bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening for Enhancement of Permethrin Toxicity by Plant Essential Oils Against Adult Females of the Yellow Fever Mosquito (Diptera: Culicidae)
Authors: Tak Jun-Hyung , Coquerel Quentin Robert Renaud , Tsikolia Maia , Bernier Ulrich R , Linthicum Kenneth , Bloomquist Jeffrey R
Published: February 2020

Aedes aegypti L. (Diptera: Culicidae) is one of the most medically important mosquito species, due to its ability to spread viruses of yellow fever, dengue fever, and Zika in humans. In this study, the insecticidal activity of 17 plant essential oils was evaluated via topical application against two strains of Ae. aegypti mosquito, Orlando (insecticide-susceptible) and Puerto Rico (pyrethroid-resistant). Initial screens with the Orlando strain showed that cucumber seed oil (2017 sample) was the most toxic, followed by sandalwood and thyme oil. When the essential oils were mixed with permethrin, they failed to show any significant synergism of insecticidal activity. Sandalwood and thyme oils displayed consistently high mortality against the resistant Puerto Rico strain, with low resistance ratios of 2.1 and 1.4, respectively. In contrast, cucumber seed oil showed significantly less activity against Puerto Rico mosquitoes, with a resistance ratio of 45. Bioactivity-guided fractionation of the 2017 sample of cucumber seed oil sample via flash column chromatography produced 11 fractions, and gas-chromatography/mass spectrometry analysis revealed that the three active fractions were contaminated with 0.33, 0.36, and 0.33% of chlorpyrifos-methyl, an organophosphorus insecticide, whereas inactive fractions did not show any trace of it. These results suggested that the insecticidal activity of cucumber seed oil was probably due to the presence of the insecticide, later confirmed with a clean batch of cucumber seed oil obtained in 2018, which showed negligible insecticidal activity. These findings demonstrate clearly the need for essential oil analysis to confirm purity before any claims are made about pesticidal potency.
Vaccine Effectiveness Against Influenza Hospitalization Among Children in the United States, 2015–2016
Authors: Feldstein Leora R , Ogokeh Constance , Rha Brian , Weinberg Geoffrey A , Staat Mary A , Selvarangan Rangaraj , Halasa Natasha B , Englund Janet A , Boom Julie A , Azimi Parvin H , Szilagyi Peter G , McNeal Monica , Harrison Christopher J , Williams John V , Klein Eileen J , Sahni Leila C , Singer Monica N , Lively Joana Y , Payne Daniel C , Fry Alicia M , Patel Manish , Campbell Angela P
Published: February 2020

Background

Annual United States (US) estimates of influenza vaccine effectiveness (VE) in children typically measure protection against outpatient medically attended influenza illness, with limited data evaluating VE against influenza hospitalizations. We estimated VE for preventing laboratory-confirmed influenza hospitalization among US children.

Methods

We included children aged 6 months–17 years with acute respiratory illness enrolled in the New Vaccine Surveillance Network during the 2015–2016 influenza season. Documented influenza vaccination status was obtained from state immunization information systems, the electronic medical record, and/or provider records. Midturbinate nasal and throat swabs were tested for influenza using molecular assays. We estimated VE as 100% × (1 – odds ratio), comparing the odds of vaccination among subjects testing influenza positive with subjects testing negative, using multivariable logistic regression.

Results

Of 1653 participants, 36 of 707 (5%) of those fully vaccinated, 18 of 226 (8%) of those partially vaccinated, and 85 of 720 (12%) of unvaccinated children tested positive for influenza. Of those vaccinated, almost 90% were documented to have received inactivated vaccine. The majority (81%) of influenza cases were in children ≤ 8 years of age. Of the 139 influenza-positive cases, 42% were A(H1N1)pdm09, 42% were B viruses, and 14% were A(H3N2). Overall, adjusted VE for fully vaccinated children was 56% (95% confidence interval [CI], 34%–71%) against any influenza-associated hospitalization, 68% (95% CI, 36%–84%) for A(H1N1)pdm09, and 44% (95% CI, –1% to 69%) for B viruses.

Conclusions

These findings demonstrate the importance of annual influenza vaccination in prevention of severe influenza disease and of reducing the number of children who remain unvaccinated or partially vaccinated against influenza.
Nonsurgical management of an asymptomatic popliteal venous aneurysm
Authors: Bajaj Vinay , Benavides Francisco , Fisher Jay
Published: February 2020

An 81-year-old male with a history of poorly controlled congestive heart failure, chronic obstructive pulmonary disease and atrial fibrillation among other comorbidities was admitted to the hospital for worsening bilateral leg swelling and cellulitis. The patient had an injury to his left medial malleolus 2 weeks prior, which failed outpatient care. During the physical exam, a soft mobile mass was palpated in the right popliteal fossa along with bilateral varicose veins, +1 pitting edema in bilateral lower extremities up to mid-calf. Duplex ultrasound revealed a saccular dilation in the right popliteal vein measuring 2.2 × 1.8 × 2.8 cm, without any evidence of superficial or deep vein thrombosis. After an extended conversation with the patient and his care team, a decision to continue with medical management with close monitoring was made. Follow-up ultrasounds performed at 1, 6 and 12 months show no changes.
Value of evidence in the rare type match problem: common source versus specific source
Authors: Van Dorp I N , Leegwater A J , Alberink I , Jongbloed G
Published: February 2020

