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  • pharmacokinetics  (2,187)
  • Arbeitsmedizin
  • Rehabilitation
  • Strömungsmechanik
  • Springer  (2,351)
  • Sage Publications  (11)
  • Bundesarbeitsgemeinschaft für Rehabilitation
  • 1
    Keywords: Medicine ; Human Physiology ; Neurosciences ; Pathology ; Rehabilitation ; Sports Medicine ; Biomedicine ; Neurosciences ; Human Physiology ; Pathology ; Sports Medicine ; Rehabilitation ; Biomedicine general ; Springer eBooks
    Description / Table of Contents: Historical perspectives in understanding traumatic brain injury and in situating disruption in CBF in the pathotrajectory of head trauma -- Situating Cerebral Blood Flow in the Pathotrajectory of Head Trauma -- Modeling of traumatic brain injury and its implications in studying the pathology of repeated mild impacts to the head -- The presence of venous damage and microbleeds in traumatic brain injury and the potential future role of angiographic and perfusion magnetic resonance imaging -- Situating the Endothelin System in the pathotrajectory of TBI-induced changes in haemodynamics -- Age and Sex Differences in Cerebral Blood Flow and Autoregulation after Pediatric Traumatic Brain Injury -- New Frontiers in Clinical Trials Aimed at Improving Outcome Following Traumatic Brain Injury
    Abstract: 〈p〉Traumatic brain injury (TBI) has caught the ear of the general public in the last few years in the context of injuries seen both in athletes and the military.℗ Despite TBI being situated as a critical problem in society for multiple decades, the underlying pathotrajectory of TBI has only recently been truly appreciated.℗ Only recently has TBI research begun to develop better models of TBI that more closely recapitulate the human condition, make new advances in our ability to image pathophysiological sequelae in the brain following TBI, place a greater emphasis on studying the vascular dysfunction that accompanies head trauma, and, very recently, explore a new understanding of how age and sex can alter outcome to brain injury.〈/p〉〈p〉While this book was developed to satisfy a wide audience, from patient to caregiver, basic scientist to clinical scientist, the overall goal is to present the most current information known about head trauma and to expose areas where we may be deficient in understanding the nuances of TBI.℗ ℗ In particular, focus will be placed on the largest gap in our knowledg途the influence of cerebral blood flow (CBF) and metabolism in outcome following injury. This volume explores such varied concepts as the influence of CBF in the pathotrajectory of TBI, modeling TBI as a means to understand underlying pathological states associated with brain injury victims, disrupted vasculature following head trauma and advanced imaging techniques, vasoreactive substances underlying disrupted blood flow, the role of age and sex on injury outcome, and the latest pre-clinical rationale for focusing on CBF and strategies to improve blood flow as a means to improve outcome in patients suffering the effects of TBI.℗ Taken together, the information contained in ́€œCerebral Blood Flow, Metabolism, and Head Traumဝ is designed to both educate and illuminate anyone associated with TBI, with the hopes of stimulating future research.〈/p〉
    Pages: : digital.
    ISBN: 9781461441489
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  • 2
    Keywords: Medicine ; Rehabilitation ; Medicine & Public Health ; Rehabilitation ; Rehabilitation Medicine ; Springer eBooks
    Description / Table of Contents: 〈p〉Pr©♭face -- Imagerie IRM du plexus brachial normale et pathologique -- M©♭thodes d€™éxploration ©♭lectrophysiologique du plexus brachial -- Nouvelles ©♭chelles d́€™©♭valuation clinique des atteintes du syst©·me nerveux p©♭riph©♭rique -- Paralysie traumatique du plexus brachial de l€™ádulte℗ : prise en charge chirurgicale initiale -- Paralysie du plexus brachial obst©♭trical. Actualit©♭s et perspectives -- Chirurgie palliative dans les s©♭quelles de l©♭sions du plexus brachial chez l€™ádulte -- Faisabilit©♭ de l€™éxploration du d©♭fil©♭ cervico-thoracobrachial sous endoscopie℗ : ©♭tude cadav©♭rique -- Prise en charge r©♭©♭ducative. Quoi de neuf℗ ? -- L€™áppareillage dans les l©♭sions du plexus brachial de l€™ádulte -- Traitement du d©♭s©♭quilibre musculaire du plexus brachial -- Prise en charge de la douleur dans les l©♭sions du plexus brachial -- Particularit©♭s de l€™éxpertise dans les suites d€™úne atteinte traumatique du plexus brachial.〈/p〉
    Abstract: 〈p〉Cet ouvrage traite de la prise en charge des traumatismes du plexus brachial chez l€™ádulte et l€™énfant. Les auteurs font une mise © jour des m©♭thodes actuelles d́€™©♭valuation clinique, iconographique et ©♭lectrophysiologique ainsi que des techniques chirurgicales pr©♭conis©♭es en fonction du stade et du type de l©♭sion. 〈/p〉〈p〉℗ 〈/p〉〈p〉Les traitements ©♭voluent ; les proc©♭dures de r©♭©♭ducation, d€™áppareillage et de prise en charge de la douleur sont ©♭troitement li©♭es au traitement chirurgical. Les d©♭marches r©♭adaptatives et r©♭paratrices sont ©♭labor©♭es en fonction du projet de vie du patient.〈/p〉〈p〉℗ 〈/p〉〈p〉Cet ouvrage s€™ádresse aux praticiens chirurgiens, m©♭decins ou param©♭dicaux qui souhaitent mettre © jour leurs connaissances dans ce domaine.〈/p〉
    ISBN: 9782817803340
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  • 3
    Keywords: Medicine ; Orthopedics ; Orthopedic surgery ; Rehabilitation ; Sports Medicine ; Endoscopic surgery ; Medicine & Public Health ; Surgical Orthopedics ; Sports Medicine ; Orthopedics ; Conservative Orthopedics ; Rehabilitation Medicine ; Minimally Invasive Surgery ; Springer eBooks
    Pages: : digital
    ISBN: 9780857296092
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  • 4
    Unknown
    London : Springer
    Keywords: Medicine ; Internal Medicine ; Physical Therapy ; Rehabilitation ; Rheumatology ; Medicine & Public Health ; Rheumatology ; Internal Medicine ; Physiotherapy ; Rehabilitation Medicine ; Springer eBooks
    Pages: : digital
    ISBN: 9781848820937
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  • 5
    Keywords: Medicine ; Neurology ; Pain Medicine ; Rehabilitation ; Psychology, clinical ; Medicine & Public Health ; Pain Medicine ; Health Psychology ; Rehabilitation ; Neurology ; Springer eBooks
    ISBN: 9781441916518
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  • 6
    Keywords: Medicine ; Human Physiology ; Orthopedics ; Rehabilitation ; Sports Medicine ; Medicine & Public Health ; Sports Medicine ; Orthopedics ; Human Physiology ; Rehabilitation ; Springer eBooks
    Edition: 3rd ed. 2012.
