bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring Response Of Disease To Heparin Therapy With The Activated Coagulation Time (ACT)
Authors: Hattersley P G , Mitsuoka J C , King J H
Published: July 2018

Believing that treatment of thromboembolic disease with heparin is treatment of a dangerous group of disorders with a potentially dangerous drug, and that sensitivity to heparin varies greatly, one patient to the next, we attempted to model heparin infusion rates to the specific needs of the patient. We gave initial doses proportionate to body weight, and monitored responses by the ACT. We chose this test because it is a precise bedside procedure which reliably reflects the variable responses of patients.

Our protocol: (1) Screen for conditions causing a high risk of bleeding on heparin; (2) Infuse an initial i.v. heparin bolus of about 50 units per kilogram of body weight; (3) Follow with pump-controlled i.v. infusion of 15 to 25 units/kilo/hr.; (4) Subsequently alter the infusion rate as needed to maintain an ACT of 150 to 190 seconds; (5) When the ACT has been established within this range, start appropriate oral doses of warfarin; (6) After 3 days or more, when the prothrombin time is 2 to 2-1/2 times the control, discontinue heparin and maintain patient on oral warfarin.

Of 100 patients with proven thromboembolic disease treated at close to this protocol, there were none with progressive thromboembolic disease; 95 patients responded, and were converted to oral warfarin; 5 developed major bleeding necessitating discontinuing heparin. Of these 5, 2 were unrecognized high risk patients who should not have received full dose heparin. The other 3 all had ACT'S well above 190 seconds.

Our conclusion: For treatment of patients with deep venous thrombosis and/or pulmonary embolism, this protocol of heparin therapy, if followed carefully is effective and reasonably safe.
Relevance Of Plasma alpha 2 Antiplasmin Measurement For Monitoring The Occurrence Of A Thrombolytic State During Urokinase Therapy. An In-Vitro Study
Authors: Musumeci V , Zappacosta B
Published: July 2018

The aim of the present study was the search of changes in laboratory parameters which can be reliably correlated to the development of an effective thrombolytic state during urokinase therapy. Artificial radiolabelled venous thrombi were prepared by leaving native blood (0.1 ml) to clot in glass tubes for 2 hours in presence of 1-2 μCi of 125I fibrinogen (Sorin Saluggia, Italy). The labelled clots were introduced into a perfusion chamber (volume 0.2 ml) provided with a plastic retention screen and placed in the focus of the detector of a Pitman Ratemeter model 235 N connected to a recorder. The perfusion chamber was connected in a close circuit through a peristaltic pump to a reservoir containing citrated whole blood (15 ml) maintained at 37°C under continuous stirring. Blood was pumped through the chamber at a flow rate of 1 ml/min. Urokinase was introduced in increasing amounts in the reservoir during a period of 5 hours and at various intervals aliquots of blood (0.3 ml) were drawn and assayed after centrifugation for plasminogen, alpha 2 antiplasmin and fibrinogen. Alpha 2 antiplasmin was assayed by using Coatest Antiplasmin from Ortho Diagnostics. Plasminogen was assayed after SK activation by using the substrate S 2251 from Ortho Diagnostics. Results showed that an effective thrombolytic states, as detected by a decrease of clot radioactivity, appeared when alpha 2 antiplasmin concentration fell at levels below 40%. The alpha 2 antiplasmin measurement could be useful for monitoring the thrombolytic effectiveness of non-standard low or moderate dosages of urokinase therapy.
The Effect Of Streptokinase On Regional Myocardial Perfusion After Coronary Ligation In Dog
Authors: Genth K , Hofmann M , Schaper W
Published: July 2018

The Influence of streptokinase(SK) on myocardial perfusion in ischemic and non-ischemic muscle was studied in 10 open-chest dogs, on each animal a sequential occlusion of 2 medium-sized coronary arteries was performed (90 min.), followed by reperfusion. Each dog served as its own control. After occlusion and reperfusion of the control artery (CA), the inital dose of SK was given (1,5 mega IU/20 min.). Thereafter test artery (TA) was occluded, followed by a maintenance dose of SK (500.000 IU/h). LVP, AOP, LVdp/dt and heart rate were recorded, MV02 was calculated by the computer (Bretschneider’s equation). Myocardial perfusion was measured after 90 min. of occlusion (tracer microspheres). M VO2 was comparable during both occlusion periods. CO (dye dilution technique) was 1,38±0,2 during CA-occlusion and 1,71±0,3 1/min. during TA-occlusion (p<0,01). In the non ischemic myocardium subepicardial and subendocardial perfusion was of equal value in both perfusion areas. Coronary ligation reduced flow drastically in the CA-region collateral flow (CF) in subendocardium was 11,8 ± 8 and 31,4 ± 12 ml/min.x100 g in the subepicardium. In The TA-region CF in the subendocardjum was 12,6 ± 5 and in the subepicardium 27,8 ± 14 ml/min.x100 g. CF was in the subendocardium significantly lower than in subepicardium in both perfusion areas (p<0,01). The present results show that CF in the ischemic myocardium cannot be modified by fibrinolysis. SK did not redistribute flow from subepicardium to subendocardium.
Human Plasminogen Activator From Heart And Vascular Endothelium
Authors: Booth N A , Bennett B
Published: July 2018

