To see the other types of publications on this topic, follow the link: INS-1 cells.
Books on the topic 'INS-1 cells'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 books for your research on the topic 'INS-1 cells.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse books on a wide variety of disciplines and organise your bibliography correctly.
1
Moerdler, Scott, and Xingxing Zang. PD-1/PDL-1 Inhibitors as Immunotherapy for Ovarian Cancer. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190248208.003.0010.
Full textAbstract:
Programmed death 1 (PD-1), a member of the B7-CD28 immunoglobulin superfamily, and its ligands PD-L1/PD-L2 inhibit T-cell activation. They also play a key role in the tumor microenvironment, allowing for cancer immune escape. PD-1 is induced on a variety of immune cells, including tumor-infiltrating lymphocytes (TILs), while PD-L1 is found on many types of solid tumors including ovarian cancer and some TILs. The use of immunocheckpoint inhibitors like anti-PD-1 and anti-PD-L1 therapies has been shown to reactivate the immune system to attack tumor cells. Ovarian cancers have been shown to be responsive to anti-PD-1 and anti-PD-L1 therapies, though immunocheckpoint inhibitors are not enough. Current research is evaluating combination therapies to improve response rates.
2
Ng, Ann, and Erin S. Williams. Sickle Cell Disease. Edited by Erin S. Williams, Olutoyin A. Olutoye, Catherine P. Seipel, and Titilopemi A. O. Aina. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190678333.003.0033.
Full textAbstract:
Sickle cell anemia (sickle cell disease) is a common hemoglobinopathy with anywhere from 90,000 to 100,000 Americans affected. This chronic condition has a predominance in populations of African descent, occurring in approximately 1 out of 365 African American births, compared to 1 out of 16,300 Hispanic births. The sickle cell trait can be detected in 1 of 13 African American births. One of the most common complications associated with sickle cell anemia, vaso-occlusive crises by sickled cells, results in severe pain. Other issues associated with this condition include acute chest syndrome, lung infections, end organ damage, and stroke. With improvements in the management and prevention of pain crises, infection, and other systemic involvement, these patients are living longer, thus increasing the potential for surgical needs. Whether it is for routine surgeries or surgeries that are due to the natural history of the disease; the pediatric anesthesiologist must be knowledgeable of the management of these patients in order to prevent morbidity and mortality.
3
Kamdar, Pravin P. Numerical simulation of Al [subscript x] Ga [subscript 1-x] As/GaAs and (Al [subscript x] Ga [subscript 1-x]) [subscript 0.47] In [subscript 0.53] As/InP bandgap engineered solar cells. 1990.
Find full text
4
Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199687039.003.0040.
Full textAbstract:
Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the extracellular matrix and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated monocytes differentiate into macrophages which acquire a specialized phenotypic polarization (protective or harmful), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoprotein via low-density lipoprotein receptor-related protein-1 receptors. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Both lipid-laden vascular smooth muscle cells and macrophages release the procoagulant tissue factor, contributing to thrombus propagation. Platelets also participate in progenitor cell recruitment and drive the inflammatory response mediating the atherosclerosis progression. Recent data attribute to microparticles a potential modulatory effect in the overall atherothrombotic process. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be modulated.
5
Moriuchi, Hiroyuki. Human T-cell Lymphotropic Virus. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190604813.003.0010.
Full textAbstract:
Human T-cell lymphotropic virus type 1 (HTLV-1), a human retrovirus that infects an estimated 10–20 million people worldwide, has endemic foci in Japan, West and Central Africa, the Caribbean, Central and South America, and Melanesia. Also, it is the etiological agent of a lymphoproliferative malignancy, adult T-cell leukemia/lymphoma (ATLL), as well as chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 can be transmitted vertically, sexually, or by blood-borne transmission. ATLL occurs in approximately 5% of carriers who are infected during early childhood, and primary prevention is the only strategy likely to reduce this fatal disease. Children born to carrier mothers acquire the virus predominantly from breastfeeding. In endemic areas, mother-to-child transmission (MTCT) can be significantly reduced by screening pregnant women for the HTLV-1 antibody, followed by replacing breastfeeding with exclusive formula feeding. Indications for serological screening and recommendations for prevention of perinatal transmission are reviewed in this chapter.
6
Hartigan-O’Connor, Dennis J., and Christian Brander. Immunology. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190493097.003.0005.
Full textAbstract:
The key factor in HIV pathogenesis is the decline in CD4+ T cells with resultant immunodeficiency and chronic inflammation. Depletion of CD4+ T cells from the gastrointestinal mucosa followed by microbial translocation and subsequent immune activation are components of disease progression in untreated patients. Symptomatic and occult opportunistic infections including cytomegalovirus contribute to chronic inflammation in persons infected with HIV. Antiretroviral therapy (ART) results in immune reconstitution, with increases in peripheral CD4+ T cell lymphocytes in most persons infected with HIV, although immune recovery is quite variable. A subset of patients with AIDS will develop immune reconstitution inflammatory syndromes after initiation of ART. Approximately 1% of persons with HIV are able to control infection without the need for ART (“elite” controllers). A variety of immune-based therapies, including hydroxyurea, growth hormone, and statins, are being studied in clinical trials and may ultimately play a role in treating persons with HIV infection.
7
Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199687039.003.0040_update_001.
Full textAbstract:
Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the intimal layer and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles attached to the extracellular matrix suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated pro-atherogenic monocytes (mainly Mon2) differentiate into macrophages which acquire a specialized phenotypic polarization (protective/M1 or harmful/M2), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoproteins via low-density lipoprotein receptor-related protein-1 receptors becoming foam cells. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels and calcium deposits increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces rich in tissue factor that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Platelets also participate in leucocyte and progenitor cell recruitment are likely to mediate atherosclerosis progression. Recent data attribute to microparticles a modulatory effect in the overall atherothrombotic process and evidence their potential use as systemic biomarkers of thrombus growth. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be prevented and modulated.
8
Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199687039.003.0040_update_002.
Full textAbstract:
Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the intimal layer and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles attached to the extracellular matrix suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated pro-atherogenic monocytes (mainly Mon2) differentiate into macrophages which acquire a specialized phenotypic polarization (protective/M1 or harmful/M2), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoproteins via low-density lipoprotein receptor-related protein-1 receptors becoming foam cells. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels and calcium deposits increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces rich in tissue factor that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Platelets also participate in leucocyte and progenitor cell recruitment are likely to mediate atherosclerosis progression. Recent data attribute to microparticles a modulatory effect in the overall atherothrombotic process and evidence their potential use as systemic biomarkers of thrombus growth. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be prevented and modulated.