    ISBN: 9781461411505
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  • 7
    Keywords: Medicine ; Dermatology ; Rehabilitation ; Surgery ; Medicine & Public Health ; Surgery ; Plastic Surgery ; Dermatology ; Rehabilitation ; Springer eBooks
    Pages: : digital.
    ISBN: 9783709103159
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  • 8
    Keywords: Medicine ; Maternal and infant welfare ; Rehabilitation ; Early childhood education ; Social work ; Developmental psychology ; Medicine & Public Health ; Maternal and Child Health ; Child and School Psychology ; Childhood Education ; Rehabilitation ; Social work ; Springer eBooks
    Pages: : digital.
    ISBN: 9781461423355
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  • 9
    Keywords: Medicine ; Anesthesiology ; Rehabilitation ; Surgery ; Medicine & Public Health ; Plastic Surgery ; Surgery ; Rehabilitation ; Anesthesiology ; Oral and Maxillofacial Surgery ; Springer eBooks
    Pages: : digital
    ISBN: 9781848821163
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  • 10
    Keywords: Medicine ; Neurology ; Physical Therapy ; Rehabilitation ; Medicine & Public Health ; Neurology ; Rehabilitation Medicine ; Physiotherapy ; Springer eBooks
    Pages: : digital
    Edition: 2012.
    ISBN: 9781447122777
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  • 11
    Keywords: Medicine ; Radiology, Medical ; Internal Medicine ; Neurology ; Neurosurgery ; Psychiatry ; Rehabilitation ; Medicine & Public Health ; Neurology ; Rehabilitation ; Internal Medicine ; Neurosurgery ; Psychiatry ; Neuroradiology ; Springer eBooks
    Pages: : digital.
    ISBN: 9781447124405
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  • 12
    Keywords: Medicine ; Neurology ; Pain Medicine ; Rehabilitation ; Medicine & Public Health ; Neurology ; Rehabilitation ; Pain Medicine ; Springer eBooks
    Pages: : digital.
    ISBN: 9788847024632
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  • 13
    Keywords: Medicine ; Human Physiology ; Neurosciences ; Neurology ; Rehabilitation ; Biomedicine ; Neurosciences ; Human Physiology ; Neurology ; Rehabilitation Medicine ; Springer eBooks
    Description / Table of Contents: Modulation of motor cortical connections through timed stimulation: animal studies -- Connection between premotor and motor cortices in primates -- Excitability of intracortical circuits in the primary motor cortex -- Effects of cortical stimulation on cortical functional connectivity: Imaging studies -- Accessing cortical connectivity using TMS -- Connections between cortical areas during grasping and modulation by brain stimulation -- Modulation of functional connectivity with transcranial direct current stimulation -- Cortical connections to motor cortex and their modulation in behavioural tasks (e.g. posterior parietal cortex, premotor cortex) -- The functional role of interhemispheric interactions in human motor control -- Functional modulation of primary motor cortex during action selection -- Enhancement of normal cortical functions through brain stimulation -- Movement disorders -- Stroke -- Multiple sclerosis -- Spinal cord injury -- Psychiatric diseases
    Abstract: 〈p〉The study and modulation of cortical connections is a rapidly growing area in neuroscience.℗ This unique book by prominent researchers in the field covers recent advances in this area.℗ The first section of the book describes studies of cortical connections, modulation of cortical connectivity and changes in cortical connections with activities such as motor learning and grasping in primates. ℗ The second section covers the use of non-invasive brain stimulation to study and modulate cortical connectivity in humans.℗ The last section describes changes in brain connectivity in neurological and psychiatric diseases, and potential new treatments that manipulate brain connectivity.℗ This book provides an up-to-date view of the study of cortical connectivity, and covers its role in both fundamental neuroscience and potential clinical applications.〈/p〉
    Pages: VIII, 365 p. 63 illus., 37 illus. in color. : digital.
    ISBN: 9783642327674
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  • 14
    Keywords: Medicine ; Radiology, Medical ; Orthopedics ; Orthopedic surgery ; Rehabilitation ; Physical Therapy ; Sports Medicine ; Medicine & Public Health ; Surgical Orthopedics ; Orthopedics ; Sports Medicine ; Imaging / Radiology ; Rehabilitation ; Physiotherapy ; Springer eBooks
    Pages: : digital
    ISBN: 9783642227691
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  • 15
    Keywords: Medicine ; Neurology ; Rehabilitation ; Medicine & Public Health ; Rehabilitation Medicine ; Neurology ; Springer eBooks
    Pages: : digital
    ISBN: 9782817802206
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  • 16
    Keywords: Medicine ; Radiology, Medical ; Radiotherapy ; Oncology ; Head / surgery ; Rehabilitation ; Medicine & Public Health ; Radiotherapy ; Oncology ; Imaging / Radiology ; Head and Neck Surgery ; Rehabilitation ; Springer eBooks
    Pages: : digital
    ISBN: 9788847018068
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  • 17
    Keywords: Medicine ; Gynecology ; Neurology ; Rehabilitation ; Urology ; Medicine & Public Health ; Urology/Andrology ; Gynecology ; Neurology ; Rehabilitation Medicine ; Springer eBooks
    Pages: : digital
    ISBN: 9783642035807
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  • 18
    Keywords: Medicine ; Orthopedics ; Rehabilitation ; Medicine & Public Health ; Orthopedics ; Rehabilitation ; Medicine/Public Health, general ; Springer eBooks
    Pages: : digital
    ISBN: 9783642171772
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  • 19
    Keywords: Medicine ; Radiology, Medical ; Radiotherapy ; Oncology ; Cancer / Surgery ; Psychotherapy ; Rehabilitation ; Medicine & Public Health ; Oncology ; Surgical Oncology ; Imaging / Radiology ; Radiotherapy ; Rehabilitation ; Psychotherapy ; Springer eBooks
    ISBN: 9782817802251
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  • 20
    Keywords: Medicine ; Nursing ; Otorhinolaryngology ; Rehabilitation ; Speech pathology ; Applied psychology ; Medicine & Public Health ; Speech pathology ; Otorhinolaryngology ; Nursing ; Rehabilitation ; Psychotherapy and Counseling ; Education (general) ; Springer eBooks
    Pages: : digital
    ISBN: 9788847018037
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  • 21
    Keywords: Medicine ; Neurosciences ; Anesthesiology ; Critical care medicine ; Neurology ; Neurosurgery ; Rehabilitation ; Medicine & Public Health ; Neurology ; Neurosurgery ; Anesthesiology ; Intensive / Critical Care Medicine ; Rehabilitation Medicine ; Neurosciences ; Springer eBooks
    Pages: XVI, 170 p. : digital.
