bluuebunny/crossref_metadata_2025_split huggingface dataset:
Der Landarzt-Abgrenzungsalgorithmus (La-Abal)
Authors: Marschner Christian , Wasem Jürgen , Heymann Romy 
Published: July 2018

ZusammenfassungVor dem Hintergrund der anhaltenden Diskussionen um die Sicherstellung der medizinischen Versorgung – insbesondere in ländlichen, strukturschwachen Regionen
Deutschlands, ist der Begriff „Landarzt“ ein häufig verwendeter Terminus. Bis dato mangelte es jedoch an einer konkreten Definition des Landarztbegriffes.
Dieses Defizit soll durch den Landarzt-Abgrenzungsalgorithmus (La-Abal) behoben werden. Anhand einer einheitlichen Abgrenzungssystematik kann nun die
Differenzierung zwischen Land- und städtisch/urban tätigen Ärzten realisiert werden. Der vorliegende Artikel gibt Auskunft darüber, ob der La-Abal generell auf
Gesamtdeutschland anwendbar ist, in welchen Regionen sich Landärzte befinden und inwieweit die als Landarztbereiche identifizierten Regionen mit hausärztlich
unterversorgten Regionen übereinstimmen. Die Methodik des La-Abals basiert im Kern auf den drei Parametern: „Grundzentrum“, „Ländliche Besiedelung“ und
„Räumliche Lage“. Einheitsgemeinden und Gemeindeverbände dienen in diesem Kontext als Analyseebene. Eindeutige, durch den La-Abal vorgegebene Bedingungen
ermöglichen es, Einheitsgemeinden/Gemeindeverbände als Landarztbereiche zu definieren und somit zu identifizieren. Als Ergebnis zeigt sich, dass der La-Abal auf
Gesamtdeutschland anwendbar ist. Des Weiteren existieren Landarztbereiche, einige davon korrespondieren mit denen als hausärztlich unterversorgt geltenden
Regionen. Der La-Abal ist ein ergebnisorientiertes, praktikables und standardisiertes Modell, das es ermöglicht, ein einheitliches Landarztverständnis zu
etablieren. Dies ist notwendig, um Antworten auf gesellschaftliche Veränderungen entwickeln und den damit einhergehenden Forderungen nach Sicherstellung der
gegenwärtigen und zukünftigen Gesundheitsversorgung gezielt planen und steuern zu können.
Signaling through G Proteins and G Protein-coupled Receptors during Platelet Activation
Authors: Brass Lawrence F , Hoxie James A , Manning David R 
Published: July 2018

SummaryRecent studies have helped to define the early events of signal transduction in platelets. The best-described of these events are those in which heterotrimeric guanine nucleotide binding regulatory proteins (G proteins) mediate the interaction between cell surface receptors for agonists and intracellular second messenger generating enzymes. To date nine different G proteins have been identified in platelets. The:r targets include phospholipases C and A2, and adenylyl cyclase. Efforts to clone the receptors that can couple to these G proteins have been successful for epinephrine, thrombin, TxA2 and platelet activating factor. Each of these is comprised of a single polypeptide with seven transmembrane domains and an extracellular N-terminus. In the case of the thrombin receptor, activation occurs by a novel mechanism in which thrombin cleaves its receptor, creating a new N-terminus that can serve as a tethered ligand. Shortly after activation, thrombin receptors become resistant to re-activation by thrombin. This desensitization, which appears to involve receptor phosphorylation and internalization, provides a potent mechanism for limiting the duration of thrombin-initiated events in platelets and other thrombin-responsive vascular cells.
Low-Dose Heparin and Deep-Vein Thrombosis after Total Hip Replacement
Authors: Mannucci P. M , Citterio Luisa E. , Panajotopoulos N 
Published: July 2018

