bluuebunny/crossref_metadata_2025 huggingface dataset:
The Resolution of Fetal Hydrops Using Combined Maternal Digoxin and Dexamethasone Therapy in a Case of Isolated Complete Heart Block at 30 Weeks Gestation
Authors: Brackley K.J. , Ismail K.M.K. , Wright J.G.C. , Kilby M.D.
Published: April 2003

The development of hydrops fetalis in cases of isolated complete heart block is associated with a very poor prognosis. Various pharmacological strategies have been proposed, involving both direct fetal access and transplacental therapy, with inconsistent results in small numbers of subjects. The optimal antenatal management will remain uncertain until multicentre controlled trials are organised. We report the complete resolution of fetal hydrops at 30 weeks of gestation using combination of maternal digoxin and dexamethasone therapy, despite persistence of the complete heart block. A Caesarean section was performed at 37 weeks of gestation due to evidence of fetal intrauterine growth restriction. The baby girl is now 8 months of age and remains well, with a heart rate of 45–50 beats per minute on no medication and without pacing.
A Comparison of the Prosodic Characteristics of the Speech of People with Parkinson’s Disease and Friedreich’s Ataxia with Neurologically Normal Speakers
Authors: Le Dorze Guylaine , Ryalls John , Brassard Christine , Boulanger Nancy , Ratté Danielle
Published: April 2003

The realization of prosody (speech rate, fundamental frequency, intonation) was investigated in a group of 10 individuals with Parkinson’s disease and a group of 10 individuals with Friedreich’s ataxia. Data from these two neurologically disordered groups were compared to individuals without neurological impairment. Both neurologically impaired groups retained some aspects of normal speech prosody, while other aspects were affected to a significant degree. The prosodic characteristics of speakers with Parkinson’s disease were distinct from those of speakers with Friedreich’s ataxia. These results were interpreted in terms of prosodic competence and prosodic performance.
Efficacy of the Accent Method of Voice Therapy
Authors: Bassiouny Samia
Published: April 2003

There is an increasing need for studies of efficacy of behavior readjustment therapy procedures in human communicative disorders. Legal, social, scientific and professional considerations point up the need for more careful documentation of the effects of treatment techniques used by phoniatricians and speech-language pathologists. This study is conducted in order to evaluate the efficacy of the accent method of voice therapy (AM). The AM is one of the holistic approaches for behavior readjustment voice therapy. It tackles collectively and simultaneously the various parameters of voice such as pitch, loudness and timbre. The results of intervention utilizing the AM in this clinical trial are assessed in a relatively controlled setup. Patients with voice problems resulting from various etiologic vocal pathologies are distributed randomly into two groups. Group 1 (G1) is given the full aspect of the AM, that is, voice hygiene advice plus the accent exercises to correct the faulty vocal technique (habit). Group 2 (G2) receives only voice hygiene advice. The AM is administered in individual sessions 20 min each, twice a week, while the voice hygiene advice counseling is given once a week. The assessment of the vocal pathology is done following a diagnostic protocol utilizing subjective as well as quasi-objective measures of evaluation. The initial assessment presents the baseline (pretest) data for both groups. The follow-up evaluations are done at mid intervention (mid-test), that is, 10 sessions for G1 and 5 sessions for G2, and at the termination of intervention/therapy (post-test). The difference in improvement between G1 and G2 at the end of the observation was generally significant in favor of G1. There were significant improvements in G1 in certain items specific for the various etiologic categories. The improvement from pretest to mid-test to post-test values followed a linear tendency. The significance of the results is discussed and the conclusions are outlined and criticized.
The Study of Child Language in South Africa
Authors: Penn Claire
Published: April 2003

This paper describes some of the research into child language that has been conducted in South Africa over the past 20 years. It is written from a clinical perspective and it describes the influence of changing demographic, social, educational and political variables on the study of child language. Specifically, the influence of the multilingual and multicultural nature of the society will be considered. Among issues discussed are the increasing research base on the acquisition of normal language, the adaptation of assessment tools and language in education.
Familial Language Impairment:More English Evidence
Authors: Gopnik Myrna
Published: April 2003

Subjects between the ages of 9 and 22 with a history of familial language impairment were tested on a wide range of linguistic tasks. The data show that they are not different from the non-impaired members of their family or from external controls in their ability to hear and understand the morphological marker for plural or to understand a narrative, but they are significantly different in recognizing or correcting grammatical errors, in producing tense or number marking, and in understanding sentences with non-canonical word order. This pattern of deficits is similar to that which occurs cross-linguistically and in on-line processing tasks. These data support the hypothesis that these subjects do not build normal representations in their grammar nor construct productive grammatical rules. However, they are able to use other means such as memory and explicit rules to simulate grammar.
Specific Language Impairments and Behavioural Problems
Authors: Coster F.W. , Goorhuis-Brouwer S.M. , Nakken H. , Spelberg H.C. Lutje
Published: April 2003

The behavioural functioning of 56 children with a specific language impairment (SLI), aged 8, 10, and 12 years, was examined by using the Child Behaviour Checklist. Parents as well as teachers filled in the questionnaire. The data shows that 48% of the children with SLI were considered to have behavioural problems either at home or in school. The problems differ significantly from the norm group on internalizing behaviour and total behaviour. The children do not demonstrate more externalizing behaviour than children in the norm group. It is hypothesized that the absence of aggressive behaviour might be a characteristic of children with SLI.
Surgical Treatment for Dysphagia of Neuromuscular Origin
Authors: Shin Takemoto , Tsuda Kuniyoshi , Takagi Seiji
Published: April 2003

