bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian Rhythms of Fibrinogen, Antithrombin III and Plasminogen in Chronic Liver Diseases of Increasing Severity
Authors: Pasqualetti Paolo , Festuccia Vittorio , Acitelli Pierluigi , Natali Laura , Collacciani Antonio , Casale Raffaele
Published: May 2009

Acquired deficiencies of fibrinogen, antithrombin III and plasminogen are reported in liver disease, and it is known that their plasma levels fluctuate during the day. The aim of this study was to investigate the circadian rhythms of these three factors in chronic liver disease. Five groups of subjects were considered: (A) 15 healthy controls; (B) 15 patients with hepatic alcoholic steatosis; (C) 15 patients with chronic active hepatitis; (D) 15 patients with compensated cirrhosis of the liver, and (E) 15 patients with decompensated cirrhosis with ascites. The levels of fibrinogen, antithrombin III and plasminogen were determined in blood samples drawn in each subject during the span of a day every 3 h starting from midnight. The time-related values were analyzed using the ‘population-mean cosinor’ method. Groups A and B presented a significant (p < 0.05) circadian rhythm for each variable, group C a significant (p < 0.05) circadian rhythm for fibrinogen and antithrombin III and groups D and E no significant (p > 0.05) circadian rhythms. Statistically significant differences (p < 0.05) were demonstrated among the groups in the mean daily levels of the three variables by ANOVA, the concentrations decreasing with disease severity. These data confirm the existence of a significant diurnal periodicity in the circulating levels of fibrinogen, antithrombin III and plasminogen in controls and suggest that liver disease is associated with progressive circadian modifications in the temporal structure of fibrinogen, antithrombin III and plasminogen, related to the stage of the liver disease. The rhythm derangements may be considered markers of evolution in liver disease.
Experimental Hemolytic Uremic Syndrome Induced by Lipopolysaccharide Irritation of Celiac Ganglia in Rats
Authors: She Liping , Kanayama Naohiro , Maradny Emad El , Halim Abdul , Maehara Kayoko , Terao Toshihiko
Published: May 2009

Although nervous system complications often appear in hemolytic uremic syndrome (HUS), the relationship between HUS and the nervous system is still not clear. We suspect that damage to the nervous system may play a role in the pathophysiology of HUS. In this context, rats received different doses of lipopolysaccharide (LPS) or saline to celiac ganglia or peritoneum. In rats treated with LPS on the celiac ganglia, a significant decrease in platelet count (p < 0.05) and a significant increase in blood urea nitrogen (p < 0.05) were found, and at the same time plasma levels of adrenaline and noradrenaline increased markedly (p < 0.05). The renal arterioles and glomeruli showed endothelial swelling and narrowing of the lumina. Intense immunostaining for von Willebrand factor and fibrinogen in glomeruli and renal vessels was also observed. These parameters were accompanied by a systolic blood pressure elevation. The results suggest that the sympathetic nervous system plays an important role in the pathogenesis of HUS.
Determination of Coagulation Inhibitor Levels and Resistance to Activated Protein C in Patients Undergoing Gastric Surgery for Benign and Malignant Disorders
Authors: Andersen B.S. , Rahr H.B. , Sørensen J.V.
Published: May 2009

The aim of the present study was to determine plasma levels of protein C antigen (PC:Ag) and activity (PC:Act), tissue factor pathway inhibitor (TFPI), protein S (PS), antithrombin (AT), heparin cofactor II (HCII), and resistance to activated protein C (APCR) before, during and after elective gastric surgery in order to compare patients with and without gastric malignancy. Blood was collected from a forearm vein of two age-matched patient groups undergoing elective gastric surgery, 9 patients with and 9 patients without gastric malignancy. The plasma levels of the parameters were determined preopera-tively, intraoperatively, and on days 1 and 7 postoperatively. On the 1st and 7th postoperative day, plasma levels of HCII were significantly lower in patients operated for gastric malignancy than in those operated for benign disorders, but levels of TFPI, PC:Act, PC:Ag, AT, PS and APCR did not differ in the postoperative period. The day-to-day variation was also rather similar in the two patient groups.
Extrinsic Coagulation Factors and Tissue Factor Pathway Inhibitor in End-Stage Chronic Renal Failure
Authors: Matsuo Takefumi , Koide Masanobu , Kario Kazuomi , Suzuki Shunji , Matsuo Miyako
Published: May 2009

The relationship between extrinsic coagulation factors, tissue factor pathway inhibitor (TFPI) and activated factor XII (FXIIa) was examined in 71 patients with end-stage chronic renal failure. They had chronic stable uremia due to regular hemodialysis. The patients were divided into two age- and sex-matched groups with and without diabetes mellitus. As extrinsic coagulation parameters, FVIIa and FVII antigen (FVIIag), tissue factor antigen and TFPI (the activity and antigen) were measured. FXIIa was measured as a marker of contact activation, and thrombin generation was evaluated using the two markers thrombin-antithrombin III complex and prothrom-bin fragment 1 + 2. In both hemodialysis groups with and without diabetes, significant elevations of FXIIa, FVIIa and tissue factor, with high levels of TFPI, were found. Thus, hyperactivation of the coagulation system was in part compensated by TFPI, and a significant increase in FXIIa could not directly affect FVIIa hyperactivation. No differences of these parameters, except for FVIIag and fragment 1+2, were found between the groups with and without diabetes. It is suggested that the long-term hemodialysis might have masked any differences due to the underlying disease in these two subgroups.
In vitro Analysis of Synergistic Effects of Fibrinolytic Agents and Prostacyclin Analogues
Authors: Spiecker Martin , Heinke Birgit , Meyer Jürgen , Darius Harald
Published: May 2009

