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Allografts are also called expression is also not induced by known upregulators such as homografts (Figure 22 buy 20mg nexium otc gastritis bile reflux diet. The trophoblast also protects Fetus allograft: Success of the haplononidentical fetus as itself from maternal cytotoxicity during gestation by express- an allograft was suggested in the 1950s by Medawar order nexium with a mastercard gastritis symptoms lap band, Brent discount nexium 20mg overnight delivery gastritis antrum diet, ing a high level of complement regulatory proteins on its sur- and Billingham to rely on four possibilities. The maternal immune system the uterus might be an immunologically privileged site, and recognizes pregnancy, i. The temporary status has focused on special- at the fetal–maternal tissue interface in pregnancy. Fetal trophoblast protects itself from sibly stimulate maternal lymphocytes in endometrial tissue to maternal cytotoxic attack by failing to express on placental synthesize cytokines and growth factors that act in a paracrine villous cytotrophoblast and syncytiotrophoblast any classical manner benefcial to trophoblast growth and differentiation. Transplantation Immunology 681 This has been called the immunotrophism hypothesis. Other cells into animals exposed to total body irradiation often cytokines released into decidual tissue include colony stimu- results in the destruction of the transplanted cells. These include macrophages, fbroblasts, and endothelium within the villous mesenchyme F1 hybrid resistance is a condition that results when two of placental tissue, thereby preventing these antibodies from inbred mouse strains are crossed and a bone marrow graft reaching the fetal circulation. Maternal antibodies against from either of the parents is rejected by the F1 offspring. Exceptions to placental trapping of deleterious maternal Homologous chromosomes are a pair of chromosomes con- IgG antibodies include maternal IgG antibodies against RhD taining the same linear gene sequences, each derived from antigen and certain maternal organ-specifc autoantibodies. An allogeneic graft is an allograft consisting of an organ, Immunoisolation describes the enclosure of allogeneic tis- tissue, or cell transplant from a donor individual or strain to sues such as pancreatic islet cell allografts within a mem- a genetically different individual or strain within the same brane that is semipermeable, but does not itself induce an species. Substances of relatively low mol wt can reach the graft through the membrane, while it remains pro- Homologous is an adjective that describes something from tected from immunologic rejection by the host. For example, an organ allotransplant from one member to a recipient member of the same species, i. This is manifested as a higher frequency malignancies, certain nonhematologic neoplasms, aplastic of tumor and shorter latency period in syngeneic hosts. In alloge- better growth of tumor in syngeneic than in heterozygous F1 neic bone marrow transplantation the recipient is irradiated hybrid hosts was initially termed syngeneic preference. When with lethal doses either to destroy malignant cells or to cre- it became apparent that selective pressure against the cells in ate a graft bed. This is principally a cell-mediated type of immune between members of different species. Xenogeneic transplanta- tion can involve concordant or discordant donors, according Heterograft: See xenograft. Natural preformed antibodies in a recipient specifc for donor Heterogeneic: See xenogeneic. The immune response to a xenotransplant or tissue transplant from one species to a recipient belonging resembles the response to an allotransplant. It also refers to are greater antigenic differences between donor and host in something from a foreign source. It procedure is being explored to possibly solve an insuffcient supply of A xenograft (Figure 22. It is also called a het- Mini pigs are a strain of diminutive pigs designed specif- erograft. Antibodies and cytotoxic T cells reject xenografts cally to serve as organ and tissue donors for use as xeno- several days following transplantation. Xenogeneic is an adjective that refers to tissues or organs transplanted from one species to a genetically different spe- Delayed xenograft rejection is a xenograft failure within cies, e. It is attributable to the genetic relationship of an individual from one species to ischemia that is a consequence of graft vascular endothe- a member of a different species. It is also called acute vascular Xenoantigen is a tissue antigens of one species that induce rejection. Chronic xenograft rejection is a xenograft failure that occurs within weeks following transplantation as a con- Xenoantibody is an antibody specifc for xenoantigen. It is also called cellular xenograft Xenoantibodies are antibodies formed in one species that rejection. Xenozoonosis is a term that describes transmission of infection that might be the consequence of xenotransplan- tation. Examples would Transplantation Immunology 683 include membrane antigens of cells or immunoglobulins Relative sibling risk: A comparison of the occurrence of from separate species. A donor is one who offers whole blood, blood products, bone marrow, or an organ to be given to another individual. There are various other reasons for between genetically identical members of a species. To be a blood donor, an indi- individuals possess the same alleles at all genetic loci. There are An isograft is a tissue transplant from a donor to an isogenic many reasons for donor rejection, including low hematocrit, recipient. Grafts exchanged between members of an inbred skin lesions, surgery, drugs, or positive donor blood tests. Brain death is the term for irreversible loss of brain func- tion without trauma to other body systems. Artifcial mainte- Isogeneic (isogenic) is an adjective implying genetic iden- nance of the subject’s respiration can be employed to preserve tity such as identical twins. Also called An organ bank is a site where selected tissues for trans- isogeneic or syngeneic. Several hospitals often share such immune response if injected into a genetically dissimilar a facility. Organs such as kidneys, liver, heart, lung, and pan- member of the same species is termed an isoantigen. Isoantigens of two individuals may or may not Organ brokerage or the selling of an organ such as a kidney have identical determinants. In the latter case they are alloge- from a living related donor to the transplant recipient, is prac- neic with respect to each other and are called alloantigens. Spleen Control cells H-Cl Isoantibody is an antibody that is specifc for an antigen Primary present in other members of the species in which it occurs. H-Cl H-Cl Secondary Isoleukoagglutinins are antibodies in the blood sera of response multiparous females and of patients receiving multiple blood transfusions that recognizes surface isoantigens of leuko- cytes and leads to their agglutination. H-Cll H-Cl Primary response Leukoagglutinin is an antibody or other substance that induces the aggregation or agglutination of white blood cells into clumps. The two parents are from different inbred strains individual to a previously nonimmune recipient host. The passive transfer of lymphocytes from an immunized individual to a nonimmune subject with immune system cells A split thickness graft is a skin graft that is only 0. Thick split thickness grafts are further resistant Lymphocyte transfer reaction: See normal lymphocyte to trauma, produce minimal contraction, and permit some transfer reaction.

