Sample records for prolonged prothrombin times

  1. Prothrombin time (PT)

    PT; Pro-time; Anticoagulant-prothrombin time; Clotting time: protime; INR; International normalized ratio ... PT is measured in seconds. Most of the time, results are given as what is called INR ( ...

  2. Blood splash in lambs-a preliminary study using the one-stage prothrombin time test.

    Restall, D J


    Lambs from a flock in which a high incidence of blood splash had been detected were examined using the one-stage prothrombin test. For comparison lambs from a commercial slaughter line were also examined. All the affected lambs and 35·4% from the slaughter line had extended prothrombin times, and a relationship between extended prothrombin times and the occurrence of blood splash was established. Investigation of the pastures grazed by the affected flock showed the presence of coumarin producing plants and grasses. Some coumarin drugs prolong one-stage prothrombin times, and more importantly, induce capillary fragility, thus predisposing animals to blood splash.

  3. Oral contraceptives and the prothrombin time.

    Pangrazzi, J; Roncaglioni, M C; Donati, M B


    Dr. De Teresa and others reported that mean prothrombin time ratio of 12 patients on long-term anticoagulation with warfarin was significantly higher when they were also taking oral contraceptives (OCs). A study of prothrombin complex activity was recently conducted in female rats treated with an estrogen-progestogen combination (lynestrenol 5 mg; mestranol 0.3 mg/kg body weight) which resulted in a 100% infertility in this species. After 1 treatment for only 1 estral cycle, OC-treated rats had a significantly longer Normotest clotting time (37.7+ or-0.5 sec) than control rats (31.0+or-0.4); the difference was even more notable after 10 cycles. Although this finding has not been reported in women on OCs, it may be that the estrogen-induced "lability" of the prothrombin complex occurs in humans only in special conditions, such as anticoagulation. Alternatively, liver dysfunction occurring among women on OCs may be responsible for reduced metabolism of warfarin, contributing to the effectiveness of the anticoagulation. Further pharmacology studies should be done to clarify the interaction between OCs and oral anticoagulants.

  4. Evaluation of Prothrombin Time and Activated Partial ...

    abnormal PT and APTT in untreated patients with diabetes mellitus. Keywords: Diabetes, Prothrombine ... may in turn enhance cardiovascular risk by increasing the likely hood of .... normalizes PT levels in diabetic patients (Standl et al,. 1996).

  5. Deceptive prothrombin and activated partial thromboplastin times in alcoholic cirrhosis.

    Sirikonda, P. R.; Spillert, C. R.; Koneru, B.; Ponnudurai, R.; Wilson, D. J.; Lazaro, E. J.


    It is believed that perioperative hemorrhage, in the hepatoportal area, results from a coagulopathy. This study determined if this could be quantitated by a modified recalcification time (MRT) test developed in our laboratory. Unlike prothrombin (PT) and activated partial thromboplastin times (APTT), the MRT is performed with whole blood to ensure the role of blood cells and chemicals (particularly tissue factor, a potent procoagulant) in the coagulation process. Candidates for liver transplantation (n = 11) were studied. Samples (5 mL) of citrated venous blood were obtained from the patients. Aliquots (1 mL) from these samples were divided into groups of vials labeled C, S, and E. Groups C and S received 20 microL saline and group E, 20 microL of saline containing 10 micrograms of Escherichia coli endotoxin (055: B5W). Vial C was incubated for 10 minutes and vials S and E for 120 minutes, all at 37 degrees C. Then, the MRT was determined on 300 microL of blood from each vial after adding 40 microL of 0.1M calcium chloride. Mean MRT values (minutes +/- standard deviation) for C (MRTC), for S (MRTS), and for E (MRTE) were compared with like values from healthy controls (n = 29). Despite prolonged PT and APTT values, MRT values were shortened in patients with cirrhosis. This hypercoagulability detected by the MRT exonerates a hemorrhagic coagulopathy and possibly implicates widened and thinned gaps in the walls of the portal venous tributaries as the cause of perioperative hemorrhage. PMID:8667440

  6. Effects of sugammadex on activated partial thromboplastin time and prothrombin time in healthy subjects.

    De Kam, Pieter-Jan; Grobara, Peter; Prohn, Marita; Höppener, Floris; Kluft, Cornelis; Burggraaf, Jacobus; Langdon, Ronald B; Peeters, Pierre


    To assess the impact of sugammadex on activated partial thromboplastin time (APTT) and international normalized ratio for prothrombin time (PT(INR)) in healthy subjects and characterize the concentration-dependency of sugammadex effects on APTT and prothrombin time (PT) in normal human plasma in vitro. Eight healthy subjects (18 - 45 years of age) were administered intravenous doses of 4 mg/kg sugammadex, 16 mg/kg sugammadex, or placebo in a randomized, placebo-controlled, three period cross-over trial. The primary endpoint was area under the curve from 2 to 60 minutes post-dose (AUC2-60min) for APTT and PT(INR). In vitro, the effects of sugammadex on APTT and PT were assessed in pooled normal human citrate plasma. In subjects dosed with 4 and 16 mg/kg sugammadex, geometric mean ratios (treated vs. placebo) for AUC2-60min were 1.085 (95% confidence interval, 0.888 - 1.325) and 1.019 (0.868 - 1.195), respectively, for APTT, and 1.047 (0.904 - 1.213) and 1.096 (0.953 - 1.261), respectively, for PT(INR). At individual timepoints, mean APTT and PT(INR) increased by up to 22% after 16 mg/kg sugammadex compared with placebo. All such increases occurred within 30 minutes post-dose. Sugammadex was generally well tolerated. In the in vitro experiments, addition of sugammadex to plasma resulted in limited, concentration dependent increases in both APTT and PT. At 200 μg/mL (the mean maximum concentration reached therapeutically), the relative increases were 29% and 19%, respectively. Administration of sugammadex is associated with a dose-related, limited and transient prolongation of APTT and PT(INR) that is unlikely to be of clinical relevance.

  7. Prothrombin Segovia: a new congenital abnormality of prothrombin.

    Rocha, E; Paramo, J A; Bascones, C; Fisac, P R; Cuesta, B; Fernandez, J


    A family with a new congenital dysprothrombinemia is presented. The propositus is a 21-yr-old man who presented simultaneously with hemartrosis of the left knee and an extensive hematoma following a minor trauma. Prothrombin time and activated partial thromboplastin time were prolonged. Prothrombin activity was very low when measured by biological assay using physiological activators (7% by one-stage method and 20% by two-stage method) or a Russel's viper venom-cephalin mixture (23%), Notechis scutatus scutatus venom (15%) and Echis carinatus venom (17%); in contrast, the level was found to be borderline to normal using Taipan viper venom (64%) and normal by both staphylocoagulase and immunologic methods. Family studies revealed consanguinity between the propositus' mother and father and both presented a 50% reduced prothrombin level when physiological activators or Echis carinatus viper venom were used. A line of identity between normal and abnormal prothrombin was observed on immunodiffusion. The migration of the abnormal prothrombin was less anodic and was not changed by the addition of calcium. The patient's serum showed 3 bands in the bidimensional immunoelectrophoresis system, whereas normal serum showed only 2 bands. The term prothrombin Segovia is proposed to define this new prothrombin abnormality.



    Full Text Available Twenty (20 adult albino mice were used in the study to determine the effect of methanolic seed extract of Persea Americana on prothrombin time (PT and activated partial thromboplastin time (APTT test. The mice were obtained and kept for 2 weeks to acclimatize. They were weighed and divided into 5 groups. Group A served as control without the extract. Groups B to E were orally administered with graded doses of 200mg, 400 mg, 800 mg and 1600mg/kg body weight per mice daily for 28 days. Blood samples were collected through the median canthus into ti-sodium citrate anticoagulant containers for the analysis of PT and APTT, using standard operative procedure. The analysis was carried out at the Haematology Laboratory of University of Nigeria Teaching Hospital (UNTH Enugu. The results showed a prolonged APTT time at all the doses of the extract when compared with the control (P and lt;0.05. The prothrombin time at the dosage of 200mg/kg did not differ when compared with the control (P and gt;0.05. The increase in PT and APTT was dose dependent. This result pattern suggests that the extract causes prolonged prothrombin time and APTT at various concentrations possibly due to its high potassium content. The extract can be recommended in anticoagulant therapy since it prolongs PT and APTT.

  9. The influence of N-acetylcysteine on the measurement of prothrombin time and activated partial thromboplastin time in healthy subjects

    Jepsen, S; Hansen, A B


    The purpose of the study was to evaluate whether the infusion of N-acetylcysteine decreased the measurement of prothrombin time and activated partial thromboplastin time (APTT) in healthy persons. N-acetylcysteine was administered intraveneously 10 mg kg-1 as a loading dose and then at a rate of 10...... mg kg-1 h-1 for 32 h in six male subjects. The intrinsic, extrinsic and common pathway of coagulation were monitored with activated partial thromboplastin time (APTT), and prothrombin time, respectively. In addition, the extrinsic coagulation pathway was monitored with the clotting activity of single...... factors II, VII, and X. No effect on the intrinsic coagulation pathway was observed. There was a significant and rapid decrease in prothrombin time. Coagulation factors II, VII and X, the three components of prothrombin time, decreased significantly to different degrees. We conclude that infusion of N...

  10. Comparison of prothrombin time tests used in the monitoring of edoxaban and their evaluation as indicators of the reversal effect.

    Iba, Toshiaki; Emmi, Mari; Hiki, Makoto; Nagayama, Masataka; Aihara, Koichiro; Tabe, Yoko; Yuri, Maiko; Ohsaka, Akimichi


    Clinical demand for the prompt assessment of the activity of direct-acting factor Xa inhibitors in the emergency care setting is increasing. In the present study, we examined whether prothrombin time (PT) tests can serve as a clinically useful indicator of anti-factor Xa activity. In the first series, the in vitro effect of edoxaban on PT was evaluated by spiking human plasma with edoxaban and measuring PT using three different commercial PT tests. In the second series, the reversal effect of prothrombin complex concentrates (PCC) and activated PCC (aPCC) in edoxaban-spiked plasma was evaluated. In the third series, PT of plasma samples from patients administered either 15 or 30 mg/day of edoxaban was assessed, and the results were compared with edoxaban concentrations determined by a calibrated anti-factor Xa activity assay. The spike test revealed that all PT reagents positively correlated with edoxaban. The sensitivity to edoxaban varied among the three reagents and Triniclot(®) Excel S showed the best performance. Prolonged PT by edoxaban was reversed by PCC and aPCC in a dose-dependent manner; however, complete reversal was not achieved. Positive correlation between anti-factor Xa activity and PT was shown in the clinical samples at the edoxaban range from 0 to >300 ng/mL.

  11. Clinical factors influencing normalization of prothrombin time after stopping warfarin: a retrospective cohort study

    Zondag Michelle


    Full Text Available Abstract Background Anticoagulation with warfarin should be stopped 4–6 days before invasive procedures to avoid bleeding complications. Despite this routine, some patients still have high International Normalized Ratio (INR values on the day of surgery and the procedure may be cancelled. We sought to identify easily available clinical characteristics that may influence the rate of normalization of prothrombin time when warfarin is stopped before surgery or invasive procedures. Methods Clinical data were collected retrospectively from consecutive cases from two cohorts, who stopped warfarin 6 days before surgery. An INR value of 1.6 or higher on the day of surgery or requirement for reversal with vitamin K the day before surgery were criteria for slow return (S to normal INR. Results Of 202 patients, 14 (7% were classified as S. Eight of the S-patients required reversal with vitamin K one day before surgery and in another case surgery was cancelled due to high INR. Baseline INR was the only variable significantly associated with classification as S in stepwise logistic regression analysis (p = 0.003. The odds ratio for being in the normal group was 0.27 (95% confidence interval 0.12–0.62 for each unit baseline INR increased. The positive predictive value of baseline INR with a cut off at > 3.0 was only 15% and for INR > 3.5 it was 33%. Conclusion Baseline INR, but not the size of the maintenance dose, is associated with the rate of normalization of prothrombin time after stopping warfarin, but it has limited utility as predictor in clinical practice. Whenever normal hemostasis is considered crucial for the safety, the INR should be checked again before the invasive procedure.

  12. Effect of acetylcysteine on prothrombin index in paracetamol poisoning without hepatocellular injury

    Schmidt, Lars E; Knudsen, Tore Tveit; Dalhoff, Kim


    Acetylcysteine treatment reduces liver damage after paracetamol overdose, but can affect the prothrombin index, which is used to assess the progress of overdose patients. We aimed to assess retrospectively the effect of intravenous acetylcysteine on the prothrombin index in patients with paraceta......Acetylcysteine treatment reduces liver damage after paracetamol overdose, but can affect the prothrombin index, which is used to assess the progress of overdose patients. We aimed to assess retrospectively the effect of intravenous acetylcysteine on the prothrombin index in patients...... with paracetamol poisoning without signs of hepatocellular injury. Prothrombin index had been recorded before, and serially during, acetylcysteine treatment in 87 patients. After initiation of treatment, prothrombin index decreased (mean 0.33, 95% CI 0.29-0.38) in all patients, and was strongly associated...... with the start of acetylcysteine infusion. In patients with uncomplicated paracetamol poisoning, a fall in this index might be misinterpreted as a sign of liver failure, leading to prolonged treatment time....

  13. Preoperative screening for coagulopathy using prothrombin time and partial thromboplastin time in patients requiring primary cranial vault remodeling.

    Genecov, David G; Por, Yong-Chen; Barcelo, Carlos Raul; Salyer, Kenneth E; Mulne, Arlynne F; Morad, Ammar B


    The aim of this study was to investigate the prevalence of abnormal preoperative screening prothrombin time and partial thromboplastin time in patients listed for primary cranial vault remodeling that required hematologic workup and their diagnoses and subsequent management. This retrospective analysis was performed from January of 2000 to December of 2003 at the International Craniofacial Institute, Dallas, Texas, on a total of 168 patients. All patients had a normal prothrombin time. Abnormally raised partial thromboplastin time was found in six patients (prevalence of 3.57 percent), one who had factor XI deficiency, one who had a borderline factor XI deficiency and circulating inhibitor, one who had an intermittent factor XI deficiency and circulating inhibitor, one who had a borderline von Willebrand's disease with low factor XII, and the remaining two who had a circulating inhibitor of coagulation. Of these six patients, the perioperative management was altered in four of five patients, and one patient declined surgery out of fear of surgical morbidity. The surgery of one patient was aborted intraoperatively because of abnormal bleeding without clot formation after the calvarial burr holes had been drilled. The mean blood loss was 183 ml for the four patients with completed surgery and 100 ml for one patient. The authors conclude that even though the prevalence of abnormal screening partial thromboplastin time in these patients was low (3.57 percent), detection of an abnormal result required preoperative correction of coagulopathy in 80 percent of cases.

  14. Mortality in vitamin K antagonist-related intracerebral bleeding treated with plasma or 4-factor prothrombin complex concentrate

    Majeed, Ammar; Meijer, Karina; Larrazabal, Ramiro; Arnberg, Fabian; Luijckx, Gert J.; Roberts, Robin S.; Schulman, Sam


    Prothrombin complex concentrates (PCC) can rapidly normalise prolonged prothrombin time, induced by vitamin K antagonists (VKA). We conducted a multicentre retrospective study to investigate whether reversal of VKA coagulopathy with 4-factor PCC improves the survival of patients with VKA-related int

  15. Effects of Tramadol Coadministration on Prothrombin Time-International Normalized Ratio in Patients Receiving Warfarin.

    Hosono, Tomomi; Kondo, Aiko; Kambayashi, Yasuyuki; Homma, Masato


     Several case studies have reported a possible drug interaction between warfarin and tramadol where tramadol coadministration enhanced the antithrombotic effects of warfarin. To assess this drug interaction, changes in prothrombin time-international normalized ratio (PT-INR) before and after tramadol coadministration were investigated in patients receiving warfarin. For this study, we examined 54 patients (male/female: 22/32, 68.4±12.7 years) who were being treated with warfarin for deep vein thrombosis, atrial fibrillation, arteriosclerosis obliterans, congestive heart failure, and other vascular diseases. Significant increases in PT-INR were observed 9.5 (1-118) d after coadministration of tramadol (1.81±0.56 vs. 2.47±1.10, ptramadol were compared with other groups of patients to find drug interaction risk factors. Logistic regression analysis revealed that lower levels of albumin (3.5 g/dL or less) [odds ratio (OR) 22.1; 95%CI 2.9-169.9]; lower eGFR (50 mL/min or less) (OR 7.7; 95%CI 1.4-42.0); and PT-INR before tramadol coadministration (OR 38.2; 95%CI 3.7-397.6) were characteristic of the PT-INR increased group. These results suggest that tramadol coadministration enhanced the antithrombotic effects of warfarin in patients with higher PT-INR, lower albumin levels and decreased renal function as the risk factors for this drug interaction.

  16. A novel prothrombin time assay for assessing the anticoagulant activity of oral factor Xa inhibitors.

    Barrett, Yu Chen; Wang, Zhaoqing; Knabb, Robert M


    Conventional prothrombin time (PT) assays have limited sensitivity and dynamic range in monitoring the anticoagulant activity of direct factor Xa inhibitors. Hence, new assays are needed. We modified a PT assay by adding calcium chloride (CaCl2) to the thromboplastin reagent to increase assay dynamic range and improve sensitivity. Effects of calcium and sodium ion concentrations, and sample handling, were evaluated to optimize assay performance. Increasing concentrations of calcium ions produced progressive increases in PT across the factor Xa inhibitor concentrations of 0 to 2500 nmol/L for razaxaban and apixaban. The greatest effect was seen when the thromboplastin reagent was diluted 1:2.25 with 100 mmol/L CaCl2 (thus selected for routine use). The optimized assay showed an interassay precision of 1.5 to 9.3 percentage coefficient of variation (%CV) for razaxaban and 3.1 to 4.6 %CV for apixaban. We conclude that the modified PT assay is likely to be suitable as a pharmacodynamic marker for activity at therapeutic concentrations of factor Xa inhibitors.

  17. The risk of early mortality of polytrauma patients associated to ISS, NISS, APACHE II values and prothrombin time.

    Mica, Ladislav; Rufibach, Kaspar; Keel, Marius; Trentz, Otmar


    The early hemodynamic normalization of polytrauma patients may lead to better survival outcomes. The aim of this study was to assess the diagnostic quality of trauma and physiological scores from widely used scoring systems in polytrauma patients. In total, 770 patients with ISS > 16 who were admitted to a trauma center within the first 24 hours after injury were included in this retrospective study. The patients were subdivided into three groups: those who died on the day of admission, those who died within the first three days, and those who survived for longer than three days. ISS, NISS, APACHE II score, and prothrombin time were recorded at admission. The descriptive statistics for early death in polytrauma patients who died on the day of admission, 1-3 days after admission, and > 3 days after admission were: ISS of 41.0, 34.0, and 29.0, respectively; NISS of 50.0, 50.0, and 41.0, respectively; APACHE II score of 30.0, 25.0, and 15.0, respectively; and prothrombin time of 37.0%, 56.0%, and 84%, respectively. These data indicate that prothrombin time (AUC: 0.89) and APACHE II (AUC: 0.88) have the greatest prognostic utility for early death. The estimated densities of the scores may suggest a direction for resuscitative procedures in polytrauma patients. "Retrospektive Analysen in der Chirurgischen Intensivmedizin"StV01-2008.

  18. Restoration of Normal Prothrombin Time/International Normalized Ratio With Fresh Frozen Plasma in Hypocoagulable Patients.

    Only, Arthur J; DeChristopher, Phillip J; Iqal, Omer; Fareed, Jawed


    Fresh frozen plasma (FFP) is an effective reversal agent for hypocoagulable patients. Its proven efficacy continues to prompt its usage as both a prophylactic and a therapeutic therapy. Although published guidelines encouraging the appropriate administration of FFP exist, overutilization continues. The purpose of these ex vivo studies was to determine the effects of succeeding volumes of FFP supplementation on hypocoagulable plasma prothrombin time/international normalized ratio (PT/INR). By analyzing the decline in PT/INR with varying volumes of FFP, a minimal required volume of FFP could be identified representing the optimal volume to administer while still providing therapeutic effect. A total of 497 plasma samples were screened for elevated PT/INR values and 50 samples were selected for inclusion in this experiment. The initial PTs/INRs ranged from 12.5 to 43.4 seconds/1.42 to 4.91. Subsequent declines in PT/INR values were analyzed following addition of 50, 100, and 150 µL of FFP to a fixed volume of 250 µL of plasma (26.4 ± 5.318 seconds/2.99 ± 0.603, 13.3 ± 1.077 seconds/1.51 ± 0.122, 11.2 ± 0.712 seconds/1.27 ± 0.081, and 10.3 ± 0.533 seconds/1.16 ± 0.06, respectively). A nonlinear relationship between decline in INR values and percentage of FFP supplementation was demonstrated. The greatest effect on INR was obtained after supplementation with 50 µL (49%). Doubling and tripling the volume of FFP lead to significantly lower declines in INR (16% and 8%, respectively). Analysis of variance indicated a statistical significance with subsequent volume supplementation of FFP, but marginal clinical benefits exist between the PTs/INRs obtainable with increased FFP volume administration.

  19. Effect of storage conditions on prothrombin time, activated partial thromboplastin time and fibrinogen concentration on canine plasma samples

    Casella, Stefania; Giannetto, Claudia; Giudice, Elisabetta


    The present study was to assess the effect of storage conditions on prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen concentration in blood samples of healthy dogs. Thirty-five dogs of various breeds were included in the study. Citrated blood samples were obtained and plasma was divided into four aliquots to assess selected clotting parameters by means of a coagulometer. The first aliquot was analysed within 1 h after collection, while the remaining 3 were stored at 8℃ for 4, 8 and 24 h, respectively. One-way repeated measures analysis of variance documented a significant decreasing effect on PT at 24 h compared to 8 h and on fibrinogen concentration after 8 and 24 h compared to sampling time and at 4 and 24 h compared to 8 h post sampling. In conclusion, the results of this study indicate that only fibrinogen appears prone to significant decrease. In fact, aPTT is not substantially affected by refrigeration for at least 24 h post sampling and PT showed a statistical difference that does not necessary indicate biological significance as the results obtained were within reference intervals for the dog. PMID:20458152

  20. Prolonged activated prothromboplastin time and breed specific variation in haemostatic analytes in healthy adult Bernese Mountain dogs

    Nielsen, Lise; Wiinberg, Bo; Kjelgaard-Hansen, Mads;


    to be determined if breed specific RIs are necessary for haemostasis tests. Activated prothromboplastin time (aPTT), prothrombin time (PT), selected coagulation factors, D-dimers, fibrinogen, von Willebrand factor and thromboelastography (TEG) were analyzed in healthy Bernese Mountain dogs using the CLSI model....... Three analytes (aPTT, TEG [MA] and TEG [G]) were different according to the CLSI model. For aPTT the new RI was markedly different (0-100 s). Whereas the new intervals for TEG (MA) and TEG (G) may be due to breed related biological variation, the cause of the prolonged RI for aPTT is at present...

  1. A novel prothrombin time method to measure all non-vitamin K-dependent oral anticoagulants (NOACs).

    Lindahl, Tomas L; Arbring, Kerstin; Wallstedt, Maria; Rånby, Mats


    There is a clinical need for point-of-care (POC) methods for non-vitamin K-dependent oral anticoagulants (NOACs). We modified a routine POC procedure: Zafena's Simple Simon™ PT-INR, a room-temperature, wet-chemistry prothrombin time method of the Owren-type. To either increase or decrease NOAC interference, two assay variants were devised by replacing the standard 10 µL end-to-end capillary used to add the citrated plasma sample to 200 µL of prothrombin time (PT) reagent by either a 20 µL or a 5 µL capillary. All assay variants were calibrated to show correct PT results in plasma samples from healthy and warfarin-treated persons. For plasmas spiked with dabigatran, apixaban, or rivaroxaban, the 20 µL variant showed markedly higher PT results than the 5 µL. The effects were even more pronounced at room temperature than at +37 °C. In plasmas from patients treated with NOACs (n = 30 for each) there was a strong correlation between the PT results and the concentration of NOACs as determined by the central hospital laboratory. For the 20 µL variant the PT response of linear correlation coefficient averaged 0.90. The PT range was INR 1.1-2.1 for dabigatran and apixaban, and INR 1.1-5.0 for rivaroxaban. Using an INR ratio between the 20 µL and 5 µL variants (PTr20/5) made the NOAC assay more robust and independent of the patient sample INR value in the absence of NOAC. Detection limits were 80 µg/L for apixaban, 60 µg/L for dabigatran, and 20 µg/L for rivaroxaban. A wet-chemistry POC PT procedure was modified to measure the concentrations of three NOACs using a single reagent.

  2. Prothrombin Time and Activated Partial Thromboplastin Time Testing: A Comparative Effectiveness Study in a Million-Patient Sample.

    Manu N Capoor

    Full Text Available A substantial fraction of all American healthcare expenditures are potentially wasted, and practices that are not evidence-based could contribute to such waste. We sought to characterize whether Prothrombin Time (PT and activated Partial Thromboplastin Time (aPTT tests of preoperative patients are used in a way unsupported by evidence and potentially wasteful.We evaluated prospectively-collected patient data from 19 major teaching hospitals and 8 hospital-affiliated surgical centers in 7 states (Delaware, Florida, Maryland, Massachusetts, New Jersey, New York, Pennsylvania and the District of Columbia. A total of 1,053,472 consecutive patients represented every patient admitted for elective surgery from 2009 to 2012 at all 27 settings. A subset of 682,049 patients (64.7% had one or both tests done and history and physical (H&P records available for analysis. Unnecessary tests for bleeding risk were defined as: PT tests done on patients with no history of abnormal bleeding, warfarin therapy, vitamin K-dependent clotting factor deficiency, or liver disease; or aPTT tests done on patients with no history of heparin treatment, hemophilia, lupus anticoagulant antibodies, or von Willebrand disease. We assessed the proportion of patients who received PT or aPTT tests who lacked evidence-based reasons for testing.This study sought to bring the availability of big data together with applied comparative effectiveness research. Among preoperative patients, 26.2% received PT tests, and 94.3% of tests were unnecessary, given the absence of findings on H&P. Similarly, 23.3% of preoperative patients received aPTT tests, of which 99.9% were unnecessary. Among patients with no H&P findings suggestive of bleeding risk, 6.6% of PT tests and 7.1% of aPTT tests were either a false positive or a true positive (i.e. indicative of a previously-undiagnosed potential bleeding risk. Both PT and aPTT, designed as diagnostic tests, are apparently used as screening tests

  3. Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation : PROTON-trial

    Arshad, Freeha; Ickx, Brigitte; van Beem, Rachel T.; Polak, Wojciech; Grune, Frank; Nevens, Frederik; Ilmakunnas, Minna; Koivusalo, Anna-Maria; Isoniemi, Helena; Strengers, Paul F. W.; Groen, Henk; Hendriks, Herman G. D.; Lisman, Ton; Pirenne, Jacques; Porte, Robert J.


    Background: In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during orthotopic liver

  4. Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial

    F. Arshad (Freeha); B. Ickx (Brigitte); R.T. van Beem (Rachel); W.G. Polak (Wojciech); F. Grüne (Frank); F. Nevens (Frederik); M. Ilmakunnas (Minna); A.M. Koivusalo (Anna-Maria); H. Isoniemi (Helena); P.F.W. Strengers; H.J.M. Groen (Henk); H.G.D. Hendriks (Herman); T. Lisman (Ton); J. Pirenne (Jacques); R.J. Porte (Robert)


    textabstractBackground: In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during

  5. Influence of blood collection systems on the prothrombin time and international sensitivity index determined with human and rabbit thromboplastin reagents.

    van den Besselaar, Anton M H P; Hoekstra, Martha M C L; Witteveen, Evelina; Didden, Jan H; van der Meer, Felix J M


    Three brands of blood collection tubes were studied for their influence on the prothrombin time (PT) and international sensitivity index (ISI) for 5 commercial thromboplastin reagents. With all reagents, PTs were shorter in Vacutainer (Becton Dickinson Vacutainer Systems, Plymouth, England) samples than in S-Monovette (Sarstedt, Nümbrecht, Germany) or Venosafe (Terumo Europe, Leuven, Belgium) samples. ISI values were higher with Vacutainer samples than with S-Monovette or Venosafe samples. The ISI differences between the tubes were small for Thromborel-S (2.1%; Dade Behring, Marburg, Germany) and Hepato Quick (1.1%; Diagnostica Stago, Asnières, France; Roche Diagnostics Nederland, Almere, the Netherlands) but greater for Neoplastin Plus (5.5%; Diagnostica Stago; Roche Diagnostics Nederland), Simplastin HTF (8.3%; bioMérieux, Durham, NC), and Innovin (8.8%; Dade Behring). The PT and ISI differences between the tubes could be explained mostly by the effect of magnesium ion contamination in the sodium citrate solutions. When PT ratios were transformed into international normalized ratios (INRs) using crossover ISI (ie, samples collected with one type of tube and ISI determined with another collection system for the PT reagent), the differences in mean INRs could be approximately 10%. For ISI calibration of reference thromboplastins, blood collection tubes should be used with minimal divalent metal ion contamination of the citrate solution.

  6. Saline obtaining and time standardization of prothrombin using thromboplastin of human placenta.

    María de Jesús Sánchez Bouza


    Full Text Available Background: Determining prothombine ‘s time is an important lab test in the study of coagulation disorders. To develop this essay the main reactive was thromboplastin , a substance that is presented in tissue and that has been obtained habitually from the human brain or certain animals but its extraction in labs or its commercial acquisition is difficult at present. Objective: To obtain Thromboplastin throughout the extraction of human placenta and to standardise the determination of pro-time into the obtained reactive Method: Placenta from normal delivery was used from which thromboplastin was obtained using a saline extraction. The reactive was compared with thromboplastin from human brain from ¨Dr. Hermanos Ameijeiras¨ Hospital in Havana City in a group of patients with and without anticoagulant treatment . With the extracted thromplastin similar or compatible results were obtained than with the habitual reactives by using easier and cheaper process.

  7. Genetics Home Reference: prothrombin thrombophilia

    ... Understand Genetics Home Health Conditions prothrombin thrombophilia prothrombin thrombophilia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Prothrombin thrombophilia is an inherited disorder of blood clotting . Thrombophilia ...

  8. Fellatio by fruit bats prolongs copulation time.

    Min Tan

    Full Text Available Oral sex is widely used in human foreplay, but rarely documented in other animals. Fellatio has been recorded in bonobos Pan paniscus, but even then functions largely as play behaviour among juvenile males. The short-nosed fruit bat Cynopterus sphinx exhibits resource defence polygyny and one sexually active male often roosts with groups of females in tents made from leaves. Female bats often lick their mate's penis during dorsoventral copulation. The female lowers her head to lick the shaft or the base of the male's penis but does not lick the glans penis which has already penetrated the vagina. Males never withdrew their penis when it was licked by the mating partner. A positive relationship exists between the length of time that the female licked the male's penis during copulation and the duration of copulation. Furthermore, mating pairs spent significantly more time in copulation if the female licked her mate's penis than if fellatio was absent. Males also show postcopulatory genital grooming after intromission. At present, we do not know why genital licking occurs, and we present four non-mutually exclusive hypotheses that may explain the function of fellatio in C. sphinx.

  9. Plasma lipids and prothrombin time in rats fed palm oil and other commonly used fats in Egypt

    Hussein, Mona M.


    Full Text Available Sprague-Dawley rats were fed for a total period of 8 weeks on six diets that were different in the source of their fat content. The fat content was provided either, palm oil or palm olein or corn oil or hydrogenated fat, or frying palm oil and mixture of corn oil + hydrogenated fat in the ratio (1:1. The latter was given to the control group. Animals fed these various experimental diets showed statistically significant differences in serum cholesterol and serum triglycerides content among all group. Increased HDL-cholesterol content was evident in animals fed on palm-olein and palm oil. The frying oil fed group showed lowest HDL-cholesterol content. In these experiments palm olein fed animals showed highest ratio of HDL-cholesterol to total cholesterol while the lowest ratio was shown in rats fed on frying oil. Prothrombin (PT and activated partial thromboplastin time (PTT showed higher values In palm oil, palm olein and corn oil diets as compared to all groups with each other.

    Ratas Sprague-Dawley fueron alimentadas durante un periodo total de 8 semanas con seis dietas diferentes en su contenido graso. El contenido graso fue proporcionado por aceite de palma u oleína de palma o aceite de maíz o grasa hidrogenada o aceite de palma de fritura y mezcla de aceite de maíz + grasa hidrogenada en la relación (1:1. El último fue dado al grupo de control. Los animales alimentados con las diferentes dietas experimentales mostraron diferencias significativas estadísticamente en el contenido en colesterol y triglicéridos en suero entre todos los grupos. El aumento en contenido HDL-colesterol fue evidente en animales alimentados con oleína de palma y aceite de palma. El grupo alimentado con aceite de fritura mostró el más bajo contenido en HDL-colesterol. En estos experimentos, los animales alimentados con oleína de palma mostraron la mayor relación de HDL-colesterol a colesterol total, mientras que la relación más baja fue mostrada

  10. Prolonged activated prothromboplastin time and breed specific variation in haemostatic analytes in healthy adult Bernese Mountain dogs.

    Nikolic Nielsen, Lise; Wiinberg, Bo; Kjelgaard Hansen, Mads; Jensen, Asger Lundorf; Kristensen, Annemarie T


    Coagulation tests are often performed in dogs suspected of haemostatic dysfunction and are interpreted according to validated laboratory reference intervals (RIs). Breed specific RIs for haematological and biochemical analytes have previously been identified in Bernese Mountain dogs, but it remains to be determined if breed specific RIs are necessary for haemostasis tests. Activated prothromboplastin time (aPTT), prothrombin time (PT), selected coagulation factors, D-dimers, fibrinogen, von Willebrand factor and thromboelastography (TEG) were analyzed in healthy Bernese Mountain dogs using the CLSI model. Three analytes (aPTT, TEG [MA] and TEG [G]) were different according to the CLSI model. For aPTT the new RI was markedly different (0-100s). Whereas the new intervals for TEG (MA) and TEG (G) may be due to breed related biological variation, the cause of the prolonged RI for aPTT is at present uncertain. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Does point of care prothrombin time measurement reduce the transfusion of fresh frozen plasma in patients undergoing major surgery? The POC-OP randomized-controlled trial

    Alberio Lorenzo


    Full Text Available Abstract Background Bleeding is a frequent complication during surgery. The intraoperative administration of blood products, including packed red blood cells, platelets and fresh frozen plasma (FFP, is often live saving. Complications of blood transfusions contribute considerably to perioperative costs and blood product resources are limited. Consequently, strategies to optimize the decision to transfuse are needed. Bleeding during surgery is a dynamic process and may result in major blood loss and coagulopathy due to dilution and consumption. The indication for transfusion should be based on reliable coagulation studies. While hemoglobin levels and platelet counts are available within 15 minutes, standard coagulation studies require one hour. Therefore, the decision to administer FFP has to be made in the absence of any data. Point of care testing of prothrombin time ensures that one major parameter of coagulation is available in the operation theatre within minutes. It is fast, easy to perform, inexpensive and may enable physicians to rationally determine the need for FFP. Methods/Design The objective of the POC-OP trial is to determine the effectiveness of point of care prothrombin time testing to reduce the administration of FFP. It is a patient and assessor blind, single center randomized controlled parallel group trial in 220 patients aged between 18 and 90 years undergoing major surgery (any type, except cardiac surgery and liver transplantation with an estimated blood loss during surgery exceeding 20% of the calculated total blood volume or a requirement of FFP according to the judgment of the physicians in charge. Patients are randomized to usual care plus point of care prothrombin time testing or usual care alone without point of care testing. The primary outcome is the relative risk to receive any FFP perioperatively. The inclusion of 110 patients per group will yield more than 80% power to detect a clinically relevant relative risk

  12. [Evaluation of a new portable device for measuring prothrombin time-internatinal normalized ratio; comparison between the conventional method and the new CoagCheck XS].

    Yamamoto, K; Hashimoto, K; Sakamoto, Y; Okuyama, H; Kawada, N; Inoue, T


    We evaluated a new portable device (CoaguCheck XS) for measuring the prothrombin time-international normalized ratio (PT-INR) in 63 patients after cardiac surgery, and compared the results with those of the conventional method. There was a good correlation between the PT-INR values measured conventionally and those obtained with the CoaguCheck XS. This new device was easy to use, data were obtained rapidly, and the results were reliable. The CoaguCheck XS will be particularly useful for outpatients. PT-INR self-management is expected to be introduced as soon as health insurance coverage is obtained.

  13. Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II plus VII plus X activity in subjects infused with the drug. Influence of time and temperature

    Thorsen, S.; Teisner, A.; Jensen, S.A.;


    Objectives: The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences...

  14. Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II+VII+X activity in subjects infused with the drug. Influence of time and temperature

    Thorsen, Sixtus; Teisner, Ane; Jensen, Søren Astrup;


    OBJECTIVES: The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences...

  15. The prothrombin time/international normalised ratio (PT/INR) line: derivation of local INR with commercial thromboplastins and coagulometers – two independent studies

    Poller, Leon; Ibrahim, S.; Keown, M.


    Background: The WHO scheme for prothrombin time (PT) standardization has been limited in application, because of its difficulties in implementation, particularly the need for mandatory manual PT testing and for local provision of thromboplastin international reference preparations (IRP). Methods...... thromboplastins and coagulometers. INRs were compared with manual certified values with thromboplastin IRP from expert centres and in the second study also with INRs from local ISI calibrations. Results: In the first study with the PT/INR Line, 8.7% deviation from certified INRs was reduced to 1.1% with human.......5% with bovine/combined reagents with local ISI calibrations and to 2.9% with the PT/INR Line. Mean INR dispersion was reduced with all thromboplastins and automated systems using the PT/INR Line. Conclusions: The procedure using the PT/INR Line provides reliable INR derivation without the need for WHO ISI...

  16. Moderate superficial hypothermia prolongs bleeding time in humans.

    Romlin, B; Petruson, K; Nilsson, K


    In vitro and in vivo studies have shown that mild systemic hypothermia influences platelet adhesion and aggregation and coagulation reactions. We wanted to test the hypothesis that mild local hypothermia in healthy volunteers with preserved core temperature increased bleeding time. A secondary aim was to evaluate if local cooling influenced whole blood coagulation measured by thrombelastograph (TEG) in the same setting. Bleeding time was measured at the left volar forearm at a baseline skin temperature of 32 degrees C and after cooling to 30 degrees C and 28 degrees C in a water bath. Skin temperature was continuously measured by contact thermistors. Measurements of coagulation by TEG were performed at baseline skin temperature before cooling and after cooling to 28 degrees C skin temperature. Tympanic membrane temperature was continuously measured. Compared with baseline, bleeding time was significantly prolonged at 30 degrees C skin temperature and further prolonged at 28 degrees C skin temperature. No significant differences were measured in any of the TEG parameters. During the procedure, tympanic membrane temperature did not change. Lowering the skin temperature from 32 degrees C to 30 degrees C and 28 degrees C with a preserved core temperature more than doubled the bleeding time. Whole blood coagulation measured by TEG was not influenced by the local cooling. In addition to core temperature, local temperature may offer information in understanding the surgical site of bleeding.

  17. 21 CFR 866.5735 - Prothrombin immunological test system.


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prothrombin immunological test system. 866.5735 Section 866.5735 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... vitro coagulation studies classified under § 864.5425 of this chapter or prothrombin time tests...

  18. An evaluation of patient self-testing competency of prothrombin time for managing anticoagulation: pre-randomization results of VA Cooperative Study #481--The Home INR Study (THINRS).

    Dolor, Rowena J; Ruybalid, R Lynne; Uyeda, Lauren; Edson, Robert G; Phibbs, Ciaran; Vertrees, Julia E; Shih, Mei-Chiung; Jacobson, Alan K; Matchar, David B


    Prior studies suggest patient self-testing (PST) of prothrombin time (PT) can improve the quality of anticoagulation (AC) and reduce complications (e.g., bleeding and thromboembolic events). "The Home INR Study" (THINRS) compared AC management with frequent PST using a home monitoring device to high-quality AC management (HQACM) with clinic-based monitoring on major health outcomes. A key clinical and policy question is whether and which patients can successfully use such devices. We report the results of Part 1 of THINRS in which patients and caregivers were evaluated for their ability to perform PST. Study-eligible patients (n = 3643) were trained to use the home monitoring device and evaluated after 2-4 weeks for PST competency. Information about demographics, medical history, warfarin use, medications, plus measures of numeracy, literacy, cognition, dexterity, and satisfaction with AC were collected. Approximately 80% (2931 of 3643) of patients trained on PST demonstrated competency; of these, 8% (238) required caregiver assistance. Testers who were not competent to perform PST had higher numbers of practice attempts, higher cuvette wastage, and were less able to perform a fingerstick or obtain blood for the cuvette in a timely fashion. Factors associated with failure to pass PST training included increased age, previous stroke history, poor cognition, and poor manual dexterity. A majority of patients were able to perform PST. Successful home monitoring of PT with a PST device required adequate levels of cognition and manual dexterity. Training a caregiver modestly increased the proportion of patients who can perform PST.

  19. Therapeutic concordance of two portable monitors and two routine automatic oral anticoagulant monitoring systems using as reference the manual prothrombin time technique.

    Vacas, Marta; Lafuente, Pedro José; Unanue, Iciar; Santos, Mónica; Iriarte, Jose Antonio


    Two models of capillary blood prothrombin time (PT) monitoring systems were evaluated for analytical performance and then compared with two routine PT systems using the reference manual technique and a high-sensitivity thromboplastin. Two sets of 60 and 80 plasmas were analyzed from anticoagulated patients stabilized over 3 months in an INR range 2-3.5 for therapy. Capillary PT determination was performed in two portable monitors, CoaguChek S and CoaguChek PT (Roche Diagnostics), and plasma automatic methods were Neoplastine/STA (Diagnostics Stago) and PT-FibrinogenHsPlus/ACL7000 (Instrumental Laboratories). Thromboplastin Bilbao (TBi), an in-house high-sensitivity rabbit thromboplastin (ISI=1.08), recommended as the reference reagent by an External Spanish Oral Anticoagulant Quality Assessment, was used in the PT manual technique. The two monitors' coefficients of correlation with the reference system were 0.74 for CoaguChek S and 0.81 for CoaguChek PT. The automatic routine systems showed a correlation of 0.92 (Neoplastine/STA) and 0.91 (PT-FbHsPlus/ACL7000). Clinical agreement expressed as the percentage of simple correlation ranged between 75.0% (CoaguChek S) and 88.9% (Neoplastine/STA). The systems having the best kappa index with the manual technique were CoaguChek PT (71.9%) and the Neoplastine/STA system (73%). The routine PT management systems exhibited better correlation and percentage of concordance when using the TBi/manual technique than did the portable monitors, which moreover performed unequally in this regard.

  20. Amphiphilic vinyl polymers effectively prolong liposome circulation time in vivo.

    Torchilin, V P; Shtilman, M I; Trubetskoy, V S; Whiteman, K; Milstein, A M


    Newly synthesized amphiphilic polyacrylamide and poly(vinyl pyrrolidone), single terminus-modified with long-chain fatty acyl groups, are able to incorporate into the liposomal membrane, and similar to poly(ethylene glycol) prolong liposome circulation in vivo and decrease liposome accumulation in the liver. Protective efficacy of modified polymers increases with the increase in the length of acyl moiety and decreases for higher molecular weight polymers. The data on amphiphilic polymer-modified liposome biodistribution are presented.

  1. Risk factors for a prolonged operative time in a single-incision laparoscopic cholecystectomy

    Sato, Norihiro; Yabuki, Kei; Shibao, Kazunori; Mori, Yasuhisa; Tamura, Toshihisa; Higure, Aiichiro; Yamaguchi, Koji


    Background: A prolonged operative time is associated with adverse post-operative outcomes in laparoscopic surgery. Although a single-incision laparoscopic cholecystectomy (SILC) requires a longer operative time as compared with a conventional laparoscopic cholecystectomy, risk factors for a prolonged operative time in SILC remain unknown.

  2. Thrombin generation, ProC(®)Global, prothrombin time and activated partial thromboplastin time in thawed plasma stored for seven days and after methylene blue/light pathogen inactivation.

    Thiele, Thomas; Hron, Gregor; Kellner, Sarah; Wasner, Christina; Westphal, Antje; Warkentin, Theodore E; Greinacher, Andreas; Selleng, Kathleen


    Methylene blue pathogen inactivation and storage of thawed plasma both lead to changes in the activity of several clotting factors. We investigated how this translates into a global loss of thrombin generation potential and alterations in the protein C pathway. Fifty apheresis plasma samples were thawed and each divided into three subunits. One subunit was stored for 7 days at 4 °C, one was stored for 7 days at 22 °C and one was stored at 4 °C after methylene blue/light treatment. Thrombin generation parameters, ProC(®)Global-NR, prothrombin time and activated partial thromboplastin time were assessed on days 0 and 7. The velocity of thrombin generation increased significantly after methylene blue treatment (increased thrombin generation rate; time to peak decreased) and decreased after storage (decreased thrombin generation rate and peak thrombin; increased lag time and time to peak). The endogenous thrombin generation potential remained stable after methylene blue treatment and storage at 4 °C. Methylene blue treatment and 7 days of storage at 4 °C activated the protein C pathway, whereas storage at room temperature and storage after methylene blue treatment decreased the functional capacity of the protein C pathway. Prothrombin time and activated partial thromboplastin time showed only modest alterations. The global clotting capacity of thawed plasma is maintained at 4 °C for 7 days and directly after methylene blue treatment of thawed plasma. Thrombin generation and ProC(®)Global are useful tools for investigating the impact of pathogen inactivation and storage on the clotting capacity of therapeutic plasma preparations.

  3. Extracorporeal Free Flap Perfusion in Case of Prolonged Ischemia Time

    Taeger, C. D.; Präbst, K; Beier, J P; Meyer, A; Horch, R E


    Summary: In free flap surgery, a clinically established concept still has to be found for the reduction of ischemia-related cell damage in the case of prolonged ischemia. Although promising results using extracorporeal free flap perfusion in the laboratory have been published in the past, until now this concept has not yet paved its way into clinical routine. This might be due to the complexity of perfusion systems and a lack of standardized tools. Here, we want to present the results of the ...

  4. Local verification and assignment of mean normal prothrombin time and International Sensitivity Index values across various instruments: recent experience and outcome from North America.

    Tange, Julie I; Grill, Diane; Koch, Christopher D; Ybabez, Roxanne J; Krekelberg, Benjamin J; Fylling, Kara A; Wiese, Cynthia R; Baumann, Nikola A; Block, Darci R; Karon, Brad S; Chen, Dong; Pruthi, Rajiv K


    Warfarin dosing relies on accurate measurements of international normalized ratio (INR), which is calculated from the prothrombin time (PT), International Sensitivity Index international sensitivity index (ISI) of the thromboplastin, and the geometric mean of normal PT (MNPT). However, ISI assignments of certain reagent/instrument combinations are frequently unavailable, especially when the reagent and instrument are not from the same manufacturer. The effort to be in compliance with widely endorsed Clinical and Laboratory Standards Institute (CLSI) guidelines by locally verifying or assigning an ISI to an unsupported reagent/instrument combination is further hindered by the lack of US Food and Drug Administration (FDA)-approved certified plasmas designated for a particular reagent/instrument combination. The objectives of the study include development of a process to verify/assign ISI and MNPT of a single thromboplastin reagent from one manufacturer across multiple instruments including several from another manufacturer and across several campuses of a single institution, the Mayo Clinic. In this study, RecombiPlasTin 2G (R2G), was evaluated on the ACL TOP 700 (IL), STA-R Evolution, STA Compact, and STA Satellite. Random normal donor samples (n = 25) were used to verify/assign MNPT. A subset of the normal donors (n = 8) and 13 warfarin pools (INR range: 1.3-3.9), created from stable warfarin patient plasma, were used for ISI verification/assignment. The manufacturer's assigned ISI was first verified on the ACL TOP 700 (reference method), then assigned on three unsupported instruments using orthogonal regression analysis. The MNPT and manufacturer assigned ISI (11.0, 0.95) were verified on the ACL TOP 700 and subsequently assigned on the STA-R Evolution (11.6, 1.04); STA Compact (11.5, 1.02); and STA Satellite (10.9, 0.99). Linear correlations of the INR results from all the four instruments demonstrated an r2 > 0.99. This process provides a reproducible approach

  5. Intrauterine expression of prothrombin in the sprague-dawley rat.

    Phillippe, Mark; Wolff, David; Saunders, Trevania; Thomas, Leandra; Chapa, Jeffrey


    Thrombin appears to underlie myometrial contractions in response to intrauterine bleeding. In a similar fashion, thrombin generated within the uterus in the absence of active bleeding could also produce contractions. These studies sought to determine whether functionally active prothrombin is expressed in the pregnant and nonpregnant rat uterus. Uteri were obtained from proestrus/estrus and timed-pregnant Sprague-Dawley rats. Western blots were performed using antithrombin antibodies. Immunohistochemical studies were performed using the same antibodies along with the Vector Elite ABC kit. Qualitative reverse transcriptase-polymerase chain reaction studies were performed using rat prothrombin-specific oligonucleotide primers. In vitro uterine contraction studies were performed using Taipan snake venom (an exogenous prothrombinase) and components of the plasma prothrombinase complex (Factors Xa and V) with and without pretreatment with thrombin inhibitors (heparin or hirudin). The Western blots demonstrated prothrombin peptides in myometrial tissue from estrus and pregnant rats. The immunohistochemical studies confirmed prothrombin peptides in both the circular and longitudinal myometrium, along with the endometrium. The reverse transcriptase-polymerase chain reaction studies demonstrated prothrombin mRNA in the endometrium and placenta, but not in the myometrial smooth muscle. The Taipan snake venom stimulated a significant increase in contractions, which were suppressed by pretreatment with heparin and hirudin. The Factor Xa and V complex also significantly stimulated uterine contractions, which were likewise inhibited by hirudin. These studies provide evidence supporting the expression of functionally active prothrombin in the pregnant and nonpregnant rat uterus. Based on the presence of its mRNA, prothrombin appears to be synthesized in the endometrium and placenta; in contrast, the myometrial smooth-muscle cells appear to sequester preformed prothrombin. These

  6. Reversing Antisense Oligonucleotide Activity with a Sense Oligonucleotide Antidote: Proof of Concept Targeting Prothrombin.

    Crosby, Jeff R; Zhao, Chenguang; Zhang, Hong; MacLeod, A Robert; Guo, Shuling; Monia, Brett P


    The tissue half-life of second-generation antisense oligonucleotide drugs (ASOs) is generally longer than traditional small molecule therapeutics. Thus, a strategy to reverse the activity of antisense drugs is warranted in certain settings. In this study, we describe a strategy employing the administration of a complementary sense oligonucleotide antidote (SOA). As a model system we have chosen to target the coagulation factor and antithrombotic drug target, prothrombin, to assess the feasibility of this approach. ASO targeting mouse prothrombin specifically suppressed >90% hepatic prothrombin mRNA levels and circulating prothrombin protein in mice. These effects were dose- and time-dependent, and as expected produced predictable increases in anticoagulation activity [prothrombin time/activated partial thromboplastin time (PT/aPTT)]. Treatment with prothrombin SOAs resulted in a dose-dependent reversal of ASO activity, as measured by a return in prothrombin mRNA levels and thrombin activity, and normalization of aPTT and PT. The antithrombotic activity of prothrombin ASOs was demonstrated in a FeCl3-induced thrombosis mouse model, and as predicted for this target, the doses required for antithrombotic activity were also associated with increased bleeding. Treatment with SOA was able to prevent prothrombin ASO-induced bleeding in a dose-dependent manner. These studies demonstrate for the first time the utility of SOAs to selectively and specifically reverse the intracellular effects of an antisense therapy.

  7. The Effects of Breaking up Prolonged Sitting Time

    Benatti, Fabiana Braga; Ried-Larsen, Mathias


    on the electronic databases PUBMED and SCOPUS was independently conducted by two researchers. Only prospective intervention studies (controlled and uncontrolled) evaluating the effects of explicitly replacing sitting time with physical activity (including standing) on metabolic parameters as outcomes were included...

  8. Difficult OptEase Filter Retrievals After Prolonged Indwelling Times

    Van Ha, Thuong G., E-mail:; Kang, Lisa; Lorenz, Jonathan; Zangan, Steven; Navuluri, Rakesh; Straus, Christopher; Funaki, Brian [University of Chicago, Section of Interventional Radiology, Department of Radiology (United States)


    PurposeThe OptEase vena cave filter (Cordis, Piscataway, NJ) is commercially available as a retrievable or permanent filter with short recommended indwelling time, presumably due to extensive contact of the filter side struts with the inferior vena cava wall and subsequent neointimal hyperplasia leading to incorporation. Our purpose was to evaluate OptEase filter retrievals with a long indwelling time period that required unconventional retrieval techniques.Materials and MethodsWe retrospectively reviewed patients who underwent OptEase filter retrieval with long undwelling times requiring additional maneuvers for retrieval. Techniques used included rigid endobronchial forceps dissection and wire-through-loop snare. Each patient underwent postretrieval venogram to evaluate for possible complications. In addition, patients had clinical follow-up 2 weeks after the retrieval procedure.ResultsThere were three patients (2 women, 1 man; average age 64 years) who underwent OptEase filter retrieval. The mean indwelling time was 6.4 months. The indwelling filters were successfully retrieved. There were no complications. Postprocedural follow-up showed no clinical pathology.ConclusionUnconventional techniques aided in the retrieval of OptEase filters with long indwelling times.

  9. Clinical application of gradient echo sequences with prolonged repetition times

    Tiling, R.; Fink, U.; Deimling, M.; Bauer, W.M.; Yousry, T.; Krauss, B.


    Studies designed to optimise image contrasts of gradient echo sequences showed, that especially repetition times between 250 and 500 ms in combination with adequate echo times and flip angles provide new image contrasts. The clinical purpose of gradient echo sequences with longer TR was systematically evaluated in 450 patients. A major advantage of GE sequences was the low signal intensity of fat and bone tissue. On the other hand differnt pathologic changes showed a high signal intensity in comparison to T/sub 2/ weighted spin echo sequences as well. With the possibility of multiple slices GE sequences were of outstanding diagnostic value especially in MR of soft tissue and of the musculoskeletal system. T/sub 2/ weighted SE sequences provided no additional informations and could therefore be omitted in a great number of examinations.

  10. Sequential thrombosis and bleeding in a woman with a prolonged activated partial thromboplastin time

    Pearce Michael I


    Full Text Available Abstract Simultaneous or sequential haemorrhage and thrombosis in the presence of a prolonged activated partial thromboplastin time (aPTT is a rare occurrence: we describe the case a 37 year old lady who developed post-delivery deep vein thrombosis treated with low molecular heparin and warfarin followed a week later by extensive bruising over legs and forearms, a significant drop in haemoglobin and a very prolonged aPTT. Further tests revealed an acquired factor VIII inhibitor at 35 Bethesda Units. We discuss the clinical and laboratory implications and provide a literature review of simultaneous thrombophilia and haemophilia in the presence of a prolonged aPTT.

  11. Prolonged time to progression with fulvestrant for metastatic breast cancer.

    Mello, Celso A L; Chinen, Ludmilla T D; da Silva, Samantha Cabral Severino; do Nascimento Matias, Carolina; Benevides, Carlos Frederico; Gimenes, Daniel Luiz; Fanelli, Marcello F


    Although the incidence of breast cancer has been declining in recent years, the disease is still one of the leading causes of cancer deaths in women. Recently, breast cancer has been treated with innovative approaches that use hormone-sensitive therapies. This is because in at least one-third of breast cancers, estrogens mediated via the estrogen receptor pathway act as endocrine growth factors. Fulvestrant has been studied as both first- and second-line therapy for locally advanced and metastatic breast cancer, but few studies have shown its effect as third-line therapy alone. To observe the disease time to progression (TTP) obtained with fulvestrant when used on metastatic breast cancer as first-, second-, and also third-line therapy. We also aimed to correlate the TTP obtained with fulvestrant with hormone receptor, HER2 expression, and metastatic site. This was a cohort study that retrospectively examined medical records of 73 postmenopausal women with advanced breast cancer who were treated with fulvestrant (250 mg/month i.m. injection) and followed at the Department of Medical Oncology at Hospital do Cancer A. C. Camargo in São Paulo, Brazil from August 2003 to December 2006. The median TTP with fulvestrant was about 11 months. When used as the first-line therapy, TTP was about 13 months; when used as second-line, TTP was about 6 months; and when used as third-line, it was about 12 months. No statistically significant difference was observed regarding the therapy line. In patients with positive ER tumors, TTP was 11 months. No significant difference in TTP was observed in negative ER tumors (TTP = 10 months). In patients with positive PgR tumors, TTP was 13 months and for negative PgR, TTP was 6 months (P = 0.008). According to the HER2 status, the TTP was 5 months for HER2+ and 10 months for HER2-. Our findings indicate that fulvestrant is an effective alternative for treatment of metastatic breast cancer.

  12. Office workers' objectively assessed total and prolonged sitting time: Individual-level correlates and worksite variations

    Nyssa T. Hadgraft


    Full Text Available Sedentary behavior is highly prevalent in office-based workplaces; however, few studies have assessed the attributes associated with this health risk factor in the workplace setting. This study aimed to identify the correlates of office workers' objectively-assessed total and prolonged (≥30 min bouts workplace sitting time. Participants were 231 Australian office workers recruited from 14 sites of a single government employer in 2012–13. Potential socio-demographic, work-related, health-related and cognitive-social correlates were measured through a self-administered survey and anthropometric measurements. Associations with total and prolonged workplace sitting time (measured with the activPAL3 were tested using linear mixed models. Worksites varied significantly in total workplace sitting time (overall mean [SD]: 79% [10%] of work hours and prolonged workplace sitting time (42% [19%], after adjusting for socio-demographic and work-related characteristics. Organisational tenure of 3–5 years (compared to tenure >5 years was associated with more time spent in total and prolonged workplace sitting time, while having a BMI categorised as obese (compared to a healthy BMI was associated with less time spent in total and prolonged workplace sitting time. Significant variations in sitting time were observed across different worksites of the same employer and the variation remained after adjusting for individual-level factors. Only BMI and organisational tenure were identified as correlates of total and prolonged workplace sitting time. Additional studies are needed to confirm the present findings across diverse organisations and occupations.

  13. Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy

    Enko, Dietmar; Mangge, Harald; Münch, Andreas; Niedrist, Tobias; Mahla, Elisabeth; Metzler, Helfried; Prüller, Florian


    Introduction The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. Materials and methods Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5’-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. Results No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 – 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. Conclusions Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced. PMID:28392742

  14. A surface-adaptive nanocarrier to prolong circulation time and enhance cellular uptake.

    Cheng, Tangjian; Ma, Rujiang; Zhang, Yumin; Ding, Yuxun; Liu, Jinjian; Ou, Hanlin; An, Yingli; Liu, Jianfeng; Shi, Linqi


    Based on the protonation/deprotonation of poly(β-amino ester) (PAE), mixed-shell micelles (MSMs) with adaptive surfaces could rapidly and reversibly change surface properties to prolong circulation time in blood (pH 7.4) and enhance cellular uptake at tumor sites (pH 6.5).

  15. Prolonged Cycle Times and Schedule Growth in Defense Acquisition: A Literature Review


    2005. As of June 12, 2013: Harmon, Bruce R., Lisa M. Ward, and Paul R. Palmer, Assessing Acquisition...research_briefs/RB194.html 78 Prolonged Cycle Times and Schedule Growth in Defense Acquisition Lush, Mona , Office of the Under Secretary of Defense for

  16. A simple method to discriminate between beta(2)-glycoprotein I- and prothrombin-dependent lupus anticoagulants

    Simmelink, MJA; Derksen, RHWM; Arnout, J; De Groot, PG


    Lupus anticoagulants (LAC) are a heterogeneous group of autoantibodies that prolong phospholipid-dependent clotting assays. The autoantibodies that cause LAC activity are predominantly directed against beta(2)-glycoprotein I (beta(2)GPI) or prothrombin. In the present study, we describe a method to

  17. As time goes by: reasons and characteristics of prolonged episodes of mechanical restraint in forensic psychiatry.

    Gildberg, Frederik A; Fristed, Peter; Makransky, Guido; Moeller, Elsebeth H; Nielsen, Lea D; Bradley, Stephen K


    Evidence suggests the prevalence and duration of mechanical restraint are particularly high among forensic psychiatric inpatients. However, only sparse knowledge exists regarding the reasons for, and characteristics of, prolonged use of mechanical restraint in forensic psychiatry. This study therefore aimed to investigate prolonged episodes of mechanical restraint on forensic psychiatric inpatients. Documentary data from medical records were thematically analyzed. Results show that the reasons for prolonged episodes of mechanical restraint on forensic psychiatric inpatients can be characterized by multiple factors: "confounding" (behaviors associated with psychiatric conditions, substance abuse, medical noncompliance, etc.), "risk" (behaviors posing a risk for violence), and "alliance parameters" (qualities of the staff-patient alliance and the patients' openness to alliance with staff), altogether woven into a mechanical restraint spiral that in itself becomes a reason for prolonged mechanical restraint. The study also shows lack of consistent clinical assessment during periods of restraint. Further investigation is indicated to develop an assessment tool with the capability to reduce time spent in mechanical restraint.

  18. Children Experiencing First-Time or Prolonged Febrile Seizure Are Prone to Stress Hyperglycemia.

    Lee, Jeong-Yong; Kim, Jung-Heon; Cho, Hyung-Rae; Lee, Jong-Seung; Ryu, Jeong-Min; Yum, Mi-Sun; Ko, Tae-Sung


    The risk factors and clinical implications of stress hyperglycemia in children with febrile seizure remain uncertain. Among 479 children with febrile seizure, the prevalence of the stress hyperglycemia (blood glucose concentration ≥ 150 mg/dL) was 10.0%. Stress hyperglycemia group included larger proportion of first-time febrile seizure, prolonged febrile seizure, and smaller proportion of short febrile seizure in comparison with the non-stress hyperglycemia group. Stress hyperglycemia group demonstrated a lower pH and higher lactate levels than the non-stress hyperglycemia group. Multivariate analysis revealed that first-time febrile seizure (aOR = 3.741, P = .004) and prolonged febrile seizure (aOR = 12.855, P febrile seizure recurrence in the emergency department was not different between the groups. These findings suggest that children experiencing first-time or prolonged febrile seizure are prone to stress hyperglycemia, and this can be related to febrile seizure severity. However, stress hyperglycemia is not predictive of early febrile seizure recurrence in the emergency department. © The Author(s) 2015.

  19. Effect of prolonging radiation delivery time on retention of gammaH2AX

    Duzenli Cheryl


    Full Text Available Abstract Background and purpose Compared to conventional external beam radiotherapy, IMRT requires significantly more time to deliver the dose. Prolonging dose delivery potentially increases DNA repair which would reduce the biological effect. We questioned whether retention of γH2AX, a measure of lack of repair of DNA damage, would decrease when dose delivery was protracted. Materials and methods Exponentially growing SiHa cervical carinoma cells were irradiated with 6 MV photons in a water tank using a VarianEX linear accelerator. Cells held at 37°C received 2 Gy in 0.5 min and 4 Gy in 1 min. To evaluate effect of dose delivery prolongation, 2 and 4 Gy were delivered in 30 and 60 min. After 24 h recovery, cells were analyzed for clonogenic survival and for residual γH2AX as measured using flow cytometry. Results Increasing the dose delivery time from 0.5 or 1 min to 30 or 60 min produced a signficant increase in cell survival from 0.45 to 0.48 after 2 Gy, and from 0.17 to 0.20 after 4 Gy. Expression of residual γH2AX decreased from 1.27 to 1.22 relative to background after 2 Gy and 1.46 to 1.39 relative to background after 4 Gy, but differences were not statistically significant. The relative differences in the slopes of residual γH2AX versus dose for acute versus prolonged irradiation bordered on significant (p = 0.055, and the magnitude of the change was consistent with the observed increase in surviving fraction. Conclusion These results support the concept that DNA repair underlies the increase in survival observed when dose delivery is prolonged. They also help to establish the limits of sensitivity of residual γH2AX, as measured using flow cytometry, for detecting differences in response to irradiation.

  20. Anatomical Location of Pathology Is Predictive of Prolonged Fluoroscopy Time During ERCP: A Multicenter American Study.

    Alkhatib, Amer A; Abdel Jalil, Ala A; Faigel, Douglas O; Pannala, Rahul; Crowell, Michael; Harrison, M E


    Different factors have been associated with prolonged fluoroscopy time (FT) during endoscopic retrograde cholangiopancreatography (ERCP). We hypothesize that FT depends on both the anatomical location of the pathology managed during ERCP and the complexity of the ERCP. Three centers participated in a retrospective multi-center cohort study. Data on patient demographics, ERCP complexity, and the location of pathology were collected. The relationships between FT and the location of pathology, ERCP complexity, patient demographics, and ERCP maneuvers, respectively, were analyzed. Prolonged FT was defined as a FT > 10 min. A total of 442 cases underwent ERCP in three different centers (301 cases, 76 cases, and 65 cases in centers A, B, and C, respectively) by six endoscopists. The median FT for all cases was 282 (range 8-3,516) s. Mean FT increased progressively according to anatomical location in the order extrahepatic cases {n = 298; mean FT 292 [95 % confidence interval (CI) 263-322] s}, pancreatic cases [n = 27; mean FT 359 (95 % CI 200-517) s], and intrahepatic cases [n = 117; mean FT 736 s (95 % CI 635-836) s]. Mean FT increased progressively with the complexity scale, with mean FT for Grade I, 218 (95 % CI 138-299) s; Grade II, 295 (95 % 261-329) s; Grade III, 586 (95 % CI 508-663) s; Grade IV, 636 (95 % CI 437-834) s. Multivariable analysis confirmed that prolonged FT was independently associated with anatomical location of the targeted pathology during ERCP-but not with ERCP complexity and endoscopy center. Prolonged FT during ERCP is associated most strongly with intrahepatic cases. FT can be used most effectively as a quality measure if it is stratified according to presence or absence of intrahepatic cases.

  1. Needle Thoracostomy for Patients with Prolonged Transport Times: A Case-control Study.

    Weichenthal, Lori; Crane, Desiree Hansen; Rond, Luke; Roche, Conal


    Introduction The use of prehospital needle thoracostomy (NT) is controversial. Some studies support its use; however, concerns exist regarding misplacement, inappropriate patient selection, and iatrogenic injury. Even less is known about its efficacy in situations where there is a delay to definitive care. Hypothesis/Aim To determine any differences in survival of patients who underwent NT in the setting of prolonged versus short transport times, and to describe differences in mechanisms and complications between the two groups. This was a retrospective, matched, case-control study of trauma patients in a four county Emergency Medical Service (EMS) system from April 1, 2007 through April 1, 2013. This system serves an urban, rural, and wilderness catchment area. A prehospital database was queried for all patients in whom NT was performed, identifying 182 patients. When these calls were limited to those with prolonged transport times, the search was narrowed to 32 cases. A matched control group, based on age and gender, with short transport times was then created as a comparison. Data collected from prehospital and hospital records included: demographics; mechanism of injury; call status; response to NT; and final outcome. Univariate and multivariate analyses were conducted, as appropriate, to assess the primary outcome of survival and to further elucidate the descriptive data. There was no difference in survival between the case and control groups, either when evaluated with univariate (34% vs 25%; P=.41) or multivariate (odds ratio=0.99; 95% CI, 0.96-1.02; P=.57) analyses. Blunt trauma was the most common mechanism in both groups, but penetrating trauma was more common in the control group (30% vs 9%; P=.003). Patients in the control group were also more likely to have no vital signs on initial assessment (62% vs 31%; P=.003). More patients in the case group were described as having clinical improvement after NT (34% vs 19%; P=.03). No complications of NT were

  2. Parsley extract inhibits in vitro and ex vivo platelet aggregation and prolongs bleeding time in rats.

    Gadi, Dounia; Bnouham, Mohamed; Aziz, Mohammed; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Legrand, Chantal; Lafeve, Françoise Fauvel; Mekhfi, Hassane


    Many cardiovascular diseases are associated with an increase in blood platelet activity. In Morocco, parsley (Petroselinum crispum, Apiaceae) is one of the medicinal herbs used to treat cardiovascular diseases such as arterial hypertension. In this study, crude aqueous extract (CAE) of parsley was evaluated for its anti-platelet activity in experimental animals on platelet aggregation in vitro and ex vivo; and on bleeding time in vivo. The in vitro aggregation was monitored after pre-incubation of platelets with CAE. The bleeding time and ex vivo aggregation were performed after oral treatment. CAE inhibited dose dependently platelet aggregation in vitro induced by thrombin, ADP, collagen and epinephrine. The oral administration of CAE (3g/kg) inhibited significantly (p<0.001) platelet aggregation ex vivo and prolonged bleeding time (p<0.001) without changes in the platelet amount. The prolongation of bleeding time by CAE may be attributed to the observed inhibition of platelet aggregation. These effects could be related in part to the polyphenolic compounds present in the extract. These results support the hypothesis that the dietary intake of parsley may be benefit in the normalization of platelet hyperactivation, in the nutritional prevention of cardiovascular diseases and are potentially interesting in the development of new prevention strategies.

  3. Valores de referência do tempo de protrombina (TP e tempo de tromboplastina parcial ativada (TTPa em cães Reference ranges of prothrombin time (PT and activated partial thromboplastin time (aPTT in dogs

    Sonia Terezinha dos Anjos Lopes


    Full Text Available Os fatores de coagulação são parte integrante da hemostasia normal, e tanto as coagulopatias hereditárias como adquiridas que envolvem este sistema são de grande importância veterinária, geralmente evidenciadas por manifestações clínicas, tais como, petéquias, equimoses, hematomas e sangramentos tardios. O presente trabalho teve por objetivo a determinação dos valores de referência do tempo de protrombina (TP e tempo de tromboplastina parcial ativada (TTPa, por métodos manuais. Para tanto, utilizou-se "kits" para dosagens humanas, devido à inexistência de produtos similares de uso específico veterinário. Foram utilizados 40 cães clinicamente sadios, sem raça definida, machos ou fêmeas, de diferentes idades. As amostras sanguíneas foram de 2,5ml cada, colhidas por venopunção cefálica e acondicionadas em tubos de centrífuga contendo 0,25ml de citrato de sódio a 3,8%. O plasma foi imediatamente separado por centrifugação e as determinações de TP e TTPa foram realizadas utilizando-se "kits" comerciais "HemoStat Thromboplastin-SIª" e "HemoStat aPTT-El b", respectivamente. Os resultados obtidos foram de 6,87 ± 1,4 segundos para o TP com valores mínimo e máximo de 4,07 e 9,67, respectivamente, e de 15,10 ± 1,6 segundos para TTPa com valores mínimo e máximo de 11,9 e 18,3, respectivamente. Conclui-se, que os valores obtidos neste trabalho podem ser utilizados como referência. Os reagentes utilizados para plasma humano podem ser empregados para o plasma de cães.The coagulation factors are part of normal hemostasis, and both hereditary and acquired coagulopathies that involve this system have an important role in veterinary medicine, generally evidenced by clinical signs such as: petechias, ecchymosis, hematomas and late hemorrhagies. The objective of this experiment was to determine reference range values of prothrombin time (PT and activated partial thromboplastin time (aPTT, for manual methods. Human commercial

  4. Risk factors for prolonged operative time in single-incision laparoscopic cholecystectomy

    Cheon, Seong Uk; Moon, Ju Ik; Choi, In Seok


    Purpose We performed 3-channel single incision laparoscopic cholecystectomy (SILC) in earlier period of this study and modified our method to 4-channel SILC using a snake retractor for better operative field in later period. This study has been designed to evaluate the risk factors for prolonged operative time in SILC. Methods From April 2010 to August 2014, 323 cases of 3-channel SILC (Konyang standard method [KSM] group) and 399 cases of 4-channel SILC (modified KSM [mKSM] group) using a sn...

