bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Phase Markers Are Associated with Reduced Plasma Lipid Levels in a Population of Hospitalized Elderly Patients
Authors: Volpato S. , Palmieri E. , Fellin R. , Zuliani G.
Published: April 2003

Background: Several epidemiological studies have documented the presence of a ‘J’ or ‘U’ association between total cholesterol levels and total mortality. Not only the mechanism underlying the association between increased mortality and low total cholesterol values is not completely clear, but the relationship itself also appears to be complex in the elderly. Objective:The aim of the study was to evaluate the possible association between some biohumoral markers of the acute phase, comorbidity, disability, and reduced levels of some lipoprotein parameters in a sample of hospitalized elderly subjects. Methods: 341 patients over 65 years of age (185 males, 156 females; mean age 76.2 years), consecutively admitted to our department from 1994 to 1995, were studied. Acute phase was defined as the simultaneous presence of: (1) increased α2-plasma protein on electrophoresis (>12%); (2) high fibrinogen concentration (>450 mg/dl), and (3) increased blood sedimentation rate (>15 and >20 mm 1 h in males and females, respectively). Results: The prevalence of signs of acute phase was higher in males and in the youngest patients, but did not change with the level of comorbidity. Patients with signs of acute phase were characterized by lower total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol levels compared to subjects without signs of acute phase; this difference was significant even after adjustment for indicators of comorbidity, disability, and nutritional status. Multivariate logistic regression analysis evidenced that the simultaneous presence of these three markers of acute phase was independently associated with low levels of total cholesterol [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1–3.9], and HDL-cholesterol (OR 2.3, 95% CI 1.2–4.2), considered as the sex-specific first quintile. Conclusion: The findings of this study demonstrate an independent association between acute phase markers and low levels of total and HDL-cholesterol, suggesting that recognized or subclinical diseases in elderly patients may determine a reduction in these plasma lipids. Low level of total and HDL-cholesterol should be considered as possible clinical markers of an underlying state of acute phase rather than a sign of malnutrition. Given the high prevalence of chronic diseases in the elderly, epidemiological studies addressing the lipid profile in this age group should take into account the possible confounding effect of the presence of signs of acute phase.
Visual Analogue Scales for Pain Assessment in Alzheimer’s Disease
Authors: Scherder Erik J.A. , Bouma Anke
Published: April 2003

Background: In earlier studies, pain assessment in patients with Alzheimer’s disease (AD) was conducted by interview, for which reliability is questionable considering the decline in expressive and receptive language abilities in AD. As similar language problems occur in young children, the reliability of pain assessment in this latter population is increased by employing visual analogue scales. Objective: By employing visual analogue scales, the current study investigated whether (1) nondemented elderly persons and AD patients comprehend the purpose of the scales and (2) AD patients, compared to nondemented elderly persons, report suffering less pain intensity and pain affect. Methods: Three visual analogue scales, i.e. the Colored Analogue Scale (CAS), the Faces Pain Scale (FPS), and the Facial Affective Scale (FAS) were administered to patients in an early and midstage of AD and to nondemented elderly persons. Results: The results show that the percentage of subjects who comprehended the CAS, FAS and FPS was for the nondemented elderly persons 100, 75 and 100%, respectively, for the early AD group 100, 50 and 60%, respectively, and for the midstage AD group 80, 20 and 30%, respectively. Furthermore, elderly persons without dementia reported experiencing more intense pain and pain affect than the early and midstage AD group. Interestingly, the early and midstage AD patients did not differ in reporting pain affect. Conclusion: Visual analogue scales may improve pain assessment in those AD patients who fully comprehend the meaning of the scales. As only the minority of midstage AD patients understood the purpose of the FAS and FPS, the search for tools, particularly to assess pain affect in this population, must continue.
Entwicklung der minimal-invasiven Mammachirurgie – Übersicht und eigene Erfahrungen
Authors: Köchli Ossi R.
Published: April 2003

Diagnostische und therapeutische Neuerungen sind beim Mammakarzinom deshalb nötig, da in den letzten Jahren immer kleinere Befunde einer Abklärung zugeführt werden. Es wird geschätzt, dass in Zukunft ein Viertel aller Patientinnen eine präinvasive Läsion (DCIS) und die Hälfte einen Tumor haben werden, der nicht grösser als 2 cm ist. Der vermehrte Einsatz von bildgebenden Verfahren, insbesondere der Mammographie, führt dazu, dass vermehrt präinvasive und kleine Mammatumoren entdeckt werden. Moderne, computergestützte stereotaktische Mammaexzisionsbiopsien, die auch ambulant durchführbar sind, sind deshalb dringend nötig. Zur Morbiditätssenkung der axillären Chirurgie beim Mammakarzinom werden aktuell neue Verfahren überprüft. Die Detektion des sogenannten «Sentinel lymph node» nach dem Selektionsprinzip ist deshalb morbiditätssenkend, weil bei negativem Befund nur der Pförtnerlymphknoten entfernt werden muss. Die endoskopische axilläre Lymphadenektomie nach Liposuktion stellt ebenfalls eine neue Methode der axillären Chirurgie dar, bei welcher die bessere Visualisierung der anatomischen Strukturen zur Morbiditätssenkung dank gewebeschonender Chirurgie beitragen kann. Ausserdem wird erstmals die Kombination dieser zwei neuen Methoden beschrieben und dokumentiert: die axilloskopische Bestimmung und Entfernung des Sentinel-Lymphknotens u.a. nach Isosulfanblau-Gabe. Diese kombinierte Methode ist allerdings technisch und zeitlich sehr aufwendig und weist keine offensichtlichen Vorteile gegenüber der offenen Sentineltechnik auf, weshalb sie zwar als machbar, aber für die tägliche Praxis als ungeeignet beurteilt werden muss. Die Zukunft gehört der offenen Sentineltechnik.
Long-Term Consequences of Deep Vein Thrombosis
Authors: Leizorovicz Alain
Published: April 2003

