bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptic Ulcer in the Very Old Patients
Authors: Seinelä Lauri , Ahvenainen Jari
Published: April 2003

Objective: To describe the clinical features of peptic ulcer in patients aged 80 years or over. Design: The patient files of 73 ulcer patients were retrospectively analyzed. Results: Peptic ulcer was found in 17% of the gastroscopies made on patients aged 80 years or over. Epigastric pain was the most common symptom (74%). Vomiting and nausea were also common symptoms. 48% of the ulcers were duodenal and 52% gastric. The majority (65%) of ulcers were Helicobacter pylori negative. H.-pylori-positive patients used acetylsalicylic acid more frequently than the H.-pylori-negative (57 vs. 43%) ones. Complications occured in 69% of the patients. Aspirin and nonsteroidal anti-inflammatory drug (NSAID) users had more often complications than the others. Conclusions: Peptic ulcer is a common clinical finding of gastroscopy in patients aged 80 years or over. Most ulcers are H.-pylori-negative and almost evenly divided between duodenal and gastric ulcers. Most of the elderly patients suffer from epigastric pain. Complications are frequent among the patients, especially in aspirin and NSAIDs users. H.-pylori-infected aspirin users are at increased risk of ulcer disease. Before starting long-term aspirin treatment in elderly patients, eradication of H.-pylori is recommended.
Physical Fitness Related to Disability in Older Persons
Authors: van Heuvelen Marieke J.G. , Kempen Gertrudis I.J.M. , Brouwer Wiebo H. , De Greef Mathieu H.G.
Published: April 2003

Background: In today’s aging society, preventing or reducing disability is important. Physical activity may serve this goal. Generally, physical activity aims to enhance physical fitness, which in turn may prevent disability. The relationship between physical fitness and disability has been much less explored than the relationship between physical activity and physical fitness. Objective: To investigate the relationship between separate components of physical fitness and disability. Methods: The subjects were a community-based sample of 176 men and 233 women aged 65 years or older. Physical fitness was assessed with performance-based tests. Disability and potential confounders were assessed during face-to-face interviews. Results: Independently of other fitness components, walking endurance, grip strength, manual dexterity and balance contributed significantly to the prediction of disability for both men and women. Flexibility of the hip and spine, flexibility of the shoulder and reaction time were not independent predictors of disability for men or women. Physical fitness explained a greater percentage of variance in disability for women (31–48%) than for men (14–34%). Although depressive symptoms, cognitive functioning (men), number of chronic conditions (women) and age (women) explained additional variance in disability, these variables did not confound the relationship between physical fitness and disability. Conclusion: Walking endurance, grip strength and manual dexterity are important unique predictors of disability. Physical activity programs should be directed at these fitness components.
Vergangenheit, Gegenwart und Zukunft der Onkologie
Authors: Winter R.
Published: April 2003

Das Thema Vergangenheit, Gegenwart und Zukunft der Onkologie wird aus der Sicht der Grazer Klinik, anhand der Forschungsergebnisse über das Zervixkarzinom, behandelt. Im Jahre 1908 veröffentlichte Walter Schauenstein eine Arbeit über histologische Untersuchungen über atypisches Plattenepithel an der Portio. Es handelte sich dabei um eine der Erstbeschreibungen des Oberflächenkarzinoms der Zervix. Nach dem 2. Weltkrieg entwickelte Ernst Navratil das Konzept der Krebsfrühdiagnose durch die Anwendung der Kolposkopie und der Zytologie. Basierend auf Erich Burghardts Kenntnissen über die Morphogenese des Zervixkarzinoms erfolgt in den 70er Jahren die Rücknahme der Radikalität bei der Behandlung frühinvasiver Formen des Zervixkarzinoms. Die Konisation und Hysterektomie haben die radikalen operativen Eingriffe beim Mikrokarzinom fast vollständig ersetzt. Heute wird das Zervixkarzinom individuell, je nach Tumorgrösse, die präoperativ mittels Magnetresonanztomographie festgestellt wird, behandelt. In jedem Fall entscheidet der Lymphknotenstatus, der intraoperativ erhoben wird, das Ausmass der Radikalität. Die Zukunft der Onkologie liegt in der Molekulargenetik. Bis heute sind jedoch für das Zervixkarzinom keine erblichen Faktoren bekannt, so dass operative Therapiekonzepte nach wie vor die Basis für die Behandlung dieser Erkrankung darstellen.
Gesundheitsökonomie der Schwangerenbetreuung und Geburt in Österreich und den Niederlanden – Ein Vergleich
Authors: Brezinka Christoph
Published: April 2003

Der wesentliche Unterschied zwischen dem niederländischen und dem österreichischen System der Schwangerenvorsorge und Geburt besteht darin, dass dies in den Niederlanden innerhalb der eerste lijn der medizinischen Basisversorgung abgewickelt wird und von der jungen Mutter zu den einzelnen Leistungen die Zahlung von Selbstbehalten erwartet wird. Schwangerenbetreuung und Geburt sollen in den Niederlanden bei der Hebamme bzw. beim Hausarzt erfolgen. In Österreich ist ein grossteils aus dem Familienlastenausgleichsfonds gespeistes Finanzierungssystem entstanden, das über den Mutter-Kind-Pass nicht nur Schwangerschaftskontrollen, Geburt und Wochenbett kostenlos macht, sondern einerseits den Ärzten, die Schwangere betreuen, für die Kontrolluntersuchungen Zusatzprämien zahlt, und andererseits auch Frauen Prämien dafür bezahlt, dass sie zu den Untersuchungen gehen. Die Funktionsweise der sehr verschiedenen Systeme und die Rollen, die Ärzte, Hebammen, Krankenhäuser und Versicherungen darin spielen, werden erläutert.
Epidermaler Wachstumsfaktor im Schwangerschaftsverlauf – Ein Prädiktor für fetale Wachstumsretardierung?
Authors: Huter O. , Kölle D. , Brezinka Ch. , Artner-Dworzak E.
Published: April 2003