  5. Prolonged in vivo circulation time by zwitterionic modification of magnetite nanoparticles for blood pool contrast agents.

    Xiao, Wangchuan; Lin, Jiang; Li, Mingli; Ma, Yongjie; Chen, Yuxin; Zhang, Chunfu; Li, Dan; Gu, Hongchen


    Long circulation time is critical for blood pool contrast agents used in high-resolution magnetic resonance angiography. For iron oxide particle contrast agents, size and surface properties significantly influence their in vivo performance. We developed a novel long-circulating blood pool contrast agent by introducing zwitterionic structure onto the particle surface. Zwitterionic structure was fabricated by 3-(diethylamino)propylamine (DEAPA) grafted onto the surface of ployacrylic acid coated magnetite nanoparticles via EDC/NHS [N-(3-dimethylaminopropyl)-N'-ethylcarbo-diimide hydrochloride/N-hydroxysuccinimide] coupling chemistry. Zwitterionic particles demonstrated five times lower macrophage cell uptake than the original particles and low cell toxicity. Magnetic resonance angiography indicated that zwitterionic nanoparticles had much longer in vivo circulation time than the original particles and were an ideal candidate for blood pool contrast agent. We suppose that zwitterionic modification by DEAPA and EDC/NHS can be used generally for coating nanoparticles with carboxyl surface and to prolong their circulating time.

  6. Avaliação da determinação do tempo de protrombina em amostras de sangue colhidas por duas diferentes técnicas Evaluation of determination of prothrombin time in blood samples using two different collection techniques

    Paulo Roberto de Melo Reis


    Full Text Available O presente trabalho tem como objetivo avaliar a interferência de diferentes técnicas de coleta sanguínea na determinação do tempo de protrombina. Duas técnicas de coleta foram utilizadas: uma, realizada pelo sistema a vácuo; a outra, realizada mediante aspiração manual com seringa de plástico. Os valores obtidos na determinação do tempo de protrombina provenientes das duas técnicas de coleta foram comparados. Foram analisadas amostras de pacientes que apresentavam tempo de protrombina normais e anormais por estarem em tratamento oral com medicação anticoagulante. A conclusão foi que o processo de coleta utilizando tanto o sistema a vácuo como a aspiração manual com seringa de plástico não interfere no resultado do teste, e os valores obtidos, comparando-se os dois métodos de coleta, não apresentaram diferenças estatisticamente significativas.The objective of the present study is to evaluate the interference of different blood collection techniques in determining prothrombin time. Two collection techniques were used. One of them uses the vacuum system and the other, manual aspiration using plastic syringe. The obtained values of determination of prothrombin time from these two techniques were compared. We analyzed patients’ samples that presented normal and non-normal prothrombin time owing to oral treatment with anticoagulant medication. The conclusion was that the collection processes using either vacuum system or manual aspiration with plastic syringe to obtain samples destined to the prothrombin time analysis do not interfere in the test result and the obtained values. In comparing both collecting techniques we did not find any significant statistical differences.

  7. A Parallelized Pumpless Artificial Placenta System Significantly Prolonged Survival Time in a Preterm Lamb Model.

    Miura, Yuichiro; Matsuda, Tadashi; Usuda, Haruo; Watanabe, Shimpei; Kitanishi, Ryuta; Saito, Masatoshi; Hanita, Takushi; Kobayashi, Yoshiyasu


    An artificial placenta (AP) is an arterio-venous extracorporeal life support system that is connected to the fetal circulation via the umbilical vasculature. Previously, we published an article describing a pumpless AP system with a small priming volume. We subsequently developed a parallelized system, hypothesizing that the reduced circuit resistance conveyed by this modification would enable healthy fetal survival time to be prolonged. We conducted experiments using a premature lamb model to test this hypothesis. As a result, the fetal survival period was significantly prolonged (60.4 ± 3.8 vs. 18.2 ± 3.2 h, P < 0.01), and circuit resistance and minimal blood lactate levels were significantly lower in the parallel circuit group, compared with our previous single circuit group. Fetal physiological parameters remained stable until the conclusion of the experiments. In summary, parallelization of the AP system was associated with reduced circuit resistance and lactate levels and allowed preterm lamb fetuses to survive for a significantly longer period when compared with previous studies.

  8. Prolonged clot lysis time increases the risk of a first but not recurrent venous thrombosis.

    Karasu, Alev; Baglin, Trevor P; Luddington, Roger; Baglin, Caroline A; van Hylckama Vlieg, Astrid


    The role of the fibrinolytic system in the development of venous thrombosis (VT) is unclear. We studied the risk of first and recurrent VT associated with reduced fibrinolysis, as measured by clot lysis time (CLT). We also studied the relationship between CLT and thrombin generation to determine if any relationship between CLT and VT was affected by thrombin generation. Analyses were performed in the Thrombophilia Hypercoagulability Environmental risk for Venous Thromboembolism Study, a two-centre population-based case-control study, including 579 patients and 338 controls, with patients followed from the event to determine incidence of recurrent VT. Hypofibrinolysis was associated with a 1·8-fold increased risk of a first VT [95% confidence interval (CI) 1·2-2·7]. Adjustment for sex, age, study location and Endogenous Thrombin Potential (ETP) did not change the result. The risk of VT was 2·9-fold increased when the 90th percentiles of prolonged CLT and high ETP were combined, with the highest risk for unprovoked first events (Odds Ratio = 4·2, 95% CI 1·3-13·5). In the follow-up study the Hazard Ratio for a recurrent VT associated with hypofibrinolysis was 1·5 (95% CI 0·9-2·6). A weak dose response effect was observed in relation to prolongation of CLT and recurrent VT. Although hypofibrinolysis constitutes a risk factor for a first VT, an association with recurrence is, at best, weak.

  9. MASP-1 Induced Clotting--The First Model of Prothrombin Activation by MASP-1.

    Lorenz Jenny

    Full Text Available Mannan-binding lectin-associated serine protease-1 (MASP-1, a protein of the complement lectin pathway, resembles thrombin in terms of structural features and substrate specificity. Due to its interplay with several coagulation factors, it has the ability to induce fibrin clot formation independent of the usual coagulation activation pathways. We have recently shown that MASP-1 activates prothrombin and identified arginine (R 155, R271, and R393 as potential cleavage sites. FXa cleaves R320 instead of R393, and thrombin cleaves R155 and R284 in prothrombin. Here we have used three arginine-to-glutamine mutants of prothrombin, R271Q, R320Q, R393Q and the serine-to-alanine active site mutant S525A to investigate in detail the mechanism of MASP-1 mediated prothrombin activation. Prothrombin wildtype and mutants were digested with MASP-1 and the cleavage products were analysed by SDS-PAGE and N-terminal sequencing. A functional clotting assay was performed by thrombelastography. We have found that MASP-1 activates prothrombin via two simultaneous pathways, either cleaving at R271 or R393 first. Both pathways result in the formation of several active alternative thrombin species. Functional studies confirmed that both R393 and R320 are required for prothrombin activation by MASP-1, whereas R155 is not considered to be an important cleavage site in this process. In conclusion, we have described for the first time a detailed model of prothrombin activation by MASP-1.

  10. Influence of prolonged setting time on permanent deformation of elastomeric impression materials.

    Balkenhol, Markus; Haunschild, Sylvia; Erbe, Christina; Wöstmann, Bernd


    Upon removal, tear forces occur in various areas of an impression. As a result, thin sulcus details may be permanently deformed, affecting the impression's accuracy. The purpose of this study was to investigate the effect of the chemistry and prolonged setting time on the permanent deformation of light-body impression materials after stretching. A dumbbell-shaped mold (2 mm x 4 mm x 75 mm) was used to prepare specimens (n=20) of 6 different impression materials (Affinis Light Body, Aquasil Ultra XLV, Express 2 Light Body Flow Quick, Flexitime Correct Flow, P2 Polyether Light, and Impregum Garant L DuoSoft). After water storage (35 degrees C), either for the manufacturer's suggested setting time or for 5 minutes, specimens were stretched by 80% using a universal testing machine at a crosshead speed of 200 mm/min. The permanent deformation (Deltal (%)) was determined after 2 hours of storage in ambient conditions. A 2-way ANOVA followed by a Games-Howell test was used to analyze the influence of material and storage time (alpha=.05). Polyether materials showed a significantly higher permanent deformation (Deltal>4% to 5%) than vinyl polysiloxane materials (P<.05). Extending the manufacturer's suggested setting time resulted in clinically relevant improvements in elastic recovery for products with a polyether backbone only. Increasing the setting time might be necessary for impression materials with a polyether backbone to improve elastic recovery.

  11. The design of an energy harvesting device for prolonging the working time of DC equipment

    Wen, Yayuan; Deng, Huaxia; Zhang, Jin; Yu, Liandong


    Energy harvesting (EH) derives from the idea of converting the ambient energy into electric energy, which can solve the problem of DC supply for some electronic equipment. PZT is a typical piezoelectric material of inorganic, which has been developed as EH devices to transfer ambient vibration energy into electric energy. However, these PZT devices require relatively violent excitation, and easy to be fatigue fracture under the resonance condition. In this paper, PVDF, which is a kind of soft piezoelectric polymer, is adopted for developing transducer. The PVDF devices are flexible and have longer life time than PZT devices under the harmonic environment. The EH researches are mainly focused on the development of energy transfer efficiency either by the mechanical structure of transducer or the improvement of circuit. However, the practicality and stability of the EH devices are important in the practical engineering applications. In this paper, a charge amplifier is introduced in the circuit in order to guarantee the stability of the battery charging under small ambient vibration conditions. The model of the mechanical structure of PVDF and the electric performance of circuit are developed. The experimental results and simulation show that the stability of battery charging is improved and the working time of DC equipment is prolonged.

  12. 南通市区黄胸鼠和褐家鼠凝血酶原时间测定分析%Prothrombin time determination of commensal rodents in Nantong city

    王智泉; 章士军


    目的 测定和分析南通市黄胸鼠和褐家鼠凝血酶原时间(PT).方法 PT测定采用仪器法,PT采用国际标准化比值(INR)表示.结果 黄胸鼠、褐家鼠及对照大白鼠的INR平均值分别为0.97、1.40和0.88;方差分析表明,黄胸鼠和褐家鼠之间的差异有统计学意义(t=0.426,P<0.05);褐家鼠和大白鼠之间的差异亦有统计学意义(t=-0.527,P<0.05);黄胸鼠和大白鼠之间差异无统计学意义(t=-0.101,P>0.05).崇川区与开发区的褐家鼠INR值经成组设计t检验差异有统计学意义(t=4.026,P<0.01),崇川区与港闸区的黄胸鼠经成组设计t检验差异无统计学意义(t=0.601,P>0.05).结论 实验所测得的黄胸鼠及褐家鼠INR值范围分别为0.60~1.92和0.84~2.29,PT值有性别、鼠种、区域间差异.%Objective To determine the prothrombin time (PT) of commensal rodents in Nantong city. Methods The instrument method was used for the determination of PT, which was expressed by international normalized ratio (INR). Results The average INR of Rattus tanezumi, R. Norvegicus and the laboratory rats was 0.97, 1.40 and 0.88 respectively. Statistical analysis showed that there was a significant difference in the INR between R. Tanezumi and R. Norvegicus (t = 0A26, P0.05) found. Also, a significant difference existed in the INR of R. Norvegicus from Chongchuan district and those from the development zone (? = 4.026, P0.05). Conclusion The INR of R. Tanezumi and R. Norvegicus is 0.60-1.92 and 0.84-2.29 respectively, with a difference in PT value between different genders, species and districts.

  13. Late-responding normal tissue cells benefit from high-precision radiotherapy with prolonged fraction delivery times via enhanced autophagy

    Yao, Qiwei; Zheng, Rong; Xie, Guozhu; Liao, Guixiang; Du, Shasha; Ren, Chen; Li, Rong; Lin, Xiaoshan; Hu, Daokun; Yuan, Yawei


    High-precision radiotherapy (HPR) has established its important role in the treatment of tumors due to its precise dose distribution. Given its more complicated delivery process, HPR commonly requires more fraction delivery time (FDT). However, it is unknown whether it has an identical response of prolonged FDT on different normal tissues. Our results showed that fractionated irradiation with prolonged FDTs (15, 36, and 50 minutes) enhanced cell surviving fractions for normal tissue cells compared with irradiation with an FDT of 2 minutes. However, the late-responding normal cell line HEI-OC1 was more responsive to prolonged FDTs and demonstrated higher surviving fractions and significantly decreased apoptosis and DNA damage compared to the acute-responding normal cell line HaCaT. Increased autophagy mediated via the ATM-AMPK pathway was observed in HEI-OC1 cells compared with HaCaT cells when irradiated with prolonged FDTs. Furthermore, treatment with the autophagy inhibitor 3-MA or ATM inhibitor KU55933 resulted in enhanced ROS accumulation and attenuation of the effect of prolonged FDT-mediated protection on irradiated HEI-OC1 cells. Our results indicated that late-responding normal tissue cells benefitted more from prolonged FDTs compared with acute-responding tissue cells, which was mainly attributed to enhanced cytoprotective autophagy mediated via the ATM/AMPK signaling pathway. PMID:25766900

  14. Impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy on hepatocellular carcinoma cell killing

    Xiao-Kang Zheng; Long-Hua Chen; Xiao Yan; Hong-Mei Wang


    AIM: To explore the impact of prolonged fraction dosedelivery time modeling intensity-modulated radiation therapy (IMRT) on cell killing of human hepatocellular carcinoma (HCC) HepG2 and Hep3B cell lines.METHODS: The radiobiological characteristics of human HCC HepG2 and Hep3b cell lines were studied with standard clonogenic assays, using standard linear-quadratic model and incomplete repair model to fit the dose-survival curves. The identical methods were also employed to investigate the biological effectiveness of irradiation protocols modeling clinical conventional fractionated external beam radiotherapy (EBRT, fraction delivery time 3 min) and IMRT with different prolonged fraction delivery time (15, 30, and 45 min). The differences of cell surviving fraction irradiated with different fraction delivery time were tested with paired t-test. Factors determining the impact of prolonged fraction delivery time on cell killing were analyzed.RESULTS: The α/β and repair half-time (T1/2) of HepG2and Hep3b were 3.1 and 7.4 Gy, and 22 and 19 min respectively. The surviving fraction of HepG2 irradiated modeling IMRT with different fraction delivery time was significantly higher than irradiated modeling EBRT and the cell survival increased more pronouncedly with the fraction delivery time prolonged from 15 to 45 min,while no significant differences of cell survival in Hep3b were found between different fraction delivery time protocols.CONCLUSION: The prolonged fraction delivery time modeling IMRT significantly decreased the cell killing in HepG2 but not in Hep3b. The capability of sub-lethal damage repair was the predominant factor determining the cell killing decrease. These effects, if confirmed by clinical studies, should be considered in designing IMRT treatments for HCC.

  15. Negative impact of prolonged cold storage time before machine perfusion preservation in donation after circulatory death kidney transplantation.

    Paloyo, Siegfredo; Sageshima, Junichiro; Gaynor, Jeffrey J; Chen, Linda; Ciancio, Gaetano; Burke, George W


    Kidney grafts are often preserved initially in static cold storage (CS) and subsequently on hypothermic machine perfusion (MP). However, the impact of CS/MP time on transplant outcome remains unclear. We evaluated the effect of prolonged CS/MP time in a single-center retrospective cohort of 59 donation after circulatory death (DCD) and 177 matched donation after brain death (DBD) kidney-alone transplant recipients. With mean overall CS/MP times of 6.0 h/30.0 h, overall incidence of delayed graft function (DGF) was higher in DCD transplants (30.5%) than DBD transplants (7.3%, P time (P = 0.0002), male recipient (P = 0.02), and longer MP time (P = 0.08) were associated with higher DGF incidence. In evaluating the joint effects of donor type (DBD vs. DCD), CS time (time (time ≥36 h (P = 0.003) across each donor type and CS time stratum, whereas the unfavorable effect of CS time ≥6 h (P = 0.01) is primarily seen among DCD recipients. Prolonged cold ischemia time had no unfavorable effect on renal function or graft survival at 12mo post-transplant. Long CS/MP time detrimentally affects early DCD/DBD kidney transplant outcome when grafts were mainly preserved by MP; prolonged CS time before MP has a particularly negative impact in DCD kidney transplantation.

  16. The effect of dehydration on muscle metabolism and time trial performance during prolonged cycling in males.

    Logan-Sprenger, Heather M; Heigenhauser, George J F; Jones, Graham L; Spriet, Lawrence L


    This study combined overnight fluid restriction with lack of fluid intake during prolonged cycling to determine the effects of dehydration on substrate oxidation, skeletal muscle metabolism, heat shock protein 72 (Hsp72) response, and time trial (TT) performance. Nine males cycled at ~65% VO2peak for 90 min followed by a TT (6 kJ/kg BM) either with fluid (HYD) or without fluid (DEH). Blood samples were taken every 20 min and muscle biopsies were taken at 0, 45, and 90 min of exercise and after the TT. DEH subjects started the trial with a -0.6% BM from overnight fluid restriction and were dehydrated by 1.4% after 45 min, 2.3% after 90 min of exercise, and 3.1% BM after the TT. There were no significant differences in oxygen uptake, carbon dioxide production, or total sweat loss between the trials. However, physiological parameters (heart rate [HR], rate of perceived exertion, core temperature [Tc], plasma osmolality [Posm], plasma volume [Pvol] loss, and Hsp72), and carbohydrate (CHO) oxidation and muscle glycogen use were greater during 90 min of moderate cycling when subjects progressed from 0.6% to 2.3% dehydration. TT performance was 13% slower when subjects began 2.3% and ended 3.1% dehydrated. Throughout the TT, Tc, Posm, blood and muscle lactate [La], and serum Hsp72 were higher, even while working at a lower power output (PO). The accelerated muscle glycogen use during 90 min of moderate intensity exercise with DEH did not affect subsequent TT performance, rather augmented Tc, RPE and the additional physiological factors were more important in slowing performance when dehydrated.

  17. Enhanced Diagnostic Yield with Prolonged Small Bowel Transit Time during Capsule Endoscopy

    Jonathan M. Buscaglia, Sumit Kapoor, John O. Clarke, Juan Carlos Bucobo, Samuel A. Giday, Priscilla Magno, Elaine Yong, Gerard E. Mullin


    Full Text Available Background: The effect of small bowel transit time (SBTT on diagnostic yield during capsule endoscopy (CE has not been previously evaluated. Our study aim was to assess the effect of SBTT on the likelihood of detecting intestinal pathology during CE. Methods: We reviewed collected data on CE studies performed at Johns Hopkins Hospital from January 2006 to June 2007. In patients investigated for anemia or obscure bleeding, the following lesions were considered relevant: ulcers, erosions, AVMs, red spots, varices, vascular ectasias, and presence of blood. In patients with diarrhea or abdominal pain, ulcers, erosions, and blood were considered relevant. Age, gender, study indication, hospital status, and quality of bowel preparation were identified as candidate risk factors affecting SBTT. Univariate logistic and linear regression analyses were performed to study the effect of SBTT on diagnostic yield. Results: Total of 212 CE studies were analyzed; most were in outpatients (n=175, 82.9% and with excellent bowel preparation (n=177, 83.5%. Mean SBTT was 237.0min (3.9hrs. Age, gender, bowel prep, hospital status, and study indication did not significantly affect SBTT. However, increased SBTT was independently associated with increased diagnostic yield; OR=1.7 in SBTT=2-4hr (p=0.41, OR=1.8 in SBTT=4-6hrs (p=0.30, OR=9.6 in SBTT=6-8hrs (p=0.05. Conclusion: Prolonged SBTT during CE (>6 hr is associated with an increased diagnostic yield. This may be due to a positive effect on image quality during a “slower” study. The use of promotility agents may adversely affect the ability of CE to detect significant intestinal pathology.

  18. Implementation of a Prolonged Infusion Guideline for Time-Dependent Antimicrobial Agents at a Tertiary Academic Medical Center.

    Hohlfelder, Benjamin; Kubiak, David W; Degrado, Jeremy R; Reardon, David P; Szumita, Paul M

    Administration of time-dependent beta-lactam antibiotic as a prolonged infusion may maximize the pharmacodynamic target of time above the minimum inhibitory concentration. We describe the implementation of a prolonged infusion at a tertiary academic medical center, and a 1-year compliance analysis with the guideline. After performing a thorough literature search, a guideline was developed by members of the Department of Infectious Diseases and Department of Pharmacy. Approval and endorsement of the guideline was obtained by the Antimicrobial Subcommittee and Pharmacy and Therapeutics Committee. Physical champions were instrumental in the implementation of the guideline institution-wide. We then performed a 1-year retrospective analysis of guideline compliance from January 1, 2011 to December 31, 2011. Noncompliant administrations were obtained from smart infusion pumps. The total number of doses administered was taken from pharmacy information resources. In total, nearly 85,000 time-dependent doses were administered. Compliance with the prolonged infusion guideline was 89%. Rates of compliance did not significantly differ between medications (P = 0.555). Obtaining support from key stakeholders in collateral services and institutional leadership was vital for the success of this guideline. Compliance with the guideline 1 year after implementation was high. Implementation of a prolonged infusion guideline is feasible with institutional support and motivation.

  19. Impact of Azithromycin on Pregnancy Prolongation in Women at Risk of Preterm Labor: A Time-to-Event Analysis.

    Goyer, Isabelle; Ferland, Gabrielle; Ruo, Ni; Morin, Caroline; Brochet, Marie-Sophie; Morin, Lucie; Ferreira, Ema


    Since 2006, the empiric use of azithromycin in women at risk of premature birth has become prevalent in our institution without any evidence of its efficacy. Although antibiotics can prolong pregnancy in preterm prolonged rupture of membranes, no published data are available for women with intact membranes. To describe the purpose of adding azithromycin to the usual treatments (cerclage, tocolysis, rest, etc.) to prolong pregnancy in women with intact membranes who are at risk of or already in preterm labour. A retrospective observational cohort study was done at a Mother-Child University Hospital Centre. Patients admitted to obstetric ward who received azithromycin between January 1(st), 2006 and August 1(st), 2010 were included. A total of 127 exposed women were matched to 127 controls through medical records and pharmacy software. A time-to-event analysis was done to compare gestational age at the time of the recorded composite event (delivery, or rupture of membranes, or second intervention to prolong pregnancy). To compare proportions of composite event at different time points, χ(2) tests were used. Patients who received azithromycin had a more severe condition at presentation. Once adjusted for confounding factors, prolongation of pregnancy (HR =1.049; CI 95%: 0.774-1.421 [p=0.758]) and gestational age at the event (HR=1.200; CI 95%: 0.894-1.609 [p=0.225]) did not differ between the groups. The proportions of women with an event ≥7 days post-diagnosis or ≥37 gestational weeks were similar. Azithromycin was added to medical therapy in a more at-risk population and no clear benefit was measured.

  20. 21 CFR 864.7720 - Prothrombin consumption test.


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prothrombin consumption test. 864.7720 Section 864.7720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... consumption test. (a) Identification. A prothrombin consumption tests is a device that measures the patient's...

  1. In vitro and in vivo studies on radiobiological effects of prolonged fraction delivery time in A549 cells.

    Jiang, Ling; Xiong, Xiao-Peng; Hu, Chao-Su; Ou, Zhou-Luo; Zhu, Guo-Pei; Ying, Hong-Mei


    Intensity-modulated radiation therapy, when used in the clinic, prolongs fraction delivery time. Here we investigated both the in vivoand in vitroradiobiological effects on the A549 cell line, including the effect of different delivery times with the same dose on A549 tumor growth in nude mice. The in vitroeffects were studied with clonogenic assays, using linear-quadratic and incomplete repair models to fit the dose-survival curves. Fractionated irradiation of different doses was given at one fraction per day, simulating a clinical dose-time-fractionation pattern. The longer the interval between the exposures, the more cells survived. To investigate the in vivoeffect, we used sixty-four nude mice implanted with A549 cells in the back legs, randomly assigned into eight groups. A 15 Gy radiation dose was divided into different subfractions. The maximum and minimum tumor diameters were recorded to determine tumor growth. Tumor growth was delayed for groups with prolonged delivery time (40 min) compared to the group receiving a single dose of 15 Gy (Pdelivery time had delayed growth compared to those with a 40 min delivery time [20' (7.5 Gy × 2 F) vs 40' (7.5 Gy × 2 F), P= 0.035; 20' (3 Gy × 5 F) vs 40' (3 Gy × 5 F); P= 0.054; 20' (1.67 Gy × 9 F) vs 40' (1.67 Gy × 9 F), P= 0.028]. A prolonged delivery time decreased the radiobiological effects, so we strongly recommend keeping the delivery time as short as possible.

  2. Quantum mechanics in non-inertial reference frames: Time-dependent rotations and loop prolongations

    Klink, W.H., E-mail: [Department of Physics and Astronomy, University of Iowa, Iowa City, IA 52242 (United States); Wickramasekara, S., E-mail: [Department of Physics and Astronomy, University of Iowa, Iowa City, IA 52242 (United States); Department of Physics, Grinnell College, Grinnell, IA 50112 (United States)


    This is the fourth in a series of papers on developing a formulation of quantum mechanics in non-inertial reference frames. This formulation is grounded in a class of unitary cocycle representations of what we have called the Galilean line group, the generalization of the Galilei group to include transformations amongst non-inertial reference frames. These representations show that in quantum mechanics, just as the case in classical mechanics, the transformations to accelerating reference frames give rise to fictitious forces. In previous work, we have shown that there exist representations of the Galilean line group that uphold the non-relativistic equivalence principle as well as representations that violate the equivalence principle. In these previous studies, the focus was on linear accelerations. In this paper, we undertake an extension of the formulation to include rotational accelerations. We show that the incorporation of rotational accelerations requires a class of loop prolongations of the Galilean line group and their unitary cocycle representations. We recover the centrifugal and Coriolis force effects from these loop representations. Loops are more general than groups in that their multiplication law need not be associative. Hence, our broad theoretical claim is that a Galilean quantum theory that holds in arbitrary non-inertial reference frames requires going beyond groups and group representations, the well-established framework for implementing symmetry transformations in quantum mechanics. -- Highlights: •A formulation of Galilean quantum mechanics in non-inertial reference frames is presented. •The Galilei group is generalized to infinite dimensional Galilean line group. •Loop prolongations of Galilean line group contain central extensions of Galilei group. •Unitary representations of the loops are constructed. •These representations lead to terms in the Hamiltonian corresponding to fictitious forces, including centrifugal and Coriolis

  3. Prolonged transition time between colostrum and mature milk in a bear, the giant panda, Ailuropoda melanoleuca.

    Griffiths, Kate; Hou, Rong; Wang, Hairui; Zhang, Zhihe; Zhang, Liang; Zhang, Tong; Watson, David G; Burchmore, Richard J S; Loeffler, I Kati; Kennedy, Malcolm W


    Bears produce the most altricial neonates of any placental mammal. We hypothesized that the transition from colostrum to mature milk in bears reflects a temporal and biochemical adaptation for altricial development and immune protection. Comparison of bear milks with milks of other eutherians yielded distinctive protein profiles. Proteomic and metabolomic analysis of serial milk samples collected from six giant pandas showed a prolonged transition from colostrum to main-phase lactation over approximately 30 days. Particularly striking are the persistence or sequential appearance of adaptive and innate immune factors. The endurance of immunoglobulin G suggests an unusual duration of trans-intestinal absorption of maternal antibodies, and is potentially relevant to the underdeveloped lymphoid system of giant panda neonates. Levels of certain milk oligosaccharides known to exert anti-microbial activities and/or that are conducive to the development of neonatal gut microbiomes underwent an almost complete changeover around days 20-30 postpartum, coincident with the maturation of the protein profile. A potential metabolic marker of starvation was detected, the prominence of which may reflect the natural postpartum period of anorexia in giant panda mothers. Early lactation in giant pandas, and possibly in other ursids, appears to be adapted for the unique requirements of unusually altricial eutherian neonates.

  4. Prolonged sedentary time and physical activity in workplace and non-work contexts: a cross-sectional study of office, customer service and call centre employees.

    Thorp, Alicia A; Healy, Genevieve N; Winkler, Elisabeth; Clark, Bronwyn K; Gardiner, Paul A; Owen, Neville; Dunstan, David W


    To examine sedentary time, prolonged sedentary bouts and physical activity in Australian employees from different workplace settings, within work and non-work contexts. A convenience sample of 193 employees working in offices (131), call centres (36) and customer service (26) was recruited. Actigraph GT1M accelerometers were used to derive percentages of time spent sedentary (customer service workers were typically the least sedentary and the most active at work. The workplace is a key setting for prolonged sedentary time, especially for some occupational groups, and the potential health risk burden attached requires investigation. Future workplace regulations and health promotion initiatives for sedentary occupations to reduce prolonged sitting time should be considered.

  5. Prothrombin Complex Concentrate Reduces Blood Product Utilization in Heart Transplantation.

    Enter, Daniel H; Zaki, Anthony L; Marsh, Megan; Cool, Nikki; Kruse, Jane; Li, Zhi; Andrei, Adin-Cristian; Iddriss, Adam; McCarthy, Patrick M; Malaisrie, S Chris; Anderson, Allen; Rich, Jonathan D; Pham, Duc Thinh


    Current practices for the reversal of warfarin prior to cardiac surgery include the use of vitamin K and fresh frozen plasma (FFP) to reduce the risk of bleeding. Although the 2010 International Society of Heart and Lung Transplantation guidelines acknowledge the use of PCC (Prothrombin Complex Concentrate), there is no clear consensus on its efficacy. The objective of this study was to assess the efficacy of 4-factor Prothrombin Complex Concentrate (4-F PCC) administration in patients requiring warfarin reversal prior to heart transplantation by determining blood product utilization perioperatively. Twenty-one patients who received 4-F PCC for warfarin reversal prior to heart transplantation were compared to a similar cohort of 39 patients who did not receive 4-F PCC from January 2011 to July 2015. Blood product utilization was collected retrospectively for the 24-hour preoperative, intraoperative, and 48-hour postoperative periods. Patients receiving 4-F PCC required fewer blood products in all 3 time periods. In the 24-hour preoperative period, 22 patients (56%) in the control group and 2 patients (10%) in the 4-F PCC groups received blood products (p<0.001). Intraoperatively, all patients received blood products. The 4-F PCC group required fewer units of packed red blood cells (median 3 vs. 7 units, p<0.001) and FFP (median 4 vs. 9 units, p<0.001). In the 48-hour postoperative period, 20 patients (51%) in the control group and 5 patients (24%) in the 4-F PCC group received blood products (p=0.04). 4-F PCC is associated with reduced blood product utilization 24 hours preoperatively and intraoperatively. Historically, the majority of patients require FFP for warfarin reversal preoperatively. In this single-center study, a significant reduction in the need for FFP was demonstrated with the use of 4-F PCC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Polyclonal neural cell adhesion molecule antibody prolongs the effective duration time of botulinum toxin in decreasing muscle strength.

    Guo, Yan; Pan, Lizhen; Liu, Wuchao; Pan, Yougui; Nie, Zhiyu; Jin, Lingjing


    This study aimed to investigate if the effective duration time of botulinum toxin A (Btx-A) could be prolonged by polyclonal neural cell adhesion molecule antibody (P-NCAM-Ab). 175 male SD rats were randomly divided into three major groups: control group (n = 25), Btx-A group (n = 25), and P-NCAM-Ab groups. P-NCAM-Ab groups were composed of five sub-groups, with 25 rats each in the dose-response study. Muscle strength of rat lower limbs was determined using a survey system. The expressions of muscle-specific receptor tyrosine kinase (MuSK) and neural cell adhesion molecule (NCAM) were determined by real-time polymerase chain reactions (RT-PCR) and western blotting (WB). The muscle strength was significantly decreased by Btx-A in Btx-A/P-NCAM-Ab groups compared with normal control group. Besides, the muscle strength of P-NCAM-Ab group was significantly decreased compared with the Btx-A group. The recovery time of muscle strength in P-NCAM-Ab group was significantly longer compared with Btx-A group. RT-PCR and WB assay showed that PNCAM-Ab delayed the increase of MuSK and NCAM after Btx-A injection. P-NCAM-Ab prolongs the effective duration time of Btx-A in decreasing muscle strength, which could provide a novel enhancement in clinical application.

  7. Associations between prolonged sedentary time and breaks in sedentary time with cardiometabolic risk in 10-14-year-old children: The HAPPY study.

    Bailey, Daniel P; Charman, Sarah J; Ploetz, Thomas; Savory, Louise A; Kerr, Catherine J


    This study examines the association between prolonged sedentary time and breaks in sedentary time with cardiometabolic risk in 10-14-year-old children. This cross-sectional design study analysed accelerometry-determined sedentary behaviour and physical activity collected over 7 days from 111 (66 girls) UK schoolchildren. Objective outcome measures included waist circumference, fasting lipids, fasting glucose, blood pressure, and cardiorespiratory fitness. Logistic regression was used for the main data analysis. After adjustment for confounders, the odds of having hypertriglyceridaemia (P = 0.03) and an increased clustered cardiometabolic risk score (P = 0.05) were significantly higher in children who engaged in more prolonged sedentary bouts per day. The number of breaks in sedentary time per day was not associated with any cardiometabolic risk factor, but longer mean duration of daily breaks in sedentary time were associated with a lower odds of having abdominal adiposity (P = 0.04) and elevated diastolic blood pressure (P = 0.01). These associations may be mediated by engagement in light activity. This study provides evidence that avoiding periods of prolonged uninterrupted sedentary time may be important for reducing cardiometabolic disease risk in children.

  8. The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer.

    Wang, Xin; Xiong, Xiao-Peng; Lu, Jiade; Zhu, Guo-Pei; He, Shao-Qin; Hu, Chao-Su; Ying, Hong-Mei


    High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P delivery time 30 min was longer than that of groups with prolonged delivery time 60 min P delivery time (P > 0.05). Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time.

  9. Defining Prolonged Dwell Time: When Are Advanced Inferior Vena Cava Filter Retrieval Techniques Necessary? An Analysis in 762 Procedures.

    Desai, Kush R; Laws, James L; Salem, Riad; Mouli, Samdeep K; Errea, Martin F; Karp, Jennifer K; Yang, Yihe; Ryu, Robert K; Lewandowski, Robert J


    Despite growth in placement of retrievable inferior vena cava filters, retrieval rates remain low. Filters with extended implantation times present a challenge to retrieval, where standard techniques often fail. The development of advanced retrieval techniques has positively impacted retrieval of retrievable inferior vena cava filters with prolonged dwell times; however, there is no precise definition of the time point when advanced techniques become necessary. We aim to define prolonged retrievable inferior vena cava filters dwell time by determining the inflection point when the risk of standard retrieval technique failure increases significantly, necessitating advanced retrieval techniques to maintain overall technical success of retrieval. From January 2009 to April 2015, 762 retrieval procedures were identified from a prospectively acquired database. We assessed patient age/sex, filter dwell time, procedural technical success, the use of advanced techniques, and procedure-related adverse events. Overall retrieval success rate was 98% (n=745). When standard retrieval techniques failed, advanced techniques were used; this was necessary 18% of the time (n=138). Logistic regression identified that dwell time was the only risk factor for failure of standard retrieval technique (odds ratio, 1.08; 95% confidence interval, 1.05-1.10; Ptechnique failure was 40.9%. Adverse events occurred at a rate of 2% (n=18; 15 minor and 3 major). The necessity of advanced techniques to maintain technical success of retrieval increases with dwell time. Patients with retrievable inferior vena cava filters in place beyond 7 months may benefit from referral to centers with expertise in advanced filter retrieval. © 2017 American Heart Association, Inc.

  10. Prolonged sedentary time and physical activity in workplace and non-work contexts: a cross-sectional study of office, customer service and call centre employees

    Thorp Alicia A


    Full Text Available Abstract Background To examine sedentary time, prolonged sedentary bouts and physical activity in Australian employees from different workplace settings, within work and non-work contexts. Methods A convenience sample of 193 employees working in offices (131, call centres (36 and customer service (26 was recruited. Actigraph GT1M accelerometers were used to derive percentages of time spent sedentary ( Results Working hours were mostly spent sedentary (77.0%, 95%CI: 76.3, 77.6, with approximately half of this time accumulated in prolonged bouts of 20 minutes or more. There were significant (p Conclusion The workplace is a key setting for prolonged sedentary time, especially for some occupational groups, and the potential health risk burden attached requires investigation. Future workplace regulations and health promotion initiatives for sedentary occupations to reduce prolonged sitting time should be considered.

  11. Prolongation of bleeding time and inhibition of platelet aggregation by low-dose acetylsalicylic acid in patients with cerebrovascular disease

    Boysen, G; Boss, A H; Ødum, Niels


    Platelet aggregation and bleeding time was measured in 43 cerebrovascular patients participating in a controlled double-blind study of low-dose acetylsalicylic acid. In 19 patients with satisfactory inhibition of the platelet aggregation obtained by 50 to 70 mg acetylsalicylic acid per day...... the bleeding time averaged 11.2 minutes in contrast to 7.0 minutes in the placebo group, p less than 0.001. This study confirms our previous findings of platelet inhibition by low-dose acetylsalicylic acid in patients with cerebrovascular disease. The prolongation of the bleeding time demonstrates that we...... are dealing not merely with an in vitro phenomenon but with a significant in vivo effect. The study provides the rationale for clinical evaluations of low-dose acetylsalicylic acid in stroke prophylaxis....

  12. In vivo relaxation time measurements on a murine tumor model--prolongation of T1 after photodynamic therapy.

    Liu, Y H; Hawk, R M; Ramaprasad, S


    RIF tumors implanted on mice feet were investigated for changes in relaxation times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T1s of water protons were observed after PDT treatment. In all experiments, 31P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T1s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T2 values after PDT treatment.

  13. The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue.

    Ng, Deborah Hl; Wong, Joshua Gx; Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C


    Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt

  14. Sensory characteristics of meat cooked for prolonged times at low temperature

    Christensen, Line Bach; Gunvig, Annemarie; Tørngren, Mari Ann


    The present study evaluated the sensory characteristics of low temperature long time (LTLT) treated Semitendinosus from pork and beef and Pectoralis profundus from chicken. Semitendinosus and Pectoralis profundus muscles were heat treated at 53°C and 58°C for Tc + 6 h, Tc + 17 h, and Tc + 30 h...

  15. Time courses of MRI BOLD signals in prolonged visual stimulation. Comparison between colors and orders

    Kashikura, Kenichi; Fujita, Hideaki; Kershaw, J.B.; Matsuura, Tetsuya; Seki, Chie [Akita Laboratory, Japan Science and Technology Corp. (Japan); Kashikura, Akemi; Ardekani, B.A.; Kanno, Iwao


    We investigated: the BOLD signal response during 270 second photic stimulation using an EPI pulse sequence; the BOLD signal response for two different color checkerboards; and the BOLD signal response during six consecutive stimulation series. Ten healthy human subjects (age 25{+-}5.5 years) were studied with a 1.5 T MRI system (Siemens Vision, Erlangen, Germany). Black and white (BW) and red and white (RW) checkerboards alternating at 8 Hz were applied in turns for a total series of six. Stimulation timing was: 30 sec. off, 15 sec. on, 15 sec. off, 270 sec. on, 15 sec. off, 15 sec. on, 15 sec. off. Acquired data were analyzed according to color and/or order: color (without considering the order); color and order (1st BW vs. 1st RW, 2nd BW vs. 2nd RW, 3rd BW vs. 3rd RW); and order (without considering the color). A t-test (p<0.001) was used for obtaining the activated areas, and simple regression and two-way repeated-measures ANOVA were used for testing the statistical significance of the BOLD response. Results were: the BOLD signal responses during sustained photic stimulation maintained a constant level for the full duration and all series, suggesting stable levels of oxygen extraction and metabolism during cortical activation; the BOLD signal responses in two colors showed no significant difference in time response, suggesting that the neuronal populations perceiving black and red give a similar time response; and the effect of habituation or fatigue as observed by a signal decrease was not obtained, although the S.D. for each subject greatly increased with time and might be an indicator for evaluation fatigue or attention. (author)

  16. Effects of Prolonged Driving on Time Headway Adopted by HGV (Heavy Goods Vehicle) Drivers


    for Human Development, for the analysis of the endocrine data. I am also greatly indebted to Mr. P. Holahan , Mr. E. Bolger, and Miss C. Higgins of the...period. Time headway for all following episodes was continuously recorded, sampled, and analysed as described in Fuller, McDonald, Holahan , and Bolger...traffic accidents, 151-160, Luxembourg: Office for Official Publications of the European Communities. Fuller, R. G. C., McDonald, N. J., Holahan , P. A

  17. The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

    Zhu Guo-Pei


    Full Text Available Abstract Background High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. Methods 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. Results The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P 0.05. Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. Conclusions The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time.

  18. Respiratory acidosis prolongs, while alkalosis shortens, the duration and recovery time of vecuronium in humans.

    Yamauchi, Masanori; Takahashi, Hiromi; Iwasaki, Hiroshi; Namiki, Akiyoshi


    To determine the effects of respiratory acidosis and alkalosis by mechanical ventilation on the onset, duration, and recovery times of vecuronium. Randomized, prospective study. Operating rooms in the Sapporo Medical University Hospital and Kitami Red Cross Hospital. 90 ASA physical status I and II patients undergoing lower abdominal surgery. Patients were randomly allocated to one of three groups by arterial carbon dioxide tension level (PaCO2; mmHg) after induction: hyperventilation group (PaCO2 = 25-35), normoventilation group (PaCO2 = 35-45), and hypoventilation group (PaCO2 = 45-55). Anesthesia was maintained by spinal block with inhalation of 50% to 66% nitrous oxide in oxygen and intermittent intravenous administration of fentanyl and midazolam with tracheal intubation. After vecuronium 0.08 mg/kg was given, onset, duration, and recovery time were measured by mechanomyography (Biometer Myograph 2,000, Odense, Denmark). There were significant differences in the duration and recovery time of vecuronium among the normoventilation group (12.7 +/- 3.3 min and 11.8 +/- 2.8 min, respectively), the hyperventilation group (10.6 +/- 3.5 min and 9.2 +/- 2.7 min, respectively; p respiratory acidosis and shortened in respiratory alkalosis.

  19. Carbohydrate Mouth Rinsing Enhances High Intensity Time Trial Performance Following Prolonged Cycling

    Luden, Nicholas D.; Saunders, Michael J.; D’Lugos, Andrew C.; Pataky, Mark W.; Baur, Daniel A.; Vining, Caitlin B.; Schroer, Adam B.


    There is good evidence that mouth rinsing with carbohydrate (CHO) solutions can enhance endurance performance (≥30 min). The impact of a CHO mouth rinse on sprint performance has been less consistent, suggesting that CHO may confer benefits in conditions of ‘metabolic strain’. To test this hypothesis, the current study examined the impact of late-exercise mouth rinsing on sprint performance. Secondly, we investigated the effects of a protein mouth rinse (PRO) on performance. Eight trained male cyclists participated in three trials consisting of 120 min of constant-load cycling (55% Wmax) followed by a 30 km computer-simulated time trial, during which only water was provided. Following 15 min of muscle function assessment, 10 min of constant-load cycling (3 min at 35% Wmax, 7 min at 55% Wmax) was performed. This was immediately followed by a 2 km time trial. Subjects rinsed with 25 mL of CHO, PRO, or placebo (PLA) at min 5:00 and 14:30 of the 15 min muscle function phase, and min 8:00 of the 10-min constant-load cycling. Magnitude-based inferential statistics were used to analyze the effects of the mouth rinse on 2-km time trial performance and the following physiological parameters: Maximum Voluntary Contract (MVC), Rating of Perceived Exertion (RPE), Heart Rate (HR), and blood glucose levels. The primary finding was that CHO ‘likely’ enhanced performance vs. PLA (3.8%), whereas differences between PRO and PLA were unclear (0.4%). These data demonstrate that late-race performance is enhanced by a CHO rinse, but not PRO, under challenging metabolic conditions. More data should be acquired before this strategy is recommended for the later stages of cycling competition under more practical conditions, such as when carbohydrates are supplemented throughout the preceding minutes/hours of exercise. PMID:27657117

  20. Prolonged time to pregnancy is associated with a greater risk of adverse outcomes.

    Raatikainen, Kaisa; Harju, Maija; Hippeläinen, Maritta; Heinonen, Seppo


    Births with known time to pregnancy (TTP) during the period 1989-2007 (n=17,114) were analyzed to investigate associations between TTP and pregnancy outcome among couples that conceived spontaneously. The adjusted odds ratio (95% confidence interval) for poor neonatal health, including low Apgar score, low umbilical vein pH, and need for neonatal intensive care, was 1.51 (1.09-2.09) in women who had a TTP of 25-36 months and 1.60 (1.18-2.19) in women who had a TTP of >or=37 months compared with women with a TTP of 0-6 months.

  1. Sublingual Nucleotides Prolong Run Time to Exhaustion in Young Physically Active Men

    Sergej M. Ostojic


    Full Text Available Although dietary nucleotides have been determined to be required for normal immune function, there is limited direct interventional evidence confirming performance-enhancing effects of sublingual nucleotides in humans. A double-blind, placebo-controlled, randomized trial was conducted to evaluate the effect of sublingual nucleotides (50 mg/day administered for 14 days in thirty young healthy physically active males, on endurance performance and immune responses. Fasting white blood cell count, natural killer cells (NKC number, NKC cytotoxic activity, and serum immunoglobulin (IgA, IgM, IgG, and time to exhaustion, peak rate of perceived exertion, peak heart rate, and peak running speed during the exercise test were measured at baseline (day 0 and post-intervention (day 14. Time to exhaustion, as well as serum immunoglobulin A and NKC cytotoxic activity, were significantly higher at day 14 (p < 0.05 in participants supplemented with nucleotides compared with those who consumed placebo. No significant differences in other parameters were observed between groups at post-intervention. No volunteers withdrew before the end of the study nor reported any vexatious side effects of supplementation. The results of the present study suggest that sublingual nucleotides may provide pertinent benefit as both an ergogenic and immunostimulatory additive in active males.

  2. Time pattern of exercise-induced changes in type I collagen turnover after prolonged endurance exercise in humans

    Langberg, Henning; Skovgaard, D; Asp, S;


    Type I collagen is known to adapt to physical activity, and biomarkers of collagen turnover indicate that synthesis can be influenced by a single intense exercise bout, but the exact time pattern of these latter changes are largely undescribed. In the present study, 17 healthy young males had...... indicate that type I collagen synthesis is accelerated in response to prolonged strenuous exercise, reaching a peak after 3 days and returning to preexercising levels 5 days after the completion of a marathon run....... their plasma concentrations of the carboxyterminal propeptide of type I procollagen (PICP), a marker of collagen formation, and the immunoactive carboxyterminal cross-linked telopeptide (ICTP), a marker of collagen resorption, measured before and immediately postexercise, as well as 1, 2, 3, 4, 5, and 6 days...

  3. Prolonged survival time of sarcoma 180-bearing mice treated with lipid microspheres-entrapped antitumor marine coral prostanoids.

    Honda, A; Mori, Y; Yamada, Y; Nakaike, S; Hayashi, H; Otomo, S


    Antitumor marine coral prostanoids (clavulone II and chlorovulone I) were entrapped into lipid microspheres of 0.2 micron diameter to make lipo-drugs. Daily treatment with lipo-chlorovulone I (1.6 mg/kg/day, i.p.) and lipo-clavulone II (12.5 mg/kg/day, i.p.) on days 1 through 5 markedly prolonged the survival time (135% ILS and 73% ILS, respectively) of mice inoculated with sarcoma 180 as compared with that of a corresponding dose of respective free chlorovulone I and clavulone II. These results suggest that lipid microspheres may be used as drug delivery carriers for antitumor coral prostanoids in vivo.

  4. Impact of Development and Accommodation Practices on Older Workers' Job Characteristics, Prolonged Fatigue, Work Engagement, and Retirement Intentions Over Time.

    Stynen, Dave; Jansen, Nicole W H; Slangen, Jos J M; Kant, IJmert


    The impact of development and accommodation practices on older workers' retirement intentions was investigated in this prospective study, together with potential pathways and the role of career stage. A subsample of full-time, older workers (n = 678) from the Maastricht Cohort Study was followed-up for 2 years. Regression analysis was conducted for three age groups. Development practices related positively with later retirement intentions in workers aged 55 to 59 years. The accommodation practice of demotion related negatively with later retirement intentions in worker aged at least 60 years. Decision latitude and work engagement were found to link development and accommodation practices with later retirement intentions in particular in workers aged 55 to 59 years. It was indicated in this prospective study that development and accommodation practices may be useful for prolonging working careers.

  5. Assessment of bacterial biodetoxification of herbicide atrazine using Aliivibrio fischeri cytotoxicity assay with prolonged contact time.

    Háhn, Judit; Szoboszlay, Sándor; Tóth, Gergő; Kriszt, Balázs


    In our study, we determined and compared the atrazine-biodetoxification ability of 41 bacterial strains and 21 consortia created of those with over 50% degradation rate in pure cultures. Biodegradation capacity was measured with GC-MS. Detoxification was assessed based on the cytotoxic effect of end-products to Aliivibrio fischeri in chronic bioluminescence inhibition assay with 25 h contact time. Chronic A. fischeri assay adapted to a microplate, which is suitable for examine numerous residues simultaneously, also appeared to be significantly more sensitive to atrazine compared to the standard acute (30 min) test. Due to its sensitivity, the chronic assay could be a valuable tool to provide a more comprehensive view of the ecological risks of atrazine and other chemicals. Thirteen strains were able to degrade more than 50% of 50 ppm atrazine. Four of these belong to Rhodococcus aetherivorans, R. qingshengii, Serratia fonticola and Olivibacter oleidegradans which species' atrazine degrading ability has never been reported before. Four consortia degrading ability was more effective than that of the creating individual strains; moreover, their residues did not show cytotoxic effects to A. fischeri. However, in several cases, the degradation products of sole strains and consortia resulted in significant bioluminescence inhibition. Thus high biodegradation (>90%) does not certainly mean the reduction or cessation of toxicity highlighting the importance of the evaluation of biological effects of degradation residues to improve the efficiency and abate the ecological risks of bioremediation techniques.

  6. Endothelin receptor antagonist attenuates inflammatory response and prolongs the survival time in a neonatal sepsis model.

    Goto, Tatenobu; Hussein, Mohamed Hamed; Kato, Shin; Daoud, Ghada Abdel-Hamid; Kato, Takenori; Kakita, Hiroki; Mizuno, Haruo; Imai, Masaki; Ito, Tetsuya; Kato, Ineko; Suzuki, Satoshi; Okada, Noriko; Togari, Hajime; Okada, Hidechika


    To evaluate effects of endothelin receptor antagonist ETR-P1/fl in a neonatal sepsis model. Eighteen anesthetized and mechanically ventilated 3-day-old piglets were divided into three groups. Six piglets received cecal ligation and perforation (CLP group). Six piglets were administrated a continuous infusion of ETR-P1/fl (0.05 mg/kg/h), an antisense homology box-derived peptide with an endothelin A receptor antagonist effect, starting 30 min after CLP (ETR-P1/fl group). Six piglets acted as the sham group. Mean arterial pressure (MAP), heart rate, cardiac output, arterial blood gas, body temp (BT), serum nitrite and nitrate (NOx), tumor necrosis factor (TNF)-α, and high-mobility group box 1 (HMGB-1) were measured before CLP and at 1, 3, 6, and 9 h after CLP. Cecal ligation and perforation exposure evoked a state of shock and showed deteriorated cardiac output, pulmonary hypertension, decreased MAP, low oxygen saturation, and base excess (BE) with elevated TNF-α, NOx, and HMGB1. ETR-P1/fl administration resulted in higher MAP at 6 and 9 h after CLP, less negative BE, lower mean pulmonary arterial pressure (mPAP)/MAP ratio at 9 h after CLP, and lower TNF-α, NOx, and HMGB-1 compared to the CLP group. BT showed no differences between the groups. Survival time in the ETR-P1/fl group was longer than in the CLP group (18.9 ± 2.3 h vs. 9.0 ± 0.8 h, p model.

  7. Efeito de alguns curares naturais e da d-Tubocurarina retardando o tempo de coagulação e o tempo de protombina do sangue humano Natural curares and d-Tubocuratine effects on human blood clothing time and prothrombine time

    João Canali


    Full Text Available In this paper the author points out to a old question of about 200 years ago in wich two kinds of opinions were discussed. BANCROFT and FONTANA in one hand atributes for the Indian arrow poison (curare the propriety of uncoagulate the blood, and C. BEBNAHDJ, B. RODRIGUES and others made an contradictory opinion upon this subject. In our experiments, we utilized 4 curares samples from indians who lives near the Brazilian border at Colombia, the famous Ticunas poison, and the alkaloid d-Tubocurarine. These poisons were added in form of emulsion in saline to the blood and blood plasma in order to perform two kinds of experiments. In one serie of experiments we observed the effect of curare on human blood coagulation time according to LEE-WHITE technic puting 0.5 ml of the various poisons emulsions previously into the tube. By this method, we have found that the emulsion containing 0.1 g of the poison in 10 ml saline was the most effective (Table II, therefore we used this curare emulsion concentration in the other serie of experiments, in which we tested the action of these venoms on the human blood plasma prothrombins time, (Quick Technic adding 0.1 ml of the saline poison emulsion to each 0.1 ml of human blood plasma. Results from these experiments can be seen on Table II. These experiments we have tried on one sample of human blood plasma plus the differents curares samples; and in another opportunity four samples of human blood plasma were tried with the curare from Ticunas indians (the most effective in this respect. Results from these experiments may be seen on Table III. All the poison tried in our experiments was previously tested on toads legs (B. crucifer to verify his curares action. All times obtained with the experiments above, show highly significant results (P<001 when compared with the blood and blood plasma mixed with in the same volume of saline. Our results, point out that BANCROFT and FONTANA views upon the effect of curare on

  8. Do Factor V Leiden and Prothrombin G20210A Mutations Predict Recurrent Venous Thromboembolism in Older Patients?

    Méan, Marie; Limacher, Andreas; Stalder, Odile; Angelillo-Scherrer, Anne; Alberio, Lorenzo; Fontana, Pierre; Beer, Hans-Jürg; Rodondi, Nicolas; Lämmle, Bernhard; Aujesky, Drahomir


    The value of genetic thrombophilia testing in elderly patients with an unprovoked venous thromboembolism is unclear. We assessed whether the Factor V Leiden and the prothrombin G20210A mutation are associated with recurrent venous thromboembolism in elderly patients in a prospective multicenter cohort study. We genotyped the Factor V Leiden and the prothrombin G20210A mutation in 354 consecutive in- and outpatients aged ≥65 years with a first unprovoked venous thromboembolism from 9 Swiss hospitals. Patients and managing physicians were blinded to testing results. The outcome was recurrent symptomatic venous thromboembolism during follow-up. We examined the association between the Factor V Leiden and the prothrombin G20210A mutation and venous thromboembolism recurrence using competing risk regression, adjusting for age, sex, and periods of anticoagulation as a time-varying covariate. Overall, 9.0% of patients had a Factor V Leiden and 3.7% had a prothrombin G20210A mutation. At 36 months of follow-up, patients with a Factor V Leiden and a prothrombin G20210A mutation had a cumulative incidence of recurrent venous thromboembolism of 12.9% (95% confidence interval [CI], 5.1%-30.8%) and 18.5% (95% CI, 4.9%-56.5%), respectively, compared with 16.7% (95% CI, 12.5%-22.1%) of patients without mutation (P = .91 by the log-rank test). After adjustment, neither the Factor V Leiden (sub-hazard ratio 0.98; 95% CI, 0.35-2.77) nor the prothrombin G20210A mutation (sub-hazard ratio 1.15; 95% CI, 0.25-5.19) was associated with recurrent venous thromboembolism. Our results suggest that testing for genetic thrombophilia may not be beneficial in elderly patients with a first unprovoked venous thromboembolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Comparison of chlorination and chloramination in carbonaceous and nitrogenous disinfection byproduct formation potentials with prolonged contact time.

    Sakai, Hiroshi; Tokuhara, Shunsuke; Murakami, Michio; Kosaka, Koji; Oguma, Kumiko; Takizawa, Satoshi


    Due to decreasing water demands in Japan, hydraulic retention times of water in piped supply systems has been extended, resulting in a longer contact time with disinfectants. However, the effects of extended contact time on the formation of various disinfection byproducts (DBPs), including carbonaceous DBPs such as trihalomethane (THM) and haloacetic acid (HAA), and nitrogenous DBPs such as nitrosodimethylamine (NDMA) and nitrosomorpholine (NMor), have not yet been investigated in detail. Herein, we compared the formation of these DBPs by chlorination and chloramination for five water samples collected from rivers and a dam in Japan, all of which represent municipal water supply sources. Water samples were treated by either filtration or a combination of coagulation and filtration. Treated samples were subjected to a DBP formation potential test by either chlorine or chloramine for contact times of 1 day or 4 days. Four THM species, nine HAA species, NDMA, and NMor were measured by GC-ECD or UPLC-MS/MS. Lifetime cancer risk was calculated based on the Integrated Risk Information System unit risk information. The experiment and analysis focused on (i) prolonged contact time from 1 day to 4 days, (ii) reduction efficiency by conventional treatment, (iii) correlations between DBP formation potentials and water quality parameters, and (iv) the contribution of each species to total risk. With an increased contact time from 1 day to 4 days, THM formation increased to 420% by chloramination. Coagulation-filtration treatment showed that brominated species in THMs are less likely to be reduced. With the highest unit risk among THM species, dibromochloromethane (DBCM) showed a high correlation with bromine, but not with organic matter parameters. NDMA contributed to lifetime cancer risk. The THM formation pathway should be revisited in terms of chloramination and bromine incorporation. It is also recommended to investigate nitrosamine formation potential by

  10. Sleep Duration and “on” Time during Different Periods of the Day and Night in Patients with Advanced Parkinson's Disease Receiving Adjunctive Ropinirole Prolonged Release

    Heinz Reichmann


    Full Text Available Patients undergoing long-term therapy for PD often experience motor fluctuations and nocturnal disturbances. In a post-hoc analysis, we explored effects of ropinirole prolonged release on sleep, night-time awakenings, and “on” time over 24 hours. Patients with advanced PD suboptimally controlled with L-dopa were randomized to adjunctive ropinirole prolonged release (2–24 mg/day or placebo for 24 weeks. Awake/asleep and, if awake, “on”/“off” status was recorded via diary cards. At week 24 last observation carried forward, changes in nighttime or daytime sleep duration were not significantly different between treatments. Of patients with baseline awakenings, a significantly higher proportion in the ropinirole prolonged release group had a reduction in awakenings versus placebo. Patients receiving ropinirole prolonged release had a significantly greater increase in amount/percentage of awake time “on”/“on” without troublesome dyskinesia during all periods assessed (including night-time and early morning, versus placebo, and higher odds for being “on” on waking. Adjunctive once-daily ropinirole prolonged release may help provide 24-hour symptom control in patients with advanced PD not optimally controlled with L-dopa.

  11. Sleep Duration and “on” Time during Different Periods of the Day and Night in Patients with Advanced Parkinson's Disease Receiving Adjunctive Ropinirole Prolonged Release

    Reichmann, Heinz; Cooper, James; Rolfe, Katie; Martinez-Martin, Pablo


    Patients undergoing long-term therapy for PD often experience motor fluctuations and nocturnal disturbances. In a post-hoc analysis, we explored effects of ropinirole prolonged release on sleep, night-time awakenings, and “on” time over 24 hours. Patients with advanced PD suboptimally controlled with L-dopa were randomized to adjunctive ropinirole prolonged release (2–24 mg/day) or placebo for 24 weeks. Awake/asleep and, if awake, “on”/“off” status was recorded via diary cards. At week 24 last observation carried forward, changes in nighttime or daytime sleep duration were not significantly different between treatments. Of patients with baseline awakenings, a significantly higher proportion in the ropinirole prolonged release group had a reduction in awakenings versus placebo. Patients receiving ropinirole prolonged release had a significantly greater increase in amount/percentage of awake time “on”/“on” without troublesome dyskinesia during all periods assessed (including night-time and early morning), versus placebo, and higher odds for being “on” on waking. Adjunctive once-daily ropinirole prolonged release may help provide 24-hour symptom control in patients with advanced PD not optimally controlled with L-dopa. PMID:21687750

  12. Low paediatric thrombin generation is caused by an attenuation of prothrombin conversion.

    Kremers, Romy M W; Wagenvoord, Rob J; de Laat, H Bas; Monagle, Paul; Hemker, H Coenraad; Ignjatovic, Vera


    Thrombin generation (TG) is decreased in children. TG is determined by two underlying processes: the conversion of prothrombin to thrombin and the inactivation of thrombin. Therefore, lower TG capacity in children can either be caused by a reduction of prothrombin conversion, an increase of thrombin inactivation, or both. In 36 children and 8 adults, TG and the factors that determine thrombin inactivation (antithrombin, α2Macroglobulin (α2M) and fibrinogen) were measured. Prothrombin conversion, thrombin inhibitor complex formation, and the overall thrombin decay capacity were determined. In silico modelling was performed to determine the contribution prothrombin conversion and thrombin inactivation to deviant paediatric TG. Both the amount of prothrombin converted and the maximal prothrombin conversion rate are significantly reduced in children as compared to adults. This is partly due to the prothrombin levels being lower and partly to a lower prothrombin conversion rate. The overall thrombin decay capacity is not significantly different in children, but α2Macroglobulin plays a more important role than it does in adults. In silico experiments demonstrate that reduced prothrombin conversion and to a lesser extent elevated α2M levels provide an explanation for low TG in children. Young age has a dual effect on prothrombin conversion. Lower plasma prothrombin levels result in decreased prothrombin conversion but the rate of prothrombin conversion is also decreased, i. e. the development of prothrombinase is lower than in adults.

  13. Falsely elevated cyclosporin and tacrolimus concentrations over prolonged periods of time due to reversible adsorption to central venous catheters.

    Hacker, Charlotte; Verbeek, Mareike; Schneider, Heike; Steimer, Werner


    Falsely elevated concentrations of immunosuppressants can be caused by reversible adsorption to central venous catheter (CVC) systems. If undetected, this may lead to dose reduction resulting in underdosage which may even entail graft-versus-host disease or organ rejection. We analyzed the adsorption and release for cyclosporine A (CsA) and tacrolimus (Tac) in vitro and in vivo. Four types of CVCs were examined in vitro: two made from polyurethane (PU), one from silicone and one from PU with an incorporated silver ion-based antimicrobial agent. All 26 CVCs analyzed in vitro showed significant reversible adsorption of CsA (n=13; p=0.001) and Tac (n=13; p=0.001, Wilcoxon signed rank test). Immediately after infusing the drugs, the mean concentrations of 6420ng/mL of CsA and 250ng/mL of Tac were measured. Flushing with NaCl lowered the drug release. Besides, blood samples of fifteen patients were taken simultaneously from all lumina of the CVC and via venipuncture. The samples from contaminated lumina showed the mean elevations by a factor of 11 for CsA (n=12) and 89 for Tac (n=3). Blood sampling for immunosuppressant monitoring should thus never be performed from lumina previously used for infusing the drug even after prolonged periods of time and extensive rinsing. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Blocking GluN2B subunits reverses the enhanced seizure susceptibility after prolonged febrile seizures with a wide therapeutic time-window.

    Chen, Bin; Feng, Bo; Tang, Yangshun; You, Yi; Wang, Yi; Hou, Weiwei; Hu, Weiwei; Chen, Zhong


    Febrile seizures (FSs), the most common type of convulsive events in infants, are closely associated with temporal lobe epilepsy (TLE) in adulthood. It is urgent to investigate how FSs promote epileptogenesis and find the potential therapeutic targets. In the present study, we showed that the phosphorylation of GluN2B Tyr1472 gradually reached peak level at 24h after prolonged FSs and remained elevated during 7days thereafter. IL-1β treatment alone, which in previous study mimicked the effect of prolonged FSs on adult seizure susceptibility, increased GluN2B Tyr1472 phosphorylation. Both IL-1 receptor antagonist (IL-1Ra) and IL-1R1 deletion were sufficient to reverse the prolonged FSs induced hyper-phosphorylation of GluN2B Tyr1472. GluN2B antagonist ifenprodil showed a wide therapeutic time-window (3days) to reverse the enhanced seizure susceptibility after prolonged FSs or IL-1β treatment. Our study demonstrated that GluN2B phosphorylation at Tyr1472 site mediated by the transient increase of IL-1β was involved in the enhanced adult seizure susceptibility after prolonged FSs, implicating GluN2B-containing NMDAR is a new potential drug target with a wide therapeutic time window to prevent epileptogenesis in patients with infantile FSs. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The use of contrast-enhanced ultrasound in the treatment of limb pseudoaneurysm with percutaneous prothrombin injection

    Zhong CHEN


    Full Text Available Objective To explore the safety and effectiveness of contrast-enhanced ultrasound (CEUS-guided percutaneous injection of prothrombin for the treatment of limb pseudoaneurysm (PSA. Methods Sixteen cases of lower limb pseudoaneurysms were treated with contrast-enhanced ultrasound (CEUS-guided percutaneous injection of prothrombin, and the size of the pseudoaneurysm, width and length of the pseudoaneurysm neck, times for compression, duration of each compression, and dose of prothrombin injection were recorded. Results In 16 pseudoaneurysm patients, there were 20 pseudoaneurysm sacs in total. One pseudoaneurysm sac was present in 13 patients, 2 sacs were present in 2, and there were 3 sacs in one patient. The mean maximum diameter of the sacs was 41.1±11.9mm. The mean width and length of these pseudoaneurysm necks were 1.9±0.5mm and 4.4±2.3mm respectively. During the process of treatment, the mean duration for compression was 6.0±2.0min, and the mean number of times of compression was 1.2±0.4. The mean dose of prothrombin injection was 411.5±118.8U. The cure rate with one-injection was 100% (16/16, and the recurrence rate was 0%. No complications was observed. Conclusions CEUS-guided percutaneous injection of prothrombin for the treatment of lower limb pseudoaneurysms is safe and effective. The size of the pseudoaneurysm sac and length of the pseudoaneurysm neck are important factors that may affect the result of the treatment. Timely recompression is an important step for increasing the cure rate. DOI: 10.11855/j.issn.0577-7402.2014.01.09

  16. Inflammation and prolonged QT time: results from the Cardiovascular Disease, Living and Ageing in Halle (CARLA study.

    Daniel Medenwald

    Full Text Available BACKGROUND: Previous research found an association of CRP with QT time in population based samples. Even more, there is evidence of a substantial involvement of the tumor necrosis factor-alpha system in the pathophysiology of cardiac arrhythmia, while the role of Interleukin 6 remains inconclusive. OBJECTIVE: To determine the association between inflammation with an abnormally prolonged QT-time (APQT in men and women of the elderly general population. METHODS: Data descend from the baseline examination of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA Study. After exclusion of subjects with atrial fibrillation and missing ECG recording the final study cohort consisted of 919 men and 797 women. Blood parameters of inflammation were the soluble TNF-Receptor 1 (sTNF-R1, the high-sensitive C-reactive protein (hsCRP, and Interleukin 6 (IL-6. In accordance with major cardiologic societies we defined an APQT above a QT time of 460 ms in women and 450 ms in men. Effect sizes and the corresponding 95% confidence intervals (CI were estimated by performing multiple linear and logistic regression analyses including the analysis of sex differences by interaction terms. RESULTS: After covariate adjustment we found an odds ratio (OR of 1.89 (95% CI: 1.13, 3.17 per 1000 pg/mL increase of sTNF-R1 in women, and 0.74 (95% CI: 0.48, 1.15 in men. In the covariate adjusted linear regression sTNF-R1 was again positively associated with QT time in women (5.75 ms per 1000 pg/mL, 95% CI: 1.32, 10.18, but not in men. Taking possible confounders into account IL-6 and hsCRP were not significantly related to APQT in both sexes. CONCLUSION: Our findings from cross-sectional analyses give evidence for an involvement of TNF-alpha in the pathology of APQT in women.

  17. Blood Coagulation Induced by Iranian Saw-Scaled Viper (Echis Carinatus Venom: Identification, Purification and Characterization of a Prothrombin Activator

    Mahdi Babaie


    Full Text Available   Objective(s: Echis carinatus is one of the venomous snakes in Iran. The venom of Iranian Echis carinatus is a rich source of protein with various factors affecting the plasma protein and blood coagulation factor. Some of these proteins exhibit types of enzymatic activities. However, other items are proteins with no enzymatic activity.   Materials and Methods: In order to study the mechanism and effect of the venom on human plasma proteins, the present study has evaluated the effect of crude venom and all fractions. A procoagulant factor (prothrombin activator was isolated from the venom of the Iranian snake Echis carinatus with a combination of gel filtration (Sephadex G-75, ion-exchange chromatography (DEAE- Sepharose and reverse phase HPLC. Furthermore, proteolytic activity of the crude venom and all fractions on blood coagulation factors such as prothrombin time (PT was studied. Results: In the present study, the PT test was reduced from 13.4 s to 8.6 s when human plasma was treated with crude venom (concentraion of venom was 1 mg/ml. The purified procoagulant factor revealed a single protein band in SDS polyacrylamide electrophoresis under reducing conditions and its molecular weight was estimated at about 65 kDa. A single-band protein showed fragment patterns similar to those generated by the group A prothrombin activators, which convert prothrombin into meizothrombin independent of the prothrombinase complex. Conclusion: This study showed that the fraction which separated from Iranian snake Echis carinatus venom can be a prothrombin activators. It can be concluded that this fraction is a procoagulant factor.

  18. Prothrombin-activator (thromboplastin) generation in the blood of water snake (Natrix piscator).

    Srivastava, V M; Dube, B; Dube, R K; Agarwal, G P


    The generation of prothrombin-activator (thromboplastin) in water snake (Natrix piscator) is clearly delayed, compared to a mammalian system, but the final activity is well comparable to that in man, when homologous sources of "phospholipid" (erythrocyte-lysate) and of substrate plasma are employed in one stage "thromboplastin generation test". The use of heterologous source of either of the above reagents resulted in significantly longer clotting times; hence the need for homologous source of above reagents in the test is emphasized for comparative studies on animal haemostasis.

  19. Effective reversal of edoxaban-associated bleeding with four-factor prothrombin complex concentrate in a rabbit model of acute hemorrhage.