Following an overt episode of deep vein thrombosis (DVT), the long-term prognosis of the patient is predominantly obscured by three natural complications: recurrence of venous thromboembolism (VTE), post-thrombotic syndrome and death. Antithrombotic treatments have been proven effective in preventing recurrence of VTE but carry the risk of major bleeding. A high mortality rate persists during the first year following an acute VTE, with a small but continuing risk beyond the first year. Recurrences of VTE account for the minority of causes of deaths. With effective initial anticoagulant treatment, the early (within approximately 3 months) risk of recurrence is 3–6%. Long-term follow-up studies have shown that although the risk of recurrence of VTE beyond the first 6 months is lower, the risk persists over several years. Approximately 25% of DVT patients remain asymptomatic in the long term but severe signs of post-thrombotic syndrome (ulceration) are observed in 2–10% of patients 10 years after DVT. Major advances have been made in the management of acute VTE but the excess risks of death, recurrence of VTE and post-thrombotic syndrome persist for several years following the initial event. Appropriate therapeutic strategies for these events are still being developed and future study should be directed towards finding the optimal regimen for patients who require prolonged treatment.
The Economic Impact of Treating Deep Vein Thrombosis with Low-Molecular-Weight Heparin: Outcome of Therapy and Health Economy Aspects
Authors: Hull Russell D. , Pineo Graham F. , Raskob Gary E.
Published: April 2003

Subcutaneous low-molecular-weight heparin (LMWH) is at least as safe and effective as classical intravenous heparin therapy for the treatment of proximal vein thrombosis. Anticoagulant monitoring and intravenous administration are not required with LMWH treatment, therefore this therapy may offer economic advantages. An economic evaluation of these therapeutic approaches was performed comparing the costs and effectiveness. The evaluation was aimed at helping decision-makers to maximize the health of the population served, subject to available resources. The American-Canadian Thrombosis Study was a multicentre, randomized, double-blind clinical trial that compared treatment by initial continuous intravenous infusion of heparin (followed by 3 months of warfarin therapy) with a once-daily dose of subcutaneous LMWH, tinzaparin sodium (followed by 3 months of warfarin treatment) in patients with acute proximal deep vein thrombosis. In the LMWH-treated group, the cost incurred for 100 patients was $399,403 (Canadian) or $335,687 (US) with a frequency of objectively documented recurrent venous thromboembolism of 2.8%. In the intravenous heparin-treated group, the cost incurred for 100 patients was $414,655 (Canadian) or $375,836 (US), with a frequency of objectively documented recurrent venous thromboembolism of 6.9%. These results show a cost saving of $15,252 (Canadian) or $40,149 (US) with the use of LMWH. Multiple sensitivity analyses did not alter the findings of the study which indicated that LMWH therapy is at least as safe and effective but less costly than intravenous heparin treatment. The potential for outpatient therapy in up to 37% of patients who are receiving LMWH would substantially augment the cost-saving. The cost-effectiveness findings presented in this paper are based on the assumption that all costs are covered by a single payer. Outpatient management in many countries will shift the healthcare costs from the healthcare payer to the patient, increasing the economic burden to the patient.
The Special Case of Venous Thromboembolism in Pregnancy
Authors: Greer Ian A.
Published: April 2003

Pulmonary thromboembolism remains a major cause of maternal death in the Western world. The frequency of antepartum deaths, including deaths in the first and second trimester, which can be associated with early pregnancy problems such as hyperemesis, is similar in number to the deaths occurring following delivery. Risk factors for deep vein thrombosis have been identified and include age >35 years, operative delivery (particularly emergency Caesarean section), obesity and a personal or family history of thrombosis or thrombophilia. These risk factors should be used to guide administration of thromboprophylaxis during both pregnancy and the post-partum period, particularly after Caesarean section. Specific consideration towards thromboprophylactic agents is required. Warfarin crosses the placenta, is a known teratogen when used in early pregnancy and can also be associated with bleeding problems in the foetus, particularly at the time of delivery. Thus, warfarin has a limited use in the antenatal period and is usually only employed in patients such as those with artificial heart valves who require long-term anticoagulation. However, as warfarin does not cross the breast in any significant amount, it is suitable during breast feeding. In contrast, heparin does not cross the placenta or the breast therefore foetal problems are not associated with this treatment. However, heparin can be associated with problems such as heparin-induced osteoporosis, allergy and heparin-induced thrombocytopenia. The risk of some of these complications can be reduced by the use of low-molecular-weight heparins. When venous thromboembolism is suspected in pregnancy, it is critically important to obtain an objective diagnosis. This will include real-time or duplex ultrasound scan of the legs to elaborate the venous system, ventilation perfusion lung scan and, occasionally, venography. Treatment of established venous thromboembolism is similar to that in the non-pregnant patient and it is likely that low-molecular-weight heparins will play a major role in thromboprophylaxis in the future.
Antithrombotic Therapy in Coronary Ischaemia: The Expanding Role of Low-Molecular-Weight Heparin
Authors: Turpie Alexander G.G.
Published: April 2003