Bei 83 Frauen, die vor der 30. Schwangerschaftswoche (SSW) wegen Verdachtes auf intrauterine Wachstumsretardierung eingewiesen worden waren, wurde bis zur Geburt des Kindes im 4-Wochen-Abstand der Harn auf epidermalen Wachstumfaktor (EGF) hin untersucht. Als Vergleich dienten die EGF-Werte im Harn von 138 gesunden Frauen, die normalgewichtige Kinder zur Welt gebracht hatten. Dreissig der 83 Frauen brachten nach der 37. SSW ein Kind zur Welt, das unter der 10er Perzentile von Hohenauer lag. Diese Frauen wiesen im Verlauf der Schwangerschaft zwar signifikant niedrigere EGF-Werte auf als die Schwangeren der Kontrollgruppe mit ihren normalgewichtigen Kindern; allerdings zeigte sich, dass durch die Streuung der Ergebnisse in beiden Kollektiven keine für die klinische Entscheidung im Einzelfall verwertbare Trennlinie zwischen «wachstumsretardiert» und «normalgewichtig» festgelegt werden kann.
Gewinnung von Stammzellen und Möglichkeiten der Stammzelltherapie
Authors: Heberle-Bors Erwin
Published: April 2003

Der Beweis der Totipotenz ausdifferenzierter Säugerzellen durch Kerntransfer in entkernte Eizellen, die Herstellung von embryonalen Stammzellkulturen des Menschen und die Gewinnung pluripotenter Stammzellen des Säugergehirns werden im Zusammenhang mit entwicklungsbiologischen Fragestellungen, ihren therapeutischen Auswirkungen und ihren ethischen Implikationen vorgestellt.
Circulating Activated Protein C inSubjects with Heterozygous Gln506-Factor V
Authors: Petäjä Jari , Hakala Leena , Rasi Vesa , Griffin John H.
Published: April 2003

Congenital resistance to activated protein C due to a point mutation in the factor V gene (Gln506-FV) is the most common genetic risk factor for familial venous thrombosis. Considering the central role of activated protein C as a physiological anticoagulant, the question of why the thrombotic risk associated with Gln506-FV was not more pronounced was asked. We hypothesized that in Gln506-FV heterozygotes, enhanced thrombin formation might preferentially activate protein C and thereby constitute a compensatory antithrombotic effect. We compared the circulatory level of activated protein C in twelve heterozygous carriers of Gln506-FV mutation with that in eighteen noncarriers in same families, and used prothrombin fragment 1+2 as a measure of thrombin generation. The circulating level of activated protein C was higher but not significantly different in heterozygotes compared with normal relatives. Activated protein C levels correlated strongly and positively with protein C antigen levels in both carriers (Spearman R 0.684, p < 0.05) and controls (Spearman R 0.642, p < 0.01). Correlation between activated protein C and prothrombin fragment 1+2 levels was of borderline significance (Spearman R 0.354, p = 0.055). In the current study, thrombin formation assessed by prothrombin fragment 1+2 levels was not significantly enhanced in subjects with heterozygous Gln506-FV compared with family members without the mutation. In conclusion, enhanced thrombin formation is not present in all healthy Gln506-FV heterozygotes in basal conditions. It seems that enhanced protein C activation by thrombin does not constitute a compensatory anticoagulant feedback loop in heterozygous carriers of Gln506-FV. However, the positive correlation between prothrombin fragment 1+2 and activated protein C suggests that, in healthy subjects and in basal conditions, thrombin upregulates the anticoagulant protein C pathway. Thus, it is questionable whether prothrombin fragment 1+2 can directly be used as an indicator of a hypercoagulable state.
Thromboprophylaxis in the Cancer Patient
Authors: Kakkar Ajay K. , Williamson Robin C.N.
Published: April 2003

Thrombosis is a common complication in patients with malignant disease resulting from tumour elaboration of procoagulants and subsequent activation of intravascular coagulation. Cancer therapies (operation, chemotherapy and the use of central venous lines) further heighten the risk of thrombosis. The risk of thrombosis in cancer operations is of sufficient magnitude to necessitate routine thromboprophylaxis, for which low-dose unfractionated heparin or the low-molecular-weight heparins (LMWHs) have been proven effective and safe. Thrombotic complications with chemotherapy have been extensively described in women receiving either adjuvant or palliative cytotoxic or hormonal therapy for breast carcinoma. The problems are common, but of all the suitable prophylactic modalities available, only oral anticoagulants have been evaluated for this indication. Thrombosis complicates the use of central venous catheters in the cancer patient and both low-dose warfarin and LMWHs are effective in protecting against line-associated thrombi. Recent evidence from the retrospective analyses of randomized studies comparing unfractionated heparin and LMWH in the treatment of deep vein thrombosis have shown a striking mortality reduction among cancer patients who received LMWH. The use of LMWHs to prolong survival in patients with advanced malignant disease is currently the subject of a prospective, randomized, placebo-controlled study.
Outpatient Therapy with Low-Molecular-Weight Heparins: New Perspectives for Treatment of Deep Vein Thrombosis
Authors: Büller H.R.
Published: April 2003

