bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombocytopenia Caused by Antigen-Antibody Reactions with Special Reference to Intravascular Coagulation
Authors: Fedder G , Prakke Elisabeth M. , Vreeken J
Published: June 2018

Soluble antigen-antibody complexes were infused in a group of non-immunized rabbits. Furthermore, antigen solutions were infused or injected into a group of rabbits, immunized with the corresponding antigen. In both groups a profound fall in the number of blood platelets was demonstrated. However, increased or decreased factor V activity was not seen in any of the rabbits; changes in the level of fibrinogen did not occur, and circulating fibrin monomers as a sign of thrombinemia could not be found.

The mechanism by which immunologieally induced thrombocytopenia can lead to diffuse intravascular coagulation is briefly discussed.
The Adsorption of Blood Coagulation Factors II, VII, IX and X from Human Plasma to Aluminium Hydroxide
Authors: Swart A. C. W , Klaassen B. H. M , Bloys-van Treslong-De Groot C. H. F , Hemker H. C
Published: June 2018

The influence of pH, adsorption time, ionic strength, buffer type and plasma concentration on adsorption and elution of the factors of the prothrombin complex from normal human ACD plasma onto A1(OH)3 is investigated. Reproducible small differences are found between the behaviour of the four factors II, VII, IX, and X.
Intravenous Infusion of a Standardised Coagulation Active Phospholipid Complex in Uremic Coagulation Deficiency
Authors: Schimpf K.l , Hanf-Hoppe H.-W , Immich H
Published: June 2018

Infusion for 90 min of 10 ml brain lipid extract brought thrombin generation and prothrombin consumption levels in uremic patients to normal for 3 h. After quick injection of the same doses (within 3 min) the effect lasted less than l1/2h. Control subjects produced hypercoagulability with the same treatment. The results of these clinical experiments, obtained with 12 subjects, were shown by analysis of variance to be statistically significant.
Fibrinogen Troyes - Fibrinogen Metz
Authors: Soria J , Soria C , Samama M , Poirot E , Kling C
Published: June 2018

Two new cases of congenital dysfibrinogenemia have been discovered. In the first case, “Fibrinogen TROYES”, the abnormality is characterized by a prolonged thrombin clotting time, the defect being due to abnormal aggregation of fibrin monomers. There is no tendency towards excessive bleeding. The abnormality is found to be present with the same intensity in one of the patient’s brothers and one of his sisters.

In the second case, “Fibrinogen METZ”, the abnormality is more pronounced, since, even in the presence of very high thrombin concentrations no clotting occurs. The abnormality is due to a defect in the release of fibrinopeptides, on addition of thrombin. The patient’s blood contains only abnormal fibrinogen. The plasma recalcification time is more prolonged than in the whole blood clotting time. The abnormality is present in both parents in heterozygote form, a milder form than in the patient who is homozygous. The patient has a moderate bleeding tendency, the parents being normal in this respect.
Induction of Immunotolerance in Hemophilia for High Titre Inhibitor Eradication: A Long-Term Follow-Up
Authors: Mariani G , Solinas S , Pasqualetti D , Ghirardini A , Verani P , Buttó S , Lopez M , Moretti T
Published: June 2018

Three hemophiliacs with high titre inhibitor were treated with a medium-high FVIII dose schedule (100 IU/kg bw daily) with the aim of inducing the immunotolerance. These patients were followed-up extensively concerning their immunological status and HIV serology. In all of them the inhibitor disappeared and normal FVIII kinetics were obtained after 22, 15 and 29 months. After eradication of the inhibitor, no recurrence took place in any of the patients. All the patients were HIV Ab positive before the beginning of the treatment. In one of them CD4+ cells fell progessively 32 months after the treatment was started, a fullblown AIDS showed up, and the patient died 5½ years after the beginning of the treatment. In the second and third patient the CD4+ cells varied widely but remained >400/μl during the whole immunotolerance treatment. The latter two patients are AIDS and ARC free so far, but patient No. 2 developed a mild-to-severe thrombocytopenia.

Considering the high cost of the treatment and the possibility that such an intensive administration of FVIII concentrates might worsen the immunological status of patients, this therapeutic procedure should only be applied with caution.
Abnormal Typical Pattern of Platelet Function and Thromboxane Generation in Unstable Angina
Authors: Zahavi M , Zahavi J , Schafer R , Firsteter E , Laniado S
Published: June 2018

Platelet aggregation (PA), platelet thromboxane B2 (TXB2) generation and 14C 5-hydroxytryptamine (5HT) release were studied in 13 patients with unstable angina, and compared to 14 patients with stable angina and 16 healthy controls. A typical pattern, distinct in 4 aspects from stable angina patients or controls, was observed in the unstable angina patients. ADP or collagen induced shape change was 3-4 times greater, the extent of epinephrine induced PA was nil or very low, the extent of collagen induced 14C 5HT release was also reduced while collagen induced platelet TXB2 generation was increased in spite of a reduced extent of PA. The extent of ADP or collagen induced PA was also significantly reduced. These results indicate a platelet membrane abnormality occurring presumably during contact of the circulating platelets with a non-occlusive thrombus observed at sites of ruptured plaques in unstable angina patients. Since also the pattern (20-30% overlap with control values) was distinct from that of stable angina patients, it might indicate an active thrombotic process.