Low-molecular-weight heparins (LMWHs) have been rigorously evaluated in the management of acute coronary ischaemia. The results of clinical trials suggest that LMWHs are effective in reducing major ischaemic outcomes in patients with unstable angina and non-Q-wave myocardial infarction. In one study, LMWH was shown to be more effective than heparin. The clinical utility of LMWHs given subcutaneously in a fixed-dose without the need for monitoring results in major cost savings. The accumulating evidence suggests that LMWHs are safe, effective alternatives to standard heparin in unstable coronary disease and offer practical and therapeutic advantages, representing an important advance in the management of acute coronary ischaemia.
Treatment of Venous Thromboembolism in Cancer Patients
Authors: Levine Mark , Rickles Frederick R.
Published: April 2003

The occurrence of venous thromboembolism complicates the management of the patient with malignant disease because of the need for anticoagulant therapy. Cancer patients have an ongoing thrombotic stimulus due to the underlying cancer and its associated treatments, but are also considered to be at increased risk for anticoagulant-related bleeding. In recent years, the results of clinical trials have demonstrated the safety and efficacy of bodyweight-adjusted subcutaneous low-molecular-weight heparin administered at home for patients with acute deep vein thrombosis. This approach is particularly attractive in patients with cancer, in whom quality of life is an important consideration. There are no trials to date which specifically address the question of the duration of oral anticoagulant therapy in cancer patients. However, data can be extrapolated from trials evaluating the duration of oral anticoagulant therapy in other high-risk patients. Hence, cancer patients should continue oral anticoagulant therapy for as long the cancer remains active (usually at least 6 months). There remain a number of unanswered questions regarding the clinical management of thromboembolism in the cancer patient.
Thromboprophylaxis in Non-Surgical Patients:Who, When and How?
Authors: Gallus A.S. , Nurmohammed M. , Kearon C. , Prins M.
Published: April 2003

Because of the serious lack of useable, relevant information, most recommendations for prevention of thrombosis in non-surgical patients are extrapolations from much larger clinical trials experienced in surgery. Directly relevant evidence comes predominantly from very small randomized trials, many of them open label and carried out more than 20 years before the introduction of more recent and important changes in clinical care that may have substantially reduced the baseline thrombosis risk. In these early studies, low-dose heparin and low-molecular-weight heparins prevented subclinical deep vein thrombosis in ischaemic stroke, myocardial infarction and among elderly medical inpatients. Although it is likely that these drugs also prevent subclinical deep vein thrombosis after spinal cord injury or other major trauma, and when patients require intensive medical care, the supporting evidence in these circumstances comes mainly from cohort studies and poorly controlled comparisons. In contrast, the heparins have not reduced mortality or demonstrably prevented pulmonary embolism after ischaemic stroke or among elderly medical inpatients in large and well-conducted clinical endpoint trials, from which no clinically important benefit could be demonstrated. From analyses it is suggested that such benefit is probably more difficult to demonstrate for medical than for surgical patients. In the absence of sufficient information that is specific to medical patients, various forms of prophylaxis known to be effective in surgery will continue to be applied in high-risk individuals. After venous thromboembolism, it now appears that the best duration of oral anticoagulant therapy to prevent a recurrence is determined to a greater extent by whether the thrombotic episode was idiopathic or triggered by a clinically recognizable cause, whether it was transient or continuing, and whether the deep vein thrombosis was extensive, limited to the calf veins or was a first or recurrent event.
Randomized Assessment of a Warfarin Nomogram for Initial Oral Anticoagulation after Venous Thromboembolic Disease
Authors: Kovacs M.J. , Cruickshank M. , Wells P.S. , Kim H. , Chin-Yee I. , Morrow B. , Boyle E. , Kovacs J.
Published: April 2003

Standard treatment for venous thromboembolism is parenteral heparin followed by warfarin. In this study we assess whether a standardized method of ordering warfarin reduces the duration of hospitalization. Consecutive patients were randomized to receive warfarin managed by attending physicians or by a nomogram. Patients were stratified according to primary or secondary venous thromboembolism. Prothrombin times were measured daily and heparin was given for a minimum of 5 days and stopped when the International Normalized Ratio was >1.9. Patients were followed for 3 months. There were 111 patients, 80 with primary and 31 with secondary venous thromboembolism. Overall there were no differences between the two warfarin groups with respect to length of admission. Given the prolonged duration of admission in many patients with secondary venous thromboembolism, a subset analysis was conducted on the 80 patients with primary venous thromboembolism. Patients in the standard group stayed significantly longer than patients in the nomogram group (6.0 vs. 5.6 days, p = 0.02). The warfarin nomogram as tested is safe and leads to a significantly shorter length of stay for patients with primary venous thromboembolism as compared to standard practice.
Risk Factors for Vascular Disease and Dementia
Authors: Breteler Monique M.B. , Bots Michiel L. , Ott Alewijn , Hofman Albert
Published: April 2003