9
Pitzalis, Costantino, Frances Humby, and Michael P. Seed. Synovial pathology. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0052.
Full textAbstract:
Synovial pathology is seen in a variety of disease states, including rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis, and systemic lupus erythmatosus (SLE). This chapter highlights recent advances that characterize the cellular composition of these tissues according to surface markers and chemokine and cytokine expression, and describes synovial functional status and response to therapeutics. In RA, after initiation, pannus migrates over and under cartilage, and into subchondral bone, in a destructive process. Cartilage-pannus junction (CPJ) is characterized as invasive or 'quiescent' or 'indistinct'. Invasive CPJ can comprise macrophages, fibroblast-like synoviocytes (FLS), mast cells, and/or neutrophils. CPJ activity is related to the state of activation of the overlying subintima. Subintimal inflammation can be graded to a variety of degrees (I–IV) according to established criteria and is illustrated. In some RA synovia, cellular aggregates organize into ectopic lymphoid structures (ELS) through the expression of lymphorganogenic signals, to exhibit T- or B-cell zones accompanied by dendritic cells and lymphangiogenesis. ELS synthesize rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACAP), considered to be indicative of aggressive disease. The selective cellular expression of macrophage and dendritic cell chemokines and cytokines such as TNF, GMCSF, TGFβ, IL-1, IL-6, IL-23, and chemokines can be seen in synovia, to form a regulated and cooperative environment that sustains the cellular organization and pathological function. Important to this process are FLS and CD68+ macrophages. CD68 expression correlates with disease severity and can be useful as a surrogate marker of disease modifying activity of therapeutics, such as anti-TNF and anti-B-cell biologics.
10
Kriemler, Susi. Exercise, physical activity, and cystic fibrosis. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199232482.003.0033.
Full textAbstract:
Cystic fibrosis (CF) is the most common genetic autosomal recessive disease of the Caucasian race, generally leading to death in early adulthood.1 The frequency of the gene carrier (heterozygote) is 1:20–25 in Caucasian populations, 1:2000 in African-Americans, and practically non-existent in Asian populations. The disease occurs in about 1 in every 2500 life births of the white population. Mean survival has risen from 8.4 years in 1969 to 32 years in 2000 due to improvements in treatment. The genetic defect causes a pathological electrolyte transport through the cell membranes by a defective chloride channel membrane transport protein [cystic fibrosis transmembrane conductance regulator (CFTR)]. With respect to the function, this affects mainly the exocrine glands of secretory cells, sinuses, lungs, pancreas, liver, and the reproductive tract of the human body leading to a highly viscous, water-depleted secretion. The secretion cannot leave the glands and in consequence causes local inflammation and destruction of various organs. The main symptoms include chronic inflammatory pulmonary disease with a progressive loss of lung function, exocrine and sometimes endocrine pancreas insufficiency, and an excessive salt loss through the sweat glands.1 A summary of the signs and symptoms of CF will be given with a special emphasis on the effect of exercise performance and capacity.
11
Salinas-Rodríguez, Sergio G., Juan Arévalo, Juan Manuel Ortiz, Eduard Borràs-Camps, Victor Monsalvo-Garcia, Maria D. Kennedy, and Abraham Esteve-Núñez, eds. Microbial Desalination Cells for Low Energy Drinking Water. IWA Publishing, 2021. http://dx.doi.org/10.2166/9781789062120.
Full textAbstract:
The world's largest demonstrator of a revolutionary energy system in desalination for drinking water production is in operation. MIDES uses Microbial Desalination Cells (MDC) in a pre-treatment step for reverse osmosis (RO), for simultaneous saline stream desalination and wastewater treatment. MDCs are based on bio-electro-chemical technology, in which biological wastewater treatment can be coupled to the desalination of a saline stream using ion exchange membranes without external energy input. MDCs simultaneously treat wastewater and perform desalination using the energy contained in the wastewater. In fact, an MDC can produce around 1.8 kWh of bioelectricity from the energy contained in 1 m3 of wastewater. Compared to traditional RO, more than 3 kWh/m3 of electrical energy is saved. With this novel technology, two low-quality water streams (saline stream, wastewater) are transformed into two high-quality streams (desalinated water, treated wastewater) suitable for further uses. An exhaustive scaling-up process was carried out in which all MIDES partners worked together on nanostructured electrodes, antifouling membranes, electrochemical reactor design and optimization, life cycle assessment, microbial electrochemistry and physiology expertise, and process engineering and control. The roadmap of the lab-MDC upscaling goes through the assembly of a pre-pilot MDC, towards the development of the demonstrator of the MDC technology (patented). Nominal desalination rate between 4-11 Lm-2h-1 is reached with a current efficiency of 40 %. After the scalability success, two MDC pilot plants were designed and constructed consisting of one stack of 15 MDC pilot units with a 0.4 m2 electrode area per unit. This book presents the information generated throughout the EU funded MIDES project and includes the latest developments related to desalination of sea water and brackish water by applying microbial desalination cells. ISBN: 9781789062113 (Paperback) ISBN: 9781789062120 (eBook)
12
Farghaly, Samir A. Adoptive Cell Immunotherapy for Epithelial Ovarian Cancer. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190248208.003.0005.
Full textAbstract:
The standard management for epithelial ovarian cancer (EOC) is a combination of aggressive debulking surgery with residual tumor of less than 1 cm and platinum-based chemotherapy. However, a high percentage of patients experience disease recurrence. Extensive efforts to find new therapeutic options have been made, albeit cancer cells develop drug resistance and malignant progression occurs. Novel therapeutic strategies are needed to enhance progression-free survival and overall survival of patients with advanced EOC. Several preclinical and clinical studies investigated feasibility and efficacy of adoptive cell therapy (ACT) in EOC. The aim of this chapter is to present an overview of ACT in EOC, focusing on Human Leukocyte Antigen (HLA)-restricted tumor infiltrating lymphocytes and MHC-independent immune effectors such as natural killer and cytokine-induced killer. The available data suggest that ACT may provide the best outcome in patients with low tumor burden, minimal residual disease, or maintenance therapy. Further preclinical studies and clinical trials are needed.