Plasma β-thromboglobulin (βTG) and TXB2 levels and serum TXB2 generation were also studied in the cardiac patients and controls and in another 10 patients with advanced peripheral occlusive arterial disease (POAD). Plasma βTG and TXB2 levels were slightly elevated in the unstable angina patients and markedly elevated in the POAD patients. Serum TXB2 generation was, however, elevated in the stable angina patients (p <0.002) and more so in the unstable angina patients (p <0.001) compared to controls or to POAD patients. This was presumably mediated through enhanced thrombin generation. These results suggest that the measured plasma βTG variable in the unstable angina patients is not useful in the assessment of in vivo platelet activation. It is presumably reflecting the sum of local enhanced platelet activation (at sites of ruptured plaques) and of reduced function of the “defective” circulating platelets. The ability of the platelets of unstable angina patients to generate large amounts of TXB2 if occurring in vivo might induce an intense coronary vasospasm.
Arterial Thrombosis Associated with Immune Thrombocytopenia: Presence of a Platelet Aggregating IgG Synergistic with Thrombin and Adrenalin
Authors: Jackson Shaun P , Jane Stephen M , Mitchell Christina A , Fernando Cortizo W , Hau Lena , Pfueller Sharron L , Salem Hatem H
Published: June 2018

We report the case of a 50-year-old lady who presented with arterial thrombosis in the setting of thrombocytopenia. Investigations confirmed the diagnosis of idiopathic thrombocytopenic purpura. A spontaneous platelet aggregating factor (SPAF) was isolated from the immunoglobulin fraction of the patient's plasma. The isolated IgG irreversibly aggregated platelet-rich plasma and washed platelets, an effect abolished by pretreating the platelets with aspirin. The activity of the IgG was greatly enhanced by subaggregatory concentrations of thrombin and adrenalin and was localized to the F(ab')2 of the molecule. Plasmapheresis in combination with anti-platelet therapy resulted in an increase in the patient's platelet count, reduced platelet aggregating activity of plasma and significant clinical improvement.

We suggest that the presence of this platelet aggregating IgG contributed to the development of thrombosis in our patient and postulate that a similar factor may explain the paradox of thrombosis observed in a select group of thrombocytopenic patients.
Factors of the Extrinsic Pathway of Blood Coagulation in Tumour Associated Macrophages
Authors: Ádány Róza , Kappelmayer János , Berényi Ernö , Szegedi Andrea , Fábián Erzsébet , Muszbek László
Published: June 2018

Despite the growing evidence implicating intratumoural fibrin formation in the progression of malignant tumours, the origin of coagulation factors that participate in extravascular clotting has not been elucidated. Using immunohistochemical methods we attempted to detect and localize clotting factors of extrinsic pathway in different human malignant tumours. Coagulation factors II, V, VII and X (FII, FV, FVII and FX) were detected in a huge number of cells showing spindle-shaped or stellate morphology. By double immunohistochemical labellings it was demonstrated that cells containing these clotting factors express monocyte/macrophage differentiation marker antigens recognized by Leu M3, Ki M7 and DAKO-macrophage monoclonal antibodies, i.e. they represent monocyte-derived, phagocytic tumour associated macrophages (TAMs). These findings suggest that TAMs can be viewed as clot cells, which in addition to the initiation of extravascular clotting by expressing procoagulant activity can also provide all the components necessary for the extrinsic thrombin formation.
Extrinsic Pathway Inhibitor in Elective Surgery: A Comparison with other Coagulation Inhibitors
Authors: Sandset P M , Høgevold H E , Lyberg T , Andersson T R , Abildgaard U
Published: June 2018

Extrinsic coagulation pathway inhibitor may be an important regulator of haemostasis to prevent thrombosis after tissue damage. The functional activity of this inhibitor was determined using a chromogenic substrate assay, and compared to the activities of anti thrombin, heparin cofactor II and protein C during the perioperative period of elective hip replacement (n = 28), cholecystectomy (n = 11), and vascular surgery (n = 5). Peroperatively, all the inhibitors decreased rather similarly and to the same degree as the decrease in albumin concentration. The decreases during hip surgery were about 2-fold the decreases observed during cholecystectomy. A significant peroperative increase in extrinsic pathway inhibitor activity was observed in vascular surgery, probably due to a bolus injection of heparin. Antithrombin, heparin cofactor II and protein C levels normalized on days 3-5 postoperatively in all three patient groups. Sustained low levels of extrinsic pathway inhibitor were observed on postoperative days 1 to 7 in hip surgery patients. Apparently, extrinsic pathway inhibitor is not an acute phase reactant. In uncomplicated surgery, the decreases of the coagulation inhibitor levels are mainly due to hemodilution.
Evaluation of Coagulometric Assays in the Assessment of Protein C Anticoagulant Activity; Variable Sensitivity of Commercial APTT Reagents to the Cofactor Effect of Protein S
Authors: D'Angelo Silvana Viganó , Gilardoni Felicia , D'Angelo Armando
Published: June 2018