There is increasing evidence that risk factors for vascular disease and stroke are associated with cognitive impairment and Alzheimer’s disease. This paper reviews current knowledge on the relationship between risk factors for stroke and Alzheimer’s disease. The focus will be on ‘classical’ risk factors, including age and gender, socioeconomic status, diabetes, cholesterol, prior cardiovascular disease, atrial fibrillation, cigarette smoking and alcohol use; as well as on factors that more recently have been recognized as putative risk factors, including APOE genotype, serum homocysteine concentration, relative abnormalities in the hemostatic and thrombotic systems, and inflammation.
Response to Activated Protein C in Subjects with and without Dementia
Authors: Bots Michiel L. , van Kooten Fop , Breteler Monique M.B. , Slagboom P. Eline , Hofman Albert , Haverkate Frits , Meijer Piet , Koudstaal Peter J. , Grobbee Diederick E. , Kluft Cornelis
Published: April 2003

We performed a cross-sectional case-control study among 295 subjects with dementia and 406 control subjects drawn from participants of the Rotterdam Study, a population-based cohort study among subjects aged 55 years or over, and from participants of the Rotterdam Stroke Databank, a hospital-based stroke registry, to evaluate the association of the factor V Leiden mutation and activated protein C (APC) response with dementia and its subtypes. The risk of dementia was 2.11-fold increased among carriers of factor V Leiden mutation relative to subjects lacking factor V Leiden mutation (95% confidence interval, CI, 0.93–4.77). The increased risks of vascular dementia and of Alzheimer’s disease were 4.28 (95% CI 1.26–14.5) and 2.15 (95% CI 0.82–5.63), respectively. No association was found for APC response. We showed a nonsignificant twofold increased risk of dementia among subjects with factor V Leiden. The association appeared to be stronger for vascular dementia.
Recent Advances in Platelet-Polymorphonuclear Leukocyte Interaction
Authors: de Gaetano Giovanni , Cerletti Chiara , Evangelista Virgilio
Published: April 2003

Epidemiological evidence suggests a positive correlation between the number of PMN and the risk of ischemic vascular disease. The observation that activated PMN induce platelet activation my provide some biological plausibility to the role of PMN in thrombogenesis. Between other PMN products, cathepsin G, a protease released during PMN activation, is a potent platelet agonist. However, the antiproteinases present in plasma could virtually abolish its activity. Indeed it was shown that, when PMN were stimulated after interaction with platelets in mixed cell population, P-selectin-mediated platelet-PMN adhesion may result in the formation of a sequestered microenvironment in which cathepsin G activity is protected by antiproteases. P-selectin-mediated adhesion was also shown to facilitate the transcellular metabolism of arachidonic acid, resulting in increased production of both thromboxane B2 and leukotriene C4. PMN adhesion to activated platelets in mixed cell suspensions subjected to high shear rate can be modeled as an adhesion cascade involving a P-selectin-dependent recognition step followed by an adhesion-strengthening interaction mediated by the β2-integrin Mac-1. Moreover, an intermediate tyrosine-kinase-dependent signal regulating β2-integrin adhesiveness is required. Indeeed activated platelets express not only P-selectin but also different β2-integrin ligands including fibrinogen and ICAM-2. Some of the functional responses elicited by P-selectin on PMN could be prevented by specific antibody to the P-selectin glycoprotein ligand-1, indicating that this adhesive receptor is able to transduce an ‘outside-in’ signal when engaged by the ligand. By using activated platelets, P-selectin-expressing CHO cells and soluble recombinant P-selectin, P-selectin was shown to trigger protein tyrosine phosphorylation in PMN and the tyrosine kinase-dependent function of Mac-1. In conclusion, adherence of activated platelets to PMN may be a key event in the sequence of thrombus formation. The recognition of the essential contribution of PMN β2-integrins in addition to P-selectin in platelet-PMN adhesion provides an additional evidence to the broad range of function and mechanisms in which PMN integrins are involved and may be potential targets for pharmacological intervention.
Antiphospholipid-Thrombosis Syndromes
Authors: Bick Rodger L. , Arun Banu , Frenkel Eugene P.
Published: April 2003

Antiphospholipid antibodies are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Based upon our experience, ∼25% of patients with unexplained venous thrombosis, ∼60% of patients with cerebrovascular thrombosis, ∼37% of patients with transient ischemic attacks, ∼18% with premature coronary artery thrombosis and ∼60% of patients with recurrent fetal loss (recurrent miscarriage syndrome) harbor antiphospholipid antibodies. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. Since the aPTT is unreliable in patients with lupus anticoagulant and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests, ELISA for IgG, IgA and IgM anticardiolipin antibodies and the dilute Russel’s viper venom time (followed by cephalin correction for confirmation) for lupus anticoagulant should be immediately ordered when suspecting the antiphospholipid syndrome in individuals with otherwise unexplained thrombotic or thromboembolic events or recurrent fetal loss. However, if one strongly suspects antiphospholipid thrombosis syndrome clinically and assays for lupus anticoagulants and anticardiolipin antibodies are negative, specific assays for all three idiotypes of phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylglycerol are available and should be considered. These may clearly be indicated for difficult diagnostic cases of fetal wastage syndrome, and cerebrovascular events, but their significance in other types of thrombosis, particularly venous, remains unclear at present. Since about 65% of patients with antiphospholipid antibodies will fail warfarin therapy (rethrombose), it is important to define this common defect and institute appropriate antithrombotic therapy for appropriate time periods.
Diagnostic Approach of Phospholipid-Dependent Antibodies
Authors: Amiral Jean
Published: April 2003