Subcutaneous administration of low-molecular-weight heparin (LMWH) has been demonstrated to be as safe and effective for treatment of acute venous thrombosis as conventional treatment with unfractionated heparin, which requires intravenous infusion. In addition, LMWHs appear to provide an improved quality of life for patients with less impairment of physical activity. The ease of administration of LMWHs could be exploited in the clinical management of patients to increase the extent of LMWH outpatient therapy and reduce the number of hospitalizations for venous thrombosis, thus providing a more cost-effective therapy than conventional heparin. Efficient support services, patient education and careful follow up will be required for home treatment to be successful.
Increase in Thrombin Generation after Coronary Thrombolysis with rt-PA or Streptokinase with Simultaneous Heparin versus Heparin Alone
Authors: Réganon E. , Ferrando F. , Vila V. , Villa P. , Martínez-Sales V. , Fayos L. , Ruano M. , Aznar J.
Published: April 2003

This study compares the extent of inhibition of thrombin generation and activity achieved in patients with acute myocardial infarction receiving fibrinolytic treatment (streptokinase SK, or rt-PA) and concomitant intravenous heparin treatment adjusted to the patients’ weight with that achieved with the same heparin regimen but without fibrinolytic therapy. The study involved 90 patients, grouped according to their treatment: SK+heparin; rt-PA+heparin, and heparin without thrombolytic agents. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), fibrinopeptide A (FPA) and activated partial thromboplastin time were measured. Patients treated with SK+heparin or rt-PA+heparin and higher F1+2 plasma levels than the patients treated with heparin alone at 12, 48 and 72 h in the case of SK+heparin, and at 12, 24, 48 and 72 h in that of rt-PA+heparin. Compared to baseline, the plasma levels of FPA were decreased in the three treatment groups at 24–48 h. There were no significant changes in TAT and FPA plasma levels among the three treatment groups at the different times. After thrombolytic therapy with both SK and rt-PA, there was an increase in thrombin generation, although high-dose intravenous heparin inhibited the different increases in thrombin associated with the thrombolytic agents to the same extent.
Epidemiology of Vascular Dementia
Authors: Leys Didier , Pasquier Florence , Parnetti Lucilla
Published: April 2003

Although epidemiological studies are limited by diagnostic uncertainties, they suggest that stroke increases the risk of dementia. The mortality rate is higher in vascular dementia (VaD) than in Alzheimer’s disease (AD). Community-based studies have provided several consistent findings: (i) age dependence with prevalence rates doubling every 5 years, (ii) a higher frequency in men and (iii) nation-to-nation differences. The prevalence of VaD ranges from 2.2% in 70- to 79-year-old women, to 16.3% in men >80 years. One sixth of acute stroke patients have preexisting dementia. The incidence of VaD has been studied much less extensively than that of AD, and substantial variations in the incidence rates have been observed: annual incidence rates (per 100,000) range from 20 to 40 between 60 and 69 years of age and from 200 to 700 over 80. The incidence rate of VaD declined over the last 2 decades, probably as a consequence of effective stroke prevention. It is generally assumed that risk factors for VaD are those of stroke, with arterial hypertension as leading factor, followed by atherosclerotic disease, low education level, alcohol abuse and heart disease. Stroke characteristics, such as lacunar infarction and left-sided hemispheric lesions, are major determinants of VaD. The cerebrovascular lesions are likely to be the only cause of dementia in strategic infarcts, in lacunar state, in hereditary cystatin C amyloid angiopathy and in CADASIL. However, white matter changes, and associated Alzheimer pathology, which are both frequent in this age category, may also contribute to the cognitive decline.
Efficacy of Unfractionated Heparin, Low Molecular Weight Heparin and Both Combined for Releasing Total and Free Tissue Factor Pathway Inhibitor
Authors: Altman Raul , Scazziota Alejandra , Rouvier Jorge
Published: April 2003

Unfractionated heparin (UFH) exerts its anticoagulant properties by increasing the inactivation of thrombin and activated factor X by antithrombin III. Apart from this main action release of tissue factor pathway inhibitor (TFPI) from endothelial cells could also be important for the antithrombotic activity of heparins. Four different heparin preparations were injected subcutaneously into 5 healthy volunteers 1 week apart: (1) UFH 2,500 IU fix dose (FixUFH), (2) 1 mg/kg body weight of low molecular weight heparin (LMWH), (3) the combined LMWH-adjusted dose plus UFH 2,500 IU fix dose (ComHep) and (4) UFH 2,500 IU/10 kg body weight (UFHvar). Plasma samples were drawn before and 1, 2, 4, 6, 12 and 24 h afterwards. FixUFH did not affect the concentration of total and free TFPI. Total TFPI increased in the 1st hour after LMWH injection from 74 to 124 ng/ml (p < 0.01), after ComHep from 82 to 144 ng/ml (p < 0.01), and after UFHvar from 91 to 113 ng/ml (p < 0.05). All observed elevations were significant at the peak value (± 2 h, p < 0.01 compared with baselines). The increase of free TFPI produced by UFHvar (74.5 and 70.5 ng/ml) was significantly higher than with LMWH (42.8 and 38.0 ng/ml) at 2 and 4 h (p < 0.001 and p < 0.01, respectively). UFHvar and ComHep but not LMWH produced a statistically significant increase of free TFPI compared with FixUFH at 2, 4 and 6 h (p < 0.01). We concluded that at comparable therapeutic doses, subcutaneous UFHvar released more free TFPI than LMWH and ComHep. A synergism between LMWH and low dose of UFH was found in 4-, 6- and 12-hour blood samples.
Antibodies against Factor VIII in Patients with Solid Tumors: Successful Treatment of Cancer May Suppress Inhibitor Formation
Authors: Sallah Sabah , Singh Paramjeet , Hanrahan L. Robert
Published: April 2003

