bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal illness and drug use in pregnancy
Authors: Elwood Mark , Little Julian , Elwood Harold 
Published: November 2023

Abstract
If neural tube defects, or even a small proportion of them, were caused either by illness in the mother, or by drugs used in pregnancy, identification of such hazards could be followed rapidly by preventive actions. Studies on both these topics have been difficult: they consist of observations of associations in time and place between such exposures and the occurrence of defects (particularly prone to difficulties of other, confounding, effects); retrospective studies comparing mothers of affected and of unaffected infants (prone to recall bias); and prospective studies comparing exposed with unexposed mothers (a strong design, but one requiring very large numbers of pregnancies to give reliable information). When an association is seen, it is very difficult to separate the effects of an illness from those of drugs used to treat that illness. Moreover, many studies are not powerful enough to show or to exclude an association specific to neural tube defects, and information on major congenital defects in aggregate must be used. As well as the problems inherent to individual studies, assessing the evidence on reproductive hazards is made more difficult by publication bias, i.e. the information which is published may not be representative of all that is available. This has been demonstrated in regard to the reproductive effects of cocaine; Koren et al. (1989) have shown that abstracts on this topic showing adverse effects were more often accepted by a major paediatric society than those showing no such effects, although in terms of size and detail, the negative studies were better.
Ethical and legal issues
Authors: Campbell Alastair 
Published: November 2023

Abstract
A quite remarkable array of both moral and legal issues is raised by the subject matter of this book. The most obvious are termination of pregnancy for fetal abnormality and selective non-treatment of handicapped neonates. But in addition, questions are raised concerning the allocation of resources, the ethics of research into primary prevention, parental rights in both the reproduction and the treatment of their offspring, social versus individual benefit in screening programmes, and ethical dilemmas in organ transplantation. In many of these topic areas there is an absence of clear and agreed guidelines. Perhaps for this reason, debate about the moral values at stake may seem inconclusive, if not futile. Yet, without such debate, decisions may be taken in a haphazard fashion, without a proper regard for their effects on the health and welfare of individuals, families, and the society as a whole. A survey of the ethical and legal debate must inevitably reveal a diversity of opinion and will provide few, if any, simple answers. On the other hand, it can serve to delineate the options for both legislative controls and ethical guidelines, and may assist the decisions taken by parents and their professional helpers. The topics discussed in this chapter will be dealt with in a roughly sequential fashion, beginning with the prenatal dilemmas involved in prevention prior to conception, screening, prenatal diagnosis, and genetic counselling, moving on to the debate about selective termination of pregnancy, and concluding with the postnatal dilemmas raised by non-treatment of affected neonates and the use of anencephalic infants as organ sources. A concluding section of the chapter will give a more general overview of the ethical and legal debate.
Conclusions
Authors: Elwood Mark , Little Julian , Elwood Harold 
Published: November 2023

Abstract
A great deal of progress into the control of neural tube defects has been made in the last decade. Antenatal diagnosis, with the choice of an induced abortion being given, is now routinely offered to high risk mothers in many countries, and is provided as a population based screening service in many moderate and high risk areas, particularly in the UK. Antenatal diagnosis in the UK has dramatically reduced the prevalence at birth of anencephalus, and very considerably reduced that of open spina bifida. Screening using a combination of alpha-fetoprotein measurements and ultrasound can lead to very high detection rates with very few false positives.
Cigarette smoking and the risk of age-related fractures
Authors: Cooper Cyrus , Wickham Carol 
Published: November 2023

Abstract
Age-related fractures constitute a major public health problem. Their incidence depends on osteoporosis and the risk of falling. Evidence exists to support an association between cigarette smoking and fracture risk. The strength of this association, however, varies with type of fracture, being stronger for vertebral than hip fracture. A clear understanding of the relationship between smoking and these fractures is fundamental to the design of preventive strategies.
The sky is the limit—prospects for the future
Authors: Ellencweig Avi Yacar 
Published: November 2023

