A. Dan. University of Rio Grande.
New headache in any patient over 50 years of age should Other disorders seen more in the tropics that may pres- raise the suspicion of giant cell (temporal) arteritis purchase bisoprolol in united states online hypertension medication. These are often diagnosed only on imaging or Jaw claudication is highly suggestive discount bisoprolol 10mg on line hypertension 14070. No signicant mortality is associated with headache disorders buy bisoprolol paypal heart attack mp3, which is one reason why they are so poorly acknowledged. Nevertheless, among the recognizable burdens imposed on people affected by headache disorders are pain and personal suffering, which may be substantial, im- paired quality of life and nancial cost. Collectively, all headache disorders probably account for double this burden (3), which would put them among the top ten causes of disability. Repeated headache attacks, and often the constant fear of the next, damage family life, social life and employment (21). For example, social activ- ity and work capacity are reduced in almost all people with migraine and in 60% of those with tension-type headache. Headache often results in the cancellation of social activities while, at work, people who suffer frequent attacks are likely to be seen as unreliable which they may be or unable to cope. This can reduce the likelihood of promotion and undermine career and nancial prospects. While people actually affected by headache disorders bear much of their burden, they do not carry it all: employers, fellow workers, family and friends may be required to take on work and duties abandoned by headache sufferers. Because headache disorders are most troublesome in the productive years (late teens to 60 years of age), estimates of their nancial cost to society are massive principally from lost working hours and reduced productivity because of impaired working effectiveness (22). In the United Kingdom, for example, some 25 million working or school days are lost every year because of migraine alone (6). Not surprisingly, headache is high among causes of consulting both general practitioners and neurologists (23, 24). One in six patients aged 16 65 years in a large general practice in the United Kingdom consulted at least once because of headache over an observed period of ve years, and almost 10% of them were referred to secondary care (25). A survey of neurologists found that up to a third of all their patients consulted because of headache more than for any other single complaint (26). Far less is known about the public health aspects of headache disorders in developing and resource-poor countries. Indirect nancial costs to society may not be so dominant where labour costs are lower but the consequences to individuals of being unable to work or to care for children may be severe. There is no reason to believe that the burden of headache in its personal elements weighs any less heavily where resources are limited, or where other diseases are also prevalent. For ex- ample, in representative samples of the general populations of the United States and the United Kingdom, only half the people identied with migraine had seen a doctor for headache-related reasons in the last 12 months and only two thirds had been correctly diagnosed (27). Most were solely reliant on over-the-counter medications, without access to prescription drugs. In a separate general-population questionnaire survey in the United Kingdom, two thirds of respondents with migraine were searching for better treatment than their current medication (28). In Japan, aware- ness of migraine and rates of consultation by those with migraine are noticeably lower (29). Over 76 Neurological disorders: public health challenges 80% of Danish tension-type headache sufferers had never consulted a doctor for headache (30). It is highly unlikely that people with headache fare any better in developing countries. The barriers responsible for this lack of care doubtless vary throughout the world, but they may be classied as clinical, social, or political and economic. Clinical barriers Lack of knowledge among health-care providers is the principal clinical barrier to effective head- ache management. This problem begins in medical schools where there is limited teaching on the subject, a consequence of the low priority accorded to it. It is likely to be even more pronounced in countries with fewer resources and, as a result, more limited access generally to doctors and effective treatments. Social barriers Poor awareness of headache extends similarly to the general public. Headache disorders are not perceived by the public as serious since they are mostly episodic, do not cause death and are not contagious. In fact, headaches are often trivialized as normal, a minor annoyance or an excuse to avoid responsibility. These important social barriers inhibit people who might otherwise seek help from doctors, despite what may be high levels of pain and disability. Surprisingly, poor awareness of headache disorders exists among people who are directly affected by them. A Japanese study found, for example, that many patients were unaware that their headaches