Plasminogen activators play a central role in fibrinolysis. At present little is known about the interrelationships and molecular properties of these protein(s). There have been conflicting reports on the number of polypeptide chains present in the active molecules; plasminogen activators, purified from human uterus and human plasma after venous occlusion, are reported to consist of two chains, each of approximately 30,000 MW, linked by disulphide bonds. In contrast, the protein purified from human vascular endothelium consists of a single chain of 67,000 MW. Evidence for proteolytic activation of a single chain precursor to a two-chain form has been obtained by Wallen, in that the protein could be isolated in the single chain form only if inhibitors of proteolysis were present throughout purification. The two-chain form was found to possess significantly greater activity. By analogy with other plasma systems, generation of an active two-chain form from a single-chain precursor may serve a regulatory function, but the role of limited proteolysis of plasminogen activator remains to be elucidated.

Using modifications of reported methods, we have obtained improved purification of plasminogen activator from human heart and vascular endothelium by similar procedures. This has allowed detailed comparison of the enzyme from these two sources, in terms of chain structure, active site labelling and carbohydrate content. In particular, the effect of variation of conditions during purification on the chain structure of the isolated molecule has been studied.
Kinetic Characterization Of The Fast Acting Plasmin Inhibitor From Human Platelets
Authors: Hansen M Sandbjerg , Petersen Lars Chr
Published: July 2018

An inhibitor of the plasma proteinase plasmin (EC 3.4.21.7) was partially purified from washed and lysed human blood platelets. The presence of the known plasma proteinase inhibitors in the preparations investigated was excluded by crossed immunoelectrophoresis and electroimmuno assay. The kinetics of the reaction between the inhibitor preparation and plasmin has been investigated using the synthetic chromogenic substrate S-2251 (D-Val-Leu-Lys-pNA).

Residual plasmin activity was measured varying the amounts of inhibitor at various fixed concentrations of substrate (S-2251). The inhibitor is of the noncompetitive type as indicated by a Dixon-plot. The reaction between inhibitor and plasmin is fast with an estimated dissociation constant of approximately. 0.1. nM. The reaction is reversible as evidenced by the following findings: 1. inhibition in the presence of high concentrations of substrate is a fast reaction, but total inhibition of plasmin is not obtained, 2. inactivation of plasmin as a function of inhibitor concentration does not follow a simple titration curve, 3. addition of tranexamic acid increases the apparent Ki, 4. the complex beetween the inhibitor and plasmin is demonstrable in crossed immunoelectrophoresis but not in SDS-polyacrylamide gel electrophoresis. The results suggest that the platelet plasmin inhibitor is a reversible inhibitor with a high affinity for plasmin.
Action Of Foy, A Polyvalent Synthetic Inhibitor On Coagulation And Fibrinolysis
Authors: Stemberger A , Haas S , Stöhr R , Blümel G
Published: July 2018

Foy(S 983), a low molecular synthetic protease inhibitor is discussed as a potential drug in acute pancreatitis and in traumatic haemorrhagic shock. Action on coagulation was tested using global clotting tests like aPTT and prothrombin time. In addition, the inhibitory effect was elucidated with chromogenic substrates on the X a- and thrombin level after exogenous or endogenous activation. This study was performed in comparison with aprotinin (TrasylolR) based on the assumption that 50 KIE aprotinin ≅ 0.1 mg Foy.

Effect on fibrinolysis was tested after streptokinase (Sk) or urokinase activation. Due to the kallikrein, Xa and thrombin inhibition Foy showed a dose dependent strong effect on the endogenous and exogenous pathway in contrast to the weak effect of aprotinin on the endogenous system via kallikrein only. Plasmin inhibition of the two drugs were similar. However Foy interfered with the Sk-plasminogen activation and is an inhibitor of urokinase. Both drugs showed a strong inhibition on proteases harvested from the secretion of fistulas of the intestinal tract which are often responsible for disturbances in wound healing.
Red Cell Properties In Haemostasis
Authors: Housley G M , Born G V R
Published: July 2018

Earlier observations of ours have suggested that, under in vitro conditions resembling those under which platelets function haemostatically in vivo, their activation is promoted by the red cells. Seme of the evidence suggested that this is through limited haemolysis with release of ADP. However, newly determined time relationships make this uncertain. Could red cells provide ADP without haemolysis?Crtheir flow properties affect the process more? To analyse the problem, we are determining dependence of red cell deformability on membrane constitution; and release of haemoglobin and adeninenucleotides under different conditions. Ten percent human red cell suspensions in physiological salines flow under constant pressures through 2, 3, 4 and 5 pm micropore filters, the flow rate measured continuously with an electronic balance. Initial flow rates are increased by fluidising agents, eg. ethanol, and decreased by agents with opposite effect. Our results are consistent with the new hypothesis of S.J. Singer on the mode of action of amphipathic agents, such as chlorpromazine, on red cell membranes.
Disseminated Intravascular Coagulation In Patients With Fatty Liver Of Pregnancy. Onset Of Dic Prior To Labor
Authors: Liebman H , Sandler R , Patch M J , McGehee W G
Published: July 2018

