bluuebunny/crossref_metadata_2025 huggingface dataset:
Action, localization and structure-function relationship of growth factors and their receptors in the prostate
Authors: Chevalier S , Aprikian AG , Beauregard G , Defoy I , Nguyen LT , Guenette RS , Tenniswood M , Chapdelaine A
Published: June 2009

Whereas the direct action of sex steroids, namely of androgens, on prostate cell division was questioned as early as in the 1970s, and remains so, the interest in prostatic growth factors (GFs) is rather recent but has expanded tremendously in the last five years. This lag period can be partly explained by the fact that, at the time, androgen receptors had just been discovered, and newly developed hormonal regimens or strategies to treat patients with prostate carcinoma (PCa) or epithelioma had generated great enthusiasm and hopes in the medical and scientific community. Another point to consider was the difficulty in maintaining prostate tissues in organ cultures and the relative novelty of culturing prostate epithelial cells in monolayers. Failures of sex steroids to elicit a direct positive response on prostate cell divisionin vitro, as seenin vivo, were interpreted as resulting from inappropriate models or culture conditions. However, the increasing number of reports confirming the lack of mitogenic activity of sex steroidsin vitro, coupled with the powerful mitogenic activity of GFs displayed in other systems, the discovery of GF receptors (GF-Rs), and the elucidation of their signalling pathways showing sex steroid receptors as potential substrates of GF-activated protein kinases gradually led to an increased interest in the putative role of GFs in prostate physiopathology. Of utmost importance was the recognition that hormone refractiveness was responsible for PCa progression, and for the poor outcome of patients with advanced disease under endocrine therapies. This problem remains a major issue and it raises several key questions that need to be solved at the fundamental and clinical levels.
Medical therapy of ectopic gestation: contemporary paradigms
Authors: Chamoun D , Wong KHH , McClamrock HD
Published: June 2009

There has been an increase in the incidence of ectopic pregnancy to epidemic proportions in many developed countries in the past two decades. In 1989, ectopic pregnancy accounted for 1.6% of all pregnancies in the United States of America. This trend may be explained by an increase in the incidence of established risk factors as well as a dramatic improvement in diagnostic tools and advances in reproductive technology. Technologic advances such as highly sensitive radioimmunoassays for the β-subunit of human chorionic gonadotropin (βhCG), the development of high-resolution ultrasound and a heightened physician awareness have revolutionized the clinical management of ectopic pregnancy, leading to earlier and more consistent diagnoses and consequently reduced maternal mortality rates. 1,3–13 Unfortunately, ectopic pregnancy is still associated with a significant morbidity and mortality and contributes substantially to health-care costs. For example ectopic pregnancy complications accounted for 13% of all pregnancy-related deaths and were the leading cause of maternal mortality in African- American women in 1989. Financially, an estimated 1.1 billion dollars was spent in the United States of America alone for the management of ectopic pregnancy in 1990.
Unstimulated in vitro fertilization revisited
Authors: Kolb Bradford Alan , Paulson Richard J
Published: June 2009

The first attempts at in vitro fertilization (IVF) of human oocytes were performed during cycles utilizing human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). These early cycles resulted in a successful conception, which unfortunately ended as a tubal gestation. The birth of Louise Brown in 1978, the first successful IVF birth, was actually achieved following fertilization during a spontaneous cycle in which ovulation was triggered with endogenous luteinizing hormone (LH).However, due to the greater margin for error afforded by larger numbers of follicles, the practice of IVF rapidly evolved towards the use of controlled ovarian hyperstimulation (COH) to achieve higher pregnancy rates. It is easy to understand why this approach evolved. Oocyte harvesting was accomplished primarily by laparoscopy. Since oocyte yield per follicle was less than 100% and fertilization rates were limited, the relatively traumatic follicle aspiration process was more likely to result in embryo transfer if a greater number of follicles was present.
The role of intraovarian regulators in the aetiology of polycystic ovarian syndrome
Authors: Almahbobi Ghanim , Trounson Alan O
Published: June 2009

The present review demonstrates that the availability of bioactive FSH and LH in PCOS is normal and that granulosa cells of PCO are not apoptotic and instead hyperexpress functional FSH receptors and may possess intact aromatase activity. Consequently, these cells respond excessively to exogenous FSH stimulation and produce high amounts of oestradiol bothin vivoandin vitro. The altered developmental capacity of follicles from PCOin vivois most likely due to the abnormal follicular milieu of PCO and the culminating effects of intrafollicular inhibitors and stimulators. The failure of ovarian oestradiol production and follicular maturation to dominancein vivomay be due to a mechanism that interferes with the function of FSH, such as intraovarian steroids and growth factors. It has previously been shown that EGF and TGFα have inhibitory actions on follicular development, aromatization and LH receptor formation. In contrast, EGF enhances early follicular recruitment and growth. Therefore, it is hypothesized that EGF/TGFα may have a causal relationship in the mechanisms of anovulatory infertility in women with PCOS. Thus, an aberration in the regulation of follicular fluid EGF and/or TGFα may result in reduced numbers of granulosa cells, cessation of follicle selection and ultimately in the creation and maintenance of PCOS. The exact mechanism by which the hyperfunction of EGF/TGFα occurs and the trigger for this hyperactivity in the ovary remain to be determined. An experimental animal model may be required to assist such investigations in the future.
Matrix metalloproteinases and their tissue inhibitors in endometrial remodelling and menstruation
Authors: Salamonsen Lois A , Woolley David E
Published: June 2009