13
Juelg, Boris, and Rajesh Gandhi. HIV Cure Strategies. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190493097.003.0006.
Full textAbstract:
Although current antiretroviral therapy (ART) is highly effective at controlling HIV-1 replication, it does not eradicate or cure the infection. HIV-1 persists quiescently in cellular reservoirs, not detected by the immune system due to the lack of active viral replication; these reservoirs represent the major obstacle for cure approaches. Reversal of HIV-1 latency and induction of virus expression by a variety of interventions may render infected cells susceptible to immune recognition and active clearance. Strategies to boost immune responses via vaccination, immunomodulation, or gene therapy are being evaluated with the aim of achieving HIV-1 control without antiretroviral therapy, if not viral eradication.
14
Fleischmann, Roy. Signalling pathway inhibitors. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0081.
Full textAbstract:
Oral, small-molecule signalling pathway inhibitors, including ones that inhibit the JAK and SyK pathways, are currently in development for the treatment of rheumatoid arthritis (RA). Tofacitinib is an orally administered small-molecule inhibitor that targets the intracellular Janus kinase 3 and 1 (JAK1/3) molecules to a greater extent than JAK2 while baricitinib (formerly INCB028050) predominantly inhibits JAK1/2. Many of the proinflammatory cytokines implicated in the pathogenesis of RA utilize cell signalling that involves the JAK-STAT pathways and therefore inhibition of JAK-STAT signalling, by targeting multiple RA-associated cytokine pathways, has the potential to simultaneously reduce inflammation, cellular activation, and proliferation of key immune cells. Fostamatinib disodium is an orally available inhibitor of spleen tyrosine kinase (SyK), which is a cytoplasmic tyrosine kinase that is an important mediator of immunoreceptor signalling in mast cells, macrophages, neutrophils, and B cells. Interruption of SyK signalling may interrupt production of tumour necrosis factor (TNF) and metalloproteinase and therefore affect RA disease activity. Tofacitinib has been investigated in multiple phase 2 and phase 3 trials which have investigated its efficacy (clinical, functional, and radiographic) and safety in patients who have failed disease-modifying anti-inflammatory drugs (DMARDs) as monotherapy or in combination with DMARDs, compared to an inhibitor of tumour necrosis factor alpha (TNFα) and in patients who have failed TNFα inhibitors. The efficacy of fostamatinib and baricitinib has been investigated in phase 2 trials; both are in large phase 3 clinical programmes. Each of these medications has demonstrated efficacy; their safety profile has been shown to be different from each other and from currently approved biological agents. This chapter discusses what is currently known and understood about their efficacy and safety.
15
Cox, Josephine H., Stuart Z. Shapiro, Liza Dawson, Cynthia Geppert, Andrew M. Siegel, and M. Patricia D’Souza. Vaccines for The Prevention and Treatment of HIV Infection. Edited by Mary Ann Cohen, Jack M. Gorman, Jeffrey M. Jacobson, Paul Volberding, and Scott Letendre. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199392742.003.0032.
Full textAbstract:
While the HIV/AIDS pandemic continues, the overall incidence of HIV infections has fallen through use of antiretroviral therapy (ART) and multiple prevention modalities. To achieve a durable end to the pandemic and avoid the requirement for daily antiretroviral medication over a lifetime, a safe and effective prophylactic vaccine remains essential. This chapter reviews current advances in prophylactic and therapeutic HIV-1 vaccine strategies and the challenges that lie ahead. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs) from infected individuals, the discovery of mechanisms of bnAb induction, and progress in understanding mechanisms of CD8 T-cell killing of HIV-infected cells and the structure of the HIV envelope trimer have opened new strategies for HIV vaccine design. On the therapeutic front, the persistence of HIV reservoirs remains a formidable obstacle to achieving sustained virological remission in HIV-infected individuals after ART is discontinued. Development of a new generation of immune-based therapeutic agents might contribute to a curative intervention. The chapter closes with an overview of ethical challenges in vaccine development and clinical testing.
16
Keegan, James, and Charles D. Deakin. Pathophysiology and management of anaphylaxis in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0314.
Full textAbstract:
Anaphylaxis is a severe life-threatening systemic hypersensitivity reaction, which occurs in approximately 10–20 per 100,000 population per annum, and accounts for 0.3% of adult critical care admissions. Anaphylaxis most commonly results from an exaggerated immune reaction to foreign antigens, prompting release of vasoactive substances from mast cells. A broad range of agents including foods, insect stings, latex, and drugs can trigger anaphylaxis. Common food allergens include nuts, shellfish, milk, and eggs. The most frequently implicated drugs include neuromuscular blocking agents (NMBAs) and antibiotics. The clinical features of anaphylaxis are variable and may occur together or in isolation. Epinephrine is the primary treatment for anaphylaxis, administered via the intramuscular route. Measurement of mast cell tryptase is essential for the diagnosis of anaphylaxis. Samples should be taken immediately, at 1–2 hours, and at 24 hours after the onset of symptoms. Investigations should be directed at identification of the trigger agent, and patients should be provided with information to enable them to avoid probable triggers and recognize future episodes.
17
Cerhan, James R., Claire M. Vajdic, and John J. Spinelli. The Non-Hodgkin Lymphomas. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190238667.003.0040.
Full textAbstract:
The non-Hodgkin lymphomas (NHL) are a heterogeneous group of over forty lymphoid neoplasms that have undergone a major redefinition over the last twenty-five years, in part due to advances in immunology and genetics as well as implementation of the WHO classification system. NHLs are considered clonal tumors of B-cells, T-cells, or natural killer (NK) cells arrested at various stages of differentiation, regardless of whether they present in the blood (lymphoid leukemia) or lymphoid tissues (lymphoma). In the United States, the age-standardized NHL incidence rate (per 100,000) doubled from 1973 (10.2) to 2004 (21.4) and then stabilized, while five-year relative survival rates improved from 42% in 1973 to 70% in 2004. Established risk factors for NHL or specific NHL subtypes include infectious agents (HTLV-1, HIV, EBV, HHV8, HCV, H. pylori), immune dysregulation (primary immunodeficiency, transplantation, autoimmunity, and immunosuppressive drugs), family history of lymphoma, and common genetic variants identified by genome-wide association studies.