Between 1995 and 1998, we treated 5 patients with anti-factor VIII antibodies and spontaneous bleeding. All patients had underlying malignant conditions. Initial control of the bleeding episodes and reduction in inhibitor titer was achieved in all patients. Disappearance of factor VIII inhibitor occurred in 3 patients after either resection of the tumor or chemotherapy. Immunosuppression therapy failed to eradicate the antibody in 2 patients with metastatic disease. Antibodies against factor VIII appearing in certain patients may be directly associated with the underlying malignancy, rather than a coincidental finding. Attempts to reduce the titer or eradicate the inhibitor may fail if recognition of the underlying condition is not sought, or an appropriate treatment of cancer is not offered.
Glycemic Control and Coagulation Inhibitors in Diabetic Patients
Authors: Altunbaş Hasan , Karayalçın Ümit , Ündar Levent
Published: April 2003

Objective: To investigate the plasma antigenic levels and functional activities of coagulation inhibitors in poorly controlled diabetic patients and the possible effect of good glycemic control on these parameters. Research Design and Methods: Both functional activities and plasma antigenic levels of coagulation inhibitors (antithrombin III, heparin cofactor II, protein C, and protein S) and plasma levels of C4b-binding protein were measured in 28 diabetic patients (13 males, 15 females; 2 IDDM, 26 NIDDM; median age 56.5 years; median duration of diabetes 5.5 years) with poor glycemic control (median HbA1c 11.8%). Twenty-three healthy subjects were enrolled as controls. Following a 3-month intensification of antihyperglycemic therapy, good glycemic control (HbA1c <8%) was achieved in 17 patients, and the plasma levels of the same parameters during this period were compared with baseline values. Results: Functional activities and plasma antigenic levels of coagulation inhibitors were comparable in poorly controlled diabetic patients and healthy subjects. In patients achieving good control after 3 months, there was a significant reduction in plasma antigenic levels of protein S (p = 0.005) and C4b-binding protein (p = 0.03); however, no difference could be observed in other parameters. HbA1c did not show any correlation with plasma antigenic levels or functional activities of coagulation inhibitors either at baseline or at 3 months of good glycemic control. Conclusions: Our findings suggest that in poorly controlled diabetic patients, coagulation inhibitors are not different from healthy controls. Short-term good glycemic control may not exert a profound effect on coagulation inhibitors except protein S and its binding protein, C4b-binding protein.
Regulation of Megakaryocytopoiesis
Authors: Caen J.P. , Han Z.C. , Bellucci S. , Alemany M.
Published: April 2003

After 35 years of research, a physiological regulator of platelet production has been identified and the recombinant protein is available. With the discovery of thrombopoietin (TPO), its potential use in a wide variety of clinical megakaryocytic and platelet disorders has been expected and clinical trials have been undertaken. To date, the reported encouraging pre-clinical studies indicate that, as with erythropoietin or G-CSF, minimal toxicity can be expected. A potential limiting side-effect of TPO could be the induction of thrombosis. Nevertheless, it is too early to know whether this cytokine will be of major therapeutic importance for patients with life-threatening thrombocytopenia, such as patients undergoing bone marrow transplantation or subjected to a high dose of chemotherapy. Several experimental and clinical studies are still needed to determine the efficacy of TPO in the prevention or the amelioration of bleeding, which is the ultimate goal for the appropriate use of cytokines with haemostatic benefit. Basic and clinical studies on regulators of megakaryocytopoiesis have rapidly progressed. Now, there is no doubt that some of these regulators are effective in correcting haematopoietic disorders of various aetiologies. Studies on negative regulators not only are important to understand the regulation of megakaryocytopoiesis in normal and pathological states but also have a potential clinical application. Some of these regulators have been shown to be effective in the treatment of essential thrombocythaemia and other myeloproliferative disorders. Platelet factor 4 (PF4) and some other chemokines are also capable of protecting progenitor cells from the cytotoxicity of chemotherapeutic drugs. However, detailed investigations are still required to determine the precise mechanism(s) of action of these regulators and to establish the optimal clinical protocols of negative regulators alone or in association with positive regulators for the treatment of various haematological diseases and cancer.
On the Coagulation of Platelet-Rich Plasma
Authors: Béguin S. , Keularts I.
Published: April 2003

Thrombin formation and blood platelet reactions are intimately linked in haemostasis and in thrombosis. In vivo, procoagulant phospholipids required for the coagulation mechanism are mainly provided by activated platelets, and thrombin is the most potent platelet activator. To study these interactions, an ancient tool of coagulation physiology, the thrombin generation test, was revived and the results obtained were reviewed. The amount of thrombin activity that develops, expressed as the endogenous thrombin potential (the area under the thrombin generation curve), is influenced by the clotting factors (except XII and XIII), the activated protein C system and natural inhibitors on the one hand and by platelet activity on the other. The platelet reactions that we found to be involved are induced by thrombin via glycoprotein (GP) IIb/IIIa activation and by fibrin via interaction with GPIb. von Willebrand factor is crucial in both reactions and therefore an obligatory factor for normal thrombin generation in the presence of platelets. All antithrombotics, be it anticoagulants (e.g. OAC, all heparins or hirudin) or antiplatelet drugs (aspirin, GPIIb/IIIa blockers) diminish thrombin generation.
The Haemostatic Balance – Astrup Revisited
Authors: Gaffney Patrick J. , Edgell Tracey A. , Whitton Colin M.
Published: April 2003

