bluuebunny/crossref_metadata_2025 huggingface dataset:
MONOCLONAL ANTIBODIES To D-DIMER: DISCREPANT LATEX AGGLUTINATION AND EIA RESULTS IN LIVER DISEASE PATIENTS
Authors: Carr JM , McKinney ML , Neuringer I , McDonagh J
Published: August 2018

Measurement of fibrin (ogen) degradation products (FDP) by latex agglutination with polyclonal antifibrinogen may be falsely elevated in liver disease due to the presence of “poorly clottable” fibrinogen in serum (Blood 67:1468, 1986). TSro monoclonal antibodies recognizing different epitopes of fibrin degradation fragment D-dimer (DD) are now commercially available. Because of the reported lack of crossreactivity of the DD monoclonals with fibrinogen, we employed them as tools to distinguish true fibrinolysis from false positive results due to liver disease. 17 citrated plasmas were evaluated by 5%SDS PAGE, nitrocellulose transfer and polyclonal antifibrinogen blotting for detection of FDP (X,ED,Y,D). Samples were then evaluated for ED by latex agglutination and by EIA (enzyme immunoassay) with the following results:

Patients in Groups 3a and 3b were jaundiced (bilirubins 3.2-27) and had either hepatitis or cirrhosis except for one patient in Group 3a who had metastatic cancer. Assay for soluble fibrin monomer (SFM) by hemagglutination was negative in group 3b but positive in 5 of 7 patients in group 3a. Neither eta recognized fibrinogen. Purified fibrin monomer gave positive results with both EIAs. Detection of fibrinolysis by latex agglutination using monoclonal anti-DD resolves the problem of false positive results seen with polyclonal antifibrinogen in patients with liver disease. Elevated SFM in the absence of disseminated intravascular coagulation (DIC) in patients with liver disease may induce false positive ED results when measured by EIA.
EVALUATION OF PLASMINOGEN IN HYPERCOAGULABLE PATIENTS
Authors: Lottenberg R , Hall J A
Published: August 2018

Sixty seven patients with spontaneous or recurrent thrombosis without obvious underlying disorders were evaluated for plasminogen abnormalities. The mean age was 33.5 years. Fifty seven had venous thrombosis, five had arterial thrombosis and five had both venous and arterial events. Seventeen patients had family members with a history of similar thrombotic events. The plasminogen antigen concentration, by Laurell immunoelectrophoresis, for the patient group was 104± 19% (62-156) compared to 102±11% (83-122) for normal controls (n=24). By amidolytic assay of plasminogen-streptokinase complexes, the activity was proportionate to the antigenic concentration for each individual. Two patients had plasminogen levels (62%, 67%) lower than 2 standard deviations of the mean. Functional alpha2-antiplasmin levels were the same for the patients (102±11%) and the controls (101±16%). Plasminogen activation in undiluted plasma was assessed by a coupled amidolytic assay using urokinase (60 IU/ml) and H-D-val-leu-lys-pNA. The mean substrate hydrolysis rate for the patient group was 1.35±0.52 10−3 absorbance units/min/min (0.56−2.75) compared to 1.32±0.27 10−3 absorbance units/min/min (0.84-−1.99) for the controls (n=34). Three patients with normal plasminogen levels had consistently low activation rates (0.56, 0.57, 0.65). Inhibition of urokinase and plasmin activity was not increased. Histidine-rich glycoprotein levels were not elevated. Electrophoretic, chromatographic and kinetic analysis of the isolated plasminogens revealed no abnormalities. To assess the high affinity lysine binding site, 40 uM epsilon aminocaproic acid was added to plasma while the change in the plasminogen activation rate relative to baseline was observed; no abnormalities were disclosed in either the patient or control populations.

In summary, two patients had significantly reduced levels of normally functioning plasminogen. Dysfunctional plasminogen was not identified in this population. We conclude that plasminogen abnormalities infrequently explain hypercoagulability. These studies also suggest that plasminogen status can be adequately evaluated by determining the antigenic concentration and functional activity of plasminogen-streptokinase complexes.
A SPECTROPHOTOMETRIC METHOD FOR FIBRIN CLOT LYSIS ASSAY
Authors: Electricwala A
Published: August 2018

Clot lysis assay is one of the many methods being used to quantitate tissue plasminogen activator in biological fluids and other media. It has been suggested that this assay may be less reproducible and subject to error due to variation between laboratories in determining the end point of clot lysis, especially at lower concentrations of the activator. It has been found that this assay method can be semi-automated by monitoring the absorbance of the fibrin clot, and determining the end point, in a spectrophotometer. Standard clots containing varying concentrations of tPA are prepared in semi-micro cuvettes, held at 37° C and the absorbance monitored continuosly at 600nm. The turbidity of the sample is increased near its lytic time, which results in a sharp absorbance peak. The time elapsed from the start to the appearence of this peak is taken as the lytic time of the clot. Using standard prepration of tPA, a straight line calibration graph of log lytic time versus log concentration is obtained, with a standard deviation for each determination of ± 5%. This method has the advantage of being simple, reproducible and less prone to operator error.
EFFECTS OF EXTRACORPOREAL CIRCULATION AND SHED MEDIASTINAL BLOOD ON FIBRINOLYTIC SYSTEM
Authors: Spannagl M , Dietrich W , Richter J A , Lill H , Schram W
Published: August 2018

There is a remarkable increase in fibrinolytic activity during extracorporeal circulation. This activity is due to the release of tissue-plasminogen activator (t-PA) (Stibbe, Kluft e. a. 1982). A reduction of blood substitution requirements can be achieved^by retransfusion of shed mediastinal blood after open heart surgery. However thereby is an additional effect on fibrinolysis. We measured following parameters of the fibrinolytic system in 20 cardiac surgical patients before operation (A), after ECC (B) before retransfusion (C), in the drainage (D) and 20 minutes after retransfusion (E):