In the so-called rare type match problem, the discrete characteristics of a crime stain have not been observed in the set of background material. To assess the strength of evidence, two competing statistical hypotheses need to be considered. The formulation of the hypotheses depends on which identification of source question is of interest (Ommen, 2017, Approximate statistical solutions to the forensic identification of source problem. (Phd thesis). South Dakota State University). Assuming that the evidence has been generated according to the beta-binomial model, two quantifications of the value of evidence can be found in the literature, but no clear indication is given when to use either of these. When the likelihood ratio is used to quantify the value of evidence, an estimate is needed for the frequency of the discrete characteristics. The central discussion is about whether or not one of the traces needs to be added to the background material when determining this estimate. In this article it is shown, using fully Bayesian methods, that one of the values of evidence from the literature corresponds to the so-called ‘identification of common source’ problem and the other to the ‘identification of specific source’ problem (Ommen, 2017, Approximate statistical solutions to the forensic identification of source problem. (Phd thesis). South Dakota State University). This means that the question whether or not one of the traces needs to be added to the background material reduces to the question whether a common source or specific source problem is under consideration. The distinction between the two values is especially important for the rare type match problem, since the values of evidence differ most in this situation.
Addressing Secondary Traumatic Stress in Trauma-Informed Schools
Authors: Sweeney Brenda , Caringi James
Published: February 2020

Public schools support, educate, and care for all children who enroll. It is also the charge of public schools to care for the staff members educating these children. Secondary traumatic stress (STS) can impact an individual’s ability to regulate emotions, leading to depression and the manifestation of other anxieties. Numbing, avoidance, hyperarousal, and the re-experiencing of intrusive thoughts are all symptoms of STS that can affect an educator’s ability to perform. Three steps are needed to address STS: knowledge generation, identification, and intervention. Trauma-informed systems including multitiered systems of support can provide a framework within which awareness, identification, and intervention can be defined. Systems for addressing STS must include broad district-level support, building-level school community planning, and individual specific assistance. The “ABCs” identified in this chapter offer strategies for identifying and addressing STS on all three levels of the public education system.
Developing School Staff Buy-In for Trauma-Informed Schools
Authors: Baker Courtney N. , Augenstern Julia M. , Moberg Stephanie A. , Robey Nyx , Saybe Megan C.
Published: February 2020

Growing awareness of the prevalence and impact of adverse childhood experiences has spurred implementation, research, and policy on trauma-informed approaches in schools. School staff buy-in to trauma-informed schools (TIS) is an essential early step to building a schoolwide trauma-informed culture. Buy-in is developed by building knowledge and shifting attitudes through a full staff professional development training on trauma. Measuring school staff attitudes relevant to TIS can help ensure the effectiveness of TIS implementation. One available tool for this purpose is the Attitudes Related to Trauma-Informed Care (ARTIC) Scale. Even when school staff develop TIS-favorable attitudes after training, the TIS initiative can be difficult to maintain. Therefore, this chapter closes with a discussion of several key factors known to support the sustainability of complex educational interventions that can be incorporated into the TIS implementation plan.
Acute Concussion in the Emergency Department
Authors: Hainline Brian , Gurin Lindsey J. , Torres Daniel M.
Published: February 2020

Concussion evaluations are very common in the Emergency Department, but there is no standardized protocol to evaluate and manage concussions. Triage to rule out more severe brain injury is becoming more uniform. For example, there are emerging guidelines and biomarkers for when a brain CT scan should be ordered for a suspected intracranial bleed or other brain structural lesion. However, the nuance of concussion diagnosis and management is less uniform, leaving many patients with a diagnosis and no clear plan for management and recovery—and this fallout can negatively impact recovery. Following concussion diagnosis, discharge instructions are key, as delayed concussion management and lack of follow-up can lead to improper early management, which too often leads to prolonged, persistent symptoms.
Acute Concussion and Cervical Spine Injury
Authors: Hainline Brian , Gurin Lindsey J. , Torres Daniel M.
Published: February 2020

If an individual has suffered an injury serious enough to cause a concussion, it is also possible that a cervical spine injury has occurred. There should always be a low threshold for suspecting cervical spine injury following concussion. Cervical spine injury should be strongly considered if concussion is associated with altered consciousness, focal cervical spine pain or tenderness, cervical spine deformity, and motor/sensory extremity deficits. If a cervical spine injury is suspected, emergency medical services should be activated, and the cervical spine should be stabilized, ideally by manual in-line stabilization. In contact/collision sport settings, it is desirable to have in place a well-rehearsed emergency action plan for evaluation and management of cervical spine injuries.
Sleep Disorder Following Concussion
Authors: Hainline Brian , Gurin Lindsey J. , Torres Daniel M.
Published: February 2020

