bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurocutaneous disorders
Authors: Baraitser Michael 
Published: November 2023

Abstract
Abstract: This common autosomal dominant condition occurs in about one in 3000 individuals. The manifestations are protean and well-known. The most common presenting features are cafe-au-lait patches (more than six, greater than 1.5 cm in diameter) and peripheral neurofibromata. Fois et al. (1993) investigated the diagnostic significance of cafeau-lait spots. Of children ascertained with typical cafe au lait spots of significant number 57% went on to develop definite NFl, and in the remainder of the patients the diagnosis was highly likely. Complications can include optic nerve gliomas, macrocephaly, short stature, scoliosis, pseudarthrosis of the tibia, hypertension due to renal artery stenosis, phaeo-chromocytoma, neurofibrosarcomas, meningiomas, and acoustic neuromas. The latter may be confined to the so-called central form of the disease (type 2, seep. 109).
Dementia
Authors: Baraitser Michael 
Published: November 2023

Abstract
Most genetisists will be faced with a clinical and radiological suggestion of the disease and only rarely will there be post-mortem confirmation in the form of senile plaques and neurofibrillary tangles. Other diseases such as prion protein disease, Pick’s dementia, frontal lobe dementia, and muti-infarct dementia must be excluded.
Anterior horn cell disorders
Authors: Baraitser Michael 
Published: November 2023

Abstract
Abstract: The mean age of onset in the familial type of motor neurone disease is about 45 years, and it therefore has an earlier age of onset than the more frequent, sporadic types. The clinical picture can be secondary to lymphomas, plasma cell dyscrasias, insulin secreting tumours, HIV, hyperthyroidism, hyperparathyroidism, and heavy metal poisoning such as mercury (Scully et al. 1995). Minor sensory signs might occur in about 20% of cases, and this is not surprising as the posterior columns as well as the spinocerebellar tracts are commonly found to be affected at post-mortem. This entity includes primary lateral sclerosis as there have been patients diagnosed as such who, after many years, develop amyotrophic lateral sclerosis (ALS).
The neuropathies
Authors: Baraitser Michael 
Published: November 2023

Abstract
HMSN type I—refers to those families with markedly slow conduction velocities: (a) those linked to 17p (mostly duplications) and those with mutations at the PMP 22 gene on 17p; those linked to chromosome 1 (the myelin protein zero gene); HMSN type II—the axonal type with only moderately slowed conduction; HMSN type III—(a) classic Dejerine-Sottas disease with onion bulb formation; (b) with amyelination; (c) with basal lamina onion bulb formation; HMSN type IV—Refsum’s disease; HMSN type V—with spasticity; HMSN type VI—with optic atrophy/deafness; HMSN X-linked.
Mitochondrial disorders
Authors: Baraitser Michael 
Published: November 2023

Abstract
Those conditions in which a major single deletion is found will have only small recur rence risks. Kearns-Sayre syndrome, Pearson’s disease, and chronic progressive external ophthalmoplegia fall into this category; but, Kearns-Sayre can rarely be caused by a duplication and it might be dominantly inherited.
Cortical Pathology: a New Generation of Quantitative Microscopic Studies
Authors: Benes Francine M 
Published: November 2023

Abstract
In the past 15 years, a wide variety of approaches have been adopted to the study of the neuropathology of schizophrenia. The quest has been given new hope as increasingly sensi tive and quantifiable microscopic techniques, such as cell counting, immunocytochemistry, receptor binding autoradiography, and in situ hybridization have been applied. Exciting possibilities have begun to develop regarding the underlying histopathology of the cerebral cortex in schizophrenia; however, caution is needed because of the preliminary nature of all the results.
Gliosis and its Implications for the Disease Process
Authors: Roberts Gareth W , Harrison Paul J 
Published: November 2023

