represent an emerging public health problem in Europe. PMID:27684204

Community-wide outbreak of haemolytic uraemic syndrome associated with Shiga toxin 2-producing Escherichia coli O26:H11 in southern Italy, summer 2013.

PubMed

Germinario, Cinzia; Caprioli, Alfredo; Giordano, Mario; Chironna, Maria; Gallone, Maria Serena; Tafuri, Silvio; Minelli, Fabio; Maugliani, Antonella; Michelacci, Valeria; Santangelo, Luisa; Mongelli, Onofrio; Montagna, Cosimo; Scavia, Gaia

2016-09-22

In summer 2013, an excess of paediatric cases of haemolytic uraemic syndrome (HUS) in a southern region of Italy prompted the investigation of a community-wide outbreak of Shiga toxin 2-producing Escherichia coli (STEC) O26:H11 infections. Case finding was based on testing patients with HUS or bloody diarrhoea for STEC infection by microbiological and serological methods. A case-control study was conducted to identify the source of the outbreak. STEC O26 infection was identified in 20 children (median age 17 months) with HUS, two of whom reported severe neurological sequelae. No cases in adults were detected. Molecular typing showed that two distinct STEC O26:H11 strains were involved. The case-control study showed an association between STEC O26 infection and consumption of dairy products from two local plants, but not with specific ready-to-eat products. E.coli O26:H11 strains lacking the stx genes were isolated from bulk milk and curd samples, but their PFGE profiles did not match those of the outbreak isolates. This outbreak supports the view that infections with Stx2-producing E. coli O26 in children have a high probability of progressing to HUS and represent an emerging public health problem in Europe. This article is copyright of The Authors, 2016.

[Microalbuminuria in pediatric patients diagnosed with hemolytic uremic syndrome].

PubMed

Cubillos C, María Paz; Del Salas, Paulina; Zambrano, Pedro O

2015-01-01

Hemolytic uremic syndrome (HUS) is characterized by the presence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. It is the leading cause of acute kidney failure in children under 3 years of age. A variable number of patients develop proteinuria, hypertension, and chronic renal failure. To evaluate the renal involvement in pediatric patients diagnosed with HUS using the microalbumin/creatinine ratio. Descriptive concurrent cohort study that analyzed the presence of microalbuminuria in patients diagnosed with HUS between January 2001 and March 2012, who evolved without hypertension and normal renal function (clearance greater than 90ml/min using Schwartz formula). Demographic factors (age, sex), clinical presentation at time of diagnosis, use of antibiotics prior to admission, and need for renal replacement therapy were evaluated. Of the 24 patients studied, 54% were male. The mean age at diagnosis was two years. Peritoneal dialysis was required in 45%, and 33% developed persistent microalbuminuria. Antiproteinuric treatment was introduce in 4 patients, with good response. The mean follow-up was 6 years (range 6 months to 11 years). The serum creatinine returned to normal in all patients during follow up. The percentage of persistent microalbuminuria found in patients with a previous diagnosis of HUS was similar in our group to that described in the literature. Antiproteinuric treatment could delay kidney damage, but further multicenter prospective studies are necessary. Copyright © 2015. Publicado por Elsevier España, S.L.U.

Quiescent complement in nonhuman primates during E coli Shiga toxin-induced hemolytic uremic syndrome and thrombotic microangiopathy.

PubMed

Lee, Benjamin C; Mayer, Chad L; Leibowitz, Caitlin S; Stearns-Kurosawa, D J; Kurosawa, Shinichiro

2013-08-01

Enterohemorrhagic Escherichia coli (EHEC) produce ribosome-inactivating Shiga toxins (Stx1, Stx2) responsible for development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI). Some patients show complement activation during EHEC infection, raising the possibility of therapeutic targeting of complement for relief. Our juvenile nonhuman primate (Papio baboons) models of endotoxin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and AKI with glomerular thrombotic microangiopathy. There were no significant increases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) or Stx2 (n = 5) in plasma samples from T0 to euthanasia at 49.5 to 128 hours post-challenge. d-dimer and cell injury markers (HMGB1, histones) confirmed coagulopathy and cell injury. Thus, complement activation is not required for the development of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical models, and benefits or risks of complement inhibition should be studied further for this infection.

CCR2-dependent Gr1high monocytes promote kidney injury in shiga toxin-induced hemolytic uremic syndrome in mice.

PubMed

Pohl, Judith-Mira; Volke, Julia K; Thiebes, Stephanie; Brenzel, Alexandra; Fuchs, Kerstin; Beziere, Nicolas; Ehrlichmann, Walter; Pichler, Bernd J; Squire, Anthony; Gueler, Faikah; Engel, Daniel R

2018-06-01

The hemolytic uremic syndrome (HUS) is a life-threatening disease of the kidney that is induced by shiga toxin-producing E.coli. Major changes in the monocytic compartment and in CCR2-binding chemokines have been observed. However, the specific contribution of CCR2-dependent Gr1 high monocytes is unknown. To investigate the impact of these monocytes during HUS, we injected a combination of LPS and shiga toxin into mice. We observed an impaired kidney function and elevated levels of the CCR2-binding chemokine CCL2 after shiga toxin/LPS- injection, thus suggesting Gr1 high monocyte infiltration into the kidney. Indeed, the number of Gr1 high monocytes was strongly increased one day after HUS induction. Moreover, these cells expressed high levels of CD11b suggesting activation after tissue entry. Non-invasive PET-MR imaging revealed kidney injury mainly in the kidney cortex and this damage coincided with the detection of Gr1 high monocytes. Lack of Gr1 high monocytes in Ccr2-deficient animals reduced neutrophil gelatinase-associated lipocalin and blood urea nitrogen levels. Moreover, the survival of Ccr2-deficient animals was significantly improved. Conclusively, this study demonstrates that CCR2-dependent Gr1 high monocytes contribute to the kidney injury during HUS and targeting these cells is beneficial during this disease. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome

PubMed Central

Abrey Recalde, Maria J.; Alvarez, Romina S.; Alberto, Fabiana; Mejias, Maria P.; Ramos, Maria V.; Fernandez Brando, Romina J.; Bruballa, Andrea C.; Exeni, Ramon A.; Alconcher, Laura; Ibarra, Cristina A.; Amaral, María M.; Palermo, Marina S.

2017-01-01

Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L, as consequence of Stx-induced endothelium damage, participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions. PMID:29068360

Chronic type B aortic dissection in association with Hemolyticuremic syndrome in a child.

PubMed

Gera, D N; Ghuge, P P; Gandhi, S; Vanikar, A V; Shrimali, J D; Kute, V B; Trivedi, H L

2013-11-01

Aortic dissection (AD) is a potentially life-threatening medical emergency usually encountered in the elderly. Here, we report a 9-year-old child who was incidentally detected to have asymptomatic chronic type B dissecting aneurysm of aorta when he presented with relapse of Hemolytic uremic syndrome (HUS) without any genetic abnormalities like Marfan or Ehler-Danlos syndrome. To the best of our knowledge, this is the first case of AD associated with HUS in a child without any known associated genetic or inherited risk factors.

Chronic type B aortic dissection in association with Hemolyticuremic syndrome in a child

PubMed Central

Gera, D. N.; Ghuge, P. P.; Gandhi, S.; Vanikar, A. V.; Shrimali, J. D.; Kute, V. B.; Trivedi, H. L.

2013-01-01

Aortic dissection (AD) is a potentially life-threatening medical emergency usually encountered in the elderly. Here, we report a 9-year-old child who was incidentally detected to have asymptomatic chronic type B dissecting aneurysm of aorta when he presented with relapse of Hemolytic uremic syndrome (HUS) without any genetic abnormalities like Marfan or Ehler-Danlos syndrome. To the best of our knowledge, this is the first case of AD associated with HUS in a child without any known associated genetic or inherited risk factors. PMID:24339527

Pathogenic role of inflammatory response during Shiga toxin-associated hemolytic uremic syndrome (HUS).

PubMed

Exeni, Ramon Alfonso; Fernandez-Brando, Romina Jimena; Santiago, Adriana Patricia; Fiorentino, Gabriela Alejandra; Exeni, Andrea Mariana; Ramos, Maria Victoria; Palermo, Marina Sandra

2018-01-25

Hemolytic uremic syndrome (HUS) is defined as a triad of noninmune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The most frequent presentation is secondary to Shiga toxin (Stx)-producing Escherichia coli (STEC) infections, which is termed postdiarrheal, epidemiologic or Stx-HUS, considering that Stx is the necessary etiological factor. After ingestion, STEC colonize the intestine and produce Stx, which translocates across the intestinal epithelium. Once Stx enters the bloodstream, it interacts with renal endothelial and epithelial cells, and leukocytes. This review summarizes the current evidence about the involvement of inflammatory components as central pathogenic factors that could determine outcome of STEC infections. Intestinal inflammation may favor epithelial leakage and subsequent passage of Stx to the systemic circulation. Vascular damage triggered by Stx promotes not only release of thrombin and increased fibrin concentration but also production of cytokines and chemokines by endothelial cells. Recent evidence from animal models and patients strongly indicate that several immune cells types may participate in HUS physiopathology: neutrophils, through release of proteases and reactive oxygen species (ROS); monocytes/macrophages through secretion of cytokines and chemokines. In addition, high levels of Bb factor and soluble C5b-9 (sC5b-9) in plasma as well as complement factors adhered to platelet-leukocyte complexes, microparticles and microvesicles, suggest activation of the alternative pathway of complement. Thus, acute immune response secondary to STEC infection, the Stx stimulatory effect on different immune cells, and inflammatory stimulus secondary to endothelial damage all together converge to define a strong inflammatory status that worsens Stx toxicity and disease.

Recombinant Human Erythropoietin Therapy for a Jehovah's Witness Child With Severe Anemia due to Hemolytic-Uremic Syndrome.

PubMed

Woo, Da Eun; Lee, Jae Min; Kim, Yu Kyung; Park, Yong Hoon

2016-02-01

Patients with hemolytic-uremic syndrome (HUS) can rapidly develop profound anemia as the disease progresses, as a consequence of red blood cell (RBC) hemolysis and inadequate erythropoietin synthesis. Therefore, RBC transfusion should be considered in HUS patients with severe anemia to avoid cardiac or pulmonary complications. Most patients who are Jehovah's Witnesses refuse blood transfusion, even in the face of life-threatening medical conditions due to their religious convictions. These patients require management alternatives to blood transfusions. Erythropoietin is a glycopeptide that enhances endogenous erythropoiesis in the bone marrow. With the availability of recombinant human erythropoietin (rHuEPO), several authors have reported its successful use in patients refusing blood transfusion. However, the optimal dose and duration of treatment with rHuEPO are not established. We report a case of a 2-year-old boy with diarrhea-associated HUS whose family members are Jehovah's Witnesses. He had severe anemia with acute kidney injury. His lowest hemoglobin level was 3.6 g/dL, but his parents refused treatment with packed RBC transfusion due to their religious beliefs. Therefore, we treated him with high-dose rHuEPO (300 IU/kg/day) as well as folic acid, vitamin B12, and intravenous iron. The hemoglobin level increased steadily to 7.4 g/dL after 10 days of treatment and his renal function improved without any complications. To our knowledge, this is the first case of successful rHuEPO treatment in a Jehovah's Witness child with severe anemia due to HUS.

Intensity-based dual model method for generation of synthetic CT images from standard T2-weighted MR images - Generalized technique for four different MR scanners.

PubMed

Koivula, Lauri; Kapanen, Mika; Seppälä, Tiina; Collan, Juhani; Dowling, Jason A; Greer, Peter B; Gustafsson, Christian; Gunnlaugsson, Adalsteinn; Olsson, Lars E; Wee, Leonard; Korhonen, Juha

2017-12-01

Recent studies have shown that it is possible to conduct entire radiotherapy treatment planning (RTP) workflow using only MR images. This study aims to develop a generalized intensity-based method to generate synthetic CT (sCT) images from standard T2-weighted (T2 w ) MR images of the pelvis. This study developed a generalized dual model HU conversion method to convert standard T2 w MR image intensity values to synthetic HU values, separately inside and outside of atlas-segmented bone volume contour. The method was developed and evaluated with 20 and 35 prostate cancer patients, respectively. MR images with scanning sequences in clinical use were acquired with four different MR scanners of three vendors. For the generated synthetic CT (sCT) images of the 35 prostate patients, the mean (and maximal) HU differences in soft and bony tissue volumes were 16 ± 6 HUs (34 HUs) and -46 ± 56 HUs (181 HUs), respectively, against the true CT images. The average of the PTV mean dose difference in sCTs compared to those in true CTs was -0.6 ± 0.4% (-1.3%). The study provides a generalized method for sCT creation from standard T2 w images of the pelvis. The method produced clinically acceptable dose calculation results for all the included scanners and MR sequences. Copyright © 2017 Elsevier B.V. All rights reserved.

Overexpression of Human S100B Exacerbates Brain Damage and Periinfarct Gliosis After Permanent Focal Ischemia

PubMed Central

Mori, Takashi; Tan, Jun; Arendash, Gary W.; Koyama, Naoki; Nojima, Yoshiko; Town, Terrence

2009-01-01

Background and Purpose We have previously demonstrated that augmented and prolonged activation of astrocytes detrimentally influences both the subacute and chronic phases of cerebral ischemia. Furthermore, we have suggested that the astrocyte-derived protein S100B may be important in these pathogenic events. However, the causal relationship between S100B and exacerbation of brain damage in vivo remains to be elucidated. Methods Using transgenic mice overexpressing human S100B (Tg huS100B mice), we examined whether S100B plays a cardinal role in aggravation of brain damage after permanent middle cerebral artery occlusion (pMCAO). Results Tg huS100B mice had significantly larger infarct volumes and worse neurological deficits at any time point examined after pMCAO as compared with CD-1 background strain-matched control mice. Infarct volumes in Tg huS100B mice were significantly increased from 1 to 3 and 5 days after pMCAO (delayed infarct expansion), whereas those in control mice were not significantly altered. S100, glial fibrillary acidic protein, and Iba1 burdens in the periinfarct area were significantly increased through to 7 days after pMCAO in Tg huS100B mice, whereas those in control mice reached a plateau at 3 days after pMCAO. Conclusions These results provide genetic evidence that overexpression of human S100B acts to exacerbate brain damage and periinfarct reactive gliosis (astrocytosis and microgliosis) during the subacute phase of pMCAO. PMID:18451356

Influenza-associated thrombotic microangiopathies.

PubMed

Bitzan, Martin; Zieg, Jakub

2017-09-07

Thrombotic microangiopathy (TMA) refers to phenotypically similar disorders, including hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP). This review explores the role of the influenza virus as trigger of HUS or TTP. We conducted a literature survey in PubMed and Google Scholar using HUS, TTP, TMA, and influenza as keywords, and extracted and analyzed reported epidemiological and clinical data. We identified 25 cases of influenza-associated TMA. Five additional cases were linked to influenza vaccination and analyzed separately. Influenza A was found in 83%, 10 out of 25 during the 2009 A(H1N1) pandemic. Two patients had bona fide TTP with ADAMTS13 activity <10%. Median age was 15 years (range 0.5-68 years), two thirds were male. Oligoanuria was documented in 81% and neurological involvement in 40% of patients. Serum C3 was reduced in 5 out of 14 patients (36%); Coombs test was negative in 7 out of 7 and elevated fibrin/fibrinogen degradation products were documented in 6 out of 8 patients. Pathogenic complement gene mutations were found in 7 out of 8 patients tested (C3, MCP, or MCP combined with CFB or clusterin). Twenty out of 24 patients recovered completely, but 3 died (12%). Ten of the surviving patients underwent plasma exchange (PLEX) therapy, 5 plasma infusions. Influenza-mediated HUS or TTP is rare. A sizable proportion of tested patients demonstrated mutations associated with alternative pathway of complement dysregulation that was uncovered by this infection. Further research is warranted targeting the roles of viral neuraminidase, enhanced virus-induced complement activation and/or ADAMTS13 antibodies, and rational treatment approaches.

Epidemiological analysis of a large enterohaemorrhagic Escherichia coli O111 outbreak in Japan associated with haemolytic uraemic syndrome and acute encephalopathy.

PubMed

Yahata, Y; Misaki, T; Ishida, Y; Nagira, M; Watahiki, M; Isobe, J; Terajima, J; Iyoda, S; Mitobe, J; Ohnishi, M; Sata, T; Taniguchi, K; Tada, Y; Okabe, N

2015-10-01

A large outbreak of enterohaemorrhagic Escherichia coli (EHEC) O111 and O157 occurred in Japan in April 2011. We conducted an unmatched case-control study and trace-back investigation to determine the source of EHEC O111 infection and risk factors for severe complications. Pulsed-field gel electrophoresis was performed to help define cases. A total of 86 individuals met the case definition. Of these, 40% experienced haemolytic uraemic syndrome (HUS), 24% acute encephalopathy, and 6% died. Illness was significantly associated with eating the raw beef dish yukhoe (odds ratio 19·64, 95% confidence interval 7·03-54·83), the likely food vehicle. EHEC O111 and its closely related stx-negative variants were found in the beef. HUS occurred most frequently in individuals aged 5-9 years, and this age group was significantly associated with acute encephalopathy. The prevalence of HUS and acute encephalopathy was higher than in previous non-O157-related outbreaks, indicating a high risk of severe complications.

Shiga toxin-converting phages and the emergence of new pathogenic Escherichia coli: a world in motion

PubMed Central

Tozzoli, Rosangela; Grande, Laura; Michelacci, Valeria; Ranieri, Paola; Maugliani, Antonella; Caprioli, Alfredo; Morabito, Stefano

2014-01-01

Shiga toxin (Stx)-producing Escherichia coli (STEC) are pathogenic E. coli causing diarrhea, hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). STEC are characterized by a constellation of virulence factors additional to Stx and have long been regarded as capable to cause HC and HUS when possessing the ability of inducing the attaching and effacing (A/E) lesion to the enterocyte, although strains isolated from such severe infections sometimes lack this virulence feature. Interestingly, the capability to cause the A/E lesion is shared with another E. coli pathogroup, the Enteropathogenic E. coli (EPEC). In the very recent times, a different type of STEC broke the scene causing a shift in the paradigm for HUS-associated STEC. In 2011, a STEC O104:H4 caused a large outbreak with more than 800 HUS and 50 deaths. Such a strain presented the adhesion determinants of Enteroaggregative E. coli (EAggEC). We investigated the possibility that, besides STEC and EAggEC, other pathogenic E. coli could be susceptible to infection with stx-phages. A panel of stx2-phages obtained from STEC isolated from human disease was used to infect experimentally E. coli strains representing all the known pathogenic types, including both diarrheagenic E. coli (DEC) and extra-intestinal pathogenic E. coli (ExPEC). We observed that all the E. coli pathogroups used in the infection experiments were susceptible to the infection. Our results suggest that the stx2-phages used may not have specificity for E. coli adapted to the intestinal environment, at least in the conditions used. Additionally, we could only observe transient lysogens suggesting that the event of stable stx2-phage acquisition occurs rarely. PMID:24999453

Molecular characterisation of human Shiga toxin-producing Escherichia coli O26 strains: results of an outbreak investigation, Romania, February to August 2016.

PubMed

Usein, Codruţa-Romaniţa; Ciontea, Adriana Simona; Militaru, Cornelia Mãdãlina; Condei, Maria; Dinu, Sorin; Oprea, Mihaela; Cristea, Daniela; Michelacci, Valeria; Scavia, Gaia; Zota, Lavinia Cipriana; Zaharia, Alina; Morabito, Stefano

2017-11-01

IntroductionAt the beginning of 2016, an increase in paediatric haemolytic uremic syndrome (HUS) cases was observed in Romania. The microbiological investigations allowed isolation of Shiga toxin-producing Escherichia coli (STEC) O26 as the causative agent from most cases. Methods: An enhanced national surveillance of HUS and severe diarrhoea was established across the country following the identification of the first cases and was carried out until August 2016. A total of 15 strains were isolated from 10 HUS and five diarrhoea cases. Strains were characterised by virulence markers (i.e. stx type/subtype, eae , ehxA genes), phylogroup, genetic relatedness and clonality using PCR-based assays, PFGE and multilocus sequence typing (MLST). The first six strains were further characterised by whole genome sequencing (WGS). Results: Five PCR-defined genotypes were distinguished. All strains from HUS cases harboured stx2a and eae , with or without stx1a , while strains from diarrhoea cases carried exclusively stx1a and eae genes. PFGE resolved strains into multiple pulsotypes, compatible with a certain geographic segregation of the cases, and strains were assigned to phylogroup B1 and sequence type (ST) 21. WGS confirmed the results of conventional molecular methods, brought evidence of O26:H11 serotype, and complemented the virulence profiles. Discussion/conclusion: This first description of STEC O26 strains from cases in Romania showed that the isolates belonged to a diverse population. The virulence content of most strains highlighted a high risk for severe outcome in infected patients. Improving the national surveillance strategy for STEC infections in Romania needs to be further considered.

Molecular characterisation of human Shiga toxin-producing Escherichia coli O26 strains: results of an outbreak investigation, Romania, February to August 2016

PubMed Central

Usein, Codruţa-Romaniţa; Ciontea, Adriana Simona; Militaru, Cornelia Mãdãlina; Condei, Maria; Dinu, Sorin; Oprea, Mihaela; Cristea, Daniela; Michelacci, Valeria; Scavia, Gaia; Zota, Lavinia Cipriana; Zaharia, Alina; Morabito, Stefano

2017-01-01

Introduction At the beginning of 2016, an increase in paediatric haemolytic uremic syndrome (HUS) cases was observed in Romania. The microbiological investigations allowed isolation of Shiga toxin-producing Escherichia coli (STEC) O26 as the causative agent from most cases. Methods: An enhanced national surveillance of HUS and severe diarrhoea was established across the country following the identification of the first cases and was carried out until August 2016. A total of 15 strains were isolated from 10 HUS and five diarrhoea cases. Strains were characterised by virulence markers (i.e. stx type/subtype, eae, ehxA genes), phylogroup, genetic relatedness and clonality using PCR-based assays, PFGE and multilocus sequence typing (MLST). The first six strains were further characterised by whole genome sequencing (WGS). Results: Five PCR-defined genotypes were distinguished. All strains from HUS cases harboured stx2a and eae, with or without stx1a, while strains from diarrhoea cases carried exclusively stx1a and eae genes. PFGE resolved strains into multiple pulsotypes, compatible with a certain geographic segregation of the cases, and strains were assigned to phylogroup B1 and sequence type (ST) 21. WGS confirmed the results of conventional molecular methods, brought evidence of O26:H11 serotype, and complemented the virulence profiles. Discussion/conclusion: This first description of STEC O26 strains from cases in Romania showed that the isolates belonged to a diverse population. The virulence content of most strains highlighted a high risk for severe outcome in infected patients. Improving the national surveillance strategy for STEC infections in Romania needs to be further considered. PMID:29183554

Dehydration upon admission is a risk factor for incomplete recovery of renal function in children with haemolytic uremic syndrome.

PubMed

Ojeda, José M; Kohout, Isolda; Cuestas, Eduardo

2013-01-01

Haemolytic uremic syndrome (HUS) is the most common cause of acute renal failure and the second leading cause of chronic renal failure in children. The factors that affect incomplete renal function recovery prior to hospital admission are poorly understood. To analyse the risk factors that determine incomplete recovery of renal function prior to hospitalisation in children with HUS. A retrospective case-control study. age, sex, duration of diarrhoea, bloody stools, vomiting, fever, dehydration, previous use of antibiotics, and incomplete recovery of renal function (proteinuria, hypertension, reduced creatinine clearance, and chronic renal failure during follow-up). Patients of both sexes under 15 years of age were included. Of 36 patients, 23 were males (65.3%; 95%CI: 45.8 to 80.9), with an average age of 2.5 ± 1.4 years. Twenty-one patients required dialysis (58%; 95% CI: 40.8 to 75.8), and 13 (36.1%; 95% CI: 19.0 to 53.1) did not recover renal function. In the bivariate model, the only significant risk factor was dehydration (defined as weight loss >5%) [(OR: 5.3; 95% CI: 1.4 to 12.3; P=.0220]. In the multivariate analysis (Cox multiple regression), only dehydration was marginally significant (HR: 95.823; 95% CI: 93.175 to 109.948; P=.085). Our data suggest that dehydration prior to admission may be a factor that increases the risk of incomplete recovery of renal function during long-term follow-up in children who develop HUS D+. Consequently, in patients with diarrhoea who are at risk of HUS, dehydration should be strongly avoided during outpatient care to preserve long-term renal function. These results must be confirmed by larger prospective studies.

A microbiological hazard of rural living: Clostridium septicum brain abscess in a child with E coli 0157 associated haemolytic uraemic syndrome

PubMed Central

Williams, Eleri J; Mitchell, Patrick; Mitra, Dipayan; Clark, Julia E

2012-01-01

Clostridium septicum infection in humans is rare and this is the second case report of focal C septicum brain abscesses associated with Escherichia coli 0157 haemolytic uraemic syndrome (HUS). The case presented in a child who lived on a rural farm. The abscesses initially progressed despite 7 months of appropriate antibiotic therapy and repeated image-guided aspiration. After definitive resection and prolonged antibiotic therapy, there was no recurrence. This case reminds us of this rare but important neurological complication of HUS and supports consideration of early definitive neurosurgical intervention in similar unusual cases. PMID:22736786

[Historical stages of Hemolytic Uremic Syndrome in Argentina (1964-2009)].

PubMed

Belardo, Marcela

2012-10-01

The aim is to present an historical time frame of Hemolytic Uremic Syndrome (HUS) in Argentina. From a public policy approach, the history of the disease is analyzed as an object of health policy and seeks to contribute in understanding the multiple dimensions of illness. As a medical and scientific issue, as a social problem and a matter of health policy, the article describes three phases ranging from its discovery up to the national program of HUS adopted in 2009. This article aims to provide an overview of developments in biomedical knowledge and the emergence of the issue in both social and political problem.

Exploiting the Nephrotoxic Effects of Venom from the Sea Anemone, Phyllodiscus semoni, to Create a Hemolytic Uremic Syndrome Model in the Rat

PubMed Central

Mizuno, Masashi; Ito, Yasuhiko; Morgan, B. Paul

2012-01-01

In the natural world, there are many creatures with venoms that have interesting and varied activities. Although the sea anemone, a member of the phylum Coelenterata, has venom that it uses to capture and immobilise small fishes and shrimp and for protection from predators, most sea anemones are harmless to man. However, a few species are highly toxic; some have venoms containing neurotoxins, recently suggested as potential immune-modulators for therapeutic application in immune diseases. Phyllodiscus semoni is a highly toxic sea anemone; the venom has multiple effects, including lethality, hemolysis and renal injuries. We previously reported that venom extracted from Phyllodiscus semoni induced acute glomerular endothelial injuries in rats resembling hemolytic uremic syndrome (HUS), accompanied with complement dysregulation in glomeruli and suggested that the model might be useful for analyses of pathology and development of therapeutic approaches in HUS. In this mini-review, we describe in detail the venom-induced acute renal injuries in rat and summarize how the venom of Phyllodiscus semoni could have potential as a tool for analyses of complement activation and therapeutic interventions in HUS. PMID:22851928

Colville Confederated Tribes' Performance Project Wildlife Mitigation Acquisitions, Annual Report 2006.

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

Whitney, Richard; Berger, Matthew; Tonasket, Patrick

2006-12-01

The Colville Confederated Tribes Wildlife Mitigation Project is protecting lands as partial mitigation for hydropower's share of the wildlife losses resulting from Chief Joseph and Grand Coulee Dams. The Mitigation Project protects and manages 54,606 acres for the biological requirements of managed wildlife species that are important to the Colville Tribes. With the inclusion of 2006 acquisitions, the Colville Tribes have acquired approximately 32,018 habitat units (HUs) towards a total 35,819 HUs lost from original inundation due to hydropower development. This annual report for 2006 briefly describes that four priority land acquisitions that were considered for enrollment into the Colvillemore » Tribes Mitigation Project during the 2006 contract period.« less

First case report of Moraxella osloensis diarrhea in a hemolytic uremic syndrome/acute renal failure child from rural coastal India-Manipal, Karnataka.

PubMed

Ballal, Mamatha; Martena, Suganthi

2013-03-01

The authors report a rare case of diarrhea caused by Moraxella osloensis in a pediatric child with Hemolytic Uremic Syndrome/Acute Renal Failure (HUS/ARF). A 6-y-old boy was referred to the Pediatric Unit with a 3 d history of bloody diarrhea with mucus and fever and decreased urine output for 6 d. Microbiological investigations were done as per CLSI guidelines. His diarrhea, and the subsequent renal failure resolved with appropriate treatment. To the best of authors' knowledge and pubmed search, this is the first case of M. osloensis causing diarrhea in a HUS/ARF pediatric patient reported from India-Manipal.

Development of a method for bacteria and virus recovery from heating, ventilation, and air conditioning (HVAC) filters.

PubMed

Farnsworth, James E; Goyal, Sagar M; Kim, Seung Won; Kuehn, Thomas H; Raynor, Peter C; Ramakrishnan, M A; Anantharaman, Senthilvelan; Tang, Weihua

2006-10-01

The aim of the work presented here is to study the effectiveness of building air handling units (AHUs) in serving as high volume sampling devices for airborne bacteria and viruses. An HVAC test facility constructed according to ASHRAE Standard 52.2-1999 was used for the controlled loading of HVAC filter media with aerosolized bacteria and virus. Nonpathogenic Bacillus subtilis var. niger was chosen as a surrogate for Bacillus anthracis. Three animal viruses; transmissible gastroenteritis virus (TGEV), avian pneumovirus (APV), and fowlpox virus were chosen as surrogates for three human viruses; SARS coronavirus, respiratory syncytial virus, and smallpox virus; respectively. These bacteria and viruses were nebulized in separate tests and injected into the test duct of the test facility upstream of a MERV 14 filter. SKC Biosamplers upstream and downstream of the test filter served as reference samplers. The collection efficiency of the filter media was calculated to be 96.5 +/- 1.5% for B. subtilis, however no collection efficiency was measured for the viruses as no live virus was ever recovered from the downstream samplers. Filter samples were cut from the test filter and eluted by hand-shaking. An extraction efficiency of 105 +/- 19% was calculated for B. subtilis. The viruses were extracted at much lower efficiencies (0.7-20%). Our results indicate that the airborne concentration of spore-forming bacteria in building AHUs may be determined by analyzing the material collected on HVAC filter media, however culture-based analytical techniques are impractical for virus recovery. Molecular-based identification techniques such as PCR could be used.

Genomic Comparison of Two O111:H- Enterohemorrhagic Escherichia coli Isolates from a Historic Hemolytic-Uremic Syndrome Outbreak in Australia.

PubMed

McAllister, Lauren J; Bent, Stephen J; Petty, Nicola K; Skippington, Elizabeth; Beatson, Scott A; Paton, James C; Paton, Adrienne W

2016-01-04

Enterohemorrhagic Escherichia coli (EHEC) is an important cause of diarrhea and hemolytic-uremic syndrome (HUS) worldwide. Australia's worst outbreak of HUS occurred in Adelaide in 1995 and was one of the first major HUS outbreaks attributed to a non-O157 Shiga-toxigenic E. coli (STEC) strain. Molecular analyses conducted at the time suggested that the outbreak was caused by an O111:H(-) clone, with strains from later in the outbreak harboring an extra copy of the genes encoding the potent Shiga toxin 2 (Stx2). Two decades later, we have used next-generation sequencing to compare two isolates from early and late in this important outbreak. We analyzed genetic content, single-nucleotide polymorphisms (SNPs), and prophage insertion sites; for the latter, we demonstrate how paired-end sequence data can be leveraged to identify such insertion sites. The two strains are genetically identical except for six SNP differences and the presence of not one but two additional Stx2-converting prophages in the later isolate. Isolates from later in the outbreak were associated with higher levels of morbidity, suggesting that the presence of the additional Stx2-converting prophages is significant in terms of the virulence of this clone. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Acoustic property reconstruction of a pygmy sperm whale (Kogia breviceps) forehead based on computed tomography imaging.

PubMed

Song, Zhongchang; Xu, Xiao; Dong, Jianchen; Xing, Luru; Zhang, Meng; Liu, Xuecheng; Zhang, Yu; Li, Songhai; Berggren, Per

2015-11-01

Computed tomography (CT) imaging and sound experimental measurements were used to reconstruct the acoustic properties (density, velocity, and impedance) of the forehead tissues of a deceased pygmy sperm whale (Kogia breviceps). The forehead was segmented along the body axis and sectioned into cross section slices, which were further cut into sample pieces for measurements. Hounsfield units (HUs) of the corresponding measured pieces were obtained from CT scans, and regression analyses were conducted to investigate the linear relationships between the tissues' HUs and velocity, and HUs and density. The distributions of the acoustic properties of the head at axial, coronal, and sagittal cross sections were reconstructed, revealing that the nasal passage system was asymmetric and the cornucopia-shaped spermaceti organ was in the right nasal passage, surrounded by tissues and airsacs. A distinct dense theca was discovered in the posterior-dorsal area of the melon, which was characterized by low velocity in the inner core and high velocity in the outer region. Statistical analyses revealed significant differences in density, velocity, and acoustic impedance between all four structures, melon, spermaceti organ, muscle, and connective tissue (p < 0.001). The obtained acoustic properties of the forehead tissues provide important information for understanding the species' bioacoustic characteristics.

Immunoproteomic Analysis To Identify Shiga Toxin-Producing Escherichia coli Outer Membrane Proteins Expressed during Human Infection

PubMed Central

Montero, David; Orellana, Paz; Gutiérrez, Daniela; Araya, Daniela; Salazar, Juan Carlos; Prado, Valeria; Oñate, Ángel; del Canto, Felipe

2014-01-01

Shiga-toxin producing Escherichia coli (STEC) is the etiologic agent of acute diarrhea, dysentery, and hemolytic-uremic syndrome (HUS). There is no approved vaccine for STEC infection in humans, and antibiotic use is contraindicated, as it promotes Shiga toxin production. In order to identify STEC-associated antigens and immunogenic proteins, outer membrane proteins (OMPs) were extracted from STEC O26:H11, O103, O113:H21, and O157:H7 strains, and commensal E. coli strain HS was used as a control. SDS-PAGE, two-dimensional-PAGE analysis, Western blot assays using sera from pediatric HUS patients and controls, and matrix-assisted laser desorption ionization–tandem time of flight analyses were used to identify 12 immunogenic OMPs, some of which were not reactive with control sera. Importantly, seven of these proteins have not been previously reported to be immunogenic in STEC strains. Among these seven proteins, OmpT and Cah displayed IgG and IgA reactivity with sera from HUS patients. Genes encoding these two proteins were present in a majority of STEC strains. Knowledge of the antigens produced during infection of the host and the immune response to those antigens will be important for future vaccine development. PMID:25156722

Reconstruction of the forehead acoustic properties in an Indo-Pacific humpback dolphin (Sousa chinensis), with investigation on the responses of soft tissue sound velocity to temperature.

PubMed

Song, Zhongchang; Zhang, Yu; Berggren, Per; Wei, Chong

2017-02-01

Computed tomography (CT) imaging and ultrasound experimental measurements were combined to reconstruct the acoustic properties (density, velocity, and impedance) of the head from a deceased Indo-Pacific humpback dolphin (Sousa chinensis). The authors extracted 42 soft forehead tissue samples to estimate the sound velocity and density properties at room temperature, 25.0  °C. Hounsfield Units (HUs) of the samples were read from CT scans. Linear relationships between the tissues' HUs and velocity, and HUs and density were revealed through regression analyses. The distributions of the head acoustic properties at axial, coronal, and sagittal cross sections were reconstructed, suggesting that the forehead soft tissues were characterized by low-velocity in the melon, high-velocity in the muscle and connective tissues. Further, the sound velocities of melon, muscle, and connective tissue pieces were measured under different temperatures to investigate tissues' velocity response to temperature. The results demonstrated nonlinear relationships between tissues' sound velocity and temperature. This study represents a first attempt to provide general information on acoustic properties of this species. The results could provide meaningful information for understanding the species' bioacoustic characteristics and for further investigation on sound beam formation of the dolphin.

Outbreak of haemolytic uraemic syndrome in Norway caused by stx2-positive Escherichia coli O103:H25 traced to cured mutton sausages

PubMed Central

Schimmer, Barbara; Nygard, Karin; Eriksen, Hanne-Merete; Lassen, Jørgen; Lindstedt, Bjørn-Arne; Brandal, Lin T; Kapperud, Georg; Aavitsland, Preben

2008-01-01

Background On 20–21 February 2006, six cases of diarrhoea-associated haemolytic uraemic syndrome (HUS) were reported by paediatricians to the Norwegian Institute of Public Health. We initiated an investigation to identify the etiologic agent and determine the source of the outbreak in order to implement control measures. Methods A case was defined as a child with diarrhoea-associated HUS or any person with an infection with the outbreak strain of E. coli O103 (defined by the multi-locus variable number tandem repeats analysis (MLVA) profile) both with illness onset after January 1st 2006 in Norway. After initial hypotheses-generating interviews, we performed a case-control study with the first fifteen cases and three controls for each case matched by age, sex and municipality. Suspected food items were sampled, and any E. coli O103 strains were typed by MLVA. Results Between 20 February and 6 April 2006, 17 cases were identified, of which 10 children developed HUS, including one fatal case. After pilot interviews, a matched case-control study was performed indicating an association between a traditional cured sausage (odds ratio 19.4 (95% CI: 2.4–156)) and STEC infection. E. coli O103:H25 identical to the outbreak strain defined by MLVA profile was found in the product and traced back to contaminated mutton. Conclusion We report an outbreak caused by a rare STEC variant (O103:H25, stx2-positive). More than half of the diagnosed patients developed HUS, indicating that the causative organism is particularly virulent. Small ruminants continue to be important reservoirs for human-pathogen STEC. Improved slaughtering hygiene and good manufacturing practices for cured sausage products are needed to minimise the possibility of STEC surviving through the entire sausage production process. PMID:18387178

Shiga Toxin-Producing Escherichia coli Infection in Jönköping County, Sweden: Occurrence and Molecular Characteristics in Correlation With Clinical Symptoms and Duration of stx Shedding.

PubMed

Bai, Xiangning; Mernelius, Sara; Jernberg, Cecilia; Einemo, Ing-Marie; Monecke, Stefan; Ehricht, Ralf; Löfgren, Sture; Matussek, Andreas

2018-01-01

Shiga toxin-producing Escherichia coli (STEC) cause bloody diarrhea (BD), hemorrhagic colitis (HC), and even hemolytic uremic syndrome (HUS). In Nordic countries, STEC are widely spread and usually associated with gastrointestinal symptoms and HUS. The objective of this study was to investigate the occurrence of STEC in Swedish patients over 10 years of age from 2003 through 2015, and to analyze the correlation of critical STEC virulence factors with clinical symptoms and duration of stx shedding. Diarrheal stool samples were screened for presence of stx by real-time PCR. All STEC isolates were characterized by DNA microarray assay and PCR to determine serogenotypes, stx subtypes, and presence of intimin gene eae and enterohaemolysin gene ehxA . Multilocus sequencing typing (MLST) was used to assess phylogenetic relationships. Clinical features were collected and analyzed using data from the routine infection control measures in the county. A total of 14,550 samples were enrolled in this 12-years period study, and 175 (1.2%) stools were stx positive by real-time PCR. The overall incidence of STEC infection was 4.9 cases per 100,000 person-years during the project period. Seventy-five isolates, with one isolate per sample were recovered, among which 43 were from non-bloody stools, 32 from BD, and 3 out of the 75 STEC positive patients developed HUS. The presence of stx2 in both stools and isolates were associated with BD ( p = 0.008, p = 0.05), and the presence of eae in isolates was related to BD ( p = 0.008). The predominant serogenotypes associated with BD were O157:H7, O26:H11, O121:H19, and O103:H2. Isolates from HUS were O104:H4 and O98: H21 serotypes. Phylogenetic analysis revealed our strains were highly diverse, and showed close relatedness to HUS-associated STEC collection strains. In conclusion, the presence of stx2 in stool was related to BD already at the initial diagnostic procedure, thus could be used as risk predictor at an early stage. STEC isolates with stx2 and eae were significantly associated with BD. The predominant serotypes associated with BD were O157:H7, O26:H11, O121:H19, and O103:H2. Nevertheless, the pathogenic potential of other serotypes and genotypes should not be neglected.

Antibody mediated rejection associated with complement factor h-related protein 3/1 deficiency successfully treated with eculizumab.

PubMed

Noone, D; Al-Matrafi, J; Tinckam, K; Zipfel, P F; Herzenberg, A M; Thorner, P S; Pluthero, F G; Kahr, W H A; Filler, G; Hebert, D; Harvey, E; Licht, C

2012-09-01

Antibody mediated rejection (AMR) activates the classical complement pathway and can be detrimental to graft survival. AMR can be accompanied by thrombotic microangiopathy (TMA). Eculizumab, a monoclonal C5 antibody prevents induction of the terminal complement cascade (TCC) and has recently emerged as a therapeutic option for AMR. We present a highly sensitized 13-year-old female with end-stage kidney disease secondary to spina bifida-associated reflux nephropathy, who developed severe steroid-, ATG- and plasmapheresis-resistant AMR with TMA 1 week post second kidney transplant despite previous desensitization therapy with immunoglobulin infusions. Eculizumab rescue therapy resulted in a dramatic improvement in biochemical (C3; creatinine) and hematological (platelets) parameters within 6 days. The patient was proven to be deficient in complement Factor H-related protein 3/1 (CFHR3/1), a plasma protein that regulates the complement cascade at the level of C5 conversion and has been involved in the pathogenesis of atypical hemolytic uremic syndrome caused by CFH autoantibodies (DEAP-HUS). CFHR1 deficiency may have worsened the severe clinical progression of AMR and possibly contributed to the development of donor-specific antibodies. Thus, screening for CFHR3/1 deficiency should be considered in patients with severe AMR associated with TMA. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

[Diet of neutropenic patients in pediatric oncology service; the experience of the university hospital of Strasbourg (HUS)].

PubMed

Mutel, T; Foeglé, J; Belotti, L; Sery, V; Bourneton, O; Hernandez, C; Lutz, P; Lavigne, T

2012-12-01

This article clarifies the choices made by the HUS concerning the ways of preparing food reserved to neutropenic children hospitalized in pediatric oncology service. We will describe the results of microbiological analysis of food realized from 2002 to 2007. A specific team prepares this food which is canned and treated by "appertisation" (autoclaving). Each dish portion produced is provided to the service only if the microbiological results are conform, that is to say free of organisms. Three thousand and seventy-eight dishes were analysed: 82.9% of the analysed packs were conform. The contamination ratio decreased significantly (P<0.001) from 2002 to 2007. The organisms which cause the majority of dishes contamination are Bacillus (44.7%) and environmental mould exhibiting sterile mycelium (8.7%). The food which is the most frequently "nonconform" is the dry food with a contamination rate of 37.9%. The identified concentrations remain mainly lower than 50 colony-forming units per millilitre (CFU/mL): 66.2% for the bacteria and 97.2% for the fungi. Considering the lack of consensus on the acceptable microbiological thresholds and on the food protection level, the HUS make it a rule to have a maximal precautionary principle. Currently, this principle appears to us to be a safety option required for the patients hospitalized in pediatric oncology service. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

[Thrombotic microangiopathy in adults].

PubMed

Barrientos, Gonzalo J; Michelangelo, Hernán

2006-01-01

Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and pregnancy associated thrombotic microangiopathy (TMA). Eight adult patients (four males and four females) with TMA who were treated between 2003 and 2004 at the Hospital Italiano de Buenos Aires were reviewed. The average age was 40. Clinical diagnosis of TMA was made on admission in four patients. During their stay in hospital, 4 patients developed HUS characteristics, three as TTP and one presented pregnancy associated TMA. All of them revealed thrombocytopenia and microangiophatic hemolytic anemia. Renal impairment was the third most frequent characteristic at presentation. The patients with TTP revealed the most severe condition. All patients received daily plasma exchange. Immunosuppressants were also used. Four patients recovered completely, 2 passed away, one remains with renal impairment and requires hemodialysis, and a colectomy was performed on one of them. The TMA syndromes are occlusive disorders associated to platelet microvascular thrombi. Systemic and renal circulations are primarily affected. TTP/HUS might represent an overlapping spectrum of idiopathic or secondary disease. Prompt recognition and treatment are vital, because high mortality occurs due to these disorders. Among the differential diagnosis of TMA we can refer to sepsis, neoplasms, systemic vasculitis, eclampsia and others. The mainstay treatments are daily plasma exchange and infusion with fresh frozen plasma. Improving the management of these diseases is required considering their high morbidity and mortality.

Extracting TSK-type Neuro-Fuzzy model using the Hunting search algorithm

NASA Astrophysics Data System (ADS)

Bouzaida, Sana; Sakly, Anis; M'Sahli, Faouzi

2014-01-01

This paper proposes a Takagi-Sugeno-Kang (TSK) type Neuro-Fuzzy model tuned by a novel metaheuristic optimization algorithm called Hunting Search (HuS). The HuS algorithm is derived based on a model of group hunting of animals such as lions, wolves, and dolphins when looking for a prey. In this study, the structure and parameters of the fuzzy model are encoded into a particle. Thus, the optimal structure and parameters are achieved simultaneously. The proposed method was demonstrated through modeling and control problems, and the results have been compared with other optimization techniques. The comparisons indicate that the proposed method represents a powerful search approach and an effective optimization technique as it can extract the accurate TSK fuzzy model with an appropriate number of rules.

Information about TTP-HUS

MedlinePlus

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Health utility scores from EQ-5D and health-related quality of life in patients with esophageal cancer: a real-world cross-sectional study.

PubMed

Doherty, M K; Leung, Y; Su, J; Naik, H; Patel, D; Eng, L; Kong, Q Q; Mohsin, F; Brown, M C; Espin-Garcia, O; Vennettilli, A; Renouf, D J; Faluyi, O O; Knox, J J; MacKay, H; Wong, R; Howell, D; Mittmann, N; Darling, G E; Cella, D; Xu, W; Liu, G

2018-06-14

Esophageal cancer and its treatment can cause serious morbidity/toxicity. These effects on health-related quality of life (HRQOL) can be measured using disease-specific scales such as FACT-E, generic scales such as EQ-5D-3L, or through symptoms. In a two-year cross-sectional study, we compared HRQOL across esophageal cancer patients treated in an ambulatory clinic and across multiple disease states, among patients with all stages of esophageal cancer. Consenting patients completed FACT-E, EQ-5D, a visual analog scale, and patient reported (PR)-ECOG. Symptom complexes were constructed from FACT-E domains. Responses were categorized by disease state: pre-, during, and post-treatment, surveillance, progression, and palliative chemotherapy. Spearman correlation and multivariable linear regression characterized these associations. In total, 199 patients completed 317 questionnaires. Mean FACT-E and subscale scores dropped from baseline through treatment and recovered during post-treatment surveillance (P < 0.001); EQ-5D health utility scores (HUS) displayed a similar pattern but with smaller differences (P = 0.07), and with evidence of ceiling effect. Among patients with stage II/III esophageal cancer, mean EQ-5D HUS varied across disease states (P < 0.001), along with FACT-E and subscales (P < 0.001). Among patients with advanced disease, there was no significant difference between baseline and on-treatment total scores, but improved esophageal cancer-specific scales were noted (P = 0.003). Strong correlation was observed between EQ-5D and FACT-E (R = 0.73), along with physical and functional subscales. In addition, the association between FACT-E and EQ-5D HUS was maintained in a multivariable model (P < 0.001). We interpret these results to suggest that in a real-world clinic setting, FACT-E, EQ-5D HUS, and symptoms were strongly correlated. Most HRQOL and symptom parameters suggested that patients had worse HRQOL and symptoms during curative therapy, but recovered well afterwards. In contrast, palliative chemotherapy had a neutral to positive impact on HRQOL/symptoms when compared to their baseline pre-treatment state.

DNA-Binding Protein HU Coordinates Pathogenicity in Vibrio parahaemolyticus.

PubMed

Phan, Ngoc Quang; Uebanso, Takashi; Shimohata, Takaaki; Nakahashi, Mutsumi; Mawatari, Kazuaki; Takahashi, Akira

2015-09-01

HU is one of the most abundant nucleoid-associated proteins in bacterial cells and regulates the expression of many genes involved in growth, motility, metabolism, and virulence. It is known that Vibrio parahaemolyticus pathogenicity is related to its characteristic rapid growth and that type III secretion system 1 (T3SS1) contributes to its cytotoxicity. However, it is not known if HU plays a role in the pathogenicity of V. parahaemolyticus. In the present study, we investigated the effect of HU proteins HU-2 (HUα) (V. parahaemolyticus 2911 [vp2911]) and HUβ (vp0920) on the pathogenicity of V. parahaemolyticus. We found that a deletion of both HU subunits (yielding the ΔHUs [Δvp0920 Δvp2911] strain), but not single deletions, led to a reduction of the growth rate. In addition, expression levels of T3SS1-related genes, including exsA (positive regulator), exsD (negative regulator), vp1680 (cytotoxic effector), and vp1671 (T3SS1 apparatus), were reduced in the ΔHUs strain compared to the wild type (WT). As a result, cytotoxicity to HeLa cells was decreased in the ΔHUs strain. The additional deletion of exsD in the ΔHUs strain restored T3SS1-related gene expression levels and cytotoxicity but not the growth rate. These results suggest that the HU protein regulates the levels of T3SS1 gene expression and cytotoxicity in a growth rate-independent manner. Nucleoid-binding protein HU regulates cellular behaviors, including nucleoid structuring, general recombination, transposition, growth, replication, motility, metabolism, and virulence. It is thought that both the number of bacteria and the number of virulence factors may affect the pathogenicity of bacteria. In the present study, we investigated which factor(s) has a dominant role during infection in one of the most rapidly growing bacterial species, Vibrio parahaemolyticus. We found that V. parahaemolyticus cytotoxicity is regulated, in a growth rate-independent manner, by the HU proteins through regulation of a number of virulence factors, including T3SS1 gene expression. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cumulative Review of Thrombotic Microangiopathy, Thrombotic Thrombocytopenic Purpura, and Hemolytic Uremic Syndrome Reports with Subcutaneous Interferon β-1a.

PubMed

Ben-Amor, Ali-Frédéric; Trochanov, Anton; Fischer, Tanya Z

2015-05-01

Rare cases of thrombotic microangiopathy (TMA), manifested as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS), have been reported with interferon β products. We performed a cumulative review of TMA cases recorded in a Global Safety Database for patients with multiple sclerosis who received subcutaneous interferon β-1a treatment. Search criteria were: all reported cases, serious and non-serious, from all sources (including non-health care professionals and clinical trial reports), regardless of event ranking and causality assessment by reporter or company. Data lock was May 3, 2014, with additional analysis of cases reported between August 1, 2014-November 30, 2014. Ninety-one patient cases (76.9% female) with 105 events were retrieved. Time to onset varied from 2 months to 14 years, and in 31.9% of patients the event occurred within 2 years of treatment initiation. Seven patients had a fatal outcome (five were secondary to other causes and two reported insufficient information). Forty-four patients recovered, 32 patients had not recovered at the time of the report, and in eight cases outcome was either not reported or unknown. Treatment was discontinued in 84.6% (77/91) of patients. In 67% (61/91) of patients, the reporter suspected a causal association between treatment and TMA/TTP-HUS. Risk factors and/or confounding factors were present in 45.1% (41/91) of patients. Early prodromal syndrome or specific patterns were not detected, although 54.9% (50/91) of cases contained insufficient information. Overall reporting rate of TMA/TTP-HUS was estimated as 7.2 per 100,000 patient-years. Reporting rates for human serum album (HSA)-containing and HSA-free formulations were 5.72 and 7.68 per 100,000 patient-years, respectively. No new signal relating specifically to increased frequency of TMA/TTP-HUS with HSA-free subcutaneous interferon β-1a was detected and no additional risk mitigation measures are required regarding the different formulations. The benefit-risk balance of subcutaneous interferon β-1a remains positive, and routine pharmacovigilance monitoring is appropriate. Ares Trading SA, Aubonne, Switzerland, a subsidiary of Merck Serono SA.

Epidemiology of Shiga toxin producing Escherichia coli in Australia, 2000-2010

PubMed Central

2012-01-01

Background Shiga toxin-producing Escherichia coli (STEC) are an important cause of gastroenteritis in Australia and worldwide and can also result in serious sequelae such as haemolytic uraemic syndrome (HUS). In this paper we describe the epidemiology of STEC in Australia using the latest available data. Methods National and state notifications data, as well as data on serotypes, hospitalizations, mortality and outbreaks were examined. Results For the 11 year period 2000 to 2010, the overall annual Australian rate of all notified STEC illness was 0.4 cases per 100,000 per year. In total, there were 822 STEC infections notified in Australia over this period, with a low of 1 notification in the Australian Capital Territory (corresponding to a rate of 0.03 cases per 100,000/year) and a high of 413 notifications in South Australia (corresponding to a rate of 2.4 cases per 100,000/year), the state with the most comprehensive surveillance for STEC infection in the country. Nationally, 71.2% (504/708) of STEC infections underwent serotype testing between 2001 and 2009, and of these, 58.0% (225/388) were found to be O157 strains, with O111 (13.7%) and O26 (11.1%) strains also commonly associated with STEC infections. The notification rate for STEC O157 infections Australia wide between 2001-2009 was 0.12 cases per 100,000 per year. Over the same 9 year period there were 11 outbreaks caused by STEC, with these outbreaks generally being small in size and caused by a variety of serogroups. The overall annual rate of notified HUS in Australia between 2000 and 2010 was 0.07 cases per 100,000 per year. Both STEC infections and HUS cases showed a similar seasonal distribution, with a larger proportion of reported cases occurring in the summer months of December to February. Conclusions STEC infections in Australia have remained fairly steady over the past 11 years. Overall, the incidence and burden of disease due to STEC and HUS in Australia appears comparable or lower than similar developed countries. PMID:22264221

Epidemiological analysis of a cluster within the outbreak of Shiga toxin-producing Escherichia coli serotype O104:H4 in Northern Germany, 2011.

PubMed

Scharlach, Martina; Diercke, Michaela; Dreesman, Johannes; Jahn, Nicola; Krieck, Manuela; Beyrer, Konrad; Claußen, Katja; Pulz, Matthias; Floride, Regina

2013-06-01

In May 2011 one of the worldwide largest outbreaks of haemolytic uraemic syndrome (HUS) and bloody diarrhoea caused by Shiga toxin-producing Escherichia coli (STEC) serotype O104:H4 occurred in Germany. One of the most affected federal states was Lower Saxony. We present the investigation of a cluster of STEC and HUS cases within this outbreak by means of a retrospective cohort study. After a 70th birthday celebration which took place on 7th of May 2011 among 72 attendants seven confirmed cases and four probable cases were identified, two of them developed HUS. Median incubation period was 10 days. Only 35 persons (48.6%) definitely answered the question whether they had eaten the sprouts that were used for garnishing the salad. Univariable analysis revealed different food items, depending on the case definition, with Odds Ratio (OR)>1 indicating an association with STEC infection, but multivariable logistic regression showed no increased risk for STEC infection for any food item and any case definition. Sprouts as the source for the infection had to be assumed based on the results of a tracing back of the delivery ways from the catering company to the sprouts producer who was finally identified as the source of the entire German outbreak. In this large outbreak several case-control studies failed to identify the source of infection. Copyright © 2012 Elsevier GmbH. All rights reserved.

Roles of the checkpoint sensor clamp Rad9-Rad1-Hus1 (911)-complex and the clamp loaders Rad17-RFC and Ctf18-RFC in Schizosaccharomyces pombe telomere maintenance.

PubMed

Khair, Lyne; Chang, Ya-Ting; Subramanian, Lakxmi; Russell, Paul; Nakamura, Toru M

2010-06-01

While telomeres must provide mechanisms to prevent DNA repair and DNA damage checkpoint factors from fusing chromosome ends and causing permanent cell cycle arrest, these factors associate with functional telomeres and play critical roles in the maintenance of telomeres. Previous studies have established that Tel1 (ATM) and Rad3 (ATR) kinases play redundant but essential roles for telomere maintenance in fission yeast. In addition, the Rad9-Rad1-Hus1 (911) and Rad17-RFC complexes work downstream of Rad3 (ATR) in fission yeast telomere maintenance. Here, we investigated how 911, Rad17-RFC and another RFC-like complex Ctf18-RFC contribute to telomere maintenance in fission yeast cells lacking Tel1 and carrying a novel hypomorphic allele of rad3 (DBD-rad3), generated by the fusion between the DNA binding domain (DBD) of the fission yeast telomere capping protein Pot1 and Rad3. Our investigations have uncovered a surprising redundancy for Rad9 and Hus1 in allowing Rad1 to contribute to telomere maintenance in DBD-rad3 tel1 cells. In addition, we found that Rad17-RFC and Ctf18-RFC carry out redundant telomere maintenance functions in DBD-rad3 tel1 cells. Since checkpoint sensor proteins are highly conserved, genetic redundancies uncovered here may be relevant to telomere maintenance and detection of DNA damage in other eukaryotes.

Roles of the Checkpoint Sensor Clamp Rad9-Rad1-Hus1 (911)-Complex and the Clamp Loaders Rad17-RFC and Ctf18-RFC in Schizosaccharomyces pombe Telomere Maintenance

PubMed Central

Khair, Lyne; Chang, Ya-Ting; Subramanian, Lakxmi; Russell, Paul; Nakamura, Toru M.

2011-01-01

While telomeres must provide mechanisms to prevent DNA repair and DNA damage checkpoint factors from fusing chromosome ends and causing permanent cell cycle arrest, these factors associate with functional telomeres and play critical roles in the maintenance of telomeres. Previous studies have established that Tel1 (ATM) and Rad3 (ATR) kinases play redundant but essential roles for telomere maintenance in fission yeast. In addition, the Rad9-Rad1-Hus1 (911) and Rad17-RFC complexes work downstream of Rad3 (ATR) in fission yeast telomere maintenance. Here, we investigated how 911, Rad17-RFC and another RFC-like complex Ctf18-RFC contribute to telomere maintenance in fission yeast cells lacking Tel1 and carrying a novel hypomorphic allele of rad3 (DBD-rad3), generated by the fusion between the DNA binding domain (DBD) of the fission yeast telomere capping protein Pot1 and Rad3. Our investigations have uncovered a surprising redundancy for Rad9 and Hus1 in allowing Rad1 to contribute to telomere maintenance in DBD-rad3 tel1Δ cells. In addition, we found that Rad17-RFC and Ctf18-RFC carry out redundant telomere maintenance functions in DBD-rad3 tel1Δ cells. Since checkpoint sensor proteins are highly conserved, genetic redundancies uncovered here may be relevant to telomere maintenance and detection of DNA damage in other eukaryotes. PMID:20505337

The Autism Diagnostic Observation Schedule, Module 4: Application of the Revised Algorithms in an Independent, Well-Defined, Dutch Sample (n = 93).

PubMed

de Bildt, Annelies; Sytema, Sjoerd; Meffert, Harma; Bastiaansen, Jojanneke A C J

2016-01-01

This study examined the discriminative ability of the revised Autism Diagnostic Observation Schedule module 4 algorithm (Hus and Lord in J Autism Dev Disord 44(8):1996-2012, 2014) in 93 Dutch males with Autism Spectrum Disorder (ASD), schizophrenia, psychopathy or controls. Discriminative ability of the revised algorithm ASD cut-off resembled the original algorithm ASD cut-off: highly specific for psychopathy and controls, lower sensitivity than Hus and Lord (2014; i.e. ASD .61, AD .53). The revised algorithm AD cut-off improved sensitivity over the original algorithm. Discriminating ASD from schizophrenia was still challenging, but the better-balanced sensitivity (.53) and specificity (.78) of the revised algorithm AD cut-off may aide clinicians' differential diagnosis. Findings support using the revised algorithm, being conceptually conform the other modules, thus improving comparability across the lifespan.

Chronic Sequelae of E. coli O157: Systematic Review and Meta-analysis of the Proportion of E. coli O157 Cases That Develop Chronic Sequelae

PubMed Central

Sargeant, Jan; Thomas, M. Kate; Fazil, Aamir

2014-01-01

Abstract Objective: This was a systematic review and meta-analysis to determine the proportion of Escherichia coli O157 cases that develop chronic sequelae. Data Sources: We conducted a systematic review of articles published prior to July 2011 in Pubmed, Agricola, CabDirect, or Food Safety and Technology Abstracts. Study Selection: Studies were selected that reported the number of E. coli O157 cases that developed reactive arthritis (ReA), hemolytic uremic syndrome (HUS), irritable bowel syndrome, inflammatory bowel disease, or Guillain Barré syndrome. Methods: Three levels of screening and data extraction of articles were conducted using predefined data fields. Meta-analysis was performed on unique outcome measures using a random-effects model, and heterogeneity was assessed using the I2 value. Meta-regression was used to explore the influence of nine study-level variables on heterogeneity. Results: A total of 82 studies were identified reporting 141 different outcome measures; 81 reported on HUS and one reported on ReA. Depending on the number of cases of E. coli O157, the estimate for the proportion of E. coli O157 cases that develop HUS ranged from 17.2% in extra-small studies (<50 cases) to 4.2% in extra-large studies (>1000 cases). Heterogeneity was significantly associated with group size (p<0.0001); however, the majority of the heterogeneity was unexplained. Conclusions: High unexplained heterogeneity indicated that the study-level factors examined had a minimal influence on the variation of estimates reported. PMID:24404780

A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum

PubMed Central

Tironi-Farinati, Carla; Geoghegan, Patricia A.; Cangelosi, Adriana; Pinto, Alipio; Loidl, C. Fabian; Goldstein, Jorge

2013-01-01

Infection by Shiga toxin-producing Escherichia coli causes hemorrhagic colitis, hemolytic uremic syndrome (HUS), acute renal failure, and also central nervous system complications in around 30% of the children affected. Besides, neurological deficits are one of the most unrepairable and untreatable outcomes of HUS. Study of the striatum is relevant because basal ganglia are one of the brain areas most commonly affected in patients that have suffered from HUS and since the deleterious effects of a sub-lethal dose of Shiga toxin have never been studied in the striatum, the purpose of this study was to attempt to simulate an infection by Shiga toxin-producing E. coli in a murine model. To this end, intravenous administration of a sub-lethal dose of Shiga toxin 2 (0.5 ηg per mouse) was used and the correlation between neurological manifestations and ultrastructural changes in striatal brain cells was studied in detail. Neurological manifestations included significant motor behavior abnormalities in spontaneous motor activity, gait, pelvic elevation and hind limb activity eight days after administration of the toxin. Transmission electron microscopy revealed that the toxin caused early perivascular edema two days after administration, as well as significant damage in astrocytes four days after administration and significant damage in neurons and oligodendrocytes eight days after administration. Interrupted synapses and mast cell extravasation were also found eight days after administration of the toxin. We thus conclude that the chronological order of events observed in the striatum could explain the neurological disorders found eight days after administration of the toxin. PMID:23383285

Effects of Escherichia coli subtilase cytotoxin and Shiga toxin 2 on primary cultures of human renal tubular epithelial cells.

PubMed

Márquez, Laura B; Velázquez, Natalia; Repetto, Horacio A; Paton, Adrienne W; Paton, James C; Ibarra, Cristina; Silberstein, Claudia

2014-01-01

Shiga toxin (Stx)-producing Escherichia coli (STEC) cause post-diarrhea Hemolytic Uremic Syndrome (HUS), which is the most common cause of acute renal failure in children in many parts of the world. Several non-O157 STEC strains also produce Subtilase cytotoxin (SubAB) that may contribute to HUS pathogenesis. The aim of the present work was to examine the cytotoxic effects of SubAB on primary cultures of human cortical renal tubular epithelial cells (HRTEC) and compare its effects with those produced by Shiga toxin type 2 (Stx2), in order to evaluate their contribution to renal injury in HUS. For this purpose, cell viability, proliferation rate, and apoptosis were assayed on HRTEC incubated with SubAB and/or Stx2 toxins. SubAB significantly reduced cell viability and cell proliferation rate, as well as stimulating cell apoptosis in HRTEC cultures in a time dependent manner. However, HRTEC cultures were significantly more sensitive to the cytotoxic effects of Stx2 than those produced by SubAB. No synergism was observed when HRTEC were co-incubated with both SubAB and Stx2. When HRTEC were incubated with the inactive SubAA272B toxin, results were similar to those in untreated control cells. Similar stimulation of apoptosis was observed in Vero cells incubated with SubAB or/and Stx2, compared to HRTEC. In conclusion, primary cultures of HRTEC are significantly sensitive to the cytotoxic effects of SubAB, although, in a lesser extent compared to Stx2.

Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

PubMed Central

Landoni, Verónica I.; Schierloh, Pablo; de Campos Nebel, Marcelo; Fernández, Gabriela C.; Calatayud, Cecilia; Lapponi, María J.; Isturiz, Martín A.

2012-01-01

The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS. PMID:22479186

Analysis of decrease in lung perfusion blood volume with occlusive and non-occlusive pulmonary embolisms.

PubMed

Ikeda, Yohei; Yoshimura, Norihiko; Hori, Yoshiro; Horii, Yosuke; Ishikawa, Hiroyuki; Yamazaki, Motohiko; Noto, Yoshiyuki; Aoyama, Hidefumi

2014-12-01

The aim of this study was to determine if lung perfusion blood volume (lung PBV) with non-occlusive pulmonary embolism (PE) differs quantitatively and visually from that with occlusive PE and to investigate if lung PBV with non-occlusive PE remains the same as that without PE. Totally, 108 patients suspected of having acute PE underwent pulmonary dual-energy computed tomography angiography (DECTA) between April 2011 and January 2012. Presence of PE on DECTA was evaluated by one radiologist. Two radiologists visually evaluated the PE distribution (segmental or subsegmental) and its nature (occlusive or non-occlusive) on DECTA and classified perfusion in lung PBV as "decreased," "slightly decreased," and "preserved". Two radiologists used a lung PBV application to set a region of interest (ROI) in the center of the lesion and measured HU values of an iodine map. In the same slice as the ROI of the lesion and close to the lesion, another ROI was set in the normal perfusion area without PE, and HUs were measured. The proportion of lesions was compared between the occlusive and non-occlusive groups. HUs were compared among the occlusive, non-occlusive, and corresponding normal groups. Twenty-five patients had 80 segmental or subsegmental lesions. There were 37 and 43 lesions in the occlusive and non-occlusive groups, respectively. The proportion of decreased lesions was 73.0% (27/37) in the occlusive group, while that of preserved lesions in the non-occlusive group was 76.7% (33/43). There was a significant difference in the proportion of lesions (P<0.001) between the two groups. HUs of the iodine map were significantly higher in the non-occlusive group than in the occlusive group (33.8 ± 8.2 HU vs. 11.9 ± 6.1 HU, P<0.001). There was no significant difference in HUs for the entire lesion between the non-occlusive (33.8 ± 8.2 HU) and corresponding normal group (34.5 ± 6.8 HU; P=0.294). Iodine perfusion tended to be visually and quantitatively preserved in lungs with nonocclusive PE. Lung PBV is required to evaluate pulmonary blood flow. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The role of gallery forests in maintaining Phlebotominae populations: potential Leishmania spp. vectors in the Brazilian savanna.

PubMed

Machado, Tâmara Dias Oliveira; Minuzzi-Souza, Thaís Tâmara Castro; Ferreira, Tauana de Sousa; Freire, Luciana Pereira; Timbó, Renata Velôzo; Vital, Tamires Emanuele; Nitz, Nadjar; Silva, Mariana Neiva; Santos, Alcinei de Souza; Sales, Nathyla Morgana Cunha; Obara, Marcos Takashi; Andrade, Andrey José de; Gurgel-Gonçalves, Rodrigo

2017-10-01

Knowledge on synanthropic phlebotomines and their natural infection by Leishmania is necessary for the identification of potential areas for leishmaniasis occurrence. To analyse the occurrence of Phlebotominae in gallery forests and household units (HUs) in the city of Palmas and to determine the rate of natural infection by trypanosomatids. Gallery forests and adjacent household areas were sampled on July (dry season) and November (rainy season) in 2014. The total sampling effort was 960 HP light traps and eight Shannon traps. Trypanosomatids were detected in Phlebotominae females through the amplification of the SSU rDNA region, and the positive samples were used in ITS1-PCR. Trypanosomatid species were identified using sequencing. A total of 1,527 sand flies representing 30 species were captured in which 949 (28 spp.) and 578 (22 spp.) were registered in July and November, respectively. In July, more specimens were captured in the gallery forests than in the HUs, and Nyssomyia whitmani was particularly frequent. In November, most of the specimens were found in the HUs, and again, Ny. whitmani was the predominant species. Lutzomyia longipalpis was commonly found in domestic areas, while Bichromomyia flaviscutellata was most frequent in gallery forests. Molecular analysis of 154 pools of females (752 specimens) identified Leishmania amazonensis, L. infantum, and Crithidia fasciculata in Ny. whitmani, as well as L. amazonensis in Lu. longipalpis, Trypanosoma sp. and L. amazonensis in Pintomyia christenseni, and L. amazonensis in both Psathyromyia hermanlenti and Evandromyia walkeri. These results show the importance of gallery forests in maintaining Phlebotominae populations in the dry month, as well as their frequent occurrence in household units in the rainy month. This is the first study to identify Leishmania, Trypanosoma, and Crithidia species in Phlebotominae collected in Palmas, Tocantins, Brazil.

Comparative Genomics of Recent Shiga Toxin-Producing Escherichia coli O104:H4: Short-Term Evolution of an Emerging Pathogen

PubMed Central

Grad, Yonatan H.; Godfrey, Paul; Cerquiera, Gustavo C.; Mariani-Kurkdjian, Patricia; Gouali, Malika; Bingen, Edouard; Shea, Terrence P.; Haas, Brian J.; Griggs, Allison; Young, Sarah; Zeng, Qiandong; Lipsitch, Marc; Waldor, Matthew K.; Weill, François-Xavier; Wortman, Jennifer R.; Hanage, William P.

2013-01-01

ABSTRACT The large outbreak of diarrhea and hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli O104:H4 in Europe from May to July 2011 highlighted the potential of a rarely identified E. coli serogroup to cause severe disease. Prior to the outbreak, there were very few reports of disease caused by this pathogen and thus little known of its diversity and evolution. The identification of cases of HUS caused by E. coli O104:H4 in France and Turkey after the outbreak and with no clear epidemiological links raises questions about whether these sporadic cases are derived from the outbreak. Here, we report genome sequences of five independent isolates from these cases and results of a comparative analysis with historical and 2011 outbreak isolates. These analyses revealed that the five isolates are not derived from the outbreak strain; however, they are more closely related to the outbreak strain and each other than to isolates identified prior to the 2011 outbreak. Over the short time scale represented by these closely related organisms, the majority of genome variation is found within their mobile genetic elements: none of the nine O104:H4 isolates compared here contain the same set of plasmids, and their prophages and genomic islands also differ. Moreover, the presence of closely related HUS-associated E. coli O104:H4 isolates supports the contention that fully virulent O104:H4 isolates are widespread and emphasizes the possibility of future food-borne E. coli O104:H4 outbreaks. PMID:23341549

Critical congenital heart disease--utility of routine screening for chromosomal and other extracardiac malformations.

PubMed

Baker, Kimberly; Sanchez-de-Toledo, Joan; Munoz, Ricardo; Orr, Richard; Kiray, Shareen; Shiderly, Dana; Clemens, Michele; Wearden, Peter; Morell, Victor O; Chrysostomou, Constantinos

2012-01-01

Objective.  Infants with critical congenital heart disease (CHD) can have genetic and other extracardiac malformations, which add to the short- and long-term risk of morbidity and perhaps mortality. We sought to examine our center's practice of screening for extracardiac anomalies and to determine the yield of these tests among specific cardiac diagnostic categories. Design.  Retrospective review of infants admitted to the cardiac intensive care unit with a new diagnosis of CHD. Subjects were categorized into six groups: septal defects (SD), conotruncal defects (CTD), single-ventricle physiology (SV), left-sided obstructive lesions (LSO), right-sided obstructive lesions (RSO), and "other" (anomalous pulmonary venous return, Ebstein's anomaly). Screening modalities included genetic testing (karyotype and fluorescent in situ hybridization for 22q11.2 deletion), renal ultrasound (RUS), and head ultrasound (HUS). Results.  One hundred forty-one patients were identified. The incidence of cardiac anomalies was: CTD (36%), SD (18%), SV (18%), LSO (14%), RSO (3%), and "other" (8%). Overall 14% had an abnormal karyotype, 5% had a deletion for 22q11.2, 28% had an abnormal RUS and 22% had abnormal HUS. Patients in SD and SV had the highest incidence of abnormal karyotype (36% and 17%); 22q11.2 deletion was present only in CTD and LSO groups (9% and 7%, respectively); abnormal RUS and HUS were seen relatively uniformly in all categories. Premature infants had significantly higher incidence of renal 43% vs. 24%, and intracranial abnormalities 46% vs. 16%. Conclusion.  Infants with critical CHD and particularly premature infants have high incidence of genetic and other extracardiac anomalies. Universal screening for these abnormalities with ultrasonographic and genetic testing maybe warranted because early detection could impact short and long-term outcomes. © 2011 Wiley Periodicals, Inc.

Quantitative risk assessment for Escherichia coli O157:H7 in frozen ground beef patties consumed by young children in French households.

PubMed

Delignette-Muller, M L; Cornu, M

2008-11-30

A quantitative risk assessment for Escherichia coli O157:H7 in frozen ground beef patties consumed by children under 10 years of age in French households was conducted by a national study group describing an outbreak which occurred in France in 2005. Our exposure assessment model incorporates results from French surveys on consumption frequency of ground beef patties, serving size and consumption preference, microbial destruction experiments and microbial counts on patties sampled from the industrial batch which were responsible for the outbreak. Two different exposure models were proposed, respectively for children under the age of 5 and for children between 5 and 10 years. For each of these two age groups, a single-hit dose-response model was proposed to describe the probability of hemolytic and uremic syndrome (HUS) as a function of the ingested dose. For each group, the single parameter of this model was estimated by Bayesian inference, using the results of the exposure assessment and the epidemiological data collected during the outbreak. Results show that children under 5 years of age are roughly 5 times more susceptible to the pathogen than children over 5 years. Exposure and dose-response models were used in a scenario analysis in order to validate the use of the model and to propose appropriate guidelines in order to prevent new outbreaks. The impact of the cooking preference was evaluated, showing that only a well-done cooking notably reduces the HUS risk, without annulling it. For each age group, a relation between the mean individual HUS risk per serving and the contamination level in a ground beef batch was proposed, as a tool to help French risk managers.

Calculating the number of shock waves, expulsion time, and optimum stone parameters based on noncontrast computerized tomography characteristics.

PubMed

Foda, Khaled; Abdeldaeim, Hussein; Youssif, Mohamed; Assem, Akram

2013-11-01

To define the parameters that accompanied a successful extracorporeal shock wave lithotripsy (ESWL), namely the number of shock waves (SWs), expulsion time (ET), mean stone density (MSD), and the skin-to-stone distance (SSD). A total of 368 patients diagnosed with renal calculi using noncontrast computerized tomography had their MSD, diameter, and SSD recorded. All patients were treated using a Siemens lithotripter. ESWL success meant a stone-free status or presence of residual fragments <3 mm, ET was the time in days for the successful clearance of stone fragments. Correlation was performed between the stone characteristics, number of SWs, and ET. Two multiple regression analysis models defined the number of SWs and ET. Two receiver operating characteristic curves plotted the best MSD cutoff value and optimum SSD for a successful ESWL. Three hundred one patients were ESWL successes. A significant positive correlation was elicited between number of SWs and stone diameter, density and SSD; between ET and stone diameter and density. Multiple regressions concluded 2 equations: Number of SWs = 265.108 + 5.103 x1 + 22.39 x2 + 10.931 x3 ET (days) = -10.85 + 0.031 x1 + 2.11 x2 x1 = stone density (Hounsfield unit [HUs]), x2 = stone diameter (mm), and x3 = SSD (mm). Receiver operating characteristic curves demonstrated a cutoff value of ≤ 934 HUs with 94.4% sensitivity and 66.7% specificity and P = .0211. The SSD curve showed that a distance ≤ 99 mm was 85.7% sensitive, 87.5% specific, P <.0001. Stone disintegration is not recommended if MSD is >934 HUs and SSD >99 mm. The required number of SWs and the expected ET can be anticipated. Copyright © 2013 Elsevier Inc. All rights reserved.

78 FR 10269 - National Primary Drinking Water Regulations: Revisions to the Total Coliform Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

... agencies incur the remaining costs. Abbreviations Used in This Document AGI--Acute Gastrointestinal Illness AIDS--Acquired Immune Deficiency Syndrome AIP--Agreement in Principle AWWA--American Water Works... Analysis HUS--Hemolytic Uremic Syndrome ICR--Information Collection Request IESWTR--Interim Enhanced...

[The 2011 HUS epidemic in Germany. Challenges for disease control: what should be improved?].

PubMed

Krause, G; Frank, C; Gilsdorf, A; Mielke, M; Schaade, L; Stark, K; Burger, R

2013-01-01

From May to July 2011 [corrected] the world's largest outbreak of hemolytic uremic syndrome (HUS) occurred in northern Germany with dramatic consequences for the population, the health care system and the food industry. In the following we examine the detection of the outbreak, epidemic management and related public communication aspects based on scientific publications, media reports as well as own and new data analyses. The subsequent 17 recommendations concern issues such as participation in and implementation of existing and new surveillance systems particularly with respect to physicians, broad application of finely tuned microbiological typing, improved personnel capacity and crisis management structures within the public health service and evidence-based communication by administrations and scientific associations. Outbreaks of similar dimensions can inevitably occur again and result in costs which will far exceed investments needed for early detection and control. This societal balance should be taken into account in spite of limited resources in the public health sector.

Mouse Models of Escherichia coli O157:H7 Infection and Shiga Toxin Injection

PubMed Central

Mohawk, Krystle L.; O'Brien, Alison D.

2011-01-01

Escherichia coli O157:H7 has been responsible for multiple food- and waterborne outbreaks of diarrhea and/or hemorrhagic colitis (HC) worldwide. More importantly, a portion of E. coli O157:H7-infected individuals, particularly young children, develop a life-threatening sequela of infection called hemolytic uremic syndrome (HUS). Shiga toxin (Stx), a potent cytotoxin, is the major virulence factor linked to the presentation of both HC and HUS. Currently, treatment of E. coli O157:H7 and other Stx-producing E. coli (STEC) infections is limited to supportive care. To facilitate development of therapeutic strategies and vaccines for humans against these agents, animal models that mimic one or more aspect of STEC infection and disease are needed. In this paper, we focus on the characteristics of various mouse models that have been developed and that can be used to monitor STEC colonization, disease, pathology, or combinations of these features as well as the impact of Stx alone. PMID:21274267

Pathogenic Potential to Humans of Bovine Escherichia coli O26, Scotland

PubMed Central

Rosser, Tracy; Allison, Lesley J.; Courcier, Emily; Evans, Judith; McKendrick, Iain J.; Pearce, Michael C.; Handel, Ian; Caprioli, Alfredo; Karch, Helge; Hanson, Mary F.; Pollock, Kevin G.J.; Locking, Mary E.; Woolhouse, Mark E.J.; Matthews, Louise; Low, J. Chris; Gally, David L.

2012-01-01

Escherichia coli O26 and O157 have similar overall prevalences in cattle in Scotland, but in humans, Shiga toxin–producing E. coli O26 infections are fewer and clinically less severe than E. coli O157 infections. To investigate this discrepancy, we genotyped E. coli O26 isolates from cattle and humans in Scotland and continental Europe. The genetic background of some strains from Scotland was closely related to that of strains causing severe infections in Europe. Nonmetric multidimensional scaling found an association between hemolytic uremic syndrome (HUS) and multilocus sequence type 21 strains and confirmed the role of stx2 in severe human disease. Although the prevalences of E. coli O26 and O157 on cattle farms in Scotland are equivalent, prevalence of more virulent strains is low, reducing human infection risk. However, new data on E. coli O26–associated HUS in humans highlight the need for surveillance of non-O157 enterohemorrhagic E. coli and for understanding stx2 phage acquisition. PMID:22377426

ATTENUATION OF ALCOHOL CONSUMPTION BY MDMA (ECSTASY) IN TWO STRAINS OF ALCOHOL PREFERRING RATS

EPA Science Inventory

Alcohol preference and manifestation of alcoholism are thought by many to be associated with serotonin (5-HT) dysfunction in the brain. hus, experiments were performed to determine the effect of acute and sub-chronic administration (s.c.) of (+/-)3,4-methylenedioxymethamphetamine...

75 FR 40925 - National Primary Drinking Water Regulations: Revisions to the Total Coliform Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-14

... discussion on docket. Abbreviations Used in This Document ADWR Airline Drinking Water Rule AGI Acute Gastrointestinal Illness AIDS Acquired Immune Deficiency Syndrome AIP Agreement in Principle AWWA American Water... Cost Analysis HUS Hemolytic Uremic Syndrome ICR Information Collection Request IESWTR Interim Enhanced...

An improved method for detection of Shiga toxin 2 in human serum

USDA-ARS?s Scientific Manuscript database

Shiga toxins (Stx) produced by Stx-producing Escherichia coli (STEC) are virulence factors that is most closely associated with hemolytic uremic syndrome (HUS), a life-threatening complication of intestinal infections by STEC. Stx have to enter into the circulation system before they can be delivere...

Mouse in vivo neutralization of Escherichia coli Shiga toxin 2 with monoclonal antibodies

USDA-ARS?s Scientific Manuscript database

Escherichia coli (E. coli) food contaminations pose serious health and food safety concerns, and have been the subject of massive food recalls. Shiga toxin 2 (Stx2)-producing E. coli has been identified as the major cause of hemorrhagic colitis and hemolytic uremic syndrome (HUS), the most severe di...

Ingested Shiga Toxin 2 (Stx2) Causes Histopathological Changes in Kidney, Spleen and Thymus Tissues and Mortality in Mice

USDA-ARS?s Scientific Manuscript database

The Shiga toxin (Stxs) producing bacterial strain, Escherichia coli O157:H7, colonizes the distal small intestine and the colon, initiating a very broad spectrum of illnesses such as hemolytic-uremic syndrome (HUS) characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal ...

Serum Shiga toxin 2 values in patients during the acute phase of post-diarrheal hemolytic uremic syndrome

USDA-ARS?s Scientific Manuscript database

Shiga toxins (Stxs) produced by Shiga toxin-producing Escherichia coli (STEC) are considered as the main causative agent, leading to the development of the hemolytic uremic syndrome (HUS); these toxins injure endothelial cells mainly the glomeruli. After passing through the intestinal wall, Stxs hav...

Outbreak of verocytotoxin-producing E. coli O145 and O26 infections associated with the consumption of ice cream produced at a farm, Belgium, 2007.

PubMed

De Schrijver, K; Buvens, G; Possé, B; Van den Branden, D; Oosterlynck, O; De Zutter, L; Eilers, K; Piérard, D; Dierick, K; Van Damme-Lombaerts, R; Lauwers, C; Jacobs, R

2008-02-14

In October 2007, an outbreak of verocytotoxin-producing Escherichia coli (VTEC) O145 and E. coli O26 occurred among consumers of ice cream produced and sold in September 2007 at a farm in the province of Antwerp (Belgium). The ice cream was consumed at two birthday parties and also eaten at the farm. Five children, aged between two and 11 years, developed haemolytic uraemic syndrome (HUS), and seven other co-exposed persons contracted severe diarrhoea. In three of the five HUS cases VTEC O145 infections were laboratory confirmed, one in association with VTEC O26. Identical isolates of E. coli O145 and O26 were detected with PCR and PFGE in faecal samples of patients and in ice cream leftovers from one of the birthday parties, in faecal samples taken from calves, and in samples of soiled straw from the farm at which the ice cream was produced. Ice cream was made from pasteurised milk and most likely contaminated by one of food handlers.

Disability pension in Malmöhus county: aspects on long-term financial effects.

PubMed

Månsson, N O; Råstam, L; Adolfsson, A

1998-06-01

The purpose of this study was to estimate the financial costs of disability pension in order to compare the financial burden and the numerical distribution of disability pension by main diagnostic groups. During three months all new disability pensions (n = 944) granted in Malmöhus county were registered. During a follow-up of approximately two and a half years, 40 subjects died and 15 pensions expired. The predominating diagnoses were musculoskeletal diseases, mental disorders including alcohol dependence, cardiovascular and neurological diseases. To analyse whether these proportions changed when the extent of the pension, age at pension and the retirement allowance were considered, the present value of the total retirement allowances was calculated. The ranking of the four predominating diagnosis categories was not affected by the extent of the pension or the age at which the pension was granted. Thus, musculoskeletal diseases still predominated, although the proportion decreased. Among unemployed subjects, mental disorders made the largest contribution to the total expenditure. The results gained may be used in further research where alternatives to disability pension for different groups of patients and/or diagnoses are investigated.

SU-E-J-218: Evaluation of CT Images Created Using a New Metal Artifact Reduction Reconstruction Algorithm for Radiation Therapy Treatment Planning

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

Niemkiewicz, J; Palmiotti, A; Miner, M

2014-06-01

Purpose: Metal in patients creates streak artifacts in CT images. When used for radiation treatment planning, these artifacts make it difficult to identify internal structures and affects radiation dose calculations, which depend on HU numbers for inhomogeneity correction. This work quantitatively evaluates a new metal artifact reduction (MAR) CT image reconstruction algorithm (GE Healthcare CT-0521-04.13-EN-US DOC1381483) when metal is present. Methods: A Gammex Model 467 Tissue Characterization phantom was used. CT images were taken of this phantom on a GE Optima580RT CT scanner with and without steel and titanium plugs using both the standard and MAR reconstruction algorithms. HU valuesmore » were compared pixel by pixel to determine if the MAR algorithm altered the HUs of normal tissues when no metal is present, and to evaluate the effect of using the MAR algorithm when metal is present. Also, CT images of patients with internal metal objects using standard and MAR reconstruction algorithms were compared. Results: Comparing the standard and MAR reconstructed images of the phantom without metal, 95.0% of pixels were within ±35 HU and 98.0% of pixels were within ±85 HU. Also, the MAR reconstruction algorithm showed significant improvement in maintaining HUs of non-metallic regions in the images taken of the phantom with metal. HU Gamma analysis (2%, 2mm) of metal vs. non-metal phantom imaging using standard reconstruction resulted in an 84.8% pass rate compared to 96.6% for the MAR reconstructed images. CT images of patients with metal show significant artifact reduction when reconstructed with the MAR algorithm. Conclusion: CT imaging using the MAR reconstruction algorithm provides improved visualization of internal anatomy and more accurate HUs when metal is present compared to the standard reconstruction algorithm. MAR reconstructed CT images provide qualitative and quantitative improvements over current reconstruction algorithms, thus improving radiation treatment planning accuracy.« less

A humidity shock leads to rapid, temperature dependent changes in coffee leaf physiology and gene expression.

PubMed

Thioune, El-Hadji; McCarthy, James; Gallagher, Thomas; Osborne, Bruce

2017-03-01

Climate change is expected to increase the frequency of above-normal atmospheric water deficits contemporaneous with periods of high temperatures. Here we explore alterations in physiology and gene expression in leaves of Coffea canephora Pierre ex A. Froehner caused by a sharp drop in relative humidity (RH) at three different temperatures. Both stomatal conductance (gs) and CO2 assimilation (A) measurements showed that gs and A values fell quickly at all temperatures after the transfer to low RH.  However, leaf relative water content measurements indicated that leaves nonetheless experienced substantial water losses, implying that stomatal closure and/or resupply of water was not fast enough to stop excessive evaporative losses.  At 27 and 35 °C, upper leaves showed significant decreases in Fv/Fm compared with lower leaves, suggesting a stronger impact on photosystem II for upper leaves, while at 42 °C, both upper and lower leaves were equally affected. Quantitative gene expression analysis of transcription factors associated with conventional dehydration stress, and genes involved with abscisic acid signalling, such as CcNCED3, indicated temperature-dependent, transcriptional changes during the Humidity Shock ('HuS') treatments.  No expression was seen at 27 °C for the heat-shock gene CcHSP90-7, but it was strongly induced during the 42 °C 'HuS' treatment. Consistent with a proposal that important cellular damage occurred during the 42 °C 'HuS' treatment, two genes implicated in senescence were induced by this treatment. Overall, the data show that C. canephora plants subjected to a sharp drop in RH exhibit major, temperature-dependent alterations in leaf physiology and important changes in the expression of genes associated with abiotic stress and senescence. The results presented suggest that more detailed studies on the combined effects of low RH and high temperature are warranted. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

SU-F-I-45: An Automated Technique to Measure Image Contrast in Clinical CT Images

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

Sanders, J; Abadi, E; Meng, B

Purpose: To develop and validate an automated technique for measuring image contrast in chest computed tomography (CT) exams. Methods: An automated computer algorithm was developed to measure the distribution of Hounsfield units (HUs) inside four major organs: the lungs, liver, aorta, and bones. These organs were first segmented or identified using computer vision and image processing techniques. Regions of interest (ROIs) were automatically placed inside the lungs, liver, and aorta and histograms of the HUs inside the ROIs were constructed. The mean and standard deviation of each histogram were computed for each CT dataset. Comparison of the mean and standardmore » deviation of the HUs in the different organs provides different contrast values. The ROI for the bones is simply the segmentation mask of the bones. Since the histogram for bones does not follow a Gaussian distribution, the 25th and 75th percentile were computed instead of the mean. The sensitivity and accuracy of the algorithm was investigated by comparing the automated measurements with manual measurements. Fifteen contrast enhanced and fifteen non-contrast enhanced chest CT clinical datasets were examined in the validation procedure. Results: The algorithm successfully measured the histograms of the four organs in both contrast and non-contrast enhanced chest CT exams. The automated measurements were in agreement with manual measurements. The algorithm has sufficient sensitivity as indicated by the near unity slope of the automated versus manual measurement plots. Furthermore, the algorithm has sufficient accuracy as indicated by the high coefficient of determination, R2, values ranging from 0.879 to 0.998. Conclusion: Patient-specific image contrast can be measured from clinical datasets. The algorithm can be run on both contrast enhanced and non-enhanced clinical datasets. The method can be applied to automatically assess the contrast characteristics of clinical chest CT images and quantify dependencies that may not be captured in phantom data.« less

Changing picture of renal cortical necrosis in acute kidney injury in developing country

PubMed Central

Prakash, Jai; Singh, Vijay Pratap

2015-01-01

Renal cortical necrosis (RCN) is characterized by patchy or diffuse ischemic destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. In addition, direct endothelial injury particularly in setting of sepsis, eclampsia, haemolytic uremic syndrome (HUS) and snake bite may lead to endovascular thrombosis with subsequent renal ischemia. Progression to end stage renal disease is a rule in diffuse cortical necrosis. It is a rare cause of acute kidney injury (AKI) in developed countries with frequency of 1.9%-2% of all patients with AKI. In contrast, RCN incidence is higher in developing countries ranging between 6%-7% of all causes of AKI. Obstetric complications (septic abortion, puerperal sepsis, abruptio placentae, postpartum haemorrhage and eclampsia) are the main (60%-70%) causes of RCN in developing countries. The remaining 30%-40% cases of RCN are caused by non-obstetrical causes, mostly due to sepsis and HUS. The incidence of RCN ranges from 10% to 30% of all cases of obstetric AKI compared with only 5% in non-gravid patients. In the developed countries, RCN accounts for 2% of all cases of AKI in adults and more than 20% of AKI during the third trimester of pregnancy. The reported incidence of RCN in obstetrical AKI varies between 18%-42.8% in different Indian studies. However, the overall incidence of RCN in pregnancy related AKI has decreased from 20%-30% to 5% in the past two decades in India. Currently RCN accounts for 3% of all causes of AKI. The incidence of RCN in obstetrical AKI was 1.44% in our recent study. HUS is most common cause of RCN in non-obstetrical group, while puerperal sepsis is leading cause of RCN in obstetric group. Because of the catastrophic sequelae of RCN, its prevention and aggressive management should always be important for the better renal outcome and prognosis of the patients. PMID:26558184

Real-World EQ5D Health Utility Scores for Patients With Metastatic Lung Cancer by Molecular Alteration and Response to Therapy.

PubMed

Labbé, Catherine; Leung, Yvonne; Silva Lemes, João Gabriel; Stewart, Erin; Brown, Catherine; Cosio, Andrea Perez; Doherty, Mark; O'Kane, Grainne M; Patel, Devalben; Cheng, Nicholas; Liang, Mindy; Gill, Gursharan; Rett, Alexandra; Naik, Hiten; Eng, Lawson; Mittmann, Nicole; Leighl, Natasha B; Bradbury, Penelope A; Shepherd, Frances A; Xu, Wei; Liu, Geoffrey; Howell, Doris

2017-07-01

Economic analyses of upcoming treatments for lung cancer benefit from real-world health utility scores (HUSs) in an era of targeted therapy. A longitudinal cohort study at Princess Margaret Cancer Centre evaluated 1571 EQ5D-3L-derived HUSs in 475 outpatients with metastatic lung cancer across various disease states. Patients with epidermal growth factor receptor (EGFR) (n = 183) and anaplastic lymphoma kinase (ALK) (n = 38) driver alterations were enriched through targeted enrolment; patients with wild-type non-small-cell lung cancer (WT NSCLC) (n = 224) and small-cell lung cancer (SCLC) (n = 30) were sampled randomly. For patients stable on most appropriate treatment, the mean HUSs were 0.81 and 0.82 in patients receiving EGFR and ALK tyrosine kinase inhibitors (TKIs) respectively (with similar HUSs across agents), which were higher than patients with WT NSCLC (0.78; P = .04) and SCLC receiving chemotherapy (0.72; P = .06). In mutation-specific comparisons, disease stability on appropriate therapy resulted in significantly higher mean HUSs (P < .002-.02) than when disease was progressing (mean HUS: EGFR, 0.70; ALK, 0.69; WT NSCLC, 0.66; SCLC, 0.52). When evaluating treatment-related toxicities, significant inverse relationships were observed between HUS and the severity of fatigue and decreased appetite in the EGFR group. There was also a significant inverse relationship between the total number of clinically significant symptoms and HUS, both in patients who were EGFR-mutated and patients with WT NSCLC. In a North American setting, HUSs generated from patients with metastatic lung cancer are higher in treated, stable patients carrying driver mutations. This is partially explainable by treatment toxicity and patient symptom differences. Such differences in scores should be considered in economic analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

Clade 8 and Clade 6 Strains of Escherichia coli O157:H7 from Cattle in Argentina have Hypervirulent-Like Phenotypes

PubMed Central

Amigo, Natalia; Mercado, Elsa; Bentancor, Adriana; Singh, Pallavi; Vilte, Daniel; Gerhardt, Elisabeth; Zotta, Elsa; Ibarra, Cristina; Manning, Shannon D.; Larzábal, Mariano; Cataldi, Angel

2015-01-01

The hemolytic uremic syndrome (HUS) whose main causative agent is enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a disease that mainly affects children under 5 years of age. Argentina is the country with the highest incidence of HUS in the world. Cattle are a major reservoir and source of infection with E. coli O157:H7. To date, the epidemiological factors that contribute to its prevalence are poorly understood. Single nucleotide polymorphism (SNP) typing has helped to define nine E. coli O157:H7 clades and the clade 8 strains were associated with most of the cases of severe disease. In this study, eight randomly selected isolates of EHEC O157:H7 from cattle in Argentina were studied as well as two human isolates. Four of them were classified as clade 8 through the screening for 23 SNPs; the two human isolates grouped in this clade as well, while two strains were closely related to strains representing clade 6. To assess the pathogenicity of these strains, we assayed correlates of virulence. Shiga toxin production was determined by an ELISA kit. Four strains were high producers and one of these strains that belonged to a novel genotype showed high verocytotoxic activity in cultured cells. Also, these clade 8 and 6 strains showed high RBC lysis and adherence to epithelial cells. One of the clade 6 strains showed stronger inhibition of normal water absorption than E. coli O157:H7 EDL933 in human colonic explants. In addition, two of the strains showing high levels of Stx2 production and RBC lysis activity were associated with lethality and uremia in a mouse model. Consequently, circulation of such strains in cattle may partially contribute to the high incidence of HUS in Argentina. PMID:26030198

The role of gallery forests in maintaining Phlebotominae populations: potential Leishmania spp. vectors in the Brazilian savanna

PubMed Central

Machado, Tâmara Dias Oliveira; Minuzzi-Souza, Thaís Tâmara Castro; Ferreira, Tauana de Sousa; Freire, Luciana Pereira; Timbó, Renata Velôzo; Vital, Tamires Emanuele; Nitz, Nadjar; Silva, Mariana Neiva; Santos, Alcinei de Souza; Sales, Nathyla Morgana Cunha; Obara, Marcos Takashi; de Andrade, Andrey José; Gurgel-Gonçalves, Rodrigo

2017-01-01

BACKGROUND Knowledge on synanthropic phlebotomines and their natural infection by Leishmania is necessary for the identification of potential areas for leishmaniasis occurrence. OBJECTIVE To analyse the occurrence of Phlebotominae in gallery forests and household units (HUs) in the city of Palmas and to determine the rate of natural infection by trypanosomatids. METHODS Gallery forests and adjacent household areas were sampled on July (dry season) and November (rainy season) in 2014. The total sampling effort was 960 HP light traps and eight Shannon traps. Trypanosomatids were detected in Phlebotominae females through the amplification of the SSU rDNA region, and the positive samples were used in ITS1-PCR. Trypanosomatid species were identified using sequencing. FINDINGS A total of 1,527 sand flies representing 30 species were captured in which 949 (28 spp.) and 578 (22 spp.) were registered in July and November, respectively. In July, more specimens were captured in the gallery forests than in the HUs, and Nyssomyia whitmani was particularly frequent. In November, most of the specimens were found in the HUs, and again, Ny. whitmani was the predominant species. Lutzomyia longipalpis was commonly found in domestic areas, while Bichromomyia flaviscutellata was most frequent in gallery forests. Molecular analysis of 154 pools of females (752 specimens) identified Leishmania amazonensis, L. infantum, and Crithidia fasciculata in Ny. whitmani, as well as L. amazonensis in Lu. longipalpis, Trypanosoma sp. and L. amazonensis in Pintomyia christenseni, and L. amazonensis in both Psathyromyia hermanlenti and Evandromyia walkeri. MAIN CONCLUSIONS These results show the importance of gallery forests in maintaining Phlebotominae populations in the dry month, as well as their frequent occurrence in household units in the rainy month. This is the first study to identify Leishmania, Trypanosoma, and Crithidia species in Phlebotominae collected in Palmas, Tocantins, Brazil. PMID:28953996

A new immunoassay for detecting all subtypes of Shiga toxins produced by Shiga toxin-producing E. coli in ground beef

USDA-ARS?s Scientific Manuscript database

Background Shiga toxin (Stx) is a common virulence factor of all Shiga toxin producing E. coli (STEC) that cause a wide spectrum of disease, including hemorrhagic colitis and hemolytic uremic syndrome (HUS). Although several commercial kits are available for detection of Stx produced by STEC, none o...

Characterization of shiga toxin-producing Escherichia coli recovered from domestic animals to determine stx variants, virulence genes, and cytotoxicity in mammalian cells

USDA-ARS?s Scientific Manuscript database

Shiga toxin-producing Escherichia coli (STEC) can cause foodborne illnesses ranging from diarrhea to severe diseases such as hemorrhagic colitis (HC), and hemolytic uremic syndrome (HUS) in humans. In this study, we determined virulence genes, stx subtypes and we evaluated the cytotoxicity in mammal...

Effect of outside air ventilation rate on VOC concentrations and emissions in a call center

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

Hodgson, A.T.; Faulkner, D.; Sullivan, D.P.

2002-01-01

A study of the relationship between outside air ventilation rate and concentrations of VOCs generated indoors was conducted in a call center. Ventilation rates were manipulated in the building's four air handling units (AHUs). Concentrations of VOCs in the AHU returns were measured on 7 days during a 13-week period. Indoor minus outdoor concentrations and emission factors were calculated. The emission factor data was subjected to principal component analysis to identify groups of co-varying compounds based on source type. One vector represented emissions of solvents from cleaning products. Another vector identified occupant sources. Direct relationships between ventilation rate and concentrationsmore » were not observed for most of the abundant VOCs. This result emphasizes the importance of source control measures for limiting VOC concentrations in buildings.« less

Self-reported short sleep duration and insomnia symptoms as predictors of post-pregnancy weight change: Results from a cohort study

PubMed Central

Rognmo, Kamilla; Sivertsen, Børge; Eberhard-Gran, Malin

2016-01-01

This study aims to investigate whether change in sleep duration and insomnia symptoms in the postpartum period is related to change in body mass index from before to 2 years after pregnancy. This study is based on self-report data from a Norwegian cohort, the AHUS Birth Cohort Study. Data were collected at 8 weeks (T1) and 2 years (T2) postpartum. Data from 812 women were analyzed. The results showed that only women with symptoms of insomnia at both T1 and T2 (persistent symptoms) had a greater increase in body mass index compared to women with no insomnia symptoms at T1 or T2.The results indicate that persistent insomnia symptoms are related to a greater increase in body mass index. PMID:27634975

Serum Shiga toxin 2 values in patients during the acute phase of diarrhoea-associated hemolytic uremic syndrome

USDA-ARS?s Scientific Manuscript database

Aim: Shiga toxins, Stx-1 and Stx-2, by injuring endothelial cells mainly of the glomeruli, are considered as the cause of D+HUS. After passing through the intestinal wall, Stxs have to be delivered via the systemic circulation to the target organs. This study was aimed at measuring free Stx-2 in ser...

Characterization of free lytic bacteriophages isolated from compost against O145 Shiga toxin-producing Escherichia coli (STEC) as a potential biocontrol agent

USDA-ARS?s Scientific Manuscript database

Shiga toxin-producing E. coli (STEC), one of the most prevalent foodborne pathogens, are notorious for hemolytic uremic syndrome (HUS) and causing high mortality among children and the elder population after infection. Besides O157 STEC, non-O157 STEC—particularly serogroup O145—is commonly associat...

Active Shiga-Like Toxin Produced by Some Aeromonas spp., Isolated in Mexico City.

PubMed

Palma-Martínez, Ingrid; Guerrero-Mandujano, Andrea; Ruiz-Ruiz, Manuel J; Hernández-Cortez, Cecilia; Molina-López, José; Bocanegra-García, Virgilio; Castro-Escarpulli, Graciela

2016-01-01

Shiga-like toxins (Stx) represent a group of bacterial toxins involved in human and animal diseases. Stx is produced by enterohemorrhagic Escherichia coli, Shigella dysenteriae type 1, Citrobacter freundii , and Aeromonas spp.; Stx is an important cause of bloody diarrhea and hemolytic uremic syndrome (HUS). The aim of this study was to identify the stx 1 /stx 2 genes in clinical strains and outer membrane vesicles (OMVs) of Aeromonas spp., 66 strains were isolated from children who live in Mexico City, and Stx effects were evaluated in Vero cell cultures. The capacity to express active Stx1 and Stx2 toxins was determined in Vero cell cultures and the concentration of Stx was evaluated by 50% lethal dose (LD 50 ) assays, observing inhibition of damaged cells by specific monoclonal antibodies. The results obtained in this study support the hypothesis that the stx gene is another putative virulence factor of Aeromonas , and since this gene can be transferred horizontally through OMVs this genus should be included as a possible causal agents of gastroenteritis and it should be reported as part of standard health surveillance procedures. Furthermore, these results indicate that the Aeromonas genus might be a potential causative agent of HUS.

Shiga toxin-producing Escherichia coli in swine: the public health perspective

PubMed Central

Tseng, Marion; Fratamico, Pina M.; Manning, Shannon D.; Funk, Julie A.

2014-01-01

Shiga toxin-producing Escherichia coli (STEC) strains are food-borne pathogens that are an important public health concern. STEC infection is associated with severe clinical diseases in human beings, including hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS), which can lead to kidney failure and death. Cattle are the most important STEC reservoir. However, a number of STEC outbreaks and HUS cases have been attributed to pork products. In swine, STEC strains are known to be associated with edema disease. Nevertheless, the relationship between STEC of swine origin and human illness has yet to be determined. This review critically summarizes epidemiologic and biological studies of swine STEC. Several epidemiologic studies conducted in multiple regions of the world have demonstrated that domestic swine can carry and shed STEC. Moreover, animal studies have demonstrated that swine are susceptible to STEC O157:H7 infection and can shed the bacterium for 2 months. A limited number of molecular epidemiologic studies, however, have provided conflicting evidence regarding the relationship between swine STEC and human illness. The role that swine play in STEC transmission to people and the contribution to human disease frequency requires further evaluation. PMID:24397985

[Hamburger consumption patterns and exposure assessment for verocytotoxigenic Escherichia coli (VTEC): simulation model].

PubMed

Signorini, M L; Marín, V; Quinteros, C; Tarabla, H

2009-01-01

A quantitative risk assessment was developed for verocytotoxigenic Escherichia coli (VTEC) associated with hamburger consumption. The assessment (simulation model) considers the distribution, storage and consumption patterns of hamburgers. The prevalence and concentration of VTEC were modelled at various stages along the agri-food beef production system using input derived from Argentinean data, whenever possible. The model predicted an infection risk of 4.45 x 10(-4) per meal for adults. The risk values obtained for children were 2.6 x 10(-4), 1.38 x 10(-5) and 4.54 x 10(-7) for infection, Hemolytic Uremic Syndrome (HUS) and mortality, respectively. The risk of infection and HUS was positively correlated with bacterial concentration in meat (r = 0.664). There was a negative association between homemade hamburgers (r = -0.116) and the risk of illness; however this association has been considered due to differences between retail and domiciliary storage systems (r = -0.567) and not because of the intrinsic characteristics of the product. The most sensitive points of the production system were identified through the risk assessment, therefore, these can be utilized as a basis to apply different risk management policies in public health.

Active Shiga-Like Toxin Produced by Some Aeromonas spp., Isolated in Mexico City

PubMed Central

Palma-Martínez, Ingrid; Guerrero-Mandujano, Andrea; Ruiz-Ruiz, Manuel J.; Hernández-Cortez, Cecilia; Molina-López, José; Bocanegra-García, Virgilio; Castro-Escarpulli, Graciela

2016-01-01

Shiga-like toxins (Stx) represent a group of bacterial toxins involved in human and animal diseases. Stx is produced by enterohemorrhagic Escherichia coli, Shigella dysenteriae type 1, Citrobacter freundii, and Aeromonas spp.; Stx is an important cause of bloody diarrhea and hemolytic uremic syndrome (HUS). The aim of this study was to identify the stx1/stx2 genes in clinical strains and outer membrane vesicles (OMVs) of Aeromonas spp., 66 strains were isolated from children who live in Mexico City, and Stx effects were evaluated in Vero cell cultures. The capacity to express active Stx1 and Stx2 toxins was determined in Vero cell cultures and the concentration of Stx was evaluated by 50% lethal dose (LD50) assays, observing inhibition of damaged cells by specific monoclonal antibodies. The results obtained in this study support the hypothesis that the stx gene is another putative virulence factor of Aeromonas, and since this gene can be transferred horizontally through OMVs this genus should be included as a possible causal agents of gastroenteritis and it should be reported as part of standard health surveillance procedures. Furthermore, these results indicate that the Aeromonas genus might be a potential causative agent of HUS. PMID:27725813

Real-time genomic investigation underlying the public health response to a Shiga toxin-producing Escherichia coli O26:H11 outbreak in a nursery.

PubMed

Moran-Gilad, J; Rokney, A; Danino, D; Ferdous, M; Alsana, F; Baum, M; Dukhan, L; Agmon, V; Anuka, E; Valinsky, L; Yishay, R; Grotto, I; Rossen, J W A; Gdalevich, M

2017-10-01

Shiga toxin-producing Escherichia coli (STEC) is a significant cause of gastrointestinal infection and the haemolytic-uremic syndrome (HUS). STEC outbreaks are commonly associated with food but animal contact is increasingly being implicated in its transmission. We report an outbreak of STEC affecting young infants at a nursery in a rural community (three HUS cases, one definite case, one probable case, three possible cases and five carriers, based on the combination of clinical, epidemiological and laboratory data) identified using culture-based and molecular techniques. The investigation identified repeated animal contact (animal farming and petting) as a likely source of STEC introduction followed by horizontal transmission. Whole genome sequencing (WGS) was used for real-time investigation of the incident and revealed a unique strain of STEC O26:H11 carrying stx2a and intimin. Following a public health intervention, no additional cases have occurred. This is the first STEC outbreak reported from Israel. WGS proved as a useful tool for rapid laboratory characterization and typing of the outbreak strain and informed the public health response at an early stage of this unusual outbreak.

Epidemiology and Clinical Manifestations of Enteroaggregative Escherichia coli

PubMed Central

Hebbelstrup Jensen, Betina; Olsen, Katharina E. P.; Struve, Carsten; Petersen, Andreas Munk

2014-01-01

SUMMARY Enteroaggregative Escherichia coli (EAEC) represents a heterogeneous group of E. coli strains. The pathogenicity and clinical relevance of these bacteria are still controversial. In this review, we describe the clinical significance of EAEC regarding patterns of infection in humans, transmission, reservoirs, and symptoms. Manifestations associated with EAEC infection include watery diarrhea, mucoid diarrhea, low-grade fever, nausea, tenesmus, and borborygmi. In early studies, EAEC was considered to be an opportunistic pathogen associated with diarrhea in HIV patients and in malnourished children in developing countries. In recent studies, associations with traveler's diarrhea, the occurrence of diarrhea cases in industrialized countries, and outbreaks of diarrhea in Europe and Asia have been reported. In the spring of 2011, a large outbreak of hemolytic-uremic syndrome (HUS) and hemorrhagic colitis occurred in Germany due to an EAEC O104:H4 strain, causing 54 deaths and 855 cases of HUS. This strain produces the potent Shiga toxin along with the aggregative fimbriae. An outbreak of urinary tract infection associated with EAEC in Copenhagen, Denmark, occurred in 1991; this involved extensive production of biofilm, an important characteristic of the pathogenicity of EAEC. However, the heterogeneity of EAEC continues to complicate diagnostics and also our understanding of pathogenicity. PMID:24982324

Subtyping of STEC by MLVA in Argentina.

PubMed

Bustamante, Ana V; Sanso, Andrea M; Parma, Alberto E; Lucchesi, Paula M A

2012-01-01

Shiga toxin-producing Escherichia coli (STEC) causes serious human illness such as hemolytic uremic syndrome (HUS). Argentina has the world's highest rate of this syndrome, which is the leading cause of acute renal failure among children. E. coli O157:H7 is the most common cause of HUS, but a substantial and growing proportion of this illness is caused by infection due to non-O157 strains. Multiple-locus variable-number tandem repeat analysis (MLVA) has become an established technique to subtype STEC. This review will address the use of routine STEC subtyping by MLVA in order to type this group of isolates and to get insight into the genetic diversity of native STEC. With regard to these objectives we modified and adapted two MLVA protocols, one exclusive for O157 and the other, a generic E. coli assay. A total of 202 STEC isolates, from different sources and corresponding to 20 serotypes, have been MLVA genotyped in our laboratory. In our experience, MLVA constitutes a very sensitive tool and enables us to perform an efficient STEC subtyping. The diversity found in many serotypes may be useful for future epidemiological studies of STEC clonality, applied to O157 as well as to non-O157 isolates.

The Autism Diagnostic Observation Schedule, Module 4: Application of the Revised Algorithms in an Independent, Well-Defined, Dutch Sample (N = 93)

ERIC Educational Resources Information Center

de Bildt, Annelies; Sytema, Sjoerd; Meffert, Harma; Bastiaansen, Jojanneke A. C. J.

2016-01-01

This study examined the discriminative ability of the revised Autism Diagnostic Observation Schedule module 4 algorithm (Hus and Lord in "J Autism Dev Disord" 44(8):1996-2012, 2014) in 93 Dutch males with Autism Spectrum Disorder (ASD), schizophrenia, psychopathy or controls. Discriminative ability of the revised algorithm ASD cut-off…

Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography

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

Paul, Jijo; Yang, Cungeng; Wu, Hui

Purpose: To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. Methods and Materials: Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from themore » daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. Results: During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R{sup 2} > 0.99) and correlates weakly with the change in GTV (R{sup 2} = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. Conclusion: Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer.« less

Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography.

PubMed

Paul, Jijo; Yang, Cungeng; Wu, Hui; Tai, An; Dalah, Entesar; Zheng, Cheng; Johnstone, Candice; Kong, Feng-Ming; Gore, Elizabeth; Li, X Allen

2017-06-01

To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from the daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R 2  > 0.99) and correlates weakly with the change in GTV (R 2  = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Fatty degeneration of the rotator cuff muscles on pre- and postoperative CT arthrography (CTA): is the Goutallier grading system reliable?

PubMed

Lee, Eugene; Choi, Jung-Ah; Oh, Joo Han; Ahn, Soyeon; Hong, Sung Hwan; Chai, Jee Won; Kang, Heung Sik

2013-09-01

To retrospectively evaluate fatty degeneration (FD) of rotator cuff muscles on CTA using Goutallier's grading system and quantitative measurements with comparison between pre- and postoperative states. IRB approval was obtained for this study. Two radiologists independently reviewed pre- and postoperative CTAs of 43 patients (24 males and 19 females, mean age, 58.1 years) with 46 shoulders confirmed as full-thickness tears with random distribution. FD of supraspinatus, infraspinatus/teres minor, and subscapularis was assessed using Goutallier's system and by quantitative measurements of Hounsfield units (HUs) on sagittal images. Changes in FD grades and HUs were compared between pre- and postoperative CTAs and analyzed with respect to preoperative tear size and postoperative cuff integrity. The correlations between qualitative grades and quantitative measurements and their inter-observer reliabilities were also assessed. There was statistically significant correlation between FD grades and HU measurements of all muscles on pre- and postoperative CTA (p < 0.05). Inter-observer reliability of fatty degeneration grades were excellent to substantial on both pre- and postoperative CTA in supraspinatus (0.8685 and 0.8535) and subscapularis muscles (0.7777 and 0.7972), but fair in infraspinatus/teres minor muscles (0.5791 and 0.5740); however, quantitative Hounsfield units measurements showed excellent reliability for all muscles (ICC: 0.7950 and 0.9346 for SST, 0.7922 and 0.8492 for SSC, and 0.9254 and 0.9052 for IST/TM). No muscle showed improvement of fatty degeneration after surgical repair on qualitative and quantitative assessments; there was no difference in changes of fatty degeneration after surgical repair according to preoperative tear size and post-operative cuff integrity (p > 0.05). The average dose-length product (DLP, mGy · cm) was 365.2 mGy · cm (range, 323.8-417.2 mGy · cm) and estimated average effective dose was 5.1 mSv. Goutallier grades correlated well with HUs of rotator cuff muscles. Reliability was excellent for both systems, except for FD grade of IST/TM muscles, which may be more reliably assessed using quantitative measurements.

Synergistic Effects Induced by a Low Dose of Diesel Particulate Extract and Ultraviolet-A in Caenorhabditis elegans: DNA Damage-Triggered Germ Cell Apoptosis

PubMed Central

2015-01-01

Diesel exhaust has been classified as a potential carcinogen and is associated with various health effects. A previous study showed that the doses for manifesting the mutagenetic effects of diesel exhaust could be reduced when coexposed with ultraviolet-A (UVA) in a cellular system. However, the mechanisms underlying synergistic effects remain to be clarified, especially in an in vivo system. In the present study, using Caenorhabditis elegans (C. elegans) as an in vivo system we studied the synergistic effects of diesel particulate extract (DPE) plus UVA, and the underlying mechanisms were dissected genetically using related mutants. Our results demonstrated that though coexposure of wild type worms at young adult stage to low doses of DPE (20 μg/mL) plus UVA (0.2, 0.5, and 1.0 J/cm2) did not affect worm development (mitotic germ cells and brood size), it resulted in a significant induction of germ cell death. Using the strain of hus-1::gfp, distinct foci of HUS-1::GFP was observed in proliferating germ cells, indicating the DNA damage after worms were treated with DPE plus UVA. Moreover, the induction of germ cell death by DPE plus UVA was alleviated in single-gene loss-of-function mutations of core apoptotic, checkpoint HUS-1, CEP-1/p53, and MAPK dependent signaling pathways. Using a reactive oxygen species (ROS) probe, it was found that the production of ROS in worms coexposed to DPE plus UVA increased in a time-dependent manner. In addition, employing a singlet oxygen (1O2) trapping probe, 2,2,6,6-tetramethyl-4-piperidone, coupled with electron spin resonance analysis, we demonstrated the increased 1O2 production in worms coexposed to DPE plus UVA. These results indicated that UVA could enhance the apoptotic induction of DPE at low doses through a DNA damage-triggered pathway and that the production of ROS, especially 1O2, played a pivotal role in initiating the synergistic process. PMID:24841043

Technical Note: Radiation properties of tissue- and water-equivalent materials formulated using the stoichiometric analysis method in charged particle therapy

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

Yohannes, Indra; Vasiliniuc, Stefan; Hild, Sebastian

Purpose: Five tissue- and water-equivalent materials (TEMs) mimicking ICRU real tissues have been formulated using a previously established stoichiometric analysis method (SAM) to be applied in charged particle therapy. The purpose of this study was an experimental verification of the TEMs-SAM against charged particle beam measurements and for different computed tomography (CT) scanners. The potential of the TEMs-SAM to be employed in the dosimetry was also investigated. Methods: Experimental verification with three CT scanners was carried out to validate the calculated Hounsfield units (HUs) of the TEMs. Water-equivalent path lengths (WEPLs) of the TEMs for proton (106.8 MeV/u), helium (107.93more » MeV/u), and carbon (200.3 MeV/u) ions were measured to be compared with the computed relative stopping powers. HU calibration curves were also generated. Results: Differences between the measured HUs of the TEMs and the calculated HUs of the ICRU real tissues for all CT scanners were smaller than 4 HU except for the skeletal tissues which deviated up to 21 HU. The measured WEPLs verified the calculated WEPLs of the TEMs (maximum deviation was 0.17 mm) and were in good agreement with the calculated WEPLs of the ICRU real tissues (maximum deviation was 0.23 mm). Moreover, the relative stopping powers converted from the measured WEPLs differed less than 0.8% and 1.3% from the calculated values of the SAM and the ICRU, respectively. Regarding the relative nonelastic cross section per unit of volume for 200 MeV protons, the ICRU real tissues were generally well represented by the TEMs except for adipose which differed 3.8%. Further, the HU calibration curves yielded the mean and the standard deviation of the errors not larger than 0.5% and 1.9%, respectively. Conclusions: The results of this investigation implied the potential of the TEMs formulated using the SAM to be employed for both, beam dosimetry and HU calibration in charged particle therapy.« less

Overexpressed Proteins in Hypervirulent Clade 8 and Clade 6 Strains of Escherichia coli O157:H7 Compared to E. coli O157:H7 EDL933 Clade 3 Strain.

PubMed

Amigo, Natalia; Zhang, Qi; Amadio, Ariel; Zhang, Qunjie; Silva, Wanderson M; Cui, Baiyuan; Chen, Zhongjian; Larzabal, Mariano; Bei, Jinlong; Cataldi, Angel

2016-01-01

Escherichia coli O157:H7 is responsible for severe diarrhea and hemolytic uremic syndrome (HUS), and predominantly affects children under 5 years. The major virulence traits are Shiga toxins, necessary to develop HUS and the Type III Secretion System (T3SS) through which bacteria translocate effector proteins directly into the host cell. By SNPs typing, E. coli O157:H7 was separated into nine different clades. Clade 8 and clade 6 strains were more frequently associated with severe disease and HUS. In this study, we aimed to identify differentially expressed proteins in two strains of E. coli O157:H7 (clade 8 and clade 6), obtained from cattle and compared them with the well characterized reference EDL933 strain (clade 3). Clade 8 and clade 6 strains show enhanced pathogenicity in a mouse model and virulence-related properties. Proteins were extracted and analyzed using the TMT-6plex labeling strategy associated with two dimensional liquid chromatography and mass spectrometry in tandem. We detected 2241 proteins in the cell extract and 1787 proteins in the culture supernatants. Attention was focused on the proteins related to virulence, overexpressed in clade 6 and 8 strains compared to EDL933 strain. The proteins relevant overexpressed in clade 8 strain were the curli protein CsgC, a transcriptional activator (PchE), phage proteins, Stx2, FlgM and FlgD, a dienelactone hydrolase, CheW and CheY, and the SPATE protease EspP. For clade 6 strain, a high overexpression of phage proteins was detected, mostly from Stx2 encoding phage, including Stx2, flagellin and the protease TagA, EDL933_p0016, dienelactone hydrolase, and Haemolysin A, amongst others with unknown function. Some of these proteins were analyzed by RT-qPCR to corroborate the proteomic data. Clade 6 and clade 8 strains showed enhanced transcription of 10 out of 12 genes compared to EDL933. These results may provide new insights in E. coli O157:H7 mechanisms of pathogenesis.

Cyclic-di-GMP signalling and biofilm-related properties of the Shiga toxin-producing 2011 German outbreak Escherichia coli O104:H4

PubMed Central

Richter, Anja M; Povolotsky, Tatyana L; Wieler, Lothar H; Hengge, Regine

2014-01-01

In 2011, nearly 4,000 people in Germany were infected by Shiga toxin (Stx)-producing Escherichia coli O104:H4 with > 22% of patients developing haemolytic uraemic syndrome (HUS). Genome sequencing showed the outbreak strain to be related to enteroaggregative E. coli (EAEC), suggesting its high virulence results from EAEC-typical strong adherence and biofilm formation combined to Stx production. Here, we report that the outbreak strain contains a novel diguanylate cyclase (DgcX)—producing the biofilm-promoting second messenger c-di-GMP—that shows higher expression than any other known E. coli diguanylate cyclase. Unlike closely related E. coli, the outbreak strain expresses the c-di-GMP-controlled biofilm regulator CsgD and amyloid curli fibres at 37°C, but is cellulose-negative. Moreover, it constantly generates derivatives with further increased and deregulated production of CsgD and curli. Since curli fibres are strongly proinflammatory, with cellulose counteracting this effect, high c-di-GMP and curli production by the outbreak O104:H4 strain may enhance not only adherence but may also contribute to inflammation, thereby facilitating entry of Stx into the bloodstream and to the kidneys where Stx causes HUS. PMID:25361688

Hounsfield unit change in root and alveolar bone during canine retraction.

PubMed

Jiang, Feifei; Liu, Sean S-Y; Xia, Zeyang; Li, Shuning; Chen, Jie; Kula, Katherine S; Eckert, George

2015-04-01

The objective of this study was to determine the Hounsfield unit (HU) changes in the alveolar bone and root surfaces during controlled canine retractions. Eighteen maxillary canine retraction patients were selected for this split-mouth design clinical trial. The canines in each patient were randomly assigned to receive either translation or controlled tipping treatment. Pretreatment and posttreatment cone-beam computed tomography scans of each patient were used to determine tooth movement direction and HU changes. The alveolar bone and root surface were divided into 108 divisions, respectively. The HUs in each division were measured. Mixed-model analysis of variance was applied to test the HU change distribution at the P <0.05 significance level. The HU changes varied with the directions relative to the canine movement. The HU reductions occurred at the root surfaces. Larger reductions occurred in the divisions that were perpendicular to the moving direction. However, HUs decreased in the alveolar bone in the moving direction. The highest HU reduction was at the coronal level. HU reduction occurs on the root surface in the direction perpendicular to tooth movement and in the alveolar bone in the direction of tooth movement when a canine is retracted. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Lifespan and Stress Resistance in Drosophila with Overexpressed DNA Repair Genes

PubMed Central

Shaposhnikov, Mikhail; Proshkina, Ekaterina; Shilova, Lyubov; Zhavoronkov, Alex; Moskalev, Alexey

2015-01-01

DNA repair declines with age and correlates with longevity in many animal species. In this study, we investigated the effects of GAL4-induced overexpression of genes implicated in DNA repair on lifespan and resistance to stress factors in Drosophila melanogaster. Stress factors included hyperthermia, oxidative stress, and starvation. Overexpression was either constitutive or conditional and either ubiquitous or tissue-specific (nervous system). Overexpressed genes included those involved in recognition of DNA damage (homologs of HUS1, CHK2), nucleotide and base excision repair (homologs of XPF, XPC and AP-endonuclease-1), and repair of double-stranded DNA breaks (homologs of BRCA2, XRCC3, KU80 and WRNexo). The overexpression of different DNA repair genes led to both positive and negative effects on lifespan and stress resistance. Effects were dependent on GAL4 driver, stage of induction, sex, and role of the gene in the DNA repair process. While the constitutive/neuron-specific and conditional/ubiquitous overexpression of DNA repair genes negatively impacted lifespan and stress resistance, the constitutive/ubiquitous and conditional/neuron-specific overexpression of Hus1, mnk, mei-9, mus210, and WRNexo had beneficial effects. This study demonstrates for the first time the effects of overexpression of these DNA repair genes on both lifespan and stress resistance in D. melanogaster. PMID:26477511

The Exonuclease Homolog OsRAD1 Promotes Accurate Meiotic Double-Strand Break Repair by Suppressing Nonhomologous End Joining.

PubMed

Hu, Qing; Tang, Ding; Wang, Hongjun; Shen, Yi; Chen, Xiaojun; Ji, Jianhui; Du, Guijie; Li, Yafei; Cheng, Zhukuan

2016-10-01

During meiosis, programmed double-strand breaks (DSBs) are generated to initiate homologous recombination, which is crucial for faithful chromosome segregation. In yeast, Radiation sensitive1 (RAD1) acts together with Radiation sensitive9 (RAD9) and Hydroxyurea sensitive1 (HUS1) to facilitate meiotic recombination via cell-cycle checkpoint control. However, little is known about the meiotic functions of these proteins in higher eukaryotes. Here, we characterized a RAD1 homolog in rice (Oryza sativa) and obtained evidence that O. sativa RAD1 (OsRAD1) is important for meiotic DSB repair. Loss of OsRAD1 led to abnormal chromosome association and fragmentation upon completion of homologous pairing and synapsis. These aberrant chromosome associations were independent of OsDMC1. We found that classical nonhomologous end-joining mediated by Ku70 accounted for most of the ectopic associations in Osrad1 In addition, OsRAD1 interacts directly with OsHUS1 and OsRAD9, suggesting that these proteins act as a complex to promote DSB repair during rice meiosis. Together, these findings suggest that the 9-1-1 complex facilitates accurate meiotic recombination by suppressing nonhomologous end-joining during meiosis in rice. © 2016 American Society of Plant Biologists. All Rights Reserved.

Subtyping of STEC by MLVA in Argentina

PubMed Central

Bustamante, Ana V.; Sanso, Andrea M.; Parma, Alberto E.; Lucchesi, Paula M. A.

2012-01-01

Shiga toxin-producing Escherichia coli (STEC) causes serious human illness such as hemolytic uremic syndrome (HUS). Argentina has the world’s highest rate of this syndrome, which is the leading cause of acute renal failure among children. E. coli O157:H7 is the most common cause of HUS, but a substantial and growing proportion of this illness is caused by infection due to non-O157 strains. Multiple-locus variable-number tandem repeat analysis (MLVA) has become an established technique to subtype STEC. This review will address the use of routine STEC subtyping by MLVA in order to type this group of isolates and to get insight into the genetic diversity of native STEC. With regard to these objectives we modified and adapted two MLVA protocols, one exclusive for O157 and the other, a generic E. coli assay. A total of 202 STEC isolates, from different sources and corresponding to 20 serotypes, have been MLVA genotyped in our laboratory. In our experience, MLVA constitutes a very sensitive tool and enables us to perform an efficient STEC subtyping. The diversity found in many serotypes may be useful for future epidemiological studies of STEC clonality, applied to O157 as well as to non-O157 isolates. PMID:22919698

Limited Evaluation of Image Quality Produced by a Portable Head CT Scanner (CereTom) in a Neurosurgery Centre.