    ISBN: 9782817801278
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  • 22
    Keywords: Medicine ; Orthopedics ; Rehabilitation ; Sports Medicine ; Medicine & Public Health ; Orthopedics ; Sports Medicine ; Rehabilitation ; Springer eBooks
    Pages: : digital
    ISBN: 9788847017023
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  • 23
    Unknown
    London : Springer
    Keywords: Medicine ; Internal Medicine ; Cardiology ; Rehabilitation ; Heart / Surgery ; Medicine & Public Health ; Cardiology ; Rehabilitation ; Cardiac Surgery ; Internal Medicine ; Springer eBooks
    Pages: : digital
    ISBN: 9781848827943
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  • 24
    Keywords: Medicine ; Rehabilitation ; Speech pathology ; Curriculum planning ; Medicine & Public Health ; Rehabilitation Medicine ; Speech pathology ; Curriculum Studies ; Springer eBooks
    Pages: : digital
    ISBN: 9788847014152
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  • 25
    Keywords: Medicine ; Family medicine ; Radiology, Medical ; Neurology ; Rehabilitation ; Medicine & Public Health ; General Practice / Family Medicine ; Neurology ; Neuroradiology ; Rehabilitation Medicine ; Springer eBooks
    Pages: : digital
    ISBN: 9782817800417
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  • 26
    Keywords: Medicine ; Emergency Medicine ; Critical care medicine ; Pneumology ; Neurology ; Rehabilitation ; Medicine & Public Health ; Pneumology/Respiratory System ; Intensive / Critical Care Medicine ; Emergency Medicine ; Rehabilitation Medicine ; Neurology ; Springer eBooks
    Pages: : digital
    ISBN: 9788847015487
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  • 27
    Keywords: Medicine ; Neurology ; Rehabilitation ; Medicine & Public Health ; Rehabilitation Medicine ; Neurology ; Springer eBooks
    Pages: : digital
    ISBN: 9782817801094
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  • 28
    Keywords: Medicine ; Orthopedics ; Orthopedic surgery ; Rehabilitation ; Medicine & Public Health ; Orthopedics ; Surgical Orthopedics ; Rehabilitation Medicine ; Springer eBooks
    Pages: : digital
    ISBN: 9783642008979
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  • 29
    Keywords: Medicine ; Neurology ; Orthopedics ; Rehabilitation ; Medicine & Public Health ; Rehabilitation ; Orthopedics ; Neurology ; Springer eBooks
    Pages: : digital
    ISBN: 9788847014787
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  • 30
    Keywords: Medicine ; Pediatrics ; Rehabilitation ; Psychology, clinical ; Developmental psychology ; Medicine & Public Health ; Rehabilitation Medicine ; Neuropsychology ; Developmental psychology ; Clinical Psychology ; Pediatrics ; Springer eBooks
    Pages: : digital
    ISBN: 9788847015753
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  • 31
    Keywords: Medicine ; Rehabilitation ; Psychology, clinical ; Medicine & Public Health ; Rehabilitation ; Neuropsychology ; Springer eBooks
    Pages: : digital
    ISBN: 9782817800349
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  • 32
    Keywords: Medicine ; Orthopedic surgery ; Rehabilitation ; Sports Medicine ; Trauma ; Medicine & Public Health ; Sports Medicine ; Surgical Orthopedics ; Traumatic Surgery ; Rehabilitation ; Medicine/Public Health, general ; Springer eBooks
    Pages: : digital
    ISBN: 9782817800073
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  • 33
    Keywords: Medicine ; Oncology ; Rehabilitation ; Quality of Life ; Quality of Life / Research ; Medicine & Public Health ; Oncology ; Rehabilitation Medicine ; Quality of Life Research ; Springer eBooks
    Pages: : digital
    ISBN: 9782287795015
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  • 34
    Electronic Resource
    Electronic Resource
    Springer
    Der Gynäkologe 33 (2000), S. 494-502 
    ISSN: 1433-0393
    Keywords: Schlüsselwörter Mammakarzinom ; Zervixkarzinom ; Korpuskarzinom ; Ovarialkarzinom ; Rehabilitation ; Keywords Oncology ; Rehabilitation ; Gynaecological carcinomas ; Physiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract In Germany about 41% of malignant neoplasies of women are carcinomas of mamma, cervix, Corpus uteri and ovary. Therapy of these malignomas consists of surgery, radio-, chemo- or hormonotherapy. Apart from therapeutic effects primary therapy may have negative effects in different physical, psychical and social aspects. These side effects are the concern of stationary oncological rehabilitation. Interdisciplinary cooperation makes it possible to consider the individual requirements of the patient.
    Notes: Zusammenfassung In Deutschland machen das Mamma-, Zervix-, Korpus- und Ovarialkarzinom ca. 41% der malignen Neoplasien bei der Frau aus. Die Behandlung dieser Malignome beinhaltet Operation, Strahlen-, Chemo- oder Hormontherapie. Neben der therapeutischen Wirkung kann es bei den Patientinnen durch die Primärbehandlung auch zu unterschiedlich ausgeprägten Beeinträchtigungen im physischen, psychischen oder sozialen Bereich kommen. An dieser Stelle greift die stationäre onkologische Rehabilitation an, die in interdisziplinärer Zusammenarbeit die individuellen Bedürfnisse der Patientinnen berücksichtigt.
    Type of Medium: Electronic Resource
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  • 35
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Schizophrenie ; Kognitive Therapie ; Kognitive Funktionsstörungen ; Strategieaufbau ; Bewältigung ; Key words Schizophrenia ; Information processing ; Cognitive therapy ; Strategy building ; Rehabilitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A critical review of current approaches and principles of cognitive remediation strategies in rehabilitation of schizophrenia is given. Selection of cognitive functions targeted in compensatory training programs could be based on results of neuropsychological predictor research on social and vocational functioning in community and neuropsychological rate limiting factors in rehabilitation. Methodological flaws in data base, missing of task analysis of more complex skills like social perception, social skills and interpersonal problem solving and the lack of evaluation of training generalization on work performance are discussed. Finally the cognitive remediation program developed in the Department of General Psychiatry and Psychotherapy/University of Freiburg, Germany is proposed. The components focused on training in attention, memory, and executive function (decision making, planning). Compensatory strategy building, and computer-mediated automatization are integrated in a group settting.