were migraine, or that this was a specic illness requiring medical care (31). The low consultation rates in developed countries may indicate that many headache sufferers are unaware that effective treatments exist. Political and economic barriers Many governments, seeking to constrain health-care costs, do not acknowledge the substantial burden of headache on society. They fail to recognize that the direct costs of treating headache are small in comparison with the huge indirect cost savings that might be made (for example by reduc- ing lost working days) if resources were allocated to treat headache disorders appropriately. Therefore the key to successful health care for headache is education (31), which rst should create awareness that headache disorders are a medical problem requiring treatment. Education of health-care providers should encompass both the elements of good management (see Box 3. Diagnosis Committing sufcient time to taking a systematic history of a patient presenting with headache is the key to getting the diagnosis right. The history-taking must highlight or elicit description of the characteristic features of the important headache disorders described above. The correct diagnosis is not always evident initially, especially when more than one headache disorder is present, but the history should awaken suspicion of the important secondary headaches. Once it is established that there is no serious secondary headache, a diary kept for a few weeks to record neurological disorders: a public health approach 77 the pattern of attacks, symptoms and medication use will usually clarify the diagnosis. Physical examination rarely reveals unexpected signs after an adequately taken history, but should include blood pressure measurement and a brief but comprehensive neurological examination including the optic fundi; more is not required unless the history is suggestive. Examination of the head and neck may nd muscle tenderness, limited range of movement or crepitation, which suggest a need for physical forms of treatment but do not necessarily elucidate headache causation. Investigations, including neuroimaging, rarely contribute to the diagnosis of headache when the history and examination have not suggested an underlying cause. Realistic objectives There are few patients troubled by headache whose lives cannot be improved by the right medical intervention with the objective of minimizing impairment of life and lifestyle (32). Cure is rarely a realistic aim in primary headache disorders, but people disabled by headache should not have unduly low expectations of what is achievable through optimum management. Medication-overuse headache and other secondary headaches are, at least in theory, resolved through treatment of the underlying cause.
Tenderness over the paranasal sinuses may be present if concomitant infection is present cheap bisoprolol 5 mg with mastercard heart attack quiz. In patients with nasal allergic disease cheap 5 mg bisoprolol mastercard prehypertension blood pressure symptoms, the ears should be examined for evidence of acute or chronic otitis media buy discount bisoprolol 10 mg online blood pressure medication starting with v, either serous or infectious in nature. Asthma Physical findings in asthmatic patients are highly variable, not only between patients but also in the same patient at different times. The rapidity with which symptoms and physical findings can appear or disappear is one of the characteristic features of the illness. During an acute attack of asthma, the patient is often tachycardic and tachypneic. The patient appears to be in respiratory distress and usually uses the accessory muscles of respiration. Mechanically, these muscles are more effective if the patient stands or sits and leans slightly forward. During an acute attack, the patient rarely will lie down unless severely exhausted. On auscultation, musical wheezes may be heard during both inspiration and expiration, and the expiratory phase of respiration may be prolonged. These auscultory findings tend to be present uniformly throughout the lungs in uncomplicated asthma exacerbation. Asymmetry of auscultory findings might be caused by concomitant disease such as pneumonia, or by a complication of the asthma itself, such as occlusion of a large bronchus with a mucous plug. In severely ill patients, extreme bronchial plugging and loss of effective mechanical ventilation may be associated with disappearance of the wheezing and a marked decrease in all audible breath sounds. In these critically ill patients, alveolar ventilation has almost disappeared, and they may be cyanotic. When the asthmatic patient is not having an acute exacerbation, there may be no demonstrable abnormalities on auscultation even when evidence of reversible airway obstruction can be demonstrated with pulmonary function studies. In many instances, asthma is chronic, and wheezes may be heard even while the patient is feeling subjectively well. In some cases, wheezes will not be heard during normal respiration but can be heard if the patient exhales forcefully. Atopic Dermatitis The findings on physical examination of a patient with atopic dermatitis