PubMed

Abdullah, Ariz Chong; Adnan, Johari Siregar; Rahman, Noor Azman A; Palur, Ravikant

2017-03-01

Computed tomography (CT) is the preferred diagnostic toolkit for head and brain imaging of head injury. A recent development is the invention of a portable CT scanner that can be beneficial from a clinical point of view. To compare the quality of CT brain images produced by a fixed CT scanner and a portable CT scanner (CereTom). This work was a single-centre retrospective study of CT brain images from 112 neurosurgical patients. Hounsfield units (HUs) of the images from CereTom were measured for air, water and bone. Three assessors independently evaluated the images from the fixed CT scanner and CereTom. Streak artefacts, visualisation of lesions and grey-white matter differentiation were evaluated at three different levels (centrum semiovale, basal ganglia and middle cerebellar peduncles). Each evaluation was scored 1 (poor), 2 (average) or 3 (good) and summed up to form an ordinal reading of 3 to 9. HUs for air, water and bone from CereTom were within the recommended value by the American College of Radiology (ACR). Streak artefact evaluation scores for the fixed CT scanner was 8.54 versus 7.46 ( Z = -5.67) for CereTom at the centrum semiovale, 8.38 (SD = 1.12) versus 7.32 (SD = 1.63) at the basal ganglia and 8.21 (SD = 1.30) versus 6.97 (SD = 2.77) at the middle cerebellar peduncles. Grey-white matter differentiation showed scores of 8.27 (SD = 1.04) versus 7.21 (SD = 1.41) at the centrum semiovale, 8.26 (SD = 1.07) versus 7.00 (SD = 1.47) at the basal ganglia and 8.38 (SD = 1.11) versus 6.74 (SD = 1.55) at the middle cerebellar peduncles. Visualisation of lesions showed scores of 8.86 versus 8.21 ( Z = -4.24) at the centrum semiovale, 8.93 versus 8.18 ( Z = -5.32) at the basal ganglia and 8.79 versus 8.06 ( Z = -4.93) at the middle cerebellar peduncles. All results were significant with P -value < 0.01. Results of the study showed a significant difference in image quality produced by the fixed CT scanner and CereTom, with the latter being more inferior than the former. However, HUs of the images produced by CereTom do fulfil the recommendation of the ACR.

Comparative Characterization of Shiga Toxin Type 2 and Subtilase Cytotoxin Effects on Human Renal Epithelial and Endothelial Cells Grown in Monolayer and Bilayer Conditions.

PubMed

Álvarez, Romina S; Sacerdoti, Flavia; Jancic, Carolina; Paton, Adrienne W; Paton, James C; Ibarra, Cristina; Amaral, María M

2016-01-01

Postdiarrheal hemolytic uremic syndrome (HUS) affects children under 5 years old and is responsible for the development of acute and chronic renal failure, particularly in Argentina. This pathology is a complication of Shiga toxin (Stx)-producing Escherichia coli infection and renal damage is attributed to Stx types 1 and 2 (Stx1, Stx2) produced by Escherichia coli O157:H7 and many other STEC serotypes. It has been reported the production of Subtilase cytotoxin (SubAB) by non-O157 STEC isolated from cases of childhood diarrhea. Therefore, it is proposed that SubAB may contribute to HUS pathogenesis. The human kidney is the most affected organ because very Stx-sensitive cells express high amounts of biologically active receptor. In this study, we investigated the effects of Stx2 and SubAB on primary cultures of human glomerular endothelial cells (HGEC) and on a human tubular epithelial cell line (HK-2) in monoculture and coculture conditions. We have established the coculture as a human renal proximal tubule model to study water absorption and cytotoxicity in the presence of Stx2 and SubAB. We obtained and characterized cocultures of HGEC and HK-2. Under basal conditions, HGEC monolayers exhibited the lowest electrical resistance (TEER) and the highest water permeability, while the HGEC/HK-2 bilayers showed the highest TEER and the lowest water permeability. In addition, at times as short as 20-30 minutes, Stx2 and SubAB caused the inhibition of water absorption across HK-2 and HGEC monolayers and this effect was not related to a decrease in cell viability. However, toxins did not have inhibitory effects on water movement across HGEC/HK-2 bilayers. After 72 h, Stx2 inhibited the cell viability of HGEC and HK-2 monolayers, but these effects were attenuated in HGEC/HK-2 bilayers. On the other hand, SubAB cytotoxicity shows a tendency to be attenuated by the bilayers. Our data provide evidence about the different effects of these toxins on the bilayers respect to the monolayers. This in vitro model of communication between human renal microvascular endothelial cells and human proximal tubular epithelial cells is a representative model of the human proximal tubule to study the effects of Stx2 and SubAB related to the development of HUS.

Brief Report: Relationship Between ADOS-2, Module 4 Calibrated Severity Scores (CSS) and Social and Non-Social Standardized Assessment Measures in Adult Males with Autism Spectrum Disorder (ASD)

ERIC Educational Resources Information Center

Morrier, Michael J.; Ousley, Opal Y.; Caceres-Gamundi, Gabriella A.; Segall, Matthew J.; Cubells, Joseph F.; Young, Larry J.; Andari, Elissar

2017-01-01

The ADOS-2 Modules 1-3 now include a standardized calibrated severity score (CSS) from 1 to 10 based on the overall total raw score. Subsequent research published CSS for Module 4 (Hus, Lord, "Journal of Autism and Developmental Disorders" 44(8):1996-2012, 2014); however more research is needed to examine the psychometric properties of…

Wafer-Scale Integration of Systolic Arrays,

DTIC Science & Technology

1985-10-01

hus wtha rbaiith hig robabili, e aubrbe orutysta mostck b(e)adstotoefwsi the cenofther cnnel thati are connted to (g.The kery ato the alevel of t...problems considered heretofore in this paper also have an interpretation in a purely graph theoretic model. Suppose we are given a two-dimensional...graphs," Magyar 7Td. Akad. Math . Kut. Int. Kozl, Vol. 5, 1960, pp. 17-61. [6] D. Fussell and P. Varman, "Fault-tolerant wafer-scale architectures for

Cyclic-di-GMP signalling and biofilm-related properties of the Shiga toxin-producing 2011 German outbreak Escherichia coli O104:H4.

PubMed

Richter, Anja M; Povolotsky, Tatyana L; Wieler, Lothar H; Hengge, Regine

2014-12-01

In 2011, nearly 4,000 people in Germany were infected by Shiga toxin (Stx)-producing Escherichia coli O104:H4 with > 22% of patients developing haemolytic uraemic syndrome (HUS). Genome sequencing showed the outbreak strain to be related to enteroaggregative E. coli (EAEC), suggesting its high virulence results from EAEC-typical strong adherence and biofilm formation combined to Stx production. Here, we report that the outbreak strain contains a novel diguanylate cyclase (DgcX)--producing the biofilm-promoting second messenger c-di-GMP--that shows higher expression than any other known E. coli diguanylate cyclase. Unlike closely related E. coli, the outbreak strain expresses the c-di-GMP-controlled biofilm regulator CsgD and amyloid curli fibres at 37°C, but is cellulose-negative. Moreover, it constantly generates derivatives with further increased and deregulated production of CsgD and curli. Since curli fibres are strongly proinflammatory, with cellulose counteracting this effect, high c-di-GMP and curli production by the outbreak O104:H4 strain may enhance not only adherence but may also contribute to inflammation, thereby facilitating entry of Stx into the bloodstream and to the kidneys where Stx causes HUS. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Recurrent seasonal outbreak of an emerging serotype of Shiga toxin-producing Escherichia coli (STEC O55:H7 Stx2a) in the south west of England, July 2014 to September 2015.

PubMed

McFarland, Noëleen; Bundle, Nick; Jenkins, Claire; Godbole, Gauri; Mikhail, Amy; Dallman, Tim; O'Connor, Catherine; McCarthy, Noel; O'Connell, Emer; Treacy, Juli; Dabke, Girija; Mapstone, James; Landy, Yvette; Moore, Janet; Partridge, Rachel; Jorgensen, Frieda; Willis, Caroline; Mook, Piers; Rawlings, Chas; Acornley, Richard; Featherstone, Charlotte; Gayle, Sharleen; Edge, Joanne; McNamara, Eleanor; Hawker, Jeremy; Balasegaram, Sooria

2017-09-07

The first documented British outbreak of Shiga toxin-producing Escherichia coli (STEC) O55:H7 began in the county of Dorset, England, in July 2014. Since then, there have been a total of 31 cases of which 13 presented with haemolytic uraemic syndrome (HUS). The outbreak strain had Shiga toxin (Stx) subtype 2a associated with an elevated risk of HUS. This strain had not previously been isolated from humans or animals in England. The only epidemiological link was living in or having close links to two areas in Dorset. Extensive investigations included testing of animals and household pets. Control measures included extended screening, iterative interviewing and exclusion of cases and high risk contacts. Whole genome sequencing (WGS) confirmed that all the cases were infected with similar strains. A specific source could not be identified. The combination of epidemiological investigation and WGS indicated, however, that this outbreak was possibly caused by recurrent introductions from a local endemic zoonotic source, that a highly similar endemic reservoir appears to exist in the Republic of Ireland but has not been identified elsewhere, and that a subset of cases was associated with human-to-human transmission in a nursery. This article is copyright of The Authors, 2017.

Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies.

PubMed

Scully, M; Cataland, S; Coppo, P; de la Rubia, J; Friedman, K D; Kremer Hovinga, J; Lämmle, B; Matsumoto, M; Pavenski, K; Sadler, E; Sarode, R; Wu, H

2017-02-01

Essentials An international collaboration provides a consensus for clinical definitions. This concerns thrombotic microangiopathies and thrombotic thrombocytopenic purpura (TTP). The consensus defines diagnosis, disease monitoring and response to treatment. Requirements for ADAMTS-13 are given. Background Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are two important acute conditions to diagnose. Thrombotic microangiopathy (TMA) is a broad pathophysiologic process that leads to microangiopathic hemolytic anemia and thrombocytopenia, and involves capillary and small-vessel platelet aggregates. The most common cause is disseminated intravascular coagulation, which may be differentiated by abnormal coagulation. Clinically, a number of conditions present with microangiopathic hemolytic anemia and thrombocytopenia, including cancer, infection, transplantation, drug use, autoimmune disease, and pre-eclampsia and hemolysis, elevated liver enzymes and low platelet count syndrome in pregnancy. Despite overlapping clinical presentations, TTP and HUS have distinct pathophysiologies and treatment pathways. Objectives To present a consensus document from an International Working Group on TTP and associated thrombotic microangiopathies (TMAs). Methods The International Working Group has proposed definitions and terminology based on published information and consensus-based recommendations. Conclusion The consensus aims to aid clinical decisions, but also future studies and trials, utilizing standardized definitions. It presents a classification of the causes of TMA, and criteria for clinical response, remission and relapse of congenital and immune-mediated TTP. © 2016 International Society on Thrombosis and Haemostasis.

Hounsfield unit values of retropharyngeal abscess-like lesions seen in Kawasaki disease.

PubMed

Sasaki, Toru; Miyata, Rie; Hatai, Yoshiho; Makita, Kohzoh; Tsunoda, Koichi

2014-04-01

Retropharyngeal abscess-like lesions are occasionally seen in computed tomography (CT) imaging of patients with Kawasaki disease (KD) and these patients often undergo unnecessary surgery. We could distinguish the lesions from true abscesses by measuring their Hounsfield unit values (HUs). To distinguish the retropharyngeal abscess-like lesions from true abscesses without any surgical procedure. We investigated six cases of KD showing such lesions on CTs, both with and without contrast enhancement (CE). We measured the HUs of those lesions and compared them with those of 10 true abscesses as controls. Abscess-like lesions of KD were well enhanced by CE, whereas abscesses showed virtually no enhancement. The mean HU in the six KD cases was 20.0 ± 4.65 (mean ± SD) on plain CTs and 35.6 ± 4.49 on contrast CTs. In abscesses, it was 30.3 ± 4.42 on plain CTs and 30.3 ± 3.57 on contrast CTs. The difference in HU values [(HU on contrast CT) - (HU on plain CT)] was defined as ΔHU. The mean ΔHU was 15.6 ± 5.36 in the six KD lesions and 0.0 ± 2.93 in abscesses, with statistical significance of p < 0.0001 by Student's t test. Thus, ΔHU value may potentially be a useful parameter for their distinction.

Characterization of enterohemorrhagic Escherichia coli O111 and O157 strains isolated from outbreak patients in Japan.

PubMed

Watahiki, Masanori; Isobe, Junko; Kimata, Keiko; Shima, Tomoko; Kanatani, Jun-ichi; Shimizu, Miwako; Nagata, Akihiro; Kawakami, Keiko; Yamada, Mikiko; Izumiya, Hidemasa; Iyoda, Sunao; Morita-Ishihara, Tomoko; Mitobe, Jiro; Terajima, Jun; Ohnishi, Makoto; Sata, Tetsutaro

2014-08-01

In April and May 2011, there was a serious food-poisoning outbreak in Japan caused by enterohemorrhagic Escherichia coli (EHEC) strains O111:H8 and O157:H7 from raw beef dishes at branches of a barbecue restaurant. This outbreak involved 181 infected patients, including 34 hemolytic-uremic syndrome (HUS) cases (19%). Among the 34 HUS patients, 21 developed acute encephalopathy (AE) and 5 died. Patient stool specimens yielded E. coli O111 and O157 strains. We also detected both EHEC O111 stx2 and stx-negative E. coli O111 strains in a stock of meat block from the restaurant. Pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem-repeat analysis (MLVA) showed that the stx-negative E. coli O111 isolates were closely related to EHEC O111 stx2 isolates. Although the EHEC O157 strains had diverse stx gene profiles (stx1, stx2, and stx1 stx2), the PFGE and MLVA analyses indicated that these isolates originated from a single clone. Deletion of the Stx2-converting prophage from the EHEC O111 stx2 isolates was frequently observed during in vitro growth, suggesting that strain conversion from an EHEC O111 stx2 to an stx-negative strain may have occurred during infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Relationship between Hounsfield unit in CT scan and gray scale in CBCT

NASA Astrophysics Data System (ADS)

Kamaruddin, Noorshaida; Rajion, Zainul Ahmad; Yusof, Asilah; Aziz, Mohd Ezane

2016-12-01

Cone-beam computed tomography (CBCT) is an imaging system which has advantages over computed tomography (CT). Recently, CBCT has become widely used for oral and maxillofacial imaging. In CT scan, Hounsfield Unit (HU) is proportional to the degree of x-ray attenuation by the tissue. In CBCT, the degree of x-ray attenuation is shown by gray scale (voxel value). The aim of the present (in vitro) study was to investigate the relationship between gray scale in CBCT and HU in CT scan. In this descriptive study, the anthropomorphic head phantom was scanned with CBCT and CT scanner. Gray scales and HUs were detected on images at the crown of the teeth, trabecular and cortical bone of mandible. The images were analyzed to obtain the gray scale value and HU value. The obtained value then used to investigate the relationship between CBCT gray scales and HUs. For the statistical analysis, t-test, Pearson's correlation and regression analysis were used. The differences between the gray scale of CBCT and HU of CT were statistically not significant, whereas the Pearson's correlation coefficients demonstrated a statistically significant correlation between gray scale of CBCT and HU of CT values. Considering the fact that gray scale in CBCT is important in pre assessment evaluation of bone density before implant treatments, it is recommended because of the lower dose and cost compared to CT scan.

Relationship between atypical depression and social anxiety disorder.

PubMed

Koyuncu, Ahmet; Ertekin, Erhan; Ertekin, Banu Aslantaş; Binbay, Zerrin; Yüksel, Çağrı; Deveci, Erdem; Tükel, Raşit

2015-01-30

In this study, we aimed to investigate the effects of atypical and non-atypical depression comorbidity on the clinical characteristics and course of social anxiety disorder (SAD). A total of 247 patients with SAD were enrolled: 145 patients with a current depressive episode (unipolar or bipolar) with atypical features, 43 patients with a current depressive episode with non-atypical features and 25 patients without a lifetime history of depressive episodes were compared regarding sociodemographic and clinical features, comorbidity rates, and severity of SAD, depression and functional impairment. Thirty four patients with a past but not current history of major depressive episodes were excluded from the comparisons. 77.1% of current depressive episodes were associated with atypical features. Age at onset of SAD and age at initial major depressive episode were lower in the group with atypical depression than in the group with non-atypical depression. History of suicide attempts and bipolar disorder comorbidity was more common in the atypical depression group as well. Atypical depression group has higher SAD and depression severity and lower functionality than group with non-atypical depression. Our results indicate that the presence of atypical depression is associated with more severe symptoms and more impairment in functioning in patients with SAD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder.

PubMed

Silverstein, Brett; Angst, Jules

2015-01-01

Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1) The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2) Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3) Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4) Most probands who report atypical depression meet criteria for "somatic depression," defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as "reactive" appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression.

Continuously-Tunable High-Repetition Rate RF-Excited CO2 Waveguide Laser,

DTIC Science & Technology

1982-07-01

may be transformed to the appropriate level at the laser head, which elimi- nates the ueed for the very high voltage power supply . Several gas lasers...Figure 5.5 is shown a picture of the rack containing the 50 W amplifier (at the bottom) the 40 V power - supply (in the middle) and the eight final-stage...experimentally. Experimentally 40.68 MHz rf-excitation of discharges between parallel plate electrodes with up to 7-8 kW peak rf- power hus been investigated

Large and ongoing outbreak of haemolytic uraemic syndrome, Germany, May 2011.

PubMed

Frank, C; Faber, M S; Askar, M; Bernard, H; Fruth, A; Gilsdorf, A; Hohle, M; Karch, H; Krause, G; Prager, R; Spode, A; Stark, K; Werber, D

2011-05-26

Since early May 2011, an increased incidence of haemolytic uraemic syndrome (HUS) and bloody diarrhoea related to infections with Shiga toxin-producing Escherichia coli (STEC) has been observed in Germany, with most cases in the north of the country. Cases reported from other European countries had travelled to this area. First results of a case–control study conducted in Hamburg suggest an association between the occurrence of disease and the consumption of raw tomatoes, cucumber and leaf salad.

Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate.

PubMed

Ingegnoli, Anna; d'Aloia, Cecilia; Frattaruolo, Antonia; Pallavera, Lara; Martella, Eugenia; Crisi, Girolamo; Zompatori, Maurizio

2010-01-01

This study was carried out to determine the underestimation rate of carcinoma upon surgical biopsy after a diagnosis of flat epithelial atypia and atypical ductal hyperplasia and 11-gauge vacuum-assisted breast biopsy. A retrospective review was conducted of 476 vacuum-assisted breast biopsy performed from May 2005 to January 2007 and a total of 70 cases of atypia were identified. Fifty cases (71%) were categorized as pure atypical ductal hyperplasia, 18 (26%) as pure flat epithelial atypia and two (3%) as concomitant flat epithelial atypia and atypical ductal hyperplasia. Each group were compared with the subsequent open surgical specimens. Surgical biopsy was performed in 44 patients with atypical ductal hyperplasia, 15 patients with flat epithelial atypia, and two patients with flat epithelial atypia and atypical ductal hyperplasia. Five cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ, three cases of flat epithelial atypia yielded one ductal carcinoma in situ and two cases of invasive ductal carcinoma, and one case of flat epithelial atypia/atypical ductal hyperplasia had invasive ductal carcinoma. The overall rate of malignancy was 16% for atypical ductal hyperplasia (including flat epithelial atypia/atypical ductal hyperplasia patients) and 20% for flat epithelial atypia. The presence of flat epithelial atypia and atypical ductal hyperplasia at biopsy requires careful consideration, and surgical excision should be suggested.

Database of Autotransplants for Breast Cancer.

DTIC Science & Technology

1996-12-01

Infections (Indicate code for atypical bacteria; 301 Herpes Simplex (HSV1, HSV2) list bacterium for non-atypical bacteria.) 302 Herpes Zoster ( Chicken pox ...for non-atypical bacteria.) 302 Herpes Zoster ( Chicken pox , Varicella) 303 Cytomegalovirus (CMV) 100 Atypical bacteria, not otherwise specified 304... Chicken pox , Varicella) 303 Cytomegalovirus (CMV) 100 Atypical bacteria, not otherwise specified 304 Adenovirus 101 Coxiella 305 Enterovirus (Coxsackie

Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

PubMed Central

Dettmar, Anne K.; Binder, Elisabeth; Greiner, Friederike R.; Liebau, Max C.; Kurschat, Christine E.; Jungraithmayr, Therese C.; Saleem, Moin A.; Schmitt, Claus-Peter; Feifel, Elisabeth; Orth-Höller, Dorothea; Kemper, Markus J.; Pepys, Mark; Würzner, Reinhard

2014-01-01

Hemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)-producing Escherichia coli. Proteinuria can occur in the early phase of the disease, and its persistence determines the renal prognosis. Stx2 may injure podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member of the pentraxin family, has been shown to protect against Stx2-induced lethality in mice in vivo, presumably by specific binding to the toxin. We therefore tested the hypothesis that SAP can protect against Stx2-induced injury of human podocytes. To elucidate the mechanisms underlying podocyte injury in HUS-associated proteinuria, we assessed Stx2-induced activation of mitogen-activated protein kinases (MAPKs) and apoptosis in immortalized human podocytes and evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2-binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was internalized and then activated p38α MAPK and c-Jun N-terminal kinase (JNK), important signaling steps in cell differentiation and apoptosis. Stx2 also activated caspase 3, resulting in an increased level of apoptosis. Coincubation of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a target of Stx2 and that SAP protects podocytes against Stx2-induced injury. SAP may therefore be a useful therapeutic option. PMID:24566618

Shopper cards data and storage practices for the investigation of an outbreak of Shiga-toxin producing Escherichia coli O157 infections.

PubMed

Barret, A-S; Charron, M; Mariani-Kurkdjian, P; Gouali, M; Loukiadis, E; Poignet-Leroux, B; Godron, A; Gault, G; Faure, M; Mailles, A

2013-09-01

An outbreak of shiga-toxin producing Escherichia coli infections occurred in southwest France in June 2012. The outbreak was investigated to identify the source of infection, and guide control measures. Confirmed outbreak cases were patients who developed bloody diarrhoea or haemolytic uremic syndrome (HUS) between 28 May and 6 July 2012, with E. coli O157 isolates showing indistinguishable patterns on pulse field gel electrophoresis (PFGE). A standardized questionnaire was administered to patients to document food consumption and other risk exposures. Their purchase was checked through their supermarket shopper card data. Six patients (four with HUS and two with bloody diarrhea) were confirmed outbreak cases. Fresh ground beef burgers from one supermarket were the only common food exposure, identified by interviews and shopper card data. The PFGE profile of shiga toxin-producing E. coli O157 isolated from the suspected beef burgers was identical to those from the human cases. The suspected beef burgers were no longer on sale at the time of investigation but three patients confirmed as outbreak cases had deep-frozen some at home. Shopper card data was particularly useful to obtain precise and reliable information on the traceability of consumed food. Despite the expired use-by date, a recall was issued for the beef burgers. This contributed to preventing other cases among consumers who had deep-frozen the beef burgers. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Jab1 Mediates Protein Degradation of Rad9/Rad1/Hus1 Checkpoint Complex

PubMed Central

Huang, Jin; Yuan, Honglin; Lu, Chongyuan; Liu, Ximeng; Cao, Xu; Wan, Mei

2009-01-01

Summary The Rad1-Rad9-Hus1 (9-1-1) complex serves a dual role as a DNA-damage sensor in checkpoint signaling and as a mediator in DNA repair pathway. However, the intercellular mechanisms that regulate 9-1-1 complex are poorly understood. Jab1, the fifth component of the COP9 signalosome complex, plays a central role in the degradation of multiple proteins and is emerging as an important regulator in cancer development. Here, we tested the hypothesis that Jab1 controls the protein stability of the 9-1-1 complex via the proteosome pathway. We provide evidence that Jab1 physically associates with the 9-1-1 complex. This association is mediated through direct interaction between Jab1 and Rad1, one of the subunits of 9-1-1 complex. Importantly, Jab1 causes the translocation of the 9-1-1 complex from the nucleus to the cytoplasm, mediating rapid degradation of the 9-1-1 complex via 26S proteasome. Furthermore, Jab1 significantly suppresses checkpoint signaling activation, DNA synthesis recovery from blockage and cell viability after replication stresses such as UV exposure, γ radiation and hydroxyurea treatment. These results suggest that Jab1 is an important regulator for 9-1-1 protein stability control in cells, which may provide novel information on the involvement of Jab1 in checkpoint and DNA repair signaling in response to DNA damage. PMID:17583730

Acute dialysis-associated peritonitis in children with D+ hemolytic uremic syndrome.

PubMed

Adragna, Marta; Balestracci, Alejandro; García Chervo, Laura; Steinbrun, Silvina; Delgado, Norma; Briones, Liliana

2012-04-01

Acute peritoneal dialysis (PD) is the preferred therapy for renal replacement in children with post-diarrheal hemolytic uremic syndrome (D+ HUS), but peritonitis remains a frequent complication of this procedure. We reviewed data from 149 patients with D+ HUS who had undergone acute PD with the aim of determining the prevalence and risk factors for the development of peritonitis. A total of 36 patients (24.2%) presented peritonitis. The median onset of peritonitis manifestations was 6 (range 2-18) days after the initiation of dialysis treatment, and Gram-positive microorganisms were the predominant bacterial type isolated (15/36 patients). The patients were divided into two groups: with or without peritonitis, respectively. Univariate analysis revealed that a longer duration of the oligoanuric period, more days of dialysis, catheter replacement, stay in the intensive care unit, and hypoalbuminemia were significantly associated to the development of peritonitis. The multivariate analysis, controlled by duration of PD, identified the following independent risk factors for peritonitis: catheter replacement [p = 0.037, odds ratio (OR) 1.33, 95% confidence interval (CI) 1.02-1.73], stay in intensive care unit (p = 0.0001, OR 2.62, 95% CI 1.65-4.19), and hypoalbuminemia (p = 0.0076, OR 1.45, 95% CI 1.10-1.91). Based on these findings, we conclude that the optimization of the aseptic technique during catheter manipulation and early nutritional support are targets for the prevention of peritonitis, especially in critically ill patients.

Microalbuminuria and early renal response to lethal dose Shiga toxin type 2 in rats.

PubMed

Ochoa, Federico; Oltra, Gisela; Gerhardt, Elizabeth; Hermes, Ricardo; Cohen, Lilian; Damiano, Alicia E; Ibarra, Cristina; Lago, Nestor R; Zotta, Elsa

2012-01-01

In Argentina, hemolytic uremic syndrome (HUS) constitutes the most frequent cause of acute renal failure in children. Approximately 2%-4% of patients die during the acute phase, and one-third of the 96% who survive are at risk of chronic renal sequelae. Little information is available about the direct effect of Shiga toxin type 2 (Stx2) on the onset of proteinuria and the evolution of toxin-mediated glomerular or tubular injury. In this work, rats were injected intraperitoneally with recombinant Escherichia coli culture supernatant containing Stx2 (sStx2; 20 μg/kg body weight) to induce HUS. Functional, immunoblotting, and immunohistochemistry studies were carried out to determine alterations in slit diaphragm proteins and the proximal tubule endocytic system at 48 hours post-inoculation. We detected a significant increase in microalbuminuria, without changes in the proteinuria values compared to the control rats. In immunoperoxidase studies, the renal tubules and glomerular mesangium showed an increased expression of transforming growth factor β(1)(TGF-β(1)). The expression of megalin was decreased by immunoperoxidase and the cytoplasm showed a granular pattern of megalin expression by immunofluorescence techniques. Western blot analysis performed in the renal cortex from sStx2-treated and control rats using anti-nephrin and anti-podocalyxin antibodies showed a decreased expression of these proteins. We suggest that the alterations in slit diaphragm proteins and megalin expression could be related to the development of microalbuminuria in response to lethal doses of Stx2.

Limited Evaluation of Image Quality Produced by a Portable Head CT Scanner (CereTom) in a Neurosurgery Centre

PubMed Central

Abdullah, Ariz Chong; Adnan, Johari Siregar; Rahman, Noor Azman A.; Palur, Ravikant

2017-01-01

Introduction Computed tomography (CT) is the preferred diagnostic toolkit for head and brain imaging of head injury. A recent development is the invention of a portable CT scanner that can be beneficial from a clinical point of view. Aim To compare the quality of CT brain images produced by a fixed CT scanner and a portable CT scanner (CereTom). Methods This work was a single-centre retrospective study of CT brain images from 112 neurosurgical patients. Hounsfield units (HUs) of the images from CereTom were measured for air, water and bone. Three assessors independently evaluated the images from the fixed CT scanner and CereTom. Streak artefacts, visualisation of lesions and grey–white matter differentiation were evaluated at three different levels (centrum semiovale, basal ganglia and middle cerebellar peduncles). Each evaluation was scored 1 (poor), 2 (average) or 3 (good) and summed up to form an ordinal reading of 3 to 9. Results HUs for air, water and bone from CereTom were within the recommended value by the American College of Radiology (ACR). Streak artefact evaluation scores for the fixed CT scanner was 8.54 versus 7.46 (Z = −5.67) for CereTom at the centrum semiovale, 8.38 (SD = 1.12) versus 7.32 (SD = 1.63) at the basal ganglia and 8.21 (SD = 1.30) versus 6.97 (SD = 2.77) at the middle cerebellar peduncles. Grey–white matter differentiation showed scores of 8.27 (SD = 1.04) versus 7.21 (SD = 1.41) at the centrum semiovale, 8.26 (SD = 1.07) versus 7.00 (SD = 1.47) at the basal ganglia and 8.38 (SD = 1.11) versus 6.74 (SD = 1.55) at the middle cerebellar peduncles. Visualisation of lesions showed scores of 8.86 versus 8.21 (Z = −4.24) at the centrum semiovale, 8.93 versus 8.18 (Z = −5.32) at the basal ganglia and 8.79 versus 8.06 (Z = −4.93) at the middle cerebellar peduncles. All results were significant with P-value < 0.01. Conclusions Results of the study showed a significant difference in image quality produced by the fixed CT scanner and CereTom, with the latter being more inferior than the former. However, HUs of the images produced by CereTom do fulfil the recommendation of the ACR. PMID:28381933

Database of Autotransplants for Breast Cancer.

DTIC Science & Technology

1998-11-01

atypical bacteria in Q.79, 81.) 301 Herpes Simplex (HSV1, HSV2) 100 Atypical bacteria, not otherwise specified 302 Herpes Zoster ( Chicken pox , Varicella...100 Atypical bacteria, not otherwise specified 302 Herpes Zoster ( Chicken pox , Varicella) 101 Coxiella 303 Cytomegalovirus (CMV) 102 Legionella 304...atypical bacteria in Q.329, 330.) 301 Herpes Simplex (HSV1, HSV2) 100 Atypical bacteria, not otherwise specified 302 Herpes Zoster ( Chicken pox , Vadcella

The effect of the position of atypical character-to-sound correspondences on reading kanji words aloud: Evidence for a sublexical serially operating kanji reading process.

PubMed

Sambai, Ami; Coltheart, Max; Uno, Akira

2018-04-01

In English, the size of the regularity effect on word reading-aloud latency decreases across position of irregularity. This has been explained by a sublexical serially operating reading mechanism. It is unclear whether sublexical serial processing occurs in reading two-character kanji words aloud. To investigate this issue, we studied how the position of atypical character-to-sound correspondences influenced reading performance. When participants read inconsistent-atypical words aloud mixed randomly with nonwords, reading latencies of words with an inconsistent-atypical correspondence in the initial position were significantly longer than words with an inconsistent-atypical correspondence in the second position. The significant difference of reading latencies for inconsistent-atypical words disappeared when inconsistent-atypical words were presented without nonwords. Moreover, reading latencies for words with an inconsistent-atypical correspondence in the first position were shorter than for words with a typical correspondence in the first position. This typicality effect was absent when the atypicality was in the second position. These position-of-atypicality effects suggest that sublexical processing of kanji occurs serially and that the phonology of two-character kanji words is generated from both a lexical parallel process and a sublexical serial process.

Localizing Circuits of Atrial Macro-Reentry Using ECG Planes of Coherent Atrial Activation

PubMed Central

Kahn, Andrew M.; Krummen, David E.; Feld, Gregory K.; Narayan, Sanjiv M.

2007-01-01

Background The complexity of ablation for atrial macro-reentry (AFL) varies significantly depending upon the circuit location. Presently, surface ECG analysis poorly separates left from right atypical AFL and from some cases of typical AFL, delaying diagnosis until invasive study. Objective To differentiate and localize the intra-atrial circuits of left atypical AFL, right atypical, and typical AFL using quantitative ECG analysis. Methods We studied 66 patients (54 M, age 59±14 years) with typical (n=35), reverse typical (n=4) and atypical (n=27) AFL. For each, we generated filtered atrial waveforms from ECG leads V5 (X-axis), aVF (Y) and V1 (Z) by correlating a 120 ms F-wave sample to successive ECG regions. Atrial spatial loops were plotted for 3 orthogonal planes (frontal, XY=V5/aVF; sagittal, YZ=aVF/V1; axial, XZ=V5/V1), then cross-correlated to measure spatial regularity (‘coherence’: range −1 to 1). Results Mean coherence was greatest in the XY plane (p<10−3 vs XZ or YZ). Atypical AFL showed lower coherence than typical AFL in XY (p<10−3), YZ (p<10−6) and XZ (p<10−5) planes. Atypical left AFL could be separated from atypical right AFL by lower XY coherence (p=0.02); for this plane coherence < 0.69 detected atypical left AFL with 84% specificity and 75% sensitivity. F-wave amplitude did not separate typical, atypical right or atypical left AFL (p=NS). Conclusions Atypical AFL shows lower spatial coherence than typical AFL, particularly in sagittal and axial planes. Coherence in the Cartesian frontal plane separated left and right atypical AFL. Such analyses may be used to plan ablation strategy from the bedside. PMID:17399632

Atypically presenting kaposiform hemangioendothelioma of the knee: ultrasound findings.

PubMed

Erdem Toslak, Iclal; Stegman, Matthew; Reiter, Michael P; Barkan, Güliz A; Borys, Dariusz; Lim-Dunham, Jennifer E

2018-04-10

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of early childhood and infancy. Kasabach-Merritt phenomenon, a common complication of KHE, is characterized by life-threatening thrombocytopenia, hemolytic anemia, and consumption coagulopathy. There may be atypical cases that do not present with Kasabach-Merritt phenomenon and do have atypical imaging findings. Knowledge of atypical imaging features may assist radiologists in identifying KHE. In this report, we present a 4-year-old case of KHE with atypical ultrasound findings.

Damage Models for Delamination and Transverse Fracture.

DTIC Science & Technology

1987-08-01

is metals mas be Aritten in this form (Leek ic and lls.\\ en tm ’r [ hus . except for consideration of hurst 19-f4 .I In analop. as th elasicits t her... exponent % . that theisirrir- must sols e siniultaneousls for f, g and 11 using the J, (but not past %alues) determines, the irrst:irtar ie dlinienionless...in this last case does r’hc’r pirrmeersl so that a J, is not necessaril% the nonlinearit% exponent appear in the equatioin for I’llp. I hc. results

Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase.

PubMed Central

McGuire, M C; Nogueira, C P; Bartels, C F; Lightstone, H; Hajra, A; Van der Spek, A F; Lockridge, O; La Du, B N

1989-01-01

A point mutation in the gene for human serum cholinesterase was identified that changes Asp-70 to Gly in the atypical form of serum cholinesterase. The mutation in nucleotide 209, which changes codon 70 from GAT to GGT, was found by sequencing a genomic clone and sequencing selected regions of DNA amplified by the polymerase chain reaction. The entire coding sequences for usual and atypical cholinesterases were compared, and no other consistent base differences were found. A polymorphic site near the C terminus of the coded region was detected, but neither allele at this locus segregated consistently with the atypical trait. The nucleotide-209 mutation was detected in all five atypical cholinesterase families examined. There was complete concordance between this mutation and serum cholinesterase phenotypes for all 14 heterozygous and 6 homozygous atypical subjects tested. The mutation causes the loss of a Sau3A1 restriction site; the resulting DNA fragment length polymorphism was verified by electrophoresis of 32P-labeled DNA restriction fragments from usual and atypical subjects. Dot-blot hybridization analysis with a 19-mer allele-specific probe to the DNA amplified by the polymerase chain reaction distinguished between the usual and atypical genotypes. We conclude that the Asp-70----Gly mutation (acidic to neutral amino acid substitution) accounts for reduced affinity of atypical cholinesterase for choline esters and that Asp-70 must be an important component of the anionic site. Heterogeneity in atypical alleles may exist, but the Asp-70 point mutation may represent an appreciable portion of the atypical gene pool. Images PMID:2915989

Discrepant epidemiological patterns between classical and atypical scrapie in sheep flocks under French TSE control measures.

PubMed

Fediaevsky, Alexandre; Gasqui, Patrick; Calavas, Didier; Ducrot, Christian

2010-09-01

The occurrence of secondary cases of atypical and classical scrapie was examined in 340 outbreaks of atypical and 296 of classical sheep scrapie detected in France during active surveillance programmes between 2002 and 2007. The prevalence of atypical scrapie in these flocks was 0.05% under selective culling and 0.07% under intensified monitoring i.e. not significantly different from that detected during active surveillance of the general population (P>0.5), whereas these figures were much higher for classical scrapie (3.67% and 0.25%, respectively, P<10(-5)). In addition the number of atypical scrapie cases per outbreak did not indicate clustering. The results suggest that atypical scrapie occurs spontaneously or is not particularly contagious, and that the control measures in force allowed appropriate control of classical scrapie but were not more efficient than active surveillance in detecting cases of atypical scrapie. Copyright 2009 Elsevier Ltd. All rights reserved.

Multiple modes of a-type potassium current regulation.

PubMed

Cai, Shi-Qing; Li, Wenchao; Sesti, Federico

2007-01-01

Voltage-dependent potassium (K+) channels (Kv) regulate cell excitability by controlling the movement of K+ ions across the membrane in response to changes in the cell voltage. The Kv family, which includes A-type channels, constitute the largest group of K+ channel genes within the superfamily of Na+, Ca2+ and K+ voltage-gated channels. The name "A-type" stems from the typical profile of these currents that results form the opposing effects of fast activation and inactivation. In neuronal cells, A-type currents (I(A)), determine the interval between two consecutive action potentials during repetitive firing. In cardiac muscle, A-type currents (I(to)), control the initial repolarization of the myocardium. Structurally, A-type channels are tetramers of alpha-subunits each containing six putative transmembrane domains including a voltage-sensor. A-type channels can be modulated by means of protein-protein interactions with so-called beta-subunits that control inactivation voltage sensitivity and other properties, and by post-transcriptional modifications such as phosphorylation or oxidation. Recently a new mode of A-type regulation has been discovered in the form of a class of hybrid beta-subunits that posses their own enzymatic activity. Here, we review the biophysical and physiological properties of these multiple modes of A-type channel regulation.

Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase

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

McGuire, M.C.; Nogueira, C.P.; Bartels, C.F.

1989-02-01

A point mutation in the gene for human serum cholinesterase was identified that changes Asp-70 to Gly in the atypical form of serum cholinesterase. The mutation in nucleotide 209, which changes codon 70 from GAT to GGT, was found by sequencing a genomic clone and sequencing selected regions of DNA amplified by the polymerase chain reaction. The entire coding sequences for usual and atypical cholinesterases were compared, and no other consistent base differences were found. The nucleotide-209 mutation was detected in all five atypical cholinesterase families examined. There was complete concordance between this mutation and serum cholinesterase phenotypes for allmore » 14 heterozygous and 6 homozygous atypical subjects tested. The mutation causes the loss of a Sau3A1 restriction site; the resulting DNA fragment length polymorphism was verified by electrophoresis of {sup 32}P-labeled DNA restriction fragments from usual and atypical subjects. Dot-blot hybridization analysis with a 19-mer allele-specific probe to the DNA amplified by the polymerase chain reaction distinguished between the usual and atypical genotypes. The authors conclude that the Asp-70 {yields} Gly mutation accounts for reduced affinity of atypical cholinesterase for choline esters and that Asp-70 must be an important component of the anionic site. Heterogeneity in atypical alleles may exist, but the Asp-70 point mutation may represent an appreciable portion of the atypical gene pool.« less

Therapeutic concentrations of antibiotics inhibit Shiga toxin release from enterohemorrhagic E. coli O104:H4 from the 2011 German outbreak

PubMed Central

2012-01-01

Background The shiga toxin-producing E. coli (STEC) O104:H4 caused a major outbreak in Germany in spring 2011. STEC are usually susceptible to common antibiotics. However, antibiotic treatment of STEC-infected patients is not recommended because STEC may enhance production and release of shiga toxins (STX) in response to antibiotics, which eventually enhances the frequency and severity of clinical symptoms, including haemolytic uraemic syndrome (HUS) and fatalities. Results We characterized the response to antibiotics of STEC O104:H4 isolates from two HUS patients during the German STEC outbreak in spring 2011 in comparison to the common STEC O157:H7. Liquid cultures of STEC O157:H7 and O104:H4 were incubated with graded dilutions of the antibiotics ciprofloxacin, meropenem, fosfomycin, gentamicin, rifampicin, and chloramphenicol. At defined times of antibiotic treatment, transcriptional activation of the STX2 gene, contents of STX and STX-activity in the culture supernatants were quantified. Unlike the common serotype O157:H7, STEC O104:H4 does not release STX in response to therapeutic concentrations of ciprofloxacin, meropenem, fosfomycin, and chloramphenicol. Conclusions In future outbreaks, the response of the respective epidemiologic STEC strain to antibiotics should be rapidly characterized in order to identify antibiotics that do not enhance the release of STX. This will eventually allow clinical studies tackling the question whether antibiotic treatment impacts on the eradication of STEC, clinical course of disease, and frequency of carriers. PMID:22853739

Effects of Antibiotics on Shiga Toxin 2 Production and Bacteriophage Induction by Epidemic Escherichia coli O104:H4 Strain

PubMed Central

Bielaszewska, Martina; Idelevich, Evgeny A.; Zhang, Wenlan; Bauwens, Andreas; Schaumburg, Frieder; Mellmann, Alexander; Peters, Georg

2012-01-01

The role of antibiotics in treatment of enterohemorrhagic Escherichia coli (EHEC) infections is controversial because of concerns about triggering hemolytic-uremic syndrome (HUS) by increasing Shiga toxin (Stx) production. During the recent large EHEC O104:H4 outbreak, antibiotic therapy was indicated for some patients. We tested a diverse panel of antibiotics to which the outbreak strain is susceptible to interrogate the effects of subinhibitory antibiotic concentrations on induction of stx2-harboring bacteriophages, stx2 transcription, and Stx2 production in this emerging pathogen. Ciprofloxacin significantly increased stx2-harboring phage induction and Stx2 production in outbreak isolates (P values of <0.001 to <0.05), while fosfomycin, gentamicin, and kanamycin insignificantly influenced them (P > 0.1) and chloramphenicol, meropenem, azithromycin, rifaximin, and tigecycline significantly decreased them (P ≤ 0.05). Ciprofloxacin and chloramphenicol significantly upregulated and downregulated stx2 transcription, respectively (P < 0.01); the other antibiotics had insignificant effects (P > 0.1). Meropenem, azithromycin, and rifaximin, which were used for necessary therapeutic or prophylactic interventions during the EHEC O104:H4 outbreak, as well as tigecycline, neither induced stx2-harboring phages nor increased stx2 transcription or Stx2 production in the outbreak strain. These antibiotics might represent therapeutic options for patients with EHEC O104:H4 infection if antibiotic treatment is inevitable. We await further analysis of the epidemic to determine if usage of these agents was associated with an altered risk of developing HUS. PMID:22391549

Correlation of contrast-enhanced MR images with the histopathology of minimally invasive thermal and cryoablation cancer treatments in normal dog prostates

NASA Astrophysics Data System (ADS)

Bouley, D. M.; Daniel, B.; Butts Pauly, K.; Liu, E.; Kinsey, A.; Nau, W.; Diederich, C. J.; Sommer, G.

2007-02-01

Magnetic Resonance Imaging (MRI) is a promising tool for visualizing the delivery of minimally invasive cancer treatments such as high intensity ultrasound (HUS) and cryoablation. We use an acute dog prostate model to correlate lesion histopathology with contrast-enhanced (CE) T1 weighted MR images, to aid the radiologists in real time interpretation of in vivo lesion boundaries and pre-existing lesions. Following thermal or cryo treatments, prostate glands are removed, sliced, stained with the vital dye triphenyl tetrazolium chloride, photographed, fixed and processed in oversized blocks for routine microscopy. Slides are scanned by Trestle Corporation at .32 microns/pixel resolution, the various lesions traced using annotation software, and digital images compared to CE MR images. Histologically, HUS results in discrete lesions characterized by a "heat-fixed" zone, in which glands subjected to the highest temperatures are minimally altered, surrounded by a rim or "transition zone" composed of severely fragmented, necrotic glands, interstitial edema and vascular congestion. The "heat-fixed" zone is non-enhancing on CE MRI while the "transition zone" appears as a bright, enhancing rim. Likewise, the CE MR images for cryo lesions appear similar to thermally induced lesions, yet the histopathology is significantly different. Glands subjected to prolonged freezing appear totally disrupted, coagulated and hemorrhagic, while less intensely frozen glands along the lesion edge are partially fragmented and contain apoptotic cells. In conclusion, thermal and cryo-induced lesions, as well as certain pre-existing lesions (cystic hyperplasia - non-enhancing, chronic prostatitis - enhancing) have particular MRI profiles, useful for treatment and diagnostic purposes.

Phylogenetic relationships of Shiga toxin-producing Escherichia coli isolated from Peruvian children

PubMed Central

Contreras, C. A.; Ruiz, J.; Lacher, D. W.; Rivera, F. P.; Saenz, Y.; Chea-Woo, E.; Zavaleta, N.; Gil, A. I.; Lanata, C. F.; Huicho, L.; Maves, R. C.; Torres, C.; DebRoy, C.; Cleary, T. G.

2011-01-01

The aim of this study was to determine the prevalence, virulence factors (stx, eae, ehxA and astA) and phylogenetic relationships [PFGE and multilocus sequence typing (MLST)] of Shiga toxin-producing Escherichia coli (STEC) strains isolated from four previous cohort studies in 2212 Peruvian children aged <36 months. STEC prevalence was 0.4 % (14/3219) in diarrhoeal and 0.6 % (15/2695) in control samples. None of the infected children developed haemolytic uraemic syndrome (HUS) or other complications of STEC. stx1 was present in 83 % of strains, stx2 in 17 %, eae in 72 %, ehxA in 59 % and astA in 14 %. The most common serotype was O26 : H11 (14 %) and the most common seropathotype was B (45 %). The strains belonged mainly to phylogenetic group B1 (52 %). The distinct combinations of alleles across the seven MLST loci were used to define 13 sequence types among 19 STEC strains. PFGE typing of 20 STEC strains resulted in 19 pulsed-field patterns. Comparison of the patterns revealed 11 clusters (I–XI), each usually including strains belonging to different serotypes; one exception was cluster VI, which gathered exclusively seven strains of seropathotype B, clonal group enterohaemorrhagic E. coli (EHEC) 2 and phylogenetic group B1. In summary, STEC prevalence was low in Peruvian children with diarrhoea in the community setting. The strains were phylogenetically diverse and associated with mild infections. However, additional studies are needed in children with bloody diarrhoea and HUS. PMID:21292859

Effect of ultra-low doses, ASIR and MBIR on density and noise levels of MDCT images of dental implant sites.

PubMed

Widmann, Gerlig; Al-Shawaf, Reema; Schullian, Peter; Al-Sadhan, Ra'ed; Hörmann, Romed; Al-Ekrish, Asma'a A

2017-05-01

Differences in noise and density values in MDCT images obtained using ultra-low doses with FBP, ASIR, and MBIR may possibly affect implant site density analysis. The aim of this study was to compare density and noise measurements recorded from dental implant sites using ultra-low doses combined with FBP, ASIR, and MBIR. Cadavers were scanned using a standard protocol and four low-dose protocols. Scans were reconstructed using FBP, ASIR-50, ASIR-100, and MBIR, and either a bone or standard reconstruction kernel. Density (mean Hounsfield units [HUs]) of alveolar bone and noise levels (mean standard deviation of HUs) was recorded from all datasets and measurements were compared by paired t tests and two-way ANOVA with repeated measures. Significant differences in density and noise were found between the reference dose/FBP protocol and almost all test combinations. Maximum mean differences in HU were 178.35 (bone kernel) and 273.74 (standard kernel), and in noise, were 243.73 (bone kernel) and 153.88 (standard kernel). Decreasing radiation dose increased density and noise regardless of reconstruction technique and kernel. The effect of reconstruction technique on density and noise depends on the reconstruction kernel used. • Ultra-low-dose MDCT protocols allowed more than 90 % reductions in dose. • Decreasing the dose generally increased density and noise. • Effect of IRT on density and noise varies with reconstruction kernel. • Accuracy of low-dose protocols for interpretation of bony anatomy not known. • Effect of low doses on accuracy of computer-aided design models unknown.

Atypical pneumonia

MedlinePlus

Walking pneumonia; Community-acquired pneumonia - atypical ... Bacteria that cause atypical pneumonia include: Mycoplasma pneumonia is caused by the bacteria Mycoplasma pneumoniae . It often affects people younger than age 40. Pneumonia due ...

Analysis of the Origin of Atypical Scanning Laser Polarimetry Patterns by Polarization-Sensitive Optical Coherence Tomography

PubMed Central

Götzinger, Erich; Pircher, Michael; Baumann, Bernhard; Hirn, Cornelia; Vass, Clemens; Hitzenberger, Christoph K.

2010-01-01

Purpose To analyze the physical origin of atypical scanning laser polarimetry (SLP) patterns. To compare polarization-sensitive optical coherence tomography (PS-OCT) scans to SLP images. To present a method to obtain pseudo-SLP images by PS-OCT that are free of atypical artifacts. Methods Forty-one eyes of healthy subjects, subjects with suspected glaucoma, and patients with glaucoma were imaged by SLP (GDx VCC) and a prototype spectral domain PS-OCT system. The PS-OCT system acquires three-dimensional (3D) datasets of intensity, retardation, and optic axis orientation simultaneously within 3 seconds. B-scans of intensity and retardation and en face maps of retinal nerve fiber layer (RNFL) retardation were derived from the 3D PS-OCT datasets. Results were compared with those obtained by SLP. Results Twenty-two eyes showed atypical retardation patterns, and 19 eyes showed normal patterns. From the 22 atypical eyes, 15 showed atypical patterns in both imaging modalities, five were atypical only in SLP images, and two were atypical only in PS-OCT images. In most (15 of 22) atypical cases, an increased penetration of the probing beam into the birefringent sclera was identified as the source of atypical patterns. In such cases, the artifacts could be eliminated in PS-OCT images by depth segmentation and exclusion of scleral signals. Conclusions PS-OCT provides deeper insight into the contribution of different fundus layers to SLP images. Increased light penetration into the sclera can distort SLP retardation patterns of the RNFL. PMID:19036999

Prevalence and correlates of atypical patterns of drug use progression: findings from the South African Stress and Health Study

PubMed Central

Myers, B; van Heerden, MS; Grimsrud, A; Myer, L; Williams, DR; Stein, DJ

2012-01-01

Objective Atypical sequences of drug use progression are thought to have important implications for the development of substance dependence. The extent to which this assumption holds for South African populations is unknown. This paper attempts to address this gap by examining the prevalence and correlates of atypical patterns of drug progression among South Africans. Method Data on substance use and other mental health disorders from a nationally representative sample of 4351 South Africans were analysed. Weighted cross tabulations were used to estimate prevalence and correlates of atypical patterns of drug use progression. Results Overall, 12.2% of the sample reported atypical patterns of drug use progression. The most common violation was the use of extra-medical drugs prior to alcohol and tobacco. Gender was significantly associated with atypical patterns of drug use with the risk pattern varying by the type of drug. None of the anxiety or mood disorders were associated with atypical patterns of use. Atypical patterns of drug use were not associated with increased risk for a lifetime substance use disorder. Conclusion Atypical patterns of drug use initiation seem more prevalent in South Africa compared to other countries. The early use of extra-medical drugs is common, especially among young women. Drug availability and social environmental factors may influence patterns of drug use. The findings have important implications for prevention initiatives and future research. PMID:21509404

Screening for atypical suicide risk with person fit statistics among people presenting to alcohol and other drug treatment.

PubMed

Conrad, Kendon J; Bezruczko, Nikolaus; Chan, Ya-Fen; Riley, Barth; Diamond, Guy; Dennis, Michael L

2010-01-15

Symptoms of internalizing disorders (depression, anxiety, somatic, trauma) are the major risk factors for suicide. Atypical suicide risk is characterized by people with few or no symptoms of internalizing disorders. In persons screened at intake to alcohol or other drug (AOD) treatment, this research examined whether person fit statistics would support an atypical subtype at high risk for suicide that did not present with typical depression and other internalizing disorders. Symptom profiles of the prototypical, typical, and atypical persons, as defined using fit statistics, were tested on 7408 persons entering AOD treatment using the Global Appraisal of Individual Needs (GAIN; Dennis et al., 2003a,b). Of those with suicide symptoms, the findings were as expected with the atypical group being higher on suicide and lower on symptoms of internalizing disorders. In addition, the atypical group was similar or lower on substance problems, symptoms of externalizing disorders, and crime and violence. Person fit statistics were useful in identifying persons with atypical suicide profiles and in enlightening aspects of existing theory concerning atypical suicidal ideation. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function

PubMed Central

Portugal, Silvia; Tipton, Christopher M; Sohn, Haewon; Kone, Younoussou; Wang, Jing; Li, Shanping; Skinner, Jeff; Virtaneva, Kimmo; Sturdevant, Daniel E; Porcella, Stephen F; Doumbo, Ogobara K; Doumbo, Safiatou; Kayentao, Kassoum; Ongoiba, Aissata; Traore, Boubacar; Sanz, Inaki; Pierce, Susan K; Crompton, Peter D

2015-01-01

Protective antibodies in Plasmodium falciparum malaria are only acquired after years of repeated infections. Chronic malaria exposure is associated with a large increase in atypical memory B cells (MBCs) that resemble B cells expanded in a variety of persistent viral infections. Understanding the function of atypical MBCs and their relationship to classical MBCs will be critical to developing effective vaccines for malaria and other chronic infections. We show that VH gene repertoires and somatic hypermutation rates of atypical and classical MBCs are indistinguishable indicating a common developmental history. Atypical MBCs express an array of inhibitory receptors and B cell receptor (BCR) signaling is stunted in atypical MBCs resulting in impaired B cell responses including proliferation, cytokine production and antibody secretion. Thus, in response to chronic malaria exposure, atypical MBCs appear to differentiate from classical MBCs becoming refractory to BCR-mediated activation and potentially interfering with the acquisition of malaria immunity. DOI: http://dx.doi.org/10.7554/eLife.07218.001 PMID:25955968

Cellular localization of the atypical isoforms of protein kinase C (aPKCζ/PKMζ and aPKCλ/ι) on the neuromuscular synapse.

PubMed

Besalduch, Núria; Lanuza, Maria A; Garcia, Neus; Obis, Teresa; Santafe, Manel M; Tomàs, Marta; Priego, Mercedes; Tomàs, Josep

2013-11-27

Several classic and novel protein kinase C (PKC) isoforms are selectively distributed in specific cell types of the adult neuromuscular junction (NMJ), in the neuron, glia and muscle components, and are involved in many functions, including neurotransmission. Here, we investigate the presence in this paradigmatic synapse of atypical PKCs, full-length atypical PKC zeta (aPKCζ), its separated catalytic part (PKMζ) and atypical lambda-iota PKC (aPKCλ/ι). High resolution immunohistochemistry was performed using a pan-atypical PKC antibody. Our results show moderate immunolabeling on the three cells (presynaptic motor nerve terminal, teloglial Schwann cell and postsynaptic muscle cell) suggesting the complex involvement of atypical PKCs in synaptic function. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Information Display System for Atypical Flight Phase

NASA Technical Reports Server (NTRS)

Statler, Irving C. (Inventor); Ferryman, Thomas A. (Inventor); Amidan, Brett G. (Inventor); Whitney, Paul D. (Inventor); White, Amanda M. (Inventor); Willse, Alan R. (Inventor); Cooley, Scott K. (Inventor); Jay, Joseph Griffith (Inventor); Lawrence, Robert E. (Inventor); Mosbrucker, Chris J. (Inventor);

Repeat Prostate Biopsy Practice Patterns in a Statewide Quality Improvement Collaborative.

PubMed

Burks, Frank N; Hu, Jonathan C; Telang, Dinesh; Liu, Alice; Hawken, Scott; Montgomery, Zack; Linsell, Susan; Montie, James E; Miller, David C; Ghani, Khurshid R

2017-08-01

We examined rebiopsies in MUSIC (Michigan Urological Surgery Improvement Collaborative) to understand adherence to guidelines recommending repeat prostate biopsy in patients with multifocal high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. We analyzed data on men undergoing repeat biopsy, practice patterns and cancer detection rates. Multivariate regression modeling was used to calculate the proportion of patients undergoing rebiopsy. We used claims data to validate the treatment classification in MUSIC. To understand reasons for not performing rebiopsy we reviewed records of a sample of patients with atypical small acinar proliferation. We identified 5,375 men with a negative biopsy, of whom 411 (7.6%) underwent repeat biopsy. In 718 men with high grade prostatic intraepithelial neoplasia, 350 with atypical small acinar proliferation and 587 with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation or atypical small acinar proliferation alone at initial biopsy the rebiopsy rate was 20.7%, 42.5% and 55.6%, respectively. The adjusted proportion of patients with rebiopsy in each practice ranged from 0% to 17.2% (p <0.001). The overall cancer detection rate at rebiopsy was 39.3%. It was highest after atypical small acinar proliferation (adjusted probability 0.39, 95% CI 0.30-0.48), and after high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation (adjusted probability 0.50, 95% CI 0.35-0.65). The greatest Gleason 7 or greatest detection rate of 41.1% was found in patients with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation. Chart review revealed that 45.5% of patients with atypical small acinar proliferation underwent prostate specific antigen testing instead of rebiopsy while 36% failed to undergo rebiopsy despite a recommendation. Rebiopsy rates vary in Michigan practices with relatively low use in men with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation or atypical small acinar proliferation alone. Quality improvement strategies should target patients with atypical small acinar proliferation and high grade prostatic intraepithelial neoplasia as they have the highest likelihood of cancer detection. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Neuroinflammation is increased in the parietal cortex of atypical Alzheimer's disease.

PubMed

Boon, Baayla D C; Hoozemans, Jeroen J M; Lopuhaä, Boaz; Eigenhuis, Kristel N; Scheltens, Philip; Kamphorst, Wouter; Rozemuller, Annemieke J M; Bouwman, Femke H

2018-05-29

While most patients with Alzheimer's disease (AD) present with memory complaints, 30% of patients with early disease onset present with non-amnestic symptoms. This atypical presentation is thought to be caused by a different spreading of neurofibrillary tangles (NFT) than originally proposed by Braak and Braak. Recent studies suggest a prominent role for neuroinflammation in the spreading of tau pathology. We aimed to explore whether an atypical spreading of pathology in AD is associated with an atypical distribution of neuroinflammation. Typical and atypical AD cases were selected based on both NFT distribution and amnestic or non-amnestic clinical presentation. Immunohistochemistry was performed on the temporal pole and superior parietal lobe of 10 typical and 9 atypical AD cases. The presence of amyloid-beta (N-terminal; IC16), pTau (AT8), reactive astrocytes (GFAP), microglia (Iba1, CD68, and HLA-DP/DQ/DR), and complement factors (C1q, C3d, C4b, and C5b-9) was quantified by image analysis. Differences in lobar distribution patterns of immunoreactivity were statistically assessed using a linear mixed model. We found a temporal dominant distribution for amyloid-beta, GFAP, and Iba1 in both typical and atypical AD. Distribution of pTau, CD68, HLA-DP/DQ/DR, C3d, and C4b differed between AD variants. Typical AD cases showed a temporal dominant distribution of these markers, whereas atypical AD cases showed a parietal dominant distribution. Interestingly, when quantifying for the number of amyloid-beta plaques instead of stained surface area, atypical AD cases differed in distribution pattern from typical AD cases. Remarkably, plaque morphology and localization of neuroinflammation within the plaques was different between the two phenotypes. Our data show a different localization of neuroinflammatory markers and amyloid-beta plaques between AD phenotypes. In addition, these markers reflect the atypical distribution of tau pathology in atypical AD, suggesting that neuroinflammation might be a crucial link between amyloid-beta deposits, tau pathology, and clinical symptoms.

A novel examination of atypical major depressive disorder based on attachment theory.

PubMed

Levitan, Robert D; Atkinson, Leslie; Pedersen, Rebecca; Buis, Tom; Kennedy, Sidney H; Chopra, Kevin; Leung, Eman M; Segal, Zindel V

2009-06-01

While a large body of descriptive work has thoroughly investigated the clinical correlates of atypical depression, little is known about its fundamental origins. This study examined atypical depression from an attachment theory framework. Our hypothesis was that, compared to adults with melancholic depression, those with atypical depression would report more anxious-ambivalent attachment and less secure attachment. As gender has been an important consideration in prior work on atypical depression, this same hypothesis was further tested in female subjects only. One hundred ninety-nine consecutive adults presenting to a tertiary mood disorders clinic with major depressive disorder with either atypical or melancholic features according to the Structured Clinical Interview for DSM-IV Axis-I Disorders were administered a self-report adult attachment questionnaire to assess the core dimensions of secure, anxious-ambivalent, and avoidant attachment. Attachment scores were compared across the 2 depressed groups defined by atypical and melancholic features using multivariate analysis of variance. The study was conducted between 1999 and 2004. When men and women were considered together, the multivariate test comparing attachment scores by depressive group was statistically significant at p < .05. Between-subjects testing indicated that atypical depression was associated with significantly lower secure attachment scores, with a trend toward higher anxious-ambivalent attachment scores, than was melancholia. When women were analyzed separately, the multivariate test was statistically significant at p < .01, with both secure and anxious-ambivalent attachment scores differing significantly across depressive groups. These preliminary findings suggest that attachment theory, and insecure and anxious-ambivalent attachment in particular, may be a useful framework from which to study the origins, clinical correlates, and treatment of atypical depression. Gender may be an important consideration when considering atypical depression from an attachment perspective. Copyright 2009 Physicians Postgraduate Press, Inc.

Preparation of A-type proanthocyanidin dimers from peanut skins and persimmon pulp and comparison of the antioxidant activity of A-type and B-type dimers.

PubMed

Dong, Xiao-qian; Zou, Bo; Zhang, Ying; Ge, Zhen-zhen; Du, Jing; Li, Chun-mei

2013-12-01

We have established a simple method for preparing large quantities of A-type dimers from peanut skin and persimmon for further structure-activity relationship study. Peanut skins were defatted with hexane and oligomeric proanthocyanidins were extracted from it with 20% of methanol, and the extract was fractionated with ethyl acetate. Persimmon tannin was extracted from persimmon with methanol acidified with 1% hydrochloric acid, after removing the sugar and small phenols, the high molecular weight persimmon tannin was partially cleaved with 6.25% hydrochloric acid in methanol. The ethyl acetate fraction from peanut skins and persimmon tannin cleaved products was chromatographed on AB-8 macroporous resin followed by Toyopearl HW-50F resin to yield about 378.3mg of A-type (epi)catechin (EC) dimer from 1 kg dry peanut skins and 34.3mg of A-type (epi)catechin-3-O-gallate (ECG) dimer and 37.7 mg of A-type (epi)gallocatechin-3-O-gallate (EGCG) dimer from 1 kg fresh persimmon fruit. The antioxidant properties of the A-type and B-type dimers were compared in five different assays, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical, hydroxyl radical, lipid peroxidation in mice liver homogenate and erythrocyte hemolysis in rat blood. Our results showed that both A-type and B-type dimers showed high antioxidant potency in a dose-dependent manner. In general, B-type dimers showed higher radical scavenging potency than A-type ones with the same subunits in aqueous systems. But in tissue or lipid systems, A-type dimers showed similar or even higher antioxidant potency than B-type ones. © 2013.

Clinical significance of the qualification of atypical squamous cells of undetermined significance: An analysis on the basis of histologic diagnoses.

PubMed

Vlahos, N P; Dragisic, K G; Wallach, E E; Burroughs, F H; Fluck, S; Rosenthal, D L

2000-04-01

This study was undertaken to evaluate the significance of further qualification of atypical squamous cells of undetermined significance in routine Papanicolaou smears. A retrospective medical records review was conducted on 316 women whose Papanicolaou smears yielded diagnoses of either atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion or atypical squamous cells of undetermined significance suggestive of a reactive process. The overall incidence of a squamous intraepithelial lesion (cervical intraepithelial neoplasia grades I, II, and III) was higher in the group with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion than in the group with results suggestive of a reactive process (41.1% vs 22.3%; P =.0344). Women with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion were 9.7 times more likely to have high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia III) develop than were women with atypical squamous cells of undetermined significance suggestive of a reactive process (95% confidence interval, 1.26-74.64). The incidence of high-grade squamous intraepithelial lesion was higher among women 35 years old (17.8% vs 6.3%; P =.0378). Women with a diagnosis of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion are more likely to have intraepithelial lesions develop than are those with atypical squamous cells of undetermined significance suggestive of a reactive process. Aggressive evaluation of cases of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion with colposcopy and cervical biopsies may be appropriate. Age should be considered as an independent factor in the plan of management.

