bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug dosing in chronic kidney disease
Authors: Olyaei Ali J. , Foster Ted A. , Lerma Edgar V.
Published: November 2015

This chapter is dedicated to the dosing of medications in patients with chronic kidney disease. It is important for clinicians to have a working understanding of basic pharmacokinetic and pharmacodynamic principles to ensure patients with chronic kidney disease achieve the therapeutic target without toxicity. This chapter will provide a systematic approach to medication dosing in patients with chronic kidney disease by obtaining a medical history and performing a thorough physical examination, calculating an accurate assessment of renal function, determining loading dose, determining a maintenance dose, and monitoring drug levels if indicated. Specific pharmacologic considerations in the setting of renal insufficiency along with drug removal by dialysis are also outlined.
Drug dosing in acute kidney injury
Authors: Golper Thomas A. , Udy Andrew A. , Lipman Jeffrey
Published: November 2015

Drug dosing in acute kidney injury (AKI) is one of the broadest topics in human medicine. It requires an understanding of markedly altered and constantly changing physiology under many disease situations, the use of the drugs to treat those variety of diseases, and the concept of drug removal during blood cleansing therapies. Early in AKI kidney function may be supraphysiologic, while later in the course there may be no kidney function. As function deteriorates other metabolic pathways are altered in unpredictable ways. Furthermore, the underlying disorders that lead to AKI alter metabolic pathways. Heart failure is accompanied by vasoconstriction in the muscle, skin and splanchnic beds, while brain and cardiac blood flow proportionally increase. Third spacing occurs and lungs can become congested. As either kidney or liver function deteriorates, there may be increased or decreased drug sensitivity at the receptor level. Acidosis accompanies several failing organs. Protein synthesis is qualitatively and quantitatively altered. Sepsis affects tissue permeability. All these abnormalities influence drug pharmacokinetics and dynamics. AKI is accompanied by therapeutic interventions that alter intrinsic metabolism which is in turn complicated by kidney replacement therapy (KRT). So metabolism and removal are both altered and constantly changing. Drug management in AKI is exceedingly complex and is only beginning to be understood. Thus, we approach this discussion in a physiological manner. Critically ill patients pass through phases of illness, sometimes rapidly, other times slowly. The recognition of the phases and the need to adjust medication administration strategies is crucial to improving outcomes. An early phase involving supraphysiologic kidney function may be contributory to therapeutic failures that result in the complication of later AKI and kidney function failure.
Pain and fatigue
Authors: McCabe Candy , Haigh Richard , Cohen Helen , Hewlett Sarah
Published: November 2015

Pain and fatigue are the prominent problems for those with a rheumatic disease, and are often underestimated by clinicians. Symptoms may fluctuate in quality and intensity over time and commonly will vary over the course of a day. For pain, clinical signs and symptoms will be dependent on the source of the pain and whether causative underlying pathology is identifiable or not. Fatigue may range from mild effects to total exhaustion and may include cognitive and emotional elements, with a complex, probably multicausal, pathway. Theoretical knowledge of potential mechanistic pathways for pain and fatigue should be used to inform assessment and treatment approaches. Best practice recommends a multidisciplinary and holistic treatment approach with the patient an active participant in the planning of their care, and self-management. Many patients with chronic musculoskeletal conditions will not achieve a pain-free or fatigue-free status. Medication use must therefore balance potential benefit against short- and long-term side effects. Rheumatology centres should offer specific fatigue and pain self-management support as part of routine care. Emphasis should be given to facilitating self-management strategies for both pain and fatigue to help the patient optimize their quality of life over years or a lifetime of symptoms. Interventions should include behaviour change and cognitive restructuring of pain/fatigue beliefs, as well as access to relevant self-help groups and charitable organizations. Referral for specialist advice from regional or national clinics on pain relief and management should be considered if pain interferes significantly with function or quality of life despite local interventions.
The systemically unwell child
Authors: Ramanan Athimalaipet V. , Akikusa Jonathan D.
Published: November 2015

The systemically unwell child is a common clinical problem in paediatrics. In most cases the cause is infection, and the child will usually improve spontaneously or following appropriate therapy. When routine investigations fail to reveal an aetiology and the child remains unwell, the differential diagnoses should be broadened to include, among others, paediatric rheumatic diseases. This chapter provides a brief overview of these conditions focusing on key clinical features, common diagnostic pitfalls, and investigations important in their diagnosis. The important rheumatologic differentials of systemic illness in children according to the age at which they typically occur and a summary of the key clinical and laboratory features of these conditions are presented. Once rheumatologic differentials relevant to the age of the child under evaluation are identified, they can be refined based on knowledge of the incidence and clinical and laboratory features of the diseases concerned.
Primary care presentation
Authors: Wise Elspeth
Published: November 2015