Sleep disorders are common in athletes and are a risk factor for development of mental health symptoms and disorders. Sleep disorder is also a risk factor for prolonged, persistent post-concussive symptoms. Individuals who have a sleep disorder following concussion are more susceptible to developing prolonged post-concussive symptoms unless the sleep disorder is properly managed. Sleep disorders are divided into primary sleep disorders such as obstructive sleep apnea, and secondary sleep disorders that may result from other conditions such as pain and post-traumatic stress disorder. The particular type of sleep disorder must be diagnosed, and will guide both nonpharmacologic and pharmacologic strategies, as warranted.
Concussion and Pituitary Dysfunction
Authors: Hainline Brian , Gurin Lindsey J. , Torres Daniel M.
Published: February 2020

Pituitary dysfunction is increasingly recognized as a possible complication of concussion. The hypothalamus and pituitary may be susceptible to shearing forces that are common in concussion. The hypothalamic-pituitary axis is critical in adolescent development, and it also plays an important role in normal adult functioning. Pituitary dysfunction can lead to symptoms of depression, lethargy, poor libido, impaired concentration, and decreased problem-solving ability; all of these symptoms are commonly observed in individuals with post-concussion persistent symptoms from other causes. Therefore, in individuals who present with persistent symptoms following concussion, pituitary dysfunction should be considered and managed appropriately.
Neck Pain Following Concussion
Authors: Hainline Brian , Gurin Lindsey J. , Torres Daniel M.
Published: February 2020

Neck pain and cervicalgia are common following concussion. The cervical spine should be carefully examined in any individual who has sustained a concussion, because neck pain may be a sign of more serious underlying cervical spine injury. Even when a more serious injury has been ruled out, it is noteworthy that the cervical structures are vulnerable to stress and injury at their end range of motion, and such motion occurs commonly in an accelerated fashion with concussion. Further, cervical spine injury may cause faulty proprioceptive input from the upper cervical spine, resulting in vestibular symptoms. Cervicalgia is a source of persistent symptoms following concussion and frequently manifests with dizziness and cervicogenic headache. Individuals with persistent symptoms of cervicalgia or cervicogenic headache may benefit from a combination of physical therapy and vestibular therapy.
Independent Medical Care
Authors: Hainline Brian , Gurin Lindsey J. , Torres Daniel M.
Published: February 2020

Sport coaches are the primary interface with athletes and have considerable influence over the athletic environment. There is an evolving cultural shift to an athlete-centered approach to sports medicine, meaning that athletes should receive medical care that is completely independent of the influence of the coach. This is an especially important concept when athletic trainers, physicians and other sports medicine personnel are housed in athletics, a space where a coach may have considerable influence. Ultimately, primary health-care providers for athletic teams or organizations should have unchallengeable, autonomous authority for all medical and return-to-play decisions in sport.
Protective Equipment
Authors: Hainline Brian , Gurin Lindsey J. , Torres Daniel M.
Published: February 2020

Helmets are designed to prevent catastrophic brain injury such as skull fractures and intracranial hemorrhage. Helmets do not prevent concussion, and are sometimes used as a weapon that may actually lead to a concussive injury. Football helmets are certified by the National Operating Committee on Standards for Athletic Equipment (NOCSAE), and the National Football League has also developed criteria for evaluating football helmets independent of NOCSAE. To mitigate concussion and repetitive head impact exposure, the head needs to be taken out of the game, irrespective of the use of helmets.
Youth Tackle Football
Authors: Hainline Brian , Gurin Lindsey J. , Torres Daniel M.
Published: February 2020

There has been an increasing movement to ban youth tackle football, despite the lack of a comprehensive and evidence-based evaluation of youth sport in general, and developmentally appropriate activities in particular. Physical illiteracy is a major concern in the United States, and youth sport provides a pathway for development of long-term engagement in sport and exercise, which results in physical literacy. The American Development Model is a comprehensive pathway that helps to assure long-term athlete development. Importantly, the American Development Model aims to assure developmentally appropriate activities, and considers not only physical development but also mental, emotional and social development. Future considerations of youth football should be within this model.
Fostering medical and health research in resource-constrained countries
Authors: Makgoba Malegapuru W. , Tollman Stephen M.
Published: February 2020

Access to quality healthcare and education for all are essential elements underpinning national development as well as prerequisites for personal well-being. This makes it important to grasp the inequalities that still prevail in human and institutional capacity, including access to and use of research resources. The goals of fostering medical research in resource-constrained countries are to bring outstanding science to bear on their medical and health problems; invest in building the requisite medical and health research systems; develop an evidence base to inform policies and programmes, resource allocation, and health practice; enhance scientific processes, findings, explanation, and ‘discovery’ by drawing on local know-how; and gain sustained engagement with policymakers, senior managers, and community leaders.
Newly discovered viruses
Authors: Froude Susannah J.A. , Hughes Harriet C.
Published: February 2020

Although humans are affected by an enormous range of microorganisms, almost all newly discovered emerging pathogens are viruses that are often zoonotic or vector-borne. These emerging viruses often have high baseline mutation rates, allowing them to adapt relatively easily to new hosts and enabling them to take advantage of new epidemiological opportunities provided by the changing environment. A range of apparently new human viral pathogens has been reported increasingly in international outbreak information over the last few years. How they will influence global public health remains to be seen. Emerging viruses that might be of particular global public health importance include, respiratory coronaviruses, Zika virus, and severe fever and thrombocytopenia syndrome virus. Other emerging viruses of importance include bocavirus, Bufavirus, PARV4, human parechovirus, Itaya, Heartland, and Bourbon virus. The human pathogenicity of other emerging viruses is less certain.
Lysosomal disease
Authors: Deegan Patrick B. , Cox Timothy M.
Published: February 2020