We investigated the in vitro thrombolytic effects of streptoki-nase, urokinase, alteplase and saruplase, alone or in combination, with the prostacyclin analogues, iloprost and taprostene. Human platelet-rich plasma was stimulated with collagen (1 μg/ml) to generate thrombi containing platelets and fibrin. Following treatment with fibrinolytic agents, lysis was allowed to proceed for 30 min and was then terminated with aprotinin (2,000 ClU/ml). To evaluate the combinatory effects of fibrinolytic agents and prostacyclin analogues, we used concentrations of fibrinolytic agents which reduced thrombi weight by less than 50%. Neither iloprost nor taprostene alone demonstrated any thrombolytic effects. Furthermore, the thrombolytic efficacies of streptokinase, alteplase and saruplase were not enhanced by prostacyclin analogues. The thrombolytic activities of alteplase and urokinase, however, were additive. Similarly, the combination of urokinase with saruplase had an additive thrombolytic effect in our in vitro model. The effects of alteplase and saruplase were synergistic at a molar ratio of 1:4.7.
Laboratory Assessment of Antithrombotic Therapy: What Tests and If So Why?
Authors: Kher André , Al Dieri Raed , Hemker Coenraad , Béguin Suzette
Published: May 2009

A critical review is given of the tests available for the assessment of the action of anticoagulants, such as heparins, oral anticoagulants and direct thrombin inhibitors, in patients under antithrombotic therapy. The principle of action and the performance of the thromboplastm time (PT), the activated partial thromboplastin time (aPTT), the whole blood clotting time, the thrombin time, the ecarin clotting time and the endogenous thrombin potential (ETP) is discussed, as well as the evidence behind the accepted therapeutic ranges. The two most common tests, PT and aPTT, respond in an essentially different way to clinically effective anticoagulation with hepa-rin and with oral anticoagulants. This means that they covar-iate with, but do not themselves represent the essential parameter influenced by anticoagulation. The experimental basis for the widely accepted two times prolongation of the aPTT as an indicator for adequate anticoagulation is shown to be meagre in the case of unfractionated heparin and lacking for the other anticoagulants. Common sources for error in the interpretation of anti-factor Xa- and anti-thrombin activity of heparins are indicated. Extensive experience with new tests like the ecarin clotting time and the ETP is still lacking. On the basis of preliminary data and in view of the importance of the enzymatic action of thrombin in the pathogenesis of thrombosis, the ETP is considered a possible candidate for a common parameter to assess different types of anticoagulants.
Postoperative Activation of the Haemostatic System - Influence of Prolonged Thromboprophylaxis in Patients Undergoing Total Hip Arthroplasty
Authors: Andersen Birthe Søgaard
Published: May 2009

Tissue injury during hip surgery results in the activation of the haemostatic system. The aim of this study was to detect markers of haemostatic activity, i.e. prothrombin fragment 1 and 2 (Fl+2), thrombin-antithrombin (TAT) complexes, fibrin degradation products (FbDP), and soluble fibrin monomers (SF), preoperatively, and on days 1, 7 and 35 in plasma of patients undergoing total hip arthroplasty. The study was part of a mul-ticentre study in which the patients were randomized to receive a subcutanous injection of low molecular weight heparin (LMWH, dalteparin, Fragmin®) once daily for 5 weeks or placebo following a 1-week LMWH treatment (once daily). Bilateral phlebography was performed between days 33 and 35 or before if patients had clinical symptoms of deep vein thrombosis. A lung scan was performed in patients with clinical symptoms of pulmonary embolism. Levels of the markers were significantly increased on day 35 in the patients receiving LMWH for 7 days compared to patients receiving LMWH for 35 days. In patients receiving LMWH for 5 weeks, levels of FbDP and SF were significantly higher during the entire study period, but TAT and Fl+2 were normalized on day 35. The markers were increased two to five times on the 1 st postoperative day in patients with diagnosed venous thromboembo-lism.
Enhanced Thrombogenicity and Altered Hemodynamics in the Cerebral Mïcrovasculature of Stroke-Prone Spontaneously Hypertensive Rats
Authors: Noguchi Takanori , Sasaki Yasuto , Seki Junji , Giddings John C. , Yamamoto Junichiro
Published: May 2009

