bluuebunny/crossref_metadata_2025 huggingface dataset:
Nesiritide: Trials and Tribulations
Authors: Arora Rohit R.
Published: June 2007

Standard therapy for acute decompensated heart failure, a major health problem, consists of intravenous diuretics, vasodilators, and positive inotropic agents. Nesiritide, a recombinant form of human B-type natriuretic peptide, is the only drug specifically approved for this indication. Recent meta-analyses have reported an increased risk of worsening renal function and 30-day mortality with nesiritide administration. These data understandably require physicians to carefully reevaluate their current use of nesiritide in patients with acute decompensated heart failure. In performing this reevaluation, it is important to consider our understanding of the underlying disease state, the limitations and results of these meta-analyses, and new data that provide additional insight into the possible risks and benefits associated with nesiritide therapy. Until additional therapeutic trials are conducted, therapeutic choices must be based on symptomatic and hemodynamic improvement and limited, imperfect available data, which may continue to support the use of nesiritide for its established indication.
Effects of Rotigaptide, a Gap Junction Modifier, on Defibrillation Energy and Resuscitation From Cardiac Arrest in Rabbits
Authors: Zhong Jing-quan , Laurent Gabriel , So Petsy Pui-Sze , Xudong Hu  , Hennan James K. , Dorian Paul
Published: June 2007

The gap junction modifier Rotigaptide (ZP123), which promotes cellular coupling, was hypothesized to decrease defibrillation thresholds during prolonged ventricular fibrillation (VF). Thirty-two New Zealand white rabbits were randomized to receive saline (control, n = 16) or Rotigaptide (n = 16). Following 4 min of untreated VF, biphasic defibrillation shocks were applied through chest wall patches, starting either at 300 volts (V) (n = 16) or 500 V (n = 16), with 200 V increasing steps to 900 V in case of shock failure. Rotigaptide significantly decreased defibrillation voltage requirements (average cumulative voltage of all shocks: 1206 ± 709 V in control group vs. 844 ± 546 V in treated group, P = .002). Rotigaptide had no effect on heart rate, QRS duration, QT interval, ventricular effective refractory period, monophasic action potential duration or on connexin 43 density using immunofluorescence. Rotigaptide improves the ability to defibrillate after untreated VF.
Observations on the Safety and Effectiveness of Dofetilide in Patients With Paroxysmal Atrial Fibrillation and Normal Left Ventricular Function
Authors: Mykytsey Andrew , Bauman Jerry L. , Razminia Mansour , Zheutlin Terry , Wang Ted , Saleem Mohammad , Leal Sergio , Kehoe Richard F.
Published: June 2007

Dofetilide is currently recommended as second-tier therapy to maintain sinus rhythm in patients with paroxysmal atrial fibrillation (PAF) and normal left ventricular function, yet limited data support this recommendation. We examined the safety and efficacy of dofetilide in this setting through a retrospective chart review. We evaluated patients who had symptomatic PAF, normal left ventricular function, and no significant valvular disease. The end points were complete suppression of symptomatic PAF and subjective symptomatic improvement with dofetilide treatment. Over a 3-year period, 34 patients who had failed previous antiarrhythmic therapy were included. Of these, 3 discontinued dofetilide treatment before discharge. Of the remaining 31 who continued treatment after discharge, it was eventually discontinued in 13. At 12 months, symptomatic improvement was observed in 18 of 31 patients, 6 of whom remained asymptomatic. Treatment with dofetilide in this study was successful in less than 1 in 5 patients. Despite careful precautions, serious proarrhythmias, the major limiting side effect of dofetilide, still occurred during long-term follow-up.
Clinical Application of the 15-Minute Family Interview: Addressing the Needs of Postpartum Families
Authors: Holtslander Lorraine
Published: June 2007

The purpose of this article is to describe the application of the 15-minute family interview to family-centered nursing practice on a postpartum unit. Guided by the five key components of the 15-minute family interview (manners, therapeutic conversation, genogram or ecomap, therapeutic questions, and commendations), clinical excerpts of interviews with families illustrate application to practice. The 15-minute family interview is not a strategic, decontextual nursing tool; rather, it is a flexible interview guide that is embedded in family nursing practice, in the relationship between the nurse and family and in the nurse’s philosophical assumptions and obligations to do well by families.
Thrombopoietin as a Drug: Biologic Expectations, Clinical Realities, and Future Directions
Authors: Haznedaroglu Ibrahim C. , Goker Hakan , Turgut Mehmet , Buyukasik Yahya , Benekli Mustafa
Published: June 2007