The architecture of the human endometrium is extensively remodelled during the course of each normal menstrual cycle, unlike most other tissues and organs which undergo very little change during adult life. During menstruation, when loss of most of the functionalis layer occurs, there is concomitant epithelial regrowth; repair of the luminal surface is complete almost as bleeding ceases. During the proliferative phase of the cycle and under the influence of rising oestrogen levels, the stromal cells, glands and blood vessels undergo rapid proliferation which results in tissue thickening. Following ovulation (around day 14 of the idealized 28-day cycle), the secretory phase of the cycle is characterized by increasing tortuosity of the spiral arterioles and glands and increased glandular secretory activity. After about day 22, decidualization of many of the stromal fibroblasts also occurs, the resultant decidual cells having many characteristics typical of epithelial cells. Periods of tissue oedema are apparent both in mid-proliferative (days 8–11) and mid-secretory (days 20–23) endometrium. Late in the cycle, there is regression of the tissue as menstruation is initiated.
Combined continuous hormone replacement therapy: an update
Authors: Udoff Laurence C , Adashi Eli Y
Published: June 2009

A growing body of information now supports the theory that oestrogen replacement therapy can substantially eliminate or attenuate the complications incurred as a result of the menopause. In particular, data support the claim that oestrogen replacement therapy for postmenopausal women is associated with the relief of vasomotor symptoms, the prevention of osteoporosis and urogenital atrophy, a lowering of cardiovascular morbidity and mortality, improved cognitive functioning, and a lower incidence of Alzheimer's disease.
Y Chromosome deletions and male infertility
Authors: de Kretser D M , Mallidis C , Ma K , Bhasin S
Published: June 2009

Approximately one in ten couples experience infertility, and in about 40% of these infertile unions there are abnormalities in the fertility of the male partner. The clinical management of these infertile men is less than satisfactory because in 40% of such patients the cause of the abnormalities of sperm production and quality is unknown. The possibility that genetic disorders may account for a proportion of these disturbances of sperm production has been raised. It is well recognized that chromosomal abnormalities such as Klinefelter's syndrome cause azoospermia and that gene defects are the basis of testicular feminization, Kallman's syndrome and Reifenstein's syndrome. With the explosion in our knowledge of the human genome, the possibility exists that other genetic disorders may form the basis of other sperma-togenic abnormalities. The past decade has witnessed the accumulation of evidence linking abnormalities of the Y chromosome with disturbances in sperm production and these observations form the basis of this review.
Fertilization and embryonic developmental capacity of epididymal and testicular sperm and immature spermatids and spermatocytes
Authors: Lacham-Kaplan Orly , Trounson Alan
Published: June 2009

Spermatogenesis in mammalian species begins after birth. The gonocytes, arrested at G2 of the cell cycle in the foetus, resume mitotic proliferation after birth. As identified in the mouse, the gonocytes migrate towards the periphery of the seminiferous cords at day 4 to day 6 after birth and are located in close contact with the basal lamina. From this stage the gonocytes are referred to as primitive type A spermatogonia. These cells continue mitotic proliferation and differentiate to form type B spermatogonia. By day 10 after birth, many of the type B spermatogonia have formed preleptotene primary spermatocytes which undergo a final phase of DNA synthesis (leptotene) prior to entering meiotic prophase (zygotene).
Sperm surface antigens and the prospects for contraceptive vaccine development
Authors: Saxty Barbara , Aitken John
Published: June 2009

It has been estimated that 500 million couples world-wide have no access to contraception and that approximately 20% of births between 1995 and 2000 will be unwanted. Such statistics have important implications for the rate of world population growth and the possibility of maintaining a sustainable population. Although political change and the empowerment of women across the world will help address these issues, it will also be important to increase the availability of contraceptives; not only the modalities that are in current use, but also novel methods that will satisfy needs that are presently unfulfilled. One such alternative could be a vaccine targeting the human spermatozoon.
Leukocytes: essential cells in ovarian function and ovulation
Authors: Norman RJ , Bonello N , Jasper MJ , Van der Hoek KH
Published: June 2009

The disciplines of reproduction and immunology, once quite discrete, are now closely associated, with compelling evidence to suggest that immune mechanisms play important roles in the cervix, uterus, fallopian tubes and ovary. Cells and mediators classically described as part of the immune system are found throughout the reproductive tract. Disorders of reproduction, including pre-eclampsia, unexplained infertility, endometriosis, recurrent miscarriage and disturbed fetal growth almost certainly have some of their origins in the dysfunction of immune regulation. There appears to be some evidence that immune disorders, such as rheumatoid arthritis and scleroderma, can manifest as infertility, before clinical disease becomes apparent.
Male infertility and the androgen receptor: molecular, clinical and therapeutic aspects
Authors: Yong EL , Wang Q , Tut TG , Ghadessy FJ , Ng SC
Published: June 2009

Idiopathic male infertility has previously been diagnosed imprecisely, and has been treated using regimes that are not based on a clear understanding of the underlying pathophysiology; however, this is gradually changing, and a more rational approach is being adopted. Testosterone and its metabolite, DHT, is allimportant for the maintenance of sperm production and this has led us to examine the AR for causes of male infertility. Some, but not all, androgen-binding studies have indicated that in a certain proportion of cases of male infertility, defective androgen binding occurs. The cloning of the AR gene allowed for a more rigorous examination of the molecular pathogenesis which turned out to be both subtle and heterogeneous. Genetic screening of a large group of men with defective spermatogenesis has indicated that up to 30% of infertile males could have variations in the androgenicity of their AR caused by polymorphisms in the length of the polyglutamine tract. Substitutions of the AR in the LBD and the DBD can also lead to reduced AR function and male infertility. In this regard, it is interesting to note that depressed spermatogenesis and prostate cancer represent opposite ends of the spectrum of AR action (Figure 6). Although empirical treatment of AR mutants in some cases has been shown to restore normal AR function and to improve spermatogenesis, a fully rational basis of treatment has to be based on an understanding of the crystallographic structure of the AR LBD. A full understanding could lead to the construction and the administration of ‘designer’ androgen analogues to treat male infertility caused by mutations of the AR gene.
Endometriosis-associated infertility
Authors: Haney AF
Published: June 2009