Abstract
In a disorder notable for its neuropathological complexity and obscurity, gliosis has been called the “ost inscrutable lesion” (Bruton et al., 1990). Establishing if gliosis is present in schizophrenia has been one of the key questions addressed in contemporary studies, because of the significant implications which it has for understanding the nature of the disorder. Put simply, gliosis would equate with a progressive, neurodegenerative process, as Kraepelin believed was the case. Conversely, an absence of gliosis, in the presence of macroscopic (Chapter 1) and cytoarchitectural (Chapters 2 to 4) alterations, can be construed as supportive of a neurodevelopmental disease process (Chapter 8). This chapter reviews the evidence and concludes that gliosis is indeed not a feature of the brain in schiz-ophrenia. The caveats to, and interpretation of, this important negative result are then discussed.
Cortical Development and Schizophrenia
Authors: Price Jack , Roberts Gareth W 
Published: November 2023

Abstract
At first sight, the idea that the development of the cerebral cortex might be of more than passing relevance to schizophrenia seems unlikely. Schizophrenia typically emerges during the third decade of life, well after the major events that mould the cerebrum are complete. Moreover, the symptoms and deficits which characterise the disorder persist throughout life for many sufferers. Nonetheless, the “neurodevelopmental hypothesis”, as elaborated in the previous chapter, has become pre-eminent. Partly, this reflects a growing body of data consistent with the hypothesis; partly, it reflects the growing dissatisfaction with older hypotheses and the perceived need for a “paradigm shift” that might release research into new, profitable areas. Nonetheless, we must not be deceived; the neurodevelopmental hypothesis as cunrently expounded is scientifically weak. The hypothesis, to quote Waddington (l 993), “takes as the primary event [in the pathogenesis of schizophrenia] changes in utero that disrupt the development of fundamental aspects of brain structure and function and that might produce the typical symptoms some two decades later, perhaps only after functional maturation or completion of other, associated, systems or processes”. Some would consider that a brave statement given the inconclusive nature of the evidence concerning the “primary event”. It also illustrates the weakness of the hypothesis: it accommodates many experimental findings, and it is difficult to conceive of an experiment whose outcome could refute it. This vagueness reflects the fact that we are all feeling our way in a diffi cult field, and the hypothesis, despite its breadth and shortcomings, at least encourages the gathering of diverse findings in the hope that a credible story might emerge. This chapter is written in the same spirit. Though it is not yet possible to describe the pathogenesis of
Changes Of Urinary Sediment Caused By Drugs
Authors: Fogazzi Giovanni B , Ponticelli Claudio , Ritz Eberhard 
Published: November 2023

Abstract
Several drugs can cause urinary sediment changes. In several instances, these changes do not have clinical implications, whilst on other occasions they may indicate renal pathologies. In the latter case, the analysis of the urinary sediment is often a clue to the correct diagnosis. Therefore, the physician should be aware of the urinary changes which can be induced by drugs. A variety of drugs may cause transient crystalluria, in isolation or in conjunction with other urinary abnormalities (Table 5.1). The factors usually favouring the formation of crystals within the tubular lumina are overdose, dehydration or hypoalbuminaemia, which increases the fraction of unbound drug which is ultrafiltered by the glomerulus [1, 2].
Cervical spine injuries
Authors: Currie David G , Ritchie Ewan , Stott Stephen 
Published: November 2023

Abstract
In victims of trauma, the head and neck should be considered as a single unit. The forces responsible for head injuries also cause injuries of the cervical spine and the two conditions are commonly associated. In one autopsy series of 312 fatal road traffic accidents, 10% had combined head and cervical spine injuries. In unconscious head-injured patients who have been injured in falls or road traffic accidents there is a 5-10% risk of a coexisting cervical spine injury.
Mental disorder and violence
Authors: Bullard Henrietta 
Published: November 2023

Abstract
The relationship between mental disorder and violence is complex and the assessment of risk is difficult and imprecise. Although there is an association between mental disorder and violence, the risk of violence in those with mental disorder is dependent on a number of variables including the type of disorder, the nature and severity of the illness, the influence of co-morbidity with drug and alcohol misuse, the history of any previous violence, and the effectiveness of treatment and management. Clinicians are poor at predicting future violence and are accurate in no more than one out of three cases (Gunn 1993). This high rate of false-positive assessments must result in the restriction of the liberty of individuals who do not pose a risk. Actuarial methods of assessing risk are based on unchanging empirical data and do not help the clinician to predict the probability of a violent outcome without considering dynamic variables, such as the patient’s willingness to be supervised, his compliance with medication, co morbid substance-misuse and his response to treatment (Buchanon 1999).
Non-accidental injury of children
Authors: Emond Alan 
Published: November 2023