Fatty liver of pregnancy (FLP) is a rare syndrome with a high maternal mortality. Bleeding complications are frequent and are associated with disseminated intravascular coagulation (DIC). We have previously demonstrated that DIC in this syndrome can be persistent, lasting 2 to 6 days, and is associated with severe depressions of functional and antigenic antithrombin III (AT III). The severe depression of AT III in this syndrome is believed to secondary to decreased hepatic synthesis and increased consumption from DIC. We have hypothesized that DIC is initiated by active labor, persists because of the low levels of AT III and may be controlled by transfusion of fresh frozen plasma or AT III concentrate. Recently we saw a patient with FLP proven by biopsy who presented with jaundice, nausea, and emesis. The patient was not in active labor. In preparation for surgical delivery, coagulation studies were done which revealed DIC (abnormal screening tests, fibrinogen of 70mg/dl, fibrin split products of 320-640 ng/dl, depressed factors V ᶓ VIII and a positive protamine sulfate test). The patient was given 1500 cc of fresh frozen plasma and viable twins were surgically delivered on the second hospital day. Following delivery DIC subsided, but infusions of plasma were continued until the fourth hospital day.

Subsequently we measured AT III using a fluorometric synthetic substrate (Protopath-see table above). From our observations on this patient we conclude (1) active labor is not necessary for the initiation of DIC in FLP (2) DIC in FLP can be associated with non-detectable functional AT III (3) transfusions of fresh frozen plasma can significantly increase functional AT III and may control DIC.
Antithrombin III And Plasminogen: Predictors For Developing Gram-Negative Septicemia
Authors: Büller H R , Bolwerk C , ten Cate J , Kahlé L H , Roos J , ten Cate J W
Published: July 2018

Gram-negative septicemia presents a particular problem to intensive care units. Our earlier observations in surgical patients suggested a relationship between bacterial infections and decreased plasma antithrombin III activity. 174 patients have been prospectively investigated pre and 10 days postoperatively. The aim of this study was to relate postoperative septicemia, verified by positive bloodculture(s) and the hemostatic profile. Daily investigation of factor II, X, AT III, α2 antiplasmin (α2AP), plasminogen (PLG), leucocytes and bacterial cultures revealed the following findings: in patients (n=36) with positive bloodcultures (gramnegative bacteria), AT III and PLG were significantly lower a few days prior to outbreak of clinical septicemia. α2AP behaviour was unaffected. Leucocyte counts provided no distinct information on developing septicemia. Therefore low AT III and PLG plasma levels in the p.o. phase are early indicators for developing septicemia. This finding is related to circulating endotoxins, estimated with a new sensitive chromogenic assay.
Comparison between a Direct and an Indirect Method for Determining Plasminogen
Authors: Hedner Ulla , Nilsson Inga Marie
Published: July 2018

A caseinolytic method for plasminogen determination using 30% ammonium sulphate to remove the inhibitors was compared with an immunochemical method in 44 apparently healthy individuals, 25 pregnant women in the third trimester, 24 patients with different liver diseases, 20 patients receiving thrombolytic therapy, 7 patients with septicemia and 9 foetuses obtained by induced legal abortion. The correlation found was strong and the regression line was found to pass near origo, indicating that the two methods measured, the same substance.

Both methods gave high plasminogen values in pregnant women and low values in patients receiving thrombolytic therapy and in foetuses.
An Accelerated Red-Cell Hemagglutination Inhibition Immunoassay for Measuring Fibrinogen Degradation Products in Human Serum
Authors: Fischer R , Furlan M , Beck E. A
Published: July 2018

A further modification of Merskey’s hemagglutination inhibition assay for measurement of fibrinogen degradation products (FDP) in human serum was developed. Blood is clotted in the presence of protamine chloride (25 u/ml), in addition to thrombin and s-aminocaproic acid, and at room temperature. Defibrination is complete within 5 min even in blood obtained from patients on heparin treatment. The hemagglutination immunoassay was also considerably accelerated by immediate addition of sensitized red cells to the mixtures of antiserum and antigen dilutions at 37° C. Accurate readings of FDP titers may thus be obtained within 20 min following venipuncture.
Removal of Thrombokinase from Commercial Thrombin
Authors: Kerwin D. M , Milstone J. H
Published: July 2018

Commercial thrombin was shown to contain appreciable amounts of thrombokinase. Passage through a DEAE-cellulose column substantially reduced the thrombokinase titer, although significant contamination could still be detected. Similarly, repeated barium sulfate adsorptions failed to remove the thrombokinase completely.

However, barium sulfate adsorptions followed by passage through a column of DEAE-cellulose resulted in an essentially complete removal of the contaminant. Thrombin, so obtained, did not accelerate activation of prothrombin in the presence of calcium, phosphatide and barium carbonate adsorbed serum.