also vary widely. In an infant 4 to 6 months of age, the initial manifestation usually is erythema and edema. Initial lesions are most likely to occur on the cheeks, in the antecubital fossa, the popliteal spaces, or about the neck and ears. The papules then may form small vesicles, and when these vesicles rupture there may be oozing and crusting. In the chronic form, lichenification of the skin is the predominant cutaneous finding. The cosmetic effects of the chronic form are often very disturbing to the patient. If such abnormalities are present, other illnesses or complications should be suspected. The differential white blood cell count is usually normal, with the frequent exception of eosinophilia that may range from 3% to 10%. Eosinophilia of 12% to 20% is seldom present in allergies to extrinsic antigens unless there is also an infection. Chest radiographs may be necessary to rule out concomitant disease or complications of asthma. Chest radiographs in patients with asthma may reveal hyperinflation or bronchial cuffing; however, most often they are normal ( 3). Conventional radiographs of the sinuses provide limited information and may have high false-positive and false-negative rates. All or some of these procedures may be necessary to establish the correct diagnosis. Gross and microscopic findings in nasal secretions and in sputum have been described in allergic patients. These changes include eosinophils, Curschmann spirals, Charcot-Leyden crystals, and Creola bodies. Although interesting findings, their presence or absence may or may not be of diagnostic value. They may yield some insight into the type and severity of the functional defect and, more importantly, may provide an objective means for assessing changes that may occur with time or may be induced by treatment. It must be remembered that single sets of values describe conditions at designated points in time, and conditions such as asthma have rapid pathophysiologic changes. A flow volume loop may demonstrate extrathoracic obstruction such as vocal cord dysfunction. Provocation Tests Although nasal or bronchial challenges with specific antigens to confirm immediate sensitivity are rarely performed in routine practice, they are nevertheless important tools in research studies. Nonspecific bronchial reactivity may be assessed with methacholine or histamine and is occasionally used in the diagnosis of asthma. Food challenges may be necessary in the diagnosis of food allergies and are performed on a regular basis in clinical practice. Double-blind placebo-controlled food challenges are the gold standard in the diagnosis of food allergies and may occasionally be required. Provocation testing should be performed in a supervised setting with emergency treatment available. Pathogenesis of Skin Testing Immediate response elicited by skin testing peaks in 15 to 20 minutes and involves production of the wheal and flare reaction characteristic of atopic sensitization. Mast cell degranulation and subsequent release of histamine is responsible for the immediate reaction ( 6). The wheal and erythema reaction can be reproduced by injection of histamine into the skin. Skin Testing Techniques Currently, two methods of skin testing are widely used: prick/puncture tests and intracutaneous tests. The tests should be read in 20 to 30 minutes, but if a large wheal reaction occurs before that time, the test site should be wiped free of antigen to reduce the possibility of a systemic reaction. Prick/Puncture Test Prick/puncture tests are more specific than intracutaneous tests in corroborating allergic disease ( 7,8). These tests can be performed with a minimum of equipment and are the most convenient and precise method of eliciting the presence of immunoglobulin E (IgE) antibodies. A drop of the allergen extract to be tested is placed on the skin surface and a needle is gently penetrated into the epidermis through the drop. If appropriate antigen concentrations are used, there is relatively little risk of anaphylaxis, although rare large local skin reactions may occur. Intracutaneous Test If the skin-prick test result is negative, an intracutaneous test is performed by injecting the allergen into the dermis. The skin is held tense and the needle is inserted almost parallel to its surface, just far enough to cover the beveled portion.
Acute bronchial asthma: Relations between clinical and physiologic manifestations buy 10mg bisoprolol with amex heart attack 1d lyrics. There are varied definitions of what constitutes an excess number of these cells in the circulation ( 1 cheap 5 mg bisoprolol with amex pulse pressure guide,2 and 3) best 5 mg bisoprolol arrhythmia word parts, but more than 400 cells/ L of blood would be considered excessive. This chapter focuses on the diagnosis and management of disorders characterized by eosinophilia. Paul Ehrlich gave the cell the name eosinophil in 1879 because of the intense staining of its granules with the acidic aniline dyes like eosin ( 5). The staining procedures he developed allowed the cell to be recognized and studied. The eosinophil count can be estimated by multiplying the percentage of eosinophils from the differential