    Notes: Zusammenfassung In dieser Übersicht werden die aktuellen Trainingsverfahren der spezifischen Rehabilitation kognitiver Funktionsstörungen schizophrener Patienten sowie Kriterien für die Auswahl der Trainingsziele dargestellt. Neuere Arbeiten zur differentiellen Bedeutung für die Prädiktion sozialen und beruflichen Funktionsniveaus sowie für das Rehabilitationspotential können gegenwärtig die Auswahl kognitiver Trainingsziele empirisch legitimieren. Die aktuelle empirische Befundlage wird kritisch diskutiert: fehlende Analyse des kognitiven Anforderungsprofils sozialen und beruflichen Funktionierens, sozialer Wahrnehmung, interpersonellen Problemlösens (task analysis); mangelndes Wissen über Transfervoraussetzungen und ihre Wirkmechanismen sowie über setting-Aspekte, fehlende Regeln für eine Integration in einen verhaltenstherapeutischen Gesamtbehandlungsplan; methodische Mängel: Einfluss von Testwiederholungseffekten, zu kleine Stichproben (power-Defizite: Übersehen statistisch signifikanter Effekte), fehlende a-Adjustierung trotz multiplen Testens und unzureichender Einbezug der Effektgeneralisierung auf rehabilitativ bedeutsame Alltagskontexte. Abschließend wird ein computerunterstütztes Bewältigungstraining in der Gruppe zur Ausweitung des Rehabilitationspotentials vorgestellt, das an der Psychiatrischen Univ.-Klinik Freiburg entwickelt und gegenwärtig an der Abteilung für Klinische und Sozialpsychiatrie, Klinikum Karlsbad Langensteinbach (Ltd. Arzt: Dr. M. Clauß) erprobt wird. Das Training ist strategieorientiert und fokussiert die Bereiche Aufmerksamkeit, verbales Kurz- und Langzeitgedächtnis sowie Handlungsplanung und -organisation/exekutive Funktionen.
    Type of Medium: Electronic Resource
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  • 36
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Stroke Unit ; Schlaganfalltherapie ; Frührehabilitation ; Integratives Behandlungskonzept ; Keywords Stroke Unit ; Acute treatment ; Rehabilitation ; Integrative treatment concept
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The experiences of a rural stroke unit since 1997 are reported. A special referral concept was developed with the emergency services and hospitals of the region. As a result, 35% of patients arrived in the stroke unit within 3 hours after onset of stroke symptoms. This corresponds with the data from larger cities. The major peculiarity of the Günzburg Stroke Unit is that, after emergency diagnostic and therapeutic procedures, 41% of the patients with mainly internistic problems were transferred to another regional hospital and only 40% were admitted to the inpatient stroke unit. Moreover, among these were an above-average proportion of patients with intracerebral hemorrhage (24% of the inpatients in 1998), and complete acute treatment and rehabilitation were carried out in the same hospital according to an integrative treatment concept. Since 1997, the average hospitalization duration decreased from 11.4 days to 5.9 days and the number of patients per month increased to an average of 22.3. The total hospitalization duration – including inpatient rehabilitation – was 33.9 days. All in all, a comparably good stroke treatment thus is possible outside urban regions.
    Notes: Zusammenfassung Die Erfahrungen einer seit 1997 bestehenden Stroke Unit im überwiegend ländlichen Raum werden berichtet. Im Rahmen eines speziellen Zuweisungskonzeptes erreichten 35% der Patienten die Klinik innerhalb von 3 h nach Symptombeginn, was den Angaben aus Ballungszentren entspricht. Wesentliche Besonderheit der Günzburger Stroke Unit ist, dass nach der “präklinischen” Notfalldiagnostik und -therapie 41% der Patienten mit im Vordergrund stehenden internistischen Problemen in die umliegenden Krankenhäuser eingewiesen und nur 40% auf der Stroke Unit aufgenommen wurden. Darüber hinaus wurden relativ viele Patienten mit intrazerebralen Blutungen (24% der stationären Patienten im Jahr 1998) versorgt, und entsprechend einem integrierten Konzept erfolgte die Akutversorgung und Frührehabilitation im Hause. Seit 1997 konnte die durchschnittliche Verweildauer auf der Stroke Unit von zunächst 11,4 auf 5,9 Tage verkürzt werden bei gleichzeitigem Anstieg der Fallzahl auf 22,3 Patienten/Monat. Die Gesamtverweildauer einschließlich Frührehabilitation lag bei 33,9 Tagen. Die Erfahrungen belegen, dass auch außerhalb von Ballungszentren eine gut vergleichbare Schlaganfallversorgung möglich ist.
    Type of Medium: Electronic Resource
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  • 37
    ISSN: 1433-7347
    Keywords: Key words Anterior cruciate ¶ligament ; Screening examination ; Rehabilitation ; Knee injuries
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: Abstract This report describes the development and current use of decision-making criteria for returning patients to high-level physical activity with nonoperative management of anterior cruciate ligament ruptures, and presents the results of treatment for patients who met our criteria as candidates for nonoperative rehabilitation and attempted to return to high-level physical activity with nonoperative management. The screening examination consists of four one-legged hop tests, the incidence of knee giving-way, a self-report functional survey, and a self-report global knee function rating. We screened 93 consecutive patients with acute unilateral anterior cruciate ligament rupture, classifying them as either candidates (n = 39, 42%) or noncandidates (n = 54, 58%) for nonoperative management. Of the 39 rehabilitation candidates 28 chose nonoperative management and returned to preinjury activity levels, 22 of whom (79%) returned to preinjury activity levels without further episodes of instability or a reduction in functional status. No patient sustained additional articular or meniscal damage as a result of rehabilitation or return to activity. The decision-making scheme described in this study shows promise in determining who can safely postpone surgical reconstruction and temporarily return to physically demanding activities. Continued study to refine and further validate the decision-making scheme is recommended.