Thrombokinase, separated by chromatography, was able to activate prothrombin very slowly in the presence of oxalate. Comparably dilute thrombin fractions and the unfractionated commercial preparation either did not possess this capability, or else this capability was obscured by a concomitant loss of thrombin.
Effect of Anticoagulating and Non-Anticoagulating Concentrations of Heparin on the Generalized Shwartzman Reaction
Authors: Corrigan J. J
Published: July 2018

Rabbits given 2 properly spaced intravenous injections of bacterial endotoxin develop bilateral renal cortical necrosis (generalized Shwartzman reaction - gSr). This renal lesion is the result of fibrin deposition secondary to diffuse intravascular clotting (DIC). Using this experimental model, the effect of anticoagulating (large) and non- anticoagulating (small) concentrations of heparin on the changes in blood platelets, plasma coagulation factors II, V, VIII and fibrinogen during the production of renal cortical necrosis was studied. The data demonstrate that all amounts of heparin given during, but not after, the period of intravascular clotting reduced the frequency of renal cortical necrosis. Anticoagulating concentrations completely prevented the renal lesion. Non-anticoagulating amounts could reduce the frequency of the renal lesions, but this effect was not predictable or consistent. Coagulation studies in the large dose group revealed thrombocytopenia reduced factors II, V, and VIII but no fibrinogen consumption. These findings suggest that heparin inhibits the formation of fibrin in vivo, thereby preventing the formation of renal cortical necrosis. The coagulation data in the small dose group differed in that fibrinogen consumption did occur. The possible explanations for the phenomenon were discussed.
Comparison of the Effects of Various Blood Plasma Expanders on Platelet Adhesiveness
Authors: Schneider J. A , Sanbar S. S , Zweifler A. J
Published: July 2018

In 30 non-anesthetized rabbits, platelet adhesiveness of arterial blood was determined before and 2, 6, and 24 h after 10 min intravenous infusions of either 20 ml isotonic saline solution (5 control rabbits), or 2.4 g each of dextran 40,000 (4 rabbits), dextran 70,000 (4 rabbits), polyvinylpyrrolidone (P. V. P.) 40,000 (8 rabbits), hydroxyethyl starch (H. E. S.) 60,000 (4 rabbits), or H. E. S. 450,000 (5 rabbits) in saline solution.

Platelet adhesiveness did not change significantly after infusions of saline, dextran 40,000, or H. E. S. 450,000. In contrast, dextran 70,000 and H. E. S. 60,000 promptly produced about one-third decrease in platelet adhesiveness which returned toward control levels 24 h after the infusions. Finally, P.V.P. also promptly diminished percent platelet adhesiveness by about one-third of control values and this effect persisted 24 h after infusion. Changes in platelet adhesiveness did not correlate with alterations in hematocrit or platelet count.

On a weight basis, P. V. P. elicits the most persistent decrease in platelet adhesiveness.
Preparation, Stabilization and Some Properties of Purified Human Plasmin*
Authors: Kline Daniel L , Fishman Jacob B ,   With the technical assistance of B. A. Lage
Published: July 2018

1. Lysine increased the solubility, decreased the SK requirement and increased the stability of plasmin prepared from purified plasminogen by SK activation.

2. A procedure is presented for the rapid and quantitative conversion of plasminogen to plasmin and storage of the plasmin in stable form at neutral pH as a lyophilized powder.

3. Approximately 10% for the plasminogen molecule was split off during its activation. No carbohydrate was lost.

4. The plasmin isolated was homogeneous in the ultracentrifuge at pH 2.5 and was quantitatively convertible to plasminogen activator by the addition of SK.
Streptokinase - Induced Proteolytic Activity with Respect to Age in Two Ethnic Groups in Israel
Authors: Rimon A , Segal S
Published: July 2018

Streptokinase-induced proteolytic (caseinolytic) activity was determined in the plasma and in the euglobulin fraction of Yemenite and Ashkenazi Jews, with respect to age.

In the plasma it was found, that in both groups the activity increased with age. In Ashkenasim, however, the activity levelled off at about 30 years of age, whereas, in Yemenites, it continued to increase with age. This was true for both sexes.

In the euglobulin fraction, the activity was also found to increase with age, but to a lesser extent, than in the plasma. This increase was more pronounced in Yemenite than in Ashkenazi Jews, and in both groups levelled off at about 30 years of age. The possible significance of these observations apropos regulation of the fibrinolytic activity in the blood, is dicussed. It is suggested that Yemenite Jews have a more effective mechanism for handling clots with advancing years.
The Fibrinotic Index and Evidence for a Balanced Regulation of Coagulation Activities*
Authors: Grannis G. F , Kazal L. A
Published: July 2018

The fibrinogen, plasma antithrombin, and thrombin activity curves of twenty-four normal individuals were determined under carefully controlled conditions of analysis. From these determinations plasma prothrombin and thromboplastic activities were calculated. These activities were defined in kinetic terminology and a theoretical rate of fibrination in plasma was calculated and used as a basis for comparing plasmas. Compensatory relationships were found among the various activities. Thus, low values of thromboplastic activity were associated with increased concentrations of prothrombin and fibrinogen; the effect of the latter activities in increasing the potential of plasma for fibrination was moderated by an increase in antithrombin activity.

The fibrin-forming potential of each plasma was calculated relative to the mean value for all plasmas, to furnish a fibrinotic index. The latter was relatively constant in spite of wide variations in discrete activities, indicating that a physiological balance is maintained among those coagulation factors responsible for fibrination.
Determination of Plasminogen in Human Plasma by a Casein Method*
Authors: Hedner Ulla , Nilsson Inga Marie
Published: July 2018

A modification of the casein method for determination of plasminogen in plasma has been devised.

1. Urokinase instead of streptokinase was used for activation of plasminogen in order to eliminate the effect of any antistreptokinase antibodies in the plasma.

2. A purified and stable plasmin preparation according to Wallén was used for preparing reference curves.

3. The plasminogen activity of plasma was converted into arbitrary casein - olytic units (ACU) defined in such a way that 10 caseinolytic units gave an extinction of 0.300.