There are a number of surgical procedures which can be used to improve swallowing in selected dysphagic patients. These include: vocal fold augmentation or medialization, cricopharyngeal myotomy, laryngeal suspension, intrahyoid myotomy, lateral thyrolaminectomy and tracheoesophageal separation procedures. This article describes these various procedures and their appropriate application to selected dysphagic patients. Results of a study of the location of the recurrent laryngeal nerve in relation to the cricopharyngeal muscle are also presented.
The Potential Future of Dysphagia: Population-Specific Diagnosis and Treatment
Authors: Logemann Jeri A.
Published: April 2003

Care of patients with dysphagia includes screening, diagnosis, treatment and management. This article examines the increasing evidence that to be most effective each of these aspects of patient care must be tailored to the patient’s medical diagnosis, specific swallowing disorders and stage of recovery or degeneration. The need to define the optimal window of intervention for each patient type is also discussed. Future research needs are emphasized.
Managing Aphasia: Then and Now
Authors: Lesser Ruth
Published: April 2003

The nature and attitudes of the professionals who ‘manage’ aphasia have changed significantly over the 75 years the IALP has existed. This review shows how IALP publications have reflected this, and considers recent developments, particularly in respect of the role played by the cognitive neuropsychological approach in evidence-based healthcare and by conversational approaches in the empowerment of aphasic people.
Vocal Fold Vibration and Voice Quality
Authors: Niimi Seiji , Miyaji Mamiko
Published: April 2003

There have been various methods proposed for diagnosing laryngeal pathology by analyzing the pathological voice. However, even if two diagnoses are the same, the voice quality might not be the same. In other words, it is difficult to diagnose laryngeal pathology only by acoustic parameters. In this study, we analyze the vibration patterns seen in various pathological cases to explain pathological voice quality.
Prevalence and Characteristics of Dysarthria in a Multiple-Sclerosis Incidence Cohort: Relation to Neurological Data
Authors: Hartelius Lena , Runmarker Björn , Andersen Oluf
Published: April 2003

Few attempts have been made to use degree and type of multiple sclerosis (MS) dysarthria in neurological evaluation. In the present study, 77 individuals drawn from an MS population were examined both by a speech pathologist and a neurologist, and data from three sources of information were subsequently combined: (1) a clinical dysarthria test procedure, (2) a perceptual analysis of speech characteristics in continuous speech, and (3) neurological deficit scoring. The speech of 15 age- and gender-matched healthy control subjects was also investigated. It was concluded that: (1) the prevalence of mild to severe dysarthria in this cohort was 51% and occurred in all components of speech production: respiration, phonation, prosody, articulation and nasality. (2) The clinical dysarthria test was sensitive in detecting subclinical speech signs. The prevalence of pathologic speech signs found on the basis of the test was found to be 62%. The prevalence of dysarthria based on the neurological evaluation alone was 20%. (3) The dysarthria of MS was a predominantly mixed dysarthria, with both ataxic and spastic speech signs frequently present in the speech of a given individual. (4) Furthermore, when a predominant type of dysarthria existed, it was not generally associated with a characteristic profile of neurological deficits. Rather, severity of speech deviation was positively correlated to overall severity of neurological involvement, type of disease course, and number of years in progression.
Effect of Speaking Rate Manipulations on Acoustic and Perceptual Aspects of the Dysarthria in Amyotrophic Lateral Sclerosis
Authors: Weismer Gary , Laures Jacqueline S. , Jeng Jing-Yi , Kent Ray D. , Kent Jane F.
Published: April 2003

The current study explored the acoustic and perceptual effects of speaking rate adjustments in persons with amyotrophic lateral sclerosis (ALS) and in neurologically normal individuals. Sentence utterances were obtained from the participants at two self-selected speaking rates: habitual and fast. Total utterance durations, segment durations, and vowel formant frequencies comprised the acoustic measures, whereas magnitude estimates of speech intelligibility and severity of speech involvement were the perceptual measures. Results showed that participants in both the neurologically normal and ALS groups were able to increase their speaking rate when asked to do so, but that the participants with ALS were significantly slower than the neurologically normal participants at both rates. Both groups of participants also showed compression of the acoustic vowel space with increased speaking rate, with the vowel spaces of participants with ALS generally being more compressed than the vowel spaces of neurologically normal participants, at either rate. Most importantly, the perceptual measures failed to show any effect of the speaking rate adjustment on scaled intelligibility or severity, for either group. These findings are discussed relative to the general issue of slow habitual speaking rates among many speakers with dysarthria, and possible explanations for the slowness. The lack of an effect of increased rate on the perception of the speech deficit among speakers with ALS argues against the idea that the habitually slow rates are a form of compensation to reduce the complexity of speech production.
Changes in Finnish Dental Consonant Articulation in Cleft Lip/Palate Children between 6 and 8 Years of Age
Authors: Laitinen Jaana , Ranta Reijo , Pulkkinen Joonas , Paaso Marjukka , Haapanen Marja-Leena
Published: April 2003