Abstract
Children have been victims of violence since ancient times, and in all societies (Finkelhor and Dziuba-Leatherman 1994). Violence has been perpetrated against them in every conceivable manner: physically, emotionally, by sexual exploitation, through neglect, and by enforced labour. Exposure and infanticide have been near universal forms of child abuse over the years, allowing many societies to ensure that only healthy newborns survive. This freedom for parents to kill defective or unwanted babies continued in some parts of Europe until the nineteenth century. In 1885, the Society for the Prevention of Cruelty to Children reported the ways in which London children were battered: by boots, crockery, pans, shovels, straps, ropes, thongs, pokers, fire, and boiling water.
Primary Hereditary Nephropathies
Authors: Tryggvason Karl 
Published: November 2023

Abstract
Congenital nephrotic syndrome (CNS) is defined as proteinuria leading to clinical symptoms such as edema soon after birth, especially at the age limit of 3 months (Rapola et al. 1992; Mauch et al. 1994). Most CNS have a genetic basis and poor outcome. Recent extensive progress in molecular genetics and biology has given new insight into the molecular basis of these diseases.
Genetic Syndromes with a Renal Component
Authors: Sandford Richard , Woolfson Robin G 
Published: November 2023

Abstract
Inherited defects in haemoglobin synthesis result in sickle cell disease and thalassaemia, and these conditions can occur alone or in combination. The heterozygote states have few clinical implications but homozygotes have profound anaemia, which is more severe in thlassaemia where dyserythropoiesis is greater.
Welfare economics and economic evaluation
Authors: Tsuchiya Aki , Williams Alan 
Published: November 2023

Abstract
It is said that there are two ‘competing views’ on economic evaluation in health care (see Brouwer and Koopmanschap (2000) for a critical overview). One is often seen as the ‘theoretically correct’ approach, that is based more firmly within the theory of welfare economics, whilst the other by comparison as some practical but not well formulated collection of rules of thumb. Another way to stylize the two approaches may be that although the first of the two may appear to have closer ties with accepted theory, it is less relevant to the particular context and background of health care resource allocation, where the objectives of the players do not entirely agree with those upheld by standard theory, whilst the second approach tries to reflect specific concerns of the health care sector.
The role and estimation of productivity costs in economic evaluation
Authors: Sculpher Mark 
Published: November 2023

Abstract
It has been recognized for some time that public sector investment decisions may have important implications for how individuals are able to allocate their time and, consequently, for the value of that time. Many cost-benefit studies have, therefore, sought to estimate how public sector projects might change how individuals spend their time, and to reflect the value of these changes within the calculus of the appraisal. Health care interventions and programmes influence the amount of time individuals are able to devote to the full range of leisure and working activities that are of value to them and to society more generally. As a branch of public sector appraisal, economic evaluation in health care has, therefore, attempted to reflect the value of changes in patterns of time allocation.
The biology of the macrophage
Authors: Ross J A , Auger M J 
Published: November 2023

Abstract
The macrophage is the major differentiated cell of the mononuclear phagocyte system. This system comprises bone marrow monoblasts and promonocytes, peripheral blood monocytes and tissue macrophages. Macrophages are widely distributed throughout the body, displaying great structural and functional heterogeneity. They are to be found in lymphoid organs, the liver, lungs, gastrointestinal tract, central nervous system (CNS), serous cavities, bone, synovium and skin, and participate in a wide range of physiological and pathological processes.
Macrophages in rheumatoid arthritis
Authors: Bresnihan B , Youssef P 
Published: November 2023