The distance between end of ECC and retransfusion was 4 to 5 hours. The t-PA activity measurements after ECC (B) were disturbed by high heparin levels. In the shed blood (D) a highly significant increase of t-PA and D-dimer was noted, whereas no inhibitor activity was measurable at this instance, indicating consumption of the inhibitor. The high inhibitor levels found before and after retransfusion are due to the longer half-live. The D-dimer concentration increases significantly after compared to before retransfusion. However following retransfusion no significant variation in plasminogen and antiplasmin and no increased bleeding tendency could be observed.
CHANGES IN FIBRINOLYTIC PARAMETERS AFTER DELIVERY
Authors: Kirch-heimer J C , Kölbl H , Christ G , Tatra G
Published: August 2018

Recent studies by Astedt et al. have shown increasing levels of plasminogen activator inhibitor during pregnancy, but the origin of the inhibitor is unknown. Levels of fibrinolytic parameters were determined in plasma collected from 18 females (age 22.7 ± 3.2, mean ± SD) after a normal medically controlled pregnancy at the time of delivery and on the following 5 days. Tissue-type plasminogen activator (tPA) antigen was measured by enzyme immunoassay, urokinase type plasminogen activator (uPA) antigen by a radioimmunoassay and plasminogen activator inhibitor (PAI ) by a functional assay. The results are summarized in the following table:

Postpartal changes in tPA antigen and PAI have been found to be significant, both decreasing after delivery and reaching normal control values for tPA on day 2 and for PAI on day 1 while uPA antigen remained normal. Since tPA levels before delivery have been found to be normal, increased levels at delivery might be caused by a release or by hormonal changes, while the decrease in PAI might again be caused by hormonal changes or by removal of the placenta.
ACQUIRED HAEMOPHILIA DUE TO FACTOR VIII INHIBITOR WITH SEVERE HAEMORRHAGES IN A 46-YEAR-OLD WOMAN SUCCESSFULLY TREATED WITH CYCLOSPORIN A
Authors: Boda Z , Hársfalvi J , Pecze K , Rak K
Published: August 2018

A formerly healthy 46-year-old woman suffering from acquired haemophilia caused by factor VIII antibodies was admitted in an unconscious state following subarachnoid haemorrhage. Treatment with prothrombin complex concentrates (taken as a whole 100 000 U of PCC, home made and 10 OOOUofFEIBA, Immuno) , steroid (Prednison 50 mg/day) and cyclophosphamide (100 mg/day) was only partially successful: neurological state improved but the haemorrhagic tendency remained. Significant haematuria, and skin and mucosal bleeding characterized her clinical picture. In the meantime, signs of non-A non-B hepatitis were observed. After recovery treatment with Cyclosporin A (Sandimmun, Sandoz) was started (250 mg/day per os) together with small dose of Prednison (15 mg/day). No PCC was applied since that time and the partial thromboplastin times (PTT) became gradually shorter. Level of factor VIII inhibitor was 160 Bethesda unit prior and 9 unit after treatment, the duration of that was 60 days till now. Factor VIII coagulant activity (VIIIC) increased from value of less than 1 percent to 13.7 percent.

Treatment of acquired haemophilia caused by factor VIII antibodies, particularly in cases with central nervous system bleeding, may be very difficult. History of our patient may indicate that patients resistent to substitution therapy, steroid and cytostatics may response well to Cyclosporin A. Therefore, its use is recommended.
PREPARATION AND CHARACTERISTIC OF A F-IX CONCENTRATE TREATED WITH TRI-(N-BUTYL) PHOSPHATE (TNBP) AND TWEEN-80
Authors: Aperador R , Navarro R , Navio G , Acosta J
Published: August 2018

This paper describes a method of preparation of F-IX concentrate, which uses 0,3% TNBP and 1% Tween-80,6 h, treatment to reduce the risk of transmitting viruses. The treated material was batch wise adsorbed on DEAE-Sephadex, washed and the F-IX concentrate was eluted with buffer on higher ionic strenght

We have tested the effect of TNBP/Tween 80 treatment on the activity of coagulation factors as well as on trombogenicity, molecular filtration, and immunological assays
COMPARISON OF THE ANTITHROMBOTIC, ANTICLOTTING AND ANTIPLATELET AGGREGATORY ACTIVITIES OFLOW MOLECULAR WEIGHT RD HEPARIN WITH HEPARIN
Authors: Fenichel R L , Carmint W , Small B , Willis J
Published: August 2018

An initial comparison of in vitro plasma anti-factor Xa (anti Xa) and activated partial thromboplastin time (APTT) values of RD heparin with heparin based upon USP units shows increased anti Xa and decreased APTT activity of RD heparin. An ex vivo experiment in rabbits in which 100 USP units/kg of RD heparinand 200 USP units/kg of heparin, when given by the subcutaneous route, reflects the significantly increased anti Xa activity generated by RD heparin as wellas its longer duration of action. No significant difference in APTT activity was observed for the two heparins, but an increased anti Xa/APTT ratio (greaterthan two) was observed for the RD heparin. Heparin (10 yg/ml), but not RD heparin, potentiated adenosinediphosphate (ADP) induced platelet aggregation in human platelet rich plasma. Subcutaneous administration of RD heparin or heparin to rabbits over the dosage range of 0.75 to 1.75 mg/kg gives similar mean dose response lines for these heparins in the thrombosis-stasis model as measured by the extent of jugular vein clotting. Administration of these heparins to rabbits on a USP unitage basis shows a significantly greater antithrombotic effect for RD heparin at 120 and 160 USP units/kg. Moreover, this experiment indicates that if the optimum dosage of 120 USP units/kgfor RD heparin is exceeded then we begin to see an indication of loss of antithrombotic activity.
CONGENITAL AFIBRINOGENAEMIA: DIAGNOSIS, CLINICAL FEATURES, FOLLOW-UP STUDY
Authors: JakloyazAy A M , dnagy Oa H
Published: August 2018