Prof. Tage Astrup first elaborated the notion that blood fluidity involved a balance between the tendency of blood to clot and for such clots to lyse. It would seem that, at that time, this haemostatic balance involved the notion that forming fibrin orchestrated its own destruction by stimulating fibrinolytic activity. In this review, we have clarified the detail of this balance and developed the thesis that Astrup’s far-sighted balance notions involve a variety of control mechanisms. These involve the notion that thrombin, being at first sight a procoagulant, can also, in conjunction with thrombomodulin, act as a stimulus of anticoagulant activity by the generation of activated protein C. The thrombin-activatable fibrinolytic inhibitor (TAFI) is also involved in this balance since the generation of thrombin provokes the neutralisation of fibrinolysis by the TAFI pathway. The kallikrein/factor XII/urokinase pathway is discussed indicating yet another aspect of balance between the generation of coagulation and fibrinolysis. The overall theme of this review, apart from an insight into various aspects of the haemostatic balance, is that blood has a strong tendency to clot when tissue is damaged, and the intact vasculature requires major anticoagulant systems to prevent clots adhering to and stabilising in the vasculature.
Statins as Cellular Antithrombotics
Authors: Fenton II John W. , Shen Garry X.
Published: April 2003

In clinical trials, statins (vastatins) reduce cardiovascular disease with cholesterol reduction, but this relationship is unclear. We reasoned that (1) thrombin (IIa) is an underlying mediator of cardiovascular events, (2) IIa mediates cellular events through its primary receptor [protease-activated receptor-1 (PAR-1)], and (3) statins inhibit an isoprenoid-dependent event between PAR-1 activation and tissue factor upregulation leading to IIa generation. In the isoprenoid pathways, statins inhibit mevalonic acid synthesis prior to divergence of the cholesterol and other pathway branches, where the latter produce cell-regulating substances (e.g., ras proteins). Through PAR-1 in platelets and other cells, IIa stimulates G-protein-coupled mechanisms including ras proteins. We hypothesize that statins exhibit antithrombotic properties at the cellular level downregulatating IIa generation and that statins may constitute a novel class of antithrombotics.
On the Identification of Beneficial and Detrimental Molecular Forms of Fibrinogen
Authors: Henschen-Edman Agnes H.
Published: April 2003

Fibrinogen is a central protein in blood coagulation. A functioning circulation system requires a precise balance between fibrin formation and removal, i.e. between the interaction of fibrin(ogen) with thrombogenic and fibrinolytic components of the blood. Fibrinogen and fibrin have also significant roles in wound healing, in tumor growth and metastasis as well as in defense mechanisms. All functions and interactions are mediated by specific structural elements of the molecule. Already in healthy individuals fibrinogen occurs in over a million nonidentical forms due to posttranslational modifications and genetic polymorphism. The various forms may show considerable differences in their functional properties. Alterations in distributions among preexisting forms as well as additional forms have been observed to accompany many types of disease. Furthermore, certain forms have been correlated with an increased risk to acquire disease. Monitoring the levels of various molecular forms is expected to be of considerable diagnostic and prognostic value in many types of disease.
Determination of the Prevalence of Fibrinogen Banks Peninsula Mutation (γ280Tyr→Cys) by PCR
Authors: Zimmermann Klaus , Turecek Peter L. , Schwarz Hans Peter
Published: April 2003

A mutation of Tyr→Cys at position 280 of the γ chain of fibrinogen was recently determined to be the cause for fibrinogen Banks peninsula. A novel polymerase chain reaction/restriction digestion assay for this mutation was developed and used for the screening of 300 apparently healthy European blood donors. None of these subjects carried the mutation.
Protein-Bound Heparin/Heparan Sulfates in Human Adult and Umbilical Cord Plasma
Authors: Xiao Hongyan , Miller Steven J. , Bang Nils U. , Faulk W. Page
Published: April 2003

We used thrombin times and a competitive radiometric assay to identify, quantitate and characterize endogenous heparin-like molecules in umbilical cord (n = 58) and normal adult (n = 25) plasma. Thrombin times for cord plasma (29.6 ± 3.6 s) were significantly longer (p ≤ 0.0005) than those for adult plasma (18.9 ± 2.3 s), suggesting increased endogenous heparins. A radiometric assay based on the displacement of 125I-heparin from protamine-Sepharose revealed that protease-digested plasma contained heparin/heparan sulfate, and plasma that was not digested with protease appeared not to contain heparin/heparan sulfate. More heparin/heparan sulfate was identified in cord than in adult plasma (p ≤ 0.05), but heparinase digestion produced significantly (p ≤ 0.001) reduced concentrations of heparin/heparan sulfate in only 39% of the samples. The lack of heparinase sensitivity in 61% of the protease-digested samples apparently was due to low molecular weight (LMW) heparins, for control heparin fragments of 5 kD that did not extend thrombin times were also less affected by heparinase, but the same LMW heparins were detected by radiometric assay. Despite normal thrombin times in all samples, the amounts of endogenous heparin/heparan sulfate identified in protease-digested samples by radiometric assay were of sufficient concentrations to produce inordinately prolonged thrombin times when compared with the same concentrations of unfractionated heparin. Collectively, these findings suggest the presence of a plasma reservoir of endogenous heparin/heparan sulfates in normal cord and adult plasma. These endogenous heparin/heparan sulfates are bound to plasma proteins, and an as yet undetermined proportion of these bound heparin/heparans are most likely LMW molecules.
Combined Administration of Dextran 70 and Dalteparin Does Not Increase Perioperative Blood Loss Compared to Dextran 70 Alone in Major Orthopedic Surgery
Authors: Dahl Ola E. , Walsøe Heidi K. , Aspelin Trude , Røise Olav , Arnesen Harald , Lyberg Torstein
Published: April 2003