The aim of this study was to clarify changes in the occurrence of misarticulations of dental consonants /r/, /s/ and /l/ between 6 and 8 years of age in cleft-affected Finnish children and to compare the effects of gender and to estimate if spacing due to changing of maxillary incisors could explain changes in articulation of these sounds. The subjects were 133 (47 girls, 86 boys) Finnish-speaking non-syndromic children with isolated cleft palate (n = 34), cleft lip/alveolus (n = 49), unilateral (n = 33), and bilateral (n = 17) cleft lip and palate. The results showed that there were no statistically significant differences between genders according to changes in articulation abilities by the age of 8 years. Eighty-one percent of the subjects with misarticulations at the age of 6 years still misarticulated at 8 years of age, and 16% of the subjects without misarticulations at the age of 6 years misarticulated at the age of 8 years; /s/ and /l/ misarticulations were eliminated more often than /r/ errors. New misarticulations were diagnosed at the age of 8 years in the same way in the groups with (14%) and without (16%) misarticulations at the age of 6 years. Dental arch spacing due to changing of maxillary incisors does not seem to explain new misarticulations of /r/, /s/ and /l/ sounds estimated at the age of 8 years.
Tool Use, Aye-Ayes, and Sensorimotor Intelligence
Authors: Sterling Eleanor J. , Povinelli Daniel J.
Published: April 2003

Humans, chimpanzees, capuchins and aye-ayes all display an unusually high degree of encephalization and diverse omnivorous extractive foraging. It has been suggested that the high degree of encephalization in aye-ayes may be the result of their diverse, omnivorous extractive foraging behaviors. In combination with certain forms of tool use, omnivorous extractive foraging has been hypothesized to be linked to higher levels of sensorimotor intelligence (stages 5 or 6). Although free-ranging aye-ayes have not been observed to use tools directly in the context of their extractive foraging activities, they have recently been reported to use lianas as tools in a manner that independently suggests that they may possess stage 5 or 6 sensorimotor intelligence. Although other primate species which display diverse, omnivorous extractive foraging have been tested for sensorimotor intelligence, aye-ayes have not. We report a test of captive aye-ayes’ comprehension of tool use in a situation designed to simulate natural conditions. The results support the view that aye-ayes do not achieve stage 6 comprehension of tool use, but rather may use trial-and-error learning to develop tool-use behaviors. Other theories for aye-aye encephalization are considered.
Locomotion and Posture in Lagothrix lagotricha
Authors: Defler Thomas R.
Published: April 2003

This long-term study of woolly monkey (Lagothrix) locomotor and postural behaviour employs methods identical to those used during a previous study of the locomotion and posture of two species of Ateles, allowing a detailed comparison between the two genera, which are strong competitors in extensive parts of the Amazon basin and northern Andes. As in Ateles, Lagothrix locomotion can be divided into five patterns, based on limb usage: quadrupedal walking and running, suspensory locomotion, climbing, bipedalism (very rare in wild woolly monkeys) and leaping. Lagothrix differs from Ateles primarily in its greater reliance on quadrupedal locomotion during both travel and feeding and on its de-emphasis of the use of suspensory locomotion as compared to Ateles, while the use of climbing and leaping is roughly equal in the two genera. Lagothrix exhibits more generalised (primitive) locomotive behaviour in accordance with its morphology, in comparison to the more specialised Ateles. The generic differences reflect differences in habitat use and particularly foraging ecology.
Size and Scaling in the Mandible of Living and Extinct Apes
Authors: Ravosa Matthew J.
Published: April 2003

The purpose of this study is to fill a gap in our knowledge of dietary and allometric determinants of masticatory function and mandibular morphology in major catarrhine clades. To extend the implications of previous work on variation in mandibular form and function in other primates, a scaling analysis was performed on 20 extinct and 7 living non-cercopithecoid catarrhines or ‘dental apes’. Results of allometric comparisons indicate that for a given jaw length, larger apes exhibit significantly more robust corpora and symphyses than smaller forms. This appears linked to size-related increases in dietary toughness and/or hardness, which in turn causes elevated mandibular loads and/or greater repetitive loading during unilateral mastication. Larger-bodied dental apes also display more curved symphyses, which also explains the positive allometry of symphysis width and height. In apes, proconsulids often evince more robust jaws while all hylobatids, Pan and Dryopithecus laietanus possess more gracile cross sections. In propliopithecids, Aegyptopithecus is always more robust than Propliopithecus. In proconsulids, Rangwapithecus and Micropithecus commonly exhibit more robust jaws whereas Dendropithecus and especially Simiolus are more gracile. Most of the larger taxa are folivorous and/or hard-object frugivorous pongids with relatively larger dentaries. Though apes have relatively wider corpora than cercopithecines due to greater axial twisting of the corpora during chewing, they are otherwise alike in robusticity levels. Smaller apes are similar to cercopithecines in evincing a relatively high degree of symphyseal curvature, while larger taxa are like colobines in having less curvature. Larger pongids resemble or even exceed colobine jaw proportions and thus appear to converge on colobines in terms of the mechanical properties of their diets.
An Accelerometry-Based System for the Assessment of Balance and Postural Sway
Authors: Kamen Gary , Patten Carolynn , Du C.Duke , Sison Steven
Published: April 2003

The aim of this investigation was to develop an inexpensive, efficient system for the clinical assessment of static and dynamic balance and postural sway using accelerometry-based measurements. Subjects consisted of 10 young (range 18–32 years) and 10 older (range 69–86 years) individuals screened for polypharmacy and history of cardiovascular, neurological or orthopedic health conditions. A lightweight uniaxial accelerometer and general-purpose microcomputer were used to obtain measurements of postural sway. Customized software was written to acquire the data and provide a real-time display consisting of amplitude and frequency characteristics of the sway profile. Intraclass reliability coefficients greater than R = 0.75 were obtained in both eyes-open and challenging-standing balance tasks. Preliminary results demonstrate that the instrumentation can be used to discriminate among balance tasks and to differentiate healthy older adults from those with a tendency toward frequent falls. Moreover, the technique described yields a simple-to-administer, inexpensive procedure that can be conducted in the home or another natural environment. Accelerometry also allows for balance training and re-learning, using tasks that might ordinarily pose a balance challenge for the older or frail adult.
Education, Activity, Health, Blood Pressure and Apolipoprotein E as Predictors of Cognitive Change in Old Age: A Review
Authors: Anstey Kaarin , Christensen Helen
Published: April 2003