A-type granites and related rocks: Evolution of a concept, problems and prospects

NASA Astrophysics Data System (ADS)

Bonin, Bernard

2007-08-01

Although A-type granites have long been recognized as a distinct group of granites, the term A-type was coined first less than thirty years ago. A-type suites occur in geodynamic contexts ranging from within-plate settings to plate boundaries, locations and times of emplacement are not random. Rare in the lower crust, as some charnockite suites, they are fairly common at shallower depths, especially at the subvolcanic level where they form ring complexes rooting caldera volcanoes. Characteristic features include hypersolvus to transsolvus to subsolvus alkali feldspar textures, iron-rich mafic mineralogy, bulk-rock compositions yielding ferroan, alkali-calcic to alkaline affinities, high LILE+HFSE abundances, and pronounced anomalies due to high degrees of mineral fractionation. Isotopic features evidence sources containing a large mantle input. Experimental data show that A-type magmas contain dissolved OH F-bearing fluids, crystallised under reduced and oxidized conditions, and yield high-temperature liquidus, favouring early crystallisation of anhydrous iron minerals, such as fayalite. Though many petrogenetic models imply solely crustal derivation, no convincing A-type liquids were produced experimentally from crustal materials, nor have any leucosomes of A-type composition been detected within migmatitic terranes. As it occurs in association with mafic igneous rocks in continents as well as on the ocean floor, A-type granite is likely to come from mantle-derived transitional to alkaline mafic to intermediate magmas. Rare felsic materials found in the meteoritic and lunar record yield dominantly A-type features. Contrary to the more common types of granite, A-type granite is, therefore, not typical of Earth and was produced in planetary environments differing from those prevailing on Earth.

Atypical Depression

MedlinePlus

... Atypical depression may occur as a feature of major depression or of mild, long-lasting depression (dysthymia). Symptoms ... depression is a serious illness that can cause major problems. Atypical depression can result in emotional, behavioral and health problems ...

Neuroprotective effect of atypical antipsychotics in cognitive and non-cognitive behavioral impairment in animal models

PubMed Central

He, Jue; Kong, Jiming

2009-01-01

Antipsychotic drugs are divided into two groups: typical and atypical. Recent clinical studies show atypical antipsychotics have advantages over typical antipsychotics in a wide variety of neuropsychiatric conditions, in terms of greater efficacy for positive and negative symptoms, beneficial effects on cognitive functioning, and fewer extra pyramidal side effects in treating schizophrenia. As such, atypical antipsychotics may be effective in the treatment of depressive symptoms associated with psychotic and mood disorders, posttraumatic stress disorder and psychosis in Alzheimer disease. In this paper, we describe the effects and potential neurochemical mechanisms of action of atypical antipsychotics in several animal models showing memory impairments and/or non-cognitive behavioral changes. The data provide new insights into the mechanisms of action of atypical antipsychotics that may broaden their clinical applications. PMID:19372744

A rare case of atypical pleomorphic adenoma arising from periocular ectopic lacrimal gland.

PubMed

Wajda, Brynn N; Mancini, Ronald; Evers, Bret; Nick Hogan, R

2018-06-23

To describe features of atypical pleomorphic adenoma, a rare clinical entity, particularly when found in ectopic periocular lacrimal gland tissue. Case report of biopsy-confirmed periocular atypical pleomorphic adenoma. A 35-year-old female presented with a unique orbital lesion found to be ectopic lacrimal gland demonstrating atypical pleomorphic adenoma on formal histopathologic review. Pleomorphic adenoma is pathologically characterized as an epithelial lesion intermixed with mesenchymal elements. It is further classified as atypical with the presence of features such as hypercellularity, regions of necrosis or hyalinization, cellular dysplasia, capsular violation, and malignant characteristics without frank local extension or distant metastases. Due to its rarity, the natural history and prognosis of atypical pleomorphic adenoma is unclear. Physicians need to recognize this entity, and complete surgical excision with strict follow-up regimens are likely warranted.

Atypical antipsychotic use and outcomes in an urban maternal mental health service.

PubMed

Hatters Friedman, Susan; Moller-Olsen, Charmian; Prakash, Chandni; North, Abigail

2016-08-01

Objective Despite many women suffering from psychosis in their childbearing years, limited data exist about the use of atypical antipsychotic agents in pregnancy. Atypical antipsychotic agents are often used to treat bipolar disorder, instead of lithium or valproate because of the known teratogenicity of those agents. As well, atypical antipsychotics are often prescribed in anxiety disorders and depression. This study sought to describe pregnancy outcomes for women prescribed atypical antipsychotics during pregnancy. Methods This retrospective review included all cases treated by Auckland Maternal Mental Health services in which atypical antipsychotic agents were utilized during pregnancy over three years. Results Over the three years, 45 pregnant women were prescribed atypical antipsychotic agents, most commonly quetiapine or olanzapine. Two-fifths (40%) were diagnosed with bipolar disorder and almost one-third (31%) with a psychotic disorder. Two-thirds (64%) were prescribed multiple psychotropic medications during their pregnancy. Instrumental delivery rates were elevated at 38%. A minority (13%) of the women developed gestational diabetes mellitus. Although 7% of infants were born premature, all were born after 35 weeks. Two major malformations were noted, similar to baseline community rates. Conclusions This naturalistic study adds to the limited literature about treatment with atypical antipsychotic agents in pregnancy, though not adequately powered to detect small differences in malformations or obstetrical outcomes. It also highlights the myriad of indications for which pregnant women are prescribed atypical antipsychotics, and the multiple other risk factors seen in this population.

Malmstrom AFB, Great Falls, Montana. Revised Uniform Summary of Surface Weather Observations (RUSSWO)

DTIC Science & Technology

1978-06-12

PRECIPITATION PSYCHROMETRIC-DRY VS WET BULB SNOWFALL MEAN & STD DEV. (DRY BULB, WIT BULB, & DEW POINT) SNOW DEPTH RELATIVE HUMIDITY PARTC SURFACE WINDS PART D...CONDITIONS FROM HOURLY OBSERVATIONS JU 00.jAN/RRI 0 RAIN FREEZING SNOW %OF SMOKE DUST % OF OSS TOTAL MONTH HUS TOURS HAt SAND TOT FOSAD/ RTO HOUS. THUNDR.ADOl...WEATHFR 1500-1700. CLAS VS MIEN(LT.) CONDITION SPEED IMEAN (KNTS) 1.3 4.6 7.10 11.16 17.21 22.27V 2833 34. 40 41.47 43.55 ?:56 % WIND cit. ISPEED N 1.1

Expression of Shiga toxin 2 (Stx2) in highly virulent Stx-producing Escherichia coli (STEC) carrying different anti-terminator (q) genes.

PubMed

Olavesen, Kristoffer K; Lindstedt, Bjørn-Arne; Løbersli, Inger; Brandal, Lin T

2016-08-01

Shiga toxins (Stx) are key virulence factors of Shiga toxin-producing Escherichia coli (STEC) during development of haemolytic uremic syndrome (HUS). It has been suggested that not only specific stx2 subtypes, but also the amount of Stx2 expressed might be essential for STEC pathogenicity. We aimed to investigate if various anti-terminator (q) genes might influence the expression level of Stx2 in highly virulent STEC. A multiplex PCR detecting q933, q21, and qO111 was run on 20 stx2a-positive STEC strains, of which 18 were HUS associated serotypes (HAS) and two non-HAS. Relative expression of Stx2 mRNA was assessed for all strains, both in non-induced and induced (mitomycin C) state. The HAS STEC carried either q933 (n = 8), qO111 (n = 8), or both (n = 2). In basal state, no STEC strains showed higher expression of Stx2 mRNA than the calibrator EDL933 (non-sorbitol fermenting (NSF) O157:H7carrying q933). Variations among strains were not associated with different q genes present, but rather related to specific serogroups. In induced state, O104:H4 strains (q933) showed higher Stx2 mRNA level than EDL933, whereas sorbitol fermenting (SF) O157:H- (qO111) and O121:H? (q933) STEC showed levels comparable with EDL933. An association between the presence of q933 and higher Stx2 level was seen within some HAS, but not all. Interestingly, the O103:H25 STEC strains, responsible for a HUS outbreak in Norway, carried both q933 and qO111. However, the Stx2 mRNA level in these strains was significantly lower than EDL933 in both states, indicating that other factors than the level of Stx2 might explain the aggressiveness of these bacteria. The two non-HAS STEC did not carry any of the examined q genes. In induced state, these bacteria showed the lowest Stx2 mRNA level compared to EDL933. One of the non-HAS STEC was not induced by mitomycin C, suggesting that stx2a might be located on a defect bacteriophage. No association between specific q genes and Stx2 mRNA expression level was revealed in stx2a-positive HAS STEC. Our results suggest that other factor(s) than specific q genes might influence the level of Stx2 produced in highly virulent STEC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Outbreak of escherichia coli O157: H7 infections after Petting Zoo visits, North Carolina State Fair, October-November 2004.

PubMed

Goode, Brant; O'Reilly, Ciara; Dunn, John; Fullerton, Kathleen; Smith, Stacey; Ghneim, George; Keen, James; Durso, Lisa; Davies, Megan; Montgomery, Sue

2009-01-01

To identify cases, describe the outbreak, implement control measures, and identify factors associated with infection or protection from infection, including contact with animals and hand hygiene practices. Case finding, a case-control study of 45 cases and 188 controls, environmental investigation, and molecular subtyping of clinical and environmental Escherichia coli O157:H7 isolates. The 2004 North Carolina State Fair. Case patients were fair visitors who had laboratory-confirmed E coli O157 infections, hemolytic uremic syndrome (HUS) diagnoses, or bloody diarrheal illnesses. Control subjects were recruited from a randomized list of persons who had purchased fair tickets online. Environmental samples from the fairgrounds were obtained from locations that had held animals during the fair. Main Exposure Visiting a petting zoo. Case finding: Summary descriptive statistics of suspected, probable, or confirmed E coli O157:H7 infections, signs, symptoms, and HUS. Environmental investigation: E coli O157:H7 isolates, pulsed-field gel electrophoresis patterns, and spatial distribution of source locations. Case-control study: Odds ratios (ORs) comparing reported fair-related activities, hygiene practices, and zoonotic disease knowledge with outcome. A total of 108 case patients were ascertained, including 41 with laboratory-confirmed illness and 15 who experienced HUS. Forty-five case patients and 188 controls were enrolled in the case-control study. Visits to a petting zoo having substantial environmental E coli O157:H7 contamination were associated with illness (age-adjusted OR, 8.2; 95% confidence interval [CI], 3.3-20.3). Among children 5 years or younger who had visited the implicated petting zoo, contact with animal manure (OR, 6.9; 95% CI, 2.2-21.9) and hand-to-mouth behaviors (OR, 10.6; 95% CI, 2.0-55.0) were associated with illness. Reported hand hygiene practices did not differ significantly (OR, 1.8; 95% CI, 0.3-9.5). Reported awareness of the risk for zoonotic disease was protective (OR, 0.1; 95% CI, 0.03-0.5). Environmental samples from the petting zoo implicated in the case-control study yielded E coli O157:H7, with indistinguishable pulsed-field gel electrophoresis patterns from the predominant strain. We describe one of the largest petting zoo outbreaks of E coli O157:H7 to date. Persons became infected after contact with manure and engaging in hand-to-mouth behaviors in a petting zoo having substantial E coli O157:H7 contamination. Use of alcohol-based hand-sanitizing gels was not protective, although knowledge of the risk for zoonotic infection was protective. Future investigations in similar outbreaks should assess risks for infection and protective measures (eg, physical barriers separating visitors from animal manure, education, and appropriate hand hygiene practices).

Mapping attractor fields in face space: the atypicality bias in face recognition.

PubMed

Tanaka, J; Giles, M; Kremen, S; Simon, V

1998-09-01

A familiar face can be recognized across many changes in the stimulus input. In this research, the many-to-one mapping of face stimuli to a single face memory is referred to as a face memory's 'attractor field'. According to the attractor field approach, a face memory will be activated by any stimuli falling within the boundaries of its attractor field. It was predicted that by virtue of its location in a multi-dimensional face space, the attractor field of an atypical face will be larger than the attractor field of a typical face. To test this prediction, subjects make likeness judgments to morphed faces that contained a 50/50 contribution from an atypical and a typical parent face. The main result of four experiments was that the morph face was judged to bear a stronger resemblance to the atypical face parent than the typical face parent. The computational basis of the atypicality bias was demonstrated in a neural network simulation where morph inputs of atypical and typical representations elicited stronger activation of atypical output units than of typical output units. Together, the behavioral and simulation evidence supports the view that the attractor fields of atypical faces span over a broader region of face space that the attractor fields of typical faces.

Atypical Brain Torque in Boys With Developmental Stuttering

PubMed Central

Mock, Jeffrey Ryan; Zadina, Janet N.; Corey, David M.; Cohen, Jeremy D.; Lemen, Lisa C.; Foundas, Anne L.

2017-01-01

The counterclockwise brain torque, defined as a larger right prefrontal and left parietal-occipital lobe, is a consistent brain asymmetry. Reduced or reversed lobar asymmetries are markers of atypical cerebral laterality and have been found in adults who stutter. It was hypothesized that atypical brain torque would be more common in children who stutter. MRI-based morphology measures were completed in boys who stutter (n=14) and controls (n=14), ages 8–13. The controls had the expected brain torque configurations whereas the boys who stutter were atypical. These results support the hypothesis that developmental stuttering is associated with atypical prefrontal and parietal-occipital lobe asymmetries. PMID:22799762

Pneumonia Updates on Legionella, Chlamydophila, and Mycoplasma Pneumonia

PubMed Central

Sharma, Lokesh; Losier, Ashley; Tolbert, Thomas; Dela Cruz, Charles S.; Marion, Chad R.

2017-01-01

SUMMARY CAP due to Legionella, Chlamydophyla, or Mycoplasma continues to be a diagnostic challenge due to the nonspecific clinical and radiographic presentations. The vague clinical presentations of atypical CAP contribute to its underdiagnosis and under-reporting. Advancements in diagnostic techniques bring hope to rapid and accurate diagnosis of atypical CAP. Macrolides and respiratory fluoroquinolones are currently the antibiotics of choice, but this may change in the near future as more antibiotics resistance patterns emerge for atypical CAP. Several controversies still exist in atypical CAP, underscoring the need for continued investigation of preventing atypical CAP and determine its association with chronic lung diseases. PMID:28159161

A-type potassium currents in smooth muscle.

PubMed

Amberg, Gregory C; Koh, Sang Don; Imaizumi, Yuji; Ohya, Susumu; Sanders, Kenton M

2003-03-01

A-type currents are voltage-gated, calcium-independent potassium (Kv) currents that undergo rapid activation and inactivation. Commonly associated with neuronal and cardiac cell-types, A-type currents have also been identified and characterized in vascular, genitourinary, and gastrointestinal smooth muscle cells. This review examines the molecular identity, biophysical properties, pharmacology, regulation, and physiological function of smooth muscle A-type currents. In general, this review is intended to facilitate the comparison of A-type currents present in different smooth muscles by providing a comprehensive report of the literature to date. This approach should also aid in the identification of areas of research requiring further attention.

Atypical Pneumonia: Updates on Legionella, Chlamydophila, and Mycoplasma Pneumonia.

PubMed

Sharma, Lokesh; Losier, Ashley; Tolbert, Thomas; Dela Cruz, Charles S; Marion, Chad R

2017-03-01

Community-acquired pneumonia (CAP) has multiple causes and is associated with illness that requires admission to the hospital and mortality. The causes of atypical CAP include Legionella species, Chlamydophila, and Mycoplasma. Atypical CAP remains a diagnostic challenge and, therefore, likely is undertreated. This article reviews the advancements in the evaluation and treatment of patients and discusses current conflicts and controversies of atypical CAP. Copyright © 2016 Elsevier Inc. All rights reserved.

Redox modulation of A-type K+ currents in pain-sensing dorsal root ganglion neurons.

PubMed

Hsieh, Chi-Pan

2008-06-06

Redox modulation of fast inactivation has been described in certain cloned A-type voltage-gated K(+) (Kv) channels in expressing systems, but the effects remain to be demonstrated in native neurons. In this study, we examined the effects of cysteine-specific redox agents on the A-type K(+) currents in acutely dissociated small diameter dorsal root ganglion (DRG) neurons from rats. The fast inactivation of most A-type currents was markedly removed or slowed by the oxidizing agents 2,2'-dithio-bis(5-nitropyridine) (DTBNP) and chloramine-T. Dithiothreitol, a reducing agent for the disulfide bond, restored the inactivation. These results demonstrated that native A-type K(+) channels, probably Kv1.4, could switch the roles between inactivating and non-inactivating K(+) channels via redox regulation in pain-sensing DRG neurons. The A-type channels may play a role in adjusting pain sensitivity in response to peripheral redox conditions.

Tracing the associations between sex, the atypical and the combined atypical-melancholic depression subtypes: A path analysis.

PubMed

Rodgers, Stephanie; Vandeleur, Caroline L; Ajdacic-Gross, Vladeta; Aleksandrowicz, Aleksandra A; Strippoli, Marie-Pierre F; Castelao, Enrique; Glaus, Jennifer; Lasserre, Aurélie M; Müller, Mario; Rössler, Wulf; Angst, Jules; Preisig, Martin

2016-01-15

Numerous studies have examined determinants leading to preponderance of women in major depressive disorder (MDD), which is particularly accentuated for the atypical depression subtype. It is thus of interest to explore the specific indirect effects influencing the association between sex and established depression subtypes. The data of 1624 subjects with a lifetime diagnosis of MDD derived from the population-based PsyCoLaus data were used. An atypical (n=256), a melancholic (n=422), a combined atypical and melancholic features subtype (n=198), and an unspecified MDD group (n=748) were constructed according to the DSM-IV specifiers. Path models with direct and indirect effects were applied to the data. Partial mediation of the female-related atypical and combined atypical-melancholic depression subtypes was found. Early anxiety disorders and high emotion-orientated coping acted as mediating variables between sex and the atypical depression subtype. In contrast, high Body Mass Index (BMI) served as a suppression variable, also concerning the association between sex and the combined atypical-melancholic subtype. The latter association was additionally mediated by an early age of MDD onset and early/late anxiety disorders. The use of cross-sectional data does not allow causal conclusions. This is the first study that provides evidence for a differentiation of the general mechanisms explaining sex differences of overall MDD by depression subtypes. Determinants affecting the pathways begin early in life. Since some of them are primarily of behavioral nature, the present findings could be a valuable target in mental health care. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetics Home Reference: atypical hemolytic-uremic syndrome

MedlinePlus

... Kidney Diseases: Kidney Failure: Choosing a Treatment That's Right for You Educational Resources (6 links) Disease InfoSearch: Hemolytic uremic syndrome, atypical MalaCards: genetic atypical hemolytic-uremic syndrome Merck Manual Consumer Version: Overview of Anemia Merck Manual Consumer Version: ...

Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association

PubMed Central

Sarkar, Siddharth; Gupta, Nitin

2017-01-01

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics. PMID:28811916

Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association.

PubMed

Sarkar, Siddharth; Gupta, Nitin

2017-08-01

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics.

Typical and atypical metastatic sites of recurrent endometrial carcinoma

PubMed Central

Krajewski, Katherine M.; Jagannathan, Jyothi; Giardino, Angela; Berlin, Suzanne; Ramaiya, Nikhil

2013-01-01

Abstract The purpose of this article is to illustrate the imaging findings of typical and atypical metastatic sites of recurrent endometrial carcinoma. Typical sites include local pelvic recurrence, pelvic and para-aortic nodes, peritoneum, and lungs. Atypical sites include extra-abdominal lymph nodes, liver, adrenals, brain, bones and soft tissue. It is important for radiologists to recognize the typical and atypical sites of metastases in patients with recurrent endometrial carcinoma to facilitate earlier diagnosis and treatment. PMID:23545091

Atypical chemokine receptors in cancer: friends or foes?

PubMed

Massara, Matteo; Bonavita, Ornella; Mantovani, Alberto; Locati, Massimo; Bonecchi, Raffaella

2016-06-01

The chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity. Here, we summarize recent results about the role of these receptors (atypical chemokine receptor 1/Duffy antigen receptor for chemokine, atypical chemokine receptor 2/D6, atypical chemokine receptor 3/CXC-chemokine receptor 7, and atypical chemokine receptor 4/CC-chemokine receptor-like 1) on the tumorigenesis process, indicating that their effects are strictly dependent on the cell type on which they are expressed and on their coexpression with other chemokine receptors. Indeed, atypical chemokine receptors inhibit tumor growth and progression through their activity as negative regulators of chemokine bioavailability, whereas, on the contrary, they can promote tumorigenesis when they regulate the signaling of other chemokine receptors, such as CXC-chemokine receptor 4. Thus, atypical chemokine receptors are key components of the regulatory network of inflammation and immunity in cancer and may have a major effect on anti-inflammatory and immunotherapeutic strategies. © Society for Leukocyte Biology.

Atypical presentations of older adults at the emergency department and associated factors.

PubMed

Limpawattana, Panita; Phungoen, Pariwat; Mitsungnern, Thapanawong; Laosuangkoon, Wannisa; Tansangworn, Natthida

2016-01-01

The objectives were to determine the prevalence of atypical presentations among older adults at the Emergency Department (ED) of a tertiary care hospital and to identify factors associated with these presentations. A retrospective medical record audit was randomly reviewed in 633 patients who were aged ≥ 65 years who attended the ED of Srinagarind Medical School Hospital in 2013. Demographic data were collected and were analyzed using descriptive statistics. Regression analysis was used to analyze the variables associated with the outcomes. The prevalence of an atypical presentation was 28.6% (181/633 cases). The failure to develop fever with a disease known to cause fever was the most common atypical presentation of illness (34.42%). Independent factors associated with atypical presentations were complicated urinary tract infection (UTI) (odds ratios (OR) 4.66, 95% confidence interval (CI) 2.0, 10.84, p=0.00) and a background of dementia (OR 3.48, 95% CI 1.38, 8.77, p=0.008). The prevalence of atypical presentations of older adults at the ED was about a third. The absence of fever with a disease known to cause fever was the most common atypical presentation. Complicated UTI and demented patients were the independent risk factors associated with the atypical presentations. Early awareness of non-specific presentations and applying comprehensive geriatric assessments among older patients at the ED is recommended. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients.

PubMed

Olivo, Gaia; Solstrand Dahlberg, Linda; Wiemerslage, Lyle; Swenne, Ingemar; Zhukovsky, Christina; Salonen-Ros, Helena; Larsson, Elna-Marie; Gaudio, Santino; Brooks, Samantha J; Schiöth, Helgi B

2018-01-01

Patients with atypical anorexia nervosa (AN) have many features overlapping with AN in terms of genetic risk, age of onset, psychopathology and prognosis of outcome, although the weight loss may not be a core factor. While brain structural alterations have been reported in AN, there are currently no data regarding atypical AN patients. We investigated brain structure through a voxel-based morphometry analysis in 22 adolescent females newly-diagnosed with atypical AN, and 38 age- and sex-matched healthy controls (HC). ED-related psychopathology, impulsiveness and obsessive-compulsive traits were assessed with the Eating Disorder Examination Questionnaire (EDE-Q), Barratt Impulsiveness Scale (BIS-11) and Obsessive-compulsive Inventory Revised (OCI-R), respectively. Body mass index (BMI) was also calculated. Patients and HC differed significantly on BMI (p < .002), EDE-Q total score (p < .000) and OCI-R total score (p < .000). No differences could be detected in grey matter (GM) regional volume between groups. The ED-related cognitions in atypical AN patients would suggest that atypical AN and AN could be part of the same spectrum of restrictive-ED. However, contrary to previous reports in AN, our atypical AN patients did not show any GM volume reduction. The different degree of weight loss might play a role in determining such discrepancy. Alternatively, the preservation of GM volume might indeed differentiate atypical AN from AN. © 2017 Wiley Periodicals, Inc.

Atypical depression is more common than melancholic in fibromyalgia: an observational cohort study.

PubMed

Ross, Rebecca L; Jones, Kim D; Ward, Rachel L; Wood, Lisa J; Bennett, Robert M

2010-06-14

It has been postulated that atypical and melancholic depression subtypes exist in depressed fibromyalgia (FM) patients, yet no study has empirically tested this hypothesis. The purpose of this study is to determine whether major depressive disorder (MDD) with atypical features and MDD with melancholic features occurs in a FM sample and to describe their demographic, clinical and diagnostic characteristics. An observational cohort study using a descriptive cross-sectional design recruited a convenience sample of 76 outpatients with FM from an academic rheumatology clinic and a community mental health practice. Diagnoses of FM were confirmed using the 1990 ACR classification guidelines. Diagnoses of MDD and diagnostic subtypes were determined using the DSM-IV-TR criteria. Clinical characteristics were measured using the Fibromyalgia Impact Questionnaire, Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement and other standardized instruments. Odds ratios were computed on subtype-specific diagnostic criteria. Correlations assessed associations between subtype diagnoses and diagnostic criteria. Of the 76 subjects with FM, 11.8% (n = 9) were euthymic, 52.6% (n = 40) met diagnostic criteria for MDD with atypical features and 35.6% (n = 27) for MDD with melancholic features. Groups did not differ on demographic characteristics except for gender (p = 0.01). The non-depressed and atypical groups trended toward having a longer duration of FM symptoms (18.05 yrs. +/- 12.83; 20.36 yrs. +/- 15.07) compared to the melancholic group (14.11 yrs. +/- 8.82; p = 0.09). The two depressed groups experienced greater severity on all clinical features compared to the non-depressed group. The atypical group did not differ clinically from the melancholic group except the latter experienced greater depression severity (p = 0.001). The atypical group demonstrated the highest prevalence and correlations with atypical-specific diagnostic criteria: (e.g., weight gain/ increased appetite: OR = 3.5, p = 0.02), as did the melancholic group for melancholic-specific criteria: (e.g., anhedonia: OR = 20, p < 0.001). Depressed fibromyalgia patients commonly experience both atypical and melancholic depressive features; however, in this study, atypical depression was 1.5 times more common than melancholic depression. This finding may have significant research and clinical implications.

Complement mutations in diacylglycerol kinase-ε-associated atypical hemolytic uremic syndrome.

PubMed

Sánchez Chinchilla, Daniel; Pinto, Sheila; Hoppe, Bernd; Adragna, Marta; Lopez, Laura; Justa Roldan, Maria Luisa; Peña, Antonia; Lopez Trascasa, Margarita; Sánchez-Corral, Pilar; Rodríguez de Córdoba, Santiago

2014-09-05

Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused by complement dysregulation. Consistently, complement inhibition therapies are highly effective in most patients with atypical hemolytic uremic syndrome. Recently, it was shown that a significant percentage of patients with early-onset atypical hemolytic uremic syndrome carry mutations in diacylglycerol kinase-ε, an intracellular protein with no obvious role in complement. These data support an alternative, complement-independent mechanism leading to thrombotic microangiopathy that has implications for treatment of early-onset atypical hemolytic uremic syndrome. To get additional insights into this new form of atypical hemolytic uremic syndrome, the diacylglycerol kinase-ε gene in a cohort with atypical hemolytic uremic syndrome was analyzed. Eighty-three patients with early-onset atypical hemolytic uremic syndrome (<2 years) enrolled in the Spanish atypical hemolytic uremic syndrome registry between 1999 and 2013 were screened for mutations in diacylglycerol kinase-ε. These patients were also fully characterized for mutations in the genes encoding factor H, membrane cofactor protein, factor I, C3, factor B, and thrombomodulin CFHRs copy number variations and rearrangements, and antifactor H antibodies. Four patients carried mutations in diacylglycerol kinase-ε, one p.H536Qfs*16 homozygote and three compound heterozygotes (p.W322*/p.P498R, two patients; p.Q248H/p.G484Gfs*10, one patient). Three patients also carried heterozygous mutations in thrombomodulin or C3. Extensive plasma infusions controlled atypical hemolytic uremic syndrome recurrences and prevented renal failure in the two patients with diacylglycerol kinase-ε and thrombomodulin mutations. A positive response to plasma infusions and complement inhibition treatment was also observed in the patient with concurrent diacylglycerol kinase-ε and C3 mutations. Data suggest that complement dysregulation influences the onset and disease severity in carriers of diacylglycerol kinase-ε mutations and that treatments on the basis of plasma infusions and complement inhibition are potentially useful in patients with combined diacylglycerol kinase-ε and complement mutations. A comprehensive understanding of the genetic component predisposing to atypical hemolytic uremic syndrome is, therefore, critical to guide an effective treatment. Copyright © 2014 by the American Society of Nephrology.

Complement Mutations in Diacylglycerol Kinase-ε–Associated Atypical Hemolytic Uremic Syndrome

PubMed Central

Sánchez Chinchilla, Daniel; Pinto, Sheila; Hoppe, Bernd; Adragna, Marta; Lopez, Laura; Justa Roldan, Maria Luisa; Peña, Antonia; Lopez Trascasa, Margarita; Sánchez-Corral, Pilar; Rodríguez de Córdoba, Santiago

2014-01-01

Background and objectives Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused by complement dysregulation. Consistently, complement inhibition therapies are highly effective in most patients with atypical hemolytic uremic syndrome. Recently, it was shown that a significant percentage of patients with early-onset atypical hemolytic uremic syndrome carry mutations in diacylglycerol kinase-ε, an intracellular protein with no obvious role in complement. These data support an alternative, complement-independent mechanism leading to thrombotic microangiopathy that has implications for treatment of early-onset atypical hemolytic uremic syndrome. To get additional insights into this new form of atypical hemolytic uremic syndrome, the diacylglycerol kinase-ε gene in a cohort with atypical hemolytic uremic syndrome was analyzed. Design, setting, participants, & measurements Eighty-three patients with early-onset atypical hemolytic uremic syndrome (<2 years) enrolled in the Spanish atypical hemolytic uremic syndrome registry between 1999 and 2013 were screened for mutations in diacylglycerol kinase-ε. These patients were also fully characterized for mutations in the genes encoding factor H, membrane cofactor protein, factor I, C3, factor B, and thrombomodulin CFHRs copy number variations and rearrangements, and antifactor H antibodies. Results Four patients carried mutations in diacylglycerol kinase-ε, one p.H536Qfs*16 homozygote and three compound heterozygotes (p.W322*/p.P498R, two patients; p.Q248H/p.G484Gfs*10, one patient). Three patients also carried heterozygous mutations in thrombomodulin or C3. Extensive plasma infusions controlled atypical hemolytic uremic syndrome recurrences and prevented renal failure in the two patients with diacylglycerol kinase-ε and thrombomodulin mutations. A positive response to plasma infusions and complement inhibition treatment was also observed in the patient with concurrent diacylglycerol kinase-ε and C3 mutations. Conclusions Data suggest that complement dysregulation influences the onset and disease severity in carriers of diacylglycerol kinase-ε mutations and that treatments on the basis of plasma infusions and complement inhibition are potentially useful in patients with combined diacylglycerol kinase-ε and complement mutations. A comprehensive understanding of the genetic component predisposing to atypical hemolytic uremic syndrome is, therefore, critical to guide an effective treatment. PMID:25135762

The atypical pneumonias: clinical diagnosis and importance.

PubMed

Cunha, B A

2006-05-01

The most common atypical pneumonias are caused by three zoonotic pathogens, Chlamydia psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii (Q fever), and three nonzoonotic pathogens, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella. These atypical agents, unlike the typical pathogens, often cause extrapulmonary manifestations. Atypical CAPs are systemic infectious diseases with a pulmonary component and may be differentiated clinically from typical CAPs by the pattern of extrapulmonary organ involvement which is characteristic for each atypical CAP. Zoonotic pneumonias may be eliminated from diagnostic consideration with a negative contact history. The commonest clinical problem is to differentiate legionnaire's disease from typical CAP as well as from C. pneumoniae or M. pneumonia infection. Legionella is the most important atypical pathogen in terms of severity. It may be clinically differentiated from typical CAP and other atypical pathogens by the use of a weighted point system of syndromic diagnosis based on the characteristic pattern of extrapulmonary features. Because legionnaire's disease often presents as severe CAP, a presumptive diagnosis of Legionella should prompt specific testing and empirical anti-Legionella therapy such as the Winthrop-University Hospital Infectious Disease Division's weighted point score system. Most atypical pathogens are difficult or dangerous to isolate and a definitive laboratory diagnosis is usually based on indirect, i.e., direct flourescent antibody (DFA), indirect flourescent antibody (IFA). Atypical CAP is virtually always monomicrobial; increased IFA IgG tests indicate past exposure and not concurrent infection. Anti-Legionella antibiotics include macrolides, doxycycline, rifampin, quinolones, and telithromycin. The drugs with the highest level of anti-Legionella activity are quinolones and telithromycin. Therapy is usually continued for 2 weeks if potent anti-Legionella drugs are used. In adults, M. pneumoniae and C. pneumoniae may exacerbate or cause asthma. The importance of the atypical pneumonias is not related to their frequency (approximately 15% of CAPs), but to difficulties in their diagnosis, and their nonresponsiveness to beta-lactam therapy. Because of the potential role of C. pneumoniae in coronary artery disease and multiple sclerosis (MS), and the role of M. pneumoniae and C. pneumoniae in causing or exacerbating asthma, atypical CAPs also have public health importance.

Usefulness of hounsfield unit and density in the assessment and treatment of urinary stones

PubMed Central

Gücük, Adnan; Üyetürk, Uğur

2014-01-01

Computed tomography (CT) is widely used to examine stones in the urinary system. In addition to the size and location of the stone and the overall health of the kidney, CT can also assess the density of the stone in Hounsfield units (HU). The HU, or Hounsfield density, measured by CT, is related to the density of the tissue or stone. A number of studies have assessed the use of HU in urology. HUs have been used to predict the type and opacity of stones during diagnosis, and the efficacy has been assessed using methods including extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), ureterorenoscopic ureterolithotripsy (URSL), and medical expulsive treatment (MET). Previous studies have focused on the success rate of HU for predicting the type of stone and of ESWL treatment. Understanding the composition of the stone plays a key role in determining the most appropriate treatment modality. The most recent reports have suggested that the HU value and its variants facilitate prediction of stone composition. However, the inclusion of data regarding urine, such as pH and presence of crystals, increases the predictive accuracy. HUs, which now form part of the clinical guidelines, allow us to predict the success of ESWL; therefore, they should be taken into account when ESWL is considered as a treatment option. However, there are currently insufficient data available regarding the value of HU for assessing the efficacy of PCNL, URSL, and MET. Studies performed to date suggest that these values would make a significant contribution to the diagnosis and treatment of urinary system stones. However, more data are required to assess this further. PMID:25374823

Escherichia coli O157:H7 infections associated with consumption of locally grown strawberries contaminated by deer.

PubMed

Laidler, Matthew R; Tourdjman, Mathieu; Buser, Genevieve L; Hostetler, Trevor; Repp, Kimberly K; Leman, Richard; Samadpour, Mansour; Keene, William E

2013-10-01

An outbreak of Escherichia coli O157:H7 was identified in Oregon through an increase in Shiga toxin-producing E. coli cases with an indistinguishable, novel pulsed-field gel electrophoresis (PFGE) subtyping pattern. We defined confirmed cases as persons from whom E. coli O157:H7 with the outbreak PFGE pattern was cultured during July-August 2011, and presumptive cases as persons having a household relationship with a case testing positive for E. coli O157:H7 and coincident diarrheal illness. We conducted an investigation that included structured hypothesis-generating interviews, a matched case-control study, and environmental and traceback investigations. We identified 15 cases. Six cases were hospitalized, including 4 with hemolytic uremic syndrome (HUS). Two cases with HUS died. Illness was significantly associated with strawberry consumption from roadside stands or farmers' markets (matched odds ratio, 19.6; 95% confidence interval, 2.9-∞). A single farm was identified as the source of contaminated strawberries. Ten of 111 (9%) initial environmental samples from farm A were positive for E. coli O157:H7. All samples testing positive for E. coli O157:H7 contained deer feces, and 5 tested farm fields had ≥ 1 sample positive with the outbreak PFGE pattern. The investigation identified fresh strawberries as a novel vehicle for E. coli O157:H7 infection, implicated deer feces as the source of contamination, and highlights problems concerning produce contamination by wildlife and regulatory exemptions for locally grown produce. A comprehensive hypothesis-generating questionnaire enabled rapid identification of the implicated product. Good agricultural practices are key barriers to wildlife fecal contamination of produce.

Shiga toxin-producing Escherichia coli: a single-center, 11-year pediatric experience.

PubMed

Schindler, Emily I; Sellenriek, Patricia; Storch, Gregory A; Tarr, Phillip I; Burnham, Carey-Ann D

2014-10-01

The aim of this study was to identify the best practices for the detection of Shiga toxin-producing Escherichia coli (STEC) in children with diarrheal illness treated at a tertiary care center, i.e., sorbitol-MacConkey (SMAC) agar culture, enzyme immunoassay (EIA) for Shiga toxin, or the simultaneous use of both methods. STEC was detected in 100 of 14,997 stool specimens submitted for enteric culture (0.7%), with 65 cases of E. coli O157. Among E. coli O157 isolates, 57 (88%) were identified by both SMAC agar culture and EIA, 6 (9%) by SMAC agar culture alone, and 2 (3%) by EIA alone. Of the 62 individuals with diarrheal hemolytic uremic syndrome (HUS) seen at our institution during the study period, 16 (26%) had STEC isolated from cultures at our institution and 15 (24%) had STEC isolated at other institutions. No STEC was recovered in 31 cases (50%). Of the HUS cases in which STEC was isolated, 28 (90%) were attributable to E. coli O157 and 3 (10%) were attributable to non-O157 STEC. Consistent with previous studies, we have determined that a subset of E. coli O157 infections will not be detected if an agar-based method is excluded from the enteric culture workup; this has both clinical and public health implications. The best practice would be concomitant use of an agar-based method and a Shiga toxin EIA, but a Shiga toxin EIA should not be considered to be an adequate stand-alone test for detection of E. coli O157 in clinical samples. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Prevention and control of enterohaemorrhagic Escherichia coli (EHEC) infections: memorandum from a WHO meeting. WHO Consultation on Prevention and Control of Enterohaemorrhagic Escherichia coli (EHEC) Infections.

PubMed Central

Reilly, A.

1998-01-01

Escherichia coli is a commonly occurring inhabitant of the intestine of humans and other animals, but there are several pathogenic types of E. coli which cause a variety of human diseases. One of these pathogenic types, E. coli O157:H7, belongs to the group of enterohaemorrhagic E. coli (EHEC) which produce potent toxins and cause a particularly severe form of disease, haemorrhagic colitis (HC). About 10% of patients with HC can go on to develop haemolytic uraemic syndrome (HUS), a life-threatening complication of E. coli O157:H7 infection that is characterized by acute renal failure, haemolytic anaemia, and thrombocytopenia. These sequelae are particularly serious in young children and older people. On average, 2-7% of patients with HUS die, but in some outbreaks among the elderly the mortality rate has been as high as 50%. This Memorandum reviews the growing importance of E. coli O157:H7 as a foodborne pathogen and reports on the issues of surveillance, outbreak investigation, and control strategies with respect to EHEC infections that were discussed at the WHO Consultation on Prevention and Control of EHEC Infections, held in Geneva on 28 April to 1 May 1997. Recommended measures for prevention and control include the following: use of potable water in food production; presentation of clean animals at slaughter; improved hygiene throughout the slaughter process; appropriate use of food processing measures; thorough cooking of foods; and the education of food handlers, abattoir workers, and farm workers on the principles and application of food hygiene. PMID:9744244

Intestinal Pathogenic Escherichia coli: Insights for Vaccine Development

PubMed Central

Rojas-Lopez, Maricarmen; Monterio, Ricardo; Pizza, Mariagrazia; Desvaux, Mickaël; Rosini, Roberto

2018-01-01

Diarrheal diseases are one of the major causes of mortality among children under five years old and intestinal pathogenic Escherichia coli (InPEC) plays a role as one of the large causative groups of these infections worldwide. InPECs contribute significantly to the burden of intestinal diseases, which are a critical issue in low- and middle-income countries (Asia, Africa and Latin America). Intestinal pathotypes such as enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) are mainly endemic in developing countries, while ETEC strains are the major cause of diarrhea in travelers to these countries. On the other hand, enterohemorrhagic E. coli (EHEC) are the cause of large outbreaks around the world, mainly affecting developed countries and responsible for not only diarrheal disease but also severe clinical complications like hemorrhagic colitis and hemolytic uremic syndrome (HUS). Overall, the emergence of antibiotic resistant strains, the annual cost increase in the health care system, the high incidence of traveler diarrhea and the increased number of HUS episodes have raised the need for effective preventive treatments. Although the use of antibiotics is still important in treating such infections, non-antibiotic strategies are either a crucial option to limit the increase in antibiotic resistant strains or absolutely necessary for diseases such as those caused by EHEC infections, for which antibiotic therapies are not recommended. Among non-antibiotic therapies, vaccine development is a strategy of choice but, to date, there is no effective licensed vaccine against InPEC infections. For several years, there has been a sustained effort to identify efficacious vaccine candidates able to reduce the burden of diarrheal disease. The aim of this review is to summarize recent milestones and insights in vaccine development against InPECs. PMID:29615989

Characterization of urinary tract infection-associated Shiga toxin-producing Escherichia coli.

PubMed

Toval, Francisco; Schiller, Roswitha; Meisen, Iris; Putze, Johannes; Kouzel, Ivan U; Zhang, Wenlan; Karch, Helge; Bielaszewska, Martina; Mormann, Michael; Müthing, Johannes; Dobrindt, Ulrich

2014-11-01

Enterohemorrhagic Escherichia coli (EHEC), a subgroup of Shiga toxin (Stx)-producing E. coli (STEC), is a leading cause of diarrhea and hemolytic-uremic syndrome (HUS) in humans. However, urinary tract infections (UTIs) caused by this microorganism but not associated with diarrhea have occasionally been reported. We geno- and phenotypically characterized three EHEC isolates obtained from the urine of hospitalized patients suffering from UTIs. These isolates carried typical EHEC virulence markers and belonged to HUS-associated E. coli (HUSEC) clones, but they lacked virulence markers typical of uropathogenic E. coli. One isolate exhibited a localized adherence (LA)-like pattern on T24 urinary bladder epithelial cells. Since the glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer) are well-known receptors for Stx but also for P fimbriae, a major virulence factor of extraintestinal pathogenic E. coli (ExPEC), the expression of Gb3Cer and Gb4Cer by T24 cells and in murine urinary bladder tissue was examined by thin-layer chromatography and mass spectrometry. We provide data indicating that Stxs released by the EHEC isolates bind to Gb3Cer and Gb4Cer isolated from T24 cells, which were susceptible to Stx. All three EHEC isolates expressed stx genes upon growth in urine. Two strains were able to cause UTI in a murine infection model and could not be outcompeted in urine in vitro by typical uropathogenic E. coli isolates. Our results indicate that despite the lack of ExPEC virulence markers, EHEC variants may exhibit in certain suitable hosts, e.g., in hospital patients, a uropathogenic potential. The contribution of EHEC virulence factors to uropathogenesis remains to be further investigated. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Heterogeneity in Induction Level, Infection Ability, and Morphology of Shiga Toxin-Encoding Phages (Stx Phages) from Dairy and Human Shiga Toxin-Producing Escherichia coli O26:H11 Isolates

PubMed Central

Bonanno, Ludivine; Petit, Marie-Agnès; Loukiadis, Estelle; Michel, Valérie

2016-01-01

Shiga toxin (Stx)-producing Escherichia coli (STEC) bacteria are foodborne pathogens responsible for diarrhea and hemolytic-uremic syndrome (HUS). Shiga toxin, the main STEC virulence factor, is encoded by the stx gene located in the genome of a bacteriophage inserted into the bacterial chromosome. The O26:H11 serotype is considered to be the second-most-significant HUS-causing serotype worldwide after O157:H7. STEC O26:H11 bacteria and their stx-negative counterparts have been detected in dairy products. They may convert from the one form to the other by loss or acquisition of Stx phages, potentially confounding food microbiological diagnostic methods based on stx gene detection. Here we investigated the diversity and mobility of Stx phages from human and dairy STEC O26:H11 strains. Evaluation of their rate of in vitro induction, occurring either spontaneously or in the presence of mitomycin C, showed that the Stx2 phages were more inducible overall than Stx1 phages. However, no correlation was found between the Stx phage levels produced and the origin of the strains tested or the phage insertion sites. Morphological analysis by electron microscopy showed that Stx phages from STEC O26:H11 displayed various shapes that were unrelated to Stx1 or Stx2 types. Finally, the levels of sensitivity of stx-negative E. coli O26:H11 to six Stx phages differed among the 17 strains tested and our attempts to convert them into STEC were unsuccessful, indicating that their lysogenization was a rare event. PMID:26826235

Health care resource utilization and direct medical costs for patients with schizophrenia initiating treatment with atypical versus typical antipsychotics in Tianjin, China.

PubMed

He, Xiaoning; Wu, Jing; Jiang, Yawen; Liu, Li; Ye, Wenyu; Xue, Haibo; Montgomery, William

2015-04-09

It is uncertain whether the extra acquisition costs of atypical antipsychotics over typical antipsychotics are offset by their other reduced resource use especially in hospital services in China. This study compared the psychiatric-related health care resource utilization and direct medical costs for patients with schizophrenia initiating atypical or typical antipsychotics in Tianjin, China. Data were obtained from the Tianjin Urban Employee Basic Medical Insurance database (2008-2010). Adult patients with schizophrenia with ≥1 prescription for antipsychotics after ≥90-day washout and 12-month continuous enrollment after first prescription was included. Psychiatric-related resource utilization and direct medical costs of the atypical and typical cohorts were estimated during the 12-month follow-up period. Logistic regressions, ordinary least square (OLS), and generalized linear models (GLM) were employed to estimate differences of resource utilization and costs between the two cohorts. One-to-one propensity score matching was conducted as a sensitivity analysis. 1131 patients initiating either atypical (N = 648) or typical antipsychotics (N = 483) were identified. Compared with the typical cohort, the atypical cohort had a lower likelihood of hospitalization (45.8% vs. 56.7%, P < 0.001; adjusted OR: 0.58, P < 0.001) over the follow-up period. Medication costs for the atypical cohort were higher than the typical cohort ($438 vs. $187, P < 0.001); however, their non-medication medical costs were significantly lower ($1223 vs. $1704, P < 0.001). The total direct medical costs were similar between the atypical and typical cohorts before ($1661 vs. $1892, P = 0.100) and after matching ($1711 vs. 1868, P = 0.341), consistent with the results from OLS and GLM models for matched cohorts. The atypical cohort had similar total direct medical costs compared to the typical cohort. Higher medication costs associated with atypical antipsychotics were offset by a reduction in non-medication medical costs, driven by fewer hospitalizations.

Atypical fibroxanthoma and pleomorphic dermal sarcoma harbor frequent NOTCH1/2 and FAT1 mutations and similar DNA copy number alteration profiles.

PubMed

Griewank, Klaus G; Wiesner, Thomas; Murali, Rajmohan; Pischler, Carina; Müller, Hansgeorg; Koelsche, Christian; Möller, Inga; Franklin, Cindy; Cosgarea, Ioana; Sucker, Antje; Schadendorf, Dirk; Schaller, Jörg; Horn, Susanne; Brenn, Thomas; Mentzel, Thomas

2018-03-01

Atypical fibroxanthomas and pleomorphic dermal sarcomas are tumors arising in sun-damaged skin of elderly patients. They have differing prognoses and are currently distinguished using histological criteria, such as invasion of deeper tissue structures, necrosis and lymphovascular or perineural invasion. To investigate the as-yet poorly understood genetics of these tumors, 41 atypical fibroxanthomas and 40 pleomorphic dermal sarcomas were subjected to targeted next-generation sequencing approaches as well as DNA copy number analysis by comparative genomic hybridization. In an analysis of the entire coding region of 341 oncogenes and tumor suppressor genes in 13 atypical fibroxanthomas using an established hybridization-based next-generation sequencing approach, we found that these tumors harbor a large number of mutations. Gene alterations were identified in more than half of the analyzed samples in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter. The presence of these alterations was verified in 26 atypical fibroxanthoma and 35 pleomorphic dermal sarcoma samples by targeted amplicon-based next-generation sequencing. Similar mutation profiles in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter were identified in both atypical fibroxanthoma and pleomorphic dermal sarcoma. Activating RAS mutations (G12 and G13) identified in 3 pleomorphic dermal sarcoma were not found in atypical fibroxanthoma. Comprehensive DNA copy number analysis demonstrated a wide array of different copy number gains and losses, with similar profiles in atypical fibroxanthoma and pleomorphic dermal sarcoma. In summary, atypical fibroxanthoma and pleomorphic dermal sarcoma are highly mutated tumors with recurrent mutations in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter, and a range of DNA copy number alterations. These findings suggest that atypical fibroxanthomas and pleomorphic dermal sarcomas are genetically related, potentially representing two ends of a common tumor spectrum and distinguishing these entities is at present still best performed using histological criteria.

Atypical sources of childhood lead poisoning in the United States: a systematic review from 1966-2006.

PubMed

Gorospe, Emmanuel C; Gerstenberger, Shawn L

2008-09-01

Lead poisoning from atypical sources, which excludes the well-established lead-based paint ingestions and exposure in occupational settings, are increasingly reported in medical literature. Our objective is to increase awareness on atypical sources of lead exposure and to formulate recommendations for their detection based on actual reported cases. We systematically retrieved and reviewed reports on pediatric lead poisoning in the U.S. from atypical sources by searching Medline, Embase, CINAHL, Academic Search Premier, AltHealth, websites of state lead poisoning prevention programs, and the U.S. Consumer Product Safety Commission database for reports published from January 1966 to December 2006. We retrieved 28 published reports that met our inclusion criteria. Of these reports, 20 are case reports and 8 case series, documenting a total of 82 incidents of lead poisoning in children from atypical sources. There are varied sources of atypical lead exposure among U.S. children. The sources were grouped in the following categories based on their utility: fashion accessories, folk remedies, imported condiments & candies, pellets & bullets, and lastly, recreational & domestic items. Based on these findings, we have formulated a questionnaire that may assist in the identification of atypical lead sources in the home.

Atypical use of PICC in infants and small children: a unicentric experience.

PubMed

Bernasconi, Filippo; Zanaboni, Clelia; Dato, Andrea; Dolcino, Andrea; Bevilacqua, Michela; Montagnini, Luigi; Disma, Nicola

2017-11-17

The peripherally inserted central catheters (PICCs) are vascular access devices (VAD) that are increasingly being used in the pediatric population. If a small vein caliber prevents positioning the catheter in the arm, the following step is to position the same catheter in the supraclavicular area, which can be defined as an off-label use or "atypical" approach, first described by Pittiruti. We retrospectively reviewed PICC positioning with puncture-site in the supra-clavicular area ("atypical" PICC insertion) and then tunneled on the chest. Nineteen atypical PICCs were positioned in 18 patients. The median age of patients at the day of implant was 14 months (IQR 3-27 months), and weight 7.5 kg (IQR 4-12 kg). Within this population, 74% of cases scheduled for a typical PICC insertion presented vein caliber too small for this procedure. For this reason, the typical PICC insertion was changed in favor of an atypical PICC procedure. Atypical PICCs were successfully used in 100% of cases without immediate complications. Atypical PICC positioning is a safe and useful alternative to the conventional technique when there is need for a central vascular access device (CVAD) for mid- or long-term therapy.

Modulation of A-type potassium channels by a family of calcium sensors.

PubMed

An, W F; Bowlby, M R; Betty, M; Cao, J; Ling, H P; Mendoza, G; Hinson, J W; Mattsson, K I; Strassle, B W; Trimmer, J S; Rhodes, K J

2000-02-03

In the brain and heart, rapidly inactivating (A-type) voltage-gated potassium (Kv) currents operate at subthreshold membrane potentials to control the excitability of neurons and cardiac myocytes. Although pore-forming alpha-subunits of the Kv4, or Shal-related, channel family form A-type currents in heterologous cells, these differ significantly from native A-type currents. Here we describe three Kv channel-interacting proteins (KChIPs) that bind to the cytoplasmic amino termini of Kv4 alpha-subunits. We find that expression of KChIP and Kv4 together reconstitutes several features of native A-type currents by modulating the density, inactivation kinetics and rate of recovery from inactivation of Kv4 channels in heterologous cells. All three KChIPs co-localize and co-immunoprecipitate with brain Kv4 alpha-subunits, and are thus integral components of native Kv4 channel complexes. The KChIPs have four EF-hand-like domains and bind calcium ions. As the activity and density of neuronal A-type currents tightly control responses to excitatory synaptic inputs, these KChIPs may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium.

Traditional and Atypical Presentations of Anxiety in Youth with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Kerns, Connor Morrow; Kendall, Philip C.; Berry, Leandra; Souders, Margaret C.; Franklin, Martin E.; Schultz, Robert T.; Miller, Judith; Herrington, John

2014-01-01

We assessed anxiety consistent (i.e., "traditional") and inconsistent (i.e., "atypical") with diagnostic and statistical manual (DSM) definitions in autism spectrum disorder (ASD). Differential relationships between traditional anxiety, atypical anxiety, child characteristics, anxiety predictors and ASD-symptomology were…

Processable high temperature resistant addition type polyimide laminating resins

NASA Technical Reports Server (NTRS)

Serafini, T. T.; Delvigs, P.

1973-01-01

Basic studies that were performed using model compounds to elucidate the polymerization mechanism of the so-called addition-type (A-type) polyimides are reviewed. The fabrication and properties of polyimide/graphite fiber composites using A-type polyimide prepolymers as the matrix are also reviewed. An alternate method for preparing processable A-type polyimides by means of in situ polymerization of monomer reactants (PMR) on the fiber reinforcement is described. The elevated temperature properties of A-type PMR/graphite fiber composites are also presented.

The impact of subdividing the "atypical" category for urinary cytology on patient management.

PubMed

Glass, Ryan; Cocker, Rubina; Rosen, Lisa; Coutsouvelis, Constantinos; Chau, Karen; Slim, Farah; Brenkert, Ryan; Sheikh-Fayyaz, Silvat; Farmer, Peter; Das, Kasturi

2016-06-01

The purpose of the study is to determine the impact of subdividing the "atypical" cytology interpretation into two groups: Atypical urothelial cells of uncertain significance (AUC-US) and Atypical urothelial cells suspicious for high-grade urothelial carcinoma (AUC-H/SHGUC), on management of patients with no prior history of UC. This is a retrospective study of "atypical" urine cytology with subsequent tissue examination occurring within six months. Cytology reports with "atypical" interpretation were reclassified into AUS-UC and AUC-H based on morphologic features identified by the Johns Hopkins system and the Paris system for urine cytology. Follow-up and categorical outcomes were compared between the reclassified AUC-US and AUC-H groups. There was no significant difference (P < 0.4539) in the rate of cytology follow-up, the follow-up cytology result (P < 0.1845), or time between follow-up cytologies (P < 0.0869) between the reclassified atypical group of AUC-H and AUC-US. There was a significant association (P < 0.0001) of rate of malignancy with the reclassified AUC-H (87.18%) compared to the AUC-US (58.68%) groups. There was no difference in follow-up between the AUC-H and AUC-US, however there was a difference in the rates of malignancy in the two groups. The AUC-H group is similar to the SHGUC group of the Paris system and can be considered as such, whereas the AUC-US group should continue to be considered atypical. We conclude that reclassification of the "atypical" category into AUC-US and AUC-H/SHGUC can reduce the rate of atypia and help in focused follow-up and targeted management. Diagn. Cytopathol. 2016;44:477-482. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Can Atypical Antipsychotic Augmentation Reduce Subsequent Treatment Failure More Effectively Among Depressed Patients with a Higher Degree of Treatment Resistance? A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Wang, Hee Ryung; Woo, Young Sup; Ahn, Hyeong Sik; Ahn, Il Min; Kim, Hyun Jung; Bahk, Won-Myong

2015-01-01

Background: Atypical antipsychotic augmentation was demonstrated to be efficacious in treatment-resistant depression (TRD) in previous meta-analyses. We investigate whether there are differences in the effect size of atypical antipsychotic augmentation in major depressive disorder according to the degree of treatment resistance. Methods: A comprehensive search of four databases identified 11 randomized controlled trials. The 11 trials, which included 3 341 participants, were pooled using a random-effects meta-analysis. Results: Atypical antipsychotic augmentation of antidepressant therapy showed superior efficacy compared to antidepressant monotherapy in TRD in terms of both response and remission rates (response, risk ratio [RR] = 1.38, 95% confidence interval [CI] = 1.25 to 1.53; remission, RR = 1.62, 95% CI = 1.42 to 1.85). In addition, regarding response rates in the TRD trials, atypical antipsychotic augmentation exhibited significantly different effect sizes according to the degree of treatment resistance (TRD 1: RR = 1.24; TRD 2: RR = 1.37; TRD 2–4: RR = 1.58). In non-TRD trials, atypical antipsychotic augmentation failed to show superior efficacy over antidepressant monotherapy in terms of remission rates (RR = 0.89; 95% CI = 0.69 to 1.14). Atypical antipsychotic augmentation of antidepressant therapy exhibits greater effect size in patients with a higher degree of treatment resistance. Conclusions: This finding strengthens the rationale for considering atypical antipsychotic augmentation among depressed patients with multiple previous treatment failures in clinical practice. The efficacy of atypical antipsychotic augmentation for non-TRD seems to be different from that for TRD and, thus, further studies of non-TRD populations are needed. PMID:25770098

The Use of Electroconvulsive Therapy in Atypical Psychotic Presentations

PubMed Central

Vasu, Devi

2007-01-01

Convulsive therapy and its progeny, electroconvulsive therapy (ECT), were originally used for the treatment of catatonic schizophrenia, and there is little doubt that ECT remains an effective intervention for the treatment of schizophrenia. However, current practice tends to favor the use of ECT in severe or treatment refractory affective disorders, and its use in schizophrenia and other nonaffective (atypical) psychotic disorders has become controversial. Case reports have suggested a role for ECT in two specific atypical psychotic disorders: Cotard's syndrome and cycloid psychosis. In this article, we review the atypical psychotic disorders and report a series of five case examples that signify the role of ECT in atypical psychotic presentations, particularly when the symptoms resemble those found in Cotard's syndrome and cycloid psychosis. PMID:20428309

The use of electroconvulsive therapy in atypical psychotic presentations: a case review.

PubMed

Montgomery, John H; Vasu, Devi

2007-10-01

Convulsive therapy and its progeny, electroconvulsive therapy (ECT), were originally used for the treatment of catatonic schizophrenia, and there is little doubt that ECT remains an effective intervention for the treatment of schizophrenia. However, current practice tends to favor the use of ECT in severe or treatment refractory affective disorders, and its use in schizophrenia and other nonaffective (atypical) psychotic disorders has become controversial.CASE REPORTS HAVE SUGGESTED A ROLE FOR ECT IN TWO SPECIFIC ATYPICAL PSYCHOTIC DISORDERS: Cotard's syndrome and cycloid psychosis. In this article, we review the atypical psychotic disorders and report a series of five case examples that signify the role of ECT in atypical psychotic presentations, particularly when the symptoms resemble those found in Cotard's syndrome and cycloid psychosis.

Atypical fibrosarcomas derived from cutaneous ganglion cell-like cells in 2 domestic Djungarian hamsters (Phodopus sungorus).

PubMed

Kondo, Hirotaka; Onuma, Mamoru; Shibuya, Hisashi; Sato, Tsuneo; Abbott, Jeffrey R

2011-07-01

Androgen-dependent atypical fibromas are benign tumors derived from ganglion-cell-like cells that are particular to Djungarian hamsters (Phodopus sungorus). Masses excised from 2 hamsters were composed of pleomorphic ganglion cell-like cells supported by small to moderate amounts of collagenous matrix. Intracytoplasmic fibrils were present in silver-stained sections, and immunohistochemistry showed that the cells expressed vimentin, androgen receptor, and, in one case, estrogen receptor α. In contrast to previously reported atypical fibromas, these tumors had features of anaplasia and were locally invasive. We diagnosed the tumors as atypical fibrosarcomas and consider them an unusual malignant counterpart of atypical fibroma. Copyright 2011 by the American Association for Laboratory Animal Science

Perianal atypical leiomyoma: A case report.

PubMed

Sun, Pingliang; Ou, Hailing; Huang, Shen; Wei, Longxiang; Zhang, Sen; Liu, Jiali; Geng, Shuguang; Yang, Kun

2017-12-01

Reports on perianal atypical leiomyoma, a perianal tumor, are rare. We confirmed a perianal atypical leiomyoma by its clinical presentation, magnetic resonance imaging findings, and immunohistochemistry. A 28-year-old female with a perianal mass found more than 4 years ago. The 5cm_4cm_4cm sized mass was located on the left side of the anus and vagina; The magnetic resonance imaging (MRI) scan revealed: A 4.1cm × 5.2cm × 4.9cm sized round mass was observed on the left side of the circumference. Perianal atypical leiomyoma. anal peripheral mass resection was performed under lumbar anesthesia. The postoperative course was uneventful, healing, the patient was discharged. Perianal atypical leiomyomas are benign tumors, but with the clinically atypical leiomyoma, it is sometimes difficult to distinguish between potential malignant smooth muscle tumors,and there may be malignant changes. Surgery should ensure complete resection, and to avoid postoperative recurrence, there should be a regular follow-up.

[Atypical cerebellar neurocytoma resembling a hemangioblastoma. A case report].

PubMed

Lista Martínez, Olalla; Rivas López, Luis Alfredo; Pombo Otero, Jorge Francisco; Amaro Cendón, Santiago; Bravo García, Christian; Villa Fernández, Juan Manuel

2014-01-01

Through August 2013, 105 cases of intracranial extraventricular neurocytoma (EVN) had been described; 6% were located in cerebellum and 22% were atypical EVN. A rare morphologic form of neurocytoma, atypical EVN has had only 24 cases reported to date. Its prognosis is poorer than the typical central neurocytoma. This case report describes an atypical cerebellar EVN, a form that has not been reported yet, hence the interest of this article. We emphasise its cystic nature and mural nodule, in an infrequent presentation. EVN are low-incidence tumours that we need to take into consideration when making the differential diagnosis of cystic cerebellar lesions with mural nodule. Given that the prognosis of atypical EVNs depends on the atypical nature and on the grade of resection, medical follow up has to be more constant, due to the greater degree of recurrence. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Detection and partial discrimination of atypical and classical bovine spongiform encephalopathies in cattle and primates using real-time quaking-induced conversion assay.

PubMed

Levavasseur, Etienne; Biacabe, Anne-Gaëlle; Comoy, Emmanuel; Culeux, Audrey; Grznarova, Katarina; Privat, Nicolas; Simoneau, Steve; Flan, Benoit; Sazdovitch, Véronique; Seilhean, Danielle; Baron, Thierry; Haïk, Stéphane

2017-01-01

The transmission of classical bovine spongiform encephalopathy (C-BSE) through contaminated meat product consumption is responsible for variant Creutzfeldt-Jakob disease (vCJD) in humans. More recent and atypical forms of BSE (L-BSE and H-BSE) have been identified in cattle since the C-BSE epidemic. Their low incidence and advanced age of onset are compatible with a sporadic origin, as are most cases of Creutzfeldt-Jakob disease (CJD) in humans. Transmissions studies in primates and transgenic mice expressing a human prion protein (PrP) indicated that atypical forms of BSE may be associated with a higher zoonotic potential than classical BSE, and require particular attention for public health. Recently, methods designed to amplify misfolded forms of PrP have emerged as promising tools to detect prion strains and to study their diversity. Here, we validated real-time quaking-induced conversion assay for the discrimination of atypical and classical BSE strains using a large series of bovine samples encompassing all the atypical BSE cases detected by the French Centre of Reference during 10 years of exhaustive active surveillance. We obtained a 100% sensitivity and specificity for atypical BSE detection. In addition, the assay was able to discriminate atypical and classical BSE in non-human primates, and also sporadic CJD and vCJD in humans. The RT-QuIC assay appears as a practical means for a reliable detection of atypical BSE strains in a homologous or heterologous PrP context.