Recent scientific developments enable to better understand the strong heterogeneity of assay methods for phospholipid (PLP)-dependent antibodies, measured as lupus anticoagulant (LA) or as anti-PLP antibodies (APA). These latter are actually targeted at complexes of β2-glycoprotein I (β2GPI) and anionic PLP and also react with insolubilized β2GPI alone in some patients. Although APA present little species specificity for β2GPI, some of them bind preferentially to complexes of human β2GPI and PLP. LAs are diagnosed with screening assays (dPT, dRVVT, KCT, APTT); their sensitivity is dependent on the concentration and type of PLPs used. They are either β2GPI or prothrombin dependent. Based on the antibody-neutralizing capacity of PLP preparations (such as hexagonal phase phosphatidylethanolamine) or their bypassing activity, confirmatory assays enable to confirm LA. LAs and APAs bind to different epitopes on β2GPI or its complexes with PLP. Major characteristics of APA assays are: the capture antigen (PLPs, β2GPI source); its optimization and density on micro-ELISA plates; the efficacy of postcoating saturation; the animal serum used for saturation and diluent; the second antibody which must avoid nonspecific interactions; the calibrators proposed and their reference to international standards; the cutoff between the normal and the pathological ranges; the assay sensitivity and overall specificity for APAs. New optimized assays have been developed to meet these criteria. They are designed with PLP-coated plates, saturated first with immunoglobulin-free human serum as a source of β2GPI, then with goat serum also used in diluent. The cutoff value is determined with at least 200 normal plasma samples (mean + 3 standard deviations or 99th percentiles) and plasma samples from patients without APAs. This approach offers both optimized specificity and sensitivity for testing APAs, along with a good standardization and it helps to measure the true APAs associated with pathology.
Oral Anticoagulant Therapy: Efficacy, Safety and the Low-Dose Controversy
Authors: Coccheri Sergio , Palareti Gualtiero , Cosmi Benilde
Published: April 2003

The issue of optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still unresolved. However, recent data suggest that short (6 weeks to 3 months), intermediate (3– 6 months) or indefinite-term anticoagulant therapy should be adopted on the basis of the classification of patients into low-, intermediate- and high-recurrence-risk groups, respectively. Oral anticoagulants have been shown to effectively prevent cardioembolic stroke in nonvalvular atrial fibrillation. Recent data seem to suggest that their safety can be ameliorated with adequate risk stratification on the basis of clinical and echocardiographic features. After unstable angina and non-Q-wave myocardial infarction, oral anticoagulant therapy (INR range 2–3) combined with aspirin has been shown to be advantageous over aspirin alone, although at the cost of a slight increase in bleeding. Bleeding complications are major drawbacks of oral anticoagulant therapy thus limiting their generalized adoption in recognized indications. To sharply reduce the bleeding risk and need of laboratory control, the low- or fixed-dose oral anticoagulant approach has been evaluated. In primary prevention and in low or low-to-moderate thrombotic risk, minidose warfarin treatment has been shown to be advantageous. In secondary prevention, and in patients at high risk for recurrent venous or arterial thrombotic events, standard range (INR 2–3) or higher level of anticoagulation is needed.
Usefulness of Screening for Congenital or Acquired Hemostatic Abnormalities in Women with Previous Complicated Pregnancies
Authors: Mello Giorgio , Parretti Elena , Martini Elisabetta , Mecacci Federico , La Torre Pasquale , Cioni Riccardo , Lucchetti Roberto , Fedi Sandra , Gori Anna Maria , Pepe Guglielmina , Prisco Domenico , Abbate Rosanna
Published: April 2003

Activated protein C resistance (APCR) is a common cause of familial thrombophilia and venous thrombosis. The aim of the study was to investigate the prevalence of APCR associated with factor V Leiden mutation and its relevance in comparison to other risk factors for thromboembolic disorders in women with a history of previous complicated pregnancies (history of fetal loss in the second and third trimester n = 34, preeclampsia n = 46). The frequency of APCR was significantly higher in women with a history of fetal loss and preeclampsia (23.5 and 26.1%, respectively) compared with a control group (3.8%). The prevalence of antithrombin, protein C and protein S deficiencies and the presence of antiphospholipid antibodies were also investigated: the prevalence of at least one disorder was 41.2% in the group with previous fetal loss, 37.0% in the group with previous preeclampsia and 7.5% in the control group.
Biochemical Characterization of a Thrombin Inhibitor from the Bloodsucking Bug Dipetalogaster maximus
Authors: Lange Ute , Keilholz Wieland , Schaub Günter A. , Landmann Hellmut , Markwardt Fritz , Nowak Götz
Published: April 2003

From the bloodsucking bug Dipetalogaster maximus, a protein with anticoagulant activity was isolated and biochemically characterized. The isolated protein, named dipetalogastin, possesses an average molecular mass of 11.8 kD. Its N-terminal sequence shows homology to rhodniin, a thrombin inhibitor isolated from the bug Rhodnius prolixus. The in vitro anticoagulant activity of dipetalogastin occurs via the inhibition of thrombin. The anticoagulant and thrombin inhibitory potency of dipetalogastin is comparable to that of recombinant hirudin. Its specific thrombin inhibitory activity is 9,300 antithrombin units/mg protein. Dipetalogastin forms only 1:1 molar complexes with thrombin. It is a tight-binding inhibitor of thrombin possessing a dissociation constant of 125 fM. It does not inhibit factor Xa or α-chymotrypsin and only weakly inhibits trypsin.
Evaluation of the Haemostatic System during Ketoacidotic Deterioration of Diabetes mellitus
Authors: İleri N.Ş. , Büyükaşık Y. , Karaahmetoglu S. , Özatlı D. , Sayınalp N. , Özcebe O.İ. , Kirazlı Ş. , Muftuoglu O. , Dündar S.V.
Published: April 2003