    Herzog, Eva; Kaspereit, Franz; Krege, Wilfried; Doerr, Baerbel; Mueller-Cohrs, Jochen; Pragst, Ingo; Morishima, Yoshiyuki; Dickneite, Gerhard


    Edoxaban is an oral, selective direct factor Xa inhibitor approved in Japan for venous thromboembolism prevention after orthopedic surgery. Data are lacking regarding reversal strategies for edoxaban; this study assessed whether four-factor prothrombin complex concentrate (Beriplex/Kcentra; CSL Behring GmbH, Marburg, Germany) can effectively reverse its effects on hemostasis using a previously described rabbit model. The study comprised assessments of thrombin generation in vitro, pharmacokinetic parameters, and edoxaban reversal in vivo. In a blinded in vivo stage, a standardized kidney incision was performed in animals (n = 11 per group) randomized to receive vehicle + saline, edoxaban (1,200 μg/kg) + saline, or edoxaban (1,200 μg/kg) + four-factor prothrombin complex concentrate (50 IU/kg). Animals were monitored for treatment impact on hemostasis and coagulation parameters. Data are median (range). Statistical tests were adjusted for multiple testing. Edoxaban administration increased blood loss (30 [2 to 44] ml) and time to hemostasis (23 [8.5 to 30.0] min) compared with the control group (3 [1 to 8] ml and 3 [2.0 to 5.0] min, respectively). Biomarkers of coagulation (prothrombin time, activated partial thromboplastin time, whole blood clotting time) and thrombin generation parameters (e.g., peak thrombin, endogenous thrombin potential, lag time) were also affected by edoxaban. Administration of four-factor prothrombin complex concentrate significantly reduced time to hemostasis (to 8 [6.5 to 14.0] min, observed P < 0.0001) and total blood loss (to 9 [4 to 22] ml, observed P = 0.0050) compared with the edoxaban + saline group. Of the biomarkers tested, prothrombin time, whole blood clotting time, and endogenous thrombin potential correlated best with clinical parameters. In a rabbit model of hemostasis, four-factor prothrombin complex concentrate administration significantly decreased edoxaban-associated hemorrhage.

  20. Saline obtaining and time standardization of prothrombin using thromboplastin of human placenta. Obtención salina y estandarización del tiempo de protrombina utilizando tromboplastina de placenta humana.

    Deysi González Sarría

    Full Text Available Background: Determining prothombine ‘s time is an important lab test in the study of coagulation disorders. To develop this essay the main reactive was thromboplastin , a substance that is presented in tissue and that has been obtained habitually from the human brain or certain animals but its extraction in labs or its commercial acquisition is difficult at present. Objective: To obtain Thromboplastin throughout the extraction of human placenta and to standardise the determination of pro-time into the obtained reactive Method: Placenta from normal delivery was used from which thromboplastin was obtained using a saline extraction. The reactive was compared with thromboplastin from human brain from ¨Dr. Hermanos Ameijeiras¨ Hospital in Havana City in a group of patients with and without anticoagulant treatment . With the extracted thromplastin similar or compatible results were obtained than with the habitual reactives by using easier and cheaper process.
    Fundamento: La determinación del tiempo de protrombina es un importante examen complementario en el estudio de los trastornos de la coagulación de la sangre. Para la realización del ensayo, se utiliza como reactivo principal tromboplastina, sustancia que se encuentra en varios tejidos y que habitualmente se ha obtenido de cerebro humano o de ciertos animales, pero su extracción en el laboratorio o su adquisición comercial en estos momentos se dificulta. Objetivos: Obtener tromboplastina a través de la extracción salina de placenta humana y estandarizar la determinación del tiempo de protrombina con el reactivo obtenido. Métodos : Se utilizó placenta de partos normales de la cual se obtuvo la tromboplastina utilizando extracción salina. Se comparó el reactivo con una tromboplastina de cerebro humano del Hospital ¨Hermanos Ameijeiras¨ de Ciudad de La Habana

  1. Providing a diet containing only maintenance levels of energy and protein during the latter stages of pregnancy resulted in a prolonged delivery time during parturition in rats.

    Tanaka, Y; Kadokawa, H


    In mammals, a prolonged delivery time during parturition is dangerous for both mother and fetus, although the mechanisms that prolong delivery are unclear. To investigate whether nutrition affects delivery time, we administered two feeds containing maintenance (L-feed) or higher (H-feed) levels of energy and protein at different points during the latter half of pregnancy and compared the effects of the various treatments on delivery time in rats. After the rats had been maintained on the L-feed and then copulated on pro-oestrus (Day 0), pregnant females were randomly allocated to one of three groups: (1) the no-improvement group, which was fed L-feed throughout gestation; (2) the early group, which was fed L-feed until Day 11 of gestation and then switched to H-feed; and (3) the late group, which was fed L-feed until Day 16 of gestation and then switched to H-feed. There was no significant difference in the number of pups among the three groups. However, delivery time was significantly longer in the no-improvement group (73.7±5.2 min) than the early (46.9±5.6 min) and late (55.4±5.5 min) groups. Consuming a maintenance diet during the latter half of pregnancy resulted in a prolonged delivery time.

  2. Factor V Leiden and Prothrombin Mutations in South of Iran

    M Karimi


    Full Text Available ABSTRACT: Introduction & Objective: Factor V Leiden and prothrombin mutation are not common but they are involved in pediatric thrombosis. The aim of this study was to evaluate the frequency of factor V Leiden & prohtrombin mutation in healthy population of Shiraz, south of Iran. Materials & Methods: In this cross-sectional study 195 healthy people (97 female and 98 male were randomly selected. Peripheral white blood cells obtained from 5 ml blood contained 1-2 mg/ml K2- EDTA. Genomic DNA extraction was performed following the protocol described by Miller et al. PCR amplification was carried out in 25μl reaction volume containing 0.5 units Taq polymerase, 200μM dNTP, 500 μM of each of the previously described primers. After initial denaturation, 35 cycles at 95◦c for 30s, and 72◦c for 20s and followed extention by 72 for 10 min were performed. About 10μl of PDR product was digested with MNI I or Mbo restriction enzymes. Results: In this study we determined factor V Leiden in 8 (4.1% and prothrombin mutation in 6 individual (3.07% of 198 cases in heterozygous form. No homozygous was seen for any of the mutations. Only one case presented a double heterozygous for factor V and prothrombin in this cohort. Conclusion: Several studies of factor V leiden and prothrombin mutations in the East of Asia showed the higher frequency of these mutations in Iran.

  3. Demonstrating Hemostasis with a Student-Designed Prothrombin Time Test

    Fardy, Richard Wiley


    Describes a blood coagulation test developed by two high school biology students. Although the test lacks some precision, results indicate that the technique is comparable to standard methods used in laboratories. (MA)

  4. 21 CFR 864.7750 - Prothrombin time test.


    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin...

  5. Ringer’s lactate, but not hydroxyethyl starch, prolongs the food intolerance time after major abdominal surgery; an open-labelled clinical trial

    Li, Yuhong; He, Rui; Ying, Xiaojiang; Hahn, Robert


    Background: The infusion of large amounts of Ringers lactate prolongs the functional gastrointestinal recovery time and increases the number of complications after open abdominal surgery. We performed an open-labelled clinical trial to determine whether hydroxyethyl starch or Ringers lactate exerts these adverse effects when the surgery is performed by laparoscopy. Methods: Eighty-eight patients scheduled for major abdominal cancer surgery (83% by laparoscopy) received a first-line fluid trea...

  6. Different outcome of six homozygotes for prothrombin A20210A gene variant

    Angiolillo Antonella


    Full Text Available Abstract Prothrombin G20210A gene variant (FII G20210A is a risk factor for venous thrombotic disease while conflicting results have been reported for the risk of arterial thrombotic events. However, vascular episodes were absent in up to 40% of the 67 homozygotes for the G20210A described so far, which indicates that the clinical expression depends on additional risk/trigger factors. We describe six homozygotes for the G20210A variant, among which the first pair of siblings (cases n. 3 and 4 reported so far that displayed a strongly heterogeneous clinical outcome. Case 1, a female of 27 years, developed a full thrombosis of common femoral, superficial and popliteal veins. She assumed oral contraceptives in the last two years. Case n. 2, 34 years old, suffered of recurrent pregnancy loss in absence of any causative alteration. Cases n. 3 and n. 5 experienced arterial thrombotic disease, i.e., juvenile myocardial infarction (40 years old and stroke (48 years old, respectively, in absence of other risk factors. Finally, cases n. 4 and 6 identified as homozygotes for the FII G20210A variant being consanguineous of symptomatic subjects bearing the variant, did not experience any episode of venous nor arterial disease. Both of them have chronic liver disease with an impairement of the prothrombin time INR. Thus, homozygotes for the G20210A are at risk for arterial (in addition to venous thromobotic events; chronic liver disease might modulate this risk.

  7. On the use of prothrombin complex concentrate in patients with coagulopathy requiring tooth extraction.

    Morimoto, Yoshinari; Niwa, Hitoshi; Nakatani, Takeshi


    In patients on high-level anticoagulant therapy (prothrombin time-international normalized ratio [PT-INR] ≥ 4.5), surgical procedures can be carried out with bridging therapy using heparin. However, surgical treatment options are severely limited in patients on high-level anticoagulant therapy and who have heparin-induced thrombocytopenia (HIT), as heparin use is contraindicated. We performed tooth extraction using prothrombin complex concentrate (PCC) in 2 HIT patients on high-level anticoagulation therapy (PT-INR ≥ 4.5). Five hundred units of PCC were administered intravenously, and after 15 minutes, it was confirmed that PT-INR was less than 2.0. Tooth extraction was then performed and sufficient local hemostasis was achieved. At 3 hours after tooth extraction, PT-INR was 2.0 or higher and later increased to 4.0 or higher, but postoperative bleeding was mostly absent. When performing tooth extraction in HIT patients on high-level anticoagulant therapy, favorable hemostatic management was achieved through sufficient local hemostasis and transient warfarin reversal using PCC.

  8. Prolonged naproxen joint residence time after intra-articular injection of lipophilic solutions comprising a naproxen glycolamide ester prodrug in the rat

    Thing, Mette; Lu, Yi; Agårdh, Li


    Intra-articular injection of oil solutions of lipophilic prodrugs that rapidly degrade to their parent compound in synovial fluid may constitute a feasible approach to increase the joint residence time of non-steroidal anti-inflammatory drugs. In this in vivo study, oil solutions of the N...... around 0.11 to 3.3h and a 30% reduction in the maximum serum concentration were observed compared to that of the parent naproxen. The similar serum profiles obtained using the two oils indicate that the release was not affected by the oil viscosity. A prolonged naproxen joint residence time in rats...

  9. Replacement of isoleucine-397 by threonine in the clotting proteinase factor IXa (Los Angeles and Long Beach variants) affects macromolecular catalysis but not L-tosylarginine methyl ester hydrolysis. Lack of correlation between the ox brain prothrombin time and the mutation site in the variant proteins.

    Spitzer, S G; Warn-Cramer, B J; Kasper, C K; Bajaj, S P


    Previously, from the plasma of unrelated haemophilia-B patients, we isolated two non-functional Factor IX variants, namely Los Angeles (IXLA) and Long Beach (IXLB). Both variants could be cleaved to yield Factor IXa-like molecules, but were defective in catalysing the cleavage of Factor X (macromolecular substrate) and in binding to antithrombin III (macromolecular inhibitor). In the present study we have identified the mutation of IXLA by amplifying the exons (including flanking regions) as well as the 5' end of the gene by polymerase-chain-reaction (PCR) method and sequencing the amplified DNA by the dideoxy chain-termination method. Comparison of the normal IX and IXLA sequences revealed only one base substitution (T----C) in exon VIII of IXLA, with a predicted replacement of Ile-397 to Thr in the mature protein. This mutation is the same as found recently for IXLB. The observation that IXLB and IXLA have the same mutation is an unexpected finding, since, on the basis of their ox brain prothrombin time (PT, a test that measures the ability of the variant Factor IX molecules to inhibit the activation of Factor X by Factor VIIa-tissue factor complex), these variants have been classified into two different groups and were thought to be genetically different. Our observation thus suggests that the ox brain PT does not reflect the locus of mutation in the coding region of the variant molecules. However, our analysis suggests that the ox brain PT is related to Factor IX antigen concentration in the patient's plasma. Importantly, although the mutation in IXLA or IXLB protein is in the catalytic domain, purified IXaLA and IXaLB hydrolyse L-tosylarginine methyl ester at rates very similar to that of normal IXa. These data, in conjunction with our recent data on Factor IXBm Lake Elsinore (Ala-390----Val mutant), strengthen a conclusion that the peptide region containing residues 390-397 of normal Factor IXa plays an essential role in macromolecular substrate catalysis and

  10. Prothrombin complex concentrate use in coagulopathy of lethal brain injuries increases organ donation.

    Joseph, Bellal; Aziz, Hassan; Pandit, Viraj; Hays, Daniel; Kulvatunyou, Narong; Tang, Andrew; Wynne, Julie; O' Keeffe, Terence; Green, Donald J; Friese, Randall S; Gruessner, Rainer; Rhee, Peter


    Coagulopathy is a defined barrier for organ donation in patients with lethal traumatic brain injuries. The purpose of this study was to document our experience with the use of prothrombin complex concentrate (PCC) to facilitate organ donation in patients with lethal traumatic brain injuries. We performed a 4-year retrospective analysis of all patients with devastating gunshot wounds to the brain. The data were analyzed for demographics, change in international normalized ratio (INR), and subsequent organ donation. The primary end point was organ donation. Eighty-eight patients with lethal traumatic brain injury were identified from the trauma registry of whom 13 were coagulopathic at the time of admission (mean INR 2.2 ± 0.8). Of these 13 patients, 10 patients received PCC in an effort to reverse their coagulopathy. Mean INR before PCC administration was 2.01 ± 0.7 and 1.1 ± 0.7 after administration (P brain injuries.

  11. Abnormal plasma prothrombin (PIVKA-II) levels in hepatocellular carcinoma.

    Kawaguchi, Y


    The concentration of abnormal prothrombin, or the protein induced by vitamin K absence or antagonist II (PIVKA-II) in 102 patients with hepatic disorders was measured by an enzyme immunoassay method. The concentration of PIVKA-II in the plasma was elevated in 11 out of 18 patients with hepatocellular carcinoma and also in a patient with hepatoblastoma. There was no correlation between serum alpha-fetoprotein and plasma PIVKA-II levels. The PIVKA-II level was normal in 11 patients who had metastatic carcinoma or cholangiocellular carcinoma. Moreover, benign diseases of the liver did not cause an elevation in PIVKA-II. PIVKA-II might be an useful marker of hepatocellular carcinoma because, like alpha-fetoprotein, its level changes in close relation to the effects of treatment.

  12. A discrete-time analysis of the effects of more prolonged exposure to neighborhood poverty on the risk of smoking initiation by age 25.

    Kravitz-Wirtz, Nicole


    Evidence suggests that individuals who initiate smoking at younger ages are at increased risk for future tobacco dependence and continued use as well as for numerous smoking-attributable health problems. Identifying individual, household, and to a far lesser extent, contextual factors that predict early cigarette use has garnered considerable attention over the last several decades. However, the majority of scholarship in this area has been cross-sectional or conducted over relatively short windows of observation. Few studies have investigated the effects of more prolonged exposure to smoking-related risk factors, particularly neighborhood characteristics, from childhood through early adulthood. Using the 1970-2011 waves of the Panel Study of Income Dynamics merged with census data on respondents' neighborhoods, this study estimates a series of race-specific discrete-time marginal structural logit models for the risk of smoking initiation as a function of neighborhood poverty, as well as individual and household characteristics, from ages four through 25. Neighborhood selection bias is addressed using inverse-probability-of-treatment weights. Results indicate that more prolonged exposure to high (>20%) as opposed to low (smoking onset by age 25, although consistent with prior literature, this effect is only evident among white and not nonwhite youth and young adults.

  13. Factor V Leiden 1691G/A and prothrombin gene 20210G/A polymorphisms as prothrombotic markers in adult Egyptian acute leukemia patients.

    El Sissy, Azza Hamdy; El Sissy, Maha H; Elmoamly, Shereef


    Factor V Leiden 1691G/A and prothrombin gene 20210G/A mutations are the most common genetic defects leading to thrombosis. This work aimed to study the FV Leiden and the prothrombin gene polymorphism in adult Egyptian patients with acute leukemia and their importance in thrombophilia screening. The study included 76 patients with acute leukemia and 100 healthy controls. Genotyping was done by real-time polymerase chain reaction technique. For factor V Leiden, the frequency of G/A mutation conferred more than 2.5-fold of increased risk of (OR 2.639 95 % CI 1.045-6.669). The frequency of factor V Leiden combined (G/A + A/A) genotypes conferred 2.83-fold of increased risk (OR 2.828, CI 1.13-7.075), The A allele conferred almost threefold increased risk (OR 2.824, 95 % CI 1.175-6.785). Despite higher frequency in patients compared to controls, there was no risk of association between prothrombin gene mutation and acute leukemia in adult Egyptians nor was there between combined genotypes of prothrombin gene mutation and factor V Leiden.

  14. A generation lost? Prolonged effects of labour market entry in times of high unemployment in the Netherlands

    Wolbers, M.H.J.


    After the economic crisis of the 1980s, concerns arose about whether the high youth unemployment at that time would produce a 'lost generation' of young people in the Netherlands. The same concerns have recently arisen about the potential effects of the current high rate of youth unemployment. The

  15. A generation lost? Prolonged effects of labour market entry in times of high unemployment in the Netherlands

    Wolbers, M.H.J.


    After the economic crisis of the 1980s, concerns arose about whether the high youth unemployment at that time would produce a 'lost generation' of young people in the Netherlands. The same concerns have recently arisen about the potential effects of the current high rate of youth unemployment. The i

  16. An antithrombotic fucoidan, unlike heparin, does not prolong bleeding time in a murine arterial thrombosis model: a comparative study of Undaria pinnatifida sporophylls and Fucus vesiculosus.

    Min, Soon-Ki; Kwon, Oh-Choon; Lee, Sub; Park, Ki-Hyuk; Kim, Jong-Ki


    The antithrombotic activities and bleeding effects of selected fucoidans (source from either Undaria pinnatifida sporophylls or from Fucus vesiculosus) have been compared with heparin in the ferric chloride-induced arterial thrombus mouse model. Thrombosis was induced by applying 5% ferric chloride for 3 min on the carotid artery region of Balb/c mouse. Five minutes prior to thrombus induction, mice were infused through the tail vein with either saline (control) or polysaccharides. Either fucoidan or heparin was dosed at 0.1, 1.25, 2.5, 5.0, 10, 25, or 50 mg/kg intravenously (i.v.) The carotid blood flow was monitored until more than 60 min post-thrombus induction. Mouse tail transection bleeding time was measured up to 60 min after making a cut in the mouse tail. Both antithrombotic and bleeding effects were observed in a dose-dependent manner for both fucoidans and heparin. Thrombus formation was totally (reflected by Doppler flow meter) inhibited at either 5 or 50 mg/kg of unfractionated Undaria fucoidan or a low-molecular-weight Undaria fucoidan fraction, respectively, without prolonging the time-to-stop bleeding compared with the control (p Fucus fucoidan at 25 mg/kg where the time-to-stop bleeding was still significantly prolonged, by as much as 8 ± 1.7 min (p < 0.02). In contrast the heparin-treated group showed total inhibition of thrombus formation even at a small dose of 0.8 mg/kg (400 IU) at which bleeding continued until 60 min. In conclusion algal fucoidans are highly antithrombotic without potential haemorrhagic effects compared with heparin in the arterial thrombus model, but this property differs from algal species to species, and from the molecular structure of fucoidans.

  17. Intrasplenic transplantation of allogeneic hepatocytes prolongs survival in anhepatic rats.

    Arkadopoulos, N; Lilja, H; Suh, K S; Demetriou, A A; Rozga, J


    To examine whether hepatocytes transplanted in the spleen can function as an ectopic liver, we performed hepatocyte transplantation in rats that were rendered anhepatic. Total hepatectomy was performed by using a novel single-stage technique. Following hepatectomy, Group 1 rats (n = 16) were monitored until death to determine survival time without prior intervention. Group 2 anhepatic rats (n = 20) were sacrificed at various times to measure blood hepatocyte growth factor (HGF) and transforming growth factor beta1 (TGF-beta1) levels. Group 3 (n = 16) rats received intrasplenic injection of isolated hepatocytes (2.5 x 10(7) cells/rat) followed by total hepatectomy after 3 days. Group 4 (n = 12) sham-transplanted rats received intrasplenic saline infusion, and after 3 days they were rendered anhepatic. Group 2, 3, and 4 rats were maintained on daily Cyclosporine A (10 mg/kg; intramuscularly). Group 1 anhepatic rats survived for 22.4 +/- 5.2 hours (standard deviation). The anhepatic state was associated with a progressive and statistically significant rise in blood HGF and TGF-beta1 levels. Rats that received hepatocyte transplantation before total hepatectomy had a significantly longer survival time than sham-transplanted anhepatic controls (34.1 +/- 8.5 vs. 15.5 +/- 4.8 hrs, P ammonia, prothrombin time, international normalized ratio, and TGF-beta1 levels when compared with sham-transplanted controls. In conclusion, intrasplenic transplantation of allogeneic hepatocytes prolonged survival, improved blood chemistry, and lowered blood TGF-beta1 levels in rats rendered anhepatic.

  18. Time-course of tomato whole-plant respiration and fruit and stem growth during prolonged darkness in relation to carbohydrate reserves.

    Gary, C; Baldet, P; Bertin, N; Devaux, C; Tchamitchian, M; Raymond, P


    To evaluate the relevance of a simple carbon balance model (Seginer et al., 1994, Scientia Horticulturae 60: 55-80) in source-limiting conditions, the dynamics of growth, respiration and carbohydrate reserves of tomato plants were observed in prolonged darkness. Four days prior to the experiments, plants were exposed to high or low light levels and CO(2) concentrations. The concentration of carbohydrates in vegetative organs was 30-50 % lower in plants that were exposed to low carbon assimilation conditions compared with those exposed to high carbon assimilation conditions. During prolonged darkness, plants with low carbohydrate reserves exhibited a lower whole-plant respiration rate, which decreased rapidly to almost zero after 24 h, and carbohydrate pools were almost exhausted in leaves, roots and flowers. In plants with high carbohydrate reserves, the whole-plant respiration rate was maintained for a longer period and carbohydrates remained available for at least 48 h in leaves and flowers. In contrast, fruits maintained fairly stable and identical concentrations of carbohydrates and the reduction in their rate of expansion was moderate irrespective of the pre-treatment carbon assimilation conditions. The time-course of asparagine and glutamine concentrations showed the occurrence of carbon stress in leaves and flowers. Estimation of source and sink activities indicated that even after low carbon assimilation, vegetative organs contained enough carbohydrates to support fruit growth provided their own growth stopped. The time of exhaustion of these carbohydrates corresponded grossly to the maintenance stage simulated by the model proposed by Seginer et al. (1994), thus validating the use of such a model for optimizing plant growth.

  19. Radiobiological evaluation of the radiation dose as used in high-precision radiotherapy: effect of prolonged delivery time and applicability of the linear-quadratic model.

    Shibamoto, Yuta; Otsuka, Shinya; Iwata, Hiromitsu; Sugie, Chikao; Ogino, Hiroyuki; Tomita, Natsuo


    Since the dose delivery pattern in high-precision radiotherapy is different from that in conventional radiation, radiobiological assessment of the physical dose used in stereotactic irradiation and intensity-modulated radiotherapy has become necessary. In these treatments, the daily dose is usually given intermittently over a time longer than that used in conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. This phenomenon is almost universarily observed in vitro. In in vivo tumors, however, this decrease in effect can be counterbalanced by rapid reoxygenation, which has been demonstrated in a laboratory study. Studies on reoxygenation in human tumors are warranted to better evaluate the influence of prolonged radiation delivery. Another issue related to radiosurgery and hypofractionated stereotactic radiotherapy is the mathematical model for dose evaluation and conversion. Many clinicians use the linear-quadratic (LQ) model and biologically effective dose (BED) to estimate the effects of various radiation schedules, but it has been suggested that the LQ model is not applicable to high doses per fraction. Recent experimental studies verified the inadequacy of the LQ model in converting hypofractionated doses into single doses. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when it is used for tumor responses in vivo, since it does not take reoxygenation into account. For normal tissue responses, improved models have been proposed, but, for in vivo tumor responses, the currently available models are not satisfactory, and better ones should be proposed in future studies.

  20. Bravo capsule system optimizes intragastric pH monitoring over prolonged time: Effects of ghrelin on gastric acid and hormone secretion in the rat

    Tobias Rudholm; Per Mikael Hellstrom; Elvar Theodorsson; Colin Allan Campbell; Peter Geoffrey McLean; Erik Naslund


    AIM: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time. METHODS: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive days. For comparison, a gastric fistula model was used. Effects of ghrelin and esomeprazole, with or without pentagastrin, on gastric pH were studied. In addition, effects of esomeprazole on plasma ghrelin, gastrin and somatostatin were analyzed. RESULTS: All rats recovered after surgery. The average 24-h pH during free feeding was 2.3±0.1 (η = 20) with a variation of 18%±6% over 5 d. Ghrelin, 2400 pmol/kg, t.i.d, increased pH from 1.7± 0.1 to 3.1±0.3 (P<0.01) as recorded with the Bravo system. After esomeprazole (1 mg/kg, 3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4±0.1, with day-to-day variation over the entire period of 8%±3%. The fistula and pH studies generated similar results. Acid inhibition with esomeprazole increased plasma ghrelin from 10±2 pmol/L to 65±26 pmol/L (P<0.001), and somatostatin from 10±2 pmol/L to 67±18 pmol/L (P <0.001). CONCLUSION: pH measurements with the Bravo capsule are reliable, and comparable to those of the gastric fistula model. The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short- and long-term evaluation of effects of drugs and hormones.

  1. Prolonged time course of glutamate-operated single channel currents in neuromuscular preparations of small crayfish and a membrane current triggered by glutamate channel gating.

    Finger, W; Martin, C; Pareto, A


    Single channel currents activated by glutamate were recorded by means of the patch-clamp technique in the abdominal superficial extensor muscle and the claw opener muscle of small (1-3 months old) and large (greater than 16 months old) crayfish. It was found that in small crayfish the time course of glutamate-operated single channel currents was prolonged by a factor of about 4 in these two preparations. In the abdominal superficial extensor muscle, single channel currents activated by 5 mmol/l glutamate had a mean burst length of tau = 2-3 ms in large crayfish and a mean burst length of tau = 8-9 ms in small crayfish. In the claw opener, for large crayfish tau congruent to 0.5 ms and for small crayfish tau = 1.5-2.5 ms resulted (500 mumol/l glutamate). Moreover, single channel currents with long time courses often slowly increased their amplitudes during the open time of the channel and current amplitudes did not decline completely to the baseline after channel closing. In addition, single channel currents with relatively constant amplitude were often followed by a small increasing and decreasing membrane current. The latter results suggest that glutamate channel gating might trigger a membrane current.

  2. Prevalence of factor Ⅴ Leiden and prothrombin G20210A in patients with gastric cancer

    Sandra Battistelli; Massimo Stefanoni; Alberto Genovese; Aurelio Vittoria; Roberto Cappelli; Franco Roviello


    AIM: To analyze the prevalence of the two commonest thrombophilic mutations, factor Ⅴ Leiden and prothrombin G20210A, in patients with gastric cancer.METHODS: One hundred and twenty-one patients with primary gastric carcinoma and 130 healthy subjects,comparable for age and sex, were investigated. Factor Ⅴ Leiden was detected by using polymerase chain reaction and restriction enzyme digestion, and prothrombin G20210A gene mutation by allele-specific PCR.RESULTS: Among the 121 cancer patients, factor Ⅴ Leiden was found in 4 cases (GA genotype: 3.3%) and prothrombin G20210A in 10 cases (GA genotype: 8.3%).Of the 130 control subjects, factor Ⅴ Leiden was detected in 6 cases (GA genotype: 4.6%) and prothrombin G20210A in 8 cases (GA genotype: 6.1%). No double heterozygous carriers of both mutations were found in either group. The prevalence of both factor Ⅴ Leiden and prothrombin G20210A variant was not statistically different between the cancer patients and the healthy subjects.CONCLUSION: Our study suggests that, in gastric cancer, the risk factors of thrombophilic cancer state are on acquired rather than on a genetic basis and that prothrombin G20210A does not seem to be a cofactor in gastric cancer pathogenesis.

  3. Cotiarinase is a novel prothrombin activator from the venom of Bothrops cotiara.

    Kitano, Eduardo S; Garcia, Thalita C; Menezes, Milene C; Tashima, Alexandre K; Zelanis, André; Serrano, Solange M T


    Snake venom serine proteinases (SVSPs) may affect hemostatic pathways by specifically activating components involved in coagulation, fibrinolysis and platelet aggregation or by unspecific proteolytic degradation. In this study, we purified and characterized an SVSP from Bothrops cotiara venom, named cotiarinase, which generated thrombin upon incubation with prothrombin. Cotiarinase was isolated by a two-step procedure including gel-filtration and cation-exchange chromatographies and showed a single protein band with a molecular mass of 29 kDa by SDS-polyacrylamide gel electrophoresis under reducing conditions. Identification of cotiarinase by mass spectrometric analysis revealed peptides that matched sequences of viperid SVSPs. Cotiarinase did not show fibrinogen-clotting, platelet-aggregating, fibrinogenolytic and factor X activating activities. Upon incubation with prothrombin the generation of thrombin was detected using the peptide substrate d-Phe-Pip-Arg-pNA. Moreover, mass spectrometric identification of prothrombin fragments generated by cotiarinase in the absence of co-factors (phospholipids, factor Va, factor Xa and Ca(2+) ions), indicated the limited proteolysis of this protein to release prothrombin 1, fragment 1 and thrombin. Cotiarinase is a novel SVSP that acts on prothrombin to release active thrombin that does not match any group of the current classification of snake venom prothrombin activators.

  4. A surface-micromachining-based inertial micro-switch with compliant cantilever beam as movable electrode for enduring high shock and prolonging contact time

    Xu, Qiu [National Key Laboratory of Science and Technology on Micro/Nano Fabrication, School of Electronics Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240 (China); Yang, Zhuoqing, E-mail: [National Key Laboratory of Science and Technology on Micro/Nano Fabrication, School of Electronics Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240 (China); Fu, Bo; Li, Jianhua; Wu, Hao [Huaihai Industrial Group Co., Ltd., Changzhi, Shanxi Province, 046012 (China); Zhang, Qihuan; Sun, Yunna; Ding, Guifu; Zhao, Xiaolin [National Key Laboratory of Science and Technology on Micro/Nano Fabrication, School of Electronics Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240 (China)


    Highlights: • The designed cantilever beam attached to the proof mass can endure a larger shock acceleration (∼1000 g order of magnitude) compared to those traditional designs (∼100 g order of magnitude). • Effect of the pulse width on the threshold acceleration, the response time and the contact time is investigated. • A constraint sleeve structure is introduced to lower the off-axis sensitivity. - Abstract: A novel laterally-driven inertial micro-switch with two L-shaped elastic cantilever beams as the movable electrode, which is attached to the proof mass, is proposed in this paper. The advantage of this design is that the contact time of the inertial micro-switch can be prolonged. Meanwhile, the micro-switch can withstand a higher shock than the traditional designs whose cantilever beams are attached to the fixed electrode. The designed inertial micro-switch was simulated and optimized with ANSYS software and fabricated on a quartz substrate by surface micromachining technology. The simulated result demonstrates that the threshold acceleration (a{sub ths}) under stable switch-on state is about 288 g and the contact time is about 198 μs when the pulse width of acceleration loads is 1 ms. At the same time, it indicates that the threshold acceleration, the response time and the contact time of designed micro-switch all increase with the pulse width of acceleration loads. The simulation of impact process in non-sensitive direction shows that the introduced constraint sleeve structure in the novel inertial micro-switch can lower the off-axis sensitivity. The fabricated micro-switch prototype has been tested by a standard dropping hammer system under shock accelerations with various amplitudes and pulse widths. The experimental measurements show that the contact time is about 150 μs when the threshold acceleration is about 288 g. It also indicates that the response time and the contact time both increase with the pulse width, which is consistent with the

  5. The application of the linear quadratic model to compensate the effects of prolonged fraction delivery time on a Balb/C breast adenocarcinoma tumor: An in vivo study.

    Nikzad, Safoora; Hashemi, Bijan; Hasan, Zuhair Saraf; Mozdarani, Hossein; Baradaran-Ghahfarokhi, Milad; Amini, Payam


    Purpose To investigate the effect of increasing the overall treatment time as well as delivering the compensating doses on the Balb/c breast adenocarcinoma (4T1) tumor. Materials and methods A total of 72 mice were divided into two aliquots (classes A and B) based on the initial size of their induced tumor. Each class was divided into a control and several treatment groups. Among the treatment groups, group 1 was continuously exposed to 2 Gy irradiation, and groups 2 and 3 received two subfractions of 1 Gy over the total treatment times of 30 and 60 min, respectively. To investigate the effect of compensating doses, calculated based on the developed linear quadratic model (LQ) model, the remaining two groups (groups 4 and 5) received two subfractions of 1.16 and 1.24 Gy over the total treatment times of 30 and 60 min, respectively. The growing curves, Tumor Growth Time (TGT), Tumor Growth Delay Time (TGDT) and the survival of the animals were studied. Results For class A (tumor size ≤ 30 mm(3)), the average tumor size in the irradiated groups 1-5 was considerably different compared to the control group as one unit (day) change in time, by amount of -160.8, -158.9, +39.4 and +44.0, respectively. While these amounts were +22.0, +17.9, -21.7 and -0.1 for class B (tumor size ≥ 400 mm(3)). For the class A of animals, the TGT and TGDT parameters were significantly lower (0 ≤ 0.05) for the groups 2 and 3, compared to group 1. There was no significant difference (p > 0.05) between groups 1, 4 and 5 in this class. There was no significant difference (p > 0.05) between all the treated groups in class B. Conclusions Increasing total treatment time affects the radiobiological efficiency of treatment especially in small-sized tumor. The compensating doses derived from the LQ model can be used to compensate the effects of prolonged treatment times at in vivo condition.

  6. Levels of acarboxy prothrombin (PIVKA-II) and coagulation factors in warfarin-treated patients.

    Umeki, S; Umeki, Y


    PIVKA-II (protein induced by vitamin K absence or antagonists-II) was determined and compared with other coagulation factors in normal subjects and patients treated with the anticoagulant warfarin. In 18 (60%) of 30 patients treated with warfarin, PIVKA-II values were 1 microgram/ml or more, although they were less than 1 microgram/ml in all 39 normal subjects (100%). In patients treated with warfarin, values of prothrombin time and partial thromboplastin time were significantly higher than those in normal subjects. However, values of hepaplastintest (normotest) and thrombotest in the patients were greatly lower than those in normal subjects. There were no significant differences between bleeding time or plasma fibrinogen values in the patients and normal subjects. The values of PIVKA-II were inversely correlated (P less than 0.01) with those of hepaplastintest and thrombotest. The measurement of PIVKA-II in the plasma should be useful in detecting vitamin K-deficient status among haemorrhagic disorders.

  7. A prothrombin activator from Bothrops erythromelas (jararaca-da-seca) snake venom: characterization and molecular cloning.

    Silva, Márcia B; Schattner, Mirta; Ramos, Celso R R; Junqueira-de-Azevedo, Inácio L M; Guarnieri, Míriam C; Lazzari, María A; Sampaio, Claudio A M; Pozner, Roberto G; Ventura, Janaina S; Ho, Paulo L; Chudzinski-Tavassi, Ana M


    A novel prothrombin activator enzyme, which we have named 'berythractivase', was isolated from Bothrops erythromelas (jararaca-da-seca) snake venom. Berythractivase was purified by a single cation-exchange-chromatography step on a Resource S (Amersham Biosciences) column. The overall purification (31-fold) indicates that berythractivase comprises about 5% of the crude venom. It is a single-chain protein with a molecular mass of 78 kDa. SDS/PAGE of prothrombin after activation by berythractivase showed fragment patterns similar to those generated by group A prothrombin activators, which convert prothrombin into meizothrombin, independent of the prothrombinase complex. Chelating agents, such as EDTA and o -phenanthroline, rapidly inhibited the enzymic activity of berythractivase, like a typical metalloproteinase. Human fibrinogen A alpha-chain was slowly digested only after longer incubation with berythractivase, and no effect on the beta- or gamma-chains was observed. Berythractivase was also capable of triggering endothelial proinflammatory and procoagulant cell responses. von Willebrand factor was released, and the surface expression of both intracellular adhesion molecule-1 and E-selectin was up-regulated by berythractivase in cultured human umbilical-vein endothelial cells. The complete berythractivase cDNA was cloned from a B. erythromelas venom-gland cDNA library. The cDNA sequence possesses 2330 bp and encodes a preproprotein with significant sequence similarity to many other mature metalloproteinases reported from snake venoms. Berythractivase contains metalloproteinase, desintegrin-like and cysteine-rich domains. However, berythractivase did not elicit any haemorrhagic response. These results show that, although the primary structure of berythractivase is related to that of snake-venom haemorrhagic metalloproteinases and functionally similar to group A prothrombin activators, it is a prothrombin activator devoid of haemorrhagic activity. This is a feature

  8. Delta(9)-tetrahydrocannabinol prolongs the immobility time in the mouse forced swim test: involvement of cannabinoid CB(1) receptor and serotonergic system.

    Egashira, Nobuaki; Matsuda, Tomomi; Koushi, Emi; Higashihara, Fuminori; Mishima, Kenichi; Chidori, Shozo; Hasebe, Nobuyoshi; Iwasaki, Katsunori; Nishimura, Ryoji; Oishi, Ryozo; Fujiwara, Michihiro


    In the present study, we investigated the effect of Delta(9)-tetrahydrocannabinol (THC), the principal psychoactive component of marijuana, on immobility time during the forced swim test. THC (2 and 6 mg/kg, i.p.) significantly prolonged the immobility time. In addition, THC at the same doses did not significantly affect locomotor activity in the open-field test. The selective cannabinoid CB(1) receptor antagonist rimonabant (3 mg/kg, i.p.) significantly reduced the enhancement of immobility by THC (6 mg/kg). Similarly, the selective serotonin (5-HT) reuptake inhibitor (SSRI) citalopram (10 mg/kg, i.p.) and 5-HT(1A/7) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.3 mg/kg, i.p.) significantly reduced this THC-induced effect. Moreover, the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide dihydrochloride (WAY100635, 1 mg/kg, i.p.) and the postsynaptic 5-HT(1A) receptor antagonist MM-77 (0.1 mg/kg, i.p.) reversed this reduction effect of 8-OH-DPAT (0.3 mg/kg). In contrast, the selective 5-HT(7) receptor antagonist (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl]phenol hydrochloride (SB269970) had no effect on this reduction effect of 8-OH-DPAT. WAY100635 (1 mg/kg) also reversed the reduction effect of citalopram (10 mg/kg). These findings suggest that the 5-HT(1A) receptors are involved in THC-induced enhancement of immobility.

  9. [Dopplerometry at prolonged pregnancy].

    Salii-Prenichi, L; Milchev, N; Markova, D; Apiosjan, Zh


    Prolonged pregnancy, associated with low amniotic fluid is a reason for the increase of fetal mortality and morbidity. There is no a define test at prolonged pregnancy which can determine which pregnancy are at a risk for adverse outcome and complications. Dopplerometry as a noninvasive method for examination of blood circulation, and especially a. cerebri media and a. umbilicalis can be used for the prediction of the outcome of prolonged pregnancy.

  10. Antibodies Against Annexin V and Prothrombin, Their Correlation with Other Anti-phospholipid Antibodies in Recurrent Pregnancy Loss


    Objective To study the findings of serum antibodies against annexin V, prothrombin,ph-inositol, ph-acid, ph-ethanolamine, ph-serine, ph-glycerol, cardiolipin, and beta2-glycoprotein I and analyze the trophoblast annexin V receptorsMethods Sera from 156 patients aged 26-41 years with recurrent pregnancy loss (3-7 times) were investigated. Eighty-four fertile healthy women aged 24-38 years were included in a control group. ELISA methods were used for detecting a panel of sera anti-phospholipid antibodies. Immunolocalization of annexin Vreceptors in 143trophoblast specimens of 156patients was investigated by the immunofluorescence technique using Annexin V-FITC, Apoptosis and Annexin V-CY3 commercial kits.Results Positivity for anti-phospholipid antibodies mainly against ph-serine, phethanolamine, and ph-inositol was found together in 80. 8% (126 out of 156 patients),anti-prothrombin antibodies in 12% (18), and anti-annexin Vantibodies in 13. 5%(21) women. No significant levels of anti-phospholipid antibodies were found in 6controls. Placenta immunohistopathology also exhibited some changes manifested by the presence of apoptotic and necrotic cells in trophoblast, and very few microthrombotization in some intervillous spaces.Conclusion Our detailed study demonstrated the prevalence of majority of antiphospholipid antibodies as a high risk factor for repeated reproductive failure. Very low microthrombosis in placentas could be explained by the changes of haemocoagulation properties out of uterus.

  11. [Prevalence of thrombophilic mutations of FV Leiden, prothrombin G20210A and PAl-1 4G/5G and their combinations in a group of 1450 healthy middle-aged individuals in the Prague and Central Bohemian regions (results of FRET real-time PCR assay)].

    Kvasnicka, Jan; Hájková, Jaroslava; Bobcíková, Petra; Kvasnicka, Tomás; Dusková, Daniela; Poletínová, Sárka; Kieferová, Veronika


    Factor V Leiden (G1691A) and prothrombin gene (FII G20210A) mutations are independent risk factors of venous thrombosis and this risk is further increased by the combined genotype 4G/4G PAI-1. The primary objective was to identify the frequency of mutations of minor alleles and genotypes of FVL, FII G20210A and PAI-1 4G/5G in healthy Caucasians in the Prague and Central Bohemia regions. The secondary objective was to identify the occurrence of their mutual combinations. Genotyping was performed in 1,450 healthy individuals (blood donors, 981 men and 469 women) using robotic DNA isolation and subsequent PCR and melting curve analysis (Light Cycler 480 System, Roche). The minor allele frequencies in FV Leiden and FII G20210A mutations were 4.5% and 1.3% respectively. The frequency of the 4G PAI-1 allele was 55.9%. The genotype frequencies were as follows: GG 91.10%, GA 8.83% and AA 0.07% for FV Leiden; GG 97.38%, GA 2.55% and AA 0.07% for FII G20210A and 4G/4G 30.69%, 4G/5G 50.34% and 5G/5G 18.97% for PAI-1. No differences in these frequencies were found between the genders. The occurrence of the combined heterozygous FII and heterozygous FV Leiden mutations was 0.14%. The PAI-1 4G/4G genotype was combined with the heterozygous FV leiden mutation in 2.83% of cases and with the heterozygous FII mutation in 0.62% of cases. The found frequencies of genotypes and alleles confirm a relatively high prevalence of hereditary thrombophilia in the Czech Republic.

  12. Prolonged unexplained fatigue in paediatrics

    Bakker, R.J.


    Prolonged Unexplained Fatigue in Paediatrics. Fatigue, as the result of mental or physical exertion, will disappear after rest, drinks and food. Fatigue as a symptom of illness will recover with the recovering of the illness. But when fatigue is ongoing for a long time, and not the result of exertio

  13. Frequency of Factor V Leiden and Prothrombin Polymorphism in South of Iran

    Javad Dehbozorgian


    Full Text Available Normal hemostasis requires balanced regulation of prothromboticand antithrombotic factors. Inherited alteration of factor Vand prothrombin gene, the G20210A mutation, increases the resistanceof factor V to degradation and booster production ofprothrombin respectively. These alterations can increase hypercoagulabilityleading to thrombotic consequences. We aimed toassess the frequencies of these mutations in a group of the populationof southern Iran. In total, 198 healthy volunteers with theage range of 1-64 years were selected and screened for factor VLeiden and prothrombin mutations using polymerase chain reactionand restriction fragment length polymorphism techniques.The carrier frequencies for factor V Leiden and prothrombin mutationin the studied cohort were 4.1% and 3.07%, respectively.In the studied area, the allele frequency of factor V ishigher than the prothrombin G20210A mutation (0.0204 v0.0153. According to the data and Hardy-Weinberger equation,the total risk of thrombosis caused by homozygosity andheterozygosity of factor V Leiden, prothrombin G20210A mutationand compound heterozygosity of these mutations areabout 1 in 500 individuals.

  14. Prolonged radiation time and low nadir hemoglobin during postoperative concurrent chemoradiotherapy are both poor prognostic factors with synergistic effect on locally advanced head and neck cancer patients

    Su NW


    Full Text Available Nai-Wen Su,1 Chung-Ji Liu,2 Yi-Shing Leu,3 Jehn-Chuan Lee,3 Yu-Jen Chen,4 Yi-Fang Chang1,51Division of Medical Oncology and Hematology, Department of Internal Medicine, 2Department of Oral and Maxillofacial Surgery, 3Department of Otorhinolaryngology, 4Department of Radiation Oncology, 5Good Clinical Research Center, Department of Medical Research, Mackay Memorial Hospital, Taipei, TaiwanBackground: Anemia, a common complication of head and neck cancer treatment, is regarded as a poor prognostic factor. We evaluated the impact of low hemoglobin (Hb levels, measured at different time points, on a consecutive cohort of patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN who underwent postoperative concurrent chemoradiotherapy (CCRT.Materials and methods: From 2002 to 2009, 140 patients were enrolled and reviewed retrospectively. Preoperative (pre-op Hb, pre-CCRT Hb, and nadir Hb during CCRT were measured and recorded. The three Hb parameters were analyzed against several well-established pathologic risk factors and radiation-associated variables. Prognostic impacts were investigated with multivariate analysis by Cox proportional hazards model.Results: On Cox regression analysis, significantly higher risk of death was associated with pre-op Hb %13 g/dL (hazard ratio [HR] =1.8; 95% confidence interval [CI], 1.1–3.1; P=0.023, nadir Hb %11 g/dL (HR =1.9; 95% CI, 1.1–3.3; P=0.020, radiation treatment time (RTT >7 weeks (HR =1.9; 95% CI, 1.1–3.3; P=0.022, and multiple positive lymph nodes (HR =2.1; 95% CI, 1.2–3.7; P=0.010, after adjusting for primary tumor site and pathologic lymphovascular invasion. Patients with poor prognosticators including low nadir Hb %11 g/dL and RTT >7 weeks had a higher risk of death (HR =4.0; 95% CI =1.6–10.2; P=0.004.Conclusion: In the treatment setting of LA-SCCHN patients who underwent postoperative CCRT, coexistance of lower nadir Hb during CCRT and prolonged RTT resulted in

  15. The frequency of factor V Leiden and prothrombin G20210A mutations in Slovak and Roma (Gypsy) ethnic group of Eastern Slovakia.

    Bôžiková, Alexandra; Gabriková, Dana; Sovičová, Adriana; Behulová, Regina; Mačeková, Soňa; Boroňová, Iveta; Petrejčíková, Eva; Soták, Miroslav; Bernasovská, Jarmila; Bernasovský, Ivan


    Factor V Leiden and prothrombin G20210A are the two most prevalent causes of inherited thrombophilia. The prevalence of these mutations varies widely in healthy Caucasian population. The aim of our study was to determine the frequency of factor V Leiden and prothrombin G20210A mutations in Slovak and Roma ethnic group from Eastern Slovakia. We analyzed 540 asymptomatic individuals (269 individuals of Slovak ethnicity and 271 individuals of Roma ethnicity) by real-time PCR method. The detected allele frequencies were 2.97 versus 6.64 % for factor V Leiden (p = 0.0049), and 0.74 versus 0.92 % for prothrombin mutation (p = 0.7463) in Slovak and Roma population, respectively. The Roma ethnic group had significantly higher prevalence of factor V Leiden mutation when compared to Slovak ethnic group. The allele frequency of factor V Leiden in ethnic Romanies from Eastern Slovakia was one of the highest in Europe. Our results confirm an uneven geographical and ethnic distribution of factor V Leiden.

  16. Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review.

    Sciascia, Savino; Sanna, Giovanni; Murru, Veronica; Roccatello, Dario; Khamashta, Munther A; Bertolaccini, Maria Laura


    Antibodies to prothrombin are detected by directly coating prothrombin on irradiated ELISA plates (aPT) or by using the phosphatidylserine/prothrombin complex as antigen (aPS/PT). Although these antibodies have both been associated with antiphospholipid syndrome (APS) and a correlation between the two assays have been reported, it seems that aPT and aPS/PT belong to different populations of autoantibodies. It was our objective to systematically review the available evidence on aPT and aPS/PT antibodies and the risk of thrombosis in APS. Medline-reports published between 1988 and 2013 investigating aPT and aPS/PT as a risk factor for thrombosis were included. Whenever possible, antibody isotype(s) and site of thrombosis were analysed. This systematic review is based on available data from more than 7,000 patients and controls from 38 studies analysing aPT and 10 aPS/PT. Antibodies to prothrombin (both aPT and aPS/PT) increased the risk of thrombosis (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.72-3.5). aPS/PT seemed to represent a stronger risk factor for thrombosis, both arterial and/or venous than aPT (OR 5.11; 95%CI 4.2-6.3 and OR 1.82; 95%CI 1.44-2.75, respectively). In conclusion, routine measurement of aPS/PT (but not aPT) might be useful in establishing the thrombotic risk of patients with previous thrombosis and/or systemic lupus erythematosus. Their inclusion as laboratory criteria for the APS should be indisputably further explored.

  17. Successful living donor kidney transplantation in a patient with prothrombin gene mutation: Case report and literature review

    Edward Shen


    Full Text Available We present a patient with known prothrombin gene mutation and a history of prior vascular events, who underwent living donor kidney transplantation. Given the presumed elevated risk of complication from known prothrombin mutation, clinical management was directed towards optimizing living donor allograft function.

  18. The effects of acute and prolonged CRAM supplementation on reaction time and subjective measures of focus and alertness in healthy college students

    Olson Mark


    Full Text Available Abstract Background The purpose of this study was to examine the effect of acute and prolonged (4-weeks ingestion of a supplement designed to improve reaction time and subjective measures of alertness, energy, fatigue, and focus compared to placebo. Methods Nineteen physically-active subjects (17 men and 2 women were randomly assigned to a group that either consumed a supplement (21.1 ± 0.6 years; body mass: 80.6 ± 9.4 kg or placebo (21.3 ± 0.8 years; body mass: 83.4 ± 18.5 kg. During the initial testing session (T1, subjects were provided 1.5 g of the supplement (CRAM; α-glycerophosphocholine, choline bitartrate, phosphatidylserine, vitamins B3, B6, and B12, folic acid, L-tyrosine, anhydrous caffeine, acetyl-L-carnitine, and naringin or a placebo (PL, and rested quietly for 10-minutes before completing a questionnaire on subjective feelings of energy, fatigue, alertness and focus (PRE. Subjects then performed a 4-minute quickness and reaction test followed by a 10-min bout of exhaustive exercise. The questionnaire and reaction testing sequence was then repeated (POST. Subjects reported back to the lab (T2 following 4-weeks of supplementation and repeated the testing sequence. Results Reaction time significantly declined (p = 0.050 between PRE and POST at T1 in subjects consuming PL, while subjects under CRAM supplementation were able to maintain (p = 0.114 their performance. Significant performance declines were seen in both groups from PRE to POST at T2. Elevations in fatigue were seen for CRAM at both T1 and T2 (p = 0.001 and p = 0.000, respectively, but only at T2 for PL (p = 0.029. Subjects in CRAM maintained focus between PRE and POST during both T1 and T2 trials (p = 0.152 and p = 0.082, respectively, whereas significant declines in focus were observed between PRE and POST in PL at both trials (p = 0.037 and p = 0.014, respectively. No difference in alertness was seen at T1 between PRE and POST for CRAM (p = 0.083, but a significant

  19. Three versus four-factor prothrombin complex concentrates for "factor-based" resuscitation in a porcine hemorrhagic shock model.

    Moe, Donald Michael; Lallemand, Michael Scott; McClellan, John Mason; Smith, Joshua Porter; Marko, Shannon T; Eckert, Matthew J; Martin, Matthew J


    Bleeding is a leading cause of preventable death following severe injury. Prothrombin complex concentrates (PCC) treat inborn coagulation disorders and reverse oral anticoagulants, but are proposed for use in "factor-based" resuscitation strategies. Few studies exist for this indication in acidosis, or that compare 3-factor (3PCC) versus 4-factor (4PCC) products. We aimed to assess and compare their safety and efficacy in a porcine model of severe hemorrhagic shock and coagulopathy. Twenty-five adult Yorkshire swine underwent 35% volume hemorrhage, ischemia-reperfusion injury, and protocolized crystalloid resuscitation. Seventeen animals were randomized at 4 hours following model creation to receive a 45-IU/kg dose of either 3PCC or 4PCC. An additional 8 animals received autologous plasma transfusion prior to 4PCC to better characterize response to PCC. Individual factor levels were drawn at 4 and 6 hours. The model created significant acidosis with mean pH 7.21 and lactate of 9.6 mmol/L. Following PCC, 66.7% of 3PCC animals and 25% of 4PCC animals (regardless of plasma administration) developed consumptive coagulopathy. The animals that developed consumptive coagulopathy had manifested the "lethal triad" with lower temperatures (36.3 vs. 37.8°C), increased acidosis (pH 7.14 vs. 7.27, base excess -12.1 vs. -6.5 mEq/L), and worse coagulopathy (prothrombin time 17.1 vs. 14.6 seconds, fibrinogen 87.9 vs. 124.1 mg/dL) (all pfactors with transient improvement of prothrombin time, but there was significant depletion of fibrinogen and platelets with no lasting improvement of coagulopathy. PCC failed to correct coagulopathy and was associated with fibrinogen and platelet depletion. Of greater concern, PCC administration resulted in consumptive coagulopathy in the more severely ill animals. The incidence of consumptive coagulopathy was markedly increased with 3PCC versus 4PCC, and these products should be used with caution in this setting. II, therapeutic.

  20. Laser-induced europium(III) luminescence as a probe of the metal ion mediated association of human prothrombin with phospholipid.

    Rhee, M J; Horrocks, W D; Kosow, D P


    7F0 leads to 5D0 excitation spectroscopy of Eu(III) has been used to investigate the Eu(III) and phospholipid binding properties of human prothrombin. The results indicate that human prothrombin contains four high-affinity Eu(III) binding sites which are distributed into two classes of binding sites. When 4 equiv of Eu(III) is bound to prothrombin, the prothrombin is capable of binding to phospholipid vesicles. The deuterium isotope effect on the lifetime of the Eu(III)-prothrombin complex and the Eu(III)-prothrombin-phospholipid complex was used to determine the number of water molecules coordinated to the Eu(III). In both complexes, each of the Eu(III)'s coordinated to 2.5 +/- 0.5 water molecules. These results indicate that the binding of the Eu(III)-prothrombin complex to the phospholipid does not require the formation of a prothrombin-Eu(III)-phospholipid bridge.

  1. Urinary prothrombin fragment 1+2 in patients with venous thrombosis and myocardial infarction

    Van Es, J.; Biere-Rafi, S.; Ahdi, M.; Kamphuisen, P.W.; Meijers, J.C.M.; Gerdes, V.E.A.


    Patients with venous-thromboembolism (VTE) and myocardial infarction (MI) have elevated prothrombin fragment 1+2 (F1+2) levels. In patients with postoperative VTE, urinary F1+2 (uF1+2) was higher than in individuals without VTE. To explore the relationship between plasma and uF1+2 we performed a pil

  2. Avaliação de fibrinogênio, tempo de tromboplastina parcial e tempo de protrombina em pacientes com infarto agudo do miocárdio Evaluation of fibrinogen, activated partial thromboplastin time and prothrombin time in patients with acute myocardial infarction

    Marinês Lavall Dias


    during the acute phase of AMI were related to cardiovascular death or a new AMI event. This incidence was higher in the age range of 44 to 75 years in men, and 56 to 90 in women. Approximately 73% of patients presented family history of coronary heart disease (CHD, 66% were smokers, 63% presented hypertension and most of them were sedentary. Increased incidence of AMI in extreme temperatures was also observed. For fibrinogen concentrations (Fbr, results demonstrated significant difference (p < 0.05 between control and AMI patients. Considering troponin (TROP, creatine kinase (CK, the MB fraction of creatine kinase (CK-MB and leukocytes count, results showed statistically significant differences. However, partial thromboplastin time activated (PTAT, total cholesterol (TC, high-density lipoprotein (HDL, low-density lipoprotein (LDL, and triglyceride levels presented no significant difference between the studied groups. In conclusion, this work demonstrated a trend towards increasing fibrinogen concentration in patients with AMI, revealing that it may be considered one of the cardiac markers for AMI.

  3. Exhaustion from prolonged gambling

    Fatimah Lateef


    Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

  4. Exhaustion from prolonged gambling

    Fatimah Lateef


    Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities.Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion.Recently, three patients were seen at theDepartment ofEmergencyMedicine, presenting with exhaustion from prolonged involvement in gambling activities.The cases serve to highlight some of the physical consequences of prolonged gambling.

  5. Deciding about treatments that prolong life

    Palliative care - treatments that prolong life; Palliative care - life support; End-of-life-treatments that prolong life; Ventilator - treatments that prolong life; Respirator - treatments that prolong life; ...

  6. An unusual cause of cerebral venous sinus thrombosis: prothrombin G20210A gene mutation.

    Porres-Aguilar, Mateo; Square, Jaime H; Storey, Raul; Rodriguez-Dunn, Simon; Mohamed-Aly, Mohamed S


    Cerebral venous sinus thrombosis represents less than 1% of all strokes, being an uncommon entity with a wide spectrum of clinical scenarios. We present a 45-year-old Hispanic female with a history of long-term oral contraceptive use who was diagnosed with cerebral venous sinus thrombosis due to a heterozygous carrier mutation in the prothrombin G20210A gene. The patient was successfully managed with intravenous heparin with favorable clinical results without adverse effects. The prevalence of inherited primary thrombophilia increases with additional risk factors such as the use of oral contraceptives that can trigger or prothrombotic events in any vascular bed. An increased prevalence in the prothrombin G20210 gene mutation has been demonstrated in the Mexican-Mestizo population. Controversy exists regarding therapy of cerebral venous sinus thrombosis; according to experts, heparin remains the cornerstone of therapy with acceptable outcomes. More clinical trials are required to evaluate long-term outcomes in this subgroup of patients.

  7. Four methods compared for measuring des-carboxy-prothrombin (PIVKA-II).

    Widdershoven, J; van Munster, P; De Abreu, R; Bosman, H; van Lith, T; van der Putten-van Meyel, M; Motohara, K; Matsuda, I


    PIVKA-II (Protein Induced by Vitamin K Absence) is abnormal des-carboxylated prothrombin, which is present in vitamin K deficiency or in patients using warfarin. With a sensitive method for PIVKA-II, biochemical vitamin K deficiency can be established before clinical symptoms occur. We give an overview of methods used to detect PIVKA-II, and four selected methods are inter-compared: (a) measuring total factor II including PIVKA-II by using Echis carinatus snake venom as an activator of prothrombin; (b) measuring PIVKA-II by using snake venom as an activator of factor II after adsorption of functional factor II onto barium sulfate; (c) electrophoresis-immunofixation method; and (d) enzyme immunoassay. We found d to be the most sensitive and reliable method for PIVKA-II.

  8. Hyaluronidase inhibitors (sodium cromoglycate and sodium auro-thiomalate) reduce the local tissue damage and prolong the survival time of mice injected with Naja kaouthia and Calloselasma rhodostoma venoms.

    Yingprasertchai, Senee; Bunyasrisawat, Srisurat; Ratanabanangkoon, Kavi


    Experiments have been carried out to find potent inhibitors of hyaluronidases of Naja kaouthia (NK) and Calloselasma rhodostoma (CR) venoms with the aim of reducing local tissue damage and systemic toxicities caused by the venoms. Seven drugs/chemicals known to inhibit hyaluronidases were tested for their activity on venom enzymes. These were: sodium cromoglycate (SC), sodium aurothiomalate (SAT), apigenin, kaemferol, phenylbutazone, oxyphenbutazone and fenoprofen. The results showed that SC or SAT at 10 mM, completely inhibited the enzymes of both venoms. In in vivo experiments, SC or SAT, when incubated with NK venom prior to injection, significantly reduced edema and myonecrosis. In the case of CR venom, hemorrhage, in addition to edema and myonecrosis, was also significantly reduced. In the independent type experiment, SC or SAT were effective if injected within 1 min after the injection of venom. At longer time intervals of 3 and 10 min the inhibitors were effective in reducing some parameters of local tissue necrosis but the extent of inhibition was lower. SC and SAT at 256 and 195 microg/mouse, respectively, significantly prolonged the survival time of mice receiving lethal doses of NK. In the case of CR venoms, the two inhibitors not only prolonged the survival time but also prevented death of mice receiving lethal doses of the venom. The other inhibitors were poorly soluble in water and were studied only on enzyme inhibition and prolongation of survival time; they were mostly ineffective. Thus, SC and SAT when injected immediately at the sites of bites can reduce the systemic and local toxicity of NK and CR venoms. These results suggest that administration of these drugs at the site of venom injection may be useful in reducing venom-induced local tissue damage.

  9. Assessment of thrombogenicity of activated and non-activated prothrombin concentrates in a rat model.

    Silberman, S.; Fareed, J; Walenga, J.


    In vitro clotting activity of rats injected with different preparations of prothrombin concentrates was measured. Animals rendered deficient in vitamin K-dependent coagulation factors by early coumadin (warfarin) pretreatment, followed by injections of concentrate preparations were also evaluated. Findings indicate a dose-related response in abnormal coagulation changes demonstrable with each preparation and lack of protection of intravascular coagulation by coumadin anticoagulation. Furtherm...

  10. Prothrombin complex concentrate for reversal of vitamin K antagonist treatment in bleeding and non-bleeding patients

    Johansen, Mathias; Wikkelsø, Anne; Lunde, Jens


    BACKGROUND: Treatment with vitamin K antagonists is associated with increased morbidity and mortality. Reversal therapy with prothrombin complex concentrate (PCC) is used increasingly and is recommended in the treatment of patients with bleeding complications undertaking surgical interventions...... of prothrombin complex concentrate does not appear to reduce mortality or transfusion requirements but demonstrates the possibility of reversing vitamin K-induced coagulopathy without the need for transfusion of fresh frozen plasma. All included trials have high risk of bias and are underpowered to detect...

  11. Prolonged labour : women's experiences

    Nystedt, Astrid


    Aim: The overall aim of this thesis was to illuminate, describe, and promote understanding of women’s experiences of prolonged labour. The thesis compromises four studies. Methods: Paper I describes a case-referent study that recruited women (n = 255) giving singleton live birth to their first child by spontaneous labour after more than 37 completed weeks’ pregnancy. Participants completed a questionnaire that investigated childbirth experiences, previous family relationships, and childhood e...

  12. The role of prothrombin complex concentrates in reversal of target specific anticoagulants.

    Babilonia, Katrina; Trujillo, Toby


    Over the past several years a new era for patients requiring anticoagulation has arrived. The approval of new target specific oral anticoagulants offers practitioners several advantages over traditionally used vitamin K antagonist agents including predictable pharmacokinetics, rapid onset of action, comparable efficacy and safety, all without the need for routine monitoring. Despite these benefits, hemorrhagic complicates are inevitable with any anticoagulation treatment. One of the major disadvantages of the new oral anticoagulants is lack of specific antidotes or reversal agents for patients with serious bleeding or need for urgent surgery. As use of the new target specific oral anticoagulants continues to increase, practitioners will need to understand both the pharmacodynamics and pharmacokinetic properties of the agents, as well as, the available literature with use of non-specific therapies to reverse anticoagulation. Four factor prothrombin complex concentrates have been available for several years in Europe, and recently became available in the United States with approval of Kcentra. These products have shown efficacy in reversing anticoagulation from vitamin K antagonists, however their usefulness with the new target specific oral anticoagulants is poorly understood. This article will review the properties of dabigatran, rivaroxaban and apixaban, as well as the limited literature available on the effectiveness of prothrombin complex concentrates in reversal of their anticoagulant effects. Additional studies are needed to more accurately define the role of prothrombin complex concentrates in patients with life threatening bleeding or who require emergent surgery, as current data is both limited and conflicting.

  13. Acarboxy prothrombin (PIVKA II) as a tumour marker for hepatocellular carcinoma and other liver diseases.

    Mohamedein, A; Yousif-Kadaru, A G; Ahmed, S A; Saida, H; Zaki, Z A; Eldin; Fedail, S S


    The clinical usefulness of plasma abnormal prothrombin, defined as protein induced by vitamin K absence or antagonist II: (PIVKA II) as a tumour marker for hepatocellular carcinoma (HCC) and other liver diseases has been evaluated. PIVKA II concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) with monoclonal antibody that reacts with PIVKA II but does not cross-react with normal prothrombin. Seventy four patients (74%) out of 100 with HCC had abnormal PIVKA II levels above 0.5 AU/ml (median = 3.4 AU/ml). The level was above 1.0 AU/ml in 66 (66%) of the patients. In contrast the level of PIVKA II was low in patients with bilharzial periportal fibrosis (median = 0.09 AU/ml), patients with liver cirrhosis (median = 0.13 AU/ml), patients with hepatitis (median = 0.025 AU/ml), and essentially undetectable in all the 34 controls. The diagnostic ability of serum alphafoetoprotein (AFP) was also evaluated in these patients. AFP alone can diagnose 51% of the HCC cases. Of the remaining patients with low or negative AFP levels (65%) can be diagnosed using PIVKA II. Abnormal prothrombin is a potential marker for the laboratory diagnosis of hepatocellular carcinoma.

  14. Purification and characterization of a prothrombin-activating protease from Nephila clavata.

    Joo, Han-Seung; Park, Gun-Chun; Cho, Woo Ri; Tak, Eunsik; Paik, Seung R; Chang, Chung-Soon


    We report upon the purification and characterization of a novel prothrombin-activating enzyme from the body fluid (total homogenates of isolated digestive tract without eggs, spinnerets and silk glands) of the spider, Nephila clavata by a combination of acetone fractionation, ion exchange, and Soybean trypsin inhibitor-Sepharose chromatography. Analysis of the purified enzyme with SDS-PAGE and gel filtration revealed a single polypeptide chain with an apparent molecular weight of 24kDa. The proteolytic activity of the enzyme was stable up to 50 degrees C, however, it became unstable over 55 degrees C. The enzyme had an optimum pH of 8, and Ca(2+) was not required for the enzyme activity. According to inhibition profiles obtained with several serine protease inhibitors such as PMSF and benzamidine, the purified protease is a member of the serine proteases. Bz-Ile-Glu(gamma-OR)- Gly-Arg-pNA and Z-Arg-Gly-Arg-pNA which are known as substrates for factor Xa, were hydrolyzed favorably by the enzyme. And the Nephila protease could produce thrombin from prothrombin at nM range, and form the turbid ring using fibrinogen-agarose plate. The results obtained confirmed that the purified protease is a potent prothrombin-activating activity belonging to the family of serine protease.

  15. Increased prothrombin, apolipoprotein A-IV, and haptoglobin in the cerebrospinal fluid of patients with Huntington's disease.

    Yen-Chu Huang

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disease caused by an unstable CAG trinucleotide repeat expansion. The need for biomarkers of onset and progression in HD is imperative, since currently reliable outcome measures are lacking. We used two-dimensional electrophoresis and mass spectrometry to analyze the proteome profiles in cerebrospinal fluid (CSF of 6 pairs of HD patients and controls. Prothrombin, apolipoprotein A-IV (Apo A-IV and haptoglobin were elevated in CSF of the HD patients in comparison with the controls. We used western blot as a semi-quantified measurement for prothrombin and Apo A-IV, as well as enzyme linked immunosorbent assay (ELISA for measurement of haptoglobin, in 9 HD patients and 9 controls. The albumin quotient (Qalb, a marker of blood-brain barrier (BBB function, was not different between the HD patients and the controls. The ratios of CSF prothrombin/albumin (prothrombin/Alb and Apo A-IV/albumin (Apo A-IV/Alb, and haptoglobin level were significantly elevated in HD. The ratio of CSF prothrombin/Alb significantly correlated with the disease severity assessed by Unified Huntington's Disease Rating Scale (UHDRS. The results implicate that increased CSF prothrombin, Apo A-IV, and haptoglobin may be involved in pathogenesis of HD and may serve as potential biomarkers for HD.

  16. What Is the Effect on Obesity Indicators from Replacing Prolonged Sedentary Time with Brief Sedentary Bouts, Standing and Different Types of Physical Activity during Working Days?

    Gupta, Nidhi; Heiden, Marina; Aadahl, Mette;


    physical activity (MVPA) time on working days was computed using validated Acti4 software. The total sedentary time and uninterrupted sedentary time spent in brief (≤5 mins), moderate (>5 and ≤30 mins), and long (>30mins) bouts, were determined for the whole day and during work and non-work time separately...

  17. 老年麻醉使用罗库溴铵后肌松时效延长的拮抗处理%Antagonism management of prolonged muscle relaxant time after rocuronium bromide in senile anesthesia

    周江生; 曾莉芷


    目的:观察使用罗库溴铵对老年麻醉肌松时效延长而采取拮抗处理的效果。方法120例使用罗库溴铵实施肌松后出现时效延长的老年麻醉患者,随机分为观察组和对照组,每组60例。两组均采用气管插管全身麻醉,使用罗库溴铵实施肌松,手术完毕对因肌松时效延长患者,观察组使用甲硫酸新斯的明联合盐酸阿托品进行拮抗,常规监护和4个成串刺激(TOF)监测TOF从0~75%,从0~90%,从0至肌松恢复拔管即刻,从拔管即刻至残余肌松完全恢复。对照组使用生理盐水2 ml,常规监护和TOF监测TOF从0~75%,从0~90%,从0至肌松恢复拔管即刻,从拔管即刻至残余肌松完全恢复。两组患者均做好积极处理并发症准备。结果观察组能够快速拮抗肌松缩短时效,对照组肌松时效延长恢复缓慢,两组比较差异具有统计学意义(P<0.05)。结论及时合理使用甲硫酸新斯的明联合盐酸阿托品进行拮抗,可明显缩短老年麻醉肌松时效延长的恢复时间,减少术后并发症。%ObjectiveTo observe antagonism management effect of prolonged muscle relaxant time after rocuronium bromide in senile anesthesia.MethodsA total of 120 senile anesthesia patients with prolonged muscle relaxant time after rocuronium bromide were randomly divided into observation group and control group, with 60 cases in each group. Both groups received tracheal intubation general anesthesia, and rocuronium bromide for muscle relaxant. The observation group received neostigmine methylsulfate combined with atropine hydrochloride for antagonism due to prolonged muscle relaxant time after surgery. Conventional nursing and train-of-four stimulation (TOF) monitoring were taken in 0~75%, 0~90%, from 0 to extubation at recovery of muscle relaxant, and from extubation at recovery of muscle relaxant to complete recovery. The control group received 2 ml of normal saline. Conventional nursing and TOF monitoring were taken in 0

  18. Exposure of human cartilage tissue to low concentrations of blood for a short period of time leads to prolonged cartilage damage: An in vitro study

    Jansen, N.W.D.; Roosendaal, G.; Bijlsma, J.W.J.; Groot, J. de; Lafeber, F.P.J.G.


