bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endocuff-assisted colonoscopy for surveillance of serrated polyposis syndrome: a multicenter randomized controlled trial
Authors: Rivero-Sánchez Liseth , López Vicente Jorge , Hernandez Villalba Luis , Puig Ignasi , Arnau-Collell Coral , Moreno Lorena , Díaz Mireia , Rodriguez de Miguel Cristina , Ocaña Teresa , Moreira Leticia , Cuatrecasas Miriam , Carballal Sabela , Sánchez Ariadna , Ortiz Oswaldo , Llach Josep , Balaguer Francesc , Pellisé María ,   on behalf of the EndoCAR group from the Spanish Gastroenterology Association and the Spanish Society of Digestive Endoscopy
Published: June 2019

Abstract
Background and study aims Serrated polyposis syndrome (SPS) is a condition with high risk for colorectal cancer. The Endocuff device has been shown to increase adenoma detection in the general and screening population. We aimed to ascertain whether Endocuff-assisted colonoscopy increases detection of serrated lesions in comparison with standard colonoscopy during the surveillance of patients with SPS.
Methods In a multicenter randomized controlled study, patients who met SPS criteria I and/or III under surveillance (previous resection of all serrated lesions ≥ 4 mm) were consecutively randomly allocated 1:1 to Endocuff-assisted colonoscopy or standard colonoscopy, performed by expert endoscopists. The main outcome was the mean number of serrated lesions detected per patient.
Results 122 patients (standard colonoscopy n = 60; Endocuff-assisted colonoscopy n = 62; 59 % men; mean age 60.6 (standard deviation [SD] 7.5) were included at 4 centers. Baseline variables (demographic data, SPS phenotype, colorectal cancer [CRC] history, cumulative polyps, and follow-up), cecal intubation rate, and withdrawal time were similar between groups. There was no statistically significant difference between Endocuff-assisted colonoscopy and standard colonoscopy for the mean number of serrated lesions detected per patient: 5.8 (95 % confidence interval [95 %CI] 4.4 – 7.2) and 5.0 (3.9 – 6.1), respectively (P = 0.36). There were also no differences between Endocuff-assisted and standard colonoscopy for detection of sessile serrated lesions (mean number per patient 2.5 [1.3 – 3.6] vs. 2.0 [1.1 – 3.0], P = 0.54) and adenomas (0.9 [0.5 – 1.3] vs. 0.5 [0.3 – 0.7], P = 0.12).
Conclusion Use of Endocuff-assisted colonoscopy did not significantly increase the number of serrated lesion detected per patient during surveillance of SPS.
PROTEIN AGGREGATES IN HEATED BLOOD PRODUCTS
Authors: Freeman L , Hornsey V , Pepper D S , Foster P R , Winkelman L , Dawes J 
Published: June 2019

Heating of blood products to reduce viral infectivity is now a standard practice. Such treatment may also modify the constituent proteins, reducing their activity or altering their structure with potentially harmful consequences for the recipient. Partially denatured proteins frequently form aggregates, which are often immunogenic and could precipitate immune complex formation, allergic reactions and kidney damage. In addition they may contribute to the development of AIDS after HIV infection by inducing a persistent state of T-cell activation.Protein aggregate formation in factor VIII and factor IX (II + X) concentrates has been investigated by fast protein liquid chromatography (FPLC), which proved to be a rapid, convenient method for this purpose. Freeze-drying alone resulted in aggregate formation in intermediate purity FVIII concentrates, but not in FIX concentrates. However, aggregates were detected after heating the FIX concentrate at 80°C for 72h in the dry state. Dry heating of intermediate purity FVIII concentrates to 68°C for 24h also increased the content of protein aggregates, which contained fibrinogen and fibronectin but little IgG. In this product, the aggregate content after heating correlated with total protein concentration. A higher purity FVIII concentrate selectively depleted in fibrinogen and fibronectin also contained protein aggregates after freeze-drying, but heating this product at 80°C for 72h resulted in a relatively small increase in aggregate content. Haemophiliacs receiving regular injections of heated concentrates are constantly exposed to protein aggregates. They should be monitored for any harmful effects, and manufacturers should aim to reduce the aggregate content of their products.
THE INTERACTION OF THE FACTOR VIII/vWF COMPLEX WITH IMMOBILISED METAL AFFINITY CHROMATOGRAPHY (IMAC) MATRICES
Authors: Saundry R H , Kopp P , Savidge G F 
Published: June 2019