The lysosome is a ubiquitous, single membrane-bond intracellular organelle which continuously recycles biological macromolecules: it not only breaks down cell components but has a dynamic role in nutrient and energy sensing that, through regulatory signalling, is critical for homeostasis and metabolic economy of the cell. More than 80 lysosomal diseases caused by single gene defects are known. Biochemical classification identifies (1) sphingolipidoses; (2) mucopolysaccharidoses; (3) glycoproteinoses; (4) glycogenosis, with or without lysosomal debris derived from subcellular organelles due to impaired autophagy; and (5) miscellaneous conditions with multiple classes of storage material such as the neuronal ceroid lipofuscinoses. Functional classification describes deficiency of (1) a specific acid hydrolase activity, (2) an activator protein, (3) a lysosomal membrane protein or transporter, or (4) abnormal post-translational modification of lysosomal proteins, and (5) abnormal biogenesis of lysosomes. A unified classification will emerge from genetic characterization integrated with clinicopathological manifestations of the individual disorders. Fabry’s and Gaucher’s diseases (glycosphingolipidoses) are probably the most frequent in the general population, but certain lysosomal diseases are over-represented in particular groups where consanguinity or endogamy is high. Other diseases discussed in this chapter include (1) cystinosis, (2) the mucopolysaccharidoses, (3) Pompe’s disease (glycogen storage disease type II), (4) Niemann–Pick diseases, (5) lysosomal acid lipase deficiency, (6) Danon’s disease, and (7) diseases more recently attributed to primary defects in lysosomes and related organelles.
Disorders of peroxisomal metabolism in adults
Authors: Wierzbicki Anthony S.
Published: February 2020

The peroxisome is a specialized organelle which employs molecular oxygen in the oxidation of complex organic molecules including lipids. Enzymatic pathways for the metabolism of fatty acids, including very long-chain fatty acids (VLCFAs), enable this organelle to carry out β-oxidation in partnership with mitochondria. A peroxisomal pathway for isoprenoid lipids derived from chlorophyll, such as phytanic acid, utilizes α-oxidation, but a default mechanism involving ω-oxidation may also metabolize phytanic acid and its derivatives. The biochemical manifestations, molecular pathology, and diverse clinical features of many peroxisomal disorders have now been clarified, offering the promise of prompt diagnosis, better management, and useful means to provide appropriate genetic counselling for affected families. At the same time, specific treatments including rigorous dietary interventions and plasmapheresis to remove undegraded toxic metabolites offer credible hope of improvement and prevention of disease in affected individuals. X-linked adrenoleukodystrophy (X-ALD)—due to mutations in the gene for an ATP-binding cassette (ABC) protein of unknown function and characterized by accumulation of unbranched saturated VLCFAs, particularly hexacosanoate (C26), in the cholesterol esters of brain white matter, adrenal cortex, and certain sphingolipids of the brain. The disease has multiple phenotypes. Most cases develop increasing handicap; management is palliative and supportive in most instances. Adult Refsum’s disease—due in most cases to mutations in the gene for phytanoyl-CoA hydroxylase (PHYH) such that patients are unable to detoxify phytanic acid by α-oxidation and have greatly elevated levels of this in their plasma. Usually presents in late childhood with progressive deterioration of night vision, the occurrence of progressive retinitis pigmentosa, and anosmia. Treatment is by restriction of dietary phytanic acid, with or without its elimination by plasmapheresis or apheresis.
α1-Antitrypsin deficiency and the serpinopathies
Authors: Lomas David A.
Published: February 2020

α1-Antitrypsin is an acute phase glycoprotein synthesized by the liver that functions as an inhibitor of a range of proteolytic enzymes, most importantly neutrophil elastase in the lung. Ninety-five per cent of severe plasma deficiency of α1-antitrypsin results from homozygosity for the Z allele (Glu342Lys), which causes the protein to undergo a conformational transition and form ordered polymers that are retained within hepatocytes as periodic acid–Schiff-positive, diastase-resistant inclusions. Clinical features— all adults homozygous for the Z allele of α1-antitrypsin have a minor degree of portal fibrosis that is often subclinical, but up to 50% have clinically evident cirrhosis and occasionally hepatocellular carcinoma. They also develop panlobular emphysema that typically affects the lung bases and is greatly exacerbated by smoking. Cor pulmonale and polycythaemia are late features. Diagnosis and management—severe genetic deficiency of α1-antitrypsin is readily diagnosed by low plasma levels and the virtual absence of the α1-band on protein electrophoresis. Patients should abstain from smoking and avoid agents that cause hepatic injury, such as excessive alcohol and obesity. Emphysema is treated along conventional lines. α1-Antitrypsin replacement therapy is widely used in North America to slow the progression of the lung disease and has recently been licensed by the European Medicines Agency, but its clinical efficacy remains contentious and it has no effect on liver disease. Clinical trials are underway to ‘knock down’ the expression of mutant Z α1-antitrypsin within hepatocytes to try to prevent cirrhosis. Other serpinopathies—the polymerization that underlies α1-antitrypsin deficiency is found in other members of the serine protease inhibitor (or serpin) superfamily to cause diseases as diverse as thrombosis (antithrombin), angio-oedema (C1 inhibitor), and dementia (neuroserpin).
Parathyroid disorders and diseases altering calcium metabolism
Authors: Thakker R.V.
Published: February 2020