    Objective. Joint bleeding, or hemarthrosis, leads in time to severe joint damage. This study was carried out to test the in vitro thresholds of exposure time and concentration that lead to irreversible joint damage, to add to the discussion on the usefulness of aspiration of the joint after a hemorr

  19. What Is the effect on obesity indicators from replacing prolonged sedentary time with brief sedentary bouts, standing and different types of physical activity during working days?

    Gupta, Nidhi; Heiden, Marina; Aadahl, Mette


    INTRODUCTION: The aim of the study was to investigate if (a) substituting total sedentary time or long sedentary bouts with standing or various types of physical activity and (b) substituting long sedentary bouts with brief sedentary bouts; is associated with obesity indicators using a cross...... sectional isotemporal substitution approach among blue-collar workers. METHODS: A total of 692 workers from transportation, manufacturing and cleaning sectors wore an Actigraph GT3X+ accelerometer on the thigh for 1-4 working days. The sedentary (sit and lie), standing, walking, and moderate to vigorous...... physical activity (MVPA) time on working days was computed using validated Acti4 software. The total sedentary time and uninterrupted sedentary time spent in brief (≤5 mins), moderate (>5 and ≤30 mins), and long (>30mins) bouts, were determined for the whole day and during work and non-work time separately...

  20. Resistance to Bleomycin in Cancer Cell Lines Is Characterized by Prolonged Doubling Time, Reduced DNA Damage and Evasion of G2/M Arrest and Apoptosis

    Qi Wang; Kangping Cui; Osvaldo Espin-Garcia; Dangxiao Cheng; Xiaoping Qiu; Zhuo Chen; Malcolm Moore; Bristow, Robert G.; Wei Xu; Der, Sandy; Geoffrey Liu


    BACKGROUND: To establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM) resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values and cell doubling times were quantified using a real time cytotoxicity assay. COMET and γ-H2AX assays, cell cycle analysis, and apoptosis assessment further investigated the mechanisms of BLM resistance in these cell ...

  1. Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis.

    Qi Wang

    Full Text Available BACKGROUND: To establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values and cell doubling times were quantified using a real time cytotoxicity assay. COMET and γ-H2AX assays, cell cycle analysis, and apoptosis assessment further investigated the mechanisms of BLM resistance in these cell lines. RESULTS: Compared with parental cell lines, real time cytotoxicity assays revealed 7 to 49 fold increases in IC50 and a mean doubling time increase of 147 % (range 64 %-352% in BLM-resistant sub-clones (p<0.05 for both. Higher maintenance BLM concentrations were associated with higher IC50 and increased doubling times (p<0.05. Significantly reduced DNA damage (COMET and γ-H2AX assays, G2/M arrest, and apoptosis (p<0.05 for each set of comparison following high-dose acute BLM exposure was observed in resistant sub-clones, compared with their BLM-sensitive parental counterparts. Three weeks of BLM-free culturing resulted in a partial return to BLM sensitivity in 3/7 BLM-resistant sub-clones (p<0.05. CONCLUSION: Bleomycin resistance may be associated with reduced DNA damage after bleomycin exposure, resulting in reduced G2/M arrest, and reduced apoptosis.

  2. Analytic validity of genetic tests to identify factor V Leiden and prothrombin G20210A.

    Emadi, Ashkan; Crim, Matthew T; Brotman, Daniel J; Necochea, Alejandro J; Samal, Lipika; Wilson, Lisa M; Bass, Eric B; Segal, Jodi B


    The objective of this study is to systematically review methods for detecting Factor V Leiden or prothrombin G20210A. English-language literature from MEDLINE, EMBASE, The Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, PsycInfo(c), 2000-December 2008. Studies assessed methods for detection of these mutations in at least 10 human blood samples and reported concordance, discordance, or reproducibility. Two investigators abstracted data on the sample selection criteria, test operators, DNA extraction, experimental test, reference standard, commercial instruments, concordance rates, explanation of any discordance, and whether discordance resolved after repetition. We assessed strength of the evidence using the GRADE criteria. We reviewed 7,777 titles and included 66 articles. The majority of the reviewed studies used PCR-RFLP or AS-PCR as the reference standard. The studies demonstrated that commercially available and precommercial tests have high analytic validity with all having greater than 99% concordance with the reference standard. With a few exceptions, discordance resolved with repetition of the test, suggesting operator or administrative errors were responsible for the discordant results. In the quality assurance studies, greater than 98% of laboratories demonstrated high, even perfect, accuracy when asked to diagnose a sample with a known mutation. The majority of errors came from a limited number of laboratories. Although not all methods may be accurate, there is high-grade evidence that genetic tests for the detection of FVL and prothrombin G20210A have excellent analytic validity. There is high-grade evidence that most, but not all, clinical laboratories test for FVL and prothrombin G20210A accurately.

  3. Prolonged naproxen joint residence time after intra-articular injection of lipophilic solutions comprising a naproxen glycolamide ester prodrug in the rat

    Thing, Mette; Lu, Yi; Agårdh, Li;


    Intra-articular injection of oil solutions of lipophilic prodrugs that rapidly degrade to their parent compound in synovial fluid may constitute a feasible approach to increase the joint residence time of non-steroidal anti-inflammatory drugs. In this in vivo study, oil solutions of the N......,N-diethyl glycolamide ester prodrug of naproxen (16mg/ml) were injected into the rat knee joint by dosing 6μl formulation per 100g body weight. The sustained release properties were compared to those of intra-articularly injected aqueous and oil solutions of naproxen by monitoring the naproxen serum concentrations over...... time. Two oils, medium-chain triglycerides and castor oil, differing with respect to viscosity were tested. After intra-articular administration of oil prodrug solutions, a significant increase in the time to maximum naproxen serum concentration from around 40 to 245min, an increase in the MRTj from...

  4. Blockade of CD40-CD154 at the time of donor-specific blood transfusion does not lead to prolonged kidney allograft survival in nonhuman primates

    Ringers, J; Haanstra, KG; Kroczek, RA; Kliem, K; Kuhn, EM; Wubben, J; Ossevoort, MA; Volk, HD; Jonker, M


    Background. In rodents it has been demonstrated that blockade of the CD40-CD154 (CD40L) pathway at the time of donor-specific blood transfusion (DST) can result in indefinite graft survival. Because it has been reported in the past that DST in monkeys can have a favorable effect on graft outcome and

  5. Low socioeconomic status is associated with prolonged times to assessment and treatment, sepsis and infectious death in pediatric fever in El Salvador.

    Ronald Gavidia

    Full Text Available BACKGROUND: Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries. Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock, and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia. We analyzed factors associated with (1 Longer times from fever onset to hospital presentation/antibiotic treatment and (2 Sepsis and infection-related mortality. METHOD: This prospective cohort study included children aged 0-16 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital, San Salvador. We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode. Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented. FINDINGS: Of 251 children enrolled, 215 had acute lymphoblastic leukemia (85.7%. Among 269 outpatient febrile episodes, median times from fever to deciding to seek medical care was 10.0 hours (interquartile range [IQR] 5.0-20.0, and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.0-3.0. Forty-seven (17.5% patients developed sepsis and 7 (2.6% died of infection. Maternal illiteracy was associated with longer time from fever to decision to seek care (P = 0.029 and sepsis (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.09-8.63; P = 0.034. More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.03-1.81; P = 0.031 and in families with an annual household income times are associated with delays in assessment and treatment of fever and with sepsis and infectious mortality in pediatric leukemia. Providing additional education to high-risk families

  6. Pre-Exercise Hyperhydration-Induced Bodyweight Gain Does Not Alter Prolonged Treadmill Running Time-Trial Performance in Warm Ambient Conditions

    Gigou, Pierre-Yves; Dion, Tommy; Asselin, Audrey; Berrigan, Felix; Goulet, Eric D. B.


    This study compared the effect of pre-exercise hyperhydration (PEH) and pre-exercise euhydration (PEE) upon treadmill running time-trial (TT) performance in the heat. Six highly trained runners or triathletes underwent two 18 km TT runs (~28 °C, 25%–30% RH) on a motorized treadmill, in a randomized, crossover fashion, while being euhydrated or after hyperhydration with 26 mL/kg bodyweight (BW) of a 130 mmol/L sodium solution. Subjects then ran four successive 4.5 km blocks alternating between 2.5 km at 1% and 2 km at 6% gradient, while drinking a total of 7 mL/kg BW of a 6% sports drink solution (Gatorade, USA). PEH increased BW by 1.00 ± 0.34 kg (P Running TT time did not differ between groups (PEH: 85.6 ± 11.6 min; PEE: 85.3 ± 9.6 min, P = 0.82). Heart rate (5 ± 1 beats/min) and rectal (0.3 ± 0.1 °C) and body (0.2 ± 0.1 °C) temperatures of PEE were higher than those of PEH (P running TT performance under warm conditions in highly-trained runners drinking ~500 mL sports drink during exercise. PMID:23016126

  7. Molecular characterization of factor V leiden G1691A and prothrombin G20210A mutations in Saudi newborns with stroke.

    Gawish, Gihan E-H


    This study examined a possible association between the mutations related to Factor V Leiden and Factor II (prothrombin) and stroke in Saudi neonates. A multiplex PCR was established to detect Factor V Leiden G1691A and prothrombin G20210A mutations in 72 neonatal stroke subjects and 70 healthy adult controls with no family history of thromboembolic diseases. The frequency of the homozygous normal genotype (GG) of both genes was found to be significantly lower in the stroke subjects than in the controls (P Factor II heterozygous mutant form (GA) and the homozygous normal Factor V (GG) (P Factor V and the homozygous normal Factor II genotypes (GG) (P = 0.0) than controls. The study concluded that prothrombin and Factor V Leiden may be important risk factors for neonatal stroke in Saudi children.

  8. Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic leukemia.

    Mulligan, Stephen P; Karlsson, Karin; Strömberg, Mats; Jønsson, Viggo; Gill, Devinder; Hammerström, Jens; Hertzberg, Mark; McLennan, Roger; Uggla, Bertil; Norman, John; Wallvik, Jonas; Sundström, Gunnel; Johansson, Hemming; Brandberg, Yvonne; Liliemark, Jan; Juliusson, Gunnar


    We conducted a randomized phase III trial to compare the efficacy and safety of two purine analogs, cladribine and fludarabine, with high-dose chlorambucil, in patients with previously untreated chronic lymphocytic leukemia (CLL). Between 1997 and 2004, 223 patients with CLL were randomly assigned to cladribine, fludarabine or chlorambucil, for six cycles of therapy with frequent health-related quality of life assessments. There was no statistical difference for the primary endpoint of overall response with cladribine (70%), fludarabine (67%) and chlorambucil (59%), or complete remission (12%, 7% and 8%), respectively. However, the median progression-free survival (25, 10, 9 months) and median time to second treatment (40, 22, 21 months) were superior with cladribine. There was no significant difference in overall survival (96, 82 and 91 months), nor in toxicity or HRQoL assessments. Monotherapy with cladribine gives superior PFS and longer response duration than fludarabine and chlorambucil as first-line treatment of CLL.

  9. Pre-exercise hyperhydration-induced bodyweight gain does not alter prolonged treadmill running time-trial performance in warm ambient conditions.

    Gigou, Pierre-Yves; Dion, Tommy; Asselin, Audrey; Berrigan, Felix; Goulet, Eric D B


    This study compared the effect of pre-exercise hyperhydration (PEH) and pre-exercise euhydration (PEE) upon treadmill running time-trial (TT) performance in the heat. Six highly trained runners or triathletes underwent two 18 km TT runs (~28 °C, 25%-30% RH) on a motorized treadmill, in a randomized, crossover fashion, while being euhydrated or after hyperhydration with 26 mL/kg bodyweight (BW) of a 130 mmol/L sodium solution. Subjects then ran four successive 4.5 km blocks alternating between 2.5 km at 1% and 2 km at 6% gradient, while drinking a total of 7 mL/kg BW of a 6% sports drink solution (Gatorade, USA). PEH increased BW by 1.00 ± 0.34 kg (P < 0.01) and, compared with PEE, reduced BW loss from 3.1% ± 0.3% (EUH) to 1.4% ± 0.4% (HYP) (P < 0.01) during exercise. Running TT time did not differ between groups (PEH: 85.6 ± 11.6 min; PEE: 85.3 ± 9.6 min, P = 0.82). Heart rate (5 ± 1 beats/min) and rectal (0.3 ± 0.1 °C) and body (0.2 ± 0.1 °C) temperatures of PEE were higher than those of PEH (P < 0.05). There was no significant difference in abdominal discomfort and perceived exertion or heat stress between groups. Our results suggest that pre-exercise sodium-induced hyperhydration of a magnitude of 1 L does not alter 80-90 min running TT performance under warm conditions in highly-trained runners drinking ~500 mL sports drink during exercise.

  10. Pre-Exercise Hyperhydration-Induced Bodyweight Gain Does Not Alter Prolonged Treadmill Running Time-Trial Performance in Warm Ambient Conditions

    Eric D. B. Goulet


    Full Text Available This study compared the effect of pre-exercise hyperhydration (PEH and pre-exercise euhydration (PEE upon treadmill running time-trial (TT performance in the heat. Six highly trained runners or triathletes underwent two 18 km TT runs (~28 °C, 25%–30% RH on a motorized treadmill, in a randomized, crossover fashion, while being euhydrated or after hyperhydration with 26 mL/kg bodyweight (BW of a 130 mmol/L sodium solution. Subjects then ran four successive 4.5 km blocks alternating between 2.5 km at 1% and 2 km at 6% gradient, while drinking a total of 7 mL/kg BW of a 6% sports drink solution (Gatorade, USA. PEH increased BW by 1.00 ± 0.34 kg (P < 0.01 and, compared with PEE, reduced BW loss from 3.1% ± 0.3% (EUH to 1.4% ± 0.4% (HYP (P < 0.01 during exercise. Running TT time did not differ between groups (PEH: 85.6 ± 11.6 min; PEE: 85.3 ± 9.6 min, P = 0.82. Heart rate (5 ± 1 beats/min and rectal (0.3 ± 0.1 °C and body (0.2 ± 0.1 °C temperatures of PEE were higher than those of PEH (P < 0.05. There was no significant difference in abdominal discomfort and perceived exertion or heat stress between groups. Our results suggest that pre-exercise sodium-induced hyperhydration of a magnitude of 1 L does not alter 80–90 min running TT performance under warm conditions in highly-trained runners drinking ~500 mL sports drink during exercise.

  11. 全血采集时间延长的多种影响因素分析%Analysis of Multiple Affecting Factors on Prolongation of Whole Blood Collecting Time

    兰竹; 谢映明; 邓白娟; 何伟团


    Objective To analyze the multiple factors affecting the whole blood-collecting time and to improve the blood quality by reducing the whole blood collecting time in gratuitous blood donation. Method We counted and analyzed all the whole blood-collecting time in a certain period of time and also analyzed the effect of multiple factors on prolongation of whole blood-collecting time by using a variety of control function, data processing capability and good communication of Compoguard Complete automatic blood-collecting mixer as well as real-time network access to computer management system of blood station. Results The ratio of prolonged whole blood-collecting time was 7.09%. In the group with prolonged blood-collecting time, the average time was 260.03 s (P<0.05) longer;average velocity was 44.17 mL/min (P<0.05) slower;mean age was 3.94 years (P<0.05) smaller. We found that there is statistical difference due to different blood-collecting method, amount of blood collected, gender, age, blood-collecting environment and nurses collecting the blood (P<0.05), Multivariate Logistic regression analysis showed that there were statistical difference in volume of blood collected, sex and age (P<0.05). The correlation coefficient were 3.91 (Exp (B)=49.92, 95%CI=23.42-106.42, P=0.00) and 1.96 (Exp (B)=7.10, 95%CI=4.60-10.96, P=0.00) when 300 mL and 400 mL blood were collected respectively;while the correlation coefficient for sex and age were-0.52 (Exp (B)=0.59, 95%CI=0.49-0.72, P=0.00) and 0.04 (Exp (B)=1.04, 95%CI=1.03-1.05, P=0.00) respectively, namely older women who collected more whole blood could bring about prolonged blood-collecting time. Conclusion Prolonged whole blood-collecting time could be effectively reduced by taking precautions targeting at factors affecting the blood-collecting time.%目的:分析影响全血采集时间的多种因素,应用于有针对性地减少无偿献血中的全血采集时间延长,以提

  12. A reduction of prothrombin conversion by cardiac surgery with cardiopulmonary bypass shifts the haemostatic balance towards bleeding.

    Kremers, Romy M W; Bosch, Yvonne P J; Bloemen, Saartje; de Laat, Bas; Weerwind, Patrick W; Mochtar, Bas; Maessen, Jos G; Wagenvoord, Rob J; Al Dieri, Raed; Hemker, H Coenraad


    Cardiac surgery with cardiopulmonary bypass (CPB) is associated with blood loss and post-surgery thrombotic complications. The process of thrombin generation is disturbed during surgery with CPB because of haemodilution, coagulation factor consumption and heparin administration. We aimed to investigate the changes in thrombin generation during cardiac surgery and its underlying pro- and anticoagulant processes, and to explore the clinical consequences of these changes using in silico experimentation. Plasma was obtained from 29 patients undergoing surgery with CPB before heparinisation, after heparinisation, after haemodilution, and after protamine administration. Thrombin generation was measured and prothrombin conversion and thrombin inactivation were quantified. In silico experimentation was used to investigate the reaction of patients to the administration of procoagulant factors and/or anticoagulant factors. Surgery with CPB causes significant coagulation factor consumption and a reduction of thrombin generation. The total amount of prothrombin converted and the rate of prothrombin conversion decreased during surgery. As the surgery progressed, the relative contribution of α2-macroglobulin-dependent thrombin inhibition increased, at the expense of antithrombin-dependent inhibition. In silico restoration of post-surgical prothrombin conversion to pre-surgical levels increased thrombin generation excessively, whereas co-administration of antithrombin resulted in the normalisation of post-surgical thrombin generation. Thrombin generation is reduced during surgery with cardiopulmonary bypass because of a balance shift between prothrombin conversion and thrombin inactivation. According to in silico predictions of thrombin generation, this new balance increases the risk of thrombotic complications with prothrombin complex concentrate administration, but not if antithrombin is co-administered.

  13. Rapid Regression of Advanced Hepatocellular Carcinoma Associated with Elevation of Des-Gamma-Carboxy Prothrombin after Short-Term Treatment with Sorafenib – A Report of Two Cases

    Takahide Nakazawa


    Full Text Available Background: Sorafenib is the first molecular-targeted agent that is effective for advanced hepatocellular carcinoma (HCC, with prolongation of survival. However, a complete response is very rare, and rapid regression of HCC after short-term treatment with sorafenib has not been reported previously. Case Reports: We describe 2 patients with advanced multiple HCC who received sorafenib for short periods of 1 or 2 weeks, respectively. Longer treatment was precluded by the development of hepatic failure as an adverse event of sorafenib. Results: HCC rapidly regressed, and both patients had a partial response (PR, despite short-term treatment. Furthermore, an early elevation of des-gamma-carboxy prothrombin (DCP was temporarily seen in both patients, with no elevation of alpha-fetoprotein. Conclusions: Sorafenib can induce rapid regression of advanced HCC even after short-term treatment, and the initial response of HCC was identical in both patients. Since early elevation of DCP was observed in our patients with PR, DCP might be a predictive biomarker of anti-tumor response. Further studies are required to clarify the mechanisms underlying the effectiveness of sorafenib, including the alteration of DCP.

  14. Quantitative real-time reverse transcription-PCR analysis reveals stable and prolonged neurotoxin cluster gene activity in a Clostridium botulinum type E strain at refrigeration temperature.

    Chen, Ying; Korkeala, Hannu; Lindén, Jere; Lindström, Miia


    The relative expression levels of six botulinum neurotoxin cluster genes in a group II Clostridium botulinum type E strain grown at 10 or 30 degrees C were investigated using quantitative real-time reverse transcription-PCR. An enzyme-linked immunosorbent assay was used to confirm neurotoxin expression. Distinct mRNA and toxin production patterns were observed at the two temperatures. The average relative mRNA levels at 10 degrees C were higher than (ntnh and p47), similar to (botE), or lower than (orfx1, orfx2, orfx3) those at 30 degrees C. The maximum botE expression levels and average neurotoxin levels at 10 degrees C were 45 to 65% of those at 30 degrees C. The relative mRNA levels at 10 degrees C declined generally slowly within 8 days, as opposed to the rapid decline observed at 30 degrees C within 24 h. Distinct expression patterns of the six genes at the two temperatures suggest that the type E neurotoxin cluster genes are transcribed as two tricistronic operons at 30 degrees C, whereas at 10 degrees C monocistronic (botE or orfx1 alone) and bicistronic (ntnh-p47 and orfx2-orfx3) transcription may dominate. Thus, type E botulinum neurotoxin production may be involved with various temperature-dependent regulatory events. In light of group II C. botulinum type E being a dangerous food-borne pathogen, these findings may be important in terms of the safety of refrigerated packaged foods of extended durability.

  15. The predictability of bleeding by prothrombin times sensitive or insensitive to PIVKA during intensive oral anticoagulation.

    Arnesen, H; Smith, P


    To evaluate the effect of PIVKA (Proteins Induced by Vitamin K Absence or Antagonism) on the bleeding tendency during oral anticoagulation, we studied consecutive patients intensively treated with warfarin (INR greater than 4.8). The level of anticoagulation was measured with the PIVKA-insensitive Normotest (NT) as well as with the PIVKA-sensitive Thrombotest (TT), and the results are expressed as per cent coagulant activity. The NT/TT ratio was determined. Twenty patients with bleeding episodes had a mean NT/TT ratio of 2.06 as compared to 2.20 in 143 patients without bleeding episodes (p = 0.08). As the NT/TT ratio was not higher in patients with bleedings, we conclude that PIVKA are of no importance for bleeding during anticoagulation with vitamin K antagonists.

  16. Comparison of plasma with whole blood prothrombin time and fibrinogen on the same instrument.

    Amukele, Timothy K; Ferrell, Chris; Chandler, Wayne L


    We compared plasma with whole blood (WB) international normalized ratio (INR) and fibrinogen using the same instrument and reagents. WBINRs were 50% higher than plasma INRs. After increasing the WB sample volume 40% and adjusting the International Sensitivity Index, WBINRs were similar to plasma INRs [adjusted WBINR = 0.99(plasma INR) - 0.02; r(2) = 0.98; n = 155], but the average difference in WB vs plasma INR was 4-fold higher than duplicate plasma INRs. Variation in hematocrit was a major determinant of the accuracy of the WBINR, with increased error at high INRs. The WB fibrinogen assay was highly dependent on the sample hematocrit (r(2) = 0.83), even after the sample volume was adjusted. Accurate WB fibrinogen measurements required a mathematical hematocrit correction. We conclude that WBINR and fibrinogen assays can be performed on point-of-care or automated analyzers, but sample volume must be adjusted to account for hematocrit. Accuracy is limited by variations in hematocrit with worsening accuracy for samples with high INRs or low fibrinogen levels.

  17. A Multiplex Allele Specific Polymerase Chain Reaction (MAS-PCR) for the Detection of Factor V Leiden and Prothrombin G20210A.

    Bagheri, Morteza; Rad, Isa Abdi


    In order to determine the frequencies of factor V Leiden and prothrombin G20210A point mutations in the Iranian population with Azeri Turkish origin. 120 unrelated individuals from general population randomly selected and were examined for factor V Leiden and prothrombin G20210A mutations using a multiplex allele specific polymerase chain reaction (MAS-PCR) assayOutcomes: The frequency of prothrombin G20210A mutation was 2.08%, which means 5 chromosomes out of 240 chromosomes had prothrombin G20210A mutation. The distribution of prothrombin 20210 GG, GA, AA genotypes and prothrombin 20210A allele were 37(92.5%), 3(7.5%), 0(0%) and 3(3.75%) in males and 78(97.5%), 2(2.5%), 0(0%) and 2(1.25%) in females, respectively. Factor V Leiden was not found in our tested group (zero chromosomes out of 240 chromosomes). Analysis of the observed frequencies in the studied groups indicates that there is no statistically significant difference between females and males, regarding prothrombin G20210A mutation (p value>0.05). This is the first study in its own kind in this population and implies that the frequency of Factor V Leiden G1691A (R506Q, FV-Leiden) allele is extremely low but the prothrombin G20210A mutation is more frequent in the tested group.

  18. Causation between occupational prolonged standing time during progestation and pregnancy related complications%孕前职业久站行为与妊娠并发症的因果效应研究

    翁婷婷; 徐叶清; 严双琴; 潘维君; 陶芳标


    目的 描述安徽省马鞍山地区孕妇在孕前和孕早期工作中站立时间以及长时间站立行为的分布特征,探索该职业暴露与妊娠高血压等常见并发症的相关性.方法 于2008年10月至2010年10月在马鞍山市妇幼保健机构招募初次建卡孕妇,建立孕产妇队列并随访至分娩.分别于孕早、中、晚期在产检医生指导下由孕产妇自填问卷,收集相关信息.结果 4644名孕妇孕前和孕早期持续站立时间百分位数P75值分别为4.0 h/d和3.0 h/d;孕前和孕早期久站行为主要分布于较低经济社会地位特征孕妇中;多因素分析结果显示,在调整可能混杂因素后,孕前久站行为与妊娠合并高血压和中度贫血均呈显著正相关,其OR值分别为2.05(95%CI:1.26~ 3.31)和1.38(95%CI:1.03~1.85).结论 孕前职业暴露于较重体力负荷的工作如长时间站立,可增加妊娠高血压等疾病的危险.%Objective To describe the epidemiological characteristics of profession related long-standing behavior during preconception and progestation,and to probe the relationship between prolonged standing jobs and the common pregnancy related complications among pregnant women,in Ma' anshan city,Anhui province.Methods In this cohort study,subjects who had their first antenatal examination at Ma' anshan Maternal and Child Care Centers were recruited under informed consent,from October 2008 to October 2010.All the information were collected through questionnaires in the first,second and third trimesters respectively.Three questionnaires were filled in by subjects under the guidance of healthcare takers.Results In the study,the 754 percentile of prolonged-standing times were 4.0 h/d and 3.0 h/d respectively in preconception and progestation.The characteristics of pregnant women with low social/economic status,prone to be involved in stand-long occupation.Results in logistic regression analysis,prolonged-standing jobs during preconception was the

  19. Des-γ-Carboxy Prothrombin (DCP as a Potential Autologous Growth Factor for the Development of Hepatocellular Carcinoma

    Yu-Sheng Zhang


    Full Text Available Des-γ-carboxy prothrombin (DCP is a prothrombin precursor produced in hepatocellular carcinoma (HCC. Because of deficiency of vitamin K or γ-glutamyl carboxylase in HCC cells, the 10 glutamic acid (Glu residues in prothrombin precursor did not completely carboxylate to γ-carboxylated glutamic acid (Gla residues, leaving some Glu residues remained in N-terminal domain. These prothrombin precursors with Glu residues are called DCPs. DCP displays insufficient coagulation activity. Since Liebman reported an elevated plasma DCP in patients with HCC, DCP has been used in the diagnosis of HCC. Recently, its biological malignant potential has been specified to describe DCP as an autologous growth factor to stimulate HCC growth and a paracrine factor to integrate HCC with vascular endothelial cells. DCP was found to stimulate HCC growth through activation of the DCP-Met-JAK1-STAT3 signaling pathway. DCP might increase HCC invasion and metastasis through activation of matrix metalloproteinase (MMPs and the ERK1/2 MAPK signaling pathway. DCP has also been found to play a crucial role in the formation of angiogenesis. DCP could increase the angiogenic factors released from HCC and vascular endothelial cells. These effects of DCP in angiogenesis might be related to activation of the DCP-KDR-PLC-γ-MAPK signaling pathway. In this article, we summarized recent studies on DCP in biological roles related to cancer progression and angiogenesis in HCC.

  20. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH)

    Steiner, Thorsten; Poli, Sven; Griebe, Martin


    of fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC) in patients with VKA-ICH. METHODS: We did an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Patients aged at least 18 years with VKA-ICH who presented within 12 h after symptom onset...

  1. Use of Prothrombin Complex Concentrate in Patients during Heart Transplantation after Implantation of a Left Ventricular Mechanical Support System

    V. V. Lomivorotov


    Full Text Available Heart transplantation in patients after implantation of mechanical cardiac support devices entails an extremely high risk for perioperative bleeding. Recombinant activated coagulation factor VII is presently used to reduce the volume of bleeding in this patient group. There are parallel data on its administration-induced thromboembolic events in the literature. This paper describes a case of using a prothrombin complex concentrate in a patient during explantation of a left ventricular bypass system and subsequent orthotopic heart transplantation in the presence of significant hypocoagulation. At the end of a surgery, 1200 IU of the agent was used at a remaining bleeding rate of more than 1000 ml/hour. Within the first 24 hours after surgery, the rate of discharge drainage was less than 100 ml/hour. A control plain chest X-ray study revealed massive left-sided hydrothorax on day 2 postsurgery. The left pleural cavity was revised under thoracoscopic guidance and 1000 ml of blood clots were evacuated. Although the administration of prothrombin complex concentrate did not guard against re-intervention, its use seems a promising strategy in life-threatening bleedings in patients after explantation of mechanical cardiac support devices. Further multicenter investigations are required to determine the efficacy and safety of prothrom-bin complex concentration in cardiac surgery. Key words: Recombinant activated coagulation factor VII, prothrombin complex concentration, mechanical cardiac support device, orthotopic heart transplantation.

  2. Des-γ-carboxy prothrombin (DCP) as a potential autologous growth factor for the development of hepatocellular carcinoma.

    Zhang, Yu-Sheng; Chu, Jia-Hui; Cui, Shu-Xiang; Song, Zhi-Yu; Qu, Xian-Jun


    Des-γ-carboxy prothrombin (DCP) is a prothrombin precursor produced in hepatocellular carcinoma (HCC). Because of deficiency of vitamin K or γ-glutamyl carboxylase in HCC cells, the 10 glutamic acid (Glu) residues in prothrombin precursor did not completely carboxylate to γ-carboxylated glutamic acid (Gla) residues, leaving some Glu residues remained in N-terminal domain. These prothrombin precursors with Glu residues are called DCPs. DCP displays insufficient coagulation activity. Since Liebman reported an elevated plasma DCP in patients with HCC, DCP has been used in the diagnosis of HCC. Recently, its biological malignant potential has been specified to describe DCP as an autologous growth factor to stimulate HCC growth and a paracrine factor to integrate HCC with vascular endothelial cells. DCP was found to stimulate HCC growth through activation of the DCP-Met-JAK1-STAT3 signaling pathway. DCP might increase HCC invasion and metastasis through activation of matrix metalloproteinase (MMPs) and the ERK1/2 MAPK signaling pathway. DCP has also been found to play a crucial role in the formation of angiogenesis. DCP could increase the angiogenic factors released from HCC and vascular endothelial cells. These effects of DCP in angiogenesis might be related to activation of the DCP-KDR-PLC-γ-MAPK signaling pathway. In this article, we summarized recent studies on DCP in biological roles related to cancer progression and angiogenesis in HCC.

  3. Portal Vein Thrombosis due to Prothrombin Gene Mutation following Sleeve Gastrectomy

    Murad Baba


    Full Text Available Introduction. Portomesenteric thrombosis is increasingly recognized as a complication of laparoscopic sleeve gastrectomy (LSG. It often presents with abdominal pain. We present a mother and her son who both developed portal vein thrombosis (PVT after LSG. Case Description. A 43-year-old woman presented complaining of sudden severe abdominal pain, two weeks after she had uncomplicated laparoscopic sleeve gastrectomy. CT scan of the abdomen and pelvis with IV contrast showed portal vein thrombosis and SMV thrombosis. Two weeks later her son had the same LSG for morbid obesity and presented with the same clinical picture. Thrombophilia workup showed heterozygous prothrombin gene mutation. Conclusions. A high index of suspicion is necessary to diagnose PVT; although rare, it can be potentially lethal. Anticoagulation therapy should be initiated immediately to limit the morbidities and improve the outcome. Patients with family history of thrombophilia should be investigated prior to any bariatric surgery and nonsurgical alternative treatments for morbid obesity should be strongly encouraged.

  4. Significance of Des-gamma-carboxy Prothrombin Production in Hepatocellular Carcinoma



    Full Text Available Serum des-gamma-carboxy prothrombin (DCP is commonly used to detect hepatocellular carcinoma (HCC. This review focuses on the clinical features of DCP-positive HCC and the molecular function of DCP in HCC. DCP-positive HCC demonstrates more aggressive clinicopathological features than DCP-negative HCC. Analysis of the biological effects of DCP revealed that DCP acts as a growth factor in both an autocrine and paracrine manner. DCP stimulates HCC cell proliferation through the Met-Janus kinase 1-signal transducer and activator of transcription 3 signaling pathway, whereas for vascular endothelial cells, it stimulates cell proliferation and migration through the kinase insert domain receptor-phospholipase C-gamma-mitogen-activated protein kinase signaling pathway.

  5. Acarboxy prothrombin (PIVKA-II) in cord plasma in the south of Thailand.

    Laosombat, V; Kenpitak, K; Wongchanchailert, M; Wiriyasateinkul, A


    Acarboxy prothrombin or PIVKA-II (protein induced by vitamin K absence or antagonist-II) was used to determine the presence of vitamin deficiency in newborn infants. Of 230 cord blood samples assayed by using ELISA method, 34.8 per cent were positive for PIVKA-II 0.13-17 AU/ml. The positive rate for PIVKA-II was greater in infants of primigravida (50.7%) than in those of multigravida (27.9%). All infants received prophylactic vitamin K, and no infant with positive PIVKA-II in cord blood subsequently had clinical bleeding. Because of the high prevalence of vitamin K deficiency in newborn infants in the South of Thailand, all newborn infants should receive prophylactic vitamin K at birth.

  6. Acarboxy prothrombin (PIVKA-II) as a marker of hepatoblastoma in infants.

    Motohara, K; Endo, F; Matsuda, I; Iwamasa, T


    We evaluated plasma PIVKA-II (protein induced by vitamin K absence or antagonist-II, acarboxy prothrombin) levels in three infants with hepatoblastoma as a tumor marker. PIVKA-II levels were highly elevated in all three patients. Vitamin K administration, performed in two patients, resulted in only moderate reduction of PIVKA-II levels. Chemotherapy against tumor cells reduced the PIVKA-II levels without exception. Immunohistochemical study of the liver tissue indicated the presence of PIVKA-II in the hepatoblastoma cell. These findings suggest that elevated PIVKA-II in these patients was not due to nutritional vitamin K deficiency, but to excess production of tumor cells. A measurement of plasma PIVKA-II may be useful as a new marker of hepatoblastoma.

  7. Magnetic resonance imaging of myocardial infarction during prothrombin complex concentrate therapy of hemophilia A

    Gruen, D.R. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States); Winchester, P.H. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States); Brill, P.W. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States); Ramirez, E. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States)


    In patients with hemophilia, prothrombin complex concentrates (PCCs) have been successfully used to bypass inhibitors to fctor VIII during bleeding episodes. The use of PCCS, including FEIBA (factor eight inhibitor bypassing activity), has been associated with thromboembolic complications. Myocardial infarction (MI) is a rare but serious complication, reported in 13 previous cases, six in the pediatric age group. In all four patients who died during the acute MI, autopsy revealed extensive myocardial hemorrhage. The hearts of three other patients examined at least 5 months after the acute MI showed no evidence of prior hemorrhage. Magnetic resonance (MR) imaging has been shown to be able to evaluate the sequelae of myocardial infarction in adults with coronary artery disease and in children with Kawasaki syndrome. We report the first case of the used of MR imaging in the evaluation of myocardial damage during the acute stage of a FEIBA-associated MI in a 10-year-old boy. (orig.)

  8. Association between prothrombin gene polymorphisms and hereditary thrombophilia in Xinjiang Kazakhs population.

    Ge, Xiao-Hu; Zhu, Feng; Wang, Bing-Lin; Wang, Chang-Min; Zhu, Bing; Guan, Sheng; Ci, Hong-Bo; Sai, Li-Mu; Jiang, Xiao-Kui; Ren, Hao; Fang, Qing-Bo; Tian, Guang-Lei


    To assess the association between polymorphisms of prothrombin gene and hereditary thrombophilia in Xinjiang Kazakhs population. Through cross-sectional investigation, permanent Kazakh population of Ili Kazakh Autonomous Prefecture was selected as the study object to measure their antithrombin III (AT-III), protein C, protein S activity and activated C protein resistance value, thus defining the situation of the crowd's hereditary thrombophilia. Sequenom Massarray detection technology was used to conduct a genotype test of the six sites selected by the case and control groups. Haploview software was used to perform linkage disequilibrium analysis of the six sites, and the impact of the interaction between genetic variations and environment on hereditary thrombophilia was researched by the use of sum model. A total of 1005 Kazakh volunteers participated in the test (332 men and 673 women), average age (41.13 ± 11.50) years; the prevalence of hereditary thrombophilia in Xinjiang Kazakh population was 31.0%, and the prevalence of AT-III deficiency, protein C deficiency, protein S deficiency and activated protein C resistance was 16.4, 14.9, 20.6 and 7.8%, respectively. The difference in allele frequency of the hereditary thrombophilia patient group at rs3136447 and rs5896 sites was statistically significant (P = 0.0483 and P = 0.0302, respectively). rs5896 and rs2070852 had high linkage disequilibrium (r = 0.99), and constituted a single-domain block 1. The rs3136447 and the rs5896 polymorphisms located in the region of the prothrombin gene may be associated with hereditary thrombophilia in the Xinjiang Kazakhs population. There is additive interactive effect of rs5896 polymorphism (CT + TT) and smoke on hereditary thrombophilia.

  9. Des-Gamma-Carboxy Prothrombin (DCP Antagonizes the Effects of Gefitinib on Human Hepatocellular Carcinoma Cells

    Yu-Sheng Zhang


    Full Text Available Background/Aims: Des-gamma-carboxy prothrombin (DCP, an aberrant prothrombin produced by hepatocellular carcinoma (HCC cells, is known as a marker for HCC. Recent studies indicated that high levels of DCP are associated with the malignant potential of HCC. In this study, we aimed to investigate the association of DCP with gefitinib treatment failure in HCC and whether DCP counteracts gefitinib-induced growth inhibition and apoptosis of HCC. Methods: The experiments were performed in HCC cell lines HepG2 and PLC/PRF/5. The effects of gefitinib on HCC in the presence or absence of DCP were evaluated by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT assay. Apoptotic cells were identified by Annexin V-FITC/PI staining. Western blotting was performed to analyze the expressions of molecules related to the apoptotic caspase-dependent pathway and epidermal growth factor receptor (EGFR pathway. Results: Gefitinib inhibited HCC cell proliferation and induced apoptosis in HCC cells. The effects of gefitinib on HCC cells were antagonized by DCP. In the presence of DCP, HCC cells were resistant to the gefitinib-induced inhibition of proliferation and stimulation of apoptosis. DCP prevented the activation of the apoptotic caspase-dependent pathway induced by gefitinib. These antagonistic effects of DCP also arose from its ability to up-regulate EGFR, c-Met and hepatocyte growth factor (HGF in HCC cells. Conclusion: DCP antagonized gefitinib-induced HCC cell growth inhibition by counteracting apoptosis and up-regulating the EGFR pathway. High levels of DCP might thus lead to low response rates or possibly no response to gefitinib in patients with HCC.

  10. Anti-phosphatidylserine-prothrombin antibodies are associated with outcome in a TIA cohort

    Michael T Mullen


    Full Text Available Background: Antiphospholipid antibodies (aPLs have been associated with thrombosis in the antiphospholipid antibody syndrome (APS and with atherosclerotic vascular events in patients without APS. We examined the significance of aPLs in transient ischemic attack (TIA.Patients/Methods: Patients with TIA <48 hours from symptom onset were prospectively enrolled. Traditional aPLs, including anti-cardiolipin (aCL and β2-glycoprotein-I (β2GPI, and newer aPLs, including anti-phosphatidylserine/prothrombin (aPS/PT, β2GPI Domain 4/5 and β2GPI Domain 1 were measured. Primary outcome was a composite of stroke or death within 90 days or identification of a high-risk stroke mechanism. Secondary outcomes were stroke or death and the presence of clinical/sub-clinical atherosclerosis. Results: Over 4.5 years, 167 patients were enrolled. 41 patients (25% had the composite endpoint. Antibodies were measured in 158 subjects. aPS/PT IgG antibodies were significantly associated with stroke/death (OR 16.3 95% CI 2.3-116.7 p=0.005 and were non-significantly associated with the composite endpoint (OR 4.7 95% CI 0.8-29.2 p=0.10. In multivariate analysis adjusting for ABCD2 risk score, aPS/PT IgG remained associated with stroke/death (OR 15.7 95% CI 2.0-125.6 p=0.009. Other aPLs were not associated with clinical outcome and no association between APLs and atherosclerosis was identifed. Conclusion: In contrast to other aPLs, anti-phosphatidylserine/prothrombin IgG antibodies are independently associated with stroke or death in patients with TIA.


    Suzanne Schneider


    Full Text Available Prolonged exercise may compromise immunity through a reduction of salivary antimicrobial proteins (AMPs. Salivary IgA (IgA has been extensively studied, but little is known about the effect of acute, prolonged exercise on AMPs including lysozyme (Lys and lactoferrin (Lac. Objective: To determine the effect of a 50-km trail race on salivary cortisol (Cort, IgA, Lys, and Lac. Methods: 14 subjects: (6 females, 8 males completed a 50km ultramarathon. Saliva was collected pre, immediately after (post and 1.5 hrs post race ( 1.5. Results: Lac concentration was higher at 1.5 hrs post race compared to post exercise (p0.05. IgA concentration, secretion rate, and IgA/Osm were lower 1.5 hrs post compared to pre race (p<0.05. Cort concentration was higher at post compared to 1.5 (p<0.05, but was unaltered from pre race levels. Subjects finished in 7.81 ± 1.2 hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at post (p<0.05 compared to pre race. Conclusions: The intensity could have been too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as IgA to changes in response to prolonged running. Results expand our understanding of the mucosal immune system and may have implications for predicting illness after prolonged running.

  12. Primary thrombophilia in Mexico. II. Factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphism in thrombophilic Mexican mestizos.

    Ruiz-Argüelles, G J; Garcés-Eisele, J; Reyes-Núñez, V; Ramírez-Cisneros, F J


    We have shown that in Mexican mestizo patients with clinical features of primary thrombophilia, 39% have activated protein C resistance phenotype, 5% protein C deficiency, and 2% protein S deficiency. In the present study, in a group of 37 thrombophilic Mexicans and 50 normal controls, we assessed the factor V G1691A (Leiden), the prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms. Four patients were found to be heterozygous for factor V Leiden, 5 heterozygous for the prothrombin 20210, 16 heterozygous, and 6 homozygous for the MTHFR 677. There were four individuals with co-segregation of alleles: two heterozygotes for the factor V Leiden/prothrombin 20210, one heterozygote for prothrombin 20210/MTHFR 677, and one heterozygote for prothrombin 20210/homozygote for MTHFR 677. For factor V Leiden, prothrombin 20210, and MTHFR 677 mutations, the allele frequencies were respectively 1% (+/-0.2%, alpha = 0.05), 7.66 (P mestizo thrombophilic patients, the low prevalence of the factor V Leiden mutation (10.8%) and the high prevalence of the prothrombin 20210 mutation (13.5%) contrast with those identified in Caucasian thrombophilic patients (21% and 6%, respectively; P mestizo patients.

  13. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type.

    Sode, Birgitte F; Allin, Kristine H; Dahl, Morten; Gyntelberg, Finn; Nordestgaard, Børge G


    ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population. We used data from 2 Danish studies that followed members of the general public from 1977 through 2010. We obtained the genotype of 66 001 white participants for ABO blood type, factor V Leiden R506Q and prothrombin G20210A. We calculated hazard ratios (HRs) and population attributable risk. Our main outcome measures were venous thromboembolism and myocardial infarction. The multivariable adjusted HR for venous thromboembolism was 1.4 (95% confidence interval [CI] 1.3-1.5) for non-O blood type (v. O blood type). For the factor V Leiden R506Q mutation, the adjusted HR was 2.2 (95% CI 2.0-2.5) for heterozygous participants and 7.0 (95%CI 4.8-10) for homozygous participants (v. participants without the mutation). For prothrombin G20210A, the adjusted HR was 1.5 (95%CI 1.2-1.9) for heterozygous participants and 11 (95% CI 2.8-44) for homozygous participants (v. participants without the mutation). When we combined ABO blood type and factor V Leiden R506Q or prothrombin G20210A genotype, there was a stepwise increase in the risk of venous thromboembolism (trend, pfactor V Leiden R506Q and 1% for prothrombin G20210A. Multivariable adjusted HRs for myocardial infarction by genotypes did not differ from 1.0. ABO blood type had an additive effect on the risk of venous thromboembolism when combined with factor V Leiden R506Q and prothrombin G20210A mutations; blood type was the most important risk factor for venous thromboembolism in the general population.

  14. Prothrombin and risk of venous thromboembolism, ischemic heart disease and ischemic cerebrovascular disease in the general population

    Weischer, Maren; Juul, Klaus; Zacho, Jeppe


    OBJECTIVE: We tested the hypotheses that Prothrombin G20210A heterozygosity associate with increased risk of venous thromboembolism (VTE), ischemic heart disease (IHD), and ischemic cerebrovascular disease (ICVD) in the general population and re-tested risk of IHD and ICVD in two case......-control studies. METHODS: 9231 individuals from the Danish general population were followed for VTE (VTE=DVT+PE), deep venous thrombosis (DVT), pulmonary embolism (PE), IHD, myocardial infarction (MI), ICVD, and ischemic stroke (IS) for a median of 24 years. Case-control studies included 2461 IHD cases and 867.......0(1.0-3.8) for MI, 1.4(0.7-3.1) for ICVD, and 2.1(0.8-5.4) for IS. CONCLUSION: Prothrombin G20210A heterozygosity alone and in combination with Factor V Leiden R506Q heterozygosity predicts 1.5 and 6.0 fold risk of IHD compared to non-carriers....

  15. [Recurrent vascular access trombosis associated with the prothrombin mutation G20210A in a adult patient in haemodialysis].

    Quintana, L F; Coll, E; Monteagudo, I; Collado, S; López-Pedret, J; Cases, A


    Vascular access-related complications are a frequent cause of morbidity in haemodialysis patients and generate high costs. We present the case of an adult patient with end-stage renal disease and recurrent vascular access thrombosis associated with the prothrombin mutation G20210A and renal graft intolerance. The clinical expression of this heterozygous gene mutation may have been favoured by inflammatory state, frequent in dialysis patients. In this patient, the inflammatory response associated with the renal graft intolerance would have favored the development of recurrent vascular access thrombosis in a adult heterozygous for prothrombin mutation G20210A. In the case of early dysfunction of haemodialysis vascular access and after ruling out technical problems, it is convenient to carry out a screening for thrombophilia.

  16. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type

    Sode, Birgitte F; Allin, Kristine H; Dahl, Morten


    ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated...... with the risk of venous thromboembolism and myocardial infarction in the general population....

  17. Outcome of Patients with Venous Thromboembolism and Factor V Leiden or Prothrombin 20210 Carrier Mutations During the Course of Anticoagulation.

    Tzoran, Inna; Papadakis, Manolis; Brenner, Benjamin; Fidalgo, Ángeles; Rivas, Agustina; Wells, Philip S; Gavín, Olga; Adarraga, María Dolores; Moustafa, Farès; Monreal, Manuel


    Individuals with factor V Leiden or prothrombin G20210A mutations are at a higher risk to develop venous thromboembolism. However, the influence of these polymorphisms on patient outcome during anticoagulant therapy has not been consistently explored. We used the Registro Informatizado de Enfermedad TromboEmbólica database to compare rates of venous thromboembolism recurrence and bleeding events occurring during the anticoagulation course in factor V Leiden carriers, prothrombin mutation carriers, and noncarriers. Between March 2001 and December 2015, 10,139 patients underwent thrombophilia testing. Of these, 1384 were factor V Leiden carriers, 1115 were prothrombin mutation carriers, and 7640 were noncarriers. During the anticoagulation course, 160 patients developed recurrent deep vein thrombosis and 94 patients developed pulmonary embolism (16 died); 154 patients had major bleeding (10 died), and 291 patients had nonmajor bleeding. On multivariable analysis, factor V Leiden carriers had a similar rate of venous thromboembolism recurrence (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.82-1.64), half the rate of major bleeding (adjusted HR, 0.50; 95% CI, 0.25-0.99) and a nonsignificantly lower rate of nonmajor bleeding (adjusted HR, 0.66; 95% CI, 0.43-1.01) than noncarriers. Prothrombin mutation carriers and noncarriers had a comparable rate of venous thromboembolism recurrence (adjusted HR, 1.00; 95% CI, 0.68-1.48), major bleeding (adjusted HR, 0.75; 95% CI, 0.42-1.34), and nonmajor bleeding events (adjusted HR, 1.10; 95% CI, 0.77-1.57). During the anticoagulation course, factor V Leiden carriers had a similar risk for venous thromboembolism recurrence and half the risk for major bleeding compared with noncarriers. This finding may contribute to decision-making regarding anticoagulation duration in selected factor V Leiden carriers with venous thromboembolism. Copyright © 2017. Published by Elsevier Inc.

  18. [False positive serum des-gamma-carboxy prothrombin after resection of hepatocellular carcinoma].

    Hiramatsu, Kumiko; Tanaka, Yasuhito; Takagi, Kazumi; Iida, Takayasu; Takasaka, Yoshimitsu; Mizokami, Masashi


    Measurements of serum concentrations of des-gamma-carboxy-prothrombin (PIVKA-II) are widely used for diagnosing hepatocellular carcinoma (HCC). Recently, when we evaluated the correlation of PIVKA-II between two commercially available PIVKA-II immunoassay kits (Lumipulse f vs. Picolumi) to introduce it in our hospital, false high values of PIVKA-II were observed in Lumipulse assay. Four(4%) of 100 serum samples showed false high values, and all of them were obtained from patients less than 2 month after curative resection of HCC. Examining additional 7 patients with HCC resection, serum samples from the 5 patients had the same trend. To elucidate the non-specific reaction by Lumipulse assay which utilized alkaline phosphatase (ALP) enzymatic reaction, inhibition assays by various absorbents such as inactive ALP and IgM antibodies were performed. Excess of inactive ALP reduced the high values of PIVKA-II. Note that anti-bleeding sheets (fibrinogen combined drug), which included bovine thrombin, were directly attached on liver of all patients with HCC resection in this study. As the sheets also contaminate ALP and probably produce IgM antibodies to ALP, the IgM may cross-react with anti-PIVKA-II antibodies directly. Taken together, it was suggested that produced antibodies against ALP derived from anti-bleeding sheets led false high values of PIVKA-II in the patients with HCC resection.

  19. Management of the Bleeding Patient Receiving New Oral Anticoagulants: A Role for Prothrombin Complex Concentrates

    Lisa M. Baumann Kreuziger


    Full Text Available Ease of dosing and simplicity of monitoring make new oral anticoagulants an attractive therapy in a growing range of clinical conditions. However, newer oral anticoagulants interact with the coagulation cascade in different ways than traditional warfarin therapy. Replacement of clotting factors will not reverse the effects of dabigatran, rivaroxaban, or apixaban. Currently, antidotes for these drugs are not widely available. Fortunately, withholding the anticoagulant and dialysis are freqnently effective treatments, particularly with rivaroxaban and dabigatran. Emergent bleeding, however, requires utilization of Prothrombin Complex Concentrates (PCCs. PCCs, in addition to recombinant factor VIIa, are used to activate the clotting system to reverse the effects of the new oral anticoagulants. In cases of refractory or emergent bleeding, the recommended factor concentrate in our protocols differs between the new oral anticoagulants. In patients taking dabigatran, we administer an activated PCC (aPCC [FELBA] due to reported benefit in human in vitro studies. Based on human clinical trial evidence, the 4-factor PCC (Kcentra is suggested for patients with refractory rivaroxaban- or apixaban-associated hemorrhage. If bleeding continues, recombinant factor VIIa may be employed. With all of these new procoagulant agents, the risk of thrombosis associated with administration of factor concentrates must be weighed against the relative risk of hemorrhage.

  20. Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives.

    Peterson, Lisa K; Willis, Rohan; Harris, E Nigel; Branch, Ware D; Tebo, Anne E


    Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy-related morbidity accompanied by persistently positive antiphospholipid antibodies (aPL). Current laboratory criteria for APS classification recommend testing for lupus anticoagulant as well as IgG and IgM anticardiolipin, and beta-2 glycoprotein I (anti-β2GPI) antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative for the recommended criteria aPL tests. While acknowledging that such patients may have clinical features that are not of an autoimmune etiology, experts also speculate that these "seronegative" patients may test negative for relevant autoantibodies as a result of a lack of harmonization and/or standardization. Alternatively, they may have aPL that target other antigens involved in the pathogenesis of APS. In the latter, autoantibodies that recognize a phosphatidylserine/prothrombin (PS/PT) complex have been reported to be associated with APS and may have diagnostic relevance. This review highlights analytical and clinical attributes associated with PS/PT antibodies, taking into consideration the performance characteristics of criteria aPL tests in APS with specific recommendations for harmonization and standardization efforts.

  1. Diagnostic Performance of Des-γ-carboxy Prothrombin for Hepatocellular Carcinoma: A Meta-Analysis

    Rong Zhu


    Full Text Available Background. There have been many reports on des-γ-carboxy prothrombin (DCP as a promising serum marker in the diagnosis of hepatocellular carcinoma (HCC; however, the results are inconsistent and even conflicting. Methods. This meta-analysis was performed to investigate the performance of DCP in the diagnosis of HCC. Following a systematic review of relevant studies, Meta-DiSc 1.4 software was used to extract data and to calculate the overall sensitivity, specificity, positive likelihood ratio (PLR, negative likelihood ratio (NLR, and diagnostic odds ratio (DOR. Data are presented as forest plots and summary receiver operating characteristic curve (SROC analysis was used to summarize the overall test performance. Results. Twelve studies were included in our meta-analysis. The overall sensitivity, specificity, PLR, and NLR of DCP for the detection of HCC in the studies included were 71% (95%CI: 68%–73%, 84% (95%CI: 83%–86%, 6.48 (95%CI: 4.22–9.93, and 0.33 (95%CI: 0.25–0.43, respectively. The area under the SROC curve was 0.8930 and the Q index was 0.8238. Significant heterogeneity was found. Conclusion. This meta-analysis indicated that DCP had moderate diagnostic accuracy in HCC. Further studies with rigorous design, large sample size, and mmultiregional cooperation are needed in the future.

  2. Risk of recurrent venous thrombosis in homozygous carriers and double heterozygous carriers of factor V Leiden and prothrombin G20210A.

    Lijfering, Willem M; Middeldorp, Saskia; Veeger, Nic J G M; Hamulyák, Karly; Prins, Martin H; Büller, Harry R; van der Meer, Jan


    Homozygous or double heterozygous factor V Leiden and/or prothrombin G20210A is a rare inherited thrombophilic trait. Whether individuals with this genetic background have an increased risk of recurrent venous thrombosis is uncertain. A case-control design within a large cohort of families with thrombophilia was chosen to calculate the risk of recurrent venous thrombosis in individuals with homozygosity or double heterozygosity of factor V Leiden and/or prothrombin G20210A. Cases were individuals with recurrent venous thrombosis, and controls were those with only 1 venous thrombosis. The cohort consisted of 788 individuals with venous thrombosis; 357 had factor V Leiden, 137 had prothrombin G20210A, 27 had factor V Leiden and/or prothrombin G20210A homozygosity, and 49 had double heterozygosity for both mutations. We identified 325 cases with recurrent venous thrombosis and 463 controls with only 1 venous thrombosis. Compared with noncarriers, crude odds ratio for recurrence was 1.2 (95% confidence interval, 0.9 to 1.6) for heterozygous carriers of factor V Leiden, 0.7 (95% confidence interval, 0.4 to 1.2) for prothrombin G20210A, 1.2 (95% confidence interval, 0.5 to 2.6) for homozygous carriers of factor V Leiden and/or prothrombin G20210A, and 1.0 (95% confidence interval, 0.6 to 1.9) for double heterozygotes of both mutations. Adjustments for age, sex, family status, first event type, and concomitance of natural anticoagulant deficiencies did not alter the risk estimates. In this study, individuals with homozygous factor V Leiden and/or homozygous prothrombin G20210A or double heterozygous carriers of factor V Leiden and prothrombin G20210A did not have a high risk of recurrent venous thrombosis.

  3. Prolongation structures for supersymmetric equations

    Roelofs, G.H.M.; Hijligenberg, van den N.W.


    The well known prolongation technique of Wahlquist and Estabrook (1975) for nonlinear evolution equations is generalized for supersymmetric equations and applied to the supersymmetric extension of the KdV equation of Manin-Radul. Using the theory of Kac-Moody Lie superalgebras, the explicit form of

  4. Clinical characteristics of patients with factor V Leiden or prothrombin G20210A and a first episode of venous thromboembolism. Findings from the RIETE Registry.

    Gadelha, Telma; Roldán, Vanessa; Lecumberri, Ramón; Trujillo-Santos, Javier; del Campo, Raquel; Poggio, Renzo; Monreal, Manuel


    The clinical characteristics of patients with factor V Leiden or prothrombin G20210A presenting with a first episode of venous thromboembolism (VTE) have not been thoroughly studied. RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the clinical characteristics of patients with factor V Leiden, prothrombin G20210A, or no thrombophilia, at presentation with a first episode of VTE. As of May 2009, 22428 patients had been enrolled with a first episode of VTE. Of these, 345 had factor V Leiden, 261 had prothrombin G20210A, and 2399 tested negative. Sixty-two percent of the VTE episodes in women with factor V Leiden or prothrombin G20210A (40% in men) were associated with an acquired risk factor. Among women, pregnancy or contraceptive use accounted for 63% and 67% of such risk factors. Patients with factor V Leiden presented with pulmonary embolism (PE) less likely than those with prothrombin G20210A (31% vs. 51%; pFactor V Leiden presented with hypoxaemia (Sat O(2) levelsfactor V Leiden or prothrombin G20210A were associated with an acquired risk factor (mostly pregnancy or contraceptive use). Only 4.5% of patients with factor V Leiden presenting with acute PE had hypoxaemia. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. In Vivo Bleeding Time and In Vitro Thrombelastography Measurements are Better Indicators of Dilutional Hypothermic Coagulopathy Than Prothrombin Time


    lation proteins. It is often worsened by massive blood or other fluid transfusion, metabolic acidosis , and hypothermia, or any combination of these...fluid replacement (he- modilution) and hypothermia without massive tissue injury or metabolic acidosis . A mild acidosis (respiratory, pH 7.3) that...massive tissue injury, large hemorrhage that di- lutes and consumes most coagulation factors and hypoperfu- sion, which causes metabolic acidosis and

  6. Thromboelastography as a Better Indicator of Postinjury Hypercoagulable State Than Prothrombin Time or Activated Partial Thromboplastin Time


    anticoagulation therapy with warfarin or antiplatelet agents , and patients with known underlying coagulopathies were excluded. In addition, 20 healthy...pectoris (22–24). Finally, key anticoagulant factors such as protein C, antithrombin III (AT III), and the tissue factor pathway inhibitor are...procoagulant and anticoagulant activity and that these processes would be similar for both injury groups. Materials and Methods This study was reviewed and

  7. Prolonged ulcerative laryngitis: a new disease entity.

    Hsiao, Tzu-Yu


    Over the last decade, a new disease entity, prolonged ulcerative laryngitis (PUL), with unique clinical presentation and prolonged disease course, has been recognized. Until now, very few studies dealing with this disease have been reported in the literature. From 1999 to 2008, we analyzed clinical data from a series of 39 PUL patients who were treated with an observational approach without implementing specific treatments. This disease affects adults, predominantly females. The age of patients in our series ranged from 26 to 76 years with a median of 49.5 years. This disease is characterized by ulcers and signs of acute inflammation on the membranous portion of the vocal folds with a prolonged clinical course. The recovery times of patients ranged from 4 to 20 weeks with an average of 9.4 weeks. The data in this study may reflect a natural history of this disease. PUL seems to be a self-limited disease, but the etiology of this disease is unknown. Specific infections or systemic inflammatory processes involving the larynx must be ruled out before diagnosis, and conservative treatments are suggested.

  8. Prevalence of factor V G1691A (Leiden) and prothrombin G20210A polymorphisms among apparently healthy Jordanians.

    Nusier, Mohamad K; Radaideh, Abdelrahman M; Ababneh, Nida'a A; Qaqish, Bara'ah M; Alzoubi, Renad; Khader, Yousef; Mersa, Janet Y; Irshaid, Nidal M; El-Khateeb, Mohammed


    Factor V Leiden and prothrombin G20210A are related genetic risk factors for venous thromboembolism (VTE). Analysis for both mutations is increasingly being performed on patients exhibiting hypercoagulability. The objective of this study was to determine the prevalence of factor V Leiden (FVL), prothrombin-G20210A (PT-G20210A) polymorphisms and their coexistence among apparently healthy Jordanians. One thousand apparently healthy individuals from representative regions of Jordan with no previous history of VTE participated in this study. The mean age of participants was 28.5+/-6.4 years (age range 18-45 years). Two hundred and eighteen subjects were APC resistant with an APC-R mean of 85.52+/-15.35 seconds; the non-resistant subjects had an APC-R mean of 159.90+/-26.96 seconds. A multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the simultaneous detection of FVL and prothrombin G20210A was used to analyze the 218 DNA samples that were APC-R resistant. Both mutations generate HindIII RFLPs and the prothrombin amplicon contains an invariant HindIII recognition sites. The multiplex PCR-RFLP of Factor V for those 218-samples was: 41 wild-type, 169 heterozygous mutant, and eight homozygous mutant individuals. For prothrombin G20210A, the multiplex PCR-RFLP identified 215 wild-type and three heterozygous mutant individuals. Factor V positive individuals (n=50) had a mean F-V activity of 78.04%+/-25.81. F-V activity among wild type (n=41), F-V Leiden heterozygous (n=169) and F-V Leiden homozygous (n=8) were 92.93%+/-16.17, 87.02%+/-15.21 and 96.14%+/-12.32, respectively. Factor II positive subjects (n=47) had a mean factor II activity of 127.96%+/-21.37. F-II activity among carriers (heterozygous, n=3) and non-carriers (normal, n=215) of PT-G20210A mutation were 107.67%+/-9.29 and 105.00%+/-17.79, respectively. The prevalence of FVL was 21.8% and there is a little likelihood of the co-inheritance of the FVL and PT-G20210A among

  9. 生长期喷钙提高锦橙果实品质及延长贮藏期%Improve fruit quality and prolong storage time of Jincheng orange by calcium sprayed in growth period

    温明霞; 石孝均


      探讨钙对柑橘果实贮藏品质及衰老的影响,为合理调控柑橘钙素营养、延长果实的贮藏保鲜期提供理论和技术支撑.通过在北碚447锦橙(Citrus sinensis Osbeck cv. Jincheng)生长的不同时期进行树体补钙,研究钙对果实贮藏品质及酶活性的影响.结果表明,在锦橙的生长期喷钙能提高果实钙含量,抑制果实贮藏过程中维生素C 等物质的氧化分解,提高果实可溶性固形物含量和糖酸比,改善果实品质.不同时期喷钙均能提高果实中抗氧化酶(CAT、SOD)活性,降低细胞壁水解酶(PG、CX)、过氧化物酶(POD)活性,减轻脂质过氧化程度,果胶的分解转化速度减慢,丙二醛、可溶性果胶的含量明显降低,从而维持果皮具有一定的强度,延缓了果实的衰老,降低烂果的发生率,延长了果实的贮藏保鲜期.其中以幼果期喷钙在提高果实钙含量、延长贮藏期等方面的效果较好,其次是果实膨大期喷钙,成熟期喷钙效果最差.在幼果期和果实膨大期喷钙是提高果实品质、延长采后果实贮藏保鲜期的重要措施.%Calcium (Ca), as an important nutrition, can regulate the physiological metabolic process and is closely related to fruit quality, the shelf life of fruit and physiological diseases during storage time. It is meaningful to study the relation of Ca nutrition and fruit quality and senescence for producing fruit with high quality, alleviating economic loss from rotten fruit and prolonging the fruit storage time. At present, there were some reports about Ca nutrition and fruit quality but many reported the effect of Ca on storage property of fruit by studying the respiration intensity and electric conductivity of fruits supplementing Ca solution on fruit during maturing stage or harvest time, few reported the effect of Ca on the inherent quality and the shelf life of fruits supplying Ca nutrition during fruit growing period. In

  10. Diagnostic value of antibodies to phosphatidylserine/prothrombin complex for antiphospholipid syndrome in Chinese patients.

    Zhu, Lei; Li, Chun; Liu, Na; Yang, Xin; Jia, R L; Mu, Rong; Su, Yin; Li, Z G


    To evaluate the diagnosis value of antibodies to phosphatidylserine/prothrombin complex (aPS/PT) in patients with antiphospholipid syndrome (APS) and to determine the clinical features of APS patients with avidity of aPS/PT. Serum samples were collected from 108 APS patients. Sixty patients with pregnancy morbidity, 37 patients with thrombosis without a history of autoimmune diseases, and 89 healthy blood donors were included as the control group. The enzyme-linked immunosorbent assay (ELISA) test was performed to detect the concentration of aPS/PT, including IgG/M, IgG, and IgM forms, in the same serum sample. The chi-square (χ2) test was used to examine the difference of frequencies of antibodies in APS patients and patients with other diseases. Spearman correlation analysis was performed to investigate the relationship between aPS/PT and other clinical/laboratory parameters. aPS/PT was detectable in 68 (63.0%) of the 108 APS patients, 12 (13.2%) of the 91 disease control patients and 1 (1.1%) of the healthy controls. It was strongly correlated with the activity of lupus anticoagulant (LA) (OR 15.952, 95% CI 7.132-35.678; P < 0.001). The frequency of aPS/PT was 56.9% in anti-cardiolipid antibody (aCL)-negative, 60.5% anti-β2 glycoprotein I antibody (aβ2GPI)-negative, and 50.0% in both aCL and aβ2GPI negative APS patients. The IgG aPS/PT was significantly associated with arterial and venous thrombosis. The aPS/PT antibody could play an important role in the diagnosis of APS, especially in patients with negative aCL and aβ2GPI. It was positively related to thrombotic events in APS.

  11. Anti-Phosphatidylserine/Prothrombin Antibodies Are Associated with Adverse Pregnancy Outcomes

    Polona Žigon


    Full Text Available Objective. To determine the prevalence and clinical association of anti-phosphatidylserine/prothrombin antibodies (aPS/PT in patients with a history of pregnancy complications relevant to antiphospholipid syndrome (APS. Materials and Methods. Two hundred and eleven patients with a history of (a three or more consecutive miscarriages before 10th week of gestation (WG (n=64, (b death of a morphologically normal fetus beyond 10th WG (n=72, (c premature birth of a morphologically normal neonate before 34th WG due to eclampsia, preeclamsia and placental insufficiency (n=33, and (d less than three unexplained consecutive miscarriages before 10th WG (n=42. Subjects sera were analyzed for lupus anticoagulant (LA, anti-cardiolipin (aCL, anti-β2-glycoprotein I (anti-β2GPI, and aPS/PT antibodies. Results. 41/169 (24.3% of patients were positive for at least one measured aPL. The highest prevalence was found for aPS/PT and aCL (13.0% and 12.4%, resp. followed by LA (7.7% and anti-β2GPI (7.1%. 11/169 with APS-related obstetric manifestations had only aPS/PT. 17.8% of patients were positive for LA or aCL and/or anti-β2GPI; however when adding the aPS/PT results, an additional 7% of patients could be evaluated for APS. Conclusion. aPS/PT are associated with recurrent early or late abortions and with premature delivery irrespective of other aPL.

  12. Meta-analysis of factor V Leiden and prothrombin G20210A polymorphism in migraine.

    Lippi, Giuseppe; Mattiuzzi, Camilla; Cervellin, Gianfranco


    Migraine is a frequent and disabling condition, which exhibits a substantial genetic background and is frequently associated with abnormalities of primary and secondary hemostasis. We performed a systematic literature search and a meta-analysis of available data about the potential associations between migraine and factor V (FV) Leiden or prothrombin (FII) G20210A gene polymorphism. The final number of studies included was 15 (all cross-sectional) about migraine and FV Leiden, and 12 (all cross-sectional) about migraine and FII G20210A polymorphism, with broad inter-study heterogeneity (I², 82 and 85%). The cumulative prevalence of the FV 1691A allele was found to be similar between cases (n = 1450; 4.9%) and controls (n = 3468; 4.7%; P = 0.74). The cumulative prevalence of the FII 20210A allele was also found to be similar between cases (n = 1226; 4.2%) and controls (n = 3144; 4.5%; P = 0.59). Nevertheless, sub-analysis of studies in adults and children revealed that both polymorphisms were not associated with migraine in adults, but FV Leiden and the FII 20210A allele were approximately two-fold more prevalent in children with migraine than in those without. In conclusion, despite migraine exhibits a clear neurovascular origin and is frequently associated with thrombotic disorders, isolate thrombophilic mutations seem to play a negligible pathogenetic role in this condition in adults, whereas the increased prevalence of FV Leiden and the FII 20210A allele in children with migraine deserves further scrutiny.

  13. Des-gamma-carboxy prothrombin as an important prognostic indicator in patients with small hepatocellular carcinoma

    Kenichi Hakamada; Norihisa Kimura; Takuya Miura; Hajime Morohashi; Keinosuke Ishido; Masaki Nara; Yoshikazu Toyoki; Shunji Narumi; Mutsuo Sasaki


    AIM:To clarify the effect of a high des-gamma-carboxy prothrombin (DCP) level on the invasiveness and prognosis of small hepatocellular carcinoma.METHODS:Among 142 consecutive patients with known DCP levels,who underwent hepatectomy because of hepatocellular carcinoma,85 patients met the criteria for small hepatocellular carcinoma,≤5 cm sized single tumor or no more than three≤3 cm sized tumors.RESULTS:The overall survival rate of the 142 patients was 92.1% for 1 year,69.6% for 3 years,and 56.9% for 5 years.Multivariate analysis showed that microscopic vascular invasion (P = 0.03) and serum DCP≥400mAU/mL (P = 0.02) were independent prognostic factors.In the group of patients who met the criteria for small hepatocellular carcinoma,DCP≥400 mAU/mL was found to be an independent prognostic factor for recurrence-free (P = 0.02) and overall survival (P = 0.0005).In patients who did not meet the criteria,the presence of vascular invasion was an independent factor for recurrence-free (P = 0.02) and overall survivals (P = 0.01).In 75% of patients with small hepatocellular carcinoma and high DCP levels,recurrence occurred extrahepatically.CONCLUSION:For small hepatocellular carcinoma,a high preoperative DCP level appears indicative for tumor recurrence.Because many patients with a high preoperative DCP level develop extrahepatic recurrence,it is necessary to screen the whole body.