1MAC principles were used to investigate the binding of Factor VIII/vWF from either Al(OH)3 - absorbed citrated PPP or cryoprecipitate using citrate-saline buffers. Factor VIII/ vWF showed high affinity for both Zn2+ - or Cu2+ - immobilised on biscarboxymethylaminoSepharose 4B at ambient room temperature, but no interaction with Ca2+, Mg2+, Mn2+ or Cd2+ - immobilised matrices.Factor VIII/vWF could be re-eluted as a single component from Zn2+ - columns using either decreasing pK, or increasing competitor ligandconcentrations. In pK gradients comprising 14mM citrate, 2.14mM CaCl2, 0.15m NaCl Factor VIII eluted at pH 6.50, whereas in pH gradients comprising 0.1m Tris, 2.5mM CaCl2 pH 7.5 and 0.1M succinate, 2.5mM CaCl2 pH 5.5 Factor VIII eluted at pH 6.06. Citrate behaves as a competitor ligand; at 4° in citrate buffer Factor VIII did not bind.In citrate-saline buffers pH 7.2 Factor VIII could be reeluted in high yield (100% Factor VIII:Ag; 70% VIII:C; 90% vWF:Ag) through application of linear competitor ligand gradients (at 11.5mM imidazole, 15.4mM dl-Eistidine, 45mM L-Lysine, or 1.7% BSA) , whereas 1.0M NaCl or 1.0M NH4Cl were ineffective. The Factor VIII activities co-eluted ahead of, but incompletely resolved from the re-eluted Fg and Fn.
If 5 mg/ml. BSA was incorporated into the buffers Factor VIII was quantitatively recovered in the column wash - through fractions leaving all the Fg and Fn bound to the matrix.
TYPE IIB VON WILLEBRAND DISEASE WITH CHRONIC THROMBOCYTOPENIA : BENEFICIAL EFFECT OF CRYOPRECIPITATE SUPERNATANT INFUSION ON PLATELET COUNT AND BLEEDING
Authors: Derlon A , Le Querrec A , Lebrun E , Tobelem G , Thomas M 
Published: June 2019

As we previously described, plasma infusion increased platelet count (PC) in four patients with IIB von Willebrand disease with severe thrombocytopenia. In a sixty years old patient in the same family, with chronic thrombocytopenia (PC = 30 000/ml) associated to an absence of large von Willebrand Factor multi-mers (vWF) in plasma, we successfully treated :1° A gastrointestinal bleeding episode with fresh frozen plasma infusion (15ml/Kg/day).2° Three months later a severe epistaxis with cryoprecipi-tate supernatant (15ml/Kg/day).During these bleeding episodes, the efficiency of these two treatments on the PC could be ascertained according to the following figureWe observed after ten days of these two treatments the following biological effects : a normalisation of vWF cross immunoelectrophoresis, of ristocetin induced normal platelet aggregation by patient's plasma, and of patient's plasma vWF binding to control platelets.In conclusion a factor appears to be present in both fresh frozen plasma and cryoprecipitate supernatant which prevents the abnormal binding of von Willebrand Factor (in this IIB von Willebrand disease) to the patient's platelets.
A VARIANT OF VON WILLEBRAND'S DISEASE (vWD) WITH IIB-TYPE MULTIMER PATTERN IN THE ABSENCE OF ENHANCED PLATELET AGGLUTINATION
Authors: Cottrell S E , Wensley R T , Burn A M , Delamore I W 
Published: June 2019