Thrombotic potential and hemodynamic changes were assessed in the cerebral microcirculation in normal rats (WKY), non-stroke-prone spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) at the age of 4, 16 and 32 weeks. Whole blood platelet aggregation revealed that the platelet aggregability in vitro was significantly depressed in SHRSP compared to WKY at 16 and 32 weeks using 2 μg/ml collagen but was similar or higher than WKY at 32 weeks using 20 or 40 μg/ml collagen. Platelet-rich thrombi were induced using a helium-neon (He-Ne) laser technique in vivo. The numbers of laser pulses required to induce an occlu-sive thrombus in arterioles were similar in the three strains at the age of 4 weeks. In contrast, the numbers of laser pulses needed to induce vascular occlusion in SHR (5.5 ± 0.7; n = 4) and SHRSP (4.9 ± 0.3; n = 4) were lower than in WKY (7.4 ± 0.3; n = 5) at the age of 16 weeks. Similar differences were observed at 32 weeks (SHR 5.8 ± 0.2; n = 6; SHRSP 4.3 ± 0.1; n = 4; WKY 7.0 ± 0.2; n = 7). Red blood cell velocities were measured in pial arterioles using a fiber-optic laser Doppler anemometer microscope. Red cell velocities and wall shear rates in SHR and SHRSP were significantly lower than those in WKY (p < 0.05) at the age of 16 weeks and were markedly lower in SHRSP than in either WKY or SHR at the age of 32 weeks. The plasma concentration of nitrite/nitrate determined by the Griess reaction was significantly reduced in SHRSP at 32 weeks compared with 4-week-old rats. These changes could contribute to the enhanced tendency to cerebro-vascular stroke in SHRSP.
Warfarin-Induced Skin Necrosis Occurring Four Days after Discontinuation of Warfarin
Authors: Wynn S.S. , Jin D.K. , Essex D.W.
Published: May 2009

Warfarin-induced skin necrosis is a rare complication of warfarin therapy. It appears between days 1 and 10 of therapy while the patient is receiving warfarin. Warfarin-induced skin necrosis occurring several days after cessation of therapy has not been reported. We report an atypical case of warfarin-induced skin necrosis which occurred 96 h after the last dose of warfarin was given while the prothrombin time was still elevated.
No Coagulation Disorders under High-Dose Volume Therapy with Low-Molecular-Weight Hydroxyethyl Starch
Authors: Stoll Martin , Treib Johannes , Schenk Joachim F. , Windisch Florian , Haass Anton , Wenzel Ernst , Schimrigk Klaus
Published: May 2009

Hydroxyethyl starch (HES) is often used for volume therapy. Since bleeding complications have been reported repeatedly, a strict dose limitation of a maximum of 1,500 ml 6% solution per day is recommended. However, many indications require higher dosages. Bleeding complications are known to be caused by an acquired von Willebrand syndrome. It has been shown that the accumulation of large molecules and their impairment in the coagulation system can be avoided by using HES preparations with a low in vivo molecular weight. However, the effects of a high-dose therapy have not been studied yet. We have investigated, how a 4-day high-dose therapy, using 3,000 ml 6% HES 70/0.5 on the 1st day and 1,500 ml on days 2-4, affects the coagulation system and hemorheological parameters of acute stroke patients. Thromboplastin time, activated partial thromboplastin time and thrombin time showed no significant changes, except for a slight, clinically irrelevant change due to dilution. The subunits of von Willebrand factor VIII showed no significant change. Hematocrit decreased from 42.3 ± 4.6 to 37.4 ± 3.9% (p < 0.05) after day 1, reaching 35.3 ± 4.2% (p < 0.01) at the end of the therapy, demonstrating a substantial volume effect. Plasmaviscosity and erythrocyte aggregation decreased slightly, however not significantly. Our study shows that even a high-dose therapy with 6% HES 70/0.5 has no influence on the coagulation system.
Annexin V Expression and Membrane Vesiculation during Activation of Leukemic Cell Lines
Authors: Xie Gui Lan , Nomura Shosaku , Fukuhara Shirou
Published: May 2009

We investigated annexin V expression and membrane vesiculation during activation of four leukemic cell lines (U937, HL60, HEL, and CMKl 1-5) in order to determine whether annexin V had a role in the coagulation abnormalities related to malignancy. After stimulation by tissue plasminogen activator, binding of a monoclonal anti-annexin V antibody to U937 cells and HL60 cells increased in comparison with binding to control cells. Stimulation with thrombin or lipopolysaccharide also induced such an increase, but U46619 did not. Following activation of U937 and HL60 cells with thrombin and lipopolysaccharide, microparticle formation increased. Tissue plasminogen activator caused an increase of micropar-ticles in U937 cells, but not HL60 cells. On the other hand, CMKl 1-5 and HEL cells did not show any increase of micro-particles. These results suggest that some agonists can potently stimulate expression of prothrombinase activity by U937 and HL60 cells. This response appears to be related to cell membrane vesiculation induced by thrombin, tissue plasminogen activator, or lipopolysaccharide, which results in the release of microparticles with binding sites for annexin V. In addition, endogenous annexin V released by leukemic cells may modulate the thrombotic activity of these microparticles.
Protective Role of Platelets in Chronic (Balb/C) and Acute (CBA/J) Plasmodium berghei Murine Malaria
Authors: Polack B. , Delolme F. , Peyron F.
Published: May 2009