Authors followed 6 cases of congenital afibrinogenae- mia (CA) by offsprings of two apparently unrelated families from the same village. The sex ratio was4.m/3.f. CA is a rare autosomal recessive disease. Controlling 76 family members authors detected 11 cases of moderate and 2 cases of severe hypofibrinogeneemia.Among them-without any bleeding tendency-the mother of one case and both parents of two siblings with CA*The lack of fibrinogen was confirmed biochemically and immunologically too. The only symptom ofthe Illness are the severe posttraumatic bleeding. They appear as epistax- is, bleeding of the gums, or anyother bleeding aiter minor or severe injuries*Intraarticular bleeding, as in haemophilia rarely occurs inCA. One of our patients had profuse haematurias, causedby renal calculi. The only therapy is the substitution with transfusions of fresh blood, plasma, or fibrinogen concentrates*The rise of posttransfusional lllnisses grows with the number of transfusions*Stomatological or surgical interventions could be performed only after correction of the dotting abnormalitySo, one of our patients was submitted to splenectomyfor spontaneous rupture at 12 years and to nephrectomy for severe pyelo-caliceal cal- culosis with 19.He recovered fully after both interventions but died at 21 years after a bicycle accidenti The five other patients deceased at the age of 5«resp. 10 months and at 6-lo-resp 12 years. In 3 cases there was a subdural hammorrhage, once an intracranial blee- dingCnon autopsiated)and once a severe intraabdoml- nal haemorrhage after an accidental traumatism of the abdominal wall. The care of the CA cases is mostly a pediatric proble. The frequency of the pottraumatic bleeding decrease with the growth*The schoolchildren are paying more attention to avoid injuries
CIRCULATING ANTICOAGULANT IN AIDS
Authors: Lefrere J J , Vittecoq D , Gozin D , Modai J
Published: August 2018

The frequency of a circulating anticoagulant has been reported to be high in AIDS, in particular in case of Pneumocystic carinii pneumonia (Pep). Twenty-five non-hemophiliac patients (23 homosexual males,1 drug addict, 1 tranfused) with AIDS were followed over a six month period. Mean age was 32 (21-42). All patients had a markedly decreased T4/T8 ratio (mean 0.12), a low absolute T4 level (mean : 155/mm3), an elevated total serum immunoglobulins level.Activated partial thromboplastin time (APTT), prothrombintime and thrombin time were measured once a week during hospitalisation. A prolonged APTT (more than 10 seconds as compared to controls) with normal prothrombin time and thrombin time was found only once in 11patients and in two or more occasions in two others.No specific factor level of intrinsic pathway wasfound low enough to explain a prolonged APTT.Evidenceofcirculating anticoagulant (failure to correct aprolonged APTT by equal mixure of normal plasma and patient plasma) was found in all these 13 patients.Nothrombotic or haemorraghic manifestations occured.AIDS manifestations were 2 Pep.1 cytomegalovirus retinitis. 2 Kaposi's sarcomas, 1 Hodgkin's disease, 2 mycobacterium avium intracellulare pulmonary infection, 4 central nervous system toxoplasmosis, 1 Cryptococcus meningitis. Amongst the 12 patients with normal APTT,3_Pcp, 2 cytomegalovirus retinitis. 2 Kaposi's sarcomas, 2 central nervous system toxoplasmosis, 1 unexplained fever, and 2 oesophagus candidiasis were diagnosed. A transiently prolonged APTT associated to a circulating inhibitor seems to be common in AIDS. Weobserved this anomaly in 52 % (13/25). In our five cases of Pcp, 3 had normal APTT. During other opportunistic infections, the circulating inhibitor was found.The similar complications seen in two groups suggest that a circulating anticoagulant is not specifically associated to any opportunistic infection and any malignancybut appearr independently from these circumstances.
INFLUENCE OF PLASMINOGEN ACTIVATOR INHIBITOR (PAI) ON THE TISSUE PLASMINOGEN ACTIVATOR (tPA) ASSAY IN EUGLOBULIN FRACTIONS AND IN PLASMA
Authors: Contant G , Martinoli J L , Thirion C
Published: August 2018

Current liquid-phase methods for thedetermination of tPA in plasma involve inactivation of both tPA and plasmin inhibitors by either plasma acidificationor euglobulin fractionation. In a firststep, our liquid-phase assay was performed in euglobulin fractions (EF) and the inactivation of PAI was monitored.In a second step, we studied the influenceof PAI onthe tPA assay in plasma.

When EF were used (1:10 dilution, pH 5.9), the reference curve was done with tPA (0 to 1 IU/ml) diluted in buffer.The diluted samples (tPA or EF) were incubated with fibrinogen fragments as Stimulator (0.5 mg/ml), an excess of plasminogen (0.15 pM/ml) and chromogenic substrate CBS 30.41 (3.75 pM/ml).The tPA level of EF obtained after venous stasis was found tobe2.7 IU/ml, whatever the dilution was (1:4 to 1:64). For EF obtained at rest, a paradoxical increase in tPA activity was found from 1:4 to 1:16 until a plateau was reached (usually ar dilution 1:16 to 1:32).This is due to the partial dissociation of tPA/PAI complexes which increases with the dilution as demonstrated by adding tPA to highly diluted (1:64) EF : noinhibition occurred. To avoid the influence of PAI and to measure the total tPA activity, a sufficient dilution was needed.