Abstract
For those looking for ways to simplify the study of health systems and to benefit from easy comparisons, this book brings no salvation. Perhaps a typology classifying health systems into a few prototypes would be more appealing. However, as we noted before, in our view the application of such typology is not realistic. Health systems simply are not adaptable to simplistic presentations based on a small number of descriptive dimensions. Based on our understanding that there is little sense in comparing health systems as such, we have suggested that modules be compared instead, since—according to our model—the modules make up the health system. Now, a crucial question remains unanswered: Can we still predict the future development of a health system based on our partial knowledge of these components called modules? Well, the answer is definitely yes. In this concluding chapter, we shall examine the effects of trends in health systems and seek to understand their implications for the future of these systems. We shall discuss these trends in relation to each separate module of our model and in the order dictated by our discussion in previous chapters.
Treatment of hypochondriasis
Authors: Warwick Hilary M C 
Published: November 2023

Abstract
This chapter concentrates on patients who fulfil the criteria for a particular sub category of somatoform disorder, hypochondriasis. It focuses especially on hypochondrias unaccompanied by other major psychiatric disorder, so-called primary hypochondriasis. The status of this category as a distinct syndrome subgroup remains controversial (Barsky, et al. 1992).
Chlamydia-induced arthritis
Authors: Zeidler Henning K , Schumacher H Ralph 
Published: November 2023

Abstract
An aetiological connection between urogenital infections with Chlamydia trachomatis and arthritis has long been presumed, but chlamydia! antigen in synovium and synovial fluid was only recently identified in patients with Reiter’s syndrome, sexually acquired reactive arthritis, and undifferentiated seronegative oligoarthritis (Ishikawa et al. 1986; Keat et al. 1987; Schumacher et al. 1988; Taylor-Robinson et al. 1988). Meanwhile, an increasing number of investigations have confirmed the presence of chlamydia! antigens, nucleic acid, and chlamydia-like particles in arthritic joints, which has led to the present view of an intraarticular inapparent infection with viable, non-culturable or difficult to culture Chlamydia (Bas et al. 1995; Beutler et al. 1994; Hammer et al. 1992; Mascia et al. 1992, Rahman et al. 1992a; Taylor-Robinson et al. 1992).
Spondyloarthropathies in children and adolescents
Authors: Rosenberg Alan M , Petty Ross E 
Published: November 2023

Abstract
With the emergence of rheumatology as an established paediatric subspecialty, it has become increasingly apparent that a wide spectrum of rheumatic diseases afflict children more frequently than had been appreciated previously. The spondyloarthropathies, once believed to occur almost exclusively in adults, are now recognized as frequently having their onsets during childhood and adolescence. In this chapter the clinical characteristics of childhood spondyloarthropathies are discussed and advances in diagnosis and management are considered.
Urinary Tract Defects and Chromosomal Disorders
Authors: Amor David J , Crespigny Lachlan De , Gardner R J Mckinlay 
Published: November 2023

Abstract
Chromosomal abnormality may be constitutional or acquired. A constitutional abnormality is present at conception (or at least from embryogenesis), and typically affects the morphogenesis of organs. An acquired abnormality arises somatically, in a person whose constitutional karyotype may be normal or (more rarely) abnormal, and cancer is the classical example. In this chapter, we focus largely on the constitutional case, but do not ignore acquired abnormalities.
Cystic Renal Diseases
Authors: Saggar-Malik Anand K 
Published: November 2023

Abstract
Renal cysts may result from a variety of causes. Table 11.1 shows a simple classification of renal cystic kidney disease. A diagnosis of multiple renal cysts is often confused with autosomal dominant polycystic kidney disease (ADPKD) which is a very common inherited cystic renal disease (Chapter 11). The clinical picture together with the location of the cyst may help in the differential diagnosis (see Table 10.1).
Trial-based economic evaluations: an overview of design and analysis
Authors: Glick Henry A , Polsky Daniel P , Schulman Kevin A 
Published: November 2023

