The Social Transformation of American Medicine is one of the most comprehensive studies on the rise of the medical profession and the development of the health care industry published to date, Starr is able to span the fields of medicine so that he discusses intelligently the economic, political, and historical developments in medical care. His wri ting is clear and succinct, his arguments are copiously footnoted, and the inferences he draws are sound. In Book I, he covers \"the rise of medical authority and the shaping of the medical system\"; in Book II, \"doctors, the State, and the coming of the corporation.\" Reviews by Daniel Bell of Harvard and George Silver of Yale call Starr's work brilliant-I would agree. I would recommend this book to anyone who wants to understand the current health care system. Starr describes the movement of the medical profession from one that was initially viewed skeptically to one that was later embraced; and now, coming full circle, to one that is viewed critically. Starr maintains that the current status of American medicine is the result of our history of accommodating professional interests while failing to exercise control over health programs, and then needing to adopt piecemeal regulations and cut-backs on programs that become too inflationary, One of the primary messages I take from this book is the importance of a com bination of forces: a profession's authority, the political climate, and the current philosophy about health care. Starr illustrates how these forces coalesce to defeat or achieve medical improvements. As occupational therapists, we are dependent on the development of the health care industry. It is wise for us to understand the forces that have an impact on medical care and what they could mean for our profession, Kay Barbara Schwartz, M.S., OTR

The social transformation of american medicine.

Neurodegenerative diseases, the leading cause of morbidity and disability, are gaining increased attention as they impose a considerable socioeconomic impact, due in part to the ageing community. Neuronal damage is a pathological hallmark of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, Huntington's disease, spinocerebellar ataxia and multiple sclerosis, although such damage is also observed following neurotropic viral infections, stroke, genetic white matter diseases and paraneoplastic disorders. Despite the different aetiologies, for example, infections, genetic mutations, trauma and protein aggregations, neuronal damage is frequently associated with chronic activation of an innate immune response in the CNS. The growing awareness that the immune system is inextricably involved in shaping the brain during development as well as mediating damage, but also regeneration and repair, has stimulated therapeutic approaches to modulate the immune system in neurodegenerative diseases. Here, we review the current understanding of how astrocytes and microglia, as well as neurons and oligodendrocytes, shape the neuroimmune response during development, and how aberrant responses that arise due to genetic or environmental triggers may predispose the CNS to neurodegenerative diseases. We discuss the known interactions between the peripheral immune system and the brain, and review the current concepts on how immune cells enter and leave the CNS. A better understanding of neuroimmune interactions during development and disease will be key to further manipulating these responses and the development of effective therapies to improve quality of life, and reduce the impact of neuroinflammatory and degenerative diseases.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/imm.12922

Inflammation in CNS neurodegenerative diseases.

The Neurology of mTOR

Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. In Western populations HD has a prevalence of 10.6-13.7 individuals per 100 000. It is characterized by cognitive, motor and psychiatric disturbance. At the cellular level mutant huntingtin results in neuronal dysfunction and death through a number of mechanisms, including disruption of proteostasis, transcription and mitochondrial function and direct toxicity of the mutant protein. Early macroscopic changes are seen in the striatum with involvement of the cortex as the disease progresses. There are currently no disease modifying treatments; therefore supportive and symptomatic management is the mainstay of treatment. In recent years there have been significant advances in understanding both the cellular pathology and the macroscopic structural brain changes that occur as the disease progresses. In the last decade there has been a large growth in potential therapeutic targets and clinical trials. Perhaps the most promising of these are the emerging therapies aimed at lowering levels of mutant huntingtin. Antisense oligonucleotide therapy is one such approach with clinical trials currently under way. This may bring us one step closer to treating and potentially preventing this devastating condition.

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Huntington's disease: a clinical review

Neurodegenerative diseases are a common cause of morbidity and cognitive impairment in older adults. Most clinicians who care for the elderly are not trained to diagnose these conditions, perhaps other than typical Alzheimer's disease (AD). Each of these disorders has varied epidemiology, clinical symptomatology, laboratory and neuroimaging features, neuropathology, and management. Thus, it is important that clinicians be able to differentiate and diagnose these conditions accurately. This review summarizes and highlights clinical aspects of several of the most commonly encountered neurodegenerative diseases, including AD, frontotemporal dementia (FTD) and its variants, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and Huntington's disease (HD). For each condition, we provide a brief overview of the epidemiology, defining clinical symptoms and diagnostic criteria, relevant imaging and laboratory features, genetics, pathology, treatments, and differential diagnosis.