Abstract
Rheumatoid arthritis (R A), with a prevalence rate of between 0.3 and 1.5 per cent, is an important cause of disability and morbidity (Wolfe, 1968). The onset of symptoms may occur at any age, with a peak between 40 and 60 years (Harris, 1997). Women are affected about three times more frequently than men. Usually, the onset is insidious and gradual over weeks to months. A more acute form, developing over days, occurs in about 15 percent. The most prominent initial symptoms are usually stiffness, pain and swelling of several joints. The joints most frequently involved early in the course of the disease are the small joints of the feet and hands, usually in a symmetric distribution, with gradual progression to the larger joints of the upper and lower limbs and, often, the cervical spine and tempero-mandibular joints. The clinical course may be severe and progressive in some, mild and self-limiting in a small minority, or intermediate with gradual deterioration in most. Ultimately, the functional outcome will depend mainly on the degree of matrix degradation that occurs in cartilage and bone. Other characteristics of RA. usually seen in more severe disease, include subcutaneous nodules and vasculitis, and manifestations which may affect the heart, lungs and nervous system.
The discovery of sumatriptan and a new class of drug for the acute treatment of migraine
Authors: Humphrey Patrick P A 
Published: November 2023

Abstract
Successful innovative drug discovery in the pharmaceutical industry depends on several critical factors, which are often overlooked in this age of information overload and anticipation of immediate success from harnessing the new technologies. First, it is important to select an appropriate, prevalent, feasible disease target for which there are no good existing therapeutic agents. Secondly, it is important to have some degree of rational understanding of the disease pathophysiology itself in order to help identify a specific drug target, usually a transmitter receptor protein or enzyme. Thirdly, an adequate amount of biological and chemical resource needs to be allocated to the research discovery process with a commitment to the long term.
Clinical pharmacokinetics of the triptans: what are the important clinical issues?
Authors: Millson David 
Published: November 2023

Abstract
The clinical development of an increasing number of migraine-specific 5-HT1B/1D agonist triptans with enhanced liphophilicity (TELs), relative to the first drug of this class sumatriptan, and with a range of different metabolic, pharmacokinetic and receptor affinity profiles, provides the potential for critically different clinical profiles. This review, based on publications, regulatory submissions (FDA) and data on file provided by all the relevant pharmaceutical companies gives a pharmacokinetic framework, identifying where clinically relevant changes in exposure may adversely affect tolerability and safety (Tables 8.1, 8.2).
Pharmacodynamics of triptans
Authors: Saxena Pramod R 
Published: November 2023

Abstract
The triptans belong to a class of drugs known as 5-HT1B/1D, previously 5-HT1-like or 5-HT1D receptor agonists’. The frst of this class, sumatriptan, is a signifcant advance in migraine therapy. Several new triptans are on the market (zolmitriptan, rizatriptan, and naratriptan), while others (eletriptan, almotriptan, frovatriptan, and donitriptan) are in clinical development (Fig. 9.1).
Rizatriptan: clinical update
Authors: Torres Gerardo 
Published: November 2023

Abstract
Rizatriptan (MAXALT®) is a novel 5-HT1B/1D receptor agonist for the acute treatment of migraine, which received approval for marketing in the United States, Europe, and other countries worldwide in 1998. The drug is available in two oral dosage strengths of 10 mg and 5 mg, with 10 mg being the recommended primary dose in most countries. In addition to conventional tablets, rizatriptan is also available in a rapidly dissolving wafer formulation that can be taken without liquids. The wafer provides convenience of administration, and may be of utility in patients who have difficulty in swallowing a tablet due to migraine-associated nausea.
Efficacy and tolerability of rizatriptan 10 mg in migraine: experience with 70 527 patient episodes
Authors: Göbel Harmut , Heinze Axel , Heinze-Kuhn K Atja , Lindner V 
Published: November 2023

Abstract
Migraine is the commonest headache disorder encountered in clinical practice. Around 25% of women and 9% of men are affected. More than half of these patients complain of severe or very severe headache and of significant limitation of their social and work activities, some being confined to bed by the attacks. Patients therefore prefer drugs with a short onset time when selecting medications to treat attacks.
Experience with eletriptan
Authors: Jackson Neville 
Published: November 2023