Discriminating between epileptic and nonepilep- cy bands in high-hypnotically susceptible individuals buy nexium pills in toronto gastritis black stool. Only a minority of women with epilepsy who plan to have children have any prepregnancy Reproductive dysfunction counselling and knowledge among health-care providers about the Reproductive dysfunction and endocrine disorders are common reproductive health of women with epilepsy is ofen inadequate purchase 40mg nexium with mastercard gastritis symptoms stomach pain. In men order nexium overnight gastritis diet , this will manifest Ideally, counselling should be provided long before pregnancy in itself as loss of libido, reduced potency and infertility; in women, by order to allow for adequate treatment measures to reduce risks. In some studies, Reproduction can be more complicated for people with epilepsy 40–70% of men with epilepsy report decreased potency and hypo- for a number of reasons related to epilepsy and to its treatment. Menstrual disorders are more common may afect the outcome of pregnancy and there are increased risks among women with epilepsy, occurring in one-third compared of obstetric complications. Seizure control can change during preg- with 12–14% in the general population [6]. Enzyme-inducing drugs such as carbamazepine, phe- ible causes for reduced fertility rates among people with epilepsy. In a cross-sec- epilepsy or risks to the fetus incurred by seizures or the drug treat- tional study, monotherapy with carbamazepine was associated with ment. However, some studies suggest that concurrent disabilities and ment in doses of at least 900 mg/day was associated with similar en- comorbidities (e. Fertility rates among people with epilepsy in 12 out of 21 men treated with valproic acid for generalized or were essentially normal in two population-based studies from focal seizures [6]. No diference was observed in linear growth ment [11], whereas a cross-sectional study of men and women with and sexual maturation [18]. When 41 girls on valproic acid were epilepsy found no diference in levels of reproductive hormones compared with 54 healthy controls, hyperandrogenism was ob- between those taking levetiracetam, carbamazepine or lamotrigine served more frequently among the valproic acid-exposed girls, but [12]. A long-term follow-up of these cohorts revealed normal endo- esis or sperm function. A small cross-sectional study As suggested in a recent comprehensive review, women with epi- of men with epilepsy suggested that all investigated drugs, carba- lepsy should be monitored for signs and symptoms of reproductive mazepine, oxcarbazepine and valproic acid, were associated with an dysfunction in conjunction with their clinical visits. This includes increase in abnormal sperm morphology [10], although the clinical assessment of menstrual cycles, occurrence of hirsutism, acne, relevance of these fndings remains to be shown. In addition to the com- mental factors can contribute to the development of this syndrome. In these studies, 30–40% of patients treated and an increased frequency of unplanned pregnancies [21]. However, whether this dose is 26 years (44% and 23%) but was similar if treatment was started at sufcient is uncertain. Taken to- Estradiol-containing oral contraceptives induce the elimination of gether, these observations confrm that valproic acid can indeed lamotrigine. This can lead as important as reported in the initial cross-sectional studies from to breakthrough seizures unless the lamotrigine dosage is adjusted. Tese changes occur rapidly and hence lamotrigine levels rise during Withdrawal of carbamazepine in seizure-free male and female the pill-free week if sequential pills are used [23]. This may induce patients has also been associated with normalization (increase) toxic symptoms. Preliminary data suggest that estradiol can have a of serum testosterone and free androgen index [17]. Pure proges- sectional studies assessed endocrine function in a younger female tagen-containing pills do not seem to afect lamotrigine serum con- population with epilepsy [18,19]. A cohort of 77 girls, 8–18 years centrations, and concomitant use of valproic acid appears to block of age, under treatment with valproic acid (n 40), carbamazepine the estradiol-induced efects on lamotrigine kinetics [24]. Howev- (n = 19) or oxcarbazepine (n = 18) were compared with 49 healthy er, as lamotrigine can reduce the bioavailability