4. Removal of the plasmin inhibitors by acidification of plasma to pH 2.0 was found to be better than using euglobulin precipitation.

5. The plasma should be tested immediately after thawing and not allowed to stand after acidification for obtaining optimal conditions.

6. The method can be used for determination of plasminogen in plasma in patients treated with ssss-ACA and AMCA.

7. The error of the method was found to be small ssss0.4.

The mean plasminogen level in a normal group of 72 was found to be 9.5 ssss 1.7 ACU/ml plasma. No variation with sex and age was found.

The method proved clinically useful. During the latter half of pregnancy the plasminogen level was found to be clearly elevated. In patients with liver cirrhosis the plasminogen level was low. It was a sensitive method for following the plasminogen content during streptokinase treatment.
The Mechanism of Activation of Cat Plasma by Streptokinase*
Authors: Mootse G , Fleming L.B , Cliffton E.E
Published: July 2018

1. The mechanism involved in the inactivation of cat plasma, serum, and plasma euglobulin by different concentrations of SK has been demonstrated.

2. Two different caseinolytic entities were graphically differentiated. They were characterized by their time of formation and stability studies.

3. With suboptimal SK concentration the development of the caseinolytic activity consisted of an initial rapid phase, followed by a slowly rising activity ; beta plasmin. With optimal SK concentration only the initial rapid caseinolytic activity was obtained (alpha plasmin).

4. It is suggested that beta plasmin was formed by a reversible reaction and was inactivated when substrate was not present. With increasing SK concentration alpha plasmin formation competed with the beta plasmin formation.

5. A comparison of potential caseinolytic activity of cat plasma, serum, and plasma euglobulin to beta and alpha plasmin is present.
The Effect of the Alkyl Tins on Platelet Aggregation
Authors: O’Brien Dr. J. R
Published: July 2018

The addition of the tri alkyl tins to stirred platelet rich plasma produces after a delay, gross platelet aggregation. The delay is decreased by Adenosine triphosphate and increased by Adenosine monophosphate. The tri alkyl tins may liberate Adenosine diphosphate from the platelets, possibly by stimulating an ATP-ase. Plasma as well as platelets can inactivate Adenosine diphosphate.
Disposable Plastic Cuvettes for Thrombelastography
Authors: Loeliger E. A , Veltkamp J. J , Mattern Mieke J , Hooij Henriëtte J
Published: July 2018

Thrombelastography can be performed by means of disposable plastic cuvettes instead of metallic cuvettes. There is no important difference between the curves obtained in cuvettes of the two different materials. Reproducibility plastic cuvettes appears to be as good as in metallic cuvettes; reproducibility seems to be even better. The use of plastic disposable cuvettes has important practical advantages.
Lauric Acid-Induced Thrombocytopenia and Thrombosis in Rabbits
Authors: Zbinden G
Published: July 2018

Intravenous injection of 0.5% lauric acid solution into rabbits caused moderate to marked thrombocytopenia. With small doses (2.5 mg/kg) this thrombocyte decrease was reversible and microscopically demonstrable thrombosis in the lungs was only seen or suspected in a small number of rabbits 10 to 30 min after lauric acid injection. High doses were followed by partly reversible thrombocytopenia and by moderate to marked, sometimes lethal, thrombosis in the lungs still demonstrable 24 hrs after injection. Repeated administration of small doses of lauric acid did not lead to a depletion of the circulating thrombocytes. Thrombocytopenic response, however, appeared to be less pronounced after the second and subsequent injections. Studies with Cr51-labeled platelets indicate that during the reversible thrombocytopenia following a small intravenous dose of lauric acid platelets are retained in various organs, particularly the lungs.
Coagulation Studies after Administration of a Fat Emulsion, Intralipid®
Authors: Cronberg S , Nilsson Inga Marie
Published: July 2018

A single infusion of a fat emulsion, Intralipid®, used for parenteral nutrition was given to 11 healthy normals, 3 patients with von Willebrand’s disease and 3 with mild or moderately severe thrombasthenia. The infusion had no effect on coagulation or the fibrinolytic system. Platelet adhesiveness, as determined with Hellem’s whole blood method, was markedly increased but not with his plasma-ADP method or with Salzman’s method. No shortening of the bleeding time was observed in the normals or in the patients with prolonged bleeding time. The change observed in platelet adhesiveness is therefore believed to be an in vitro artefact with no clinical relevance.
Comparative Studies of Fibrinolytic Inhibitors in Vitro
Authors: Maki M , Beller F. K
Published: July 2018

EACA, AMCHA, Trasylol and Soya bean trypsin inhibitor were compared in regard to their inhibition potency as enzyme and activator inhibitors in vitro, in different test systems. The ratio in all systems for Trasylol and STI was 1:4/6 depending on the test system used. Both substances are only slightly less active as activator inhibitors than as plasmin inhibitors. The difference however, is so small that Trasylol as well as STI can be regarded as good activator inhibitors in vitro. Both substances inhibit plasmin as well as activator competitively and differ therefore with EACA and AMCHA.

EACA and AMCHA are activator inhibitors and considerably less inactive in regard to plasmin inhibition. The already known fact that EACA inhibits the activator competitively was confirmed for AMCHA. The latter substance is 6-8 times more potent, than EACA.