When the tPA assay was performed in plasma, ∝ 2 antiplasmin (∝ 2AP) was shown to be mainly responsiblefor a gradual loss of tPA and for inhibition of plasmin generation (using anti ∝2AP IgG). To maintain the concentration of ∝2AP constant in samples, they were 1:10 diluted in a tPA/PAI depleted plasma (plasmin inhibitors were brought in excess by the depleted plasma). The reference curve was done with tPA (0 to2 IU/ml) diluted in the depleted plasma instead of buffer. TPA activities were shown in plasma obtained after venous stasis, when low PAI values (0 to 2.5 IU/ml) were associated. No tPA activity was found in plasma obtained at rest, associated with normal PAI values. It can be concluded that a tPA activity is displayed only when PAI is saturated by released tPA.A free tPA activity can be detected in plasma, while in the EF, the tPA measured is dissociated from tPA/PAI complexes.
EFFECTS OF PENTOSAN POLYSULPHATE (EXMLRON) ON FIBRINOLYSIS
Authors: Haglund O , Wibell L , Saldeen T
Published: August 2018

Decreased fibrinolytic capacity is thought to be an important ccnponent in the pathqgenesis of different thrombotic states. There is a need for agents improving the fibrinolytic capacity, especially perorally (p.o.) active drugs. Since long the semi-synthetic heparinoid Pentosan Polysulphate (PPS) has been shown to have a stimulating effect on fibrinlysis when given parenterally. Alsop.o. administered drug has been claimedto improve fibrinolysis. However, the degree of gastrointestinal resorption has not been thoroughly assessed and the mechanism behind the effect of PPS cn fibrinolysis is not known.

8 healthy male volcnteers and 14 patients with a history of venous thrombosis were studied. Before and after administration of PPS blood samples were taken and plasminogen activator activity (tPA-act), antigen (tPA-ag) and plasminogen activator inhibitor (PAI) were determined. The volonteers were given 50 ng PPS i.v. and blood was sanpled before and after 30 minutes. In a second experiment they received 400 rrg PPS p.o. follwed by blood sarrpling after 2 hours. They also received 400 ng of PPS daily p.o. for 25 days. The patient group were given 500 ng PPS p.o. 8 a.m. and blood was collected 6 hours later. To exclude influence of diumal variation blood was also taken 2 p.m. the day before. The plasma level of PPS after p.o. administration was determined by a sensitive modified radioassay for heparin.

30 minutes after i.v. injection of PPS PAI was essentially unchanged, tPA-ac-tivity was slightly increased but tPA-ag showed a strongly significant decrease. 400 ng PPS p.o. resulted in an increase in tPA-ag after 2 hours. 400 ng PPS durirg 25 days resulted in a significant decrease of PAI with no charges in tPA-act and tPA-ag. 500 ng FEB given as a single dose in the morning did not cause greater charges of PAI than expected from the diumal variation. The uptake of PPS following p.o. administration is lav with a bioavailability of only 0,5 − 1 %.

The low bioavailability of p.o. adninistrered PPS suggest that some of the ad-vantagous effects of PPS on fibrinolysis migjnt be caused through local effects in the intestine. The strong decrease of tPA-ag without significant changes in the other parameters may reflect an accelerated elimination of tPA-PAI-ccnplex. The mechanism of the inproved fibrinlysis following adninistration of PPS is still unsettled but our resluts may indicate that PPS initially facilitates the elimination of the tPA-PAI complex with a secondary increase of the tPA-ag. The tPA-ag may bind to PAI with a secondary decrease of the active component of this inhibitor. However, a more direct effect of PPS cn PAI cannot be excluded.
PARTICULATE CONTAMINATION OF DRUGS: THEIR EFFECT ON PLATELET KINETICS AND THE PULMONARY CIRCULATION
Authors: Backhouse C M , Galvin D AJ , Harper R A , Meek A C , McCollum C N
Published: August 2018

More than 107 particulate contaminants >2um and many more <2um are infused daily in parenteral medications to intensive care patients. They may form emboli with aggregated platelets and damage pulmonary vasculature [1], perhaps contributing to alveolar fibrosis in very premature babies. We studied this possibility in neonatal pigs.

Nineteen newborn pigs were randomised to either daily 0.2um filtered salineas controls, or infusions of particles similar to drug contaminants at 10x greater than the patient equivalent dose/kg given via subcutaneous injection portals with tunnelled central venous catheters. Four weeks later, autologous platelets were labelled with llllndium and arterial and Swann Ganz catheters inserted under general anaesthesia. Before particle or filtered saline infusion and at 5 and 20 minutes later platelet count, lung platelet uptake, mean arterial pressure (BP), pulmonary vascular resistance, pulmonary shunt and alveolar-arterial P02 difference were measured.

Initially, there were no significant differences between the groups indicating no measureable effect from chronic particle dosing over 4 weeks. Within 30 sec of bolus particle injection BP fell from a mean ( ± sem) of 68.9+2.1mmHg to 61.0±2.1 (p<0.01, paired t-test) but returned to normal within 5 minutes. This was not seen with controls or particle injections given over 5 minutes. Platelet counts fell in the particle group from 660±43 (x109/L) to 584±46 at 20 minutes (p<0.01) but lung platelet accumulation was insignificant.

Transient fall in blood pressure due to contaminating particles can be avoided by slow injection or 0.2um in-line filters. Particles stimulate a loss of circulating platelets but with insignificant pulmonary accumulation and no impairment of pulmonary function after 4 weeks of daily particle injection at considerably higher doses than patients receive.