SummaryThe effect of subcutaneous low-dose heparin on postoperative deep-vein thrombosis (D. V. T.) (diagnosed by the 125I-labelled fibrinogen test) has been investigated in a trial of 143 patients undergoing the operation of total hip replacement. Two randomized studies were carried out: in one the scanning for D.V.T. was carried out daily for 7 days post operatively and in the other for 15 days. In both, the incidence of D.V.T. was significantly lower in the heparin-treated patients (P<0.005). Bilateral D.V.T. was also prevented (P<0.05), through the extension of D.V.T. to the distal veins of the thigh was not significantly reduced. Heparin treatment was, however, followed by a higher incidence of severe postoperative bleeding (P< 0.02) and wound haematoma formation (P< 0.005), and the postoperative haemoglobin was significantly lower than in the control group (P<0.005). A higher number of transfused blood units was also needed by the heparin treated patients (P<0.001).
Effects of Matrix Contact during Gel Filtration of Human Platelets in Plasma
Authors: Lindon Jack N. , Rodvien Robert , Waugh David F. 
Published: July 2018

SummaryWhen gel filtration is used to transfer platelets from plasma into an established environment, alterations in platelet characteristics may result from the change in environment or from the effects of platelet contact with the gel matrix. To approach the problem of evaluating the relative contributions from these sources, a Sepharose 2B matrix was employed and platelets transferred from citrate anticoagulated PRP into autologous PPP to yield plasma-GFP. Platelet recoveries averaged 93 %. PRP: plasma-GFP pairs were found to be indistinguishable with respect to: morphology; ADP, thrombin or collagen-induced aggregation response; uptake of 5-hydroxytryptamine (5-HT) or adenosine; and thrombin or collagen-induced release of accumulated 5-HT or adenosine. Pairs are distinguishable by prostaglandin E2 synthesis assayed immediately after filtration.
Platelet Dysfunction in Migraine: Effect of Self-Medication with Aspirin
Authors: Deshmukh Sunanda V. , Meyer John Stirling , Mouche Richard J. 
Published: July 2018

SummaryCirculating microembolic index (CMI) was determined by drawing one blood sample into EDTA-formalin and the other into DTA alone in patients with migraine and compared with matched normal controls. Platelet aggregates, if any, are fixed in EDTA-formalin but dis- aggregated by EDTA. Ratios of these two counts approximate “unity” in normals and are proportionately less than unity, depending on the number of platelet aggregates. 26 untreated migraineurs and 19 migraineurs with history of self-medication with aspirin taken within 72 hours of the test, were studied in headache-free intervals. Results were compared with those from 20 healthy, age and sex matched volunteers, without migraine, who were medication- free for at least one week. Mean CMI in untreated migraineurs (0.77±0.03 SEM) was significantly lower than the mean in normal controls (0.94±0.02, p. <0.002). Migraineurs with selfadministration of aspirin had mean CMI of 0.88±0.02, differing significantly from untreated migraineurs (p <0.01) but not from normal controls (0.1<p<0.2). Results suggest excessive platelet aggregation in migraineurs which tends to be corrected by treatment with platelet inhibitors such as aspirin.
Release, Aggregation and Lysis of Human Platelets by Antilymphocyte Globulin and Antiplatelet Serum
Authors: Lekas Nicholas , Rosenberg J. C 
Published: July 2018

SummaryHuman platelets labeled with 51Cr were used to determine the contribution made by platelet lysis to the platelet release reaction and platelet aggregation induced by rabbit antihuman platelet serum (APS) and equine antihuman thymocyte globulin (ATG). Platelets were tested in both plasma (PRP) and non-plasma containing media. Antibodies directed against platelets, either as APS or ATG, induced significant amounts of platelet release and aggregation, as well as some degree of lysis, in the absence of complement. The presence of complement increased platelet lysis and aggregation, but not the release reaction. Non-immune horse gamma globulin produced different responses depending upon whether platelets were investigated in PRP or non-plasma containing media. Aggregation was seen in the latter but not the former. These differences can be explained by the presence of plasma components which prevent non-specific immune complexes from causing platelet aggregation. Since platelets in vivo are always in a plasma medium, one must be wary of utilizing data from platelet studies in synthetic plasma-free media as the basis of explaining clinical events. These observations demonstrate at least two, and possibly three, different mechanisms whereby ATG could activate platelets causing thrombotic complications and thrombocytopenia, i.e., via 1) specific and, 2) non-specific non-lytic pathways and 3) a lytic pathway.
An immunological Method for Detection of the Carrier of Hemophilia B
Authors: Matsuoka Matsuzo , Ito Masakazu , Takahashi Kaoru , Sakuragawa Nobuo 
Published: July 2018