After the cloning of thrombopoietin (c-mpl ligand, Tpo) in 1994, 2 recombinant thrombopoietic growth factors, full-length glycosylated recombinant human Tpo (reHuTPO) and polyethylene glycol conjugated megakaryocyte growth and development factor (PEG-reHuMGDF), have been studied in humans in a variety of clin- ical settings. Both thrombopoietins are generally well tolerated if ad- ministered intravenously (IV). The c-mpl ligands produce a dose-re- lated enhancement of platelet levels, reduce nonmyeloablative chemotherapy-induced mild thrombocytopenia, and mobilize hematopoietic progenitors. On September 11, 1998, the development of PEG-reHuMGDF was suspended in the U.S., due to formation of the neutralizing anti-Tpo antibody. Those neutralizing antibodies lead to thrombocytopenia and pancytopenia in some patients receiv- ing subcutaneous (SC) PEG-reHuMGDF. Japanese investigators in- dicate that the probability of antibody formation against PEG- reHuMGDF is low when the drug is administered IV instead of SC. reHuTPO has a more favorable safety profile from the point of anti- body production. The c-mpl ligands can improve apheresis yields when administered to normal platelet donors. Preliminary data about the use of PEG-reHuMGDF in myelodysplasia, aplastic anemia, and immune thrombocytopenic purpura are promising. Tpo is usually not effective in myeloablative thrombocytopenia when bone marrow hematopoietic progenitors are not present. The major obstacle for the thrombopoietins is their delayed action for managing clinical thrombocytopenia. This review will focus on the biologic basis, cur- rent clinical experience, and future directions for the use of throm- bopoietic molecules as drugs. The identification of a safe, effective, and potent pharmacologic platelet growth factor could significantly improve the management of thrombocytopenia-induced bleeding.
Primary Thrombophilia in Mexico III: A Prospective Study of the Sticky Platelet Syndrome
Authors: Ruiz-Argúelles Guillermo J. , López-Martinez Briceida , Cruz-Cruz Donají , Esparza-Silva Lucía , Reyes-Aulis Ma. Belén
Published: June 2007

During an 18-month period, 10 consecutive Mexican mestizos with a clinical marker associated with a primary hypercoagulable state were studied. The assessment of the sticky platelet syndrome (SPS) was done by the method described by Mammen. In addition, the activated protein C resistance phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, tissue-type plasminogen activator activity, plasminogen activator inhibitor activity, plasminogen activator inhibitor type 1, IgG and IgM isotypes of anti-phospholipid antibodies, homocysteine levels, the factor V gene Leiden mutation, the 677 C->T mutation in the 5,10-methylen-tetrahydrofolate-reductase (MTHFR), and the G20210A polymorphism in the 3′-untranslated region of the prothrombin gene were studied. Six patients with the SPS were identified: only one displayed this as the single thrombophilic abnormality; in five others, additional thrombosis-prone conditions were found: heterozygosity for the MTHFR 677 gene mutation in five cases; and, in one case each, heterozygosity for the factor V Leiden mutation, heterozygosity for the factor II G20210A mutation, and antiphospholipid antibodies in another. Four of the six patients had a family history of thrombophilia. All patients were treated with aspirin and no new vasoocclusive episodes have been recorded. SPS in not an infrequent finding in Mexican mestizo thrombophilic patients and may contribute to thrombophilia.
Effects of a Synthetic Factor Xa Inhibitor (JTV-803) on Various Laboratory Tests
Authors: Tobu Mahmut , Iqbal Omer , Hoppensteadt Debra A. , Shultz Christopher , Jeske Walter , Fareed Jawed
Published: June 2007

Synthetic direct inhibitors of factor Xa are capable of prolonging the global anticoagulant assay times in a concentration-dependent fashion. The relative degree of thrombin generation inhibition at an equivalent prolongation is not similar to the results observed with heparins and oral anticoagulant drugs. In addition, the direct factor Xa inhibitors prolong the Russell' viper venom test (RVVT) and Heptest clotting times. Ecarin clotting time (ECT) and thrombin time (TT) remain unaffected. The kinetics of factor Xa inhibition are markedly different than those observed with pentasac-charide and heparins. Therefore, the methods developed for heparins and pentasaccharides may not be applicable for the monitoring of factor Xa inhibitors. To test the feasibility of using the prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), Heptest, thrombin time, RVVT, ECT, and a modified anti-Xa amidolytic assay, to monitor a synthetic factor Xa inhibitor, normal human pool plasma samples were spiked with a synthetic factor Xa inhibitor in the concentration range of 0 to 1 μg/mL and 0 to 25 μg/mL. Different laboratory tests were performed and INR and other ratios were calculated. The anticoagulant effects on whole blood were measured using the activated clotting time (ACT). Further studies on the effect of factor Xa inhibitor on platelet aggregation; factor II, VII, and X functional levels; and fibrinopeptide A (FPA) generation were carried out at equivalent INR levels in comparison to oral anticoagulant and antithrombin agents. FPA generation at equivalent anticoagulant level in comparison to heparin (twice the baseline) was also carried out. Factor Xa inhibitor produced a concentration-dependent prolongation of the ACT. ACT was doubled at a concentration of 4 to 5 μg/mL. There was a marked difference in the prolongation of the PT by a synthetic factor Xa inhibitor dependent on the ISI of the PT reagent used. When the results were calculated to determine INR, marked variations were noted between the recombinant thromboplastin and rabbit brain thromboplastin. The rabbit brain thromboplastin reagent gave markedly high INR values. Similar results were observed when different aPTT reagents were studied. In the anti-Xa assay, modification of the incubation time was employed to extend the proper sensitivity range. These studies warrant further investigation to understand the mechanism of action of factor Xa inhibitors.
Thrombocytosis and Recurrent Hepatic Outflow Obstruction (Budd-Chiari Syndrome) After Successful Thrombolysis: Case Report and Literature Review
Authors: Randi Maria Luigia , Sartori Maria Teresa , Luzzatto Guido , Ruzzon Elisabetta , Boccagni Patrizia , Ragazzi Roberto , Girolami Antonio
Published: June 2007