The control of body calcium involves a balance—chiefly under the control of parathyroid hormone (PTH)—between the amounts that are absorbed from the gut, deposited into bone and into cells, and excreted from the kidney. Abnormalities of the parathyroid glands themselves will cause derangements of calcium homeostasis and several clinical disorders. PTH oversecretion due to parathyroid tumours, which affect 3 in 1000 of the population, is a major cause of hypercalcaemia which may be associated with kidney stones, osteoporosis, and peptic ulcers. PTH deficiency, which results in hypocalcaemia and occurs in 1 in 4000 live births, may be associated with epilepsy, tetany, cataracts, skeletal malformations, and abnormal dentition. This chapter will review the physiological and biochemical mechanisms underlying extracellular calcium homeostasis, the clinical features of hypercalcaemia and hypocalcaemia, the clinical disorders associated with abnormal calcium homeostasis and their management, and the genetic basis for disorders of calcium metabolism.
Crohn’s disease
Authors: Parkes Miles , Raine Tim
Published: February 2020

Crohn’s disease is a common form of chronic inflammatory bowel disease. Typically involving one or more of the terminal ileum, colon, and perineum, it causes patchy transmural inflammation characterized microscopically by granulomata. Common complications include fibrotic strictures, fistulas, and abscesses. The initiating trigger is unknown, but an unregulated mucosal immune response to commensal bacteria drives the chronic inflammation. Variants in several genes involved in innate immunity are strongly associated, and smoking also increases the risk. Crohn’s disease confers significant morbidity but low mortality. Treatment of acute inflammatory disease is usually with corticosteroids or (occasionally) therapeutic diets, the latter particularly in children. For steroid dependence, frequent relapse, or objective evidence of uncontrolled mucosal inflammation, immunosuppression is indicated with immunomodulator or biological therapy or a combination of the two. First-line immunomodulators are azathioprine or 6-mercaptopurine, with methotrexate used as second-line therapy. Antitumour necrosis factor-α (anti-TNFα) antibody therapy can induce rapid remission of resistant disease and has a key role in maintaining remission in such cases. Despite increased use of immunosuppressants, 70 to 80% of patients require surgery in the long term, most commonly for ileal stricturing. Timely, conservative surgery is the key, minimizing the length of small-bowel resected and using laparoscopic approaches where possible. For colonic disease requiring surgery, segmental colectomy or subtotal colectomy with ileorectal anastomosis are preferred, but significant rectal or perianal involvement may require proctocolectomy and ileostomy. Perianal Crohn’s disease is treated medically with antibiotics, azathioprine, and anti-TNF antibody therapy, and surgically with abscess drainage and placement of seton sutures through fistulas where possible. Some fistulas heal with intensive medical therapy. Others may warrant attempts at surgical repair if they produce unacceptable symptoms.
Ulcerative colitis
Authors: Sanderson Jeremy , Irving Peter
Published: February 2020

Ulcerative colitis is a chronic relapsing and remitting disease in which chronic inflammation affects the rectum and extends proximally to a variable extent. The precise aetiology remains unknown but involves an interplay between reduced diversity in the gut microbiota and a genetically dysregulated gut immune system and epithelial barrier.

Typical presentation of mild or moderate disease is with a gradual onset of symptoms including diarrhoea, rectal bleeding, and the passage of mucus. Severe disease is characterized by anorexia, nausea, weight loss, and severe diarrhoea, with the patient likely to look unwell with fever, tachycardia, and other signs of volume depletion, and the abdomen may be distended and tympanitic, with reduced bowel sounds and marked colonic tenderness. Diagnosis is usually made on the basis of exclusion of infective colitis by stool culture and the finding of typical diffuse inflammation in the rectum and above at sigmoidoscopy. Management requires rapid control of symptoms with induction therapy followed by maintenance of remission. Mild disease is typically treated with 5-aminosalicyclic acid delivered both orally and by enema, and moderate disease by 5-aminosalicyclic acid and steroids. Patients with severe disease require hospital admission, intravenous steroids, and daily review by both a physician and a surgeon experienced in the management of ulcerative colitis. Ciclosporin or infliximab are used as rescue therapies for steroid-resistant acute severe ulcerative colitis, but colectomy should not be delayed when this is required. Maintenance therapy with immunomodulators and biological therapies are both effective at maintaining remission, and several new biologicals are in clinical trials.
Gastrointestinal infections
Authors: O’Brien Sarah
Published: February 2020

