bluuebunny/crossref_metadata_2025 huggingface dataset:
Squamous carcinoma of the anus
Authors: Sebag-Montefiore David , Harrison Mark , Glynne-Jones Rob
Published: May 2013

Squamous cell cancer (SCC) of the anus is a rare cancer whose incidence appears to be increasing. Anal cancers are more common in women than men ( 1 , 2 ) and just under half the patients are over the age of 65. An indolent natural history and a low rate of distant metastases ( 3 , 2 ) determine locoregional control as the primary aim of treatment. The relative 5-year survival rate is 62 % ( 4 ) , and has changed little for patients treated in the last two decades.
Lymphomas
Authors: Gospodarowicz Mary K , Tsang Richard W , Hodgson David C , Hoskin Peter
Published: May 2013

Chapter 10 discusses the management of the most common forms of non-Hodgkin and Hodgkin lymphomas; particularly those presentations treated with RT or combined modality therapy.
Quality assurance in radiotherapy
Authors: Diez Patricia , Aird Edwin GA
Published: May 2013

Chapter 17 covers QA of the patient pathway, concentrating on QC of treatment planning and delivery. There will also be discussion on relevant legislation associated with the radiotherapy process as well as a section on QA for clinical trials.
Principles of surgery
Authors: McLatchie Greg , Borley Neil
Published: May 2013

Terminology in surgery 24

History taking and making notes 26

Common surgical symptoms 28

Examination and investigation of the patient

Evaluation of breast disease 30

Evaluation of the neck 32

Evaluation of the abdomen 34

Abdominal investigations 36

Evaluation of pelvic disease 38

Evaluation of peripheral vascular disease ...
Upper gastrointestinal surgery
Authors: McLatchie Greg , Borley Neil
Published: May 2013

Upper gastrointestinal endoscopy 272

Oesophageal motility disorders 274

Pharyngeal pouch 276

Hiatus hernia 278

Gastro-oesophageal reflux disease 280

Oesophageal tumours 282

Peptic ulcer disease 284

Gastric tumours 286

Chronic intestinal ischaemia 288

Surgery for morbid obesity 290

Small bowel tumours 292

Acute haematemesis 294

Acute upper GI perforation ...
Liver, pancreatic, and biliary surgery
Authors: McLatchie Greg , Borley Neil
Published: May 2013

Jaundice—causes and diagnosis 312

Jaundice—management 314

Gall bladder stones 316

Common bile duct stones 318

Chronic pancreatitis 320

Portal hypertension 322

Cirrhosis of the liver 324

Pancreatic cancer 326

Cancer of the liver, gall bladder, and biliary tree 328

Acute variceal haemorrhage 330

Acute pancreatitis ...
Abdominal wall
Authors: McLatchie Greg , Borley Neil
Published: May 2013

Abdominal wall hernias 336

Inguinal hernia 338

Femoral hernia 340

Umbilical and epigastric hernias 342

Incisional hernias 344

Other types of hernia 346

Rectus sheath haematoma 347

Groin disruption 348

Acute groin swelling 350

No disease of the human body, belonging to the province of the surgeon, requires in its treatment a better combination of accurate anatomical knowledge with surgical skill than hernia in all its varieties...
Paediatric surgery
Authors: McLatchie Greg , Borley Neil
Published: May 2013

Principles of managing paediatric surgical cases 424

Acute abdominal emergencies—overview 426

Oesophageal atresia 428

Pyloric stenosis 430

Malrotation and volvulus 432

Intussusception 434

Hirschsprung's disease 436

Rare causes of intestinal obstruction 438

Abdominal wall defects 440

Necrotizing enterocolitis (NEC) 442

Inguinal hernia and scrotal swellings ...
Cardiothoracic surgery
Authors: McLatchie Greg , Borley Neil
Published: May 2013

Basics 620

Principles of cardiac surgery 622

Coronary artery disease 626

Valvular heart disease 628

Cardiothoracic ICU 630

Lung cancer 632

Pleural effusion 634

Pneumothorax 636

Mediastinal disease 638

(see p. 55)

• Give 10–20mmol K+ via central line to get serum K...
Transplantation
Authors: McLatchie Greg , Borley Neil
Published: May 2013

Basic transplant immunology 676

Immunosuppression and rejection 678

Transplant recipients 682

Transplant donors 684

Heart and lung transplantation 690

Kidney transplantation 692

Pancreas and islet transplantation 694

Liver transplantation 696

Small bowel transplantation 698

Allorecognition is the identification of antigen as ‘non-self ‘. It is a function mainly of the adaptive immune response, but is dependent on priming by an inflammatory response from the innate immune system; such a response occurs in transplantation, both from the inflammatory response to surgery and ischaemia-reperfusion injury in the graft....
Multiple Sclerosis
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

Multiple sclerosis (MS), the most common cause of disability due to a neurological disease in young adults, can pose a challenging diagnosis. In this chapter, we summarize the typical symptomatology and the radiographic and paraclinical findings in MS. In addition, we briefly review candidate differential diagnostic entities, the current diagnostic criteria, and therapeutic options.
Acute Disseminated Encephalomyelitis
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