For many patients their first presentation to a medical professional with a musculoskeletal complaint is in a primary care setting. They may have as little as 10 minutes to explain their problem, be examined, and have a management plan determined. Quite commonly the musculoskeletal problem may present as an aside—by the way doctor, while I’m here’. All of this presents a challenge to the assessing primary care physician, who may have had little specific training for what makes up a large part of their workload. What training they have had may be inappropriate for their day-to-day job, as it is often secondary care led. The conditions that are classically seen in a secondary care setting and that are emphasized in the medical school curriculum are rarely seen in primary care. Patients also may not necessarily present with the classical symptoms described in textbooks; often it is over time, and with repeated contact, that the diagnosis may become more obvious. This chapter looks at the prevalence data for primary care and discusses the routine workload of a primary care physician.
Nervous system
Authors: Graham Andrew , Galton Clare
Published: November 2015

Rheumatological conditions may be complicated by a
variety of both central and peripheral nervous system disorders. Common complications such as
entrapment neuropathies are familiar to rheumatologists but accurate diagnosis of less
common neurological disorders may be challenging; careful clinical reasoning is essential,
supplemented where necessary by imaging, neurophysiology, and other special investigations
including cerebrospinal fluid examination. Complications vary according to the nature of the
background condition. In rheumatoid arthritis, neurological involvement is typically related
to the mechanical consequences of advancing disease; most commonly, entrapment neuropathies such as carpal
tunnel syndrome and cervical myelopathy due to atlantoaxial subluxation. By contrast,
neurological involvement in systemic lupus erythematosus (SLE) tends to occur earlier in the
disease course, with a much wider range of manifestations. The management of stroke or
seizures in SLE is not necessarily any different from that in the general population, unless
complicated by the antiphospholipid syndrome. However, less common neurological syndromes
may demand more specific investigation and treatment. For example, longitudinally extensive
transverse myelitis and recurrent optic neuritis (neuromyelitis optica, or Devic’s disease)
is frequently associated with antibodies to aquaporin-4, and is highly likely to relapse
unless treated vigorously with humoral immunosuppression. Nervous system involvement in
vasculitis is common. Finally, not all neurological disorder in rheumatological disease is
necessarily due to the underlying condition; neurological complications of disease-modifying
therapy are increasingly recognized, in particular central and peripheral nervous system
demyelination associated with TNF-α‎‎ inhibitors.
Comorbidities of rheumatic disease
Authors: Sokka Tuulikki , Puolakka Kari , Turesson Carl
Published: November 2015

All other diseases that coexist with a disease of interest are called comorbidities. Comorbidities in inflammatory rheumatic diseases may be associated with persistent inflammatory activity or disease-related organ damage, or may be related to medications. Lifestyle choices such as smoking or physical inactivity contribute to comorbidity. Patients with rheumatic diseases meet health professionals regularly and are more often tested for osteoporosis or cholesterol levels than individuals without rheumatic disease, which may contribute to a higher prevalence of some comorbidities. Comorbidities can also be unrelated to rheumatic diseases or their treatments. In this chapter, we discuss the impact of comorbidities to the patient. We emphasize the importance to review and manage comorbidities in usual daily rheumatology clinic, to improve outcomes of patients with rheumatic diseases.
Genetics of juvenile rheumatic diseases
Authors: Hinks Anne , Thomson Wendy
Published: November 2015

Juvenile rheumatic diseases are heterogeneous, complex genetic diseases; to date only juvenile idiopathic arthritis (JIA) has been extensively studied in terms of identifying genetic risk factors. The MHC region is a well-established risk factor but in the last few years candidate gene and large-scale genome-wide association studies have been utilized in the search for non-HLA risk factors. There are now 17 JIA susceptibility loci which reach the genome-wide significance threshold for association and a further 7 regions with evidence for association in more than one study. In addition, some subtype-specific associations are emerging. These risk loci now need to be investigated further using fine-mapping strategies and then appropriate functional studies to show how the variant alters the gene function. This knowledge will not only lead to a better understanding of disease pathogenesis for juvenile rheumatic diseases but may also aid in the classification of these heterogeneous diseases. It may identify new pathways for potential therapeutic targets and help in the prediction of disease outcome and response to treatment.
Vascular biology
Authors: Thornton Clare , Mason Justin
Published: November 2015