SummaryThis paper presents the results of an immunological study of hemophilia B and its carriers which used two kinds of antibodies, a heterologous antibody of high specificity and a homologous antibody developed in a patient with severe hemophilia B.1. The factor IX related antigen for hemophilia B could be determined by a neutralization test and not by a precipitation reaction.2. The activity of factor IX in a definite carrier of hemophilia B was significantly lower than that of factor VIII in a definite carrier of hemophilia A.3. In hemophilia B, there were no differences between the factor IX antigen determined by either the heterologous rabbit antibodies or the homologous antibodies. And there was no discrepancy between the factor IX antigen and the factor IX activity. Therefore, we cannot use this discrepancy for the detection of a carrier of hemophilia B.4. However, there was a discrepancy between the factor IX antigen determined by the neutralization test and the factor IX procoagulant activity in the patients of both hemophilia BM and hemophilia B+. The identical results were obtained in the cases of carriers of both hemophilia BM and hemophilia B+. These facts are very useful for the detection of carriers of hemophilia BM and hemophilia B+.
Effects of Ions on ADP-Induced Aggregation of Bovine or Human Platelets
Authors: Waugh David F. , Lindon Jack N. 
Published: July 2018

SummaryEffects of divalent cations on ADP-induced aggregation response were examined. Bovine platelets were transferred by Sepharose 2B gel filtration from citrate-PRP into citrate free buffer (buffer-GFP). Response increases, reaches a maximum and decreases with increasing calcium and/or magnesium concentration. For either calcium or magnesium alone, increasing response is proportional to a rate coefficient and, through an apparent ion-platelet association constant, to the fraction of platelet critical sites bound to cation. With both ions present, bound magnesium appears to inhibit bound calcium in excess of that accounted for by competition and a lower rate coefficient for bound magnesium. With citrate present in buffer-GFP, apparent association constants increase, excess magnesium inhibition is present, but systems are path dependent. Initial conditions appear to establish a response which is thereafter immutable to environmental magnesium alteration. Citrate-PRP resembles buffer-GFP: response is sensitive to the selective removal of calcium and excess magnesium inhibition is present. With heparin-PRP, response is immutable to the selective removal of ~90% of initial calcium. The dependency of response inhibition observed at high divalent cation concentrations indicates that aggregation is not due to interplatelet cross linking by ions. Ion effects are similar for bovine and human platelets.
Clottability and Cross-Linking Reactivity of Fibrin(ogen) Following Differential Release of Fibrinopeptides A and B
Authors: Furlan M , Seelich T , Beck E. A 
Published: July 2018

SummaryHuman fibrinogen was treated at pH 6.0, 7.3 and 9.0 with thrombin, batroxobin (thrombinlike fraction of Bothrops atrox venom) or an extract of the venom from Ancistrodon contortrix contortrix. These three enzymes released the NH2-terminal fibrinopeptides A and B at different rates. Thrombin-free, preactivated factor XIII (factor XIIIa) was added to incubation mixtures to stabilize resulting fibrin(ogen) aggregates. Cross-linking of γ-chains and the size of covalently linked fibrin-fibrinogen oligomers were studied in an early stage of fibrinopeptide cleavage using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate.Batroxobin (pH 7.3) and thrombin (pH. 6.0) preferentially released fibrinopeptide A, and resulting fibrin aggregates became rapidly insoluble. However, when fibrinopeptide B was removed with the contortrix enzyme, soluble cross-linked oligomers appeared initially. The opaque fibrin clots, produced by thrombin (pH 6.0) or contortrix procoagulant fraction (pH 7.3), were found to be devoid of α-polymers even after prolonged incubation with factor XIIIa. Our data suggest that the solubility and opacity of fibrin networks are not primarily related to the type of the cross-link (γ-γ versus α-α interactions).
In Vivo Anticoagulant and Antiplatelet Effect of D-Phe-Pro-Arg-H and D-MePhe-Pro-Arg-H
Authors: Bagdy Dániel , Barabás Éva , Szabó Gabriella , Bajusz Sándor , Széll Erzsébet 
Published: July 2018