Acute disseminated encephalomyelitis (ADEM), a fulminant episode of demyelinating disease, which can be confused with a first episode of multiple sclerosis (MS), can present with transiently severe neurological deficits requiring hospitalization and support care. In this chapter, we review the important differential diagnostic and therapeutic considerations and how best to differentiate ADEM from an initial presentation of MS.
Progressive Multifocal Leukoencephalopathy Syndrome and Immune Reconstitution Inflammatory Syndrome
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

Progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the central nervous system caused by the JC virus, typically manifests in severely immunocompromised conditions, ranging from HIV/AIDS to lymphoproliferative malignancies to the consequence of immunosuppressant medications such as natalizumab, a monoclonal antibody approved for the treatment of relapsing forms of MS. In this chapter, we discuss the typical symptomatology and radiographic findings of PML and how to distinguish it from those of MS. In addition, we review the management of PML in natalizumab-treated MS patients as well as the features of immune reconstitution inflammatory syndrome (IRIS), the potentially life-threatening consequence of natalizumab withdrawal in patients with PML.
HTLV Myelopathy
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

Infection due to the human T-lymphocytic 1 (HTLV-1) virus can result in a myelopathy involving the thoracolumbar spinal cord, which typically manifests clinically as a spastic paraparesis—hence its alternative moniker tropical spastic paraparesis. In this chapter, we summarize the diagnostic approach to a patient with a spastic paraparesis and the key points, which assist in narrowing down the lengthy differential diagnosis to HTLV-1.
Antiphospholipid Antibody Syndrome
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

There can be considerable overlap between the neurological sequelae of antiphospholid antibody syndrome (ACAS) and multiple sclerosis, creating a frustrating diagnostic dilemma for clinicians. In this chapter, we review the common features and distinct clinical manifestations of ACAS as well as the diagnostic criteria for ACAS. In addition, we discuss the therapeutic consideration of antiplatelet or anticoagulant therapy.
Sjögren’s Syndrome
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

Primary Sjögren’s syndrome involves the cardinal siccal syndrome of xerostomia and xeroophthalmia. Neurological manifestations generally affect the peripheral nervous system in the form of neuropathy but can also target the central nervous system and overlap with demyelinating diseases such as multiple sclerosis and neuromyelitis optica. In this chapter, we review the systemic and neurologic features of Sjögren’s syndrome, and how to approach a patient with neurological symptoms secondary to Sjögren’s syndrome.
Neuropsychiatric Systemic Lupus Erythematosus
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

Systemic lupus erythematosus (SLE) is a chronic, autoimmune, inflammatory multi-organ disorder, which can affect the nervous system either directly or indirectly, or as an adverse event secondary to the immunotherapies used to treat the disease. In this chapter, we review the diagnostic criteria for SLE, the possible ways it can affect the central and peripheral nervous systems, and therapeutic options.
Celiac Disease
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

Neurological involvement of celiac disease is a controversial topic and estimated to occur in 6-10% of patients. Cerebellar (‘gluten’) ataxia and peripheral sensory neuropathy are the most common neurological manifestations of celiac disease. In this chapter, we review the multiple neurological manifestations of celiac disease, the utility of available diagnostic serologic tests, and the variable therapeutic responses to gluten restriction diets.
Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

The diagnostic approach to a patient with chronic peripheral neuropathy can be daunting, with several candidate etiologies. In this chapter, we review the typical symptomatology, temporal course, examination, and laboratory findings, which raise suspicion for chronic inflammatory demyelinating polyneuropathy, and discuss the available therapeutic modalities.
Bickerstaff’s Brain Stem Encephalitis
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

Bickerstaff’s brain stem encephalitis is an idiopathic autoimmune condition considered part of the spectrum of GQ1b mediated diseases such as Miller Fisher variant of Guillain-Barré syndrome. In this chapter, we review the upper and lower motor neuron features and typical laboratory findings, and discuss the most common clinical course, prognosis, and important treatment considerations.
NMDA Receptor Encephalitis
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

NMDA receptor encephalitis is a rare and underdiagnosed autoimmune mediated, often paraneoplastic, syndrome seen in young women with idiopathic neuropsychiatric illness. It is a potentially fatal illness and early identification and treatment can have critical prognostic implications. In this chapter, we review the typical clinical and laboratory features, which should raise suspicion for this condition, and therapeutic and supportive care recommendations.
Stiff Person Syndrome
Authors: Miller Aaron E. , DeAngelis Teresa M.
Published: May 2013

Stiff person syndrome is an important autoimmune mediated disorder to consider in patients with unexplained pain and muscular rigidity. We review the proposed diagnostic criteria, common clinical features, and important serologic and electrophysiological tests to aid in diagnosis as well as medical and rehabilitative therapeutic options. In addition, we discuss the identification and management of possible paraneoplastic presentations.
Voltage-Gated Na+ Channels
Authors: Mantegazza Massimo , Catterall William A.
Published: May 2013