Vascular biology is the study of the physiology of the vasculature and how it may be the target for disease processes. An understanding of vascular biology is central to the study of rheumatic disease for three reasons: it is an integral part of a functioning immune system; it is the primary site of pathology in many conditions; and it is the site of the important secondary complications of chronic inflammation, endothelial dysfunction and atherosclerosis. Vascular biology requires a detailed knowledge of the anatomy and physiology of the vasculature and its constituent vessels. The multistep process by which leucocytes interact with endothelium lining postcapillary venules in order to leave the circulation and migrate towards a site of inflammation is central to the pathology of inflammatory disease. The vasculature is the primary site of injury in several rheumatic diseases, including the vasculitides. It may also be damaged by chronic inflammation, leading to endothelial dysfunction and accelerated atherosclerosis. Thrombosis is also a critical pathological process in several chronic inflammatory diseases, particularly the anti-phospholipid antibody syndrome and Behçet’s syndrome. The vascular endothelium is central to angiogenesis, the process of new capillary outgrowth, upon which synovial proliferation in inflammatory arthritis is dependent. Angiogenesis is inhibited by current anti-rheumatic therapies and may become a target for novel anti-rheumatic drugs. An increasing area of research concerns the direct effects of drugs used in the treatment of atherosclerosis and inflammatory disease on the endothelium, and whether these agents are beneficial or harmful. Of particular interest to rheumatologists are the vascular effects of statins, disease-modifying anti-rheumatic drugs (DMARDs), immunosuppressants, and cyclooxygenase inhibitors.
Rheumatoid arthritis—management
Authors: Deighton Chris
Published: November 2015

Influential guidelines on rheumatoid arthritis (RA) management agree on most key recommendations. Early diagnosis of persistent synovitis, and identification of poor prognostic markers, is essential. Rapid intervention is vital with drugs to suppress inflammation, slow down damaging disease components, and prevent disability.
The label of RA covers a broad spectrum of disease severity, and there is controversy about:
• whether the same interventions are needed for all patients
• whether monotherapy or combination treatment is appropriate
• the role of steroids in RA
• the appropriate introduction of biological therapies.
Treating to specified targets is optimal evidence-based practice, where patients are reviewed regularly for disease activity assessments, and inadequate control rectified. Aiming for remission is the ultimate goal, though for some patients minimal disease activity may be appropriate. Patient education addressing self-management is important, and the multidisciplinary team (MDT: specialist nurses, physiotherapists, occupational therapists, podiatrists, psychologists) needs to be involved from the start to minimize the impact on quality of life of the patient.
For established disease, rapid access is important for flares, and to consider whether disease management could be improved. An intermittent overview of established disease is important with access to the MDT, and assessments for comorbidities such as ischaemic heart disease, osteoporosis, and depression, as well as complications of the disease itself such as cervical spine disease, vasculitis, and lung and eye complications. An informed patient needs to be central to all decision making.
Polymyositis and dermatomyositis
Authors: Chinoy Hector , Cooper Robert G.
Published: November 2015

Polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM) form part of the idiopathic inflammatory myopathies (IIM), a heterogeneous group of rare autoimmune diseases characterized by an acquired proximal muscle weakness, raised muscle enzymes (including creatine kinase), inflammatory cell infiltrates in muscle biopsy tissue, electrophysiological abnormalities, and presence of circulating myositis-specific/myositis-associated autoantibodies. The underlying aetiology of IIM is poorly understood, but likely involves interactions between environmental and genetic risk factors. Myositis may also manifest in association with other connective tissue disorders. The predominant clinical presentation of IIM is skeletal muscle weakness, but many extramuscular features can also occur.
Access to good neuropathological support is essential in securing an accurate IIM diagnosis and excluding non-inflammatory myopathies, although IBM is often difficult to distinguish from PM. Antibody testing can help define IIM clinical subtypes, including cancer-associated myositis, predict prognosis, and help in optimizing treatment decisions. MRI can be invaluable for differentiating disease activity from damage, and detecting treatment-induced interval changes. Therapeutic effectiveness of new and existing treatments (where the evidence base remains poor) depends on making a prompt diagnosis and initiating early and appropriately aggressive treatment to prevent establishment of muscle damage.
This chapter attempts to summarize the salient features of IIM and update the reader about currently used diagnostics and treatment paradigms in this rare and understudied disease.
Sjögren’s syndrome—management
Authors: Ng Wan-Fai , Vissink Arjan , Theander Elke , Figueiredo Francisco
Published: November 2015