A 62 year old man with vWD has suffered from repeated episodes of melaena - his son and daughter have inherited the disorder with few symptoms so far. Laboratory findings in them include consistently prolonged bleeding times, normal factor VIII coagulant activity and decreased ristocetin cofactor activity. Levels of von Willebrand factor (vWf) antigen were lower measured by immunoradiometric assay than by Laurell immunoelectrophoresis. Analysis of vWf structure by SDS agarose gel electrophoresis showed loss of only the large multimers in plasma and the triplet structure of the smaller multimers showed sub-bands more intense than normal. However, the platelets contain the whole series of multimers with a similar pattern to normal. This was suggestive of type IIB vWD but agglutination of the patients' platelet-rich plasma with low concentrations of ristocetin was not enhanced. Agglutination was reduced compared to normal platelet-rich plasma at a final ristocetin concentration of 1 and 2 mg/ml and absent at a final concentration of 0.5 mg/ml. Platelet-type vWD was eliminated as addition of normal plasma or cryoprecipitate to patient's platelet-rich plasma did not produce spontaneous aggregation.The patient has never had thrombocytopenia. We feel that this family demonstrates further the heterogeneity of vWD.
EFFECTS OF DDAVP INFUSION ON FVIII/vWF IN THREE CASES OF ACQUIRED TYPE II VON WILLEBRAND'S DISEASE
Authors: GOUDEMAND J , CARON C , JUDE B , PARQUET A , MAZURIER C 
Published: June 2019

The response to a single intravenous infusion of DDAVP (0.4 μg/kg) was studied in 3 patients with acquired type II von Willebrand's disease associated with monoclonal gammopathy (2 cases) or chronic lymphocytic leukaemia (1 case). The Simplate bleeding time (BT) was prolonged to 10-26 min, FVIII:C, vWF:Ag (ELISA) and vWF:RiCof activities were respectively decreased to 0.15-0.48, 0.18-0.30 and 0.06-0.48 U/ml. Circulating inhibitor to FVIII/vWF were demonstrated in the 3 cases. Plasma vWF multimeric analysis was performed by SDS-agarose, electrophoresis and densitometric patterns were recorded. In that way, each well-separated multimeric unit can be expressed as a percentage of the total area under the curve representing the total vWF. Whereas the large (slower-moving) multimers (numbered 6 and more) represented 52.8-63.2 % of the total vWF in normal plasma (n = 9), they could account only for 12.5-28.7 % of the total vWF in the patients' plasma. In addition, a progressive decrease in the relative intensity of the multimers as their size increased, in a similar manner as is seen in type lie vWD, was demonstrated. The triplet structure seen in normal plasma was undetectable in 2 patients but present in the 3rd one.Following infusion of DDAVP, the prolonged BT was normalized for 2 hr in 2 patients and transiently shortened in the 3rd one. FVIII:C, vWF:Ag and vWF:RiCof activities were increased to normal levels and remained higher than 0.5 U/ml for respectively 4-24 hr, 3-13 hr and 2-4.5 hr. The multimeric pattern could be considered as completely normalized in 2 patients and greatly improved in the 3rd one. The triplet structure was apparent in the 3 cases. The vWF multimeric structure returned to the preinfusion pattern by 5 hr in 2 patients and approximately 10 hr in the last one. These results demonstrate that endothelial cells from these patients are able to synthesize and release vWF with a full complement of multimers. Furthermore they show that the loss of the larger vWF multimers occurs after vWF has been released into the circulation.
FACTOR VIII:C (F VIII:C) AND VON WILLEBRAND FACTOR ANTIGEN (vWFag) IN RENAL TRANSPLANT RECIPIENTS IMMUNOSUPPRESSED WITH CYCLOSPORIN A (CyA)
Authors: Huser B , Lämmle B , Tran T H , Mihatsch M J , Thiel G , Duckert F 
Published: June 2019