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

PubMed Central

Andréoletti, Olivier; Orge, Leonor; Benestad, Sylvie L.; Beringue, Vincent; Litaise, Claire; Simon, Stéphanie; Le Dur, Annick; Laude, Hubert; Simmons, Hugh; Lugan, Séverine; Corbière, Fabien; Costes, Pierrette; Morel, Nathalie; Schelcher, François; Lacroux, Caroline

2011-01-01

Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed. PMID:21347349

An ophthalmologist survey-based study of the atypical presentations and current treatment practices of ocular toxoplasmosis in India.

PubMed

Basu, Soumyava; Biswas, Jyotirmay; Pleyer, Uwe; Pathangay, Avinash; Manohar Babu, B

2011-10-01

The last two decades have seen a paradigm shift in the understanding of ocular toxoplasmosis. Post-natally acquired infection with its atypical presentations, has emerged as a common form of the disease. We conducted a questionnaire-based survey to investigate the characteristics of atypical presentations and current treatment practices of ocular toxoplasmosis, in India. A written questionnaire was distributed to ophthalmologists at two major uveitis meetings, held in Hyderabad, India in January, 2009. It evaluated characteristics of atypical presentations of ocular toxoplasmosis and specific treatment-related issues in India. Of 37 respondents who completed the questionnaire, 28 (75.6%) found atypical presentations in less than one-fourth of ocular toxoplasmosis patients. Atypical presentations were mostly seen as primary retinitis lesion, and in healthy immuno-competent individuals. Most ophthalmologists (n = 28, 75.6%) thought viral retinitis to be the most common differential diagnosis for atypical ocular toxoplasmosis and relied on serological tests (n = 19, 51.3%) for the diagnosis. Twenty-three (62.1%) respondents treated all patients with active lesions. A diverse range of treatment regimens were used, trimethoprim-sulphamethoxazole combination being most common (n = 12, 32.4%). Corticosteroids were included in all regimens. Atypical presentations of ocular toxoplasmosis were identified by all ophthalmologists, participating in the survey, though not commonly by most. Treatment practices were diverse, reflecting the lack of consensus on this issue.

Atypical Headbanging Presentation of Idiopathic Sleep Related Rhythmic Movement Disorder: Three Cases with Video-Polysomnographic Documentation

PubMed Central

Yeh, Shih-Bin; Schenck, Carlos H.

2012-01-01

Study Objectives: To describe three cases of sleep related, idiopathic rhythmic movement disorder (RMD) with atypical headbanging, consisting of head punching and head slapping. Methods: Three consecutive patients (2 males [11 and 13 years old) and one female [22 years old]) presented with atypical headbanging of 6 years, 7 years, and 17 years duration. In 2 cases, typical rhythmic headbanging (with use of the head) shifted after 3-4 years to atypical headbanging, with frontal head punching that was quasi-rhythmic. In one case, atypical headbanging (head-slapping) was the initial and only RMD. There was no injury from the headbanging. Prenatal, perinatal, developmental, behavioral-psychological, medical-neurological, and family histories were negative. Clinical evaluations and nocturnal video-polysomnography with seizure montage were performed on all patients. Results: Atypical headbanging was documented in all 3 cases; episodes always emerged late in the sleep cycle: from N2 sleep in 11 episodes, from REM sleep in 4 episodes, and from N1 sleep in 1 episode. Epileptiform activity was not detected. Clonazepam therapy was substantially effective in 1 case but not effective in 2 cases. Conclusions: These 3 cases of idiopathic atypical headbanging expand the literature on this RMD variant, as to our knowledge only one previously documented case has been reported. Citation: Yeh SB; Schenck CH. Atypical headbanging presentation of idiopathic sleep related rhythmic movement disorder: three cases with video-polysomnographic documentation. J Clin Sleep Med 2012;8(4):403-411. PMID:22893771

Typical and Atypical Dementia Family Caregivers: Systematic and Objective Comparisons

ERIC Educational Resources Information Center

Nichols, Linda O.; Martindale-Adams, Jennifer; Burns, Robert; Graney, Marshall J.; Zuber, Jeffrey

2011-01-01

This systematic, objective comparison of typical (spouse, children) and atypical (in-law, sibling, nephew/niece, grandchild) dementia family caregivers examined demographic, caregiving and clinical variables. Analysis was of 1,476 caregivers, of whom 125 were atypical, from the Resources for Enhancing Alzheimer's Caregivers Health (REACH I and II)…

Cognitive Function and Depression in Symptom Resolution in Schizophrenia Patients Treated with an Atypical Antipsychotic

ERIC Educational Resources Information Center

Stip, Emmanuel; Mancini-Marie, Adham

2004-01-01

Objective: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. Design: A prospective open trial with an atypical antipsychotic (olanzapine). Patients: One hundred and thirty-four patients meeting diagnostic criteria for…

Why Does Joint Attention Look Atypical in Autism?

PubMed Central

Gernsbacher, Morton Ann; Stevenson, Jennifer L.; Khandakar, Suraiya; Goldsmith, H. Hill

2014-01-01

This essay answers the question of why autistic children are less likely to initiate joint attention (e.g., use their index finger to point to indicate interest in something) and why they are less likely to respond to bids for their joint attention (e.g., turn their heads to look at something to which another person points). It reviews empirical evidence that autistic toddlers, children, adolescents, and adults can attend covertly, even to social stimuli, such as the direction in which another person’s eyes are gazing. It also reviews empirical evidence that autistics of various ages understand the intentionality of other persons’ actions. The essay suggests that autistics’ atypical resistance to distraction, atypical skill at parallel perception, and atypical execution of volitional actions underlie their atypical manifestations of joint attention. PMID:25520747

Helicobacter infections with rare bacteria or minimal gastritis: Expecting the unexpected.

PubMed

Glickman, Jonathan N; Noffsinger, Amy; Nevin, Daniel T; Ray, Mukunda; Lash, Richard H; Genta, Robert M

2015-07-01

The routine use of special stains for detection of Helicobacter remains controversial. To determine the frequency of histologically atypical Helicobacter infection. All gastric biopsies received at a large pathology reference laboratory over a 6-month period were stained for Helicobacter, and the histologic and clinicopathologic parameters evaluated. Amongst 7663 Helicobacter-positive biopsies, 823 (10.7%) did not show typical chronic active gastritis with numerous Helicobacter organisms, and were therefore considered histologically atypical. Rare Helicobacter pylori organisms accounted for 58.0% of all atypical infections; the next most common atypical Helicobacter infection was that with minimal or no gastric inflammation (23.3% of atypical infections). Patients in these groups did not differ demographically from those with other forms of atypical or typical Helicobacter infection, although a small subgroup (6%) was more likely to have had a previously treated infection. In many of these atypical infections, Helicobacter would not have been suspected based on the histologic findings alone, and would have been missed without routine special stains. Performing a sensitive stain could prevent additional testing and allow prompt treatment of the affected patients, thus substantially reducing the risk for peptic ulcer and gastric cancer and preventing the transmission of the infection to family members. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

CD200 is a useful diagnostic marker for identifying atypical chronic lymphocytic leukemia by flow cytometry.

PubMed

Ting, Y S; Smith, S A B C; Brown, D A; Dodds, A J; Fay, K C; Ma, D D F; Milliken, S; Moore, J J; Sewell, W A

2018-05-27

Immunophenotyping by flow cytometry is routinely employed in distinguishing between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Inclusion of CD200 has been reported to contribute to more reliable differentiation between CLL and MCL. We investigated the value of CD200 in assessment of atypical CLL cases. CD200 expression on mature B cell neoplasms was studied by eight-color flow cytometry in combination with a conventional panel of flow cytometry markers. The study included 70 control samples, 63 samples with CLL or atypical CLL phenotype, 6 MCL samples, and 40 samples of other mature B cell neoplasms. All CLL samples were positive for CD200, whereas MCL samples were dim or negative for CD200. Of the CLL samples, 7 were atypical by conventional flow cytometry, with Matutes scores ≤3. These cases were tested for evidence of a t(11;14) translocation, characteristic of MCL, and all were negative, consistent with their classification as atypical CLL. All these atypical CLL samples were strongly positive for CD200. CD200 proved to be a useful marker for differentiation between CLL and MCL by flow cytometry. In particular, CD200 was useful in distinguishing CLL samples with atypical immunophenotypes from MCL. © 2018 John Wiley & Sons Ltd.

Atypical headbanging presentation of idiopathic sleep related rhythmic movement disorder: three cases with video-polysomnographic documentation.

PubMed

Yeh, Shih-Bin; Schenck, Carlos H

2012-08-15

To describe three cases of sleep related, idiopathic rhythmic movement disorder (RMD) with atypical headbanging, consisting of head punching and head slapping. Three consecutive patients (2 males [11 and 13 years old) and one female [22 years old]) presented with atypical headbanging of 6 years, 7 years, and 17 years duration. In 2 cases, typical rhythmic headbanging (with use of the head) shifted after 3-4 years to atypical headbanging, with frontal head punching that was quasi-rhythmic. In one case, atypical headbanging (head-slapping) was the initial and only RMD. There was no injury from the headbanging. Prenatal, perinatal, developmental, behavioral-psychological, medical-neurological, and family histories were negative. Clinical evaluations and nocturnal video-polysomnography with seizure montage were performed on all patients. Atypical headbanging was documented in all 3 cases; episodes always emerged late in the sleep cycle: from N2 sleep in 11 episodes, from REM sleep in 4 episodes, and from N1 sleep in 1 episode. Epileptiform activity was not detected. Clonazepam therapy was substantially effective in 1 case but not effective in 2 cases. These 3 cases of idiopathic atypical headbanging expand the literature on this RMD variant, as to our knowledge only one previously documented case has been reported.

The relationship between atypical depression and insülin resistance in patients with polycystic ovary syndrome and major depression.

PubMed

Özdemir, Osman; Kurdoglu, Zehra; Yıldız, Saliha; Özdemir, Pınar Güzel; Yilmaz, Ekrem

2017-12-01

In this study, we aimed to examine the relationship between atypical depression and insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS) and major depression. A total of 176 subjects (69 patients with PCOS, 58 patients with depression, and 49 healthy controls) were included in the study. The Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), the Beck Hopelessness Scale (BHS), and the Scale for Suicide Ideation (SSI) were administered. Data concerning their height, weight, fasting a.m. serum levels of insulin, glucose level, and total testosterone level were collected from all participants. The body mass index (BMI) and the Homeostasis Model Assessment Insulin Resistance index (HOMA-IR) were both calculated. 34 (49.3%) of the PCOS patients met the criteria for depression. 26 (76.5%) of them had atypical depression, 8 (23.5%) had non-atypical depression. 27 (46.6%) of the 58 depressed patients had atypical depression. Insulin resistance was higher in the PCOS patients than in the control subjects and the depression patients. There was no association between atypical depression and IR in patients with PCOS and depression. We concluded that there is no relationship between IR and atypical depression. Copyright © 2017. Published by Elsevier B.V.

Clinical characterisation of pneumonia caused by atypical pathogens combining classic and novel predictors.

PubMed

Masiá, M; Gutiérrez, F; Padilla, S; Soldán, B; Mirete, C; Shum, C; Hernández, I; Royo, G; Martin-Hidalgo, A

2007-02-01

The aim of this study was to characterise community-acquired pneumonia (CAP) caused by atypical pathogens by combining distinctive clinical and epidemiological features and novel biological markers. A population-based prospective study of consecutive patients with CAP included investigation of biomarkers of bacterial infection, e.g., procalcitonin, C-reactive protein and lipopolysaccharide-binding protein (LBP) levels. Clinical, radiological and laboratory data for patients with CAP caused by atypical pathogens were compared by univariate and multivariate analysis with data for patients with typical pathogens and patients from whom no organisms were identified. Two predictive scoring models were developed with the most discriminatory variables from multivariate analysis. Of 493 patients, 94 had CAP caused by atypical pathogens. According to multivariate analysis, patients with atypical pneumonia were more likely to have normal white blood cell counts, have repetitive air-conditioning exposure, be aged <65 years, have elevated aspartate aminotransferase levels, have been exposed to birds, and have lower serum levels of LBP. Two different scoring systems were developed that predicted atypical pathogens with sensitivities of 35.2% and 48.8%, and specificities of 93% and 91%, respectively. The combination of selected patient characteristics and laboratory data identified up to half of the cases of atypical pneumonia with high specificity, which should help clinicians to optimise initial empirical therapy for CAP.

The Combinatorics of Local Constraints in Model-Based Recognition and Localization,

DTIC Science & Technology

1984-04-01

InCn ted alo0ng! th le 1111;i nor nria. T[hus, a secornd sensory point can 1,e cli aractcr: it’o ti this spare ’)N ;a uni~t vector in offset by some...number of independent constraints, defining the swept volume IVu,,ne! then the expec ted bound on the number of interpretations for k ± 1 sensory points...t It ll r I to our oart icu r c:1,:CCC;i ’erivv -xplicrt xpe(’ ted Counts Cit the or2 f C .Tlterpret at ons conitiro \\\\2tli ~ ’CCF pOilnts, 1C C I)YI

Estrogen Receptor Expression in Atypical Hyperplasia: Lack of Association with Breast Cancer

PubMed Central

Barr Fritcher, Emily G.; Degnim, Amy C.; Hartmann, Lynn C.; Radisky, Derek C.; Boughey, Judy C.; Anderson, Stephanie S.; Vierkant, Robert A.; Frost, Marlene H.; Visscher, Daniel W.; Reynolds, Carol

2011-01-01

Background Estrogen receptor (ER) is expressed in normal and malignant breast epithelium, and expression levels have been found to increase with age in normal breast epithelium but not in atypical hyperplasia (AH) and carcinoma in situ. Here we assess ER expression in AH and its association with later breast cancer. Methods ER expression was assessed immunohistochemically in archival sections from 246 women with AH who had open benign breast biopsy from 1967–1991. The ACISRIII (Dako, Carpinteria, CA) was utilized to calculate ER expression in all atypical foci. Using multivariate linear regression, we examined associations of ER expression with age at biopsy, indication for biopsy, type of atypia, number of atypical foci, involution status, and family history. Breast cancer risk across levels of ER expression was also assessed compared to the Iowa SEER control population. Results Among 246 women, 87 (35%) had atypical ductal hyperplasia (ADH), 141 (57%) had atypical lobular hyperplasia (ALH), and 18 (7%) had both. Forty-nine (20%) developed breast cancer (median follow-up of 14.4 years). Multivariate analysis indicated that type of atypia and age at diagnosis were significantly associated with ER percent staining and intensity [p<0.05]. ER expression was increased in women with ADH and/or those over age 55. ER expression did not significantly impact breast cancer risk in patients diagnosed with atypia. Conclusion We found increasing ER expression in atypical hyperplasia with increasing age. ER expression in atypical hyperplasia does not further discriminate breast cancer risk in women with atypia. PMID:21209395

Atypical ulcers: wound biopsy results from a university wound pathology service .

PubMed

Tang, Jennifer C; Vivas, Alejandra; Rey, Andrea; Kirsner, Robert S; Romanelli, Paolo

2012-06-01

Chronic wounds are an increasing health burden across the continuum of care and encountered by a wide variety of healthcare providers and physicians of all specialties. The majority of chronic wounds are caused by vascular insufficiency, neuropathy, or prolonged pressure. Wounds caused by other underlying health conditions or external factors such as radiation or spider bites are usually referred to as atypical. Although a wound biopsy generally is recommended in the case of refractory, nonhealing ulcers or when wounds present with atypical signs and symptoms, little is known about the distribution of atypical ulcers. A retrospective, descriptive study was conducted to describe the proportion and differential diagnosis of atypical ulcer biopsies received during a 2-year period by the wound pathology division in the division of Dermatopathology at the University of Miami Department of Dermatology and Cutaneous Surgery. Of the 350 wound biopsies received for diagnostic purposes, 104 (29.7%) were due to atypical causes. The majority of specimens were neoplasms (n = 24). Pyoderma gangrenosum was the most common atypical diagnosis encountered (n = 14). Vasculitis, predominantly leukocytoclastic vasculitis, and external causes were diagnosed in 16 and 15 biopsies, respectively. This study represents the first published case series of atypical ulcer biopsy results from a wound pathology division. Although the prevalence results cannot be generalized and are likely lower in the general population of patients with nonhealing wounds, the results confirm the usefulness of obtaining wound biopsies to provide a definitive diagnosis and to guide care.

Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study.

PubMed

Peng, Mei; Gao, Keming; Ding, Yiling; Ou, Jianjun; Calabrese, Joseph R; Wu, Renrong; Zhao, Jingping

2013-08-01

This study aims to investigate the developmental effects of atypical antipsychotics on infants who were born to mothers taking an atypical antipsychotic throughout pregnancy. The developmental progress of 76 infants who experienced fetal exposure to atypical antipsychotics was compared to that of 76 matched control infants who had no fetal exposure to any antipsychotics. Planned assessment included Apgar score, body weight, height, and the cognitive, language, motor, social-emotional, and adaptive behavior composite scores of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Student's t test and Chi-square analysis were used as appropriate. Repeated measurements were evaluated by analysis of covariance. At 2 months of age, the mean composite scores of cognitive, motor, social-emotional, and adaptive behavior of BSID-III were significantly lower in atypical antipsychotic-exposed infants than the controls. More atypical antipsychotic-exposed infants had delayed development in cognitive, motor, social-emotional, and adaptive behavior domains as defined by the composite score of <85 in these subscales of BSID-III. At 12 months of age, there were no significant differences between the two groups in all mean composite scores of BSID-III. More atypical antipsychotic-exposed infants had low birth weight than the controls (13.2 vs. 2.6 %, P = 0.031), although there were no significant difference in mean birth weight and height between the two groups. Fetal exposure to atypical antipsychotics may cause short-term delayed development in cognitive, motor, social-emotional, and adaptive behavior, but not in language, body weight, or height.

Analysis of clinical characteristics and antipsychotic medication prescribing practices of first-episode schizophrenia in Israel: a naturalistic prospective study.

PubMed

Strous, Rael D; Bar, Faina; Keret, Noa; Lapidus, Raya; Kosov, Nikolai; Chelben, Joseph; Kotler, Moshe

2006-01-01

Investigation of the clinical presentation and treatment of first-episode psychosis is important in order to exclude effects of age, chronic illness, long-term treatment and institutionalization. The aim of this descriptive study was to investigate the management practices of first-episode schizophrenia in a cohort of patients in Israel and to document use of the various "typical" or "atypical" antipsychotic agents. Fifty-one consecutive patients (26 M, 25 F) with first-episode psychosis were recruited for study participation and were administered either typical or atypical antipsychotic medications in a naturalistic manner. While an approximately equal number of subjects received typical and atypical medications at illness onset, a prominent shift to atypical antipsychotic treatment occurred over the study course; 18 subjects had medication class shifts: 17 from typical to atypical, and one from atypical to typical. Negative symptoms did not affect length of hospitalization, but were associated with aggression. Higher depression rates were noted in patients with long hospitalizations who received typical antipsychotic medications. Immigrants were admitted at an age approximately four years older than native-born Israelis. The prominent shift from "typical" to "atypical" antipsychotic medications may indicate sensitivity of first-episode psychotic patients to side-effects of "typical" medications and prominence of use of atypical medications in this patient subpopulation be it due to improved efficacy over time or successful marketing. Unique cultural and population characteristics may contribute to the manifestation of first-episode psychosis and suggest the importance of more effective outreach to the immigrant population in order to manage an apparent treatment delay.

Real frequency of ordinary and atypical sub-trochanteric and diaphyseal fractures in France based on X-rays and medical file analysis.

PubMed

Beaudouin-Bazire, Constance; Dalmas, Noémie; Bourgeois, Julie; Babinet, Antoine; Anract, Philippe; Chantelot, Christophe; Farizon, Frédéric; Chopin, Florence; Briot, Karine; Roux, Christian; Cortet, Bernard; Thomas, Thierry

2013-03-01

Atypical sub-trochanteric and femoral shaft fractures have been reported in patients treated with bisphosphonates. Their incidence has been determined from registered data analysis using international codes. Therefore, the aim of our study was to estimate the real frequency of typical and atypical sub-trochanteric or diaphyseal fractures, based on radiological and clinical data compared to registered data. In the registers of three large French University Hospitals, patients identified with International Classification of Diseases, 10th Revision diagnosis codes for sub-trochanteric or diaphyseal fracture were selected. Frequencies of ordinary and atypical fractures were calculated after both registered data, radiological and clinical files analysis. Among the 4592 patients hospitalized for a femoral fracture over 5 years, 574 were identified to have had a sub-trochanteric or femoral shaft fracture. 47.7% of the sub-trochanteric and femoral shaft fractures were misclassified, predominantly in the sub-trochanteric fractures subset. 12 patients had an atypical fracture (4% of the sub-trochanteric and femoral shaft fractures) and 11 fractures presented radiological features of atypical fractures, whereas clinical files analysis revealed they were pathological or traumatic fractures. Atypical fractures frequency is very low. Because of their low frequency and the unreliability of registered databases, the risk of atypical fractures is very difficult to estimate retrospectively. A prospective study is needed to clarify the risk factors associated with these fractures. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Characterization of atypical language activation patterns in focal epilepsy.

PubMed

Berl, Madison M; Zimmaro, Lauren A; Khan, Omar I; Dustin, Irene; Ritzl, Eva; Duke, Elizabeth S; Sepeta, Leigh N; Sato, Susumu; Theodore, William H; Gaillard, William D

2014-01-01

Functional magnetic resonance imaging is sensitive to the variation in language network patterns. Large populations are needed to rigorously assess atypical patterns, which, even in neurological populations, are a minority. We studied 220 patients with focal epilepsy and 118 healthy volunteers who performed an auditory description decision task. We compared a data-driven hierarchical clustering approach to the commonly used a priori laterality index (LI) threshold (LI < 0.20 as atypical) to classify language patterns within frontal and temporal regions of interest. We explored (n = 128) whether IQ varied with different language activation patterns. The rate of atypical language among healthy volunteers (2.5%) and patients (24.5%) agreed with previous studies; however, we found 6 patterns of atypical language: a symmetrically bilateral, 2 unilaterally crossed, and 3 right dominant patterns. There was high agreement between classification methods, yet the cluster analysis revealed novel correlations with clinical features. Beyond the established association of left-handedness, early seizure onset, and vascular pathology with atypical language, cluster analysis identified an association of handedness with frontal lateralization, early seizure onset with temporal lateralization, and left hemisphere focus with a unilateral right pattern. Intelligence quotient was not significantly different among patterns. Language dominance is a continuum; however, our results demonstrate meaningful thresholds in classifying laterality. Atypical language patterns are less frequent but more variable than typical language patterns, posing challenges for accurate presurgical planning. Language dominance should be assessed on a regional rather than hemispheric basis, and clinical characteristics should inform evaluation of atypical language dominance. Reorganization of language is not uniformly detrimental to language functioning. © 2014 American Neurological Association.

Behavioral Activation for the Treatment of Atypical Depression: A Pilot Open Trial

ERIC Educational Resources Information Center

Weinstock, Lauren M.; Munroe, Mary K.; Miller, Ivan W.

2011-01-01

Psychosocial interventions for atypical depression (AD) have been relatively ignored in the clinical research literature, despite evidence that the atypical subtype of major depression is marked by earlier age of onset, longer duration of mood episode, greater symptom severity, and poorer response to pharmacologic treatment. Given the symptom…

Insecure Attachment States of Mind and Atypical Caregiving Behavior among Foster Mothers

ERIC Educational Resources Information Center

Ballen, Natasha; Bernier, Annie; Moss, Ellen; Tarabulsy, George M.; St-Laurent, Diane

2010-01-01

The current study examined the links between attachment state of mind (assessed with the Adult Attachment Interview) and atypical parenting behavior among 39 foster mothers. Insecure states of mind were associated with increased atypical parenting while interacting with the foster child, whereas unexpectedly, an unresolved state of mind was not.…

Motor Skill Abilities in Toddlers with Autistic Disorder, Pervasive Developmental Disorder-Not Otherwise Specified, and Atypical Development

ERIC Educational Resources Information Center

Matson, Johnny L.; Mahan, Sara; Fodstad, Jill C.; Hess, Julie A.; Neal, Daniene

2010-01-01

Motor skills were assessed in 397 toddlers, and it was demonstrated that atypically developing toddlers exhibited significantly greater motor skill abilities than toddlers with autistic disorder. No significant difference on gross or fine motor skill abilities were found between atypically developing toddlers and toddlers with pervasive…

[Development of an Atypical Response Scale.

ERIC Educational Resources Information Center

Mendelsohn, Mark; Linden, James

The development of an objective diagnostic scale to measure atypical behavior is discussed. The Atypical Response Scale (ARS) is a structured projective test consisting of 17 items, each weighted 1, 2, or 3, that were tested for convergence and reliability. ARS may be individually or group administered in 10-15 minutes; hand scoring requires 90…

Medulloblastoma with Atypical Dynamic Imaging Changes: Case Report with Literature Review.

PubMed

Song, Shuang-Shuang; Wang, Jian-Hong; Fu, Wei-Wei; Li, Ying; Sui, Qing-Lan; Liu, Xue-Jun

2017-09-01

We analyzed a case of medulloblastoma with atypical dynamic imaging changes retrospectively to summarize the atypical magnetic resonance imaging (MRI) features of medulloblastoma by reviewing the literature. An atypical case of medulloblastoma in the cerebellar hemisphere confirmed by pathology was analyzed retrospectively, and the literature about it was reviewed. The radiologic findings of the patient were based on 3 examinations. The first examination showed that the cortex of the bilateral cerebellar hemisphere had diffuse nodular thickening, with a high signal on diffusion-weighted imaging and significant enhancement. Contrast enhancement MRI 1 year later showed the signal of cerebellar hemisphere returned to normal but revealed an enhanced nodule. A reexamination 6 months later showed an irregular mass with a high-density shadow in the cerebellar vermis on CT scan. The T2-weighted image revealed multiple degenerative cysts, and the mass had significant enhancement. The radiologic characteristics of atypical medulloblastomas vary in adults and children. Understanding the radiologic characteristics of medulloblastomas, such as MRI features, age of onset, and location of atypical medulloblastomas, can help improve the diagnosis of medulloblastomas. Copyright © 2017. Published by Elsevier Inc.

Side effects induced by the acute levodopa challenge in Parkinson's Disease and atypical parkinsonisms.

PubMed

Vasta, Rosario; Nicoletti, Alessandra; Mostile, Giovanni; Dibilio, Valeria; Sciacca, Giorgia; Contrafatto, Donatella; Cicero, Calogero Edoardo; Raciti, Loredana; Luca, Antonina; Zappia, Mario

2017-01-01

Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40-13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD.

Genetic structure of typical and atypical populations of Candida albicans from Africa.

PubMed

Forche, A; Schönian, G; Gräser, Y; Vilgalys, R; Mitchell, T G

1999-11-01

Atypical isolates of the pathogenic yeast Candida albicans have been reported with increasing frequency. To investigate the origin of a set of atypical isolates and their relationship to typical isolates, we employed a combination of molecular phylogenetic and population genetic analyses using rDNA sequencing, PCR fingerprinting, and analysis of co-dominant DNA nucleotide polymorphisms to characterize the population structure of one typical and two atypical populations of C. albicans from Angola and Madagascar. The extent of clonality and recombination was assessed in each population. The analyses revealed that the structure of all three populations of C. albicans was predominantly clonal but, as in previous studies, there was also evidence for recombination. Allele frequencies differed significantly between the typical and the atypical populations, suggesting very low levels of gene flow between them. However, allele frequencies were quite similar in the two atypical C. albicans populations, suggesting that they are closely related. Phylogenetic analysis of partial sequences encoding the nuclear 26S rDNA demonstrated that all three populations belong to a single monophyletic group, which includes the type strain of C. albicans. Copyright 1999 Academic Press.

The majority of atypical cpb2 genes in Clostridium perfringens isolates of different domestic animal origin are expressed.

PubMed

Kircanski, Jasmina; Parreira, Valeria R; Whiteside, Samantha; Pei, Yanlong; Prescott, John F

2012-10-12

This study examined the prevalence and expression of the "consensus" and the "atypical"cpb2 genes in Clostridium perfringens isolates from cattle, chickens, dogs, goats, horses, pigs and sheep using polymerase chain reaction (PCR), sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting. Almost all porcine isolates (12/14) carried and expressed the consensus form of cpb2 but, when present in 108 non-porcine isolates, the gene was usually the atypical form (40 atypical versus 9 consensus). Western blotting showed expression in 30 of 40 (75%) atypical cpb2-positive isolates, considerably more frequently than reported previously. CPB2 was expressed by almost all (20/21) the consensus cpb2-positive isolates, regardless of source. Copyright © 2012 Elsevier B.V. All rights reserved.

The predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the DUAG trial of moclobemide versus clomipramine.

PubMed

Bech, P; Stage, K B; Larsen, J K; Vestergaard, P; Gram, L F

2012-11-01

To investigate to what extent the primary depression subtype atypical depression can predict differential outcome of the mono-amino-oxidase inhibitor (MAO-I) moclobemide and the tricyclic antidepressant clomipramine in the Danish University Antidepressant Group Study (DUAG). In a randomised, double blind trial, a total of 117 patients with major depression were treated over 6 weeks with either 400 mg moclobemide or 150 mg clomipramine. A baseline principal component analysis (PCA) was performed to identify atypical symptoms on the combined depression scales (Hamilton Depression Scale (HAM-D(17)) and the Quantitative Scale for Atypical Depression (QSAD)). The primary outcome scale was the subscale HAM-D(6) which contains the pure items of depression. PCA identified two items with loadings opposite to the other depression items within HAM-D(17) and QSAD, namely increased duration of sleep and increased appetite (atypical neurovegetative symptoms). Patients with a positive score at baseline on these items were classified as having atypical depression. In total 13 patients were classified as having atypical depression. Within this group of patients 8 received clomipramine and 5 patients received moclobemide. At endpoint the moclobemide treated patients had a significantly better response than the clomipramine treated (P=0.036), effect size 1.42, when using HAM-D(6) as outcome. However, in the 104 patients classified as having typical depression clomipramine was superior to moclobemide (P=0.034), effect size 0.47. The number of patients with atypical neurovegetative symptoms was very small and no placebo arm was included. It is very important to screen for atypical depression (increased duration of sleep/increased appetite) in the acute therapy of patients with major depression. Our results add to the body of evidence that monoamine oxidase inhibitors are superior to tricyclic antidepressants in this sub-group of patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values.

PubMed

Meltzer, H Y; Matsubara, S; Lee, J C

1989-10-01

The pKi values of 13 reference typical and 7 reference atypical antipsychotic drugs (APDs) for rat striatal dopamine D-1 and D-2 receptor binding sites and cortical serotonin (5-HT2) receptor binding sites were determined. The atypical antipsychotics had significantly lower pKi values for the D-2 but not 5-HT2 binding sites. There was a trend for a lower pKi value for the D-1 binding site for the atypical APD. The 5-HT2 and D-1 pKi values were correlated for the typical APD whereas the 5-HT2 and D-2 pKi values were correlated for the atypical APD. A stepwise discriminant function analysis to determine the independent contribution of each pKi value for a given binding site to the classification as a typical or atypical APD entered the D-2 pKi value first, followed by the 5-HT2 pKi value. The D-1 pKi value was not entered. A discriminant function analysis correctly classified 19 of 20 of these compounds plus 14 of 17 additional test compounds as typical or atypical APD for an overall correct classification rate of 89.2%. The major contributors to the discriminant function were the D-2 and 5-HT2 pKi values. A cluster analysis based only on the 5-HT2/D2 ratio grouped 15 of 17 atypical + one typical APD in one cluster and 19 of 20 typical + two atypical APDs in a second cluster, for an overall correct classification rate of 91.9%. When the stepwise discriminant function was repeated for all 37 compounds, only the D-2 and 5-HT2 pKi values were entered into the discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation.

PubMed

Fakhouri, Fadi; Fila, Marc; Provôt, François; Delmas, Yahsou; Barbet, Christelle; Châtelet, Valérie; Rafat, Cédric; Cailliez, Mathilde; Hogan, Julien; Servais, Aude; Karras, Alexandre; Makdassi, Raifah; Louillet, Feriell; Coindre, Jean-Philippe; Rondeau, Eric; Loirat, Chantal; Frémeaux-Bacchi, Véronique

2017-01-06

The complement inhibitor eculizumab has dramatically improved the outcome of atypical hemolytic uremic syndrome. However, the optimal duration of eculizumab treatment in atypical hemolytic uremic syndrome remains debated. We report on the French atypical hemolytic uremic syndrome working group's first 2-year experience with eculizumab discontinuation in patients with atypical hemolytic uremic syndrome. Using the French atypical hemolytic uremic syndrome registry database, we retrospectively identified all dialysis-free patients with atypical hemolytic uremic syndrome who discontinued eculizumab between 2010 and 2014 and reviewed their relevant clinical and biologic data. The decision to discontinue eculizumab was made by the clinician in charge of the patient. All patients were closely monitored by regular urine dipsticks and blood tests. Eculizumab was rapidly (24-48 hours) restarted in case of relapse. Among 108 patients treated with eculizumab, 38 patients (nine children and 29 adults) discontinued eculizumab (median treatment duration of 17.5 months). Twenty-one patients (55%) carried novel or rare complement genes variants. Renal recovery under eculizumab was equally good in patients with and those without complement gene variants detected. After a median follow-up of 22 months, 12 patients (31%) experienced atypical hemolytic uremic syndrome relapse. Eight of 11 patients (72%) with complement factor H variants, four of eight patients (50%) with membrane cofactor protein variants, and zero of 16 patients with no rare variant detected relapsed. In relapsing patients, early reintroduction (≤48 hours) of eculizumab led to rapid (<7 days) hematologic remission and a return of serum creatinine to baseline level in a median time of 26 days. At last follow-up, renal function remained unchanged in nonrelapsing and relapsing patients compared with baseline values before eculizumab discontinuation. Pathogenic variants in complement genes were associated with higher risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Prospective studies are needed to identify biomarkers predictive of relapse and determine the best strategy of retreatment in relapsing patients. Copyright © 2016 by the American Society of Nephrology.

Thrombomodulin Mutations in Atypical Hemolytic–Uremic Syndrome

PubMed Central

Delvaeye, Mieke; Noris, Marina; De Vriese, Astrid; Esmon, Charles T.; Esmon, Naomi L.; Ferrell, Gary; Del-Favero, Jurgen; Plaisance, Stephane; Claes, Bart; Lambrechts, Diether; Zoja, Carla; Remuzzi, Giuseppe; Conway, Edward M.

2012-01-01

BACKGROUND The hemolytic–uremic syndrome consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. The common form of the syndrome is triggered by infection with Shiga toxin–producing bacteria and has a favorable outcome. The less common form of the syndrome, called atypical hemolytic–uremic syndrome, accounts for about 10% of cases, and patients with this form of the syndrome have a poor prognosis. Approximately half of the patients with atypical hemolytic–uremic syndrome have mutations in genes that regulate the complement system. Genetic factors in the remaining cases are unknown. We studied the role of thrombomodulin, an endothelial glycoprotein with anticoagulant, antiinflammatory, and cytoprotective properties, in atypical hemolytic–uremic syndrome. METHODS We sequenced the entire thrombomodulin gene (THBD) in 152 patients with atypical hemolytic–uremic syndrome and in 380 controls. Using purified proteins and cell-expression systems, we investigated whether thrombomodulin regulates the complement system, and we characterized the mechanisms. We evaluated the effects of thrombomodulin missense mutations associated with atypical hemolytic–uremic syndrome on complement activation by expressing thrombomodulin variants in cultured cells. RESULTS Of 152 patients with atypical hemolytic–uremic syndrome, 7 unrelated patients had six different heterozygous missense THBD mutations. In vitro, thrombomodulin binds to C3b and factor H (CFH) and negatively regulates complement by accelerating factor I–mediated inactivation of C3b in the presence of cofactors, CFH or C4b binding protein. By promoting activation of the plasma procarboxypeptidase B, thrombomodulin also accelerates the inactivation of anaphylatoxins C3a and C5a. Cultured cells expressing thrombomodulin variants associated with atypical hemolytic–uremic syndrome had diminished capacity to inactivate C3b and to activate procarboxypeptidase B and were thus less protected from activated complement. CONCLUSIONS Mutations that impair the function of thrombomodulin occur in about 5% of patients with atypical hemolytic–uremic syndrome. PMID:19625716

Cerebral Hemodynamics in Patients with Hemolytic Uremic Syndrome Assessed by Susceptibility Weighted Imaging and Four-Dimensional Non-Contrast MR Angiography.

PubMed

Löbel, Ulrike; Forkert, Nils Daniel; Schmitt, Peter; Dohrmann, Thorsten; Schroeder, Maria; Magnus, Tim; Kluge, Stefan; Weiler-Normann, Christina; Bi, Xiaoming; Fiehler, Jens; Sedlacik, Jan

2016-01-01

Conventional magnetic resonance imaging (MRI) of patients with hemolytic uremic syndrome (HUS) and neurological symptoms performed during an epidemic outbreak of Escherichia coli O104:H4 in Northern Europe has previously shown pathological changes in only approximately 50% of patients. In contrast, susceptibility-weighted imaging (SWI) revealed a loss of venous contrast in a large number of patients. We hypothesized that this observation may be due to an increase in cerebral blood flow (CBF) and aimed to identify a plausible cause. Baseline 1.5T MRI scans of 36 patients (female, 26; male, 10; mean age, 38.2±19.3 years) were evaluated. Venous contrast was rated on standard SWI minimum intensity projections. A prototype four-dimensional (time resolved) magnetic resonance angiography (4D MRA) assessed cerebral hemodynamics by global time-to-peak (TTP), as a surrogate marker for CBF. Clinical parameters studied were hemoglobin, hematocrit, creatinine, urea levels, blood pressure, heart rate, and end-tidal CO2. SWI venous contrast was abnormally low in 33 of 36 patients. TTP ranged from 3.7 to 10.2 frames (mean, 7.9 ± 1.4). Hemoglobin at the time of MRI (n = 35) was decreased in all patients (range, 5.0 to 12.6 g/dL; mean, 8.2 ± 1.4); hematocrit (n = 33) was abnormally low in all but a single patient (range, 14.3 to 37.2%; mean, 23.7 ± 4.2). Creatinine was abnormally high in 30 of 36 patients (83%) (range, 0.8 to 9.7; mean, 3.7 ± 2.2). SWI venous contrast correlated significantly with hemoglobin (r = 0.52, P = 0.0015), hematocrit (r = 0.65, P < 0.001), and TTP (r = 0.35, P = 0.036). No correlation of SWI with blood pressure, heart rate, end-tidal CO2, creatinine, and urea level was observed. Findings suggest that the loss of venous contrast is related to an increase in CBF secondary to severe anemia related to HUS. SWI contrast of patients with pathological conventional MRI findings was significantly lower compared to patients with normal MRI (mean SWI score, 1.41 and 2.05, respectively; P = 0.04). In patients with abnormal conventional MRI, mean TTP (7.45), mean hemoglobin (7.65), and mean hematocrit (22.0) were lower compared to patients with normal conventional MRI scans (mean TTP = 8.28, mean hemoglobin = 8.63, mean hematocrit = 25.23). In contrast to conventional MRI, almost all patients showed pathological changes in cerebral hemodynamics assessed by SWI and 4D MRA. Loss of venous contrast on SWI is most likely the result of an increase in CBF and may be related to the acute onset of anemia. Future studies will be needed to assess a possible therapeutic effect of blood transfusions in patients with HUS and neurological symptoms.

Antiepileptic effect of olanzapine in epilepsy patients with atypical depressive comorbidity.

PubMed

Qiu, Xiangmiao; Zingano, Bianca; He, Shixu; Zhu, Xi; Peng, Anjiao; Duan, Jianan; Wolf, Peter; Chen, Lei

2018-06-15

Depression is relatively common among patients with epilepsy, but often with predominant atypical symptoms. Some antiepileptic drugs show positive psychotropic effects, but these are not always sufficient to stabilize mood in epilepsy patients. Antidepressants are recommended to treat atypical depression but are not always effective and present a certain risk of seizure provocation. Thus, new treatment options are welcome. Here, we describe three cases of refractory epilepsy with atypical depression in which olanzapine, contrary to its earlier reported proconvulsant effect, showed excellent antidepressant action and resulted in seizure control. Possible mechanisms of this action are discussed.

Celiac disease in 87 children with typical and atypical symptoms in Black Sea region of Turkey.

PubMed

Dinler, Gönül; Atalay, Erdal; Kalayci, Ayhan Gazi

2009-11-01

Celiac disease presents with a spectrum of clinical disorders. The variety of clinical presentations largely depends on age and extraintestinal findings. This study aimed to determine typical and atypical cases according to presenting symptoms and to evaluate their biochemical and pathological parameters. Eighty-seven patients with celiac disease in our unit between 2000 and 2007 were reviewed. Their diagnosis was made by serological and histological examination. The patients were divided into two groups according to their typical or atypical symptoms. The mean age of the patients at diagnosis was 8.2 years (range, 1-18 years), but patients presenting with typical symptoms were younger than those presenting with atypical symptoms. The patients in the two groups did not differ significantly in sex, weight and height Z scores except age. Diarrhea (96.3%), abdominal distention (65.4%) and failure to thrive (60%) were the most common clinical presentations in the typical group, and short stature (62.5%) and anemia (31.2%) were the most common in the atypical group. Total/subtotal villous atrophy was significantly higher in the typical group than in the atypical group. Many children with celiac disease show an atypical form. The understanding of presentations of celiac disease may prevent delayed diagnosis. Celiac disease should be specially investigated in patients with recurrent iron deficiency anemia, short stature and autoimmune disorders.

Baselining PMU Data to Find Patterns and Anomalies

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

Amidan, Brett G.; Follum, James D.; Freeman, Kimberly A.

This paper looks at the application of situational awareness methodologies with respect to power grid data. These methodologies establish baselines that look for typical patterns and atypical behavior in the data. The objectives of the baselining analyses are to provide: real-time analytics, the capability to look at historical trends and events, and reliable predictions of the near future state of the grid. Multivariate algorithms were created to establish normal baseline behavior and then score each moment in time according to its variance from the baseline. Detailed multivariate analytical techniques are described in this paper that produced ways to identify typicalmore » patterns and atypical behavior. In this case, atypical behavior is behavior that is unenvisioned. Visualizations were also produced to help explain the behavior that was identified mathematically. Examples are shown to help describe how to read and interpret the analyses and visualizations. Preliminary work has been performed on PMU data sets from BPA (Bonneville Power Administration) and EI (Eastern Interconnect). Actual results are not fully shown here because of confidentiality issues. Comparisons between atypical events found mathematically and actual events showed that many of the actual events are also atypical events; however there are many atypical events that do not correlate to any actual events. Additional work needs to be done to help classify the atypical events into actual events, so that the importance of the events can be better understood.« less

Sporadic pediatric meningiomas: a neuroradiological and neuropathological study of 15 cases.

PubMed

Huntoon, Kristin; Pluto, Charles P; Ruess, Lynne; Boué, Daniel R; Pierson, Christopher R; Rusin, Jerome A; Leonard, Jeffrey

2017-08-01

OBJECTIVE Sporadic meningiomas have been classified in many different ways. Radiographically, these lesions can be described as occurring in either typical or atypical locations. The purpose of this study was to determine if there are any histopathological differences between sporadic meningiomas that arise in these varying locations in children. METHODS The neuroimaging, histopathological findings, and clinical records in patients with sporadic pediatric meningiomas not associated with neurofibromatosis Type 2 or prior radiation therapy were retrospectively reviewed. Tumors were classified by radiological findings as either typical or atypical, and they were categorized histopathologically by using the latest WHO nomenclature and grading criteria. RESULTS Fifteen sporadic meningiomas in pediatric patients were biopsied or resected at the authors' institution between 1989 and 2013. Five (33%) were typical in radiographic appearance and/or location and 10 (67%) were atypical. Four (80%) typical meningiomas were WHO Grade I tumors. Most (60%) of the atypical meningiomas were WHO Grade II or III. CONCLUSIONS This study is the largest series of sporadic pediatric meningiomas in atypical locations to date. Although sporadic meningiomas are relatively infrequent in children, those with atypical imaging, specifically those with apparently intraparenchymal and intraosseous locations, may be more common than previously recognized. In this study, pediatric sporadic meningiomas arising in atypical locations, in particular intraparenchymal meningiomas, may be of higher histopathological grade. The authors' findings should alert clinicians to the potential for more aggressive clinical behavior in these tumors.

Clinical and Etiological Characteristics of Atypical Hand-Foot-and-Mouth Disease in Children from Chongqing, China: A Retrospective Study.

PubMed

Yan, Xiang; Zhang, Zhen-Zhen; Yang, Zhen-Hua; Zhu, Chao-Min; Hu, Yun-Ge; Liu, Quan-Bo

2015-01-01

Hand-foot-and-mouth disease (HFMD) is a disease that had similar manifestations to chickenpox, impetigo, and measles, which is easy to misdiagnose and subsequently causes delayed therapy and subsequent epidemic. To date, no study has been conducted to report the clinical and epidemiological characteristics of atypical HFMD. 64 children with atypical HFMD out of 887 HFMD children were recruited, stool was collected, and viral VP1 was detected. The atypical HFMD accounted for 7.2% of total HFMD in the same period (64/887) and there were two peaks in its prevalence in nonepidemic seasons. Ten children (15.6%) had manifestations of neurologic involvement, of whom 4 (6.3%) were diagnosed with severe HFMD and 1 with critically severe HFMD, but all recovered smoothly. Onychomadesis and desquamation were found in 14 patients (21.9%) and 15 patients (23.4%), respectively. The most common pathogen was coxsackievirus A6 (CV-A6) which accounted for 67.2%, followed by nontypable enterovirus (26.6%), enterovirus 71 (EV-A71) (4.7%), and coxsackievirus A16 (A16) (1.5%). Atypical HFMD has seasonal prevalence. The manifestations of neurologic involvement in atypical HFMD are mild and usually have a good prognosis. CV-A6 is a major pathogen causing atypical HFMD, but not a major pathogen in Chongqing, China.

The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: a longitudinal MRI study.

PubMed

Nicolo, John-Paul; Berger, Gregor E; Garner, Belinda A; Velakoulis, Dennis; Markulev, Connie; Kerr, Melissa; McGorry, Patrick D; Proffitt, Tina-Marie; McConchie, Mirabel; Pantelis, Christos; Wood, Stephen J

2010-01-01

Pituitary volume is currently measured as a marker of hypothalamic-pituitary-adrenal hyperactivity in patients with psychosis despite suggestions of susceptibility to antipsychotics. Qualifying and quantifying the effect of atypical antipsychotics on the volume of the pituitary gland will determine whether this measure is valid as a future estimate of HPA-axis activation in psychotic populations. To determine the qualitative and quantitative effect of atypical antipsychotic medications on pituitary gland volume in a first-episode psychosis population. Pituitary volume was measured from T1-weighted magnetic resonance images in a group of 43 first-episode psychosis patients, the majority of whom were neuroleptic-naïve, at baseline and after 3months of treatment, to determine whether change in pituitary volume was correlated with cumulative dose of atypical antipsychotic medication. There was no significant baseline difference in pituitary volume between subjects and controls, or between neuroleptic-naïve and neuroleptic-treated subjects. Over the follow-up period there was a negative correlation between percentage change in pituitary volume and cumulative 3-month dose of atypical antipsychotic (r=-0.37), i.e. volume increases were associated with lower doses and volume decreases with higher doses. Atypical antipsychotic medications may reduce pituitary gland volume in a dose-dependent manner suggesting that atypical antipsychotic medication may support affected individuals to cope with stress associated with emerging psychotic disorders.

Atypical depressive symptoms and obesity in a national sample of older adults with major depressive disorder.

PubMed

Chou, Kee-Lee; Yu, Kar-Ming

2013-06-01

The objectives of this study are to present findings on the rate of obesity associated with classic, atypical, and undifferentiated depression by comparing with those without depression in a nationally representative sample of United States older adults. The authors used data from the 2001 to 2002 National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), which included 10,557 adults 60 years of age and older. Chi-square tests were used to compare classic, atypical, and undifferentiated as well as nondepressed control in sociodemographic characteristics. Then, logistic regressions adjusting for sociodemographic characteristics were used to evaluate associations of rate of current obesity (defined as Body Mass Index (BMI) > 30) across the three depressive groups (classic, atypical, and undifferentiated depression) and nondepressed control. Lifetime, current, and past depression were examined. Significant differences were found between atypical and classic depression in sex, age, marital status, race, and personal income. After adjusting for sex, age, marital status, race, and personal income, the rate of obesity was significantly greater for respondents with atypical depression than respondents with classic, undifferentiated depression, or without depression. Same results were found in lifetime, current, and past depression. Our findings suggest that the heterogeneity of depression should be considered when examining the effect of depression on obesity in old age. Prevention measures should be designed and delivered to older adults with atypical depression. © 2013 Wiley Periodicals, Inc.

Effects of Physical Atypicality on Children's Social Identities and Intergroup Attitudes

ERIC Educational Resources Information Center

Patterson, Meagan M.; Bigler, Rebecca S.

2007-01-01

Individuals vary in the degree to which they are representative, or typical, of their social groups. To investigate the effects of atypicality on intergroup attitudes, elementary-school-age children (N = 97) attending a summer school program were assigned to novel color groups that included typical (blue or green) and atypical (light blue or light…

Atypical Speech and Language Development: A Consensus Study on Clinical Signs in the Netherlands

ERIC Educational Resources Information Center

Visser-Bochane, Margot I.; Gerrits, Ellen; van der Schans, Cees P.; Reijneveld, Sijmen A.; Luinge, Margreet R.

2017-01-01

Background: Atypical speech and language development is one of the most common developmental difficulties in young children. However, which clinical signs characterize atypical speech-language development at what age is not clear. Aim: To achieve a national and valid consensus on clinical signs and red flags (i.e. most urgent clinical signs) for…

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

PubMed Central

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

Embracing the Unusual: Feeling Tired and Happy Is Associated with Greater Acceptance of Atypical Ideas

ERIC Educational Resources Information Center

Middlewood, Brianna L.; Gallegos, Jonathan; Gasper, Karen

2016-01-01

Three studies examined the hypothesis that feeling tired along with feeling happy might be linked to the acceptance of atypical ideas. Consistent with this hypothesis, across 3 studies and using 2 different measures of accepting atypical ideas, feelings of happiness and tiredness interacted. When people were high in tiredness, as happiness…

Atypical Activation during the Embedded Figures Task as a Functional Magnetic Resonance Imaging Endophenotype of Autism

ERIC Educational Resources Information Center

Spencer, Michael D.; Holt, Rosemary J.; Chura, Lindsay R.; Calder, Andrew J.; Suckling, John; Bullmore, Edward T.; Baron-Cohen, Simon

2012-01-01

Atypical activation during the Embedded Figures Task has been demonstrated in autism, but has not been investigated in siblings or related to measures of clinical severity. We identified atypical activation during the Embedded Figures Task in participants with autism and unaffected siblings compared with control subjects in a number of temporal…

A Review of Methods in the Study of Attention in Autism

ERIC Educational Resources Information Center

Ames, Catherine; Fletcher-Watson, Sue

2010-01-01

Atypical attention, while not a diagnostic feature, is common in individuals with autism spectrum disorders (ASD). The study of these atypicalities has recently gained in both quantity and quality, due in part to an increased focus on attentional atypicalities as one of the earliest signs of ASD in infancy. A range of attentional processes and…

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review.

PubMed

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

Factors Related to the Expression of Typical and Atypical Repetitive Movements of Young Children with Intellectual Disability.

ERIC Educational Resources Information Center

Wehmeyer, Michael L.

1994-01-01

This paper reviews research describing developmentally typical and atypical repetitive motor movements of children with and without disabilities. It then reports findings of a study of nine preschool-aged children with developmental delay and atypical stereotypies. Predictors of repetitive movements included level of functioning, age, ambulation,…

A Study of the Familial and Career Attitudes of College Women Enrolled in Typical and Atypical Programs.

ERIC Educational Resources Information Center

Wilson, Marian L.

A study was conducted to determine if a disparity exists between the familial and occupational attitudes of women in typical and atypical careers. Questionnaire responses of 225 undergraduate women in three typical careers (home economics, nursing, and elementary education) and three atypical careers (engineering, pharmacy, and agriculture)…

Summary of the comparative effectiveness review on off-label use of atypical antipsychotics.

PubMed

Maher, Alicia R; Theodore, George

2012-06-01

Conventional and atypical antipsychotic medications are approved by the FDA for treatment of schizophrenia and bipolar disorder. Over many decades, the widespread use of conventional antipsychotics produced various side effects requiring additional medications, such as the atypical antipsychotics. Beginning in 2006, 9 atypical antipsychotic drugs have been approved by the FDA for indications that were previously off-label uses: aripiprazole (as augmentation for major depressive disorder [MDD] and for autism spectrum disorders), asenapine, clozapine, iloperidone, olanzapine (in combination with fluoxetine for MDD and bipolar depression), paliperidone, quetiapine (quetiapine and quetiapine XR [extended release] as monotherapy in bipolar depression and quetiapine XR as augmentation for MDD), risperidone (for autism spectrum disorders), and ziprasidone. In 2006, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of off-label uses of atypical antipsychotics. Since that time, numerous studies have been published evaluating these therapies in various new off-label uses; new or increased adverse effects have been observed with off-label uses; new atypical antipsychotics have been approved; and previously off-label uses have been approved for some atypical antipsychotics. Hence, AHRQ published an updated review in September 2011 that summarized the benefits and harms of atypical antipsychotics in the treatment of attention-deficit hyperactivity disorder/attention deficit disorder (ADHD), anxiety, behavioral disturbances of dementia and severe geriatric agitation, depression, eating disorders, insomnia, obsessive-compulsive disorder (OCD), personality disorder, post-traumatic stress disorder (PTSD), substance use and dependence disorders, and Tourette's syndrome. The new report also investigated topics for which data in the previous report were found to be insufficient to make conclusions, including subpopulations (i.e., race/ethnicity, gender) that would benefit most from atypical antipsychotics, appropriate dose, and time needed to see clinical improvement. The 2011 review included the following atypical antipsychotics: aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone; no clinical trials were found for off-label use of the 3 most recently FDA-approved atypical antipsychotics (asenapine, iloperidone, and paliperidone). To (a) familiarize health care professionals with the methods and findings from AHRQ's 2011 Comparative Effectiveness Review (CER) of off-label use of atypical antipsychotics, (b) encourage consideration of the clinical and managed care applications of the review findings, and (c) identify limitations and gaps in the existing research with respect to the benefits and risks of off-label use of atypical antipsychotics. Antipsychotic medications are FDA approved for the treatment of schizophrenia and bipolar disorder. Conventional antipsychotics have been widely used for decades and spurred the development of the atypical antipsychotics. Atypical antipsychotics were produced and are now being used for patients who may have experienced various side effects while using conventional antipsychotics.In 2006, an AHRQ study reviewed off-label uses of atypical antipsychotics (excluding clozapine because of its association with potentially fatal bone marrow suppression and the requirement for frequent blood tests for safety monitoring). Findings indicated that the most common off-label uses of these drugs included depression, OCD, PTSD, personality disorders, Tourette's syndrome, autism, and agitation in dementia. The reviewers concluded in 2006 that overall there was not sufficiently high strength of evidence of efficacy for any off-label use of atypical antipsychotics. There was, however, strong evidence for an increased risk of adverse events with off-label use, including significant weight gain and sedation and increased mortality among the elderly.Since the 2006 review, significant developments occurred in the use of atypical antipsychotics, including FDA approval of the atypical antipsychotics asenapine, iloperidone, and paliperidone and FDA approval of previous off-label uses: (a) quetiapine and quetiapine XR as monotherapy in bipolar depression; (b) quetiapine XR as augmentation therapy for MDD; (c) aripiprazole as augmentation therapy for MDD; (d) olanzapine/fluoxetine combination for MDD; (e) olanzapine/fluoxetine combination for bipolar depression; and (f) risperidone and aripiprazole for autism spectrum disorders. Additional studies have been published for new off-label uses, and there have been reports of new or increased adverse effects for off-label uses.Further review of previously insufficient information was warranted on subpopulations where treatment modification such as dosing may increase efficacy. The 2006 review did not have sufficient information to make conclusions regarding subpopulations (i.e., race/ethnicity, gender) that would benefit most from atypical antipsychotics, appropriate dosing, and the duration of treatment needed to see clinical improvement. The updated AHRQ report in 2011 reviewed off-label uses of atypical antipsychotic medications in anxiety, ADHD, behavioral disturbances of dementia and severe geriatric agitation, MDD, eating disorders, insomnia, OCD, PTSD, personality disorders, substance abuse, and Tourette's syndrome; autism was included in the 2006 review but is now reviewed in a separate report of the comparative effectiveness of antipsychotics for on-label uses. The significant findings in the updated review include (a) small but statistically significant benefits for olanzapine, aripiprazole, and risperidone for elderly patients with dementia; (b) quetiapine appears superior to placebo for general anxiety disorder (GAD); (c) risperidone was associated with benefits in the treatment of OCD; and (d) adverse events are common. Atypical antipsychotics were not effective in the treatment of eating disorders or personality disorder. The evidence did not support the use of atypical antipsychotics in the treatment of substance abuse, and data were inconclusive for the use of these medications for insomnia. The number needed to harm (NNH) was calculated for adverse events in elderly patients, including risk of death (NNH = 87), stroke (NNH = 53 for risperidone), extrapyramidal symptoms (NNH = 10 for olanzapine and NNH = 20 for risperidone), and urinary symptoms (NNH = 16 to 36). Adverse events in nonelderly adults included weight gain (particularly with olanzapine), fatigue, sedation, akathisia (with aripiprazole), and extrapyramidal symptoms.

Hitting a moving target: evolution of a treatment paradigm for atypical meningiomas amid changing diagnostic criteria.

PubMed

Pearson, Blake E; Markert, James M; Fisher, Winfield S; Guthrie, Barton L; Fiveash, John B; Palmer, Cheryl A; Riley, Kristen

2008-01-01

The World Health Organization (WHO) reclassified atypical meningiomas in 2000, creating a more clear and broadly accepted definition. In this paper, the authors evaluated the pathological and clinical transition period for atypical meningiomas according to the implementation of the new WHO grading system at their institution. A total of 471 meningiomas occurring in 440 patients between 1994 and 2006 were retrospectively reviewed to determine changes in diagnostic rates, postoperative treatment trends, and early outcomes. Between 1994 and 2000, the incidence of the atypical meningiomas ranged from 0 to 3/year, or 4.4% of the meningiomas detected during the entire period. After 2002, the annual percentage of atypical meningiomas rose over a 2-year period, leveling off at between 32.7 and 35.5% between 2004 and 2006. The authors also found a recent trend toward increased use of adjuvant radiation therapy for incompletely resected atypical meningiomas. Prior to 2003, 18.7% were treated with this therapy; after 2003, 34.4% of lesions received this treatment. Incompletely resected tumors were treated with some form of radiation 76% of the time. In cases of complete resection, most patients were not given adjuvant therapy but were expectantly managed by close monitoring using serial imaging and by receiving immediate treatment for tumor recurrence. The overall recurrence rate for expectantly managed tumors was 9% over 28.2 months, and 75% of recurrences responded to delayed radiation therapy. The authors documented a significant change in the proportion of meningiomas designated as atypical during a transition period from 2002 to 2004, and propose a conservative strategy for the use of radiation therapy in atypical meningiomas.

Lipid profile in antipsychotic drug users: A comparative study

PubMed Central

Roohafza, Hamidreza; Khani, Azam; Afshar, Hamid; Garakyaraghi, Mohammad; Amirpour, Afshin; Ghodsi, Basir

2013-01-01

BACKGROUND Schizophrenic patients who receive antipsychotic drugs may be highly prone to metabolic disorders such as weight gain, dyslipidemia, and insulin resistance. The objective of the present study was to compare the effect of atypical and conventional antipsychotics on lipid profile. METHODS 128 schizophrenic patients were enrolled into the study. Patients were divided into two groups. One group had received one type of atypical antipsychotic drug, and, the other, one type of conventional antipsychotic drug. They were considered as atypical and conventional groups. Moreover, both groups had not used any other antipsychotic drugs during the past year. Demographic data and food frequency questionnaire were completed by the participants. Serum triglyceride, total cholesterol (TC), high-density lipoprotein and low-density lipoprotein (LDL) cholesterols, and apolipoprotein A and B (Apo B) were tested by blood sample drawing after 12 hours of fasting through the antecubital vein. Student’s t-test was used to compare atypical and conventional groups. RESULTS There was no significant difference in age, gender, duration of illness, period of drug consumption, and age at onset of illness in the two groups. Patients in the atypical group used clozapine and risperidone (46.9%) more than olanzapine. In the conventional group 81.3% of patients used phenothiazines. Comparison between lipid profile in the conventional and atypical groups showed a significantly higher mean in TC (P = 0.01), LDL (P = 0.03), and Apo B (P = 0.01) in conventional group than the atypical group. CONCLUSION In schizophrenic patients, the level of lipid profile had been increased in both atypical and conventional antipsychotic users, especially conventional users, so the effect of antipsychotic drugs should be investigated periodically. PMID:23766777

A 20-year and 46,000-specimen journey to Paris reveals the influence of reporting systems and passive peer feedback on pathologist practice patterns.

PubMed

VandenBussche, Christopher J; Allison, Derek B; Gupta, Mohit; Ali, Syed Z; Rosenthal, Dorothy L

2018-05-14

An important goal of The Paris System for Reporting Urinary Cytology (TPS) is to reduce unnecessary atypical diagnoses given to urinary tract cytology (UTC) specimens. Since implementation of TPS at the study institution in 2016, the institutional atypical rate has declined only slightly. The authors speculated that TPS might not have had an immediate impact because several faculty members were involved in TPS committees and because TPS contains elements that already had been integrated into institutional practice. To identify factors contributing to alterations in the institutional atypical rate, the authors examined their practice over the last 22 years. UTC specimens submitted to the study laboratory between August 11, 1995, and August 10, 2017, were identified. Specimens were linked to the responsible pathologist, specimen diagnosis and type, association with high-grade urothelial carcinoma, and relevant cytomorphologic features. An increase in the institutional atypical rate occurred between 2002 and 2005. The atypical rate among individual pathologists also peaked during this same time. The increase coincided with an increase in the use of UTC and the arrival of a pathologist with a higher rate of atypical diagnoses. A substantial decrease in the institutional atypical rate occurred between 2005 and 2010 and coincided with the creation of the Johns Hopkins Hospital Template, the authors' first standardized reporting system for UTC specimens. The use of reporting systems (Johns Hopkins Hospital Template and TPS) has coincided with decreases in the institutional atypical rate at the study institution. An individual pathologist may influence the practice patterns of his or her colleagues, resulting in fluctuations in the institutional rate of atypia over time. Cancer Cytopathol 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Atypicalities in cortical structure, handedness, and functional lateralization for language in autism spectrum disorders.

PubMed

Lindell, Annukka K; Hudry, Kristelle

2013-09-01

Language is typically a highly lateralized function, with atypically reduced or reversed lateralization linked to language impairments. Given the diagnostic and prognostic role of impaired language for autism spectrum disorders (ASDs), this paper reviews the growing body of literature that examines patterns of lateralization in individuals with ASDs. Including research from structural and functional imaging paradigms, and behavioral evidence from investigations of handedness, the review confirms that atypical lateralization is common in people with ASDs. The evidence indicates reduced structural asymmetry in fronto-temporal language regions, attenuated functional activation in response to language and pre-linguistic stimuli, and more ambiguous (mixed) hand preferences, in individuals with ASDs. Critically, the evidence emphasizes an intimate relationship between atypical lateralization and language impairment, with more atypical asymmetries linked to more substantive language impairment. Such evidence highlights opportunities for the identification of structural and functional biomarkers of ASDs, affording the potential for earlier diagnosis and intervention implementation.

Review of Part 67 of the Federal Air Regulations and the Medical Certification of Civilian Airmen. Volume 1

DTIC Science & Technology

1983-01-01

schizoaffective disorder and atypical psycho3, infantile autism , childhood onset pervasive developmental disorder, and atypical pervasive devvlopmental...classified, including schizophreniform disorder, brief reactive psychosis, schizoaffective disorder and atypical psychosis, infantile autism ...procedures if the applicant !S free of symptoms and postoperative complications. After splenectomy, vaccination against pneumococcus is recommended, Awms and

TABS Manual for the Temperament and Atypical Behavior Scale: Early Childhood Indicators of Developmental Dysfunction.