18
Ajithkumar, Thankamma, Ann Barrett, Helen Hatcher, and Natalie Cook. Genito-urinary cancer. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199235636.003.0009.
Full textAbstract:
Renal cell carcinoma (RCC) accounts for approximately 2% of cancer diagnosis worldwide. It has the highest mortality of any urological cancer. Clear-cell renal cell carcinoma (CC-RCC) is the commonest RCC. CC-RCC has the highest prevalence in Eastern Europe and is the fifth commonest solid tumour in the UK. Incidence of primary CC-RCC rises after the age of 40 years old and there is a 2:1 male to female ratio....
19
Beattie, R. Mark, Anil Dhawan, and John W.L. Puntis. Hirschsprung's disease. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198569862.003.0039.
Full textAbstract:
Hirschprung's disease 280Neuronal intestinal dysplasia 281Intestinal pseudo-obstruction 281Hirschsprung's disease is the absence of ganglion cells in the myenteric plexus of the most distal bowel. Presentation is with constipation. Incidence is 1 in 5000. Long-segment Hirschsprung's disease is familial, with equal sex incidence. The gene is on chromosome 10. It is associated with Down's syndrome and there is a high frequency of other congenital abnormalities....
20
Klingenberg, Roland, and Ulf Müller-Ladner. Mechanisms of inflammation. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0270.
Full textAbstract:
This chapter provides a brief summary of the immune pathogenesis of atherosclerosis, highlighting shared features with inflammatory pathways in rheumatoid arthritis (RA) described in detail in Chapter 25.4. RA constitutes a prototype autoimmune disease primarily affecting the joints but also the heart and vessels associated with increased cardiovascular mortality. Recent years have produced a wealth of novel insights into the diversity of immune cell types which either propagate or dampen inflammation in atherogenesis. Expansion of this inherent anti-inflammatory component carried by regulatory T cells may constitute a new therapeutic target to harness the progression of atherosclerotic cardiovascular disease. Among the various inflammatory mediators involved in RA pathology, cytokines (tumour necrosis factor-α and interleukin-6) have gained major interest as therapeutic targets with approved therapies available. In light of the many common features in the pathogenesis of RA and atherosclerosis, these biologics are currently being evaluated in cardiovascular patients. The recently published CANTOS trial showed that IL-1 inhibition reduced adverse cardiovascular events in patients with coronary artery disease demonstrating that inflammation is a genuine therapeutic target. The near future will provide more information whether inflammation is a bona fide cardiovascular risk factor based on completion of several clinical trials using anti-inflammatory approaches in patients with both cardiovascular disease and rheumatoid arthritis.
21
Franceschi, Silvia, Hashem B. El-Serag, David Forman, Robert Newton, and Martyn Plummer. Infectious Agents. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190238667.003.0024.
Full textAbstract:
Eleven infectious agents (seven viruses, three parasites, and one bacterium) have been classified by the International Agency for Research on Cancer as carcinogenic to humans for one or more cancer sites: hepatitis B virus; hepatitis C virus; thirteen types of human papillomavirus (HPV); human immunodeficiency virus type 1 (HIV-1); human T-cell leukemia virus type 1; Epstein-Barr virus; Kaposi sarcoma herpesvirus; Helicobacter pylori; Opisthorchis viverrini; Clonorchis sinensis; and Schistosoma haematobium. Other infectious agents, such as Merkel cell polyomavirus, Plasmodium falciparum, and cutaneous HPVs, have been classified as “probably carcinogenic” or “possibly carcinogenic.” Accurate biomarkers of chronic infection have been essential for estimating risk and ascribing a causal role to infectious agents in cancer. Of the 14 million cases of cancer estimated to have occurred worldwide in 2012, 2.2 million were caused by infectious agents. Vaccination and screen-and-treat programs have the potential for greatly reducing the burden of cancer caused by infections.
22
Walsh, Stephen B. Approach to the patient with renal tubular acidosis. Edited by Robert Unwin. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0036.
Full textAbstract:
The renal tubular acidoses are a collection of syndromes characterized by defective urinary acidification. These syndromes have classically caused some confusion, and many opine that the widely used numerical system (type 1, 2) should be abandoned. We consider distal renal tubular acidosis and proximal renal tubular acidosis separately, and briefly cover hypoaldosteronism. Distal (Type 1) renal tubular acidosis is a syndrome of hypokalaemia, metabolic acidosis, kidney stones, nephrocalcinosis, and osteomalacia or rickets. It is caused by failure of the acid secreting α-intercalated cells in the distal nephron. Proximal (Type 2) renal tubular acidosis is a syndrome of metabolic acidosis that is almost always accompanied by the Fanconi syndrome of glycosuria, phosphaturia, uricosuria, aminoaciduria, and low-molecular-weight proteinuria. It is caused by a failure of bicarbonate reabsorption by the proximal tubular cells. Type 3 or mixed renal tubular acidosis, as originally described, has vanished (or was originally incompletely described). It is sometimes used to describe a mutation of carbonic anhydrase II, which causes both proximal and distal renal tubular acidosis, as well as cerebral calcification and osteopetrosis. Type 4 or hypoaldosteronism is a syndrome of hyperkalaemia and mild metabolic acidosis. It is due to a lack of aldosterone or resistance to its action.
23
Noordenbos, Troy, and Dominique Baeten. Immune mechanisms: innate immunity. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198734444.003.0007.
Full textAbstract:
Innate immune mechanisms are strongly implied in the pathophysiology of spondyloarthritis (SpA). This chapter discusses available data on the role of the innate immune system in relation to HLA-B27, genetic associations, and the cellular and molecular characteristics of disease target tissue. Regarding the linkage with MCH-class I molecule HLA-B27, the chapter discusses the arthritogenic peptide hypothesis and three popular antigen-independent theories. The genetic architecture of the disease argues against a role for the adaptive immune system and identifies cytokine pathways, such as IL-1, TNF, and IL-23/IL-17. In experimental as well as in human SpA, the importance of these cytokine pathways are confirmed by effective reduction of signs and symptoms upon blockade of specific molecules. In-depth cellular and molecular analysis of the target tissue identifies a contribution of cells with strong innate features, rather than cells of the adaptive immune system.
24
Sybert, Virginia P. Tumors/Hamartomas. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190276478.003.0010.