Management of Sjögren’s syndrome (SS) encompasses confirmation of diagnosis, disease assessment, and treatment of glandular and systemic manifestations including special situations such as pregnancy and SS-related lymphoma. The American European Consensus Group (AECG) classification criteria 2002 are the current gold standard for the diagnosis of SS. Salivary gland sialometry, sialochemistry, and ultrasound and tear osmolarity may be useful adjuncts. Recently, preliminary classification criteria of the American College of Rheumatology have been introduced as an alternative to the AECG criteria. Symptoms of SS are non-specific and must be actively explored. When assessing patients with SS, it is important to consider not only objective parameters such as abnormalities in blood tests and changes in tear and salivary flow, but also patient-reported outcome measures and impact on quality of life. Current management of patients with SS is hampered by the lack of evidence-based strategies. The symptoms experienced by patients with SS are often not fully appreciated by clinicians, which may contribute to the suboptimal management of the condition. Management of fatigue remains a major challenge and a holistic, multidisciplinary approach is recommended. Factors that may contribute to fatigue should be fully addressed. Recent advances in the understanding of the pathogenic mechanisms of SS have informed more targeted therapeutic strategies with some promising data. Optimal management of SS requires expertise from different disciplines. Combined clinics with rheumatology, oral medicine, and ophthalmology input will improve care and communications as well as reduce the number of clinic visits for patients and healthcare-related cost. Effective link between pSS specialists, dentists, opticians, and general practitioners will facilitate early diagnosis and reduce risk of long-term disability of SS.
Clinical features of ANCA-associated vasculitis
Authors: Gross Wolfgang L. , Holle Julia U.
Published: November 2015

The primary ANCA-associated vasculitides are granulomatosis with polyangiitis (Wegener’s, GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome, CSS). They predominantly affect small (and medium-sized) vessels and share a variable association with ANCA (anti-neutrophil cytoplasm antibody) directed against neutrophil proteinase 3 (PR3, mainly in GPA) and myeloperoxidase (MPO, mainly in MPA and CSS). Crescentic necrotizing glomerulonephritis and alveolar haemorrhage due to pulmonary capillaritis represent classical (vasculitic) organ manifestations of the ANCA-associated vasculitides (AAV). MPA occurs as a ’pure’ small (to medium-size) vessel vasculitis, whereas GPA and CSS are characterized by additional distinct clinical and pathological features. In GPA, granulomatous lesions of the upper and/or lower respiratory tract are a hallmark of the disease. Granulomatous lesions may be large in appearance and occur as space-consuming, infiltrating, and destructive inflammatory masses. GPA is believed to follow a stagewise course with an initial localized form, restricted granulomatous lesions of the upper and/or lower respiratory tract without clinical signs of vasculitis, and a consecutive generalization to systemic vasculitis which may be either non-organ-threatening (early systemic) or organ- and life- threatening (generalized GPA). Rarely, patients arrest in the localized stage and do not progress to systemic disease. In EGPA asthma, hypereosinophilia and eosinophilic organ infiltration (e.g. eosinophilic myocarditis) are typical features of the disease apart from vasculitis. Similarly to GPA, EGPA follows a stagewise course: asthma and eosinophilia may precede full-blown disease for several months or years. Recent cohort studies suggest different phenotypes in EGPA (predominantly vasculitic and MPO-ANCA-positive and predominantly with eosinophilic organ infiltration, usually ANCA-negative). This chapter focuses on the clinical features of the primary AAV and their outcome.
Treatment of ANCA-associated vasculitis
Authors: Jayne David
Published: November 2015

The goals of treatment in anti-neutrophil cytoplasm antibody (ANCA) vasculitis are to stop vasculitic activity, to prevent vasculitis returning, and to address longer-term comorbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk. Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as methotrexate or azathioprine, to prevent relapse. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Additional therapy with intravenous methylprednisolone and plasma exchange is employed in severe presentations with failing vital organ function.
Drug toxicity contributes to comorbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem, with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn. Disease relapse occurs in 50% and requires early detection at a stage when it will not adversely affect outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator.
Outcomes of vasculitis depend heavily on the level of tissue damage at diagnosis, especially renal dysfunction, but are also influenced by patient age, ANCA subtype, disease extent, and response to therapy. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)is treated along similar principles to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis but the persistence of steroid-dependent asthma in over one-third and differences in pathogenesis has suggested alternative treatment approaches. Chronic morbidity results from tissue damage and is especially common in the upper and lower respiratory tract and kidneys. Tracheobronchial disease is a severe late complication of GPA, while deafness, nasal obstruction, and chronic sinusitis are sequelae of nasal and ear vasculitis. Chronic infection of damaged epithelial surfaces acts as a drive for vasculitic activity and adequate infection control is necessary for stable remission. Chronic kidney disease can stabilize for many years but the risks of endstage renal disease (ESRD) are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful, with similar outcomes to other causes of ESRD.
Polymyalgia rheumatica
Authors: Dasgupta Bhaskar , Raine Charles
Published: November 2015