Despite intense clinical interest, increasing numbers of infertile couples with endometriosis-associated infertility and ever more sophisticated diagnostic technology, optimal treatment of the infertility remains frustrating. In the absence of mechanical compromise of the pelvic viscera, there is no treatment directed towards the endometriosis itself, medical or surgical, which alleviates the infertility experienced by these couples. The reason for this lack of therapeutic progress is most likely related to the lack of consensus regarding the mechanism(s) by which the endometriosis or its pathophysiology may cause infertility. The possibility that infertility from another, as yet unidentifiable, cause(s) results in repetitive, nonconceptive, ovulatory menstrual cycles and leads to the development of endometriosis remains just as viable a hypothesis. The most useful current therapeutic approach is to consider these couples as having ‘unexplained’ infertility and utilize nonspecific cycle fecundity enhancement such as controlled ovarian hyperstimulation with intrauterine insemination or IVF. Since the fecundity of women with endometriosis in the later reproductive years continues to rapidly decline, this represents their most cost-effective option. While these nonspecific treatments may normalize the cycle fecundity, they are expensive and fraught with the hazards of multiple gestation and ovarian hyperstimulation. While efforts to reduce the risks of this approach are being made, improved therapeutic success with less hazard and cost will continue to remain elusive until the mechanism(s) of the infertility associated with endometriosis is conclusively defined.
A critical evaluation of ovarian tissue cryopreservation and grafting as a strategy for preserving the human female germline
Authors: Shaw JM , Dawson KJ , Trounson AO
Published: June 2009

Ovarian tissue freezing has been used successfully in animals and it has recently begun to be offered clinically to young women who have medical conditions with a high risk of sterility. Although no frozen human ovarian grafts have yet been returned to the donor and resulted in a pregnancy, there are many indications that this procedure should be feasible. Although live young have been derived from frozen grafts in several species, research should aim to make further improvements to the cryopreservation and grafting procedures to optimize follicle survival, and hence minimize the amount of tissue that needs to be collected, stored and returned. Ovarian tissue freezing, particular if used in combination with egg and embryo freezing, should allow a patient to safeguard their chance of becoming a parent later (Table 1). In cases where the patient has a systemic cancer or infection and malignant cells or viruses may be present in the systemic circulation and the gonadal tissue, ovarian tissue could be collected and frozen, but grafting is not currently recommended (Table 3).
Fertility drugs and cancer
Authors: Venn AJ , Healy DL
Published: June 2009

The short-term risks of fertility drug treatment, such as ovarian hyperstimulation syndrome, are well recognised by clinicians providing infertility treatment. There is uncertainty, however, about whether there are any longterm risks such as an increased risk of breast or gynaecological cancer. The possibility of such long-term risks is sometimes a concern for couples who are considering or receiving infertility treatment and their concerns need to be discussed using the best available evidence. The need for appropriate evaluation of long-term health effects of treatment with fertility drugs, including cancer, has been highlighted in major reviews of infertility treatments in Australia and Canada.
Hand in Hand or Under the Thumb? A New Perspective on Social Welfare in Japan
Authors: Rosario Laratta
Published: June 2009

The nature of the relationship between state and nonprofit organisations in Japan is usually described in one of two ways. It is either disparaged as an example of co-optation and state domination, with nonprofit organisations always having been the subservient partner, or lauded as the apotheosis of co-operation and interdependence. By focusing on the historical background of the welfare system in Japan, and particularly on the legal framework in which the nonprofit sector has developed, this paper attempts to explain how each has influenced the other and highlights key factors which may have been underestimated or misinterpreted in the past.
Social Policy and Cultural Services: A Study of Scottish Border Museums as Implementers of Social Inclusion
Authors: McCall Vikki
Published: June 2009

This article examines the findings of an exploratory case study based on local authority museums in the Scottish Borders to assess the impact of social inclusion policies from the Scottish Parliament. Taken from museum curators' perspectives, the findings suggest that social inclusion policies have not filtered through the system to reach the curators due to unclear government policy and confusion regarding terminology, strategy and guidelines. Curators found it difficult to engage with social inclusion discourse, despite employing socially inclusive actions in everyday practice. The relationship between the local community and museum was seen to be unique and multi-layered, with a perceived dimension of community ownership, which has implications for social policy on central, local and individual levels.
Challenging Boundaries to ‘Employability’: Women Apprentices in a Non-Traditional Occupation
Authors: Andrew Alison
Published: June 2009

This article is based on a case study of women apprentices and workers in a ‘non-traditional’ occupation for women, engineering construction. The article argues that the concept of ‘employability’ is not gender neutral, and that gendered assumptions about who is and is not ‘employable’ for particular work can disadvantage women seeking training and work in non-traditional industries or dissuade them from applying to do so. Approaches to employability which emphasise individual attributes underplay the significance of gender inequalities and wider discourses of gender.
Devolution and Entrenched Household Poverty: Is Scotland Less Mobile?
Authors: Morelli Carlo , Seaman Paul
Published: June 2009