  14. Clinical evaluation of plasma abnormal prothrombin (PIVKA-II) in patients with hepatocellular carcinoma.

    Fujiyama, S; Morishita, T; Sagara, K; Sato, T; Motohara, K; Matsuda, I


    The clinical usefulness of plasma abnormal prothrombin, defined as a protein induced by vitamin K absence or antagonist-II: PIVKA-II, as a tumor marker for hepatocellular carcinoma (HCC), was evaluated. Plasma PIVKA-II concentration was determined by an enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody specific for PIVKA-II. Forty-one (65%) out of 63 patients with HCC had an abnormal PIVKA-II level above 0.13 arbitrary units (AU)/ml; the level was above 0.3 AU/ml in 33 patients (52%) and above 0.5 AU/ml in 27 patients (43%). On the other hand, most of the 282 patients with various liver diseases other than HCC had normal or slightly elevated levels of PIVKA-II. Their values were all below 0.5 AU/ml, with the exception of 2 patients with decompensated liver cirrhosis. The patients with PIVKA-II values above 0.5 AU/ml were strongly suspected of having HCC. Plasma PIVKA-II levels were not related to serum alpha-fetoprotein (AFP) levels, but were above 0.5 AU/ml in 14 (44%) out of the 32 patients whose serum AFP levels were below 400 ng/ml. In some patients with HCC, PIVKA-II was increased throughout the course of the disease, and in others it normalized after surgical resection of the tumor. We conclude that the plasma PIVKA-II assay by the ELISA method using a monoclonal antibody is a useful diagnostic tool for monitoring HCC, particularly in HCC patients with low AFP levels.

  15. Multicentric evaluation of a new assay for prothrombin fragment F1+2 determination.

    Bruhn, H D; Conard, J; Mannucci, M; Monteagudo, J; Pelzer, H; Reverter, J C; Samama, M; Tripodi, A; Wagner, C


    A multicenter study of a recently developed ELISA for the determination of prothrombin fragment F1+2 was performed in order to evaluate analytical and clinical aspects. Mean intra-assay and inter-assay reproducibility were found to be 11.0 and 12.6%, respectively. The measuring range covered by the calibration curve reaches from 0.04 to 10.0 nM/l F1+2. Testing 133 healthy subjects a reference range of 0.37 to 1.11 nM/l F1+2 (2.5-97.5 percentile) with a median of 0.66 nM/l F1+2 was calculated. Minor difficulties with blood sampling (venous occlusion for 2 min) did not affect F1+2 plasma concentrations. Significantly increased F1+2 levels were measured in patients with leukemia (p < 0.0001), severe liver disease (p < 0.005) and after myocardial infarction (p < 0.01). Elevated F1+2 concentration before the beginning of heparin therapy (1.25 nM/l) decreased to 0.77 nM/l (p < 0.0001) after 1 day of therapy. For patients in the stable phase of oral anticoagulant therapy decreasing F1+2 concentrations were measured with increasing INR. F1+2 levels were already significantly reduced in patients with INR < 2.0 (0.56 nM/l; p = 0.0005). Thus F1+2 determination may be helpful in identifying activation processes as well as in monitoring anticoagulant therapy.

  16. Prolonged fever after Infliximab infusion

    Jennifer; Katz; Michael; Frank


    Pharmacologic management for ulcerative colitis (UC) has recently been expanded to include antitumor necrosis factor (TNF) therapy for severe disease. Infliximab, a chimeric monoclonal antibody directed again TNF α was first tested in patients with Crohn’s disease. In addition to serious infections, malignancy, drug induced lupus and other autoimmune diseases, serum sickness-like reactions, neurological disease, and infusion reactions further complicate the use of Infliximab. We report a case of prolonged fever after Infliximab infusion to treat steroid refractory UC.

  17. Plasma levels of plasminogen activator inhibitor type 1, factor VIII, prothrombin activation fragment 1+2, anticardiolipin, and antiprothrombin antibodies are risk factors for thrombosis in hemodialysis patients.

    Molino, Daniela; De Santo, Natale G; Marotta, Rosa; Anastasio, Pietro; Mosavat, Mahrokh; De Lucia, Domenico


    Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non-systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition

  18. Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance.

    Takagi, Yuki; Murata, Moe; Kozuka, Toshihiro; Nakata, Yukiko; Hasebe, Ryo; Tamura, Shogo; Takagi, Akira; Matsushita, Tadashi; Saito, Hidehiko; Kojima, Tetsuhito


    Antithrombin (AT) and thrombomodulin (TM) play important roles in the process of natural anticoagulation in vivo. Recently, we reported that the prothrombin Yukuhashi mutation (p.Arg596Leu) was associated with AT and TM resistance-related thrombophilia. To assess the AT and TM resistances associated with other missense mutations by single base substitution in the Arg596 codon, we generated recombinant variants (596Gln, 596Trp, 596Gly, and 596Pro) and investigated the effects on AT and TM anticoagulant functions. All variants except 596Pro were secreted in amounts comparable to that of the wild-type but exhibited variable procoagulant activities. After a 30-minute inactivation by AT, the relative residual activity of wild-type thrombin decreased to 15 ± 4.0 %, in contrast to values of all variants were maintained at above 80 %. The thrombin-AT complex formation, as determined by enzyme-linked immunosorbent assay, was reduced with all tested variants in the presence and absence of heparin. In the presence of soluble TM (sTM), the relative fibrinogen clotting activity of wild-type thrombin decreased to 16 ± 0.12 %, whereas that of tested variants was 37 %-56 %. In a surface plasmon resonance assay, missense Arg596 mutations reduced thrombin-TM affinity to an extent similar to the reduction of fibrinogen clotting inhibition. In the presence of sTM or cultured endothelial-like cells, APC generation was enhanced differently by variant thrombins in a thrombin-TM affinity-dependent manner. These data indicate that prothrombin Arg596 missense mutations lead to AT and TM resistance in the variant thrombins and suggest that prothrombin Arg596 is important for AT- and TM-mediated anticoagulation.

  19. Differences in urinary prothrombin fragment 1 + 2 levels after total hip replacement in relation to venous thromboembolism and bleeding events

    Borris, L C; Breindahl, M; Lassen, M R;


    events. PATIENTS/METHODS: This study was conducted in parallel with a prospective, dose-finding study evaluating the efficacy and safety of different doses of rivaroxaban (Xarelto, Bayer HealthCare AG, Wuppertal, Germany) for thromboprophylaxis, relative to enoxaparin. Deep vein thrombosis was diagnosed......BACKGROUND: Prothrombin fragment 1 + 2 is excreted in urine (uF1 + 2) as a result of thrombin generation and, therefore, may be a useful marker of coagulation status. OBJECTIVES: To assess uF1 + 2 levels after total hip replacement (THR) in patients with venous thromboembolism (VTE) and bleeding...

  20. Kinetics of the activation of human prothrombin by human coagulation factor Xa. Initial rate studies in the presence of Ca2+ and phospholipid.

    Kosow, D P; Orthner, C L


    Steady state kinetic studies have been performed to investigate the formation of thrombin from prothrombin by human coagulation Factor Xa in the presence of Ca2+ and phospholipid. The concentration of ligand which gives 50% of the maximum velocity (K0.5) is 2.3 mM for Ca2+, 7.4 microM for phospholipid, and 0.006 microM for prothrombin. Hill plots of the Ca2+ enhancement of the reaction give a Hill coefficient of 3.1, indicating positive cooperativity. The initial velocity patterns are consistent with an ordered addition of reactants with phospholipid as the second reactant to bind to the enzyme. Although our results do not differentiate between Ca2+ or the prothrombin substrate as the first reactant to bind to Factor Xa, it is established that Ca2+ can bind to Factor Xa in the absence of the other reactants. Thus, the most probable order of addition of reactants is Ca2+, phospholipid, and the prothrombin substrate. Plots of (v)-1 versus (prothrombin)-1 or (v)-1 versus [(Ca2+)3]-1 at several constant concentrations of phospholipid indicate that the major effect of phospholipid is to increase the turnover number of Factor Xa.

  1. Homozygous factor V Leiden and double heterozygosity for factor V Leiden and prothrombin mutation.

    Saemundsson, Ymir; Sveinsdottir, Signý Vala; Svantesson, Henrik; Svensson, Peter J


    The most common forms of familial thrombophilia are factor V Leiden (FVL) and prothrombin mutation (PTM). Homozygous FVL and PTM have long been feared conditions thought to cause high rates of morbidity and mortality. To analyse clinical features in patients with homozygous FVL and PTM, as well as patients with double heterozygosity for FVL and PTM. All patients with homozygous FVL, PTM or double heterozygosity in the MATS database of 1465 consecutive unselected patients were analysed regarding age at inclusion venous thromboembolism (VTE), age at first thrombosis, recurrence, clinical course and acquired risk factors. We found 36 patients homozygous for FVL. Patients homozygous for FVL were younger than controls at group level (56 ± 18 vs. 63 ± 17, p < 0.02). Homozygous women were younger than female controls (50 ± 19 vs. 63 ± 18, p < 0.002). No difference was observed when comparing male subjects. Women were younger than men at inclusion thrombosis (50 ± 19 vs. 65 ± 14, p < 0.02) and at first thrombosis (47 ± 19 vs. 64 ± 14, p < 0.01). Deep venous thrombosis (DVT) was seen in 33 patients (92 %), 6 (17 %) had pulmonary embolism (PE) and 3 (8 %) had combined DVT and PE. PE was less frequent in homozygous FVL women compared to female controls (p < 0.03). VTE recurred in 3 subjects during the duration of the study. Odds ratio for VTE in homozygous FVL patients compared to controls was 13.9 (95 % CI 9.9-19.7). We found no subjects with homozygous PTM. Double heterozygosity for FVL and PTM was seen in 12 subjects. There was no difference in age at inclusion VTE between double heterozygotes and controls (59 ± 16 vs. 63 ± 17, ns.). DVT was seen in 92 % at inclusion, 8 % had PE. Mean age at first VTE was 52 ± 17 (27-82). Consecutive homozygous FVL patients had a higher age at first thrombosis than previously described. Homozygous females are affected at an earlier age than homozygous men and female controls. It seems that

  2. Serum des-R prothrombin activation peptide fragment 2: a novel prognostic marker for disseminated intravascular coagulation.

    Chung, Soie; Kim, Ji-Eun; Kim, Hyun Kyung; Yeon, Eun Hee; Shin, Yong Sung; Kim, Chul Woo


    Disseminated intravascular coagulation (DIC) is diagnosed based on the combination of predisposing underlying conditions and laboratory tests for plasma coagulation markers. Because the collection of blood plasma samples is a fastidious procedure, the serum sample method may be preferred for measurement of coagulation markers when feasible. The novel serum marker des-R prothrombin activation peptide fragment 2 (des-R F2) was measured using a sandwich enzyme-linked immunosorbent assay in 181 patients suspected of having DIC. Thrombin generation potential was estimated with a calibrated automated thrombogram. Serum des-R F2 was generated with an in vitro clotting process within a serum separation tube after blood collection. Carboxypeptidase inhibitor inhibited the formation of des-R F2 during in vitro clotting. Low levels of prothrombin and thrombin generation potential resulted in low serum des-R F2 levels. Serum des-R F2 was significantly decreased in overt DIC. Levels of des-R F2 correlated with DIC severity and other coagulation markers. Of note, the decrease in serum des-R F2 levels was a significant marker for predicting mortality. The serum marker, des-R F2, can be used for the investigation of DIC severity and prognosis. It should be considered a useful marker, especially when only serum samples are available. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Prolonged energy harvesting for ingestible devices.

    Nadeau, Phillip; El-Damak, Dina; Glettig, Dean; Kong, Yong Lin; Mo, Stacy; Cleveland, Cody; Booth, Lucas; Roxhed, Niclas; Langer, Robert; Chandrakasan, Anantha P; Traverso, Giovanni


    Ingestible electronics have revolutionized the standard of care for a variety of health conditions. Extending the capacity and safety of these devices, and reducing the costs of powering them, could enable broad deployment of prolonged monitoring systems for patients. Although prior biocompatible power harvesting systems for in vivo use have demonstrated short minute-long bursts of power from the stomach, not much is known about the capacity to power electronics in the longer term and throughout the gastrointestinal tract. Here, we report the design and operation of an energy-harvesting galvanic cell for continuous in vivo temperature sensing and wireless communication. The device delivered an average power of 0.23 μW per mm(2) of electrode area for an average of 6.1 days of temperature measurements in the gastrointestinal tract of pigs. This power-harvesting cell has the capacity to provide power for prolonged periods of time to the next generation of ingestible electronic devices located in the gastrointestinal tract.

  4. Sponsored parachute jumps--can they cause prolonged pain?

    Straiton, N; Sterland, J


    A survey of parachute injuries sustained in 1984 at a local parachute club was made using hospital notes and a questionnaire. The overall injury rate was 0.2%. The injury rate in first time jumpers was 1.1%. The injuries often resulted in a prolonged hospital stay, time off work and residual pain and disability. Injury rates may be reduced by more prolonged and intensive training preceding the first jumps. Those people not interested in parachuting as a regular sport and who jump once only in...

  5. Sponsored parachute jumps--can they cause prolonged pain?

    Straiton, N; Sterland, J


    A survey of parachute injuries sustained in 1984 at a local parachute club was made using hospital notes and a questionnaire. The overall injury rate was 0.2%. The injury rate in first time jumpers was 1.1%. The injuries often resulted in a prolonged hospital stay, time off work and residual pain and disability. Injury rates may be reduced by more prolonged and intensive training preceding the first jumps. Those people not interested in parachuting as a regular sport and who jump once only in order to raise money for charity are at risk of serious injury and perhaps should consider less dangerous alternatives.

  6. The effect of the administration of vitamin K2 to the pregnant women on the activities of prothrombin group in cord blood.


    Background: Hemorrhagic disease of the newborn (HDN) is a hemorrhage at the neonatal period. The most dangerous form of HDN is intracranial bleeding which may be fatal. The most frequent cause of HDN is deficiency of vitamin K dependent factors or prothrombin group.Objective: The aim of the study is to know the effect of the administration of vitamin K2 to the pregnant women on the activities of prothrombin gourp in cord blood.Methods: This was experimental design. Forty pregnant women were e...

  7. Prolonged QT interval in Rett syndrome


    Rett syndrome is a severe neurodevelopmental disorder of unknown aetiology. A prolonged QT interval has been described previously in patients with Rett syndrome. To investigate QT prolongation and the presence of cardiac tachyarrhythmias in Rett syndrome electrocardiography and 24 hour Holter monitoring were performed prospectively in a cohort of 34 girls with Rett syndrome. The corrected QT value was prolonged in nine patients. Compared with a group of healthy controls of a...

  8. Identification of a Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitor, BIP-135, that Prolongs the Median Survival Time of Δ7 SMA KO Mouse Model of Spinal Muscular Atrophy.

    Chen, Po C; Gaisina, Irina N; El-Khodor, Bassem F; Ramboz, Sylvie; Makhortova, Nina R; Rubin, Lee L; Kozikowski, Alan P


    The discovery of upregulated glycogen synthase kinase-3 (GSK-3) in various pathological conditions has led to the development of a host of chemically diverse small molecule GSK-3 inhibitors, such as BIP-135. GSK-3 inhibition emerged as an alternative therapeutic target for treating spinal muscular atrophy (SMA) when a number of GSK-3 inhibitors were shown to elevate survival motor neuron (SMN) levels in vitro and to rescue motor neurons when their intrinsic SMN level was diminished by SMN-specific short hairpin RNA (shRNA). Despite their cellular potency, the in vivo efficacy of GSK-3 inhibitors has yet to be evaluated in an animal model of SMA. Herein, we disclose that a potent and reasonably selective GSK-3 inhibitor, namely BIP-135, was tested in a transgenic Δ7 SMA KO mouse model of SMA, and found to prolong the median survival of these animals. In addition, this compound was shown to elevate the SMN protein level in SMA patient-derived fibroblast cells as determined by western blot, and was neuroprotective in a cell-based, SMA-related model of oxidative stress-induced neurodegeneration.

  9. An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies

    Khorsand, Nakisa; Veeger, Nic J. G. M.; van Hest, Reinier M.; Ypma, Paula F.; Heidt, Jeroen; Meijer, Karina


    Background Despite years of experience with vitamin K antagonist-associated bleeding events, there is still no evidence to help identify the optimal treatment with prothrombin complex concentrates. Variable dosing and fixed dose strategies are being used. In this observational prospective two-cohort

  10. Risk of Recurrent Venous Thrombosis in Homozygous Carriers and Double Heterozygous Carriers of Factor V Leiden and Prothrombin G20210A

    Lijfering, Willem M.; Middeldorp, Saskia; Veeger, Nic J. G. M.; Hamulyak, Karly; Prins, Martin H.; Bueller, Harry R.; van der Meer, Jan


    Background-Homozygous or double heterozygous factor V Leiden and/or prothrombin G20210A is a rare inherited thrombophilic trait. Whether individuals with this genetic background have an increased risk of recurrent venous thrombosis is uncertain. Methods and Results-A case-control design within a lar

  11. Risk of Budd-Chiari syndrome associated with factor V Leiden and G20210A prothrombin mutation: a meta-analysis.

    Peijin Zhang

    Full Text Available BACKGROUND: Various studies have demonstrated that factor V Leiden (FVL and G20210A prothrombin mutation contribute to the risk of Budd-Chiari syndrome (BCS, while other studies provided conflicting findings. In order to derive more precise estimations of the relationships, a meta-analysis was performed. METHODS: Eligible articles were identified through search of databases including Pubmed, Chinese Biomedical Database (CBM, Chinese, and Chinese National Knowledge Infrastructure (CNKI, Chinese. Odd ratios (ORs with 95% confidence intervals (CIs were calculated using random- or fixed- model. RESULTS: Finally, twelve studies were included for FVL and nine studies were included for G20210A prothrombin mutation. With respect to FVL, significantly increased BCS risk was found in the overall population (OR = 6.29, 95%CI = 4.23-9.36. Subgroup analyses suggested that FVL was associated with an increased risk of BCS in the population with high background mutation prevalence (>1% in the normal population. No significant association was found between BCS and G20210A prothrombin mutation (OR = 1.78, 95%CI = 0.77-4.11. CONCLUSION: The presence of FVL should be evaluated in patients with BCS. Conversely, G20210A prothrombin mutation is not significantly associated with risk of BCS. Large-scale well designed studies are necessary to be conducted to further confirm or refute the observed association.

  12. Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T

    Simone, Benedetto; De Stefano, Valerio; Leoncini, Emanuele


    Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden, FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes ha...

  13. Mesenteric vein thrombosis in a patient heterozygous for factor V Leiden and G20210A prothrombin genotypes.

    Karmacharya, Paras; Aryal, Madan Raj; Donato, Anthony


    Mesenteric venous thrombosis (MVT) is a rare but life threatening form of bowel ischemia. It is implicated in 6%-9% of all cases of acute mesenteric ischemia. The proportion of patients with primary (or idiopathic) MVT varies from 0% to 49%, with a decrease in frequency secondary to more recent availability of newer investigations for hypercoagulability. The presence of factor V Leiden (FVL) and prothrombin G20210A mutations (PGM) have been well documented in these cases. However, there have been scarce case reports describing MVT in heterozygotes of both these mutations occurring simultaneously and its implications on long term management. Our case describes acute MVT in a previously asymptomatic young patient with no prior history of venous thromboembolism. The patient was found to be heterozygous for FVL and PGM and treated with lifelong anticoagulation with warfarin (goal international normalized ratio: 2-3) and avoidance of hormonal contraceptives.

  14. Des-gamma-carboxy prothrombin (PIVKA-II)-producing mediastinal embryonal carcinoma with features of hepatoid differentiation.

    Hasegawa, Yasuyuki; Tomita, Katsuyuki; Hashimoto, Kiyoshi; Shigeoka, Yasushi; Watanabe, Masanari; Yamasaki, Akira; Shimizu, Eiji


    The case of a 48-year-old man with primary nonseminomatous embryonal carcinoma at the posterior mediastinum is described. The patient displayed extremely high plasma levels of Des-gamma-carboxy prothrombin (PIVKA-II) (4040 mAU/ml). Ultrasonography and dynamic computed tomography ruled out hepatocellular carcinoma (HCC) or liver metastasis. After preoperative systemic chemotherapy, total tumor resection was performed. Postoperatively, the plasma levels of PIVKA-II returned to within the normal range (24 mAU/ml). An immnohistochemical study using anti-PIVKA-II monoclonal antibody revealed the cytoplasmic expression of PIVK4-II in the carcinoma cells. These results indicate that tumor cells, which are manifested as hepatoid differentiation, may produce PIVKA-II. This case seems to be the first case reported in which PIVKA-II was produced by nonseminomatous mediastinal embryonal carcinoma without HCC or liver metastasis.

  15. Clinical significance of factor V leiden and prothrombin G20210A-mutations in cerebral venous thrombosis - comparison with arterial ischemic stroke.

    Beye, Aida; Pindur, Gerhard


    Cerebrovascular diseases are considered in a different way concerning their etiology with regard to arterial and venous occlusion. The role of thrombophilia in this context remains undetermined. For this reason, a case-control study was conducted including a total of 202 patients (154 females, 48 males) aged from 18 to 76 years (mean: 39.8 years) suffering either from cerebral sinus venous thrombosis (n = 101) or from arterial ischemic stroke (n = 101). Study groups were evaluated on the basis of age- and gender-matched pairs. Gene mutations of factor V-1691 (factor V Leiden) and prothrombin-20210 being considered as the most common thrombophilia markers were analyzed in this study. Factor V Leiden-mutations were found in 16.8% of patients with cerebral sinus venous thrombosis (CVT) and in 17.8% of patients with arterial ischemic stroke (AIS), which was significantly more frequent than in controls at a rate of 4.95% (ORs: 3.89 and 4.16). Prothrombin-mutations were significantly more frequent in CVT at a rate of 14.9% versus 2.97% in controls (OR: 5.70). This does not apply for AIS showing a rate of 4.95% prothrombin-mutations. Rates of factor V Leiden-mutations are not different in CVT compared with AIS. In contrast, however, prothrombin-mutations were significantly more frequent in CVT than in AIS with a rate of 14.9% versus 4.95% (OR 3.35). Furthermore, 3 cases with combined heterozygosity of factor V Leiden- and prothrombin-mutation have been identified in CVT, but not in AIS or controls. All of the above mentioned mutations were exclusively heterozygous. We conclude from these data that thrombophilia in terms of factor V Leiden genotype is a risk factor for both CVT and AIS in equal measure. In contrast, prothrombin-20210-mutations were different playing a significant role in the pathogenesis of cerebral sinus vein- thrombosis, but not in arterial ischemic stroke. Also, the combined occurrence of heterozygous prothrombin- and factor V Leiden

  16. Phenotypic presentation of thrombophilia in double heterozygote for factor v leiden and prothrombin 20210 G>A mutations: Case report

    Nagorni-Obradović Ljudmila


    Full Text Available Physicians usually do not suspect pulmonary thromboembolism in younger patients except in those who have thrombophilia. In those latter patients some special conditions such as trauma or surgery may provoke the disease. In some adult persons, thrombophilia may still remain unrecognized, until appearance of additional conditions influence development of thrombosis. A 55-year-old Caucasian female, non-smoker, experienced sudden chest pain and hemoptysis without chest trauma. History taking revealed type 2 diabetes mellitus and hypothyroidism. She was overweight with body mass index 29.0. The review of the family history revealed that her father and mother died of brain infarction, while her 22-year-old son and 24-year-old daughter were healthy. Due to suspicion for thrombosis, multi-slice computerized tomography thorax scan was done and pulmonary embolism was diagnosed. Although without clear risk factor for thrombosis in our patient, we performed laboratory investigation for congenital thrombophilia. Genetic analysis showed double heterozygous for factor V Leiden and prothrombin 20210 G>A mutations. Congenital thrombophilia was risk factor for thrombosis in our patient but haemostatic imbalance was not previously clinically recognized. She had two pregnancies without complications. Appearance of other associative factors such as endocrine disorders - hypothyroidism and metabolic syndrome with diabetes type 2, and overweigh were additional potential triggers for clinical manifestation of pulmonary thromboembolism in her adult age. Her children underwent genetic analysis, too. The son was also double heterozygous for factor V Leiden and prothrombin 20210 G>A mutations, while daughter was heterozygous for factor V Leiden, and none had clinical signs of thrombosis. [Projekat Ministarstva nauke Republike Srbije, br. ON175081 i br. ON 175091

  17. Prolonged Pregnancy: Methods, Causal Determinants and Outcome

    Olesen, Annette Wind

    Summary Prolonged pregnancy, defined as a pregnancy with a gestational length of 294 days or more, is a frequent condition. It is associated with an increased risk of fetal and maternal complications. Little is known about the aetiology of prolonged pregnancy. The aims of the thesis were 1...

  18. Prenatal risk indicators of a prolonged pregnancy

    Olesen, Annette Wind; Westergaard, Jes Grabow; Olsen, Jørn


    BACKGROUND: Few prenatal risk factors of prolonged pregnancy, a pregnancy of 42 weeks or more, are known. The objective was to examine whether sociodemographic, reproductive, toxicologic, or medical health conditions were associated with the risk of prolonged pregnancy. METHODS: Data from the Dan...

  19. Plasma lipids and prothrombin time in rats fed palm oil and other commonly used fats in Egypt

    Hussein, Mona M.; Salama, Fawzy M.; Ebada, Karina M.


    Sprague-Dawley rats were fed for a total period of 8 weeks on six diets that were different in the source of their fat content. The fat content was provided either, palm oil or palm olein or corn oil or hydrogenated fat, or frying palm oil and mixture of corn oil + hydrogenated fat in the ratio (1:1). The latter was given to the control group. Animals fed these various experimental diets showed statistically significant differences in serum cholesterol and serum triglycerides content amo...

  20. 过期妊娠胎儿的分娩方式及妊娠终止时机差异性预后影响分析%Analysis of the Effect of Different Mode of Delivery and Pregnancy Termination Timing for Prolonged Pregnancy on the Fetal Outcome



    目的:分析过期妊娠胎儿的分娩方式及妊娠终止时机差异性对预后的影响。方法回顾性分析某院2012年5月—2014年11月收治的100例过期妊娠产妇(研究组)及同期80例延期产妇(对照组)临床资料,探究不同分娩方式及妊娠终止时机对胎儿预后的影响。结果研究组顺产胎儿中新生儿窒息8例(25%)、胎儿窘迫15例(46.9%),与剖宫产新生儿窒息3例(4.4%)、胎儿窘迫12例(17.6%)相比较,差异有统计学意义(P<0.05);研究组胎儿窘迫27例(27%)、新生儿窒息11例(11%)、产后出血11例(11%)、产程延长25例(25%),对照组分别为12例(15%)、2例(2.5%)、4例(5%)、3例(3.8%),组间差异有统计学意义(P<0.05)。结论过期妊娠产妇采取剖宫产能够有效降低胎儿窘迫、新生儿窒息发生率,提高胎儿预后,而延期妊娠产妇应加强临床产检、适时终止妊娠,以避免形成过期妊娠,影响胎儿预后。%ObjectiveTo analyze the effect of different mode of delivery and pregnancy termination timing for prolonged pregnancy on the fetal outcome.Methods A retrospective analysis was conducted on the clinical data of 100 puerperants with prolonged pregnancy(study group) and 80 puerperants with delayed pregnancy(control group) admitted in our hospital from May 2012 to November 2014. And the effect of different mode of delivery and pregnancy termination timing on the prognosis of fetal outcome was investigated.Results In the study group, of the fetuses delivered naturally, there were 8 cases with neonatal asphyxia(25%), 15 cases with fetal distress(46.9%); of the fetuses delivered by cesarean section, there were 3 cases with neonatal asphyxia(4.4%), 12 cases with fetal distress(17.6%), the differences in neonatal asphyxia and fetal distress between the fetuses delivered naturally and those delivered by cesarean section in the study group were statistically significant(P<0.05). In the study group, there were 27 cases

  1. 过期妊娠分娩方式及终止妊娠时机与胎儿预后的分析研究%Analysis of Delivery Mode and Time of Ending Pregnancy for Prolonged Pregnancy and Fetus Prognosis



      目的:探讨过期妊娠分娩方式及终止妊娠时机与胎儿预后的关系。方法:以病例对照研究方法分析2009年1月-2012年12月共86例过期妊娠及684例延期妊娠病例。结果:过期妊娠剖宫产胎儿窘迫率及新生儿窒息率显著低于阴道产,而产后出血率比较差异无统计学意义;过期妊娠组的胎儿窘迫率及新生儿窒息率均显著高于延期妊娠组,但羊水过少发生率比较差异无统计学意义。结论:加强宣教,定期产验,延期妊娠时加强胎儿监护,积极采取恰当的处理,终止妊娠,以减少过期妊娠的发生;发生过期妊娠时放宽剖宫产指征,及时终止妊娠,均有利于降低胎儿窘迫、新生儿窒息、新生儿死亡率。%Objective:To explore the relationship between delivery mode and time of ending pregnancy of prolonged pregnancy with fetus prognosis.Method:86 cases of prolonged pregnancy and 684 cases of delayed pregnancy from January 2009 to December 2012 were analyzed by case-control method.Result:The fetal distress rate and neonatal asphyxia rate of prolonged pregnancy caesarean section were significantly lower than those of vaginal delivery,but there was no significant difference in postpartum hemorrhage rate;the fetal distress rate and neonatal asphyxia rate of prolonged pregnancy were significantly higher than those of delayed pregnancy,but there was no significant difference in the incidence rate of oligohydramnios.Conclusion:Strengthening education,regular prenatal examination, reinforcing fetus supervision in delayed pregnancy,handling actively and properly and ending the pregnancy should be taken to decrease delayed pregnancy. Relaxing the indication cesarean section,ending pregnancy in time when delayed pregnancy is occurred both can help reduce the occurrence rate of fetal distress, asphyxia neonatorum and newborn mortality.

  2. Thrombin generation capacity of prothrombin complex concentrate in an in vitro dilutional model.

    Oliver Grottke

    Full Text Available BACKGROUND: The use of PCC for the treatment of trauma-induced coagulopathy potentially increase the risk of thromboembolism and disseminated intravascular coagulation, which is addressed to an imbalance of both pro- and anticoagulants. As PCCs differ in composition, we used an in vitro dilutional approach to assess the overall thrombin generation of five different PCCs through various laboratory assays. METHODS: The vitamin K-dependent coagulation factors, heparin, and antithrombin were assessed in five commercially available PCCs. The procoagulant potential of the PCCs was assessed in plasma and whole blood from 4 healthy donors by means of classical coagulation assays, thrombin generation assay and thromboelastometry. In order to reflect coagulopathy, whole blood was diluted to 80, 60, 40, and 20% with Ringer's lactate solution. RESULTS: The five different PCCs were characterised by comparable levels of factors II, VII, IX and X (all around 20-30 IU/mL, whereas the heparin (0 to 17.6 IU/mL and antithrombin (0.06 to 1.29 IU/mL levels were remarkably different between manufactures. In vitro dilution of blood induced a prolongation of the PT and aPTT, and attenuation of thrombin generation and ExTem induced thromboelastometry. Overall, non- or low-heparin containing PCCs restored the in vitro dilutional coagulopathy, whereas PCCs containing heparin have an anticoagulant effect. The thrombin generation assay showed to be the most sensitive method for assessment of PCC effects. CONCLUSIONS: This study shows that most available PCCs are not balanced regarding their pro- and anticoagulants. The effect of measured differences in thrombin generation among different PCCs requires further investigations to elaborate the clinical meaning of this finding in the treatment of trauma induced coagulopathy.

  3. Prolonged Grief in Palliative Family Caregivers: A Pilot Study in a Portuguese Sample.

    Coelho, Alexandra; Delalibera, Mayra; Barbosa, António; Lawlor, Peter


    Caregivers are particularly vulnerable to experience intense levels of distress following the loss. The aim of this prospective pilot study is to determine the incidence of prolonged grief disorder symptoms among caregivers. A total of 73 bereaved families responded to the Prolonged Grief Disorder Evaluation Instrument (PG-13) at 6 and 12 months following their loss. The incidence of prolonged grief disorder at the first assessment was 28.8%, and it decreased to 15.1% at the second assessment. The prevalence of prolonged grief disorder declined significantly over time (p = .041). In the second evaluation, six bereaved individuals continued to meet criteria for a diagnosis of prolonged grief disorder, 15 remitted, and 4 new (incident) cases emerged. The important differences in values that occur after 12 months suggest time is important in distinguishing between those at risk for persistent distress and those whose grief symptomatology will decrease with time.

  4. Risk Factors of Prolonged Postoperative Pleural Effusion After Repair of Tetralogy of Fallot

    Chi-Ming Liang


    Conclusion: Prolonged PE is a significant morbidity after TOF repair. The risk factors for prolonged PE are gender, age at repair, body weight, bypass time, low oxygen saturation before surgery, wound infection after surgery, duration of endotracheal intubation, length of hospital stay, and Nakata index. Oxygen saturation before surgery and wound infection were major risk factors while age at repair was a confounder.

  5. QT Prolongation due to Graves’ Disease

    Zain Kulairi


    Full Text Available Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status.

  6. Hippocampal Abnormalities in Prolonged Febrile Seizures

    J Gordon Millichap


    Full Text Available Apparent diffusion coefficient (ADC measurements were used to characterize hippocampal edema within 5 days of a prolonged febrile seizure (PFS in a study at Great Ormond Street Hospital, London, UK.

  7. MRI Abnormalities After Prolonged Febrile Seizures

    J Gordon Millichap


    Full Text Available The clinical, radiologic, and laboratory findings of 17 Asian patients with encephalopathy following a prolonged febrile seizure were reviewed retrospectively at Kameda Medical Center, and other centers in Japan and San Francisco, USA.

  8. QT Prolongation due to Graves' Disease

    Deol, Nisha; Tolly, Renee; Manocha, Rohan; Naseer, Maliha


    Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status. PMID:28154763

  9. What Is the Effect on Obesity Indicators from Replacing Prolonged Sedentary Time with Brief Sedentary Bouts, Standing and Different Types of Physical Activity during Working Days? A Cross-Sectional Accelerometer-Based Study among Blue-Collar Workers.

    Nidhi Gupta

    Full Text Available The aim of the study was to investigate if (a substituting total sedentary time or long sedentary bouts with standing or various types of physical activity and (b substituting long sedentary bouts with brief sedentary bouts; is associated with obesity indicators using a cross sectional isotemporal substitution approach among blue-collar workers.A total of 692 workers from transportation, manufacturing and cleaning sectors wore an Actigraph GT3X+ accelerometer on the thigh for 1-4 working days. The sedentary (sit and lie, standing, walking, and moderate to vigorous physical activity (MVPA time on working days was computed using validated Acti4 software. The total sedentary time and uninterrupted sedentary time spent in brief (≤5 mins, moderate (>5 and ≤30 mins, and long (>30mins bouts, were determined for the whole day and during work and non-work time separately. The obesity indicators, BMI (kg/m2, waist circumference (cm and fat percentage were objectively measured. Isotemporal substitution modelling was utilized to determine the linear association with obesity indicators of replacing 30 min of total sedentary time or long sedentary bouts with standing, walking or MVPA and separately replacing 30 min of long sedentary bouts with brief sedentary bouts.Workers [mean (standard deviation, SD; age = 45.1 (9.9 years, BMI = 27.5 (4.9 kg/m2, %BF = 29.6 (9.5, waist circumference = 94.4 (13.0 cm] sat for 2.4 hours (~32% of the measured time, SD = 1.8 hours across the day during work period and 5.5 hours (~62% of the measured time, SD = 1.5 hours during non-work period. Most of the sedentary time was accrued in moderate bouts [work = 1.40 (SD = 1.09 hours] during work and in long bouts during non-work [2.7 (SD = 1.4 hours], while least in long sedentary bouts during work [work = 0.5 (SD = 0.9] and in brief sedentary bouts [0.5 hours (SD = 0.3] during non-work. Significant associations with all obesity indicators were found when 30 min of total

  10. Effect of large contrast agent dose and prolong scanning time on the image quality of CT portal venous phase images in patients with liver cirrhosis%延长扫描时间和大剂量对比剂对肝硬化患者门静脉期CT图像质量的影响

    鲁慧; 杨剑


    目的:探讨大剂量对比剂及延长扫描时间对肝硬化患者门静脉期CT图像质量的影响。方法选取75例肝硬化患者,其中采用常规时间常规剂量扫描(60 s,1.5 ml/kg)患者为对照组(25例),延长扫描时间(70 s)患者为延长组(25例),在延长扫描时间的基础上增加对比剂剂量(2.5 ml/kg)患者为大剂量组(25例),不同延长扫描时间和不同扫描剂量肝静脉、肝实质、门静脉强化峰值、平均强化峰值时间与图像质量双盲目测评分值的差异。结果延长扫描时间后,延长组肝静脉、肝实质、门静脉强化峰值、静脉与肝实质差值、图像质量评分为(206.4±3.6)Hu、(110±13)Hu、(188±13)Hu、(74±11)Hu、(3.0±1.2)分,均明显高于对照组,肝实质、门静脉平均强化峰值时间明显低于对照组,2组比较差异具有统计学意义(P<0.05);在延长扫描时间的基础上增大对比剂剂量后,大剂量组上述指标分别为(218±11)Hu、(115±14)Hu、(214±16)Hu、(86±13)Hu、(3.6±0.7)分、(63.8±2.9)s、(44±5)s,均明显优于延长组,2组比较差异具有统计学意义(P<0.05)。结论延长扫描时间(70 s)和增加对比剂剂量(2.5 ml/kg)在一定程度上改善肝硬化患者门静脉期CT图像质量,有利于获取更清晰的CT图像。%Objective To discuss effect of large contrast agent dose and prolonged scanning time on the image quality of CT portal venous phase images in patients with liver cirrhosis. Methods Seventy-five cases of liver cirrho-sis were divided into three groups, which used the conventional time and dose scan (60 s, 1.5 ml/kg) were chosen as control group (25 cases), prolonged scanning time (70 s) and conventional dose scan were as prolonged group (25 cases), high dose (2.5 ml/kg) and prolonged scanning time were as high dose group (25 cases). The

  11. Prolonging sensor networks lifetime using convex clusters

    Payam Salehi


    Full Text Available Reducing the energy consumption of nodes in sensor networks and prolonging the network life time has been proposed as one of the most important challenges facing researchers in the field of sensor networks. Therefore, designing an energy-aware protocol to gather data from network level and transmitting it to sink is placed on the agenda at this paper. After presenting an analysis of the processes of clustering in sensory networks and investigating the effect of sending interval on the amount of energy consumption, We have shown that if the use of convex static casters be done such as all the communications within the cluster with the sending distance less than the optimal threshold, it Will help to increase the lifetime of nodes. also have shown that if we create a virtual backbone between cluster heads to transfer far cluster heads data from sink to sink , will has a significant impact on increasing the network lifetime. For this reason, a detailed discussion on how to determine the size of clusters and partitioning of the network environment to them is presented in Chapter 4.Simulation results show considerable improvement of the proposed algorithm.


    Ah. Yusuf


    Full Text Available Introduction: Decision for cesarean section may lead to the stress for women in delivery. Stress response requires longer recovery time in post cesarean section patients. Most of patients who experience stress before and after surgical is associated with wound healing delay. When this condition continues, the wound will have a higher risk of infection. The objective of this study was to analyze correlation between stress and wound healing phase in post cesarean section patients. Method: A cross sectional design was used in this study. The population were women with cesarean section, both elective or emergency, in Delivery Room I RSU Dr. Soetomo Surabaya. Samples were recruited by using purposive sampling, with 28 samples who met to the inclusion criterias. The observed variables were stress and wound healing phase in post cesarean section patient. Stress data were collected by interview and wound healing measurement done by observation on the 3rd day post cesarean section. Result: The result showed that women with stress experience wound healing delay. The characteristic of wound healing delay was prolonged on inflammation phase, nevertheless there was presence of granulation tissue. Spearman’s rho correlation showed that correlation value r=0.675 with p=0.000. Discussion: It can be concluded that there was strong significant correlation between stress and wound healing phase in post cesarean section patients. It is important to give this information to the patients with cesarean section in order to prevent stress and delay in wound healing phase.

  13. Combined heterozygosity of factor V leiden and the G20210A prothrombin gene mutation in a patient with cerebral cortical vein thrombosis.

    Liu, X Y; Gabig, T G; Bang, N U


    Cerebral venous thrombosis (CVT) is a rare type of stroke with a variety of causes. Several reports have suggested that either factor V Leiden or G20210A prothrombin gene mutation is associated with an increased risk of CVT. The genetic thrombophilias are typically associated with other predisposing factors. We report a unique case of CVT in a patient with both the factor V Leiden and the G20210A prothrombin gene mutations without other identifiable precipitating factors in a 28-year-old white male in good health. MRI and cerebral arterial angiography showed cerebral cortical venous thrombosis. This case suggests that combined heterozygous individuals may be particularly prone to spontaneous thrombosis, like CVT.

  14. 替莫唑胺联合小剂量缓激肽对延长胶质瘤大鼠生存期的观察%Observe effects of Temozolomide combined with low dose Bradykinin in prolonging survival time of rat with glioma

    于倩; 宋飞; 刘贺; 白莉娜


    Objective To investigate the effect of Temozolomide combined with low dose Bradykinin for glioma therapy. Methods To use the stereotactic method to establish the C6 glioma model rats,and lest the glioma growth by MRI. Observerd the survival condition of the models treated with Temozolomide and Temozolomide with low dose Bradykinin,studied the survival times in different groups by statistical analysis. Resnlts Temozolomide could prolong the survival times of the models,and prolonged more signally after treated with low dose Bradykinin. Conclusion Temozolomide has curative effect for glioma,low dose Bradykinin can open blood brain barrier,temozolomide combined with low dose Bradykinin can treat glioma effectively,prolong the survival times of the rat models.%目的 探讨替莫唑胺联合小剂量缓激肽对胶质瘤的治疗作用.方法 立体定向法建立大鼠C6胶质瘤模型,MRI检测胶质瘤生长情况.观察常规使用替莫唑胺及替莫唑胺联合小剂量缓激肽后C6胶质瘤大鼠的生存情况,不同组别大鼠的生存期进行统计学分析.结果 替莫唑胺可以有效延长C6胶质瘤大鼠的生存期,联合小剂量缓激肽后C6胶质瘤大鼠的生存期延长更显著.结论 替莫唑胺对胶质瘤有治疗作用,小剂量缓激肽可以选择性开放血脑屏障,替莫唑胺联合小剂量缓激肽可以有效治疗胶质瘤,延长大鼠生存期.

  15. Clinical impact of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations among sickle cell disease patients of Central India.

    Nishank, Sudhansu Sekhar; Singh, Mendi Prema Shyam Sunder; Yadav, Rajiv


    It is known that patients with sickle cell disease (SCD) present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises and also during the steady state of the disease. We determined whether the presence of the factor prothrombin gene G20210A variant, factor V gene G1691A mutation (factor V Leiden), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms may be risk factors for vascular complications in individuals with SCD. The study involved 150 patients with sickle cell anemia and 150 healthy controls of Central India. Genotyping of three thrombophilic mutations was carried out by PCR-RFLP methods using MnlI, Hind III, and Hinf I, respectively, for factor V Leiden, prothrombin, and MTHFR mutations. Patients with SCD had significantly higher prevalence of mutant variants of MTHFR gene (28.0% heterozygotes and 14.6% homozygotes) and FVL gene (14.6% heterozygotes) as compared to normal/control individuals, but complete absence of mutant variants of prothrombin gene. The patients with SCD having mutant variants of MTHFR and FVL genes showed higher incidence of pain in chest, abdomen, and bone joints along with early age of onset of clinical manifestations as well as frequent dependence on blood transfusion than those patients with SCD having wild variants of these thrombotic genes. As compared to control subjects, SCD individuals having mutant variants of FVL and MTHFR genes had significant association with higher levels of prothrombin fragment (F1+2), D-dimer, thrombin-antithrombin (TAT), and lower level of protein C. MTHFR C677T and FVL G1691A polymorphisms may be risk factors for increased vascular complications in patient with SCD. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Quality of drug label information on QT interval prolongation

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H;


    characteristics (SPC) of recently approved medicinal products. METHODS: Drug labels of products centrally approved in Europe between 2006 and 2012 were screened. Of drugs including the term 'QT' in the SPC, the message on QT-prolongation ('no prolongation'/'unclear drug-QT association'/'possibly QT......-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. RESULTS: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT......-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT...

  17. Left Ventricular Function After Prolonged Exercise in Equine Endurance Athletes

    Flethøj, M.; Schwarzwald, C. C.; Haugaard, M. M.;


    Background: Prolonged exercise in human athletes is associated with transient impairment of left ventricular (LV) function, known as cardiac fatigue. Cardiac effects of prolonged exercise in horses remain unknown. Objectives :To investigate the effects of prolonged exercise on LV systolic...

  18. Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury.

    Grottke, Oliver; Braunschweig, Till; Spronk, Henri M H; Esch, Stephanie; Rieg, Annette D; van Oerle, Rene; ten Cate, Hugo; Fitzner, Christina; Tolba, Rene; Rossaint, Rolf


    Despite increasing use of prothrombin complex concentrate (PCC) to treat hemorrhage-associated coagulopathy, few studies have investigated PCC in trauma, and there is a particular lack of safety data. This study was performed to evaluate PCC therapy in a porcine model of coagulopathy with blunt liver injury. Coagulopathy was induced in 27 anesthetized pigs by replacing approximately 70% blood volume with hydroxyethyl starch 130/0.4 and Ringer's lactate solution; erythrocytes were collected and retransfused. Ten minutes after trauma, animals randomly received PCC (35 or 50 IU/kg) or saline. Coagulation parameters including thromboelastometry, thrombin generation, and blood loss were monitored for 2 hours. Internal organs were examined macroscopically and histologically to determine the presence of emboli and assess liver injury. Total blood loss was significantly lower and survival was higher in both PCC groups versus the control group (P < .05). These outcomes appeared to be dose-independent. Thromboembolism was found in all animals treated with 50 IU/kg PCC; 44% also showed signs of disseminated intravascular coagulation. Liver injury was similar in all animals. In conclusion, 35 IU/kg PCC safely improved coagulation and attenuated blood loss. However, the higher dose of PCC (50 IU/kg) appeared to increase the risk of thromboembolism and disseminated intravascular coagulation.

  19. Safety and efficacy of prothrombin complex concentrate as first-line treatment in bleeding after cardiac surgery.

    Cappabianca, Giangiuseppe; Mariscalco, Giovanni; Biancari, Fausto; Maselli, Daniele; Papesso, Francesca; Cottini, Marzia; Crosta, Sandro; Banescu, Simona; Ahmed, Aamer B; Beghi, Cesare


    Bleeding after cardiac surgery requiring surgical reexploration and blood component transfusion is associated with increased morbidity and mortality. Although prothrombin complex concentrate (PCC) has been used satisfactorily in bleeding disorders, studies on its efficacy and safety after cardiopulmonary bypass are limited. Between January 2005 and December 2013, 3454 consecutive cardiac surgery patients were included in an observational study aimed at investigating the efficacy and safety of PCC as first-line coagulopathy treatment as a replacement for fresh frozen plasma (FFP). Starting in January 2012, PCC was introduced as solely first-line treatment for bleeding following cardiac surgery. After one-to-one propensity score-matched analysis, 225 pairs of patients receiving PCC (median dose 1500 IU) and FFP (median dose 2 U) were included. The use of PCC was associated with significantly decreased 24-h post-operative blood loss (836 ± 1226 vs. 935 ± 583 ml, p surgery setting, the use of PCC compared with FFP was associated with decreased post-operative blood loss and RBC transfusion requirements. However, PCC administration may be associated with a higher risk of post-operative AKI.

  20. 异常凝血酶原和肝细胞癌%Des-gamma-carboxy-prothrombin and Hepatocellular carcinoma

    袁联文; 唐伟; 幕内·雅敏


    目前肝细胞癌(hepatocellular carcinoma,HCC)的诊断主要有影像学诊断和血清肿瘤标志物的检测.异常凝血酶原(des-gamma-carboxy-prothrombin,DCP)又被称为PIVKA-Ⅱ(protein induced by vita-min K absence or antagonist-Ⅱ),与AFP(alpha-fetoprotein)和AFP-L3(alpha-fetoprotein L3 fraction)一样被认为是一种很有价值的肝细胞癌血清肿瘤标志物.在HCC的检测诊断上,它们之间无明显相关关系,而表现为一定的互补性,结合影像学诊断,动态观测HCC高危(肝炎、肝硬化)人群,这些血清肿瘤标志物有助于HCC的早期发现,同时对HCC的手术疗效的评价、预后的估评有着一定的指导意义.

  1. Factor V Leiden, Prothrombin and MTHFR Mutation in Patients with Preeclamsia, Intrauterine Growth Restriction and Placental Abruption.

    Livrinova, Vesna; Lega, Marija Hadzi; Dimcheva, Anita Hristova; Samardziski, Igor; Isjanovska, Rozalinda


    Factor V Leiden, Prothrombin and MTHFR gene mutation, could have an influence in pregnancy with adverse outcome Preeclamsia, IUGR and Placental abruption. The aim of this study is to investigate the presence of above mentioned inherited thrombophilias and its statistical significance, distribution among the complicated and normal pregnancy, and relative risk for carrier of mutation to develop preeclampsia, IUGR and placental abruption. Prospective cohort study is implemented at University Clinic for Obstetric and Gynecology in Skopje, Republic of Macedonia. The study included 109 delivered patients: 40 with preeclapmsia, 22 with IUGR, 17 with placental abruption and 30 as control group with normal pregnancy. The amount of 3 ml venous blood has been used for detection of these point mutations using ThromboStrip -Opegen, QIAGEN kit manufactured for thrombotic risk. The highest frequency was found: in the group with preeclampsia 35% were MTHFR homozygous, IUGR -MTHFR heterozygous 45%, Placental abruption- 52.9% MTHFR heterozygous, and in the control group without thrombophilia 56.7%. There were combined thrombophilia in 3 patients. There aren`t statistical significance in presence of thrombophilia among groups (p > 0.05). Statistical significance (p Factor V Leiden heterozygous was 4.50 (0.47Factor V Leiden for placental abruption. Further investigations with more patients are warranted.

  2. Possible incorrect genotyping of heterozygous factor V Leiden and Prothrombin 20210 gene mutations by the GeneXpert assay.

    Marturano, Alessandro; Bury, Loredana; Gresele, Paolo


    The GeneXpert analyzer is a hands-off system for the detection of Factor V Leiden and of Prothrombin G20210A (GPRO) gene thrombophilic mutations. Although the system is efficient and easy to use, we report the rare possibility of incorrect genotyping. 1648 samples were evaluated using the GeneXpert HemosIL Factor II and Factor V assay: 1319 were freshly analyzed while 329 were frozen, thawed and diluted with saline prior to analysis to avoid clogging of the instrument syringe. Two samples, both heterozygous, one for the factor V Leiden and the other for the GPRO gene, were incorrectly genotyped as homozygous for the relative mutation. Inspection of the Ct values and amplification curves and genotyping with PCR revealed the correct genotype as heterozygous for factor V Leiden and GPRO mutation. The GeneXpert HemosIL Factor II and Factor V assay is an automated, fast genotyping assay requiring almost no sample manipulation, advantageous characteristics if compared with other PCR-based methods. However, an inattentive use of it can generate incorrect diagnosis. A careful handling of the sample, in particular correct dilution of frozen/thawed samples before analysis, and the inspection of the amplification curves and Ct values are required to avoid artifacts. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Diagnostic performance of des-γ-carboxy prothrombin (DCP) for hepatocellular carcinoma: a bivariate meta-analysis.

    Gao, P; Li, M; Tian, Q B; Liu, Dian-Wu


    Serum markers are needed to be developed to specifically diagnose Hepatocellular carcinoma (HCC). Des-γ-carboxy prothrombin (DCP) is a promising tool with limited expense and widely accessibility, but the reported results have been controversial. In order to review the performance of DCP for the diagnosis of HCC, the meta-analysis was performed. After a systematic review of relevant studies, the sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively) were pooled using a bivariate meta-analysis. Potential between-study heterogeneity was explored by meta-regression model. The post-test probability and the likelihood ratio scattergram to evaluate clinical usefulness were calculated. Based on literature review of 20 publications, the overall sensitivity, specificity, PLR and NLR of DCP for the detection of HCC were 67% (95%CI, 58%-74%), 92% (95%CI, 88%-94%), 7.9 (95%CI, 5.6-11.2) and 0.36 (95%CI, 0.29-0.46), respectively. The area under the bivariate summary receiving operating characteristics curve was 0.89 (95%CI, 0.85-0.92). Significant heterogeneity was present. In conclusion, the major role of DCP is the moderate confirmation of HCC. More prospective studies of DCP are needed in future.

  4. Plasma abnormal prothrombin (PIVKA-II): a new and reliable marker for the detection of hepatocellular carcinoma.

    Takikawa, Y; Suzuki, K; Yamazaki, K; Goto, T; Madarame, T; Miura, Y; Yoshida, T; Kashiwabara, T; Sato, S


    We evaluated the clinical usefulness of a protein induced by vitamin K absence, antagonist-prothrombin (PIVKA-II), in detecting hepatocellular carcinoma (HCC) specifically in patients with liver cirrhosis, and the possible correlation between levels of PIVKA-II and pathological features of HCC. Plasma levels of PIVKA-II and alpha-fetoprotein (AFP) were measured in 628 patients with various diseases, including 253 with liver cirrhosis and 116 with HCC. PIVKA-II was detected (greater than or equal to 0.1 arbitrary unit/mL) in 54.3% of HCC and the concentration showed a positive correlation with the tumour size. As a screening test for the detection of HCC, PIVKA-II produced values comparable with those of AFP with a sensitivity, specificity and validity of 52.8, 98.8 and 51.6% respectively. Sixteen of 45 patients (37%) with HCC who had low AFP (less than 100 ng/mL) levels were positive for PIVKA-II. No apparent relationship, however, could be found between the levels of PIVKA-II and the aetiology or pathological findings of HCC. These results suggest that PIVKA-II can be a reliable marker for detecting HCC in patients with liver cirrhosis.

  5. Prothrombin complex concentrate administration for bleeding associated with non-vitamin K antagonist oral anticoagulants: The SAMURAI-NVAF study.

    Yoshimura, Sohei; Sato, Shoichiro; Todo, Kenichi; Okada, Yasushi; Furui, Eisuke; Matsuki, Takayuki; Yamagami, Hiroshi; Koga, Masatoshi; Takahashi, Jun C; Nagatsuka, Kazuyuki; Arihiro, Shoji; Toyoda, Kazunori


    Antidotes appropriate for non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are not yet in widespread clinical use. Efficacy of prothrombin complex concentrate (PCC) in NOAC-associated bleeding remains unclarified. Ten NOAC users (4 women, median 74years old) who developed major bleeding and received PCC were prospectively enrolled. Eight single-center NOAC users (0 women, median 74years old) with intracerebral hemorrhage, who over the same period did not receive PCC, were studied for comparison. Of the 10 PCC-treated patients, 8 developed intracerebral hemorrhage, 1 developed subdural hematoma, and another developed gastrointestinal bleeding. The median size of intracerebral hemorrhage was 8mL, relatively lower than the reported size for patients without NOACs. Patients received a median of 1000IU or 16IU/kg of PCC. Before and 1h after PCC administration, the median PT-INR changed from 1.41 to 1.09 (pbleeding and were given relatively low doses of PCC. The effect of PCC on early cessation of bleeding was unclear, while the therapy did not trigger thromboembolic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies.

    Khorsand, Nakisa; Veeger, Nic J G M; van Hest, Reinier M; Ypma, Paula F; Heidt, Jeroen; Meijer, Karina


    Despite years of experience with vitamin K antagonist-associated bleeding events, there is still no evidence to help identify the optimal treatment with prothrombin complex concentrates. Variable dosing and fixed dose strategies are being used. In this observational prospective two-cohort study, we aimed to assess the non-inferiority of a low fixed PCC dose (1,040 IU Factor IX) compared to the registered variable dosing regimen based on baseline International Normalized Rate, bodyweight, and target International Normalized Rate, to counteract vitamin K antagonists in a bleeding emergency in a daily clinical practice setting. Non-inferiority of the fixed prothrombin complex concentrate dose was hypothesized with a margin of 4%. Main end points were proportion of patients reaching the target International Normalized Rate (complex concentrate treatment, and successful clinical outcome. Target International Normalized Rate was reached in 92% of the fixed dose patients (n=101) versus 95% of variable dose patients (n=139) resulting in a risk difference of -2.99% (90% CI: - 8.6 to 2.7) (non-inferiority not confirmed). Clinical outcome was successful in 96% and 88% of fixed versus variable dose, respectively, with a risk difference of 8.3% (90% CI: 2.7-13.9; non-inferiority confirmed). Although a lower fixed prothrombin complex concentrate dose was associated with successful clinical outcome, fewer patients reached the target International Normalized Rate.

  7. Concomitant homozygosity for the prothrombin gene variant with mild deficiency of antithrombin III in a patient with multiple hepatic infarctions: a case report

    Macheta M


    Full Text Available Abstract Introduction Hereditary causes of visceral thrombosis or thrombosis should be sought among young patients. We present a case of a young man presenting with multiple hepatic infarctions resulting in portal hypertension due to homozygosity of the prothrombin gene mutation not previously described in literature. Case presentation A 42-year-old Caucasian man with a previous history of idiopathic deep vein thrombosis 11 years earlier presented with vague abdominal pains and mildly abnormal liver function tests. An ultrasound and computed tomography scan showed evidence of hepatic infarction and portal hypertension (splenic varices. A thrombophilia screen confirmed a homozygous mutation for the prothrombin gene mutation, with mildly reduced levels of anti-thrombin III (AT III. Subsequent testing of his father and brother revealed heterozygosity for the same gene mutation. Conclusion Hepatic infarction is unusual due to the rich dual arterial and venous blood supply to the liver. In the absence of an arterial or haemodynamic insult causing hepatic infarction, a thrombophilia should be considered. To our knowledge, this is the first reported case of a hepatic infarction due to homozygosity of the prothrombin gene mutation. It is unclear whether homozygotes have a higher risk of thrombosis than heterozygotes. In someone presenting with a first thrombosis with this mutation, the case for life-long anticoagulation is unclear, but it may be necessary to prevent a second and more severe second thrombotic event, as occurred in this case.

  8. Elevated levels of antibodies against phosphatidylserine/prothrombin complex and/or cardiolipin associated with infection and recurrent purpura in a child: a forme fruste of antiphospholipid syndrome?

    Kinoshita, Yuri; Mayumi, Nobuko; Inaba, Motoyuki; Igarashi, Touru; Katagiri, Ichigen; Kawana, Seiji


    Antiphospholipid syndrome is an autoimmune disorder characterized by the occurrence of venous and arterial thrombosis, as well as morbidity in pregnancy, in the presence of anti-phospholipid antibodies. The diagnosis of antiphospholipid syndrome is usually established based on clinical and laboratory findings by strictly following the 2006 Sapporo classification. However, the diagnosis remains challenging owing to the ongoing debates on the serological criteria. We report a case we describe as forme fruste antiphospholipid syndrome in which these criteria were not fulfilled. Purpura appeared repeatedly in a female infant starting from the age of 6 months and following episodes of upper respiratory infections and vaccinations. The levels of anti-cardiolipin IgG antibodies and anti-phosphatidylserine/prothrombin complex antibodies were elevated in accordance with these events. Histopathological evaluation revealed multiple small vessel thrombi in the dermis and adipose tissue. After 2 weeks of treatment with aspirin and heparin, the cutaneous symptoms subsided. Infection has long been associated with antiphospholipid syndrome, and anti-phosphatidylserine/prothrombin antibodies are considered a new marker for the diagnosis of antiphospholipid syndrome. Forme fruste antiphospholipid syndrome should be considered even if the antiphospholipid syndrome diagnostic criteria are not completely fulfilled, especially in the presence of elevated levels of anti-phosphatidylserine/prothrombin antibodies and known preceding infections.

  9. Effect of Prolonged Preparation time on the Quality of Fresh Frozen Plasma and cold Precipitation%延长制备时间对新鲜冰冻血浆和冷沉淀质量的影响



    Objective To study and analysis to extend the time of preparation of impact on the quality of fresh frozen plasma and cryoprecipitate. Methods To collect fresh frozen plasma,a total of 40 doses,prep-aration time is 6 h,8 h,10 h and 12 h,its average can be divided into control group and observation group, control group of fresh frozen plasma preparation time for 10 h and 12 h,the preparation of fresh frozen plasma in the observation group for 6 h and 8 h,tome of quick-freezing machine should be used in two groups was car-ried out on the preparation of fresh frozen plasma quick-frozen,precipitation and the cold fresh frozen plasma preparation,detection of two groups of fresh frozen plasma clotting factorⅧcontent,and fibrinogen in cryoⅧcontent and blood coagulation factors. Results Observation group of fresh frozen plasma coagulation factorⅧcontent,as well as cold precipitation of clotting factor Ⅷ content were higher than control group( P 0. 05). Conclusion To extend the time of preparation of fresh frozen plasma clotting factor Ⅷ content has great influence,while the impact on the content of fibrinogen.%目的:研究和分析延长制备时间对新鲜冰冻血浆和冷沉淀质量的影响。方法收集新鲜冰冻血浆共40人份,制备的时间分别是6 h、8 h、10 h和12 h,将其平均分为对照组和观察组,对照组中的新鲜冰冻血浆的制备时间为10 h和12 h,观察组中的新鲜冰冻血浆的制备时间为6 h和8 h,两组均使用多美达速冻机对制备的新鲜冰冻血浆进行速冻,并用新鲜冰冻血浆进行冷沉淀的制备,检测两组新鲜冰冻血浆的凝血因子Ⅷ的含量,以及冷沉淀中纤维蛋白原和凝血因子Ⅷ的含量。结果观察组新鲜冰冻血浆的凝血因子Ⅷ含量,以及冷沉淀中的凝血因子Ⅷ的含量均高于对照组( P0.05)。结论延长制备时间对新鲜冰冻血浆中凝血因子Ⅷ含量有着很大影响,而对纤维蛋白原的含量的影响则不大。

  10. Univariate Risk Factors for Prolonged Mechanical Ventilation in Patients Undergoing Prosthetic Heart Valves Replacement Surgery


    Data from 736 patients undergoing prosthetic heart valve replacement surgery and concomitant surgery (combined surgery) from January 1998 to January 2004 at Union Hospital were retrospectively reviewed. Univariate logistic regression analyses were conducted to identify risk factors for prolonged mechanical ventilation. The results showed that prolonged cardiopulmonary bypass duration, prolonged aortic cross clamp time and low ejection fraction less than 50 percent (50 %)were found to be independent predictors for prolonged mechanical ventilation. Meanwhile age,weight, and preoperative hospital stay (days) were not found to be associated with prolonged mechanical ventilation. It was concluded that, for age and weight, this might be due to the lower number of old age patients (70 years and above) included in our study and genetic body structure of majority Chinese population that favor them to be in normal weight, respectively.

  11. Prolonged acute hepatitis A mimicking autoimmune hepatitis

    Rintaro Mikata; Osamu Yokosuka; Fumio Imazeki; Kenichi Fukai; Tatsuo Kanda; Hiromitsu Saisho


    AIM: We report a case with a prolonged course of hepatitisA, with alanine aminotransferase (ALT) higher than 500 IU/Lfor more than 2 mo.METHODS: A middle-aged woman had an elevated IgG level of more than 2 000 mg/dL, positive arti-nudear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings were compatible with prolonged acute hepatitis, although acute onset of autoimmune hepatitis could not be ruled out.RESULTS: It was assumed that she developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis. Treatment with UDCAproved to be effective.

  12. Increased expression of miR-126 and miR-10a predict prolonged relapse-free time of primary oestrogen receptor-positive breast cancer following tamoxifen treatment.

    Hoppe, Reiner; Achinger-Kawecka, Joanna; Winter, Stefan; Fritz, Peter; Lo, Wing-Yee; Schroth, Werner; Brauch, Hiltrud


    Adjuvant tamoxifen is a valid treatment option for women with oestrogen receptor (ER)-positive breast cancer. However, up to 40% of patients experience distant or local recurrence or die. MicroRNAs have been suggested to be important prognosticators in breast cancer. This study aims to identify microRNAs with the potential to predict tamoxifen response. We performed a global microRNA screen (1105 human microRNAs) in primary tumours of six matched pairs of postmenopausal, ER-positive breast cancer patients treated with tamoxifen, who were either recurrence free or had developed a recurrence (median follow up: 8.84 years; range: 1.28-12.7 years). Patients of this discovery set and the 81 patients of the validation set (median follow up: 8.64 years; range: 0.21-19.85 years) were treated at the Robert Bosch Hospital, Stuttgart, Germany, between 1986 and 2005. Out of the top 20 deregulated microRNAs (12 up-regulated, eight down-regulated) miR-126 (Hazard Ratio (HR) = 0.56, 95% confidence interval (CI): 0.38-0.83; Holm-adj. P = 0.022) and miR-10a (HR = 0.53, 95% CI: 0.33-0.85; Holm-adj. P = 0.031) were identified as significant predictors of tamoxifen outcome by multivariate Cox regression analysis in the independent validation set of 81 postmenopausal, ER-positive patients. Kaplan-Meier survival analyses based on cut-offs determined by receiver operating characteristics curves confirmed that a higher expression of miR-126 and miR-10a in the patients tumour was associated with longer relapse-free time (log-rank P = 0.037, Ptamoxifen. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Safety information on QT-interval prolongation

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H;


    Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approve......) was moderate (kappa 0.434). However, the agreement in expected clinical decisions based on the product labels was much higher (kappa 0.673). The US drug label tends to be more explicit, especially when it considers absence of QT effects....

  14. Smoking prolongs the infectivity of patients with tuberculosis.

    Siddiqui, U A


    We sought to establish if smokers on anti-tuberculosis treatment are more likely to have a prolonged period of infectivity, compared to non-smoking tuberculosis patients, in a low tuberculosis prevalence country. We conducted a cross-sectional, retrospective study in Ireland that recruited 53 microbiologically confirmed cases of pulmonary tuberculosis (PTB). The age-sex adjusted odds ratios (AOR) suggest that the infectivity status of PTB on treatment was four times more likely to be prolonged beyond 6-8 weeks, if the cases had a smoking history (AOR: 4.42; 95% CI: 1.23; 15.9). Smoking was associated with delayed sputum smear conversion in PTB patients on treatment.

  15. Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

    Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle


    Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica.

  16. Atraumatic femoral neck fracture secondary to prolonged lactation induced osteomalacia

    Dhammapal Sahebrao Bhamare


    Full Text Available Presenting a case of atraumatic fracture neck femur secondary to 2 years of prolonged lactation. A 26-year-old lactating mother presented with pain in left hip from last 12 months. She was apparently alright before and during pregnancy. Plain radiograph showed a complete undisplaced fracture of femoral neck. Osteomalacia was diagnosed by radiological and serological investigations. The fracture was fixed using AO type cannulated cancellous screws. The fracture showed good clinical and radiological union at 3 months. Literature review shows that this is a first case of atraumatic fracture of neck femur due to prolonged lactational osteomalacia. It showed that even apparently healthy Indians are susceptible to osteomalacia, more so during pregnancy and lactation and can be presented as atraumatic fracture. Although considered relatively stable, a compression type incomplete fracture neck femur may progress to a complete fracture if not treated in time.

  17. Factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase mutations and stillbirth: the Stillbirth Collaborative Research Network.

    Silver, Robert M; Saade, George R; Thorsten, Vanessa; Parker, Corette B; Reddy, Uma M; Drews-Botsch, Carey; Conway, Deborah; Coustan, Donald; Dudley, Donald J; Bukowski, Radek; Rowland Hogue, Carol J; Pinar, Halit; Varner, Michael W; Goldenberg, Robert; Willinger, Marian


    An evaluation for heritable thrombophilias is recommended in the evaluation of stillbirth. However, the association between thrombophilias and stillbirth remains uncertain. We sought to assess the association between maternal and fetal/placental heritable thrombophilias and stillbirth in a population-based, case-control study in a geographically, racially, and ethnically diverse population. We conducted secondary analysis of data from the Stillbirth Collaborative Research Network, a population-based case-control study of stillbirth. Testing for factor V Leiden, prothrombin G20210A, methylene tetrahydrofolate reductase C677T and A1298C, and plasminogen activating inhibitor (PAI)-1 4G/5G mutations was done on maternal and fetal (or placental) DNA from singleton pregnancies. Data analyses were weighted for oversampling and other aspects of the design. Odds ratios (OR) were generated from univariate models regressing stillbirth/live birth status on each thrombophilia marker. Results were available for ≥1 marker in 488 stillbirths and 1342 live birth mothers and 405 stillbirths and 990 live birth fetuses. There was an increased odds of stillbirth for maternal homozygous factor V Leiden mutation (2/488; 0.4% vs 1/1380; 0.0046%; OR, 87.44; 95% confidence interval, 7.88-970.92). However, there were no significant differences in the odds of stillbirth for any other maternal thrombophilia, even after stratified analyses. Fetal 4G/4G PAI-1 (OR, 0.63; 95% confidence interval, 0.43-0.91) was associated with decreased odds of stillbirth. Other fetal thrombophilias were similar among groups. Most maternal and fetal thrombophilias were not associated with stillbirth. Maternal factor V Leiden was weakly associated with stillbirth, and the fetal PAI-1 4G/4G polymorphism was associated with live birth. Our data do not support routine testing for heritable thrombophilias as part of an evaluation for possible causes of stillbirth. Copyright © 2016. Published by Elsevier Inc.

  18. Plasminogen activator inhibitor-1 4G/5G polymorphism, factor V Leiden, prothrombin mutations and the risk of VTE recurrence.

    Sundquist, Kristina; Wang, Xiao; Svensson, Peter J; Sundquist, Jan; Hedelius, Anna; Larsson Lönn, Sara; Zöller, Bengt; Memon, Ashfaque A


    Plasminogen-activator inhibitor (PAI)-1 is an important inhibitor of the plasminogen/plasmin system. PAI-1 levels are influenced by the 4G/5G polymorphism in the PAI-1 promoter. We investigated the relationship between the PAI-1 polymorphism and VTE recurrence, and its possible modification by factor V Leiden (FVL) and prothrombin (PTM) mutations. Patients (n=1,069) from the Malmö Thrombophilia Study were followed from discontinuation of anticoagulant treatment until diagnosis of VTE recurrence or the end of the study (maximum follow-up 9.8 years). One hundred twenty-seven patients (11.9 %) had VTE recurrence. PAI-1 was genotyped by TaqMan PCR. Cox regression analysis adjusted for age, sex and acquired risk factors of VTE showed no evidence of an association between PAI-1 genotype and risk of VTE recurrence in the study population as a whole. However, by including an interaction term in the analysis we showed that FVL but not PTM modified the effect of PAI-1 genotype: patients with the 4G allele plus FVL had a higher risk of VTE recurrence [hazard ratio (HR) =2.3, 95 % confidence interval (CI) =1.5-3.3] compared to patients with the 4G allele but no FVL (reference group) or FVL irrespective of PAI-1 genotype (HR=1.8, 95 % CI=1.3-2.5). Compared to reference group, 5G allele irrespective of FVL was associated with lower risk of VTE recurrence only when compared with 4G allele together with FVL. In conclusion, FVL has a modifying effect on PAI-1 polymorphism in relation to risk of VTE recurrence. The role of PAI-1 polymorphism as a risk factor of recurrent VTE may be FVL dependent.