white blood cell count by the total number of white blood cells. For example, in our institution, if the percentage on the automated differential is 20% or greater, the blood smear will be examined manually. In patients with leukopenia, the percentages of eosinophils may be increased, but not their absolute number. The number of eosinophils in the blood has a diurnal variation, being highest at night ( 3,5) and falling in the morning when endogenous glucocorticoid levels increase ( 3). Thus, a condition promoting eosinophilia could e masked if it occurred in the presence of such events. Under normal circumstances, eosinophils are found almost exclusively in the circulation and the gastrointestinal mucosa ( 2). The usual lifespan of the eosinophil in the circulation is about 4 days, but eosinophils survive for weeks within tissues ( 2,9). Thus, blood eosinophil numbers do not necessarily reflect the extent of eosinophil involvement in affected tissues in various diseases ( 2,3). Immunofluorescent stains with monoclonal antibodies directed against the cationic proteins from the granules are used to detect eosinophils in the tissues. Molecular basis for selective eosinophil trafficking in asthma: a multistep paradigm. Eosinophils exit the circulation and migrate to mucosal surfaces: lung, gut, lower genitourinary tract ( 2,14). This migration is mediated by adhesion molecules on endothelial and eosinophil surfaces. Through binding of P-selectin glycoprotein ligand 1 on eosinophils with P-selectin on endothelial cells, rolling and margination of eosinophils occurs (12,15). With the binding of integrins and their ligands, the rolling stops, and the eosinophil adheres more firmly to the endothelium and then migrates out of the vascular compartment. These include platelet-activating factor, complement components (C3a and C5a), and chemokines. Mature eosinophils produce their toxic and inflammatory effects by the release of mediators stored in their specific granules. These proteins are responsible for direct cytotoxic effects in part by producing hydrogen peroxide and halide acids generated by eosinophil peroxidase ( 2). Eosinophil cationic protein can disrupt membranes by causing pore formation that facilitates the entry of other toxic molecules. In the respiratory epithelium, activated eosinophil granule products can impair cilia beating and increase vascular permeability. Current and new therapies for eosinophil-mediated disease interfere with these imbalances. It is beyond the scope of this chapter to discuss all causes of eosinophilia in detail, but Table 33. These references include the original description of disease, a review of the clinical presentation, or an update on the possible immunopathogenic mechanisms involved. Below there is a review of some of the causes of eosinophilic infiltration of blood and tissues most pertinent to the allergist-immunologist and not covered in other chapters. Diseases most frequently associated with eosinophilia of blood or tissues Infections and Eosinophilia: Helminthic Diseases In developing countries, helminthic diseases are the most common cause of eosinophilia, whereas in developed countries, atopic diseases are most common. Infections with bacteria and most viruses are generally associated with eosinopenia. However, it has been established recently that respiratory syncytial virus stimulates endothelial cells to produce eosinophil chemoattractants and activates eosinophils ( 10). These findings may explain in part how viral infections trigger asthma exacerbations. With the exception of Isospora belli and Dientamoeba fragilis, protozoan infections do not elicit eosinophilia. In parasitic infections associated with eosinophilia, the level of peripheral blood eosinophilia may be modest or even nonexistent if the infection is well contained in tissues such as in an echinococcal cyst. The levels of peripheral eosinophilia may fluctuate as these cysts leak or adult filiaria migrate. Blood eosinophil levels tend to parallel the extent of tissue involvement and may be very marked as, for example, in disseminated Strongyloides species infection. It is particularly important to diagnose Strongyloides species infection, which sometimes may be dormant and unrecognized in a patient for years. Potentially fatal dissemination of this helminth can occur if the patient becomes immunosuppressed or receives corticosteroids, which is also the treatment for many other eosinophilic conditions (20,21 and 22). Serial stool examinations with appropriate serologic tests are the initial diagnostic tests for many helminthic infections ( 23) (Fig. For strongyloidiasis, if these tests are negative, examination of duodenojejunal aspirate or tissue biopsy or the Enterotest string method should be considered. Among the drugs most frequently reported are nitrofurantoin, minocycline, and nonsteroidal antiinflammatory agents. Although numerous drugs have been cited, in many cases, these citations are based on case reports, as is evident from those provided in Table 33. When information is based on case reports, it is not clear how often eosinophilia occurs in all of the patients who take the drug. Furthermore, it