This chapter reviews advances in pathogenesis; European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria with clinical, laboratory, and ultrasound criteria for classification as polymyalgia rheumatica (PMR); the heterogeneity and overlap between PMR, inflammatory arthritis, and large-vessel vasculitis as illustrated by representative cases; pathogenesis; recent guidelines on early and correct recognition, investigations, and management of PMR; the scope of disease-modifying agents; socio-economic impact, outcomes, and patient experience in PMR. It also discusses areas for future research including clinical trials with biological agents and newer steroid formulations, standardized outcome assessments, and the search for better biomarkers in PMR.
Endovascular approach to the trauma patient
Authors: Diamantopoulos Athanasios , Katsanos Konstantinos
Published: November 2015

A 34-year-old male was admitted to the A&E department as a result of a motorcycle accident. The patient complained of mild left upper quadrant abdominal pain. He had normal vital signs and was haemodynamically stable. His haemoglobin (Hb) was 13.5g/dl on admission. As per institute protocol the patient underwent abdominal ultrasonography (US), which at the time showed no signs of intra-abdominal free fluid or other site-specific organ injury. The patient was admitted to the hospital for observation and reassessment as necessary. An hour later the patient started complaining of worsening pain and a second haemoglobin sample showed a drop of 2.1g/dl (Hb = 11.4g/dl). As active bleeding was suspected, the patient underwent a contrast-enhanced CT scan which identified contrast extravasation in the spleen. The consensus was to immediately transfer him to the angiographic suite for embolization in order to control the bleeding. Selective angiography of the splenic artery verified the presence of an intra-parenchymal active bleeding site and the appropriate branches were selectively catheterized and embolized using a microcatheter and microcoils with a satisfactory final angiographic result. The patient had an uneventful recovery without any signs of post-embolization syndrome and was discharged from the hospital three days later. In this case we discuss the indications and techniques used in the endovascular management of trauma-related injuries.
Percutaneous varicelectomy: coils or sclerosant agents?
Authors: Venettucci Piero , Krokidis Miltiadis , Iaccarino Vittorio
Published: November 2015

Varicocele is the most common treatable cause of male infertility. However, definitive treatment is very challenging, and there is a high recurrence rate after the majority of surgical and percutaneous procedures. A meticulous knowledge of the anatomy and the physiology of the venous plexus of the internal spermatic vein is required to understand the principles of endovascular treatment and to make the most appropriate choice of the required embolic agent. In this case we describe a 19-year-old male who was treated with surgical ligation but varicocele recurred two years later. The patient was treated with percutaneous sclerotheraphy with excellent results.
Malignant biliary strictures: covered or uncovered stents?
Authors: Krokidis Miltiadis , Hatzidakis Adam
Published: November 2015

The vast majority of cases of malignant jaundice are due to a non-operable tumour. Palliation is of paramount importance for the quality of life of such patients. Stents have an established role in the palliation of malignant biliary disease, aiming for drainage of bile towards the duodenum and the resolution of jaundice. The first stents that were introduced in clinical practice were plastic; these were soon replaced by self-expandable metallic stents because of their longer patency. However, bare metallic stents tend to become occluded by tumour in-growth and therefore covered metallic stents were developed. We describe a case where a covered metallic stent was used for the palliation of a patient with malignant jaundice due to a pancreatic adenocarcinoma, and we review the current evidence in the literature.
Vertebroplasty of the cervical spine
Authors: Tsoumakidou Georgia , Gangi Afshin
Published: November 2015

A case of cervical level primary aneurysmal bone cyst treated percutaneously with vertebroplasty is discussed. The patient presented with local pain due to vertebral body fracture with no signs of radiculopathy or neurological deficit. The procedure was performed under general anaesthesia and combined CT-fluoroscopic guidance. An anterior approach was used with the needle trajectory between the carotid sheath laterally, and the thyroid gland and oesophagus medially. The patient was symptom free immediately after the procedure. The short- and long-term clinical and imaging follow-up was satisfactory
Percutaneous neurolytic coeliac plexus block
Authors: Galea Angie , Guinness Richard , Watkinson Anthony
Published: November 2015

Coeliac axis neurosis involves injection of a neuroleptic agent under imaging guidance into the retrocrural space. This is a palliative technique that is generally used to control pain secondary to pancreatic cancer. This case highlights the key steps involved using a practical example and discusses anatomy, indications, complications, and results. Whilst nothing can replace hands-on experience, a few technical, clinical, and expert tips are offered to familiarize the radiologist with the challenging concepts involved in this uncommon procedure.
Video Protocols and Techniques for Movement Disorders
Authors: Barton Brandon R , Hall Deborah A
Published: November 2015