Abstract
In response to increasing health care costs, countries around the world have been exploring methods for their control. At the more macro level, responses have included greater risk sharing between payers, providers, and patients as well as a greater reliance on market-oriented incentives. At the more micro-level, government regulators, health care providers, members of managed care formulary committees, payers, and patients have begun to evaluate the value for the cost of individual medical therapies.
Handling uncertainty in economic evaluation and presenting the results
Authors: Briggs Andrew H 
Published: November 2023

Abstract
Economic evaluations of health care interventions are increasingly common, with the growth of the economic evaluation literature now widely documented (Pritchard 1998; Briggs and Gray 1999; Stone et al.2000). Uncertainty in economic evaluation is pervasive, entering the evaluative process at every stage. It is useful to distinguish uncertainty related to the data requirements of a study (the resource use and health outcome consequences of a particular intervention and the data required to value those consequences) from uncertainty related to the process of evaluation.
Molecular basis of macrophage activation: from gene expression to phenotypic diversity
Authors: Hamilton T A 
Published: November 2023

Abstract
Mononuclear phagocytes represent a host-wide system of cells which provide a broad range of physiologically important services (Adams and Hamilton, 1984, 1992a; Nathan and Cohn. 1995: Van Rooijen et al., 1996; Bosque et al., 1997; Gordon. 1998). Not surprisingly, members of this cell system can exhibit a diverse array of characteristics. The mononuclear phagocyte lineage develops in the bone marrow and, following entry into the circulation, seeds essentially all tissues. Thus, under resting conditions, the differences between macrophages in different organ locations are likely to result from developmental signals encountered within individual tissue sites. Such differences are not the consequence of ‘activation’ as they reflect the specific physiology of each tissue and are stable over time. Examples of such developmentally distinct mononuclear phagocyte populations include microglia. Kupffer cells, splenic macrophages and the spectrum of myeloid dendritic cells.
Macrophages in bacterial infection
Authors: Heale J -P , Speert D P 
Published: November 2023

Abstract
Bacterial pathogens must breach normal host defenses to establish invasive infections. The macrophage stands guard at potential portals of entry to discourage such intruders and to maintain sterility of deep tissues. Despite the rich panoply of antimicrobial devices available to the macrophage, many bacterial species have developed means of resisting these normal tidal mechanisms. Some bacteria are able to persist within macrophages and some are even dependent upon this intracellular haven for their survival. This chapter will provide an overview of the macrophage’s antibacterial activities and will describe some of the strategies used by intra- and extracellular pathogens to overcome these normal host defense mechanisms.
Macrophages in the central nervous system
Authors: Matyszak M K , Perry V H 
Published: November 2023

Abstract
A dominant theme in studies of the central nervous system (CNS) is the relationship between structure and function. The wide diversity of neuronal forms is believed to reflect differences in their functions. With the use of immunocytochemistry and antibodies directed against components of the plasma membrane of macrophages, it has become clear that tissue macrophages also have a wide diversity of forms (Figure 13.1). These morphological differences reflect not only adaptations of the monocyte to the local microenvironment, but also heterogeneity in functional capabilities, expression of membrane receptors and biosynthetic capacity (Gordon et al., 1988). The adaptation of a monocyte appears to reach its greatest degree of morphological specialization in the microglia, the resident tissue macrophages of the CNS.
Use of mathematical models to simulate and predict macrophage activity in diseased tissues
Authors: Byrne H M , Owen M R 
Published: November 2023