The role of blood platelets in the pathogenesis of malaria remains unclear. In this study we investigated the role of experimentally caused thrombocytopaenia in chronic (Balb/C) and acute (CBA/J) Plαsmodium-berghei-induced murine malaria. A group of 30 Balb/C mice were rendered thrombocyto-paenic by injection of anti-mouse platelet serum given every 2 days from day 2 to day 8 after malaria infection. Compared with the control group, thrombocytopaenic mice showed a greater mortality. The Kaplan-Meier estimate of the risk of death was 4.37-fold higher in the thrombocytopaenic group. Parasitaemia and weight loss was in agreement with the protective effect of platelets. In the acute malaria model, the survival rate was less significant but the estimated risk of death was 1.7-fold higher in the treated group. These results suggesting a protective role of platelets in murine malaria are not in line with previous reports of the literature. Taken together our data suggest, however, that platelets, similarly to some inflammatory cytokines like TNF, play a dual role in the pathogenesis of malaria. Depending on experimental conditions, e.g. the time of onset of thrombocytopaenia, the beneficial role of platelets may outweigh the deleterious one.
Acquired Type 2a von Willebrand’s Disease: Response to Immunoglobulm Infusion
Authors: Sampson B. , Anderson D.R. , Dugal M. , Ing V.W. , Zayed E.
Published: May 2009

A 75-year-old male presented with new symptoms of a bleeding diathesis associated with a decline in the functional activity of von Willebrand factor (type 2a von Willebrand’s disease). Replacement therapy was ineffective and he was subsequently treated with intravenous immunoglobulm (Ivlg). Ivlg not only caused symptomatic improvement but was shown to transiently restore the depleted von Willebrand factor intermediate and high molecular weight multimers. Subsequent periodic Ivlg infusions have been used successfully to treat bleeding complications in this patient over the past 3 years. A secondary cause for the acquired von Willebrand’s disease has not been identified.
A Highly Specific Functional Test for Factor V Leiden: A Modified Tissue Factor Assay for Activated Protein C Resistance
Authors: Arkel Y.S. , Ku D.-H. , Kamiyama M. , Pajaro R. , Alder H. , Marchand A.
Published: May 2009

We compared the sensitivity and specificity of a tissue factor-based assay (FVR) with the addition of a phospholipid/silica preparation, to the commercially available aPTT-based method, APCR (CoatestTM), and a modified aPTT-based method (APCM) which utilized factor V-depleted plasma, for the detection of the factor V Leiden mutation. A total of 110 patients were included in this study. This included 32 patients on coumadin therapy, 7 patients on heparin therapy, 5 patients on both anticoagulants therapy, and 24 patients who were positive for anticardiolipin antibody (ACL) and/or lupus inhibitor (LI). Our data demonstrate that the FVR is not affected by anticoagulation treatment or ACL/LI antibodies, whereas in the APCR method, 33 patients cannot be determined either due to the anticoagulant therapy or presence of the ACL and/or LI. With the APCM method, the clotting end-point could not be determined in 1 patient due to the presence of a strong LI. The additional phospholipid/silica material utilized in the FVR enhanced the APC degradation of factor Va and therefore sharpened the demarcation between the factor V Leiden-positive and -negative patients. The sensitivity for the APCR, APCM and FVR was 42, 97 and 100% respectively. The specificity for the APCR, APCM and FVR was 94,96 and 100% respectively.
Pathogenesis of Thrombosis in Coronary Artery Disease
Authors: Chesebro James H. , Rauch Ursula , Fuster Valentin , Badimon Juan J.
Published: May 2009

Arterial thrombosis in the acute coronary syndromes is precipitated by plaque disruption. This occurs in lesions with a large lipid core, a thin fibrous cap, macrophages infiltrating the fibrous cap, and a lipid core with a high tissue-factor content. This results in acute platelet deposition and rapid growth of mural thrombus which unfavorably influences the rheology of blood flow to produce more thrombus, and propagates additional thrombosis by the high thrombogenicity of the mural thrombus overlying the disrupted culprit arterial lesion. Acute therapy in the hospital and subacute therapy beyond the hospital phase for as long as 1.5-3 months with aspirin plus anti-coagulation, such as low-molecular-weight heparin, or oral anticoagulation, reduces thrombotic occlusion, myocardial infarction, death, and need for coronary revascularization.
Low-Molecular-Weight Heparins and Unstable Angina – Current Perspectives
Authors: Turpie Alexander G.G.
Published: May 2009

Thrombosis is responsible for most acute manifestations of coronary artery disease, including unstable angina and non-Q-wave myocardial infarction (MI). Antiplatelet therapy plays a major role in reducing the risk of ischaemic events in such patients. Since thrombin generation is key in the pathogenesis of thrombosis, recent studies have focussed on thrombin inhibition in the management of acute ischaemia. Heparin is the most widely used anticoagulant for acute management of thrombosis and is the treatment of choice in the prevention and treatment of venous thrombo-embolism. Heparin given in therapeutic doses intravenously has been shown to be more effective than aspirin at reducing the risk of death or MI in patients with unstable angina. Low-molecular-weight heparins (LMWHs) have improved pharmacologic and pharmacokinetic properties over standard heparin that may result in greater efficiency and safety. LMWH may be given in fixed doses subcutaneously without monitoring, resulting in greater clinical utility and cost-effectiveness compared with standard heparin. A number of LMWHs – dalteparin, enoxaparin and nadroparin – have been evaluated in unstable angina. In a small open trial, nadroparin reduced the risk of ischaemic outcomes compared with aspirin alone or a combination of aspirin and standard heparin. Dalteparin has been evaluated in two large clinical trials in the management of unstable angina. The Low-Molecular-Weight Heparin (Fragmin) During Instability in Coronary Artery Disease (FRISC) trial showed that dalteparin resulted in a 63% reduction in risk of death or acute MI compared with aspirin alone. The Fragmin in Unstable Coronary Artery Disease (FRIC) trial showed that dalteparin was as effective as intravenous heparin. Enoxaparin resulted in a statistically significant 16% reduction in the combined outcome of death, MI and recurrence of angina in comparison with standard heparin in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial. There is accumulating evidence that LMWHs are safe and effective alternatives to standard heparin in unstable coronary artery disease and that they offer practical and therapeutic advantages.
Markers of Hypercoagulability in Cancer Patients
Authors: Mannucci P.M.
Published: May 2009