Movement-disorder neurology is an inherently visual-based subspecialty in which the type of movement, its distribution, and its impact on activities or rest are the most important elements that lead to accurate diagnosis. No amount of words in a chart can convey as much useful information as the direct visualization of the patient at rest and during activity. Despite the importance of videotaping to the field, there has been no standardization of protocols for videotaping movement disorders patients. Video recordings help document the phenomenology of the movements, their anatomical distributions, their impact on activities of daily living, and responses to treatment. Further, they are teaching tools that can help educate health professionals so that they can rate the severity of a given disorder, providing a visual document to review and discuss with one’s peers. The challenges of visual recording are several, and we will cover technical issues as well as medical decisions on exactly what to film and how to capture the essential features of a given patient’s disorder. We have chosen videos out of our recent practice that represent the “real life,” practical application of videotaping in practice. The most important overall impact of careful videotaping is improved patient care.
Dyskinesia
Authors: Barton Brandon R. , Hall Deborah A.
Published: November 2015

Dyskinesia is a general term that refers to any kind of abnormal/bad (dys-) involuntary movements (-kinesia). Dyskinesias in Parkinson Disease (PD) can be both choreic and dystonic in nature, and are a nearly universal complication of drug therapy in PD. Videos done specifically to measure dyskinesias in PD are most helpful in settings for screening for clinical trials and pre-surgical evaluations. Tardive dyskinesia (TD) is a general term that applies to movement disorders resulting from long-term therapy with dopamine receptor-blocking medications. The most common manifestation of TD are repetitive, stereotypic chewing-like movements of the mouth, jaw, and/or tongue. Many patients also have combined choreic movements of the limbs.
Instructions for the Videographer
Authors: Barton Brandon R. , Hall Deborah A.
Published: November 2015

The videographer helps to pick the appropriate videotaping protocol, maximize accuracy and completeness of video exams, and interact with clinical staff to provide further clinical information about the patient. Though a dedicated videographer is ideal to complete the full protocol, many institutions may not have staffing to accomplish this degree of detailed video documentation; in this case the videographer (a physician or medical trainee) may only be able to highlight the main features of the examination. Efficient communication will make the video session effective. The protocol for each movement disorder should be followed as closely as possible. General rules of courtesy and professionalism should be emphasized.
Deep Brain Stimulation
Authors: Barton Brandon R. , Hall Deborah A.
Published: November 2015

Placement of a deep brain stimulator (DBS) may occur as an effective treatment in patients with multiple diagnoses, although this si most commonly done for Parkinson disease (PD) and essential tremor. Patients with PD are videotaped both on and off their dopaminergic medication in order for the DBS team to assess appropriateness for surgery. The goal is to assess how effective the dopaminergic medications are improving their symptoms, since the success of the surgery is proportional to the degree of their medication response. Patients with diagnoses other than PD may be taped with this protocol either on medications or on and off medication, although sometimes the disease-specific protocol is used instead. The DBS protocol focuses on parkinsonism, especially speech and gait.
On the physical requirements for a pre-reionization origin of the unresolved near-infrared background
Authors: Helgason K , Ricotti M , Kashlinsky A , Bromm V
Published: November 2015

The study of the cosmic near-infrared background (CIB) light after subtraction of resolved sources can push the limits of current observations and yield information on galaxies and quasars in the early universe. Spatial fluctuations of the CIB exhibit a clustering excess at angular scales ∼1° whose origin has not been conclusively identified, but disentangling the relative contribution from low- and high-redshift sources is not trivial. We explore the likelihood that this signal is dominated by emission from galaxies and accreting black holes (BHs) in the early Universe. We find that, the measured fluctuation signal is too large to be produced by galaxies at redshifts z > 8, which only contribute ∼0.01–0.05 nW m−2 sr−1 to the CIB. Additionally, if the first small mass galaxies have a normal initial mass function, the light of their ageing stars (fossils) integrated over cosmic time contributes a comparable amount to the CIB as their pre-reionization progenitors. In order to produce the observed level of CIB fluctuation without violating constraints from galaxy counts and the electron optical depth of the IGM, minihaloes at z > 12 must form preferably top-heavy stars with efficiency f* ≳ 0.1 and at the same time maintain a very low escape fraction of ionizing radiation, fesc < 0.1 per cent. If instead the CIB fluctuations are produced by high-z BHs, one requires vigorous accretion in the early universe reaching ρacc ≳ 105 M⊙ Mpc−3 by z ≃ 10. This growth must stop by z ∼ 6 and be significantly obscured not to overproduce the soft cosmic X-ray background and its observed coherence with the CIB. We therefore find the range of suitable high-z explanations to be narrow, but could possibly be widened by including additional physics and evolution at those epochs.
Development of a DNA Microarray-Based Assay for the Detection of Sugar Beet Root Rot Pathogens
Authors: Liebe Sebastian , Christ Daniela S. , Ehricht Ralf , Varrelmann Mark
Published: November 2015