of gestagens [25], Reproductive Aspects of Epilepsy Treatment 313 Table 23. Drugs in which the clearance is Drugs that increase the clearance Drugs that do not affect the induced by estradiol-containing of oral contraceptives clearance of oral contraceptives oral contraceptives Carbamazepine Ethosuxumide Lamotrigine Eslicarbazepine acetate Gabapentin Valproic acid Felbamate Lacosamide Lamotriginea Levetiracetam Oxcarbazepine Pregabalin Phenobarbital Retigabine Perampanel Tiagabine Primidone Valproic acid Phenytoin Vigabatrin Rufnimide Zonisamide Topiramate (at dosages >200 mg/day) a Lamotrigine does not affect estradiol concentrations but has a modest effect (18% reduction in plasma concentration) on the norgestrel component of the combined oral contraceptive. It has therefore been suggested that for women taking lamo- a few such reports have been published. In contrast, prolonged sei- trigine, the combined contraceptive pill can be used with tricycling zure activity, such as status epilepticus, may be a serious threat to or continuous use to avoid fuctuations in lamotrigine serum con- the fetus as well as to the woman. Given the choice of two drugs similar in all other women with status epilepticus (12 of whom were convulsive) [28]. The possibility of using com- nancy are not associated with an increased risk of birth defects. Generalized tonic–clonic seizures during labour can cause fetal Pregnancy in women with epilepsy asphyxia. Focal seizures that impair consciousness may also impose In the treatment of epilepsy during pregnancy, maternal and fetal risks because the mother’s ability to cooperate during the delivery risks associated with uncontrolled seizures need to be weighed is lost. Nevertheless, Effects of maternal seizures on the fetus there is a general consensus among physicians that generalized ton- Epileptic seizures in a pregnant woman may have adverse efects ic–clonic seizures in particular should be avoided during pregnancy on the fetus, in addition to risks for the woman. With respect to for the sake of the well-being of the fetus as well as the mother. Maternal risks with uncontrolled seizures Tonic–clonic seizures are associated with transient lactic acidosis, Epilepsy is a serious condition and uncontrolled seizures occasion- which is likely to be transferred to the fetus. This concern appears to be fetal heart rate, which is a common response to acidosis, has been particularly relevant during pregnancy. Fourteen deaths were epilepsy-related, of which afects uterine blood fow and thus the fetus. An estimated 1 in ternal abdominal trauma could also, theoretically, cause injury to 1000 women with epilepsy died during or shortly afer pregnancy the fetus or placental abruption. Despite these efects, intrauterine compared with 1 in 10 000 in the general population. This appears to be mainly because of a decrease Seizure control during pregnancy and delivery in drug binding to plasma proteins and/or an increase in drug me- The largest prospective study of seizure control in pregnancy to tabolism and elimination. A decrease in protein binding will result date reported that 59% of 1736 women remained seizure-free in lower total drug levels but leave unchanged the unbound, active throughout pregnancy [27]. Earlier studies, mainly from special- concentration of the drug, which is the relevant concentration in ized epilepsy centres, indicated that approximately one-third of the treated mother as well as for exposure to the fetus. Prospective studies of fewer selected women with phenobarbital decline by up to 50% [34]. Total concentrations of epilepsy suggest that the proportion of women who deteriorate is carbamazepine decline to a lesser extent and the changes in un- smaller [26]. Some of the observed changes in seizure frequency bound concentrations are insignifcant [28]. Marked decreases in are likely to be explained by the normal spontaneous fuctuations total phenytoin concentrations to about 40% of prepregnancy levels in seizure occurrence, but it appears that some periods of pregnan- have been reported [34], whereas free concentrations decreased to cy are associated with a signifcant increase in seizures. For valproic acid, no signifcant changes were alized tonic–clonic seizure occurs during labour in about 1–2% noted in unbound concentrations despite a fairly marked decrease of pregnancies of women with epilepsy and within 24 hours afer in total concentrations [34].