In 17 consecutive cadaveric kidney transplant recipients F VIII:C and vWFag were repeatedly determined before transplantation and during 4 months thereafter. Graft biopsy was performed in 12 patients for deterioration of renal function. F VIII:C was determined by a one stage clotting assay using F VIII:C deficient substrate plasma. vWFag was assayed by electroimmunoassay using specific rabbit anti-human vWFag antibodies. Results of F VIII:C and vWFag are expressed referring to NHP as 100%.Results: 2/17 patients lost their graft due to irreversible vascular rejection, 2/17 patients had reversible vascular rejection, 2/17 patients developped glomerulonephritis, 6/17 patients showed acute or chronic CyA nephrotoxicity. In 5/17 patients graft biopsy was not necessary. Despite normalisation of renal function (serum creatinine levels<150umol/L) in 9 out of 17 patients F VIII:C (239 ± 66% to 408 ± 74%, mean ± SD) remained elevated in all 17 patients. vWFag (181 ± 29% to 454 ± 84%) was normalised in only 2 out of 17 patients. CyA dosis and CyA blood levels were not correlated with F VIII:C and vWFag. All 4 patients with histological vascular rejection, both patients with later developping glomerulonephritis and 3 out of 6 patients with later developping CyA nephrotoxicity showed F VIII:C/vWFag quotients > 1 (1,1 to 1,3) Four out of 5 patients with well functioning graft had F VIII:C/ vWFag quotients consistently <1 (0,68 to 0,92).Conclusion: 1. The elevated F VIII:C and vWFag levels in chronic renal failure are not normalised during 4 months of observation despite normalisation of renal function by transplantation and immunosuppression with CyA.2. A quotient F VIII :C/vWFag < 1 may indicate a good prognosis for kidney allograft function in the absence of CyA nephrotoxicity whereas later developping graft rejection or glomerulonephritis were associated with F VIII:C/vWFag>1.
CHANGES IN PLASMA t-PA, PAI AND FACTOR VIII FOLLOWING I. V. AND S. C. INJECTION OF DDAVP IN HEALTHY VOLUNTEERS
Authors: MacGregor I R , Roberts E , Prowse C V , Booth N A , Broomhead A , Litka P 
Published: June 2019

DDAVP is used effectively to induce a haemostatic response in certain types of haemophilia A and von Willebrands disease, but the accompanying increase in fibrinolytic activity is an unwanted effect. Here we have quantified the extent and time course of changes in t-PA, its physiological inhibitor PAI and factor VIII moieties, using functional and immunometric assays, following i.v. and s.c. injection of DDAVP 0.4 ug kg-1 in 6 normal volunteers in a double blind crossover study.T-PA, factor VIII and vWF values increased after dosing and the area under the response versus time curve was higher after i.v. than s.c. injection. Conversely levels of PAI activity decreased, with lower minimum values for i.v. than s.c. and a correspondingly lower area under the response curve for the former route. In several subjects PAI activity fell to zero during the sampling period. The times to the first occurrence of maximum response were determined. The median values for factor VIII were 40 and 90 min for i.v. and s.c. respectively. For vWF they were 60 and 80 min. For t-PA activity they were 20 and 60 min indicating that the release of factor VIII and vWF was delayed compared with t-PA activity. PAI-1 antigen was assayed by ELISA to investigate clearance of PA inhibitor and was compared with changes in PAI activity during the infusion of DDAVP and after a subsequent venous occlusion.The results indicate that fibrinolytic and haemostatic responses follow different time courses from each other, both after i.v. and s.c. administration of DDAVP, that are reproducible from subject to subject. The use of specific assays has permitted determination of the fibrinolytic response to DDAVP to be assessed in terms of changes in pro and antifibrinolytic components.
VIRUS SAFETY OF ANTITHROMBIN III CONCENTRATE KYBERNIN P - APROSPECTIVE CLINICAL TRIAL
Authors: Clemens R , Wirl G , Velten C , Röthig H J 
Published: June 2019