Full textAbstract:
Chapter 10 covers Basal Cell Nevus Syndrome, Cowden Syndrome, Cylindromatosis, Dysplastic Nevus Syndrome, Epidermal Nevus, Gardner Syndrome, Giant congenital nevocytic nevus, Hereditary Keratoacanthomas, Hereditary Leiomyomatosis and renal cell cancer, Infantile Myofibromatosis, Multiple Endocrine Neoplasia Types 1, 2A, and 2B/3, Pilomatricoma, Proteus Syndrome, Sebaceous Nevus Syndrome, and Tumoral Calcinosis. Each condition is discussed in detail, including dermatologic features, associated anomalies, histopathology, basic defect, treatment, mode of inheritance, prenatal diagnosis, and differential diagnosis.
25
Lloyd, Peter, Sarah Doaty, and Bevra H. Hahn. Aetiopathogenesis of systemic lupus erythematosus. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198739180.003.0002.
Full textAbstract:
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of immune dysregulation, autoreactive B and T cells, and the production of a broad, heterogeneous group of autoantibodies (autoAb). The pathogenesis of lupus can be divided into three stages: 1) genetic predisposition and environmental exposures, 2) loss of tolerance, and 3) immune activation. In this chapter we will discuss the aetiopathogenesis of systemic lupus erythematosus with emphasis placed on key autoantibodies, cytokines, the innate and adaptive immune system, tolerance, NETosis, genetics and epigenetics, environmental triggers and the role of gender.
26
Ajithkumar, Thankamma, Ann Barrett, Helen Hatcher, and Natalie Cook. Skin cancer. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199235636.003.0011.
Full textAbstract:
Basal cell carcinoma (BCC) is a slow growing, locally invasive (hence called rodent ulcer) malignant epidermal skin tumour. The exact incidence is difficult to obtain although there is a worldwide trend in increasing incidence. Approximately 1 million new cases are diagnosed per year in the USA....
27
Barker, Richard. The supply of new medicine—unlimited? Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199600663.003.0002.
Full textAbstract:
Chapter 1 describes the supply of new medical technology which exploits the huge advances we are making in bioscience, the build-up a profound understanding of how the beautiful molecular machines of the living cell actually work, and how they link together in the almost unimaginably complex system that is our body, and asks what fresh pharmaceutical innovations are on the horizon? Will gene and cell therapy reach the diseases that drugs cannot reach? Is ‘Personalized medicine’ practical? What will converging technologies—therapeutics, diagnostics, informatics, nanotechnology—bring us?
28
Shotliff, Kevin. Diabetes mellitus. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0184.
Full textAbstract:
Diabetes mellitus, often referred to simply as diabetes, is a syndrome of disordered metabolism (insulin deficiency and/or insulin resistance) resulting in abnormally high blood glucose levels (hyperglycaemia). Currently, 2%–6% of the UK population have diabetes; worldwide, 189 million people were known to have diabetes in 2003 and this may reach 324 million by 2025. Type 1 diabetes is due to the destruction of insulin-producing pancreatic beta cells, and type 2 diabetes to combined insulin resistance and relative insulin deficiency. Other types of diabetes are also recognized. This topic reviews clinical features, diagnosis, and management of diabetes mellitus.
29
Young, Benjamin. Classes of Antiretrovirals. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190493097.003.0019.
Full textAbstract:
Results of the randomized, international INSIGHT START clinical trial provide definitive proof of the benefit of antiretroviral therapy initiation in asymptomatic individuals with CD4+ counts greater than 500 cells/mm3. There are six different classes of antiretroviral agents: two types of reverse transcriptase inhibitors, two types of entry inhibitors, one class of inhibitors of HIV protease, and one class of inhibitors of HIV integrase. Combination antiretroviral therapy is recommended for all people living with HIV. The primary goal of combination antiretroviral therapy is to achieve viral suppression. Each antiretroviral class targets a unique step in the replication cycle of HIV-1.
30
Bird, Mark F., and David G. Lambert. Deorphanization of ORL-1/LC132 by reverse pharmacology in two landmark studies. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0026.
Full textAbstract:
Deorphanization of ORL-1/LC132 in 1995 by reverse pharmacology in two simultaneously published landmark studies added a new member to the opioid family of G-protein coupled receptors. Meunier and Reinscheid used cells expressing recombinant ORL-1 (human) or LC132 (rat) and the presumed intracellular inhibition of cyclic AMP formation to ‘fish’ for endogenous peptide ligands in rat whole-brain and pig hypothalamic extracts. Both studies reported the isolation of a 17-amino-acid peptide, which was named nociceptin and orphanin FQ by the two authors, respectively. The behaviour of the isolated peptide was a complete surprise, as a general hyperalgesia was observed when the peptide was administered at supraspinal sites. We now know that this peptide has, in fact, anti-opioid action, particularly in the medulla. The endogenous peptide exerts a multitude of effects both in the nervous system and, unlike classical opioids, has efficacy in neuropathic pain.
31
Jackson, Nicola. Butler Machine Tool Co. Ltd v Ex-Cell-O Corporation (England) Ltd [1979] 1 WLR 401, Court of Appeal. Oxford University Press, 2018. http://dx.doi.org/10.1093/he/9780191866135.003.0003.
Full textAbstract:
Essential Cases: Contract Law provides a bridge between course textbooks and key case judgments. This case document summarizes the facts and decision in Butler Machine Tool Co. Ltd v Ex-Cell-O Corporation (England) Ltd [1979] 1 WLR 401, Court of Appeal. The document also includes supporting commentary from author Nicola Jackson.
32
Araujo, Abelardo Q.-C. Neurological Manifestations of the Human T-lymphotropic Virus Type 1. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0161.
Full textAbstract:
The human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about 20 million individuals worldwide. Its typical neurological presentation is of a chronic, slowly progressive myelopathy named “HTLV-1-associated myelopathy/tropical spastic paraparesis” (HAM/TSP). HAM/TSP emerges as the tip of the iceberg among numerous other neurological clinical syndromes caused by this virus, such as inflammatory myopathies, polyneuropathies, ALS-like syndromes, dysautonomia, etc. HAM/TSP designates a spastic paraparesis with neurogenic bladder, and minor sensory signs. Pathologically, HAM/TSP is characterized initially by perivascular lymphocytic cuffing and mild parenchymal mononuclear infiltrates affecting mainly the thoracic spinal cord. This is followed by gliosis and scarring in later stages. The neuropathogenesis of HTLV-1 is still poorly understood but is apparently immune mediated. The therapy of TSP/HAM remains basically symptomatic.