ERIC Educational Resources Information Center

Neisworth, John T.; Bagnato, Stephen J.; Salvia, John; Hunt, Frances M.

This manual describes the rationale, use, and validity of the Temperament and Atypical Behavior Scale (TABS), a norm-referenced measure of dysfunctional behavior appropriately used with infants and young children between the ages of 11 and 71 months. TABS is intended to identify children who are developing atypically or are at risk for atypical…

Hypercalcemia: an unusual etiology of a common menopausal symptom.

PubMed

Roark, Abrea; Wilson, Brian P; Eyster, Kathleen M; Timmerman, Gary L; Allard, Brandon L; Hansen, Keith A

2011-06-01

To describe atypical vasomotor symptoms that were secondary to primary hyperparathyroidism. Case report. University medical center. A 57-year-old, postmenopausal woman with recalcitrant hot flushes. Parathyroid adenomectomy. Vasomotor symptom relief. Postoperative relief of atypical vasomotor symptoms. A patient 17 years postmenopause presented with atypical vasomotor symptoms that did not respond to hormone therapy and proved to be due to hypercalcemia secondary to primary hyperparathyroidism. An atypical manifestation of a common condition or an uncharacteristic therapeutic response should alert health care providers to the possibility of a different diagnosis. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A naturally occurring cowpox virus with an ectromelia virus A-type inclusion protein gene displays atypical A-type inclusions.

PubMed

Okeke, Malachy Ifeanyi; Hansen, Hilde; Traavik, Terje

2012-01-01

Human orthopoxvirus (OPV) infections in Europe are usually caused by cowpox virus (CPXV). The genetic heterogeneity of CPXVs may in part be due to recombination with other OPV species. We describe the characterization of an atypical CPXV (CPXV-No-H2) isolated from a human patient in Norway. CPXV-No-H2 was characterized on the basis of A-type inclusion (ATI) phenotype as well as the DNA region containing the p4c and atip open reading frames. CPXV-No-H2 produced atypical V(+/) ATI, in which virions are on the surface of ATI but not within the ATI matrix. Phylogenetic analysis showed that the atip gene of CPXV-No-H2 clustered closely with that of ectromelia virus (ECTV) with a bootstrap support of 100% whereas its p4c gene is diverged compared to homologues in other OPV species. By recombination analysis we identified a putative crossover event at nucleotide 147, downstream the start of the atip gene. Our results suggest that CPXV-No-H2 originated from a recombination between CPXV and ECTV. Our findings are relevant to the evolution of OPVs. Copyright © 2011 Elsevier B.V. All rights reserved.

Diagnostic value of progesterone receptor, p16, p53 and pHH3 expression in uterine atypical leiomyoma.

PubMed

Liang, Yun; Zhang, Xiaofei; Chen, Xiaoduan; Lü, Weiguo

2015-01-01

The differential diagnosis between atypical leiomyoma and leiomyosarcoma may be hard based on morphological criterion at times. It would be helpful to find out biomarkers that can be used to distinguish them. The aim of the study was to investigate the diagnostic value of progesterone receptor (PR), p16, p53 and pHH3 expression in a series of uterine smooth muscle tumors. Immunohistochemical expression of PR, p16, p53 and pHH3 was investigated on 32 atypical leiomyomas, 15 leiomyosarcomas and 15 usual leomyomas. The difference in expression was compared between atypical leiomyoma and other groups. The expression of PR, p16, and pHH3 was found significantly different between atypical leiomyomas and leiomyosarcomas, but lack of significant difference between atypical leiomyomas and usual leiomyomas. There was no significant difference with regard to p53 distribution among these uterine smooth muscle tumors. High p16, pHH3 expression and low PR expression preferred the diagnosis of leiomyosarcoma. The panel of antibodies used in this study is a useful complementary analysis in the assessment of problematic uterine smooth muscle tumors.

Diagnostic value of progesterone receptor, p16, p53 and pHH3 expression in uterine atypical leiomyoma

PubMed Central

Liang, Yun; Zhang, Xiaofei; Chen, Xiaoduan; Lü, Weiguo

2015-01-01

The differential diagnosis between atypical leiomyoma and leiomyosarcoma may be hard based on morphological criterion at times. It would be helpful to find out biomarkers that can be used to distinguish them. The aim of the study was to investigate the diagnostic value of progesterone receptor (PR), p16, p53 and pHH3 expression in a series of uterine smooth muscle tumors. Immunohistochemical expression of PR, p16, p53 and pHH3 was investigated on 32 atypical leiomyomas, 15 leiomyosarcomas and 15 usual leomyomas. The difference in expression was compared between atypical leiomyoma and other groups. The expression of PR, p16, and pHH3 was found significantly different between atypical leiomyomas and leiomyosarcomas, but lack of significant difference between atypical leiomyomas and usual leiomyomas. There was no significant difference with regard to p53 distribution among these uterine smooth muscle tumors. High p16, pHH3 expression and low PR expression preferred the diagnosis of leiomyosarcoma. The panel of antibodies used in this study is a useful complementary analysis in the assessment of problematic uterine smooth muscle tumors. PMID:26261614

Can metabolic side effects of antipsychotics be reversed by lifestyle changes?

PubMed

Bolger, Alistair; Verdolini, Norma; Agius, Mark

2014-11-01

Antipsychotics, particularly atypical antipsychotics, are known to have metabolic side effects such as; weight gain, hyperlipidaemia and insulin resistance. This is problematic as metabolic syndrome can be a precursor to many diseases, including type II diabetes and coronary heart disease. In an attempt to overcome these side-effects, lifestyle changes have been recommended in tandem with commencement of atypical antipsychotics, but is this effective at halting metabolic syndrome? There is some evidence suggesting that lifestyle changes can reduce weight gain caused by atypical antipsychotics. However, there seems to be a paucity of evidence about whether this correlates with correction of metabolic dysregulation. Moreover, there is a lack of research into the precise mechanism of metabolic syndrome as caused by atypical antipsychotics,as well as a lack of evidence into how exercise remedies this. Furthermore, there is research to suggest that the pathophysiology of psychosis may lead to metabolic dysregulation independently of treatment. Lifestyle changes should still be part of a treatment as they seem to partially reverse metabolic changes seen with atypical antipsychotics. However, more research is needed to identify weight independent mechanisms for metabolic dysregulation seen in those taking atypical antipsychotics in order to solve this pressing issue.

COMBINED 24-HOURS ESOPHAGEAL PH MONITORING AND MULTICHANNEL INTRALUMINAL IMPEDANCE FOR COMPARISON OF GASTROESOPHAGEAL REFLUX IN CHILDREN WITH TYPICAL VERSUS ATYPICAL SYMPTOMS OF GASTROESOPHAGEAL REFLUX DISEASE.

PubMed

Dehghani, Seyed Mohsen; Taghavi, Seyed Alireza; Javaherizadeh, Hazhir; Nasri, Maryam

2016-01-01

- Gastroesophageal reflux disease is the most common esophageal disorder in pediatrics. - The aim of this study was to compare reflux parameters of typical and atypical symptoms of gastroesophageal reflux disease using 24-hour esophageal pH monitoring and multichannel intraluminal impedance in pediatric population. - In this prospective study, 43 patients aged less than 18 year with suspected gastroesophageal reflux disease were enrolled. The patients were divided into two groups based on the main presenting symptoms (typical versus atypical). Twenty four-hour pH monitoring and multichannel intraluminal impedance were performed in all the patients for comparing these two group regarding association of symptoms and reflux. Number of refluxes, pH related reflux, total reflux time, reflux more than 5 minutes, longest time of the reflux, lowest pH at reflux, reflux index were recorded and compared. Data comparison was done using SPSS. - The mean age of the patients was 5.7±3.4 years and 65.1% were male. Out of 43 patients 24 cases had typical symptoms and 19 had atypical symptoms. The mean reflux events detected by multichannel intraluminal impedance was more than mean reflux events detected by pH monitoring (308.4±115.8 vs 69.7±66.6) with P value of 0.037, which is statistically significant. The mean symptom index and symptom association probability were 35.01% ± 20.78% and 86.42% ± 25.79%, respectively in multichannel intraluminal impedance versus 12.73% ± 12.48% and 45.16% ± 42.29% in pH monitoring (P value <0.001). Number of acid reflux was 46.26±47.16 and 30.9±22.09 for atypical and typical symptoms respectively. The mean symptom index was 18.12% ± 13.101% and 8.30% ± 10.301% in atypical and typical symptoms respectively (P=0.034). Bolus clearance was longer in atypical symptoms compared typical symptoms(P<0.05). - Symptom index was significantly higher in atypical symptoms compared to typical symptoms. Higher number of acid reflux was found in children with atypical symptoms of reflux. Longer duration of bolus clearance was found in group with atypical symptoms of reflux.

Frequency of celiac disease in adult patients with typical or atypical malabsorption symptoms in isfahan, iran.

PubMed

Emami, Mohammad Hassan; Kouhestani, Soheila; Karimi, Somayeh; Baghaei, Abdolmahdi; Janghorbani, Mohsen; Jamali, Nahid; Gholamrezaei, Ali

2012-01-01

Aim. Atypical presentations of celiac disease (CD) have now been shown to be much more common than classical (typical) form. We evaluated the frequency of CD among adult patients with typical or atypical symptoms of CD. Materials and Methods. Patients referred to two outpatient gastroenterology clinics in Isfahan (IRAN) were categorized into those with typical or atypical symptoms of CD. IgA antitissue transglutaminase antibody was assessed and followed by duodenal biopsy. In patients for whom endoscopy was indicated (independent of the serology), duodenal biopsy was taken. Histopathological changes were assessed according to the Marsh classification. Results. During the study period, 151 and 173 patients with typical and atypical symptoms were evaluated (mean age = 32.8 ± 12.6 and 35.8 ± 14.8 years, 47.0% and 56.0% female, resp.). Frequency of CD in patients with typical and atypical symptoms was calculated, respectively, as 5.9% (9/151) and 1.25% (3/173) based on positive serology and pathology. The overall frequency was estimated as at least 9.2% (14/151) and 4.0% (7/173) when data of seronegative patients were also considered. Conclusions. CD is more frequent among patients with typical symptoms of malabsorption and these patients should undergo duodenal biopsy, irrespective of the serology. In patients with atypical symptoms, serological tests should be performed followed by endoscopic biopsy, and routine duodenal biopsy is recommended when endoscopic evaluation is indicated because of symptoms.

Comparison of Endoscopic and Histological Findings between Typical and Atypical Celiac Disease in Children.

PubMed

Semwal, Pooja; Gupta, Raj Kumar; Sharma, Rahul; Garg, Kapil

2018-04-01

Celiac disease is a common non-communicable disease with varied presentations. Purpose of this study was to find the duodeno-endoscopic features in celiac disease and to compare duodeno-endoscopic and histological findings between typical and atypical celiac disease in children. Hospital based observational study was conducted at Sir Padampat Mother and Child Health Institute, Jaipur from June 2015 to May 2016. Patients were selected and divided in two groups- typical and atypical celiac disease based upon the presenting symptoms. Upper gastrointestinal endoscopy and duodenal biopsy was performed for serology positive patients. Results were analysed using appropriate statistical test of significance. Out of 101 enrolled patients, 47.5% were male. Age ranged from 1 to 18 years. Study showed that 54.5% were typical and 45.5% were atypical. Patients presenting with atypical symptoms were predominantly of older age group. On endoscopy, scalloping, mosaic pattern, reduced fold height and absent fold height; and in histology, advanced Marsh stage were significantly higher in the typical group. Awareness of atypical presentations as well as duodeno-endoscopic features may have considerable practical importance for the diagnosis of celiac disease in children. Scalloping, mosaic pattern, reduced fold height and nodularity are main endoscopic markers of celiac disease in children. Endoscopic markers of duodenal mucosa may be important in early diagnosis of celiac disease, in children subjected to endoscopy for atypical presentations or indication other than suspected celiac disease.

Bullying, Physical Aggression, Gender-Atypicality, and Sexual Orientation in Samoan Males.

PubMed

Semenyna, Scott W; Vasey, Paul L

2017-07-01

Bullying is characterized by the repeated attempts of a group or individual to gain social advantage by the use of relational, verbal, or physical aggression against a target, especially when there is a perceived or actual power imbalance (Espelage & Swearer, 2003). One consistent finding is that gay (i.e., androphilic) males report higher rates of victimization due to bullying in adolescence than their heterosexual (i.e., gynephilic) counterparts. Western data indicate that gender-atypical behavior, regardless of sexual orientation, is a key predictor of victimization due to bullying. Androphilic males generally display childhood gender-atypicality, including reduced levels of physical aggression, which may cause bullies to perceive them as "easy" targets. In order to test the associations between sexual orientation, childhood gender-atypicality, and recalled victimization due to bullying, a sample of Samoan gynephilic men (n = 100) were compared to a group of Samoan transgender androphilic males (n = 103), known as fa'afafine. Although the fa'afafine reported far more childhood gender-atypicality, the two groups did not differ significantly on measures of physical aggression or their reported rates of victimization due to bullying. Additionally, greater physical aggression, not gender-atypicality, was the only significant predictor of being bullied in both men and fa'afafine. These results suggest that there is nothing inherent in sexual orientation or childhood gender-atypicality that would potentiate victimization from bullying. Instead, the cultural context in which a bully functions influences the extent to which these are "acceptable" reasons to target certain individuals.

Melancholic and atypical depression as predictor and moderator of outcome in cognitive behavior therapy and pharmacotherapy for adult depression.

PubMed

Cuijpers, Pim; Weitz, Erica; Lamers, Femke; Penninx, Brenda W; Twisk, Jos; DeRubeis, Robert J; Dimidjian, Sona; Dunlop, Boadie W; Jarrett, Robin B; Segal, Zindel V; Hollon, Steven D

2017-03-01

Melancholic and atypical depression are widely thought to moderate or predict outcome of pharmacological and psychological treatments of adult depression, but that has not yet been established. This study uses the data from four earlier trials comparing cognitive behavior therapy (CBT) versus antidepressant medications (ADMs; and pill placebo when available) to examine the extent to which melancholic and atypical depression moderate or predict outcome in an "individual patient data" meta-analysis. We conducted a systematic search for studies directly comparing CBT versus ADM, contacted the researchers, integrated the resulting datasets from these studies into one big dataset, and selected the studies that included melancholic or atypical depressive subtyping according to DSM-IV criteria at baseline (n = 4, with 805 patients). After multiple imputation of missing data at posttest, mixed models were used to conduct the main analyses. In none of the analyses was melancholic or atypical depression found to significantly moderate outcome (indicating a better or worse outcome of these patients in CBT compared to ADM; i.e., an interaction), predict outcome independent of treatment group (i.e., a main effect), or predict outcome within a given modality. The outcome differences between patients with melancholia or atypical depression versus those without were consistently very small (all effect sizes g < 0.10). We found no indication that melancholic or atypical depressions are significant or relevant moderators or predictors of outcome of CBT and ADM. © 2016 Wiley Periodicals, Inc.

Incidence of Tardive Dyskinesia with Atypical and Conventional Antipsychotic Medications: Prospective Cohort Study

PubMed Central

Woods, Scott W.; Morgenstern, Hal; Saksa, John R.; Walsh, Barbara C.; Sullivan, Michelle C.; Money, Roy; Hawkins, Keith A.; Gueorguieva, Ralitza V.; Glazer, William M.

2011-01-01

Objective Most previous studies of the incidence of tardive dyskinesia with atypical compared to conventional antipsychotics have not had tardive dyskinesia as their primary focus. The current study aimed to compare the incidence of tardive dyskinesia with atypical vs. conventional antipsychotics using methods similar to those from a previous prospective cohort study at our site in the 1980s. Method 352 initially tardive dyskinesia-free psychiatric outpatients were examined for a new diagnosis of tardive dyskinesia every 6 months for up to 4 years at a community mental health center. At baseline, subjects were receiving conventional antipsychotics only (23%), atypicals only (64%), or both (14%). Only 26 subjects had never received conventional antipsychotics. Results Compared with subjects treated with conventional antipsychotics alone since the previous visit, the adjusted tardive dyskinesia incidence rate-ratio for subjects treated with atypical antipsychotics alone was 0.68 (95% confidence interval 0.29 to 1.64). The incidence and prevalence of tardive dyskinesia was similar to previous findings at this site in the 1980s. Conclusion The incidence of tardive dyskinesia with recent exposure to atypical antipsychotics alone was more similar to that for conventional antipsychotics than in most previous studies. Despite high penetration of atypical antipsychotics into clinical practice, the incidence and prevalence of tardive dyskinesia appeared relatively unchanged since the 1980s. Clinicians should continue to monitor for tardive dyskinesia, and researchers should continue to pursue efforts to treat or prevent it. PMID:20156410

Treatment of Low-Risk Endometrial Cancer and Complex Atypical Hyperplasia With the Levonorgestrel-Releasing Intrauterine Device.

PubMed

Pal, Navdeep; Broaddus, Russell R; Urbauer, Diana L; Balakrishnan, Nyla; Milbourne, Andrea; Schmeler, Kathleen M; Meyer, Larissa A; Soliman, Pamela T; Lu, Karen H; Ramirez, Pedro T; Ramondetta, Lois; Bodurka, Diane C; Westin, Shannon N

2018-01-01

To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer. This retrospective case series included all patients treated with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial cancer from January 2003 to June 2013. Response rates were calculated and the association of response with clinicopathologic factors, including age, body mass index, and uterine size, was determined. Forty-six patients diagnosed with complex atypical hyperplasia or early-grade endometrial cancer were treated with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI 57-89) at 6 months; 80% (95% CI 52-96) in complex atypical hyperplasia, 67% (95% CI 30-93) in grade 1 endometrial cancer, and 75% (CI 35-97) in grade 2 endometrial cancer. Of the clinicopathologic features evaluated, there was a trend toward the association of lack of exogenous progesterone effect in the pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter was 1.3 cm larger in women who did not respond to the IUD (P=.04). Levonorgestrel-releasing IUD therapy for the conservative treatment of complex atypical hyperplasia or early-grade endometrial cancer resulted in return to normal histology in a majority of patients.

How Category Structure Influences the Perception of Object Similarity: The Atypicality Bias

PubMed Central

Tanaka, James William; Kantner, Justin; Bartlett, Marni

2011-01-01

Why do some faces appear more similar than others? Beyond structural factors, we speculate that similarity is governed by the organization of faces located in a multi-dimensional face space. To test this hypothesis, we morphed a typical face with an atypical face. If similarity judgments are guided purely by their physical properties, the morph should be perceived to be equally similar to its typical parent as its atypical parent. However, contrary to the structural prediction, our results showed that the morph face was perceived to be more similar to the atypical face than the typical face. Our empirical studies show that the atypicality bias is not limited to faces, but extends to other object categories (birds) whose members share common shape properties. We also demonstrate atypicality bias is malleable and can change subject to category learning and experience. Collectively, the empirical evidence indicates that perceptions of face and object similarity are affected by the distribution of stimuli in a face or object space. In this framework, atypical stimuli are located in a sparser region of the space where there is less competition for recognition and therefore, these representations capture a broader range of inputs. In contrast, typical stimuli are located in a denser region of category space where there is increased competition for recognition and hence, these representation draw a more restricted range of face inputs. These results suggest that the perceived likeness of an object is influenced by the organization of surrounding exemplars in the category space. PMID:22685441

Atypical autoerotic deaths

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

Gowitt, G.T.; Hanzlick, R.L.

1992-06-01

So-called typical' autoerotic fatalities are the result of asphyxia due to mechanical compression of the neck, chest, or abdomen, whereas atypical' autoeroticism involves sexual self-stimulation by other means. The authors present five atypical autoerotic fatalities that involved the use of dichlorodifluoromethane, nitrous oxide, isobutyl nitrite, cocaine, or compounds containing 1-1-1-trichloroethane. Mechanisms of death are discussed in each case and the pertinent literature is reviewed.

"Atypical" Pleomorphic Lipomatous Tumor: A Clinicopathologic, Immunohistochemical and Molecular Study of 21 Cases, Emphasizing its Relationship to Atypical Spindle Cell Lipomatous Tumor and Suggesting a Morphologic Spectrum (Atypical Spindle Cell/Pleomorphic Lipomatous Tumor).

PubMed

Creytens, David; Mentzel, Thomas; Ferdinande, Liesbeth; Lecoutere, Evelyne; van Gorp, Joost; Atanesyan, Lilit; de Groot, Karel; Savola, Suvi; Van Roy, Nadine; Van Dorpe, Jo; Flucke, Uta

2017-11-01

The classification of the until recently poorly explored group of atypical adipocytic neoplasms with spindle cell features, for which recently the term atypical spindle cell lipomatous tumor (ASLT) has been proposed, remains challenging. Recent studies have proposed ASLT as a unique entity with (in at least a significant subset of cases) a specific genetic background, namely deletions/losses of 13q14, including RB1 and its flanking genes RCBTB2, DLEU1, and ITM2B. Similar genetic aberrations have been reported in pleomorphic liposarcomas (PLSs). This prompted us to investigate a series of 21 low-grade adipocytic neoplasms with a pleomorphic lipoma-like appearance, but with atypical morphologic features (including atypical spindle cells, pleomorphic [multinucleated] cells, pleomorphic lipoblasts and poor circumscription), for which we propose the term "atypical" pleomorphic lipomatous tumor (APLT). Five cases of PLS were also included in this study. We used multiplex ligation-dependent probe amplification to evaluate genetic changes of 13q14. In addition, array-based comparative genomic hybridization was performed on 4 APLTs and all PLSs. Multiplex ligation-dependent probe amplification showed consistent loss of RB1 and its flanking gene RCBTB2 in all cases of APLT. This genetic alteration was also present in all PLSs, suggesting genetic overlap, in addition to morphologic overlap, with APLTs. However, array-based comparative genomic hybridization demonstrated more complex genetic alterations with more losses and gains in PLSs compared with APLTs. APLTs arose in the subcutis (67%) more frequently than in the deep (subfascial) soft tissues (33%). With a median follow-up of 42 months, recurrences were documented in 2 of 12 APLTs for which a long follow-up was available. Herein, we also demonstrate that APLTs share obvious overlapping morphologic, immunohistochemical, genetic and clinical characteristics with the recently defined ASLT, suggesting that they are related lesions that form a spectrum (atypical spindle cell/pleomorphic lipomatous tumor).

Effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care.

PubMed

Stargardt, Tom; Weinbrenner, Susanne; Busse, Reinhard; Juckel, Georg; Gericke, Christian A

2008-06-01

In two recent randomised clinical trials, a meta-analysis and in an effectiveness study analysing routine data from the U.S. Veterans Administration the superiority of the newer atypical drugs over typical antipsychotic drugs, concerning both their efficacy and their side-effect profile, has been questioned. To analyse the effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care. Cohort study using routine care data from a statutory sickness fund with 5.4 million insured in Germany. To be included, patients had to be discharged with a diagnosis of schizophrenia in 2003 and fulfil membership criteria. Main outcome measures were rehospitalisation rates, mean hospital bed days, mean length of stay, cost of inpatient and pharmaceutical care to the sickness fund during follow-up and medication used to treat side-effects. 3121 patients were included into the study. There were no statistically significant differences in the effectiveness of atypical and typical antipsychotics on rehospitalisation during follow-up (rehospitalisation rate ratio 1.07, 95% confidence interval 0.86 to 1.33). However, there were consistent observations of atypical antipsychotics being more effective for severe cases of schizophrenia (14.6% of study population; >61 prior bed days per year in 2000-2002) in the follow-up period, whereas for the other severity strata typical antipsychotics seemed more effective in reducing various rehospitalisation outcomes. Patients treated with atypical antipsychotics received significantly less prescriptions for anticholinergics or tiaprid (relative risk 0.26, 95% confidence interval 0.18 to 0.38). The effectiveness of atypical antipsychotics for schizophrenia on rehospitalisation measures appeared similar to that of typical antipsychotics. With the exception of severe cases, the higher costs for atypical antipsychotics were not offset by savings from reduced inpatient care. Major limitations include the lack of statistical power for subgroup analyses, the lack of clinical severity scale data and of life-course medical history data which both increase the risk of residual confounding by disease severity. This study provides evidence that the effectiveness of atypical and typical antipsychotics measured in terms of hospital readmissions appears to be similar in routine care. From a clinical perspective, this study provides evidence that the effectiveness of atypical and typical antipsychotics measured in terms of hospital readmissions appears to be similar in routine care. Routine data studies can yield valuable information for policy decision-makers on the costs and the effectiveness of pharmaceuticals in routine care, complementing efficacy data from randomised clinical trials currently used for licensing and reimbursement decisions. The non-significant differences in the effectiveness of atypical compared to typical antipsychotics according to severity of disease should be investigated in a prospective observational study or in a randomised clinical trial.

Atypical preeclampsia – Gestational proteinuria

PubMed Central

Stevens, Amy B.; Brasuell, Diane M.; Higdon, Rebecca N.

2017-01-01

There are many rural areas where obstetric care is predominately performed by family medicine physicians. As such, it is important for family medicine physicians to stay up to date with the latest obstetric guidelines. Preeclampsia is a well-established disorder and the guidelines for screening and treatment are well known. However, atypical presentations of preeclampsia have been less studied. Notably, what constitutes atypical preeclampsia and when to be concerned for increased morbidity and mortality in the mother and neonate. This report describes a unique case in which a woman with proteinuria of pregnancy developed atypical preeclampsia with severe features. This report discusses the care that was given by a practicing family medicine physician and the reasoning behind it. PMID:29417031

Mitochondrial function is altered in horse atypical myopathy.

PubMed

Lemieux, Hélène; Boemer, François; van Galen, Gaby; Serteyn, Didier; Amory, Hélène; Baise, Etienne; Cassart, Dominique; van Loon, Gunther; Marcillaud-Pitel, Christel; Votion, Dominique-M

2016-09-01

Equine atypical myopathy in Europe is a fatal rhabdomyolysis syndrome that results from the ingestion of hypoglycin A contained in seeds and seedlings of Acer pseudoplatanus (sycamore maple). Acylcarnitine concentrations in serum and muscle OXPHOS capacity were determined in 15 atypical myopathy cases. All but one acylcarnitine were out of reference range and mitochondrial respiratory capacity was severely decreased up to 49% as compared to 10 healthy controls. The hallmark of atypical myopathy thus consists of a severe alteration in the energy metabolism including a severe impairment in muscle mitochondrial respiration that could contribute to its high death rate. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Influence of mandibular morphology on the hyoid bone in atypical deglutition: a correlational study.

PubMed

Machado, Almiro J; Crespo, Agrício N

2011-11-01

evaluate the possible correlation with the radiographic position of the hyoid bone and mandibular angle in lateral radiographs of children with atypical deglutition. This was an observational study using cephalometric analysis of lateral teleradiographs for the distances of H-MP (hyoid to mandibular plane). Spearman's correlation analysis was performed with MA (mandibular angle) in two groups: the experimental group with atypical deglutition and the control group normal deglutition. Both groups included subjects in mixed dentition stage. there was a significant moderate negative correlation between MA (mandibular angle) and hyoid bone (H-MP) in the normal group (R = -0.406, p = 0.021). However, there was no significant correlation between the MA and H-MP (R = 0.029, p = 0.83) in the group with atypical deglutition. there is a moderate negative correlation between the position of the hyoid bone and mandibular angle in the group of normal swallowing and there is no correlation between variables H-MP and MA in the group of atypical swallowing.

High prevalence of atypical hyperplasia in the endometrium of patients with epithelial ovarian cancer.

PubMed

Mingels, Marjanka J J M; Masadah, Rina; Geels, Yvette P; Otte-Höller, Irene; de Kievit, Ineke M; van der Laak, Jeroen A W M; van Ham, Maaike A P C; Bulten, Johan; Massuger, Leon F A G

2014-08-01

The aim of the present study is to determine the prevalence of endometrial premalignancies in women diagnosed with epithelial ovarian cancer (EOC). Endometrial and ovarian specimens of 186 patients with EOC were retrospectively selected using the nationwide pathology network and registry, and sections were comprehensively reviewed: 136 (73%) serous, 19 (10%) endometrioid, 15 (8%) mucinous, seven (4%) clear cell, and nine (5%) undifferentiated. Immunohistochemical phenotypes were compared for patients with serous EOC with concurrent endometrial pathology. In 31%, endometrial (pre)malignancy was found: carcinoma in 3%, endometrial intraepithelial carcinoma (EIC) in 4%, and atypical hyperplasia in 24%. Atypical hyperplasia was found in 47% of endometrioid EOCs but in 7% to 33% of other subtypes. Body mass index was higher concurrent to atypical hyperplasia (P=.001). Serous EOC and EIC immunophenotypes were comparable, whereas atypical hyperplasia was expressed differently. Apart from synchronous endometrial carcinoma, endometrial premalignancies should be taken into account when determining optimal treatment for women diagnosed with EOC. Copyright© by the American Society for Clinical Pathology.

Immunohistochemical differentiation of atypical hyperplasia vs. carcinoma in situ of the breast.

PubMed

Masood, S; Sim, S J; Lu, L

1992-01-01

The distinction between atypical hyperplasia and carcinoma in situ in breast lesions can be difficult. The identification of myoepithelial cell layers may be helpful in establishing a diagnosis of proliferative breast disease vs. intraepithelial neoplasia. We reviewed pathologic material on 20 cases of atypical hyperplasia and 29 cases of carcinoma in situ. Immunohistochemical stains were employed against muscle-specific actin, S-100 protein, and cytokeratin to identify myoepithelial cells and to recognize different staining patterns. In atypical hyperplasia, muscle-specific actin staining identified myoepithelial cells in fine branching fibrovascular layers or as scattered cells between other proliferating cells. This pattern was absent in carcinoma in situ. S-100 protein showed more positive staining in atypical hyperplasia than in carcinoma in situ with patterns distinct from muscle-specific actin. Immunostaining for cytokeratin demonstrated distinctly different patterns between the two lesions. This study suggests that muscle-specific actin, S-100 protein, and cytokeratin in combination may assist in distinguishing proliferative breast disease with atypia from carcinoma in situ.

Atypical infectious mononucleosis in a patient receiving tumor necrosis factor alpha inhibitory treatment.

PubMed

Sari, Ismail; Birlik, Merih; Akar, Servet; Onen, Fatos; Kargi, Aydanur; Akkoc, Nurullah

2009-05-01

The objective is to report a case of atypical acute infectious mononucleosis in a juvenile ankylosing spondylitis patient who was treated with infliximab. A 20-year-old man was hospitalized for the evaluation of lymphadenopathy and systemic symptoms. His symptoms developed at the eighth week of the infliximab treatment and he required hospitalization. Lymph node biopsy was performed and he was diagnosed as atypical infectious mononucleosis (absence of fever, pharyngitis, lymphocytosis and negative atypical lymphocytosis on blood smear). Infections have become major concerns in patients treated with TNF-blocking agents. In theoretical base, it is not surprising as TNF-alpha has a crucial role in the body's defense against both bacterial and viral invasion. Blocking the action of TNF may also change the course of the disease and could lead to a delay in the diagnosis. TNF-alpha-blocking treatment may mask the typical symptoms of infectious mononucleosis and atypical cases should be included in the differential diagnosis of lymphadenopathy in patients receiving anti-TNF-alpha agents.

Generic penetration in the retail atypical antipsychotic market.

PubMed

Lenderts, Susan; Kalali, Amir H; Buckley, Peter

2010-03-01

In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

Generic Penetration in the Retail Atypical Antipsychotic Market

PubMed Central

Kalali, Amir H; Buckley, Peter

2010-01-01

In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty. PMID:20436769

Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

PubMed

Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F

2010-07-01

Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.

A diagnostic algorithm for atypical spitzoid tumors: guidelines for immunohistochemical and molecular assessment.

PubMed

Cho-Vega, Jeong Hee

2016-07-01

Atypical spitzoid tumors are a morphologically diverse group of rare melanocytic lesions most frequently seen in children and young adults. As atypical spitzoid tumors bear striking resemblance to Spitz nevus and spitzoid melanomas clinically and histopathologically, it is crucial to determine its malignant potential and predict its clinical behavior. To date, many researchers have attempted to differentiate atypical spitzoid tumors from unequivocal melanomas based on morphological, immonohistochemical, and molecular diagnostic differences. A diagnostic algorithm is proposed here to assess the malignant potential of atypical spitzoid tumors by using a combination of immunohistochemical and cytogenetic/molecular tests. Together with classical morphological evaluation, this algorithm includes a set of immunohistochemistry assays (p16(Ink4a), a dual-color Ki67/MART-1, and HMB45), fluorescence in situ hybridization (FISH) with five probes (6p25, 8q24, 11q13, CEN9, and 9p21), and an array-based comparative genomic hybridization. This review discusses details of the algorithm, the rationale of each test used in the algorithm, and utility of this algorithm in routine dermatopathology practice. This algorithmic approach will provide a comprehensive diagnostic tool that complements conventional histological criteria and will significantly contribute to improve the diagnosis and prediction of the clinical behavior of atypical spitzoid tumors.

Variety in emotional life: within-category typicality of emotional experiences is associated with neural activity in large-scale brain networks

PubMed Central

Barrett, Lisa Feldman; Barsalou, Lawrence W.

2015-01-01

The tremendous variability within categories of human emotional experience receives little empirical attention. We hypothesized that atypical instances of emotion categories (e.g. pleasant fear of thrill-seeking) would be processed less efficiently than typical instances of emotion categories (e.g. unpleasant fear of violent threat) in large-scale brain networks. During a novel fMRI paradigm, participants immersed themselves in scenarios designed to induce atypical and typical experiences of fear, sadness or happiness (scenario immersion), and then focused on and rated the pleasant or unpleasant feeling that emerged (valence focus) in most trials. As predicted, reliably greater activity in the ‘default mode’ network (including medial prefrontal cortex and posterior cingulate) was observed for atypical (vs typical) emotional experiences during scenario immersion, suggesting atypical instances require greater conceptual processing to situate the socio-emotional experience. During valence focus, reliably greater activity was observed for atypical (vs typical) emotional experiences in the ‘salience’ network (including anterior insula and anterior cingulate), suggesting atypical instances place greater demands on integrating shifting body signals with the sensory and social context. Consistent with emerging psychological construction approaches to emotion, these findings demonstrate that is it important to study the variability within common categories of emotional experience. PMID:24563528

Syllabic patterns in typical and atypical phonological development: ultrasonographic analysis.

PubMed

Vassoler, Aline Mara de Oliveira; Berti, Larissa Cristina

2018-01-01

Objective The present study aims to compare the production of syllabic patterns of the CVC and CV types performed by Brazilian children with typical and atypical phonological development through ultrasonography of tongue. Methods Ten children (five with typical and with five atypical phonological development) recorded nine pairs of words from the syllables: CCV and CV. The images and audios were captured simultaneously by the Articulate Assistant Advanced software. The data were submitted to perceptive analysis and ultrasonographic articulatory analysis (the area between the tip and the blade of the tongue). The area measurements were submitted to one-way repeated measures ANOVA. Results ANOVA demonstrated a significant effect for the clinical condition (typical and atypical), (F (1.8) = 172.48, p> 0.000) forthe area measurements. In both syllabic patterns (CCV and CV) the atypical children showed greater values ​​of the area between the tip and the blade of the tongue. Regarding the syllabic patterns analyzed, the statistical test showed no significant effect (F (1.8)=0.19, p>0.658). Conclusion The use of a greater area of ​​the tongue by children with atypical phonological development suggests the non-differentiation of the tip and the anterior body gestures of the tongue in the production of CV and CCV.

Atypical activation during the Embedded Figures Task as a functional magnetic resonance imaging endophenotype of autism

PubMed Central

Holt, Rosemary J.; Chura, Lindsay R.; Calder, Andrew J.; Suckling, John; Bullmore, Edward T.; Baron-Cohen, Simon

2012-01-01

Atypical activation during the Embedded Figures Task has been demonstrated in autism, but has not been investigated in siblings or related to measures of clinical severity. We identified atypical activation during the Embedded Figures Task in participants with autism and unaffected siblings compared with control subjects in a number of temporal and frontal brain regions. Autism and sibling groups, however, did not differ in terms of activation during this task. This suggests that the pattern of atypical activation identified may represent a functional endophenotype of autism, related to familial risk for the condition shared between individuals with autism and their siblings. We also found that reduced activation in autism relative to control subjects in regions including associative visual and face processing areas was strongly correlated with the clinical severity of impairments in reciprocal social interaction. Behavioural performance was intact in autism and sibling groups. Results are discussed in terms of atypical information processing styles or of increased activation in temporal and frontal regions in autism and the broader phenotype. By separating the aspects of atypical activation as markers of familial risk for the condition from those that are autism-specific, our findings offer new insight into the factors that might cause the expression of autism in families, affecting some children but not others. PMID:23065480

A novel DPP6 isoform (DPP6-E) can account for differences between neuronal and reconstituted A-type K(+) channels.

PubMed

Maffie, Jonathon; Blenkinsop, Timothy; Rudy, Bernardo

2009-01-16

The channels mediating most of the somatodendritic A-type K(+) current in neurons are thought to be ternary complexes of Kv4 pore-forming subunits and two types of auxiliary subunits, the K(+) channel interacting proteins (KChIPs) and dipeptidyl-peptidase-like (DPPL) proteins. The channels expressed in heterologous expression systems by mixtures of Kv4.2, KChIP1 and DPP6-S resemble in many properties the A-type current in hippocampal CA1 pyramidal neurons and cerebellar granule cells, neurons with prominent A-type K(+) currents. However, the native currents have faster kinetics. Moreover, the A-type currents in neurons in intermediary layers of the superior colliculus have even faster inactivating rates. We have characterized a new DPP6 spliced isoform, DPP6-E, that produces in heterologous cells ternary Kv4 channels with very fast kinetics. DPP6-E is selectively expressed in a few neuronal populations in brain including cerebellar granule neurons, hippocampal pyramidal cells and neurons in intermediary layers of the superior colliculus. The effects of DPP6-E explain past discrepancies between reconstituted and native Kv4 channels in some neurons, and contributes to the diversity of A-type K(+) currents in neurons.

A prescription survey of antipsychotic use in England and Wales following the introduction of NICE guidance.

PubMed

MacE, Shubhra; Taylor, David

2005-01-01

Objective : In the United Kingdom (UK) the National Institute for Clinical Excellence (NICE) has recommended the use of atypical antipsychotics for the treatment of schizophrenia. As part of its guidance it discourages the concurrent use of typical and atypical antipsychotics. In previous prescribing surveys antipsychotic polypharmacy has been noted to be widespread. We sought to evaluate atypical antipsychotic prescribing after the publication of NICE guidance. Method : We invited psychiatric centres in England and Wales to participate, in March 2004, in an atypical antipsychotic prescribing survey of hospital in-patients. Results : Thirty-six in-patient units submitted data for 2012 patients. After exclusions, 1092 patients were eligible. Of these, 28.6% (312) were prescribed a typical alongside an atypical antipsychotic and 19.3% (211) were prescribed high-dose antipsychotics. Co-prescription was more prevalent in patients aged 40 years and above (32.0 vs. 25.3%; P=0.018). It was also noted that in centres employing senior pharmacists, co-prescription was more common (28.6 vs. 14.3%; P=0.03). High-dose treatment was more commonly observed in patients of a white ethnic background (20.6 vs. 13.9%; P=0.02) as well as in patients aged 40 years and above (24.4 vs. 15.0%; P<0.001). Prescription of anticholinergics was significantly more prevalent in those receiving atypical and typical combinations than atypicals alone (26.0 vs. 12.0%; P<0.001). Conclusions : Antipsychotic polypharmacy remains commonplace. Similarly the prescription of high-dose antipsychotics is also widespread.

Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin.

PubMed

Tatara, Ayaka; Shimizu, Saki; Masui, Atsushi; Tamura, Miyuki; Minamimoto, Shoko; Mizuguchi, Yuto; Ochiai, Midori; Mizobe, Yusuke; Ohno, Yukihiro

2015-11-01

Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200mg/kg, the potency being 1/3-1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose-dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin. Copyright © 2015 Elsevier Inc. All rights reserved.

The Efficacy of Acute Electroconvulsive Therapy in Atypical Depression

PubMed Central

Husain, Mustafa M.; McClintock, Shawn M.; Rush, A. John; Knapp, Rebecca G.; Fink, Max; Rummans, Teresa A.; Rasmussen, Keith; Claassen, Cynthia; Petrides, Georgios; Biggs, Melanie M.; Mueller, Martina; Sampson, Shirlene; Bailine, Samuel H.; Lisanby, Sarah H.; Kellner, Charles H.

2013-01-01

Objective This study examined the characteristics and outcomes of patients with major depressive disorder (MDD), with or without atypical features, who were treated with acute bilateral electroconvulsive therapy (ECT). Method Analyses were conducted with 489 patients who met DSM-IV criteria for MDD. Subjects were identified as typical or atypical on the basis of the Structured Clinical Interview for DSM-IV obtained at baseline prior to ECT. Depression symptom severity was measured by the 24-item Hamilton Rating Scale for Depression (HAM-D24) and the 30-item Inventory of Depressive Symptomatology–Self-Report (IDS-SR30). Remission was defined as at least a 60% decrease from baseline in HAM-D24 score and a total score of 10 or below on the last 2 consecutive HAM-D24 ratings. The randomized controlled trial was performed from 1997 to 2004. Results The typical (N = 453) and atypical (N = 36) groups differed in several sociodemographic and clinical variables including gender (p = .0071), age (p = .0005), treatment resistance (p = .0014), and age at first illness onset (p < .0001) and onset of current episode (p = .0008). Following an acute course of bilateral ECT, a considerable portion of both the typical (67.1%) and the atypical (80.6%) groups reached remission. The atypical group was 2.6 (95% CI = 1.1 to 6.2) times more likely to remit than the typical group after adjustment for age, psychosis, gender, clinical site, and depression severity based on the HAM-D24. Conclusion Acute ECT is an efficacious treatment for depressed patients with typical or atypical symptom features. PMID:18278988

Atypical antipsychotics, insulin resistance and weight; a meta-analysis of healthy volunteer studies.

PubMed

Burghardt, Kyle J; Seyoum, Berhane; Mallisho, Abdullah; Burghardt, Paul R; Kowluru, Renu A; Yi, Zhengping

2018-04-20

Atypical antipsychotics increase the risk of diabetes and cardiovascular disease through their side effects of insulin resistance and weight gain. The populations for which atypical antipsychotics are used carry a baseline risk of metabolic dysregulation prior to medication which has made it difficult to fully understand whether atypical antipsychotics cause insulin resistance and weight gain directly. The purpose of this work was to conduct a systematic review and meta-analysis of atypical antipsychotic trials in healthy volunteers to better understand their effects on insulin sensitivity and weight gain. Furthermore, we aimed to evaluate the occurrence of insulin resistance with or without weight gain and with treatment length by using subgroup and meta-regression techniques. Overall, the meta-analysis provides evidence that atypical antipsychotics decrease insulin sensitivity (standardized mean difference=-0.437, p<0.001) and increase weight (standardized mean difference=0.591, p<0.001) in healthy volunteers. It was found that decreases in insulin sensitivity were potentially dependent on treatment length but not weight gain. Decreases in insulin sensitivity occurred in multi-dose studies <13days while weight gain occurred in studies 14days and longer (max 28days). These findings provide preliminary evidence that atypical antipsychotics cause insulin resistance and weight gain directly, independent of psychiatric disease and may be associated with length of treatment. Further, well-designed studies to assess the co-occurrence of insulin resistance and weight gain and to understand the mechanisms and sequence by which they occur are required. Copyright © 2018 Elsevier Inc. All rights reserved.

Recognition of Atypical Symptoms of Acute Myocardial Infarction: Development and Validation of a Risk Scoring System.

PubMed

Li, Polly W C; Yu, Doris S F

Atypical symptom presentation in patients with acute myocardial infarction (AMI) is associated with longer delay in care seeking and poorer prognosis. Symptom recognition in these patients is a challenging task. Our purpose in this risk prediction model development study was to develop and validate a risk scoring system for estimating cumulative risk for atypical AMI presentation. A consecutive sample was recruited for the developmental (n = 300) and validation (n = 97) cohorts. Symptom experience was measured with the validated Chinese version of the Symptoms of Acute Coronary Syndromes Inventory. Potential predictors were identified from the literature. Multivariable logistic regression was performed to identify significant predictors. A risk scoring system was then constructed by assigning weights to each significant predictor according to their b coefficients. Five independent predictors for atypical symptom presentation were older age (≥75 years), female gender, diabetes mellitus, history of AMI, and absence of hyperlipidemia. The Hosmer and Lemeshow test (χ6 = 4.47, P = .62) indicated that this predictive model was adequate to predict the outcome. Acceptable discrimination was demonstrated, with area under the receiver operating characteristic curve as 0.74 (95% confidence interval, 0.67-0.82) (P < .001). The predictive power of this risk scoring system was confirmed in the validation cohort. Atypical AMI presentation is common. A simple risk scoring system developed on the basis of the 5 identified predictors can raise awareness of atypical AMI presentation and promote symptom recognition by estimating the cumulative risk for an individual to present with atypical AMI symptoms.

Atypical antipsychotics for psychosis in adolescents.

PubMed

Kumar, Ajit; Datta, Soumitra S; Wright, Stephen D; Furtado, Vivek A; Russell, Paul S

2013-10-15

Schizophrenia often presents in adolescence, but current treatment guidelines are based largely on studies of adults with psychosis. Over the past decade, the number of studies on treatment of adolescent-onset psychosis has increased. The current systematic review collates and critiques evidence obtained on the use of various atypical antipsychotic medications for adolescents with psychosis. To investigate the effects of atypical antipsychotic medications in adolescents with psychosis. We reviewed in separate analyses various comparisons of atypical antipsychotic medications with placebo or a typical antipsychotic medication or another atypical antipsychotic medication or the same atypical antipsychotic medication but at a lower dose. We searched the Cochrane Schizophrenia Group Register (October 2011), which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies and contacted study authors and relevant pharmaceutical companies to ask for more information. We included all relevant randomised controlled trials (RCTs) that compared atypical antipsychotic medication with placebo or another pharmacological intervention or with psychosocial interventions, standard psychiatric treatment or no intervention in children and young people aged 13 to 18 years with a diagnosis of schizophrenia, schizoaffective disorder, acute and transient psychoses or unspecified psychosis. We included studies published in English and in other languages that were available in standardised databases. Review authors AK and SSD selected the studies, rated the quality of the studies and performed data extraction. For dichotomous data, we estimated risk ratios (RRs) with 95% confidence intervals (CIs) using a fixed-effect model. When possible, for binary data presented in the 'Summary of findings' table, we calculated illustrative comparative risks. We summated continuous data using the mean difference (MD). Risk of bias was assessed for included studies. We included 13 RCTs, with a total of 1112 participants. We found no data on service utilisation, economic outcomes, behaviour or cognitive response. Trials were classified into the following groups. 1. Atypical antipsychotics versus placebo: Only two studies compared one atypical antipsychotic medication with placebo. In one study, the number of non-responders treated with olanzapine was not different from the number treated with placebo (1 RCT, n = 107, RR 0.84, 95% CI 0.65 to 1.10); however, significantly more (57% vs 32%) people left the study early (1 RCT, n = 107, RR 0.56, 95% CI 0.36 to 0.87) from the placebo group compared with the olanzapine group. With regard to adverse effects, young people treated with aripiprazole had significantly lower serum cholesterol compared with those given placebo (1 RCT, n = 302, RR 3.77, 95% CI 1.88 to 7.58). 2. Atypical antipsychotics versus typical antipsychotics: When the findings of all five trials comparing atypical antipsychotic medications with a typical antipsychotic medication were collated, no difference in the mean end point Brief Psychiatric Rating Scale (BPRS) score was noted between the two arms (5 RCTs, n = 236, MD -1.08, 95% CI -3.08 to 0.93). With regard to adverse effects, the mean end point serum prolactin concentration was much higher than the reference range for treatment with risperidone, olanzapine and molindone in one of the studies. However, fewer adolescents who were receiving atypical antipsychotic medications left the study because of adverse effects (3 RCTs, n = 187, RR 0.65, 95% CI 0.36 to 1.15) or for any reason (3 RCTs, n = 187, RR 0.62, 95% CI 0.39 to 0.97).3. One atypical antipsychotic versus another atypical antipsychotic: The mean end point BPRS score was not significantly different for people who received risperidone compared with those who received olanzapine; however, the above data were highly skewed. Overall no difference was noted in the number of people leaving the studies early because of any adverse effects between each study arm in the three studies comparing olanzapine and risperidone (3 RCTs, n = 130, RR 1.15, 95% CI 0.44 to 3.04). Specific adverse events were not reported uniformly across the six different studies included in this section of the review; therefore it was difficult to do a head-to-head comparison of adverse events for different atypical antipsychotic medications.4. Lower-dose atypical antipsychotic versus standard/higher-dose atypical antipsychotic: Three studies reported comparisons of lower doses of the atypical antipsychotic medication with standard/higher doses of the same medication. One study reported better symptom reduction with a standard dose of risperidone as compared with a low dose (1 RCT, n = 257, RR -8.00, 95% CI -13.75 to -2.25). In another study, no difference was reported in the number of participants not achieving remission between the group receiving 10 mg/d and those who received 30 mg/d of aripiprazole (1 RCT, n = 196, RR 0.84, 95% CI 0.48 to 1.48). Similarly in the other study, authors reported no statistically significant difference in clinical response between the two groups receiving lower-dose (80 mg/d) and higher-dose (160 mg/d) ziprasidone, as reflected by the mean end point BPRS score (1 RCT, n = 17, MD -4.40, 95% CI -19.20 to 10.40). No convincing evidence suggests that atypical antipsychotic medications are superior to typical medications for the treatment of adolescents with psychosis. However, atypical antipsychotic medications may be more acceptable to young people because fewer symptomatic adverse effects are seen in the short term. Little evidence is available to support the superiority of one atypical antipsychotic medication over another, but side effect profiles are different for different medications. Treatment with olanzapine, risperidone and clozapine is often associated with weight gain. Aripiprazole is not associated with increased prolactin or with dyslipidaemia. Adolescents may respond better to standard-dose as opposed to lower-dose risperidone, but for aripiprazole and ziprasidone, lower doses may be equally effective. Future trials should ensure uniform ways of reporting.

[Modern tendencies in treatment of atypical glandular hyperplasia--our and foreign experience].

PubMed

Ivanov, S; Kovachev, E; Tsonev, A; Abbud, A

2010-01-01

Our aim was to summarize our and foreign experience in the field of diagnosis, progression and modern treatment of precancer of the endometrium-the atypical glandular hyperplasia. We researched 750 cases with glandular and atypical glandular hyperplasia for 10 years period (2000-2010). The hyperplasia were followed up for progression from glandular hyperplasia into atypical glandular hyperplasia and early endometrial cancer. The hyperplasias were evaluated with or without progestagen hormonal therapy. All patients were treated by D&C before and after the hormonal treatment. The main symptom in all patients was the postmenopausal bleeding (72% from the cases). In 90% of the patients (675) there was obesity. Exogenous use of estrogens was found in 30% (225) of the patients. The cases with complex hyperplasia in 12% (65/525) progressed into atypical glandular hyperplasia and in 4% (21/525) progressed into endometrial cancer. The patients with atypical glandular hyperplasia in 60% (90/150) progressed into endometrial cancer. Remission was observed in 70% of the patients (194/278) with glandular hyperplasia and progestagen treatment. The remission was detected by the golden standart (D&C). The patients without hormonal treatment and with complex glandular hyperplasia have in 15% (37/247) remission. Except with progestagen therapy, we have also 15 patients treated with GnRh-analogs (Zoladex a 3.6 mg) for 3-6 months. For them we have 80% (12/15) remission. The glandular hyperplasia without atypical cells can be influenced by the hormonal treatment with progestagens and GnRh-analogs. Nevertheless this hormonal treatment--before and after we have to perform D&C and to follow up patients by ultrasound measuring the endometrial thickness. If the fertility plans of the patients are over and if they are in postmenopause with histological result from D&C-atypical glandular hyperplasia--we have to treat them more radically with simple total hysterectomy.

Diagnostic accuracy of atypical p-ANCA in autoimmune hepatitis using ROC- and multivariate regression analysis.

PubMed

Terjung, B; Bogsch, F; Klein, R; Söhne, J; Reichel, C; Wasmuth, J-C; Beuers, U; Sauerbruch, T; Spengler, U

2004-09-29

Antineutrophil cytoplasmic antibodies (atypical p-ANCA) are detected at high prevalence in sera from patients with autoimmune hepatitis (AIH), but their diagnostic relevance for AIH has not been systematically evaluated so far. Here, we studied sera from 357 patients with autoimmune (autoimmune hepatitis n=175, primary sclerosing cholangitis (PSC) n=35, primary biliary cirrhosis n=45), non-autoimmune chronic liver disease (alcoholic liver cirrhosis n=62; chronic hepatitis C virus infection (HCV) n=21) or healthy controls (n=19) for the presence of various non-organ specific autoantibodies. Atypical p-ANCA, antinuclear antibodies (ANA), antibodies against smooth muscles (SMA), antibodies against liver/kidney microsomes (anti-Lkm1) and antimitochondrial antibodies (AMA) were detected by indirect immunofluorescence microscopy, antibodies against the M2 antigen (anti-M2), antibodies against soluble liver antigen (anti-SLA/LP) and anti-Lkm1 by using enzyme linked immunosorbent assays. To define the diagnostic precision of the autoantibodies, results of autoantibody testing were analyzed by receiver operating characteristics (ROC) and forward conditional logistic regression analysis. Atypical p-ANCA were detected at high prevalence in sera from patients with AIH (81%) and PSC (94%). ROC- and logistic regression analysis revealed atypical p-ANCA and SMA, but not ANA as significant diagnostic seromarkers for AIH (atypical p-ANCA: AUC 0.754+/-0.026, odds ratio [OR] 3.4; SMA: 0.652+/-0.028, OR 4.1). Atypical p-ANCA also emerged as the only diagnostically relevant seromarker for PSC (AUC 0.690+/-0.04, OR 3.4). None of the tested antibodies yielded a significant diagnostic accuracy for patients with alcoholic liver cirrhosis, HCV or healthy controls. Atypical p-ANCA along with SMA represent a seromarker with high diagnostic accuracy for AIH and should be explicitly considered in a revised version of the diagnostic score for AIH.

Evolution of A-Type Macrosegregation in Large Size Steel Ingot After Multistep Forging and Heat Treatment

NASA Astrophysics Data System (ADS)

Loucif, Abdelhalim; Ben Fredj, Emna; Harris, Nathan; Shahriari, Davood; Jahazi, Mohammad; Lapierre-Boire, Louis-Philippe

2018-03-01

A-type macrosegregation refers to the channel chemical heterogeneities that can be formed during solidification in large size steel ingots. In this research, a combination of experiment and simulation was used to study the influence of open die forging parameters on the evolution of A-type macrosegregation patterns during a multistep forging of a 40 metric ton (MT) cast, high-strength steel ingot. Macrosegregation patterns were determined experimentally by macroetch along the longitudinal axis of the forged and heat-treated ingot. Mass spectroscopy, on more than 900 samples, was used to determine the chemical composition map of the entire longitudinal sectioned surface. FORGE NxT 1.1 finite element modeling code was used to predict the effect of forging sequences on the morphology evolution of A-type macrosegregation patterns. For this purpose, grain flow variables were defined and implemented in a large scale finite element modeling code to describe oriented grains and A-type segregation patterns. Examination of the A-type macrosegregation showed four to five parallel continuous channels located nearly symmetrical to the axis of the forged ingot. In some regions, the A-type patterns became curved or obtained a wavy form in contrast to their straight shape in the as-cast state. Mass spectrometry analysis of the main alloying elements (C, Mn, Ni, Cr, Mo, Cu, P, and S) revealed that carbon, manganese, and chromium were the most segregated alloying elements in A-type macrosegregation patterns. The observed differences were analyzed using thermodynamic calculations, which indicated that changes in the chemical composition of the liquid metal can affect the primary solidification mode and the segregation intensity of the alloying elements. Finite element modeling simulation results showed very good agreement with the experimental observations, thereby allowing for the quantification of the influence of temperature and deformation on the evolution of the shape of the macrosegregation channels during the open die forging process.

The Extracellular Domain of Myelin Oligodendrocyte Glycoprotein Elicits Atypical Experimental Autoimmune Encephalomyelitis in Rat and Macaque Species

PubMed Central

Curtis, Alan D.; Taslim, Najla; Reece, Shaun P.; Grebenciucova, Elena; Ray, Richard H.; Rosenbaum, Matthew D.; Wardle, Robert L.; Van Scott, Michael R.; Mannie, Mark D.

2014-01-01

Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund’s adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund’s adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6–7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and brainstem, and atypical disease induction. PMID:25303101

The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

PubMed

Curtis, Alan D; Taslim, Najla; Reece, Shaun P; Grebenciucova, Elena; Ray, Richard H; Rosenbaum, Matthew D; Wardle, Robert L; Van Scott, Michael R; Mannie, Mark D

2014-01-01

Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund's adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and brainstem, and atypical disease induction.

[Surgical treatment of precancer and cancer of endometrium].

PubMed

Ivanov, S; Khadzhiolov, N; Batashki, I

2007-01-01

Our aim was to evaluate occult presence of endometrial cancer in patients with atypical glandular hiperplasia and to compare the histological prognostic factors according to the status of the lymph nodes and the grading of the occult tumour. 306 patients were evaluated retrospectvely for the period of 1990-2007. They were operated one month after the hostological diagnostic atypical glandular hiperplasia obtained by D&C. All patients were with vaginal bleeding. The patients who had concomitant presence of endometrial hyperplasia and endometrial cancer were excluded from the study. One hundred patients (group A) with atypical glandular hyperplasia were compared with 206 patients (group B) without atypical glandular hyperplasia obtained by D&C. Mann and Witney test and chi-square test were used for statistical evaluation.. There was no difference between the age and the menopausal status in the two groups, only there was higher parity in group B. In group A patients with atypical glandular hyperlasia we found in 50% endometrial cancer intraoperatively, in 40% endometrial hyperplasia and in 10% normal endometrium. In the second group B were included the patients without atypical hyperplasia from D&C. In group B were found in 6% endometrial cancer in 44% endometrial hyperplasia and in 50% normal endometrium. In 30 patients was performed complete surgical staging. Six patients were with metastatic lymph nodes. All of them were with grading 2 (4 patients) and grading 3 (2 patients), and also with infiltration in the lymph-vascular spaces. Four patients were with nonendometrioid tumours (type 2 endometrial cancer). The careful preoperative and intraoperative evaluation of the endometrium is very important in patients with atypical glandular hyperplasia. It is reasonable to use frozen section in the time of hysterectomy for patients with atypical glandular hyperplasia. If tumour with grading 2/3 nonendometrioid cancer with lymph-vascular space invasion, is found-complete surgical staging is needed.

From appearance to essence: 10 years review of atypical amniotic fluid embolism.

PubMed

Shen, Fangrong; Wang, Lu; Yang, Weiwen; Chen, Youguo

2016-02-01

Amniotic fluid embolism (AFE) is an unpredictable and unpreventable complication of maternity. The presentation may range from relatively subtle clinical events to sudden maternal cardiac arrest. However, the neglected diagnosis of non-classical form of AFE (atypical AFE) is very common. The aim of this study was to examine population-based regional data from Suzhou, China. Based on the analysis of all available case reports, we put forward an outline of atypical AFE and investigate whether any variation identified could be ascribed to methodology. Retrospective study from January 2004 to December 2013, 53 cases was identified from the database of Center for Disease Control (CDC) in the city of Suzhou. We investigated the presentations of atypical AFE and maternal characteristics with potential factors underlying AFE. Multiple-regression analysis was used to calculate adjusted odds ratios (ORs) and 95 % confidence intervals (CIs). The incidence of AFE was 6.91 per 100,000 deliveries (53/766,895). Seventeen deaths occurred, a mortality rate of 32 %. Atypical AFE may as the earlier stage or mild form of AFE, there was no death case in the study with timely remedy. The atypical AFE appear is obstetric hemorrhage and/or pulmonary and renal dysfunction postpartum. Hyperfibrinolysis and coagulopathy may the early laboratory findings of atypical AFE. Atypical and classical AFE shared the same risks, such as advanced maternal age, placental abnormalities, operative deliveries, eclampsia, cervical lacerations, and induction of labor. Staying alert to premonitory symptoms of AFE is critical to turn it to a remediable disease. Patient complaints such as breathlessness, chest pain, feeling cold, distress, panic, a feeling of nausea, and vomiting should elicit close attention. The management of a suspected episode of amniotic fluid embolism is generally considered to be supportive. Hysterectomy must be performed if there is further progression of symptoms. Due to advances in acute care, mortality has decreased in recent years, highlighting the importance of early detection and treatment.

Evolution of A-Type Macrosegregation in Large Size Steel Ingot After Multistep Forging and Heat Treatment

NASA Astrophysics Data System (ADS)

Loucif, Abdelhalim; Ben Fredj, Emna; Harris, Nathan; Shahriari, Davood; Jahazi, Mohammad; Lapierre-Boire, Louis-Philippe

2018-06-01

A-type macrosegregation refers to the channel chemical heterogeneities that can be formed during solidification in large size steel ingots. In this research, a combination of experiment and simulation was used to study the influence of open die forging parameters on the evolution of A-type macrosegregation patterns during a multistep forging of a 40 metric ton (MT) cast, high-strength steel ingot. Macrosegregation patterns were determined experimentally by macroetch along the longitudinal axis of the forged and heat-treated ingot. Mass spectroscopy, on more than 900 samples, was used to determine the chemical composition map of the entire longitudinal sectioned surface. FORGE NxT 1.1 finite element modeling code was used to predict the effect of forging sequences on the morphology evolution of A-type macrosegregation patterns. For this purpose, grain flow variables were defined and implemented in a large scale finite element modeling code to describe oriented grains and A-type segregation patterns. Examination of the A-type macrosegregation showed four to five parallel continuous channels located nearly symmetrical to the axis of the forged ingot. In some regions, the A-type patterns became curved or obtained a wavy form in contrast to their straight shape in the as-cast state. Mass spectrometry analysis of the main alloying elements (C, Mn, Ni, Cr, Mo, Cu, P, and S) revealed that carbon, manganese, and chromium were the most segregated alloying elements in A-type macrosegregation patterns. The observed differences were analyzed using thermodynamic calculations, which indicated that changes in the chemical composition of the liquid metal can affect the primary solidification mode and the segregation intensity of the alloying elements. Finite element modeling simulation results showed very good agreement with the experimental observations, thereby allowing for the quantification of the influence of temperature and deformation on the evolution of the shape of the macrosegregation channels during the open die forging process.

Atypical performance patterns on Delis-Kaplan Executive Functioning System Color-Word Interference Test: Cognitive switching and learning ability in older adults.

PubMed

Berg, Jody-Lynn; Swan, Natasha M; Banks, Sarah J; Miller, Justin B

2016-09-01

Cognitive set shifting requires flexible application of lower level processes. The Delis-Kaplan Executive Functioning System (DKEFS) Color-Word Interference Test (CWIT) is commonly used to clinically assess cognitive set shifting. An atypical pattern of performance has been observed on the CWIT; a subset of individuals perform faster, with equal or fewer errors, on the more difficult inhibition/switching than the inhibition trial. This study seeks to explore the cognitive underpinnings of this atypical pattern. It is hypothesized that atypical patterns on CWIT will be associated with better performance on underlying cognitive measures of attention, working memory, and learning when compared to typical CWIT patterns. Records from 239 clinical referrals (age: M = 68.09 years, SD = 10.62; education: M = 14.87 years, SD = 2.73) seen for a neuropsychological evaluation as part of diagnostic work up in an outpatient dementia and movement disorders clinic were sampled. The standard battery of tests included measures of attention, learning, fluency, executive functioning, and working memory. Analyses of variance (ANOVAs) were conducted to compare the cognitive performance of those with typical versus atypical CWIT patterns. An atypical pattern of performance was confirmed in 23% of our sample. Analyses revealed a significant group difference in acquisition of information on both nonverbal (Brief Visuospatial Memory Test-Revised, BVMT-R total recall), F(1, 213) = 16.61, p < .001, and verbal (Hopkins Verbal Learning Test-Revised, HVLT-R total recall) learning tasks, F(1, 181) = 6.43, p < .01, and semantic fluency (Animal Naming), F(1, 232) = 7.57, p = .006, with the atypical group performing better on each task. Effect sizes were larger for nonverbal (Cohen's d = 0.66) than verbal learning (Cohen's d = 0.47) and semantic fluency (Cohen's d = 0.43). Individuals demonstrating an atypical pattern of performance on the CWIT inhibition/switching trial also demonstrated relative strengths in semantic fluency and learning.

