bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring pancreatic pathology in Plasmodium falciparum malaria patients
Authors: Glaharn Supattra , Punsawad Chuchard , Ward Stephen A. , Viriyavejakul Parnpen 
Published: July 2018

AbstractHypoglycaemia is an important complication of Plasmodium falciparum malaria infection, which can be lethal if not treated. A decrease in blood sugar (BS) level has been correlated with disease severity, parasitaemia and the use of certain antimalarial drugs. This study explored the relationship between pancreatic pathology, including the expressions of insulin and glucagon in the islets of Langerhans, and the BS levels in P. falciparum malaria patients. Pancreatic tissues from malaria patients were divided into three groups, namely those with BS < 40 mg/dl, BS = 40–120 mg/dl, and BS > 120 mg/dl. In P. falciparum malaria, pancreatic tissues showed numerous parasitised red blood cells (PRBCs) in the capillaries, oedema, acinar necrosis and the presence of inflammatory cells. The islet size and the expression of insulin were significantly increased in P. falciparum malaria patients with hypoglycaemia. In addition, insulin expression was positively correlated with islet size and negatively correlated with BS levels. This pioneer study documents an increase in insulin expression and an increase in islet size in hypoglycaemic patients with P. falciparum malaria. This could contribute to the pathogenesis of hypoglycaemia and provides evidence for the potential need to effectively manage the hypoglycaemia seen in malaria infection.
Solid-phase synthesis of peptides containing aminoadipic semialdehyde moiety and their cyclisations
Authors: Kijewska Monika , Waliczek Mateusz , Cal Marta , Jaremko Łukasz , Jaremko Mariusz , Król Maria , Kołodziej Marta , Lisowski Marek , Stefanowicz Piotr , Szewczuk Zbigniew 
Published: July 2018

AbstractPathological levels of oxidative stress (OS) have been implicated in many diseases including diabetes mellitus, neurodegenerative diseases, inflammatory diseases, atherosclerosis, and cancer. Studies of oxidative stress are however complicated by the low concentration of oxidation products. To resolve this problem, we tested a new derivative of aminoadipic semialdehyde (Fmoc-Aea-OH) in the solid-phase synthesis of carbonylated peptides. We prepared a series of peptides with free and acetylated N-terminal amino groups using the Fmoc-Aea-OH reagent. LC-MS, ESI-MS, and MS/MS spectra confirmed the sequences of the modified peptides, although the LC-MS and ESI-MS spectra were dominated by signals corresponding to dehydration products. NMR studies of acetylated products revealed that the dominant product formed in this reaction contains a 1,2,3,4-tetrahydropyridine-2-carboxylic acid residue. Another side reaction in this system was the cleavage of the amide bond between the Aea residue and the amino acid moiety preceding it resulting in the formation of a side product with a six-membered ring at the N-terminus (2,3,4,5-tetrahydropyridine-2-carboxylic acid residue). We found that, depending on the peptide sequence, one of those side products is predominant. Our work suggests new methods for the solid-state synthesis of peptides containing unnatural amino acids.
Etiology and Prognosis of Severe Ventriculomegaly Diagnosed at Late Gestation
Authors: Dall’Asta Andrea , van Oostrum Noortje , Basheer Sheikh , Paramasivam Gowrishankar , Ghi Tullio , Galli Letizia , Groenenberg Irene , Tangi Amanda , Accorsi Patrizia , Echevarria Monica , Angeles Rodríguez Perez Maria , Albaiges Baiget Gerard , Prefumo Federico , Frusca Tiziana , Go Attie , Lees Christoph 
Published: July 2018