33
Weyker, Paul David, Christopher Allen-John Webb, and Tricia E. Brentjens. Hypovolemic Shock. Edited by Matthew D. McEvoy and Cory M. Furse. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190226459.003.0097.
Full textAbstract:
Broadly defined, hypovolemia represents inadequate circulating plasma volume leading to decreased cardiac preload and thus decreased cardiac output and blood pressure. Many classification schemes have been proposed to categorize hypovolemia based on relative levels of decreased plasma volume. Common causes of hypovolemic shock during the perioperative period include hemorrhage and diuretic use. In general, studies support a conservative hemoglobin goal of about 7 g/dL as compared with a liberal goal of 10 g/dL in hemodynamically stable patients without active cardiac ischemia or risk factors. In patients with large volume blood loss, institutionally approved massive transfusion protocols can help provide blood products quickly. The trauma literature supports a balanced massive transfusion protocol using a 1:1:1 (plasma:platelet:red blood cell) strategy of transfusion.
34
Beattie, R. Mark, Anil Dhawan, and John W.L. Puntis. Cystic fibrosis. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198569862.003.0021.
Full textAbstract:
Gastrointestinal manifestations 156Management of gastrointestinal symptoms in children with CF 158Nutrition in CF 158Nutritional management 159Vitamins 160The incidence of cystic fibrosis (CF) is around 1 in 2500. Cases are diagnosed as a consequence of population screening or high-risk screening, or following presentation with clinical symptoms typical of the disorder. The basic defect is in the CFTR (cystic fibrosis transmembrane conductance regulator) protein which codes for a cyclic adenosine monophosphate-regulated chloride transporter in epithelial cells of exocrine organs. This is involved in salt and water balance across epithelial surfaces. The gene is on chromosome 7. There are multiple known mutations, the most common being ...
35
Ajithkumar, Thankamma, Ann Barrett, Helen Hatcher, and Natalie Cook. Thoracic tumours. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199235636.003.0006.
Full textAbstract:
Primary tracheal tumours represent <1% of all respiratory malignancies and can arise from the respiratory epithelium, salivary glands, and mesenchymal structures of the trachea. Most tumours in adults are benign while this is the case in only 30% of tumours in children. Primary tumours in adults are predominantly of adenoid cystic or squamous cell histology (Gaissert et al. 2006)....
36
Livingston, Schuyler, Benjamin Young, Martin Markowitz, Poonam Mathur, and Bruce L. Gilliam. HIV Virology. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190493097.003.0017.
Full textAbstract:
HIV is a member of the lentivirus subfamily of retroviruses. Two distinct groups of viruses are pathogenic in humans: HIV-1 and HIV-2. Both are transmitted sexually and known to cause immunodeficiency disease. HIV enters the cell through use of the CD4 receptor and chemokine co-receptors, primarily CCR5 and CXCR4. The viral genome is transcribed from RNA to DNA by reverse transcriptase and integrated into the host genome by integrase. The HIV genome encodes 15 proteins, comprising three categories: structural, regulatory, and accessory. After budding from the host cell, the virus matures into its infectious form through cleavage of viral precursor proteins by protease.
37
Roman, Eve, Alexandra Smith, and Lorelei Mucci. Leukemias. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780190676827.003.0028.
Full textAbstract:
Leukemias are a diverse group of acute and chronic haematological malignancies, that account for 2% to 3% of cancers globally. Recent advances in molecular biology and therapy have transformed the landscape for several leukemia subtypes changing some, but by no means all, from rapidly fatal diseases to treatable conditions with a good prognosis. In general, however, this progress has not been matched by new aetiological insights. Albeit accounting for a relatively small proportion, genetic predisposition syndromes such as neurofibromatosis, Li-Fraumeni and Trisomy 21, have the biggest impact in children and young adults. At older ages, established chemical, physical and biological risk factors, which explain only a small proportion of the total disease burden, include chemotherapy for a preceding cancer, ionizing radiation, and the viral infections human T-cell lymphotropic virus type 1 (HTLV-1) which causes the rare adult T-cell leukemia/lymphoma (ATLL) and the human immunodeficiency virus (HIV) which is associated with an increased risk of acute lymphoid leukaemias. Workplace exposures to potential carcinogens such as benzene, butadiene, and styrene have also been linked to increased risk of leukemia.
38
Voll, Reinhard E., and Barbara M. Bröker. Innate vs acquired immunity. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0048.
Full textAbstract:
The innate and the adaptive immune system efficiently cooperate to protect us from infections. The ancient innate immune system, dating back to the first multicellular organisms, utilizes phagocytic cells, soluble antimicrobial peptides, and the complement system for an immediate line of defence against pathogens. Using a limited number of germline-encoded pattern recognition receptors including the Toll-like, RIG-1-like, and NOD-like receptors, the innate immune system recognizes so-called pathogen-associated molecular patterns (PAMPs). PAMPs are specific for groups of related microorganisms and represent highly conserved, mostly non-protein molecules essential for the pathogens' life cycles. Hence, escape mutants strongly reduce the pathogen's fitness. An important task of the innate immune system is to distinguish between harmless antigens and potentially dangerous pathogens. Ideally, innate immune cells should activate the adaptive immune cells only in the case of invading pathogens. The evolutionarily rather new adaptive immune system, which can be found in jawed fish and higher vertebrates, needs several days to mount an efficient response upon its first encounter with a certain pathogen. As soon as antigen-specific lymphocyte clones have been expanded, they powerfully fight the pathogen. Importantly, memory lymphocytes can often protect us from reinfections. During the development of T and B lymphocytes, many millions of different receptors are generated by somatic recombination and hypermutation of gene segments making up the antigen receptors. This process carries the inherent risk of autoimmunity, causing most inflammatory rheumatic diseases. In contrast, inadequate activation of the innate immune system, especially activation of the inflammasomes, may cause autoinflammatory syndromes.
39
Wiffen, Philip, Marc Mitchell, Melanie Snelling, and Nicola Stoner. Therapy-related issues: endocrine system. Oxford University Press, 2012. http://dx.doi.org/10.1093/med/9780199603640.003.0021.