  19. Prolonged bradycardia, asystole and outcome of high spinal cord injury patients: Risk factors and management

    Shaikh, Nissar; Rhaman, M. A.; Raza, Ali; Shabana, Adel; Malstrom, Mahommad Faisal; Al-Sulaiti, Ghanem


    Background: High spinal cord injury (HSCI) is one of the devastating traumatic injuries. 80% of these patients are young male, and 93% will have major neurological disabilities. There is a paucity of literature about prolonged bradycardia in HSCI patients. The aim of this study was to know the prevalence, risk factors, precipitating factors for prolonged bradycardia in the HSCI patients. Materials and Methods: All patients who were admitted to the Intensive Care Unit (ICU) of a tertiary hospital, with spinal cord injury above level of dorsal (D4) were enrolled in this study prospectively. Patient's demographic data, mechanism, level and type of spinal injury, associated injuries, injury severity score (ISS), spinal shock, vasopressors used, time of occurrence of bradycardia, treatment for bradycardia, precipitating as well as risk factors and outcome were recorded. Results: During the study period, a total of 138 patients were admitted to the ICU with HSCI. Majority of patients were male. The most frequently associated injury in these patients was skeletal fractures (38.4%). Most common complication was pneumonia 56 (41%). Forty-five (33%) of the total patients had prolonged bradycardia; 87% of these patients had pneumonia when bradycardia occurred. 53.4% had cardiac asystole. 29 (21%) patients had bradycardia at the time of endotracheal suctioning, whereas 27 (20%) patients developed bradycardia at the time of positioning. Majority of the patients were managed conservatively. Those HSCI patients who developed prolonged bradycardia, their ISS score was statistically higher, ICU and hospital stay was significantly higher compared with those HSCI patient who did not have prolonged bradycardia. Multivariate analysis revealed that hypotension on admission; pneumonia, and tracheostomy were risk factors for the development of prolonged bradycardia in HSCI patients. Conclusion: Prolonged bradycardia was associated with significantly higher incidence of asystole

  20. Carotid Baroreflex Function During Prolonged Exercise

    Raven, P. B.


    Astronauts are often required to work (exercise) at moderate to high intensities for extended periods while performing extra-vehicular activities (EVA). Although the physiologic responses associated with prolonged exercise have been documented, the mechanisms involved in blood pressure regulation under these conditions have not yet been fully elucidated. An understanding of this issue is pertinent to the ability of humans to perform work in microgravity and complies with the emphasis of NASA's Space Physiology and Countermeasures Program. Prolonged exercise at a constant workload is know to result in a progressive decrease in mean arterial pressure (MAP) concomitant with a decrease in stroke volume and a compensatory increase in heart rate. The continuous decrease in MAP during the exercise, which is related to the thermoregulatory redistribution of circulating blood volume to the cutaneous circulation, raises the question as to whether there is a loss of baroreflex regulation of arterial blood pressure. We propose that with prolongation of the exercise to 60 minutes, progressive increases on central command reflect a progressive upward resetting of the carotid baroreflex (CBR) such that the operating point of the CBR is shifted to a pressure below the threshold of the reflex rendering it ineffectual in correcting the downward drift in MAP. In order to test this hypothesis, experiments have been designed to uncouple the global hemodynamic response to prolonged exercise from the central command mediated response via: (1) continuous maintenance of cardiac filling volume by intravenous infusion of a dextran solution; and (2) whole body surface cooling to counteract thermoregulatory cutaneous vasodialation. As the type of work (exercise) performed by astronauts is inherently arm and upper body dependent, we will also examine the physiologic responses to prolonged leg cycling and arm ergometry exercise in the supine positions with and without level lower body negative

  1. Neural compensation within the human triceps surae during prolonged walking.

    Cronin, Neil J; Peltonen, Jussi; Sinkjaer, Thomas; Avela, Janne


    During human walking, muscle activation strategies are approximately constant across consecutive steps over a short time, but it is unknown whether they are maintained over a longer duration. Prolonged walking may increase tendinous tissue (TT) compliance, which can influence neural activation, but the neural responses of individual muscles have not been investigated. This study investigated the hypothesis that muscle activity is up- or down-regulated in individual triceps surae muscles during prolonged walking. Thirteen healthy subjects walked on a treadmill for 60 min at 4.5 km/h, while triceps surae muscle activity, maximal muscle compound action potentials, and kinematics were recorded every 5 min, and fascicle lengths were estimated at the beginning and end of the protocol using ultrasound. After 1 h of walking, soleus activity increased by 9.3 ± 0.2% (P triceps surae muscles and that changes in muscle activation are generally mirrored by changes in muscle fascicle length. These findings also support the notion of muscle-specific changes in TT compliance after prolonged walking and highlight the ability of the CNS to maintain relatively constant movement patterns in spite of neuromechanical changes in individual muscles.

  2. The impact on the radiobiological effect of lung squamous cancer cell line H520 with prolonged fraction delivery time%照射时间延长对肺鳞癌细胞株H520放射生物效应的影响

    李磊; 孟玲楠; 高纯子; 林珊; 李瑛; 韩波


    目的观察常规剂量分割照射模式下单次照射时间延长对肺癌细胞系H520放射生物效应的影响.方法 (1)肺鳞癌细胞株H520离体培养,分组进行照射,利用克隆形成实验计算细胞存活比率(SF);(2)细胞给予总剂量为2Gy、4Gy、6Gy、8Gy的照射,并按照每日单次照射时间的不同分为A组(照射2分钟组)、B1组(照射10分钟组)、B2组(照射30分钟组).观察延长照射时间对肺鳞癌细胞株H520存活比率的影响.结果 伴随单次照射总时间的延长,实验细胞的存活比率逐渐提高,接受照射总剂量为8Gy的H520细胞株,A组细胞存活比率为1.9%;B1组和B2组存活比率分别为2.35%和3.42%.A组与B2组之间的差异具有统计学意义(P<0.05).结论 常规剂量分割模式下延长单次照射时间,显著降低了放射治疗对H520细胞的生物效应.%Objective The purpose of this study was to observe the radiobiological effects of lung squamous cancer cell line H520 irradiated over prolonged single fraction delivery time in the conventional dose fractionated mode. Methods (1)The H520 cell lines were cultured in vitro, and then irradiated by groups. Its survival fractions(SF)were calculated with standard clonogenic assays.( 2 )The total doses of 2 Gy,4 Gy,6 Gy,8 Gy were given to the cells,which were divided into groups by different single fraction delivery time:group A( group irradiated for 2 mins ),group Bl( group irradiated for 10 mins ),and group B2( group irradiated for 30 mins ),and observed the impact on the survival fractions of H520 cell line with prolonged fraction delivery time. Results The cell surviving fractions increased when the interfraction interval was longer. The values of SF 8 Gy were 1. 9% in group A,2.35% in group B1,and increased to 3. 42% in group B2 ,respectively. The difference between group A and group B2 was statistically significant(P<0.05 ). Conclusion The prolonged fraction delivery time would significantly decrease the

  3. [Actinomycosis of the minor pelvis associated with prolonged use of intrauterine contraceptive devices (IUD)].

    Durdević, S; Vejnović, T; Novakov, A


    Pelvic actinomycosis is a rare disorder caused by Gram-positive anaerobic bacteria Actinomyces Israeli, and it is commonly associated with the prolonged use of IUD. The authors present two cases of pelvic actinomycosis in patients who used IUD for prolonged periods of time (eight and fourteen years). The diagnostic procedure in both cases lasted long and the definite diagnosis was made only after the pathohistological examination of the material taken during the surgical treatment. Actinomyces Israeli should be considered as one of the causes of the diagnosed pelvic inflammation especially when it is associated with the prolonged use of IUD.

  4. A review of the clinical utility of INR to monitor and guide administration of prothrombin complex concentrate to orally anticoagulated patients

    Sølbeck, Sacha; Ostrowski, Sisse R; Johansson, Pär I


    the initiation steps of the haemostatic process. The objective of the present review was to reassess the evidence for using INR as a tool to guide administration of prothrombin complex concentrates (PCC) to OAC patients. A Medline and Cochrane database search was conducted using the following keywords...... evidence for the usefulness of INR as a tool to monitor and guide reversal of OAC induced coagulopathy in patients with PCC, which is expected given that it is a plasma-based assay only reflecting a limited part of the haemostatic process....

  5. Emergency management of major bleeding in a case of maxillofacial trauma and anticoagulation: utility of prothrombin complex concentrates in the shock room

    Alessandro Morotti


    Full Text Available Life-threatening bleeding in anticoagulation with Warfarin is an emergency challenging issue. Several approaches are available to treat bleeding in either over-anticoagulation or propeanticoagulation, including vitamin K, fresh frozen plasma and prothrombin complex concentrates (PCC administration. In coexisting trauma-induced bleeding and anticoagulation, reversal of anticoagulation must be a rapid and highly effective procedure. Furthermore the appropriate treatment must be directly available in each shock rooms to guarantee the rapid management of the emergency. PCC require a simple storage, rapid accessibility, fast administration procedures and high effectiveness. Here we report the utility of PCC in management of a craniofacial trauma in proper-anticoagulation.

  6. A case of catastrophic antiphospholipid antibody syndrome complicated with systemic lupus erythematosus, double positive for anti-cardiolipin/β₂ glycoprotein I and anti-phosphatidylserine/prothrombin autoantibodies.

    Hirakawa, Eri; Saito, Kazuyoshi; Hirata, Shintaro; Atsumi, Tatsuya; Koike, Takao; Tanaka, Yoshiya


    A 16-year-old male with severe thrombocytopenia and progressive multiple organ infarctions was diagnosed as having catastrophic antiphospholipid syndrome (CAPS) complicated with systemic lupus erythematosus, and was successfully treated with combination of anticoagulants, corticosteroids, plasma exchange, and intravenous cyclophosphamide. Antibodies to phosphatidylserine/prothrombin (PS/PT) complex and cardiolipin (CL)/β(2)-glycoprotein I (β(2)GPI) were simultaneously detected, indicating that the different pathways of both PS/PT and CL/β(2)GPI might be associated with the radical manifestation of CAPS.

  7. Prothrombin G20210A mutation is associated with young-onset stroke: the genetics of early-onset stroke study and meta-analysis.

    Jiang, Baijia; Ryan, Kathleen A; Hamedani, Ali; Cheng, Yuching; Sparks, Mary J; Koontz, Deborah; Bean, Christopher J; Gallagher, Margaret; Hooper, W Craig; McArdle, Patrick F; O'Connell, Jeffrey R; Stine, O Colin; Wozniak, Marcella A; Stern, Barney J; Mitchell, Braxton D; Kittner, Steven J; Cole, John W


    Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a white case-control population and additionally performed a meta-analysis. From the population-based Genetics of Early Onset Stroke (GEOS) study, we identified 397 individuals of European ancestry aged 15 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, age, oral contraceptive use, migraine, and smoking status. A meta-analysis of 17 case-control studies (n=2305 cases <55 years) was also performed with and without GEOS data. Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5; 95% confidence interval [CI]=0.9-6.5; P=0.07). However, among adults aged 15 to 42 years (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9; 95% CI=1.2-28.1; P=0.03), whereas adults aged 42 to 49 years were not (OR=1.4; 95% CI=0.4-5.1; P=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults ≤55 years (OR=1.4; 95% CI=1.1-1.9; P=0.02), with significance increasing with addition of the GEOS results (OR=1.5; 95% CI=1.1-2.0; P=0.005). The prothrombin G20210A mutation is associated with ischemic stroke in young adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger young adult population requires replication.

  8. Severe bradycardia and prolonged hypotension in ciguatera.

    Chan, Thomas Yan Keung


    Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

  9. [Prolonged pain in neonates: retrospective analysis].

    Lilla, Michèle; Stadelman-Diaw, Corinne; Ramelet, Anne-Sylvie


    Infants hospitalised in neonatology are inevitably exposed to pain repeatedly. Premature infants are particularly vulnerable, because they are hypersensitive to pain and demonstrate diminished behavioural responses to pain. They are therefore at risk of developing short and long-term complications if pain remains untreated. Compared to acute pain, there is limited evidence in the literature on prolonged pain in infants. However, the prevalence is reported between 20 and 40 %. This single case study aimed to identify the bio-contextual characteristics of neonates who experienced prolonged pain. This study was carried out in the neonatal unit of a tertiary referral centre in Western Switzerland. A retrospective data analysis of seven infants' profile, who experienced prolonged pain ,was performed using five different data sources. The mean gestational age of the seven infants was 32weeks. The main diagnosis included prematurity and respiratory distress syndrome. The total observations (N=55) showed that the participants had in average 21.8 (SD 6.9) painful procedures that were estimated to be of moderate to severe intensity each day. Out of the 164 recorded pain scores (2.9 pain assessment/day/infant), 14.6 % confirmed acute pain. Out of those experiencing acute pain, analgesia was given in 16.6 % of them and 79.1 % received no analgesia. This study highlighted the difficulty in managing pain in neonates who are exposed to numerous painful procedures. Pain in this population remains underevaluated and as a result undertreated.Results of this study showed that nursing documentation related to pain assessment is not systematic.Regular assessment and documentation of acute and prolonged pain are recommended. This could be achieved with clear guidelines on the Assessment Intervention Reassessment (AIR) cyclewith validated measures adapted to neonates. The adequacy of pain assessment is a pre-requisite for appropriate pain relief in neonates.

  10. Napping and Human Functioning during Prolonged Work


    alternative to napping is prolonged wakefulness. Polyphasic sleep , with frequent naps rather than a single sleep period per 24 hours, is natural for both the...very young and for the aged. It is not practiced by most adults, perhaps because of societal demands. Possibly a polyphasic sleep schedule could be...Functioning 1.2 Scope of this Chapter 2. REVIEW OF LITERATURE 2.1 Partial Sleep Deprivation Studies 2.2 Nap Studies: Four Nap Factors Affecting Performance

  11. Prolonged grief: setting the research agenda

    Rita Rosner


    Full Text Available Background: Prolonged grief disorder is proposed for the International Classification of Diseases (ICD-11, though it was rejected as a diagnosis for DSM-5. Objective: This review outlines findings and defines important areas for future research viewed from a lifespan perspective. Results: The development and psychometric evaluation of measures for the new diagnosis is paramount, specifically for children and adolescents. Treatments need to be adapted for specific subgroups and research findings have to be disseminated into various professional settings.

  12. The Frequency of Factor V Leiden, Prothrombin G20210A and Methylenetetrahydrofolate Reductase C677T Mutations in Migraine Patients

    Ruhsen Öcal


    Full Text Available OBJECTIVE: Migraine is an independent risk factor for ischemic stroke, but its pathophysiology is still unclear. Genetic factors that predispose patients to thrombosis have been studied in patients with migraine to highlight the pathogenesis, but the results remain controversial. In this study, the frequencies of factor V Leiden (FVL, prothrombin (Pt G20210A and methylenetetrahydrofolate reductase (MTHFR C677T mutations were investigated. METHODS: One hundred and sixty patients aged of 15 to 55 years with no history of systemic disease and who had been diagnosed as migraine according to the International Headache Society (IHS diagnostic criteria at Baskent University Hospital Neurology Outpatient Clinics were investigated for FVL, Pt G20210A and MTHFR C677T mutations from their genomic DNA, and the results were compared with those of healthy controls. RESULTS: One hundred and fifty five (96.9% of 160 migraine patients were homozygote normal, 5 (3.1% were heterozygote and none of them were homozygote mutant for FVL. The control group had 9.8% heterozygote individuals but the difference between the percentages was not statistically significant (p> 0.05. There were no homozygote mutant individuals in the Turkish population study in normal subjects like our study. Thirty nine (24.4% of 160 migraine patients were heterozygote and 8 (5% were homozygote mutant for MTHFR C677T. The control group had 37 (34.9% heterozygote and 6 (5.6% homozygote mutant individuals. The difference between the percentages was not statistically significant (p= 0.15. Three (1.9% of 160 migraine patients were heterozygote and 5 (2.9% of the control group were heterozygote mutant for Pt G20210A mutation. The control group had 37 (34.9% heterozygote and 6 (5.6% homozygote mutant individuals. The difference between the percentages was not statistically significant (p= 0.420. CONCLUSION: Our study indicates that FVL, Pt G20210A and MTHFR C677T gene mutations, which are considered

  13. Lack of association between factor V Leiden and prothrombin G20210A polymorphisms in Tunisian subjects with a history of myocardial infarction.

    Berredjeb Ben Slama, Dhouha; Fekih-Mrissa, Najiba; Haggui, Abdeddayem; Nsiri, Brahim; Baraket, Nadia; Haouala, Habib; Gritli, Nasreddine


    Myocardial infarction is a multifactorial disease. It is provoked by occlusions in the coronary arteries resulting from exposure to multiple risk factors. To study the risk of myocardial infarction associated with the gene polymorphisms of factor V Leiden and factor II (G20210A). Cases consisted of 100 myocardial infarction patients who were hospitalized in the Principal Military Hospital of Tunis and 200 control subjects with no history of myocardial infarction. The prevalence of the factor V Leiden was higher in myocardial infarction patients (9%) than in control subjects (6%) with an OR=1.55 (95% CI=0.58-4.12), whereas the prevalence of prothrombin G20210A mutation was 3% and 2.5% in the patient and control groups, respectively [OR=1.21 (95% CI=0.22-5.94)]. Our results indicate that neither factor V Leiden nor the prothrombin G20210A contributed to the risk factors for myocardial infarction. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Association of factor V Leiden, Janus kinase 2, prothrombin, and MTHFR mutations with primary Budd-Chiari syndrome in Egyptian patients.

    El Sebay, Hatem M; Safan, Manal A; Daoud, Ashraf A; Tayel, Safaa I; Nouh, Mohamed A; El Shafie, Shymaa


    Budd-Chiari syndrome (BCS) is defined as obstruction of hepatic venous outflow anywhere from the small hepatic veins to the suprahepatic inferior vena cava. The pathogenesis of BCS is still not fully understood. This study aimed to evaluate the association of factor V Leiden (FVL), Janus kinase 2 (JAK2), prothrombin, and methylene tetrahydrofolate reductase (MTHFR) mutations with primary BCS. The study was carried out on 35 patients with primary BCS and 15 age and gender matched healthy individuals as a control group. Genotyping of FVL, prothrombin, and MTHFR mutations was determined by GENEQUALITY AB-THROMBO TYPE kit based on the reverse hybridization principle. JAK2 mutation was determined by polymerase chain reaction-restriction fragment length polymorphism. There was a statistically significant difference between patients and controls regarding FVL, MTHFR C677T, and MTHFR A1298C mutations with odds ratio of 1.83, 2.0, and 1.79, respectively. Hetero MTHFR C677T, hetero FVL, and hetero MTHFR A1298C were the most common etiological factors being responsible for 57.1, 42.9, and 42.9% of primary BCS cases, respectively. It could be concluded that BCS is a multifactorial disease; in the current study, MTHFR C677T mutation was the most common cause of disease. Identification of one cause of BCS should not eliminate investigations for detection of other etiological factors. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  15. Prolonged labour as indication for emergency caesarean section

    Maaløe, Nanna; Sorensen, B L; Onesmo, R


    To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour.......To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour....

  16. Laryngotracheal Injury following Prolonged Endotracheal Intubation

    J. Mehdizadeh


    Full Text Available Background: Prolonged endotracheal intubation is a growing method for supporting ventilation in patients who require intensive care. Despite considerable advancement in endotracheal intubation, this method still has some complications; the most important is laryngo-tracheal injuries. Methods: Over a 2-year period, this retrospective study was conducted on 57 patients with history of prolonged intubation who were referred to the ENT Department of Amir Alam Hospital. For each patient, a complete evaluation including history, physical examination, and direct laryngoscopy and bronchoscopy was done under general anesthesia. Results: Fifty-seven patients (44 male; mean age, 23.014.7 years were studied. Mean intubation period was 15.88 days. The most common presenting symptom was dyspnea (62%. Head trauma was responsible for most cases of intubation (72.4%. The most common types of tracheal and laryngeal lesions were tracheal (56.9% and subglottic (55.2% stenosis, respectively. Mean length of tracheal stenosis was 0.810.83 cm. There was a statistically significant relationship between length of tracheal stenosis and intubation period (P=0.0001 but no relation was observed between tracheal stenosis and age, sex, and etiology of intubation (All P=NS. Among the glottic lesions, inter- arytenoids adhesion was the most common lesion (25.9%. No statistically significant relation was found between glottic and subglottic lesions and age, sex and intubation period (all P=NS. Length of stenosis and intubation period was significantly greater in tracheal/ subglottic lesions than those in glottic/ supraglottic lesions (all P=NS. Conclusion: After prolonged endotracheal intubation, laryngo-tracheal lesions had no relation with patient’s age, sex, and cause of intubation.There was direct relation between length of tracheal stenosis and intubation period. Glottic lesions were more commonly observed in head trauma patients. Lesion length and intubation

  17. [Prolonged acute pancreatitis after bone marrow transplantation].

    De Singly, B; Simon, M; Bennani, J; Wittnebel, S; Zagadanski, A-M; Pacault, V; Gornet, J-M; Allez, M; Lémann, M


    Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids.

  18. Prolonged parenteral nutrition after neonatal gastrointestinal surgery

    Estmann, Anne; Qvist, Niels; Husby, Steffen


    INTRODUCTION: Long-term treatment with parenteral nutrition (PN) may be essential for survival in infants after neonatal gastrointestinal surgery. It seemed well indicated in a population-based study to estimate the need for long-term PN and to characterize the infants that received TPN with regard...... to diagnosis and clinical course. METHODOLOGY: This study reviews the clinical course of infants with gastrointestinal disease (gastroschisis, intestinal atresia, omphalocele, volvulus, Hirschsprung's disease and necrotizing enterocolitis) with a prolonged need for parenteral nutrition in the Western part...

  19. Survival of soil bacteria during prolonged desiccation.

    Chen, M.; Alexander, M.


    A determination was made of the kinds and numbers of bacteria surviving when two soils were maintained in the laboratory under dry conditions for more than half a year. Certain non-spore-forming bacteria were found to survive in the dry condition for long periods. A higher percentage of drought-tolerant than drought-sensitive bacteria was able to grow at low water activities. When they were grown in media with high salt concentrations, bacteria generally became more tolerant of prolonged drought and they persisted longer. The percent of cells in a bacterial population that remained viable when exposed to drought stress varied with the stage of growth.

  20. Prolonged parenteral nutrition after neonatal gastrointestinal surgery

    Estmann, Anne; Qvist, Niels; Husby, Steffen


    INTRODUCTION: Long-term treatment with parenteral nutrition (PN) may be essential for survival in infants after neonatal gastrointestinal surgery. It seemed well indicated in a population-based study to estimate the need for long-term PN and to characterize the infants that received TPN with regard...... to diagnosis and clinical course. METHODOLOGY: This study reviews the clinical course of infants with gastrointestinal disease (gastroschisis, intestinal atresia, omphalocele, volvulus, Hirschsprung's disease and necrotizing enterocolitis) with a prolonged need for parenteral nutrition in the Western part...

  1. Media Impacts on Women's Fertility Desires: A Prolonged Exposure Experiment.

    Knobloch-Westerwick, Silvia; Willis, Laura E; Kennard, Ashley R


    Media exposure may have implications for family planning, a public health issue of key importance. Drawing on social comparison theory and social identity theory, a prolonged exposure experiment examined whether media portrayals of women's social roles affect fertility desires among 166 American, nonstudent, never married, childless women ages 21-35 years old. After sign-up and baseline sessions, participants viewed magazine pages five days in a row. Stimuli presented women in either mother/homemaker roles, beauty ideal roles, or professional roles. Three days later, participants again indicated their number of desired children and time planned until first birth. Exposure to mother/homemaker and beauty ideal portrayals increased the number of desired children across time. Exposure to professional portrayals increased the time planned until 1st birth compared to beauty ideal portrayals-this impact was partially mediated by a shift toward more progressive gender norms (per social identity theory) and assimilation (per social comparison theory).

  2. High efficiency holographic Bragg grating with optically prolonged memory

    Khoo, Iam Choon; Chen, Chun-Wei; Ho, Tsung-Jui


    In this paper, we show that photosensitive azo-dye doped Blue-phase liquid crystals (BPLC) formed by natural molecular self-assembly are capable of high diffraction efficiency holographic recording with memory that can be prolonged from few seconds to several minutes by uniform illumination with the reference beam. Operating in the Bragg regime, we have observed 50 times improvement in the grating diffraction efficiency and shorter recording time compared to previous investigations. The enabling mechanism is BPLC’s lattice distortion and index modulation caused by the action of light on the azo-dopant; upon photo-excitation, the azo-molecules undergo transformation from the oblong-shaped Trans-state to the bent-shaped Cis-state, imparting disorder and also cause the surrounding BPLC molecules to undergo coupled flow & reorientation leading to lattice distortion and index modulation. We also showed that the same mechanism at work here that facilitates lattice distortion can be used to frustrate free relaxation of the lattice distortion, thereby prolonging the lifetime of the written grating, provided the reference beam is kept on after recording. Due to the ease in BPLC fabrication and the availability of azo-dopants with photosensitivity throughout the entire visible spectrum, one can optimize the controlling material and optical parameters to obtain even better performance.

  3. Influence of a Prolonged Tennis Match Play on Serve Biomechanics.

    Martin, Caroline; Bideau, Benoit; Delamarche, Paul; Kulpa, Richard


    The aim of this study was to quantify kinematic, kinetic and performance changes that occur in the serve throughout a prolonged tennis match play. Serves of eight male advanced tennis players were recorded with a motion capture system before, at mid-match, and after a 3-hour tennis match. Before and after each match, electromyographic data of 8 upper limb muscles obtained during isometric maximal voluntary contraction were compared to determine the presence of muscular fatigue. Vertical ground reaction forces, rating of perceived exertion, ball speed, and ball impact height were measured. Kinematic and upper limb kinetic variables were computed. The results show decrease in mean power frequency values for several upper limb muscles that is an indicator of local muscular fatigue. Decreases in serve ball speed, ball impact height, maximal angular velocities and an increase in rating of perceived exertion were also observed between the beginning and the end of the match. With fatigue, the majority of the upper limb joint kinetics decreases at the end of the match. No change in timing of maximal angular velocities was observed between the beginning and the end of the match. A prolonged tennis match play may induce fatigue in upper limb muscles, which decrease performance and cause changes in serve maximal angular velocities and joint kinetics. The consistency in timing of maximal angular velocities suggests that advanced tennis players are able to maintain the temporal pattern of their serve technique, in spite of the muscular fatigue development.

  4. Lifetime Prolonging Algorithms for Underwater Sensor Networks

    GUO Zhong-wen; LI Zhi-wei; YU Lei


    Underwater acoustic modem technology has attained a level of maturity to support underwater acoustic sensor networks (UASNs) which are generally formed by acoustically connected sensor nodes and a surface station providing a link to an on-shore control center. While many applications require long-term monitoring of the deployment area, the battery-powered network nodes limit the lifetime of UASNs. Therefore, designing a UASN that minimizes the power consumption while maximizing lifetime becomes a very difficult task. In this paper, a method is proposed to determine the optimum number of clusters through combining an application-specific protocol architecture and underwater acoustic communication model so as to reduce the energy dissipation of UASNs. Deploying more sensor nodes which work alternately is another way to prolong the lifetime of UASNs. An algorithm is presented for selecting sensor nodes and putting them into operation in each round, ensuring the monitoring to the whole given area. The present results show that the algorithm can help prolong system lifetime remarkably when it is applied to other conventional approaches for sensor networks under the condition that the sensor node density is high.

  5. Prolonged self-paced exercise in the heat - environmental factors affecting performance

    Junge, Nicklas; Jørgensen, Rasmus; Flouris, Andreas D


    In this review we examine how self-paced performance is affected by environmental heat stress factors during cycling time trial performance as well as considering the effects of exercise mode and heat acclimatization. Mean power output during prolonged cycling time trials in the heat (≥30°C) was ...

  6. Prolonged Paroxysmal Sympathetic Storming Associated with Spontaneous Subarachnoid Hemorrhage

    Yan Liu


    Full Text Available Paroxysmal sympathetic storming (PSS is a rare disorder characterized by acute onset of nonstimulated tachycardia, hypertension, tachypnea, hyperthermia, external posturing, and diaphoresis. It is most frequently associated with severe traumatic brain injuries and has been reported in intracranial tumors, hydrocephalous, severe hypoxic brain injury, and intracerebral hemorrhage. Although excessive release of catecholamine and therefore increased sympathetic activities have been reported in subarachnoid hemorrhage (SAH, there is no descriptive report of PSS primarily caused by spontaneous SAH up to date. Here, we report a case of prolonged PSS in a patient with spontaneous subarachnoid hemorrhage and consequent vasospasm. The sympathetic storming started shortly after patient was rewarmed from hypothermia protocol and symptoms responded to Labetalol, but intermittent recurrence did not resolve until 3 weeks later with treatment involving Midazolam, Fentanyl, Dexmedetomidine, Propofol, Bromocriptine, and minimizing frequency of neurological and vital checks. In conclusion, prolonged sympathetic storming can also be caused by spontaneous SAH. In this case, vasospasm might be a precipitating factor. Paralytics and hypothermia could mask the manifestations of PSS. The treatment of the refractory case will need both timely adjustment of medications and minimization of exogenous stressors or stimuli.

  7. Joint contracture following prolonged stay in the intensive care unit

    Clavet, Heidi; Hébert, Paul C.; Fergusson, Dean; Doucette, Steve; Trudel, Guy


    Background Prolonged immobility during a critical illness may predispose patients to the development of joint contracture. We sought to document the incidence of, the risk factors for and the reversibility of joint contractures among patients who stayed in a tertiary intensive care unit (ICU) for 2 weeks or longer. Methods We conducted a chart review to collect data on the presence of and risk factors for joint contractures in the shoulders, elbows, hips, knees and ankles among patients admitted to the ICU between January 2003 and March 2005. Results At the time of transfer out of the ICU, at least 1 joint contracture was recorded in 61 (39%) of 155 patients; 52 (34%) of the patients had joint contractures of an extent documented to impair function. Time spent in the ICU was a significant risk factor for contracture: a stay of 8 weeks or longer was associated with a significantly greater risk of any joint contracture than a stay of 2 to 3 weeks (adjusted odds ratio [OR] 7.09, 95% confidence interval (CI) 1.29–38.9; p = 0.02). Among the variables tested, only the use of steroids conferred a protective effect against joint contractures (adjusted OR 0.35, 95% CI 0.14–0.83; p = 0.02). At the time of discharge to home, which occurred a median of 6.6 weeks after transfer out of intensive care, 50 (34%) of the 147 patients not lost to follow-up still had 1 or more joint contractures, and 34 (23%) of the patients had at least 1 functionally significant joint contracture. Interpretation Following a prolonged stay in the ICU, a functionally significant contracture of a major joint occurred in more than one-third of patients, and most of these contractures persisted until the time of discharge to home. PMID:18332384

  8. [Sideroblastic anemia after prolonged linezolid therapy].

    Kakimoto, Tsunayuki; Nakazato, Tomonori; Miura, Reiko; Kurai, Hanako; Yamashita, Daisuke; Sagara, Yuko; Ishida, Akaru


    Linezolid is an effective and well-tolerated antibiotic for the treatment of infections caused by Gram-positive pathogens. Some reports have shown that linezolid treatment for more than 2 weeks has been associated with reversible bone marrow suppression, especially thrombocytopenia and anemia. We encountered a case of sideroblastic anemia following prolonged linezolid therapy in a laryngeal cancer patient. He received linezolid therapy for multiple abscesses due to MRSA. Before treatment, the Hb level was 12.5 g/dl and then slowly decreased to 5.9 g/dl for 2 months during treatment. Ringed sideroblasts were detected in the bone marrow. Linezolid was discontinued and the Hb level was slowly increased. This case was considered to reflect a rare complication of linezolid therapy.

  9. Multifactorial QT Interval Prolongation and Takotsubo Cardiomyopathy

    Michael Gysel


    Full Text Available A 71-year-old woman collapsed while working as a grocery store cashier. CPR was performed and an AED revealed torsades de pointes (TdP. She was subsequently defibrillated resulting in restoration of sinus rhythm with a QTc interval of 544 msec. Further evaluation revealed a diagnosis of Takotsubo Cardiomyopathy (TCM contributing to the development of a multifactorial acquired long QT syndrome (LQTS. The case highlights the role of TCM as a cause of LQTS in the setting of multiple risk factors including old age, female gender, hypokalemia, and treatment with QT prolonging medications. It also highlights the multifactorial nature of acquired LQTS and lends support to growing evidence of an association with TCM.

  10. Neurohumoral responses during prolonged exercise in humans

    Nybo, Lars; Nielsen, Bodil; Blomstrand, Eva


    in the hyperthermic trial, with a concomitant increase in perceived exertion (P brain had a small release of tryptophan (arteriovenous difference of -1.2 +/- 0.3 micromol/l), whereas a net balance was obtained during the two exercise trials. Both the arterial and jugular venous dopamine levels...... became elevated during the hyperthermic trial, but the net release from the brain was unchanged. During exercise, the O2/CHO was similar across trials, but, during recovery from the hyperthermic trial, the ratio decreased to 3.8 +/- 0.3 (P ...This study examined neurohumoral alterations during prolonged exercise with and without hyperthermia. The cerebral oxygen-to-carbohydrate uptake ratio (O2/CHO = arteriovenous oxygen difference divided by arteriovenous glucose difference plus one-half lactate), the cerebral balances of dopamine...

  11. Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study

    H.L.A. Janssen (Harry); J.P. Vandenbroucke; F.R. Rosendaal (Frits); B. van Hoek (Bart); J.R. Meinardi; F.P. Vleggaar (Frank); S.H. van Uum; E.B. Haagsma (Els); F.J.M. van der Meer; J. van Hattum (Jan); R.A. Chamuleau; R.P.R. Adang (Rob)


    textabstractIn a collaborative multicenter case-control study, we investigated the effect of factor V Leiden mutation, prothrombin gene mutation, and inherited deficiencies of protein C, protein S, and antithrombin on the risk of Budd-Chiari syndrome (BCS) and portal vein thrombosi

  12. Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B. Evidence for defects affecting the latent catalytic site.

    P. Usharani; Warn-Cramer, B J; Kasper, C K; BAJAJ, S. P.


    Abnormal factor IX variant proteins were isolated from the plasmas of three unrelated severe hemophilia-B families that had been previously shown to contain functionally impaired molecules immunologically similar to normal factor IX. The families studied were: (1) a patient with markedly prolonged ox brain prothrombin time, designated factor IX Bm Lake Elsinore (IXBmLE); (b) three patients (brothers) with moderately prolonged ox brain prothrombin time, designated factor IX Long Beach (IXLB); ...

  13. Antibodies to phosphatidylserine/prothrombin complex in suspected antiphospholipid syndrome in the absence of antibodies to cardiolipin or Beta-2-glycoprotein I.

    Sanfelippo, M J; Joshi, A; Schwartz, Sl; Meister, J A; Goldberg, J W


    Antibodies to phosphatidylserine/prothrombin (aPS/PT) complex were measured in 728 serum specimens from patients suspected of having antiphospholipid syndrome (APS), but without diagnostic elevations in the levels of antibodies to cardiolipin or Beta-2 Glycoprotein 1 (β2-GP1). Of the 728 specimens, 41 had elevated levels of aPS/PT. Thrombotic events occurred in 11 of the 22 patients with accessible medical histories. Six of the patients with accessible medical records also had laboratory evidence of the lupus anticoagulant. The identification of aPS/PT in patients without evidence of antibodies to cardiolipin, β2-GP1, or the lupus anticoagulant can contribute to the identification of APS in patients that may go undetected with current testing methods.

  14. [Effects on the coagulation-fibrinolysis system of a single oral dose of mesoglycan at the beginning and at the end of a prolonged treatment in man].

    Blardi, P; Messa, G; Puccetti, L; La Placa, G; Ghezzi, A


    We evaluated the mesoglycan effects on the coagulative-fibrinolytic system in 10 patients with euglobulin lysis time (ELT) over 180 minutes. A mathematical model was used to analyze such phenomena. 100 mg of mesoglycan was administered to 10 patients for 14 days. The following parameters were evaluated: tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), euglobulin lysis time (ELT), plasminogen, alpha 2 antiplasmin, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin clotting time (TCT), and fibrinogen. Those parameters were evaluated on the first and on the last day of the mesoglycan treatment at the following times: 0 (basal), 2, 4, 6, 8, 10 and 12 hours. Our results suggest that the mesoglycan is able to reduce a profibrinolytic activity without any influence on the coagulative-fibrinolytic system, at the baseline conditions and after chronic administration. The pharmacodynamic study and the statistical analysis using our mathematic model resulted to be statistically significant.

  15. Prolonged pain and disability are common after rib fractures.

    Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John


    The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Knee abduction angular impulses during prolonged running with wedged insoles.

    Lewinson, Ryan T; Worobets, Jay T; Stefanyshyn, Darren J


    Wedged insoles may produce immediate effects on knee abduction angular impulses during running; however, it is currently not known whether these knee abduction angular impulse magnitudes are maintained throughout a run when fatigue sets in. If changes occur, this could affect the clinical utility of wedged insoles in treating conditions such as patellofemoral pain. Thus, the purpose of this study was to determine whether knee abduction angular impulses are altered during a prolonged run with wedged insoles. It was hypothesized that knee abduction angular impulses would be reduced following a prolonged run with wedged insoles. Nine healthy runners participated. Runners were randomly assigned to either a 6-mm medial wedge condition or a 6-mm lateral wedge condition and then ran continuously overground for 30 min. Knee abduction angular impulses were quantified at 0 and 30 min using a gait analysis procedure. After 2 days, participants returned to perform the same test but with the other wedge type. Two-way repeated-measures analysis of variance was used to evaluate main effects of wedge condition and time and interactions between wedge condition and time (α = 0.05). Paired t-tests were used for post hoc analysis (α = 0.01). No interaction effects (p = 0.958) were found, and knee abduction angular impulses were not significantly different over time (p = 0.384). Lateral wedge conditions produced lesser knee abduction angular impulses than medial conditions at 0 min (difference of 2.79 N m s, p = 0.006) and at 30 min (difference of 2.76 N m s, p < 0.001). It is concluded that significant knee abduction angular impulse changes within wedge conditions do not occur during a 30-min run. Additionally, knee abduction angular impulse differences between wedge conditions are maintained during a 30-min run.

  17. The Prothrombin G20210A Mutation is Associated with Young-Onset Stroke: The Genetics of Early Onset Stroke Study and Meta-Analysis

    Jiang, Baijia; Ryan, Kathleen A.; Hamedani, Ali; Cheng, Yuching; Sparks, Mary J.; Koontz, Deborah; Bean, Christopher J.; Gallagher, Margaret; Hooper, W. Craig; McArdle, Patrick F.; O'Connell, Jeffrey R.; Stine, O. Colin; Wozniak, Marcella A.; Stern, Barney J.; Mitchell, Braxton D.; Kittner, Steven J.; Cole, John W.


    Background and Purpose Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young-adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a Caucasian case-control population and additionally performed a meta-analysis Methods From the population-based Genetics of Early Onset Stroke (GEOS) study we identified 397 individuals of European ancestry aged 15-49 years with first-ever ischemic stroke and 426 matched-controls. Logistic regression was used to calculate odds ratios in the entire population and for subgroups stratified by gender, age, oral contraceptive use, migraine and smoking status. A meta-analysis of 17 case-control studies (n=2305 cases stroke did not achieve statistical significance (OR=2.5,95%CI=0.9-6.5,p=0.07). However, among adults aged 15-42 (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9,95%CI=1.2-28.1,p=0.03), whereas adults ages 42-49 were not (OR=1.4,95%CI=0.4-5.1,p=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults stroke in young-adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger-young adult population requires replication. PMID:24619398

  18. The relationship between factor V Leiden, prothrombin G20210A, and MTHFR mutations and the first major thrombotic episode in polycythemia vera and essential thrombocythemia.

    Trifa, Adrian P; Cucuianu, Andrei; Popp, Radu A; Coadă, Camelia A; Costache, Roxana M; Militaru, Mariela S; Vesa, Ştefan C; Pop, Ioan V


    Arterial and venous thrombosis are the most frequent complications in patients with polycythemia vera and essential thrombocythemia. We sought to demonstrate a possible contribution of the factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) 677 C > T and 1298 A > C mutations to the thrombotic risk in patients with polycythemia vera and essential thrombocythemia along with other biological features of these patients. We included 86 patients with polycythemia vera, of which 34 (39.5 %) had major thrombosis and 95 patients with essential thrombocythemia, of which 22 (23.1 %) had major thrombosis. In the whole cohort of patients, only the factor V Leiden mutation was significantly associated with both arterial and venous thrombosis in univariate and multivariate analysis (odds ratio (OR) = 4.3; 95 % confidence interval (CI) = 1.5-12.5; p = 0.008 and OR = 4.3; 95 % CI = 1.2-15.9; p = 0.02, respectively). Other factors significantly associated with thrombosis in both univariate and multivariate analysis were male sex (OR = 2.8, 95 % CI = 1.4-5.4, p = 0.002 and OR = 3.5, 95 % CI = 1.6-7.6, p = 0.002, respectively) and the JAK2 V617F mutation (OR = 5.5, 95 % CI = 2.1-15, p = 0.0001 and OR = 6.9, 95 % CI = 2.2-21.2, p = 0.001, respectively). In conclusion, among the four mutations analyzed (factor V Leiden, prothrombin G20210A, and MTHFR 677 C > T and 1298 A > C), only factor V Leiden is a major contributor to thrombosis in polycythemia vera and essential thrombocythemia.

  19. The progress on preparation of human prothrombin complex concentrates%人凝血酶原复合物制备工艺研究现状

    包正琦(综述); 何彦林(审校)


    Prothrombin complex concentrates are haemostatic blood products containing four vitamin K -dependent clotting factors (II, VII, IX and X).It is produced by ion-exchange chromatography on DEAE Sephadex A-50 resin from large pool plasma.Preparation technology,the choose of materials,quality control and optimization of critical parameters play a critical role in quality control of PCC .This paper mainly summarizes the preparation of PCC technology conditions , materi-als, critical parameters and the control strategy of coagulation factor activation .%人凝血酶原复合物( Prothrombin complex concentrates ,PCC)是一种含有凝血因子II、VII、IX、X四种维生素K依赖性凝血因子,能够促进血液凝固的血浆蛋白制剂。目前,多数生产厂家采用DEAE Sephadex A-50凝胶从混合血浆中制备PCC。 PCC制备工艺的选择、制备原料的挑选及质量控制、关键工艺参数的优化及控制等方面对PCC制品的质量至关重要。因此,主要对PCC的制备工艺、制备原料、关键工艺参数的优化及生产过程中凝血因子活化的控制策略进行了综述。

  20. Prolonging β-lactam infusion: a review of the rationale and evidence, and guidance for implementation.

    MacVane, Shawn H; Kuti, Joseph L; Nicolau, David P


    Given the sparse antibiotic pipeline and the increasing prevalence of resistant organisms, efforts should be made to optimise the pharmacodynamic exposure of currently available agents. Prolonging the infusion duration is a strategy used to increase the percentage of the dosing interval that free drug concentrations remain above the minimum inhibitory concentration (fT>MIC), the pharmacodynamic efficacy driver for time-dependent antibiotics such as β-lactams. β-Lactams, the most commonly prescribed class of antibiotics owing to their efficacy and safety profile, have been the mainstay of therapy since the discovery of penicillin over 60 years ago. Mounting evidence, including the use of population pharmacokinetic modelling and Monte Carlo simulation, suggests that prolonging the infusion time of β-lactam antibiotics may have advantages over standard infusion techniques, including an enhanced probability of achieving requisite fT>MIC exposures, lower mortality and potentially reductions in infection/antibiotic-related costs. As a result of these favourable attributes, clinical practice guidelines support the use of prolonged-infusion β-lactams in the treatment of many severe infections. This article discusses the rationale and evidence for prolonging the infusion of β-lactam antibiotics and provides guidance for the implementation of a prolonged-infusion programme.

  1. Prolonged Temozolomide Maintenance Therapy in Newly Diagnosed Glioblastoma.

    Skardelly, Marco; Dangel, Elena; Gohde, Julia; Noell, Susan; Behling, Felix; Lepski, Guilherme; Borchers, Christian; Koch, Marilin; Schittenhelm, Jens; Bisdas, Sotirios; Naumann, Aline; Paulsen, Frank; Zips, Daniel; von Hehn, Ulrike; Ritz, Rainer; Tatagiba, Marcos Soares; Tabatabai, Ghazaleh


    The impact of prolonging temozolomide (TMZ) maintenance beyond six cycles in newly diagnosed glioblastoma (GBM) remains a topic of discussion. We investigated the effects of prolonged TMZ maintenance on progression-free survival (PFS) and overall survival (OS). In this retrospective single-center cohort study, we included patients with GBM who were treated with radiation therapy with concomitant and adjuvant TMZ. For analysis, patients were considered who either completed six TMZ maintenance cycles (group B), continued with TMZ therapy beyond six cycles (group C), or stopped TMZ maintenance therapy within the first six cycles (group A). Patients with progression during the first six TMZ maintenance cycles were excluded. Clinical data from 107 patients were included for Kaplan-Meier analyses and 102 for Cox regressions. Median PFS times were 8.1 months (95% confidence interval [CI] 6.1-12.4) in group A, 13.7 months (95% CI 10.6-17.5) in group B, and 20.9 months (95% CI 15.2-43.5) in group C. At first progression, response rates of TMZ/lomustine rechallenge were 47% in group B and 13% in group C. Median OS times were 12.7 months (95% CI 10.3-16.8) in group A, 25.2 months (95% CI 17.7-55.5) in group B, and 28.6 months (95% CI 24.4-open) in group C. Nevertheless, multivariate Cox regression for patients in group C compared with group B that accounted for imbalances of other risk factors showed no different relative risk (RR) for OS (RR 0.77, p = .46). Our data do not support a general extension of TMZ maintenance therapy beyond six cycles. The Oncologist 2017;22:570-575 IMPLICATIONS FOR PRACTICE: Radiation therapy with concomitant and adjuvant temozolomide (TMZ) maintenance therapy is still the standard of care in patients below the age of 65 years in newly diagnosed glioblastoma. However, in clinical practice, many centers continue TMZ maintenance therapy beyond six cycles. The impact of this continuation is controversial and has not yet been addressed in

  2. New Heterogeneous Clustering Protocol for Prolonging Wireless Sensor Networks Lifetime

    Md. Golam Rashed


    Full Text Available Clustering in wireless sensor networks is one of the crucial methods for increasing of network lifetime. The network characteristics of existing classical clustering protocols for wireless sensor network are homogeneous. Clustering protocols fail to maintain the stability of the system, especially when nodes are heterogeneous. We have seen that the behavior of Heterogeneous-Hierarchical Energy Aware Routing Protocol (H-HEARP becomes very unstable once the first node dies, especially in the presence of node heterogeneity. In this paper we assume a new clustering protocol whose network characteristics is heterogeneous for prolonging of network lifetime. The computer simulation results demonstrate that the proposed clustering algorithm outperforms than other clustering algorithms in terms of the time interval before the death of the first node (we refer to as stability period. The simulation results also show the high performance of the proposed clustering algorithm for higher values of extra energy brought by more powerful nodes.

  3. Tracheoesophageal fistula--a complication of prolonged tracheal intubation.

    Paraschiv, M


    Tracheoesophageal fistula most commonly occurs as a complication of prolonged tracheal intubation. The incidence decreased after the use of low pressure and high volume endotracheal cuffs, but the intensive care units continue to provide such cases. The abnormal tracheoesophageal communication causes pulmonary contamination (with severe suppuration) and impossibility to feed the patient. The prognosis is reserved, because most patients are debilitated and ventilator dependent, with severe neurological and cardiovascular diseases. The therapeutic options are elected based on respiratory, neurological and nutritional status. The aim of conservative treatment is to stop the contamination (drainage gastrostomy, feeding jejunostomy) and to treat the pulmonary infection and biological deficits. Endoscopic therapies can be tried in cases with surgical contraindication. Operation is addressed to selected cases and consists in the dissolution of the fistula, esophageal suture with or without segmental tracheal resection associated. Esophageal diversion is rarely required. The correct indication and timing of surgery, proper surgical technique and postoperative care are prerequisites for adequate results.

  4. The clinical study of prothrombin precursor protein in monitoring anticoagulation%凝血酶原前体蛋白在抗凝监测中的临床研究

    朱平; 刘菁; 黄劲松; 舒峻; 周志凌; 庄建; 吴若彬; 肖学钧; 郑少忆; 陈寄梅; 卢聪; 范瑞新; 郭惠明


    目的 探讨凝血酶原前体蛋白(PIVKA-Ⅱ)在华法林抗凝治疗监测中的意义.方法 动态监测60例心脏机械瓣膜置换术后行抗凝治疗病人(实验组)的血浆PIVKA-Ⅱ浓度、凝血酶原时间(prothrombin time,PT)、国际标准化比率(international normalized ratio,INR),比较3者出现明显异常的最早时间,分析PIVKA-Ⅱ与PI'及INR之间的相关性.结果 实验组首次服华法林后6h,血浆PIVKA-Ⅱ浓度即出现明显异常,并随时间增加而增高;实验组首次服华法林后60 h,PT出现明显异常,并随时间增加而增高;实验组首次服华法林后24 h,INR出现明显异常,并随时间增加而增高;线性相关分析,结果显示PIVKA-Ⅱ浓度与PT呈正相关(r=0.786,P<0.01);PIVKA-Ⅱ浓度与INR呈正相关(r=0.737,P<0.01).结论 在抗凝治疗的患者中,通过监测患者的血浆PIVKA-Ⅱ浓度可以有效地监测其抗凝程度,联合监测患者的血浆PIVKA-Ⅱ浓度、PT、INR则更能早期、有效的监测患者抗凝程度.

  5. Comparison between Prothrombin Complex Concentrate (PCC) and Fresh Frozen Plasma (FFP) for the Urgent Reversal of Warfarin in Patients with Mechanical Heart Valves in a Tertiary Care Cardiac Center.

    Fariborz Farsad, Bahram; Golpira, Reza; Najafi, Hamideh; Totonchi, Ziae; Salajegheh, Shirin; Bakhshandeh, Hooman; Hashemian, Farshad


    Fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) reverse oral anticoagulants such as Warfarin. We compared the standard dosage of FFP and PCC in terms of efficacy and safety for patients with mechanical heart valves undergoing interventional procedures while receiving Warfarin. Fifty patients were randomized (25 for each group) with mechanical heart valves [international normalized ratio (INR) >2.5]. FFP dosage was administered based on body weight (10-15 mL/Kg), while PCC dosage was administered based on both body weight and target INR. INR measurements were obtained at different time after PCC and FFP infusion. The mean ± SD of INR pre treatment was not significantly different between the PCC and FFP groups. However, over a 48-hour period following the administration of PCC and FFP, 76% of the patients in the PCC group and only 20% of the patients in the FFP group reached the INR target. Five (20%) patients in the PCC group received an additional dose of PCC, whereas 17 (68%) patients in the FFP group received a further dose of FFP (P=0.001). There was no significant difference between the two groups in Hb and Hct before and during a 48-hour period after PCC and FFP infusion. As regards safety monitoring and adverse drug reaction screening in the FFP group, the INR was high (INR > 2.5) in 86% of the patients. There was no report of hemorrhage in both groups. PCC reverses anticoagulation both effectively and safely while having the advantage of obviating the need to extra doses.

  6. Prolonged cholestasis and ductopenia associated with tenoxicam.

    Trak-Smayra, Viviane; Cazals-Hatem, Dominique; Asselah, Tarik; Duchatelle, Veronique; Degott, Claude


    Cholestatic liver diseases leading to progressive destruction of intra-hepatic bile ducts and ductopenia encompass multiple etiologies. Pathophysiology and natural history of drug-induced cholangiopathies remain unclear. We report a case of prolonged ductopenia attributed to Tenoxicam (Tilcotil o--a non-steroidal anti-inflammatory drug of the oxicam family) ingested at therapeutic dose. A 36 year-old male patient was admitted for jaundice and Lyell syndrome starting 1 week after the ingestion of Tenoxicam. Liver biopsy showed cholestasis, non-suppurative cholangitis and polymorphous inflammatory infiltrate of the portal tracts (round cells, macrophages an eosinophils). Treatment with ursodesoxycholic acid and cholestyramine was instituted and the patient was asymptomatic 1 year after. Three years later mild biological cholestasis persisted and ductopenia was evidenced on liver biopsy. In this report we found that: (1) The toxicity of tenoxicam was probably mediated by an immunoallergic mechanism (Lyell syndrome and eosinophils on histology); (2) ductopenia was secondary to inflammatory cholangitis. Factors responsible for this chronic evolution are still unknown (genetic predisposition, vascular factors, etc.); and (3) the presence of ductopenia contrasted with the "clinical recovery" of the disease suggesting accessory bile drainage by cholangioles or partial reconstruction of the biliary tree.

  7. Persistent telomere cohesion triggers a prolonged anaphase.

    Kim, Mi Kyung; Smith, Susan


    Telomeres use distinct mechanisms (not used by arms or centromeres) to mediate cohesion between sister chromatids. However, the motivation for a specialized mechanism at telomeres is not well understood. Here we show, using fluorescence in situ hybridization and live-cell imaging, that persistent sister chromatid cohesion at telomeres triggers a prolonged anaphase in normal human cells and cancer cells. Excess cohesion at telomeres can be induced by inhibition of tankyrase 1, a poly(ADP-ribose) polymerase that is required for resolution of telomere cohesion, or by overexpression of proteins required to establish telomere cohesion, the shelterin subunit TIN2 and the cohesin subunit SA1. Regardless of the method of induction, excess cohesion at telomeres in mitosis prevents a robust and efficient anaphase. SA1- or TIN2-induced excess cohesion and anaphase delay can be rescued by overexpression of tankyrase 1. Moreover, we show that primary fibroblasts, which accumulate excess telomere cohesion at mitosis naturally during replicative aging, undergo a similar delay in anaphase progression that can also be rescued by overexpression of tankyrase 1. Our study demonstrates that there are opposing forces that regulate telomere cohesion. The observation that cells respond to unresolved telomere cohesion by delaying (but not completely disrupting) anaphase progression suggests a mechanism for tolerating excess cohesion and maintaining telomere integrity. This attempt to deal with telomere damage may be ultimately futile for aging fibroblasts but useful for cancer cells.

  8. [Prospective study of patients with prolonged fever].

    Calderón, E; Legorreta, J; Sztabinski, G; Hernández, M; Wilkins, A; Gómez, D; Dávila, A


    A prospective study was made in 283 patients who attended IMAN's Children's Hospital, with fever the main symptom. A clinical and paraclinical procedure was designed for the study of each patient. 112 patients were eliminated because they did not follow the established criteria. All patients had acute infectious diseases considered trivial; 85% were 3 weeks to 2 years of age. They all had an antibacterial treatment without precise diagnosis. It was considered that on admission the patients showed a normal course in the natural history of the basic disease. The study group included 171 patients 2 months to 13 years of age; 62.5% had fever due to infection, 12.2% to collagenopathies, 7% to neoplasias 5.2% to miscellaneous causes and 12.8% were not diagnosed. The most common infectious causes for prolonged fever were tuberculosis, upper respiratory infections, amoebic liver abscess, typhoid fever and malaria. Careful questioning and clinical examination were enough to enlighten diagnosis in more than 80% of the patients.

  9. Gluteal Compartment Syndrome After Prolonged Immobilisation

    H.L. Liu


    Full Text Available Muscles in the gluteal region are confined by distinct fascial attachments which can potentially result in compartment syndrome. A 74-year-old chronic drinker was admitted to the medical ward after being found drunk on the street. He noticed acute painful swelling of the right side of his buttock the following morning and recalled a slip and fall prior to his blackout. The whole right half of the buttock was tense with erythematous overlying skin. Examination revealed sciatic nerve palsy and myoglobinuria. Emergency fasciotomy and debridement were performed. Intra-operative pressure measurement confirmed a grossly elevated intra-compartmental pressure. Gluteal compartment syndrome is an extremely rare condition and has only been scantily documented previously in case reports. Early diagnosis is crucial but delay recognition is common from lack of knowledge of the condition and readily results in permanent sciatic nerve injury and acute renal shutdown from myoglobinuria. Awareness of the condition, early diagnosis and prompt exploration provide the only chance of avoiding these devastating consequences. Acute swelling diffusely affecting the whole or one side of the buttock, a history of trauma and prolonged local pressure impingement associated with pain out of proportion to the clinical signs should raise a suspicion of this rare condition.

  10. Prolonged labour associated with lower expression of syndecan 3 and connexin 43 in human uterine tissue

    Malmström Anders


    Full Text Available Abstract Background Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour. Methods Uterine isthmic biopsies were collected from non-pregnant (n = 7, term pregnant women not in labour (n = 14, in normal labour (n = 7 and in prolonged labour (n = 7. mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy. Results In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p Conclusion The high expression of syndecan 3 and connexin 43 and their co-localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for these proteins in the co-ordination of myometrial contractility.

  11. Green teeth are a late complication of prolonged conjugated hyperbilirubinemia in extremely low birth weight infants.

    Battineni, Sireesha; Clarke, Paul


    Eruption of green, discolored teeth affecting the primary dentition has been described in association with congenital viral infection, sepsis, hemolytic jaundice, and cholestasis. The purpose of this paper was to present the cases of 3 extremely low birth weight preterm infants who were noted to have green teeth at the corrected ages of 10 to 12 months. All had a history of prolonged conjugated hyperbilirubinemia during their time in neonatal intensive care. For infants with prolonged conjugated hyperbilirubinemia, extreme preterm birth and/or extremely low birth weight may be additional risk factors predisposing to the eruption of green teeth in later infancy.

  12. Prolonged spring oestrus in mares: The use of progestogens with specific reference to proligestone

    Holst, W. van der; Laar, P. H. van; Oldenkamp, E. P.


    The problems of prolonged spring oestrus in mares, which is often associated with multifollicular ovaries (MFO), are described in the context of the need to produce foals early in the year. The results obtained, in terms of pregnancy and time of ovulation, after the intramuscular administration of a

  13. Efficacy of the "baby-sitter" procedure after prolonged denervation.

    Mersa, B; Tiangco, D A; Terzis, J K


    This study was undertaken to evaluate whether 40 percent of the hypoglossal nerve, which showed optimal efficacy in restoring orbicularis oculi muscle (OOM) function after different percentages of partial neurectomy in a previous study would be effective after prolonged denervation time. Twenty Sprague-Dawley rats were divided into four groups. In first-stage surgery the left facial nerve of all animals was transected at the level of the stylomastoid foramen and main zygomatic branch. Group A (controls) consisted of animals with only left facial nerves transected (no repair). In Groups B, C, and D the facial nerve was transected and the facial musculature was denervated for a period of 4, 8, and 12 weeks respectively. During a second-stage procedure, a 40 percent neurectomy was performed on the hypoglossal nerve. Subsequently, a nerve transfer was performed by coaptations of a saphenous nerve graft to the neurectomized hypoglossal nerve and the main zygomatic branch of the facial nerve that innervated the OOM. Behavioral analysis of blink reflex, electrophysiology, and axon and motor end-plate counts in Groups B, C, and D showed superior results compared to Group A. There was no statistically significant difference observed among Groups B, C, and D (p > 0.05). Despite the diminished number of axons in the zygomatic branch and motor end-plates in the orbicularis oculi muscle after 12 weeks of denervation, there was still sufficient muscle target recovery to effect some eye closure in all groups except the controls. This study demonstrated in this model that the 40 percent partial neurectomy of the XII to VII component of the "baby-sitter" procedure was effective even after prolonged denervation.

  14. [Prolonged pregnancy--prostaglandins as the cause of labor onset].

    Rath, W


    The causes of prolonged pregnancy are still largely unknown and their investigation requires a detailed observation of potential birth-initiating stimuli on the endocrine and biomolecular level. A large number of clinical and biochemical studies point to the central importance of prostaglandins for the beginning of human birth. The main places of origin of the intensified prostaglandin formation and release are the amnion and the decidua which has "macrophage-like" properties and functions. The superordinate regulation and trigger mechanisms for intensified uterine prostaglandin production has not been sufficiently investigated either. Possible factors currently being debated include local changes in estrogen and progesterone biosynthesis in fetal membranes and decidua, subclinical inflammatory reactions with the activation of macrophages and the consecutive release of cytokines, and a loss of maternal immune tolerance with a time-determined rejection reaction. In addition, the substances inhibiting and stimulating prostaglandin synthesis have been detected in the amniotic fluid, fetal membranes and decidua. The fetus itself also plays an important part in the initiation of labor. Prolongation may be due to anatomic functional disturbances of the one hand which prevent the activation of the fetal hypothalamic-hypophyseal-adrenal axis and the release of the birth-initiating stimuli originating in the fetus; on the other hand, an elevated immune tolerance with a delayed rejection reaction or the lack of "bacterial stimulus" may inhibit the activation of the macrophages and hence the formation of cytokines. The consequences would be the development and release of a quantity of prostaglandins from the fetal membranes and decidua insufficient to overcome the pregnancy-maintaining safety systems.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Encephalitis with Prolonged but Reversible Splenial Lesion

    Alena Meleková


    Full Text Available Introduction: The splenium of the corpus callosum has a specific structure of blood supply with a tendency towards blood-brain barrier breakdown, intramyelinic edema, and damage due to hypoxia or toxins. Signs and symptoms of reversible syndrome of the splenium of the corpus callosum typically include disorientation, confusion, impaired consciousness, and epileptic seizures. Case report: A previously healthy 32-year-old man suffered from weakness, headache, and fever. Subsequently, he developed apathy, ataxia, and inability to walk, and therefore was admitted to the hospital. Cerebrospinal fluid showed protein elevation (0.9 g/l and pleocytosis (232/1 ul. A brain MRI showed hyperintense lesions in the middle of the corpus callosum. The patient was treated with antibiotics, and subsequently, in combination with steroids. Two months later, the hyperintense lesions in the splenium and the basal ganglia had disappeared. Almost seven months since his hospitalization in the Department of Neurology, the patient has returned to his previous employment. He now does not exhibit any mental changes, an optic edema and urological problems have improved. In addition, he is now actively engaged in sports. Conclusion: We have described a case of a 32-year-old man with confusion, ataxia, and inability to stand and walk. The man developed a febrile meningeal syndrome and a hyperintense lesion of the splenium, which lasted for two months. Neurological changes, optic nerve edema, and urinary retention have resolved over the course of seven months. We think that the prolonged but transient lesion of the splenium may have been caused by encephalitis of viral origin.

  16. Diaphragmatic energetics during prolonged exhaustive exercise.

    Manohar, M; Hassan, A S


    The present study was carried out to examine diaphragmatic O2 extraction and lactate and ammonia production during prolonged exhaustive exercise. Experiments were performed on nine healthy exercise-conditioned ponies in which catheters had been implanted in the phrenic vein previously. Blood-gas variables and lactate and ammonia concentrations were determined on simultaneously obtained arterial and phrenic-venous blood samples at rest and during 30 min of exertion at 15 mph + 7% grade (heart rate, 200 beats/min; approximately 90% of maximum). Arterial O2 tension and saturation were maintained near resting value but CO2 tension decreased markedly with exercise, and because of increased hemoglobin concentration, arterial O2 content rose. Concomitantly, phrenic venous O2 tension, saturation and content decreased markedly (23.6 +/- 1 mm Hg, 24.5 +/- 2%, 5.2 +/- 0.3 ml/dl at 3 min of exertion) and significant fluctuations did not occur as exercise duration progressed to 30 min. Diaphragmatic arteriovenous O2 content difference and O2 extraction rose from 4 +/- 0.3 to 16 +/- 0.5 ml/dl and from 30 +/- 3 to 75 +/- 1% at 3 min of exercise, and significant deviations did not occur as exercise duration progressed. Arterial lactate and ammonia levels increased during exercise, indicating their release from working limb muscles. Phrenic-venous values of lactate and ammonia did not exceed arterial values. Ponies sweated profusely and were unable to keep up with the belt speed in the last 4 to 5 min of exercise. Constancy of phrenic arteriovenous O2 content difference in exercise indicated ability to adjust perfusion in diaphragm so as to adequately meet its O2 needs.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Exceptionally prolonged tooth formation in elasmosaurid plesiosaurians

    Kear, Benjamin P.; Larsson, Dennis; Lindgren, Johan; Kundrát, Martin


    Elasmosaurid plesiosaurians were globally prolific marine reptiles that dominated the Mesozoic seas for over 70 million years. Their iconic body-plan incorporated an exceedingly long neck and small skull equipped with prominent intermeshing ‘fangs’. How this bizarre dental apparatus was employed in feeding is uncertain, but fossilized gut contents indicate a diverse diet of small pelagic vertebrates, cephalopods and epifaunal benthos. Here we report the first plesiosaurian tooth formation rates as a mechanism for servicing the functional dentition. Multiple dentine thin sections were taken through isolated elasmosaurid teeth from the Upper Cretaceous of Sweden. These specimens revealed an average of 950 daily incremental lines of von Ebner, and infer a remarkably protracted tooth formation cycle of about 2–3 years–other polyphyodont amniotes normally take ~1–2 years to form their teeth. Such delayed odontogenesis might reflect differences in crown length and function within an originally uneven tooth array. Indeed, slower replacement periodicity has been found to distinguish larger caniniform teeth in macrophagous pliosaurid plesiosaurians. However, the archetypal sauropterygian dental replacement system likely also imposed constraints via segregation of the developing tooth germs within discrete bony crypts; these partly resorbed to allow maturation of the replacement teeth within the primary alveoli after displacement of the functional crowns. Prolonged dental formation has otherwise been linked to tooth robustness and adaption for vigorous food processing. Conversely, elasmosaurids possessed narrow crowns with an elongate profile that denotes structural fragility. Their apparent predilection for easily subdued prey could thus have minimized this potential for damage, and was perhaps coupled with selective feeding strategies that ecologically optimized elasmosaurids towards more delicate middle trophic level aquatic predation. PMID:28241059

  18. Fatigue associated with prolonged graded running.

    Giandolini, Marlene; Vernillo, Gianluca; Samozino, Pierre; Horvais, Nicolas; Edwards, W Brent; Morin, Jean-Benoît; Millet, Guillaume Y


    Scientific experiments on running mainly consider level running. However, the magnitude and etiology of fatigue depend on the exercise under consideration, particularly the predominant type of contraction, which differs between level, uphill, and downhill running. The purpose of this review is to comprehensively summarize the neurophysiological and biomechanical changes due to fatigue in graded running. When comparing prolonged hilly running (i.e., a combination of uphill and downhill running) to level running, it is found that (1) the general shape of the neuromuscular fatigue-exercise duration curve as well as the etiology of fatigue in knee extensor and plantar flexor muscles are similar and (2) the biomechanical consequences are also relatively comparable, suggesting that duration rather than elevation changes affects neuromuscular function and running patterns. However, 'pure' uphill or downhill running has several fatigue-related intrinsic features compared with the level running. Downhill running induces severe lower limb tissue damage, indirectly evidenced by massive increases in plasma creatine kinase/myoglobin concentration or inflammatory markers. In addition, low-frequency fatigue (i.e., excitation-contraction coupling failure) is systematically observed after downhill running, although it has also been found in high-intensity uphill running for different reasons. Indeed, low-frequency fatigue in downhill running is attributed to mechanical stress at the interface sarcoplasmic reticulum/T-tubule, while the inorganic phosphate accumulation probably plays a central role in intense uphill running. Other fatigue-related specificities of graded running such as strategies to minimize the deleterious effects of downhill running on muscle function, the difference of energy cost versus heat storage or muscle activity changes in downhill, level, and uphill running are also discussed.

  19. Prolonged latency of preterm premature rupture of membranes and risk of neonatal sepsis.

    Drassinower, Daphnie; Friedman, Alexander M; Običan, Sarah G; Levin, Heather; Gyamfi-Bannerman, Cynthia


    Preterm premature rupture of membranes (PPROM) is associated with inflammation and infection, and it may involve the loss of a barrier to ascending infection from the vagina, and it is possible that prolonged PPROM could be an independent risk factor for neonatal sepsis. The objective of the study was to determine whether prolonged latency after PPROM is associated with an increased risk of neonatal sepsis. This secondary analysis of the randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy evaluated whether the time interval between diagnosis of PPROM and delivery was associated with an increased risk of neonatal sepsis. Latency time was categorized by weeks of latency (0 weeks to ≥ 4 weeks). The primary outcome was confirmed neonatal sepsis. Logistic regression was used to control for confounders. A total of 1596 patients with PPROM were analyzed, of whom 1390 had a neonatal sepsis occurred in 15.5% of patients in the cohort. In the univariate analysis, patients in the prolonged PPROM group were less likely to have neonatal sepsis (6.8% vs 17.2%, relative risk, 0.40 95% confidence interval, 0.24-0.66). This relationship was retained in the multivariable model; patients with prolonged PPROM ≥ 4 weeks had an adjusted odds ratio of 0.21 (95% confidence interval, 0.10-0.41) for neonatal sepsis. Neonatal sepsis was also significantly associated with earlier gestational age at rupture of membranes. Prolonged exposure to an intrauterine environment of PPROM does not increase the risk of neonatal sepsis; prolonged PPROM ≥ 4 weeks was associated with decreased risk of neonatal sepsis. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Genomewide Mutational Diversity in Escherichia coli Population Evolving in Prolonged Stationary Phase.

    Chib, Savita; Ali, Farhan; Seshasayee, Aswin Sai Narain


    Prolonged stationary phase is an approximation of natural environments presenting a range of stresses. Survival in prolonged stationary phase requires alternative metabolic pathways for survival. This study describes the repertoire of mutations accumulating in starving Escherichia coli populations in lysogeny broth. A wide range of mutations accumulates over the course of 1 month in stationary phase. Single nucleotide polymorphisms (SNPs) constitute 64% of all mutations. A majority of these mutations are nonsynonymous and are located at conserved loci. There is an increase in genetic diversity in the evolving populations over time. Computer simulations of evolution in stationary phase suggest that the maximum frequency of mutations observed in our experimental populations cannot be explained by neutral drift. Moreover, there is frequent genetic parallelism across populations, suggesting that these mutations are under positive selection. Finally, functional analysis of mutations suggests that regulatory mutations are frequent targets of selection. IMPORTANCE Prolonged stationary phase in bacteria, contrary to its name, is highly dynamic, with extreme nutrient limitation as a predominant stress. Stationary-phase cultures adapt by rapidly selecting a mutation(s) that confers a growth advantage in stationary phase (GASP). The phenotypic diversity of starving E. coli populations has been studied in detail; however, only a few mutations that accumulate in prolonged stationary phase have been described. This study documented the spectrum of mutations appearing in Escherichia coli during 28 days of prolonged starvation. The genetic diversity of the population increases over time in stationary phase to an extent that cannot be explained by random, neutral drift. This suggests that prolonged stationary phase offers a great model system to study adaptive evolution by natural selection.