Abstract
Objectives We sought to assess the causes and outcomes of severe VM diagnosed de novo after 24 weeks of gestation where a mid-trimester anomaly scan was described as normal.
Methods Multicenter retrospective study of five European fetal medicine centers. The inclusion criteria were normal anatomy at the mid-trimester scan, uni/bilateral finding of posterior ventricle measuring ≥ 15 mm after 24 weeks with neonatal and postnatal pediatric and/or neurological assessment data.
Results Of 74 potentially eligible cases, 10 underwent termination, the outcome was missing in 19 cases and there was 1 neonatal death. Therefore, 44 formed the study cohort with a median gestation at diagnosis of 32 + 0 weeks (25 + 6 – 40 + 5). VM was unilateral in five cases. Agenesis of the corpus callosum (ACC) and grade III/IV intraventricular hemorrhage (IVH) accounted for 14 cases each. ACC was isolated in 9 fetuses. Obstructive abnormalities included 5 arachnoid and 1 cavum velum interpositum cyst. Four fetuses had an associated suspected or confirmed genetic condition, 2 congenital infections, 1 abnormal cortical development and the etiology was unknown in 3/44. Postnatal assessment at median 20 months (3 – 96) showed 22/44 (50 %) normal, 7 (16 %) mildly abnormal and 15 (34 %) severely abnormal neurodevelopmental outcomes.
Conclusion One half of babies with severe VM diagnosed after 24 weeks have normal infant outcome with ACC and IVH representing the most common causes. Etiology is the most important factor affecting the prognosis of fetuses with severe VM diagnosed at late gestation.
Ultrasound-Assisted Tumor Surgery in Breast Cancer – A Prospective, Randomized, Single-Center Study (MAC 001)
Authors: Hoffmann Jürgen , Marx Mario , Hengstmann Andreas , Seeger Harald , Oberlechner Ernst , Helms Gisela , Röhm Carmen , Ott Claudia , Wallwiener Diethelm , Stäbler Annette , Wiesinger Benjamin , Hartkopf Andreas D. , Brucker Sara Y. , Hahn Markus 
Published: July 2018

Abstract
Purpose Breast-conserving therapy is associated with a risk of tumor-involved margins. For intraoperative orientation, non- palpable or indistinctly palpable lesions are wire-marked prior to surgery. Ultrasound-guided surgery has the potential to reduce the number of tumor-involved margins. In the MAC 001 trial we evaluated ultrasound-guided breast-conserving surgery compared to wire-guided surgery with regard to free tumor margins, duration of surgery and resection volume.
Materials and Methods In this randomized, prospective, single-center controlled trial, patients with ductal invasive breast cancer were recruited for either ultrasound-guided or wire localization surgery. Primary outcomes were tumor-free resection margins, the reoperation rate and the resection volume in each group. The results were analyzed by intention to treat. The trial was registered under ClinicalTrials.gov NCT02222675.
Results 56 patients were assessed, and 47 patients were evaluated in the trial. 93 % (25/27) of the patients in the ultrasound arm had an R0 reoperation compared to 65 % (13/20) in the wire localization control arm. This result was statistically significant (p = 0.026). No statistical difference was found for the resection volume or the duration of surgery between the two arms. No major complication was seen in either arm.
Conclusion Ultrasound-assisted breast surgery significantly increases the possibility of tumor-free margins and therefore reduces the risk of reoperations. Breast surgeons should be trained in ultrasound and ultrasound should be available in every breast surgery operating room.
The Relationship between the Etiology of Profound Prelingual Sensorineural Hearing Loss and the Results of Vestibular-Evoked Myogenic Potentials
Authors: Takeuti Alice , Correa Ana , Leao Elisa , Favero Mariana 
Published: July 2018

Introduction Cervical vestibular-evoked myogenic potentials (cVEMPs) are biphasic, short latency potentials, which represent the inhibition of the contraction of the sternocleidomastoid muscle (SCM) mediated by the saccule, the inferior vestibular nerve, the vestibular nuclei and the medial vestibular spinal tract.
Objective To evaluate the response of cVEMPs in individuals with profound prelingual bilateral cochlear hearing loss.
Methods A prospective case-control study. A total of 64 volunteers, divided into a study group (31 patients with profound prelingual sensorineural hearing loss) and a control group (33 subjects matched for age and gender with psychoacoustic thresholds of ≤ 25 dB HL between 500 and 8,000 Hz) were submitted to the cVEMP exam. The causes of hearing loss were grouped by etiology and the involved period.
Results The subjects of the study group are more likely to present changes in cVEMPs compared to the control group (35.5% versus 6.1% respectively; p = 0.003), with an odds ratio (OR) of 8.52 (p = 0.009). It means that they had 8.52-fold higher propensity of presenting altered cVEMP results. There were no statistically significant differences between the latencies, the interamplitude and the asymmetry index. Regarding the etiology, there was a statistically significant difference when the cause was infectious, with an OR of 15.50 (p = 0.005), and when the impairment occurred in the prenatal period, with an OR of 9.86 (p = 0.009).
Conclusion The present study showed abnormalities in the sacculocolic pathway in a considerable portion of individuals with profound prelingual sensorineural hearing loss due to infectious and congenital causes, as revealed by the cVEMP results.
Associations of Factor VIII and von Willebrand Factor with Age, Race, Sex, and Risk Factors for Atherosclerosis
Authors: Conlan Maureen G , Folsom Aaron R , Finch Andrea , Davis C E , Sorlie Paul , Marcucci Gretchen , Wu Kenneth K ,   For the ARIC Study Investigators
Published: July 2018