Approximately two thirds of cases of hepatic flow obstruction are due to myeloproliferative disorders. Restoration of hepatic blood flow is the essential goal of treatment. Thrombolytic therapy seems to achieve good results at least in selected cases. A 32year-old woman is presented, with an intermittent increase in platelet count (526-725 x 109/L), two previous spontaneous abortions and acute symptomatic occlusion of hepatic veins, and in whom a diagnosis of essential thrombocythemia was initially carried out in agreement with the polycythemia vera study group criteria. She received recombinant tissue plasminogen activator followed by heparin with restoration of normal hepatic outflow. Asymptomatic re-occlusion of the hepatic veins was observed 1 year later, despite adequate continuous warfarin treatment. Angiography showed marked narrowing of the intrahepatic cava vein due to extrinsic compression by an enlarged liver, not due to a new thrombosis so that no specific intervention could be performed. In the presence of a clearly documented hepatic vein thrombosis, thrombolytic therapy should be considered. The patient was given low-molecular-weight heparin with a dramatic reduction in previously elevated fibrinogen level and a good control of the hepatic function.
Simultaneous Deep Venous Thrombosis and Acquired Factor VIII Inhibitor
Authors: Deitcher Steven R. , Carman Teresa L. , Kottke-Marchant Kandice
Published: June 2007

Acquired hemophilia A is a life-threatening immune-mediated hemorrhagic disorder that is most often found in individuals older than 50 who present with an unexplained activated partial thromboplastin time (aPTT) prolongation and clinically significant bleeding. The prolonged aPTT associated with acquired hemophilia A reflects factor VIII activity deficiency due to neutralizing or clearing autoantibodies. Deep venous thrombosis, in contrast, is a veno-occlusive disorder associated with several distinct hypercoagulable states that can result in significant morbidity and mortality due to pulmonary embolism, thrombus extension, and the post-thrombotic syndrome. A prolonged a PYI in the setting of thrombosis may reflect the presence of a lupus anticoagulant. In the absence of accurate diagnosis and the immediate institution of specific therapy, both disorders can be fatal. Three cases of acquired factor VIII inhibitors that included a prolonged aPTT, bleeding, and duplex ultrasound evidence of deep venous thrombosis are presented. The diagnostic and therapeutic challenges posed by these cases as well as a proposed mechanism by which pathologic thrombosis can develop in a patient with a life-threatening bleeding disorder are discussed.
The LONFLIT4-VENORUTON Study A Randomized Trial Prophylaxis of Flight-Edema in Normal Subjects
Authors: Belcaro Gianni , Cesarone Maria Rosaria , Nicolaides Andrew N. , Geroulakos George , Acerbi Giovanni , Candiani Carlo , Griffin Maura , Bavera Peter , Dugall Mark , Brandolini Rossella , Renzo Andrea Di , Ricci Andrea , Ippolito Edmondo , Winford Michelle , Golden Gerard
Published: June 2007

This study evaluated the protective effects of Venoruton on the development of flight edema in normal subjects travelling in economy in long-haul flights (8-9 hours). Edema is a relevant aspect of long-haul flights affecting both venous patients and normal subjects. Edema and flight microangiopathy were studied in a group of 164 subjects randomized (after informed consent) into two groups to evaluate prophylaxis in 8 to 9-hour flights. The treatment group received Venoruton (hydroxyethyl rutosides) 1 g twice daily for 3 days (2 days before the flight and the day of the flight). The control group received comparable placebo. Edema was evaluated with a composite edema score based on the edema tester, on the measurements of ankle circumference, volume measurements, subjective swelling, and on a discomfort score. Items 1, 4, and 5 are based on an analogue scale line (I to 10) directly defined by the subjects before and after the flights. Of the included subjects, 151 completed the study. Dropouts were due to poor compliance, travelling, or connection problems. Age and gender distribution were comparable in the two groups as were risk factor distributions. The level of edema at inclusion was comparable in the two groups of subjects. After the flight there was an average score of 6.7 (SD 1.7) in the control group, while in the Venoruton group the score was on average 3 (SD 1.1) (p < 0.05). In the control group 77% of the subjects had an evident increase in ankle circumference and volume, which was clearly visible at inspection and associated with discomfort. In the Venoruton group, edema was clearly present only in 8% of subjects (associated with discomfort rated between 3 and 6 on the analogue scale line) and it was mild, not associated with symptoms. Therefore the control of flight edema with Venoruton was clear both considering parametric data (circumference and volume) and non-parametric (analogue scale lines) measurements. The combined evaluation of the edema score is significantly favorable for subjects under prophylaxis with Venoruton.
Increased Fibrin Polymerization Rate in Patients with Primary Antiphospholipid Syndrome and Systemic Lupus Erythematosus
Authors: De Pablo Paola , Ramírez Alvaro , Cortina Evelyn , Peña Aurora De la , Zamora José , Izaguirre Raúl , Amigo Mary-Carmen
Published: June 2007