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Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases

Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials.

/pdf/huntington-disease-natural-history-biomarkers-and-prospects-2g32wa0b57.pdf

Huntington disease: natural history, biomarkers and prospects for therapeutics

Background: Reviews of the epidemiology of Huntington's disease (HD) suggest that its worldwide prevalence varies widely. This review was undertaken to confirm th

/pdf/the-prevalence-of-huntington-s-disease-4r7cbix2qg.pdf

The Prevalence of Huntington's Disease.

Stigma, history, and Huntington's disease

Objectives The prevalence of Huntington9s disease (HD) recorded in the UK primary care records has increased twofold between 1990 and 2010. This investigation was undertaken to assess whether this might be due to an increased incidence. We have also undertaken a systematic review of published estimates of the incidence of HD. Setting Incident patients with a new diagnosis of HD were identified from the primary care records of the Clinical Practice Research Datalink (CPRD). The systematic review included all published estimates of the incidence of HD in defined populations. Participants A total of 393 incident cases of HD were identified from the CPRD database between 1990 and 2010 from a total population of 9 282 126 persons. Primary and secondary outcome measures The incidence of HD per million person-years was estimated. From the systematic review, the extent of heterogeneity of published estimates of the incidence of HD was examined using the I 2 statistic. Results The data showed that the incidence of HD has remained constant between 1990 and 2010 with an overall rate of 7.2 (95% CI 6.5 to 7.9) per million person-years. The systematic review identified 14 independent estimates of incidence with substantial heterogeneity and consistently lower rates reported in studies from East Asia compared with those from Australia, North America and some—though not all—those from Europe. Differences in incidence estimates did not appear to be explained solely by differences in case ascertainment or diagnostic methods. Conclusions The rise in the prevalence of diagnosed HD in the UK, between 1990 and 2010, cannot be attributed to an increase in incidence. Globally, estimates of the incidence of HD show evidence of substantial heterogeneity with consistently lower rates in East Asia and parts of Europe. Modifiers may play an important role in determining the vulnerability of different populations to expansions of the HD allele.

https://bmjopen.bmj.com/content/bmjopen/6/2/e009070.full.pdf

Incidence of adult Huntington's disease in the UK: a UK-based primary care study and a systematic review.

In the 100 years since the death of George Huntington in 1916, the disorder he described as a ‘medical curiosity’ has become a focus of intense medical and scientific interest, in part because of the contribution of families in generating knowledge about this family disease. As many writers have noted, George Huntington’s own family played a crucial role in defining this illness (Harper, 2002). What has been less appreciated is that the affected families he described also played a role, in ways that George Huntington himself acknowledged. Not quite 22 years old (Fig. 1), just graduated from the College of Physicians and Surgeons in New York City, and with little clinical experience, no established medical practice, and no patients of his own with the disorder, he wrote an account in 1872 that William Osler considered one of the most succinct and accurate portraits of a disease ever written (Osler, 1893). It was not the earliest medical account of hereditary chorea but it was certainly the most complete. And for social and cultural as well as medical and scientific reasons, it played a far more important role in defining the discrete clinical entity that soon came to be known as ‘Huntington’s chorea’ and by the late 1960s, as ‘Huntington’s disease’. Despite considerable recognition during his lifetime, George Huntington remained a small town family physician but not a provincial or isolated one. He was aware that his paper had drawn the attention of the medical profession at home and abroad and that this had helped reveal the disease in many parts of the world. He was in touch with some eminent clinicians of his day, including Osler, and an invited speaker on Huntington’s chorea at medical societies such as the influential New York Neurological Society. At a time when medicine was becoming …

Alice Wexler

Papers

Huntington disease: natural history, biomarkers and prospects for therapeutics

The Prevalence of Huntington's Disease.

Stigma, history, and Huntington's disease

Incidence of adult Huntington's disease in the UK: a UK-based primary care study and a systematic review.

George Huntington: a legacy of inquiry, empathy and hope.