Compared to optogenetics discount nexium uk autoimmune gastritis definition, it certainly benefts from under the parvalbumin or somatostatin promoters) buy nexium with a mastercard gastritis lipase. Chemical–ge- tostatin-interneurons alone was less efective in reducing seizure netic approaches may cheap 40 mg nexium with amex gastritis diet kidney, however, ofer a useful preventative treat- activity in vitro. Newer studies have confrmed that optogenetic ment strategy in patients with prolonged auras or well-recognized inhibition of principal cells can inhibit seizures in other seizure seizure clusters, such as in catamenial epilepsy. Particular thanks are given to Dr Ka- treatment approach and at which time point in their disease this ren Cundy (nee Nilsen), coauthor of previous editions of this chap- should be considered. We would like to thank Focal drug delivery systems certainly show promise, although Dr. Michael Zandi and Rachael Hansford of Advances in Clinical more detailed long-term studies in a range of experimental models, Neuroscience & Rehabilitation and the editors of Epilepsia (Wiley), including behavioural outcomes, are needed. Neuronal grafing, on for granting permission to reproduce a previously published fgure. Surgical ever, in addition to the limitations posed by the models used, the Treatment of the Epilepsies, 2nd edn. Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures. Epilepsia insult and transplantation was short: (i) when specifc known lesions 2010; 51: 1721–1728. Local perfusion of diazepam attenuates interictal and ictal events in the bicuculline model of epilepsy in rats. Long-lasting attenuation of amygdala-kindled brain that is not acutely damaged, and that achieving long-term graf seizures afer convection-enhanced delivery of botulinum neurotoxins a and B survival in cortical brain regions is especially difcult. Characterization of the tetanus toxin model of refractory focal neocortical epilepsy in the rat. Focal delivery of standard antiepileptic drugs in lepsy patients who have a normal life expectancy. Antiepileptic efect of gap-junction blockers in the prevention of epileptogenesis afer an acute insult, such as a se- a rat model of refractory focal cortical epilepsy. Radiation-controlled focal pharmacology in the thera- vere traumatic brain injury or a stroke. The to achieve control over promoter activity and specifcity to ensure intracerebral administration of phenytoin using controlled-release polymers that the therapeutic gene reaches the diseased cells. Efects of subdural application of lido- a non-integrating lentivirus with an inducible promoter system. Epidural pentobarbital delivery can prevent locally induced neocortical seizures in rats: the prospect of transmeninge- and have been shown to allow modulation of epileptic activity in al pharmacotherapy for intractable focal epilepsy. Neurosci Lett 2010; 469: studies, we do not yet know whether the benefts might only be 421–424. Seizure suppression in transient, even with a permanent therapeutic local manipulation, kindled rats by intraventricular grafing of an adenosine releasing synthetic poly- given the known highly adaptable capacity of the brain in terms of mer. Adeno-associated virus vector-mediated expression and constitutive cy of liposome-entrapped amiloride and free amiloride in animal models of secretion of galanin suppresses limbic seizure activity. Evolu- expression attenuates epileptogenesis-associated neuroinfammation and reduces tion and prospects for intracranial pharmacotherapy for refractory epilepsies: the spontaneous recurrent seizures. Neuropeptide Y gene therapy decreases chronic long-term, implanted seizure advisory system in patients with drug-resistant epi- spontaneous seizures in a rat model of temporal lobe epilepsy. Concise review: prospects of stem cell therapy for tem- pental treatment for status epilepticus. Mild hypothermia for refractory focal status three-dimensional graf reconstruction study. Exp cooling suppresses spontaneous epileptiform activity without changing the corti- Neurol 2000; 161: 535–561. Efect of neural transplants death by adeno-associated virus vector galanin expression and secretion. Strategies for promoting anti-seizure mediated by adeno-associated virus vector neuropeptide Y expression in the rat efects of hippocampal fetal cells grafed into the hippocampus of rats exhibiting hippocampus. Biomaterials 2006; 27: gene therapy in a rodent model of focal neocortical epilepsy. Millisecond-timescale, ge- mus as a tool for interrupting seizures afer cortical injury. Principles for applying optogenetic tools de- tivation of inhibitory interneurons during epileptiform activity. High-performance genetically targetable optical ral dynamics in the nonhuman primate brain. An optical neural interface: in vivo control attenuation of focal neocortical seizures. Neural sub- manufacture of a lentiviral vector for gene therapy of Parkinson’s disease. Tuning arousal with optogenetic modula- tricular adenosine on penicillin-induced epileptiform activity in rats. China and India, the two most populous countries can bolster access of patients with surgically remediable nations in the world, are home to a quarter of the people with epilepsy syndromes to surgical treatment. The capability to identify and adequately treat people with epi- taining successful epilepsy surgery programmes in resource-limit- lepsy is compromised by poverty, illiteracy, inefcient and unevenly ed countries are dealt with below. We also outline possible strat- distributed healthcare systems, and social stigma and misconcep- egies to overcome these barriers, particularly how to optimally tions associated with the disease. Improvements in this scenario ob- utilize locally available limited technologies and human resources viously depend on multilevel action, but necessarily include the es- in order to develop pragmatic epilepsy surgery models that can tablishment of specialized epilepsy centres. Such eforts achieve seizure freedom for a minimum of 12 months or for a peri- in the industrialized world to support and disseminate advances od three times the previous longest seizure-free period, whichever is that make epilepsy surgery more cost-efective are already aiding longer [5]. Yet, epilepsy surgery continues to remain one of demic support to train at well-established epilepsy centres in richer the most underutilized of all accepted medical interventions world- countries. Such training has been crucial to promote the efective wide [10,11], and even more so in the resource-limited regions. Tere are ing a successful epilepsy surgery programme in resource-limited The Treatment of Epilepsy. A major challenge is to reconcile the need to make epilepsy High epilepsy burden surgery widely available with the need for expertise to make this Widespread poverty happen. The most important resource to implement successful sur- High rate of illiteracy and lack of awareness about epilepsy among gical programmes is well-trained personnel. As discussed below, public advances in epilepsy surgery research have streamlined the process Social stigma, superstitions and lack of faith in modern medicine of presurgical work up for a signifcant proportion of patients with Lack of epilepsy training in postgraduate curriculum surgically remediable epilepsy syndromes. The most reliable way to Misguided fears about risks of epilepsy surgery translate these advances into practical and efective protocols for Inadequate, unequal and ineffcient healthcare facilities countries with limited resources is through solid training of the Lack of trained professionals and infrastructure specialists who will lead the process. More recently, specialists are Little interest among the trained personnel to initiate epilepsy being trained locally, at least at some centres in countries with lim- surgery programmes ited resources such as Brazil and India.