The main event in blood coagulation is the thrombincatalyzed conversion of fibrinogen into fibrin. This singular transformation of a soluble protein into an insoluble polymeric network occurs with faultless precision. Abnormalities of fibrin polymerization can lead to hemorragic and thrombotic disorders. Increased fibrinogen plasma concentration (Fg) and fibrin polymerization rate (FPR) could be additional risk factors associated with atherothrombosis in antiphospholipid syndrome (APS) and in systemic lupus erythematosus (SLE). Our objective was to investigate Fg and FPR in consecutive patients with APS and SLE. Thirty-nine patients and 31 ageand gender-matched healthy controls were studied. Sixteen patients had primary APS, 13 patients had SLE, and 10 patients had SLE plus APS. The mean of the FPR was significantly increased (0.2799 ± 0.091) in patients with APS plus SLE as compared with the control group (0.2052 ± 0.055) (p<0.05). Fg was higher in APS plus SLE (3.15 g/L ± 0.43) and in primary APS (3.03 g/L ± 0.29) than in controls (2.87 g/L ± 0.49). Our results demonstrated an increased FPR in patients with APS plus SLE. This phenomenon could be an additional risk factor for thrombosis in these autoimmune diseases.
PCR-RFLP Detection of PAI-2 Variants in Myocardial Infarction
Authors: Buyru Nur , Altinisik Julide , Gurel Cigdem Bayram , Ulutin Turgut
Published: June 2007

PAI-2 is one of the regulators of the fibrinolytic system. The importance of the fibrinolytic cascades in the pathogenesis of myocardial infarction has been demonstrated by many investigators. Recently, some investigators have shown that two variants of PAI-2, designated A and B, are associated with the formation of large molecular PAI-2 complexes. This polymorphism is therefore present a genetic predisposition for the development of coronary artery disease and multiple sclerosis. Therefore, the prevalence of this polymorphism among 45 patients with MI and 20 control subjects was investigated. The AA genotype of the PAI-2 gene was found to be more frequent among those subjects with MI. These data provide evidence that a polymorphism of the PAI-2 gene is associated with an increased risk of MI.
Congenital Absence of the Inferior Vena Cava and Genetic Coagulation Abnormalities: A Rare Associated Risk Factor for Recurrent Idiopathic Deep Vein Thrombosis
Authors: Parma Matteo , Belotti Daniela , Marinoni Sara , Pogliani Enrico Maria
Published: June 2007

Congenital absence of the inferior vena cava (AIVC) has been reported as a risk factor of deep vein thrombosis (DVT) in young people. DVT is caused by an interaction between congenital coagulation abnormalities and acquired risk factors. We observed an 18-year-old patient with AIVC who developed recurrent deep vein thrombosis at the left leg. Molecular studies showed an etherozigousity for FV Leiden gene (G1691A) and a homozigousity for methylenetetraidrofolate reductase gene (C677T) in absence of folate and vitamin B12 deficiency. After the second DVI episode, the patient has been treated with heparin and oral anticoagulant without discontinuation.
The Altered Hemorheologic Parameters in Thromboangiitis Obliterans: A New Insight
Authors: Bozkurt A. Kursat , Koksal Cengiz , Ercan Meltem
Published: June 2007

The hemorheologic abnormalities were studied in patients suffering from thromboangiitis obliterans (TAO) and compared findings with those of patients suffering from critical limb ischemia because of peripheral atherosclerotic obstructive disease (PAOD) and the healthy subjects. This prospective study included 20 patients with TAO, 20 patients with PAOD, and 20 healthy subjects. Hematocrit, plasma fibrinogen, red blood cell rigidity, and blood and plasma viscosity were determined in all groups. Hematocrit values of the TAO group were significantly higher than those of the PAOD group and the control group (p<0.001 and p<0.001, respectively). BV at a shear rate of 6.00 sec-1 was higher in TAO than the PAOD and control (p<0.01 and p<0.05, respectively). BV at a shear rate of 225 sec-1 was higher in the TAO and PAOD than the control (p<0.001 and p<0.001, respectively) and also PAOD values were higher than the TAO (p<0.05). RBC rigidity was higher in the TAO and PAOD than the control (p<0.001 and p<0.05, respectively) and these values were higher in PAOD than the TAO (p<0.05). These results show the impairment in hemorheologic parameters in TAO may provide a new insight into the treatment of patients with TAO in the active period of the disease.
Acute Myocardial Infarction in a Patient with Essential Thrombocythemia Treated with Glycoprotein Ilb/Illa Inhibitor
Authors: Gül Çetin , Kürüm Turhan , Demir Muzaffer , Özbay Gültaç , Vural Özden , Iqbal Omer , Fareed Jawed
Published: June 2007

Essential thrombocythemia (ET) rarely causes obstruction of coronary arteries or acute myocardial infarction. Treatment of acute myocardial infarction in patients with ET may be a problem due to the important role of platelets in the pathogenesis of infarction. There is no reported case of acute myocardial infarction with essential thrombocythemia treated with a glycoprotein lIb/Illa inhibitor. In this report, a 49-year-old woman with essential thrombocythemia, admitted with a diagnosis of acute inferolateral myocardial infarction, was treated with tirofiban, a glycoprotein IIb/IIIa receptor blocker.
An Increase of Anticardiolipin Antibody in Association with Stroke and Chronic Chemical Exposure
Authors: Chen Wei-Hsi , Lui Chun-Chung , Chen Chung-Jen , Liu Jia-Shou
Published: June 2007

