University of Massachusetts at Boston. F. Gambal, MD: "Purchase online Keftab no RX - Quality online Keftab no RX".
Unfortunately generic keftab 125 mg on-line infection 13 lyrics, intranasal steroids have marginal effects in improving olfactory function keftab 750 mg visa xelent antibiotic. The latter result is best achieved with brief courses of systemic corticosteroids purchase keftab 250 mg fast delivery treatment for recurrent uti in pregnancy. Intranasal steroids exert little effect on associated sinus disease order discount keftab online antibiotic jaw pain, as evidenced by lack of improvement in sinus radiographs over a 12-month interval (31). Leukotriene antagonists are effective antiasthmatic agents and are particularly effective in aspirin-sensitive patients. However, there have been no published controlled clinical trials of antileukotriene agents in the treatment of nasal polyps ( 32). Long-term treatment with daily intranasal glucocorticoids is safe and has not been reported to result in atrophic changes in nasal mucosa ( 33). If polyps fail to respond to intranasal glucocorticoids, a brief 5- to 7-day course of oral prednisone (30 35 mg/day) may be effective. Once nasal polyps have been reduced in size with prednisone, maintenance dosages of intranasal glucocorticoids should be resumed to prevent recurrence. Coexistent sinus infection may render individuals refractory to intranasal glucocorticoids and therefore should be treated with an appropriate course of antibiotics. If all attempts at medical management have failed, surgical intervention should be recommended, particularly in the presence of chronic sinusitis that has been refractory to antibiotics. Simple polypectomy may be indicated for complete nasal obstruction, which causes extreme discomfort. If nasal polyps are associated with persistent ethmoid sinusitis with obstruction of the osteomeatal complex, a more extensive surgical procedure is required. Sphenoethmoidectomy with complete marsupialization of the ethmoid sinus and resection of the middle turbinate is a definitive procedure that has been reported to effectively prevent recurrence of nasal polyps in approximately 85% of treated patients ( 34). Outcomes of endoscopic sinus surgery are less favorable among aspirin triad patients compared with patients with chronic sinusitis who are aspirin insensitive. Asthmatic patients undergoing nasal polypectomy or sinus surgery had previously been regarded to be at risk for postoperative bronchospasm, but this outcome rarely occurs. Nonspecific airway responsiveness determined by methacholine challenge does not increase significantly in patients with asthma after nasal polypectomy (36). After recovery from polypectomy or sphenoethmoidectomy, maintenance intranasal glucocorticoids should be instituted to prevent recurrence of nasal polyps (37). This procedure should be performed exclusively by a subspecialist and considered only in aspirin-sensitive patients refractory to conventional therapies. Lamblin reported results of a 4-year longitudinal study in two groups of patients with nasal polyposis. Nasal polyps were responsive to nasal steroids in the first group, whereas the other group required nasal surgical intervention (ethmoidectomy). This suggests that ethmoidectomy does not result in long-term benefit for asthma in steroid-unresponsive patients with nasal polyposis ( 38). Sinusitis is an inflammatory disorder of the mucosal lining of the paranasal sinuses that may be initiated by either infectious or noninfectious factors. Regardless of initiating events, the four physiologic derangements that contribute to the evolution of infectious sinusitis are as follows: (a) decreased patency of the sinus ostia; (b) a decrease in the partial pressure of oxygen within the sinus cavities caused by impairment of ventilatory exchange; (c) diminished mucociliary transport; and (d) compromise of mucosal blood flow. Viral upper respiratory infections often precede acute bacterial sinus infections. Bacterial sinusitis has long been considered a complication of seasonal or perennial allergic rhinitis, although no good data support this assumption. Cigarette smokers and individuals with vasomotor rhinitis are more susceptible to recurrent or chronic sinusitis. The microbial pathogens implicated in acute maxillary sinusitis have been studied extensively. Identification of bacterial pathogens has been achieved by culturing antral aspirates obtained by needle puncture of the maxillary sinus. Bacterial species represented included Streptococcus pneumoniae in 92 (41%); Haemophilus influenzae in 79 (35%); anaerobes in 17 (7%); streptococcal species in 16 (7%); Moraxella catarrhalis in 8 (4%); Staphylococcus aureus in 7 (33%); and other miscellaneous organisms in 8 (4%) ( 41). Cultures of nasopharyngeal specimens are useless because they do not reflect bacterial isolates