Clinical observations have indicated the frequent development of thrombotic complications during diabetic ketoacidosis (DKA). This study aimed to examine whether haemostatic changes that could lead to a thrombotic tendency occur during ketoacidosis. Plasma levels of in vivo haemostatic markers reflecting activation degrees of the coagulation system, fibrinolytic system, platelets and endothelium were assayed in 34 patients with DKA, both at diagnosis and 1 week after recovery. We found coagulation system and platelet activation and endothelial injury/activation in the patients at diagnosis of DKA. Although significant improvements were observed after recovery, only platelet activity was completely normalized. Fibrinolytic activity was also increased, both at diagnosis and after recovery, compared to the control group. However, although coagulation activity was prominently increased at diagnosis compared to the recovery period, there was no change in fibrinolytic activity in the same periods; on the contrary, the fibrinolytic capacity of the endothelium was diminished at diagnosis of DKA compared to the recovery period, suggesting the presence of relative hypofibrinolysis during DKA. Indications for a role of hyperglycaemia in the emergence of haemostatic disturbances during DKA were observed.
Constructing One’s Self in the City of the Silent: Dialogue, Symbols, and the Role of ‘As-If’ in Self-Development
Authors: Josephs Ingrid E.
Published: April 2003

Although contemporary psychology claims that the self is related to one’s social and material world, elaborations of how this process occurs are few. The process is developmental in nature, as it entails the transformation of the present person-world relationship. From this perspective, how one establishes a relation to the grave after the loss of a loved one is a challenging topic for study: The grave is an aspect of the material world which is not only intimately related to the social world (with the deceased), but also to the flow of time as a meeting point of past and future in one’s present here-and-now context. From a microgenetic developmental perspective, the grave is seen as transformed into a polyvalent personal symbol in one’s attempt to make sense of life, death, and dying, as well as one’s own unknown future. Further, using the grave as a symbol, one can continue to relate to the deceased through the construction of an internal dialogue. Rather than being characterized by rationality or logic, this process implies the transcendence of the world ‘as-is’ by the future-oriented ‘as-if-could-be’, in which both the person and the world as-is, as well as the person’s constructed past, are transformed. From an ontogenetic developmental perspective, it is argued that this as-if mode of approaching and making sense of the world is not inferior or immature, but is rather an important characteristic of human development across all age groups. Interview data clearly show the role of as-if functioning in self-reorganization in adults following the loss of a loved one. The process of self-reorganization centers on the grave as both a physical and symbolic entity and an internalized dialogic partner.
Learning to Stand Alone: The Contemporary American Transition to Adulthood in Cultural and Historical Context
Authors: Arnett Jeffrey Jensen
Published: April 2003

Conceptions of the transition to adulthood in the contemporary American majority culture are examined, and compared to conceptions cross-culturally and historically. Perspectives from other places and times are presented first, indicating that there is a widespread view that the transition to adulthood involves the gradual development of character qualities such as impulse control and diligence but culminates in marriage as the ultimate marker of the transition to adulthood. Findings from several recent American studies are then presented, indicating that for contemporary young Americans the preeminent criteria for the transition to adulthood are the individualistic character qualities of accepting responsibility for one’s self and making independent decisions, along with becoming financially independent; marriage, in contrast, ranks very low. New data are presented to illustrate young Americans’ conceptions of the transition to adulthood. Reasons are discussed for the prominence of individualistic criteria in American society and the prominence of marriage in other places and times. The concept of emerging adulthood is presented as a new way of conceptualizing the period between adolescence and young adulthood.
The Evolving Nature of Self-Identity across Four Levels of History
Authors: Dien Dora Shu-fang
Published: April 2003

Drawing upon Erikson’s theory of psychosocial development and current social constructionist perspective, self-identity is defined as a life story which is socially constructed and constantly being revised throughout the life span, and which provides a sense of continuity despite change. The cultural identity of a group (ethnic or national) is constructed and reconstructed in a similar manner guided by the principles of self-esteem, continuity, distinctiveness, and self-efficacy. A native of Taiwan, the author uses her own experiences with the Chinese, the Japanese, and the American cultures to illustrate the integrative process of self-construction as one moves from one cultural milieu to another. The Vygotsky/Scribner framework serves to illuminate the interinfluences of four levels of history – the general history of humanity, the history of individual societies, the life history of the individual in society, and the history of a particular psychological system (in this instance self-identity) – in this highly individualized process.
Identification of Two Novel Mutations in the Hydroxymethylbilane Synthase Gene in Three Patients from Two Unrelated Families with Acute Intermittent Porphyria
Authors: Ong Patricia M.L. , Lanyon W. George , Hift Richard J. , Halkett Janet , Cramp Celia E. , Moore Michael R. , Connor J. Michael
Published: April 2003