Background: Cross-sectional studies have identified a number of health and lifestyle factors that correlate with cognitive function in old age. It is important to know whether these factors also predict change in cognitive function over time. Objective: To evaluate published findings on genetic, health and lifestyle predictors of cognitive change in late adulthood. Methods: Studies reporting data on education, health, blood pressure, activity and apolipoprotein E (APOE) as predictors of cognitive change were reviewed. A total of 34 studies were identified that reported data on these predictors. The average follow-up period of studies reviewed was 7.68 years. Results: Results showed that education, hypertension, objective indices of health and cardiovascular disease, and APOE were associated with cognitive change. Results regarding the effect of physical activity on cognitive change were inconclusive. Conclusion: Despite the lack of data on some predictors, the longitudinal trends are generally consistent with cross-sectional findings on predictors of cognitive performance in old age. More research is required to compare the influence of predictors on different types of cognitive abilities.
Omphalozele und Gastroschisis in Tirol – Inzidenz und Epidemiologie 1985–1996
Authors: Penz Hugo , Menardi Gesine , Brezinka Christoph
Published: April 2003

Im Laufe der letzten Jahre nahm die Inzidenz der Gastroschisis in zahlreichen Ländern zu, während die der Omphalozele zurückging. Auch in Tirol ist diese Entwicklung zu beobachten: Die Inzidenz der Lebendgeburten mit einer Omphalozele nahm von 1:6000 (1985–1990) auf 1:10349 (1991–1996) ab, während die der Gastroschisis in denselben Vergleichszeiträumen von 1:4363 auf 1:2875 zunahm. Die betroffenen Schwangerschaften waren der Bevölkerungsdichte entsprechend über das Bundesland Tirol verteilt, es zeigte sich keine regionale Häufung. Anhand der Berufe der betroffenen Mütter war eine gleichmässige Verteilung über das soziale Spektrum festzustellen, Frauen aus benachteiligten Schichten waren nicht häufiger betroffen. Durch die zunehmende frühe Erfassung der ventralen Fehlbildungen mittels Ultraschall ist in den nächsten Jahren eine weitere Verschiebung bei den Inzidenzen der Lebendgeborenen zu erwarten.
Wirkung von selektiven Östrogen-Rezeptor-Modulatoren auf östrogensensitive Gewebe
Authors: Jirecek Stefan , Pavo Imre , Huber Johannes C.
Published: April 2003

Selektive Östrogen-Rezeptor-Modulatoren (SERMs) agieren ausschliesslich über den Östrogenrezeptor und haben gewebespezifische und agonistische und antagonistische Eigenschaften. Alle beschriebenen SERMs haben im Knochen und im kardiovaskulären System einen östrogenen Effekt: Sie hemmen den postmenopausalen Verlust der Knochendichte und beeinflussen positiv Plasmalipoproteine und einige Gerinnungsfaktoren. Das Ziel dieser Arbeit ist es, die Wirkungsweisen der SERMs in den östrogenabhängigen Geweben Brust und Endometrium zu beschreiben. Es gibt, abhängig von deren chemischer Struktur, zwei Typen von SERMs, die klinisch erprobt sind: die Triphenyläthylene und die Benzothiophene. Tamoxifen ist der Prototyp der SERMs mit der Struktur der Triphenyläthylene. Tamoxifen, wie alle anderen SERMs, ist im Brustgewebe ein Östrogenantagonist und wird weltweit zur adjuvanten Behandlung von Brustkarzinomen eingesetzt. Neue Arbeiten weisen auf die Fähigkeit von Tamoxifen hin, bei Risikopatientinnen Brustkrebs verhindern zu können. Wegen der partiellen östrogenen Wirkung von Tamoxifen auf das Endometrium kommt es in der Praxis zu einer Endometriumhypertrophie und zu einem erhöhten Endometriumkarzinomrisiko. Andere SERMs mit der gleichen Struktur, Droloxifen, Toremifen und Idoxifen, könnten bei der Behandlung von Brustkarzinomen ähnlich wie Tamoxifen einsetzbar sein. Vorteile der neuen SERMs mit triphenyläthylener Struktur könnten eine verminderte agonistische Wirkung auf das Endometrium und ein verbessertes toxikologisches Profil sein. Raloxifen, ein Benzothiophen, hat eine andere chemische Struktur als die Triphenyläthylene und besitzt eine ihnen ähnliche antagonistische Wirkung auf das Brustgewebe. Klinische Studien mit Raloxifen zeigten bei postmenopausalen Patientinnen mit Osteoporose eine signifikante Verringerung von neu diagnostizierten Brustkarzinomfällen im Vergleich zu Plazebo. Im Gegensatz zu Tamoxifen konnte in klinischen Studien mit Raloxifen kein stimulierender Effekt auf das Endometrium festgestellt werden.
‘Ovarian Tissue Banking’ – erste Ergebnisse
Authors: Imhof M. , Hofstetter G. , Bergmeister H. , Rudas M. , Kain R. , Wenzl R. , Huber J.C.
Published: April 2003