Gastrointestinal infections, especially diarrhoea and vomiting, are responsible for substantial morbidity, mortality, and socioeconomic penalties worldwide. Poor sanitation, inadequate water supplies, and globalization of food production, processing, and retailing increase the risk of large epidemics of food- and waterborne outbreaks of gastrointestinal disease. Acute diarrhoea can be caused by a range of pathogens. Gastrointestinal pathogens usually cause three principal syndromes: acute watery diarrhoea, acute bloody diarrhoea (inflammatory diarrhoea or dysentery), and persistent diarrhoea. They can also cause systemic disease. Patients who do not have high fever (>38.5°C), systemic illness, tenesmus, bloody diarrhoea, a prolonged course (>2 weeks), or dehydration require neither investigation nor treatment. Investigation is required in patients with any of these features, with faecal specimens examined by culture (bacterial pathogens and some protozoa), microscopy (ova, cysts, and parasites), immunoassays (some protozoa and viruses), and molecular methods, usually polymerase chain reaction (PCR) or reverse transcriptase PCR (bacterial toxin genes and viruses). A specific laboratory diagnosis is useful epidemiologically and therapeutically. Oral rehydration therapy is the priority for patients with mild to moderate diarrhoea as long as vomiting is not a major feature. Antimicrobial therapy is not recommended or usually required for uncomplicated diarrhoea, but antibiotic treatment is beneficial for cholera, giardiasis, cyclosporiasis, shigellosis, symptomatic traveller’s diarrhoea, Clostridium difficile diarrhoea, and typhoid. Antimotility drugs are useful in controlling moderate to severe diarrhoea in adults but they are not generally recommended for infants and young children under the age of 4 years. Strict attention to food and water precautions and hand washing helps reduce the risk of gastrointestinal infections. Immunization has not yet proved successful for combating many gastrointestinal pathogens, with the notable exception of rotavirus.
Asthma
Authors: Nanzer-Kelly Alexandra , Cullinan Paul , Menzies-Gow Andrew
Published: February 2020

Asthma is a chronic inflammatory disease of the bronchial airways that is characterized pathologically by a desquamative eosinophilic bronchitis and clinically by reversible airway narrowing and increased airway responsiveness to non-specific provocative stimuli. The condition is common, frequently disabling, and can cause death. In the Western world it now affects more than 10% of children and more than 5% of adults, and in England and Wales it is the cause of more than 100,000 hospital admissions and is the certified cause of death of 1,000–1,500 people each year. The risk of developing asthma is increased in atopic individuals, and in asthmatics natural allergen exposure induces asthma and airway hyper-responsiveness. Viral infections, most commonly with rhinoviruses, cause 80–85% of exacerbations of asthma in children and 50–75% in adults.
Miscellaneous conditions presenting to the rheumatologist
Authors: Carter Stuart , Dunkley Lisa , Adebajo Ade
Published: February 2020

Musculoskeletal symptoms can occur in a variety of diseases, or as drug side effects. Presentations and conditions discussed in this section include: multisystem diseases (e.g. adult-onset Still’s disease, acute sarcoid arthritis, and amyloidosis);

paraneoplastic syndromes (e.g. hypertrophic pulmonary osteoarthropathy, remitting seronegative symmetrical synovitis with pitting oedema, and tumour-induced osteomalacia); skin manifestations of rheumatic disease (e.g. panniculitis, neutrophilic dermatoses, and multicentric reticulohistiocytosis); primary joint pathology and synovial disorders (e.g. pigmented vilonodular synovitis, synovial osteochondromatosis, Charcot joint); rheumatic manifestations of haematological disease (e.g. haemophilia, sickle cell disease, leukaemia, lymphoma, and polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin abnormalities); rheumatic manifestations of metabolic disease (e.g. hereditary haemochromatosis, Wilson’s disease); disorders of the spine and axial skeleton (e.g. Tietze’s syndrome, diffuse idiopathic skeletal hyperostosis, and alkaptonuria); drug-induced rheumatic syndromes (e.g. statin-induced myopathy, drug-induced tendinopathy, drug-induced lupus, and allopurinol hypersensitivity).
Malignant diseases of the urinary tract
Authors: Eisen Tim , Hamdy Freddie C. , Huddart Robert A.
Published: February 2020

Bladder cancer—the seventh commonest cancer in the United Kingdom and the fourth most common in men. Nonmuscle-invasive disease is usually treated by transurethral resection with postoperative intravesical chemotherapy with mitomycin or bacillus Calmette–Guérin. Local muscle-invasive disease in patients who are fit enough is usually treated with radical cystoprostatectomy and cisplatin-based chemotherapy. Metastatic disease is typically treated with cisplatin-based chemotherapy. Renal cell cancer—approximately 3% of the total cancer burden. For operable patients with no distant disease, the treatment of choice is nephron-sparing (if possible) or radical nephrectomy. Metastatic renal cancer can behave in a very variable manner. Palliative nephrectomy may be required for bleeding or pain. First-line systemic treatment is with antiangiogenic tyrosine kinase inhibitors targeting vascular endothelial growth factor receptor signalling. Prostate cancer—second most common cause of male cancer deaths in the Western world. Most cases are asymptomatic at presentation, being detected following measurement of serum prostate-specific antigen (PSA) or after digital rectal examination, although screening by measurement of PSA remains a contentious issue. Clinically localized prostate cancer is treated with active monitoring, radiotherapy, or minimally invasive surgery. Locally advanced disease is likely to progress and requires intervention, usually in the form of androgen deprivation therapy and radiotherapy. First-line treatment for metastatic prostate cancer is androgen deprivation therapy; second-line treatment may be with newer antiandrogens in combination with steroids and cytotoxics. Testicular cancer—affects predominantly young adult men in whom they are the most common malignant tumours. For most patients, initial management consists of an inguinal orchidectomy, with or without immediate adjuvant therapy. Standard treatment of metastatic germ cell tumours is with a combination of bleomycin, etoposide, and cisplatin.
Inherited skin disease
Authors: Maruthappu Thiviyani , Kelsell David P.
Published: February 2020