SummaryD-Phe-Pro-Arg-H and D-MePhe-Pro-Arg-H synthetized in our institute were administered to mice, rats, rabbits and beagle dogs. The kinetics of the anticoagulant and antiplatelet effect was recorded by measuring various clotting parameters, platelet count and aggregation, and evaluated as proposed by Verstraete and Verwilghen. The minimum effective doses were found to be 0.25-0.5 mg kg-1h-1 by intravenous continuous infusions and 0.5-1.0 mg/kg by single injections. The dose-dependent prolongation of clotting times appeared after application within minutes and returned to baseline values as a function of dose. Blood level of the inhibitors was determined by a bioassay. Unlike heparin, no higher starting dose was required to reach the anticoagulant threshold level, i.e. 0.03-0.1 ¼g/ml whole blood. The peptides did not cause significant changes in platelet count and function or in hemodynamic parameters (blood pressure, heart rate and ECG) and in respiration. They blocked platelet aggregation induced by thrombin ex vivo specifically. No rebound effect or bleeding could be demonstrated even after subtoxic doses of the compounds. The onset of the anticoagulant and antithrombotic effect appeared within 60 min after single oral doses and lasted for 3-6 h. In close correlation with the anticoagulant effect a complete or significant inhibition of platelet aggregation induced by thrombin ex vivo could also be recorded by using 5-10 mg/kg doses.
Thrombin Activity by Intrinsic Activation of Plasma In-Vitro Accelerates with Increasing Age of the Donor
Authors: Ibbotson S H , Tate G M , Davies J A 
Published: July 2018

SummaryThrombotic diseases increase in incidence with advancing years and this might be partly due to an increased propensity for fibrin formation in older individuals. Accordingly we decided to investigate whether the time taken to generate 50% thrombin activity in vitro varied with the age of the plasma donor. Coagulation was initiated in defibrinated, diluted plasma by contact activation and thrombin activity measured using the chromogenic substrate, S2238. The rate of thrombin generation was assessed by measuring the time taken to reach 50% maximal activity (T50/s). There was a highly significant negative correlation between T50 and age, T50 declining from 93 s at 19 years to 71 s at 65 years (r = −0.637, p <0.0001). A strong negative correlation was demonstrated between T50 and FVII level (r = -0.415, p = 0.0007) and FVIII: C level (r = -0.465, p = 0.0001). Although FVII concentration correlated with age (r = 0.307, p = 0.014) no relationship was seen between age and FVIII :C. These data suggest that coagulation rates in plasma accelerate with age.
D-Dimer and Thrombin-Antithrombin III Complexes in Patients with Clinically Suspected Pulmonary Embolism
Authors: Demers Christine , Ginsberg Jeffrey S , Johnston Marilyn , Brill-Edwards Patrick , Panju Akbar 
Published: July 2018

SummaryOne hundred and fifty-six consecutive patients with clinically suspected pulmonary embolism (PE) had blood drawn to measure levels of D-dimer and thrombin-antithrombin (TAT) complexes and underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance plethysmography (IPG); pulmonary angiography was performed in 10 patients. Patients were classified as: PE-positive (positive pulmonary angiography or high probability lung scan or non-high probability lung scan and abnormal IPG) or, PE-negative (normal lung scan or normal pulmonary angiography) or PE-unlikely (non-high probability lung scan and normal serial IPG and absence of venous thromboembolism in follow-up). Thirty patients were classified as PE-positive, 64 as PE-negative and 62 patients as PE-unlikely. PE-positive patients were treated with anticoagulants, whereas PE-negative and PE-unlikely patients were not. PE-unlikely patients were followed for 3 months with repeat IPG and clinical evaluation for the occurrence of venous thromboembolism. The sensitivities, specificities, positive predictive values and negative predictive values of the D-dimer and TAT complex assays were calculated for patients classified as PE-positive and PE-negative. In addition, the prevalences of normal D-dimer and TAT complex assays were calculated for PE-unlikely patients.Cutoffs of 300 ng/ml for D-dimer and 3.5 μg/ml for TAT complexes provided sensitivities of 96% for both assays, negative predictive values of 97% for D-dimer and 96% for TAT complexes and specificities of 52% for D-dimer and 51% for TAT complexes. The specificities of the assays were higher in patients without comorbid conditions and in outpatients. Among PE-unlikely patients, 14 had normal D-dimer levels and 5 had normal levels of TAT complexes. None of these patients developed venous thromboembolism in follow-up.Our study indicates that: 1) PE is highly unlikely in patients who have D-dimer levels of less than 300 ng/ml and/or levels of TAT complexes below 3.5 μg/ml, and 2), because of their relatively low positive predictive values, further investigation is required if levels of D-dimer and/or TAT complexes are above these cutoffs. These results should be confirmed in future clinical management trials.
A Collaborative Study to Establish an International Standard for Alpha-Thrombin
Authors: Gaffney P J , Heath A B , Fenton II J W 
Published: July 2018