Chemotherapie und Strahlentherapie bewirken bei jungen Frauen mit onkologischen Erkrankungen oft eine starke Reduktion der ovarialen Funktion mit menopausalen Beschwerden und Infertilität. Die teilweise oder vollständige Erhaltung des Ovars könnte nach Reimplantation die Hormonproduktion wiederherstellen und eine natürliche Empfängnis ermöglichen. Gewebescheiben von Ovarien konnten bereits erfolgreich reimplantiert werden, waren aber nur von kurzer Lebensdauer. Die Retransplantation kryopräservierter ganzer Ovarien wird nach Vorversuchen an Schweinen zurzeit bei Schafen durchgeführt. Hormonproduktion und Schwangerschaft sollen die ovariale Funktion beweisen.
Laserkonisationen und -vaporisationen der Portio
Authors: Kieni S. , Rageth J.C.
Published: April 2003

Fragestellung: Analyse der Histologiepräparate und der Krankheitsverläufe nach Lasereingriffen an der Portio. Methode: Von 136 Lasereingriffen (110 Konisationen und 26 Vaporisationen) fanden 103 (76%) ambulant und 122 (89%) unter Lokalanästhesie statt. Ergebnisse: 94 (85%) der 110 Konisationen erfolgten histologisch im Gesunden. Verlauf nach 12 (11%) nicht im Gesunden erfolgten Konisationen: 5mal normale Zytologie, 4mal keine Dysplasie im Hysterektomiepräparat, 1mal CIN III im Hysterektomiepräparat, 1mal CIN I im Wertheim-Präparat und 1mal unbekannt. Verlauf nach 4 fraglich im Gesunden erfolgten Exzisionen: 3mal normale Zytologie und 1mal Hysterektomie ohne Restdysplasie: Acht postoperative Blutungen mussten mit Bikoagulation versorgt werden. Schlussfolgerungen: Die Lasertherapie ermöglicht vor allem ektozervikal ein ausserordentlich präzises Vorgehen, kann meist ambulant und unter Lokalanästhesie durchgeführt werden und führt im Vergleich zu anderen Methoden nicht zu mehr Komplikationen. Erfolgt die Resektion nicht im Gesunden, findet sich im weiteren Verlauf nur selten eine Dysplasiepersistenz. Deshalb ist ein exspektatives Vorgehen bei vorhandenem Kinderwunsch zu verantworten.
Wirkung von transdermaler oder oraler Östradiolgabe auf die Ausscheidung vasoaktiver Mediatoren bei postmenopausalen Frauen
Authors: Mueck A.O. , Seeger H. , Lippert T.H.
Published: April 2003

Fragestellung: Wirken die transdermale (n = 20) und die orale (n = 20) Östradiolsubstitution auf die renale Ausscheidung von vasoaktiven Substanzen bei postmenopausalen Frauen? Methode: Als vasoaktive Substanzen wurden Prostazyklin und Thromboxan, zyklisches Guanosinmonophosphat, das die systemische Stickstoffmonoxidproduktion reflektieren kann, Serotonin, Relaxin, Insulin und Melatonin im 8-Stunden-Nachturin vor und nach 2- und 4wöchiger Östradiolbehandlung bestimmt. Ergebnisse: Die Ausscheidung von Prostazyklin und Thromboxan wurde, als Prostazyklin/Thromboxan-Quotient berechnet, durch beide Anwendungsformen zugunsten der Prostazyklinproduktion erhöht. Für die Ausscheidung von zyklischem Guanosinmonophosphat wurden nur geringgradige Veränderungen beobachtet. Die Produktion von Serotonin, Relaxin und Insulin wurde nur unter transdermaler Behandlung gesteigert. Für Melatonin wurden keine Veränderungen registriert. Schlussfolgerungen: Die hormonelle Substitutionstherapie mit Östradiol bei postmenopausalen Frauen kann, sowohl bei transdermaler als auch bei oraler Gabe, die Ausscheidung verschiedener vasoaktiver Substanzen erhöhen, welche auf vasorelaxierende Östrogenwirkungen hinweisen. Durch die transdermale Applikation wurde dabei eine höhere Wirksamkeit erzielt, obwohl wesentlich geringere Dosen verabreicht wurden. Möglicherweise lässt sich dies durch die bei transdermaler Applikation erfolgende kontinuierliche Einwirkung auf die östrogenen Endorgane erklären.
Reactivity of Platelets from Healthy Individuals and from Patients with Hematologic Diseases following Incubation with Pegylated RecombinantHuman Megakaryocyte Gr owth and Development Factor in vitro
Authors: Matzdorff A.C. , Kemkes-Matthes B. , Pralle H.
Published: April 2003

Platelets express the receptor for thrombopoietin. It is possible that thrombopoietin modulates platelet reactivity. We examined the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet activation in vitro using flow cytometry. We compared samples from healthy individuals and from patients with various hematologic diseases (AML, myeloma, postchemotherapy). Citrated whole blood was incubated with PEG-rHuMGDF (10 or 100 ng/ml), then a mild stimulus was added (0.1 U thrombin/ml). Blood from healthy individuals showed a significantly higher degree of platelet activation (CD62p expression), microparticle generation, and aggregate formation after incubation with PEG-rHuMGDF+thrombin versus thrombin alone (p < 0.05). However, this difference could not be shown for platelets from patients with thrombocytopenia or other hematologic diseases. The use of PEG-rHuMGDF should be safe and not cause an additional risk of thromboocclusive disease in these patients.
Are Symptomatic Endpoints Acceptable in Venous Thromboprophylactic Studies?
Authors: Prentice C.
Published: April 2003