In the last few years, several assays have been developed that permit the evaluation, with a high degree of sensitivity, of the level of activation of the coagulation system. Some of these tests have been used in cancer patients, in an attempt to monitor the risks of tumour progression and the development of thromboembolic complications. Even though coagulation activation markers are often abnormally elevated, the results available so far do not indicate that they are useful in the clinical management of individual cancer patients.
Prevention of Venous Thromboembolism in Cancer Using Low-Molecular-Weight Heparins
Authors: Kakkar A.K. , Williamson R.C.N.
Published: May 2009

Patients with cancer are at increased risk for venous and arterial thromboembolism and the principal interventions in such patients – surgical operation, chemotherapy or venous catheterization – heighten this risk. Thromboprophylaxis is indicated in cancer patients undergoing surgical operation and there is also evidence that thrombopropylaxis appears beneficial during chemotherapy, particularly for breast cancer, and possibly for ovarian and pancreatic carcinoma. Low-molecular-weight heparins (LMWHs) have shown promise as a thromboprophylactic agent in oncology patients, and offer significant benefits over standard heparin because of their improved safety profile and ease of use. There is emerging evidence that LMWHs may also favourably influence survival, possibly as a result of direct anti-tumour effects.
Treatment of Thrombotic Disorders in Cancer Patients
Authors: Levine M.
Published: May 2009

Cancer patients are in a hypercoagulable state. The pathogenesis of thrombosis in malignancy is multifactorial with mechanisms including release of procoagulants by tumour cells, comorbid predisposing factors (bed rest, infection, surgery, etc.) and anti-cancer drugs. Cancer patients with established venous thromboembolism are more likely to develop recurrent venous thromboembolism during treatment with oral anticoagulants. This paper reviews the use of heparin for the treatment of thrombotic disorders in cancer patients. Treatment of acute venous thrombosis comprises initial heparin administration, which for a cancer patient should last for at least 5 days, followed by administration of oral anticoagulants. Low-molecular-weight heparins (LMWHs) have been shown to be as safe and effective as standard heparin for the treatment of acute deep vein thrombosis. Recent meta-analyses have revealed lower mortality rates with LMWH than with standard heparin, indicating that LMWH may exert an inhibitory effect on tumour growth that is not observed with standard heparin.
Renal Allograft Calcification – Prevalence and Etiology in Pediatric Patients
Authors: Habbig Sandra , Beck Bodo B. , Feldkötter Markus , Körber Friederike , Laffeber Charlie , Verkoelen Carl , Mihatsch Michael J. , Hoppe Bernd
Published: May 2009

Background: Calcification of renal allografts has been reported in adult kidney transplant (KTx) recipients with a widely differing prevalence (2–60%). Persistent hyperparathyroidism, hypercalcemia and concomitant hypercalciuria were identified as major risk factors. We aimed to determine the prevalence and risk factors for such calcifications in children. Methods: We investigated histological stains of routine graft biopsies from pediatric KTx patients for renal calcifications and determined the urinary excretion of lithogenic (oxalate, calcium) and stone-inhibitory substances (citrate). Results: In our series of transplant patients, tubular calcification was found in 16 of the 36 (44.4%) KTx biopsies by an additional Kossa stain. This transplant calcification was not associated with any singular risk factor and was not correlated to a worse transplant outcome. Conclusion: Although our pediatric findings confirm the reported incidence rates of KTx calcification in adults, we could neither identify hypercalciuria as a risk factor nor confirm any negative influence on graft function. However, long-term studies are clearly needed to prove or disprove a negative impact of calcifications on graft function.
Factors Influencing Uptake of Pharmacogenetic Testing in a Diverse Patient Population
Authors: O’Daniel J. , Lucas J. , Deverka P. , Ermentrout D. , Silvey G. , Lobach D.F. , Haga S.B.
Published: May 2009

Background: The successful integration of pharmacogenetic (PGx) testing into clinical care will require attention to patient attitudes. In this study, we aimed to identify the major reasons why patients would or would not consider PGx testing and whether these factors differed by race, socioeconomic and insurance status, and medical history. Methods: We developed and conducted a survey within the adult patient population of the Duke Family Medicine Center. Results: Of 75 completed surveys (65% African-American), 77% indicated they were ‘very likely’ or ‘somewhat likely’ to take a PGx test. Respondents who had experienced a side effect were significantly more likely to indicate they would take a PGx test and expressed greater interest in learning more about testing than those who had not. Drug safety and effectiveness were the major reasons to have PGx testing. Privacy concerns and lack of insurance coverage for testing were the major reasons to decline testing. Conclusions: We found no differences in interest in PGx tests by race or socioeconomic status, but found stronger interest from those with a history of side effects and private insurance. While the overall support of PGx testing is encouraging, greater reassurance of medical privacy and development of educational resources are needed.
Results of Reconstruction with Jejunal Pouch after Gastrectomy: Correlation with Gastrointestinal Motor Activity
Authors: Shibata Chikashi , Ueno Tatsuya , Kakyou Masayuki , Kinouchi Makoto , Sasaki Iwao
Published: May 2009