Considerable advances in our understanding of inherited skin diseases have been made over the last decade as a result of high throughput sequencing technologies, including next generation sequencing and whole exome sequencing. The genetic basis of a myriad of monogenic epidermal disorders and syndromes including blistering diseases, ichthyoses, palmoplantar keratodermas, and the ectodermal dysplasias have now been elucidated. However, most patients referred from primary care to the dermatology clinic will be seeking treatment for a few common skin disorders such as psoriasis, eczema, and acne. The genetic basis of these disorders is rather more complex, but progress has been made through genome-wide association studies, which, for example, have linked susceptibility variants in the gene for filaggrin (FLG) and SPINK5 to atopic eczema, and IL23R and many other immune-related genes to psoriasis.
Tumours of the skin
Authors: O’Toole Edel
Published: February 2020

A variety of tumours, both benign and malignant, are found in skin. Benign skin lesions, such as seborrhoeic keratoses and skin tags, are often just a cosmetic nuisance, but some benign skin lesions can be a component of diseases with serious medical consequences (e.g. neurofibromatosis or LEOPARD syndrome). Skin cancer is the most common human cancer and its incidence continues to increase. It most commonly affects older, fair-skinned individuals who have had either acute intermittent exposure to ultraviolet light or chronic ultraviolet light exposure. Organ transplant recipients have a 200-fold increased risk of squamous cell carcinoma. About 2% of patients who develop skin cancer have a genetic predisposition, for example, Gorlin’s syndrome in basal cell carcinoma and familial melanoma syndromes in malignant melanoma. Mutations in the PTCH gene cause Gorlin’s syndrome, and loss of heterozygosity at that locus is also present in most sporadic basal cell carcinoma.
Introduction and approach to the patient with neurological disease
Authors: Compston Alastair , Kennard Christopher
Published: February 2020

Clinical neurology uses conversation, detailed questioning, and discussion, observation, structured examination, and selective investigation to formulate the patients’ problems into an anatomical and pathological framework. The competent neurologist identifies and probes relevant components of the history, reliably elicits the physical signs, knows which investigations are necessary and relevant, appreciates the most likely underlying diagnosis and mechanism of disease, and communicates relevant information to the patient accurately, intelligibly, and sensitively. This system has evolved over several centuries, during which much knowledge has accumulated on structure and function in health and disease, the reliability of physical signs and laboratory investigations, and the nosology of disease.
Disturbances of higher cerebral function
Authors: Nestor Peter J.
Published: February 2020

Clinicopathological and imaging studies indicate strong associations between particular disorders of cognition and focal disease in the brain, but not all focal lesions induce specific loss of higher functions. Neuropsychological research has deepened our understanding by suggesting organizational frameworks for human cognitive faculties. Modern scientific study of higher cerebral function began in the late 19th century with the case studies of Broca and Wernicke. Their observations of language disorders associated with damage to the left hemisphere gave rise to the notion that specific mental faculties could be dissociated from each other and localized to specific regions within the cerebral hemisphere. Since that time clinicopathological and, more recently, imaging studies have established associations between specific cognitive disorders and focal brain lesions; these studies also show that some lesions do not give rise to highly specific deficits.
The unconscious patient
Authors: Bates David
Published: February 2020

Prolonged loss of consciousness (coma, defined as a Glasgow Coma Score of 8 or less) is seen commonly: (1) following head injury, (2) after an overdose of sedating drugs, and (3) in the situation of ‘non-traumatic coma’, where there are many possible diagnoses, but the most common are postanoxic, postischaemic, systemic infection, and metabolic derangement (e.g. hypoglycaemia). Urgent assessment is required to identify and, where possible, correct the pathological cause, and protect the brain from the development of irreversible damage. Specific treatment (if any) will depend upon the particular cause of coma, but—whatever the cause—long-term attention is required to the patient’s respiration, skin, circulation, and bladder and bowel function, seizures must be controlled, and the level of consciousness should be regularly assessed and monitored.
Brainstem syndromes
Authors: Bates David
Published: February 2020