Chemoprophylaxis with subcutaneous low-molecular-weight heparin has been shown to reduce deep vein thrombosis detected by surrogate endpoints such as fibrinogen scanning and venography. However, there have been few trials which have assessed clinical endpoints attributed to fatal and non-fatal pulmonary embolism following surgery. As these clinical endpoints are rare, large-scale trials using vascular mortality, vascular morbidity and the incidence of haemorrhage as clinical endpoints need to be performed to assess the efficacy of chemical thromboprophylaxis. The benefit of using clinical endpoints against the risk of haemorrhage should also be evaluated.
What Are the Most Reliable Detection Methods for Deep Vein Thrombosis and Pulmonary Embolism to be Used as Endpoints in Trials of Venous Thromboprophylaxis?
Authors: Davidson B.L.
Published: April 2003

Numerous considerations and controversies attend the question of which endpoints to use in venous thromboembolism prophylaxis trials. In this paper, a rationale is presented for a new approach that simplifies certain aspects of endpoint detection in deep vein thrombosis and pulmonary embolism trials, and complicates others. The goal of this approach is to use reliably ascertainable endpoints that are clinically relevant and most probably predictive of clinical efficacy, in order to optimally inform the drug development process.
Early versus Delayed Introduction of Oral Vitamin K Antagonists in Combination with Low-Molecular-Weight Heparin in the Treatment of Deep Vein Thrombosis
Authors: Leroyer C. , Bressollette L. , Oger E. , Mansourati J. , Chèze-LeRest C. , Nonent M. , Buchmuller A. , Tardy B. , Decousus H. , Parent F. , Simonneau G. , Juste K. , Ill P. , Abgrall J.F. , Clavier J. , Mottier D. , fortheANTENOXStudyGroup &
Published: April 2003

Objective: To compare oral anticoagulant treatment (fluindione) started on either the 1st or the 10th day of a low-molecular-weight heparin (enoxaparin) treatment for deep vein thrombosis confirmed by venography. Design: An open, multicenter, randomized study in two parallel treatment groups. Interventions: All patients received enoxaparin, 1 mg/kg s.c. twice daily, and oral fluindione, 20 mg once daily, either beginning on day 1 or on day 10 of the enoxaparin treatment. Enoxaparin was discontinued once the international normalized ratio under fluindione was stable between 2.0 and 3.0 over 2 days. Fluindione treatment was maintained during a 3-month follow-up period. Outcome Measurements: Specific examinations (venography and/or V/Q lung scanning and/or angiography) were performed only in the event of a clinically suspected recurrence of venous thromboembolism during the 3-month follow-up period. All cases were blindly assessed by an independent Reading Committee. Results: A clinically suspected venous thromboembolism was confirmed by objective tests in 1 of 223 patients (group of delayed introduction of fluindione; n = 111). Equivalence was demonstrated between the two treatment schedules (p < 0.0001) for a maximal difference of 10% (90% confidence interval: –2.42 to 0.58). The mean duration of hospitalization was significantly reduced (p = 0.0001) in the group with early introduction of fluindione. The incidence of hemorrhage was comparable between the two treatment groups. Conclusion: Early and delayed introduction of oral anticoagulant treatment in association with subcutaneous enoxaparin in patients with deep vein thrombosis was shown to be equivalent in preventing the recurrence of venous thromboembolism. In patients with early introduction of oral anticoagulant, hospitalization was significantly reduced.
Influence of HIV-Infection on the Karnofsky Score and General Social Functioning in Patients with Hemophilia
Authors: Wenzel T. , Pindur G. , Mörsdorf S. , Giacchi J.
Published: April 2003

Quality of live, defined by different models, has become a major focus of research in chronic disorders. Patients with hemophilia have been found to suffer seriously from the impact of HIV infection. To compare the impact of HIV infection on HIV-positive and HIV-negative patients, we evaluated a group of 60 patients, 30 being positive and 30 negative, suffering from hemophilia, using the Karnofsky index of functioning besides more general social and clinical data. Most patients (n = 53) suffered from hemophilia A. The mean Karnofsky score decreased from 65.22 to 63.43 in the HIV-infected group between 1988 and 1991, but increased from 77.7 to 82.2 in the HIV-negative group; differences were not significant, though differences were significant between the HIV-infected and HIV-negative groups. The Karnofsky score remained constant or increased in 26 (86.6%) of the HIV-negative patients, in contrast to 50% in the infected group. Seven patients, all from the infected group, had died in 1991. The initial Karnofsky score was not a prognosticator of survival. The group as a whole was socially well integrated. Consequently, the Karnofsky score can be a useful instrument in evaluating the global quality of live in HIV-infected patients, though a careful evaluation of results is necessary and a low initial score does not predict survival.
Value of Screening Instruments in the Diagnosis of Post-Stroke Dementia
Authors: de Koning Inge , van Kooten Fop , Koudstaal Peter J.
Published: April 2003

Brief dementia screening instruments, or mental status tests are frequently used to screen for cognitive impairment. We discuss the strengths and weaknesses of existing mental status tests in dementia screening in general. Most screening instruments that are used in clinical practice are developed to detect dementia compatible with Alzheimer’s disease, and their value in detecting dementia after stroke is less well known. A stroke may cause both cortical and subcortical deficits, and the clinical expression of post-stroke dementia is different from that of Alzheimer’s disease. Existing brief mental status tests have limited value in this patient group because they tend to ignore specific problems which may occur in stroke patients. Some expanded screening instruments, like the CAMCOG, are more useful and have additional diagnostic value. With the growing interest in research for vascular factors in dementia over the past years, however, a specific screening instrument for post-stroke dementia would be a valuable contribution.
Possible Link between Lipid Metabolism and Cerebral Amyloid Angiopathy in Alzheimer’s Disease: A Role for High-Density Lipoproteins?
Authors: Mulder M. , Terwel D.
Published: April 2003