in the sinuses. Viruses are cultured from 8% of aspirates, whereas 15% to 40% of antral aspirates are sterile. Common isolates include rhinovirus, influenza type A, and parainfluenza viruses ( 42). Viruses were isolated from 4% of pediatric patients, and 20% of cultured aspirates were sterile. Anaerobic bacteria have been cultured from 88% of antral aspirates of adult patients with chronic sinusitis but are seldom identified in children ( 44,45). This organism is saprophytic, is abundant in the natural environment, and may be isolated easily from the throat and stools of normal individuals. Mucor can become an invasive pathogen in diabetic, leukemic, or otherwise immunosuppressed patients. Similarly, invasive aspergillosis may involve the paranasal sinuses in the immunocompromised host ( 47). Allergic fungal sinusitis is an increasingly recognized syndrome occurring in nonimmunocompromised atopic patients with hypertrophic rhinitis and nasal polyps, which may result from local hypersensitivity responses to a variety of mold spores colonizing the sinus cavities. Abundant mucin found within the sinuses demonstrates numerous eosinophils and Charcot-Leyden crystals; fungal stains reveal the presence of noninvasive hyphae ( 48,77). Atypical mycobacteria can cause sinusitis in patients with acquired immunodeficiency syndrome ( 49). Clinical Presentation Episodes of acute sinusitis are most commonly preceded by symptoms suggestive of viral upper respiratory tract infections or other environmental stimuli, which can cause mucosal inflammation, hypertrophy, and obstruction of the sinus ostia. Common presenting symptoms include frontal or maxillary head pain, fever, and mucopurulent or bloody nasal discharge. Pain cited as coming from the upper molars may be an early symptom of acute maxillary sinusitis. Children with acute maxillary sinusitis present most often with cough, nasal discharge, and fetid breath, whereas fever is less common ( 43). Symptoms associated with chronic sinusitis are less fulminant; facial pain, headache, and postnasal discharge are common symptoms. The clinician should be aware that chronic maxillary sinusitis may result from primary dental infections (i. Pain associated with temporomandibular dysfunction may be incorrectly diagnosed as chronic sinusitis. Individuals with sinusitis may experience severe facial pain associated with rapid changes in position (e. Episodes of acute or chronic sinusitis may be manifestations of other underlying problems.
This group also identified clinical factors that are associated with the diagnosis of sinusitis purchase 250mg keftab free shipping 5th infection. These are grouped into two categories: major factors and minor factors ( Table 40 purchase keftab with mastercard antimicrobial gorilla glass. The presence of two or more major factors or one major and two minor factors is considered a strong history for sinusitis discount keftab online virus outbreak 2014. A stream purulent of mucus may be apparent draining from beneath the middle turbinate purchase 500mg keftab otc antibiotics how do they work. Endoscopically directed cultures of this drainage may be of particular value in guiding antibiotic therapy ( 5). Major and minor factors in the diagnosis of sinusitis Classification of sinusitis as acute, subacute, recurrent acute, or chronic is dependent on temporal patterns. A diagnosis of chronic sinusitis requires that signs and symptoms consistent with a strong history for sinusitis persist for longer than 12 weeks. Patients also may have acute exacerbations of chronic sinusitis in which they experience worsening of the chronic baseline signs and symptoms or the development of new ones. These patients do not have complete resolution of symptoms between exacerbations, in contrast to those with recurrent acute sinusitis. Given the multifactorial nature of its etiology and the diversity of signs and symptoms, chronic sinusitis can be considered a syndrome. The resulting improvement in sinus ventilation and drainage often promotes relief of inflammation and resolution of symptoms. Rhinoscopic Diagnosis Nasal endoscopy is an extension of the physical examination that offers significant insight into the pathologic factors at work in chronic sinusitis. For centuries, the standard of diagnosis was visualization anteriorly using a nasal speculum and posteriorly using an angled mirror placed in the pharynx. Rhinoscopy using a rigid fiberoptic telescope, however, is considered more accurate and thorough, and can be performed at a reasonable cost ( 15). Several scopes are available to provide visualization with different angles of deflection ( Fig. The zero degree telescope, for example, gives a direct and magnified view of structures directly in front of the tip of the scope. In contrast, the 30 degree scope evaluates structures located at a 30 degree inclination from the long axis