EACA, AMCHA, Trasylol and STI given in combination resulted in an additive or synergistic action, rather than a potentiating one as has been described in vivo.
Influence of Certain Drugs on the Adhesiveness of Human, Rat, and Rabbit Blood Platelets in Vitro
Authors: Reber K , Studer A
Published: July 2018

This is a comparative study of the methods described by H. P. Wright and O’Brien for determining the adhesiveness of thrombocytes. An attempt is made to characterize and statistically correlate both techniques. With the aid of a Coulter Counter for thrombocyte counts, a normal range is presented for human, rat, and rabbit blood. Anticoagulants used are sodium citrate and Heparin.

The influence of Cocaine and the Serotonin antagonist Ro 3-0837 was studied on these same substrates, to determine a pharmacological interference with results of either Wright’s test or O’Brien’s. Both drugs are found to induce a statistically significant increase in the “thrombocyte count” as compared to the corresponding controls. These effects are not real but to be attributed to an increase in particle count due to thrombocyte fragmentation as a consequence of drug application. There is no evidence for the claim that these drugs decrease the adhesiveness of thrombocytes.

Numerical results of both tests often show a high and statistically significant correlation, especially following the addition of Ro 3-0837. Such is not true of individual blood samples to which no drug has been added. Evidentally, both tests are not specific for the same characteristic of normal blood platelets. But, when Ro 3-0837 is added, the breakdown of unstable platelets is induced; and the corresponding increase in count of thrombocyte fragments is expressed by both tests in the same fashion.
Thrombose als ein Vorgang in »strömendem Blut«: Wechselwirkung fluiddynamischer, rheologischer und enzymologischer Ereignisse beim Ablauf von Thrombozytenaggregation und Fibrinpolymerisation
Authors: Schmid-Schönbein H.
Published: July 2018

Einer der am meisten verbreiteten Irrtümer in der Hämostaseologie ist die Vorstellung, daß das Blut zuerst stillstehen müsse, um dann gerinnen zu können. Ausgehend von der seit genau einem Jahrhundert (nämlich seit Eberth und Schimmelbusch, 1888 [20]) experimentell gesicherten Tatsache, daß Blut zwar im Stillstand gerinnen kann, sich aber Thromben in vivo ausschließlich bei erhaltener, wenngleich gestörter Strömung bilden können, wird eine umfassende Theorie der Wechselwirkung zwischen Strömung und dem Ablauf thrombotischer Prozesse entwickelt. Die Theorie basiert auf einer detaillierten Analyse der biophysikalischen Grundlagen der physiologischen »Fließfähigkeit« des Blutes, der rheologischen Analyse all der Vorgänge, die die Fließfähigkeit einschränken, sowie der Interpretation der kinematischen, dynamischen und hämorrheologischen Wirkungen, die vom Vorgang der »Scherdeformation« des Blutes ausgehen können. Erst die klare Trennung unterschiedlicher »Strömungseffekte« läßt dann verstehen, wie verschiedene, im Körper vorkommende Strömungsanomalien wirken, die sich allesamt an »nichtzylindrischen« Gefäßabschnitten in Form von »Sekundärströmungen« manifestieren und bei denen es sich um laminare Wirbel handelt. Kennt man die Voraussetzungen für die Bildung geschlossener laminarer Wirbel, lassen sich die biochemischen Folgen (die sich aus ihrer Funktion als »Strömungsreaktoren« für enzymati-sche und zytologische Reaktionen erklären) leicht vorhersagen. Somit läßt sich eine einheitliche Theorie für alle »natürlichen« hämostatischen Reaktionen ebenso wie für die »pathologischen« Formen der Thrombose in vivo und in künstlichen Organen entwik-keln. Sie greift die Grundgedanken auf, die Virchow (94) bei der Postulierung der Kooperativität zwischen »Wandschäden«, »Hyperkoagulabilität« und »gestörter Strömung« bei thrombotischen Vorgängen formuliert hat, erweitert sie jedoch im Lichte zeitgenössischer enzymologischer, zy-tologischer und fluiddynamischer Einsichten zu einer Theorie über streng lokalisierbare hämostaseologische Wechselwirkungen. Diese Vorgänge sind biologisch auf kurzfristige, unspezifische »Reparaturaufgaben« für Gefäßdefekte programmiert, können jedoch bei langfristiger, repetitiver Aktivität zu (atherogenen) Gefäßläsionen Anlaß geben.
Endoscope Image Capture System with Mirrorless Camera
Authors: Wei Li , Burke John , Benet Arnau , Aghi Manish , Gurrola Jose , El-Sayed Ivan
Published: July 2018

Modern endoscopic surgery relies on capturing high fidelity images for a multitude of purposes. One method of capturing images involves incorporating infrared and 4 k resolution video in the image capture system. However, the price of such whole image capture systems remains expensive and potentially cost prohibitive for some practitioners. A major need exists for less expensive alternatives. Herein, we introduce a method of using a mirrorless camera for the purposes of an endoscope capture device. This system comprises components that are all readily commercially available. Sample pictures taken by this system are provided and the potential function of mirrorless camera is explored. This image capture system provides reasonable quality images, should be more reasonably affordable and easily implementable in variety of practices, and will help decrease the barriers to producing research in the area of endoscopic surgery.
Otologic Findings Based on no Complaints in a Pediatric Examination
Authors: Demir Emine , Topal Sevgi , Atsal Gorkem , Erdil Mehmet , Coskun Zerrin , Dursun Engin
Published: July 2018

Introduction the otological evaluation is highly significant in those branches of medicine in which the general evaluation of the patient is conducted by general practitioners and pediatricians.