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  • 38
    ISSN: 1433-7347
    Keywords: Key words Knee injury ; Patellar dislocation ; Isokinetic testing ; Muscle performance ; Rehabilitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: Abstract Eighty-two patients (50 women, 32 men) underwent isokinetic muscle testing on average 13 years after a conservatively treated unilateral primary patellar dislocation. Three study groups were formed according to the natural history of recovery: group A (n = 32), patients with only primary conservative treatment; group B (n = 34) patients with conservative (group B1; ¶n = 24) or surgical (group B2; n = 10) treatment of redislocations; group C (n = 16) patients with other residual complaints (anterior knee, pain subluxations) requiring surgery. The Cybex 6000 dynamometer system was used as the testing machine for quadriceps and hamstrings muscles, with proportional deficits of peak torque as the test parameter. Isokinetic testing revealed both quadriceps and hamstring muscle atrophy even after long-term recovery from injury. There were statistically significant differences between the three study groups at both tested speeds of quadriceps muscles ¶(60 rad/s, P 〈 0.002; 180 rad/s, ¶P 〈 0.009). Groups B1 and B2 presented similar results. The muscle performance findings are probably due to more than one factor: primary immobilization, poor outcome, patellofemoral degeneration, redislocations, and residual knee complaints followed by surgery and deficiency in motor control of thigh muscle had – together or separately – an effect on muscle performance.
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  • 39
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Intensivmedizin ; Lebensqualität ; Polytrauma ; Langzeitergebnisse ; Rehabilitation ; Keywords Quality of life ; Intensive care ; Multiple trauma ; Long-term outcome ; Rehabilitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Introduction. Long-term treatment in surgical intensive care units (SICU) subjects the patient to a high degree of somatic, psychological, and social stress. The aim of this study was to determine their outcome in terms of quality of life and health status. Methods. All patients from a 4-year period in a SICU with a length of stay (LOS) of 30 days or more were included. All survivors were interviewed and examined after 35±14 months; they also completed several questionnaires (Munich Inventory for Quality of Life and Health Status, POMS, and Spitzer Quality of Life Index). Results. One hundred one patients fulfilled the inclusion criteria, and 46 survived until follow-up. Forty-one (89%) could be traced and examined. Male:female ratio was 31:10, age 42±17 years, and LOS 51±19 days, Diagnoses on admittance were multiple trauma (n=32) and other (n=9). When classifying patients according to physical impairment, one third each showed no, mediocre, or severe limitations. Subjective appraisal of quality of life and well-being was sufficient for about half the patients in every test. Trauma victims experienced more severe impairment of quality of life. There were no differences between sex, age, or time until follow-up. Conclusion. After prolonged SICU treatment, about half of the patients report limitations in their quality of life as a result of their illness and the subsequent treatment. Some patients, in particular after trauma, exhibit striking psychosocial problems despite satisfactory somatic treatment results. These problems can be positively addressed in rehabilitative efforts.
    Notes: Zusammenfassung Fragestellung. Die Langzeitbehandlung auf Intensivstationen (ICU) bedeutet eine erhebliche somatische, psychische und soziale Belastung für die Patienten. Um die Ergebnisse im Langzeitverlauf beurteilen zu können, wurden nach der Entlassung Lebensqualität und Gesundheitszustand von Überlebenden untersucht. Methodik. Alle Patienten, die während eines 4 Jahres Zeitraumes auf einer operativen ICU mindestens 30 Tage in Behandlung gewesen waren, wurden in die Untersuchung eingeschlossen. Die Überlebenden wurden 35±14 Monate nach der Entlassung körperlich untersucht und ausführlich befragt. Zur Anwendung kamen außerdem Selbst- und Fremdbeurteilungsskalen (Münchner Inventar für Lebensqualität und Gesundheit, POMS, Spitzer Quality-of-life-Index). Ergebnisse. 101 Patienten wurden mindestens 30 Tage behandelt. Die Mortalität bis zur Nachuntersuchung betrug 55%. Von den 46 verbleibenden Patienten konnten 41 (89%) untersucht werden (m/w=31/10; Alter 41,6±17,2 Jahre; Liegedauer 51±19 Tage; Diagnosen: Trauma n=32, andere n=9). Je ein Drittel der Patienten zeigten keine, mittlere oder schwere körperliche Beeinträchtigungen. Lebensqualität und Gesundheit wurden von ca. der Hälfte, unabhängig vom Testverfahren, als zufriedenstellend beurteilt. Traumapatienten waren in allen Bereichen stärker belastet. Es zeigte sich keine Abhängigkeit von Alter, Geschlecht und Zeitraum bis zur Nachuntersuchung. Schlussfolgerungen. Patienten nach Langzeitintensivbehandlung weisen etwa zur Hälfte deutliche Einschränkungen ihrer Lebensqualität auch als Folge der Erkrankung oder Behandlung auf. Besonders Traumapatienten geben trotz somatisch zufriedenstellender Behandlungsergebnisse erhebliche Probleme im psychosozialen Bereich an, die rehabilitativen Maßnahmen zugänglich sind.
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  • 40
    ISSN: 1434-3924
    Keywords: Schlüsselwörter Vordere Kreuzbandruptur ; Lig.-patellae-Transplantat ; Rehabilitation ; Physiotherapie ; Krafttraining ; Keywords Anterior cruciate ligament ; Rehabilitation ; Physiotherapie ; Muscle strengthening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: In a prospective randomized study, all 133 consecutive ACL ruptures, operated by two experienced surgeons in 1997, were assessed in terms of the benefit derived from four different rehabilitation programs. In all cases an arthroscopically assisted autogenous bone-patellar tendon–bone technique was used. The following four rehabilitation programs were compared: (1) a simple home-based program; (2) home-based program plus physiotherapy for a period of 12 weeks postoperatively; (3) home-based program plus a muscle strengthening program for a period of 3 months, starting 3 months postoperatively; and (4) home-based program plus physiotherapy plus muscle strengthening program (as detailed in 1 and 3 above). Clinical assessments and controls were conducted at 6 and 12 weeks. At 6 months, in addition, an isometric muscle strength measurement (MedX) concerning extension and flexion, comparing the affected leg with the unaffected leg, was applied. The results of these assessments are consistently the same in all four groups: 6 months postoperatively, loss of muscle strength in extension was 50%. No apparent benefit could be detected from either physiotherapy or muscle strengthening or from the combined application of those methods as compared to the home-based program. In conclusion, our investigation shows that a simple home program, supervised by the surgeon, leads to highly satisfactory results in virtually all cases.