A chemical worker working with urea-formaldehyde resin hazard for 20 years suffered cerebral ischemia in association with an increase of blood beta2-glycoprotein I-dependent anticardiolipin antibody (aCL)-IgG and IgM isotype, and a prolongation of activated partial thromboplastin time (aPTT). Major histocompatibility complex antigen showed DR4 positivity. On follow-up for over 6 years, aCL-IgG and aPTT decreased to reference range but aCL-IgM was still abnormally high despite a cessation of exposure. This patient highlights the induction of antibody-mediated thrombosis in chronic chemical exposure, especially in an individual with subclinical autoimmune disorder. The role of environment for coagulopathic vascular thrombosis is warranted for investigation.
The Use of a Surgical Patch Coated With Human Coagulation Factors in Surgical Routine: A Multicenter Postauthorization Surveillance
Authors: Haas Sylvia
Published: June 2007

Local hemostyptic agents are of great value to significantly reduce bleeding complications and various devices have become available for clinical use. The aim of this multicenter postauthorization surveillance was to study the surgeons’ expectations regarding efficacy and safety of the surgical patch coated with human coagulation factors (TachoSil) under routine clinical conditions. A total of 408 patients had been included in this trial and the patients had to have an expected increased bleeding risk either due to patient related hemorrhagic risk factors or operations associated with an expected increase of bleeding complications. The main types of surgical interventions were operations on the liver (26%), vascular system (16%), gastrointestinal tract (10%), heart (8%), kidney (7%), thorax (7%), spleen (4%), and pancreas (4%). Other operations (18%) were reported in the fields of neurosurgery, urology, gynecology, dermatology, and on the thyroid gland. Based on subjective assessments the results have shown that TachoSil has met the surgeons’ expectations to be efficacious and safe as a hemostatic treatment in a broad variety of surgical interventions. The observed benefits far exceed the frequencies of complications and many of the observed benefits easily translate into cost savings. In almost 50% of the cases the surgeons thought that the use of the topical hemostat TachoSil may have led to savings in blood component therapy. The savings of intra- and postoperative transfusions may lead to less frequent transfusion-related adverse effects and the lower probability of postoperative complications is of clinical importance. In particular, it is worth mentioning that based on the surgeons’ assessment, the use of TachoSil may have helped to save the organ in 17% of the cases. Thus, these clinically relevant benefits may offer opportunities for improvements of hemostasis in patients at risk for bleeding complications and may facilitate the management of excessive bleeding.
Classification and Characterization of Hereditary Types 2A, 2B, 2C, 2D, 2E, 2M, 2N, and 2U (Unclassifiable) von Willebrand Disease
Authors: Michiels Jan Jacques , Berneman Zwi , Gadisseur Alain , van der Planken Marc , Schroyens Wilfried , van de Velde Ann , van Vliet Huub
Published: June 2007

All variants of type 2 von Willebrand disease (VWD) patients, except 2N, show a defective von Willebrand factor (VWF) protein (on cross immunoelectrophoresis or multimeric analysis), decreased ratios for VWF:RCo/Ag and VWF:CB/Ag and prolonged bleeding time. The bleeding time is normal and FVIII:C levels are clearly lower than VWF:Ag in type 2N VWD. High resolution multimeric analysis of VWF in plasma demonstrates that proteolysis of VWF is increased in type 2A and 2B VWD with increased triplet structure of each visuable band (not present in types 2M and 2U), and that proteolysis of VWF is minimal in type 2C, 2D, and 2E variants that show aberrant multimeric structure of individual oligomers. VWD 2B differs from 2A by normal VWF in platelets, and increased ristocetine-induced platelet aggregation (RIPA). RIPA, which very likely reflects the VWF content of platelets, is normal in mild, decreased in moderate, and absent in severe type 2A VWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D, variable in 2E, and normal in 2N. VWD 2M is usually mild and characterized by decreased VWF:RCo and RIPA, a normal or near normal VWF multimeric pattern in a low resolution agarose gel. VWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically featured by low VWF:RCo and RIPA with the relative lack of high large VWF multimers. VWD type 2C is recessive and shows a characteristic multimeric pattern with a lack of high molecular weight multimers, the presence of one single-banded multimers instead of triplets caused by homozygosity or double hereozygosity for a mutation in the multimerization part of VWF gene. Autosomal dominant type 2D is rare and characterized by the lack of high molecular weight multimers and the presence of a characteristic intervening subband between individual oligimers due to mutation in the dimerization part of the VWF gene. In VWD type 2E, the large VWF multimers are missing and the pattern of the individual multimers shows only one clearly identifiable band, and there is no intervening band and no marked increase in the smallest oligomer. 2E appears to be less well defined, is usually autosomal dominant, and accounts for about one third of patients with 2A in a large cohort of VWD patients.
Chronic Refractory Idiopathic Thrombocytopenic Purpura (ITP) and Anti-CD20 Monoclonal Antibody: A Case Report
Authors: Latifzadeh S. Z. , Entezari V.
Published: June 2007

Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disorder characterized by accelerated and premature destruction of platelets by reticuloendothelial system. CD20, a trans-membrane B-cell-specific antigen, is a potential target for treatment of certain malignant and nonmalignant plasma cell disorders including refractory ITP. Rituximab is a genetically engineered human anti-CD20 monoclonal antibody, which is approved for the treatment of low-grade non-Hodgkin’s lymphoma. Recent clinical reports suggest that rituximab may be useful in treating certain patients with chronic refractory ITP. A 59-year-old woman with refractory ITP was placed on rituximab (four weekly doses of 375 mg/m2) and her condition and platelet count were observed for 18 months. There was a gradual increase in platelet count and she was symptom free in this period and no side effects of the drug were reported. Anti-CD20 antibodies are likely to be used in the treatment of refractory ITP cases, but further studies about treatment schedule and criteria for patient selection should be done.
The Effects of Long-term Smoking on Endothelial Nitric Oxide Synthase mRNA Expression in Human Platelets as Detected With Real-time Quantitative RT-PCR
Authors: Shimasaki Yukio , Saito Yoshihiko , Yoshimura Michihiro , Kamitani Shigeki , Miyamoto Yoshihiro , Masuda Izuru , Nakayama Masafumi , Mizuno Yuji , Ogawa Hisao , Yasue Hirofumi , Nakao Kazuwa
Published: June 2007