Voltage-gated Na+ channels initiate action potentials in neurons and other excitable cells, and they are responsible for propagation of action potentials along nerves, muscle fibers, and the neuronal somatodendritic compartment.1 They are complexes of a large pore-forming α subunit and smaller auxiliary β subunits.2,3 Multiple genes encode Na+ channel subunits, and the distinct Na+ channel subtypes have subtle differences in functional properties, differential expression in excitable cells, and differential distribution in subcellular compartments.2,4 These differences in function and localization contribute to the specialized functional roles of Na+ channels in neuronal physiology and pharmacology.
Voltage-Gated Calcium Channels in Epilepsy
Authors: Cain Stuart M. , Snutch Terrance P.
Published: May 2013

Voltage-gated calcium channels are integral membrane proteins that form calcium-selective pores in the plasma membrane (Fig. 6–1). Calcium ions flowing into the cell are driven by an electrochemical gradient generated by a high concentration of calcium outside the cell to a low calcium concentration inside. In neurons the rapid influx of calcium depolarizes the cell membrane potential due to its divalent positive charge and mediates biophysical processes such as action potential firing and membrane potential oscillations. A second effect of calcium ion influx is to regulate the intracellular signaling pathways and biochemical machinery required for physiological functions such as neurotransmitter release. Cells contain numerous calcium-sensitive proteins, such as enzymes and DNA transcription factors that can be up- or downregulated by the binding of calcium ions. Due to the highly complex and widespread effects of calcium channels, even small alterations in their expression or biophysical properties can induce pathophysiological changes in the brain with the potential to induce epileptic seizures.
Cell Death and Survival Mechanisms after Single and Repeated Brief Seizures
Authors: Henshall David C. , Meldrum Brian S.
Published: May 2013

Brief seizures can cause neuronal death in animal models. There is emerging evidence that apoptosis-associated signaling pathways are activated by these seizures, but so far we only have proof that these contribute to cell death in models of status epilepticus. There is little evidence that spontaneous seizures in epileptic animals cause acute cell death, but these animals nevertheless display alterations in apoptosis-associated pathways. In humans, there is evidence that recurrent seizures cause subtle or diffuse neuron loss in affected structures. Histopathological analyses have found a molecular signature of apoptosis-associated signaling in resected neocortical and hippocampal material from pharmocoresistant TLE patients.
Potassium Channelopathies of Epilepsy
Authors: Brenner Robert , Wilcox Karen S.
Published: May 2013

An exceedingly large number of familial and de novo channelopathies in several different types of potassium channels have already been found to underlie, or be associated with, many types of epilepsy. Given that the role of most potassium channels is to contribute to the maintenance of membrane hyperpolarization and repolarization, it is not surprising that loss-of-function mutations contribute to epilepsy. However, recently described potassium channelopathies resulting in gain of function can also, paradoxically, result in epilepsy. Furthermore, as many LQTS mutations arise in potassium channels, a link between epilepsy, SUDEP, and LQTS, as has now been observed for KCNQ1, may begin to inform prevention strategies for patients at risk for SUDEP. Finally, animal models harboring human mutations found in potassium channels have contributed greatly to our understanding of the mechanisms whereby specific channelopathies contribute to epilepsy, and it is anticipated that as this field continues to develop, advances in treatment strategies for patients will also be elucidated from such animal models.
Progressive Myoclonus Epilepsy of Lafora
Authors: Serratosa José M. , Minassian Berge A. , Ganesh Subramaniam
Published: May 2013

Lafora disease is an autosomal recessive form of progressive myoclonus epilepsy characterized by a severe course that leads to death in 5–10 years in most patients. Patients present with myoclonic, absence, and generalized tonic-clonic seizures at onset, typically at around age 14–15 years. As the disease progresses, difficulties in speech generation and gait as well as cognitive decline appear. Seizures soon become intractable and, due to a rapidly progressing dementia, patients become severely incapacitated and die. Lafora bodies are the characteristic hallmark and consist of an abnormal, poorly branched, intracellular glucose polymer accumulating in many tissues, including heart, skeletal muscle, liver, and brain. They can be observed on optic microscopy as periodic acid–Schiff-positive (PAS) cytoplasmic inclusions. Lafora bodies thus resemble glycogen with reduced branching, suggesting an alteration in glycogen metabolism as the cause of their accumulation. Since the localization of the first gene for Lafora disease in 1995, major advances have led to a better understanding of the basic mechanisms involved in this adolescent-onset and deadly disease.
Animal Models for Evaluating Antiepileptogenesis
Authors: White H. Steve
Published: May 2013