Although apolipoprotein E4 (ApoE4) is a well-established risk factor for the development of Alzheimer’s disease (AD), it is unclear how ApoE affects the progression of the disease. β-amyloid (Aβ) is a major constituent of cerebrovascular amyloid deposits in brains of subjects with Alzheimer’s disease. In cerebrospinal fluid and in plasma, Aβ is normally present in association with high density lipoproteins (HDL). These lipoproteins may play a role in the removal of excess cholesterol from the brain through interaction with ApoE and heparan sulphate proteoglycans (HSPG) in the subendothelial space of cerebral microvessels. At the same time, HDL may have a role in maintaining Aβ soluble and in mediating its clearance. Therefore, similar factors, e.g. HDL, ApoE and HSPG, may be involved in the regulation of reverse cholesterol transport in the brain and in the processing of Aβ. Alterations in the process of cholesterol secretion from the brain may contribute to the deposition of Aβ in the vascular wall.
Role of APOE in Dementia:A Critical Reappraisal
Authors: de Knijff Peter , van Duijn Cornelia M.
Published: April 2003

The apolipoprotein E (APOE) gene is strongly associated to the risk of Alzheimer’s disease (AD). More specifically, it seems undisputed that the APOE*4 allele plays an important role in the pathogenesis of AD. However, does this imply that it is ApoE4 which causes the increased susceptibility for AD? Empirical findings in non-Caucasians leave space for at least one alternative hypothesis: not the ApoE4 polymorphism but other defects in, or close to the APOE gene, could be responsible. We discuss this hypothesis, based on population and evolutionary genetic evidence.
Secondary Prevention of Venous Thromboembolism: A Role for Low-Molecular-Weight Heparin
Authors: Monreal Manuel , Roncales F. Javier , Ruiz Joan , Muchart Jordi , Fraile Manuel , Costa Joan , Hernandez José Angel
Published: April 2003

Background: After a short initial course of heparin therapy, patients with venous thrombo-embolism (VTE) require continuing anticoagulant therapy for several months after hospital discharge. At present, two small-scale studies have compared the efficacy and safety of low-molecular-weight heparin (LMWH) with warfarin in the secondary prevention of VTE. Patients and Methods: We studied 654 consecutive patients, 202 with pulmonary embolism (PE) and 452 patients with deep vein thrombosis (DVT) of the lower limbs. 220/654 patients (34%) were considered to have some contraindications to coumarin, and were discharged on LMWH (dalteparin, Fragmin®, 10,000 IU s.c. once daily). The remaining 434/654 patients were asked to choose between either coumarin or LMWH: 190 patients preferred LMWH and 244 coumarin. Patients were followed up for a 3-month (DVT patients) or 6-month (PE patients) period. Results: 14/654 patients (2%) developed recurrent VTE while on anticoagulant therapy. One in every three recurrent episodes was PE (which was fatal in 2/5 patients), and half of the recurrent DVT were located in the contralateral leg. We failed to find any differences between patients receiving LMWH and those on coumarin therapy, but recurrences were more common in patients with cancer (hazard ratio: 17.15; 95% CI: 4.0–73.5; p < 0.001). 21 patients (3.3%) bled (major bleeding 5 patients; minor bleeding 16). Bleeding was more common in patients on coumarin therapy (hazard ratio: 3.14; 95% CI: 1.20–8.22; p = 0.02). Conclusions: Long-term LMWH therapy proved to be both effective and safe in the long-term treatment of VTE. Thus, we suggest long-term LMWH therapy should be considered for patients with contraindications to coumarin, or those with difficulties in coming to laboratory control.
Comparative Study of a Portable Monitor for Prothrombin Time Determination, Coaguchek®, with Three Systems for Control of Oral Anticoagulant Treatment
Authors: Vacas M. , Lafuente P.J. , Cuesta S. , Iriarte J.A.
Published: April 2003

Self-testing of oral anticoagulation is a new possibility related to the development of portable capillary whole blood prothrombin time monitors. The aim of this study was to evaluate one of this monitors, Coaguchek®, with respect to its comparability with our routine prothrombin time determination system, as well as with the reference manual technique and two thromboplastins of high sensitivity, Manchester Reagent and one manufactured in our center, Thromboplastin Bilbao, in a group of patients on oral anticoagulant treatment. Although a correlation of r = 0.9271 was found between international normalized ratio (INR) values of Coaguchek and our routine method, Neoplastine/STA analyzer, the difference of the INR scatter increased with the magnitude of measurement, being lowest for INR between the portable monitor and Manchester Reagent and Thromboplastin Bilbao, with a similar coefficient of correlation, r = 0.8948 and r = 0.8905, respectively. A test was performed showing a 65.6% agreement with the INR values of the STA analyzer, 66.4% with Manchester Reagent and 73.4% with Thromboplastin Bilbao. On the basis of this correspondence with laboratory prothrombin time results Coaguchek may be considered as a possible option for monitoring anticoagulated patients even though patients should be given instructions and advice as regards the management and interpretation of the results.
Platelet Signal Transduction Pathways: Could We Organize Them into a ‘Hierarchy’?
Authors: Lévy-Toledano Sylviane
Published: April 2003