is possible that a case report can describe a true association between the drug and eosinophilia, or temporally associated but causally unrelated events, such as an association between eosinophilia and the underlying disease. Asthma and associated eosinophilia may wax and wane as part of the disease course, and this may be incidental to whether a drug is taken. In contrast, doses of systemic steroids for asthma may have been reduced when inhaled steroids were added, resulting in an increase in peripheral blood eosinophilia. Thus, the true association may be between the extent of eosinophilia and the underlying asthma, and not the drug used for treatment. Drug-induced reactions most commonly associated with eosinophilia of blood or tissues When taking a history for possible therapeutic agents associated with eosinophilia, inquiry about the use of agents used in complementary and alternative medicine and over-the-counter preparations should be made. For example, contaminated L-tryptophan and rapeseed oil were associated with the eosinophilia-myalgia syndrome (29,30). Patients should also be asked about the use of illicit drugs because cocaine and heroin use is sometimes associated with eosinophilia. In 1975, Chusid and colleagues (34) proposed diagnostic criteria that still are used today: (a) blood eosinophilia greater than 1500/ L persisting for more than 6 months; (b) exclusion of diseases associated with eosinophilia-like parasitic infections, allergic diseases, or medications; and (c) organ involvement. When damage occurs, it is the same as would occur with eosinophilic infiltration of the tissue in other eosinophil-related diseases, such as tropical endomyocardial fibrosis ( 36).
The K cell has no specificity for the antigen that is bound to the antibody cheap bisoprolol amex blood pressure variability, only for the Fc portion of the bound antibody buy bisoprolol 5 mg with amex blood pressure 55. Mast Cells and Granulocytes A variety of other cells are involved in some immune responses buy discount bisoprolol 10mg online blood pressure chart wiki, particularly those involving inflammation ( Table 1. Neutrophils are drawn to sites of inflammation by cytokines, where their phagocytic activity and production of enzymes and other soluble mediators contribute to the inflammation. Eosinophils ( 75,76) are involved in immune responses against large parasites, such as roundworms, and are apparently capable of killing them by direct contact. These cells migrate to the fetal liver and then (beginning about 80 days after fertilization) to the bone marrow, where they remain for life. Primary lymphoid organs consist of the bone marrow and thymus, where B and T lymphocytes, respectively, mature. B cells undergo their development, including generation of immunoglobulin receptors, while in the bone marrow. This intimate contact between recirculating cells facilitates the close interactions needed to initiate immune responses and generate appropriately sensitized cells, whose activities may then be expressed throughout the body ( 2,3 and 4). B lymphocytes responding to T-dependent antigens require two signals for proliferation and differentiation: (a) the binding of their surface immunoglobulin by appropriate specific antigen, and (b) the binding of cytokines (e. The help provided by T cells acts only over a short range; thus, the T and B cells must be in fairly intimate contact for these interactions to occur successfully. Splenic or lymph node T cells (or both) from the individual in question (responder) are mixed with lymphocytes from another individual (sensitizer) against whom the response is to be evaluated. The two cell populations are incubated together for 4 to 5 days, after which time tritiated thymidine is added to the culture for a few hours. If the responder cells actively proliferate as a result of the recognition of foreign antigens on the sensitizing cells, significant increases of thymidine incorporation (over control levels) can be measured. Individuals presensitized against a particular antigen, then later challenged intradermally with a small amount of the same antigen, display local inflammatory responses 24 to 72 hours later at the site of challenge. Perhaps the best known example is a + positive tuberculin skin test (Mantoux test). The activated macrophages exhibit an increased size and activity, enabling them to destroy and phagocytize the antigenic stimulus. However, because macrophages are not antigen specific, they may also destroy normal cells and tissues in the local area, referred to as innocent bystander destruction. In this regard, the immune system provides the body with a means for minimizing or preventing disease. This is most clearly illustrated by individuals who have defects in immune function (immunodeficiency disease) resulting from genetic, developmental, infective, or therapeutic causes. Because of its destructive potential, however, the immune system is also capable of causing disease when confronted with inappropriate antigenic stimulation or loss of regulatory control ( 88). Transplantation Transplantation involves the ability to replace damaged or diseased body parts by transplanting