Background/Aims: To investigate if restoration of esophago-intestinal or esophago-gastric continuity with a jejunal pouch after total or proximal gastrectomy has clinical benefits. Methods: We reviewed all relevant reports published after 1990 that dealt with the clinical results of reconstruction with a jejunal pouch after total and proximal gastrectomies and correlated those findings with results for gastrointestinal motility. Reports were chosen from a search of the literature using PubMed. Results: After total gastrectomy, the benefit of a jejunal J pouch interposition was not apparent compared to simple jejunal interposition; indeed, one trial concluded that simple interposition was better than pouch interposition in terms of food intake. In contrast, results with a jejunal J pouch during Roux-en-Y (RY) type reconstruction were better than with conventional RY reconstruction in terms of food intake, nutritional status, body weight (BW) and symptoms. Advantages were also shown for a jejunal pouch with an inverted U shape interposed between the esophagus and residual stomach after proximal gastrectomy. Reconstruction using a jejunal pouch after proximal gastrectomy was better than esophagogastrostomy or simple jejunal interposition in terms of food intake, BW and symptoms. There were not enough data to conclude any benefits of a jejunal J pouch between the gastric remnant and the duodenum after distal gastrectomy. Conclusions: Clinical results of restoration of intestinal continuity with a jejunal pouch after total and proximal gastrectomies may be attributed, at least in part, to the relationship between the motor activity of the gastric remnant, duodenum and jejunal pouch.
A Genetic System Based on Simulated Crossover: Stability Analysis and Relationships with Neural Nets
Authors: Carpentieri Marco
Published: May 2009

We consider a marginal distribution genetic model based on crossover of sequences of genes and provide relations between the associated infinite population genetic system and the neural networks. A lower bound on population size is exhibited stating that the behavior of the finite population system, in the case of sufficiently large sizes, can be approximated by the behavior of the corresponding infinite population system. Assumptions on fitness and individual chromosomes are provided implying that the behavior of the finite population genetic system remains consistent with the behavior of the associated infinite population genetic system for suitably long trajectories. The attractors (with binary components) of the infinite population genetic system are characterized as equilibrium points of a discrete (neural network) system that can be considered as a variant of a Hopfield's network; it is shown that the fitness is a Lyapunov function for the variant of the discrete Hopfield's net. Our main result can be summarized by stating that the relation between marginal distribution genetic systems and neural nets is much more general than that already shown elsewhere for other simpler models.
Pair Approximations of Takeover Dynamics in Regular Population Structures
Authors: Payne Joshua L. , Eppstein Margaret J.
Published: May 2009

In complex adaptive systems, the topological properties of the interaction network are strong governing influences on the rate of flow of information throughout the system. For example, in epidemiological models, the structure of the underlying contact network has a pronounced impact on the rate of spread of infectious disease throughout a population. Similarly, in evolutionary systems, the topology of potential mating interactions (i.e., population structure) affects the rate of flow of genetic information and therefore affects selective pressure. One commonly employed method for quantifying selective pressure in evolutionary algorithms is through the analysis of the dynamics with which a single favorable mutation spreads throughout the population (a.k.a. takeover time analysis). While models of takeover dynamics have been previously derived for several specific regular population structures, these models lack generality. In contrast, so-called pair approximations have been touted as a general technique for rapidly approximating the flow of information in spatially structured populations with a constant (or nearly constant) degree of nodal connectivities, such as in epidemiological and ecological studies. In this work, we reformulate takeover time analysis in terms of the well-known Susceptible-Infectious-Susceptible model of disease spread and adapt the pair approximation for takeover dynamics. Our results show that the pair approximation, as originally formulated, is insufficient for approximating pre-equibilibrium dynamics, since it does not properly account for the interaction between the size and shape of the local neighborhood and the population size. After parameterizing the pair approximation to account for these influences, we demonstrate that the resulting pair approximation can serve as a general and rapid approximator for takeover dynamics on a variety of spatially-explicit regular interaction topologies with varying population sizes and varying uptake and reversion probabilities. Strengths, limitations, and potential applications of the pair approximation to evolutionary computation are discussed.
A Strategy with Novel Evolutionary Features for the Iterated Prisoner's Dilemma
Authors: Li Jiawei , Kendall Graham
Published: May 2009

In recent iterated prisoner's dilemma tournaments, the most successful strategies were those that had identification mechanisms. By playing a predetermined sequence of moves and learning from their opponents' responses, these strategies managed to identify their opponents. We believe that these identification mechanisms may be very useful in evolutionary games. In this paper one such strategy, which we call collective strategy, is analyzed. Collective strategies apply a simple but efficient identification mechanism (that just distinguishes themselves from other strategies), and this mechanism allows them to only cooperate with their group members and defect against any others. In this way, collective strategies are able to maintain a stable population in evolutionary iterated prisoner's dilemma. By means of an invasion barrier, this strategy is compared with other strategies in evolutionary dynamics in order to demonstrate its evolutionary features. We also find that this collective behavior assists the evolution of cooperation in specific evolutionary environments.
Observing Learned Object-specific Functional Grasps Preferentially Activates the Ventral Stream
Authors: Valyear Kenneth F. , Culham Jody C.
Published: May 2009