The Scottish National Party led Scottish Government has identified household poverty as a key focus for its anti-poverty strategy. The government's ‘Solidarity Target’ seeks to both increase wealth and increase the share of total income gained by the bottom three deciles. The ability to demonstrate the advantages of policy divergence within Scotland, relative to the other parts of the United Kingdom, is central to the government's aim of gaining support for increased powers for the devolved government. This paper seeks to provide evidence on one aspect of the government's anti-poverty strategy: the degree to which Scotland differs from the rest of the UK over levels of entrenched poverty. The paper demonstrates that not only does Scotland have greater entrenched poverty but that the changes in mobility since the 1990s have impacted on Scotland to a lesser degree than the rest of the UK.
Poverty and Social Justice in the Devolved Scotland: Neoliberalism Meets Social Democracy?
Authors: Scott Gill , Mooney Gerry
Published: June 2009

Drawing on current debates in social policy, this paper considers the extent to which social justice has and is informing social policy making in devolved Scotland. Relating to the work of social justice theorists Young, Fraser and Lister in particular, it critically examines some key Scottish social policy measures since 1999, considering some of the ways in which these have been constructed in terms of social justice and which make claims to the Scottish national. Through a focus on the issue of anti-poverty policies, the paper explores the ways in which the dominant policy approaches of the Scottish Government have reflected an uneven and tension-loaded balance between the enduring legacies of Scottish social democracy and the influences of neoliberal economics.
Introduction: Social Policy in the Devolved Scotland: Towards a Scottish Welfare State?
Authors: Mooney Gerry , Wright Sharon
Published: June 2009

Ten years have passed since devolution was implemented for Scotland, Wales and Northern Ireland. This anniversary is worthy of note for all scholars of UK social welfare, not just those with a specialist interest in political reform or the ‘Celtic’ nations, because reflection on the first decade of devolution inspires a rethink of some of the basic working assumptions of social policy analysis (see below, also Mooney et al., 2006), for example the extent to which the notion of a UK welfare state remains meaningful (cf. McEwen and Parry, 2005). This themed section provides an opportunity to consider the impact of devolution on broader understandings of polity, policy and practice as well as pointing to further possible divergences in and across the UK. These are explored in relation to key areas of social welfare intervention in Scotland, focussing particularly on poverty, inequality and social justice; immigration and the experiences of labour migrants in rural areas; the use of private finance; key literature and useful sources.
Review Article:Social Policy in Scotland Since Devolution
Authors: Viebrock Elke
Published: June 2009

With the advent of devolution, it is increasingly difficult to talk about a unitary UK social policy as policy developed by the Parliament in Westminster does not apply automatically or equally to the non-English UK nations. Devolution in 1999 created not only opportunities for increasing policy divergence across the UK, but has provided the potential for more research specifically focussed on Scotland. These opportunities are clearly reflected in the growing body of literature in recent years on devolution in general and its impact on various policy fields. This article considers the effects of devolution on social policy in Scotland since 1999. The aim of this review is to identify the key literature and to present the main debates and findings from relevant research.
The complexities of negotiating governance change: introducing managerialism in Italy
Authors: TOUSIJN WILLEM , GIORGINO VINCENZO MARIO BRUNO
Published: June 2009

Since the beginning of the 1990s, health policy in Italy has been characterised by continuous reform as reflected by the frequency of new measures. Importantly, the reforms have changed considerably many aspects of the health-care system, including the governance of medical performance. The new measures fall into two types: regionalisation and transformation of local providers into ‘health-care enterprises’. In relation to the governance of medical performance, more specifically, the reforms have entailed the introduction of budgeting and quality assurance, the creation of new managerial roles, and the transformation of existing roles, as well as the introduction of new mechanisms for evaluating medical performance. In terms of the specific forms of governance, the reforms have reinforced hierarchy-based forms of governing intermeshed with party governance, and have re-defined professional self-regulation by strengthening collective forms of professional self-regulation. The design and implementation of the reforms are subject to a complex process of negotiation, which involves a wide range of actors spread across different levels of governance and takes place in relation to all aspects of the governance of medical performance.
Antipsychotika
Authors: Cattapan-Ludewig Katja , Seifritz Erich
Published: June 2009

Antipsychotika werden in Substanzen der ersten (konventionell, sogenannt typisch) und zweiten Generation (modern, sogenannt atypisch) unterteilt. Aufgrund des Wirkungs- und Nebenwirkungsprofils gelten die Substanzen der zweiten Generation als Mittel der Wahl bei Schizophrenie und Psychosen. Antipsychotika der ersten und zweiten Generation werden auch in der Akuttherapie der Manie, die der zweiten Generation zudem als Erhaltungstherapie der bipolaren Erkrankung eingesetzt. Einige Substanzen der zweiten Generation zeigten sich zudem effektiv in der Akutbehandlung der bipolaren Depression und als Augmentation zu einem Antidepressivum bei unipolaren Depressionen. Des Weiteren existiert in der klinischen Praxis ein großer „off-label“-Gebrauch von Antipsychotika, z. B. bei Persönlichkeitsstörungen. Neben der oralen Darreichungsform gibt es Antipsychotika auch zur parenteralen Anwendung, zur schnell wirksamen Akutbehandlung oder als Depotpräparat. Das Nebenwirkungsprofil der Antipsychotika der ersten Generation umfasst insbesondere extrapyramidal-motorische Nebenwirkungen. Die Antipsychotika der zweiten Generation bilden hinsichtlich Wirkung und Nebenwirkung eine sehr heterogene Gruppe. Einige Substanzen aus dieser Gruppe können insbesondere zu Gewichtszunahme und einem metabolischen Syndrom führen.
Stimmungsstabilisierer
Authors: Hatzinger Martin
Published: June 2009