In vivo expression of protein C activity is dependent on the availability of the activated protein C (APC) cofactor protein S. In the clinical laboratory, measurement of protein C anticoagulant activity is mostly performed in modified APTT assays. We have evaluated 13 commercial APTT reagents for their sensitivity to the cofactor effect of protein S by comparing APC-dependent clotting time prolongations in normal plasma and in protein S depleted plasma. In normal plasma, the sensitivities of the APTT reagents to the anticoagulant effect of APC were markedly different and correlated with the sensitivity of reagents to factor V and VIII. Reagents containing soy phosphatides appeared more sensitive than reagents containing phospholipid of animal origin. Analysis of dose-response curves obtained in normal plasma distinguished one group of reagents showing clotting time prolongations linearly related to the APC concentrations, a second group showing a log-linear relationship and a third group showing a log-log relationship. In protein S depleted plasma, sensitivity of APTT reagents to APC was in general proportional to that observed in normal plasma. However, for some reagents dose-response curves were qualitatively different in normal and in protein S depleted plasma. With all the APTT reagents, APC-dependent clotting time prolongations corresponding to 30-80% of APC anticoagulant activity observed in normal plasma, were observed in protein S depleted plasma. At variance, in a modified Xa one-stage clotting assay, negligible clotting time prolongations were observed in protein S depleted plasma, indicating that over 90% of the APC anticoagulant activity was protein S dependent in this assay system. Dilution of a relative insensitive APTT reagent effectively increased its sensitivity to the cofactor effect of protein S, suggesting that different phospholipid content and/or composition might be responsible for the different sensitivity of APTT reagents to protein S.

These results question the validity of APTT based assays for the identification of qualitative protein C abnormalities with defective interaction with protein S.
The Effect of Some Instruments for Prothrombin Time Testing on the International Sensitivity Index (ISI) of Two Rabbit Tissue Thromboplastin Reagents
Authors: Poggio Marina , Besselaar Antonius M H P van den , Velde Edo A van der , Bertina Rogier M
Published: June 2018

Two commercial rabbit tissue thromboplastins were calibrated against the International Reference Preparation for rabbit thromboplastin (coded RBT/79) by one laboratory using the manual technique, a semi-automatic electro-mechanical coagulometer and three different automatic photo-optical instruments. The calibration of the two reagents was performed in three and two different exercises, respectively, and showed good reproducibility of the procedure. The purpose of calibration is providing a formula for the assessment of the International Normalized Ratio (INR) for patients receiving oral anticoagulants. The World Health Organization (WHO) model for thromboplastin calibration leads to the equation INR = RISI, in which R is the prothrombin time ratio and ISI the International Sensitivity Index of the calibrated thromboplastin/instrument system. This equation was adequate for one reagent, but not for the other when it was used in combination with the four instruments. At therapeutic intensities of anticoagulation, the deviation from the WHO-model observed for the second reagent was clinically insignificant. The WHO model was fully adequate when the second reagent was used with the manual technique. For both thromboplastins, there were statistically significant differences in ISI between the four instruments. The largest difference-amounting to approximately 10%-was observed between two photo-optical instruments. The order of instruments with increasing ISI was the same for the two reagents. It is recommended that thromboplastin manufacturers specify the instruments used for calibration of their reagent.
Protein C Inhibitor from Human Plasma: Characterization of Native and Cleaved Inhibitor and Demonstration of Inhibitor Complexes with Plasma Kallikrein
Authors: Laurell Martin , Stenflo Johan
Published: June 2018

Protein C inhibitor (PCI) was purified from human plasma using immunoaffinity chromatography and heparin Sepharose chromatography, a method that allowed the purification of active and inactive inhibitor. PCI purified from outdated plasma was inactive and either in complex with plasma kallikrein or proteo-lytically degraded. Sequence analysis of cleaved PCI and of complexes between PCI and activated protein C or urokinase identified the previously recognized inhibitor cleavage site Arg354-Ser355. Two additional cleavage sites were observed in the modified inhibitor i.e. Arg357-Leu358 and Arg362-Leu363 which probably represent secondary cleavage of the inhibitor. Furthermore the sequence analysis of the inhibitor, whether purified from fresh or outdated plasma, revealed that it was microheterogeneous in the NH2-terminus as a result of cleavage by a trypsin like enzyme(s).
The Incidence and Clinical Significance of Amiodarone and Acenocoumarol Interaction
Authors: Caraco Yoseph , Chajek-Shaul Tova
Published: June 2018

Acenocoumarol sensitivity index (ASI) was calculated in 36 patients receiving amiodarone and acenocoumarol concomitantly, by dividing the acenocoumarol daily dose (μg kg−1 day−1) by the prothrombin ratio expressed as International Normalised Ratio (INR). It was found to be significantly lower (4.2 ± 0.3 pg kg−1 day−1) than the ASI (11 ± 0.6 μg kg−1 day−1) determined in 35 patients in the control group, who received acenocoumarol and not amiodarone. In 15 patients, ASI was 13.2 ± 1.4 and 4.2 ± 0.6 μg kg−1 day−1 before and after initiation of amiodarone therapy, respectively. In 5 patients, ASI was 6.2 ± 0.6 μg kg−1day−1, while patients were receiving both medications, and 28.1 ± 6.1 μg kg−1 day−1 following discontinuation of amiodarone therapy. ASI determined while patients were on both medications was not affected by the presence of mild impaired renal or liver function. In 7 patients treated with both drugs concomitantly, severe bleeding diathesis developed. It is concluded that amiodarone augmented the anticoagulant effect of acenocoumarol in all patients receiving both drugs. An initial reduction of acenocoumarol daily dose by 50% and further adjustment of acenocoumarol dose according to daily prothrombin ratio is recommended. It is also suggested that acenocoumarol dose should be adjusted after cessation of amiodarone therapy.
The Nature of Synergy between Tissue-Type and Single Chain Urokinase-Type Plasminogen Activators
Authors: Fry Edward T A , Mack David L , Sobel Burton E
Published: June 2018