The classic presentation of brainstem syndromes, including the long tracts and deficits of cranial nerve nuclei, commonly causes crossed cranial nerve and motor or sensory long tract deficits; the cranial nerve lesions are ipsilateral to the lesion and the long tract signs are contralateral. It is important to assess the extracranial vascular supply to the posterior circulation, especially to listen for bruits over the subclavian vessels and to record the pulse and blood pressure in both upper limbs, remembering that the vertebral arteries arise from the subclavian vessels. Apart from the cranial nerve and long tract deficits, there may be ataxia, vertigo, the presence of an internuclear ophthalmoplegia and unreactive pupils, the symptoms of diplopia and oscillopsia, and the finding of nystagmus or ocular paresis.
Diseases of the spinal cord
Authors: Jacob Anu , Larner Andrew J.
Published: February 2020

The spinal cord is subject to numerous pathological processes which may be intrinsic (intramedullary) and/or extrinsic (extramedullary) to the cord. Many diseases can affect the spinal cord. Those of particular note include spondylotic myelopathy, multiple sclerosis, transverse myelitis, subacute combined degeneration of the cord, genetic and vascular disorders, syringomyelia, injury/trauma, motor neuron disease, and cancer—the most common spinal cord tumours are metastasis, astrocytoma, ependymoma, lymphoma. Specific medical and surgical treatments are determined by the particular cause of myelopathy. These may arrest progression, but function that has been lost may not recover fully. Prognosis of acute cord compression is directly related to the time delay between symptom onset and relief of compression. Chronic disability as a consequence of spinal cord disease requires intensive neurorehabilitation.
Spinal cord injury and its management
Authors: Masri(y) Wagih El , Barnes Michael
Published: February 2020

Spinal cord injury most commonly affects young men as a consequence of road traffic accidents, violence, and sports injuries. The incidence is increasing in older people, mainly due to falls. Appropriate management of the individual at the scene of an accident is vital to avoid unnecessary worsening of a spinal cord injury. Those who are unconscious should be assumed to have a cervical spine injury, with the head and neck held firmly in a neutral position using a semi-rigid collar, and transportation on a spinal board with a head immobilizer. With appropriate management, initial mortality from spinal cord injury is less than 5%. Most of those with complete somatosensory loss will recover up to three myotomes below the level of the injury, and with ongoing support are able to lead dignified, healthy, fulfilling, enjoyable, productive, and often competitive lives.
Structure and function of muscle
Authors: Hanna Michael G. , Bugiardini Enrico
Published: February 2020

The motor unit—the final common pathway for all voluntary muscle activity—is composed of an anterior horn cell, its peripheral axon, the axon terminal branches, the associated neuromuscular junctions, and the muscle fibres innervated. The muscle cells are multinucleate units with unique structures adapted for response to metabolic, nervous, and autocrine signals. Meanwhile, there are also different types of motor units: type 1—rich in mitochondria and specialized for oxidative metabolism of fat; type 2—larger fibres with abundant glycogen that generate energy by glycosis and are critical for short-lived muscle contraction. Knowledge of the underlying molecular cell biology, neurophysiology, and biochemical energetics of muscle provides a useful basis for understanding the symptoms, signs, and pathogenesis of clinical disorders affecting the muscles. Mutations in sarcolemmal proteins, such as dystrophin, cause diseases with widespread effects on skeletal muscle function, the heart, and survival.
Delirium
Authors: Sheehan Bart
Published: February 2020

Delirium is one of the most common psychiatric problems encountered in elderly medical inpatients. It involves a fluctuating cognitive impairment with reduced alertness and often with poorly formed delusions and/or visual hallucinations. The main differential diagnosis is from dementia, although delirium is more likely to develop in patients with existing dementia. Almost any medical condition that affects brain function may cause delirium. Infection is the most common cause, and it is important to consider prescribed drugs as a cause and to remember drug and alcohol withdrawal. Imperatives in management are first to keep the patient safe from harm (they may wander or put themselves in danger), and second to find and correct the cause. Urgent medical investigation and treatment is required as long periods of delirium put the patient at risk of harm, including permanent cognitive impairment.
Clinical anatomy of the pelvis and the reproductive organs
Authors: Ind Thomas
Published: February 2020

Proficient surgery requires good basic surgical skills and an understanding of the relevant anatomy. The time when a surgeon watched an operation, performed the same procedure, and then taught it has elapsed. Routine formulaic surgical procedures have become outdated and modern surgical practice is focused on individual patients and their specific needs. The main focus of surgery is now dedicated to the competent obtainment of skills and a complete understanding of human anatomy and its variations. This chapter focuses on the main anatomical structures encountered during gynaecological surgery. The anatomy of the pelvis in relation to the fetal skull is also covered.
Maternal physiology
Authors: Vousden Nicola , Shennan Andrew H.
Published: February 2020

Pregnancy is a time of dramatic adaptation to all physiological systems. The purpose is to provide a suitable environment for the growth and development of the fetus, and to protect and prepare the mother for the process of labour and lactation. This chapter provides an overview of the major changes to the haematological, immune, cardiovascular, respiratory, renal, gastrointestinal, and endocrine systems, as well as an overview of uterine and mammary physiology. Perhaps the most dramatic changes are seen in the haematological and cardiovascular systems with an increase in plasma volume of 50% and an increase in cardiac output of 35–40%, with a reduction in peripheral vascular resistance of 40% in nulliparous women. The relevance of these changes, along with the other major systems, to the clinical findings of healthy pregnant women is described, in addition to consideration of pregnancy complications that may occur.