The mother self-identifes as African American buy generic nexium gastritis full symptoms, while her husband self-identifes as Caucasian of central European descent order nexium 20 mg with mastercard gastritis diet x garcinia. The patient’s mother has no rel- evant family history of lung disease buy 40mg nexium otc gastritis diet milk, while the patient’s father has a strong family history of emphysema and liver disease. A thorough history and physical should focus on wheeze triggers, family history, associated atopic and allergic comorbidities, and identifying potential alternative sources of wheezing. If asthma is diagnosed, symptom severity will help guide therapy with bronchodilators, inhaled corticosteroids, and additional medications as per current guidelines. The Z-allele and S-allele are the most common pathogenic mutations among populations of European genetic ancestry. However, genetic research has made great strides in determining genetic risk factors that may contribute to the pathogenesis of these complex diseases, and has helped reveal pathways for potential treatment and for further study. At any last few decades, leading to major changes in how we under- area of variation in the human genome, di erences in stand complex respiratory disease. Simple a powerful tool for both genetic and epigenetic investigation one-base changes are known as single nucleotide polymor- using modern techniques. Small insertions or deletions encompass- linkage studies helped locate genetic risk factors on the mega- base scale. Most recently, the application of genome-wide sources of variation in the genome encompassing hundreds genotyping approaches as well as whole genome sequencing to millions of base pairs. Polymorphisms are alternative study designs that recruit a ected probands in protein-coding regions (exons) can change the translated (e. Broadly, genetic diseases morphisms in linkage disequilibrium, meaning that the can be classi ed as Mendelian or non-Mendelian (complex). When a statistically signi cant association between a While this chapter is primarily focused on the relationship genetic variant and a phenotype is discovered, it indicates of genetic variation to disease, the complex interaction of one of two possibilities. Once genetic gure, a point higher on the y-axis indicates greater statisti- information is obtained for a group of subjects, those data cal evidence for a region’s association with the phenotype, could be used to examine multiple di erent related pheno- and the genome-wide signi cance threshold is o en noted types, as long as care is taken to account for the method of on the y-axis. Genetic studies may help in uence characterization ed subjects as atopic or nonatopic. It has been hypothesized within these asthma-associated loci are hypothesized to that this result may re ect the limited ability of genotyp- exert their action through modulating eosinophilic in am- ing platforms to accurately assess the more diverse com- mation and 2 immune response pathways in the lung. A uct is a protein found in natural killer cells, memory T-cells, double-blind, randomized, placebo-controlled, proof- and dendritic cells that interact with tumor-necrosis-factor of-concept study showed that subjects treated with the alpha receptor type-133 to modulate in ammatory signal- monoclonal antibody showed decreased levels of allergen- ing cascades. While not all have been robustly repli- cated to date, they remain as potential objectives for fur- 3. Many association in individuals identifying as African American genetic studies have focused on moderate, severe, or very and African Caribbean. Additionally, whole genome sequenc- wide signi cance in meta-analysis (chromosome 13q14. A large-scale, is associated with air ow obstruction in two large consortium-based genomewide association study of cohorts. Current status and future research gene is associated with asthma in three ethnically directions. Meta- sis and management of Alpha-1 antitrypsin de - analysis of genome-wide association studies of ciency in the adult. Genomic variants associated with asthma susceptibility in medicine and lung diseases. Regional visualization of genome-wide association A sequence variant on 17q21 is associated with age scan results. Positional with neuronal cell death in Alzheimer’s disease brain cloning of a novel gene in uencing asthma from chro- and hippocampal neurons. Novel insights into lymphopoietin gene promoter polymorphisms are the genetics of smoking behaviour, lung function, and associated with susceptibility to bronchial asthma. Allele-speci c regula- ciation analyses for lung function and chronic obstruc- tion of matrix metalloproteinase-12 gene activity is tive pulmonary disease identify new loci and potential associated with coronary artery luminal dimensions druggable targets. Meta- a candidate gene for chronic obstructive pulmo- analyses of genome-wide association studies identify nary disease susceptibility and is necessary for multiple loci associated with pulmonary function. Genome- soluble receptor for advanced glycation endprod- wide association and large-scale follow up identi es ucts is a biomarker of emphysema and associated 16 new loci in uencing lung function. The genomic genomic signatures of type 2 in ammation in chronic origins of asthma. He also complains of post-viral cough that “goes all the way down to his chest” and which requires an antibiotic. His past medical history revealed seasonal hay fever with occasional wheeze and cough, sometimes after playing football, for which he used to take salbutamol for relief. On physical examination, he showed mild decrease in air entry on both sides with end expiratory wheeze. For