Enhancement of thrombolysis with combinations of tissue-type and single chain urokinase plasminogen activators (t-PA and scu-PA) has been demonstrated in vivo but has not been seen consistently in vitro. This study was designed to characterize interactions between t-PA and scu-PA with respect to rate of and extent of thrombolysis in vitro and to delineate mechanisms responsible. Combinations of t-PA and scu-PA at selected concentrations synergistically enhanced thrombolysis in vitro compared with thrombolysis induced by either activator alone. Enhanced thrombolysis did not occur at the expense of fibrin specificity since the extent of fibrinogenolysis and consumption of α2-antiplasmin were significantly less with synergistic combinations of t-PA and scu-PA compared with equi-effective concentrations of either activator alone. Attenuation of complex formation of t-PA and two chain u-PA (tcu-PA), formed from scu-PA, with plasma proteins did not appear to contribute to enhancement of thrombolysis as assessed by fibrin autography. Binding of 125I-t-PA to thrombi was increased by 27% at 1 hr and by 21% at 2 hr in the presence of scu-PA (p <0,001 for both). Conversion of scu-PA to tcu-PA was enhanced when thrombi were exposed to scu-PA in the presence of t-PA. Results of this study indicate that t-PA and scu-PA at selected concentrations enhance thrombolysis in vitro synergistically without compromising fibrin specificity. Enhanced binding of t-PA to thrombi in the presence of scu-PA and enhanced conversion of scu-PA to tcu-PA appear to contribute to synergy between t-PA and scu-PA for thrombolysis.
Effect of Standard Heparin and a Low Molecular Weight Heparin on Thrombolytic and Fibrinolytic Activity of Single-Chain Urokinase Plasminogen Activator In Vitro
Authors: Lourenço D M , Dosne A M , Kher A , Samama M
Published: June 2018

The effect of unfractioned heparin (UH) and low molecular weight heparin (LMWH) (Kabi 2165 - Fragmin®) on in vitro scu-PA thrombolytic and fibrinogenolytic activity was investigated. Thrombolytic activity was evaluated by following lysis of radiolabeled plasma clot immersed in plasma in presence of scu-PA alone or with either form of heparin. A 200 IU/ml scu-PA concentration produced clot lysis within 7 hr. UH or LMWH led to a slightly faster clot lysis which was statistically significant only at the 2nd and 3rd hour. No significant difference could be evidenced between UH and LMWH effect. During clot lysis, plasmin, generated within the clot led to a gradual transformation of scu-PA to tcu-PA, specially after a 4-hr incubation. Appearance of tcu-PA activity in the plasma surrounding the clot was significantly inhibited by either form of heparin. This finding contrasts with results observed in purified systems and suggests the presence of heparin-dependent plasma factor(s) inhibiting tcu-PA formation or its activity. Possible candidates might be anti-thrombin III and PAI-3.

No fibrinogen breakdown was observed when plasma was incubated for 7 hr at 37° C in presence of scu-PA alone (200 IU/ ml) or with either form of heparin. However, in presence of a plasma clot, an important fibrinogen breakdown was observed during clot lysis reflecting the action of plasmin and/or tcu-PA generated within the clot, in the surrounding plasma. Fibrinogenolysis was less pronounced in the presence of both heparin preparations possibly as a consequence of the reduction in the tcu-PA level. These results underline the importance of plasma factors in the interaction of heparin with plasminogen activators such as scu-PA.
The Differential Glycosylation of Human Pro-Urokinase from Various Recombinant Mammalian Cell Lines Does Not Affect Activity and Binding to PAI-1
Authors: Sarubbi Edoardo , Nolli M Luisa , Robbiati Federico , Soffientini Adolfo , Parenti Franco , Cassani Giovanni
Published: June 2018

Human chromosomal DNA encoding single-chain urokinase-type Plasminogen Activator (scu-PA, or pro-urokinase) was inserted in an expression plasmid and transfected in human A431, mouse LB6 and CHO cells. LB6 cells were also transfected with a Bovine Papilloma Virus derivative containing the scu-PA gene. Human scu-PA was purified from cell supernatants of recombinant clones and characterized for structure and function.

All recombinant scu-PAs are undistinguishable from human urine-derived scu-PA for peptide backbone, but possess a higher sugar content, as revealed by SDS-PAGE analysis after digestion with glycopeptidase F. This difference is partly due to an increased sialic acid content, as shown by analysis of neuraminidase-treated scu-PAs.

No difference was found, however, among recombinant and natural scu-PAs in the kinetics of conversion into two-chain active forms (tcu-PAs) by human plasmin, and in the KM and kcat values of tcu-PA activity on the chromogenic substrate S-2444 and on human plasminogen. Also, recombinant and non-recombinant tcu-PAs displayed similar dose-response curves for binding to the endothelial inhibitor PAI-1.

In conclusion, the glycosylation pattern of u-PA does not affect its interaction with the plasma proteins directly involved in its fibrinolytic function.
Epitope Mapping of the Anti-Urokinase Monoclonal Antibody 5B4 by Isolated Domains of Urokinase
Authors: Corti Angelo , Sarubbi Edoardo , Soffientini Adolfo , Nolli M Luisa , Zanni Arturo , Galimberti Marina , Parenti Franco , Cassani Giovanni
Published: June 2018

The amino terminal fragment (ATF) of urokinase-type plasminogen activator (uPA) is a degradation product comprising the entire growth factor-like and kringle domains. It has been previously shown that ATF is able to bind to the u-PA receptor through the growth factor-like domain and that the anti u-PA monoclonal antibody 5B4 (Mab 5B4) binds to ATF preventing u-PA receptor binding. To localize more precisely the epitope recognized by Mab 5B4, ATF was subfragmented by controlled enzymatic proteolysis with V8 protease.