    Notes: In einer prospektiven, randomisierten Studie wurden alle 133, während des Jahrs 1997 mittels autologem Lig.-patellae-Transplantat durch 2 erfahrene Chirurgen versorgten vorderen Kreuzbandrupturen in 4 verschieden intensive postoperative Rehabilitationsgruppen eingeteilt. Anhand von protokollierten Verlaufskontrollen nach 6 Wochen, 3 Monaten und 6 Monaten wurde die Effizienz der 4 Rehabilitationsprogramme überprüft. Zusätzlich zum einfachen, durch den Operateur kontrollierten Heimprogramm verordnete Physiotherapiesitzungen vermochten den Frühverlauf nicht zur verbessern. Vergleichende, isometrische Kraftmessungen des operierten gegenüber dem unverletzten Bein (MedX) zeigten in allen 4 Gruppen eine Kraftdifferenz von ungefähr 50% bezüglich der Extension nach 6 Monaten. Auch ein intensives Krafttraining im Zeitraum 3–6 Monate postoperativ vermochte das Kraftdefizit am operierten Bein nicht zu verkleinern. Aufgrund unserer Untersuchungsergebnisse von 4 verschiedenen Rehabilitationsprogrammen nach vorderer Kreuzbandrekonstruktion mit autologem Lig.-patellae-Transplantat, arthroskopisch assistiert, erachten wir in der Regel ein einfaches, vorzugsweise durch den Operateur kontrolliertes Nachbehandlungsschema, in Eigentherapie als Heimprogramm absolviert, zum fristgerechten Erreichen eines guten Operationsresultats für ausreichend.
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  • 41
    Electronic Resource
    Electronic Resource
    Springer
    Arthroskopie 13 (2000), S. 186-190 
    ISSN: 1434-3924
    Keywords: Schlüsselwörter Revisionseingriffe ; Rotatorenmanschettenläsion ; Ultraschall ; Rehabilitation ; Keywords Revision operations ; Rotator cuff tears ; Ultrasound ; Rehabilitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Twenty-four consecutive patients (14 male, 10 female, average age 58 years, 40–73 years) were included in the study during their stationary rehabilitation program. They were examined clinically and by ultrasound an average of 32 days (18–50 days) after operation. Anamnestic and clinical findings did not reveal a clear suspicion of a re-tear. All of the patients showed considerable morphologic and structural sonographic alterations of the rotator cuff. Reliable sonographic signs concomitant with a tear were seen in 18 patients, in 16 cases within the supraspinous muscle. We found 8 type II, 11 type III, and 6 type IV images. Only two of the patients undergoing a revision operation due to a subcutaneous necrosis had changes of blood patterns. Whereas the sonographic criteria for primary tears of the rotator cuff are well defined, re-tears pose real diagnostic problems, especially in case of lack of an earlier postoperative control. Only the lack of sonographic imaging of the rotator cuff compared to earlier postoperative sonographic findings allows a reliable diagnosis of a re-tear, because other pathologic alterations of form and echogenicity are common preoperatively. Owing to this, we recommend an early postoperative ultrasound control as a basic finding, enabling a sufficient control in the further course of rehabilitation.
    Notes: In der Anschlussheilbehandlung nach Eingriffen an der Rotatorenmanschette wurden 24 konsekutive Patienten [14 Männer, 10 Frauen, Durchschnittsalter 58 Jahre (40– 73 Jahre)] durchschnittlich 32 Tage (18–50 Tage) postoperativ klinisch und sonographisch untersucht. Anamnestisch und klinisch waren keine eindeutigen Hinweise auf Rezidivläsionen zu finden. Alle Patienten zeigten erhebliche morphologische und strukturelle Ultraschallveränderungen der Rotatorenmanschette. Sichere sonographische Rupturzeichen fanden sich bei 18 Patienten, davon 16-mal im Bereich des M. supraspinatus. Typ-II-Bilder wurden 8-mal, Typ-III-Bilder 11-mal und Typ-IV-Bilder 6-mal gefunden. Nur jene 2 Patienten, die aufgrund einer subkutanen Nekrosebildung revidiert werden mussten, zeigten Auffälligkeiten der Laborwerte. Während die sonographischen Kriterien für die Diagnose einer primären Rotatorenmanschettenruptur klar definiert sind, stellen Rerupturen den Untersucher vor erhebliche Probleme, insbesondere, wenn frühere postoperative Vergleichsbefunde fehlen. Nur die im Vergleich zu Vorbefunden fehlende sonographische Darstellung der Rotatorenmanschette erlaubt die sichere Diagnose einer Reruptur, da in der Regel bereits präoperativ pathologische Veränderungen der Form und Echogenität der Rotatorenmanschette häufig sind. Daher ist eine frühe postoperative Ultraschalluntersuchung als Basisbefund zu empfehlen, um eine Verlaufskontrolle zu ermöglichen.
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  • 42
    ISSN: 1434-3924
    Keywords: Schlüsselwörter Knietrauma ; Propriozeption ; Neuromuskuläre Veränderungen ; Koordination ; Rehabilitation ; Keywords Knee trauma ; Proprioception ; Neuromuscular alterations ; Coordination ; Rehabilitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Despite some alterations of receptor thresholds after knee trauma and surgical treatment joint receptors provide the prerequisites for correct proprioception. The peripheral afferent pathway, the spinal and central stimulus processing and the peripheral efferent pathway are intact. Alterated peripheral sensory perception is caused by the knee trauma induced change of proprioception. A reduction of absolute torque, active range of movement, modified muscle selection and delay in neuromuscular latency time are observed. Postoperative exercise should enable the patient to gather positive sensory experience enclose to activities of daily living.
    Notes: Nach Knietraumen und operativer Versorgung sind die Voraussetzungen zur korrekten Propriozeption gegeben. Der peripher-afferente Schenkel, die spinale und zentrale Reizverarbeitung sowie der peripher-efferente Schenkel sind nach Kniebinnentraumen und -operationen intakt. Veränderte peripher-sensorische Wahrnehmungen (Afferenzen) sind durch das Knietrauma bedingt. Es kommt zu einer Reduktion des absoluten Krafteinsatzes und der aktiven Beweglichkeit, zu einer Veränderung der Muskelselektion sowie zu Verlängerungen neuromuskulärer Reaktionszeiten. Postoperative Übungen müssen es dem Patienten ermöglichen, alltagsnahe positive sensorische Erfahrungen zu sammeln.