SummarySeveral coagulation proteins have been implicated as possible risk factors for the development of atherosclerotic diseases, among which are factor VIII and von Willebrand factor. As part of the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study designed to assess risk factors for the development of atherosclerotic diseases, baseline measurements of factor VIII and von Willebrand factor (vWF) were performed to determine their relationship to the development of atherosclerosis. We herein report the associations of factor VIII and vWF with constitutional, lifestyle, and biochemical factors. Factor VIII and vWF were strongly correlated with each other (r = 0.73), and, therefore, had similar associations with risk factors. Mean levels of both factors were higher in women than in men, in blacks than in whites, and increased with age. In univariate analysis, both were positively associated with diabetes, body mass index, waist-to-hip ratio, serum insulin, and plasma triglycerides. Both were negatively associated with alcohol intake, educational level, physical activity (with some exceptions), and HDL-cholesterol. No correlations were observed between factor VIII or vWF and plasma LDL-cholesterol or lipoprotein(a). Although factor VIII was negatively associated with smoking in both sexes, vWF was not associated with smoking status. Most of these associations were confirmed in multivariate analysis. The strongest associations observed were of factor VIII and vWF with race and diabetes. In multivariate analysis, blacks had factor VIII and vWF levels 15 to 18 percentage points higher than whites, and diabetics had factor VIII and vWF levels 11 to 18 percentage points higher than non-diabetics. These associations must be taken into account when analyzing the possible role of factor VIII and vWF in the development of atherosclerotic diseases.
Treatment of Severe Venous Thrombo-Embolism with Intravenous Hirudin (HBW 023): An Open Pilot Study
Authors: Parent Florence , Bridey Françoise , Dreyfus Marie , Musset Dominique , Grimon Gilles , Duroux Pierre , Meyer Dominique , Simonneau Gérald 
Published: July 2018

SummaryRecombinant Hirudin (rH) is an anticoagulant agent with a specific antithrombin activity independent of antithrombin III. We report the results of the first open pilot study on the curative treatment of acute venous thrombo-embolism (VTE) with rH (HBW 023) in ten patients. The dose of rH tested was 0.07 mg/kg (i.v. bolus) followed by 0.05 mg kg-1 h-1 (i.v. infusion) for 5 days, without activated partial thromboplastin time (APTT) adjustment. Within the trial, no death, VTE recurrence or major bleeding was observed; lung scan pulmonary vascular obstruction improved from 44 to 37%, whereas the venographic Marder score was unchanged; APTT ratio ranged between 1.2 and 2.8. The dose of rH assessed in this study seems to be safe and efficient in the treatment of acute VTE.
The In Vitro Production of Thromboxane B2 by Platelets of Diabetic Patients Is Normal at Physiological Concentrations of lonized Calcium
Authors: Falcon Cristina R , Cattaneo Marco , Ghidoni Alberto , Mannucci Pier Mannuccio 
Published: July 2018

SummaryPlatelets of patients with diabetes and no evidence of macroangiopathy produce normal amounts of thromboxane (Tx) B2 in vivo, whereas they usually show increased production in vitro. Since in vitro studies have been usually performed in citrated PRP, we tested the hypothesis that the discrepancy between in vivo and in vitro studies is due to the low concentration of plasma ionized calcium ([Ca
2+
]o) that is present in citrated PRP. In fact, low [Ca
2+
]o artifactually potentiates the platelet TxB2 production in vitro. Forty patients with diabetes mellitus and 37 matched Controls were studied. Blood was anticoagulated with citrate, the thrombin inhibitor D-phenylalanyl-l-prolyl-l-chloromethylketone (PPACK) or both anticoagulants. Platelet aggregation, release of 14C-serotonin and TxB2 production were induced in platelet rieh plasma (PRP) by several agonists. The following results were obtained: i) Citrated PRP: Arachidonic acid induced aggregation (p <0.01) and TxB2 production (p <0.02) were significantly greater in patients than in Controls. No statistically significant differences were found with other agonists. ii) PPACK PRP: No statistically significant difference was found between diabetic platelets and Controls, iii) PPACK plus citrate PRP: The results were not different from those obtained with citrate alone. Therefore, our results show that diabetic platelets produce normal amounts of TxB2 in vitro when the [Ca2+]o is physiological.
Pharmacokinetics of Recombinant Factor VIIa in the Rat – A Comparison of Bio-, Immuno- and Isotope Assays
Authors: Thomsen Mads Krogsgaard , Diness Viggo , Nilsson Povl , Rasmussen Søren Nørgaard , Taylor Trevor , Hedner Ulla 
Published: July 2018