1. Chia C, Cattell V. The role of platelets in mesangial localisation: carbon uptake in thrombocytopaenic rats. BrJ Exp Path 1985; 66: 465-474.
DIFFERENT INTEGRITIES OF GP Ilb/Ilia COMPLEX ARE REQUIRED FOR ADP- OR THROMBIN-INDUCED AGGREGATIONS
Authors: Tanoue K , Yamazaki H
Published: August 2018

A relation between the integrity of platelet GP IIb/IIIa complex and aggregability by ADP or thrombin was studied on intact platelets with EDTA-induced irreversibly dissociated GP IIb/IIIa complex. Human platelets were washed once and suspended in Ca-, Mg-free HEPES-Tyrode's solution (pH 7d). Aliquots of the suspensions were incubated with 2mM EDTA at 37°C for 2 to 60 min. Control platelets were incubated at 22°C. Then, kwM CaCl2 were added to the samples, which were incubated for another 30 min at 37°C. The platelets were washed twice with HEPES-Tyrode1s solution (pH 6.7). For the measurement of amounts of GP IIb/IIIa complex, the platelets were solubilized with 1% Triton X-100 to 1+ X 10 /yl, five yl of which were subjected to crossed immunoelectrophoresis using constant volumes of anti-platelet antibody. The areas under the immunbprecipitates of GP IIb/IIIa complexes were measured as the amounts of GP Ilb/IIIa complex. For the aggregation studies, the platelets were suspended in HEPES- Tyrode's solution (pH 7d). ADP-aggregations were measured in the presence of added 1mg/ml fibrinogen and 2mM Ca. Platelets incubated with EDTA or CaCl2 at 22°C showed the same amounts of GP IIb/IIIa complex.

ADP-aggregability declined more rapidly than the decrease GP Ilb/IIIa complex. In contrast, thrombin-aggregation were much better maintained than ADP-Aggregation during the incubation with 2mM EDTA. These results suggest either that the integrity of GP Ilb/IIIa complex required for ADP-aggregation is more strict than for thrombin-aggregation, or that thrombin-aggreagtion can be
caused by an alternative mechanism which does not require the integrity of GP Ilb/IIIa complex.
ANTITHROMBIN-III SUPPLEMENTATION ATTENUATES DISSEMINATED INTRAVASCULAR COAGULATION IN THEE.COLI ENDOTOXEMIC DOG MODEL
Authors: Hauptman J G , Hassouna H I , Penner J A , Bell T G , Emerson T E
Published: August 2018

We reported previously that disseminated intravascular coagulation (DIC) occurs early during E. coli endotoxemia in the rat, before the development of serious cardiovascular, metabolic or biochemical abnormalities, and that pretreatment with large doses of purified human antithrombin-III (AT-III; 250 U/kg) markedly attenuates DIC and increases survival (PC0.05). The present study was an extension ofan earlier one in which pretreatment of dogs with a low dose ofhuman AT-III (50 U/kg) provided borderline protection against DIC during endotoxemia. In the present study, mongrel dogs were anesthetized with sodium pentobarbital, continuously monitored over a 21 hour protocol and given full fluid support. Twenty-three dogs were given iv infusions of E. coli endotoxin (0.5mg/kg) at times zero and 15 hours. Of these, seven received iv infusions of purified human AT-III (250 U/kg) 30 minutes prior to endotoxin; 16 received no AT-III and served as controls. Comparing the AT-III treated with the control group, there was significantimprovement in the activated partial thromboplastin time and prothrombin time (P<0.05). Also, fibrinogenand fibrin degradation products were improved significantly in the AT-III treated group (P<0.05). Platelet counts decreased in both groups and there was no between group difference (P>0.05). There was no s i gni fi cant between group differences in other parameters (e.g. hemodynamic, acid-base, metabolic). These data are in agreement with earlier studies in the endotoxemic rat which show that ore occurs early in endotoxemia, that DIC occurs before the development of serious abnormalities in other systems and that AT-III supplementation significantly attenuates OIC. This study supports the hypothes1s that AT-III supplementation is efficacious in conditions of impending OIC such as gram-negative endotoxemia/septicemia.
SYNERGISTIC EFFICACY OF COMBINING ANTITHROMBIN-III AND ALPHA 1-PROTEINASE INHIBITOR PROPHYLAXIS IN THE ENDOTOXEMIC SHEEP PULMONARY DYSFUNCTION MODEL
Authors: Emerson T E , Redens T B
Published: August 2018

The adult respiratory distress syndrome (ARDS) isa serious, often fatal condition associated with septicemia/endotoxemia and Other inflammatory disease states. It is characterized by increased microvascular permeability to protein and pulmonary edema, amongother pathologies. Neutrophil elastase, thrombin andfibrin induced pulmonary microemboli are possible mediators of this pathology. The present study was to determine the effect of pretreatment with large doses of anti thrombin-111 (AT-III), a major inhibitor of coagulation and alpha 1-proteinase inhibitor (al-PI), a major inhibitor of neutrophil elastase, alone and in combination, on selected indices of ARDS in the sheep lung lymph fistula model. Range sheep weighing 35-45 kg were maintained under Halothane anesthesia and surgically prepared the day of the experiment. The sheep were randomized and given iv infusions of 250 U/kg purified human AT-III alone (n=7), 100 mg/kg purified human al-PI alone (n=6), AT-III/al-PI combined (n=5), or an equal volume of normal saline (n=6). Measurements were taken before and hourly after iv challenge with 2 ug/kg E. coli endotoxin. Lunglymph flow increased between 220% - 2802Tof control in the AT-III only, al-PI only, and saline control groups (P<0.05), but did not increase in the AT-III/al-PI combined group (P>0.05). The lymph to plasma protein concentration ratio increased significantly in all groups (P<0.05). Transvascular protein flow and clearance increased, but the increases were significantly greater in the AT-III alone, al-PI alone andsaline control groups compared to the AT-III/al-PI combined group. Pulmonary artery pressure increased initially in all groups (PC0.05) but returned to a level near baseline by 2 hours. Pulmonary artery wedgepressure did not change significantly in any group (P>0.05). This study shows that combined AT-III and al-PI prophylaxis prevented or significantly attenuated indices of ARDS, while neither AT-III alone nor al-PI alone did during 5 hours of endotoxemia. The data suggest that AT-III/al-PI combined protects against ARDS in this model and that the protective effectis synergistic.
ENDOTHELIAL BASEMENT MEMBRANE PROTEOGLYCAN (PG) ALTERATIONS IN DEOXYCORTICOSTERONE (DOCA)-NaCl -INDUCED HYPERTENSIVE RAT MESENTERIC ARTERIES
Authors: Richardson M , Lee R M K W
Published: August 2018