Three subfragments of 4,000 Mr (F-4k), 11,000 Mr (F-llk) and
12,0 Mr (F-12k) were purified from the reaction mixture and characterized. SDS-PAGE under reducing and non-reducing conditions, N-terminal aminoacid sequence analysis and C-terminal aminoacid analysis of each fragment indicate that F-4k and F-llk correspond to intact growth factor-like domain and kringle domain (residues 4-43 and 44-135 respectively) while F-12k corresponds to the kringle. domain cleaved in the first loop at the glu52-gly53 bond.

By Western blot and competitive binding experiments we show that Mab 5B4 recognizes an epitope located on the kringle domain of u-PA and that the binding is strongly reduced when the kringle contains an additional cleavage in its first loop.

Since the receptor binding site of u-PA has been previously shown to be located on the growth factor-like domain, Mab 5B4 inhibits the binding of uPA to its cellular receptor likely by steric hindrance.

Besides the proven utility in epitope localization of anti u-PA monoclonal antibodies, these u-PA fragments may represent powerful tools for studies of structure-function relationship of u-PA.
Aggregation to Thrombin and Collagen of Platelets from a Glanzmann Thrombasthenic Patient Lacking Glycoproteins IIb and IIIa
Authors: McGregor Lilian , Hanss Michel , Sayegh Amal , Calvette Juan J , Trzeciak Marie-Christine , Ville Danielle , Catimel Bruno , Viala Jean-Jacques , Dechavanne Marc , McGregor John L
Published: June 2018

The aim of this study was to investigate the platelets of a Glanzmann thrombasthenic patient, which in citrated PRP failed to respond to various agonists, but aggregated and secreted to high concentrations of thrombin (0.36, 0.72 and 1 U/ml) and collagen (4, 10 and 20 μg/ml) when washed and resuspended in a Tyrode-albumin solution (containing 2 mM Ca2+). Aggregation of the patient platelets was not affected by anti-IIb/IIIa monoclonal antibody (P18) which strongly inhibits thrombin or collagen induced aggregation of normal platelets. Washed platelets of this patient did not aggregate to ADP (10-100 μM) in the presence of added fibrinogen (2 mg/ml) nor bind 125I-labelled fibrinogen (40 to 320 μg/ml) when thrombin-stimulated. Different anti-IIb/IIIa monoclonal antibodies (P2, P18) when used in binding or crossed immunoelectrophoretic studies showed a complete absence of the IIb-IIIa glycoprotein complex on the patient platelets. Moreover, glycoproteins IIb or IIIa were absent on silver-stained twodimensional (non-reduced/reduced) polyacrylamide gel separations of the patient platelets and were not detected by Western blots used in combination with anti-PLA1 (antigen present on Ilia), anti-Leka (antigen present on IIb). This study shows that platelets lacking glycoproteins IIb or IIIa can aggregate in response to high concentrations of collagen or thrombin when resuspended in the presence of physiological concentrations of calcium. Results obtained in this study could indicate the existence of other mechanisms (other than the IIb-IIIa glycoprotein complex) involving glycolipids, heparans, proteoglycans, and/or unknown membrane glycoproteins to mediate platelet aggregation of stimulated thrombasthenic platelets.
Effect of the Concentration of Ca2+ in the Suspending Medium on the Responses of Human and Rabbit Platelets to Aggregating Agents
Authors: Packham M A , Bryant N L , Guccione M A , Kinlough-Rathbone R L , Mustard J F
Published: June 2018

The effect of the concentration of Ca2+ in the suspending medium of human and rabbit platelets on aggregation, release of 14C-serotonin, and TXB2 formation in response to ADP, thrombin, l-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (PAF), collagen and arachidonic acid was studied in either platelet-rich plasma anticoagulated with D-phenylalanyl-prolyl-arginyl chloromethylketone (PPACK) or citrate, or suspensions of washed platelets in modified Tyrode-albumin solutions containing 1 mM Mg2+ and concentrations of added Ca2+ ranging from 0 to 5 mM. In response to ADP, thrombin, or PAF, human platelets were stimulated to form TXA2 by close platelet contact in a low- Ca2+ medium; at physiological concentrations of Ca2+, TXB 2formation was much less and declined progressively as the concentration of Ca2+ was raised. When the formation of TXA 2was blocked with aspirin or indomethacin, aggregation and release by human platelets were strongest at physiological concentrations of Ca2+. Rabbit platelet responses differed markedly from those of human platelets because close contact of rabbit platelets in a low-Ca2+ medium did not promote TXA2 formation. Rabbit platelet responses were more strongly inhibited by the lack of added Ca2+ in the medium than the responses of human platelets, possibly because rabbit platelets do not contain releasable Ca2+.