  1. QT interval prolongation after Premature Ventricular Contractions (PVCs

    Mohammed Haroon Rashid


    Full Text Available Long QT syndrome (LQTS is an inherited ion channelopathy resulting in abnormal ventricular repolarization and abnormal prolongation of QT interval on the ECG. Syncope, fainting, cardiac arrest, and sudden death are common manifestations of LQTS. We present a case report that describes a patient with prolonged QT interval after extrasystoles and a family history of sudden cardiac deaths.

  2. Computer mouse use predicts acute pain but not prolonged or chronic pain in the neck and shoulder

    Andersen, JH; Harhoff, M.; Grimstrup, S.


    BACKGROUND: Computer use may have an adverse effect on musculoskeletal outcomes. This study assessed the risk of neck and shoulder pain associated with objectively recorded professional computer use. METHODS: A computer programme was used to collect data on mouse and keyboard usage and weekly...... quartile increase in weekly mouse usage time. Mouse and keyboard usage time did not predict the onset of prolonged or chronic pain in the neck or shoulder. Women had higher risks for neck and shoulder pain. Number of keystrokes and mouse clicks, length of the average activity period, and micro-pauses did...... not influence reports of acute or prolonged pain. A few psychosocial factors predicted the risk of prolonged pain. CONCLUSIONS: Most computer workers have no or minor neck and shoulder pain, few experience prolonged pain, and even fewer, chronic neck and shoulder pain. Moreover, there seems...

  3. Prevalence of factor V Leiden and prothrombin G20210A mutation in a large French population selected for nonthrombotic history: geographical and age distribution.

    Mazoyer, Elisabeth; Ripoll, Laurent; Gueguen, René; Tiret, Laurence; Collet, Jean-Philippe; dit Sollier, Claire Bal; Roussi, Jacqueline; Drouet, Ludovic


    Among inherited risk factors for venous thrombosis, the most common are the FV-G1691A and FII-G20210A polymorphisms. The FV-G1691A polymorphism is preferentially observed in Europe, with differences between European countries. The FII-G20210A polymorphism is observed all over the world. The study was designed to compare the prevalence of the FV-G1691A and FII-G20210A polymorphisms in a large French population of unrelated individuals with no thrombotic disease history and to determine the age and geographical distributions. Over a period of 18 months, 6154 individuals were included throughout France and FV-G1691A and FII-G20210A polymorphisms were determined. The FV-G1691A prevalence was 3.84% (95% confidence interval 3.35-4.33) and the FII-G20210A prevalence was 3.07% (95% CI 2.63-3.51). A north-east/south-west gradient was observed in the FV-G1691A geographical distribution. No difference was observed in the geographical distribution of FII-G20210A polymorphism nor in the age distribution of the two polymorphisms. The prevalence of the two polymorphisms was similar whatever the blood group (O or non-O). Plasma D-dimers were significantly higher in healthy individuals with FV-G1691A but not in individuals with FII-G20210A. Thirty percent of variation in plasma prothrombin level was explained by environmental factors (serum cholesterol, age, oral contraception, hormonal replacement therapy, body mass index, sex) and genetic factors (FII-G20210A). As expected, individuals with FII-G20210A displayed higher plasma prothrombin level compared with individuals with wild type. However, this was not associated with a modification of the fibrin clot elastic modulus. This study shows a differential distribution of the two polymorphisms among the French territory. These polymorphisms confer a very mild hypercoagulable state as shown by the limited increased in basal D-dimers in mutated FV-G1691A populations and only a trend that does not reach statistical significance for FII

  4. Late recovery of awareness in prolonged disorders of consciousness -a cross-sectional cohort study.

    Yelden, Kudret; Duport, Sophie; James, Leon M; Kempny, Agnieszka; Farmer, Simon F; Leff, Alex P; Playford, E Diane


    To detect any improvement of awareness in prolonged disorders of consciousness in the long term. A total of 34 patients with prolonged disorders of consciousness (27 vegetative state and seven minimally conscious state; 16 males; aged 21-73) were included in the study. All patients were initially diagnosed with vegetative/minimally conscious state on admission to our specialist neurological rehabilitation unit. Re-assessment was performed 2-16 years later using Coma Recovery Scale-Revised. Although remaining severely disabled, 32% of the patients showed late improvement of awareness evidenced with development of non-reflexive responses such as reproducible command following and localization behaviors. Most of the late recoveries occurred in patients with subarachnoid hemorrhage (5/11, 45.5%). The ages of patients within the late recovery group (Mean = 45, SD = 11.4) and non-recovery group (Mean = 43, SD = 15.5) were not statistically different (p = 0.76). This study shows that late improvements in awareness are not exceptional in non-traumatic prolonged disorders of consciousness cases. It highlights the importance of long-term follow up of patients with prolonged disorders of consciousness, regardless of the etiology, age, and time passed since the brain injury. Long-term follow up will help clinicians to identify patients who may benefit from further assessment and rehabilitation. Although only one patient achieved recovery of function, recovery of awareness may have important ethical implications especially where withdrawal of artificial nutrition and hydration is considered. Implications for rehabilitation Long-term regular follow-up of people with prolonged disorders of consciousness is important. Albeit with poor functional outcomes late recovery of awareness is possible in both traumatic and non-traumatic prolonged disorders of consciousness cases. Recovery of awareness has significant clinical and ethical implications especially where

  5. The reliability of point-of-care prothrombin time testing. A comparison of CoaguChek S and XS INR measurements with hospital laboratory monitoring.

    Ryan, F


    The development of point-of-care (POC) testing devices enables patients to test their own international normalized ratio (INR) at home. However, previous studies have shown that when compared with clinical laboratory values, statistically significant differences may occur between the two methods of INR measurement. The aim of this study was to evaluate the accuracy of the CoaguChek S and XS POC meters relative to clinical laboratory measurements. As part of a randomized, crossover patient self-testing (PST) study at Cork University Hospital, patients were randomized to 6 months PST or 6 months routine care by the anticoagulation management service. During the PST arm of the study, patients measured their INR at home using the CoaguChek S or XS POC meter. External quality control was performed at enrollment, 2 months and 4 months by comparing the POC measured INR with the laboratory determined value. One hundred and fifty-one patients provided 673 paired samples. Good correlation was shown between the two methods of determination (r = 0.91), however, statistically significant differences did occur. A Bland-Altman plot illustrated good agreement of INR values between 2.0 and 3.5 INR units but there was increasing disagreement as the INR rose above 3.5. Eighty-seven per cent of all dual measurements were within the recommended 0.5 INR units of each other. This study adds to the growing evidence that POC testing is a reliable and safe alternative to hospital laboratory monitoring but highlights the importance of external quality control when these devices are used for monitoring oral anticoagulation.

  6. Elevated prothrombin time on routine preoperative laboratory results in a healthy infant undergoing craniosynostosis repair: Diagnosis and perioperative management of congenital factor VII deficiency

    Kareen L. Jones


    Conclusion: A thorough history and physical examination with a high clinical suspicion are vital in preventing hemorrhage during surgeries in children with coagulopathies. Abnormal preoperative lab values should always be confirmed and addressed before proceeding with high-risk surgery. A multidisciplinary discussion is essential to optimize the risk-benefit ratio during the perioperative period.

  7. Prolonged closed cardiac massage using LUCAS device in out-of-hospital cardiac arrest with prolonged transport time

    Edouard Matevossian


    Full Text Available Edouard Matevossian1, Dietrich Doll4, Jakob Säckl1, Inga Sinicina5, Jürgen Schneider2, Gerhard Simon3, Norbert Hüser11Department of Surgery, 2Department of Anesthesiology and Intensive-Care Medicine; 3Department of Radiology, Technische Universität of Munich, Germany; 4Department of Visceral, Vascular and Thoracic Surgery, Philips University of Marburg, Marburg, Germany; 5Institute of Clinical Forensic Medicine, Ludwig-Maximilian University of Munich, Munich, GermanyAbstract: Saving more human lives through more effective reanimation measures is the goal of the new international guidelines on cardiopulmonary resuscitation as the decisive aspect for survival after cardiovascular arrest is that basic resuscitation should start immediately. According to the updated guidelines, the greatest efficacy in cardiac massage is only achieved when the right compression point, an adequate compression depth, vertical pressure, the correct frequency, and equally long phases of compression and decompression are achieved. The very highest priority is placed on restoring continuous circulation. Against this background, standardized continuous chest compression with active decompression has contributed to a favorable outcome in this case. The hydraulically operated and variably adjustable automatic Lund University Cardiac Arrest System (LUCAS device (Jolife, Lund, Sweden undoubtedly meets these requirements. This case report describes a 44-year-old patient who – approximately 15 min after the onset of clinical death due to apparent ventricular fibrillation – received cardiopulmonary resuscitation, initially by laypersons and then by the emergency medical team (manual chest compressions followed by situation-adjusted LUCAS compressions. Sinus rhythm was restored after more than 90 min of continuous resuscitation, with seven defibrillations. Interventional diagnostic workup did not reveal a causal morphological correlate for the condition on coronary angiography. After a 16-day period of hospital convalescence, with preventive implantation of an implantable cardioverter defibrillator and several weeks of rehabilitation, the patient was able to return home with no evidence of health impairment.Keywords: resuscitation, cardiac arrest, cardiac massage, LUCAS

  8. Dexamethasone added to mepivacaine prolongs the duration of analgesia after supraclavicular brachial plexus blockade.

    Parrington, Simon J; O'Donnell, Dermot; Chan, Vincent W S; Brown-Shreves, Danielle; Subramanyam, Rajeev; Qu, Melody; Brull, Richard


    Corticosteroids have been used successfully to prolong the duration of local anesthetic action after peripheral nerve and epidural blockade. We hypothesized that the addition of dexamethasone to mepivacaine would prolong the duration of analgesia after ultrasound-guided supraclavicular brachial plexus block for patients undergoing upper-limb surgery. After Federal Health Department and institutional review board approval, 45 adult patients undergoing elective hand or forearm surgery under supraclavicular brachial plexus blockade were randomized to receive either 30 mL mepivacaine 1.5% plus dexamethasone 8 mg (4 mg/mL), or 30 mL mepivacaine 1.5% plus 2 mL normal saline. The primary outcome measure was duration of analgesia. Secondary outcomes included onset times of sensory and motor blockade, pain and satisfaction scores, analgesic consumption, and block-related complications. Patient characteristics were similar between groups. The median duration of analgesia was significantly prolonged in the Dexamethasone group (332 mins; interquartile range, 225-448 mins) compared with the Normal Saline group (228 mins; interquartile range, 207-263 mins; P = 0.008). The onset times of sensory and motor block were similar between the groups. Complications were minor and transient and did not differ between groups at 2 weeks postoperatively. The addition of dexamethasone to mepivacaine prolongs the duration of analgesia but does not reduce the onset of sensory and motor blockade after ultrasound-guided supraclavicular block compared with mepivacaine alone.

  9. Prolonged chewing at lunch decreases later snack intake.

    Higgs, Suzanne; Jones, Alison


    Prolonged chewing of food can reduce meal intake. However, whether prolonged chewing influences intake at a subsequent eating occasion is unknown. We hypothesised that chewing each mouthful for 30s would reduce afternoon snack intake more than (a) an habitual chewing control condition, and (b) an habitual chewing condition with a pauses in between each mouthful to equate the meal durations. We further hypothesised that this effect may be related to effects of prolonged chewing on lunch memory. Forty three participants ate a fixed lunch of sandwiches in the laboratory. They were randomly allocated to one of the three experimental groups according to a between-subjects design. Appetite, mood and lunch enjoyment ratings were taken before and after lunch and before snacking. Snack intake of candies at a taste test 2h after lunch was measured as well as rated vividness of lunch memory. Participants in the prolonged chewing group ate significantly fewer candies than participants in the habitual chewing group. Snack intake by the pauses group did not differ from either the prolonged or habitual chewing groups. Participants in the prolonged chewing group were less happy and enjoyed their lunch significantly less than participants in other conditions. Appetite ratings were not different across groups. Rated vividness of lunch memory was negatively correlated with intake but there was no correlation with rated lunch enjoyment. Prolonged chewing of a meal can reduce later snack intake and further investigation of this technique for appetite control is warranted.

  10. Management of Bleeding in Post-liver Disease, Surgery and Biopsy in Patients With High Uncorrected International Normalized Ratio With Prothrombin Complex Concentrate: An Iranian Experience.

    Parand, Alireza; Honar, Naser; Aflaki, Khashayar; Imanieh, Mohammad Hadi; Haghighat, Mahmood; Cohan, Nader; Haghpanah, Sezaneh; Marietta, Marco; Serati, Zahra; Haghbin, Saeedeh; Karimi, Mehran


    To evaluate the efficacy of prothrombin complex concentrate (PCC) in the management of bleeding in patients with liver disease and patients undergoing surgery or biopsy who had a high uncorrected international normalized ratio (INR). In this study, we examined an Iranian sample and investigated the efficacy of PCC to manage bleeding in patients with liver disease and also patients with high uncorrected INR who were scheduled for surgery or biopsy. A total of 25 patients including 16 patients with post-liver disease bleeding (group 1) and 9 patients with high uncorrected INR who were scheduled for surgery or biopsy (group 2) were enrolled. All patients were treated with 25 IU/kg PCC, and efficacy was defined as any reduction in or cessation of bleeding episodes and correction of INR before surgery or biopsy. The patients were also evaluated for any adverse effects. INR decreased significantly in both groups of patients, with no bleeding episodes during or after the study in group 1 and during or after surgery/biopsy in group 2. All patients tolerated the therapy well without any significant adverse effects. The efficacy of PCC therapy was satisfactory in this study. PCC therapy in patients with liver disease and patients undergoing surgery or biopsy seems to be effective and safe, and may be a good treatment strategy for these patients, if fresh frozen plasma or vitamin K are not effective.

  11. Dietary factor VII activation does not increase plasma concentrations of prothrombin fragment 1+2 in patients with stable angina pectoris and coronary atherosclerosis

    Bladbjerg, E-M; Münster, A M; Marckmann, P


    for triglycerides, activated FVII (FVIIa), FVII protein concentration (FVII:Ag), prothrombin fragment 1+2 (F1+2), and soluble fibrin. Triglyceride levels increased from fasting levels on both diets, but they increased most markedly on the high-fat diet. FVIIa and FVIIa/FVII:Ag increased with the high-fat diet...... and decreased with the low-fat diet. For both diets, FVII:Ag and F1+2 decreased slightly. No postprandial changes were observed for soluble fibrin. Postprandial mean values of triglycerides, FVIIa, FVII:Ag, and FVIIa/FVII:Ag were significantly higher for the high-fat diet than for the low-fat diet. Our findings...... confirm that high-fat meals cause immediate activation of FVII. The clinical implication is debatable because FVII activation was not accompanied by an increase in plasma F1+2 concentrations in patients with severe atherosclerosis. However, a local thrombin generation on the plaque surface cannot...

  12. Maternal factor V Leiden and prothrombin mutations do not seem to contribute to the occurrence of two or more than two consecutive miscarriages in Caucasian patients.

    Baumann, Kristin; Beuter-Winkler, Petra; Hackethal, Andreas; Strowitzki, Thomas; Toth, Bettina; Bohlmann, Michael K


    We analysed the prevalence of the most common hereditary thrombophilia (hTP) - factor V Leiden (FVL) mutation, prothrombin 20210 G>A substitution (PT) - and the 677 C>T replacement in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene in Caucasian patients with a history of two and more consecutive recurrent miscarriages (RMs) as compared to healthy controls with an identical ethnic background and at least one live birth. A multicenter analysis of three hTP was performed in 641 RM patients identically screened at specialized university centres. The study groups consisted of 240 patients with 2 (1) and 401 patients with >2 miscarriages (2) and were compared with 157 controls. There was no significant difference in the prevalence of the hTP between RM patients and controls nor within the two study groups. Subgroup analysis showed that the homozygous MTHFR polymorphism was significantly more prevalent in the study group 2 as compared to study group 1 (13.9 versus 7.9%, P = 0.02). In Caucasians, maternal FVL or PT mutations do not seem to contribute to the pathophysiology of RM, irrespective of the number of miscarriages. However, the role of the homozygous MTHFR polymorphism merits further investigation. © 2013 John Wiley & Sons Ltd.

  13. Factor V G1691A (Leiden and prothrombin G20210A gene mutation status, and thrombosis in patients with chronic myeloproliferative disorders

    Nur Soyer


    Full Text Available Objective: The aim of this study was to examine Factor V G1691A (Leiden (FVL and prothrombin G20210A (PT gene mutation status, and their relationship with thrombosis in patients with chronic myeloproliferative disorders (CMPDs.Materials and Methods: The study included 160 patients with a CMPD that were regularly followed-up between 1993 and 2009. FVL and PT mutation status was established based on blood samples analyzed via PCR using specific primers.Results: The frequency of FVL and PT mutation was 12.5% and 4.4%, respectively. In total, 27 episodes of thrombosis occurred in 24 (15% of the patients, and there wasn’t an association between the observed thrombotic events, and FVL or PT mutations. Hepatic vein thrombosis was noted in 3 patients that had FVL mutation, of which 1 also had PT mutation.Conclusion: We did not observe a relationship between thrombosis, and FVL or PT mutations in CMPD patients; however, 3 of the patients that had hepatic vein thrombosis also had FVL mutation. Larger studies are needed to more clearly determine if all CMPD patients with hepatic vein thrombosis need be investigated for FVL and PT mutation.

  14. Thrombophilic risk of individuals with rare compound factor V Leiden and prothrombin G20210A polymorphisms: an international case series of 100 individuals.

    Lim, Ming Y; Deal, Allison M; Kim, Steven; Musty, Michael D; Conard, Jacqueline; Simioni, Paolo; Dutrillaux, Fabienne; Eid, Suhair S; Middeldorp, Saskia; Halbmayer, Walter M; Boneu, Bernard; Moia, Marco; Moll, Stephan


    The risk of thrombosis in individuals with rare compound thrombophilias, homozygous factor V Leiden (FVL) plus heterozygous prothrombin G20210A (PTM), homozygous PTM plus heterozygous FVL, and homozygous FVL plus homozygous PTM, is unknown. We identified, worldwide, individuals with these compound thrombophilias, predominantly through mailing members of the International Society on Thrombosis and Haemostasis. Physicians were sent a clinical questionnaire. Confirmatory copies of the genetic results were obtained. One hundred individuals were enrolled; 58% were female. Seventy-one individuals had a venous thrombosis (includes superficial and deep vein thrombosis, and pulmonary embolism), 4 had an arterial thrombosis and 6 had both. Nineteen individuals had never had a thrombotic event. Thrombosis-free survival curves demonstrated that 50% of individuals had experienced a thrombotic event by 35 yrs of age, while 50% had a first venous thromboembolic event (VTE; includes all venous thrombosis except superficial thrombosis) by 41 yrs of age; 38.2% of first VTEs were unprovoked. 37% of patients had at least one VTE recurrence. Seventy percent of first pregnancies carried to term and not treated with anticoagulation were thrombosis-free. In conclusion, patients with these rare compound thrombophilias are not exceedingly thrombogenic, even though they have a substantial risk for VTE. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Prothrombin fragment 1 + 2 (F1 + 2) in effluent is a useful marker for peritoneal permeability in peritoneal dialysis patients using neutral dialysate.

    Sakurada, Tsutomu; Kojima, Shigeki; Oishi, Daisuke; Koitabashi, Kenichiro; Miyamoto, Masahito; Shirai, Sayuri; Shibagaki, Yugo; Yasuda, Takashi; Sato, Takeo; Kimura, Kenjiro


    To clarify the influence of neutral dialysate (ND) on peritoneum, we examined changes in peritoneal permeability and in various markers of the coagulation and fibrinolytic system in effluent and the correlations between peritoneal permeability and those markers in peritoneal dialysis (PD) patients using ND. We evaluated 14 patients (8 men, 6 women; mean age: 58.6 +/- 12.0 years) who started PD using ND. The peritoneal equilibration test (PET) was performed to assess dialysate-to-plasma ratio for creatinine (D/P Cr) as peritoneal permeability. Coagulation markers [thrombin-antithrombin complex, fibrin monomer (FM), prothrombin fragment 1+2 (F1 + 2)] and fibrinolytic markers (fibrin degradation products, D-dimer) in effluent were also measured. At 2 years, FM in effluent was significantly lower (p = 0.006). The other markers and the D/P Cr did not change significantly. At the initiation of PD and at 2 years, D/P Cr was significantly correlated with F1 + 2 (r = 0.70 and 0.76 respectively, p permeability in PD patients using ND.

  16. The effects of vitamin K on the generation of des-gamma-carboxy prothrombin (PIVKA-II) in patients with hepatocellular carcinoma.

    Sakon, M; Monden, M; Gotoh, M; Kobayashi, K; Kanai, T; Umeshita, K; Endoh, W; Mori, T


    The clinical significance of des-gamma-carboxy prothrombin (PIVKA-II) in hepatocellular carcinoma (HCC) was investigated in 112 patients with and without vitamin K administration. The positivity rate of PIVKA-II was significantly decreased in patients receiving vitamin K (28.5%), compared with those without vitamin K administration (54.5%, p less than 0.05). The plasma levels of vitamin K derivatives [phylloquinone (VK1), menaquinone-4 (MK4), and menaquinone-7 (MK7)] measured were not decreased in patients with HCC, but were significantly increased in MK4 and VK1 + MK4 + MK7. The amount of PIVKA-II in plasma did not correlate with the plasma levels of vitamin K derivatives. However, PIVKA-II was decreased by the administration of vitamin K, and all of the six patients with more than 5.0 ng/ml of VK1 + MK4 + MK7 were within normal limits, whereas half of 32 patients with less than that had abnormal levels of PIVKA-II. Thus, it was suggested that PIVKA-II was not elevated due to vitamin K deficiency, but might result from the impaired metabolism or availability of vitamin K in the tumor. Therefore, PIVKA-II should be measured without vitamin K administration.

  17. Supplementation of Ascorbic Acid in Weanling Horses Following Prolonged Transportation

    Michelle Stives


    Full Text Available Though horses synthesize ascorbic acid in their liver in amounts that meet their needs under normal circumstances, prolonged stress results in low plasma concentrations due to enhanced utilization and renal excretion and can reduce immune function. It was hypothesized that plasma ascorbic acid could be maintained in weanling horses by oral supplementation following prolonged transportation. Weanlings were supplemented with no ascorbic acid (Tx 0: n = 4, 5 grams ascorbic acid twice daily for 5 days (Tx 1: n = 4 or for 10 days (Tx 2: n = 4 following >50 hours of transportation. Supplementation caused slight (P < 0.2 increases in plasma ascorbic acid concentrations. Both supplemented groups had decreased (P < 0.05 plasma concentrations for 1 to 3 weeks following cessation of supplementation, possibly due to increased renal excretion or suppressed hepatic synthesis. Supplementation of ascorbic acid following prolonged stress will increase plasma concentrations, but prolonged supplementation should be avoided.

  18. Prolonged spontaneous emission and dephasing of localized excitons in air-bridged carbon nanotubes

    Sarpkaya, Ibrahim; Zhang, Zhengyi; Walden-Newman, William; Wang, Xuesi; Hone, James; Wong, Chee W.; Strauf, Stefan


    The bright exciton emission of carbon nanotubes is appealing for optoelectronic devices and fundamental studies of light-matter interaction in one-dimensional nanostructures. However, to date, the photophysics of excitons in carbon nanotubes is largely affected by extrinsic effects. Here we perform time-resolved photoluminescence measurements over 14 orders of magnitude for ultra-clean carbon nanotubes bridging an air gap over pillar posts. Our measurements demonstrate a new regime of intrinsic exciton photophysics with prolonged spontaneous emission times up to T1=18 ns, about two orders of magnitude better than prior measurements and in agreement with values hypothesized by theorists about a decade ago. Furthermore, we establish for the first time exciton decoherence times of individual nanotubes in the time domain and find fourfold prolonged values up to T2=2.1 ps compared with ensemble measurements. These first observations motivate new discussions about the magnitude of the intrinsic dephasing mechanism while the prolonged exciton dynamics is promising for applications.

  19. Prolongation structure of the Landau–Lifshitz equation

    Roelofs, G.H.M.; Martini, R.


    The prolongation method of Wahlquist and Estabrook is applied to the Landau–Lifshitz equation. The resulting prolongation algebra is shown to be isomorphic to a subalgebra of the tensor product of the Lie algebra so(3) with the elliptic curve v α 2−v β 2=j β−j α (α,β=1,2,3), which is essentially a s

  20. What prolongs a butterfly's life?: Trade-offs between dormancy, fecundity and body size.

    Elena Haeler

    Full Text Available In butterflies, life span often increases only at the expense of fecundity. Prolonged life span, on the other hand, provides more opportunities for oviposition. Here, we studied the association between life span and summer dormancy in two closely related species of Palearctic Meadow Brown butterflies, the endemic Maniola nurag and the widespread M. jurtina, from two climatic provenances, a Mediterranean and a Central European site, and tested the relationships between longevity, body size and fecundity. We experimentally induced summer dormancy and hence prolonged the butterflies' life in order to study the effects of such a prolonged life. We were able to modulate longevity only in Mediterranean females by rearing them under summer photoperiodic conditions (light 16 h : dark 8 h, thereby more than doubling their natural life span, to up to 246 days. Central European individuals kept their natural average live span under all treatments, as did Mediterranean individuals under autumn treatment (light 11: dark 13. Body size only had a significant effect in the smaller species, M. nurag, where it affected the duration of dormancy and lifetime fecundity. In the larger species, M. jurtina, a prolonged adult life span did, surprisingly, not convey any fecundity loss. In M. nurag, which generally deposited fewer eggs, extended life had a fecundity cost. We conclude that Mediterranen M. jurtina butterflies have an extraordinary plasticity in aging which allows them to extend life span in response to adverse environmental conditions and relieve the time limitation on egg-laying while maintaining egg production at equal levels.

  1. Outcome of Induction of Labour in Prolonged Pregnancy.

    Nasrin, S; Islam, S; Shahida, S M; Begum, R A; Haque, N


    This was a hospital based prospective clinical study conducted among women having prolonged pregnancy to assess the outcome of induction of labour in prolonged pregnancy cases. One hundred and thirty nine women having uncomplicated prolonged pregnancy were studied. The study was carried out in Sir Salimullah Medical College & Mitford Hospital, Dhaka from 01 July 2010 to 30 March 2011. In this study 66% of the respondents had vaginal delivery on routine induction of labour and in 34% cases induction failed. Ninety three percent (93%) of the multigravida had vaginal delivery and in primigravida their vaginal delivery rate was 47.5%. Regarding cervical condition for delivery, 75% of the respondents having favourable cervix had vaginal delivery and in case of unfavourable cervix respondents, they had 55% cases of vaginal delivery. About the foetal outcome it was evidenced from this study that the perinatal adverse outcome increases with the increasing age of gestation beyond 40 completed weeks of gestation. This study showed that the use of prostaglandins for cervical ripening and by confirming the diagnosis of prolonged pregnancy, the delivery outcome in prolonged pregnancy can be improved. The study also showed that induction of labour is not associated with any major complications and the routine induction of labour in prolonged pregnancy is beneficial for both mother and the baby.

  2. Diagnosis, antenatal surveillance and management of prolonged pregnancy: current perspectives.

    Vitale, S G; Marilli, I; Rapisarda, A M; Iapichino, V; Stancanelli, F; Cianci, A


    Prolonged pregnancy is defined as a pregnancy that extends beyond 42 weeks of gestation (294 days) from the first day of the last normal menstrual period. An accurate estimation of the 'natural' incidence of prolonged pregnancy would require meticulous early pregnancy dating. The use of ultrasound to establish gestational age reduces the number of pregnancies that are classified as prolonged. Prolonged pregnancy is associated with an increased perinatal mortality and morbidity in pregnancies which appear to be otherwise low risk. Postterm births are easily preventable by intervening to deliver with the use of induction of labor. Thus, this potentially problematic condition deserves further attention and careful consideration. The focus of this article is to review and challenge some current concepts surrounding the diagnosis and management of prolonged pregnancy. We outline how to identify those women with prolonged pregnancy and which is the appropriate moment to start monitoring the fetal wellbeing. Finally we address the question of benefits and hazards of induction of labor strategies.

  3. Recovery in skeletal muscle contractile function after prolonged hindlimb immobilization

    Fitts, R. H.; Brimmer, C. J.


    The effect of three-month hindlimb immobilization (IM) in rats on contractile properties of slow-twitch soleus (SOL), fast-twitch extensor digitorum longus, and fast-twitch superficial region of the vastus lateralis were measured after 0, 14, 28, 60, and 90 days of recovery on excized, horizontally suspended muscles stimulated electrically to maximal twitch tension. IM caused decreases in muscle-to-body weight ratios for all muscles, with no complete recovery even after 90 days. The contractile properties of the fast-twitch muscles were less affected by IM than those of the slow-twitch SOL. The SOL isometric twitch duration was shortened, due to reduced contraction and half-relaxation time, both of which returned to control levels after 14 days of recovery. The peak tetanic tension, P(O), g/sq cm,, decreased with IM by 46 percent in the SOL, but recovered by the 28th day. The maximum shortening velocity was not altered by IM in any of the muscles. Thus, normal contractile function could recover after prolonged limb IM.

  4. Prolonged sleep fragmentation of mice exacerbates febrile responses to lipopolysaccharide

    Ringgold, Kristyn M.; Barf, R. Paulien; George, Amrita; Sutton, Blair C.; Opp, Mark R.


    Background Sleep disruption is a frequent occurrence in modern society. Whereas many studies have focused on the consequences of total sleep deprivation, few have investigated the condition of sleep disruption. New Method We disrupted sleep of mice during the light period for 9 consecutive days using an intermittently-rotating disc. Results Electroencephalogram (EEG) data demonstrated that non-rapid eye movement (NREM) sleep was severely fragmented and REM sleep was essentially abolished during the 12 h light period. During the dark period, when sleep was not disrupted, neither NREM sleep nor REM sleep times differed from control values. Analysis of the EEG revealed a trend for increased power in the peak frequency of the NREM EEG spectra during the dark period. The fragmentation protocol was not overly stressful as body weights and water consumption remained unchanged, and plasma corticosterone did not differ between mice subjected to 3 or 9 days of sleep disruption and home cage controls. However, mice subjected to 9 days of sleep disruption by this method responded to lipopolysaccharide with an exacerbated febrile response. Comparison with existing methods Existing methods to disrupt sleep of laboratory rodents often subject the animal to excessive locomotion, vibration, or sudden movements. This method does not suffer from any of these confounds. Conclusions This study demonstrates that prolonged sleep disruption of mice exacerbates febrile responses to lipopolysaccharide. This device provides a method to determine mechanisms by which chronic insufficient sleep contributes to the etiology of many pathologies, particularly those with an inflammatory component. PMID:23872243

  5. Adhesive polydopamine coated avermectin microcapsules for prolonging foliar pesticide retention.

    Jia, Xin; Sheng, Wen-bo; Li, Wei; Tong, Yan-bin; Liu, Zhi-yong; Zhou, Feng


    In this work, we report a conceptual strategy for prolonging foliar pesticide retention by using an adhesive polydopamine (PDA) microcapsule to encapsulate avermectin, thereby minimizing its volatilization and improving its residence time on crop surfaces. Polydopamine coated avermectin (Av@PDA) microcapsules were prepared by emulsion interfacial-polymerization and characterized by Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, field-emission scanning electron microscope, and transmission electron microscopy. The in situ synthesis route confers Av@PDA microcapsules with remarkable avermectin loading ability of up to 66.5% (w/w). Kinetic study of avermectin release demonstrated that Av@PDA microcapsules exhibit sustained- and controlled-release properties. The adhesive property of Av@PDA microcapsules on different surfaces was verified by a comparative study between Av@PDA and passivated Av@SiO2 and Av@PDA@SiO2 capsules with silica shell. Moreover, PDA shell could effectively shield UV irradiation and so protect avermectin from photodegradation, making it more applicable for foliar spraying. Meanwhile, it is determinated that Av@PDA microcapsules have good mechanical stability property.

  6. Can the rat donor liver tolerate prolonged warm ischemia ?

    Ji Qi Yan; Hong Wei Li; Wei Yao Cai; Ming Jun Zhang; Wei Ping Yang


    The last two decades of the twentieth century have witnessed increasingly successful rates of liver transplantation. The number of liver transplantations has increased steadily while the number of organ donors has remained relatively constant. Thus a great disparity has developed between the demand and supply of donor organs and remains a major limiting factor for further expansion of liver transplantation. Although many procedures, such as split liver[1] , living-related transplantation[2] , and xenotransplantation[3], have been attempted clinically to overcome the shortage, it is hoped that livers harvested from non-heart-beating donors (NHBDs) would alleviatethe problem of organ shortage, which again becomes the focus of attention[4-9]. However, sensitivity of the liver to warm ischemia remains a major worry for use of theNHBDs. The aim of this animal study was to assess if murine liver could tolerate prolonged period of warm ischemia and to determine the optimum timing of intervention in the cadaver donor in order to preserve liver viability.

  7. Drugs, QTc prolongation and sudden cardiac death

    S.M.J.M. Straus (Sabine)


    textabstract__Abstract__ The term sudden cardiac death pertains to an unexpected death from cardiac causes within a short time period and has been described throughout history. The ancient Egyptians inscribed on the tomb of a nobleman some 4500 years ago that he had died suddenly and without appare

  8. Drugs, QTc prolongation and sudden cardiac death

    S.M.J.M. Straus (Sabine)


    textabstract__Abstract__ The term sudden cardiac death pertains to an unexpected death from cardiac causes within a short time period and has been described throughout history. The ancient Egyptians inscribed on the tomb of a nobleman some 4500 years ago that he had died suddenly and without

  9. Prolonged penile strangulation with metal clamps

    Chirag Patel; Richard Kim; Michael Delterzo; Run Wang


    Various different objects have been reported to strangulate the penis. We reported on a patient who used metal radiator clamps for an extended period of time. Workup included history, physical examination and urinalysis. The patient was taken to the operating room for further evaluation with cystourethroscopy and orthopedic wire cutters were used to break the metal bands.

  10. Development of prolonged standing strain index to quantify risk levels of standing jobs.

    Halim, Isa; Omar, Abdul Rahman


    Many occupations in industry such as metal stamping workers, electronics parts assembly operators, automotive industry welders, and lathe operators require working in a standing posture for a long time. Prolonged standing can contribute to discomfort and muscle fatigue particularly in the back and legs. This study developed the prolonged standing strain index (PSSI) to quantify the risk levels caused by standing jobs, and proposed recommendations to minimize the risk levels. Risk factors associated with standing jobs, such as working posture, muscles activity, standing duration, holding time, whole-body vibration, and indoor air quality, were the basis for developing the PSSI. All risk factors were assigned multipliers, and the PSSI was the product of those multipliers. Recommendations for improvement are based on the PSSI; however, extensive studies are required to validate their effectiveness. multipliers, and the PSSI was the product of those multipliers. Recommendations for improvement are based on the PSSI; however, extensive studies are required to validate their effectiveness.

  11. Prolonged perceived stress and saliva cortisol in a large cohort of Danish public service employees

    Mikkelsen, Sigurd; Forman, Julie Lyng; Fink, Samuel


    . METHODS: In 2007, 4467 Danish public service employees participated in a study of stress and mental health, and 3217 participated in a follow-up in 2009. Perceived stress during the past 4 weeks was assessed by Cohen's four item perceived stress scale. Participants were asked to collect saliva 30 min......PURPOSE: It is well known that acute stress can lead to a transient increase in cortisol secretion, but the effects of prolonged stress on cortisol secretion are uncertain. This study examines the cross-sectional and longitudinal associations between prolonged perceived stress and salivary cortisol...... after awakening and at approximately 20:00 in the evening. The cortisol dependence on perceived stress was examined in regression analyses adjusted for effects of potential confounders. We adjusted for a large variation in saliva sampling times by modelling the time trajectory of cortisol concentrations...

  12. The impact of prolonged violent video-gaming on adolescent sleep: an experimental study.

    King, Daniel L; Gradisar, Michael; Drummond, Aaron; Lovato, Nicole; Wessel, Jason; Micic, Gorica; Douglas, Paul; Delfabbro, Paul


    Video-gaming is an increasingly prevalent activity among children and adolescents that is known to influence several areas of emotional, cognitive and behavioural functioning. Currently there is insufficient experimental evidence about how extended video-game play may affect adolescents' sleep. The aim of this study was to investigate the short-term impact of adolescents' prolonged exposure to violent video-gaming on sleep. Seventeen male adolescents (mean age = 16 ± 1 years) with no current sleep difficulties played a novel, fast-paced, violent video-game (50 or 150 min) before their usual bedtime on two different testing nights in a sleep laboratory. Objective (polysomnography-measured sleep and heart rate) and subjective (single-night sleep diary) measures were obtained to assess the arousing effects of prolonged gaming. Compared with regular gaming, prolonged gaming produced decreases in objective sleep efficiency (by 7 ± 2%, falling below 85%) and total sleep time (by 27 ± 12 min) that was contributed by a near-moderate reduction in rapid eye movement sleep (Cohen's d = 0.48). Subjective sleep-onset latency significantly increased by 17 ± 8 min, and there was a moderate reduction in self-reported sleep quality after prolonged gaming (Cohen's d = 0.53). Heart rate did not differ significantly between video-gaming conditions during pre-sleep game-play or the sleep-onset phase. Results provide evidence that prolonged video-gaming may cause clinically significant disruption to adolescent sleep, even when sleep after video-gaming is initiated at normal bedtime. However, physiological arousal may not necessarily be the mechanism by which technology use affects sleep.

  13. Delayed replantation after prolonged dry storage

    Anita Rao


    Full Text Available Management of tooth avulsion in the permanent dentition often presents a challenge. Definitive treatment planning and consultation with specialists is seldom possible at the time of emergency treatment. Replantation of the avulsed tooth can restore esthetic appearance and occlusal function shortly after the injury. This article describes the management of a patient with an avulsed maxillary permanent incisor that had been air-dried for about 40 h. The replanted incisor retained its esthetic appearance and functionality 1 year after replantation, yet the long-term prognosis is not good because of progressive replacement root resorption.

  14. The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies.

    Marc A Rodger


    Full Text Available BACKGROUND: Factor V Leiden (FVL and prothrombin gene mutation (PGM are common inherited thrombophilias. Retrospective studies variably suggest a link between maternal FVL/PGM and placenta-mediated pregnancy complications including pregnancy loss, small for gestational age, pre-eclampsia and placental abruption. Prospective cohort studies provide a superior methodologic design but require larger sample sizes to detect important effects. We undertook a systematic review and a meta-analysis of prospective cohort studies to estimate the association of maternal FVL or PGM carrier status and placenta-mediated pregnancy complications. METHODS AND FINDINGS: A comprehensive search strategy was run in Medline and Embase. Inclusion criteria were: (1 prospective cohort design; (2 clearly defined outcomes including one of the following: pregnancy loss, small for gestational age, pre-eclampsia or placental abruption; (3 maternal FVL or PGM carrier status; (4 sufficient data for calculation of odds ratios (ORs. We identified 322 titles, reviewed 30 articles for inclusion and exclusion criteria, and included ten studies in the meta-analysis. The odds of pregnancy loss in women with FVL (absolute risk 4.2% was 52% higher (OR = 1.52, 95% confidence interval [CI] 1.06-2.19 as compared with women without FVL (absolute risk 3.2%. There was no significant association between FVL and pre-eclampsia (OR = 1.23, 95% CI 0.89-1.70 or between FVL and SGA (OR = 1.0, 95% CI 0.80-1.25. PGM was not associated with pre-eclampsia (OR = 1.25, 95% CI 0.79-1.99 or SGA (OR 1.25, 95% CI 0.92-1.70. CONCLUSIONS: Women with FVL appear to be at a small absolute increased risk of late pregnancy loss. Women with FVL and PGM appear not to be at increased risk of pre-eclampsia or birth of SGA infants. Please see later in the article for the Editors' Summary.

  15. Neural effects of prolonged mental fatigue: a magnetoencephalography study.

    Ishii, Akira; Tanaka, Masaaki; Shigihara, Yoshihito; Kanai, Etsuko; Funakura, Masami; Watanabe, Yasuyoshi


    Mental fatigue, manifest as a reduced efficiency for mental work load, is prevalent in modern society. It is important to understand the neural mechanisms of mental fatigue and to develop appropriate methods for evaluating mental fatigue. In this study we quantified the effect of a long-duration mental fatigue-inducing task on neural activity. We used magnetoencephalography (MEG) to examine the time course change of neural activity over the long duration of the task trials. Nine healthy male volunteers participated in this study. They performed two mental fatigue-inducing tasks on separate days. The order of task presentation was randomized in a single-blinded, crossover fashion. Each task consisted of 25-min mental fatigue-inducing 0- or 2-back task session for three times. Subjective rating of mental fatigue sensation and electrocardiogram, and resting state MEG measurements were performed just before and after each task session. MEG data were analyzed using narrow-band adaptive spatial filtering methods. Alpha band (8-13 Hz) power in the visual cortex decreased after performing the mental fatigue-inducing tasks, and the decrease of alpha power was greater when they performed 2-back task trials. The decrease in alpha power was positively associated with the self-reported level of mental fatigue sensation and sympathetic nerve activity level. These results demonstrate that performing the prolonged mental fatigue-inducing task causes overactivation of the visual cortex, manifest as decreased alpha power in this brain region. Our results increase understanding of the neural mechanisms of mental fatigue and can be used to develop new quantitative methods to assess mental fatigue.

  16. Prolonged cannabis withdrawal in young adults with lifetime psychiatric illness.

    Schuster, Randi Melissa; Fontaine, Madeleine; Nip, Emily; Zhang, Haiyue; Hanly, Ailish; Eden Evins, A


    Young adults with psychiatric illnesses are more likely to use cannabis and experience problems from use. It is not known whether those with a lifetime psychiatric illness experience a prolonged cannabis withdrawal syndrome with abstinence. Participants were fifty young adults, aged 18-25, recruited from the Boston-area in 2015-2016, who used cannabis at least weekly, completed the Structured Clinical Interview for DSM-IV to identify Axis I psychiatric diagnoses (PD+ vs PD-), and attained cannabis abstinence with a four-week contingency management protocol. Withdrawal symptom severity was assessed at baseline and at four weekly abstinent visits using the Cannabis Withdrawal Scale. Cannabis dependence, age of initiation, and rate of abstinence were similar in PD+ and PD- groups. There was a diagnostic group by abstinent week interaction, suggesting a difference in time course for resolution of withdrawal symptoms by group, F(4,46)=3.8, p=0.009, controlling for sex, baseline depressive and anxiety symptoms, and frequency of cannabis use in the prior 90days. In post hoc analyses, there was a difference in time-course of cannabis withdrawal. PD- had significantly reduced withdrawal symptom severity in abstinent week one [t(46)=-2.2, p=0.03], while PD+ did not report improved withdrawal symptoms until the second abstinent week [t(46)=-4.1, p=0.0002]. Cannabis withdrawal symptoms improved over four weeks in young people with and without a lifetime psychiatric diagnosis. However, those with a psychiatric illness reported one week delayed improvement in withdrawal symptom severity. Longer duration of cannabis withdrawal may be a risk factor for cannabis dependence and difficulty quitting. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Prolonged myelination in human neocortical evolution.

    Miller, Daniel J; Duka, Tetyana; Stimpson, Cheryl D; Schapiro, Steven J; Baze, Wallace B; McArthur, Mark J; Fobbs, Archibald J; Sousa, André M M; Sestan, Nenad; Wildman, Derek E; Lipovich, Leonard; Kuzawa, Christopher W; Hof, Patrick R; Sherwood, Chet C


    Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.




    In a pressurized heavy water reactor, following loss of the primary coolant, severe core damage would begin with the depletion of the liquid moderator, exposing the top row of internally-voided fuel channels to steam cooling conditions on the inside and outside. The uncovered fuel channels would heat up, deform and disassemble into core debris. Large inventories of water passively reduce the rate of progression of the accident, prolonging the time for complete loss of engineered heat sinks. ...

  19. Sulphasalazine: a safe, effective agent for prolonged control of rheumatoid arthritis. A comparison with sodium aurothiomalate.

    Bax, D E; Amos, R S


    The place of sulphasalazine in the management of rheumatoid arthritis over prolonged periods of time has been compared and contrasted with that of sodium aurothiomalate. One hundred and forty-three patients (59 on sulphasalazine, 84 on sodium aurothiomalate) have been treated for periods of up to 42 months. Sulphasalazine is highly effective for some patients, though probably less frequently than sodium aurothiomalate. However, its safety profile is far superior, and very long-term treatment ...

  20. Phentolamine mesylate: It′s role as a reversal agent for unwarranted prolonged local analgesia

    Harpreet Singh Grover; Anil Gupta; Neha Saksena; Neha Saini


    Administration of local anesthesia is an integral procedure prior to dental treatments to minimize the associated pain. It is learned that its effect stays more than the time required for the dental procedure to be completed. This prolonged soft tissue anesthesia (STA) can be detrimental, inconvenient, and unnecessary. Phentolamine mesylate, a Food and Drug Administration-approved drug essentially serves the purpose of faster recovery from numbness at the site of local anesthesia. This articl...

  1. Sulphasalazine: a safe, effective agent for prolonged control of rheumatoid arthritis. A comparison with sodium aurothiomalate.

    Bax, D E; Amos, R S


    The place of sulphasalazine in the management of rheumatoid arthritis over prolonged periods of time has been compared and contrasted with that of sodium aurothiomalate. One hundred and forty-three patients (59 on sulphasalazine, 84 on sodium aurothiomalate) have been treated for periods of up to 42 months. Sulphasalazine is highly effective for some patients, though probably less frequently than sodium aurothiomalate. However, its safety profile is far superior, and very long-term treatment ...

  2. Correcting magnesium deficiencies may prolong life

    Rowe WJ


    Full Text Available William J RoweFormer Assistant Clinical Professor of Medicine, Medical University of Ohio at Toledo, Ohio, USAAbstract: The International Space Station provides an extraordinary facility to study the accelerated aging process in microgravity, which could be triggered by significant reductions in magnesium (Mg ion levels with, in turn, elevations of catecholamines and vicious cycles between the two. With space flight there are significant reductions of serum Mg (P < 0.0001 that have been shown in large studies of astronauts and cosmonauts. The loss of the functional capacity of the cardiovascular system with space flight is over ten times faster than the course of aging on Earth. Mg is an antioxidant and calcium blocker and in space there is oxidative stress, insulin resistance, and inflammatory conditions with evidence in experimental animals of significant endothelial injuries and damage to mitochondria. The aging process is associated with progressive shortening of telomeres, repetitive DNA sequences, and proteins that cap and protect the ends of chromosomes. Telomerase can elongate pre-existing telomeres to maintain length and chromosome stability. Low telomerase triggers increased catecholamines while the sensitivity of telomere synthesis to Mg ions is primarily seen for the longer elongation products. Mg stabilizes DNA and promotes DNA replication and transcription, whereas low Mg might accelerate cellular senescence by reducing DNA stability, protein synthesis, and function of mitochondria. Telomerase, in binding to short DNAs, is Mg dependent. On Earth, in humans, a year might be required to detect changes in telomeres, but in space there is a predictably much shorter duration required for detection, which is therefore more reasonable in time and cost. Before and after a space mission, telomere lengths and telomerase enzyme activity can be determined and compared with age-matched control rats on Earth. The effect of Mg supplementation

  3. Optimism in prolonged grief and depression following loss: A three-wave longitudinal study.

    Boelen, Paul A


    There is considerable evidence that optimism, the predisposition to have generalized favorable expectancies for the future, is associated with numerous desirable outcomes. Few studies have examined the association of optimism with emotional distress following the death of a loved one. Doing so is important, because optimism may be an important target for interventions for post-loss psychopathology. In the current study, we examined the degree to which optimism, assessed in the first year post-loss (Time 1, T1), was associated with symptom levels of prolonged grief and depression six months (Time 2, T2) and fifteen months (Time 3, T3) later, controlling for baseline symptoms and also taking into account positive automatic cognitions at T1. Findings showed that higher optimism at T1 was associated with lower concurrent prolonged grief and depression severity. Higher optimism at T1 was also inversely related with depression symptom severity at T2 and T3, but not prolonged grief severity at T2 and T3. Implications of these findings are discussed.

  4. Prolonged ventilation post cardiac surgery - tips and pitfalls of the prediction game

    Knapik Piotr


    Full Text Available Abstract Background Few available models aim to identify patients at risk of prolonged ventilation after cardiac surgery. We compared prediction models developed in ICU in two adjacent periods of time, when significant changes were observed both in population characteristics and the perioperative management. Methods We performed a retrospective review of two cohorts of patients in our department in two subsequent time periods (July 2007 - December 2008, n = 2165; January 2009 - July 2010, n = 2192. The study was approved by the Institutional Ethics Committee and the individual patient consent was not required. Patients were divided with regard to ventilation time of more or less than 48 hours. Preoperative and procedure-related variables for prolonged ventilation were identified and multivariate logistic regression analysis was performed separately for each cohort. Results Most recent patients were older, with more co-morbidities, more frequently undergoing off-pump surgery. At the beginning of 2009 we also changed the technique of postoperative ventilation. Percentage of patients with prolonged ventilation decreased from 5.7% to 2.4% (p Conclusions Prediction models for postoperative ventilation should be regularly updated, particularly when major changes are noted in patients' demographics and surgical or anaesthetic technique.

  5. Constrained spheroids for prolonged hepatocyte culture.

    Tong, Wen Hao; Fang, Yu; Yan, Jie; Hong, Xin; Hari Singh, Nisha; Wang, Shu Rui; Nugraha, Bramasta; Xia, Lei; Fong, Eliza Li Shan; Iliescu, Ciprian; Yu, Hanry


    Liver-specific functions in primary hepatocytes can be maintained over extended duration in vitro using spheroid culture. However, the undesired loss of cells over time is still a major unaddressed problem, which consequently generates large variations in downstream assays such as drug screening. In static culture, the turbulence generated by medium change can cause spheroids to detach from the culture substrate. Under perfusion, the momentum generated by Stokes force similarly results in spheroid detachment. To overcome this problem, we developed a Constrained Spheroids (CS) culture system that immobilizes spheroids between a glass coverslip and an ultra-thin porous Parylene C membrane, both surface-modified with poly(ethylene glycol) and galactose ligands for optimum spheroid formation and maintenance. In this configuration, cell loss was minimized even when perfusion was introduced. When compared to the standard collagen sandwich model, hepatocytes cultured as CS under perfusion exhibited significantly enhanced hepatocyte functions such as urea secretion, and CYP1A1 and CYP3A2 metabolic activity. We propose the use of the CS culture as an improved culture platform to current hepatocyte spheroid-based culture systems.

  6. Análise da mutação G20210A no gene da protrombina (fator II em pacientes com suspeita de trombofilia no sul do Brasil Analysis of prothrombin G20210A mutation (factor II in patients with suspected trombophilia in Southern Brazil

    Marcos Edgar Herkenhoff


    Full Text Available INTRODUÇÃO: A protrombina (fator II é uma proteína sanguínea sintetizada no fígado com a presença de vitamina K. É a precursora da trombina, que induz a formação de fibrina. Foi descrita uma mutação no gene da protrombina G20210A, associada diretamente a altos níveis de protrombina no sangue e, consequentemente, à trombofilia. Essa variante alélica consiste em mutação pontual, também chamada de polimorfismo de nucleotídeo simples (SNP, ocasionando a troca de uma guanina por uma adenina no nucleotídeo 20210, localizado em um sítio de clivagem do precursor do ácido ribonucleico mensageiro (mRNA. Essa troca caracteriza o alelo A e a ausência da mutação do alelo G. OBJETIVO: Quantificar o número de indivíduos homozigotos para alelo G, homozigotos para alelo A e heterozigotos, cujas amostras foram enviadas para o laboratório Genolab Análises Genéticas, abrangendo os estados do Paraná e Santa Catarina, no período de 1º de janeiro de 2009 a 10 de outubro de 2010. MÉTODOS: Análise de mutação pontual por reação em cadeia da polimerase em tempo real (RT-PCR. RESULTADOS: Obtivemos o número de 243 indivíduos e desse total 51,03% eram oriundos do estado do Paraná, enquanto 48,97%, oriundos do estado de Santa Catarina. Do total analisado, 88,89% possuíam o genótipo para homozigoto G, e nenhum indivíduo foi encontrado com mutação para homozigoto A. Apenas 11,11% possuíam genótipo heterozigoto. O estado de Santa Catarina apresentou frequência superior para genótipo heterozigoto em relação ao Paraná. CONCLUSÃO: Este estudo mostrou que é recomendável a identificação do genótipo para esse gene em pacientes com suspeita de trombofilia nos dois estados.INTRODUCTION: Prothrombin (factor II is a blood protein synthesized in the liver in the presence of vitamin K. It is a thrombin precursor, which induces fibrin formation. Prothrombin G20210A mutation and high prothrombin levels have been closely associated

  7. Nucleic acid therapy for lifespan prolongation: Present and future

    Wing-Fu Lai


    Lifespan prolongation is a common desire of the human race. With advances in biotechnology, the mechanism of aging has been gradually unraveled, laying the theoretical basis of nucleic acid therapy for lifespan prolongation. Regretfully, clinically applicable interventions do not exist without the efforts of converting theory into action, and it is the latter that has been far from adequately addressed at the moment. This was demonstrated by a database search on PubMed and Web of Science, from which only seven studies published between 2000 and 2010 were found to directly touch on the development of nucleic acid therapy for anti-aging and/or longevity enhancing purposes. In light of this, the objective of this article is to overview the current understanding of the intimate association between genes and longevity, and to bring the prospect of nucleic acid therapy for lifespan prolongation to light.

  8. Severe postpartum sepsis with prolonged myocardial dysfunction: a case report

    Chen Katherine T


    Full Text Available Abstract Introduction Severe sepsis during pregnancy or in the postpartum period is a rare clinical event. In non obstetric surviving patients, the cardiovascular changes seen in sepsis and septic shock are fully reversible five to ten days after their onset. We report a case of septic myocardial dysfunction lasting longer than ten days. To the best of our knowledge, this is the first report of prolonged septic myocardial dysfunction in a parturient. Case presentation A 24 year old Hispanic woman with no previous medical history developed pyelonephritis and severe sepsis with prolonged myocardial dysfunction after a normal spontaneous vaginal delivery. Conclusions Septic myocardial dysfunction may be prolonged in parturients requiring longer term follow up and pharmacologic treatment.

  9. QT prolongation in a child with thyroid storm

    Albert, Benjamin B; Eckersley, Luke Gerard; Skinner, Jonathan Robert; Jefferies, Craig


    Summary A 12-year-old girl presented with an acute confusional state and a 2-year history of weight loss, anxiety, agitation and recurrent fever. Thyroid function tests confirmed severe hyperthyroidism, and a diagnosis of thyroid storm was made (Burch and Wartofsky score=75). ECG showed a prolonged QTc interval of 506 ms. Acute treatment for thyroid storm consisted of Lugol's iodine, prednisolone, carbimazole and propranolol. She made a steady recovery and by 3 months her thyroid function had normalised; a repeat ECG showed a QTc within the normal range (430 ms). There was no relevant family history. This is a case of QTc prolongation with hyperthyroidism and normalisation with euthyroidism. It is not commonly recognised that hyperthyroidism in children may be associated with QTc prolongation. QTc measurement should be incorporated into management protocols for hyperthyroidism. PMID:24729112

  10. Bartonella henselae Infective Endocarditis Detected by a Prolonged Blood Culture

    Mito, Tsutomu; Hirota, Yusuke; Suzuki, Shingo; Noda, Kazutaka; Uehara, Takanori; Ohira, Yoshiyuki; Ikusaka, Masatomi


    A 65-year-old Japanese man was admitted with a 4-month history of fatigue and exertional dyspnea. Transthoracic echocardiography revealed a vegetation on the aortic valve and severe aortic regurgitation. Accordingly, infective endocarditis and heart failure were diagnosed. Although a blood culture was negative on day 7 after admission, a prolonged blood culture with subculture was performed according to the patient's history of contact with cats. Consequently, Bartonella henselae was isolated. Bartonella species are fastidious bacteria that cause blood culture-negative infective endocarditis. This case demonstrates that B. henselae may be detected by prolonged incubation of blood cultures. PMID:27746451

  11. Prolonged nerve blockade in a patient treated with lithium

    Lehavi A


    Full Text Available Amit Lehavi, Boris Shenderey, Yeshayahu (Shai KatzDepartment of Anesthesiology, Rambam Health Care Campus, Haifa, IsraelAbstract: We report a case of a patient, chronically treated with oral lithium, who presented with an extremely prolonged (42-hour duration of sensory and motor paralysis following an uneventful infraclavicular block for hand surgery that was performed under ultrasound guidance using bupivacaine and lidocaine. Due to its direct effect on nerve conduction of action potential, we propose that lithium may have had a role in the unusually prolonged duration of a peripheral nerve block.Keywords: nerve blockade, lithium, duration, anesthesia

  12. Changes in the human blood coagulating system during prolonged hypokinesia

    Filatova, L. M.; Anashkin, O. D.


    Changes in the coagulating system of the blood were studied in six subjects during prolonged hypokinesia. Thrombogenic properties of the blood rose in all cases on the 8th day. These changes are explained by stress reaction due to unusual conditions for a healthy person. Changes in the blood coagulating system in the group subjected to physical exercise and without it ran a practically parallel course. Apparently physical exercise is insufficient to prevent such changes that appear in the coagulating system of the blood during prolonged hypokinesia.

  13. Hypoglycaemia and QT interval prolongation in type 1 diabetes

    Christensen, Toke Folke; Cichosz, Simon Lebech; Tarnow, L.


    hypoglycaemia varies greatly between studies. METHODS: We studied ten adults with type 1 diabetes (age 41±15years) without cardiovascular disease or neuropathy. Single-blinded hypoglycaemia was induced by a subcutaneous insulin bolus followed by a control episode on two occasions separated by 4weeks. QT....... CONCLUSIONS: Hypoglycaemia as experienced after a subcutaneous injection of insulin may cause QTc prolongation in type 1 diabetes. However, the magnitude of prolongation is less than typically reported during glucose clamp studies, possible because of the study design with focus on minimizing unwanted study...

  14. Backup and Ultimate Heat Sinks in CANDU Reactors For Prolonged SBO Accidents

    Nitheanandan, T.; Brown, M. J. [Atomic Energy of Canada Limited, Ontario (Canada)


    In a pressurized heavy water reactor, following loss of the primary coolant, severe core damage would begin with the depletion of the liquid moderator, exposing the top row of internally-voided fuel channels to steam cooling conditions on the inside and outside. The uncovered fuel channels would heat up, deform and disassemble into core debris. Large inventories of water passively reduce the rate of progression of the accident, prolonging the time for complete loss of engineered heat sinks. The efficacy of available backup and ultimate heat sinks, available in a CANDU 6 reactor, in mitigating the consequences of a prolonged station blackout scenario was analysed using the MAAP4-CANDU code. The analysis indicated that the steam generator secondary side water inventory is the most effective heat sink during the accident. Additional heat sinks such as the primary coolant, moderator, calandria vault water and end shield water are also able to remove decay heat; however, a gradually increasing mismatch between heat generation and heat removal occurs over the course of the postulated event. This mismatch is equivalent to an additional water inventory estimated to be 350,000 kg at the time of calandria vessel failure. In the Enhanced CANDU 6 reactor ∼2,040,000 kg of water in the reserve water tank is available for prolonged emergencies requiring heat sinks.

  15. Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children.

    Ashrafi, Mahmoud Reza; Khosroshahi, Nahid; Karimi, Parviz; Malamiri, Reza Azizi; Bavarian, Behrouz; Zarch, Anoushiravan Vakili; Mirzaei, Mehdi; Kompani, Farshid


    A Prolonged convulsive seizure is the most common neurological medical emergency with poor outcome. An ideal anticonvulsant should be easy-to-use, effective, and safe, and it should also have a long-lasting effect. Benzodiazepines, give via the intravenous or rectal route have generally been used as first-line drugs. In small children, IV access can be difficult and time consuming. Midazolam is a potent anticonvulsant and is rapidly absorbed from the rectal, nasal, and buccal mucosa. Our aim was to evaluate the efficacy and usability of buccal midazolam in controlling seizures in children with acute prolonged seizures, by comparing it with rectal diazepam. Ninety-eight patients were enrolled, with 49 patients in each treatment group. In the buccal midazolam group, 42 (88%) patients were controlled in less than 4 min of drug administration, and all of the patients were controlled within 5 min of drug administration. In the rectal diazepam group, 24 (49%) patients were controlled in less than 4 min and 40 (82%) patients were controlled within 5 min of drug administration. The time for drug administration and drug effect was significantly less with buccal midazolam than with rectal diazepam (p valuediazepam group, 7 (14%) parents were satisfied. Buccal midazolam was significantly more acceptable than rectal diazepam (p valuediazepam but more convenient to use in the controlling acute prolonged seizures in children, especially in situations in which there is a difficulty in gaining IV access, for example, in infants.

  16. Prolonged second stage of labor is associated with low Apgar score.

    Altman, Maria; Sandström, Anna; Petersson, Gunnar; Frisell, Thomas; Cnattingius, Sven; Stephansson, Olof


    There is no consensus on the effects of a prolonged second stage of labor on neonatal outcomes. In this large Swedish population-based cohort study, our objective was to investigate prolonged second stage and risk of low Apgar score at 5 min. All nulliparous women (n = 32,796) delivering a live born singleton infant in cephalic presentation at ≥37 completed weeks after spontaneous onset of labor between 2008 and 2012 in the counties of Stockholm and Gotland were included. Data were obtained from computerized records. Exposure was time from fully retracted cervix until delivery. Logistic regression analyses were used to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Adjustments were made for maternal age, height, BMI, smoking, sex, gestational age, sex-specific birth weight for gestational age and head circumference. Epidural analgesia was included in a second model. The primary outcome measure was Apgar score at 5 min Apgar score Apgar score Apgar score.




    The efficacy of available backup and ultimate heat sinks, available in a CANDU 6 reactor, in mitigating the consequences of a prolonged station blackout scenario was analysed using the MAAP4-CANDU code. The analysis indicated that the steam generator secondary side water inventory is the most effective heat sink during the accident. Additional heat sinks such as the primary coolant, moderator, calandria vault water and end shield water are also able to remove decay heat; however, a gradually increasing mismatch between heat generation and heat removal occurs over the course of the postulated event. This mismatch is equivalent to an additional water inventory estimated to be 350,000 kg at the time of calandria vessel failure. In the Enhanced CANDU 6 reactor ∼2,040,000 kg of water in the reserve water tank is available for prolonged emergencies requiring heat sinks.

  18. Prognosis in prolonged coma patients with diffuse axonal injury assessed by somatosensory evoked potential

    Xiujue Zheng; Mantao Chen; Jingqi Li; Fei Cao


    A total of 43 prolonged coma patients with diffuse axonal injury received the somatosensory evoked potential examination one month after injury in the First Affiliated Hospital, School of Medicine, Zhejiang University in China. Somatosensory evoked potentials were graded as normal, abnormal or absent (grades I–III) according to N20 amplitude and central conduction time. The outcome in patients with grade III somatosensory evoked potential was in each case unfavorable. The prognostic accuracy of grade III somatosensory evoked potential for unfavorable and non-awakening outcome was 100% and 80%, respectively. The prognostic accuracy of grade I somatosensory evoked potential for favorable and wakening outcome was 86% and 100%, respectively. These results suggest that somatosensory evoked potential grade is closely correlated with coma severity and degree of recovery. Somatosensory evoked potential is a valuable diagnostic tool to assess prognosis in prolonged coma patients with diffuse axonal injury.

  19. [Prolonged release of chlorambucil and etoposide from poly-3-oxybutyrate-based microspheres].

    Filatova, E V; Iakovlev, S G; Bonartsev, A P; Makhina, T K; Myshkina, V L; Bonartseva, G A


    Microspheres were obtained on the basis of poly(3-oxibutyrate) (POB) with the inclusion of the Chlorambucil and Etoposide cytostatic drugs in a polymer matrix, and the morphology, kinetics of drug release from microspheres, and the interaction between microspheres and tumor cells in vitro were studied. Data on the kinetics of drug release suggests that a prolonged release occurs by drug diffusion from the polymer matrix at the initial stage and at the expense of hydrolytic degradation of the polymer at a later stage. A study of the biocompatibility and biological activity of biopolymeric microspheres showed that chlorambucil operates actively and strongly inhibits the growth of cultured cells for a short time (24 h). Etoposide acts weaker (the percentage of cell growth suppression during 48 h does not exceed 50%), but subsequently it has a basis for the creation of new dosage forms with prolonged action of Etoposide and chlorambucil for cancer therapy.

  20. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder

    Baandrup, Lone; Lindschou, Jane; Winkel, Per


    OBJECTIVES: We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder. METHODS: Randomised, placebo-controlled, blinded, parallel superiority trial of 24 weeks duration. Participants were randomised...... to prolonged-release melatonin 2 mg daily versus matching placebo and were continuously guided to gradually reduce their usual benzodiazepine dosage. The primary outcome was mean benzodiazepine daily dosage at 24 weeks. Secondary outcomes included pattern of benzodiazepine dosage over time, benzodiazepine...... cessation proportion, and benzodiazepine withdrawal symptoms. RESULTS: In total, 86 patients (21-74 years) were enrolled: 42 were randomised to melatonin versus 44 to placebo. We found no significant effect of melatonin on mean benzodiazepine dosage at 24 weeks (melatonin group 8.01 mg versus placebo group...

  1. Risk of placenta-mediated pregnancy complications or pregnancy-related VTE in VTE-asymptomatic families of probands with VTE and heterozygosity for factor V Leiden or G20210 prothrombin mutation.

    Cordoba, Iris; Pegenaute, Carlota; González-López, Tomás José; Chillon, Carmen; Sarasquete, Maria Eugenia; Martin-Herrero, Francisco; Guerrero, Carmen; Cabrero, Mónica; Garcia Sanchez, Maria Helena; Pabon, Pedro; Lozano, Francisco Santiago; Gonzalez, Marcos; Alberca, Ignacio; González-Porras, José Ramón


    Few studies have evaluated the risk of pregnancy-related adverse events in asymptomatic relatives of probands for VTE and factor V Leiden or the G20210A variant. The antepartum management of this population ranges from antepartum anticoagulation therapy to clinical surveillance. To evaluate the risk of placenta-mediated pregnancy complications and pregnancy-related VTE in VTE-asymptomatic families of probands with VTE and who are heterozygous carriers of either factor V Leiden or PT-G20210A mutation. One hundred and fifty-eight relatives, who had 415 pregnancies, were retrospectively evaluated. Odds ratios and 95% confidence intervals were calculated to compare pregnancy outcomes between women with and without thrombophilia. In the factor V Leiden group, 22 placenta-mediated pregnancy events of 152 pregnancies (14.4%) were reported, compared with 25 adverse events of 172 pregnancies in the G20210A prothrombin group (14.5%) and 13 adverse events of 91 pregnancies in the non-carrier group (14.2%). Carriers of factor V Leiden or G20210A prothrombin were not associated with a higher risk of pregnancy-adverse outcomes compared with non-carriers: OR 1.02 (95% CI, 0.40-2.25) and 1.25 (95% CI, 0.48-3.24), respectively. Four episodes of pregnancy-associated VTE of 415 pregnancies (0.96%) were recorded. Two episodes of VTE in the G20210A group, one in the factor V Leiden group, and one episode in the non-carrier group were noted. In VTE-asymptomatic relatives of probands with VTE, the presence of factor V Leiden or the G20210A prothrombin mutation in heterozygosis should not lead to a decision to instigate antepartum prophylaxis. © 2012 John Wiley & Sons A/S.

  2. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    Cros, C., E-mail: [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Skinner, M., E-mail: [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Moors, J. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Lainee, P. [Sanofi-Aventis R and D, 371, rue du Pr Joseph Blayac, 34184 Montpellier Cedex 04 (France); Valentin, J.P. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom)


    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two

  3. Repeated Prolonged Exercise Decreases Maximal Fat Oxidation in Older Men

    Morville, Thomas; Rosenkilde, Mads; Munch-Andersen, Thor


    INTRODUCTION/PURPOSE: Fat metabolism and muscle adaptation was investigated in 6 older trained men (age: 61 ± 4 years; VO2max: 48 ± 2 mL kg min) following repeated prolonged exercise). METHODS: 2706 km (1,681 miles) cycling was performed over 14 days and a blood sample and a muscle biopsy were...

  4. Prolonged unassisted survival in an infant with anencephaly.

    Dickman, Holly; Fletke, Kyle; Redfern, Roberta E


    Anencephaly is one of the most lethal congenital defects. This case report is of an anencephalic infant who lived to 28 months of life and defies current literature. She is the longest surviving anencephalic infant who did not require life-sustaining interventions. This case presents the obstacles that arose from this infant's prolonged life and recommendations based on these findings.

  5. Single Prolonged Stress Disrupts Retention of Extinguished Fear in Rats

    Knox, Dayan; George, Sophie A.; Fitzpatrick, Christopher J.; Rabinak, Christine A.; Maren, Stephen; Liberzon, Israel


    Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress…

  6. Intrinsic motivation and amotivation in first episode and prolonged psychosis.

    Luther, Lauren; Lysaker, Paul H; Firmin, Ruth L; Breier, Alan; Vohs, Jenifer L


    The deleterious functional implications of motivation deficits in psychosis have generated interest in examining dimensions of the construct. However, there remains a paucity of data regarding whether dimensions of motivation differ over the course of psychosis. Therefore, this study examined two motivation dimensions, trait-like intrinsic motivation, and the negative symptom of amotivation, and tested the impact of illness phase on the 1) levels of these dimensions and 2) relationship between these dimensions. Participants with first episode psychosis (FEP; n=40) and prolonged psychosis (n=66) completed clinician-rated measures of intrinsic motivation and amotivation. Analyses revealed that when controlling for group differences in gender and education, the FEP group had significantly more intrinsic motivation and lower amotivation than the prolonged psychosis group. Moreover, intrinsic motivation was negatively correlated with amotivation in both FEP and prolonged psychosis, but the magnitude of the relationship did not statistically differ between groups. These findings suggest that motivation deficits are more severe later in the course of psychosis and that low intrinsic motivation may be partially independent of amotivation in both first episode and prolonged psychosis. Clinically, these results highlight the importance of targeting motivation in early intervention services.

  7. Single Prolonged Stress Disrupts Retention of Extinguished Fear in Rats

    Knox, Dayan; George, Sophie A.; Fitzpatrick, Christopher J.; Rabinak, Christine A.; Maren, Stephen; Liberzon, Israel


    Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress…

  8. The impact of obesity on physiological responses during prolonged exercise

    Eijsvogels, T.M.H.; Veltmeijer, M.T.; Schreuder, T.H.A.; Poelkens, F.; Thijssen, D.H.J.; Hopman, M.T.E.