Endothelium-derived nitric oxide (NO) plays an important role in the prevention of platelet aggregation and adhesion to the vascular wall. Endothelial nitric oxide synthase (eNOS) and L-arginine/NO pathway are both present in human platelets. Platelet-derived NO inhibits excessive activation and aggregation of platelets. However, the expression level of the eNOS gene in human platelets has yet to be elucidated. The current study investigates the individual expression level of platelet eNOS mRNA using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection method. eNOS mRNA expression was examined in platelets isolated from 50 subjects: 11 male smokers, 15 male nonsmokers, and 24 female non-smokers. After extraction of platelet total RNA, eNOS (target) and GAPDH (internal control) mRNA expression levels were quantitated using real-time RT-PCR. The expression levels of eNOS mRNA (relative copy numbers) were significantly lower in male smokers (59±17) than in male nonsmokers (195±71, P < .03), and higher in female nonsmokers (285±60) than in the male nonsmokers (195±71, P < .03). By multiple linear regression analysis, cigarette smoking ( P = .008) and diabetes mellitus ( P = .047) were found to be significantly negative predictors, and antioxidant (vitamin E) treatment ( P = .01) was a significantly positive predictor of platelet eNOS mRNA expression. Age, other medications, and other risk factors for coronary artery disease were not significant. Using this method, eNOS mRNA abundance in human platelets was detected and quantitated in real-time. The intraplatelet eNOS mRNA expression levels were significantly decreased in cigarette smokers. Low platelet NO synthesis in smokers may result in the augmentation of platelet aggregation and thrombus formation, developing into acute coronary syndromes.
Inhibition of Thrombin in Plasma by Heparin or Arginine
Authors: Stief Thomas W.
Published: June 2007

The inhibition of plasmatic thrombin is of clinical importance in a broad range of diseases. To obtain reliable data the assay system should be as similar to physiology as possible. Using a newly developed physiologic assay system for fibrinogen/thrombin interaction (the FIFTA), the inhibition of plasmatic thrombin by heparin or by arginine was studied. The standard fibrinogen functional turbidimetric assay (FIFTA) was performed, varying heparin or arginine concentrations and varying the time point the inhibitor was added to the FIFTA. Plasmatic heparin concentrations equal to or greater than 0.63 IU/mL completely inhibit thrombin in the assay system described. The IC50 is 0.1 IU/mL heparin. Heparin can only inhibit fibrin generation within the first 2 minutes at room temperature (RT=23°C). The 50% inhibitory time point, that is, the time point that a 10 IU/mL final concentration of heparin results in 50% inhibition of FIFTA, is 30 seconds at RT. A final arginine concentration of at least 125 mM in the first 100 seconds of the FIFTA reaction at RT completely inhibits turbidity increase. Half-maximal turbidity increase occurs at 63 mM arginine. Final arginine concentrations of at least 250 mM completely inhibit turbidity increase, when arginine acts in the first 4 minutes (RT) of the thrombin/ fibrinogen interaction. A final arginine concentration of 477 mM added at the 12-minute or 30-minute thrombin/ fibrinogen reaction time point decreases the resulting turbidity by 50% after an additional 30 minutes at RT. Pathologic disseminated intravascular coagulation occurs in a multitude of diseases; in common is always the generation of thrombin either by the contact phase or by the tissue factor phase of coagulation. Such pathologically elevated thrombin activity in blood or blood products must be prevented or inhibited. This study demonstrates the efficiency of two physiologic thrombin inhibitors: heparin and arginine.
Treatment of Deep Vein Thrombosis With Enoxaparin in Pediatric Cancer Patients Receiving Chemotherapy
Authors: Stine Kimo C. , Saylors Robert L. , Suzanne Saccente C. , Becton David L.
Published: June 2007

There are few data regarding the use of enoxaparin in children undergoing myelosuppressive therapy for malignancies even though thrombosis is a known risk in pediatric patients with malignancies. Low-molecular-weight heparin such as enoxaparin has become widely used in adult patients with thrombosis. The purpose of this study was to review the utilization of low-molecular-weight heparin, enoxaparin (Lovenox), in children with cancer at our institution who had thrombosis while undergoing myelosuppressive chemotherapy. In particular we were interested in the efficacy of enoxaparin in these patients, and in whether these children were able to continue their chemotherapy without adjustment or interruption secondary to bleeding complications. We conducted a retrospective review from 1999 through April 1, 2004. Seven patients (4—17 years of age) were identified. Diagnosis included B-precursor acute lymphoblastic leukemia (ALL) (n=three), T-ALL, Hodgkin's disease, anaplastic large cell lymphoma, and rhabdomyosarcoma (n=one each). Six patients had a deep vein thrombus (DVT) or clot of the vena cava. One of these six patients also had a pulmonary embolus. One patient presented with manifestations of a unilateral cerebral vascular accident without evidence of DVT. Most patients were screened for known hypercoaguable abnormalities. Treatment was enoxaparin, 1—1.5 mg/kg/dose twice daily to maintain a heparin anti-Xa level of 0.5—1.5 IU/mL till clot resolution. The dose was then decreased to daily for a total of 3—6 months of therapy. All patients had resolution of their thrombosis within 1—2 months of initiation of enoxaparin, and none required delays or dose reduction of their chemotherapy regimens while on anticoagulation, though some were supported by blood and platelet transfusions. Enoxaparin was safely administered to this series of seven patients for thrombotic complications in children undergoing cancer chemotherapy.
Optimal Preview Control of Active Suspensions with Integral Constraint
Authors: El Madany Mohammed , Abduljabbar Zuhair , Foda Mosaad
Published: June 2007