Hypertension is associated with increased endothelial permeability. This has been previously associated with endothelial desquamation or alterations in junctional architecture.To determine if this increase in endothelial permeability was associated with changes in the basement membrane, especially the heperan sulphate (HS) PG, ruthenium red-stained sections of the superior mesenteric arteries of DOCA-NaCl treated rats were examined by transmission electron microscopy. After 3 weeks of treatment, some rats were hypertensive (DOCA-H), but some remained normotensive(DOCA-N). The intimal PG distribution was compared between DOCA-H, DOCA-N, and untreated normotensive controls. Compared to untreated controls, in DOCA-H arteries there was a reduction in basement membrane, including HS, and a small increase in other PGs. In DOCA-N arteries there was a much smaller change in PGdisribution. In the DOCA-H rats, there was evidence of increased endothelial permeability as shown by sub-endothelial oedema, and an increase in the wet/dryweight ratio of the kidneys.

It is therefore possible that hypertension induces changes in endothelial cell metabolism which affect the production or maintenance of the basement membrane. Since the changes were not observed in the DOCA-Narteries they are not a result of the treatment. HS is generally accepted to be involved in the control of endothelial permeability, thus the observed loss of HS from hypertensive arteries may result in the increased endothelial permeability.

Supported by The Heart and Stroke Foundation of Ontario.
Pulmonary embolism four days after interruption of therapy with rivaroxaban
Authors: Göndör Gabor , Stöllberger Claudia
Published: August 2018

Thrombosis after cessation of anticoagulation, also named rebound thrombosis, is a matter of concern and controversy. There are only few published data about occurrence of rebound thrombosis associated with non-vitamin K-antagonist oral anticoagulant drugs (NOACs). We report on a 58-year-old male with paroxysmal atrial fibrillation (AF) with a CHA2DS2VASC score of 4 who developed central pulmonary embolism four days after interruption of rivaroxaban because of parotid surgery. He had received 40 mg enoxaparin/d. The parotid gland was partially resected within 6 hours without blood loss. Pulmonary embolism and AF occurred on the first postoperative day. He recovered with low-molecular-weight heparin in therapeutic dosages and amiodarone and was discharged with phenprocoumon.

The relevance of a rivaroxaban rebound phenomenon, manifesting as arterial embolism, stroke or venous thromboembolism should be clarified. It should be assessed if rebound-phenomena also exist for the NOACs dabigatran, apixaban and edoxaban. Thus, the randomized trials and registries investigating patients with AF or venous thromboembolism should be re-analysed and, based on these data, recommendations should be developed for situations in which NOAC-therapy has to be interrupted or ceased.
Endoscopic ultrasound-guided entero-enterostomy for the treatment of afferent loop syndrome: a multicenter experience
Authors: Brewer Gutierrez Olaya , Irani Shayan , Ngamruengphong Saowanee , Aridi Hanaa , Kunda Rastislav , Siddiqui Ali , Dollhopf Markus , Nieto Jose , Chen Yen-I , Sahar Nadav , Bukhari Majidah , Sanaei Omid , Canto Marcia , Singh Vikesh , Kozarek Richard , Khashab Mouen
Published: August 2018

Background Afferent loop syndrome (ALS) is traditionally managed surgically and, more recently, endoscopically. The role of endoscopic ultrasound-guided entero-enterostomy (EUS-EE) has not been well described. The aim of this study was to assess the technical and clinical success and safety of EUS-EE.

Methods This was a multicenter, retrospective series at six centers in patients with ALS treated by EUS-EE. Data on patients treated with enteroscopy-assisted luminal stenting (EALS) at a single center were also collected.

Results 18 patients (mean age 64.2 years, 72 % post-pancreaticoduodenectomy, 10 female) underwent EUS-EE. The most common symptoms were vomiting (27.8 %) and jaundice (33.3 %). Clinical success included resolution of symptoms in 88.9 % and improvement to allow hospital discharge in 11.1 %. Technical success was achieved in 100 % of cases, with a mean procedure time of 29.7 minutes. The most common procedure was a gastro-jejunostomy (72.2 %). Three adverse events (16.7 %) occurred (two mild, one moderate). When compared with data on EALS, patients treated with EUS-EE needed fewer re-interventions (16.6 % vs. 76.5 %; P < 0.001).