Platelet activation results in shape change, release of granule contents, aggregation and clot retraction. An intense intracellular ‘machinery’ is engaged to achieve these functions. Thrombin is one of the most important agonists for platelet recruitment and aggregation which is mediated by the binding of fibrinogen to its adhesive receptor: the glycoprotein (GP) IIb/IIIa complex or integrin αIIbβ3. The numerous biological processes consecutive to thrombin binding to platelet membrane are mainly controlled by phosphorylation mechanisms organized into signalling pathways. Schematically, the phospholipase Cβ pathway activated by G protein coupled to the seven transmembrane thrombin receptors, provides the first intracellular relay and would generate regulators such as protein kinase C, phosphorylated pleckstrin but also modifications of the intracellular domain of β3. This inside-out signalling would lead to some changes in the extracellular domain of GPIIb/IIIa increasing access of fibrinogen to the receptor. Ligand interaction with GPIIb/IIIa induced reorganization of the cytoskeleton and would mediate the outside-in signals which involve a series of intracellular events including tyrosine kinases, phosphatidylinositol 3 kinases, MAP kinases and phosphatases. Some of these pathways and/or signalling metabolites could be associated to some well-characterized platelet functions: cortactin phosphorylation is involved in platelet shape change, phosphatidylinositol 3 kinase (p85) in the stabilisation of platelet aggregates and MAP kinase (p44) in postaggregation events. But in fact the sequence of events which has been described has to be viewed as integrated networks. At least three biochemical processes govern the highly integrated organization to send just the appropriate quanta of signal for a specific need: the reorganisation of the cytoskeleton following the binding of fibrinogen to αIIbβ3, the structure of the signal transducers that contain SH2, SH3, and PH domains leading to the formation of macromolecules of signalling and the crosstalk phenomena between the different pathways. Elucidating the mechanisms of such networks becomes an increasingly exciting project.
Clinical Aspects and Laboratory Problems in Hereditary Thrombophilia
Authors: Samama Meyer-Michel , Gerotziafas Grigoris , Conard Jacqueline , Horellou Marie-Hélène , Elalamy Ismaïl
Published: April 2003

Hereditary thrombophilia is a multifactorial disease which is mono- or plurigenic and its clinical expression is associated with a heterogeneous expression. Factor V (FV) Leiden and FII gene mutations are more frequent than antithrombin, and protein C and S deficiencies. All thrombophilias are not the same. Heterozygous carriers of FV Leiden or FII gene mutation have a weaker risk of venous thrombosis. The mean age at the first episode is older in the former and higher rate of recurrences is observed in the latter. The cosegregation of mutations significantly increases the risk of thrombosis. Both mutations have a geographic and ethnic distribution in relation with a gene founder effect. Clinical expression consists of deep or superficial venous thrombosis with or without pulmonary embolism, thromboses at unusual sites (e.g. cerebral, portal, mesenteric) or with an increased incidence of fetal loss and abortion. A precipitating cause is present in more than 50% of patients. The risk pf arterial thromboses seems to be restricted to some protein S and FII gene mutations. Laboratory diagnosis strategy should be oriented by careful selection of patients and preanalytical variables should be considered. It is highly probable that other unindentified gene mutations are, at least partly, other causes of the heterogeneous expression of hereditary thrombophilia.
Effects of Clopidogrel on Platelet Activation and Coagulation of Non-Anticoagulated Rat Blood under High Shear Stress
Authors: Taka Tomomi , Okano Emi , Seki Junji , Yamamoto Junichiro
Published: April 2003

Clopidogrel is a new thienopyridine derivative similar to ticlopidine, which inhibits adenosine diphosphate-induced platelet aggregation. The in vitro effects of clopidogrel on shear-induced platelet activation and coagulation were assessed after oral administration to rats, by subjecting non-anticoagulated blood to haemostatometry. Clopidogrel significantly inhibited shear-induced platelet activation and coagulation 2 h after administration at doses of 7.5 and 15 mg/kg. Both ticlopidine (200 mg/kg) and aspirin (200 mg/kg) inhibited shear-induced platelet activation, but not coagulation. The peak inhibition of plaetelet activation by clopidogrel occurred 2 h after oral administration, but significant inhibition persisted even after 24 h. These results suggest that clopidogrel could be a more potent antithrombotic agent than ticlopidine or aspirin, and also that ADP plays an important role in shear-induced platelet activation.
Effect of Ticlopidine on Platelet-Derived Microparticles in Patients with Connective Tissue Diseases
Authors: Kagawa Hideo , Nomura Shosaku , Nagahama Minori , Ozaki Yoshio , Fukuhara Shirou
Published: April 2003

We evaluated the plasma concentrations of platelet activation markers and platelet-derived microparticles (PMP) in patients with connective tissue diseases complaining of peripheral circulation disorders (n = 16) and studied the effect of ticlopidine hydrochloride (ticlopidine) on PMP generation. There were significant differences in the levels of PMP and a platelet activation marker between before and after treatment with ticlopidine (PMP: 695 ± 393 vs. 354 ± 206/104 platelets, p < 0.01; platelet CD63: 9.13 ± 5.64 vs. 5.22 ± 2.74%, p < 0.05). On the other hand, markers of vascular endothelium, such as vascular endothelium-derived small vesicles and serum thrombomodulin levels, were not affected by the administration of ticlopidine. Levels of cytokines and soluble adhesion molecules remained unchanged by ticlopidine administration. These findings suggest that ticlopidine may be useful for the inhibition of PMP-dependent vascular damage in patients with connective tissue diseases complaining of peripheral circulation disorders.