In all studies of human platelets in media with low concentrations of Ca2+, the additional contribution to platelet responses of TXA2 formed because of close platelet contact should be considered because TXA2 formation is not usually stimulated in this way at physiological concentrations of Ca2+. When TXA2 formation is blocked, aggregation and release responses to all agonists are greatest at physiological concentrations of Ca2+. Thus, the responses of human platelets in media with low concentrations of Ca2+ (citrated platelet-rich plasma or artificial media to which no Ca2+ has been added) are abnormal in at least two ways, and do not correspond to the responses at physiological concentrations of Ca2+.
Failure of Preactivated Human Blood Platelets to Restore Defective Thromboxane Synthesis despite Prolonged Incubation in Plasma
Authors: Stockschläder Marcus , Scharf Rüdiger E
Published: June 2018

Acquired platelet storage pool disease has been shown to be associated with reduced platelet thromboxane synthesis. However, the mechanisms for this dysfunction are incompletely understood. The present experiments were designed to evaluate some of the possible defects which may account for impaired thromboxane formation in human platelets previously exposed to thrombin in vitro. Washed platelets pretreated with 0.5 U/ml thrombin for 20 sec and subsequently recovered as single degranulated platelets were incapable of forming normal amounts of thromboxane upon a second stimulation with thrombin (as compared to Tyrode-pretreated control platelets). In contrast, thrombin-degranulated platelets released additional amounts of thromboxane in response to arachidonate, or collagen, indicating that short-time exposure to thrombin does not irreversibly inactivate platelet cyclooxygenase or thromboxane synthetase. Upon incubation of the thrombin-pretreated platelets in autologous plasma in the presence of 14C-arachidonate, the label became associated with the platelets to the same extent as with control platelets. However, the platelets did not recover their ability to synthesize normal amounts of thromboxane upon restimulation with thrombin, and only about half of the label was lost from the thrombin-pretreated platelets as compared to control platelets in response to thrombin. The ability of collagen to cause loss of 14C-arachidonate and formation of thromboxane was the same regardless of whether or not the platelets had been pretreated with thrombin. Incubation of platelets in plasma in the presence of added arachidonate for 90 min resulted in complete refractoriness to a second stimulation with thrombin but not with collagen. However, the control platelets also lost most of their ability to synthesize thromboxane when incubated with arachidonate for 90 min and thereafter stimulated with thrombin. Thus, the presence of added arachidonate affects the thrombin-inducible thromboxane synthesis after prolonged incubation of human platelets in plasma. Our observations suggest that depletion of endogenous arachidonate is not a major cause for the defective thrombin-induced thromboxane synthesis in thrombin-pretreated platelets. It is more likely that impaired mobilization of endogenous arachidonic acid explains this dysfunction. Defective mobilization of arachidonate in thrombin-degranulated platelets may be due to agonists-specific receptor desensitization, but the responsible mechanism has not been identified.
Adhesion of Polymorphonuclear Leukocytes to Protein-Coated and Platelet Adherent Surfaces
Authors: Morley D J , Feuerstein I A
Published: June 2018

Since protein adsorption and platelet adhesion are likely to precede significant contact of leukocytes with the surfaces of artificial organs, we have chosen to study polymorphonuclear leukocyte (PMN) adhesion in a sequential manner. The work presented here deals with the effects of flow and surface type on PMN adhesion to fibrinogen- and albumin-coated glass. We compared direct adhesion to adsorbed protein with adhesion to adsorbed protein having adherent platelets. These experiments were designed to see if PMN's might preferentially adhere to albumin or fibrinogen and whether a particular morphological form of adherent platelet could promote PMN adhesion. The adhesion of PMN's to spread platelets on albumin or fibrinogen occurs to a greater extent than in the absence of platelets. Adhesion of PMN's to spread platelets may be an important mechanism for their depletion from the circulation during artificial organ use. .
Procoagulant Activity of Endocardial Vegetations and Blood Monocytes in Rabbits with Streptococcus sanguis Endocarditis
Authors: Buiting A G M , Thompson J , van der Keur D , Schmal-Bauer W C , Bertina R M
Published: June 2018

To investigate activation of the coagulation system in bacterial endocarditis, we determined the procoagulant activity of blood monocytes isolated from rabbits with Streptococcus sanguisinfected or sterile catheter-induced endocardial vegetations. This activity was determined directly after isolation from the peripheral blood and after stimulation in vitro by either endotoxin or by phagocytosis of S. sanguis. The procoagulant activity of the vegetations of these rabbits was also determined.

The procoagulant activity of blood monocytes of rabbits with S. sanguis endocarditis was found to be similar to the activity of monocytes of rabbits with sterile vegetations, both at the time of isolation and after stimulation in vitro by exposure to endotoxin or phagocytosis of bacteria. The procoagulant activity of infected vegetations was significantly higher than that of sterile vegetations. We conclude that in bacterial endocarditis the coagulation system is activated locally at the site of the vegetation. Triggering probably occurs by thromboplastin generated by monocytes activated by phagocytosis of bacteria on the vegetational surface.
Revision Microvascular Decompression for Trigeminal Neuralgia and Hemifacial Spasm: Factors Associated with Surgical Failure
Authors: Ravina Kristine , Strickland Ben , Rennert Robert , Bakhsheshian Joshua , Russin Jonathan , Giannotta Steven
Published: June 2018

Objective To investigate risk factors for symptom recurrence in patients requiring a revision microvascular decompression (MVD) for trigeminal neuralgia (TN) or hemifacial spasm (HFS).

Design Retrospective review of a prospectively maintained database.

Participants Seventeen consecutive patients undergoing revision MVD at our institution between January 1993 and September 2017.