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  • 43
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 44
    ISSN: 1573-904X
    Keywords: oral absorption ; humans ; dogs ; rats ; interspecies scale-up ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To conduct a retrospective evaluation of using dog as ananimal model to study the fraction of oral dose absorbed (F) of 43drugs in humans and to briefly discuss potential factors that mighthave contributed to the observed differences in absorption. Methods. Mean human and dog absorption data obtained under fastedstate of 43 drugs with markedly different physicochemical andpharmacological properties and with mean F values ranging from 0.015 to1.0 were obtained from the literature. Correlation of F values betweenhumans and dogs was studied. Based on the same references, additionalF data for humans and rats were also obtained for 18 drugs. Results. Among the 43 drugs studied, 22 drugs were virtuallycompletely absorbed in both dogs and humans. However, the overallcorrelation was relatively poor (r2 = 0.5123) as compared to the earlier ratvs. human study on 64 drugs (r2 = 0.975). Several drugs showed muchbetter absorption in dogs than in humans. Marked differences in thenonliner absorption profiles between the two species were found forsome drugs. Also, some drugs had much longer Tmax values andprolonged absorption in humans than in dogs that might be theoreticallypredicted. Data on 18 drugs further support great similarity in F betweenhumans and rats reported earlier from our laboratory. Conclusions. Although dog has been commonly employed as ananimal model for studying oral absorption in drug discovery anddevelopment, the present study suggests that one may need to exercise cautionin the interpretation of data obtained. Exact reasons for the observedinterspecies differences in oral absorption remain to be explored.
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  • 45
    ISSN: 1573-904X
    Keywords: in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
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  • 46
    ISSN: 1573-904X
    Keywords: benzodiazepines ; pharmacokinetics ; EEG ; operational model of agonism ; receptor binding ; muscimol-induced Cl−uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. A mechanism-based model is applied to analyse adaptivechanges in the pharmacodynamics of benzodiazepines upon chronictreatment in rats. Methods. The pharmacodynamics of midazolam was studied in ratswhich received a constant rate infusion of the drug for 14 days, resultingin a steady-state concentration of 102 ± 8 ng·ml−1. Vehicle treated ratswere used as controls. Concentration-EEG effect data were analysed onbasis of the operational model of agonism. The results were comparedto data obtained in vitro in a brain synaptoneurosomal preparation. Results. The relationship between midazolam concentration and EEGeffect was non-linear. In midazolam pre-treated rats the maximum EEGeffect was reduced by 51 ± 23 μV from the original value of 109 ±15 μV in vehicle treated group. Analysis of this change on basis ofthe operational model of agonism showed that it can be explained bya change in the parameter tissue maximum (Em) rather than efficacy(τ). In the in vitro studies no changes in density, affinity or functionalityof the benzodiazepine receptor were observed. Conclusions. It is concluded that the observed changes in theconcentration-EEG effect relationship of midazolam upon chronic treatmentare unrelated to changes in benzodiazepine receptor function.
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  • 47
    ISSN: 1573-904X
    Keywords: luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Population models for thepharmacokinetic-pharmacodynamic relationship for cetrorelix (CET), a luteinising hormone-releasinghormone (LH-RH) antagonist, and the pharmacodynamic response ontestosterone production were investigated in rats and dogs. Methods. The plasma concentrations of CET and testosterone weredetermined after intravenous and subcutaneous injections. Thepopulation PK/PD-models were developed using P-PHARM software. Results. Absolute bioavailability of cetrorelix was 100% in rats and97% in dogs. In rats, the pharmacokinetics was explained by atwo-compartment model with saturable absorption, while athree-compartment model was used in dogs. Testosterone suppression in both specieswas described by a sigmoid Emax model with maximum effect (Emax)considered as total hormonal suppression. The duration of testosteronesuppression in rats was longer at higher doses. The populationelimination half-lifes after iv-dose were 3.0 h in rats and 9.3 h in dogs.Population mean estimates of IC50 were 1.39 and 1.24 ng/ml in ratsand dogs, respectively. Conclusions. A population pharmacokinetic model was developed toexplain the dissolution rate limited absorption from the injection site.The suppression of testosterone could be described by an indirectinhibitory sigmoid Emax model. In both species 1-2 ng/ml CET inplasma was necessary to suppress testosterone production.
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  • 48
    ISSN: 1573-904X
    Keywords: methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
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  • 49
    ISSN: 1573-904X
    Keywords: SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetichematoregulatory peptide, in healthy volunteers and in patientswith adenocarcinoma.Methods. SK&F 107647 pharmacokinetics were evaluated in 2dose-escalation studies. Volunteers received SK&F 107647 as single15-minute iv infusion doses of 1, 10, 100, 500, and 1000 μg/kg. Cancerpatients received 2-hour iv infusions of 0.001, 0.01, 0.1 and 1μg/kg once daily for 10 days. Drug concentrations were quantified in plasmaand urine of healthy volunteers and on days 1 and 10 in plasma ofcancer patients receiving the two top dose levels.Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101ml/hour/kg; mean volume of distribution at steady-state (Vss)rangedfrom 175 to 268 ml/kg. Most of the administered dose was renallyexcreted as intact peptide within 24 hours postinfusion. In patients,mean CL was 57.6 ml/hour/kg, mean Vss ranged from 128 to 150ml/kg and terminal half-life from 2.1 to 3.4 hours. There was littleaccumulation of drug. In both studies, linear pharmacokinetics wasobserved. Clearance approached normal glomerular filtration rate(GFR) in volunteers and correlated with creatinine clearance incancer patients.Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a smallVss, and clearance, primarily renal, approaching normal GFR.
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  • 50
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds and 29 drugs from literature sources. When the exponent bivwas higher than 0.85, BRW was incorporated into the allometricrelationship (CLu*BRW = a · Wbiv). This approach was also applied tothe prediction of CLu/F for 10 Parke-Davis compounds. Human oralt1/2, Cmax, AUC, and bioavailability were estimated based onallometrically predicted pharmacokinetic (PK) parameters. Results. Human CL and CL/F were more accurately estimated usingunbound drug concentration and the prediction was further improvedwhen BRW was incorporated into the allometric relationship. ForParke-Davis compounds, the predicted human CL and CL/F werewithin 50-200% and 50-220% of the actual values, respectively. Theestimated human oral t1/2, Cmax, and AUC were within 82-220%,56-240%, and 73-190% of the actual values for all 7 compounds,suggesting that human oral PK parameters of those drugs could bereasonably predicted from animal data. Conclusions. Results from the retrospective analysis indicate thatallometric scaling of free concentration could be applied to orallyadministered drugs to gain knowledge of drug disposition in man, and to helpdecision-making at early stages of drug development.