KChIP1 modulation of Kv4.3-mediated A-type K(+) currents and repetitive firing in hippocampal interneurons.

PubMed

Bourdeau, M L; Laplante, I; Laurent, C E; Lacaille, J-C

2011-03-10

Neuronal A-type K(+) channels regulate action potential waveform, back-propagation and firing frequency. In hippocampal CA1 interneurons located at the stratum lacunosum-moleculare/radiatum junction (LM/RAD), Kv4.3 mediates A-type K(+) currents and a Kv4 β-subunit of the Kv channel interacting protein (KChIP) family, KChIP1, appears specifically expressed in these cells. However, the functional role of this accessory subunit in A-type K(+) currents and interneuron excitability remains largely unknown. Thus, first we studied KChIP1 and Kv4.3 channel interactions in human embryonic kidney 293 (HEK293) cells and determined that KChIP1 coexpression modulated the biophysical properties of Kv4.3 A-type currents (faster recovery from inactivation, leftward shift of activation curve, faster rise time and slower decay) and this modulation was selectively prevented by KChIP1 short interfering RNA (siRNA) knockdown. Next, we evaluated the effects of KChIP1 down-regulation by siRNA on A-type K(+) currents in LM/RAD interneurons in slice cultures. Recovery from inactivation of A-type K(+) currents was slower after KChIP1 down-regulation but other properties were unchanged. In addition, down-regulation of KChIP1 levels did not affect action potential waveform and firing, but increased firing frequency during suprathreshold depolarizations, indicating that KChIP1 regulates interneuron excitability. The effects of KChIP1 down-regulation were cell-specific since CA1 pyramidal cells that do not express KChIP1 were unaffected. Overall, our findings suggest that KChIP1 interacts with Kv4.3 in LM/RAD interneurons, enabling faster recovery from inactivation of A-type currents and thus promoting stronger inhibitory control of firing during sustained activity. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

A-type and I-type granitoids and mylonitic granites of Hassan Salaran area of SE Saqqez, Kurdistan, Iran

NASA Astrophysics Data System (ADS)

Abdullah, Fakhraddin Mohammad; Saeed Ahmad, Sheler

2014-05-01

The Hassan Salarn area is located 20km to southeast of Saqqez city in Kurdistan Province, western Iran. In this area there are two distinct granitic rock suites consisting A-type and I-type granites and also mylonitic granites. These A-type and I-type granites have various petrological and geochemical characteristics. They also have different origins and petrogenesis. A-type granitoids comprise alkali feldspar granite, syenogranite and quartz alkali feldspar syenite, whereas I-type granitoids are composed of monzogranite, granodiorite and tonalite. Geochemically, A-type granitoids are peralkaline and acmite-normative but I-type granitoids are subalkaline (calc-alkaline), metaluminous and diopside-normative. A-type granitoids are also ferroan alkali and ferroan alkali-calcic whereas I-type granitoids are magnesian and calcic. A-type granitoids resemble to within plate granites and post-orogenic granites whereas I-type granitoids resemble to volcanic arc granites. A-type granitoids contain higher concentrations of alkalies, Zr, Rb, Nb, Y, Th, Ce, high FeO/MgO ratios and lower concentrations of Mg, Ca and Sr, resembling post-orogenic A-type granites. It is possible that heat from a mantle-derived magma which intruded into the lower crust, and/or rapid crustal extension have been essential generation of approriate melts producing A-type granitoids. Thus we can conclude that A-type granitoids were generated from a mixed mantle-crust source. Negative Nb anomalies and low contents of Ti and P probably indicate a subduction-related origin for protolith of I-type granitoids. Negative Nb anomalies and enrichment in Ce relative to its adjacent elements can be related to involvement of continental crust in magmatic processes. I-type granitoids are also enriched in Rb, Ba, K, Th, Ce and depleted in Nb, Zr and Y, indicating that they have had interacted with crust. I-type granitoids may result from contamination of mantle-derived magmas by continental crust during a subduction event. The mylonitic granites are elongated masses with a NE-SW trend and their contacts with the A-type and I-type granitoids are fault contact. Hand specimens have a layered appearance with green bands made from chlorite and epidote and grey to white bands with quartz and feldspar. These rocks contain plagioclase, quartz and orthoclase under the microscope. Also fine-grained minerals such as quartz, sericite, epidote, chlorite and opaque minerals make the groundmass wrapping the porphyroclasts. Pressure shadows around porphyroclasts of plagioclase and quartz and crystallization of fine-grained quartz and sericite in these places along with intense alteration of plagioclase to epidote and sericite, existence of quartz with different sizes, andaluse extinction in quartz crystals, and elongation of chlorites, resulted from dynamic recrystallisation of biotites all indicate effect of stresses on the rocks. Considering the similar mineralogical composition of the mylonitic rocks with I-type granitoid, it could be concluded that the granodioritic magma, after intrusion and solidification, is changed to mylonite in a shear zone due to tectonical forces.

SU-D-202-03: Statistical Segmentation On Quantitative CT for Assessing Spatial Tumor Response During Radiation Therapy Delivery

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

Schott, D; Chen, X; Klawikowski, S

2016-06-15

Purpose: Develop a method to segment regions of interest (ROIs) in tumor with statistically similar Hounsfield unit (HU) values and/or HU changes during chemoradiation therapy (CRT) delivery, to assess spatial tumor treatment response based on daily CTs during CRT delivery. Methods: Generate a three region map of ROIs with differential HUs, by sampling neighboring voxels around a selected voxel and comparing to the mean of the entire ROI using a t-test. The cumulative distribution function, P, is calculated from the t-test. The P value is assigned to be the value at the selected voxel, and this is repeated over allmore » voxels in the initial ROI. Three regions are defined as: (1-P) < 0.00001 (mid region), and 0.00001 < (1-P) (mean greater than baseline and mean lower than baseline). The test is then expanded to compare daily CT sets acquired during routine CT-guided RT delivery using a CT-on-rails. The first fraction CT is used as the baseline for comparison. We tested 15 pancreatic head tumor cases undergoing CRT, to identify the ROIs and changes corresponding to normal, fibrotic, and tumor tissue. The obtained ROIs were compared with MRI-ADC maps acquired pre- and post-CRT. Results: The ROIs in 13 out of 15 patients’ first fraction CTs and pre-CRT MRIs matched the general region and slices covered, as well as in 6 out of the 9 patients with post-CRT MRIs. The high HU region designated by the t-test was seen to correlate with the tumor region in MR, and these ROIs are positioned within the same region over the course of treatment. In patients with poorly delineated tumors in MR, the t-test was inconclusive. Conclusion: The proposed statistical segmentation technique shows the potential to identify regions in tumor with differential HUs and HU changes during CRT delivery for patients with pancreas head cancer.« less

Exhaled volatile substances mirror clinical conditions in pediatric chronic kidney disease

PubMed Central

Obermeier, Juliane; Trefz, Phillip; Happ, Josephine; Schubert, Jochen K.; Staude, Hagen

2017-01-01

Monitoring metabolic adaptation to chronic kidney disease (CKD) early in the time course of the disease is challenging. As a non-invasive technique, analysis of exhaled breath profiles is especially attractive in children. Up to now, no reports on breath profiles in this patient cohort are available. 116 pediatric subjects suffering from mild-to-moderate CKD (n = 48) or having a functional renal transplant KTx (n = 8) and healthy controls (n = 60) matched for age and sex were investigated. Non-invasive quantitative analysis of exhaled breath profiles by means of a highly sensitive online mass spectrometric technique (PTR-ToF) was used. CKD stage, the underlying renal disease (HUS; glomerular diseases; abnormalities of kidney and urinary tract or polycystic kidney disease) and the presence of a functional renal transplant were considered as classifiers. Exhaled volatile organic compound (VOC) patterns differed between CKD/ KTx patients and healthy children. Amounts of ammonia, ethanol, isoprene, pentanal and heptanal were higher in patients compared to healthy controls (556, 146, 70.5, 9.3, and 5.4 ppbV vs. 284, 82.4, 49.6, 5.30, and 2.78 ppbV). Methylamine concentrations were lower in the patient group (6.5 vs 10.1 ppbV). These concentration differences were most pronounced in HUS and kidney transplanted patients. When patients were grouped with respect to degree of renal failure these differences could still be detected. Ammonia accumulated already in CKD stage 1, whereas alterations of isoprene (linked to cholesterol metabolism), pentanal and heptanal (linked to oxidative stress) concentrations were detectable in the breath of patients with CKD stage 2 to 4. Only weak associations between serum creatinine and exhaled VOCs were noted. Non-invasive breath testing may help to understand basic mechanisms and metabolic adaptation accompanying progression of CKD. Our results support the current notion that metabolic adaptation occurs early during the time course of CKD. PMID:28570715

Oral Intoxication of Mice with Shiga Toxin Type 2a (Stx2a) and Protection by Anti-Stx2a Monoclonal Antibody 11E10

PubMed Central

Russo, L. M.; Melton-Celsa, A. R.; Smith, M. A.; Smith, M. J.

2014-01-01

Shiga toxin (Stx)-producing Escherichia coli (STEC) strains cause food-borne outbreaks of hemorrhagic colitis and, less commonly, a serious kidney-damaging sequela called the hemolytic uremic syndrome (HUS). Stx, the primary virulence factor expressed by STEC, is an AB5 toxin with two antigenically distinct forms, Stx1a and Stx2a. Although both toxins have similar biological activities, Stx2a is more frequently produced by STEC strains that cause HUS than is Stx1a. Here we asked whether Stx1a and Stx2a act differently when delivered orally by gavage. We found that Stx2a had a 50% lethal dose (LD50) of 2.9 μg, but no morbidity occurred after oral intoxication with up to 157 μg of Stx1a. We also compared several biochemical and histological parameters in mice intoxicated orally versus intraperitoneally with Stx2a. We discovered that both intoxication routes caused similar increases in serum creatinine and blood urea nitrogen, indicative of kidney damage, as well as electrolyte imbalances and weight loss in the animals. Furthermore, kidney sections from Stx2a-intoxicated mice revealed multifocal, acute tubular necrosis (ATN). Of particular note, we detected Stx2a in kidney sections from orally intoxicated mice in the same region as the epithelial cell type in which ATN was detected. Lastly, we showed reduced renal damage, as determined by renal biomarkers and histopathology, and full protection of orally intoxicated mice with monoclonal antibody (MAb) 11E10 directed against the toxin A subunit; conversely, an irrelevant MAb had no therapeutic effect. Orally intoxicated mice could be rescued by MAb 11E10 6 h but not 24 h after Stx2a delivery. PMID:24379294

Shiga Toxin 2 and Lipopolysaccharide Induce Human Microvascular Endothelial Cells To Release Chemokines and Factors That Stimulate Platelet Function

PubMed Central

Guessous, Fadila; Marcinkiewicz, Marek; Polanowska-Grabowska, Renata; Kongkhum, Sudawadee; Heatherly, Daniel; Obrig, Tom; Gear, Adrian R. L.

2005-01-01

Shiga toxins (Stxs) produced by Shigella dysenteriae type 1 and enterohemorrhagic Escherichia coli are the most common cause of hemolytic-uremic syndrome (HUS). It is well established that vascular endothelial cells, mainly those located in the renal microvasculature, are targets for Stxs. The aim of the present research was to evaluate whether E. coli-derived Shiga toxin 2 (Stx2) incubated with human microvascular endothelial cells (HMEC-1) induces release of chemokines and other factors that might stimulate platelet function. HMEC-1 were exposed for 24 h in vitro to Stx2, lipopolysaccharide (LPS), or the Stx2-LPS combination, and chemokine production was assessed by immunoassay. More interleukin-8 was released than stromal cell-derived factor 1α (SDF-1α) or SDF-1β and RANTES. The Stx2-LPS combination potentiated chemokine release, but Stx2 alone caused more release of SDF-1α at 24 h than LPS or Stx2-LPS did. In the presence of low ADP levels, HMEC-1 supernatants activated platelet function assessed by classical aggregometry, single-particle counting, granule secretion, P-selectin exposure, and the formation of platelet-monocyte aggregates. Supernatants from HMEC-1 exposed only to Stx2 exhibited enhanced exposure of platelet P-selectin and platelet-THP-1 cell interactions. Blockade of platelet cyclooxygenase by indomethacin prevented functional activation. The chemokine RANTES enhanced platelet aggregation induced by SDF-1α, macrophage-derived chemokine, or thymus and activation-regulated chemokine in the presence of very low ADP levels. These data support the hypothesis that microvascular endothelial cells exposed to E. coli O157:H7-derived Stx2 and LPS release chemokines and other factors, which when combined with low levels of primary agonists, such as ADP, cause platelet activation and promote the renal thrombosis associated with HUS. PMID:16299328

Infection in burn patients in a referral center in Colombia.

PubMed

Ramirez-Blanco, Carlos Enrique; Ramirez-Rivero, Carlos Enrique; Diaz-Martinez, Luis Alfonso; Sosa-Avila, Luis Miguel

2017-05-01

Worldwide, burns are responsible for more than 300,000 deaths annually; infection is a major cause of morbidity and mortality in these patients. Early identification and treatment of infection improves outcome. Toward this end it's necessary to identify the institutions flora and organisms that most frequently produces infection. To characterize infections developed by burn patients hospitalized at the University Hospital of Santander (HUS). Burn patients hospitalized in the HUS from January 1 to December 2014 were followed. Medical information regarding infections, laboratory and pathology reports were obtained. Statistical analysis with measures of central tendency, proportions, global and specific incidence density plus overall and specific incidence was obtained. For the microbiological profile proportions were established. 402 burn patients were included, 234 (58.2%) men and 168 (41.8%) women, aged between 6 days and 83 years, median 12.5 years. The burn agents include scald (52.5%), fire (10.0%), gasoline (9.2%), electricity (7.5%), among others. Burn area ranged from 1% to 80% TBS. Cumulative mortality was 1.5%. 27.8% of burned patients had one or more infections. Identified infections include folliculitis (27.0%), urinary tract infection (19.0%), infection of the burn wound (10.4%), pneumonia (8.6%), Central venous catheter (7.4%), bloodstream infection (7.4%) and skin grafts infection (4.3%) among others. Bacteria were responsible for 88.5% of the cases and fungi 11.5%. The most frequently isolated germs were P. aeruginosa, A. baumannii, E. coli, S. aureus and K. pneumoniae. Most gram-negative bacteria were sensitive to Amikacin, gram positive bacteria were sensitive to multiple antibiotics. Burns is a severe trauma that occurs in adult and pediatric patients, has several causative agents and can compromise the patient's life. The burned patient is at risk for a variety of infections. According to the type of infection it is possible to infer the most common causative organisms and their antibiotic sensitivity/resistance which allow a directed early empiric treatment. Copyright © 2016. Published by Elsevier Ltd.

Real-Time PCR Assay for Detection and Differentiation of Shiga Toxin-Producing Escherichia coli from Clinical Samples

PubMed Central

Klein, Eileen J.; Galanakis, Emmanouil; Thomas, Anita A.; Stapp, Jennifer R.; Rich, Shannon; Buccat, Anne Marie; Tarr, Phillip I.

2015-01-01

Timely accurate diagnosis of Shiga toxin-producing Escherichia coli (STEC) infections is important. We evaluated a laboratory-developed real-time PCR (LD-PCR) assay targeting stx1, stx2, and rfbEO157 with 2,386 qualifying stool samples submitted to the microbiology laboratory of a tertiary care pediatric center between July 2011 and December 2013. Broth cultures of PCR-positive samples were tested for Shiga toxins by enzyme immunoassay (EIA) (ImmunoCard STAT! enterohemorrhagic E. coli [EHEC]; Meridian Bioscience) and cultured in attempts to recover both O157 and non-O157 STEC. E. coli O157 and non-O157 STEC were detected in 35 and 18 cases, respectively. Hemolytic uremic syndrome (HUS) occurred in 12 patients (10 infected with STEC O157, one infected with STEC O125ac, and one with PCR evidence of STEC but no resulting isolate). Among the 59 PCR-positive STEC specimens from 53 patients, only 29 (54.7%) of the associated specimens were toxin positive by EIA. LD-PCR differentiated STEC O157 from non-O157 using rfbEO157, and LD-PCR results prompted successful recovery of E. coli O157 (n = 25) and non-O157 STEC (n = 8) isolates, although the primary cultures and toxin assays were frequently negative. A rapid “mega”-multiplex PCR (FilmArray gastrointestinal panel; BioFire Diagnostics) was used retrospectively, and results correlated with LD-PCR findings in 25 (89%) of the 28 sorbitol-MacConkey agar culture-negative STEC cases. These findings demonstrate that PCR is more sensitive than EIA and/or culture and distinguishes between O157 and non-O157 STEC in clinical samples and that E. coli O157:H7 remains the predominant cause of HUS in our institution. PCR is highly recommended for rapid diagnosis of pediatric STEC infections. PMID:25926491

Genetic Relatedness and Novel Sequence Types of Non-O157 Shiga Toxin-Producing Escherichia coli Strains Isolated in Argentina.

PubMed

Cadona, Jimena S; Bustamante, Ana V; González, Juliana; Sanso, A Mariel

2016-01-01

Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen responsible for severe disease in humans such as hemolytic uremic syndrome (HUS) and cattle, the principal reservoir. Identification of the clones/lineages is important as several characteristics, among them propensity to cause disease varies with STEC phylogenetic origin. At present, we do not know what STEC clones, especially of non-O157:H7, are circulating in Argentina. To fill this knowledge gap we assessed the genetic diversity of STEC strains isolated in Argentina from various sources, mostly cattle and food, using multilocus sequence typing (MLST). Our objectives were to determine the phylogenetic relationships among strains and to compare them with strains from different geographic origins, especially with those from clinical human cases, in order to evaluate their potential health risk. A total of 59 STEC isolates from 41 serotypes were characterized by MLST. Analysis using EcMLST database identified 38 sequence types (ST), 17 (45%) of which were new STs detected in 18 serotypes. Fifteen out of 38 STs identified were grouped into 11 clonal groups (CGs) and, 23 not grouped in any of the defined CGs. Different STs were found in the same serotype. Results highlighted a high degree of phylogenetic heterogeneity among Argentinean strains and they showed that several cattle and food isolates belonged to the same STs that are commonly associated with clinical human cases in several geographical areas. STEC is a significant public health concern. Argentina has the highest incidence of HUS in the world and this study provides the first data about which STEC clones are circulating. Data showed that most of them might pose a serious zoonotic risk and this information is important for developing public health initiatives. However, the actual potential risk will be defined by the virulence profiles, which may differ among isolates belonging to the same ST.

A PKM Generated by Calpain Cleavage of a Classical PKC Is Required for Activity-Dependent Intermediate-Term Facilitation in the Presynaptic Sensory Neuron of "Aplysia"

ERIC Educational Resources Information Center

Farah, Carole A.; Hastings, Margaret H.; Dunn, Tyler W.; Gong, Katrina; Baker-Andresen, Danay; Sossin, Wayne S.

2017-01-01

Atypical PKM, a persistently active form of atypical PKC, is proposed to be a molecular memory trace, but there have been few examinations of the role of PKMs generated from other PKCs. We demonstrate that inhibitors used to inhibit PKMs generated from atypical PKCs are also effective inhibitors of other PKMs. In contrast, we demonstrate that…

Atypical H-Type Bovine Spongiform Encephalopathy in a Cow Born after the Reinforced Feed Ban on Meat-and-Bone Meal in Europe

PubMed Central

Guldimann, Claudia; Gsponer, Michaela; Drögemüller, Cord; Oevermann, Anna

2012-01-01

The significance of atypical bovine spongiform encephalopathies (BSE) in cattle for controlling the BSE epidemic is poorly understood. Here we report a case of atypical H-type BSE in a cow born after the implementation of the reinforced feed ban in Europe. This supports an etiology of H-type BSE unrelated to that of classical BSE. PMID:23035195

Impact of Modafinil Add-on with Atypical Anti-psychotics on Excessive Daytime Drowsiness

PubMed Central

Prasuna, P Lakshmi; Sudhakar, TP

2015-01-01

Background: Atypical antipsychotic drugs are known to cause many side effects which include daytime drowsiness. So many add on drugs are tried to reduce the same. Materials and Methods: 72 patients who were on atypical antipsychotic drugs were randomly assigned to either Modafinil or placebo and were followed for a period of 12 weeks. Daytime drowsiness, was taken at baseline, week 3, and at week 12 by using VAS, EDD scales. Results: The results were analyzed and showed that the Modafinil add on therapy significantly reduced the daytime Drowsiness. Conclusions: Modafinil could be a potential candidate in selected group of patients to decrease some of the unwanted adverse events like daytime drowsiness produced by atypical antipsychotics. PMID:26702168

Identification of atypical flight patterns

NASA Technical Reports Server (NTRS)

Statler, Irving C. (Inventor); Ferryman, Thomas A. (Inventor); Amidan, Brett G. (Inventor); Whitney, Paul D. (Inventor); White, Amanda M. (Inventor); Willse, Alan R. (Inventor); Cooley, Scott K. (Inventor); Jay, Joseph Griffith (Inventor); Lawrence, Robert E. (Inventor); Mosbrucker, Chris (Inventor)

2005-01-01

Method and system for analyzing aircraft data, including multiple selected flight parameters for a selected phase of a selected flight, and for determining when the selected phase of the selected flight is atypical, when compared with corresponding data for the same phase for other similar flights. A flight signature is computed using continuous-valued and discrete-valued flight parameters for the selected flight parameters and is optionally compared with a statistical distribution of other observed flight signatures, yielding atypicality scores for the same phase for other similar flights. A cluster analysis is optionally applied to the flight signatures to define an optimal collection of clusters. A level of atypicality for a selected flight is estimated, based upon an index associated with the cluster analysis.

Atypical choroid plexus papilloma: spontaneous resolution of diffuse leptomeningeal contrast enhancement after primary tumor removal in 2 pediatric cases.

PubMed

Scala, Marcello; Morana, Giovanni; Milanaccio, Claudia; Pavanello, Marco; Nozza, Paolo; Garrè, Maria Luisa

2017-09-01

Atypical choroid plexus papillomas can metastasize in the form of leptomeningeal seeding. Postoperative chemotherapy is the recommended first-line treatment when gross-total removal is not achieved or in cases of disseminated disease. Here the authors report on 2 children with atypical choroid plexus papillomas and MRI findings of diffuse leptomeningeal enhancement at diagnosis, later presenting with spontaneous resolution of the leptomeningeal involvement after removal of the primary lesions. Observations in this report expand our knowledge about the natural history and biological behavior of these tumors and highlight the role of close neuroimaging surveillance in the management of atypical choroid plexus papillomas in cases with MRI evidence of diffuse leptomeningeal enhancement at presentation.

Atypical Cutaneous Manifestations in Syphilis.

PubMed

Ivars Lleó, M; Clavo Escribano, P; Menéndez Prieto, B

2016-05-01

Although the diversity of the clinical manifestations of syphilis is well-known, atypical presentations can also occur. Such atypical presentations are associated with a high risk of transmission as a result of diagnostic confusion and treatment delays owing to the disease's ability to mimic other common skin diseases, deviate from classic clinical presentations, and adopt unique forms. Cases of atypical syphilis have been described most frequently in patients with concomitant human immunodeficiency virus (HIV) infection. Because the incidence of syphilis has been growing over recent years -particularly in patients with HIV co-infection- dermatologists need to be familiar with the less well-known clinical presentations of this venereal disease. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.

PubMed

Oliver, Dominik; Lien, Cheng-Chang; Soom, Malle; Baukrowitz, Thomas; Jonas, Peter; Fakler, Bernd

2004-04-09

Voltage-gated potassium (Kv) channels control action potential repolarization, interspike membrane potential, and action potential frequency in excitable cells. It is thought that the combinatorial association between distinct alpha and beta subunits determines whether Kv channels function as non-inactivating delayed rectifiers or as rapidly inactivating A-type channels. We show that membrane lipids can convert A-type channels into delayed rectifiers and vice versa. Phosphoinositides remove N-type inactivation from A-type channels by immobilizing the inactivation domains. Conversely, arachidonic acid and its amide anandamide endow delayed rectifiers with rapid voltage-dependent inactivation. The bidirectional control of Kv channel gating by lipids may provide a mechanism for the dynamic regulation of electrical signaling in the nervous system.

A rapid procedure for the detection and isolation of enterohaemorrhagic Escherichia coli (EHEC) serogroup O26, O103, O111, O118, O121, O145 and O157 strains and the aggregative EHEC O104:H4 strain from ready-to-eat vegetables.

PubMed

Tzschoppe, Markus; Martin, Annett; Beutin, Lothar

2012-01-03

Human infections with Enterohaemorrhagic Escherichia coli strains (EHEC) as agents of Haemorrhagic Colitis (HC) and Haemolytic Uraemic Syndrome (HUS) are frequently associated with the consumption of EHEC contaminated foodstuffs of different origins. EHEC O26, O103, O111, O118, O121, O145 and O157 strains are responsible for the majority of HC and HUS cases worldwide. In May 2011, the emerging aggregative EHEC O104:H4 strain caused a large outbreak with high HUS incidence in northern Germany. Contaminated sprouted seeds were suspected to be the vehicles of transmission. The examination of vegetables retailed for raw consumption revealed low numbers of E. coli (<100 cfu/g) together with high titres of Enterobacteriaceae and Pseudomonas (approx. 5.6 × 10⁷ cfu/g). Specific methods of EHEC detection adapted to vegetables are not yet published. Therefore, we have developed a rapid and sensitive method for detecting low EHEC contamination in vegetables (1-10 cfu/25 g) with artificially EHEC contaminated ready-to-eat salads. A 6-hour enrichment period in BRILA-broth was sufficient to detect 1-10 EHEC from spiked samples after plating 0.1 ml portions of enrichment culture on selective TBX-agar and CHROMagar STEC plates that were incubated at 44 °C overnight. Unlike EHEC strains, the growth of bacteria of the plant flora was substantially inhibited at 44 °C. DNA for real-time PCR detection of EHEC characteristic genes (stx(1), stx(2), eae, ehxA, and O-antigen associated) was prepared with bacteria grown on TBX-agar plates. The storage of EHEC inoculated salad samples for 72 h at 6 °C resulted in a significant reduction (mean value 14.6%) of detectable EHEC, suggesting interference of EHEC with the resident plant microflora. CHROMagar STEC was evaluated as a selective medium for the detection of EHEC strains. Growth on CHROMagar STEC was closely associated with EHEC O26:[H11], O111:[H8], O118:H16, O121:[H19], O145:[H28], O157:[H7] and aggregative EHEC O104:H4 strains and with the presence of the terB gene (tellurite resistance). TerB sequences were found in 87.2% of 235 EHEC but only in only 12.5% of 567 non-EHEC strains. EHEC strains which did not grow on CHROMagar STEC were negative for terB as frequently observed with EHEC O103:H2 (52.9%) and sorbitol-fermenting O157:NM strains (100%). The enrichment and detection method was applied in the examination of sprouted seeds incriminated as vehicles in the EHEC O104:H4 outbreak in Germany. Aggregative EHEC O104:H4 could be detected and isolated from a sample of sprouted seeds which was suspected as vector of transmission of EHEC O104 to humans. Copyright © 2011 Elsevier B.V. All rights reserved.

Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death

PubMed Central

Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Hall, Kathi; Stein, C. Michael

2009-01-01

Background Users of typical antipsychotics have increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which have largely replaced the older agents in clinical practice. Methods We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotics in a retrospective cohort of Tennessee Medicaid enrollees. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonuser controls. To assess residual confounding related to antipsychotic indication, we performed a secondary analysis of antipsychotic users with no baseline diagnosis of schizophrenia or related psychoses, propensity-score matched with nonusers. Results Current users of both typical and atypical antipsychotics had greater rates of sudden cardiac death than did nonusers of any antipsychotic, with adjusted incidence-rate ratios (IRRs) of 2.00 (95% CI, 1.69–2.35) and 2.27 (1.89–2.73), respectively. Former antipsychotic users had no significantly increased risk (IRR = 1.13 [0.98–1.30]). For both classes of drugs, the risk for current users increased significantly with dose. For typical antipsychotics the IRRs increased from 1.31 (0.97–1.77) for low doses to 2.42 (1.91–3.06) for high doses (p<.001). For atypical agents the IRRs increased from 1.59 (1.03–2.46) for low doses to 2.86 (2.25–3.65) for high doses (p=.015). The IRR for atypical vs typical antipsychotics was 1.14 (.93–1.39). Similar findings were present in the propensity-score matched cohort. Conclusion Current users of both typical and atypical antipsychotics had a similar, dose-related increased risk of sudden cardiac death. PMID:19144938

Atypical anticipatory postural adjustments during gait initiation among individuals with sub-acute stroke.

PubMed

Rajachandrakumar, Roshanth; Fraser, Julia E; Schinkel-Ivy, Alison; Inness, Elizabeth L; Biasin, Lou; Brunton, Karen; McIlroy, William E; Mansfield, Avril

2017-02-01

Anticipatory postural adjustments, executed prior to gait initiation, help preserve lateral stability when stepping. Atypical patterns of anticipatory activity prior to gait initiation may occur in individuals with unilateral impairment (e.g., stroke). This study aimed to determine the prevalence, correlates, and consequences of atypical anticipatory postural adjustment patterns prior to gait initiation in a sub-acute stroke population. Forty independently-ambulatory individuals with sub-acute stroke stood on two force plates and initiated gait at a self-selected speed. Medio-lateral centre of pressure displacement was calculated and used to define anticipatory postural adjustments (shift in medio-lateral centre of pressure >10mm from baseline). Stroke severity, motor recovery, and functional balance and mobility status were also obtained. Three patterns were identified: single (typical), absent (atypical), and multiple (atypical) anticipatory postural adjustments. Thirty-five percent of trials had atypical anticipatory postural adjustments (absent and multiple). Frequency of absent anticipatory postural adjustments was negatively correlated with walking speed. Multiple anticipatory postural adjustments were more prevalent when leading with the non-paretic than the paretic limb. Trials with multiple anticipatory postural adjustments had longer duration of anticipatory postural adjustment and time to foot-off, and shorter unloading time than trials with single anticipatory postural adjustments. A high prevalence of atypical anticipatory control prior to gait initiation was found in individuals with stroke. Temporal differences were identified with multiple anticipatory postural adjustments, indicating altered gait initiation. These findings provide insight into postural control during gait initiation in individuals with sub-acute stroke, and may inform interventions to improve ambulation in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

Bone density, body composition, and psychopathology of anorexia nervosa spectrum disorders in DSM-IV vs DSM-5

PubMed Central

Schorr, Melanie; Thomas, Jennifer J.; Eddy, Kamryn T.; Dichtel, Laura E.; Lawson, Elizabeth A.; Meenaghan, Erinne; Paskal, Margaret Lederfine; Fazeli, Pouneh K.; Faje, Alexander T.; Misra, Madhusmita; Klibanski, Anne; Miller, Karen K.

2016-01-01

Objective DSM-5 revised diagnostic criteria for anorexia nervosa (AN) by eliminating the amenorrhea requirement, liberalizing weight and psychological criteria, and adding the formal diagnosis of “atypical AN” for individuals with AN psychological symptoms without low weight. We sought to determine whether bone density (BMD) is impaired in women diagnosed with AN using the new, more liberal DSM-5 criteria. Method Cross-sectional study of 168 women, 18–45y: 1) AN by DSM-IV (DSM-IV)(n=37), 2) AN by DSM-5 but not DSM-IV criteria (DSM-5)(n=33), 3) atypical AN (ATYPICAL)(n=77), 4) healthy comparison group (HC)(n=21). Measurements included dual energy x-ray absorptiometry, Eating Disorder Examination-Questionnaire, Eating Disorder Inventory-2, Hamilton Depression and Anxiety Rating Scales. Results BMD Z-score <−1.0 was present in 78% of DSM-IV, 82% of DSM-5, and 69% of ATYPICAL. Mean Z-scores were comparably low in DSM-IV and DSM-5, intermediate in ATYPICAL, and highest in HC. Lack of prior low weight or amenorrhea was, but history of overweight/obesity was not, protective against bone loss. Mean lean mass and percent fat mass were significantly lower in all AN groups than HC. DSM-IV, DSM-5 and ATYPICAL had comparable psychopathology. Discussion Despite liberalizing diagnostic criteria, many women diagnosed with AN and atypical AN using DSM-5 criteria have low BMD. Presence or history of low weight and/or amenorrhea remain important indications for DXA. Loss of lean mass, in addition to fat mass, is present in all AN groups, and may contribute to low BMD. The deleterious effect of eating disorders on BMD extends beyond those with current low weight and amenorrhea. PMID:27527115

Improvement of diagnostic agreement among pathologists in resolving an "atypical glands suspicious for cancer" diagnosis in prostate biopsies using a novel "Disease-Focused Diagnostic Review" quality improvement process.

PubMed

Shah, Rajal B; Leandro, Gioacchino; Romerocaces, Gloria; Bentley, James; Yoon, Jiyoon; Mendrinos, Savvas; Tadros, Yousef; Tian, Wei; Lash, Richard

2016-10-01

One of the major goals of an anatomic pathology laboratory quality program is to minimize unwarranted diagnostic variability and equivocal reporting. This study evaluated the utility of Miraca Life Sciences' "Disease-Focused Diagnostic Review" (DFDR) quality program in improving interobserver diagnostic reproducibility associated with classification of "atypical glands suspicious for adenocarcinoma" (ATYP) in prostate biopsies. Seventy-one selected prostate biopsies with a focus of ATYP were reviewed by 8 pathologists. Participants were blinded to the original diagnosis and were first asked to classify the ATYP as benign, atypical, or limited adenocarcinoma. DFDR comprised a "theoretical consensus" (in which pathologists first reached consensus on the morphological features they considered relevant for the diagnosis of limited prostatic adenocarcinoma), a didactic review including relevant literature, and "practical consensus" (pathologists performed joint microscopic sessions, reconciling each other's observations and positions evaluating a separate unique slide set). Participants were finally asked to reclassify the original 71 ATYP cases based on knowledge gleaned from DFDR. Pre- and post-DFDR interobserver reproducibility of overall diagnostic agreement was assessed. Interobserver reproducibility measured by Fleiss κ values of pre- and post-DFDR was 0.36 and 0.59, respectively (P=.006). Post-DFDR, there were significant improvement for "100% concordance" (P=.011) and reduction for "no consensus" (P=.0004) categories. Despite a lower pre-DFDR reproducibility for non-uropathology fellowship-trained (n=3, κ=0.38) versus uropathology fellowship-trained (n=5, κ=0.43) pathologists, both groups achieved similarly high post-DFDR κ levels (κ=0.58 and 0.56, respectively). DFDR represents an effective tool to formally achieve diagnostic consensus and reduce variability associated with critical diagnoses in an anatomic pathology practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Deleterious sucking habits and atypical swallowing in children with otitis media with effusion.

PubMed

Ralli, Giovanni; Ruoppolo, Giovanni; Mora, Renzo; Guastini, Luca

2011-10-01

The aim of this study was to investigate the possible correlation between otitis media with effusion, bad sucking habits and atypical swallowing in children affected by otitis media with effusion. 65 children, aged from 7 to 12 years, observed in the ENT Department of the "La Sapienza" University of Rome, were enrolled in the study group (group A). All children were affected by otitis media with effusion for more than 3 months. As control group, 60 healthy children, aged from 7 to 12 years were identified (group B). All the children underwent medical history, with evaluation of the sucking habits, ENT examination, tympanometry, orthodontic examination and evaluation of swallowing. In the orthodontic examination the variables analyzed were: maximum mouth opening, right and left mandibular lateral movements and mandibular protrusion. Atypical swallowing was considered to occur when lip activity produced strong tension in the perioral musculature, and/or the tip of the tongue was placed or pushed against the anterior teeth during swallowing. In the group A, atypical swallowing was found in 33/65 subjects out of the 65 children (50.7%). In the control group (group B) 16/60 children (26.6%) showed atypical swallowing. Compared with group B, deleterious sucking habits were significantly higher (p<0.05) in the study group (28/65 vs. 12/60). In both the study and control group, deleterious sucking habits were present in almost all children with atypical swallowing (28/33 in group A and 12/16 in group B). Our data suggest a correlation between otitis media with effusion, deleterious sucking habits and prevalence of atypical swallowing. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects

PubMed Central

Johns, D G; Behm, D J; Walker, D J; Ao, Z; Shapland, E M; Daniels, D A; Riddick, M; Dowell, S; Staton, P C; Green, P; Shabon, U; Bao, W; Aiyar, N; Yue, T-L; Brown, A J; Morrison, A D; Douglas, S A

2007-01-01

Background and purpose: Atypical cannabinoids are thought to cause vasodilatation through an as-yet unidentified ‘CBx' receptor. Recent reports suggest GPR55 is an atypical cannabinoid receptor, making it a candidate for the vasodilator ‘CBx' receptor. The purpose of the present study was to test the hypothesis that human recombinant GPR55 is activated by atypical cannabinoids and mediates vasodilator responses to these agents. Experimental approach: Human recombinant GPR55 was expressed in HEK293T cells and specific GTPγS activity was monitored as an index of receptor activation. In GPR55-deficient and wild-type littermate control mice, in vivo blood pressure measurement and isolated resistance artery myography were used to determine GPR55 dependence of atypical cannabinoid-induced haemodynamic and vasodilator responses. Key results: Atypical cannabinoids O-1602 and abnormal cannabidiol both stimulated GPR55-dependent GTPγS activity (EC50 approximately 2 nM), whereas the CB1 and CB2-selective agonist WIN 55,212-2 showed no effect in GPR55-expressing HEK293T cell membranes. Baseline mean arterial pressure and heart rate were not different between WT and GPR55 KO mice. The blood pressure-lowering response to abnormal cannabidiol was not different between WT and KO mice (WT 20±2%, KO 26±5% change from baseline), nor was the vasodilator response to abnormal cannabidiol in isolated mesenteric arteries (IC50 approximately 3 μ M for WT and KO). The abnormal cannabidiol vasodilator response was antagonized equivalently by O-1918 in both strains. Conclusions: These results demonstrate that while GPR55 is activated by atypical cannabinoids, it does not appear to mediate the vasodilator effects of these agents. PMID:17704827

Insulin-sensitive phospholipid signaling systems and glucose transport. Update II.

PubMed

Farese, R V

2001-04-01

Insulin provokes rapid changes in phospholipid metabolism and thereby generates biologically active lipids that serve as intracellular signaling factors that regulate glucose transport and glycogen synthesis. These changes include: (i) activation of phosphatidylinositol 3-kinase (PI3K) and production of PIP3; (ii) PIP3-dependent activation of atypical protein kinase Cs (PKCs); (iii) PIP3-dependent activation of PKB; (iv) PI3K-dependent activation of phospholipase D and hydrolysis of phosphatidylcholine with subsequent increases in phosphatidic acid (PA) and diacylglycerol (DAG); (v) PI3K-independent activation of glycerol-3-phosphate acylytansferase and increases in de novo synthesis of PA and DAG; and (vi) activation of DAG-sensitive PKCs. Recent findings suggest that atypical PKCs and PKB serve as important positive regulators of insulin-stimulated glucose metabolism, whereas mechanisms that result in the activation of DAG-sensitive PKCs serve mainly as negative regulators of insulin signaling through PI3K. Atypical PKCs and PKB are rapidly activated by insulin in adipocytes, liver, skeletal muscles, and other cell types by a mechanism requiring PI3K and its downstream effector, 3-phosphoinositide-dependent protein kinase-1 (PDK-1), which, in conjunction with PIP3, phosphorylates critical threonine residues in the activation loops of atypical PKCs and PKB. PIP3 also promotes increases in autophosphorylation and allosteric activation of atypical PKCs. Atypical PKCs and perhaps PKB appear to be required for insulin-induced translocation of the GLUT 4 glucose transporter to the plasma membrane and subsequent glucose transport. PKB also appears to be the major regulator of glycogen synthase. Together, atypical PKCs and PKB serve as a potent, integrated PI3K/PDK-1-directed signaling system that is used by insulin to regulate glucose metabolism.

PTEN loss represses glioblastoma tumor initiating cell differentiation via inactivation of Lgl1.

PubMed

Gont, Alexander; Hanson, Jennifer E L; Lavictoire, Sylvie J; Parolin, Doris A; Daneshmand, Manijeh; Restall, Ian J; Soucie, Mathieu; Nicholas, Garth; Woulfe, John; Kassam, Amin; Da Silva, Vasco F; Lorimer, Ian A J

2013-08-01

Glioblastoma multiforme is an aggressive and incurable type of brain tumor. A subset of undifferentiated glioblastoma cells, known as glioblastoma tumor initiating cells (GTICs), has an essential role in the malignancy of this disease and also appears to mediate resistance to radiation therapy and chemotherapy. GTICs retain the ability to differentiate into cells with reduced malignant potential, but the signaling pathways controlling differentiation are not fully understood at this time. PTEN loss is a very common in glioblastoma multiforme and leads to aberrant activation of the phosphoinositide 3-kinase pathway. Increased signalling through this pathway leads to activation of multiple protein kinases, including atypical protein kinase C. In Drosophila, active atypical protein kinase C has been shown to promote the self-renewal of neuroblasts, inhibiting their differentiation along a neuronal lineage. This effect is mediated by atypical protein kinase c-mediated phosphorylation and inactivation of Lgl, a protein that was first characterized as a tumour suppressor in Drosophila. The effects of the atypical protein kinase C/Lgl pathway on the differentiation status of GTICs, and its potential link to PTEN loss, have not been assessed previously. Here we show that PTEN loss leads to the phosphorylation and inactivation of Lgl by atypical protein kinase C in glioblastoma cells. Re-expression of PTEN in GTICs promoted their differentiation along a neuronal lineage. This effect was also seen when atypical protein kinase C was knocked down using RNA interference, and when a non-phosphorylatable, constitutively active form of Lgl was expressed in GTICs. Thus PTEN loss, acting via atypical protein kinase C activation and Lgl inactivation, helps to maintain GTICs in an undifferentiated state.

Novel antipsychotics: issues and controversies. Typicality of atypical antipsychotics.

PubMed Central

Stip, E

2000-01-01

The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including "extrapyramidal side effects," "cognition," "schizophrenia" and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the "standard" atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term "spectrum of atypicality." For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown. PMID:10740987

Incidence of tardive dyskinesia with atypical versus conventional antipsychotic medications: a prospective cohort study.

PubMed

Woods, Scott W; Morgenstern, Hal; Saksa, John R; Walsh, Barbara C; Sullivan, Michelle C; Money, Roy; Hawkins, Keith A; Gueorguieva, Ralitza V; Glazer, William M

2010-04-01

Most previous studies of the incidence of tardive dyskinesia with atypical antipsychotics compared with conventional antipsychotics have not had tardive dyskinesia as their primary focus. The current study aimed to compare the incidence of tardive dyskinesia with atypical vs conventional antipsychotics using methods similar to those from a previous prospective cohort study at our site in the 1980s. Three hundred fifty-two initially tardive dyskinesia-free psychiatric outpatients (diagnosed at baseline using the Structured Clinical Interview for DSM-IV) were examined for a new diagnosis of tardive dyskinesia (using the Abnormal Involuntary Movement Scale and Glazer-Morgenstern criteria) every 6 months for up to 4 years at a community mental health center. At baseline, subjects were receiving conventional antipsychotics only (23%), atypicals only (64%), or both (14%). Only 26 subjects had never received conventional antipsychotics. Baseline evaluations were conducted from November 2000 through May 2003. Follow-ups were conducted through February 2005. Compared with subjects treated with conventional antipsychotics alone since the previous visit, the adjusted tardive dyskinesia incidence rate-ratio for subjects treated with atypical antipsychotics alone was 0.68 (95% CI, 0.29-1.64). The incidence and prevalence of tardive dyskinesia was similar to previous findings at this site in the 1980s. The incidence of tardive dyskinesia with recent exposure to atypical antipsychotics alone was more similar to that for conventional antipsychotics than in most previous studies. Despite high penetration of atypical antipsychotics into clinical practice, the incidence and prevalence of tardive dyskinesia appeared relatively unchanged since the 1980s. Clinicians should continue to monitor for tardive dyskinesia, and researchers should continue to pursue efforts to treat or prevent it. Copyright 2010 Physicians Postgraduate Press, Inc.

Impact of Atypical Antipsychotic Therapy on Leptin, Ghrelin, and Adiponectin

PubMed Central

Jin, Hua; Meyer, Jonathan M.; Mudaliar, Sunder; Jeste, Dilip V.

2009-01-01

Background Many adverse effects of atypical antipsychotic treatment are associated with antagonism of monoamine receptors; however, data indicate that important metabolic effects, such as hypertriglyceridemia and impairment in glucose/insulin homeostasis, may not be related to these mechanisms, leading investigators to explore alternative hypotheses. Promising candidates include a possible impact of antipsychotics on peptide hormonal regulators of metabolic control such as leptin, ghrelin, and adiponectin. The purpose of this review is to summarize recent data on changes in these hormones during atypical antipsychotic treatment. Methods A Medline search was performed for papers published from January 1999 to January 2007 using key words antipsychotic, atypical antipsychotic, and individual atypical antipsychotic drug names cross-referenced with leptin, ghrelin, and adiponectin. Results The bulk of the published work focused on changes in body weight and serum leptin, with far less data on ghrelin, and adiponectin, and non-weight metabolic changes. Leptin changes were directly related to a medication’s weight gain liability, with no added antipsychotic effects on leptin signaling. Conflicting results emerged for the other markers, but all three long-term studies on ghrelin showed increased levels in patients on atypical antipsychotics with weight gain liabilities. Conclusions Leptin increases during antipsychotic treatment are a result of weight gain rather than a direct impact of atypical antipsychotics on leptin physiology. Preliminary long-term data show increased ghrelin levels, but this finding must be replicated. The association with antipsychotic effects on glucose and lipid metabolism and these hormones remains virtually unstudied. Future research should indicate whether ghrelin and other peptide hormones may be useful predictors of weight gain or metabolic changes in patients on antipsychotics. PMID:18206351

Short-term cognitive improvement in schizophrenics treated with typical and atypical neuroleptics.

PubMed

Rollnik, Jens D; Borsutzky, Marthias; Huber, Thomas J; Mogk, Hannu; Seifert, Jürgen; Emrich, Hinderk M; Schneider, Udo

2002-01-01

Atypical neuroleptics seem to be more beneficial than typical ones with respect to long-term neuropsychological functioning. Thus, most studies focus on the long-term effects of neuroleptics. We were interested in whether atypical neuroleptic treatment is also superior to typical drugs over relatively short periods of time. We studied 20 schizophrenic patients [10 males, mean age 35.5 years, mean Brief Psychiatric Rating Scale (BPRS) score at entry 58.9] admitted to our hospital with acute psychotic exacerbation. Nine of them were treated with typical and 11 with atypical neuroleptics. In addition, 14 healthy drug-free subjects (6 males, mean age 31.2 years) were enrolled in the study and compared to the patients. As neuropsychological tools, a divided attention test, the Vienna reaction time test, the Benton visual retention test, digit span and a Multiple Choice Word Fluency Test (MWT-B) were used during the first week after admission, within the third week and before discharge (approximately 3 months). Patients scored significantly worse than healthy controls on nearly all tests (except Vienna reaction time). Clinical ratings [BPRS and Positive and Negative Symptom Scale for Schizophrenia (PANSS)] improved markedly (p < 0.01), without a significant difference between typical and atypical medication. Clinical improvement (PANSS total score) correlated with less mistakes on the Benton test (r = 0.762, p = 0.017) and an improvement on the divided attention task (r = 0.705, p = 0.034). Neuropsychological functioning (explicit memory, p < 0.01; divided attention, p < 0.05) moderately improved for both groups under treatment but without a significant difference between atypical and typical antipsychotic drugs. Over short periods of time (3 months), neuropsychological disturbances in schizophrenia seem to be moderately responsive to both typical and atypical neuroleptics. Copyright 2002 S. Karger AG, Basel

Screening frequency and atypical cells and the prediction of cervical cancer risk.

PubMed

Chen, Yun-Yuan; You, San-Lin; Koong, Shin-Lan; Liu, Jessica; Chen, Chi-An; Chen, Chien-Jen

2014-05-01

To evaluate the screening efficacy and importance of atypical squamous cells and atypical glandular cells in predicting subsequent cervical cancer risk. This national cohort study in Taiwan analyzed associations between Pap test screening frequency and findings in 1995-2000 and subsequent risk of squamous cell carcinoma and adenocarcinoma after 2002. Women aged 30 years or older in 1995 without a cervical cancer history were included. Multivariate-adjusted hazard ratios and their 95% confidence intervals (CIs) were assessed using Cox regression analysis. During a total follow-up of 31,693,980 person-years in 2002-2008, 9,471 squamous cell carcinoma and 1,455 adenocarcinoma cases were newly diagnosed, resulting in 2,067 deaths. The risk of developing and dying from squamous cell carcinoma decreased significantly with increasing attendance frequency between 1995 and 2000 (all P values for trend<.001). Women who attended more than three screenings in 1995-2000 had 0.69-fold and 0.35-fold decrease in incidence and mortality of adenocarcinoma, respectively, compared with women who never attended any screenings. Abnormal cytologic findings were significant predictors of the incidence and mortality of cervical cancers. The adjusted hazard ratio (95% CI) of developing squamous cell carcinoma was 29.94 (22.83-39.25) for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions, and the adjusted hazard ratio (95% CI) of developing adenocarcinoma was 49.43 (36.49-66.97) for atypical glandular cells. Significant reductions in cervical adenocarcinoma occurred in women who attend three or more annual screenings in 6 years. High-grade atypical squamous cells and atypical glandular cells are important predictors of subsequent adenocarcinoma and squamous cell carcinoma. II.

Endometrial cancer arising from atypical complex hyperplasia: The significance in an endometrial biopsy and a diagnostic challenge

PubMed Central

Byun, Jung Mi; Jeong, Dae Hoon; Kim, Young Nam; Cho, En Bee; Cha, Ju Eun; Sung, Moon Su; Lee, Kyung Bok

2015-01-01

Objective We investigated the features of endometrial hyperplasia with concurrent endometrial cancer that had been diagnosed by endometrial sampling. Further, we attempted to identify an accurate differential diagnostic method. Methods We retrospectively studied 125 patients who underwent a diagnostic endometrial biopsy or were diagnosed after the surgical treatment of other gynecological lesions, such as leiomyoma or polyps. Patients were diagnosed between January 2005 and December 2013 at Busan Paik Hospital. Clinical and histopathological characteristics were compared in patients who had atypical endometrial hyperplasia with and without concurrent endometrial cancer. Results The patients were grouped based on the final pathology reports. One hundred seventeen patients were diagnosed with endometrial hyperplasia and eight patients were diagnosed with endometrioid adenocarcinoma arising from atypical hyperplasia. Of the 26 patients who had been diagnosed with atypical endometrial hyperplasia by office-based endometrial biopsy, eight (30.8%) were subsequently diagnosed with endometrial cancer after they had undergone hysterectomy. The patients with endometrial cancer arising from endometrial hyperplasia were younger (39.1 vs. 47.2 years, P=0.0104) and more obese (body mass index 26.1±9.6 vs. 23.8±2.8 kg/m2, P=0.3560) than the patients with endometrial hyperplasia. The correlation rate between the pathology of the endometrial samples and the final diagnosis of endometrial hyperplasia was 67.3%. Conclusion In patients with atypical endometrial hyperplasia, the detection of endometrial cancer before hysterectomy can decrease the risk of suboptimal treatment. The accuracy of endometrial sampling for the diagnosis of concurrent endometrial carcinoma was much lower than that for atypical endometrial hyperplasia. Therefore, concurrent endometrial carcinoma should be suspected and surgical intervention should be considered in young or obese patients who present with atypical endometrial hyperplasia. PMID:26623410

Sonographic features of thyroid nodules that may help distinguish clinically atypical subacute thyroiditis from thyroid malignancy.

PubMed

Pan, Fu-shun; Wang, Wei; Wang, Yan; Xu, Ming; Liang, Jin-yu; Zheng, Yan-ling; Xie, Xiao-yan; Li, Xiao-xi

2015-04-01

The purpose of this study was to evaluate sonographic features for distinguishing clinically atypical subacute thyroiditis from malignant thyroid nodules. A total of 165 hypoechoic thyroid nodules without calcification in 135 patients with histologic diagnosis were included in this study. These nodules were classified into 2 groups: a thyroiditis group (55 nodules in 36 patients) and a malignancy group (110 nodules in 99 patients). The sonographic features of the groups were retrospectively reviewed. No significant differences were detected for the variables of marked echogenicity, a taller-than-wide shape, and mixed vascularity. However, a poorly defined margin was detected more frequently in the thyroiditis group than the malignancy group (P < .05); it yielded a high capability for differential diagnosis of atypical subacute thyroiditis, with sensitivity and specificity of 87.3% and 80.9%, respectively. Centripetal reduction echogenicity was observed exclusively in the thyroiditis group, with high specificity (100%) but low sensitivity (21.8%) for atypical subacute thyroiditis diagnosis. All of the thyroiditis nodules with a positive color signal showed noninternal vascularity (negative predictive value, 100%). There is a considerable overlap between the sonographic features of atypical subacute thyroiditis and thyroid malignancy. However, the margin, echogenicity, and vascularity type are helpful indicators for differential diagnosis of atypical subacute thyroiditis. © 2015 by the American Institute of Ultrasound in Medicine.

Variety in emotional life: within-category typicality of emotional experiences is associated with neural activity in large-scale brain networks.

PubMed

Wilson-Mendenhall, Christine D; Barrett, Lisa Feldman; Barsalou, Lawrence W

2015-01-01

The tremendous variability within categories of human emotional experience receives little empirical attention. We hypothesized that atypical instances of emotion categories (e.g. pleasant fear of thrill-seeking) would be processed less efficiently than typical instances of emotion categories (e.g. unpleasant fear of violent threat) in large-scale brain networks. During a novel fMRI paradigm, participants immersed themselves in scenarios designed to induce atypical and typical experiences of fear, sadness or happiness (scenario immersion), and then focused on and rated the pleasant or unpleasant feeling that emerged (valence focus) in most trials. As predicted, reliably greater activity in the 'default mode' network (including medial prefrontal cortex and posterior cingulate) was observed for atypical (vs typical) emotional experiences during scenario immersion, suggesting atypical instances require greater conceptual processing to situate the socio-emotional experience. During valence focus, reliably greater activity was observed for atypical (vs typical) emotional experiences in the 'salience' network (including anterior insula and anterior cingulate), suggesting atypical instances place greater demands on integrating shifting body signals with the sensory and social context. Consistent with emerging psychological construction approaches to emotion, these findings demonstrate that is it important to study the variability within common categories of emotional experience. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Impact of radiotherapy in atypical meningioma recurrence: literature review.

PubMed

Pereira, Benedito Jamilson Araújo; de Almeida, Antônio Nogueira; Paiva, Wellingson Silva; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi

2018-03-19

Evaluate whether radiotherapy (RT) after the neurosurgical treatment of atypical meningiomas (AM) has an impact on the reduction rate of recurrence. A Medline search through October 2017 using "atypical meningioma" returned 1277 papers for initial review. Inclusion criteria were as follows. We analyzed the database and included articles in which the anatomic pathological classification of atypical meningiomas was in accordance with WHO 2007 or WHO 2016 criteria, patients > 18 years of age, and there was postoperative external beam radiation to the tumor bed. Exclusion criteria were WHO grade I or III meningioma, patients who underwent whole-brain radiation, RT used as salvage therapy for recurrence, palliative dose of RT (< 45 Gy), recurrent AMs, and multiple AMs. Papers reporting outcomes in which atypical and anaplastic meningiomas were analyzed together were rejected, as were papers with small samples that may compromise evaluation. After filtering our initial selection, only 17 papers were selected. After reviewing the seventeen articles including a total of 1761 patients (972 female and 799 male; 1.21 female/1.0 male), the difference in proportion of tumor recurrence between patients with and without radiotherapy after neurosurgical procedure was 1.0448, 95% CI [0.8318 to 1.3125], p value = 0.7062. On the basis of this review, there is no evidence to suggest that RT decreases the rate of recurrence in patients with atypical meningiomas.

Atypical E2f functions are critical for pancreas polyploidization

PubMed Central

Moreno, Eva; Toussaint, Mathilda J. M.; Tooten, Peter C. J.; van Essen, Saskia C.; van Liere, Elsbeth A.; Youssef, Sameh A.; Bongiovanni, Laura; de Bruin, Alain

2018-01-01

The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age. PMID:29329320

Genomes of rumen bacteria encode atypical pathways for fermenting hexoses to short-chain fatty acids.

PubMed

Hackmann, Timothy J; Ngugi, David Kamanda; Firkins, Jeffrey L; Tao, Junyi

2017-11-01

Bacteria have been thought to follow only a few well-recognized biochemical pathways when fermenting glucose or other hexoses. These pathways have been chiseled in the stone of textbooks for decades, with most sources rendering them as they appear in the classic 1986 text by Gottschalk. Still, it is unclear how broadly these pathways apply, given that they were established and delineated biochemically with only a few model organisms. Here, we show that well-recognized pathways often cannot explain fermentation products formed by bacteria. In the most extensive analysis of its kind, we reconstructed pathways for glucose fermentation from genomes of 48 species and subspecies of bacteria from one environment (the rumen). In total, 44% of these bacteria had atypical pathways, including several that are completely unprecedented for bacteria or any organism. In detail, 8% of bacteria had an atypical pathway for acetate formation; 21% of bacteria had an atypical pathway for propionate or succinate formation; 6% of bacteria had an atypical pathway for butyrate formation and 33% of bacteria had an atypical or incomplete Embden-Meyerhof-Parnas pathway. This study shows that reconstruction of metabolic pathways - a common goal of omics studies - could be incorrect if well-recognized pathways are used for reference. Furthermore, it calls for renewed efforts to delineate fermentation pathways biochemically. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Atypical E2f functions are critical for pancreas polyploidization.

PubMed

Matondo, Ramadhan B; Moreno, Eva; Toussaint, Mathilda J M; Tooten, Peter C J; van Essen, Saskia C; van Liere, Elsbeth A; Youssef, Sameh A; Bongiovanni, Laura; de Bruin, Alain

2018-01-01

The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

Skin self-examinations and visual identification of atypical nevi: comparing individual and crowdsourcing approaches.

PubMed

King, Andy J; Gehl, Robert W; Grossman, Douglas; Jensen, Jakob D

2013-12-01

Skin self-examination (SSE) is one method for identifying atypical nevi among members of the general public. Unfortunately, past research has shown that SSE has low sensitivity in detecting atypical nevi. The current study investigates whether crowdsourcing (collective effort) can improve SSE identification accuracy. Collective effort is potentially useful for improving people's visual identification of atypical nevi during SSE because, even when a single person has low reliability at a task, the pattern of the group can overcome the limitations of each individual. Adults (N=500) were recruited from a shopping mall in the Midwest. Participants viewed educational pamphlets about SSE and then completed a mole identification task. For the task, participants were asked to circle mole images that appeared atypical. Forty nevi images were provided; nine of the images were of nevi that were later diagnosed as melanoma. Consistent with past research, individual effort exhibited modest sensitivity (.58) for identifying atypical nevi in the mole identification task. As predicted, collective effort overcame the limitations of individual effort. Specifically, a 19% collective effort identification threshold exhibited superior sensitivity (.90). The results of the current study suggest that limitations of SSE can be countered by collective effort, a finding that supports the pursuit of interventions promoting early melanoma detection that contain crowdsourced visual identification components. Copyright © 2013 Elsevier Ltd. All rights reserved.

Serotonin Transporter Genotype (5HTTLPR) Moderates the Longitudinal Impact of Atypical Attachment on Externalizing Behavior.

PubMed

Humphreys, Kathryn L; Zeanah, Charles H; Nelson, Charles A; Fox, Nathan A; Drury, Stacy S

2015-01-01

To test whether genotype of the serotonin transporter-linked polymorphic region (5HTTLPR) and atypical attachment interact to predict externalizing psychopathology prospectively in a sample of children with a history of early institutional care. Caregiver report of externalizing behavior at 54 months was examined in 105 children initially reared in institutional care and enrolled in the Bucharest Early Intervention Project, a randomized controlled trial of high quality foster care. 5HTTLPR genotype, attachment status at 42 months of age (typical [secure, avoidant, or ambivalent] or atypical [disorganized-controlling, insecure-other]), and their interaction were examined as predictors of externalizing behavior at age 54 months. 5HTTLPR genotype and atypical attachment at age 42 months interacted to predict externalizing behavior at age 54 months. Specifically, children with the s/s genotype with an atypical attachment had the highest externalizing scores. However, s/s children with a typical attachment demonstrated the lowest externalizing scores, even after controlling for intervention group status. There was no association between attachment status and externalizing behavior among children carrying at least 1 copy of the l allele. These findings indicate that genetic variation in the serotonergic system moderates the association between atypical attachment status and externalizing in young children. Our findings suggest that children, as a result of genetic variability in the serotonergic system, demonstrate differential sensitivity to the attachment relationship.

Serotonin Transporter Genotype (5HTTLPR) Moderates the Longitudinal Impact of Atypical Attachment on Externalizing Behavior

PubMed Central

Humphreys, Kathryn L.; Zeanah, Charles H.; Nelson, Charles A.; Fox, Nathan A.; Drury, Stacy S.

2015-01-01

Objective To test whether genotype of the serotonin transporter-linked polymorphic region (5HTTLPR) and atypical attachment interact to predict externalizing psychopathology prospectively in a sample of children with a history of early institutional care. Methods Caregiver report of externalizing behavior at 54 months was examined in 105 children initially reared in institutional care and enrolled in the Bucharest Early Intervention Project, a randomized controlled trial of high quality foster care. 5HTTLPR genotype, attachment status at 42 months of age (typical [secure, avoidant, or ambivalent] or atypical [disorganized-controlling, insecure-other]), as well as their interaction, were examined as predictors of externalizing behavior at age 54 months. Results 5HTTLPR genotype and atypical attachment at age 42 months interacted to predict externalizing behavior at age 54 months. Specifically, children with the s/s genotype with an atypical attachment had the highest externalizing scores. However, s/s children with a typical attachment demonstrated the lowest externalizing scores, even after controlling for intervention group status. There was no association between attachment status and externalizing behavior among children carrying at least one copy of the l allele. Discussion These findings indicate that genetic variation in the serotonergic system moderates the association between atypical attachment status and externalizing in young children. Our findings suggest that children, as a result of genetic variability in the serotonergic system, demonstrate differential sensitivity to the attachment relationship. PMID:25933228

[Clinico-pathologic Characteristics of Adult Patients with Atypical Infectious Mononucleosis].

PubMed

Yu, Ya-Ping; Song, Ping; An, Zhi-Ming; Zhou, Xiao-Gang; Li, Feng; Wang, Li-Ping; Mei, Jian-Gang; Zhai, Yong-Ping

2016-12-01

To investigate the clinicopathologic characteristics of adult patients with atypical infectious mononucleosis(IM). From January 2003 to December 2013, a total of 5 cases of atypical IM misdiagnosed as lymphoma were selected, and the clinico-pathological characteristics and efficacy of treatment were analyzed. Biopsy of lymph node or tonsil was performed to evaluate the possibility of lymphoma. Peripheral blood EBV antibody and EBV-DNA were examined by ELISA and real-time fluorescence quantitative PCR, respectively. All the cases were considered as lymphoma on the basis of morphological features in initial evaluation before relapse. These features included a florid immunoblastic proliferation, distortion of the underlying nodal or tonsillar architecture and the presence of necrosis. The immunophenotypic features, EBV encoded RNA (EBER) in situ hybridization and the gene rearrangement of immunoglobulin or T cell receptor may be helpful for the distinction of atypical IM from lymphoma. IM as EBV-related lymphoproliferative process shows marked clinical and histological diversity. Atypical case of IM may mimic many different type of lymphoma in clinical and pathologic features, and the misdiagnosis should be avoided by using molecular and pathological examination.