SummarySince 1975 an International Standard for Thrombin of low purity has been used. While this standard was stable and of value for calibrating thrombins of unknown potency the need for a pure a-thrombin standard arose both for accurate calibration and for precise measurement of thrombin inhibitors, notably hirudin. An international collaborative study was undertaken to establish the potency and stability of an ampouled pure a-thrombin preparation. A potency of 97.5 international units (95% confidence limits 86.5-98.5) was established for the new a-thrombin standard (89/ 588) using a clotting-assay procedure. Stability data at various elevated temperatures indicated that the standard could be transported and stored with no significant loss of potency.Ampoules of lyophilised a-thrombin (coded 89/588) have been recommended as an International Standard for a-thrombin with an assigned potency of 100 international units per ampoule by the International Society for Thrombosis and Haemostasis (Thrombin and its Inhibitors Sub-Committee) in Barcelona, Spain in July 1990 while the Expert Committee on Biological Standardisation and Control of the World Health Organisation will consider its status at its next meeting in Geneva in 1991.
Gemfibrozil Reduces Plasma Prothrombin Fragment F1+2 Concentration, a Marker of Coagulability, in Patients with Coronary Heart Disease
Authors: Wilkes H C , Meade T W , Barzega S , Foley A J , Hughes L O , Bauer K A , Rosenberg R D , Miller G J 
Published: July 2018

SummaryThe effects of gemfibrozil on several indices of haemostatic activity were explored in male patients with coronary heart disease (CHD). Sixty-three of 71 patients completed a crossover study in which gemfibrozil 1,200 mg/day and matching placebo were each taken in randomised order for 2 months in a doubleblind manner, separated by a 2-month washout period. Serum cholesterol decreased by an average (95% confidence interval) of 12 (9 to 15)% and non-fasting triglyceride concentration by 43 (34 to 51)% during active treatment. Plasma prothrombin fragment Fi + 2 concentration, a marker of the in vivo rate of generation of thrombin, was 25 (12 to 37)% lower on average while on gemfibrozil than during the placebo phase. Factor VII coagulant activity (VIIC) and antigen concentration, and fibrinopeptide A concentration were not influenced by gemfibrozil in the group overall. However, the VIIC response appeared to be dependent upon the untreated cholesterol level. Hypercholesterolaemic men (cholesterol >6.5 mmol/1) experienced a significant reduction in VIIC averaging 6% of standard during active therapy. Other effects of gemfibrozil were a 5 (2 to 9)% increase in plasma fibrinogen by a gravimetric method, an 11 (8 to 13)% increase in platelet count, and a 6 (2 to 10)% reduction in white cell count. The reduced incidence of CHD following gemfibrozil therapy in hyperlipidaemic patients may arise in part through a reduction in procoagulant activity and thus the risk of an occlusive coronary thrombosis.
Insertions/Deletions in the Antithrombin Gene: 3 Mutations Associated with Non-Expression
Authors: Daly Martina , Perry David J , Harper Paul L , Daly Helena M , Roques Antoine W W , Carrell Robin W 
Published: July 2018

SummaryWe have investigated the molecular basis of antithrombin deficiency in 3 individuals, 2 of whom had a proven family history of thromboembolic disease. An approximate 50% reduction in functional and immunologic levels of antithrombin was detected in plasma from the propositi indicating an allelic deficiency of antithrombin. In each case direct sequencing of amplified DNA revealed a novel mutation involving single bases: two being insertions, of a T in codon 48 and an A in codon 208, and the third being the deletion of an A in codon 370. The three mutations, which were confirmed by cloning and sequencing the normal and variant alleles, all caused frameshifts leading to premature termination of protein translation. In no case could a truncated antithrombin be detected in plasma from the propositus suggesting either that it fails to be secreted, or is rapidly degraded.