The need to find a therapy that will prevent or delay the development of epilepsy in the susceptible individual is evident, and many of the required tools have already been developed. Nonetheless, there are many practical challenges and hurdles at both the preclinical and clinical levels that must be overcome before a cure can be developed. Prior to embarking on a clinical trial, there should be some evidence that a hypothetical therapy is effective in one or more animal models of epileptogenesis. However, unlike the animal models routinely employed in the search for novel anticonvulsant compounds, the animal models of epileptogenesis that are currently available have not been validated clinically. Unfortunately, clinical validation will not be provided until the first truly antiepileptic or disease-modifying therapy has been found to be effective in an appropriately designed clinical trial. With this in mind, it is still unknown what preclinical evidence of efficacy would be required before one would be willing to embark on an expensive clinical trial that involves a path not yet paved by past experience. Nevertheless, the scientific community should not be discouraged from pursing this approach but should clearly be aware of the limitations of the existing models and employ caution when designing preclinical studies and interpreting the results obtained.
Drug Resistance
Authors: Gorter Jan A. , Potschka Heidrun
Published: May 2013

Despite the ongoing development of novel AEDs, drug resistance remains a major problem in the clinical management of epilepsy patients. Thus, strategies to break new grounds in the development of novel AEDs or alternative therapeutic approaches are urgently needed. Based on epidemiological data as well as experimental studies, several hypotheses have been proposed to explain the phenomenon of drug resistance. These hypotheses suggest specific implications for future drug development and clinical therapeutic management. However, clinical evidence for the drug resistance mechanisms is still limited. Therefore, novel tools to study putative resistance mechanisms in individual patients are needed. New techniques might also guide individualized therapeutic decisions in the future.
Reversing Disorders of Neuronal Migration and Differentiation in Animal Models
Authors: Manent Jean-Bernard , LoTurco Joseph J.
Published: May 2013

In this chapter, we review results from animal models that begin to provide evidence that genetically based developmental abnormalities leading to epilepsy can be reversed by reactivating developmental programs. The abnormalities reversed include disruptions in neuronal migration and differentiation. Moreover, molecular genetic and pharmacological interventions in animal models have been shown to reduce morphological disruptions, seizures, and associated behavioral impairments. Significant challenges remain, particularly with respect to translating the approaches used in animal models into viable human therapies. However, the diversity of both the methods used and the disruptions successfully targeted to date should encourage future research and therapy development in this area.
History of Brain Death
Authors: Wijdicks Eelco F.M.
Published: May 2013

Chapter 1 discusses the history of brain death, how clinical criteria were developed to define brain death, and current international guidelines in place.
Procurement after Brain Death
Authors: Wijdicks Eelco F.M.
Published: May 2013

Chapter 5 discusses the practice of organ procurement after brain death, and the criteria established for doing so.
A National Institute of Mental Health Perspective on Geriatric Mood Disorder Research
Authors: Evans Jovier D. , Niederehe George
Published: May 2013

The mission of the National Institute of Mental Health (NIMH) is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. The Geriatrics Research Branch approaches this mission by supporting research on the etiology and pathophysiology of mental disorders of late life, the treatment of persons with these disorders, and the prevention of these disorders and their consequences. This chapter reviews new opportunities for research in geriatric mood and anxiety disorders across the translational research continuum from basic mechanisms of aging and disease to the development and implementation of community based services and interventions. New directions for the field of geriatric mental health research are also discussed.
Public Health Burden of Late-Life Mood Disorders
Authors: Park Mijung , Unützer Jürgen
Published: May 2013

This chapter reviews the public health burden associated with late-life mood disorders. Mood disorders cause substantial distress for affected individuals, their families and larger society directly and indirectly. We review the associations between mood disorders, disability, and quality of life. Mood disorders also increase morbidity and mortality directly and through their interactions with other chronic medical conditions. We present several mechanisms for increased medical burden related to late-life mood disorders. We examine the burden of mood disorders on formal care, and on broader informal care systems such as family and loved ones. Finally, we present strategies for addressing public health burden of late-life mood disorders through prevention, early detection, and effective treatment programs.
Non-Major Depression
Authors: Vahia Ipsit V. , Kulkarni Ganesh , Meeks Thomas W. , Jeste Dilip V.
Published: May 2013

Non-major depression is an increasingly recognized clinical issue in older adults, as a growing body of evidence points to deleterious effects of this condition on emotional, cognitive and physical health. Yet, research in this area has been limited. This chapter aims to identify the primary clinical and research issues relevant to non-major depression, including a clarification of the nosology, epidemiology, clinical outcomes and comorbidity and treatment modalities.
Bereavement and Complicated Grief in Older Adults
Authors: Shear M. Katherine , Ghesquiere Angela , Katzke Michael
Published: May 2013

Bereavement is one of the most common experiences of aging. Losing a loved one at any age is widely understood as one of life’s most painful and disruptive experiences. About 75% of the 2.5 million people who die every year in the United States, occur among people 65 years of age or older. Their close friends and relatives are most affected by bereavement, many of these are also older adults. This chapter outlines a framework for understanding bereavement and grief in general and in older people specifically, describes the healing process and points to some possible pitfalls in its course. A significant minority of bereaved people experience grief complications that prolong and intensify acute grief. This chapter describes the syndrome of complicated grief and identifies treatments that have been helpful.
Substance Abuse Comorbidity
Authors: Oslin David W. , Helstrom Amy
Published: May 2013