of the instrument in the direction of the bevel. Flexible endoscopy is preferable for patient comfort prior to the performance of endoscopy, the nose is often topically decongested and anesthetized with a combination of phenylephrine or oxymetazoline (for decongestion), and lidocaine or pontocaine (for anesthesia). Decongestion temporarily shrinks the inflamed nasal mucosa, allowing the scope greater access to critical areas. The topical anesthesia improves patient comfort and compliance during the examination. In examining patients who have a history consistent with sinusitis, specific pathology that is not evident by a speculum examination may be detected by fiberoptic rhinoscopy. These may contribute to the development of chronic sinusitis by causing ostial obstruction. In the absence of symptoms and mucosal inflammatory changes, findings such as a deviated septum or a concha bullosa are considered incidental. In each particular case, the surgeon must assess the degree of pathology and the contribution of anatomic abnormalities to that pathology. An additional role of diagnostic rhinoscopy is to rule out the presence of benign or malignant neoplasms of the nose and paranasal sinuses. These pathologies can cause anatomic obstruction of sinus drainage and thus produce symptoms of chronic sinusitis. Suspicious lesions observed rhinoscopically can be examined via biopsy with endoscopic guidance, often in the office setting. The differential diagnosis of sinonasal masses includes benign and malignant salivary gland tumors, inverting papilloma, and sinonasal carcinoma. These entities are relatively rare; their discussion is beyond the scope of this chapter. It is nonetheless important that to note that rhinoscopic examination may reveal pathology that may not be suspected on the initial history and physical examination in a patient with symptoms of chronic sinusitis. Radiologic Diagnosis Imaging has become a critical element in the diagnosis of sinusitis, the extent of inflammatory disease, and the evaluation of sinonasal anatomy. Prior to this, imaging studies for sinusitis were conventional radiography and polytomography. Its utility in sinonasal imaging, however, is limited secondary to its inability to display fine bony detail. In fact, several staging systems have been developed attempting to grade the severity of sinusitis based on these variables ( 17). The presence of bony anatomic variations that may contribute to the pathology of chronic sinusitis also can be detected. Medical therapy should usually be the first-line treatment in uncomplicated cases, with an antibiotic course generally recommended for a minimum duration of 4 to 6 weeks. In cases of extensive polyp disease, surgery is not curative but does improve symptoms. These patients often require revision surgery and are committed to long-term topical or oral steroid therapy. Thus, surgery is considered palliative in these cases because it cannot address the underlying pathophysiologic process ( 18). In these cases, adenoidectomy is first-line surgical therapy if the adenoid pad is enlarged (21). The ethmoid sinus system forms the skull base, and the frontal, maxillary, and ethmoid sinuses surround the orbit ( Fig. Unless orbital or intracranial complications are pending, it is preferable to avoid operating in the setting of acute symptom exacerbations in order to minimize the risks of perioperative bleeding and other complications. Also, the use of aspirin and other nonsteroidal antiinflammatory drugs is discouraged within 2 weeks of surgery. Intraoperative Procedure After the administration of general anesthesia or sedation, topical anesthetics and vasoconstrictors are applied. Under endoscopic visualization, lidocaine with epinephrine is injected submucosally at key points. This provides vasoconstriction and obviates the need for deeper planes of systemic anesthesia. When it is deemed that septal deviation contributes to ostial obstruction, a septoplasty (straightening of the septum) is performed. In some instances, septoplasty is necessary to allow surgical access (passage of the endoscope and forceps) to posterior areas in the nasal cavity. Also, the middle turbinate may be collapsed onto the lateral nasal wall and must be fractured medially, or even partially resected, for access to the osteomeatal complex. The same situation can exist if the turbinate is hypertrophic or pneumatized concha bullosa.