Activity of single-agent decitabine in atypical chronic myeloid leukemia.

PubMed

Hausmann, Heidi; Bhatt, Vijaya R; Yuan, Ji; Maness, Lori J; Ganti, Apar K

2016-12-01

Atypical chronic myeloid leukemia is a rare entity that presents diagnostic and therapeutic challenges. Traditionally utilized therapeutic agents such as hydroxyurea or interferon result in a median survival of approximately two years, thus warranting identification of better options. We report a 49-year-old Caucasian female, who presented with extreme leukocytosis (white blood cells of 148,300/µL) with left shift, severe anemia, and thrombocytopenia. Following a diagnosis of atypical chronic myeloid leukemia, she was started on intravenous decitabine. She subsequently developed paraneoplastic vasculitis of large arteries, which responded to high-dose glucocorticoid. Decitabine therapy resulted in an excellent hematologic response, transfusion independence, and successful transition to an allogeneic peripheral stem cell transplantation. However, the patient subsequently succumbed to the complications of acute graft-versus-host-disease. This case illustrates an association between atypical chronic myeloid leukemia and steroid-responsive paraneoplastic vasculitis and highlights the single-agent disease activity of decitabine in atypical chronic myeloid leukemia, which may be utilized as a bridging therapy to allogeneic stem cell transplantation. © The Author(s) 2015.

Absence of the BRAF mutation in HBME1+ and CK19+ atypical cell clusters in Hashimoto thyroiditis: supportive evidence against preneoplastic change.

PubMed

Nasr, Michel R; Mukhopadhyay, Sanjay; Zhang, Shengle; Katzenstein, Anna-Luise A

2009-12-01

An association between Hashimoto thyroiditis and papillary thyroid carcinoma has been postulated for decades. We undertook this study to identify potential precursors of papillary thyroid carcinoma in Hashimoto thyroiditis using a combination of morphologic, immunohistochemical, and molecular techniques. For the study, samples from 59 cases of Hashimoto thyroiditis were stained with antibodies to HBME1 and cytokeratin (CK)19. Tiny HBME1+ and CK19+ atypical cell clusters were identified and analyzed for the BRAF mutation by the colorimetric Mutector assay and allele-specific polymerase chain reaction. HBME1+ and CK19+ atypical cell clusters were identified in 12 (20%) of 59 cases. The minute size (<1 mm) of the clusters and the incomplete nuclear changes precluded a diagnosis of papillary microcarcinoma. The atypical cell clusters from all 12 cases were negative for BRAF. The absence of the BRAF mutation in these atypical cell clusters suggests that they may not be preneoplastic. Caution should be exercised in interpreting positive HBME1 or CK19 staining in Hashimoto thyroiditis.

Taxonomic and ad hoc categorization within the two cerebral hemispheres.

PubMed

Shen, Yeshayahu; Aharoni, Bat-El; Mashal, Nira

2015-01-01

A typicality effect refers to categorization which is performed more quickly or more accurately for typical than for atypical members of a given category. Previous studies reported a typicality effect for category members presented in the left visual field/right hemisphere (RH), suggesting that the RH applies a similarity-based categorization strategy. However, findings regarding the typicality effect within the left hemisphere (LH) are less conclusive. The current study tested the pattern of typicality effects within each hemisphere for both taxonomic and ad hoc categories, using words presented to the left or right visual fields. Experiment 1 tested typical and atypical members of taxonomic categories as well as non-members, and Experiment 2 tested typical and atypical members of ad hoc categories as well as non-members. The results revealed a typicality effect in both hemispheres and in both types of categories. Furthermore, the RH categorized atypical stimuli more accurately than did the LH. Our findings suggest that both hemispheres rely on a similarity-based categorization strategy, but the coarse semantic coding of the RH seems to facilitate the categorization of atypical members.

Defectors, not norm violators, are punished by third-parties.

PubMed

Bone, Jonathan; Silva, Antonio S; Raihani, Nichola J

2014-07-01

Punishment of defectors and cooperators is prevalent when their behaviour deviates from the social norm. Why atypical behaviour is more likely to be punished than typical behaviour remains unclear. One possible proximate explanation is that individuals simply dislike norm violators. However, an alternative possibility exists: individuals may be more likely to punish atypical behaviour, because the cost of punishment generally increases with the number of individuals that are punished. We used a public goods game with third-party punishment to test whether punishment of defectors was reduced when defecting was typical, as predicted if punishment is responsive to norm violation. The cost of punishment was fixed, regardless of the number of players punished, meaning that it was not more costly to punish typical, relative to atypical, behaviour. Under these conditions, atypical behaviour was not punished more often than typical behaviour. In fact, most punishment was targeted at defectors, irrespective of whether defecting was typical or atypical. We suggest that the reduced punishment of defectors when they are common might often be explained in terms of the costs to the punisher, rather than responses to norm violators.

An update of safety of clinically used atypical antipsychotics.

PubMed

Orsolini, L; Tomasetti, C; Valchera, A; Vecchiotti, R; Matarazzo, I; Vellante, F; Iasevoli, F; Buonaguro, E F; Fornaro, M; Fiengo, A L C; Martinotti, G; Mazza, M; Perna, G; Carano, A; De Bartolomeis, A; Di Giannantonio, M; De Berardis, D

2016-10-01

The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/'typical' APs. We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)). A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

Side effects as influencers of treatment outcome.

PubMed

Sharif, Zafar

2008-01-01

Research relative to the efficacy of a therapeutic agent commands a clinician's greatest interest, but treatment decisions are made based on optimizing efficacy and tolerability/safety considerations. Second-generation atypical antipsychotic drugs are a study in the importance of taking a careful look at the full benefit-risk profile of each drug. The disorders that atypical antipsychotics are approved to treat--schizophrenia, schizoaffective disorder, and bipolar disorder--are associated with an increased rate of certain medical comorbidities compared to the general population. Between-drug differences in efficacy are relatively modest for the atypicals, or between atypicals and conventionals, while differences in safety and tolerability are larger and more clinically relevant. The current article will provide a brief summary of safety-related issues that influence treatment outcome and choice of drug.

Geochemical, modal, and geochronologic data for 1.4 Ga A-type granitoid intrusions of the conterminous United States

USGS Publications Warehouse

du Bray, Edward A.; Holm-Denoma, Christopher S.; San Juan, Carma A.; Lund, Karen; Premo, Wayne R.; DeWitt, Ed

2015-08-10

In addition, Kisvarsanyi (1972) suggests that iron-copper deposits in the St. Francois Mountains of southeastern Missouri are petrogenetically associated with 1.4 Ga A-type granitoids that occur in that region. Similarly, Dall’Agnol and others (2012) summarize important global associations between A-type granitoid rocks and a variety of important ore deposit types, particularly tin, high-field-strength elements (Zr, Hf, Nb, Ta), rare-earth elements, and iron oxide-copper-gold deposits. Consequently, the need to better understand relations between A-type granitoid rocks, tectonic setting, and magma petrogenesis, as well as their genetic associations with important types of ore deposits, suggests that developing a definitive geochemical, modal, and geochronologic database for these rocks in the conterminous United States is of considerable value.

Spontaneous Regression of Pulmonary Nodules Presenting as Epstein-Barr Virus-related Atypical Infectious Mononucleosis.

PubMed

Shinozuka, Jun; Awaguni, Hitoshi; Tanaka, Shin-Ichiro; Makino, Shigeru; Maruyama, Rikken; Inaba, Tohru; Imashuku, Shinsaku

2016-07-01

Pulmonary nodules associated with Epstein-Barr virus (EBV)-related atypical infectious mononucleosis have rarely been described. A 12-year-old Japanese boy, upon admission, revealed multiple small round nodules (a total of 7 nodules in 4 to 8 mm size) in the lungs on computed tomography. The hemorrhagic pharyngeal tonsils with hot signals on 18F-fluorodeoxyglucose-positron emission tomography-computed tomography were biopsied revealing the presence of EBV-encoded small nuclear RNA (EBER)-positive cells; however, no lymphoma was noted. The patient was diagnosed as having atypical EBV-infectious mononucleosis associated with primary EBV infection. Pulmonary nodules markedly reduced in numbers and sizes spontaneously over a 2-year period. Differential diagnosis of pulmonary nodules in childhood should include atypical EBV infection.

Disseminated cutaneous atypical mycobacteriosis by M. chelonae after sclerotherapy of varicose veins in a immunocompetent patient: a case report*

PubMed Central

Murback, Nathalia Dias Negrão; Higa Júnior, Minoru German; Pompílio, Maurício Antônio; Cury, Eunice Stella Jardim; Hans Filho, Gunter; Takita, Luiz Carlos

2015-01-01

Atypical mycobacteria are saprophytic organisms not transmitted from person to person, which affect mainly immunosuppressed but also immunocompetent individuals. We present a case of atypical mycobacteriosis after a vascular procedure, with widespread cutaneous lesions associated with polyarthralgia. Mycobacterium chelonae was identified by the polymerase chain reaction (PCR) method. The patient showed improvement after treatment with three antibiotics. Mycobacterium chelonae causes skin lesions after invasive procedures. The clinical form depends on the immune state of the host and on the entry points. The diagnosis is based essentially on culture and the mycobacteria is identified by PCR. We highlight the importance of investigating atypical mycobacteriosis when faced with granulomatous lesions associated with a history of invasive procedures. PMID:26312697

Shipping Containers as Structural Systems.

DTIC Science & Technology

1977-07-01

hi moms ’ ef for t to r - ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ — --- :~~~~~~~~~~~~ - ‘ - - —--_ _ _ _ iui:iittt: lut i :u h i ur mmu u i e tm h...t hus ’ n e hi m i_ I beett imo sits ’ im ui p rt us’s’ tile mit i_’it huer hei rs’ or i_ ht u ni m m , t ime field t e s ts , l’x pedi eu tt r u m

Database of Autotransplants for Breast Cancer.

DTIC Science & Technology

1997-12-01

atypical bacteria; 301 Herpes Simplex (HSV1, HSV2) list bacterium for non-atypical bacteria.) 302 Herpes Zoster (Chicken pox, Varicella ) 100 Atypical...o 00 Varicella 500. 10 o0 Other, specify: 501. Documented viral infection: Virus involved: 1 U Yes Yes No o 0 No 502. 1 0 o0 Cytomegalovirus (CMV) 8 0...Unknown 503. 1 o 00 Human Herpes Virus Type 6 (HHV6) 504. 1 0o Herpes Simplex Virus (HSV) 505. 1 o 0 Varicella 506. 1 0 0 0 Other, specify: 507

Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

PubMed

Ryan, Aisling M; Bermingham, Niamh; Harrington, Hugh J; Keohane, Catherine

2006-12-01

Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

[Auricular sporotrichosis. Atypical case report simulating bacterial cellulitis].

PubMed

Ochoa-Reyes, Juan; Ramos-Martínez, Ernesto; Treviño-Rangel, Rogelio; González, Gloria M; Bonifaz, Alexandro

Sporotrichosis is the most common subcutaneous or implantation mycosis in Mexico. The case of a preauricular cutaneous-fixed sporotrichosis simulating atypical bacterial cellulitis is reported in an elderly patient with no history of trauma. The biopsy showed a suppurative granuloma with scarce yeast. Sporothrix schenckii was identified in the culture and confirmed by molecular biology. She was treated with itraconazole and a clinical and mycological cure was obtained. The case of atypical presentation is presented, coming from a semi-arid zone with extreme weather.

Atypical Opioid Mechanisms of Control of Injury-Induced Cutaneous Pain by Delta Receptors

DTIC Science & Technology

2017-07-01

AWARD NUMBER: W81XWH-15-1-0076 TITLE: Atypical Opioid Mechanisms of Control of Injury-Induced Cutaneous Pain by Delta Receptors PRINCIPAL...subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT...SUBTITLE Atypical Opioid Mechanisms of Control of Injury-Induced 5a. CONTRACT NUMBER Cutaneous Pain by Delta Receptors 5b. GRANT NUMBER 5c. PROGRAM

Why vocal production of atypical sounds in apes and its cerebral correlates have a lot to say about the origin of language.

PubMed

Meguerditchian, Adrien; Taglialatela, Jared P; Leavens, David A; Hopkins, William D

2014-12-01

Ackermann et al. mention the "acquisition of species-atypical sounds" in apes without any discussion. In our commentary, we demonstrate that these atypical sounds in chimpanzees not only include laryngeal sounds, but also have a major significance regarding the origins of language, if we consider looking at their context of use, their social properties, their relations with gestures, their lateralization, and their neurofunctional correlates as well.

Diagnoses associated with use of atypical antipsychotics in a commercial health plan: a claims database analysis.

PubMed

Citrome, Leslie; Kalsekar, Iftekhar; Guo, Zhenchao; Laubmeier, Kimberly; Hebden, Tony

2013-12-01

Atypical antipsychotics are indicated for specific psychiatric conditions; however, they are frequently used for US Food and Drug Administration-nonapproved indications. This study assessed the types of medical diagnoses associated with atypical antipsychotic prescriptions in commercial health care plans. This retrospective cohort study used the OptumInsight commercial data set from January 2008 to June 2011. The index date was defined as the earliest date of prescription for the atypical antipsychotics aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone, from January 1, 2009, through June 30, 2010. Medical claims during a 2-year period (12 months before and 12 months after the index date) were used to identify relevant diagnostic codes from the International Classification of Diseases, Ninth Edition, Clinical Modification associated with the antipsychotic prescription. A logistic regression analysis was conducted to examine the predictors of use of atypical antipsychotics without a relevant diagnosis, that is, schizophrenia, bipolar, or major depressive disorder (MDD). Of 18,352 patients included in the analysis, 3593 (19.5%) who filled a prescription for atypical antipsychotics did not have an approved diagnosis. Off-label utilization varied, with approximately a quarter of patients with prescriptions for quetiapine (24.1%), risperidone (23.1%), or olanzapine (21.8%) being without a relevant diagnostic code, whereas proportions were lower for patients prescribed aripiprazole (14.0%) or ziprasidone (13.1%). Of those with a psychiatric disorder other than schizophrenia, bipolar disorder, or MDD, approximately a third of prescriptions were for anxiety disorders, with similar proportions across all atypical antipsychotics. Patients were often prescribed quetiapine for substance abuse (22.7%), whereas patients with "other psychiatric conditions" were prescribed risperidone (26.3%) or ziprasidone (25.0%). The logistic regression analysis indicated that patients prescribed olanzapine, quetiapine, or risperidone were significantly more likely to have no diagnostic code for schizophrenia, bipolar disorder, or MDD compared with patients prescribed aripiprazole. Nearly a fifth of commercially insured patients were prescribed atypical antipsychotics, in particular, olanzapine, quetiapine, or risperidone, for diagnoses that were not aligned with US Food and Drug Administration-approved indications. 2013 The Authors. Published by Elsevier HS Journals, Inc. All rights reserved.

Atypical autoantibodies in patients with primary Sjögren syndrome: clinical characteristics and follow-up of 82 cases.

PubMed

Ramos-Casals, Manuel; Nardi, Norma; Brito-Zerón, Pilar; Aguiló, Sira; Gil, Victor; Delgado, German; Bové, Albert; Font, Josep

2006-04-01

To analyze the clinical characteristics, follow-up, and fulfillment of classification criteria for other systemic autoimmune diseases (SAD) in patients with primary Sjögren syndrome (SS) and atypical autoantibodies. We studied 402 patients diagnosed with primary SS seen consecutively in our Department since 1994. We considered anti-DNA, anti-Sm, anti-RNP, anti-topoisomerase1/Scl70, anticentromere (ACA), anti-Jo1, anti-neutrophil cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aPL), and lupus anticoagulant as atypical autoantibodies. The patients were prospectively followed after inclusion into the protocol, focusing on the development of features that might lead to the fulfillment of classification criteria for additional SAD. As a control group, we selected an age-sex-matched subset of patients with primary SS without atypical autoantibodies. Eighty-two (20%) patients showed atypical autoantibodies (36 had aPL, 21 anti-DNA, 13 ANCA, 10 anti-RNP, 8 ACA, 6 anti-Sm, 2 anti-Scl70, and 1 anti-Jo-1 antibodies). There were 77 (94%) women and 5 (6%) men, with a mean age of 57 years. Patients with atypical autoantibodies had no statistical differences in the prevalence of the main sicca features, extraglandular manifestations (except for a higher prevalence of Raynaud's phenomenon, 28% versus 7%, P=0.001), immunological markers, and in the fulfillment of the 2002 classification criteria, compared with the control group. After a follow-up of 534 patient-years, 13 (16%) of the 82 patients with atypical autoantibodies developed an additional SAD (systemic lupus erythematosus in 5 cases, antiphospholipid syndrome in 4, limited scleroderma in 3, and microscopic polyangiitis in 1) compared with none in the control group (P<0.001). This study shows an immunological overlap (defined by the presence of autoantibodies considered typical of other SAD) in 20% of our patients with primary SS. However, the clinical significance of these atypical autoantibodies varies widely depending on the autoantibodies detected, with a broad spectrum of prevalence and clinical patterns of disease expression, and a specific predilection for association with some SAD in preference to others.

Geochemical constraints on genesis of Paleoproterozoic A-type granite in the south margin of North China Craton

NASA Astrophysics Data System (ADS)

Xue, Shuo; Xu, Yang; Ling, Ming-Xing; Kang, Qing-Qing; Jiang, Xiao-Yan; Sun, Sai-Jun; Wu, Kai; Zhang, Zhe-Kun; Luo, Ze-Bin; Liu, Yu-Long; Sun, Weidong

2018-04-01

Paleoproterozoic A-type granites are widely outcropped in the North China Craton (NCC), particularly in the Trans-North China Orogen. However, their genesis and tectonic significance remain obscure. Here we report systematic studies on geochronology and geochemical characteristics of A-type granite in Huayangchuan, south margin of the NCC. The samples are enriched in total alkali (K2O + Na2O > 8.97 wt%), and depleted in MgO (0.84-0.93 wt%), CaO (1.28-1.90 wt%) and P2O5 (0.18-0.20 wt%), with high FeOT/MgO (5.69-6.67). They are characterized by high Zr + Y + Nb + Ce values (1293-1392 ppm) and 10,000 × Ga/Al ratios (3.14-3.35), which are typical characteristics of A-type granite. The Huayangchuan A-type granite can be further classified as A1-type subgroup based on particular geochemical features, e.g., low Y/Nb (0.87-1.00) and Yb/Ta (0.88-1.10). High precision zircon U-Pb dating of the A-type granite by secondary ion mass spectrometry (SIMS) yields Paleoproterozoic 207Pb/206Pb ages of 1829.5 ± 2.5 Ma. The low zircon ɛHf(t) values (-6.97 to -10.45), along with zircon Hf model age of 2.7-2.9 Ga, indicate that the Huayangchuan A-type granite was derived from partial melting of the ancient continental crust with contribution of enriched mantle components. The low zircon δ18O composition (4.00 to 6.78‰) indicates that the zircons were crystallized from low δ18O magmas, which derived from the crust metasomatized by low δ18O mantle fluids or melts. The E-W trend A1-type granitic plutons in the NCC are generally outcropped in a rift tectonic regime, which is consistent with the development of the mantle plume in the Xiong'er district. The large volume of basaltic magmas, generated by mantle plume head, underplated the lower continental crust and formed the Huayangchuan A-type granite.

Clinical Profile of Atypical Manifestations of Dengue Fever.

PubMed

Pothapregada, Sriram; Kamalakannan, Banupriya; Thulasingam, Mahalakshmy

2016-06-01

To study the clinical profile and outcome of the atypical manifestations of dengue fever in children. All children (0-12 y of age) diagnosed and confirmed as dengue fever at a tertiary care hospital at Puducherry, between the 1st of August 2012 and January 31st 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization (WHO) guidelines 2011 for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies and the data was analyzed using SPSS 16.0 statistical software. Out of 254 children admitted with dengue fever, non-severe dengue and severe dengue were seen in 62.6 % and 37.4 % respectively. Atypical manifestations were seen in 106 cases (41.7 %). Mean age of presentation was 6.9(3.3) y. M: F ratio was 1.2:1. The common manifestations of severe dengue infection were shock (37.4 %), bleeding (20.1 %) and multi-organ dysfunction (2.4 %). The most common atypical manifestations of dengue fever were lymphadenopathy (41.7 %), splenomegaly (21.2 %), biphasic fever (18.1 %), hepatitis (11.4 %), febrile diarrhea (6.3 %), refractory shock (2.4 %) and impaired consciousness (1.9 %). The other atypical manifestations present were portal hypertension, acalculous cholecystitis, appendicitis, acute respiratory distress syndrome (ARDS), myocarditis, pericardial effusion, paroxysmal supraventricular tachycardia (PSVT), myositis, acute kidney injury (AKI), hemophagocytic syndrome and disseminated intravascular coagulopathy (DIC). Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.4 %) and out of them four presented with impaired consciousness (66.6 %). The common causes for poor outcome were multiorgan failure, encephalopathy and refractory shock. The atypical manifestations of dengue fever are no more a rare entity. Clinicians should have a high index of suspicion and vigilance for atypical manifestations of dengue fever as lack of timely detection and management could be fatal. Impaired consciousness was the most ominous atypical manifestation of severe dengue infection.

Atypical Odontalgia (Phantom Tooth Pain)

MedlinePlus

... atypical facial pain, phantom tooth pain, or neuropathic orofacial pain, is characterized by chronic pain in a tooth ... such as a specialist in oral medicine or orofacial pain. The information contained in this monograph is for ...

Secondary Cutaneous Amyloidosis Associated with Mycosis Fungoides

DTIC Science & Technology

2018-02-16

hypomelanosis, or idiopathic guttate hypomelanosis. Histologically. an atypical intraepidennallymphoid infiltrate was seen with scattered foci of g!obulat...fungoides, post-inflammatory hypomelanosis, or idiopathic guttate hypomelanosis. Histologically, an atypical intraepidermal lymphoid infiltrate was seen

Pulmonary cytology in chrysotile asbestos workers

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

Kobusch, A.B.; Simard, A.; Feldstein, M.

1984-01-01

The prevalence of atypical cytology has been determined in relation to age, smoking and asbestos exposure for male workers employed in 3 mines in the Province of Quebec. Overall participation was 71%. Out of 867 participating workers, 626 (72%) presented a deep cough specimen within normal limits, 74 (8.5%) a specimen with mild atypical metaplasia and 10 (1.2%) a specimen with moderate atypical metaplasia. Four lung carcinoma were identified. Five percent of the workers initially interviewed did not return their specimen and 12.7% had unsatisfactory test results. Proportions of cellular atypical increased with age and asbestos exposure. Using logistic regressionmore » analysis, estimated probabilities of abnormal cytology for workers aged 25 years when started mining increased with both years of asbestos exposure and exposure index measured in fibres per cubic centimeter.« less

Children's reasoning about gender-atypical preferences in different settings.

PubMed

Conry-Murray, Clare

2013-05-01

Two age groups of children, 5- and 6-year-olds (n=30) and 8- and 9-year-olds (n=26), made judgments about which of two items a character should choose: a gender-typical item or a gender-atypical item that was preferred by the character. Judgments were made about situations where the character was (a) in a familiar public setting and (b) in a country where the reversed preference was typical for that culture. At both ages and in both settings, a majority of responses endorsed the character's atypical preference. However, at both ages, endorsements of the atypical preferences were significantly less frequent in the familiar public setting that in the norm-reversed setting, and justifications indicated that there would be social consequences for defying gender norms in the familiar setting. Copyright © 2012 Elsevier Inc. All rights reserved.

FLARES ON A-TYPE STARS: EVIDENCE FOR HEATING OF SOLAR CORONA BY NANOFLARES?

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

Švanda, Michal; Karlický, Marian, E-mail: michal@astronomie.cz

We analyzed the occurrence rates of flares on stars of spectral types K, G, F, and A, observed by Kepler . We found that the histogram of occurrence frequencies of stellar flares is systematically shifted toward a high-energy tail for A-type stars compared to stars of cooler spectral types. We extrapolated the fitted power laws toward flares with smaller energies (nanoflares) and made estimates for total energy flux to stellar atmospheres by flares. We found that, for A-type stars, the total energy flux density was at least four-times smaller than for G stars. We speculate that this deficit in energymore » supply may explain the lack of hot coronae on A-type stars. Our results indicate the importance of nanoflares for heating and formation of the solar corona.« less

Use of atypical antipsychotics in the elderly: a clinical review

PubMed Central

Gareri, Pietro; Segura-García, Cristina; Manfredi, Valeria Graziella Laura; Bruni, Antonella; Ciambrone, Paola; Cerminara, Gregorio; De Sarro, Giovambattista; De Fazio, Pasquale

2014-01-01

The use of atypical antipsychotic drugs in the elderly has become wider and wider in recent years; in fact, these agents have novel receptor binding profiles, good efficacy with regard to negative symptoms, and reduced extrapyramidal symptoms. However, in recent years, the use of both conventional and atypical antipsychotics has been widely debated for concerns about their safety in elderly patients affected with dementia and the possible risks for stroke and sudden death. A MEDLINE search was made using the words elderly, atypical antipsychotics, use, schizophrenia, psychosis, mood disorders, dementia, behavioral disorders, and adverse events. Some personal studies were also considered. This paper reports the receptor binding profiles and the main mechanism of action of these drugs, together with their main use in psychiatry and the possible adverse events in elderly people. PMID:25170260

Use of Atypical Antipsychotics in Nursing Homes and Pharmaceutical Marketing

PubMed Central

Pimentel, Camilla B.; Donovan, Jennifer L.; Field, Terry S.; Gurwitz, Jerry H.; Harrold, Leslie R.; Kanaan, Abir O.; Lemay, Celeste A.; Mazor, Kathleen M.; Tjia, Jennifer; Briesacher, Becky A.

2014-01-01

BACKGROUND Many nursing home (NH) residents are prescribed atypical antipsychotics despite US Food and Drug Administration warnings of increased risk of death in older adults with dementia. Aggressive pharmaceutical marketing has been cited as a potential cause, although data are scarce. The objectives of this study were to describe the current extent and type of pharmaceutical marketing in NHs in one state, and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. DESIGN Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. SETTING 41 NHs in Connecticut. PARTICIPANTS NH administrators, directors of nursing and medical directors (n = 93, response rate 75.6%). MEASUREMENTS Quantitative data, including prescription drug dispensing data (September 2009–August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing and NH quality. Qualitative data, including semi-structured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. RESULTS Leadership at 46.3% of NHs (19/41) reported pharmaceutical marketing encounters, consisting of educational training, written/Internet-based materials and/or sponsored training. No association was detected between the level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. CONCLUSION NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. PMID:25688605

Unusual cardiac paraganglioma mimicking an atypical carcinoid tumor of the lung

PubMed Central

Evans, Mark; Wang, Beverly; Delrosario, J. Lawrence; Cheng, Timmy; Milliken, Jeffrey

2018-01-01

We present a case of unusual cardiac paraganglioma (PG) initially misdiagnosed as atypical carcinoid tumor of the lung and discuss key clinical and pathologic characteristics that guide surgical management of these rare chromaffin cell tumors. A 64-year-old female with persistent cough and back pain was found to have a 4 cm × 3 cm mass abutting multiple cardiopulmonary structures. A biopsy was performed at an outside institution and pathology reported “atypical neuroendocrine carcinoma, consistent with carcinoid”. The patient was transferred to our institution and pericardial resection with right pneumonectomy was performed to excise the tumor. Histology of the mass was that of PG with multiple ethanol embolizations. Immunohistochemical examination revealed that type I (chief) cells were positive for neuroendocrine markers (chromogranin A and synaptophysin), while type II (sustentacular) cells were positive for S100. There was no evidence of atypical carcinoid tumor in the lung. PG is an entity of chromaffin cell tumors that often affects the adrenal glands and carotid body. PG rarely occurs in the thoracic region, accounting for just 1–2% of all PG. Proper diagnosis of cardiac PG is challenging owing to its rare prevalence, subtle symptoms of presentation, and the neuroendocrine histopathological features it shares with atypical carcinoids. These tumors are typically benign and are best treated by surgical resection. Our report examines the approach to appropriate diagnosis of cardiac PG vs. atypical carcinoid, preoperative management, and surgical treatment by describing successful resection through thoracotomy without the use of cardiopulmonary bypass. PMID:29600100

Telemetry-assisted early detection of STEMI in patients with atypical symptoms by paramedic-performed 12-lead ECG with subsequent cardiological analysis.

PubMed

Campo Dell' Orto, Marco; Hamm, Christian; Liebetrau, Christoph; Hempel, Dorothea; Merbs, Reinhold; Cuca, Colleen; Breitkreutz, Raoul

2017-08-01

ECG is an essential diagnostic tool in patients with acute coronary syndrome. We aimed to determine how many patients presenting with atypical symptoms for an acute myocardial infarction show ST-segment elevations on prehospital ECG. We also aimed to study the feasibility of telemetric-assisted prehospital ECG analysis. Between April 2010 and February 2011, consecutive emergency patients presenting with atypical symptoms such as nausea, vomiting, atypical chest pain, palpitations, hypertension, syncope, or dizziness were included in the study. After basic measures were completed, a 12-lead ECG was written and telemetrically transmitted to the cardiac center, where it was analyzed by attending physicians. Any identification of an ST-elevation myocardial infarction resulted in patient admission at the closest coronary angiography facility. A total of 313 emergency patients presented with the following symptoms: dyspnea, nausea, vomiting, dizziness/collapse, or acute hypertension. Thirty-four (11%) patients of this cohort were found to show ST-segment elevations on the 12-lead ECG. These patients were directly admitted to the closest coronary catheterization facility rather than the closest hospital. The time required for transmission and analysis of the ECG was 3.6±1.2 min. Telemetry-assisted 12-lead ECG analysis in a prehospital setting may lead to earlier detection of ST-elevation myocardial infarction in patients with atypical symptoms. Thus, a 12-lead ECG should be considered in all prehospital patients both with typical and atypical symptoms.

The impact of sex and language dominance on material-specific memory before and after left temporal lobe surgery.

PubMed

Helmstaedter, C; Brosch, T; Kurthen, M; Elger, C E

2004-07-01

Recent findings raised evidence that in early-onset left temporal lobe epilepsy, women show greater functional plasticity for verbal memory than men. In particular, women with lesion- or epilepsy-driven atypical language dominance show an advantage over men. The question asked in this study was whether there is evidence of sex- and language dominance-dependent late, i.e. adult age, plasticity for verbal memory when epilepsy surgery is performed in these patients. Pre- and 1-year postoperative memory performance was evaluated in 169 patients (94 males and 75 females) who underwent left temporal lobe surgery and who had WADA testing of hemispheric language dominance prior to surgery. Verbal memory and figural memory were assessed by list-learning paradigms. According to the Bonn intracarotid amobarbital test (IAT) protocol, patients were categorized into left dominant or atypically dominant (right, incomplete left or right, and bilateral dominant) groups. Results were controlled for the hypothesized sex differences. Thirty-four percent of men and 47% of women displayed patterns of atypical language dominance. Atypical dominance was related to an early onset of epilepsy. Men showed a larger time window for development of atypical dominance but, differently from women, the pattern of atypical dominance was more strictly determined by the age at onset of epilepsy. Atypically dominant women showed better verbal memory than typically dominant women or men. After surgery, right dominant patients had better verbal memory outcome than patients with bilateral or left language dominance who showed significant memory loss. No effect of sex on verbal memory change was found. Figural memory deteriorated in men and improved in women, when they were not left dominant. Seizure outcome had no effect on performance changes. It was concluded that better preserved verbal memory in atypically dominant women before surgery indicates greater benefit from atypical dominance in women than men with regard to the initial damage associated with left hemisphere epilepsy. Later in life, when epilepsy surgery causes additional damage, no such sex difference is observed, indicating that the women's advantage over men is fixed to an early time window in life. Postoperative changes in figural memory suggest dynamics in crowding and suppression patterns. Whether this reflects late plasticity and compensation needs further demonstration. For clinical practice, it is important to note that incomplete right hemisphere and bilateral language dominance do not protect against verbal memory loss after left-sided temporal lobe surgery. Copyright 2004 Guarantors of Brain

Atypical presentations of gastroesophageal reflux disease.

PubMed

Heidelbaugh, Joel J; Gill, Arvin S; Van Harrison, R; Nostrant, Timothy T

2008-08-15

Gastroesophageal reflux disease typically manifests as heartburn and regurgitation, but it may also present with atypical or extraesophageal symptoms, including asthma, chronic cough, laryngitis, hoarseness, chronic sore throat, dental erosions, and noncardiac chest pain. Diagnosing atypical manifestations of gastroesophageal reflux disease is often a challenge because heartburn and regurgitation may be absent, making it difficult to prove a cause-and-effect relationship. Upper endoscopy and 24-hour pH monitoring are insensitive and not useful for many patients as initial diagnostic modalities for evaluation of atypical symptoms. In patients with gastroesophageal reflux disease who have atypical or extraesophageal symptoms, aggressive acid suppression using proton pump inhibitors twice daily before meals for three to four months is the standard treatment, although some studies have failed to show a significant benefit in symptomatic improvement. If these symptoms improve or resolve, patients may step down to a minimal dose of antisecretory therapy over the following three to six months. Surgical intervention via Nissen fundoplication is an option for patients who are unresponsive to aggressive antisecretory therapy. However, long-term studies have shown that some patients still require antisecretory therapy and are more likely to develop dysphagia, rectal flatulence, and the inability to belch or vomit.

Treatment of category generation and retrieval in aphasia: Effect of typicality of category items.

PubMed Central

Kiran, Swathi; Sandberg, Chaleece; Sebastian, Rajani

2011-01-01

Purpose: Kiran and colleagues (Kiran, 2007, 2008; Kiran & Johnson, 2008; Kiran & Thompson, 2003) have previously suggested that training atypical examples within a semantic category is a more efficient treatment approach to facilitating generalization within the category than training typical examples. The present study extended our previous work examining the notion of semantic complexity within goal-derived (ad-hoc) categories in individuals with aphasia. Methods: Six individuals with fluent aphasia (range = 39-84 years) and varying degrees of naming deficits and semantic impairments were involved. Thirty typical and atypical items each from two categories were selected after an extensive stimulus norming task. Generative naming for the two categories was tested during baseline and treatment. Results: As predicted, training atypical examples in the category resulted in generalization to untrained typical examples in five out the five patient-treatment conditions. In contrast, training typical examples (which was in examined three conditions) produced mixed results. One patient showed generalization to untrained atypical examples, whereas two patients did not show generalization to untrained atypical examples. Conclusions: Results of the present study supplement our existing data on the effect of a semantically based treatment for lexical retrieval by manipulating the typicality of category exemplars. PMID:21173393

Myasthenia Gravis: Unusual Presentations and Diagnostic Pitfalls.

PubMed

Rodolico, Carmelo; Parisi, Daniela; Portaro, Simona; Biasini, Fiammetta; Sinicropi, Stefano; Ciranni, Annamaria; Toscano, Antonio; Messina, Sonia; Musumeci, Olimpia; Vita, Giuseppe; Girlanda, Paolo

2016-08-30

Myasthenia gravis (MG) is an autoimmune disorder presenting with fluctuating, fatigable muscle weakness. Initial symptoms classically involve ocular and proximal limb muscles. Rarely, MG may onset with unusual features, so it can be misdiagnosed with other neuromuscular diseases. To describe unusual and atypical presentations of MG in a large cohort of patients, considering and discussing diagnostic difficulties and pitfalls. We report on 21 out of 508 MG patients, coming to our department in the last 27 years and presenting with atypical or unusual features. The diagnosis was achieved performing a careful clinical examination, a proper neurophysiological assessment, the neostigmine test, the AChR and MuSK antibodies assay and chest CT-scan. Patients with atypical/unusual MG onset were the 4.4% of all MG patients population. We describe seven different clinical categories: asymmetric distal upper limbs weakness, foot drop, isolated triceps brachii weakness and foot drop, post exertional axial weakness with dropped head, acute facial dyplegia, limb-girdle MG and MG with sudden lower limbs weakness and recurrent falls. Atypical and unusual presentations may increase the risk to misdiagnose or delay MG diagnosis. Isolated limb-girdle presentation is the most frequent atypical form in our series.

Unique Neural Characteristics of Atypical Lateralization of Language in Healthy Individuals

PubMed Central

Biduła, Szymon P.; Przybylski, Łukasz; Pawlak, Mikołaj A.; Króliczak, Gregory

2017-01-01

Using functional magnetic resonance imaging (fMRI) in 63 healthy participants, including left-handed and ambidextrous individuals, we tested how atypical lateralization of language—i. e., bilateral or right hemispheric language representation—differs from the typical left-hemisphere dominance. Although regardless of their handedness, all 11 participants from the atypical group engaged classical language centers, i.e., Broca's and Wernicke's areas, the right-hemisphere components of the default mode network (DMN), including the angular gyrus and middle temporal gyrus, were also critically involved during the verbal fluency task. Importantly, activity in these regions could not be explained in terms of mirroring the typical language pattern because left-hemisphere dominant individuals did not exhibit similar significant signal modulations. Moreover, when spatial extent of language-related activity across whole brain was considered, the bilateral language organization entailed more diffuse functional processing. Finally, we detected significant differences between the typical and atypical group in the resting-state connectivity at the global and local level. These findings suggest that the atypical lateralization of language has unique features, and is not a simple mirror image of the typical left hemispheric language representation. PMID:28983238

Petrogenesis of selected A-type granitic intrusions from Central Eastern Desert of Egypt

NASA Astrophysics Data System (ADS)

Hassan, Tharwat; Asran, Asran; Amron, Taha; Hauzenberger, Christoph

2014-05-01

The Pan-African orogeny in the Arabian-Nubian Shield was terminated by intrusion of A-type granites (~ 595 Ma; Greenberg, 1981) and its volcanic equivalents. Subsequent to the intrusions of these granitic bodies the shield was exhumed. Eroded A-type granite pebbles were found in the molasse sediments that were deposited in intermountain basins. Therefore the A-type granites provide information about the last stage of the Pan-African geochemical system. Preliminary whole-rock geochemical data of three granitic intrusions (Kadabora, Um Naggat and El shiekh Salem) from the Central Eastern Desert of Egypt; indicate that all of them are peraluminous and with A-type characteristics. These intrusions show low CaO content (average 0.43 %wt), high FeOT/MgO ratio (10.46-121.88), high Na2O+K2O (average 8.04 %wt), marked enrichment of high field strength elements (Y, Nb and Ga except Zr), depletion in MgO (0.01-0.11 %wt) and with low concentration of Sr and Ba. The studied granitoids were emplaced in within plate tectonic regime. References: Greenberg, J.K. (1981): Characteristic and origin of Egyptian younger granites. Bull. Geol. Soc. Am. Part 1, v.92: 224-232.

Atypical lymphocytosis in leptospirosis: a cohort of hospitalized cases between 1996 and 2009 in State of Rio de Janeiro, Brazil.

PubMed

Damasco, Paulo Vieira; Avila, Carlos André Lins; Barbosa, Angélica Tápia; Ribeiro Carvalho, Marilza de Moura; Pereira, Geraldo Moura Batista; Lemos, Elba Regina Sampaio de; Bóia, Márcio Neves; Pereira, Martha Maria

2011-10-01

Leptospirosis is a zoonotic disease found in tropical and temperate countries, and its clinical diagnostic confusion with arboviruses (dengue fever, oropouche fever and yellow fever), Brazilian spotted fever, viral hepatitis and hantaviruses has been an ongoing public health concern. The aim of this observational study was to demonstrate an association between findings of atypical lymphocytosis and the progression of endemic leptospirosis. A retrospective analysis was performed on the demographic, epidemiological, clinical and laboratory aspects of 27 human leptospirosis cases that occurred over a period of 13 years (1996-2009) with no reported epidemic outbreaks in Rio de Janeiro, Brazil. The overall mortality rate was 11.1% in our cohort of hospitalized cases. However, there was no mortality among patients with atypical lymphocytosis (OR = 11.1; 95% CI = 1.12-110.9; p = 0.04). Two patients who were in the septicemic phase showed signs of expansion of γδ T cell responses in peripheral blood. Atypical lymphocytosis may be observed in patients with leptospirosis. Our observations suggest that these atypical leukocyte subsets are associated with partial protection during the disease course of leptospirosis.

Clinical studies of pigmented lesions in human skin by using a multiphoton tomograph

NASA Astrophysics Data System (ADS)

Balu, Mihaela; Kelly, Kristen M.; Zachary, Christopher B.; Harris, Ronald M.; Krasieva, Tatiana B.; König, Karsten; Tromberg, Bruce J.

2013-02-01

In vivo imaging of pigmented lesions in human skin was performed with a clinical multiphoton microscopy (MPM)-based tomograph (MPTflex, JenLab, Germany). Two-photon excited fluorescence was used for visualizing endogenous fluorophores such as NADH/FAD, keratin, melanin in the epidermal cells and elastin fibers in the dermis. Collagen fibers were imaged by second harmonic generation. Our study involved in vivo imaging of benign melanocytic nevi, atypical nevi and melanoma. The goal of this preliminary study was to identify in vivo the characteristic features and their frequency in pigmented lesions at different stages (benign, atypical and malignant) and to evaluate the ability of in vivo MPM to distinguish atypical nevi from melanoma. Comparison with histopathology was performed for the biopsied lesions. Benign melanocytic nevi were characterized by the presence of nevus cell nests at the epidermal-dermal junction. In atypical nevi, features such as lentiginous hyperplasia, acanthosis and architectural disorder were imaged. Cytological atypia was present in all the melanoma lesions imaged, showing the strongest correlation with malignancy. The MPM images demonstrated very good correlation with corresponding histological images, suggesting that MPM could be a promising tool for in vivo non-invasive pigmented lesion diagnosis, particularly distinguishing atypical nevi from melanoma.

Atypical squamous and glandular cells of undetermined significance (ASCUS and AGUS) of the uterine cervix.

PubMed

Cenci, M; Vecchione, A

2000-01-01

ASCUS (Atypical Squamous Cells of Undetermined Significance) and AGUS (Atypical Glandular Cells of Undetermined Significance), or AGCUS, are two acronyms introduced in 1988 by The Bethesda System (TBS) for reporting borderline cytological changes in cervical cytology. ASCUS and AGUS categories should be subclassified. Five ASCUS subgroups were proposed: 1) ASCUS due to processing defects, 2) with "mature" cytoplasm, 3) in post-menopausal women (a--in the setting of atrophy and b--with estrogen stimulation), 4) atypical metaplasia, and 5) ASCUS with keratinized cytoplasm. AGUS subgroups may be subcategorized in endometrial or endocervical on the basis of origin. Endocervical AGUS should be further qualified, but the analysis of atypical glandular cells may be really difficult and the conclusive diagnosis is frequently "AGUS not otherwise specified". The subclassification of ASCUS and AGUS is useful for an appropriate clinical management, but pertinent patient information (such as age, date of last menstrual period, mechanical therapies, tamoxifen therapy, and others) is needed to avoid an overdiagnosis and consequently an overtreatment. In fact various subgroups require different clinical management. Therefore, an effective communication between cytopathologists and referring physicians is essential in the analysis of squamous and glandular atypias.

A-type dimeric epigallocatechin-3-gallate (EGCG) is a more potent inhibitor against the formation of insulin amyloid fibril than EGCG monomer.

PubMed

Nie, Rong-Zu; Zhu, Wei; Peng, Jin-Ming; Ge, Zhen-Zhen; Li, Chun-Mei

2016-06-01

Because fibrillary protein aggregates is regarded to be closely associated with many diseases such as Alzheimer's disease, diabetes, and Parkinson's disease, growing interest and researches have been focused on finding potential fibrillation inhibitors. In the present study, the inhibitory effects of epigallocatechin-3-gallate (EGCG) and A-type dimeric epigallocatechin-3-gallate (A-type EGCG dimer) on the formation of insulin fibrillation were compared by multi-dimensional approaches including thioflavin-T (ThT) fluorescence assay, 1-anilinonaphthalene-8-sulfonic (ANS) fluorescence assay, dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and circular dichroism (CD) spectroscopy. Our results confirmed that A-type EGCG dimer is a more potent inhibitor against the formation of bovine insulin amyloid fibril than EGCG. In addition, A-type EGCG dimer could not only inhibit insulin amyloid fibril formation, but also change the aggregation pathway and induce bovine insulin into amorphous aggregates. The results of the present study may provide a new guide on finding novel anti-amyloidogenic agents. Copyright © 2016 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

Recognition and assessment of atypical and ambiguous genitalia in the newborn.

PubMed

Davies, Justin H; Cheetham, Timothy

2017-10-01

The baby with atypical or ambiguous genitalia is usually born in secondary care. For most clinicians, this is an unfamiliar and challenging scenario with the potential for life-long ramifications arising from a consultation led by an unprepared clinician. Language needs to be used carefully with particular clarity when liaising with parents, local health professionals and the specialist multidisciplinary team. Confidence in the recognition and assessment of atypical or ambiguous genitalia in a newborn will guide the local clinician when deciding on the initial investigations required and is a foundation for subsequent management. The local team have key roles in the initial support for parents as well as managing expectations at a time of great uncertainty. There are numerous different diagnoses that can result in atypical or ambiguous genitalia. The clinical findings should guide the initial investigations, and there are many pitfalls when it comes to interpreting the results. The aim of this article is to provide an initial approach to the management of a baby born with atypical or ambiguous genitalia. © 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.

Medicolegal aspects of atypical firearm injuries: a case report.

PubMed

Gürses, Murat Serdar; Akan, Okan; Eren, Bülent; Durak, Dilek; Türkmen, Nursel; Cetin, Selçuk

2014-01-01

Our case was a twenty year-old man, who was injured during the military duty with G3 infantry rifle in the training area. An atypical firearm entry wound on the left side of sternum which was 4.5 cm in diameter, and was surrounded by six irregular skin burn wounds by a flash-suppressor and a 0.7 cm diameter firearm exit wound at space on the left midscapular line. Our case emphasizes that the interpretation of properties of these atypical firearm entry wounds need to be carefully assessed by physicians.

Atypical psychotic symptoms and Dandy-Walker variant.

PubMed

Williams, Aislinn J; Wang, Zhenni; Taylor, Stephan F

2016-10-01

New-onset psychotic symptoms often respond well to antipsychotic treatment; however, symptoms may be difficult to treat when an underlying brain malformation is present. Here, we present a case of atypical psychotic symptoms in the context of a congenital cerebellar malformation (Dandy-Walker variant). The patient ultimately improved with paliperidone palmitate after multiple antipsychotic medication trials (both oral and one long-acting injectable) were ineffective. Neuroimaging may provide valuable diagnostic and prognostic information in cases of new-onset psychosis with atypical features and treatment resistance, even in the absence of neurologic signs and symptoms.

[Facial diplegia with atypical paresthesia. A variant of Guillain-Barré syndrome].

PubMed

Dal Verme, Agustín; Acosta, Paula; Margan, Mercedes; Pagnini, Cecilia; Dellepiane, Eugenia; Peralta, Christian

2015-01-01

Guillain-Barré syndrome is an acute demyelinating disease which presents in a classic form with muscular weakness and the lack of reflexes. There are multiple variations and atypical forms of the disease, being facial diplegia with paresthesia one of them. Also, the absence of reflexes in this syndrome is typical but not constant, since 10% of patients present reflexes. We describe a case of atypical presentation with bilateral facial palsy, paresthesia, brisk reflexes and weakness in the lower limbs in a 33 year old woman.

Prader-Willi syndrome: a case report with atypical developmental features.

PubMed

Sewaybricker, Letícia E; Guaragna-Filho, Guilherme; Paula, Georgette B; Andrade, Juliana G R; Tincani, Bruna J; D'Souza-Li, Lília; Lemos-Marini, Sofia H V; Maciel-Guerra, Andréa T; Guerra-Júnior, Gil

2014-09-01

To describe the case of a male Prader-Willi syndrome (PWS) patient with atypical development features. We report the case of a male adolescent with confirmed diagnosis of PWS which presents atypical phenotype. The patient progressed with spontaneous and complete pubertal development, stature in the normal range, and weight control without any pharmacological treatment, except metformin. PWS is an imprinting paternally inherited disorder of 15q11-13 characterized by hypotonia in infant age, hyperphagia, varied degrees of mental retardation, behavior problems, hypogonadism, short stature, and other less common findings.

Atypical scrapie in sheep from a UK research flock which is free from classical scrapie

PubMed Central

Simmons, Hugh A; Simmons, Marion M; Spencer, Yvonne I; Chaplin, Melanie J; Povey, Gill; Davis, Andrew; Ortiz-Pelaez, Angel; Hunter, Nora; Matthews, Danny; Wrathall, Anthony E

2009-01-01

Background In the wake of the epidemic of bovine spongiform encephalopathy the British government established a flock of sheep from which scrapie-free animals are supplied to laboratories for research. Three breeds of sheep carrying a variety of different genotypes associated with scrapie susceptibility/resistance were imported in 1998 and 2001 from New Zealand, a country regarded as free from scrapie. They are kept in a purpose-built Sheep Unit under strict disease security and are monitored clinically and post mortem for evidence of scrapie. It is emphasised that atypical scrapie, as distinct from classical scrapie, has been recognised only relatively recently and differs from classical scrapie in its clinical, neuropathological and biochemical features. Most cases are detected in apparently healthy sheep by post mortem examination. Results The occurrence of atypical scrapie in three sheep in (or derived from) the Sheep Unit is reported. Significant features of the affected sheep included their relatively high ages (6 y 1 mo, 7 y 9 mo, 9 y 7 mo respectively), their breed (all Cheviots) and their similar PRNP genotypes (AFRQ/AFRQ, AFRQ/ALRQ, and AFRQ/AFRQ, respectively). Two of the three sheep showed no clinical signs prior to death but all were confirmed as having atypical scrapie by immunohistochemistry and Western immunoblotting. Results of epidemiological investigations are presented and possible aetiologies of the cases are discussed. Conclusion By process of exclusion, a likely explanation for the three cases of atypical scrapie is that they arose spontaneously and were not infected from an exterior source. If correct, this raises challenging issues for countries which are currently regarded as free from scrapie. It would mean that atypical scrapie is liable to occur in flocks worldwide, especially in older sheep of susceptible genotypes. To state confidently that both the classical and atypical forms of scrapie are absent from a population it is necessary for active surveillance to have taken place. PMID:19208228

Digital image analysis supports a nuclear-to-cytoplasmic ratio cutoff value of 0.5 for atypical urothelial cells.

PubMed

Hang, Jen-Fan; Charu, Vivek; Zhang, M Lisa; VandenBussche, Christopher J

2017-09-01

An elevated nuclear-to-cytoplasmic (N:C) ratio of ≥0.5 is a required criterion for the diagnosis of atypical urothelial cells (AUC) in The Paris System for Reporting Urinary Cytology. To validate the N:C ratio cutoff value and its predictive power for high-grade urothelial carcinoma (HGUC), the authors retrospectively reviewed the urinary tract cytology specimens of 15 cases of AUC with HGUC on follow-up (AUC-HGUC) and 33 cases of AUC without HGUC on follow-up (AUC-N-HGUC). The number of atypical cells in each case was recorded, and each atypical cell was photographed and digitally examined to calculate the nuclear size and N:C ratio. On average, the maximum N:C ratios of atypical cells were significantly different between the AUC-HGUC and AUC-N-HGUC cohorts (0.53 vs 0.43; P =.00009), whereas the maximum nuclear sizes of atypical cells (153.43 μM 2 vs 201.47 μM 2 ; P = .69) and the number of atypical cells per case (10.13 vs 7.88; P = .12) were not found to be significantly different. Receiver operating characteristic analysis demonstrated that the maximum N:C ratio alone had high discriminatory capacity (area under the curve, 79.19%; 95% confidence interval, 64.19%-94.19%). The optimal maximum N:C ratio threshold was 0.486, giving a sensitivity of 73.3% and a specificity of 84.8% for predicting HGUC on follow-up. The identification of AUC with an N:C ratio >0.486 has a high predictive power for HGUC on follow-up in AUC specimens. This justifies using the N:C ratio as a required criterion for the AUC category. Individual laboratories using different cytopreparation methods may require independent validation of the N:C ratio cutoff value. Cancer Cytopathol 2017;125:710-6. © 2017 American Cancer Society. © 2017 American Cancer Society.

Atypical aetiology in patients hospitalised with community-acquired pneumonia is associated with age, gender and season; a data-analysis on four Dutch cohorts.

PubMed

Raeven, Vivian M; Spoorenberg, Simone M C; Boersma, Wim G; van de Garde, Ewoudt M W; Cannegieter, Suzanne C; Voorn, G P Paul; Bos, Willem Jan W; van Steenbergen, Jim E

2016-06-17

Microorganisms causing community-acquired pneumonia (CAP) can be categorised into viral, typical and atypical (Legionella species, Coxiella burnetii, Mycoplasma pneumoniae, and Chlamydia species). Extensive microbiological testing to identify the causative microorganism is not standardly recommended, and empiric treatment does not always cover atypical pathogens. In order to optimize epidemiologic knowledge of CAP and to improve empiric antibiotic choice, we investigated whether atypical microorganisms are associated with a particular season or with the patient characteristics age, gender, or chronic obstructive pulmonary disease (COPD). A data-analysis was performed on databases from four prospective studies, which all included adult patients hospitalised with CAP in the Netherlands (N = 980). All studies performed extensive microbiological testing. A main causative agent was identified in 565/980 (57.7 %) patients. Of these, 117 (20.7 %) were atypical microorganisms. This percentage was 40.4 % (57/141) during the non-respiratory season (week 20 to week 39, early May to early October), and 67.2 % (41/61) for patients under the age of 60 during this season. Factors that were associated with atypical causative agents were: CAP acquired in the non-respiratory season (odds ratio (OR) 4.3, 95 % CI 2.68-6.84), age <60 year (OR 2.9, 95 % CI 1.83-4.66), male gender (OR 1.7, 95 % CI 1.06-2.71) and absence of COPD (OR 0.2, 95 % CI 0.12-0.52). Atypical causative agents in CAP are associated with respectively non-respiratory season, age <60 years, male gender and absence of COPD. Therefore, to maximise its yield, extensive microbiological testing should be considered in patients <60 years old who are admitted with CAP from early May to early October. NCT00471640 , NCT00170196 (numbers of original studies).

Bone density, body composition, and psychopathology of anorexia nervosa spectrum disorders in DSM-IV vs DSM-5.

PubMed

Schorr, Melanie; Thomas, Jennifer J; Eddy, Kamryn T; Dichtel, Laura E; Lawson, Elizabeth A; Meenaghan, Erinne; Lederfine Paskal, Margaret; Fazeli, Pouneh K; Faje, Alexander T; Misra, Madhusmita; Klibanski, Anne; Miller, Karen K

2017-04-01

DSM-5 revised the diagnostic criteria for anorexia nervosa (AN) by eliminating the amenorrhea requirement, liberalizing weight and psychological criteria, and adding the formal diagnosis of "atypical AN" for individuals with AN psychological symptoms without low weight. We sought to determine whether bone density (BMD) is impaired in women diagnosed with AN using the new, more liberal, DSM-5 criteria. Cross-sectional study of 168 women, 18 - 45y: (1) AN by DSM-IV (DSM-IV AN) (n = 37), (2) AN by DSM-5 but not DSM-IV criteria (DSM-5 AN) (n = 33), (3) atypical AN (ATYPICAL AN) (n = 77), (4) healthy comparison group (HC) (n = 21). Measurements included dual energy X-ray absorptiometry, Eating Disorder Examination-Questionnaire, Eating Disorder Inventory-2, Hamilton Depression and Anxiety Rating Scales. BMD Z-score <-1.0 was present in 78% of DSM-IV, 82% of DSM-5, and 69% of ATYPICAL. Mean Z-scores were comparably low in DSM-IV and DSM-5, intermediate in ATYPICAL, and highest in HC. Lack of prior low weight or amenorrhea was, but history of overweight/obesity was not, protective against bone loss. Mean lean mass and percent fat mass were significantly lower in all AN groups than HC. DSM-IV, DSM-5, and ATYPICAL had comparable psychopathology. Despite liberalizing diagnostic criteria, many women diagnosed with AN and atypical AN using DSM-5 criteria have low BMD. Presence or history of low weight and/or amenorrhea remain important indications for DXA. Loss of lean mass, in addition to fat mass, is present in all AN groups, and may contribute to low BMD. The deleterious effect of eating disorders on BMD extends beyond those with current low weight and amenorrhea. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:343-351). © 2016 Wiley Periodicals, Inc.

Natural course of typical and atypical parenchymal solitary cysticercus granuloma of the brain: a 3-year prospective clinico-radiological study.

PubMed

Kumar, Neeraj; Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Gupta, Rakesh Kumar; Verma, Rajesh; Sharma, Praveen Kumar

2016-02-01

To evaluate the role of advanced magnetic resonance (MR) sequences (fast imaging employing steady-state acquisition (FIESTA), T2 star-weighted angiography (SWAN) and spoiled gradient recalled echo (SPGR)) in patients with single small enhancing computed tomography lesions and scolex demonstration in typical and atypical parenchymal neurocysticercosis. In this study, 59 patients of new-onset seizures with single small enhancing computed tomography lesions of the brain were included. Along with routine MR sequences, advanced MR sequences, like SWAN, FIESTA, and pre and post-contrast SPGR, were performed. Follow-up MR studies focussing on the morphology of the lesions and demonstration of scolex were performed 6 monthly for 3 years. The majority of patients (62.7%) were men with partial seizure as the most common manifestation. On SPGR, contrast lesions were identified as either 'typical' (42, 71.2%) or 'atypical' (17, 28.8%). In the typical lesion group, SWAN and FIESTA sequences detected scolex in 30 (71.4%) and 32 (76.2%), respectively. The combination of SPGR-contrast, FIESTA and SWAN sequences detected scolex in 35 (83.3%) patients compared to 19 (45.2%) by routine sequences (P < 0.001). In the atypical lesion group, SWAN and FIESTA sequences detected scolex in 15 (88.2%) and 16 (94.1%) patients, respectively. The combination of SPGR-contrast, FIESTA and SWAN sequences detected scolex in 16 (94.1%) patients compared to 10 (58.8%) by routine sequences (P < 0.001). Follow-up showed greater resolution with lesser calcification in the typical group compared to the atypical group. This study provides an insight into the natural course of typical and atypical solitary cysticercus granuloma lesions, and the utility of SPGR-contrast, FIESTA and SWAN MR sequences in scolex demonstration and identification of atypical lesions. © The Author(s) 2015.

Clinical outcome in patients with peripherally-sited atypical lipomatous tumours and dedifferentiated liposarcoma.

PubMed

Kalimuthu, Sangeetha N; Tilley, Charles; Forbes, Georgina; Ye, Hongtao; Lehovsky, Katie; Pillay, Nischalan; Seddon, Beatrice M; O'Donnell, Paul; Pollock, Robin; Tirabosco, Roberto; Amary, M Fernanda; Flanagan, Adrienne M

2015-04-01

The reported incidence of local recurrence of peripheral atypical lipomatous tumours is highly variable and is likely to reflect the different inclusion criteria of cases, and the design of previous studies. We aimed to study the incidence of local recurrence of 90 cases of atypical lipomatous tumours and an additional 18 cases of de novo dedifferentiated liposarcoma. All tumours were diagnosed on the basis of MDM2 amplification: all patients had their first treatment in the same specialist sarcoma unit and were followed for a minimum of 60 months. The tumours were diagnosed between 1997 and 2009 and followed until the end of 2014. Seventy cases (78%) of atypical lipomatous tumours were located in the thigh (mean size 195 mm on presentation). Eight atypical lipomatous tumours (8.9%) recurred locally, of which 50% recurred after 60 months. The only two tumours with intralesional excisions recurred. Seven of the eight recurrent tumours were detected by the patient by self-examination. One case recurred a second time as a dedifferentiated liposarcoma. Seventeen per cent of the de novo dedifferentiated liposarcomas recurred within 60 months of presentation. Extending the study period revealed that atypical lipomatous tumour could recur up to 40 years after the first surgery. Furthermore, of 26 tumours that recurred in the extended study, 27% recurred more than once, and three of the seven that recurred more than once transformed into a dedifferentiated liposarcoma. We recommend that, following post-operative wound care, patients with atypical lipomatous tumour are referred back to their general practitioner for follow up, but that in the event of a suspected recurrence they have rapid access back to the specialist unit using a 'supported discharge' scheme. In the event of an intralesional excision and if a lesion recurs, patients are followed in a specialist unit at regular intervals: whether MRI scanning is a valuable means of monitoring such patients is unclear and requires an evidence base.

Q fever community-acquired pneumonia in a patient with Crohn's disease on immunosuppressive therapy.

PubMed

Nausheen, Sara; Cunha, Burke A

2007-01-01

Community-acquired pneumonia (CAP) may be caused by typical or atypical pathogens. The three most common zoonotic atypical pathogens are Chlamydophila psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii (Q fever). Atypical CAPs are suggested by a distinctive pattern of extrapulmonary organ involvement. Zoonotic CAP may be differentiated from nonzoonotic CAP (Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionnaire's disease) by a recent zoonotic vector contact history. Zoonotic atypical CAP occurs sporadically, but not randomly, and require close association with the appropriate zoonotic vector to transmit the infection. CAP accompanied by the extrapulmonary finding of splenomegaly in a normal host limits differential diagnostic possibilities to Q fever and psittacosis. Splenomegaly does not occur with other typical or atypical CAP. Another common extrapulmonary finding occurs with some atypical pneumonias, that is, Q fever, psittacosis, and Legionnaire's disease is early mild/transient elevations of serum transaminases indicative of (hepatic) extrapulmonary organ involvement. The case presented is a middle-aged man with longstanding Crohn's disease who was further immunosuppressed by chronic prednisone therapy. The patient presented with CAP and extrapulmonary findings, that is, splenomegaly and increased serum transaminases. He denied recent contact with birds or animals. Because Crohn's disease and Q fever CAP may be accompanied by splenomegaly, the cause of his splenomegaly was a diagnostic dilemma. The patient was treated with levofloxacin. Serologic tests for atypical pathogens (Q fever, psittacosis, Legionnaire's disease, C. pneumoniae, and M. pneumoniae) were ordered. Enzyme-linked immunosorbent assay serology for Q fever was positive with elevated acute immunoglobulin-M (phase II) titers. Re-questioning of the patient revealed a recent exposure to a neighbor's parturient cat, providing the necessary zoonotic vector contact history for Q fever. The patient responded to levofloxacin, which resulted in resolution of the patient's symptoms, right lower lobe pneumonia, and splenomegaly. Because a prior abdominal computed tomography scan indicated no splenomegaly and his splenomegaly resolved with antimicrobial therapy, the splenomegaly was related to Q fever CAP.

Dysfunctional metacognition and drive for thinness in typical and atypical anorexia nervosa.

PubMed

Davenport, Emily; Rushford, Nola; Soon, Siew; McDermott, Cressida

2015-01-01

Anorexia nervosa is complex and difficult to treat. In cognitive therapies the focus has been on cognitive content rather than process. Process-oriented therapies may modify the higher level cognitive processes of metacognition, reported as dysfunctional in adult anorexia nervosa. Their association with clinical features of anorexia nervosa, however, is unclear. With reclassification of anorexia nervosa by DSM-5 into typical and atypical groups, comparability of metacognition and drive for thinness across groups and relationships within groups is also unclear. Main objectives were to determine whether metacognitive factors differ across typical and atypical anorexia nervosa and a non-clinical community sample, and to explore a process model by determining whether drive for thinness is concurrently predicted by metacognitive factors. Women receiving treatment for anorexia nervosa (n = 119) and non-clinical community participants (n = 100), aged between 18 and 46 years, completed the Eating Disorders Inventory (3(rd) Edition) and Metacognitions Questionnaire (Brief Version). Body Mass Index (BMI) of 18.5 kg/m(2) differentiated between typical (n = 75) and atypical (n = 44) anorexia nervosa. Multivariate analyses of variance and regression analyses were conducted. Metacognitive profiles were similar in both typical and atypical anorexia nervosa and confirmed as more dysfunctional than in the non-clinical group. Drive for thinness was concurrently predicted in the typical patients by the metacognitive factors, positive beliefs about worry, and need to control thoughts; in the atypical patients by negative beliefs about worry and, inversely, by cognitive self-consciousness, and in the non-clinical group by cognitive self-consciousness. Despite having a healthier weight, the atypical group was as severely affected by dysfunctional metacognitions and drive for thinness as the typical group. Because metacognition concurrently predicted drive for thinness in both groups, a role for process-oriented therapy in adults is suggested. Implications are discussed.