While rates of alcohol and illicit drug use begin to decline with age, individuals who abuse alcohol and other substances in late life may be at increased risk of a number of negative physical and mental health outcomes that are often exacerbated with advancing age. Demographic changes in the population suggest that the prevalence of substance misuse in later life may be increasing. Depression is frequently comorbid with substance use and the presence of each disorder can negatively impact the course and recovery of the other. This chapter will focus on the intersection between the use and abuse of addictive substances and the presence and course of depressive disorders. Considerations for assessment and treatment for these comorbid presentations among older adults, such as integrated models of care, are discussed.
Comorbid Pain Disorders
Authors: Karp Jordan F. , McGovern Jonathan
Published: May 2013

Painful conditions in late-life are frequent and often comorbid with affective disorders, anxiety, and insomnia. Psychiatrists and geriatric mental health clinicians must be familiar with common pain disorders, the pathophysiology of chronic pain, and the screening, diagnosis, and treatment of common pain conditions when comorbid with psychiatric syndromes. This is particularly important for older adults with dementing disorders and other conditions which impair communication about internal states. In addition to pharmacologic treatments, psychosocial interventions like cognitive behavioral therapy play a significant role in the treatment of chronic pain, especially when the pain is comorbid with depression and anxiety. Geriatric mental health clinicians should engage rehabilitation specialists like physical and occupational therapy in planning treatment for these complex patients.
Electroconvulsive Therapy and Neuromodulation in the Treatment of Late-Life Mood Disorders
Authors: McDonald William M. , Vahabzadeh Arshya
Published: May 2013

Electroconvulsive therapy (ECT) isrecognized as one of the most effectivetreatments for severe mood disorders. Increasingly ECT has been used in the treatment of elderly mood disorders and research in ECT over the last 70 years has informed the field as to the optimal techniques, parameters and indications for the use of ECT in elders. In this chapter the use of ECT in late-life depression, bipolar disorder, and neuropsychiatric disorders will be outlined as well as the essential elements of the medical assessment prior to ECT and the side effects of ECT. The increasing use of continuation and maintenance ECT will also be discussed in relationship to the use of these therapies in the elderly. Finally,the newersubconvulsiveneuromodulatory interventions including transcranial magnetic stimulation and deep brain stimulation will be discussed as these treatments relate to the treatment of late-life mood disorders.
Prevention of Depression in Later Life
Authors: Beekman Aartjan T. F. , Cuijpers Pim , Smit Filip
Published: May 2013

This chapter focuses on the prevention of depression among older people. During the past decades the ground work has been done to facilitate effective prevention of prevention at all ages. Much of this work has been done in older people. Different strategies for preventing depression are described and their feasibility and effectiveness are systematically assessed. Ethical and economical issues are then discussed with the aim to show that, although we are drawing nearer to the point where large scale implementation of prevention is possible, improving the reach and implementation of preventative interventions in mental health remains necessary.
Depression Medication Treatment Adherence in Later Life
Authors: Zivin Kara , Kavanagh Janet , Maixner Susan , Sirey Jo Anne , Kales Helen C.
Published: May 2013

While depression in older adults has been detected, diagnosed, and treated more frequently in recent years, substantial gaps in effective treatment remain. Improving adherence to depression treatment can be viewed as the “next frontier” in the treatment of late-life depression. In this chapter, we conceptualize and review the current evidence for key patient-level factors associated with depression treatment adherence among older adults. Factors are categorized according to whether their potential for impact on adherence might be influenced by specialized treatment approaches or interventions, as: 1) modifiable; 2) potentially modifiable; and 3) non-modifiable. A number of these factors are illustrated by a real-world clinical case. Finally, we discuss developing effective interventions to improve adherence to depression treatment in older adults.
Depression in Long-Term Care
Authors: Hui Christina , Sultzer David L.
Published: May 2013

Depression is common in long-term care settings, particularly among the nursing home population. The nursing home is a unique venue in which to provide psychiatric care. The characteristics of the LTC population, the psychosocial environment, and federal legislation are all factors that influence delivery and subsequent outcomes of mental health services in the nursing home. This chapter reviews the epidemiology, assessment, and treatment of depression in the context of the nursing home. The role of the mental health consultant and the changing nature of LTC are also discussed.
Late-Life Depression in the Primary Care Setting
Authors: Wittink Marsha , Duberstein Paul , Lyness Jeffrey M.
Published: May 2013

The primary care setting is critical for recognizing and addressing a wide range of depression symptoms in late-life. However, multiple factors discourage older adults and their primary care physicians from taking a proactive role in addressing depression. In this chapter, we explain the limitations of a biomedical approach to depression care, which emphasizes particular treatments but ignores fundamental behaviors, namely communication and decision-making, that are vital to patient-centered treatment outcomes. We introduce an alternative approach to patient-centered mental health care that leverages recent developments in communication and decision-making and is consistent with the legitimization of patients as decision makers with expertise in their own circumstances.
Molecular Imaging in Late-Life Depression
Authors: Kumar Anand , Ajilore Olusola , Forester Brent , Deseda Jaime , Woodward Matthew , Rhodes Emma
Published: May 2013