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Drug-induced reactions most commonly associated with eosinophilia of blood or tissues When taking a history for possible therapeutic agents associated with eosinophilia proven 375mg keftab antibiotic classes, inquiry about the use of agents used in complementary and alternative medicine and over-the-counter preparations should be made keftab 125mg line iv antibiotics for sinus infection. For example buy discount keftab on line bacteria 25 degrees, contaminated L-tryptophan and rapeseed oil were associated with the eosinophilia-myalgia syndrome (29 order keftab 125 mg with amex infection list,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). In one patient, eosinophils expressing the Bcl-2 gene, whose products inhibit apoptosis, have been described ( 42). It is not clear from this information whether those patients with clones of abnormal T cells will progress to T-cell neoplasia ( 40,43). Some patients may develop very high white blood cell counts (>90,000/ L), which is associated with a poor prognosis ( 36). Examination of the bone marrow reveals increased numbers of eosinophils, often 30% to 60% of marrow cells. There are increased numbers of early forms compared with normal bone marrow, but blast forms are not usually present ( 36). When blast forms are present in the blood or make up more than 10% of the eosinophils in the marrow, the diagnosis is eosinophilic leukemia. Patients with these latter findings are less likely to respond to corticosteroids and may require cytotoxic agents. Cardiac damage is thought to progress through three stages: acute necrosis, the development of endocardial thrombi, and endocardial fibrosis ( 36,44). It is hypothesized that treatment in the first stage with corticosteroids will prevent progression to the other nonreversible stages ( 36). The second stage is characterized by thrombi in either ventricle and occasionally in the atrium. In the third stage, fibrosis may lead to entrapment of the chordae tendineae and resultant mitral or tricuspid valve insufficiency or a restrictive cardiomyopathy. Clinically, patients may present with dyspnea, chest pain, or congestive heart failure. Patients who have urticaria or angioedema as skin manifestations tend to have a better prognosis; they are more likely to have no cardiac or neurologic manifestations (36). Biopsy specimens of the papular and nodular lesions are characterized by perivascular infiltrates of eosinophils, neutrophils, and mononuclear cells without evidence of vasculitis ( 36). Neurologic involvement occurs in 54% of cases and has three forms: thromboembolic disease resulting from thrombotic cardiac disease, primary central nervous system dysfunction (36), and peripheral neuropathy. Clinically, patients who present with thromboembolic events have had strokes or transient ischemic attacks. Visual symptoms, occurring in 23% of patients, are also attributed to microemboli or possibly local thrombi. Central nervous system dysfunction is manifested as gait disturbances, behavioral changes, memory loss, or upper motor neuron signs such as increased muscle tone. Peripheral neuropathy may be expressed as mononeuritis multiplex with symmetric or asymmetric sensory deficits or painful paresthesias, or as motor neuropathies. Pulmonary involvement is believed to occur as a secondary manifestation of congestive heart failure or of embolic events originating from right ventricular thrombi or by primary infiltration of the lung by eosinophils. Thus, chest radiographs may show evidence of congestive heart failure, pleural effusions, or infiltrates. Treatment begins with corticosteroids (usually prednisone, 1 mg/kg/day for several weeks and then on alternate days). Hydroxyurea (1 to 2 g/day) ( 37) is used for patients who do not respond adequately to corticosteroids. Interferon-a administered subcutaneously in several dosage regimens has also been reported to be effective ( 38,40). The syndrome is characterized by a necrotizing vasculitis in patients with asthma and eosinophilia. Diagnostic criteria formulated by the American College of Rheumatology, yielding a sensitivity of 85% and a specificity of 99. Because it is relatively rare and therefore not readily recognized, the diagnosis may be missed. The mean age of onset is 38 years; men are affected slightly more frequently than women ( 47). Typically, asthma or rhinitis precedes the development of the other manifestations by a mean of 8. Virtually all patients have pulmonary involvement as asthma or bilateral migratory pulmonary infiltrates (48). The most common gastrointestinal symptoms are abdominal pain, nausea or vomiting, diarrhea, and hematochezia. Myalgias and arthralgias are the most common musculoskeletal symptoms; however, true arthritis is rare (3,47). Distribution of clinical manifestations in Churg-Strauss syndrome Laboratory studies are most notable for fluctuating peripheral blood eosinophilia, with peaks ranging from 20% to 90% of the differential white blood cell count. Perinuclear antineutrophil cytoplasmic antibodies directed against myeloperoxidase occur in 50% to 70% of patients ( 48,49). Biopsy of involved tissues is characterized by necrotizing vasculitis of the small arteries and veins, eosinophils, and extravascular granulomas. Without treatment, the prognosis