In one popular account of the human visual system, two streams are distinguished, a ventral stream specialized for perception and a dorsal stream specialized for action. The skillful use of familiar tools, however, is likely to involve the cooperation of both streams. Using functional magnetic resonance imaging, we scanned individuals while they viewed short movies of familiar tools being grasped in ways that were either consistent or inconsistent with how tools are typically grasped during use. Typical-for-use actions were predicted to preferentially activate parietal areas important for tool use. Instead, our results revealed several areas within the ventral stream, as well as the left posterior middle temporal gyrus, as preferentially active for our typical-for-use actions. We believe these findings reflect sensitivity to learned semantic associations and suggest a special role for these areas in representing object-specific actions. We hypothesize that during actual tool use a complex interplay between the two streams must take place, with ventral stream areas providing critical input as to how an object should be engaged in accordance with stored semantic knowledge.
Early Top–Down Control of Visual Processing Predicts Working Memory Performance
Authors: Rutman Aaron M. , Clapp Wesley C. , Chadick James Z. , Gazzaley Adam
Published: May 2009

Selective attention confers a behavioral benefit on both perceptual and working memory (WM) performance, often attributed to top–down modulation of sensory neural processing. However, the direct relationship between early activity modulation in sensory cortices during selective encoding and subsequent WM performance has not been established. To explore the influence of selective attention on WM recognition, we used electroencephalography to study the temporal dynamics of top–down modulation in a selective, delayed-recognition paradigm. Participants were presented with overlapped, “double-exposed” images of faces and natural scenes, and were instructed to either remember the face or the scene while simultaneously ignoring the other stimulus. Here, we present evidence that the degree to which participants modulate the early P100 (97–129 msec) event-related potential during selective stimulus encoding significantly correlates with their subsequent WM recognition. These results contribute to our evolving understanding of the mechanistic overlap between attention and memory.
Neural Correlates of Motion-induced Blindness in the Human Brain
Authors: Schölvinck Marieke L. , Rees Geraint
Published: May 2009

Motion-induced blindness (MIB) is a visual phenomenon in which highly salient visual targets spontaneously disappear from visual awareness (and subsequently reappear) when superimposed on a moving background of distracters. Such fluctuations in awareness of the targets, although they remain physically present, provide an ideal paradigm to study the neural correlates of visual awareness. Existing behavioral data on MIB are consistent both with a role for structures early in visual processing and with involvement of high-level visual processes. To further investigate this issue, we used high field functional MRI to investigate signals in human low-level visual cortex and motion-sensitive area V5/MT while participants reported disappearance and reappearance of an MIB target. Surprisingly, perceptual invisibility of the target was coupled to an increase in activity in low-level visual cortex plus area V5/MT compared with when the target was visible. This increase was largest in retinotopic regions representing the target location. One possibility is that our findings result from an active process of completion of the field of distracters that acts locally in the visual cortex, coupled to a more global process that facilitates invisibility in general visual cortex. Our findings show that the earliest anatomical stages of human visual cortical processing are implicated in MIB, as with other forms of bistable perception.
Dissociating Source Memory Decisions in the Prefrontal Cortex: fMRI of Diagnostic and Disqualifying Monitoring
Authors: Gallo David A. , McDonough Ian M. , Scimeca Jason
Published: May 2009

We used event-related fMRI to study two types of retrieval monitoring that regulate episodic memory accuracy: diagnostic and disqualifying monitoring. Diagnostic monitoring relies on expectations, whereby the failure to retrieve expected recollections prevents source memory misattributions (sometimes called the distinctiveness heuristic). Disqualifying monitoring relies on corroborative evidence, whereby the successful recollection of accurate source information prevents misattribution to an alternative source (sometimes called recall to reject). Using criterial recollection tests, we found that orienting retrieval toward distinctive recollections (colored pictures) reduced source memory misattributions compared with a control test in which retrieval was oriented toward less distinctive recollections (colored font). However, the corresponding neural activity depended on the type of monitoring engaged on these tests. Rejecting items based on the absence of picture recollections (i.e., the distinctiveness heuristic) decreased activity in dorsolateral prefrontal cortex relative to the control test, whereas rejecting items based on successful picture recollections (i.e., a recall-to-reject strategy) increased activity in dorsolateral prefrontal cortex. There also was some evidence that these effects were differentially lateralized. This study provides the first neuroimaging comparison of these two recollection-based monitoring processes and advances theories of prefrontal involvement in memory retrieval.
Object-guided Spatial Attention in Touch: Holding the Same Object with Both Hands Delays Attentional Selection
Authors: Gillmeister Helge , Adler Julia , Forster Bettina
Published: May 2009