In 13 healthy male volunteers a prospective clinical trial was performed to evaluate virus safety of the antithrombin III concentrate Kybernin P in regard to hepatitis B, non-A/non-Band HIV transmission. As the volunteers were participants of a pharmacokinetic study they received either a fixed dosage of 1000 units Kybernin P asbolus injection or a dosage of 50 units per kg body weight as short-term infusion. Two different batches of Kybernin P were used.Whereas in all 13 volunteers virussafety in hepatitis non-A/non-B and HAV transmission could be monitored, only those volunteers who were not vaccinated (n=3) against hepatitis B or who had no protecting antibodies of anti-HB type despite vaccination (n=3)were to be included in the hepatitis B monitoring.All 13 volunteers were followed-upfor 1 year according to the standardsof the International Committee on Thrombosis and Hemostasis (ICTH). For detection of a potential hepatitis non-A/non-B transmission transaminases (AST, ALT) were determined in biweekly intervals during the first 6 months of the observation period and thereafter in monthly intervals. Hepatitis B seromar-kers as well as anti-HIV wereassessed bimonthly. Furthermore, all volunteers were clinically examined at every follow-up.None of the 13 volunteers revealedan increase of transaminases to the 2.5 fold of the upper normal level which is considered to be the borderlinelevel for hepatitis non-A/non-B diagnosis. Furthermore, in none of the volunteers a seroconversion for hepatitis B or HIV could be detected. Thus, Kybernin P is to be considered as hepatitis B, hepatitis non-A/non-B and HIV safe.
PHARMACOLOGIC INEQUIVALENCE OF LOW MOLECULAR WEIGHT HEPARINS
Authors: Fareed J , Walenga J M , Hoppensteadt D , Emanuele R N , Racanell A 
Published: June 2019

Compared to unfractionated heparin, low molecular weight heparins (LMWHs) have been found to exhibit marked variations in in vitro effects due to variations in molecular weight and structure. Moreover, when the in vitro potency of these agents is equally adjusted bypharmacopeial assay (current and proposed) wide variations in the in vivo responses have been noted. These variations were strongly dependent on the route of administration. Utilizing defined animal models, a systematic comparative study of the in vivo responses of seven commercial LMWHs was undertaken. Choay Fraxiparine (CY 216} Choay CY 222, NovoLHN, Kabi Fragmin, Opocrin 2123 (OP), Hepar RD 11885 (RD), Pharmuka Enoxaparin (PK) and Choay porcine mucosal heparin (PMH) were tested in identical settings at equigravimetric dosages. The graded results are given in the following.Wide variations in the in vivo pharmacologic and toxicity responseswere noted suggesting that different LMWHs are not bioequivalent at equigravimetric levels. When these responses were expressed in anti-factor Xa or pharmacopeial potency, these differences were further magnified. The clinically reported dosimetric and safety problems may be minimized by profiling LMWHs in defined in vivo test systems to optimize their safety/efficacy ratio.
A TRIAL OF SUBCUTANEOUS VERSUS INTRAVENOUS ADMINISTRATION OF LOW MOLECULAR WEIGHT (LMW) HEPARIN AND UNFRACTIONATED (UF) HEPARIN IN THE TREATMENT OF ESTABLISHED DEEP VENOUS THROMBOSIS (DVT)
Authors: Parker C J , Huber D E , Hedges A R , Kakkar V V 
Published: June 2019