is poor with 50% dying within 3 months of the onset of vasculitis ( 49). Some investigators believe that the early use of cyclophosphamide (Cytoxan) prevents irreversible organ damage ( 47). Eosinophilic Pneumonias The eosinophilic pneumonias are a group of disorders characterized by blood or tissue eosinophilia and pulmonary infiltrates. This term was intended to describe the more inclusive category of pulmonary diseases characterized by eosinophilic infiltrates with or without peripheral blood eosinophilia. Later, other related syndromes, such as acute eosinophilic pneumonia, were described. There are four eosinophilic pneumonias not discussed earlier: tropical pulmonary eosinophilia, Lffler syndrome, and chronic and acute eosinophilic pneumonia. Excellent reviews ( 45,49) provide further details and a description of several others for which space does not allow inclusion here. Most patients with Lffler syndrome have either a parasitic infection or drug reaction, although no cause can be found in about one third of cases. Patients are generally at least 30 years of age ( 6,54), and many have a history of atopy. Blood eosinophilia is present in about 90%, but its absence does not exclude the diagnosis (55).
The latex-derived profilin shows cross-reactivity with IgE from 36 patients with ragweed allergy (98) keftab 500 mg lowest price infection home remedy. A high degree of cross-reactivity can be expected because of the homology of enolases present in different organisms (Cladosporium species) and plants (tomato) keftab 250 mg without prescription antibiotics for sinus infection how long does it take to work. However order keftab 750 mg mastercard antibiotics for uti and birth control, preliminary studies in our laboratory of 26 health care workers with latex allergy failed to show IgE binding with the recombinant latex and fungal enolases (unpublished results) discount keftab 500 mg without prescription vyrus 986 m2 for sale. This type 1 chitinase shares homology with N-terminal hevein domain and also shares epitopes with chitinases from avocado and banana ( 92,93). The cross-reactivity and immune responses of Hev b 11 in allergic reaction have not been fully elucidated; hence, it is designated as a minor allergen in latex allergy. This 30-kDa protein exhibits extensive sequence homology with chitinase and lysozymes from various sources (75,83). Purified hevamine demonstrated IgE reactivity with only 1 in 29 latex-allergic sera tested and hence are not considered as an important allergen in inducing latex allergy ( 83). The lack of a hevein-like domain near the N-terminal region of the protein may be responsible for its minimal allergenicity in latex-allergic patients. Several other latex allergens have been identified by two-dimensional immunoblotting and microsequencing ( 75). These proteins with sequence similarities to spinach, rice, and tomato triose phosphate isomerases and several proteosane subunits are yet to be purified and characterized for their role in latex allergy. Two-dimensional immunoblot demonstrates more than 200 peptides, with more than 50 spots demonstrating immune reactivity with IgE. This widespread cross-reactivity among various plant proteins may be due to the presence of common T- and B-cell epitopes in them. Although extensive work has been carried out to identify the proteins involved in latex allergy, not much information is available on the cross-reactivity of latex allergens with proteins from other sources. In a recent study, Beezhold and associates demonstrated the co-sensitization between latex and various foods by skin-prick testing ( 120). Cross-reactive allergens in banana appear in several molecular weight ranges between 23 and 47 kDa and in avocado between 27 and 91 kDa ( 121,122 and 123). Akasawa and colleagues identified an avocado chitinase as one of the cross-reacting proteins using sera from latex-allergic patients ( 124). Yagami and co-workers proposed that the pathogenesis-related latex proteins such as chitinase and b-1,3-glucanase are potential cross-reacting proteins because they are common in different plant families and have comparable amino acid sequences and immunologic properties (91). In a recent study, Blanco and colleagues showed that chestnut and avocado type 1 chitinases with N-terminal hevein-like domain are the major allergens that cross-react with latex and suggested that type 1 chitinases are the pan allergens responsible for the latex-fruit syndrome ( 119). The cross-reactivity between fruits, pollen, and latex is also attributed to the highly conserved plant allergen profilin identified in all these different species ( 30). These results demonstrated a mutual boosting effect of pollen and latex sensitization in vivo, which may be seen also in polysensitized plant allergic patients. This study confirmed that mice stimulated with latex proteins develop a