Previous research has shown that attention to a specific location on a uniform visual object spreads throughout the entire object. Here we demonstrate that, similar to the visual system, spatial attention in touch can be object guided. We measured event-related brain potentials to tactile stimuli arising from objects held by observers' hands, when the hands were placed either near each other or far apart, holding two separate objects, or when they were far apart but holding a common object. Observers covertly oriented their attention to the left, to the right, or to both hands, following bilaterally presented tactile cues indicating likely tactile target location(s). Attentional modulations for tactile stimuli at attended compared to unattended locations were present in the time range of early somatosensory components only when the hands were far apart, but not when they were near. This was found to reflect enhanced somatosensory processing at attended locations rather than suppressed processing at unattended locations. Crucially, holding a common object with both hands delayed attentional selection, similar to when the hands were near. This shows that the proprioceptive distance effect on tactile attentional selection arises when distant event locations can be treated as separate and unconnected sources of tactile stimulation, but not when they form part of the same object. These findings suggest that, similar to visual attention, both space- and object-based attentional mechanisms can operate when we select between tactile events on our body surface.
The Saint, the Warlord, and the Emperor: Discourses of Braj Bhakti and Bundelā Loyalty
Authors: Pauwels Heidi
Published: May 2009

This paper investigates the way in which bhakti was used by upwardly mobile Rajputs in their struggle to come to terms with their role as local powerbrokers for the centralizing imperial regime. I will present the case study of the Bundelās in the mid-sixteenth century. I will study their complex relationships with the newly established Mughals and their expressions of devotion, particularly in connection with the newly (re)established pilgrimage center of Braj. The paper documents a shift from an older form of religion to bhakti under Madhukar Shāh (r. 1552-92). This change may well have functioned as a bid for local legitimacy, an assertion of regional independence vis à vis the Mughal empire, and was directed against its imperial rhetoric. However, this study also shows that although Madhukar promotes bhakti for his own purpose, the bhakti saint-advisor of the king explicitly resists such socio-political functionality of the religious insights he has to offer. Cette contribution se situe au milieu du XVIème siècle, une période qui vit le régime impérial des Moghol récemment instauré se centralisant. Elle explore la bhakti comme vecteur de l'ascension sociale des Rajput qui n'acceptèrent de sitôt de jouer le rôle de conseillers locals du pouvoir impérial. L'examen des Bundelās vise à dévoiler leurs relations complexes avec les Moghol et leur discours dévotionnel, particulièrement celui relatif au centre de pèlerinage de Braj récemment (r)établi. La contribution témoigne d une part que sous le règne de Madhukar Shāh (1552-'92) une forme plus ancienne de réligion se transforma en bhakti, ce qui soulève des interrogations sur la construction de la légitimité des ces seigneurs locals qui revendiquèrent l'indépendance régionale vis-à-vis l empire Moghol. D'autre part elle démontre que bienque Madhukar favorisât la bhakti pour ses fins propres, le saint-adviseur résista nettement de réduire bhakti à un rôle socio-économique.
Fātimid Ambassadors in Bobastro: Changing Religious and Political Allegiances in the Islamic West
Authors: Enamorado Virgilio Martínez
Published: May 2009

This article focuses on the visit by two Fātimid dā'īs (missionaries or propagandists) to 'Umar ibn Hafsūn, a controversial figure in the history of Muslim Spain. Emphasising the significance of the gifts they brought to Bobastro, Ibn Hafsūn's headquarters, this article analyses the diplomatic relations between North Africa and Islamic Spain in the 10th century and the earliest introduction of Shī'ism in Western Europe. Cette contribution porte sur la visite de deux dā'īs fātimides (missionaires ou propagandistes) à 'Umar ibn Hafsūn qui fut un personnage contesté dans l'histoire de l'Espagne musulmane. Un examen détaillé des cadeaux apportés par eux à Bobastro, le siège de 'Umar ibn Hafsūn, mène à l'analyse des relations diplomatiques entre le Maghreb et l'Andalus au Xème siècle à l'aube de l'introduction de la doctrine chiite en Europe occidental.
The Fiscal and Constitutional Program of Egypt's Traditional Elites in 1879: A Documentary and Contextual Analysis of “al-Lā'iha al-Wataniyya” (“The National Program”)
Authors: EzzelArab AbdelAziz
Published: May 2009

This article analyzes “al-Lā'iha al-Wataniyya,” a proposal adopted in April 1879 by Egypt's economic and political elites as an expression of resistance to the fiscal program of European control. The document was a blueprint for a power redistribution that was aimed at confining European influence while confirming the curtailment of Khedivial authority to the benefit of the elites at large. It furthermore enlarged the power of a specific group within those elites, the indigenous Egyptian notables. This article is relevant for the study of the dynamics between local elites and foreign powers not only in Egypt, but also in the wider context of colonial history in the nineteenth century. Cet article détaille al-Lā'iha al-Wataniyya, un projet adopté en avril 1879 par les élites politico-économiques d'Egypte. C'est ainsi qu'elles expriment leur opposition au programme fiscal imposé par les Européens. Il s'agit d'un programme envisageant d'une part la répartition du pouvoir en restreignant l'influence européenne, et d'autre part la réduction le mandat du Khedive au profit des élites dans son ensemble, prévoyant surtout l'accroissement du pouvoir des notables autochtones de l'Egypte. Cette contribution s'avéra utile pour la recherche du dynamisme entre élites locales et puissances étrangères, non seulement en Egypte, mais dans l'histoire coloniale entier.