Conclusion EUS-EE seems to be safe and effective in the treatment of ALS. Indirect comparison with EALS suggested that EUS-EE is associated with a reduced need for re-intervention.
Investigating positive oxide charge in the SiO2/3C-SiC MOS system
Authors: Cherkaoui Karim , Blake Alan , Gomeniuk Yuri Y. , Lin Jun , Sheehan Brendan , White Mary , Hurley Paul K. , Ward Peter J.
Published: August 2018

This paper investigates the origin of the fixed positive oxide charge often experimentally observed in Metal Oxide Semiconductor (MOS) structures of SiO2 formed on cubic silicon carbide (3C-SiC). The electrical properties of MOS structures including either thermally grown SiO2 or deposited SiO2 by Plasma Enhanced Chemical Vapour Deposition (PECVD) on epitaxial 3C-SiC layers grown directly on Si are investigated. MOS structures with a range of oxide thickness values subjected to different thermal treatments were studied. It was found that both thermally grown and deposited SiO2 on 3C-SiC exhibit similar positive charge levels indicating that the charge originates from interface states at the 3C-SiC surface and not from the oxide. The nature of this surface charge in the SiO2/3C-SiC system is also discussed based on the current data and previously published results.
Invited Article: Bragg stacks with tailored disorder create brilliant whiteness
Authors: Meiers D. T. , Heep M.-C. , von Freymann G.
Published: August 2018

The scales of white beetles strongly scatter light within a thin disordered network of chitin filaments. There is no comparable artificial material achieving such a high scattering strength within a thin layer of low refractive index material. Several analyses investigated the scattering but could not explain the underlying concept. Here a model system is described, which has the same optical properties as the white beetles’ scales in the visible wavelength range. With some modification, it also explains the behavior of the structures in the near infrared range. The comparison of the original structure and the model system is done by finite-difference time-domain calculations. The calculations show excellent agreement with the beetles’ scales with respect to the reflectance, the time-of-flight, and the intensity distribution in the far-field.
Coherent single spin controlled in a quadruple quantum dot system
Authors: Patrick Chris
Published: August 2018

Four individual electron spins — the most yet — are manipulated coherently.
Remoteness promotes biological invasions on islands worldwide
Authors: Moser Dietmar , Lenzner Bernd , Weigelt Patrick , Dawson Wayne , Kreft Holger , Pergl Jan , Pyšek Petr , van Kleunen Mark , Winter Marten , Capinha César , Cassey Phillip , Dullinger Stefan , Economo Evan P. , García-Díaz Pablo , Guénard Benoit , Hofhansl Florian , Mang Thomas , Seebens Hanno , Essl Franz
Published: August 2018

Significance

Islands are hotspots of alien species invasions, and their distinct biodiversity is particularly vulnerable to invading species. While isolation has shaped natural colonization of islands for millions of years, globalization in trade and transport has led to a breakdown of biogeographical barriers and subsequent colonization of islands by alien species. Using a large dataset of 257 subtropical and tropical islands, we show that alien richness increases with increasing isolation of islands. This pattern is consistent for plants, ants, mammals, and reptiles, and it cannot simply be explained by island economics and trade alone. Geographical isolation does not protect islands from alien species, and island species richness may reach a new dynamic equilibrium at some point, likely at the expense of many endemic species.
Designing anticipatory policies through the use of ICTs
Authors: Capano Giliberto , Pavan Elena
Published: August 2018

This paper seeks to achieve a better understanding of how and under what conditions current digital communication technologies can become an asset to the design of effective policies. In order to do so, we bridge two strands of reflection that have hitherto developed quite independently – i.e. policy design studies and researches on the use of information and communication technologies (ICTs) to reform the public sector. We start from the assumption that different governmental political and technical capacities shape different spaces for action and thus different types of policy design in which policy-makers can involve citizens via ICTs in three modes: co-design; design fine-tuning; crowdsourced policy design. According to this framework, we analyse three different ‘revelatory case studies’ in which ICTs have been employed by governments while designing policies: Iceland’s recent experiment to redraft collectively its constitution; La Buona Scuola, the latest Italian public education law; and the Finnish Avoin Misteriö, a platform for crowdsourced legislation. By exploring the different modes in which ICTs have been integrated in the formulation of these three policies, we show that it is possible to disentangle different and more or less effective ways of exploiting ICTs’ networking and communicative potential for designing successful public policies.
cpPredictor: a web server for template-based prediction of RNA secondary structure
Authors: Jelínek Jan , Pánek Josef
Published: August 2018

We present the cpPredictor webserver that implements a novel template-based method for prediction of secondary structure of RNA. The method outperforms available prediction methods as it uses RNA structures of related molecules, either predicted or experimentally identified, as structural templates. The server aims at three major tasks: i) prediction of RNA secondary structures that are difficult to predict by available methods, ii) characterization of uncharacterized RNAs as compatible or incompatible with a chosen template structure and iii) an identification of the most relevant structure among different candidate structures of a single RNA ambiguously predicted by available methods. The web server is accompanied with a comprehensive documentation.

Availability and implementation

The web server is freely available at http://cppredictor.elixir-czech.cz/. The source code of the cpPredictor algorithm is freely available from the webserver under the Apache License, Version 2.0.
Prevalence of problem drinking and associated factors in a representative German sample of adolescents and young adults
Authors: Wartberg L , Kriston L , Thomasius R
Published: August 2018

Background

Alcohol use in youth is regarded as an important public health concern and in a recent survey in 35 European countries, every third student reported heavy episodic drinking. While prevalence estimates for problem drinking in adults from representative population samples are available, corresponding numbers for adolescents in Germany are currently lacking.

Methods

A representative sample of 1531 12–25 years old in Germany was investigated with a standardized questionnaire concerning problem drinking (assessed with the AUDIT-C) and psychosocial aspects (anxiety with the GAD-2, depressive symptoms with the PHQ-2 and smoking behavior). Due to missing values, we could calculate prevalence estimates, chi-square tests and logistic regression analyses for 1490 cases.

Results

The 1-year prevalence of problem drinking in 12–25 years old in Germany was 18.2%. Overall, 5.0% of the adolescents (aged 12–17 years) and 27.7% of the young adults (aged 18–25 years) reported problem drinking in the last year. Young adult males more often showed problem drinking than females, while no gender differences in adolescents were observed. Problem drinking was associated with male gender, higher age, smoking behavior and depressive symptoms.