Abstract
The key role played by macrophages in developmental biology, normal physiology and the progression of many diseases is now well accepted, and is underlined by the range of subjects already discussed in this book. Whilst the involvement of macrophages in, for example, angiogenesis (Bennet and Schulz, 1993; Polverini et al., 1977), bacterial and parasitic infections (see Chapters 5 and 6) and human immunodeficiency virus (HIV) infection (see Chapter 4, and Wodarz et al., 1999) is undisputed, their precise function is not always well understood. For example, on the basis of current, experimental evidence, it is not clear whether the presence of macrophages within solid tumors is a good prognostic indicator: in breast carcinoma, extensive macrophage infiltration is significantly associated with poor prognosis (Leek et al., 1996), whereas in other cancers the association between infiltration and prognosis has not been established. The difficulty in making general predictions about macrophage behavior is undoubtedly linked to their multifaceted nature: an individual macrophage is capable of performing a large repertoire of functions, with a combination of its location, activation status and the stimuli to which it is being subjected controlling the action that is undertaken. Faced with such a complex cell, the prospect of using mathematical techniques to provide additional insight into the role that macrophages play in human biology may appear alternately naive and infeasible. However, closer inspection of the phenomena in which macrophages are implicated reveals several common features that can, and should, be exploited when developing mathematical models. For example, the preferential (or chemotactic) migration of macrophages to hypoxic sites at which they are activated to express angiogenic factors such as vascular endothelial growth factor (VEGF) is characteristic of not only wound healing but also tumor angiogenesis and rheumatoid arthritis. Equally, the ability of macrophages to engulf and destroy foreign bodies is integral to the immune system’s ability to combat bacterial and parasitic infections and is often compromised by HIV infection.
expression in human vasculature
Authors: Mosley Michael , Mansfield Roy , McHarg Aileen 
Published: November 2023

Abstract
Triptans are 5-HT1 receptor agonists with high affinity and selectivity for 5-HT1B, 5-HT1D, and 5-HT1F receptors, and have been shown to be effective as acute treatments of migraine. Although the pathophysiology of migraine is uncertain, it is believed that pain-associated migraine arises from excessive dilation of intracranial blood vessels and the resulting increased neurosecretory activity within the trigeminovascular system. Selective 5-HT1 receptor subtype agonists and antagonists have indicated that the vasomotor dysfunction associated with migraine is mediated by 5-HT1B receptors.
Comparison of triptan-induced contractions in human cerebral versus coronary arteries
Authors: Uddman Erik , Edvinsson Lars 
Published: November 2023

Abstract
The effect of triptan treatment in migraine headache is believed to be mediated through several pathways, one of which is the activation of contractile 5-HT1B/1D receptors on cerebral arteries. Immunocytochemistry and mRNA studies have shown expression of 5-HT1B but not 5-HT1D receptors in human cerebral and middle meningeal arteries, respectively.
The relevance of hepatic intrinsic clearance and brain penetration on the doses used for 5-HT1B/1D agonists (triptans) in the treatment of migraine
Authors: Morgan Paul , McCleverty Paul , McHarg Aileen , Milton K Ashley 
Published: November 2023

Abstract
Various 5-hydroxytryptamine (5-HT1B/1D) agonists (triptans) have been shown to be effective in the treatment of migraine with a range of doses required to achieve efficacy, despite similar in vitro potency. Recent papers have speculated that limited brain penetration of eletriptan is the main reason for its higher dose requirement. However, these studies only considered total drug concentrations in brain and plasma which has no pharmacological relevance. In fact a fundamental tenet in linking pharmacokinetic and pharmacodynamic phases is that only free drug in the systemic circulation and tissues is available for clearance, distribution, and to exert pharmacological effects.
Consistency of pain relief over multiple migraine attacks following treatment with rizatriptan
Authors: Dahlöf Carl G H , Lipton Richard B , Lines Christopher R , Kramer Mark S , Reines Scott A , Polis Adam B , Ferrari Michel D 
Published: November 2023

Abstract
Migraine is a chronic disorder which is characterized by episodic attacks with a median frequency of one to two per month. Having a treatment which is consistently effective over multiple attacks is an important priority for migraine patients. The efficacy of antimigraine medications over a series of attacks has usually been evaluated in longterm, open-label studies which were primarily designed to assess safety. These studies generally lack a placebo control, for ethical reasons and to optimize patient compliance. Randomized, blinded, placebo-controlled clinical trials (RBCTs), which are the gold standard for determining treatment effects, have typically only assessed efficacy during treatment of a single migraine attack. There have been a small number of RBCTs looking at response to treatment in up to four attacks.
Naratriptan: the gentle triptan
Authors: Salonen Reijo 
Published: November 2023