Main Outcome Measures The incidence and causes for revision MVDs were recorded. Response to revision MVD for TN was tracked using the Barrow Neurological Institute (BNI) grading scale. Response to revision MVD for HFS was graded as “no improvement,” “some relief,” or “complete resolution” of symptoms.

Results Revision MVD rate for the senior author across all MVDs performed in this period was 1.9% for TN and 9.3% for HFS. Initial MVD failure was primarily caused by active inflammation and/or scarring and adhesions in 5/17 patients, malposition/slippage of Teflon in 3/17 patients, and insufficient Teflon in 1/17 patients. Without other factors, a new site of neurovascular conflict was identified in 4/17 patients, while the same site of neurovascular conflict was found in 3/17 patients. No cause could be identified in 1/17 patients. Scarring was found primarily in the TN group and was associated with symptom persistence.

Conclusion Revision MVD for recurrent TN and HFS is an effective procedure offering the prospect of a complete cure. Proper Teflon use is crucial for surgical success. Scarring after initial MVD is a negative prognostic factor requiring destructive treatment consideration. Although morbidity rates were slightly increased with revision versus original MVDs, the complications were non-disabling and resolved over time.
A Neonate with Exaggerated Startle and Tonic Spasms
Authors: Keshavan Shivan , Peruri Guruprasad , Suthar Renu , Angurana Suresh Kumar , Saini Lokesh , Sahu Jitendra
Published: June 2018

Hyperekplexia is a rare, potentially treatable inherited disorder of glycinergic neurotransmission, which is characterized by neonatal onset exaggerated startle response to somatosensory, auditory stimuli, and episodic tonic spasm. Prolonged tonic spasms can be life-threatening and associated with apnea and bradycardia. Awareness about this condition avoids misdiagnosis such as tonic seizures and epilepsy. We describe a term newborn with episodic tonic stiffness mistaken for seizures. Classical exaggerated startle reaction, positive head retraction response to glabellar tap, and characteristic video electroencephalogram confirmed the diagnosis.
Corrosion–microstructure interrelations in new low-lead and lead-free brass alloys
Authors: Stålnacke Emil , Claesson Erik , Obitz Charlotta , Lilja Mirjam , Odqvist Joakim , Hagström Joacim , Rod Olivier
Published: June 2018

Stress-relieving heat treatment has been reported to deplete the corrosion resistance of new low-lead and lead-free brass alloys. How the heat treatment, processing and material composition relates to the microstructure and corrosion performance is not well understood. The present study aims to fill this knowledge gap by mapping stress-relieving annealing conditions and different standardised compositions to their respective microstructures and dezincification performance. It was found that loss of corrosion resistance was only the most severe for alloys with higher aluminium and iron content. These alloys displayed significant precipitation of intermetallic aluminium arsenide particles on grain boundaries, twins and lead particles, as well as the formation of β-phase along grain boundaries.

This paper is part of a Thematic Issue on Copper and its Alloys.
Estimation of yttrium oxide microstructural parameters using the Williamson–Hall analysis
Authors: Emil Elif , Gürmen Sebahattin
Published: June 2018

Yttrium oxide (Y2O3) particles were synthesised from a yttrium nitrate solution via ultrasonic spray pyrolysis (USP) method. The effects of temperature and precursor concentration on morphology and microstructural parameters were investigated. Y2O3 particles were characterised by scanning-electron-microscope energy-dispersive spectroscopy, Raman spectroscopy and X-ray diffraction analysis. Based on X-ray peak broadening, the crystallite size was calculated using the modified Debye–Scherrer (MDS) method. Furthermore, the crystallite size, crystal strain and the energy density of the crystal were evaluated using the Williamson–Hall (W–H) analysis integrated with the uniform deformation model, the uniform stress deformation model and the uniform deformation energy density model. A comparative evaluation of Y2O3 crystallite size using the MDS and W–H methods was carried out.

This is part of a thematic issue on Nanoscale Materials Characterisation and Modeling by Advances Microscopy Methods - EUROMAT.
All-Cause and Cause-Specific Mortality Rates of Patients Treated for Alcohol use Disorders: A Meta-Analysis
Authors: Abdul-Rahman Abdul-Kareem , Card Timothy R. , Grainge Matthew J. , Fleming Kate M.
Published: June 2018

Background: Although alcohol use disorders (AUDs) are known to increase the relative risk of all-cause and some cause-specific mortality, the absolute mortality rates of the AUD population are unknown. Such knowledge would benefit planners of the provision of services for this population, including in prioritizing the identification and/or treatment of diseases likely to cause their death. Methods: We conducted a systematic review of studies in English, reporting the cause-specific mortality rates among people treated for AUDs. Number of deaths by cause and total person-years of follow-up were extracted. All-cause and cause-specific mortality rates per 1000 person-years were meta-analyzed assuming random effects. Results: Thirty-one studies were included. Participants were mainly middle-aged males. The quality of studies was generally good. A total of 6768 all-cause deaths in 276,990.7 person-years of follow-up (36,375 patients) were recorded, and the pooled all-cause mortality rate was 27.67/1000 person-years (py) (95% confidence interval [CI]: 23.9, 32.04). The most common cause of death in the AUD population was cardiovascular disease (CVD) (6.9/1000 py; 95% CI: 5.61, 8.49), followed by gastrointestinal deaths (5.63/1000 py; 95% CI: 4.1, 7.74), unnatural deaths (4.95/1000 py; 95% CI: 4.01, 6.09)), neoplasms, respiratory diseases, and substance use disorders. Conclusions: Patients with AUDs have increased rates of all-cause and cause-specific mortality compared with the general population. Like the general population, they are most likely to die of CVD. In contrast to the general population, gastrointestinal and unnatural deaths are the next most common causes of death. We believe these facts should be considered when planning health care services for patients with AUDs.
Role of androgens in energy metabolism affecting on body composition, metabolic syndrome, type 2 diabetes, cardiovascular disease, and longevity: lessons from a meta-analysis and rodent studies
Authors: Harada Naoki
Published: June 2018