A prospective open-labeled clinical study was carried out to compare the safety of dextran 70 and low molecular weight heparin (dalteparin; DD group) versus dextran 70 alone (D group) in patients subjected to elective hip replacement surgery. Dalteparin, 5,000 IU/day and dextran 70, 500 ml during surgery and on the first postoperative day were administered to 214 patients. Dextran 70 alone was infused in 44 patients, 500 ml during surgery and on the 1st, 3rd and 5th postoperative day. Mean total blood loss during the operation and until the 2nd postoperative day was 1,708 ml in the DD group and 1,712 ml in the D group (p = 0.79). During the 1st postoperative week, no group differences were found in the relative number of patients that received packed red blood cells (p = 0.95), the amount of transfused packed red blood cells (p = 1.0) and changes in hemoglobin concentrations (p = 0.69). The present results suggest that dextran 70 and dalteparin can be combined in recommended doses without significantly increasing perioperative bleeding in patients undergoing hip replacement surgery. Bone traumatization and insufficient plugging of surgical traumatized bone surfaces with bone cement favor bleeding. Further well-designed studies are needed to evaluate the safety and efficacy of this regimen.
Soluble P-Selectin and Proinflammatory Cytokines in Patients with Polygenic Type IIa Hypercholesterolemia
Authors: Ferroni Patrizia , Basili Stefania , Vieri Mario , Martini Francesca , Labbadia Giancarlo , Bellomo Ada , Gazzaniga Pier Paolo , Cordova Corrado , Alessandri Cesare
Published: April 2003

Plasma soluble P-selectin (sP-selectin), β-thromboglobulin (β-TG), von Willebrand Factor (vWF), prothrombin factor 1+2 (F1+2), IL-6 and IL-1β levels were analyzed in 35 consecutive patients with polygenic type IIa hypercholesterolemia (HC) and 35 age- and sex-matched healthy subjects. sP-selectin (p < 0.005), β-TG (p < 0.05) and IL-1β (p < 0.02) levels were higher in HC patients than healthy subjects whereas no significant difference was observed for vWF. sP-selectin directly correlated with β-TG (p < 0.05) and IL-1β levels (p < 0.005), but not with the other variables analyzed. A direct correlation was observed between F1+2 and IL-6 (p < 0.05), total cholesterol (p < 0.05) or LDL cholesterol (p < 0.05). We conclude that HC is associated with an increase of plasma sP-selectin levels, and that sP-selectin may be considered as a marker of in vivo platelet activation in type IIa polygenic HC. The correlations observed among the variables analyzed in the study suggest that proinflammatory cytokines might play a role in the prothrombotic state often associated with HC.
Recombinant Thrombomodulin Inhibits Thrombin-Induced Vascular Endothelial Growth Factor Production in Neuronal Cells
Authors: Sarker Krishna Pada , Yamahata Hitoshi , Nakata Masanori , Arisato Takayo , Nakajima Toshihiro , Kitajima Isao , Maruyama Ikuro
Published: April 2003

Thrombin is a serine protease which is generated from its precursor prothrombin by the activation of the blood coagulation cascade. Thrombin converts fibrinogen to fibrin, activates platelets and several coagulation factors, and plays a central role in thrombosis and hemostasis by regulating platelet aggregation and blood coagulation. Here, we show that thrombn enhanced vascular endothelial growth factor (VEGF) production in a dose- and time-dependent manner in the supernatant of cultured PC-12 cells, as determined by enzyme-linked immunosorbent assay (ELISA). Thrombin receptor agonist peptide (SFLLRNPNDKYEPF, TRAP) exerted an effect similar to thrombin on VEGF production. Thrombin-induced VEGF production was significantly attenuated by recombinant human thrombomodulin (rTM) and its minimal functional domain E456. Furthermore, the antioxidant N-acetyl-L-cysteine (NAC) markedly inhibited thrombin-induced VEGF production. Thus, rTM and NAC apparently inhibited the effect of thrombin on VEGF production in neuronal cells.
Darwin’s Baby and Baby’s Darwin: Mutual Recognition in Observational Research
Authors: Conrad Rachel
Published: April 2003

Psychology has traditionally considered scientific objectivity to be enabled by the detachment and disembodiment of an observer at a distance. As an alternative, an embodied, relational stance of the observer to the observed provides understanding of mutual developmental processes not available through adhering to standard assumptions about objectivity. A textual analysis of Charles Darwin’s pronominal terms in the diary version of his observations on his oldest child, and in the published paper based on these observations, assessed the degree to which Darwin identified himself as detached observer or as embodied participant in these two texts. Results of the textual analysis indicated that, in the diary version, Darwin increasingly identified himself as embodied participant in interaction with his baby, in a manner coordinated with changes Darwin described in his baby’s recognition of himself and of Darwin. The embodied, relational vision which Darwin practiced as an observer of his child was not evident in the subsequently published scientific account. This paper demonstrates the value of textual analyses in elucidating possible disjunctions among a scientist’s observations, the mode of recording these observations, and the use the scientist makes of these recorded observations in texts written for scientific publication. Such analyses can aid in psychology’s examination of its assumptions concerning objectivity and subjectivity in science.
Gradual Belief Change in Children
Authors: Schwitzgebel Eric
Published: April 2003