In this paper we consider the application of stochastic optimal control theory to the design of an active vehicle suspension with preview control. An integral constraint is included in the performance index to achieve better attitude control characteristics. The two-degree-of-freedom vehicle model travels with constant velocity on both random and deterministic roadways. Information relating to roadway disturbances about to be encountered by the moving vehicle is assumed to be sensed and this information is used by the active control scheme to prepare the system for the ensuing input. We examine the effect of preview control on vehicle performance characteristics in terms of ride comfort, suspension deflection, road-holding ability, control force, and power requirements. The performance characteristics of the devised multivariable controller are evaluated and compared with those of the pertinent active suspension systems based on state variable feedback and conventional passive systems.
A Closure Procedure for Random Vibration Parametric Resonances
Authors: Bobryk R. V. , Chrzeszczyk A. , Stettner L.
Published: June 2007

We investigate the mean-square stability for single-degree-of-freedom linear systems with random parametric excitation. The excitation is assumed to be of the form of a Gaussian stationary non-white process. We propose a new numerical approach to determine regions of parametric resonances based on a closure procedure for hierarchy of moment equations. Mean-square stability charts are obtained using the numerical analysis of eigenvalues for large-scale matrices. The results show three parametric resonances for narrow-band excitations.
Personal Style and Hearing Aid Fitting
Authors: Traynor Robert M. , Holmes Alice E.
Published: June 2007

Why do I have to drag information out of some patients? Why is another patient so talkative? Why didn't this patient like the XYZ 2002 digital hearing aid when she had the same degree, type, and configuration of hearing impairment as the patient I successfully fit last month? Could the answer be as basic as a difference in personality?
The Envoy® Totally Implantable Hearing System, St. Croix Medical
Authors: Kroll Kai , Grant Iain L. , Javel Eric
Published: June 2007

The Totally Implantable Envoy® System is currently undergoing clinical trials in both the United States and Europe. The fully implantable hearing device is intended for use in patients with sensorineural hearing loss. The device employs piezoelectric transducers to sense ossicle motion and drive the stapes. Programmable signal processing parameters include amplification, compression, and variable frequency response. The fully implantable attribute allows users to take advantage of normal external ear resonances and head-related transfer functions, while avoiding undesirable earmold effects. The high sensitivity, low power consumption, and high fidelity attributes of piezoelectric transducers minimize acoustic feedback and maximize battery life ( Gyo, 1996 ; Yanagihara, (1987) and 2001 ). The surgical procedure to install the device has been accurately defined and implantation is reversible.
Effects of Compression on Speech Acoustics, Intelligibility, and Sound Quality
Authors: Souza Pamela E.
Published: June 2007

The topic of compression has been discussed quite extensively in the last 20 years (eg, Braida et al., 1982; Dillon, 1996 , 2000 ; Dreschler, 1992 ; Hickson, 1994 ; Kuk, 2000 and 2002; Kuk and Ludvigsen, 1999 ; Moore, 1990 ; Van Tasell, 1993 ; Venema, 2000 ; Verschuure et al., 1996; Walker and Dillon, 1982 ). However, the latest comprehensive update by this journal was published in 1996 ( Kuk, 1996 ). Since that time, use of compression hearing aids has increased dramatically, from half of hearing aids dispensed only 5 years ago to four out of five hearing aids dispensed today ( Strom, 2002b ). Most of today's digital and digitally programmable hearing aids are compression devices ( Strom, 2002a ). It is probable that within a few years, very few patients will be fit with linear hearing aids. Furthermore, compression has increased in complexity, with greater numbers of parameters under the clinician's control. Ideally, these changes will translate to greater flexibility and precision in fitting and selection. However, they also increase the need for information about the effects of compression amplification on speech perception and speech quality. As evidenced by the large number of sessions at professional conferences on fitting compression hearing aids, clinicians continue to have questions about compression technology and when and how it should be used. How does compression work? Who are the best candidates for this technology? How should adjustable parameters be set to provide optimal speech recognition? What effect will compression have on speech quality? These and other questions continue to drive our interest in this technology. This article reviews the effects of compression on the speech signal and the implications for speech intelligibility, quality, and design of clinical procedures.
The Effects of Digital Noise Reduction on the Acceptance of Background Noise
Authors: Mueller H. Gustav , Weber Jennifer , Hornsby Benjamin W. Y.
Published: June 2007