Abstract
Naratriptan, the second selective 5-HT1B/1D agonist to be introduced for the acute treatment of migraine, was developed by the maker of the inaugural 5-HT1B/1D agonist sumatriptan. Sumatriptan transformed migraine therapy by promptly relieving migraine pain in the majority of patients and rapidly returning them to normal daily functioning. While sumatriptan revolutionized migraine therapy, it is not devoid of limitations. Naratriptan was developed with the aim of providing a sumatriptan complement with a placebo-like tolerability profile and a lower recurrence rate.
Almotriptan
Authors: Pascual Julio 
Published: November 2023

Abstract
Currently available triptans are not ideal for at least for 20–30% of patients due to side-effects and/or response failure. Almotriptan is a new selective 5-HT1B/1D receptor agonist developed by Almirall-Prodesfarma, Lundbeck, and Pharmacia-Upjohn for the symptomatic treatment of migraine. In this manuscript the fundamental basic properties and the clinical experience with oral almotriptan will be reviewed.
The triptan threshold score: a score to help patients identify the best moment to take triptans
Authors: Göbel Harmut , Heinze Axel , Heinze-Kuhn Katja , Austermann K , Chryssafopoulos D , Keil R 
Published: November 2023

Abstract
When using triptans to treat migraine attacks it is important to ensure accurate timing of triptan intake. Early intake and late intake of triptans will both result in unsatisfactory treatment results. If the triptan is taken too early it may be unnecessary or inefficient, because the headache might show a spontaneous remission or might only develop into a tension-type headache. Patients with frequent migraine attacks may develop drug-induced headache as a result of overfrequent intake. On the other hand, if the triptan is taken too late it may not act fast enough or the results may be unsatisfactory1–3. Many patients with frequent headaches suffer both from migraine and from tension-type headaches; here, too, it is important to know the right time to take the triptan.
Tobacco advertising and promotion
Authors: Saffer Henry 
Published: November 2023

Abstract
If tobacco advertising and promotion increase cigarette consumption, they are issues for public health policy. Although public health advocates assert that tobacco advertising does increase cigarette consumption, there is a significant empirical literature that finds little or no effect of tobacco advertising on smoking. In this chapter, these empirical studies are examined more closely with several important insights emerging from the analysis. The chapter also provides new empirical research from 102 countries on the effect of tobacco advertising. The primary conclusion of this research is that a comprehensive set of tobacco advertising bans can reduce tobacco consumption and that a limited set of advertising bans will have little or no effect.
Clean indoor-air laws and youth access restrictions
Authors: Woollery Trevor , Asma Samira , Sharp Donald 
Published: November 2023

Abstract
The development of public policy on tobacco is incomplete without the consideration of clean indoor air and youth access policies. Clean indoor-air laws protect non-smokers from the dangers of environmental tobacco smoke and implicitly transfer property rights to ambient air from smokers to non-smokers, but also have economic costs for individuals and businesses. Numerous studies conclude that comprehensive clean indoor-air policies lead to significant reductions in smoking prevalence and average cigarette consumption among continuing smokers. Youth access laws limit the supply of tobacco products to adolescents, who are deemed too young to fully comprehend the risks of consuming tobacco products. The existing empirical evidence on the impact of limits on youth smoking is mixed. For both clean-air laws and youth access restrictions, economic theory justifies government intervention in an inefficient tobacco market. The laws work best when drafted comprehensively without pre-emptive provisions. Clean indoor-air policies can, in some instances, be self-enforcing, while youth access policies depend crucially on aggressive enforcement to ensure compliance. Overall, the global coverage of clean indoor air and youth access policies is minimal. While high-income countries as a group have histories of clean indoor air and, to a lesser extent, youth access laws, low-income and middle-income countries are in the nascent stages of developing such policies.
Experimental models of vascular dementia: a focus on white matter disease and incomplete infarction
Authors: Sarti Cristina , Pantoni Leonardo 
Published: November 2023

Abstract
The concept of vascular dementia has changed over the last few years (Desmond 1996). The use of both the words ‘dementia’ and ‘vascular’ has been criticized, and replacement by the term ‘vascular cognitive impairment’ proposed (Hachinski and Bowler 1993).