“Molecular imaging” elucidates discrete biological processes, including levels of cerebral proteins, measures of axonal and myelin integrity and biochemical pathways. Positron Emission Tomography (PET) has been used to demonstrate an abnormal deposition of neuritic plaques and the presence of neurofibrillar tangles in Alzheimer’s disease. Recent PET studies have shown similar pathophysiology in geriatric depression. Diffusion Tensor Imaging (DTI) has been used to detect microstructural brain changes in white matter. These findings have been associated with disease severity, treatment response/resistance and cognitive impairment in late-life depression. Magnetic Resonance Spectroscopy (MRS) can be used to quantify the regional or global concentrations of cerebral proton and phosphorus biochemical markers. This methodology may yield insight into facets of neuropsychiatric disorders including neurotransmission, bioenergetic metabolism and cell membrane integrity. This chapter serves as an introduction to these neuroimaging techniques and their application in studying geriatric neuropsychiatric illnesses.
Cognitive Biomarkers in Depression
Authors: Robinson Oliver J. , Sahakian Barbara J.
Published: May 2013

This chapter provides an overview of the altered cognitive performance in depression and discusses how measuring this impairment using neurocognitive tasks can reveal cognitive biomarkers. The difference between state biomarkers (which may aid in the treatment of disorders) and trait biomarkers (which may detect risk for disorders prior to their onset) is discussed, and the distinct effects of late-life depression on biomarkers are examined. The putative underlying causes of the biomarkers are then examined via functional imaging, models in healthy individuals, and genetic studies. The effects of treatment on biomarkers are discussed before concluding by emphasizing the possibility of using cognitive biomarkers to promote resilience in younger people and hence prevent the onset of late-life depression.
Pharmacogenetics of Late-Life Depression
Authors: Murphy Greer M.
Published: May 2013

There have been relatively few studies on pharmacogenetic predictors of antidepressant response in the elderly. The focus has been primarily on either pharmacokinetic markers such as CYP2D6 polymorphisms that affect drug levels, or pharmacodynamic markers such as serotonin receptor and transporter polymorphisms that influence drug interactions with neurons. So far, nothing of demonstrated clinical value has emerged from these investigations of antidepressant pharmacogenetics in late-life depression. Psychiatric pharmacogenetics is handicapped by small sample sizes, lack of replication studies, and problems in study design. Many of these difficulties are shared with the broader pharmacogenetics field as a whole. However, with further research the potential exists to identify genetic markers that could guide prescribing of antidepressants specifically in the elderly population.
The Hpa Axis and Late-Life Depression
Authors: Sudheimer Keith , Flournoy John , Gershon Anda , Demuth Bevin , Schatzberg Alan , O’Hara Ruth
Published: May 2013

HPA dysregulation may be an important mechanism underlying the pathophysiology of depression. The involvement of HPA impairment is all the more complex in late life depression due to a) age-associated changes in HPA function; b) the significant number of medical comorbidities experienced by older adults; and c) increased variability with age in terms of exposure and response to environmental stressors. In this chapter we describe the HPA axis and the effects of aging on this system, addressing associations between HPA functioning, depression, and aging. Finally we discuss potential mediators and moderators that could underlie interactions between HPA axis function, aging and depression, including genetic markers, stress, and medical comorbidities.
Clinical Prediction Models
Authors: Wesley K. Thompson Ji-in Choi, , Anderson Stewart
Published: May 2013

Clinical trials of mood disorders in late-life frequently use time to the occurrence of an event as the primary study outcome. In recent years it has become common to collect additional variables repeatedly over multiple time points, augmenting the primary time-to-event outcome, including variables related to physical health and functioning, biological correlates of illness, contextual variables such as negative life events, and cognitive impairments. In this chapter we describe “joint models,” which incorporate these longitudinal data to predict future time-to-event outcomes. These predictive models can be useful in a clinical setting where interest centers on using a set of patient characteristics, obtained over multiple time points, to obtain a prognosis regarding onset of mental illness. Joint models also allow for updatable individualized prediction of clinical outcomes as more data become available on a given patient over time.
Integration of Biological, Clinical, and Psychosocial Predictors of Treatment Response Variability in Late-Life Depression
Authors: Garand Linda , Whyte Ellen M. , Butters Meryl A. , Skidmore Elizabeth R. , Karp Jordan F. , Dew Mary Amanda
Published: May 2013

Progress has been made in delineating factors that contribute to treatment response variability in late life depression, yet large gaps remain in the literature. Much of the scientific effort to date has focused on understanding factors’ individual rather than combined effects. Within studies of individual effects, the emphasis has been on the impact of biological and clinical factors on the magnitude and speed of late-life treatment response. Less attention has been given to the role of intrapersonal and environmental factors in treatment outcomes. Although durability of response has less often been the focus of research than magnitude and speed of initial response, the same pattern of emphasis on biological and clinical factors appears, with considerably less information on intrapersonal and environmental influences on patient outcomes.
Genetic Techniques and Their Application to Bipolar Disorder
Authors: Vederman Aaron C. , McInnis Melvin G.
Published: May 2013