    Background:Prolonged, moderate-intensity exercise training is routinely prescribed to subjects with obesity. In the general population, this type of exercise can lead to fluid and sodium imbalance. However, little is known whether obesity alters the risk of fluid and sodium imbalances.Objective:This

  9. Examining potential contraindications for prolonged exposure therapy for PTSD

    Minnen, A. van; Harned, M.S.; Zöllner, L.; Mills, K.


    Although prolonged exposure (PE) has received the most empirical support of any treatment for posttraumatic stress disorder (PTSD), clinicians are often hesitant to use PE due to beliefs that it is contraindicated for many patients with PTSD. This is especially true for PTSD patients with comorbid p

  10. Cerebral ammonia uptake and accumulation during prolonged exercise in humans

    Nybo, Lars; Dalsgaard, Mads K.; Steensberg, Adam


    We evaluated whether peripheral ammonia production during prolonged exercise enhances the uptake and subsequent accumulation of ammonia within the brain. Two studies determined the cerebral uptake of ammonia (arterial and jugular venous blood sampling combined with Kety-Schmidt-determined cerebra...

  11. Prolonged drought results in starvation of African elephant (Loxodonta africana)

    Wato, Yussuf A.; Heitkonig, Ignas; Wieren, van Sipke E.; Wahungu, Geoffrey; Prins, Herbert H.T.; Langevelde, van Frank


    Elephant inhabiting arid and semi-arid savannas often experience periods of drought, which, if prolonged, may cause mortality. During dry periods, elephant aggregate around water sources and deplete local forage availability. However, the relationships between adult elephant mortality and both hi

  12. The carotid baroreflex is reset following prolonged exercise in humans

    Hart, E. C.; Rasmussen, P.; Secher, N. H.


    Alterations in the carotid baroreflex (CBR) control of arterial pressure may explain the reduction in arterial pressure and left ventricular (LV) function after prolonged exercise. We examined the CBR control of heart rate (HR) and mean arterial pressure (MAP), in addition to changes in LV function......, pre- to post-exercise....

  13. Economic viability of beef cattle grazing systems under prolonged drought

    Prolonged drought in the Southern Great Plains of the USA in recent years has raised concerns about vulnerability of beef cattle grazing systems under adverse climate change. To help address the economic viability of beef grazing operations in the Southern Great Plains, this paper provides an econom...

  14. Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures

    Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle


    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal…

  15. The Prolonged Neonatal Admission: Implications for our National Children's Hospital

    McGlacken-Byrne, SM


    A significant number of neonates are admitted to tertiary paediatric units for prolonged stays annually, despite limited availability of neonatal beds. As the three Dublin paediatric hospitals merge, this pressure will be transferred to our new National Children’s Hospital.\\r\

  16. Prolongation Structure of Semi-discrete Nonlinear Evolution Equations


    Based on noncommutative differential calculus, we present a theory of prolongation structure for semi-discrete nonlinear evolution equations. As an illustrative example, a semi-discrete model of the nonlinear Schr(o)dinger equation is discussed in terms of this theory and the corresponding Lax pairs are also given.

  17. Prolonged drought results in starvation of African elephant (Loxodonta africana)

    Wato, Yussuf A.; Heitkonig, Ignas; Wieren, van Sipke E.; Wahungu, Geoffrey; Prins, Herbert H.T.; Langevelde, van Frank


    Elephant inhabiting arid and semi-arid savannas often experience periods of drought, which, if prolonged, may cause mortality. During dry periods, elephant aggregate around water sources and deplete local forage availability. However, the relationships between adult elephant mortality and both

  18. Assessing QT Interval Prolongation and its Associated Risks with Antipsychotics

    Nielsen, Jimmi; Graff, Claus; Kanters, Jørgen K.


    markers for TdP have been developed but none of them is clinically implemented yet and QT interval prolongation is still considered the most valid surrogate marker. Although automated QT interval determination may offer some assistance, QT interval determination is best performed by a cardiologist skilled...

  19. Assessing QT interval prolongation and its associated risks with antipsychotics

    Nielsen, Jimmi; Graff, Claus; Kanters, Jørgen K.


    markers for TdP have been developed but none of them is clinically implemented yet and QT interval prolongation is still considered the most valid surrogate marker. Although automated QT interval determination may offer some assistance, QT interval determination is best performed by a cardiologist skilled...

  20. Effect of prolonged bed rest on the anterior hip muscles.

    Dilani Mendis, M; Hides, Julie A; Wilson, Stephen J; Grimaldi, Alison; Belavý, Daniel L; Stanton, Warren; Felsenberg, Dieter; Rittweger, Joern; Richardson, Carolyn


    Prolonged bed rest and inactivity is known to cause muscular atrophy with previous research indicating that muscles involved in joint stabilisation are more susceptible. The anterior hip muscles are important for hip joint function and stability but little is known about the effects of prolonged inactivity on their function. This study investigated the effect of prolonged bed rest on the size of the anterior hip muscles and their pattern of recovery. The effect of resistive vibration exercise (RVE) as a countermeasure to muscle atrophy was also investigated. 12 male participants, randomly assigned to either a control or an exercise group, underwent 8 weeks of bed rest with 6 months follow-up. Changes in muscle cross-sectional area (CSA) of the iliacus, psoas, iliopsoas, sartorius and rectus femoris muscles were measured by magnetic resonance imaging at regular intervals during bed rest and recovery phases. CSAs of iliopsoas and sartorius decreased at the hip joint (piliacus, psoas, and rectus femoris CSAs were unchanged (p>0.05). No significant difference was found between the two groups for all muscles (all p>0.1), suggesting inefficacy of the countermeasure in this sample. These findings suggest that prolonged bed rest can result in the atrophy of specific muscles across the hip joint which may affect its stability and function.

  1. Prolonged idiopathic gastric dilatation following revascularization for chronic mesenteric ischemia.

    Gauci, Julia L; Stoven, Samantha; Szarka, Lawrence; Papadakis, Konstantinos A


    A 71-year-old female presented with nausea, emesis, early satiety, and abdominal distension following revascularization for chronic mesenteric ischemia. Computed tomography angiogram showed gastric dilatation. Esophagogastroduodenoscopy, small bowel follow through, and paraneoplastic panel were negative. Gastric emptying was delayed. Despite conservative management, she required a percutaneous endoscopic jejunostomy. The development of a prolonged gastroparetic state has not been previously described.

  2. Delirium in Prolonged Hospitalized Patients in the Intensive Care Unit

    Vahedian Azimi


    Full Text Available Background Prolonged hospitalization in the intensive care unit (ICU can impose long-term psychological effects on patients. One of the most significant psychological effects from prolonged hospitalization is delirium. Objectives The aim of this study was to assess the effect of prolonged hospitalization of patients and subsequent delirium in the intensive care unit. Patients and Methods This conventional content analysis study was conducted in the General Intensive Care Unit of the Shariati Hospital of Tehran University of Medical Sciences, from the beginning of 2013 to 2014. All prolonged hospitalized patients and their families were eligible participants. From the 34 eligible patients and 63 family members, the final numbers of actual patients and family members were 9 and 16, respectively. Several semi-structured interviews were conducted face-to-face with patients and their families in a private room and data were gathered. Results Two main themes from two different perspectives emerged, 'patients' perspectives' (experiences during ICU hospitalization and 'family members' perspectives' (supportive-communicational experiences. The main results of this study focused on delirium, Patients' findings were described as pleasant and unpleasant, factual and delusional experiences. Conclusions Family members are valuable components in the therapeutic process of delirium. Effective use of family members in the delirium caring process can be considered to be one of the key non-medical nursing components in the therapeutic process.

  3. Management and outcome of prolonged pregnancies in Shariati university hospital

    Eslamian L.


    Full Text Available Background: There is dearth of reports from Iran regarding the prevalence of postterm pregnancy and its complications. The present study was conducted to evaluate the prevalence, management and outcome of prolonged pregnancies.Methods: This cross-sectional study included data from the hospital records of all women referred to Shariati Hospital, Tehran, from 2001 to 2002 with pregnancies of more than 40 weeks in duration. Pregnancies ≥40-42 weeks were considered postdate and those more than 42 weeks postterm pregnancy. The data compiled from the hospital records were subjected to t, χ2 and Mann-Whitney U tests.Results: Of the 1500 deliveries in this hospital, 98 patients were included in this study, 66.3% of whom were nullipara and 33.7% multipara. The prevalence of postterm pregnancy was estimated to be 3.3%. Cervix dilation of 2 cm or less on admission occurred in 65 women (73.3%. The mean Bishop score was 4.31. Of the 62 fetuses that underwent assessment tests, 54 (87.1% were normal. The median time between the last test and induction of labor was 2.1 days, and 2.6 days for cesarean deliveries, which was not a significant difference (P=0.6. Cervical ripening with misoprostrol was performed in 36 cases (36.7% and was successful in 18 cases. In this group, the median time for cervical ripening in multiparas was significantly less than nulliparas (4 vs. 7 hrs, P=0.004. Women not subjected to cervical ripening had a higher cesarean rate than those who did undergo cervical ripening (74.7% vs. 66.1%, although this difference was not significant (P=0.9. Vaginal and cesarean delivery rates showed no significant difference between cases that underwent induction with oxytocin and those subjected to cervical ripening with misoprostol (P=0.9. The mean Apgar score was 9.5, with all scores above 6. There were no cases of neonatal hypoglycemia, hypocalcemia, NICU admission or prenatal death. The mean nursery stay was 1.84 days with a range of 1-8 days

  4. Transient increase of interleukin-1β after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling.

    Feng, Bo; Tang, Yangshun; Chen, Bin; Xu, Cenglin; Wang, Yi; Dai, Yunjian; Wu, Dengchang; Zhu, Junmin; Wang, Shuang; Zhou, Yudong; Shi, Liyun; Hu, Weiwei; Zhang, Xia; Chen, Zhong


    It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1β (IL-1β) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1β alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1β treatment. Prolonged FS or early-life IL-1β treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1β-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1β/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS.

  5. Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA1 pyramidal cells in rat hippocampus.

    Gage, P W; Robertson, B


    Spontaneous inhibitory postsynaptic currents (i.p.s.cs) were recorded in voltage-clamped CA1 neurones in rat hippocampal slices. The exponential decay of i.p.s.cs was prolonged by concentrations of sodium pentobarbitone as low as 50 microM. With concentrations up to 100 microM, there was no change in the amplitude or rise time of the currents but current amplitude was depressed at 200 microM. The prolongation of currents increased with drug concentration within the range tested (50 to 200 mic...

  6. Experimental and theoretical study of the transport of silver nanoparticles at their prolonged administration into a mammal organism

    Antsiferova, A. A.; Buzulukov, Yu. P.; Kashkarov, P. K.; Kovalchuk, M. V.


    The transport of silver nanoparticles in the organism of laboratory animals has been investigated. A mathematical model of the biokinetics of prolonged administration of nonmetabolizable and nonaglomerating pharmaceutical preparations is proposed, and its analytical solution is found. Based on the experimental data on the prolonged introduction and excretion of colloidal silver nanoparticles and the numerical approximation of the solutions to the equations for the proposed model, time dependences of the silver mass content in brain and blood are obtained and some other important biokinetic parameters are determined. It is concluded that both chronic1 and subchronic2 peroral application of these nanoparticles as an biologically active additive or antiseptic is potentially dangerous.

  7. Fragmento 1+2 da protrombina em indivíduos submetidos à angiografia coronariana Prothrombin fragment 1+2 in subjects undergoing coronary angiography

    Luciana M. Lima


    transforms the prothrombin into thrombin and breaks up prothrombin fragment 1+2 (F1+2. F1+2 plasma levels reflect the thrombin generation and can be used as in vivo markers of hypercoagulability since the thrombin is an unstable and easily degraded substance that cannot be directly measured in the plasma. The present study aims at determining the F1+2 plasma levels of a group of subjects undergoing coronary angiography, attempting to establish a possible correlation between this parameter and the severity of the coronary artery disease. F1+2 plasma levels were determined in blood samples of 17 subjects with absence of atheromatosis in coronary arteries (controls, 12 subjects presenting mild/moderate atheromatosis and 28 subjects presenting severe atheromatosis, using the Enzignost F1+2 (Behring® Diagnostics GmbH, Marburg, Germany diagnostic Kit. Significant differences between the averages for the three groups in respect to the evaluated parameters were not found. Therefore, F1+2 plasma level averages for the three groups did not point to a state of hypercoagulability in the studied population. However, 73.7% of the individuals were taking acetylsalicylic acid, which may have influenced the F1+2 plasma levels, considering that this medicine promotes the inhibition of the enzyme cyclo-oxygenase, diminishing the release of thromboxane A2 and the platelet aggregation. Therefore, it is presumed that platelet activation reduction could be contributing to a lower formation of thrombin and, consequently, diminishing the hypercoagulability potential.

  8. Assessment of Muscle Fatigue Associated with Prolonged Standing in the Workplace

    Omar, Abdul Rahman; Saman, Alias Mohd; Othman, Ibrahim


    Objectives The objectives of this study were to determine the psychological fatigue and analyze muscle activity of production workers who are performing processes jobs while standing for prolonged time periods. Methods The psychological fatigue experienced by the workers was obtained through questionnaire surveys. Meanwhile, muscle activity has been analyzed using surface electromyography (sEMG) measurement. Lower extremities muscles include: erector spinae, tibialis anterior, and gastrocnemius were concurrently measured for more than five hours of standing. Twenty male production workers in a metal stamping company participated as subjects in this study. The subjects were required to undergo questionnaire surveys and sEMG measurement. Results Results of the questionnaire surveys found that all subjects experienced psychological fatigue due to prolonged standing jobs. Similarly, muscle fatigue has been identified through sEMG measurement. Based on the non-parametric statistical test using the Spearman's rank order correlation, the left erector spinae obtained a moderate positive correlation and statistically significant (rs = 0.552, p < 0.05) between the results of questionnaire surveys and sEMG measurement. Conclusion Based on this study, the authors concluded that prolonged standing was contributed to psychological fatigue and to muscle fatigue among the production workers. PMID:22953228

  9. An experimental study on embankment failure induced by prolonged immersion in floodwater

    Yu-long Luo


    Full Text Available Prolonged immersion in floodwater is one of the main causes of embankment failure or dam breaks, although failure mechanisms have not been extensively studied. In this study, an embankment model was constructed to investigate the influence of prolonged immersion in floodwater on the failure of an embankment. The results indicate that: (1 the phreatic surface gradually rises and negative pore pressures gradually dissipate with the time of prolonged immersion in floodwater, and, finally, a stable and fully saturated state is reached; (2 observable cracks and a heave phenomenon are found near the downstream toe and in the top stratum of the foundation, which are attributed to the large uplift pressure on the interface between the top stratum and the pervious substratum, the tremendous impact effect induced by the rapid rise in water level, and the reduction of shear strength of heavy silt loam. The present study enhances our in-depth knowledge of the mechanisms of embankment failure induced by floodwater, and provides experimental data for validation of mathematical models of the embankment seepage failure.


    Laura Guidetti


    Full Text Available The objective of the study was to verify whether young males' balance was affected by 30min prolonged treadmill running (TR at individual ventilatory (IVT and anaerobic (IAT thresholds in recovery time. The VO2max, IAT and IVT during an incremental TR were determined. Mean displacement amplitude (Acp and velocity (Vcp of center of pressure were recorded before (pre and after (0min post; 5min post; and 10min post prolonged TR at IAT and IVT, through posturographic trials performed with eyes open (EO and closed (EC. Significant differences between IVT and IAT for Vcp, between EO and EC for Acp and Vcp, were observed. The IAT induced higher destabilizing effect when postural trials were performed with EC. The IVT intensity produced also a destabilizing effect on postural control immediately after exercise. An impairment of postural control after prolonged treadmill running exercise at IVT and IAT intensity was showed. However, destabilizing effect on postural control disappeared within 10min after IAT intensity and within 5min after IVT intensity

  11. Effect of prolonged freezing of semen on exosome recovery and biologic activity.

    Welch, Jennifer L; Madison, Marisa N; Margolick, Joseph B; Galvin, Shannon; Gupta, Phalguni; Martínez-Maza, Otoniel; Dash, Chandravanu; Okeoma, Chioma M


    Exosomes are important vehicles of intercellular communication that shape host responses to physiologic, tumorigenic, and pathogenic conditions. The composition and function of exosomes are dynamic and depends on the state and condition of the cellular source. In prior work, we found that semen exosomes (SE) from healthy donors who do not use illicit drugs potently inhibit HIV-1. Following semen donation, specimens are either used immediately or frozen for use at a later time. It has been shown that short-term freezing of semen has no effect on SE-mediated HIV-1 inhibition. However, the effect of illicit drugs and prolonged freezing on SE bioactivity is unknown. Here, we show preservation of SE physical properties, (morphology, concentration, intensity/size) irrespective of illicit drug use or duration of semen freezing. Interestingly, illicit drugs and prolonged freezing decreased the levels of SE-bound CD63/CD9 and acetylcholinesterase activity respectively. Furthermore, we show differential effects of illicit drug use and prolonged freezing on SE-mediated HIV-1 inhibition. Our results highlight the importance of the source of SE and condition of semen storage on SE content and function. In-depth evaluation of donor drug-use and duration of semen storage on SE cargo and bioactivity will advance our understanding of SE composition and function.

  12. [Prolonged esophageal pH monitoring utilization in the diagnosis of pathologic reflux in neonates

    Mezzacappa, M A; Collares, E F


    OBJECTIVES: To present indications and results of prolonged esophageal pH monitoring in diagnosing pathologic gastroesophageal reflux in newborns during their stay in the neonatal unit. METHODS: This retrospective descriptive-analytical study of 85 prolonged esophageal pH monitoring in neonates was performed, between October 1995 and March 1998, in a tertiary intensive care unity. A Digitrapper MKIII device, pH probes with one or two channels, and antimony electrodes were utilized. The probe was placed 3 cm above the gastroesophageal junction. RESULTS: The main indications of this esophageal pH study were hypoxemia episodes demanding supplemental oxygen, and caffeine resistant apnea. The means -/+ SD of birth-weight and gestational age in the patients evaluated were, respectively, 1,204-/+460 g and 30.5 -/+ 2.9 weeks. There was no statistical difference observed in newborns with and without pathologic gastroesophageal reflux according to clinical manifestations and monitoring conditions. Forty-eight newborns (56.4%) presented 17.6-/+9.1% of the whole examination time with a pH below 4. Of these patients, 31.1% presented birth-weight below 1,000 g. Duodenogastroesophagic was diagnosed in two cases. Of the studied premature with chronic lung disease, 66.7% presented pathologic reflux. CONCLUSION: Prolonged pH esophageal monitoring is helpful in the differential diagnosis of the unspecific and very frequent clinic manifestations in very low birth-weight infants.

  13. Stream thermal heterogeneity prolongs aquatic-terrestrial subsidy and enhances riparian spider growth.

    Uno, Hiromi


    Emerging aquatic insects from streams are important food sources for riparian predators, yet their availability is seasonally limited. Spatial heterogeneity in stream water temperature was found to spatially desynchronize the emergence timing of aquatic insects, and prolong their flight period, potentially enhancing consumer growth. While a mayfly Ephemerella maculata emergence lasted for 12-22 d in local sites along a river, mayflies emerged 19 days earlier from warmer than cooler sites. Therefore, the overall emergence of E. maculata from the river lasted for 37 d, and adult swarms were observed over that same period in an adjacent reproductive habitat. A feeding experiment with the riparian spider Tetragnatha versicolor showed that a prolonged subsidy, as would occur in a heterogeneous river, led to higher juvenile growth than a synchronous pulsed subsidy of equal total biomass, as would typify a more homogeneous river. Since larger female adult spiders produce more eggs, spiders that received prolonged subsidy as juveniles should achieve higher fecundity. Restoring spatial heterogeneity in streams may benefit not only stream communities but also riparian predators.

  14. Effect of prolonged freezing of semen on exosome recovery and biologic activity

    Welch, Jennifer L.; Madison, Marisa N.; Margolick, Joseph B.; Galvin, Shannon; Gupta, Phalguni; Martínez-Maza, Otoniel; Dash, Chandravanu; Okeoma, Chioma M.


    Exosomes are important vehicles of intercellular communication that shape host responses to physiologic, tumorigenic, and pathogenic conditions. The composition and function of exosomes are dynamic and depends on the state and condition of the cellular source. In prior work, we found that semen exosomes (SE) from healthy donors who do not use illicit drugs potently inhibit HIV-1. Following semen donation, specimens are either used immediately or frozen for use at a later time. It has been shown that short-term freezing of semen has no effect on SE-mediated HIV-1 inhibition. However, the effect of illicit drugs and prolonged freezing on SE bioactivity is unknown. Here, we show preservation of SE physical properties, (morphology, concentration, intensity/size) irrespective of illicit drug use or duration of semen freezing. Interestingly, illicit drugs and prolonged freezing decreased the levels of SE-bound CD63/CD9 and acetylcholinesterase activity respectively. Furthermore, we show differential effects of illicit drug use and prolonged freezing on SE-mediated HIV-1 inhibition. Our results highlight the importance of the source of SE and condition of semen storage on SE content and function. In-depth evaluation of donor drug-use and duration of semen storage on SE cargo and bioactivity will advance our understanding of SE composition and function. PMID:28338013

  15. PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

    Raimundo M. G. del Moral


    Full Text Available We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN and other renal lesions related to prolonged cold ischemia/reperfusion (IR in kidneys preserved at 4°C in University of Wisconsin (UW solution. Material and Methods. We used 30 male Parp1+/+ wild-type and 15 male Parp10/0 knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinylbutoxyl]-1(2H-isoquinolinone (DPQ at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ. We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp10/0 knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

  16. Causes of Prolonged Length of Stay for Patients Referred to the Emergency Department; a Cross-Sectional Study

    Mohammad Nasr-Esfahani


    Full Text Available  Introduction: Prolonged length of stay and failure to timely disposition of patients in the emergency department (ED lead to negative impact on the quality of service presentation, increasing dissatisfaction, and finally violence. Therefore, assessing the causes of prolonged length of stay for patients in this ward and presenting some applicable solutions against it, can significantly help improving the quality of services and more satisfaction of patients. The present study was designed with the aim of evaluating the causes of prolonged length of stay for patients in the ED. Methods: In a cross-sectional study, the causes of prolonged length of stay for admitted patients were assessed in the ED of Alzahra Hospital, Esfahan, Iran, during the fall 2010. A checklist was prepared with 11 cases included: age, gender, triage level, the time of receiving admission code and discharging from ED, the chief compliant of patient, hospitalization and discharge services, date of hospitalization, and the outcome for all patients. The lack of available bed in the ward, request for doing tests and unnecessary consultations, delay in entering the samples to the laboratory, delay in visit and disposition of patients by senior resident on duty, need to therapeutic proceedings by another service, delay in informing the resident of the related service, lack of coordination between the other wards and ED for patient's transportation, and financial inability of the patient were considered as the probable causes of prolonged length of stay. Finally, gathered data was analyzed by using SPSS version 18.Results: 95 (18.8% patients had prolonged ED length of stay (>6 hours with the hospitalization mean of 10.4±5.5 hours. Prolonged length of stay cases were significantly higher in patients under 30 years old (p=0.0001, in weekends (p=0.05, and second level triage (p=0.01. The most mean of prolonged length of stay were related to the surgery service with 20.0±21.2 hours

  17. Delayed recovery due to exaggerated acid, base and electrolyte imbalance in prolonged laparoscopic repair of diaphragmatic hernia

    Rakesh Garg


    Full Text Available The acid, base and electrolyte changes are usually observed in the perioperative settings. We report a case of prolonged laparoscopic repair of left-sided diaphragmatic hernia which involved a lot of tissue handling and fluid replacement leading to acid, base and electrolyte imbalance. A 42-year-old male underwent prolonged laparoscopic repair under general anesthesia. Intraoperatively, surgeon reported that contents of hernia includes bowel along with mesentery, spleen and lot of fatty tissue The blood loss was about 2 L which was replaced with 1 L of colloid and 7.5 L of lactated ringer. Near the end of surgery arterial blood gas analysis revealed metabolic acidosis, hyperkalemia, and hypocalcemia leading to delayed recovery. We conclude prolonged laparoscopic surgery involving lot of tissue handling including gut and fat should be monitored for acid, base, electrolyte imbalance and corrected timely to have uneventful rapid recovery.

  18. Very prolonged stay in the intensive care unit after cardiac operations: early results and late survival.

    Silberman, Shuli; Bitran, Daniel; Fink, Daniel; Tauber, Rachel; Merin, Ofer


    Prolonged intensive care unit (ICU) stay is a surrogate for advanced morbidity or perioperative complications, and resource utilization may become an issue. It is our policy to continue full life support in the ICU, even for patients with a seemingly grim outlook. We examined the effect of duration of ICU stay on early outcomes and late survival. Between 1993 and 2011, 6,385 patients were admitted to the ICU after cardiac surgery. Patients were grouped according to length of stay in the ICU: group 1, 2 days or less (n = 4,631; 73%); group 2, 3 to 14 days (n = 1,423; 22%); group 3, more than 14 days (n = 331; 5%). Length of stay in ICU for group 3 patients was 38 ± 24 days (range, 15 to 160; median 31). Clinical profile and outcomes were compared between groups. Patients requiring prolonged ICU stay were older, underwent more complex surgery, had greater comorbidity, and a higher predicted operative mortality (p < 0.0001). They had a higher incidence of adverse events and increased mortality (p < 0.0001). Of the 331 group 3 patients, 60% were discharged: survival of these patients at 1, 3, and 5 years was 78%, 65%, and 52%, respectively. Operative mortality as well as late survival of discharged patients was proportional to duration of ICU stay. Current technology enables keeping sick patients alive for extended periods of time. Nearly two thirds of patients requiring prolonged ICU leave hospital, and of these, 50% attain 5-year survival. These data support offering full and continued support even for patients requiring very prolonged ICU stay. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

    Piccinelli Marco


    Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

  20. [Beta lactam antibiotics and the question of dose regimen for severe infection. Prolonged infusion theoretically appealing--yet no evidence of clinical benefit].

    Leander, Gunilla; Eliasson, Erik; Hanberger, Håkan; Giske, Christian


    Patients with severe sepsis/septic shock have a high mortality. Beta-lactam antibiotics are normally first line treatment. This antimicrobial class has been associated with time-dependent efficacy. It is therefore plausible that administration as prolonged infusion will increase the therapeutic effect, as compared to short term bolus injections, which is the most common practice today. We have reviewed 14 randomized controlled studies to investigate whether prolonged infusion provides lower mortality and/or increased clinical cure. In summary, convincing advantages with prolonged infusion could not be found, however randomized studies are heterogeneous, and it cannot be excluded that some subgroups of critically ill patients could benefit from such treatment.

  1. Prolonged relaxation after stimulation of the clasping muscle of male frog, Rana japonica, during the breeding season.

    Ishii, Yoshiki; Tsuchiya, Teizo


    We investigated the mechanical properties of the flexor carpi radialis muscle (FCR), a forelimb muscle used mainly for amplexus in the breeding season (February to March), of the male Japanese brown frog, Rana japonica. In the present experiment, the changes in force and stiffness of the FCR before, during, and after contraction were measured at 4 degrees C. The total time from the end of stimulation to the end of relaxation was about 30 min. The time course of this prolonged relaxation was fitted by two exponential decay processes. Stiffness decreased during prolonged relaxation, but stayed higher than force, when normalized to peak values. These mechanical properties of the FCR were different from those of the glutaeus magnus muscle (GM) in the hindlimb, used for jumping. When a quick release was applied to the FCR during relaxation, the force recovered gradually after a sudden decrease. The time course of this force recovery was fitted by a single exponential term, and the rate constant decreased as the prolonged relaxation proceeded. The possible involvement of active process(es) in the prolonged relaxation is discussed.

  2. Deep, prolonged torpor by pregnant, free-ranging bats

    Willis, Craig K. R.; Brigham, R. Mark; Geiser, Fritz


    Many mammals save energy during food shortage or harsh weather using controlled reductions in body temperature and metabolism called torpor. However, torpor slows offspring growth, and reproductive individuals are thought to avoid using it because of reduced fitness resulting from delayed offspring development. We tested this hypothesis by investigating torpor during reproduction in hoary bats ( Lasiurus cinereus, Vespertilionidae) in southern Canada. We recorded deep, prolonged torpor bouts, which meet the definition for hibernation, by pregnant females. Prolonged torpor occurred during spring storms. When conditions improved females aroused and gave birth within several days. Our observations imply a fitness advantage of torpor in addition to energy conservation because reduced foetal growth rate could delay parturition until conditions are more favourable for lactation and neonatal survival.

  3. Diagnostic and clinical considerations in prolonged grief disorder.

    Maercker, Andreas; Lalor, John


    This review focuses on the similarities and differences between prolonged grief disorder (PGD) and post-traumatic stress disorder (PTSD). It highlights how a PTSD-related understanding aids the investigation and clinical management of PGD. Grief has long been understood as a natural response to bereavement, as serious psychological and physiological stress has been regarded as a potential outcome of extreme or traumatic stress. PTSD was first included in DSM-III in 1980. In the mid-1980s, the first systematic investigation began into whether there is an extreme or pathological form of mourning. Meanwhile, there is much research literature on complicated, traumatic, or prolonged grief This literature is reviewed in this article, with the following questions: Is it possible to distinguish normal from non-normal grief? Which clinical presentation does PGD have-and how does this compare with PTSD? Finally, diagnostic, preventive, and therapeutic approaches and existing tools are presented.

  4. Effect of prolonged chemical challenges on selected properties of silorane

    de Jesus, Vivian CBR; Martinelli, Natan Luiz; Pascotto, Renata Corrêa

    Objectives: The purpose of this study was to investigate the effect of prolonged chemical challenges on water sorption, solubility, and roughness of a silorane-based material when compared to methacrylate-based composites. Methods: Initial roughness and mass were registered for specimens (n=24...... phosphoric acid, 75% ethanol or distilled water for 7, 14, 21, and 180 days, when new measurements were performed. Subsequently, specimens were dehydrated until a constant mass was obtained. Water sorption and solubility were calculated after 180 days of immersion in the different solutions. Data were...... differences in water sorption and solubility were detected amongst the investigated composites (pwater sorption (with similar values to Filtek Z250 and Filtek Z350XT) and low solubility (with similar values to Filtek Z250) after prolonged immersion...

  5. QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

    De Bruin, Marie L; Hoes, Arno W; Leufkens, Hubert G M


    Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice......, and subsequently focused on several specific groups of patients who could be extremely vulnerable for drug-induced arrhythmias. We performed a case-control study in which patients (cases), hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared with their matched controls regarding current...... use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTc...

  6. Infection prevention and control during prolonged human space travel.

    Mermel, Leonard A


    Prolonged human spaceflight to another planet or an asteroid will introduce unique challenges of mitigating the risk of infection. During space travel, exposure to microgravity, radiation, and stress alter human immunoregulatory responses, which can in turn impact an astronaut's ability to prevent acquisition of infectious agents or reactivation of latent infection. In addition, microgravity affects virulence, growth kinetics, and biofilm formation of potential microbial pathogens. These interactions occur in a confined space in microgravity, providing ample opportunity for heavy microbial contamination of the environment. In addition, there is the persistence of aerosolized, microbe-containing particles. Any mission involving prolonged human spaceflight must be carefully planned to minimize vulnerabilities and maximize the likelihood of success.

  7. Reversal of prolonged isoniazid-induced coma by pyridoxine.

    Brent, J; Vo, N; Kulig, K; Rumack, B H


    Isoniazid overdose is known to result in the rapid onset of seizures, metabolic acidosis, and prolonged obtundation. Pyridoxine has been reported to be effective in treating isoniazid-induced seizures. We report three cases of obtundation secondary to isoniazid overdose that was immediately reversed by intravenous pyridoxine. In two of these cases, status seizures were stopped by intravenous pyridoxine administration, but the patients remained comatose for prolonged periods. The comas were immediately reversed by the administration of additional pyridoxine. In the third case, the patient's lethargy was treated by intravenous pyridoxine on presentation and was followed by immediate awakening. Pyridoxine is effective in treating not only isoniazid-induced seizures, but also the mental status changes associated with this overdose. The dose required to induce awakening may be higher than that required to control seizures.

  8. Prolonged apnea following modified electroconvulsive therapy with suxamethonium

    T M Omprakash


    Full Text Available A 36-year-old male from an urban middleclass family with strained relationship among family members was referred from a corporate hospital for further management of psychological problem. As he was attempting suicide repeatedly, Electroconvulsive Therapy (ECT was planned. After preoperative assessment and preparation, modified ECT was done with thiopentone and 0.5 mg/kg of suxamethonium. Apnea following suxamethonium was prolonged for 2 hours. Subsequent enquiry revealed that patient was treated for organophosphate poisoning and was on ventilator support for 15 days. This was concealed by the relatives. On searching patient previous records, Butyrylcholinesterase levels were very low, i.e., 350 u/l (normal reference range is 5 500 - 12 500 u/l. Prolonged suxamethonium apnea should be anticipated in patients with recent history of organophosphate poisoning; it is advisable to estimate the levels of butyrylcholinesterase and avoid suxamethonium in patients with low enzyme levels.

  9. MRI findings of prolonged post-traumatic sternal pain

    Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne [University Hospital of Berne, Department of Diagnostic, Pediatric and Interventional Radiology, Berne (Switzerland); Steinbach, Lynne [University of California San Francisco, Department of Radiology, San Francisco, CA (United States)


    The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

  10. Disseminated Mycobacterium celatum disease with prolonged pulmonary involvement

    Patsche, Cecilie Blenstrup; Svensson, Erik; Wejse, Christian


    Mycobacterium celatum is a rare cause of human infection, causing disseminated disease in immunosuppressed individuals. Infections localized to the lungs and the lymph nodes have also been reported in immunocompetent individuals. The existing literature on the subject is limited as are experience....... The treatment regimen was changed to azithromycin, ciprofloxacin, and pyrazinamide and the treatment duration was prolonged to a total of 24 months, with good effect....

  11. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

    Christina Bognet


    Full Text Available Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL solutions, with or without epinephrine 5 µg/mL (1:200,000 in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001 or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001. Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.

  12. Prolonged morphine administration alters protein expression in the rat myocardium

    Drastichova Zdenka; Skrabalova Jitka; Neckar Jan; Kolar Frantisek; Novotny Jiri


    Abstract Background Morphine is used in clinical practice as a highly effective painkiller as well as the drug of choice for treatment of certain heart diseases. However, there is lack of information about its effect on protein expression in the heart. Therefore, here we aimed to identify the presumed alterations in rat myocardial protein levels after prolonged morphine treatment. Methods Morphine was administered to adult male Wistar rats in high doses (10 mg/kg per day) for 10 days. Protein...

  13. Risk Factors of Prolonged Hospitalization in Patients with Hyperemesis Gravidarum

    Hasan Onur Topcu


    Conclusion: Number of vomiting per day and maternal serum TSH levels could help physicians to estimate the risk of prolonged hospitalization; however further investigations are needed in large population studies. Identifying the high risk patients is important both for prevention of HEG and beginning appropriate antiemetic treatment to avoid complications to reduce the economic costs. [Cukurova Med J 2015; 40(1.000: 113-118

  14. Emotional attentional control predicts changes in diurnal cortisol secretion following exposure to a prolonged psychosocial stressor.

    Lenaert, Bert; Barry, Tom J; Schruers, Koen; Vervliet, Bram; Hermans, Dirk


    Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been associated with several psychological disorders. Hence, the identification of individual difference variables that predict variations in HPA-axis activity represents an important challenge for psychiatric research. We investigated whether self-reported attentional control in emotionally demanding situations prospectively predicted changes in diurnal salivary cortisol secretion following exposure to a prolonged psychosocial stressor. Low ability to voluntarily control attention has previously been associated with anxiety and depressive symptomatology. Attentional control was assessed using the Emotional Attentional Control Scale. In students who were preparing for academic examination, salivary cortisol was assessed before (time 1) and after (time 2) examination. Results showed that lower levels of self-reported emotional attentional control at time 1 (N=90) predicted higher absolute diurnal cortisol secretion and a slower decline in cortisol throughout the day at time 2 (N=71). Difficulty controlling attention during emotional experiences may lead to chronic HPA-axis hyperactivity after prolonged exposure to stress. These results indicate that screening for individual differences may foster prediction of HPA-axis disturbances, paving the way for targeted disorder prevention.

  15. Physiological Stress Responses to Prolonged Exposure to MS-222 and Surgical Implantation in Juvenile Chinook Salmon

    Wagner, Katie A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Woodley, Christa M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Seaburg, Adam [Univ. of Washington, Seattle, WA (United States); Skalski, John R. [Univ. of Washington, Seattle, WA (United States); Eppard, Matthew B. [U.S. Army Corps of Engineers, Portland, OR (United States)


    While many studies have investigated the effects of transmitters on fish condition, behavior, and survival, to our knowledge, no studies have taken into account anesthetic exposure time in addition to tag and surgery effects. We investigated stress responses to prolonged MS-222 exposure after stage 4 induction in surgically implanted juvenile Chinook salmon (Oncorhynchus tshawytscha). Survival, tag loss, plasma cortisol concentration, and blood Na+, K+, Ca2+, and pH were measured immediately following anesthetic exposure and surgical implantation and 1, 7, and 14 days post-treatment. Despite the prolonged anesthetic exposure, 3-15 minutes post Stage 4 induction, there were no mortalities or tag loss in any treatment. MS-222 was effective at delaying immediate cortisol release during surgical implantation; however, osmotic disturbances resulted, which were more pronounced in longer anesthetic time exposures. From day 1 to day 14, Na+, Ca2+, and pH significantly decreased, while cortisol significantly increased. The cortisol increase was exacerbated by surgical implantation. There was a significant interaction between MS-222 time exposure and observation day for Na+, Ca2+, K+, and pH; variations were seen in the longer time exposures, although not consistently. In conclusion, stress response patterns suggest stress associated with surgical implantation is amplified with increased exposure to MS-222.

  16. Calcium Imaging of AM Dyes Following Prolonged Incubation in Acute Neuronal Tissue.

    Cameron, Morven; Kékesi, Orsolya; Morley, John W; Tapson, Jonathan; Breen, Paul P; van Schaik, André; Buskila, Yossi


    Calcium-imaging is a sensitive method for monitoring calcium dynamics during neuronal activity. As intracellular calcium concentration is correlated to physiological and pathophysiological activity of neurons, calcium imaging with fluorescent indicators is one of the most commonly used techniques in neuroscience today. Current methodologies for loading calcium dyes into the tissue require prolonged incubation time (45-150 min), in addition to dissection and recovery time after the slicing procedure. This prolonged incubation curtails experimental time, as tissue is typically maintained for 6-8 hours after slicing. Using a recently introduced recovery chamber that extends the viability of acute brain slices to more than 24 hours, we tested the effectiveness of calcium AM staining following long incubation periods post cell loading and its impact on the functional properties of calcium signals in acute brain slices and wholemount retinae. We show that calcium dyes remain within cells and are fully functional >24 hours after loading. Moreover, the calcium dynamics recorded >24 hrs were similar to the calcium signals recorded in fresh tissue that was incubated for 24hrs after dissection. These methods will not only extend experimental time for those using acute neuronal tissue, but also may reduce the number of animals required to complete experimental goals.

  17. Protrombina mutante em indivíduos sob investigação de trombofilia Mutant prothrombin in individuals under thrombophilia investigation

    Catarina Paula da Silva Ramos


    coagulation factor II, prothrombin G20210A (PTCR, constitutes the second most prevalent genetic defect associated with the predisposition to thrombosis or thrombophilia. In Brazil, the study of this risk factor is relatively recent and there is little available data in medical literature. OBJECTIVE: The aim of this study was to determine the frequency of PTCR in 285 individuals being investigated for thrombophilia at Fundação de Hematologia e Hemoterapia de Pernambuco (HEMOPE/PE. MATERIAL AND METHOD: The molecular biology technique used was restriction enzyme/polymerase chain reaction (RE/PCR, using specific primers and the Hind III enzyme. RESULTS: The frequency of PTCR was 6% in heterozygosis. The presence of the mutation was similar among individuals under and over 45 years old. DISCUSSION: The presence of PTCR may have been a relevant factor for the episodes of thrombosis, and the low median age of the group suggests that other genetic causes of thrombophilia must be investigated inasmuch as most publications associate the presence of genetic risk factor with thrombotic events in individuals under 45 years old. CONCLUSIONS: Our findings showed that the frequency of PTCR in the studied population is similar to the results published in medical literature for selected patients with thromboembolism and they confirm the importance of molecular testing at different age groups.

  18. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

    Levent SÜTÇİGİL


    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies.

  19. Prolonged symptoms in sporadic hemiplegic migraine: aura or migrainous infarction?

    Lai, Tzu-Hsien; Hong, Chien-Tai


    Sporadic hemiplegic migraine is a rare form of migraine associated with motor weakness during the aura phase. While the aura usually lasts less than 1 hour, patients with sporadic hemiplegic migraine frequently have prolonged weakness. A 60-year-old male had sporadic hemiplegic migraine after a head injury at the age of 14. He presented to our emergency department with a typical migraine attack except prolonged right limbs weakness and numbness (>1 day). Brain magnetic resonance imaging showed an acute infarction in the left posterior medial pons. He recovered completely from motor weakness but still complained of residual numbness in his right limbs three months later. We report the first adult case of sporadic hemiplegic migraine with migrainous infarction located in the pons. Since patients with hemiplegic migraine often have prolonged aura, it is easy to be confused with a migrainous infarction. The case report highlights that migrainous infarction is a complication difficult to diagnose and treat early, especially in patients with hemiplegic migraine.

  20. Secondary bacteraemia in adult patients with prolonged dengue fever.

    Premaratna, R; Dissanayake, D; Silva, F H D S; Dassanayake, M; de Silva, H J


    Although dengue management guidelines do not advice on use of antibiotics in dengue shock syndrome, unrecognised bactraemia is likely to contribute to morbidity and mortality. To assess the occurance of secondary bacteraemia in adult patients with prolonged dengue fever. A prospective study was conducted recruiting patients with confirmed acute dengue infection who had prolonged fever (>5 days). Two sets of blood cultures were taken in such patients prior to institution of antibiotic therapy. Demographic, clinical, haematological and biochemical parameters were recorded. Development of ascites and pleural effusions were detected using ultrasonography. Fourty patients (52.5% males) with a mean age of 29.8 years (SD 13.6) were studied. The average duration of fever was 7.9 days (SD 1.8). Ten patients (25%) had bacterial isolates in their blood cultures; Staphylococcus aureus (n=2), coliforms (n=3), pseudomonas (n=1) and 4 had mixed growths. The culture positive group had severe body aches at admission and higher fever, third space fluid accumulation, a significant drop in platelets and a higher CRP. A quarter of dengue patients with prolonged fever had a bacterial isolate. Culture positive patients appeared more ill with body aches and had higher degrees of fever during the latter part of the illness. Increased vascular permeability may predispose to bacterial seepage into blood. Although white cell count is not helpful in detecting bacteraemia, low platelet count and elevation of CRP seem to be helpful.

  1. A centrally mediated prolonged hypotension produced by oxotremorine or pilocarpine

    Dage, R.C.


    1 Oxotremorine, methyloxotremorine, pilocarpine or arecoline were given intravenously to anaesthetized cats, dogs or rats, and intraperitoneally to conscious normotensive and spontaneously hypertensive rats, pretreated with doses of methylatropine that completely blocked peripheral muscarinic receptors, to ascertain their effects on blood pressure and heart rate. 2 Oxotremorine but not methyloxotremorine produced a prolonged hypotension in cats and dogs but not in rats. Heart rate was not changed. Pilocarpine, although less potent, produced an identical effect, whereas the effect of arecoline was short by comparison. The hypotensive effect of these drugs was reversed by atropine. 3 In dogs, oxotremorine produced a prolonged hypotension with no change in heart rate or cardiac output. 4 A decrease in spontaneous sympathetic nerve activity accompanied the hypotension in cats. Both effects were reversed by atropine but could be reinvoked by large doses of oxotremorine. 5 The oxotremorine-induced hypotension in cats was not altered by decerebration but was abolished by high cervical spinal section. 6 The results indicate that the prolonged hypotension elicited by oxotremorine is mediated by an action at muscarinic receptors in the brain stem resulting in a decrease in sympathetic nerve activity and peripheral resistance but not heart rate or cardiac output. PMID:760887

  2. Prolonged job strain and subsequent risk of cancer in women

    Vesterlund, Gitte K.; Høeg, Beverley L.; Johansen, Christoffer


    Background: The role of psychological stress in cancer risk is continuously debated. Stress at work is the most common form of stress and previous studies have shown inconsistent results regarding cancer risk. In this longitudinal study, we examined the association between prolonged job strain ac....... Since a large proportion of cancer patients perceive psychological stress as a possible cause of their cancer disease, it is of importance to communicate these findings to the public.......Background: The role of psychological stress in cancer risk is continuously debated. Stress at work is the most common form of stress and previous studies have shown inconsistent results regarding cancer risk. In this longitudinal study, we examined the association between prolonged job strain...... across six years and subsequent cancer risk. Methods and materials: We used data from 6571 cancer-free women from the Danish Nurse Cohort aged 45–70 years at inclusion, and self-reported questionnaires on job strain at baseline in 1993 and again in 1999. Prolonged job strain was defined as high job...

  3. Treatment of postcatheterization femoral arteriovenous fistulas with simple prolonged bandaging

    ZHOU Tao; LIU Zhen-jiang; ZHOU Sheng-hua; SHEN Xiang-qian; LIU Qi-ming; FANG Zhen-fei; HU Xin-qun; LI Jiang; L(U) Xiao-lin


    Background The methods for the treatment of postcatheterization femoral arteriovenous fistulas (AVF-s) - simple observation, ultrasound guided compression, covered stents implantation and coil embolization have poor outcome.Surgery is the standard method for treatment of femoral AVFs, but it is a traumatic operation. In this study, we report the results of the treatment of postcatheterization femoral AVFs by simple prolonged compressing bandage.Methods To treat iatrogenic femoral AVFs caused by transfemoral catheterization, prolonged binding with elastic or common bandage was applied in 16 cases. Catheterization was performed in 7 cases for radiofrequency current catheter ablation, in 4 for occlusion of congenital heart disease, in 3 for percutaneous coronary intervention, in 1 for coronary angiography and in 1 for right heart catheterization.Results All iatrogenic femoral AVFs were healed after simple binding with elastic or common bandage for 4-46 days (mean (15±10) days). During the period of binding, local skins ulceration occurred at puncture site in two cases and femoral vein thrombus was found in one patient. During 6-24 months (mean (11.8±3.6) months) followup with colour Doppler ultrasonography, no recurrent arteriovenous shunting or other complications were observed.Conclusion The results suggest that simple prolonged bandaging for postcatheterization femoral AVFs is an effective and economical procedure.

  4. Opioid/naloxone prolonged release combinations for opioid induced constipation

    Shailendra Kapoor


    I read with great interest the recent article by Chen et a/in a recent issue of your esteemed journal.The article is highly thought provoking.One emerging therapeutic alternative for opioid induced constipation is the emergence of opioid/naloxone prolonged release combinations.For instance,naloxone when administered in a 1∶2 ratio with oxycodone reverses the inhibitory effect of oxycodone on the gastrointestinal tract.The advantage of oxycodone/naloxone prolonged release (OXN) is that while its anti-nociceptive efficacy is equivalent to that of oxycodone prolonged release (OXC),it significantly decreases the "Bowel Function Index" thereby ameliorating symptoms of opioid induced constipation to a large extent.Schutter et al in a recent study have reported a decrease in the bowel function index from 38.2 to 15.1.Similarly,L(o)wenstein et al in another recent study have reported that following a month of therapy,complete spontaneous bowel movements per week is increased from one in OXC therapy to three in OXN therapy.

  5. Prolonged upright posture induces calcified hypertrophy in the cartilage end plate in rat lumbar spine.

    Bian, Qin; Liang, Qian-Qian; Wan, Chao; Hou, Wei; Li, Chen-Guang; Zhao, Yong-Jian; Lu, Sheng; Shi, Qi; Wang, Yong-Jun


    Both forelimbs of rats were amputated and these rats were kept in the custom-made cages to keep prolonged and repeated upright posture. Changes of bone were observed in the lumbar vertebrae at three different time points after the surgery. To investigate the effect of prolonged and repeated upright posture on the cartilage end plate of rat lumbar vertebrae. Previous studies show calcified hypertrophy is related to mechanical stress, but there are no clear evidences to indicate whether or not long-term and repeated assumption of the upright posture could result in calcified hypertrophy in cartilage end plate of rat lumbar spine. The forelimbs of 30 rats were amputated when they were 1 month old. These rats were kept in the custom-made cages and were forced to stand upright on their hind-limbs and tails to obtain water and food. Normal rats of the same ages kept in regular cages were used as control. The rats were killed at 5, 7, and 9 months after the surgery and lumbar vertebrae samples were harvested for micro-CT, histologic, and immunohistochemical studies. Total RNA isolated from these samples were used for real-time RT-PCR of type X collagen (Col10α1), vascular endothelial growth factor (VEGF), and transforming growth factor β1 (TGF-β1). Micro-CT showed increased inner part of cartilage end plate. Histologic revealed peripheral hypertrophy of disc after the surgery. Immunostaining and real-time RT-PCR showed increased protein and mRNA expression of type X collagen, VEGF, and TGF-β1. Prolonged upright posture induces cartilage end plate calcification and hypertrophy in rat lumbar spine.

  6. [Prolonged weaning: S2k-guideline published by the German Respiratory Society].

    Schönhofer, B; Geiseler, J; Dellweg, D; Moerer, O; Barchfeld, T; Fuchs, H; Karg, O; Rosseau, S; Sitter, H; Weber-Carstens, S; Westhoff, M; Windisch, W


    Mechanical ventilation (MV) is an essential part of modern intensive care medicine. MV is performed in patients with severe respiratory failure caused by insufficiency of the respiratory muscles and/or lung parenchymal disease when/after other treatments, i. e. oxygen, body position, secretion management, medication or non invasive ventilation have failed.In the majority of ICU patients weaning is routine and does not present any problems. Nevertheless 40-50 % of the time during mechanical ventilation is spent on weaning. About 20 % of patients need continued MV despite resolution of the conditions which originally precipitated the need for MV.There maybe a combination of reasons; chronic lung disease, comorbidities, age and conditions acquired in ICU (critical care neuromyopathy, psychological problems). According to an International Consensus Conference the criteria for "prolonged weaning" are fulfilled if patients fail at least three weaning attempts or require more than 7 days of weaning after the first spontaneous breathing trial. Prolonged weaning is a challenge. An inter- and multi-disciplinary approach is essential for weaning success. Complex, difficult to wean patients who fulfill the criteria for "prolonged weaning" can still be successfully weaned in specialised weaning units in about 50% of cases.In patients with unsuccessful weaning, invasive mechanical ventilation has to be arranged either at home or in a long term care facility.This S2-guideline was developed because of the growing number of patients requiring prolonged weaning. It is an initiative of the German Respiratory Society (Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin e. V., DGP) in cooperation with other societies engaged in the field.The guideline is based on a systematic literature review of other guidelines, the Cochrane Library and PubMed.The consensus project was chaired by the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der




    Full Text Available This study was designed to find possible relationship between QTc prolongation and erythrocyte or plasma lithium concentrations. Fifty-six patients with bipolar disorder entered this case- control study. Subjects were between 17 to 63 years of age and were receiving lithium alone, or lithium plus haloperidol or lithium plus thioridazine. The exclusion criteria were past history of cardiovascular, hepatic, renal or metabolic disorders or using other medications known to cause rhythm disturbances. The case group included males with QTc 450ms and females with QTc470ms while the control group included males and females with QTc<450 and QTc< 470ms, respectively. Serum sodium and potassium levels, erythrocyte and plasma lithium concentrations as well as lithium ratio were determined for all subjects and compared between the case and control groups by independent sample t-test. The mean of these levels were not different between the case and control groups. Additionally, no correlations were found between QTc and erythrocyte or plasma lithium concentration, lithium ratio, serum sodium or potassium levels. Analyzing the data for patients treated with lithium alone showed no significant correlations between QTc prolongation and erythrocyte or plasma lithium concentration, lithium ratio or serum potassium level. However, a significant correlation was found between serum sodium concentration and QTc prolongation. It should be noted that QTc prolongation occurred six times more in patients who were taking thioridazine and lithium concomitantly. This study noted no influence of sex or co-administration of haloperidol with lithium on QTc prolongation. It is concluded that plasma or erythrocyte lithium levels may not be able to predict QTc prolongation and its consequences.

  8. Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation

    Carneiro, Lionel; Geller, Sarah; Hébert, Audrey; Repond, Cendrine; Fioramonti, Xavier; Leloup, Corinne; Pellerin, Luc


    Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (neuropeptides. Moreover, insulinemia was increased and caused a decrease in glucose production despite an increased resistance to insulin. The present study confirms that ketone bodies reaching the brain stimulates food intake. Moreover, we provide evidence that a prolonged hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms. Finally, this study shows that brain exposure to ketone bodies alters insulin signaling and consequently glucose homeostasis. PMID:27708432

  9. Electro-acupuncture to prevent prolonged postoperative ileus:A randomized clinical trial

    M; Kay; Garcia; Joseph; S; Chiang; Bob; Thornton; J; Lynn; Palmer; Jennifer; McQuade; Lorenzo; Cohen


    AIM:To examine whether acupuncture can prevent prolonged postoperative ileus(PPOI)after intraperitoneal surgery for colon cancer. METHODS:Ninety patients were recruited from the Fudan University Cancer Hospital,Shanghai,China. After surgery,patients were randomized to receive acupuncture(once daily,starting on postoperative day 1, for up to six consecutive days)or usual care.PPOI was defined as an inability to pass flatus or have a bowel movement by 96 h after surgery.The main outcomes were time to first fl...

  10. Comparison between amniotomy, oxytocin or both for augmentation of labor in prolonged latent phase: a randomized controlled trial.

    Nachum, Zohar; Garmi, Gali; Kadan, Yfat; Zafran, Noah; Shalev, Eliezer; Salim, Raed


    A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase. Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1), oxytocin (group 2) or both (group 3). A group of women who progressed spontaneously without intervention composed the control group (group 4). The primary outcome was the duration of time from initiation of augmentation until delivery. A total of 213 women were consented and randomized to group 1 (70 women), group 2 (72 women) and group 3 (71 women). Group 4 was composed from additional 70 women. A mean reduction of 120 minutes in labor duration was observed among group 3 compared to group 1 (p = 0.08) and 180 minutes compared to group 2 and 4 (p = 0.001). Women in group 3 had a shorter length of time from augmentation until the beginning of the active phase and a shorter first stage of labor than group 1 (p = 0.03), group 2 (p = 0.001) and group 4 (p = 0.001). Satisfaction was greater among group 3 and 4. Mode of delivery and neonatal outcome were comparable between the groups. Labor augmentation by combined amniotomy and oxytocin among women with a prolonged latent phase at term seems superior compared to either of them alone.

  11. Prolonged storage of packed red blood cells for blood transfusion.

    Martí-Carvajal, Arturo J; Simancas-Racines, Daniel; Peña-González, Barbra S


    A blood transfusion is an acute intervention, used to address life- and health-threatening conditions on a short-term basis. Packed red blood cells are most often used for blood transfusion. Sometimes blood is transfused after prolonged storage but there is continuing debate as to whether transfusion of 'older' blood is as beneficial as transfusion of 'fresher' blood. To assess the clinical benefits and harms of prolonged storage of packed red blood cells, in comparison with fresh, on recipients of blood transfusion. We ran the search on 1st May 2014. We searched the Cochrane Injuries Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase (OvidSP), CINAHL (EBSCO Host) and two other databases. We also searched clinical trials registers and screened reference lists of the retrieved publications and reviews. We updated this search in June 2015 but these results have not yet been incorporated. Randomised clinical trials including participants assessed as requiring red blood cell transfusion were eligible for inclusion. Prolonged storage was defined as red blood cells stored for ≥ 21 days in a blood bank. We did not apply limits regarding the duration of follow-up, or country where the study took place. We excluded trials where patients received a combination of short- and long-stored blood products, and also trials without a clear definition of prolonged storage. We independently performed study selection, risk of bias assessment and data extraction by at least two review authors. The major outcomes were death from any cause, transfusion-related acute lung injury, and adverse events. We estimated relative risk for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings. We identified three randomised clinical trials, involving a total of 120 participants, comparing packed red blood cells with ≥ 21 days storage


    Ilkka Väänänen


    Full Text Available The purpose of this study was to describe the physiological responses to daily repeated acute but non-competitive prolonged exercise during a 4-day march and a 2-day cross-country ski event to the cardiorespiratory, autonomic nervous, musculoskeletal and endocrine systems. Mood states were also evaluated after these repeated exercises. The data of these short-term follow-up (reversal field trials was collected from healthy, 23 to 48 year old Finnish male soldiers in 1993 (n=6 and 1994 (n=15 during the "International Four-Day Long-Distance March" in Nijmegen, The Netherlands, and from ten healthy, 22 to 48 year old Finnish male participants in 1995 during a 2-day Finlandia Ski Race in Lahti, Finland. Acute cardiovascular responses were estimated by measuring the heart rate during exercise. The responses of the autonomic nervous system were estimated by measuring the heart rates during the orthostatic test. The musculoskeletal responses were estimated by measuring the perceived pains, flexibility, functional strength, use of elastic energy and oedemic changes of the lower extremities. Hormonal responses were estimated from the urinary excretion of catecholamines, and the concentrations of serum cortisol, testosterone, luteinizing (LH and follicle stimulating hormone (FSH. Mood states were assessed with the Profile of Mood States (POMS questionnaire. Daily walking time was 7-10 hours while the skiing time was 3 hours. Average heart rate during walking was 59% and skiing 87% of maximum heart rate. Morning heart rate in the supine position increased progressively through the marching period but not through the skiing experiment. After the first day, perceived pain increased significantly and remained at a similarly increased level until the end of the exercise period. Leg measurements showed no signs of oedema, decreases in flexibility, or functional strength. Catecholamine excretion rates during marches indicated cumulatively increased

  13. Prolonged Incubation of Acute Neuronal Tissue for Electrophysiology and Calcium-imaging.

    Cameron, Morven A; Kekesi, Orsolya; Morley, John W; Bellot-Saez, Alba; Kueh, Sindy; Breen, Paul; van Schaik, André; Tapson, Jonathan; Buskila, Yossi


    Acute neuronal tissue preparations, brain slices and retinal wholemount, can usually only be maintained for 6 - 8 h following dissection. This limits the experimental time, and increases the number of animals that are utilized per study. This limitation specifically impacts protocols such as calcium imaging that require prolonged pre-incubation with bath-applied dyes. Exponential bacterial growth within 3 - 4 h after slicing is tightly correlated with a decrease in tissue health. This study describes a method for limiting the proliferation of bacteria in acute preparations to maintain viable neuronal tissue for prolonged periods of time (>24 h) without the need for antibiotics, sterile procedures, or tissue culture media containing growth factors. By cycling the extracellular fluid through UV irradiation and keeping the tissue in a custom holding chamber at 15 - 16 °C, the tissue shows no difference in electrophysiological properties, or calcium signaling through intracellular calcium dyes at >24 h postdissection. These methods will not only extend experimental time for those using acute neuronal tissue, but will reduce the number of animals required to complete experimental goals, and will set a gold standard for acute neuronal tissue incubation.

  14. Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study

    Michael Becka


    Full Text Available Dual antiplatelet therapy with acetylsalicylic acid and a thienopyridine, such as clopidogrel, is effective for the secondary prevention of cardiovascular events in patients with acute coronary syndrome, but there is still a substantial residual risk of recurrence. Although anticoagulant therapy with a vitamin K antagonist (e.g. warfarin in conjunction with antiplatelet therapy has been shown to reduce the risk of cardiovascular events, the rates of bleeding were increased with these combination therapies; hence, triple therapy with warfarin is currently only recommended in patients at low risk of bleeding. In addition, there are other limitations associated with vitamin K antagonist therapy, including the need for routine coagulation monitoring and dose adjustment to maintain the treatment within the therapeutic range. Rivaroxaban is an oral, direct Factor Xa inhibitor; in clinical practice, it is likely that rivaroxaban will be given to patients who also receive antiplatelet therapy, such as clopidogrel. This randomized, non-blinded, three-way crossover study investigated the effect of rivaroxaban on bleeding time when co­administered with clopidogrel. In addition, the influence of clopidogrel on the safety, tolerability, pharmacodynamics and pharmacokinetics of rivaroxaban was investigated. Of 27 healthy male subjects who received a single 300 mg dose of clopidogrel, 14 were identified as clopidogrel responders and were then randomized to the following three treatments: (A two doses of clopidogrel on two consecutive days (300 mg on day 1; 75 mg on day 2; (B one dose of rivaroxaban (15 mg; or (C a combination of treatments A and B (rivaroxaban given on day 2. All treatments were well tolerated. Bleeding time with co­administration of rivaroxaban and clopidogrel was significantly prolonged in four subjects, compared with either drug alone: combination treatment increased the overall least squares-means to 3.77 times baseline (90% confidence

  15. Efficacy and safety of prolonged-release melatonin in insomnia patients with diabetes: a randomized, double-blind, crossover study

    Garfinkel D


    Full Text Available Doron Garfinkel1, Mariana Zorin2, Julio Wainstein2, Zipora Matas3, Moshe Laudon4, Nava Zisapel4,51Geriatric Palliative Department, Shoham Geriatric Medical Center, Pardes Hana, Israel; 2Diabetes Unit, 3Biochemistry Laboratory, The E Wolfson Medical Center, Holon, Israel; 4Neurim Pharmaceuticals Ltd, 5Department of Neurobiology, Tel Aviv University, Tel Aviv, IsraelBackground: Diabetes is a major comorbidity in insomnia patients. The efficacy and safety of prolonged-release melatonin 2 mg in the treatment of glucose, lipid metabolism, and sleep was studied in 36 type 2 diabetic patients with insomnia (11 men, 25 women, age 46–77 years.Methods: In a randomized, double-blind, crossover study, the subjects were treated for 3 weeks (period 1 with prolonged-release melatonin or placebo, followed by a one-week washout period, and then crossed over for another 3 weeks (period 2 of treatment with the other preparation. All tablets were taken 2 hours before bedtime for a period of 3 weeks. In an extension period of 5 months, prolonged-release melatonin was given nightly to all patients in an open-label design. Sleep was objectively monitored in a subgroup of 22 patients using wrist actigraphy. Fasting glucose, fructosamine, insulin, C-peptide, triglycerides, total cholesterol, high-density and low-density lipoprotein cholesterol, and some antioxidants, as well as glycosylated hemoglobin (HbA1c levels were measured at baseline and at the end of the study. All concomitant medications were continued throughout the study.Results: No significant changes in serum glucose, fructosamine, insulin, C-peptide, antioxidant levels or blood chemistry were observed after 3 weeks of prolonged-release melatonin treatment. Sleep efficiency, wake time after sleep onset, and number of awakenings improved significantly with prolonged-release melatonin as compared with placebo. Following 5 months of prolonged-release melatonin treatment, mean HbA1c (±standard deviation was

  16. Characterizing prolonged heat effects on mortality in a sub-tropical high-density city, Hong Kong

    Ho, Hung Chak; Lau, Kevin Ka-Lun; Ren, Chao; Ng, Edward


    Extreme hot weather events are likely to increase under future climate change, and it is exacerbated in urban areas due to the complex urban settings. It causes excess mortality due to prolonged exposure to such extreme heat. However, there is lack of universal definition of prolonged heat or heat wave, which leads to inadequacies of associated risk preparedness. Previous studies focused on estimating temperature-mortality relationship based on temperature thresholds for assessing heat-related health risks but only several studies investigated the association between types of prolonged heat and excess mortality. However, most studies focused on one or a few isolated heat waves, which cannot demonstrate typical scenarios that population has experienced. In addition, there are limited studies on the difference between daytime and nighttime temperature, resulting in insufficiency to conclude the effect of prolonged heat. In sub-tropical high-density cities where prolonged heat is common in summer, it is important to obtain a comprehensive understanding of prolonged heat for a complete assessment of heat-related health risks. In this study, six types of prolonged heat were examined by using a time-stratified analysis. We found that more consecutive hot nights contribute to higher mortality risk while the number of consecutive hot days does not have significant association with excess mortality. For a day after five consecutive hot nights, there were 7.99% [7.64%, 8.35%], 7.74% [6.93%, 8.55%], and 8.14% [7.38%, 8.88%] increases in all-cause, cardiovascular, and respiratory mortality, respectively. Non-consecutive hot days or nights are also found to contribute to short-term mortality risk. For a 7-day-period with at least five non-consecutive hot days and nights, there was 15.61% [14.52%, 16.70%] increase in all-cause mortality at lag 0-1, but only -2.00% [-2.83%, -1.17%] at lag 2-3. Differences in the temperature-mortality relationship caused by hot days and hot nights

  17. Effect of prolonged free-walking fatigue on gait and physiological rhythm.

    Yoshino, Kohzoh; Motoshige, Tomoko; Araki, Tsutomu; Matsuoka, Katsunori


    This study examined the ways in which gait patterns and physiological rhythms such as those of muscle activity (tibialis anterior (TA) and biceps femoris (BF)) and cardiac activity are affected by the fatigue induced by prolonged free walking. Twelve normal subjects who walked for 3 h at their preferred pace were divided into two groups according to whether their mean gait cycle time (reciprocal of stride rate) during the second 90 min was higher (Group A: n=8) or lower (Group B: n=4) than that during the first 90 min. For Group A, the level of subjective fatigue during the walking task was significantly higher and the heart rate at rest was significantly lower than Group B. In Group A, prolonged walking significantly decreased the mean power frequency of the electromyography from TA, increased the variability of gait rhythm, decreased the largest Lyapunov exponent of the vertical component of back-waist acceleration, and decreased the amplitude of the vertical component of back-waist acceleration. Taking the onset timings of these changes into account, we propose that subjects who tire easily during prolonged walking first show local muscle fatigue at TA followed by instability of gait rhythm and then they slow their gait rhythm to enhance local dynamic stability. For both groups we constructed a physical fatigue index described by linear regression of gait and physiological variables. When we compared the subjective fatigue level with the fatigue level predicted using the index, we obtained a relatively high correlation coefficient for both groups (r=0.77).

  18. Design of novel injectable cationic microspheres based on aminated gelatin for prolonged insulin action.

    Morimoto, Kazuhiro; Chono, Sumio; Kosai, Tadashi; Seki, Toshinobu; Tabata, Yasuhiko


    The aim of this study was to prepare two types of injectable cationized microspheres based on a native gelatin (NGMS) and aminated gelatin with ethylenediamine (CGMS) to prolong the action of insulin. Release of rhodamin B isothiocyanate insulin from CGMS was compared with that from NGMS under in-vitro and in-vivo conditions. Lower release of insulin from CGMS compared with that from NGMS was caused by the suppression of initial release. The disappearance of 125I-insulin from the injection site after intramuscular administration by NGMS and CGMS had a biphasic profile in mice. Almost all the 125I-insulin had disappeared from the injection site one day after administration by NGMS. The remaining insulin at the injection site after administration by CGMS was prolonged, with approximately 59% remaining after one day and 16% after 14 days. The disappearance of CGMS from the injection site was lower than that of NGMS. However, the difference in these disappearance rates was not great compared with those of 125I-insulin from the injection site by NGMS and CGMS. The time course of disappearance of 125I-CGMS from the injection site was similar to that of 125I-insulin by CGMS. The initial hypoglycaemic effect was observed 1 h after administration of insulin by NGMS, thereafter its effect rapidly disappeared. The hypoglycaemic effect was observed 2-4 h after administration by CGMS and continued to be exhibited for 7 days. The prolonged hypoglycaemic action by CGMS depended on the time profiles of the disappearance of insulin from muscular tissues, which occurs due to the enzymatic degradation of CGMS.

  19. Prolonged and recurrent global seafloor anoxia in the Early Triassic from uranium isotopic evidence

    Lau, K. V.; Maher, K.; Kelley, B. M.; Yu, M.; Lehrmann, D. J.; Payne, J.


    The end-Permian extinction and prolonged Early Triassic recovery of marine ecosystems have been attributed in part to marine anoxia. However, the spatial and temporal extent of anoxic waters during Early Triassic time remains poorly understood. To better constrain the evolution of seawater conditions, we present a record of δ238/235U and uranium concentrations collected from the Great Bank of Guizhou, a Late Permian to Late Triassic isolated carbonate platform in the Nanpanjiang Basin, South China. The isotopic composition and concentration of uranium are independent constraints on paleoredox conditions and can be used as indicators for the global extent of ocean anoxia. Our δ238/235U results demonstrate that two large negative excursions of up to ~-0.4‰ occurred in the Induan and in the Spathian, before stabilizing in the Middle Triassic at Late Permian values. Uranium concentrations mirror the isotopic trends, reaching sustained minima of less than 0.2 ppm that correspond to the most negative isotopic values. By placing these observational constraints on a box model of the geological uranium cycle, we calculate that up to half of the continental shelves may have been affected during the two pulses of bottom-water anoxia. The expansion, contraction, and re-expansion of extreme low-oxygen conditions could explain many unresolved aspects of the prolonged recovery of marine ecosystems. The recurrence of widespread anoxia during Spathian time may have interrupted the recovery of marine organisms that began in the more oxic waters of the Smithian. These episodes of significant and prolonged bottom-water anoxia coincide with the most negative δ13C values, suggesting that Early Triassic perturbations to the global carbon cycle were tightly coupled to changes in ocean redox chemistry.

  20. Hydrogen/deuterium exchange study of subtilisin Carlsberg during prolonged exposure to organic solvents.

    Fasoli, Ezio; Ferrer, Amaris; Barletta, Gabriel L


    It has been previously reported that prolonged exposure of an enzyme to organic solvents leads to substantial decrease of activity. This effect was found to be unrelated to the catalysts' structure or their possible aggregation in organic solvents, and up to the present day the cause for activity loss remains unclear. In the present work, the structural dynamics of the serine protease subtilisin Carlsberg (SC) have been investigated during prolonged exposure to two organic solvents by following hydrogen/deuterium (H/D) exchange of mobile protons. The enzyme, after lyophilization, was incubated in organic solvents at controlled deuteriated water activity for different times and the H/D exchange was allowed to take place. The amount of deuterium exchanged was evaluated by (2)H NMR, which in turn gave us a picture of the changing dynamics of our model enzyme during incubation and under different experimental conditions. Our results show that the flexibility of SC decreases during prolonged storage in 1,4-dioxane (Diox) and acetonitrile (ACN) as indicated by the observed 3- to 10-fold decrease in the apparent rate constants of exchange (k) of fast exchangeable protons (FEP) and slow exchangeable protons (SEP) in the protein. Our study also shows that SC is more flexible in ACN than in Diox (k 3-20 times higher in ACN for the FEP and SEP), suggesting that enzyme dynamics are affected by solvent physicochemical properties. Additionally, the enzyme dynamics are also affected by the method of preparation: decreased flexibility (k decreases 3- to 10-fold for FEP and SEP) is observed when the enzyme is chemically modified with poly ethylene glycol (PEGylated) or colyophilized with crown ethers. A possible relationship between activity, enantioselectivity (E), and structural dynamics is discussed, demonstrating that direct correlations, as have been attempted in the past, are hampered by the multi-variable nature and complexity of the system.