Sugar beet root rot diseases that occur during the cropping season or in storage are accompanied by high yield losses and a severe reduction of processing quality. The vast diversity of microorganism species involved in rot development requires molecular tools allowing simultaneous identification of many different targets. Therefore, a new microarray technology (ArrayTube) was applied in this study to improve diagnosis of sugar beet root rot diseases. Based on three marker genes (internal transcribed spacer, translation elongation factor 1 alpha, and 16S ribosomal DNA), 42 well-performing probes enabled the identification of prevalent field pathogens (e.g., Aphanomyces cochlioides), storage pathogens (e.g., Botrytis cinerea), and ubiquitous spoilage fungi (e.g., Penicillium expansum). All probes were proven for specificity with pure cultures from 73 microorganism species as well as for in planta detection of their target species using inoculated sugar beet tissue. Microarray-based identification of root rot pathogens in diseased field beets was successfully confirmed by classical detection methods. The high discriminatory potential was proven by Fusarium species differentiation based on a single nucleotide polymorphism. The results demonstrate that the ArrayTube constitute an innovative tool allowing a rapid and reliable detection of plant pathogens particularly when multiple microorganism species are present.
Dissociated Prostate Regeneration under the Renal Capsule
Authors: Zong Yang , Goldstein Andrew S. , Witte Owen N.
Published: November 2015

Tissue recombination models are useful for studying cancer initiation, progression, and metastasis. They also provide an in vivo environment in which to investigate the functional role of stem cells in tissue repair. In this protocol, we describe in detail the dissociated prostate regeneration assay. Dissociated adult murine prostate cells are combined with embryonic urogenital sinus mesenchymal cells and implanted under the renal capsule. Morphological tissue structures with appropriate epithelial–stroma interactions are reconstituted in the grafts.
Homogenization of Mammalian Cells
Authors: de Araújo Mariana E.G. , Lamberti Giorgia , Huber Lukas A.
Published: November 2015

Homogenization is the name given to the methodological steps necessary for releasing organelles and other cellular constituents as a free suspension of intact individual components. Most homogenization procedures used for mammalian cells (e.g., cavitation pump and Dounce homogenizer) rely on mechanical force to break the plasma membrane and may be supplemented with osmotic or temperature alterations to facilitate membrane disruption. In this protocol, we describe a syringe-based homogenization method that does not require specialized equipment, is easy to handle, and gives reproducible results. The method may be adapted for cells that require hypotonic shock before homogenization. We routinely use it as part of our workflow to isolate endocytic organelles from mammalian cells.
Isolation of Early and Late Endosomes by Density Gradient Centrifugation
Authors: de Araújo Mariana E.G. , Lamberti Giorgia , Huber Lukas A.
Published: November 2015

Density gradient centrifugation is a common method for separating intracellular organelles. During centrifugation, organelles float or sediment until they reach their isopycnic position within the gradient. The density of an organelle depends on its content, size, shape, and the lipid:protein ratio. The degree of separation between different organelles will therefore be highly dependent on how different their isopycnic points are in a given buffer. Separation will also depend on the medium used to prepare the gradient, whether it is sucrose (the most common) or an alternative. Here we describe the use of both continuous and discontinuous (step) gradients to isolate endocytic organelles.
Sample Preparation and Data Acquisition for μs-ALEX
Authors: Kapanidis Achillefs , Majumdar Devdoot , Heilemann Mike , Nir Eyal , Weiss Shimon
Published: November 2015

This protocol describes the preparation of samples and data acquisition for microsecond-alternating laser excitation. Sample preparation requires a dilution that ensures the detection of single events.
Voltage-Sensitive Dye Imaging of Population Signals in Brain Slices
Authors: Baker Bradley , Gao Xin , Wolff Brian S. , Jin Lei , Cohen Lawrence B. , Bleau Chun X. , Wu J.-Y.
Published: November 2015

In a bright-field measurement from a vertebrate brain stained by superfusing a solution of the dye over the surface, each pixel in a camera receives light from a substantial number (thousands) of neurons and neuronal processes (population signals). Because of scattering and out-of-focus light, this will be true even if the pixel size corresponds to a small area of the brain. In this situation, the voltage-sensitive dye signal will be a population average of the change in membrane potential of all of these neurons and processes. Many investigators have published voltage-sensitive dye imaging studies of population activities in brain slices. Their methods, including choice of dyes, illumination intensity, and imaging device, vary across a large spectrum. Here we present a protocol for visualizing spatiotemporal patterns in rodent neocortex in vitro. Detecting these patterns requires high-sensitivity imaging in single trials, because averaging will obscure the complex dynamics of the spatiotemporal patterns.
Analysis of Recombination and Chromosome Structure during Yeast Meiosis
Authors: Börner G. Valentin , Cha Rita S.
Published: November 2015