Beschränkte sich in der herkömmlichen Sichtweise die bipolare Erkrankung auf die manisch-depressive Krankheit, so erfuhr das Diagnosekonzept in den letzten Jahren mit der Einführung der möglichen Diagnosestellungen im Rahmen des bipolaren Spektrums eine erhebliche Erweiterung. Dementsprechend sind diese Erkrankungen sehr viel weiter gefasst und treten gegenüber den früheren Konzepten in einer deutlich höheren Prävalenz in der Allgemeinbevölkerung auf. Für die differenzielle Wahl eines Stimmungsstabilisierers kristallisierte sich hierbei die Einteilung des klinischen Verlaufes in Bipolar I und II mit oder ohne Rapid Cycling als wichtiges Kriterium heraus. Zudem spielt das psychopathologische Erscheinungsbild z. B. euphorische versus dysphorische Manie, und der Schweregrad, sowie die Intensität des Langzeitverlaufs (Phasenfrequenz) eine wichtige Rolle für die Indikationsstellung. Lithium und Valproat sind Mittel der ersten Wahl, wobei in Spezialfällen heute auch Lamotrigin als erste Wahl aufgeführt wird. Carbamazepin hingegen wird aufgrund der Datenlage und des Nebenwirkungsprofils zunehmend zurückhaltender als First-line Medikation eingesetzt. In den letzten Jahren wurden viele neuere atypische Antipsychotika mit einer Indikation im bipolaren Störungsbereich untersucht. Einige davon sind für die Akutbehandlung insbesondere der Manie, aber auch der Depression zugelassen, teilweise liegen auch Daten zur Langzeitprophylaxe vor. Die psychopharmakologischen Indikationen zum differenziellen Einsatz von Stimmungsstabilisierern sind dementsprechend komplex geworden und bedürfen klarer Richtlinien.
Aktuelle Therapiemöglichkeiten von Angststörungen
Authors: Delini-Stula Alexandra , Holsboer-Trachsler Edith
Published: June 2009

Für die Behandlung von Angststörungen steht eine breite Palette von Präparaten aus verschiedenen chemischen und pharmakologischen Klassen und mit unterschiedlichen Wirkungsmechanismen zur Verfügung. Die Kriterien für eine optimale, ideale Therapie, d.h. schnelle und zuverlässige Wirkung, kein Missbrauch und Abhängigkeitspotential, geringe systemische Toxizität und eine allgemein gute Verträglichkeit, werden durch kein Präparat vollständig erfüllt. Die Auswahl des geeigneten Pharmakons orientiert sich in der Regel an der Anzahl der klinischen Studien für die Wirksamkeit und am Nebenwirkungsprofil sowie am Ausprägungsgrad der Angststörung. Die Vorteile von Benzodiazepinen – schneller Wirkungseintritt und fehlende systemische Toxizität – werden eingeschränkt durch die Gefahr des potentiellen Missbrauches und der Abhängigkeit. Bei den Antidepressiva sind der langsame Wirkungseintritt, zahlreiche Nebenwirkungen und Interaktionen zwar kompensiert durch fehlenden Missbrauch und Abhängigkeit, aber sind limitierende Faktoren in den akuten oder Notfallsituationen. Kombinationstherapien von Antidepressiva und Benzodiazepinen sowie spezifischer Psychotherapie können die Responserate erhöhen. Die Entwicklungsstrategien von neuen Behandlungsverfahren basieren auf neuen pathophysiologischen Erkenntnissen und lassen auf gezieltere Substanzen hoffen.
Antidementiva
Authors: Müller-Spahn Franz , Sollberger Daniel , Wollmer Axel
Published: June 2009

Die Behandlung von Demenzkranken umfasst verschiedene Therapiekomponenten. Dazu zählen im Wesentlichen die Besserung der Hirnleistungsstörungen, die Besserung der Alltagskompetenz sowie die Verminderung der Verhaltensauffälligkeiten. Die Therapieziele ändern sich in Abhängigkeit vom Schweregrad der Erkrankung. Häufig dominieren Verhaltensauffälligkeiten, die die kognitive Leistungsfähigkeit zusätzlich beeinträchtigen. Eine kausale Therapie der Alzheimer-Demenz steht uns heute nicht zur Verfügung. Aus den Erkenntnissen der molekularen Biologie ergeben sich jedoch hoffnungsvolle, neue Therapieansätze, die sich im Wesentlichen auf den Amyloid- und Tau-Protein-Stoffwechsel konzentrieren. Therapeutische Angriffspunkte zielen auf die Hemmung der Amyloid-Bildung, den Abbau von Plaques, die Hemmung der Amyloid-induzierten Neurotoxizität, die Hemmung der Neurofibrillenbildung sowie die Förderung des Nervenzellwachstums ab. Am Erfolg versprechendsten dürfte die Immunisierung gegen Aβ als Antigen oder die Gabe von monoklonalen Antikörpern zukünftig sein.Die Wirksamkeit von Acetylcholinesterase-Hemmern wurde für die leichte bis mittelgradig ausgeprägte Alzheimer-Demenz in vielen klinischen Studien belegt. Sie bewirken eine zeitlich begrenzte Verzögerung der Symptomprogression und gelten heute als Mittel der ersten Wahl. Die Wirksamkeit von Memantin wurde für die Behandlung der mittelschweren und schweren Alzheimer-Demenz nachgewiesen.Dagegen ist die wissenschaftliche Datenlage zur Behandlung der vaskulären Demenz deutlich schwächer. Kontrollierte Studien mit positiven Effekten liegen für alle derzeit verfügbaren Cholinesterase-Hemmer sowie für Memantin vor. Nicht medikamentöse Therapieverfahren sind unverzichtbare Behandlungsbausteine und orientieren sich im Wesentlich an dem jeweiligen Krankheitsstadium. Die wissenschaftliche Datenlage zur Wirksamkeit und Verträglichkeit von Neuroleptika bei Demenzkranken ist ungeachtet der enormen Verordnungszahlen insgesamt unzureichend. Deshalb wird nach wie vor eine strenge individuelle Nutzen-Risiko-Abwägung vor allem unter Berücksichtigung kardio-vaskulärer Besonderheiten und des substanzspezifischen Nebenwirkungspotenzials empfohlen.
Therapie der Insomnie
Authors: Hemmeter Ulrich Michael , Thum Andreas
Published: June 2009