In a randomized clinical trial of 100 patients, the in vivo antithrombotic effects of a subcutaneously administered LMW heparin fraction (CY216) used in the treatment of established DVT, was compared with UF heparin administered by either intravenous or subcutaneous routes.Venograms were used to make the initial diagnosis, and efficacy of treatment was assessed by a repeat venogram done on day 6. Comparison of the venograms were done blind by an expert radiologist.Patients were randomized to one of three groups: Group 1 received subcutaneous CY216; Group 2 received subcutaneous UF heparin: Group 3 received continuous intravenous UF heparin. Random patients from each group had detailed haematological tests consisting of twicedaily KCCT and anti-Xa levels. Extension of thrombus occurred in significantly morepatients receiving intravenous heparin than subcutaneous heparin (p-0.02).There was no difference between the two subcutaneousgroups. There were no haematological complications.We conclude that subcutaneous administratiyon of heparin is the treatment of choice in the treatment of DVT.
ARE THE SYMPTOMS OF THE POST PHLEBITIC LIMB ALWAYS POST THROMBOTIC
Authors: Parker C J , Huber D E , Hedges A R , Kakkar V V 
Published: June 2019

The term ‘post phlebitic syndrome’ implies a previous history of deep venous thrombosis. To test the validity of this assumption, 106 patients who had routine post-operative bilateral ascending venography following total hip replacement were reviewed five years later.Patients were assessed clinically for symptoms and signs of the ‘post phlebitic syndrome’ (pain, swelling, induration, pigmentation, ulceration and varicose veins). Haemodynamic changes were assessed by foot volumetry and an objective score was derived by computer analysisThirty patients (28%) had post-operative DVT. 50% of all patients had at least one symptom or sign of the post phlebitic limb. Pain was present in 9 limbs; swelling in 13; induration in 18; pigmentation in 55, and varicose veins in 53 limbs.At five years there was no significant difference in the incidence of symptoms, signs or haemadynamic changes of the post phlebitic syndrome between limbs with or without a previous DVT. We conclude that deep vein thrombosis is not the only factor involved in the aetiology of the post phlebitic limb.
ALTERATIONS IN THE COAGULATION AND FIBRINOLYTIC SYSTEMS AS PREDISPOSING FACTORS IN THE DEVELOPMENT OF DEEP VENOUS THROMBOSIS (DVT)
Authors: Tengborn L , Wallmark A 
Published: June 2019

From Jan. 1982 to Jan. 1987, 1213 patients were investigated either because of thrombotic episode(s) or thrombosis heredity. Diagnosis of DVT was confirmed by phlebography in 567 cases. Patients were first examined at least three months after an acute episode.Methods. Anti thrombin (AT) and plasminogen were assayed, using chromogenic substrates S-2238 and S-2251 , respectively, followed if values were low by immunochemical assessment. Furthermore, fibrinogen, thrombin and reptilase times, APTT, P…P were assessed. Only in the latter study period was protein C activity determined (129 cases). Fibrinolysis was assayed on fibrin plates after 20 min venous occlusion of the arms. In 1984 only, plasminogen activator inhibitor of endothelial cell type (PAI 1) was measured in most DVT patients (n=75).Results. DVT first occurred by the age of 45 in 337 patients, of whom five had AT deficiency (four classic and one abnormal), one had low and another abnormal plasminogen), one had abnormal fibrinogen, seven had lupus anticoagulants (LA), and 72 (21%) had decreased lysis on fibrin plates. Defective fibrinolysis was re-investigated in 42 patients; at check-up 13 were found to have normalised. Of the 75 patients from 1984, fibrinolysis on fibrin plates was normal in 50 cases, of which PAI 1 was normal in 44 and increased in six; of the remaining 25 patients from 1984, fibrin plate activity was decreased, PAI 1 was normal in five cases and increased in 20.DVT first occurred after the age of 45 in 230 patients, of whom none had pathological AT or protein C, five had LA, and one had abnormal plasminogen; of the 51 (22%) patients found to have defective fibrinolysis, 29 were re-investigated at check-up and 14 of them found to have normalised.Conclusion. Alterations in coagulation inhibitors are rare in patients with DVT. A more frequent finding, although intraindividual fluctuations occur, is defective vessel wall fibrinolysis.