The last decade has witnessed a dramatic increase in the advancement and use of genetic technique to investigate the potential causes and treatment targets for a variety of medical conditions. Bipolar disorder is strongly familial, with very high heritability rates, making it an ideal candidate for genetic investigations. This chapter discusses some of the recent advances in these techniques and provides examples of use in bipolar disorder to provide context for additional genetics discussions in this book. In particular, this chapter outlines how these techniques let away from single genes as comprehensive risks for bipolar disorder to broader models that consider additive effects of small risks from multiple genetic variants. The chapter also examines epigenetic approaches to studying bipolar illness and how these approaches might complement standard genetic techniques. Other more specialized approaches including functional genetics and pharmacogenetics are considered. The chapter ends by integrating these discussions into consideration of a systems biology approach to complex conditions like bipolar disorder.
General Genetics of Bipolar Disorder
Authors: Nurnberger John I.
Published: May 2013

Bipolar disorder runs in families and is strongly heritable,. Twin and adoption studies suggest that the phenomenology of bipolar disorder is under strong genetic control, although there are clearly environmental factors as well. The population rates of mood disorders are increasing, particularly in familieswith a history of mood disorder, consistent with a genetic-environmental interaction. Genetic liability for mood disorders may exist across a spectrum of phenotypes (e.g., Bipolar I Disorder, Bipolar II Disorder, Major Depression), which makes isolating specific genetic factors for any single phenotype more challenging. Nonetheless, various genetic approaches, including linkage studies, candidate gene association studies, epigenetic and gene expression studies, high-risk studies, and genome-wide association studies have identified a growing list of gene variants that may contribute to the risk of developing bipolar disorder. In this chapter, we review these findings and summarize current knowledge regarding the genetics of bipolar illness.
Integrating Imaging and Genetic Research
Authors: Perlis Roy H. , Blumberg Hilary P.
Published: May 2013

Neuroimaging studies demonstrate a convergence of findings in showing abnormalities in a corticolimbic system including the ventral prefrontal and anterior cingulate cortices and amygdala, their limbic, striatothalamic and cerebellar connections sites, and in the structure and function of the connections. Genetic association studies likewise have begun to implicate common variation in genes that may moderate development, plasticity and functioning of the corticolimbic system. This chapter reviews combined imaging and genetics studies of bipolar disorder that hold promise for further elucidating the molecular mechanisms that contribute to the brain changes of bipolar disorder. In addition to considering their direct implications for understanding the pathophysiology of this illness, the chapter addresses how such studies may inform future investigations by establishing more homogeneous patient populations. Finally, it takes an even broader perspective and considers the point at which such integrated studies may be directly applied to guide clinical practice and personalized treatment.
Failure to Awaken After Surgery
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Failure to awaken fully after surgery is a common reason for consultation. One example of a patient with a postoperative stroke is presented to illustrate the discussion on differential diagnosis.
Paroxysmal Sympathetic Hyperactivity
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

An underappreciated and undertreated condition that may cause potentially life threatening complications. The difficulties with management and short- and long-term pharmacologic approaches are discussed.
Decisions in Persistent Vegetative State
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Early on the diagnosis of a persistent vegetative state and its important long-term implications remains tentative at best. Long-term care of debilitated neurologic patients requires placement of a tracheostomy and percuteous gastrostomy. Timing and indications are discussed in this chapter.
Approach to Organ Donation
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Physicians have the obligation to approach an organ procurement agency after brain death or after the decision to proceed with withdrawal of life support measures. The two main procedures—donation after brain death and donation after cardiac death—are discussed in this chapter.
Applied Anatomy of the Heart and Great Vessels
Authors: Wright R. Scott
Published: May 2013

An understanding of the anatomy of the heart and great vessels is vital to the practice of cardiology. This chapter covers the following components of cardiac anatomy: mediastinum, pericardium, the great vessels (aorta, pulmonary artery, superior and inferior venae cavae), cardiac chambers (atria, ventricles), valves, leaflets, coronary circulation, and the cardiac conduction system. Enlargement of a cardiac chamber or great vessel may displace or compress an adjacent noncardiac structure. Congenital heart diseases related to anatomy are also reviewed.
Noncardiac Surgery in Patients With Heart Disease
Authors: Askew III J. Wells , Shub Clarence
Published: May 2013