Major cognitive developments are unlikely to happen instantaneously. Consequently, children must frequently pass through periods of being ‘in between’ genuine understanding and failure to understand. The current literatures on false belief understanding and object permanence largely fail to recognize the importance of such in-between states of understanding. Recent philosophical accounts of belief also fail to make sufficient room for such in-between states. An approach based on Ryle’s [1949] account of belief is recommended and is compared with some other approaches, including the competence/performance approach and contextualist approaches.
Choosing Biases, Using Power and Practicing Resistance: Moral Development in a World without Certainty
Authors: Walker Janet S.
Published: April 2003

In contrast to the modernist models which have dominated the psychological study of moral development in recent decades, the model of moral development presented here rests on the premise that situations in the real world are inherently ambiguous, and that their moral significance in particular is profoundly underdetermined by available ‘facts’. Under these conditions, our interpretations of moral events are necessarily biased by the interpretive habits in our repertoire. These habits of cognition – which simultaneously perceive the moral world and constitute it – are founded in early socialization, and are then directed and shaped throughout life by reflection and by our experience. The description of the model is buttressed by research results, including a study of narratives collected from working class African-, European-, and Mexican-American men and women.
Coronary Brachytherapy and Restenosis
Authors: Latchem Donald , Urban Philip
Published: April 2003

The antiproliferative effects of radiotherapy have been used clinically for over 100 years to treat several benign disorders. More recently, several experimental studies have convincingly demonstrated that the use of intracoronary radiotherapy results in marked modulation of the restenotic process. Currently, several systems are undergoing clinical evaluation. Radiotherapy with gamma radiation has been conclusively shown to have a major impact on the long-term prevention of restenosis following percutaneous intervention. Several systems using beta radiation, delivering a more localised form of radiotherapy, have also been used with very promising results in the short to mid-term. Whilst inhibition of restenosis at the target site is a consistent finding, both forms of radiotherapy can be complicated by recurrences at the edges and by late thrombotic occlusion. Both these limitations should be minimised by improved lesion coverage by the radiation source and by prolonged (6 months) anti-platelet therapy. Although there is clear convergence of evidence to suggest that many radiotherapy systems are highly effective in the short and mid-term, a prolonged follow-up period over several years will be necessary to make a definitive conclusion about their wide-scale clinical application.
Adult-Onset Primary Open Angle Glaucoma Does Not Localize to Chromosome 2cen-q13 in North American Families
Authors: Allingham R.R. , Wiggs J.L. , Damji K.F. , Herndon L. , Youn J. , Tallett D.A. , Jones K.H. , Del Bono E.A. , Reardon M. , Haines J.L. , Pericak-Vance M.A.
Published: April 2003

Glaucoma is one of the leading causes of irreversible blindness in the world and is characterized by elevated intraocular pressure, optic nerve atrophy, and progressive visual field loss. Primary open angle glaucoma (POAG) is the most common subtype of glaucoma in the United States. Recently, Stoilova and coworkers [Genomics 1996;36:142–150] identified a locus for POAG on chromosome 2 (2cen-q13) in families primarily located in the United Kingdom. We examined families with POAG identified within the US for linkage to the 2cen-q13 locus. A total of 18 families with POAG were used in the analysis. Of 77 family members, 46 were classified as affected and 31 were either glaucoma suspects or considered normal. Eight highly polymorphic and informative markers flanking and distributed throughout the region were used. Parametric lod score analysis was performed using both a dominant and recessive low penetrance or ‘affecteds-only’ model. Multipoint affected sibpair exclusion mapping was also performed. Lod score (both models) and sibpair analysis excluded linkage of the POAG phenotype to the 2cen-q13 region in these families. These data suggest that the chromosome 2cen-q13 locus does not explain a substantial amount of genetic variation in familial POAG.
Population Study of Common Glucose-6-Phosphate Dehydrogenase Mutations in Kuwait
Authors: Samilchuk Elena , D’Souza Brendan , Al-Awadi Sadika
Published: April 2003

DNA samples from 206 unrelated Kuwaitis of both sexes, i.e. 200 randomly selected individuals and 6 glucose-6-phosphate-dehydrogenase (G6PD)-deficient probands, have been analyzed by the PCR/RFLP technique for mutations underlying the most common G6PD-deficient variants (Mediterranean and A–). At the first step all samples were studied for the 563C→T and 376A→G mutations, then the samples positive for 376A→G were further analyzed for 202G→A, 680G→T and 968T→C mutations. Three mutations (563C→T, 376A→G and 202G→A) were found to be present in the Kuwaiti population at polymorphic frequencies (0.0503, 0.0215 and 0.0111, respectively). Nineteen out of 20 unrelated Kuwaiti chromosomes with 563C→T had Mediterranean haplotype as judged by 1311C→T polymorphism. The frequency of G6PD-deficient genotypes was 4.5% (5.73% in males and 2.56% in females).
Hereditary Desmoid Disease in a Family with a Germline Alu I Repeat Mutation of the APC Gene
Authors: Halling Kevin C. , Lazzaro Carlo R. , Honchel Ronald , Bufill José A. , Powell Steven M. , Arndt Carola A.S. , Lindor Noralane M.
Published: April 2003

Two families with autosomal dominantly inherited desmoid tumors have recently been shown to have germline mutations at the 3′ end of the APC gene. We subsequently identified an Amish family with autosomal dominantly inherited desmoid tumors. Genetic analysis performed on one family member, a 47-year-old man with multiple desmoid tumors and no colon polyps, revealed a protein truncating mutation in the middle of the APC gene. The truncating mutation is the result of a 337-bp insertion of an Alu I sequence into codon 1526 of the APC gene. The presence of a poly(A) tail at the 3′ end of the insertion suggests that the Alu I sequence was inserted by a retrotranspositional event. Germline insertions of Alu I sequences have occasionally been reported to cause other genetic diseases including type I neurofibromatosis, hereditary site-specific breast cancer (BRCA2), and hemophilia B. However, this is the first report of a germline mutation of the APC gene resulting from an Alu I insertion.
Familiality of Quantitative Metabolic Traits in Finnish Families with Non-Insulin-Dependent Diabetes mellitus
Authors: Watanabe Richard M. , Valle Timo , Hauser Elizabeth R. , Ghosh Soumitra , Eriksson Johan , Kohtamäki Kimmo , Ehnholm Christian , Tuomilehto Jaakko , Collins Francis S. , Bergman Richard N. , Boehnke Michael
Published: April 2003