organs from one individual to another. Unfortunately, the immune system is exquisitely adept at recognizing nonself and rejecting transplanted organs from donors differing genetically from the recipient ( 89). Because a genetically perfect match between host and donor in humans exists only between identical twins, transplantation surgeons are forced to minimize or eliminate the recipient immune response against the transplanted organ. Ideally, only the ability of the immune system to react to the antigens on the transplanted organ would be diminished (i. However, we currently must rely on drugs that depress the immune system in a relatively nonspecific fashion, thus leaving the patient susceptible to potentially fatal opportunistic infections. Bone marrow transplantation represents a special case in which the graft itself comprises immunocompetent tissue and the host is either immunodeficient or immunosuppressed. There are several possible scenarios under which such undesirable responses might be initiated. Autoimmune responses may arise when antigens that have been normally sequestered from the immune system (e. Having never been detected previously by the immune system as it developed its sense of self versus nonself, such antigens are now seen as foreign. Third, immune responses against determinants on infectious agents may generate clones of lymphocytes with receptors capable of cross-reacting with self antigens (cross-reactive antigens). A classic example is rheumatic fever, which results from immune responses against streptococcal antigens that are cross-reactive with molecules found on cardiac tissue. For example, the onset of systemic lupus erythematosus is associated with age and an accompanying decline in suppressor T-cell function. Immune Complex Diseases The humoral immune response is generally efficient in eliminating antigen antibody complexes through the phagocytic cells of the reticuloendothelial system. There are, however, situations in which antigen antibody complexes (involving IgG and IgM antibodies) reach such high concentrations that they precipitate out of solution and accumulate in tissues, often unrelated to the source of the antigen. This may lead to systemic or localized inflammation as the complexes bind and activate serum complement components, attract phagocytic cells, and induce the release of proteolytic enzymes and other mediators of inflammation. Attempts to clear depositions of antigen antibody complexes often damage the tissues and organs involved. Such situations most often arise as a secondary effect of situations in which there is a persistence of antigen (e. Among the most commonly damaged sites are the kidneys, of which the filtration apparatus tends to accumulate deposited complexes (glomerulonephritis); the synovial joint membranes (rheumatoid arthritis); the skin (rashes); and the endothelial walls of blood vessels (arteritis). Contact Dermatitis Contact dermatitis is an example of a normally protective T-cell mediated immune response that becomes harmful under certain circumstances. Allergies and Anaphylaxis (Immediate Hypersensitivity) Allergies and anaphylaxis represent antigen-specific immunologic reactions involving IgE antibodies bound (by their Fc domain) to the membranes of mast cells and basophils (95). Immediate hypersensitivity may develop against a wide array of environmental substances and may be localized (e. For example, autoimmune responses, asthmatic and allergic responses, and the host responses against transplanted tissues or organs all represent situations in which such tolerance would be desirable. Immunosuppression is the elimination of all immune responses, regardless of the specificity of those responses. This may occur naturally, as in the case of individuals who are deficient in immune function for genetic reasons (e. Alternatively, it may be intentionally imposed by the application of radiation, drugs, or other therapeutic reagents (e. Such procedures, however, impose a new set of risks because their nonspecificity leaves the patient (or experimental animal) open to infections by opportunistic pathogens. Immunologic tolerance is the specific acquired inability of individuals to respond to a specific immunogenic determinant toward which they would otherwise normally respond. Tolerance is more desirable than immunosuppression because it eliminates or inactivates only those lymphocytes involved in the responses of concern, leaving the remainder of the immune system intact to deal with opportunistic infections. The natural induction of tolerance during the development of the immune system prevents immune responses against self antigens ( self tolerance), thus preventing autoimmunity (97,98). Tolerance may be induced in both T and B lymphocytes, although tolerance of T cells generally requires lower doses of antigen and is effective for a longer period of time. In addition, because B lymphocytes require T-cell help, the induction of tolerance in T cells often also diminishes corresponding antibody responses. The means by which specific tolerance is induced and maintained involve three general mechanisms, all of which probably occur in various situations.