Objectives To investigate the otologic findings and their incidences in the sample, which consisted of patients who presented to the pediatric outpatient clinic with non-otologic complaints.

Methods Patients, aged between 2 and 16 years, who had neither otorhinolaryngological complaints nor history of surgery by the otolaryngology (ear, nose and throat, ENT) department were included in the present study. The findings detected in the external auditory system and in the tympanic membranes as well as the otorhinolaryngologists' otologic examination findings of the referred patients were recorded from the files of each patient along with the applied medical and surgical treatments, and diagnostic investigations.

Results Of a total of 973 patients evaluated, 129 (13.2%) were referred to the ENT outpatient clinic due to any otologic pathology. In the otorhinolaryngological examinations, false positivity was detected in 12 (1.2%) patients, and pathological findings were detected in 117 (12%) patients who received the following diagnoses: 68 (6.9%) had otitis media with effusion(OME); 37 (3.8%) had cerumen impactions; 8 (0.8%) had acute otitis media (AOM); 2 (0.2%) had ticks in the external auditory canal; 2 (0.2%) had a retraction pocket in tympanic membrane; 1 (0.1%) had unilateral central dry perforation of the tympanic membrane; and 1(0.1%) had congenital cholesteatoma.

Conclusion Any complications and sequelae that may develop due to any pathologies and predominantly infections can be prevented by an early diagnosis, which can be made by means of a simple examination, performed merely with an otoscope. Pediatricians and general practitioners should be in close contact with otorhinolaryngologists regarding the pathologies they identify.
Pyruvate Carboxylase Deficiency Type C: A Rare Cause of Acute Transient Flaccid Paralysis with Ketoacidosis
Authors: Sinclair Graham , Stockler-Ipsiroglu Sylvia , Horvath Gabriella , Almomen Momen
Published: July 2018

Pyruvate carboxylase (PC) is a biotin-containing enzyme that is responsible for the adenosine triphosphate-dependent carboxylation of pyruvate to oxaloacetate, a key intermediate in the tricarboxylic acid cycle. PC deficiency (OMIM 266150) is a rare autosomal recessive metabolic disease, causing elevation of pyruvate, lactate, and alanine. Three types of PC deficiency have been described in the literature; A, B, and C. Type A PC deficiency, also called infantile or North American type, is characterized by infantile onset acidosis, failure to thrive, and developmental delay. The second subtype or type B, the neonatal or French form, presents usually in the neonatal period, mostly in the first 72 hours of life with severe lactic acidosis, truncal hypotonia, and seizures. The third type is called type C, is extremely rare with few cases published in the literature. In this case report, we present an 11-month-old girl who presented with acute flaccid paralysis, lethargy, and constipation with elevated ketones and lactate. She was confirmed genetically and biochemically to have PC deficiency type C. The patient's unusual presentation expands the clinical phenotype of this extremely rare disease.
Protein synthesis observed in vivo using injected deuterated amino acids and Raman scattering
Authors: Michaud Sarah
Published: July 2018

Combining intra-arterial delivery of deuterated amino acids with stimulated Raman scattering microscopy to observe in vivo protein metabolism in mouse models.
‘Secularism’ as understood and interpreted by Hindu
nationalists
Authors: Iwanek Krzysztof
Published: July 2018

This article focuses on how Hindu nationalists interpret the term ‘secularism’ in
Hindi. I will refer to two Hindi translations of ‘secularism’:
dharmnirpekṣtā and panthnirpekṣtā. The
first one means indifference towards religion and the second indifference
towards communities. My main point is that the Hindu nationalists’ strategy of
referring to old, Sanskrit meanings of dharm (which means ‘law’
and ‘order’ aside ‘religion’ and other concepts) make it possible for them to criticise dharmnirpekṣtā and choose
panthnirpekṣtā instead. Their position is that the state
can only be indifferent to communities and not to dharm, as the
latter would also mean being indifferent to ‘law’ and ‘order’. Such an approach
helps the Hindu nationalists to claim to be in agreement with the idea of
secular Indian state on one hand and promote their religion-linked ideology on
the other.
IgA—about the unexpected
Authors: Macpherson Andrew J. , Ganal-Vonarburg Stephanie C.
Published: July 2018

In this issue of JEM, Nakajima et al. (https://doi.org/10.1084/jem.20180427) demonstrate that glycan-dependent, epitope-independent IgA coating of intestinal bacteria alters bacterial gene expression and metabolism. This conferred coated bacteria with fitness within the mucus niche and contributed to intestinal homeostasis through cross-phylum interactions.
Influence of Genetics and Gender in Takotsubo Syndrome: Unexplored Areas of an Incompletely Understood Disease
Authors: Longobardo Luca , Zito Concetta , Carerj Scipione , Caracciolo Giuseppe , Khandheria Bijoy K.
Published: July 2018