Modern hearing aids commonly employ digital noise reduction (DNR) algorithms. The potential benefit of these algorithms is to provide improved speech understanding in noise or, at the least, to provide relaxed listening or increased ease of listening. In this study, 22 adults were fitted with 16-channel wide-dynamic-range compression hearing aids containing DNR processing. The DNR includes both modulation-based and Wiener-filter-type algorithms working simultaneously. Both speech intelligibility and acceptable noise level (ANL) were assessed using the Hearing in Noise Test (HINT) with DNR on and DNR off. The ANL was also assessed without hearing aids. The results showed a significant mean improvement for the ANL (4.2 dB) for the DNR-on condition when compared to DNR-off condition. Moreover, there was a significant correlation between the magnitude of ANL improvement (relative to DNR on) and the DNR-off ANL. There was no significant mean improvement for the HINT for the DNR-on condition, and on an individual basis, the HINT score did not significantly correlate with either aided ANL (DNR on or DNR off). These findings suggest that at least within the constraints of the DNR algorithms and test conditions employed in this study, DNR can significantly improve the clinically measured ANL, which may result in improved ease of listening for speech-in-noise situations.
The Development of the Nucleus® Freedom™ Cochlear Implant System
Authors: Patrick James F. , Busby Peter A. , Gibson Peter J.
Published: June 2007

Cochlear Limited (Cochlear™) released the fourth-generation cochlear implant system, Nucleus® Freedom™, in 2005. Freedom is based on 25 years of experience in cochlear implant research and development and incorporates advances in medicine, implantable materials, electronic technology, and sound coding. This article presents the development of Cochlear's implant systems, with an overview of the first 3 generations, and details of the Freedom system: the CI24RE receiver-stimulator, the Contour Advance™ electrode, the modular Freedom processor, the available speech coding strategies, the input processing options of SmartSound™ to improve the signal before coding as electrical signals, and the programming software. Preliminary results from multicenter studies with the Freedom system are reported, demonstrating better levels of performance compared with the previous systems. The final section presents the most recent implant reliability data, with the early findings at 18 months showing improved reliability of the Freedom implant compared with the earlier Nucleus 3 System. Also reported are some of the findings of Cochlear's collaborative research programs to improve recipient outcomes. Included are studies showing the benefits from bilateral implants, electroacoustic stimulation using an ipsilateral and/or contralateral hearing aid, advanced speech coding, and streamlined speech processor programming.
Issues Associated With the Measurement of Psychosocial Benefits of Group Audiologic Rehabilitation Programs
Authors: Preminger Jill E.
Published: June 2007

The purpose of this review is to describe the psychosocial effects of hearing loss, review the literature that has attempted to measure the psychosocial benefits of group audiologic rehabilitation programs, and offer suggestions for the design of future studies. The psychosocial aspects of hearing loss are multidimensional and may include the emotional, cognitive, interpersonal, behavioral, and physical responses to hearing loss. As a result of the stigma of hearing loss, individuals may isolate themselves, avoid social interactions, and/or bluff their way through communication breakdowns. Participation in group audiologic rehabilitation programs is a straightforward way to deal with the stigma and the loss of social identity associated with hearing loss, and these groups are an ideal forum for teaching communication strategies. Yet, the literature on the efficacy of group audiologic rehabilitation has produced equivocal results. Several factors may have contributed to the lack of psychosocial benefits reported in the literature, including the theoretical framework upon which the program was designed, the actual class content, the effectiveness of the outcome measures, and the demographic characteristics of the participants in the programs. Future research should determine (1) if the theoretical framework and/or the content covered in group audiologic rehabilitation programs influences the psychosocial outcomes, (2) if instructor training influences psychosocial outcomes, (3) the ideal test battery to assess the psychosocial benefits of group audiologic rehabilitation programs, (4) the participant demographic and personality characteristics that influence psychosocial outcomes, and (5) whether experienced hearing aid users have different hearing-loss related psychosocial needs than new hearing aid users.
Can Agencies Continue to Use the Companionship Services Exemption?
Authors: Gilliland John C.
Published: June 2007

The companionship services exemption is an important way many private duty agencies are relieved of the requirement to pay minimum wage and overtime pay under the federal Fair Labor Standards Act. However, a recent decision of a U.S. Court of Appeals held for the first time that this exemption cannot be used by third-party employers such as agencies. Although it is significant, that decision is only binding in New York, Vermont, and Connecticut, and the agency involved could still avoid liability because of other defenses. Depending on their specific situations, agencies in other states may reasonably conclude to continue to use the exemption.
Child and familial pathways to academic achievement and behavioral adjustment: A prospective six-year study of children with and without ADHD
Authors: Latimer W. W. , August G. J. , Newcomb M. D. , Realmuto G. M. , Hektner J. M. , Mathy R. M.
Published: June 2007

This longitudinal study examined familial and child predictors of academic achievement and behavioral adjustment.

Participants included 115 children with ADHD and 59 normative comparisons. Data analyses spanned three assessment waves from elementary-through secondary-school grades. We evaluated the degree to which child and familial factors present during middle school mediated relationships between childhood ADHD, subsequent academic achievement, and behavioral adjustment during high school.

We found that emotional and behavioral well-being of ADHD children during middle school mediated relations between childhood ADHD and adverse academic and behavioral outcomes during high school. In addition, familial factors in middle school years predicted the behavioral adjustment of children in both the ADHD and non-ADHD groups. Academic achievement during high school was strongly associated with previous achievement levels.

Our results provide support for tailoring preventive interventions to the unique needs of children with ADHD and their parents at various stages of adolescent development.