The guidelines for the perioperative evaluation and management of patients undergoing noncardiac surgery focus on patients undergoing noncardiac surgery who are at risk of perioperative cardiac morbidity or mortality. This at-risk group includes patients with known CAD, patients with recent signs or symptoms suggestive of CAD, and asymptomatic patients older than 50 years who have the potential for coronary artery atherosclerosis. In general, a conservative approach is recommended. Expensive, noninvasive or invasive preoperative testing (eg, coronary angiography and revascularization) is rarely warranted just “to get the patient through an operation.” Rather, the indications for extensive perioperative testing or revascularization are generally similar to those in a nonoperative setting, and its use should be limited to clinical scenarios in which the results will specifically influence patient management.
Positron Emission Tomography
Authors: Chareonthaitawee Panithaya
Published: May 2013

Positron emission tomography (PET) has emerged as a valuable clinical tool for the management of known or suspected coronary artery disease. Several factors have contributed to its increased use: greater availability of PET scanners, FDA approval for clinical cardiac application, reimbursement by the Centers for Medicare and Medicaid Services, and greater access to the tracers needed. With increased use of cardiac PET imaging, evidence for its clinical usefulness is rapidly expanding and demonstrating high diagnostic accuracy and incremental prognostic value. Several inherent characteristics of PET contribute to its high spatial, temporal, and contrast resolution: coincidence detection, built-in attenuation correction, and high-energy tracers. Risks, contraindications and clinical applications are reviewed.
Cardiac Radiography
Authors: Breen Jerome F. , Callahan Mark J. , Lloyd Margaret A.
Published: May 2013

Chest radiographs that show cardiac abnormality are a very important part of cardiology examinations. The image of the heart and great vessels on the chest radiograph is a 2-dimensional display of dynamic 3-dimensional structures. The cardiovascular silhouette varies not only with the abnormality but also with body habitus, age, respiratory depth, cardiac cycle, and position of the patient. Cardiac radiography can be used to assess chamber size, blood flow, pericardial disease, and cardiac masses. Radiography in the setting of implanted cardicac devices is also reviewed.
Stress Test Selection
Authors: Allison Thomas G.
Published: May 2013

Cardiac stress testing is an integral part of clinical cardiology. This chapter focuses on the relative advantages and limitations of each technique to ensure that the appropriate test is performed on the appropriate patient. This chapter addresses stress testing from the standpoint of making a diagnosis or establishing prognosis in patients with suspected or known CAD. Exercise ECG testing can ultimately provide adequate detection of CAD and risk stratification in the majority of patients. In those who require further assessment with imaging, the choice of stress imaging technique requires careful consideration of the individual patient characteristics. In many cases, either stress echocardiography or myocardial perfusion imaging may be appropriate; the preferred test often depends on local expertise, available facilities, and considerations of cost-effectiveness.
Indications for Invasive and Noninvasive Electrophysiologic Testing
Authors: Boilson Barry A. , Brady Peter A.
Published: May 2013

Electrophysiologic testing can be used with the following goals: accurate diagnosis of an arrhythmia and its mechanisms; establishment of the etiologic factors of syncope; determination of prognosis in the clinical setting of arrhythmia; risk stratification for sudden cardiac death; acquisition of data regarding indications for ICD or pacemaker implantation; and guidance of antiarrhythmic therapy with drugs, ablation, or surgery. The maneuvers performed during an EP study vary depending on the indication. The decision to proceed with invasive EP testing should include consideration of risks to the patient versus potential yield, and informed consent is essential.
Arrhythmias in Congenital Heart Disease
Authors: Mcleod Christopher J. , Brady Peter A.
Published: May 2013

The number of persons with congenital heart disease who survive into adulthood has increased dramatically in the past few decades. In this population, arrhythmias are a major cause of late morbidity and mortality and may herald worsening underlying hemodynamic changes and associated poorer outcomes. In addition, the risk of sudden cardiac death is high, especially in certain repaired malformations. Device (pacing and defibrillator) therapy is often complicated and may require thoracotomy for epicardial lead placement. Common types of congenital heart disease, including atrial septal defects, ventricular septal defects, tetralogy of Fallot, and Ebstein anomaly, are reviewed.
Implantable Cardioverter-Defibrillator Troubleshooting
Authors: Boilson Barry A.
Published: May 2013

This chapter reviews common problems that present on ICD interrogation which are likely to be encountered in clinical practice. Since their adoption over 20 years ago, ICDs are now commonplace, and the ability to understand basic ICD interrogation and troubleshooting is an essential requirement in most general cardiology practices. The evolution of ICD technology has resulted in increasing complexity of arrhythmia-recognition algorithms used by modern ICD microprocessors, but the basic principles have not changed in that an ICD can still be considered a sophisticated pacemaker device which has a limited capacity to analyze and treat ventricular tachyarrhythmia.
Autonomic Function Testing
Authors: Venkatachalam K. L.
Published: May 2013

Syncope may be defined as a transient loss of consciousness due to a temporary limitation in cerebral blood flow. Causes of syncope include the following: low systemic blood pressure, reduced cerebral blood flow, and miscellaneous causes of cerebral dysfunction (metabolic, endocrine, and electrolyte abnormalities). The autonomic nervous system may have a role in syncopal and near-syncopal episodes. The focus of this chapter is autonomic function assessment related to cardiology and, specifically, to the evaluation of a patient referred for syncope.