Schlafstörungen treten sehr häufig in der Bevölkerung auf (bis zu 35 %). Ein gestörter Schlaf kann zu Störungen der kognitiven Leistungsfähigkeit und der Tagesbefindlichkeit, aber auch zu metabolischen Störungen führen. Bereits vorbestehende körperliche und mentale Erkrankungen können durch die Insomnie intensiviert werden. Das Erkennen einer Schlafstörung und deren diagnostische Einordnung ist daher von großer Relevanz. Die Behandlung von Schlafstörungen richtet sich nach deren Ätiologie und Intensität. Bei sekundären Insomnien steht immer die Behandlung der Grunderkrankung an erster Stelle. Es kann aber auch eine unmittelbare parallel beginnende, spezifische Therapie der Insomnie begleitend notwendig sein. Vor Beginn einer symptomatischen Pharmakotherapie sollte in jedem Fall die Möglichkeit nicht-pharmakologischer Interventionen geprüft werden. An medikamentösen Behandlungen stehen für die zeitlich limitierte Behandlung primär die Nicht-Benzodiazepinhypnotika zur Verfügung. Bei längerfristig notwendiger Therapie können schlafanstoßende Antidepressiva und auch hypnotisch wirksame Neuroleptika (jeweils ohne anticholinerge Komponente) eingesetzt werden. Klassische Benzodiazepine, Antihistaminika und Medikamente mit anticholinerger Wirksamkeit sind aufgrund des Nebenwirkungsspektrums insbesondere bei längerfristiger Behandlung und bei älteren Patienten zu vermeiden.
Pharmakotherapie von Abhängigkeits- und Entzugssyndromen
Authors: Walter Marc , Wiesbeck Gerhard A.
Published: June 2009

Störungen durch psychotrope Substanzen umfassen im engeren Sinn die akute Intoxikation, den schädlichen Gebrauch, die Abhängigkeit sowie die Entzugssyndrome. Im erweiterten Sinn können komorbide psychische Störungen sowie somatische Folgeschäden auftreten. In der Akutbehandlung erfolgen zunächst die Entgiftung und der Entzug psychotroper Substanzen, anschließend dienen die medikamentöse Rückfallprophylaxe oder eine Substitutionsbehandlung zur Stabilisierung bei bestehender Abhängigkeitserkrankung. Die Pharmakotherapie ist neben den psychosozialen Therapien ein entscheidender Grundpfeiler in der Behandlung der Abhängigkeitserkrankungen und Entzugssyndrome. In dieser Übersicht werden evidenzbasierte medikamentöse Behandlungsstrategien der häufigsten substanzbezogenen Störungsbilder anhand aktueller Leitlinien beschrieben und diskutiert. Für die Alkoholabhängigkeit werden langwirksame Benzodiazepine oder Clomethiazol im Entzug sowie Acamprosat und Naltrexon für die Rückfallprophylaxe empfohlen. Für die Cannabisabhängigkeit existieren bisher noch keine etablierten pharmakotherapeutischen Konzepte zur Rückfallsprophylaxe. Für die Kokainabhängigkeit besteht die grösste Evidenz im Entzug für antriebssteigernde trizyklische Antidepressiva. Auch für die Kokainabhängigkeit gibt es derzeit noch keine ausreichend gesicherte Evidenz für eine Rückfallprophylaxe. Stimmungsstabilisierer wie Topiramat und Tiagabin sowie Disulfiram stellen hier Behandlungsalternativen dar. Gesichert ist die Gabe von Methylphenidat für die Kokainabhängigkeit bei komorbider Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung. Für die Opioidabhängigkeit stellt die Substitutionsbehandlung mit Methadon oder Buprenorphin die Therapie der ersten Wahl dar. Für die Tabakabhängigkeit kann die Nikotinersatztherapie für den Entzug und die medikamentöse Behandlung mit Bupropion oder Vareniclin als Rückfallprophylaxe empfohlen werden.
Psychopharmaka in Schwangerschaft und Stillzeit – Risiken und Möglichkeiten bei Frauen mit einer bipolaren affektiven Störung
Authors: Krüger Stephanie
Published: June 2009