instance, air ow limitation, and symptoms, likely increases the probability of overlap with increasing age. Prednisolone in combination with bron- exhibit reversibility of airway obstruction. Asthma usually develops dur- Asthma is a chronic immunologically-mediated lung disease ing the early childhood years, then proceeds to a remis- associated with defects in the normal airway repair mecha- sion phase in the adolescent or young adulthood years and nisms, resulting in airway in ammation and remodeling, may reappear during middle age. However, in adult-onset which together contribute to most of the clinical manifesta- asthma, the patients typically start exhibiting symptoms tion of the disease. Nevertheless, not all individu- which is more frequently associated with atopy that develops als with atopy are asthmatics and not all asthma patients exhibit in the early childhood, showing signs of reversible air ow increased allergic response. Asthma smoking-induced emphysema and chronic bronchitis, which patients demonstrate increased sensitivity of the airways to a 44 Asthma-chronic obstructive pulmonary disease overlap (a) (b) Figure 4. For instance, in individuals geneti- and in ltration of in ammatory cells into the bronchial wall cally predisposed to atopy, repeated exposures to environmental resulting in chronic in ammation; all of which contributes to allergens elicits an increased 2 cytokine response that pro- airway remodeling and subsequent sub-epithelial brosis due motes speci c IgE responses, however non-atopic patients may to abnormal repair mechanisms. Moreover, the distal airways in particular are highly sensitive to stimuli, such airway capillaries may dilate and leak. As a consequence of this as cigarette smoke, perfumes, cold air, and other non-speci c microvascular leakage, edema, impaired mucociliary clear- stimuli. In asthma, in ammatory cells, par- migration, hyperplasia or hypertrophy, epithelial shedding, ticularly eosinophils and T cells, are recruited into the central 4. Comorbidities, including depression, diabetes, hyper- phil in ltration and mast cell activation frequently observed in tension, osteoporosis, lung cancer, or coronary artery disease, asthma are driven by the activation of 2 cells. Pathologically, small airway abnormalities and parenchymal destruction are two di er- 4. In contrast, pathological changes in the lung cigarette smoke exposure contributes to airway remodeling parenchyma result in air ow limitation due to the reduction and centrilobular emphysema. While airway in ammation is driven sion, metabolic syndrome, heart failure, ischemic heart by eosinophilic and 2 pathways in asthma, neutrophils disease, renal disease, and anemia.

The careful identification with ultrasound imaging of all structures in proximity to the glossopharyngeal nerve prior to needle placement is crucial to decreasing the incidence of the potentially fatal complications cheap nexium express gastritis symptoms blood. Incremental dosing while carefully monitoring the patient for signs of local anesthetic toxicity can further decrease the risk to the patient order nexium canada xiphoid gastritis. Although these complications are usually transitory in nature buy nexium 20 mg online definition of gastritis in english, their dramatic appearance can be quite upsetting to the patient; therefore, the patient should be warned of such prior to the procedure. Although both glossopharyngeal neuralgia and Eagle syndrome share some common symptoms, glossopharyngeal neuralgia can be distinguished from Eagle syndrome in that the pain of glossopharyngeal neuralgia is characterized by paroxysms of shock-like pain in a 98 manner more analogous to trigeminal neuralgia rather than the sharp, shooting pain on head and neck movement that is associated with Eagle syndrome. Because both glossopharyngeal neuralgia and Eagle syndrome may be associated with serious cardiac bradyarrhythmias and syncope, the clinician must distinguish between the two syndromes as the ultimate curative treatments for each of these syndromes are very different. All patients thought to be suffering from glossopharyngeal neuralgia should be evaluated for multiple sclerosis due to the high incidence of the both diseases occurring together (Fig. The clinician should always evaluate the patient who suffers from pain in this anatomic region for occult tumors of the larynx, hypopharynx, posterior tongue, and anterior triangle of the neck as they may present with clinical symptoms that can mimic glossopharyngeal neuralgia (Figs. A patient with retromolar trigone cancer who was treated with surgery and had recurrent right posterior oral pain and mild trismus. The non–contrast-enhanced T1-weighted (T1W) image (A), contrast-enhanced T1W image (B), and T2-weighted image (C) show enhancing scarlike material (arrows) that was biopsied twice under computed tomography guidance, returning only fibrous tissue. The effects of glossopharyngeal nerve block on postoperative pain relief after tonsillectomy: the importance of the extent of obtunded gag reflex as a clinical indicator. In: Comprehensive Atlas of Ultrasound- Guided Pain Management Injection Techniques. The temporal styloid process extends from the temporal bone in a caudad and ventral direction and serves as the cephalad attachment of the stylohyoid ligament. The vagus nerve exits from the jugular foramen in proximity to the vagus and accessory nerve and the internal jugular vein and passes just inferior to the styloid process (Fig. All three nerves lie in the groove between the internal jugular vein and internal carotid artery with vagus nerve lying caudad to the glossopharyngeal nerve with its downward course superficial to the jugular