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  • 51
    ISSN: 1573-904X
    Keywords: α1-acid glycoprotein ; protein binding ; dissociation rate ; species difference ; physiological model ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The extremely low clearance and small distribution volumeof UCN-01 in humans could be partly due to the high degree of bindingto hAGP (1,2). The quantitative effects of hAGP on the pharmacokineticsof UCN-01 at several levels of hAGP and UCN-01 were estimatedin rats given an infusion of hAGP to mimic the clinical situation anda physiological model for analysis was developed. Methods. The plasma concentrations of UCN-01 (72.5–7250 nmol/kgiv) in rats given an infusion of hAGP, 15 or 150 nmol/h/kg, weremeasured by HPLC. Pharmacokinetic analysis under conditionsassuming rapid equilibrium of protein binding and incorporating thedissociation rate was conducted. Results. The Vdss and CLtot of UCN-01 (725 nmol/kg iv) in ratsgiven an infusion of hAGP, 150 nmol/h/kg, fell to about 1/250 and 1/700that in control rats. The Vdss and CLtot following 72.5–7250nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9–688ml/kg and 3.18–32.9 ml/h/kg, respectively, indicating non-linearitydue to saturation of UCN-01 binding. The CLtot estimated by thephysiological model assuming rapid equilibrium of UCN-01 bindingto hAGP, was six times higher than the observed value while the CLtotestimated by the model incorporating koff, measured using DCC, wascomparable with the observed value. Conclusions. These results suggest that the slow dissociation ofUCN-01 from hAGP limits its disposition and elimination.
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  • 52
    ISSN: 1573-904X
    Keywords: 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the in vivo specific binding andpharmacokinetics of a 1,4-dihydropyridine (DHP) calcium channel antagonist, PN200-110, in the senescent brain, using senescence-accelerated pronemice (SAMP8) and senescence-resistant mice (SAMR1). Methods. Blood, brain, and heart samples were taken periodically fromSAMR1 and SAMP8 following intravenous injection of (+)-[3H]PN200-110, and the concentration of (+)-[3H]PN 200-110 in the plasmaand tissues was determined. In addition, the in vivo specific bindingof (+)-[3H]PN 200-110 in the brains of SAMR1 and SAMP8 wasmeasured periodically after intravenous injection of the radioligand. Results. There was very little significant difference between SAMR1and SAMP8 in terms of the half-life (t1/2), total body clearance (CLtot),steady-state volume of distribution (Vdss), and AUC for the plasmaconcentration of (+)-[3H]PN 200-110 after intravenous injection ofthe radioligand. The brain concentration (AUCbrain) for (+)-[3H]PN200-110 and the brain/plasma AUC ratio (AUCbrain/AUCplasma) weresignificantly lower in SAMP8 than in SAMR1, and the heartconcentration (AUCheart) and the heart/plasma AUC ratio (AUCheart/AUCplasma)were similar in both strains. Also, the brain/plasma unbound AUCratio (AUCbrain/AUCplasma-free) for (+)-[3H]PN 200-110 wassignificantly lower in SAMP8 than in SAMR1. The in vivo specific binding(AUCspecific binding, maximal number of binding sites: Bmax) of(+)-[3H]PN 200-110 was significantly lower in brain particulate fractionsof SAMP8 than SAMR1. Conclusions. The concentration and in vivo specific binding of(+)-[3H]PN 200-110 was significantly reduced in the senescent brain. Thesimultaneous analysis of the concentrations of centrally acting drugsand the in vivo specific binding in the brain in relation to theirpharmacokinetics may be valuable in evaluating their CNS effects.
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  • 53
    ISSN: 1573-904X
    Keywords: morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by drug was used for in vivo calibration of the MD probes. Morphine was infused (10 or 40 mg/kg) over 10 min intravenously. Nociception, measured by the electrical stimulation vocalisation method, and blood gas status were determined. Results. The half-life of unbound morphine in striatum was 44 min compared to 30 min in venous and arterial blood (p 〈 0.05). The BBB equilibration of morphine, expressed as the ratio of areas under the curve between striatum and venous blood, was less than unity (0.28 ± 0.09 and 0.22 ± 0.17 for 10 and 40 mg/kg), respectively, indicating active efflux of morphine across the BBB. The concentration-effect relationship exhibited a clear hysterisis with an effect delay half-life of 32 and 5 min based on arterial blood and brain ECF concentrations, respectively. Conclusions. Eighty five percent of the effect delay was caused by morphine transport across the BBB, indicating possible involvement of rate limiting mechanisms at the receptor level or distributional phenomena for the remaining effect delay of 5 min.
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  • 54
    ISSN: 1573-904X
    Keywords: aspergillosis ; pharmacokinetics ; amphotericin B ; biodistribution ; liposomes ; cholesterol hemisuccinate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study compared the biodistribution of two amphotericin B formulations in normal and Aspergillus infected mice. Amphotericin B cholesterol hemisuccinate vesicles (ABCV) which reduces the toxicity of amphotericin B and thereby enhances its therapeutic efficacy in a murine model of aspergillosis was compared with conventional amphotericin B deoxycholate suspension (AmBDOC). Methods. ABCV (12 mg/kg wt) and AmBDOC (2 mg/kg wt) were intravenously administered to normal and A.fumigatus infected mice. The concentration of amphotericin B in plasma and other organs was determined at different time points. Results. It was observed that ABCV had a significantly different pharmacokinetic profile compared to conventional amphotericin B. In comparison to AmBDOC significantly lower levels of amphotericin B were observed in kidneys and plasma, the major target organs of toxicity. Animals receiving ABCV demonstrated high levels of amphotericin B in liver (38% retention till 48 h) and spleen (2.6% retention till 48 h) in comparison to AmBDOC (7.3% and 0.21% retention in liver and spleen respectively till 48 h). Biodistribution studies of ABCV in infected mice demonstrated that there was a moderate enhancement in levels of amphotericin B in liver, spleen, lungs and kidneys as compared to normal mice and the plasma levels were reduced. However, such observations were not made after AmBDOC administration to infected mice except for kidneys in which there was a marked increase in uptake as compared to normal mice. Conclusions. Our results suggest that prolonged retention of high concentrations of ABCV in reticuloendothelial system organs is the reason for its reduced toxicity. Enhanced localization of the drug at the infected site may lead to improvement in therapeutic efficacy.
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  • 55