Full textAbstract:
Diabetes mellitus 444Monitoring and control 449Thyroid disorders 450Diabetes mellitus (DM) affects approximately 4% of the UK population. In 2009, Diabetes UK reported that 2.6 million people in the UK have diabetes.Type 2 diabetes accounts for 90% of all diabetes and is a result of insulin resistance and pancreatic β-cell dysfunction. Type 1 diabetes results from an absolute insulin deficiency secondary to autoimmune dysfunction....
40
Walsh, Denis M., and Philippe Huneman. Introduction: Challenging the Modern Synthesis. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780199377176.003.0012.
Full textAbstract:
The modern evolutionary synthesis arose out of the conjunction of the Mendelian theory of inheritance and the neo-Darwinian theory of population change early in the 20th century.1 In the nearly 100 years since its inception, the modern evolutionary synthesis has grown to encompass practically all fields of comparative biology—ecology, ethology, paleontology, systematics, cell biology, physiology, genetics, development. Theodosius Dobzhansky’s dictum—“nothing in biology makes sense except in the light of evolution” (...
41
Wilson, John W., and Lynn L. Estes. Antiretroviral Therapy for HIV Infection. Oxford University Press, 2012. http://dx.doi.org/10.1093/med/9780199797783.003.0134.
Full textAbstract:
• Obtain confirmatory human immunodeficiency virus (HIV) testing by rapid test or enzyme-linked immunosorbent assay (ELISA); optimally repeat HIV viral load (VL) and CD4 T-cell (CD4) count 2 times before initiation of therapy; a substantial change in CD4 count is generally >30%• Perform VL immediately before treatment initiation (or change in therapy) and again 2–8 weeks later; for the latter, the optimal decrease would be at least 1 log...
42
Kahn, S. Lowell. Fibrin Sheath Removal Techniques. Edited by S. Lowell Kahn, Bulent Arslan, and Abdulrahman Masrani. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199986071.003.0045.
Full textAbstract:
Although autogenous arteriovenous fistula creation is the gold-standard dialysis access, catheters represent between 40% and 60% of dialysis access in the United States. Catheters are placed for a variety of reasons, commonly as temporary access for acute renal failure or as a bridge to a more permanent access in patients with end-stage renal disease. Fibrin sheaths represent a heterogeneous matrix of cells and debris that form around catheters and are a known common cause of catheter failure and central venous stenosis. Their formation is ubiquitous in the dialysis population, occurring with 80–100% of catheters within 1 week of implantation. This chapter presents several techniques for the management of the fibrin sheath—the traditional catheter stripping technique, the internal catheter stripping technique, and the fibrin sheath angioplasty technique.
43
Sebag-Montefiore, David, Mark Harrison, and Rob Glynne-Jones. Squamous carcinoma of the anus. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199696567.003.0008.
Full textAbstract:
Squamous cell cancer (SCC) of the anus is a rare cancer whose incidence appears to be increasing. Anal cancers are more common in women than men ( 1 , 2 ) and just under half the patients are over the age of 65. An indolent natural history and a low rate of distant metastases ( 3 , 2 ) determine locoregional control as the primary aim of treatment. The relative 5-year survival rate is 62 % ( 4 ) , and has changed little for patients treated in the last two decades.
44
Weller, Michael, Michael Brada, Tai-Tong Wong, and Michael A. Vogelbaum. Astrocytic tumours: diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, and gliomatosis cerebri. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199651870.003.0003.
Full textAbstract:
Astrocytic gliomas are primary brain tumours thought to originate from neural stem or progenitor cells. They are assigned grades II, III, or IV by the World Health Organization according to degree of malignancy as defined by histology. The following molecular markers are increasingly used for diagnostic subclassification or clinical decision-making: 1p/19q co-deletion status, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and isocitrate dehydrogenase 1 and 2 mutation status. Extent of resection is a favourable prognostic factor, but surgery is never curative. Radiotherapy prolongs progression-free survival across all astrocytic glioma entities. Alkylating agent chemotherapy is an active treatment in particular for patients with MGMT promoter-methylated tumours. Anti-angiogenic therapies have failed to improve survival, and the current focus of major clinical trials is on novel targeted agents or on immunotherapy.
45
Matin, Rubeta, Jane McGregor, and Catherine Harwood. Skin cancer. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0259.
Full textAbstract:
Skin cancer is very common in the UK, and its incidence is rising rapidly. There are two broad classes of primary skin cancer: non-melanoma and melanoma. Non-melanoma skin cancer is the commonest form (100 000 cases diagnosed annually in the UK), accounting for nine out of ten skin cancers and includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Cutaneous melanoma is less common (10 000 cases diagnosed in the UK annually) but confers a significantly worse prognosis and accounts for 75% of skin cancer related deaths. There are also a number of other, rarer, non-melanoma skin cancers (e.g. appendageal carcinomas, Merkel cell carcinoma, sarcomas, vascular malignancies, and cutaneous lymphomas); however, these account for less than 1% of all skin cancers in the UK and so will not be specifically discussed in this chapter. Cutaneous metastases can occur secondary to any internal cancer or, indeed, to skin cancer (e.g. melanoma). In most cases, cutaneous metastasis occurs after the diagnosis of a primary cancer and usually in late stages of the disease but, in some cases, it may be the first presentation, in which case it should prompt a thorough investigation for the primary malignancy.
46
Abhishek, Abhishek, and Michael Doherty. Pathophysiology of calcium pyrophosphate deposition. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199668847.003.0049.
Full textAbstract:
Calcium pyrophosphate (CPP) dihydrate crystals form extracellularly. Their formation requires sufficient extracellular inorganic pyrophosphate (ePPi), calcium, and pro-nucleating factors. As inorganic pyrophosphate (PPi) cannot cross cell membranes passively due to its large size, ePPi results either from hydrolysis of extracellular ATP by the enzyme ectonucleotide pyrophosphatase/phosphodiesterase 1 (also known as plasma cell membrane glycoprotein 1) or from the transcellular transport of PPi by ANKH. ePPi is hydrolyzed to phosphate (Pi) by tissue non-specific alkaline phosphatase. The level of extracellular PPi and Pi is tightly regulated by several interlinked feedback mechanisms and growth factors. The relative concentration of Pi and PPi determines whether CPP or hydroxyapatite crystal is formed, with low Pi/PPi ratio resulting in CPP crystal formation, while a high Pi/PPi ratio promotes basic calcium phosphate crystal formation. CPP crystals are deposited in the cartilage matrix (preferentially in the middle layer) or in areas of chondroid metaplasia. Hypertrophic chondrocytes and specific cartilage matrix changes (e.g. high levels of dermatan sulfate and S-100 protein) are related to CPP crystal deposition and growth. CPP crystals cause inflammation by engaging with the NALP3 inflammasome, and with other components of the innate immune system, and is marked with a prolonged neutrophilic inflitrate. The pathogenesis of resolution of CPP crystal-induced inflammation is not well understood.