vein. To identify the location of the styloid process, an imaginary line is drawn between the mastoid process and the angle of the mandible. The anatomy of the vagus nerve and its relationship to the carotid artery and jugular vein. The nerve has also been implicated in the evolution of vagal neuralgia which presents in a manner analogous to glossopharyngeal neuralgia although the pain distribution may be less well defined. Syncope and bradyarrhythmias have been associated with compromise of the vagus nerve by tumors, the styloid process and stylohyoid ligament, or aneurysms of the internal carotid artery. Schwannomas of the vagus nerve may also produce significant clinical symptoms (Fig. Two patients presenting with mucosally inapparent primary cancer of the palatine tonsil. A: Anatomic section to show the gross anatomic structures that must be understood in order to detect such submucosal cancers. The important relationship is that between the normal tonsillar tissue within the tonsillar fossa (arrow) and the surrounding constrictor muscle. B,C: Patient 1 presented with a level 2 enlarged lymph node and right-sided otalgia. D: Contrast-enhanced computed tomograph shows enlargement of the right palatine tonsil and infiltration of the adjacent parapharyngeal space (arrows) and thickening of the anterior tonsillar pillar (arrowhead). Differentiation between schwannoma of the vagus nerve and schwannoma of the cervical sympathetic chain by imaging diagnosis. An imaginary line is drawn from the mastoid process to the angle of the mandible (Fig. After preliminary identification of the approximate location of the styloid process, a linear ultrasound transducer is then placed over the previously identified approximate location of the styloid process in the transverse plane (Fig. Proper placement of the linear ultrasound transducer over the previously identified styloid process. Color Doppler may be utilized to help confirm location of the vessels and their relationship to the styloid process (Fig. Care should be taken to identify abnormal masses or tumors that are compressing the vagus nerve as it travels toward the thorax as well as to identify primary tumors involving the 103 nerve (Fig. Oblique ultrasound image demonstrating the relationship of the styloid process to the carotid artery. Differentiation between schwannoma of the vagus nerve and schwannoma of the cervical sympathetic chain by imaging diagnosis. Differentiation between schwannoma of the vagus nerve and schwannoma of the cervical sympathetic chain by imaging diagnosis. It is characterized by paroxysms of shock-like pain into the thyroid and laryngeal areas. Attacks of vagal neuralgia may be precipitated by coughing, yawning, and swallowing. Because both vagus neuralgia, glossopharyngeal neuralgia, and Eagle syndrome may be associated with serious cardiac bradyarrhythmias and syncope, the clinician must distinguish between these syndromes as the ultimate curative treatments are very different. Given the exceedingly low incidence of vagus neuralgia relative to other causes of pain in this anatomic region including pain secondary to malignancy, vagus neuralgia must be considered a diagnosis of exclusion. The clinician should always evaluate the patient who suffers from pain in this anatomic region for occult tumors of the larynx, hypopharynx, posterior tongue, and anterior triangle of the neck as they may present with clinical symptoms that can mimic vagus neuralgia. In: Comprehensive Atlas of Ultrasound- Guided Pain Management Injection Techniques. The fibers coalesce to form the spinal accessory nerve which ascends through the foramen magnum and travels along the inner skull to exit the cranium via the jugular foramen along with the glossopharyngeal and vagus nerves (Fig. The spinal accessory nerve has two branches, a small cranial root and a larger spinal root. The fibers of the larger spinal root pass inferiorly and posteriorly to exit beneath the posterior border of the sternocleidomastoid muscle at the junction of the upper and middle third of the muscle to lie on top of the levator scapulae and middle scalene muscles ventral as it passes in an inferocaudal course toward the anterior border of the trapezius muscle (Fig. The spinal accessory nerve provides motor innervation to the sternocleidomastoid and trapezius muscles while providing minimal sensory innervation (Fig. The spinal accessory nerve ascends through the foramen magnum and travels along the inner skull to exit the cranium via the jugular foramen along with the glossopharyngeal and vagus nerves. The anatomy of the spinal accessory nerve and its relationship to the sternocleidomastoid and trapezius muscles and the carotid artery and jugular vein. The fibers of the larger spinal root pass inferiorly and posteriorly to exit beneath the posterior border of the sternocleidomastoid muscle at the junction of the upper and middle third of the muscle to lie on top of the levator scapulae and middle scalene muscles ventral as it passes in an inferiocaudad course toward the anterior border of the trapezius muscle. The spinal accessory nerve provides motor innervation to the sternocleidomastoid 108 and trapezius muscles while providing minimal sensory innervation. It is subject to injury by stretching, blunt trauma, compression, entrapment, knife and gunshot wounds and by iatrogenic injuries during biopsies of the cervical lymph nodes, face lift surgery, carotid endarterectomy, excision of tumors, abscess incision and drainage, coronary artery bypass surgery, internal jugular vein cannulation, and radiation therapy (Fig. Intraoperative findings showing complete transection of the spinal accessory nerve following lymph node biopsy.