We have screened the hydroxymethylbilane synthase cDNAs of 3 patients from 2 families suffering from acute intermittent porphyria (AIP) from Scotland and South Africa using heteroduplex and chemical cleavage of mismatch analyses. Direct sequencing was used to characterise the mutations. The two novel mutations identified were a missense mutation at nucleotide position 64 in exon 3 (R22C) and a single base-pair deletion in exon 15. These mutations are predicted to affect the normal function of the enzyme and, therefore, are expected to be the primary cause of disease in these patients.
Linkage of Autosomal Recessive Primary Congenital Glaucoma to the GLC3A Locus in Roms (Gypsies) from Slovakia
Authors: Plášilová Martina , Feráková Eva , Kádasi Ludovít , Poláková Helena , Gerinec Anton , Ott Jürg , Ferák Vladimír
Published: April 2003

The autosomal recessive form of primary congenital glaucoma (gene symbol GLC3) has been recently mapped to two different loci, GLC3A (at 2p21), and GLC3B (at 1p36), respectively, on families of Turkish and Saudi Arabian provenance. This disorder is known to occur with an extremely high incidence in Roms (Gypsies) in Slovakia. We performed a standard linkage analysis on a sample of 7 Slovak Gypsy families comprising 18 affected members, and found significant linkage with four STR markers from the chromosomal region of 2p21 (D2S1788, D2S1346, D2S2328, and D2S1356), without heterogeneity. This finding demonstrates that in the Rom population of Slovakia, primary congenital glaucoma is due to the locus GLC3A, and consequently, to the mutation(s) in the cytochrome P4501B1 gene, which has been recently identified as the principal cause of the disease. Roms represent the third population, in which the disorder has been mapped to GLC3A.
Automatic Selection ofLoop Breakers for GeneticLinkage Analysis
Authors: Becker Ann , Geiger Dan , Schäffer Alejandro A.
Published: April 2003

Pedigree loops pose a difficult computational challenge in genetic linkage analysis. The most popular linkage analysis package, LINKAGE, uses an algorithm that converts a looped pedigree into a loopless pedigree, which is traversed many times. The conversion is controlled by user selection of individuals to act as loop breakers. The selection of loop breakers has significant impact on the running time of the subsequent linkage analysis. We have automated the process of selecting loop breakers, implemented a hybrid algorithm for it in the FASTLINK version of LINKAGE, and tested it on many real pedigrees with excellent performance. We point out that there is no need to break each loop by a distinct individual because, with minor modification to the algorithms in LINKAGE/FASTLINK, a single individual that participates in multiple marriages can serve as a loop breaker for several loops. Our algorithm for finding loop breakers, called LOOPBREAKER, is a combination of: (1) a new algorithm that is guaranteed to be optimal in the special case of pedigrees with no multiple marriages and (2) an adaptation of a known algorithm for breaking loops in general graphs. The contribution of this work is the adaptation of abstract methods from computer science to a challenging problem in genetics.
Screening 25 Dystrophin Gene Exons for Deletions in Arab Children with Duchenne Muscular Dystrophy
Authors: Haider M.Z. , Bastaki L. , Habib Y. , Moosa A.
Published: April 2003

Forty-two Arab children with Duchenne muscular dystrophy (DMD) were studied for intragenic deletions in 25 exons of the dystrophin gene using three different multiplex PCR sets each amplifying a total of 9, 9 and 6 different exons, respectively. Exon 22 was amplified individually. Deletions were found in 78, 76 and 12% of DMD patients with each of the three sets, respectively. With all the three sets, the detection rate increased to 86% (36 of 42 patients). Fifty percent of the deleted exons were located in the distal hot spot, 8% in the proximal hot spot while 42% were scattered over both. This study, the first in an Arab population and only the second to use three PCR multiplex sets, documents one of the highest deletion detection rates in DMD.
Fluorescence in situ Hybridization of psu dic(X)(Xpter-Xq21::Xq21-Xpter) in Two Patients with Turner’s Syndrome
Authors: Fernández Rosa , Pásaro Eduardo
Published: April 2003

Dicentric X chromosomes of different derivations were present in 6 out of a total of 42 patients with Turner’s syndrome. The most unusual cases were observed in 2 patients having a psu dic(X)(Xpter-Xq21::Xq21-Xpter) in mosaic form who were examined by fluorescence in situ hybridization. Alu-PCR products from hybrid cell lines were used as partial chromosome paints for the p arm of the human X chromosomes. The other 4 patients displayed isodicentric idic(Xq) in mosaic form. One of the patients displayed 9 cell lines originating from the accumulation of isodicentric idic(Xq) chromosomes, along with loss of chromosome material which resulted in fragments of varying size.
A Novel Missense Mutation in the DNA Mismatch Repair Gene hMLH1 Present among East Asians but Not among Europeans
Authors: Wang Yaping , Friedl Waltraut , Lamberti Christof , Nöthen Markus M. , Kruse Roland , Propping Peter
Published: April 2003

In a search for germline mutations in the DNA mismatch repair genes hMSH2 and hMLH1 in Chinese patients with colorectal cancer we identified a novel missense mutation (V384D) in exon 12 of the hMLH1 gene in 4 out of 26 individuals. This mutation had not been observed in any of 109 German patients who either fulfill the clinical criteria of hereditary nonpolyposis colorectal cancer or had developed colorectal cancer at an early age. In a second series of experiments, DNA samples of 80 healthy Japanese and 100 healthy Germans were examined for the presence of the V384D mutation. It was observed in 4 Japanese, but in none of the German individuals. Thus, the V384D mutation seems to be confined to the East-Asian population. Since this missense mutation occurs at a less conserved region of the hMLH1 gene, it may represent a nonfunctional polymorphism. However, a role in the pathogenesis of colorectal cancer cannot be ruled out from the present study.
Saami Mitochondrial DNA Reveals Deep Maternal Lineage Clusters
Authors: Delghandi Madjid , Utsi Egil , Krauss Stefan
Published: April 2003