47
Gibson, K. Michael, Cornelis Jakobs, and Philip L. Pearl. Succinic Semialdehyde Dehydrogenase Deficiency. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199972135.003.0029.
Full textAbstract:
Succinic semialdehyde dehydrogenase (SSADH) deficiency presents with intellectual disability, disproportionate deficit in expressive language, hypotonia, ataxia, and seizures.1,2 (1 Pearl et al 2011; 2 Vogel et al 2012). A diagnosis of autism spectrum disorder frequently occurs, correlated with neuropsychiatric morbidity (ADHD, OCD, PDD). 1,3 The biochemical hallmark, γ-hydroxybutyric acid (GHB), is elevated in physiological fluids, as is γ-aminobutyrate (GABA) in cerebrospinal fluid (CSF).4,5 Both species are neuroactive. Clinical manifestations are universally present in early childhood, although diagnosis delayed to adulthood has been reported.6 Acute decompensation or complications relate primarily to seizures, intercurrent illnesses sometimes associated with respiratory dysfunction in the setting of hypotonia, or adverse medication responses. Diagnostic confirmation requires urine organic acid analysis (increased GHB) with confirmation via enzyme assay (white cells) and/or molecular characterization of the aldehyde dehydrogenase 5a1 (ALDH5A1) gene.
48
Servais, Aude, and Bertrand Knebelmann. Cystinuria. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199972135.003.0024.
Full textAbstract:
Cystinuria (OMIM #220100) is an autosomal recessive disorder of a dibasic amino acid transport in the apical membrane of epithelial cells of the renal proximal tubule and small intestine. It leads to increased urinary cystine excretion and recurrent urolithiasis. The cystine transporter is an heterodimeric transporter which is composed of a heavy subunit, rBAT, linked to a light subunit, b0,+AT. Two genes, SLC3A1 (solute carrier family 3 member 1) and SLC7A9, coding for rBAT and b0,+AT, account for the genetic basis of cystinuria. Cystinuria may lead to obstruction, infections, and ultimately to renal insufficiency. The diagnosis of cystinuria mainly relies on stone analysis, urinary cystine measurement, or urinary cystine crystal identification. Medical treatment is based upon a stepwise strategy using hydration and alkalinization as basic measures, with the addition of thiol derivatives in refractory cases. Urological interventions are often indicated for the management of cystine stones >5 mm in diameter.
49
Cui, Zhao, Neil Turner, and Ming-hui Zhao. Antiglomerular basement membrane disease. Edited by Neil Turner. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0073_update_001.
Full textAbstract:
Cyclophosphamide and plasma exchange are the standard of care in rapidly progressive glomerulonephritis or lung haemorrhage caused by antiglomerular basement membrane (anti-GBM) disease, and it is unusual to encounter patients at earlier stages. Steroids are universally used in addition. There is some evidence that plasma exchange may not be a critical part of treatment at an earlier stage. There is no more than anecdotal evidence for other therapies. Slower-onset therapies such as antibodies to B cells are rarely appropriate. If untreated, patients with severe anti-GBM disease will not recover renal function and are at risk of pulmonary haemorrhage. Evidence for the pathogenicity of circulating anti-GBM antibodies provides rationale for removal of circulating antibodies as rapidly as possible, whilst simultaneously inhibiting their synthesis. This was behind the introduction of the combination of plasma exchange with immunosuppressive therapy in mid 1970s, which revolutionized outcomes. Plasmapheresis aims to remove circulating pathogenic antibodies against GBM and possibly other mediators; cyclophosphamide prevents further synthesis of autoantibodies; and steroids act as anti-inflammatory agents to attenuate the glomerular inflammatory response initiated by anti-GBM antibodies. It is clear from experimental models and occasional observations in man that the anti-cell mediated effects of current therapies are important too. Outcomes vary, but in general patient survival is now good, while renal survival remains poor, in many series less than 50% at 1 year. Treatment is toxic and after an early peak in deaths due to pulmonary haemorrhage, secondary infections are the next threat. It may therefore be best not to immunosuppress patients with a very poor renal prognosis who appear to be at low risk of pulmonary haemorrhage. Treatment can usually be curtailed after 3 months without recurrence. ANCA and anti-GBM antibodies occur together in some patients. This is typically an older group which often has features of vasculitis, and the anti-GBM response may often be secondary. Longer treatment as for small vessel vasculitis is usually indicated.
50
Sebastio, Gianfranco, Manuel Schiff, and Hélène Ogier de Baulny. Lysinuric Protein Intolerance and Hartnup Disease. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199972135.003.0025.
Full textAbstract:
Lysinuric protein intolerance (LPI) is an inherited aminoaciduria caused by defective cationic amino acid transport at the basolateral membrane of epithelial cells in intestine and kidney. LPI is caused by mutations in the SLC7A7 gene, which encodes the y+LAT-1 protein, the catalytic light chain subunit of a complex belonging to the heterodimeric amino acid transporter family. Symptoms usually begin after weaning with refusal of feeding, vomiting, and consequent failure to thrive. Hepatosplenomegaly, hematological anomalies, and neurological involvement including hyperammonemic coma will progressively appear. Lung involvement (specifically pulmonary alveolar proteinosis), chronic renal disease that may lead to end stage renal disease, and hemophagocytic lymphohistiocytosis with macrophage activation all represent complications of LPI that may appear at any time from childhood to adulthood. The great variability of the clinical presentation frequently causes misdiagnosis or delayed diagnosis. The basic therapy of LPI consist of a low-protein diet, low-dose citrulline supplementation, nitrogen-scavenging compounds to prevent hyperammonemia, lysine, and carnitine supplements.