Für Frauen mit einer bipolaren Erkrankung sind Schwangerschaft und Postpartumperiode mit einem erhöhten Risiko für neue, vor allem depressive Episoden verknüpft. Oftmals bleiben diese Episoden unerkannt, so dass die Symptomatik schwerer wird, unter Umständen sogar chronifiziert, und Mutter und Kind einem unnötigen Risiko aussetzt. Auf der anderen Seite muss in den ersten 12 Wochen der Schwangerschaft berücksichtigt werden, dass jede medikamentöse Behandlung das Kind gewissen Risiken aussetzt, so dass einer Entscheidung für oder gegen eine Pharmakotherapie der bisherige Krankheitsverlauf und die Schwere der aktuellen sowie vorangegangener Episoden zugrunde gelegt werden sollten. Die Planung der Schwangerschaft ist dabei unabdingbar, denn die Organogenese ist zum Zeitpunkt des Bekanntwerdens der Schwangerschaft für die meisten Organe schon so weit vorangeschritten, dass teratogene Schäden bedingt durch Psychopharmaka meist schon entstanden sind. Das bedeutet, dass man schon bei jungen Frauen mit affektiven Störungen, selbst wenn diese noch keinen Kinderwunsch haben, die Sensibilität für dieses Thema wecken muss, damit Schwangerschaften nicht ungeplant entstehen und Mutter und Ungeborenes nicht einem unnötigen Risiko ausgesetzt werden. Im Hinblick auf die „klassischen“ Phasenprophylaktika ist Lithium neben Lamotrigin eine der sichersten Substanzen, wobei letzteres nicht zur Prophylaxe einer Bipolar-I Störung geeignet ist und es Hinweise auf ein erhöhtes Risiko für Schäden des Gesichtsschädels gibt. Valproinsäure birgt ein erhöhtes Risiko für Neuralrohrdefekte, allerdings ist die Höhe dieses Risikos dosis- und darreichungsformabhängig. In Bezug auf eine antidepressive Therapie in der Schwangerschaft ist es wichtig, sich vor allem mit den perinatalen Komplikationen der Antidepressiva auseinanderzusetzen, denn bezüglich teratogenes Sicherheitsprofil sind die meisten Substanzen sicher, soweit das die bisherige Datenlage zeigt. Peri- und postpartal besteht ebenfalls ein erhöhtes Risiko für affektive Störungen. Hier reicht das Spektrum von kurzen Auffälligkeiten, die ohne Behandlung wieder abklingen, bis hin zu schweren postpartalen psychotischen Störungen. Die Therapie richtet sich hier vor allem nach dem Stillwunsch der Mutter.
Pflegebedürfnisse nierentransplantierter Jugendlicher: eine deskriptive Querschnittstudie in einem Schweizer Spital
Authors: Kleinknecht Michael , Neuhaus Thomas J. , Landolt Markus A.
Published: June 2009

Verschiedene Studien weisen darauf hin, dass die 5-Jahres-Transplantat-Überlebensrate bei Jugendlichen nach einer Nierentransplantation signifikant geringer ist als bei jüngeren Patienten. Eine Ursache dafür kann die mangelnde Einhaltung der Behandlungsvorgaben sein. Es gibt empirische Hinweise, dass Pflegefachleute nierentransplantierte Jugendliche in ihrer Lebenssituation unterstützen können und sich dies positiv auf die Einhaltung der Behandlungsvorgaben auswirkt. Ziel der Studie war, Kenntnisse über die Themen zu erhalten, zu denen nierentransplantierte Jugendliche von Pflegefachleuten Unterstützung erwarten und wie wichtig diese sind. Dazu wurden in einer deskriptiven Querschnittserhebung 27 Jugendliche im Alter von zwölf bis 18 Jahren anhand eines in einer Fokusgruppe entwickelten Fragebogen interviewt. Die 43 vorgegebenen Themen wurden von den Jugendlichen mit einem Stimmenanteil von 20 % bis 100 % als «sehr wichtig» eingestuft. Es zeigte sich, dass die Informationen über die Krankheit und Behandlung am wichtigsten sind, gefolgt von der Unterstützung durch das technisch-organisatorische Behandlungs- und Betreuungsangebot sowie den Informationen und der Unterstützung zur persönlichen Lebensweise und -gestaltung. Diese Themen können als Set allgemein pflegerelevanter Variablen angesehen werden, die für das fokussierte Assessment und die Planung der Pflege in der Praxis eingesetzt werden können. Damit die Studienergebnisse praktisch zum Tragen kommen und Adoleszente von Pflegefachleuten in ihrer Lebenssituation unterstützt werden können, ist es notwendig, entsprechende Pflegestrategien sowie Patienten- und Familien-Schulungskonzepte zu erarbeiten.
Screening-Verfahren zur Identifikation einer Dysphagie bei älteren Menschen – Ein systematischer Literaturüberblick
Authors: Simon Mario , Reuther Sven , Schreier Maria Magdalena , Bartholomeyczik Sabine
Published: June 2009