Stress cardiomyopathy, also known as “Takotsubo syndrome” (TS), is a complex disease that typically affects postmenopausal women. The pathophysiology is still largely unknown, but evidence of a frequent association between TS and stressful events has evoked the hypothesis of a pathophysiologic role of sympathetic overdrive in the myocardial dysfunction. However, despite several studies, the role gender plays in TS onset remains unclear because stress cardiomyopathy also has been described in young women and in men. Moreover, although several cases of a familial cluster of TS have been reported, no responsible gene mutations or polymorphisms have been clearly identified so far, and neither the modality of transmission or the true impact of genetic background. In this review, we discuss the role of gender in the onset, course, and outcomes of TS and we report the available data about polymorphisms and gene mutations so far investigated, trying to critically analyze the evidence reported in the literature.
Optimal regularization for a class of linear inverse problem
Authors: Valentine Andrew P , Sambridge Malcolm
Published: July 2018

Most linear inverse problems require regularization to ensure that robust and meaningful solutions can be found. Typically, Tikhonov-style regularization is used, whereby a preference is expressed for models that are somehow ‘small’ and/or ‘smooth’. The strength of such preferences is expressed through one or more damping parameters, which control the character of the solution, and which must be set by the user. However, identifying appropriate values is often regarded as a matter of art, guided by various heuristics. As a result, such choices have often been the source of controversy and concern. By treating these as hyperparameters within a hierarchical Bayesian framework, we are able to obtain solutions that encompass the range of permissible regularization parameters. Furthermore, we show that these solutions are often well-approximated by those obtained via standard analysis using certain regularization choices which are—in a certain sense—optimal. We obtain algorithms for determining these optimal values in various cases of common interest, and show that they generate solutions with a number of attractive properties. A reference implementation of these algorithms, written in Python, accompanies this paper.
Meta-Analysis: The Influence of Preoperative Infliximab Use on Postoperative Complications of Crohn’s Disease
Authors: Xu YanYan , Yang LiSheng , An Ping , Zhou Bing , Liu Gang
Published: July 2018

Background

Infliximab (IFX) is a breakthrough treatment for refractory Crohn’s disease (CD) whose effect on postoperative complications of CD remains controversial. The purpose of this study was to conduct a meta-analysis examining the effect of IFX on postoperative complications of CD.

Methods

We searched “PubMed,” “EMBASE,” and “Cochrane Library” databases from inception of each database until March 2018. All eligible articles were screened according to the inclusion criteria. The cumulative overall, major, minor, infectious, noninfectious, surgical, and medical complications, as well as reoperation, readmission, and mortality of CD patients who received IFX and underwent ileocolonic resection were extracted and analyzed using Review Manager 5.3. The random effects model was used to calculate the odds ratio (OR) and 95% confidence interval (CI).

Results

A total of 18 nonrandomized controlled trial studies, with 1407 patients who received IFX and 4589 patients who did not were identified. The incidence of complications was 9.38%–60.56% in the IFX group and 12.73%–53.85% in the control group. Overall, major, minor, infectious, noninfectious, surgical, and medical complications could be assessed in 16, 12, 11, 14, 12, 12, and 11 studies, respectively. There were no statistically significant differences between the 2 groups for any complication (P > 0.05, all comparisons). Reoperation (P = 0.70), readmission (P = 0.22) and mortality (P = 0.86) showed no significant difference between the 2 groups. Subgroup analysis showed that complications were not significantly different among the countries represented in the studies.

Conclusions

Based on this analysis, there does not appear to be an association between preoperative IFX treatment and postoperative complications of CD; IFX appears relatively safe for preoperative use in the treatment of CD.
Meigs to Modern Times: The Evolution of Debulking Surgery in Advanced Ovarian Cancer
Authors: Schorge John O. , Bregar Amy J. , Durfee John , Berkowitz Ross S.
Published: July 2018

(Abstracted from Gynecol Oncol 2018;149:447–454)

This historical perspective provides context for the development cytoreductive surgery, and its current role in the treatment of advanced ovarian cancer. It discusses the visionary approach of Joe V.
Early Versus 6–12 Week Postpartum Glucose Tolerance Testing for Women With Gestational Diabetes
Authors: Carter E. B. , Martin S. , Temming L. A. , Colditz G. A. , Macones G. A. , Tuuli M. G.
Published: July 2018

(Abstracted from J Perinatol 2018;38:118–121)

Women with pregnancies complicated by gestational diabetes mellitus (GDM) are at a significantly increased risk of developing type 2 diabetes mellitus (T2DM), hypertension, and cardiovascular disease. Diabetes screening for women with GDM is recommended 6 to 12 weeks following delivery, although this is an arbitrary time point developed to coincide with the routine postpartum visit.
Using a Multifaceted Quality Improvement Initiative to Reverse the Rising Trend of Cesarean Births
Authors: Ogunyemi Dotun , McGlynn Sara , Ronk Anne , Knudsen Patricia , Andrews-Johnson Tonyie , Raczkiewicz Angeline , Jovanovski Andrew , Kaur Sangeeta , Dykowski Mark , Redman Mark , Bahado-Singh Ray
Published: July 2018

(Abstracted from J Matern Fetal Neonatal Med 2018;31:567–579)

One in 3 births in the United States is a cesarean delivery, which is associated with both increased morbidity and higher health care costs than vaginal delivery. In the United States, the primary cesarean delivery rate is approximately 17%, whereas the nulliparous term singleton vertex (NTSV) rate is 26%.