The mitochondrial DNA of 62 Saami from the north of Norway was analyzed in the D loop hypervariable region I and II and sequences were compared to other gene pools. Two major (lineage 1 and 2) and two minor (lineage 3 and 4) maternal lineage clusters were found. Lineage 1 (56.9% of all hitherto analyzed Saami samples) contains a substantial number of branching haplotypes which are unknown in European gene pools. Lineage 2 (31.5%) and lineage 4 (3.6%) have few branching points and are present at a low rate throughout European gene pools. Lineage 3 (4.7%) has polymorphisms characteristic of circumpolar lineages.
160Thr Mutation in the Rhodopsin Gene Associated withRet initis pigmentosa
Authors: Capeans Carmen , Blanco Maria J. , Lareu Maria V. , Salas Antonio , Piñeiro Antonio , Sánchez-Salorio Manuel , Carracedo Angel
Published: April 2003

Mutations in the rhodopsin gene were studied in 23 unrelated Spanish patients with sporadic retinitis pigmentosa (RP). A codon 160 Thr C→A transition was found in 4 of the 23 patients vs. none of the 159 controls (p < 0.001) suggesting that this mutation may be an informative marker in RP.
New DNA Polymorphisms Define Ethnically Distinct Haplotypes in the Human Transferrin Receptor Gene
Authors: van Landeghem G.F. , Beckman L.E. , Sikström C. , Saha N. , Kučinskas V. , Beckman L.
Published: April 2003

In a study of transferrin receptor (TFR) polymorphism in different ethnic groups using PCR and restriction cleavage we found a new Hin6I polymorphism in intron 7 and confirmed a tentative BanI polymorphism in exon 4 reported by Evans and Kemp [Gene 1997;199:123–131]. In all ethnic groups there was a complete and highly significant (p < 10–10) linkage disequilibrium where all BanI 1 alleles were linked to Hin6I 1 alleles. Furthermore in the European populations, but not in the Chinese, there was a close correlation between the three BanI-Hin6I haplotypes and the alleles of a previously described three-allelic RsaI polymorphism in the TFR gene studied by Southern blotting. There were distinct ethnic differences in TFR allele and haplotype frequencies. Thus the Saamis were significantly different from the other European ethnic groups, and the Lithuanians had a significantly increased frequency of the BanI 2-Hin6I 1 haplotype, suggesting that this marker may be informative in tracing prehistoric migrations and admixture by Baltic peoples. The new TFR polymorphisms and haplotypes may also be useful markers in studies of interactions with the transferrin and hemochromatosis genes, the genetic influence on body iron stores and disease associations.
Genetic Polymorphisms of Apolipoproteins A-IV, E and H in Koreans
Authors: Kim Hyun Sup , Kamboh M. Ilyas
Published: April 2003

A South Korean population from Kongju (n = 350) was screened by isoelectric focusing and immunoblotting procedures to determine the distribution of genetic variations in 3 apolipoprotein genes including APOA-IV, APOE and APOH. Although the known APOA-IV protein polymorphism was not observed, sporadic examples of 2 putative new variants were identified. The frequencies of the APOE*2, APOE*3 and APOE*4 alleles were 0.069, 0.823 and 0.107, respectively. At the APOH structural locus 3 common alleles, APOH*1 (0.010), APOH*2 (0.913) and APOH*3 (0.073) were observed. In addition, a unique APOH allele designated APOH*3 Kongju was identified in this Korean population.
Evidence for Genetic Heterogeneity Supports Clinical Differences in Congenital Myasthenic Syndromes
Authors: Menold Marisa M. , Sadeh Menachem , Lennon Felicia , Blatt Ilan , Goldhammer Yochanan , Yamaoka Larry H. , Vance Jeffery M. , Pericak-Vance Margaret A.
Published: April 2003

Congenital myasthenic syndromes (CMS) define a diverse group of disorders, all of which compromise neuromuscular transmission. Symptoms can be present at birth or appear during childhood, and can range in severity. Both autosomal dominant and recessive forms exist, and a number of clinical subtypes have been described. The cause of many cases of CMS has been traced to mutations in the genes for the acetylcholine receptor (AChR) subunits, previously mapped to chromosomes 2 and 17. Recently, an additional form of CMS known as familial infantile myasthenia (FIM) was linked to chromosome 17p. The gene for FIM has not yet been identified. We examined the DNA from 5 families of Iranian Jewish origin (6 affected individuals) who have been diagnosed with a phenotypically unique form of CMS. Four of the families are consanguinous, and all families originate from the same geographical region, thus it is highly likely that they would carry the same ancestral CMS mutation. We examined these families for linkage to the regions on chromosomes 2 and 17 containing the AChR subunit genes, and to the region on 17p to which FIM was localized. Our data excludes linkage to these regions, suggesting that the clinical differences seen among patients with CMS correlate with locus heterogeneity, and that a defect in a different gene is responsible for the CMS in these patients.