The anatomy of the brachial plexus and surrounding structures at the supraclavicular level discount nexium online gastritis symptoms fatigue. Note the relationship of the brachial plexus to the subclavian artery buy nexium cheap online diet untuk gastritis akut, superior border of the first rib order nexium with visa gastritis treatment, lung, and anterior and middle scalene muscles. Proper placement of the linear ultrasound transducer over the previously identified margin of the sternocleidomastoid muscle at the supraclavicular region. The brachial plexus, the lung, subclavian artery, and the first rib are identified (Fig. Color Doppler can be used to further delineate the subclavian artery and other vascular structures (Fig. The transducer is rotated into the longitudinal plane and the plexus is evaluated in the long axis. Transverse ultrasound image of the brachial plexus at the level of the supraclavicular region. Transverse color Doppler view of the brachial plexus (arrows) and the subclavian artery at the supraclavicular level. The transducer is returned to a transverse plane and the brachial plexus is imaged as the transducer is slowly moved distally to the infraclavicular region (Fig. The ultrasound transducer is then rotated so it is aligned with the superior aspect of the transducer pointing at the acromioclavicular joint and the inferior aspect of the transducer pointing at the patient’s ipsilateral nipple, and an ultrasound image is obtained (Figs. Placement of the transducer in this position will provide a short axis view of the axillary artery and cords of the brachial plexus with the artery appearing as a round pulsatile structure surrounded by the medial, lateral, and posterior cords of the brachial plexus (Fig. The axillary artery, the cords of the brachial plexus, the intercostal muscle and the pleura and lung, are then identified. Color Doppler can be used to further delineate the axillary artery and any other vascular structures (Fig. The transducer is rotated into the longitudinal plane and the plexus cords and vessels are evaluated in the long axis. To reach the cords of the brachial plexus at the infraclavicular level, the needle must traverse the skin, subcutaneous tissue, and pectoralis major and minor muscles. To evaluate the brachial plexus at the infraclavicular level, an imaginary line is drawn from the acromioclavicular joint to the ipsilateral nipple to aid in placement of the ultrasound transducer. Proper placement of the linear ultrasound transducer at the infraclavicular level. Transverse color Doppler view of the brachial plexus and the axillary artery at the infraclavicular level. As the brachial plexus is being imaged with ultrasound, care must be taken to identify abnormalities, including tumors, abscess, nerve trauma, inflammation, and other causes of brachial plexus compromise (Figs. Some of the roots are globular in shape and the others fusiform (right and left coronal sonograms were fused photographically and displayed vertically). A: the tumor appears on ultrasound as a solitary rounded mass (S) with smooth contours and hypoechoic texture. Diffuse infiltration of nerve roots by metastatic breast carcinoma associated with postirradiation fibrosis. A: the right coronal sonogram shows normal appearance of C5 and C6 roots of the brachial plexus (arrowheads). B: the left coronal view in the same patient shows a diffuse hypoechoic thickening of the same roots (arrowheads). The caliber of the affected roots is significantly enlarged in comparison with the contralateral nerves and a loss of the normal nerve tapering distally can be noted (same scaling factor on both images). High-resolution sonography detects extraforaminal nerve pathology in patients initially diagnosed with cervical disc disease: a case series. C: Transverse sonogram showing an arteriovenous fistula compressing the anterior interosseous nerve. High- resolution sonography detects extraforaminal nerve pathology in patients initially diagnosed with cervical disc disease: a case series. Acute brachial plexus injury in a 25-year-old motorcyclist with total plexus palsy following a traffic accident. Distal to the transection level, heterogeneous signal in the soft tissues (asterisk) of the supraclavicular area is seen. When compared with the left side, note the swollen appearance and more vertical course of the affected right roots. Ultrasound imaging of the plexus can supplement information obtained from the targeted history and physical examination to allow for the prompt diagnosis of brachial plexus disorders. The use of magnetic resonance and computed tomographic imaging combined with electromyography and nerve conduction testing will further strengthen the diagnosis. Neuraxial anesthesia and analgesia in patients with preexisting central nervous system disorders. An ultrasound study of the phrenic nerve in the posterior cervical triangle: implications for the interscalene brachial plexus block. In: Comprehensive Atlas of Ultrasound-Guided Pain Management Injection Techniques. The rounded head of the humerus articulates with the pear-shaped glenoid fossa of the scapula (Fig. The joint’s articular surface is covered with hyaline cartilage, which is susceptible to arthritis and degeneration. The rim of the glenoid fossa is composed of a fibrocartilaginous layer called the glenoid labrum (Fig. The most mobile joint in the human body, the glenohumeral joint is surrounded by a relatively lax capsule that allows the wide range of motion of the shoulder joint, albeit at the expense of decreased joint stability. The joint capsule is lined with a synovial membrane, which attaches to the articular cartilage. This membrane gives rise to synovial tendon sheaths and bursae that are subject to inflammation. Cross-sectional anatomy of the glenohumeral joint demonstrating the labrum and synovium. Along with the accessory ligaments of the shoulder, these major ligaments provide strength to the shoulder joint. The strength of the shoulder joint also is dependent on short muscles that surround the joint: the subscapularis, the supraspinatus, the infraspinatus, and the teres minor. These muscles and their attaching tendons are susceptible to trauma and to wear and tear from overuse and misuse. The joint’s articular cartilage is susceptible to damage, which left untreated, will result in arthritis with its associated pain and functional disability. Osteoarthritis of the joint is the most common form of arthritis that results in shoulder joint pain and functional disability, with rheumatoid arthritis, posttraumatic arthritis, and rotator cuff tear arthropathy also causing arthritis of the glenohumeral joint (Fig. Less common causes of arthritis-induced shoulder joint pain include the collagen vascular diseases, infection, villonodular synovitis, and Lyme disease. Acute infectious arthritis of the glenohumeral joint is best treated with early diagnosis, with culture and sensitivity of the synovial fluid and prompt initiation of antibiotic therapy.