Type 2 diabetes mellitus (NIDDM) is a complex disorder encompassing multiple metabolic defects. There exists strong evidence for a genetic component to NIDDM; however, to date there have been few reports of linkage between genetic markers along the genome and NIDDM or NIDDM-related quantitative traits. We sought to determine whether individual quantitative traits which determine glucose tolerance exhibit familiality in Finnish families with at least one NIDDM-affected sibling pair. Tolbutamide-modified frequently sampled intravenous glucose tolerance tests (FSIGT) were performed on unaffected offspring (n = 431) and spouses (n = 154) of affected sibling pairs sampled for the Finland-United States Investigation of NIDDM Genetics (FUSION) study. FSIGT data were analyzed using the Minimal Model to obtain quantitative measures of insulin sensitivity (SI), glucose effectiveness (SG), and insulin secretion assessed as the acute insulin response to glucose (AIR). The disposition index (DI), a measure of insulin resistance-corrected β-cell function, was also derived as the product of SI and AIR. Variance components analysis was used to determine for each trait, the heritability (h2), the proportion of the total trait variance accounted for by additive genes. After adjustment for age, gender, and body mass index, h2 estimates were: SG: 18 ± 9%, SI: 28 ± 8%, AIR: 35 ± 8%, and DI: 23 ± 8%. We conclude that there is strong evidence for modest heritability of Minimal-Model-derived NIDDM-related quantitative traits in unaffected spouses and offspring of Finnish affected sibling pairs.
The Future of Path Analysis, Segregation Analysis, and Combined Models for Genetic Dissection of Complex Traits
Authors: Rao D.C. , Province M.A.
Published: April 2003

Appropriate combined models are discussed for the analysis of complex traits. It is argued that combined models may be necessary for optimally extracting the information from family studies. It is further argued that, especially as we face genes with much smaller effects, our ability to find these genes will depend on how precisely and accurately we are able to model the interrelationships. We need these newer models and methods for optimally extracting the information from family data, and we also need to reorient ourselves as to how we interpret the very information extracted. It is projected that path and segregation analysis, as seen in terms of combined models, will be useful in the new millennium.
Identification of a Prevalent Nonsense Mutation (W283X) and Two Novel Mutations in the Porphobilinogen Deaminase Gene of Swiss Patients with Acute Intermittent Porphyria
Authors: Schneider-Yin Xiaoye , Bogard Catherine , Rüfenacht Ursula B. , Puy Hervé , Nordmann Yves , Minder Elisabeth I. , Deybach Jean-Charles
Published: April 2003

Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by decreased activity of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthetic pathway. We report the first molecular analysis of PBGD gene mutations in AIP patients of Swiss origin. The PBGD gene of 18 Swiss AIP patients was analyzed by denaturing gradient gel electrophoresis screening of the genomic DNA and direct sequencing. Thirteen of the 18 patients (72%) carried a nonsense mutation G849→A, W283X. In addition, 4 different mutations including 2 novel mutations (Q217L and Q292X), were identified in the 5 remaining AIP patients originating from both German- and Italian-speaking regions of Switzerland.
Alkaline Serine Proteinase: A Major Allergen of Aspergillus oryzae and Its Cross-Reactivity with Penicillium citrinum
Authors: Shen Horng-Der , Lin Win-Ling , Tam Ming F. , Wang Soo-Ray , Tsai Jaw-Ji , Chou Hong , Han Shou-Hwa
Published: April 2003

Background:Aspergillus species are common indoor airborne fungi and have been considered as causative agents of human allergic disorders. However, allergens of different Aspergillus species have not been effectively characterized. The object of this study was to identify and characterize IgE-binding components of Aspergillus oryzae. Methods. Allergens of A. oryzae were identified by immunoblot analysis using sera from asthmatic patients. The N-terminal amino acid sequences of allergens thus identified were determined by Edman degradation. The antigenic and the allergenic cross-reactivities between allergens of different fungi were analyzed by immunoblotting and immunoblot inhibition analysis, respectively, using a monoclonal antibody (MoAb) 55A against the 33-kD major allergen of Penicillium citrinum and a mixture of IgE-containing asthmatic serum samples. Results: Thirteen components of A. oryzae ranging in apparent molecular weight from 16 to 42 kD react with IgE antibodies. A 34-kD component that showed intense IgE-binding reactivity and was detectable in the highest frequency in our asthmatic serum samples tested was considered a major allergen of A. oryzae. The 34-kD component also reacted with MoAb 55A. Results from immunoblot inhibition studies also demonstrated the IgE cross-reactivity between the 34-kD major allergens of A. oryzae and P. citrinum. In addition, the sequence of the N-terminal 18 amino acid residues of the 34-kD major allergen of A. oryzae was found to be identical to that of the alkaline serine proteinase from the same Aspergillus species. Conclusion: The 34-kD major allergen of A. oryzae is an alkaline serine proteinase. There is IgE cross-reactivity between the major serine proteinase allergens of A. oryzae and P. citrinum.