predominantly T H2 cytokine response. The results indicated that eosinophils and IgE antibodies play a major role in the immunopathogenesis of latex-induced allergy and anaphylaxis. In another study, latex-immunized mice evaluated by body plethysmography exhibited a significant change in pulmonary conductance (G L) and compliance (Cdyn) consistent with an asthma-like response. The latex-allergic response in this study is unique in that the direct challenge with latex antigen itself resulted in a significant airway response (128). The accumulated data from animal models suggest that the nature of sensitization in patients may be solely dependent on the type of antibody production and the pattern of cytokine expression by allergen-specific T lymphocytes ( 126,127,128 and 129). The studies using crude ammoniated latex, nonammoniated latex cytosol, and extracts demonstrated enhanced lymphoproliferative responses in latex sensitized patients ( 130). The distinct serologic patterns of patients against purified allergens were also reflected in their cell-mediated immune responses against these allergens. The monoclonal antibody affinity purified Hev b 3 exhibited proliferative responses in spina bifida patients, but not in health care workers ( 81). In another study, purified Hev b 1 induced lymphoproliferation in 52% of latex-allergic patients, compared with 25% of latex-exposed healthy subjects, suggesting that Hev b 1 is a relevant allergen in health care workers ( 133). Whereas, Hev b 2 showed stimulation in 56% patients, with more than 70% correlation between stimulation index and specific serum IgE binding ( 112). In a separate study, recombinant Hev b 5 demonstrated T-cell stimulation in five of six health care workers with latex allergy ( 134). In vitro study conducted using overlapping synthetic peptides of latex allergen Hev b 1 demonstrated that B lymphocytes of patients recognized several epitopes within the same allergen ( 137) (Table 31. In two separate studies, linear and conformational epitopes of prohevein have been identified; in both the studies, two linear epitopes were detected in the N-terminal region of Hev b 6 (114,141). B-cell epitopes of Hev b 6 specific for IgE antibody with sera from either latex-sensitized spina bifida patients or health care workers or common for both patients groups were reported. The IgE-binding epitopes of Hev b 1 and Hev b 3 were studied with sera from both health care workers and spina bifida patients with latex allergy ( 110). Of the eight epitopes of Hev b 1 that reacted with sera from the spina bifida patients, only three near the C-terminal end showed binding with the sera of health care workers. For Hev b 3, however, common epitopes for spina bifida patients and health care workers were identified near the C-terminal region of the protein (110). To reduce latex sensitization, the only immediate measure is the avoidance of latex products and exposure to latex allergens. Given the ubiquity of latex in the environment and the cost-effectiveness of latex products, complete avoidance may be an impossible proposition. Hence, as an alternative measure, immunotherapy has been attempted to reduce the disease severity and improve the quality of life of allergic individuals. The first oral latex desensitization was carried out in three health care workers, in whom nonammoniated latex extract was administered at 1 mg of proteins two to three times daily (142). After the treatment, participants were able to return to their jobs without undue symptoms. The major drawback of these immunotherapeutic trials is the use of a crude aqueous mixture containing both allergenic and nonallergenic components. In another study, immunotherapy was carried out in a latex-sensitized hospital worker using ammoniated latex extract ( 143). There was steady improvement of the clinical symptoms in the subject without a significant change in lymphocyte subpopulation and serum immunoglobulin levels. Despite the success of these initial uncontrolled trials, immunotherapy of latex allergy is not advisable with the currently available allergen preparations. There is a need for the pharmacologic-grade recombinant allergens with immunologic properties comparable to the natural allergens for specific immunotherapy. Allergen-specific therapy appears feasible in the near future because of the availability of an increasing number of functional latex allergens. The allergen-specific therapy may aim at prevention of allergy, induction of tolerance, or modification of ongoing immune responses ( 144,145 and 146). In an approach to induce T-cell nonresponsiveness in patients, strategies have been directed at synthetic peptides representing major T-cell epitopes administered to induce T-cell tolerance and anergy. Another approach may use allergen fragments with disrupted conformational epitopes but intact T-cell epitopes.