Testosterone is a sex hormone produced by testicular Leydig cells in males. Blood testosterone concentrations increase at three time-periods in male life–fetal, neonatal (which can be separated into newborn and infant periods), and pubertal stages. After peaking in the early 20s, the blood bioactive testosterone level declines by 1–2% each year. It is increasingly apparent that a low testosterone level impairs general physical and mental health in men. Here, this review summarizes recent systematic reviews and meta-analyses of epidemiological studies in males (including cross-sectional, longitudinal, and androgen deprivation studies, and randomized controlled testosterone replacement trials) in relation to testosterone and obesity,  body composition, metabolic syndrome, type 2 diabetes, cardiovascular disease, and longevity. Furthermore, underlying mechanisms are discussed using data from rodent studies involving castration or androgen receptor knockout. This review provides an update understanding of the role of testosterone in energy metabolism.

Abbreviations AR: androgen receptor; CV: cardiovascular; FDA: US Food and Drug Administration; HFD: high-fat diet; KO: knockout; MetS: metabolic syndrome; RCT: randomized controlled trial; SHBG: sex hormone binding globulin; SRMA: systematic review and meta-analysis; TRT: testosterone replacement therapy; T2DM:type 2 diabetes mellitus
An overview of anal intraepithelial neoplasia
Authors: Buzard Corina L. , Rizzolo Denise
Published: June 2018

Anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma (ASCC) are on the rise in the United States, especially among men who have sex with men, HIV-positive or other immunocompromised patients, and women with a history of cervical, vaginal, or vulvar cancer. Strong evidence supports the human papillomavirus as the causative factor in anal dysplasia; reducing the risk of HPV infection can reduce rates of ASCC. High-risk patients should be screened for AIN, but no universal screening guidelines exist, and more studies are needed to develop a national protocol for screening and management of patients with AIN.
What RNs Can Do to Improve the Health of Their Communities
Authors: Ross Barry
Published: June 2018

We can make a difference in the places we learn, pray, work, and live.
Joint Commission Issues Alert Addressing Violence Against Health Care Workers
Authors: Stockwell Serena
Published: June 2018

Document includes steps institutions can take to protect and prepare staff.
Antibiotic Treatment for Clostridium difficile Infection in Adults
Authors: Wilson Amanda
Published: June 2018

Editor's note: This is a summary of a nursing care–related systematic review from the Cochrane Library. For more information, see http://nursingcare.cochrane.org.
Azithromycin Reduces Childhood Deaths in Africa
Authors: Rosenberg Karen
Published: June 2018

According to this study:

Mass distribution of oral azithromycin to children in sub-Saharan Africa significantly lowered childhood mortality, as compared with placebo.

It is possible that the development of antibiotic resistance could erase the difference, although that effect was not seen in this trial.
Nonprescription Treatments are an Option for Many Women with Postmenopausal Vulvovaginal Symptoms
Authors: Rosenberg Karen
Published: June 2018

According to this study:

Active treatment with either vaginal estradiol tablets or vaginal moisturizer provided no additional benefit over placebo in women with postmenopausal vulvovaginal symptoms.

Many women can be treated with a nonprescription vaginal lubricating gel.
Sensitivity to Melody, Rhythm, and Beat in Supporting Speech-in-Noise Perception in Young Adults
Authors: Yates Kathryn M. , Moore David R. , Amitay Sygal , Barry Johanna G.
Published: June 2018

Objectives:

Musicians appear to have an enhanced ability to perceive speech-in-noise, prompting suggestions that musical training could be used to help people who struggle to communicate in noisy environments. This study assessed the role of sensitivity to beat, rhythm, and melody in supporting speech-in-noise perception.

Design:

This is an exploratory study based on correlation. The study included 24 normally hearing young adult participants with a wide range of musical training and experience. Formal and informal musical experience was measured with the training subscale of the Goldsmiths’ Musical Sophistication Index. Speech reception thresholds (SRT) were measured using the Matrix Sentence Test and three different speech-spectrum-shaped noise maskers: unmodulated and sinusoidally amplitude-modulated (modulation frequency, f
m = 8 Hz; modulation depths: 60 and 80%). Primary predictors were measures of sensitivity to beat, rhythm, and melody. Secondary predictors were pure-tone frequency discrimination and auditory working memory (digit span). Any contributions from these two predictors were to be controlled for as appropriate.

Results:

Participants with more musical experience and greater sensitivity to rhythm, beat, and melody had better SRTs. Sensitivity to beat was more strongly linked with SRT than sensitivity to either rhythm or melody. This relationship remained strong even after factoring out contributions from frequency discrimination and auditory working memory.

Conclusions:

Sensitivity to beat predicted SRTs in unmodulated and modulated noise. We propose that this sensitivity maximizes benefit from fluctuations in signal-to-noise ratio through temporal orienting of attention to perceptually salient parts of the signal. Beat perception may be a good candidate for targeted training aimed at enhancing speech perception when listening in noise.