Ältere Menschen haben aufgrund altersphysiologischer Veränderungen und der Häufung neurologischer Erkrankungen ein erhöhtes Risiko, an Schluckstörungen zu leiden. Die Folgen davon können Mangelernährung, Dehydratation und nicht selten lebensbedrohliche Pneumonien durch die Aspiration von festen und flüssigen Nahrungsbestandteilen in das respiratorische System sein. Dysphagie stellt daher für Pflegende in Alten- und Pflegeheimen eine Herausforderung dar. Ziel dieser Literaturübersicht ist es, geeignete Screening-Instrumente zur Erfassung eines Risikos für Schluckstörungen zur Nutzung von Pflegenden zu ermitteln und deren Anwendbarkeit in der Praxis zu beurteilen. Dafür wurden die Datenbanken CINAHL®, Ovid Medline® und EMBASE® nach Screening-Instrumenten durchsucht und nach definierten Auswahlkriterien 10 Instrumente in die Analyse einbezogen. Die meisten Instrumente wurden von logopädischen Experten entwickelt, lediglich zwei Instrumente stammen von Pflegewissenschaftlern. Alle Instrumente enthalten einen Schlucktest und fokussieren auf Patienten mit einem Apoplex in der Akutphase. Weitere Kriterien, die bei der Ermittlung einer Schluckstörung eine Rolle spielen, sind z. B. der Gesundheitszustand, die Einnahme von Psychopharmaka und die Körperhaltung. Alle Instrumente werden als einfach in der Anwendung beschrieben. Sie sind hinsichtlich ihrer Güte getestet, aber zumeist für den Einsatz in der stationären Altenpflege nicht geeignet. Die zwei von Pflegewissenschaftlern entwickelten Instrumente können nur bedingt für die Zielgruppe der Bewohner in Alten- und Pflegeheimen empfohlen werden, da beide Instrumente nicht bei betagten Menschen getestet wurden und nur von einem Instrument zufriedenstellende Werte zur Reliabilität und Validität vorliegen. Daher sollten ein für die Zielgruppe orientiertes Screening-Verfahren sowie entsprechende Schulungsmaßnahmen für Pflegende entwickelt werden.
Possible relationship between nonvolcanic tremor and the 1998–2001 slow slip event, south central Alaska
Authors: Peterson Chloe L. , Christensen Douglas H.
Published: June 2009

We document the occurrence of nonvolcanic tremor (NVT) in south central Alaska for 3 months of each year between 1999 and 2001 to provide a first‐order attempt to understand the relationship between NVT and a large slow slip event that occurred over a 2 to 3 year period between 1998 and 2001. The majority of the NVT signals observed after the onset of the slow slip event are bursts lasting between 10 and 15 min with frequencies ranging from 1 to 6 Hz. By the summer of 2001 the quantity of NVT has decreased dramatically from the previous summers, and episodes rarely last up to 10 min. The decrease in NVT activity in the summer of 2001 is coincident with the end of the slow slip event. There is a clear spatial correlation between the observed NVT and the slow slip event, with most of the NVT events located on the downdip edge of the region of highest slip. Depth estimates range widely over the region, with approximately half concentrated near the interpreted North America‐Yakutat/Pacific plate interface and the remainder located above the plate interface. However, owing to inadequate station coverage and poor knowledge of the local structure, determining accurate depths is difficult and thus the relationship between the NVT and the plate interface is problematic. This is the first study giving evidence that the relationship between slow slip events and NVT seen in Cascadia and southwest Japan may also exist in Alaska.
Automated Solar Activity Prediction: A hybrid computer platform using machine learning and solar imaging for automated prediction of solar flares
Authors: Colak T. , Qahwaji R.
Published: June 2009

The importance of real‐time processing of solar data especially for space weather applications is increasing continuously. In this paper, we present an automated hybrid computer platform for the short‐term prediction of significant solar flares using SOHO/Michelson Doppler Imager images. This platform is called the Automated Solar Activity Prediction tool (ASAP). This system integrates image processing and machine learning to deliver these predictions. A machine learning‐based system is designed to analyze years of sunspot and flare data to create associations that can be represented using computer‐based learning rules. An imaging‐based real‐time system that provides automated detection, grouping, and then classification of recent sunspots based on the McIntosh classification is also created and integrated within this system. The properties of the sunspot regions are extracted automatically by the imaging system and processed using the machine learning rules to generate the real‐time predictions. Several performance measurement criteria are used and the results are provided in this paper. Also, quadratic score is used to compare the prediction results of ASAP with NOAA Space Weather Prediction Center (SWPC) between 1999 and 2002, and it is shown that ASAP generates more accurate predictions compared to SWPC.
Exhumation history of the Higher Himalayan Crystalline along Dhauliganga‐Goriganga river valleys, NW India: New constraints from fission track analysis
Authors: Patel R. C. , Carter A.
Published: June 2009

New apatite and zircon fission track data collected from two transects along the Dhauliganga and Goriganga rivers in the NW Himalaya document exhumation of the Higher Himalayan Crystalline units. Despite sharing the same structural configuration and rock types and being separated by only 60 km, the two study areas show very different patterns of exhumation. Fission track (FT) data from the Dhauliganga section show systematic changes in age (individual apatite FT ages range from 0.9 ± 0.3 to 3.6 ± 0.5 Ma,r2= 0.82) that record faster exhumation across a zone that extends from the Main Central Thrust to north of the Vaikrita thrust. By contrast, FT results from the Goriganga Valley show a stepwise change in ages across the Vaikrita thrust that suggests Quaternary thrust sense displacement. Footwall samples yield a weighted mean apatite age of 1.6 ± 0.1 Ma compared to 0.7 ± 0.04 Ma in the hanging wall. A constant zircon fission track age of 1.8 ± 0.4 Ma across both the footwall and hanging wall shows the 0.9 Ma difference in apatite ages is due to movement on the Vaikrita thrust that initiated soon after ∼1.8 Ma. The Goriganga section provides clear evidence for >1 Ma of tectonic deformation in the brittle crust that contrasts with previous exhumation studies in other areas of the high Himalaya ranges; these studies have been unable to decouple the role of climate erosion from tectonics. One possibility why there is a clear tectonic signal in the Goriganga Valley is that climate erosion has not yet fully adjusted to the tectonic perturbation.