Abstract
Eletriptan (Relpax?) is a potent and selective 5-HT1B/1D agonist that has been developed as an oral therapy for the acute relief of migraine symptoms. Specifcally, eletriptan was designed with the potential for high clinical efficacy and a rapid onset of action and the drug exhibits improved pharmacological and pharmacokinetic properties compared with oral sumatriptan. This review will summarize the current data relating to the pharmacological and pharmacokinetic profile of eletriptan and provide an overview of the current clinical experience with eletriptan.
Which triptan for which patient?
Authors: Tfelt-Hansen Peer 
Published: November 2023

Abstract
From a clinicians point of view there is no doubt that the introduction of triptans, the first one being sumatriptan, is a major breakthrough in the treatment of migraine. Randomized clinical trials (RCTs) have demonstrated the efficacy of triptans in the treatment of migraine1,2. RCTs should be regarded as scientific experiments that cannot answer all clinical questions, and from RCTs with triptans there is not enough evidence to answer the question: which triptan for which patient? In clinical practice the choice among triptans will, therefore, be based on a mixture of evidence from RCTs and clinical experiences with these drugs.
The Framig 99 survey III: therapeutical behaviour of migraineurs
Authors: Lucas C , Lantéri-Minet M , Leroy L 
Published: November 2023

Abstract
Objective: Framig 99 is a cross-sectional epidemiology survey on migraine that was performed in France in 1999. Framig 99 (III) focuses on the therapeutical behaviour of migraineurs.
Triptan plus NSAID with a long half-life: increase of efficacy and reduction of headache recurrence in acute migraine
Authors: Göbel Hartmut , Heinze Axel , Heinze-Kuhn Katja , Zumbroich Vera 
Published: November 2023

Abstract
Triptans have been proved to be effective and well-tolerated drugs for the treatment of acute migraine attacks. Whereas the onset of action is rapid, however, a certain percentage of patients—ranging between 20% and 40% in studies depending on the kind of triptan used—report headache recurrence1,2. Headache recurrence is defined as a return of migraine headache of at least moderate intensity within 24 h of the first—effective—treatment of a migraine attack.
The triptans in clinical practice: discussion summary
Authors: Goadsby Peter J 
Published: November 2023

Abstract
The session began with three overview lectures, the first presenting direct headto-head comparisons (Goadsby), the second comparing triptans by a large metaanalysis (Ferrari), and the third offering a personal perspective of the place of triptans in clinical practice (Tfelt-Hansen). These presentations generated a number of questions from the audience. The issue of how the sustained pain-ree data were analysed was discussed. It was commented by Dr Ferrari that these had been done without subtraction of the placebo response because of a number of methodological considerations, including difficulties with considering placebo recurrence.
New aspects of bone biology
Authors: Vernejoul Marie-Christine de , Marie Pierre J 
Published: November 2023

Abstract
Bone is formed of an abundant calcified extracellular matrix. This tissue serves three main functions: mechanical, protective for the vital organs, and metabolic as a reserve of ions, especially calcium and phosphorus. Bone tissue undergoes continual renewal in order to maintain the mechanical competence of the bone matrix. This remodeling is performed by two cell types: osteoclasts which resorb calcified matrix and osteoblasts which synthesize new bone matrix. Both cell types interact during bone remodeling, a process that allows continuous renewal of the bone matrix. In adult human bone the bone remodeling cycle lasts approximately three months. About one million bone remodeling units are present in the human skeleton and are activated sequentially. The remodeling sequence starts with a first phase of activation, which corresponds to osteoclast differentiation. The second phase corresponds to resorption by osteoclasts of ancient matrix, which lasts about 15 days. Then comes the reversal phase: osteoblast precursors start filling the resorption cavity. This coupling process between resorption and formation is dependent on the release from the ancient matrix by osteoclasts of local factors that are able to stimulate proliferation and/or differentiation of osteoblasts. Osteoblasts will then synthesize and mineralize the new bone matrix. This sequence leads to the maintenance of bone mass and to an equilibrated balance between resorption and formation during adulthood.