Meiosis is a diploid-specific differentiation program that consists of a single round of genome duplication followed by two rounds of chromosome segregation. These events result in halving of the genetic complement, which is a requirement for formation of haploid reproductive cells (i.e., spores in yeast and gametes in animals and plants). During meiosis I, homologous maternal and paternal chromosomes (homologs) pair and separate, whereas sister chromatids remain connected at the centromeres and separate during the second meiotic division. In most organisms, accurate homolog disjunction requires crossovers, which are formed as products of meiotic recombination. For the past two decades, studies of yeast meiosis have provided invaluable insights into evolutionarily conserved mechanisms of meiosis.
Consumer responses to pharmaceutical-company-sponsored disease information websites and DTC branded websites
Authors: Huh Jisu , Shin Wonsun
Published: November 2015

Purpose

– This study aims to investigate pharmaceutical company-sponsored disease information websites that are created and operated by pharmaceutical companies. Without clear indication of the site ownership, these websites look like non-advertising health information websites. Consumers’ responses to pharmaceutical company-sponsored disease information websites were examined in comparison to their responses to typical direct-to-consumer (DTC) drug brand websites.

Design/methodology/approach

– A field experiment was conducted with a representative sample of US adults. Study subjects were randomly assigned to one of three live websites: pharmaceutical company-sponsored disease information website; DTC brand website with a high level of trust cues; and DTC brand website with a low level of trust cues. After viewing the assigned websites, participants completed an online questionnaire. The questionnaire included measurements for perceived website trust, attitude toward the website, intention to use information, perceived importance of prescription drug information, perceived health, prescription drug use, disposition to trust, prior experience with the website and demographic information.

Findings

– The pharmaceutical company-sponsored disease information website generated higher website trust and more positive attitude and information use intention than the DTC drug brand websites. The results suggest that company-sponsored disease information websites may present some ethical issues related to website identity information transparency, which seems to inhibit consumers’ persuasion knowledge activation and proper coping responses. Because such websites look like non-advertising health information websites, consumers tend to evaluate them more positively and place higher trust in them than typical DTC drug brand websites with clear advertiser identification.

Originality/value

– This is the first study examining pharmaceutical company-sponsored disease information websites, a relatively new form of covert DTC online advertising with potential ethical concerns due to the site identity transparency issues. This study’s findings suggest that consumers are likely to be more trusting and receptive of information presented in websites taking the form of a non-advertising health information website than in DTC brand websites.
Do consumers perceive their doctors as influenced by pharmaceutical marketing communications?
Authors: Wei Mei-Ling , Delbaere Marjorie
Published: November 2015

Purpose

– This paper aims to explore whether and how consumers perceive the impact of pharmaceutical marketing on their own doctor’s prescribing behaviors, and subsequent responses toward their doctor’s advice.

Design/methodology/approach

– Three experimental studies were conducted. Studies 1 and 2 are based on text-based manipulations and undergraduate student research participants. Study 3 uses image-based manipulations and average adult consumers.

Findings

– Study 1 demonstrates that consumers can be quite skeptical about their doctor’s motives for prescribing certain brand-name drugs; in particular, consumers can construe doctors as agents of persuasion for prescribed brands. Study 2 shows that this can result not only in choosing generic drugs over prescribed brands but also in opting out of pharmaceuticals altogether by choosing alternatives like natural remedies. Study 3 further demonstrates that these effects can be easily triggered by visual cues in a non-student sample.

Originality/value

– This research builds on the existing literature on pharmaceutical marketing communications, and extends the theory of persuasion knowledge into healthcare settings.
The layers of relational communication in evaluating health care services
Authors: Kang Doo Syen , CHOY SYNG POM
Published: November 2015

Purpose

– This study aims to determine communication factors in various social settings that influence a comprehensive evaluation process ranging from information search before selecting a service organization to a service value assessment after using healthcare services.

Design/methodology/approach

– An empirical study using structural equation modeling tests the relationships among factors of the social environment in pre- and post-consumption evaluations with a sample of over 400 outpatients.

Findings

– The results indicate that service value evaluations are influenced by health-related communications with family before being diagnosed, opinions from family and friends in the decision-making process and interaction with other patients after choosing a hospital. The level of evaluation is mediated by how willing consumers are to exchange thoughts and ideas with others.

Research limitations/implications

– Future studies could consider the differences in gender and culture, and include more various resources such as patients from different hospitals and geographical areas for better generalizability.

Practical implications

– The paper identifies the importance of understanding how social relationships are involved in creating satisfied customers who will be loyal, generate good news and recommend services to others. The findings are conducive to planning and executing public relations strategies throughout the pre- and post-purchase process.

Originality/value

– Unlike the previous research that focused on service provider-oriented factors influencing customer satisfaction, the study investigates the effect of consumer-oriented social elements on service value evaluation to extend the horizon of public relations planning.