SummaryRecombinant human factor VII a (rFVIIa) is an activated coagulation factor for intravenous use as a haemostatic agent in haemophiliacs who generate antibodies against factor VIII or IX. Plasma kinetic studies are important for the understanding of the action of rFVIIa which is exerted in the vascular compartment of the body, more specifically on the vessel walls at the site of injury. In the present study, rats were dosed 100 or 500 μg/kg 125I-rFVIIa i. V., without any side effects being observed, and the plasma profile of rFVIIa was studied by 3 different assays that were shown to correlate well at early times post-dose: trichloroacetic acid (TCA)-precipitable drug-related radioactivity, rFVIIa antigen determination by ELISA technique, and the assay of clot activity which is the only clinically applicable assay. The plasma concentration curve could be resolved into 1-3 exponentials, depending on the FVIIa detection principle that was employed. Initially, there was a short (ca. 10 min) phase of increasing concentrations before the attainment of C
max. This was followed by a plasma recovery (C
max × plasma volume/dose) in the vicinity of one half of the administered dose. The initial volume of distribution (V
1) corresponded to the vascular compartment whereas the volume of distribution at steady state (V
ss) was somewhat larger. Whole body clearance (CL-B) of rFVIIa was approx. 1 ml/min per kg, and mean residence time (MRT) and the half-life assumed to be associated with the loss of biological activity was approx. 1 h and 20-45 min, respectively. From these plasma data, rFVIIa appears to be a low clearance compound with limited tissue distribution and a short half-life. Tissue distribution studies showed that high 125I levels, assumed to be rFVIIa-related, included mineralised bone and well-perfused organs such as the liver which suggested that this organ was responsible for a major proportion of CL-B. Finally, mass balance studies showed that almost 90% of the administered radioactivity could be accounted for following an i. v. dose, predominantly as non drug-related radioactivity, even though a small amount of TCA-precipitable radioactivity was excreted via the biliary route. In conclusion, dose- or sex-dependent plasma kinetics and tissue distribution within a dose range of 100 to 500 μg/kg of rFVIIa was not observed. In the early and pharmacologically relevant phase after rFVIIa administration there appears to be good agreement between the various plasma assays employed in the study, indicating that the clot assay yields useful information in studies of rFVIIa plasma pharmacokinetics.
Heparin-Induced Thrombocytopenia (HIT): An Overview of 230 Patients Treated with Orgaran (Org 10172)
Authors: Magnani H N 
Published: July 2018

SummaryHeparin-induced thrombocytopenia (HIT) with thrombosis occurs in about 1 in 2,000 heparin-treated patients. The arterial or venous thromboses may threaten life and limb hence alternative anticoagulation is needed. Some alternative treatments are possible i.e. LMWH, Ancrod, prostacyclin analogues, Dextran, aspirin and oral anticoagulants, but each has its drawbacks. This report reviews treatment of HIT patients with Orgaran (Org 10172), a low molecular weight heparinoid.Because of its proven antithrombotic activity Orgaran was used to treat 230 HIT patients. One hundred and fifty, nine patients presented with at least one thrombotic problem, which in 88 was due to the heparin use. 92.8% of the patients were considered to have adequately responded to Orgaran during the treatment period. Fifty-nine deaths (25.7%) occurred of which 7 (3.0%) were attributed to Orgaran use. The remaining 52 deaths, 27 of which occurred after Orgaran treatment was successfully terminated, were due to the severe underlying disorders in these patients. These results and the lower cross-reactivity rate (≈10%) with the heparin-induced antibody compared with that of the LMWH (>90%) suggest that although problems remain, Orgaran can be a valuable alternative treatment for patients who suffer from HIT and who require anticoagulation.
Influence of Platelet Membrane Sialic Acid and Platelet-Associated IgG on Ageing and Sequestration of Blood Platelets in Baboons
Authors: Kotzé H F , Wyk V van , Badenhorst P N , Heyns A du P , Roodt J P , Lötter M G 
Published: July 2018

SummaryPlatelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of Sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the Sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of Sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/108 platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p <0.001), and there was an exponential correlation between the shortening of the mean platelet life span and the amount of sialic acid removed. The increase in platelet-associated IgG was 0.112 (median, range 0.007 to 0.309) fg/platelet (n = 25, p <0.001) after 0.79 (median, range 0.00 to 6.70) nmol sialic acid/108 platelets was removed (p <0.001). There was an exponential correlation between the shortening of mean platelet life span after the removal of sialic acid and the increase in platelet-associated IgG. The results suggest that platelet membrane sialic acid influences ageing of circulating platelets, and that the loss of sialic acid may have exposed a senescent cell antigen that binds IgG on the platelet membrane. The antibody-antigen complex may then provide a signal to the macrophages that the platelet is old, and can be phagocytosed and destroyed.
Functional Analysis of the Arg91GIn Substitution in the Factor VIII Binding Domain of von Willebrand Factor Demonstrates Variable Phenotypic Expression
Authors: Lavergne J M , Piao Y , Ribba A S , Girma J P , Siguret V , Piétu G , Boyer-Neumann C , Schandelong A , Bahnak B R , Meyer D 
Published: July 2018

SummaryAn Arg91Gln substitution in the mature von Willebrand factor (vWF) has been associated with defective binding of vWF to factor VIII (FVIII). We studied four families with members initially classified as having type I von Willebrand disease (vWD) who were either homozygous or heterozygous for the Arg91Gln change. The first family was the original case described by Nishino et al. (1) where three members were homozygous for the Gln91 allele. They had a low FVIII coagulant activity:vWF antigen (VIIIC:vWFAg) ratio, from 0.29 to 0.44, and the ability of their plasma vWF to bind FVIII was markedly decreased. All the heterozygous members had normal vWF and FVIII levels but the capacity of their plasma vWF to bind FVIII was reduced and intermediate between the homozygous members and normals. The affected individual from the second family was heterozygous for the Gln91 allele and demonstrated a VIIIC:vWFAg ratio of 0.98. The FVIII binding assay confirmed the heterozygous status indicating that the moderately low levels of vWF were due to reduced expression of both alleles. The propositus from the third family was also heterozygous and had below normal levels of vWF as well as a low VIIIC:vWFAg ratio of 0.34; however, FVIII binding to her plasma vWF was similar to that of the homozygous individuals suggesting that Gln91-vWF was the major circulating form. Her daughter who has type I vWD inherited the allele without the Gln91 mutation indicating that the expression of this allele was indeed impaired. The heterozygous patient in the fourth family had a vWF level of 24 U/dl but an VIIIC:vWFAg ratio greater than 2. Her plasma vWF showed normal FVIII binding implying that the Gln91 mutation was linked to a defect that repressed the expression of the allele. The Arg91Gln substitution appears to decrease but not eradicate FVIII binding suggesting a critical concentration of vWF be attained before the defect becomes phenotypically important.
Surgery and Environmental Influence as Risk-Factors for the Development of Deep Vein Thrombosis in Animal Experiments
Authors: Hoffmann R , Schimmer R C , Largiadèr F 
Published: July 2018

SummaryThe aim of this experimental study was to determine whether deep vein thrombosis (DVT) in animals occurs after osteosynthesis of the femur, and whether a postoperative drop in air pressure increases the frequence of DVT Thus, osteosynthesis of the femur was performed in 10 New Zealand rabbits. Postoperatively a drop in air pressure of 300 hPA was induced. After 40 h in the pressure cabin ascending phlebography was performed (Group A). In a control-group of 10 other rabbits surgery was performed without postoperative drop in air pressure (Group B) while in a second control only the drop in air pressure was induced without surgery (Group C).The phlebographic studies showed DVT in 4 out of 10 rabbits in group A. In group B there was no demonstrable DVT while in group C one ease of DVT was seen. The difference between group A and group B and C is statistically significant. In conclusion, a rapid drop in air pressure seems to have significant impact on the pathogenesis of DVT in rabbits after osteosynthesis of the femur.