Conclusions

According to the study findings, problem drinking is widespread in 12–25 years old in Germany.
Xanthomonas campestris Promotes Diffusible Signal Factor Biosynthesis and Pathogenicity by Utilizing Glucose and Sucrose from Host Plants
Authors: Zhang Chunyan , Lv Mingfa , Yin Wenfang , Dong Tingyan , Chang Changqing , Miao Yansong , Jia Yantao , Deng Yinyue
Published: August 2018

The plant pathogen Xanthomonas campestris pv. campestris produces diffusible signal factor (DSF) quorum sensing (QS) signals to regulate its biological functions and virulence. Our previous study showed that X. campestris pv. campestris utilizes host plant metabolites to enhance the biosynthesis of DSF family signals. However, it is unclear how X. campestris pv. campestris benefits from the metabolic products of the host plant. In this study, we observed that the host plant metabolites not only boosted the production of the DSF family signals but also modulated the expression levels of DSF-regulated genes in X. campestris pv. campestris. Infection with X. campestris pv. campestris induced changes in the expression of many sugar transporter genes in Arabidopsis thaliana. Exogenous addition of sucrose or glucose, which are the major products of photosynthesis in plants, enhanced DSF signal production and X. campestris pv. campestris pathogenicity in the Arabidopsis model. In addition, several sucrose hydrolase–encoding genes in X. campestris pv. campestris and sucrose invertase–encoding genes in the host plant were notably upregulated during the infection process. These enzymes hydrolyzed sucrose to glucose and fructose, and in trans expression of one of these enzymes, CINV1 of A. thaliana or XC_0805 of X. campestris pv. campestris, enhanced DSF signal biosynthesis in X. campestris pv. campestris in the presence of sucrose. Taken together, our findings demonstrate that X. campestris pv. campestris applies multiple strategies to utilize host plant sugars to enhance QS and pathogenicity.
Genome-wide Mapping for Stripe Rust Resistance Loci in Common Wheat Cultivar Qinnong 142
Authors: Zeng Qingdong , Wu Jianhui , Liu Shengjie , Chen Xianming , Yuan Fengping , Su Pingping , Wang Qilin , Huang Shuo , Mu Jingmei , Han Dejun , Kang Zhensheng , Chen X. M.
Published: August 2018

Stripe rust caused by Puccinia striiformis f. sp. tritici threatens worldwide wheat production. Growing resistant cultivars is the best way to control this disease. Chinese wheat cultivar Qinnong 142 (QN142) has a high level of adult-plant resistance to stripe rust. To identify quantitative trait loci (QTLs) related to stripe rust resistance, we developed a recombinant inbred line (RIL) population from a cross between QN142 and susceptible cultivar Avocet S. The parents and 165 F6 RILs were evaluated in terms of their stripe rust infection type and disease severity in replicated field tests with six site-year environments. The parents and RILs were genotyped with single-nucleotide polymorphism (SNP) markers. Four stable QTLs were identified in QN142 and mapped to chromosome arms 1BL, 2AL, 2BL, and 6BS. The 1BL QTL was probably the known resistance gene Yr29, the 2BL QTL was in a resistance gene-rich region, and the 2AL and 6BS QTLs might be new. Kompetitive allele specific polymerase chain reaction markers developed from the SNP markers flanking these QTLs were highly polymorphic in a panel of 150 wheat cultivars and breeding lines. These markers could be used in marker-assisted selection for incorporating the stripe rust resistance QTL into new wheat cultivars.
Do Overweight Adolescent Idiopathic Scoliosis (AIS) Patients Have an Increased Perioperative Risk for Posterior Spinal Fusion (PSF) Surgery?
Authors: Chan Chris Yin Wei , Mohamad Siti Mariam , Tan Shun Herng , Loh Ling Hui , Lim Jun Ni , Chiu Chee Kidd , Hasan Mohd Shahnaz , Kwan Mun Keong
Published: August 2018

Study Design.

A retrospective study.

Objective.

The aim of this study was to compare the perioperative outcome of posterior spinal fusion (PSF) between overweight (OW) adolescent idiopathic scoliosis (AIS) patients and the healthy-weight (HW) patients using propensity score matching analysis.

Summary of Background Data.

Obesity was found to increase postoperative surgical complications compared with the nonobese group. In scoliosis correction surgery, association of OW and perioperative risks had been explored, but most studies were retrospective in nature.

Methods.

From 374 patients, two comparable groups were matched using propensity score matching analysis with one-to-one nearest neighbor matching and a caliper of 0.2. There were 46 HW and OW patients in each group. The main outcome measures were intraoperative blood loss, use of allogeneic blood transfusion, operative time, duration of hospital stay post-surgery, total patient-controlled analgesia (PCA) morphine usage, perioperative complications, side bending flexibility (SBF), and correction rate (%).

Results.

The mean age was 13.3 ± 1.7 and 13.2 ± 1.7 years for HW and OW groups, respectively. The majority of the patients were Lenke 1 curves; 32.6% (HW) and 26.1% (OW) with an average Cobb angle of 69.0 ± 19.1° and 68.8 ± 18.4° for each group, respectively. The two groups were comparable. The operation time was 145.2 ± 42.2 and 154.4 ± 48.3 minutes for HW and OW groups, respectively (P > 0.05). The intraoperative blood loss was almost similar in both groups; 955.1 ± 497.7 mL (HW group) and 1011.8 ± 552.7 mL (OW group) (P > 0.05). Total PCA morphine used was higher in OW group (30.4 ± 22.7 mg) than in the HW group (16.2 ± 11.3 mg). No complication was observed in HW group, while in OW group, one patient (2.2%) developed intraoperative seizure.

Conclusion.

OW AIS patients (≥85th percentile) had similar mean operative time, intraoperative blood loss, allogeneic transfusion rate, length of stay, and perioperative complications compared with HW AIS patients.

Level of Evidence: 3