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By: N. Bram, M.B. B.A.O., M.B.B.Ch., Ph.D.
Assistant Professor, Wayne State University School of Medicine
Alcoholics and patients who are acutely or chronically ill (especially if hospitalized) often demonstrate oropharyngeal colonization with aerobic or facultative gram-negative bacilli and S asthma risk factors generic singulair 10 mg with amex. Among the anaerobes asthma definition empathy generic singulair 4mg free shipping, organisms more likely to asthma juice discount 5 mg singulair with amex cause infection as sole agents are Fusobacterium nucleatum, F. Both the size of the bacterial inoculum and the role of associated organisms and host defenses are important. The various types of aspiration-related pleuropulmonary infections-pneumonitis (the initial stage), necrotizing pneumonia (multiple excavations < 2 cm in diameter), lung abscess (one or more cavities 2 cm in diameter communicating with a bronchus), and empyema-should be considered as one process with a continuum of changes. A predilection for infection in dependent segments is seen, particularly the posterior segments of the upper lobes and the superior segments of the lower lobes, but the location of the abscess depends on gravity and the position of the subject. Normally, the aspirated material is handled effectively by ciliary action, cough, and alveolar macrophages. Endotracheal tubes impair coughing, impede pulmonary clearance mechanisms, and allow leakage of oropharyngeal secretions into the tracheobronchial tree. Thick or particulate matter and foreign bodies are not easily removed and can produce bronchial obstruction and atelectasis. In pneumonia following aspiration of gastric contents, gastric acid and enzymes are the primary offending agents. Subdiaphragmatic infection may extend to the lung by way of lymphatic vessels, directly through the diaphragm, or by way of the blood stream. Following cavitation, putrid sputum is noted in 50% or more of patients, and hemoptysis may be seen. Weeks to months of malaise and low-grade fever may be associated with cough, weight loss, and anemia. In edentulous persons with intact oropharyngeal function, lung abscesses are uncommon and suggest the presence of an obstructing lesion of the bronchus (carcinoma or other) or pulmonary embolus. A similar radiographic appearance can be seen with a variety of conditions other than bacterial lung abscess (see Table 83-1), so definitive bacterial confirmation is required. Radiography occasionally reveals mediastinal lymphadenopathy, making the differential diagnosis include tuberculosis, fungal infection, and lung cancer. Infected cysts or bullae and pulmonary sequestration are often evident with radiography. The spectrum of organisms causing lung abscess has widened as patients present with more complex medical and surgical conditions. Antibiotic resistance has emerged and the number of immunocompromised persons has increased. Expectorated sputum cannot be used for anaerobic culture because large numbers of anaerobes are present in the indigenous flora. Bacteremia is uncommon in aspiration pneumonia, and all organisms involved in the lung abscess may not be recovered in blood cultures. Empyema fluid constitutes an excellent source for anaerobic (and aerobic) culture. Transtracheal aspiration bypasses the normal flora of the upper respiratory tract, but contamination with indigenous flora can be a problem, and the procedure is now seldom performed. Two approaches that are preferable to transtracheal aspiration are the use of a protected specimen brush and the use of bronchoalveolar lavage. The protected specimen brush procedure involves sampling with a bronchial brush protected within a telescoping plugged double-catheter via a fiberoptic bronchoscope. It is essential that the technique be used exactly as described and that cultures be done quantitatively. For the protected specimen brush procedure, 103 to 104 or more colony-forming units per milliliter is significant. The small volume of material obtained and the difficulty in anaerobic transport are concerns. Quantitative culture of fluid obtained by bronchoalveolar lavage, during or without bronchoscopy, also provides reliable results. Demonstration of bacteria intracellularly in at least 3 to 5% of cells in bronchoalveolar lavage fluid is good evidence of pneumonia, and the morphology of those bacteria is extremely useful in directing therapy.
The mechanism that determines whether a stem cell simply self-renews or differentiates is probably governed by the different signaling pathways used between cell-surface receptors and the cell nucleus asthma natural remedies buy singulair uk, but the precise pathway for each cytokine remains poorly defined asthmatic bronchitis benzonatate order discount singulair on line. Cell proliferation and differentiation are also influenced by interleukins and the local hematopoietic microenvironment asthmatic bronchitis 39 generic 10mg singulair otc, which is defined by extracellular matrix proteins and their stromal elements. Colony-stimulating factors are rarely lineage specific and usually influence multiple steps in hemolymphopoiesis, often in synergy with as many as four or five other factors. As cells mature, they lose receptors for most cytokines, especially those that influence early cell development such as stem cell factor. However, once the cells have matured, they express receptors for chemokines, which help direct the cells to sites of inflammation. Based on kinetic studies, four cellular compartments containing myeloid cells are generally recognized: (1) the marrow mitotic compartment; (2) the marrow post-mitotic and storage compartment; (3) the vascular compartment, which in the case of neutrophils is divided into a circulating pool and a marginating pool; and (4) the tissue compartments. Early progenitor cells in the marrow are then stimulated to proliferate and differentiate. This step markedly shortens the time of maturation of myeloid precursors through the post-mitotic pool. Increased numbers of neutrophils are then released from the marrow storage compartment into the circulation. These same neutrophils are then primed by either granulocyte or granulocyte-macrophage colony-stimulating factor for enhanced bactericidal activities. The neutrophil is a terminally differentiated, non-dividing cell that is well equipped for removing microorganisms. The cell is packed with granules whose contents kill and degrade target microorganisms. Azurophil granules contain proteases and other hydrolytic enzymes, defensins, other microbicidal peptides, and myeloperoxidase, a Cl- -oxidizing enzyme. Specific granules contain, among other things, apolactoferrin, collagenase, and an as yet unidentified enzyme that releases C5a from complement component C5. The membranes of the granules contain receptors for chemoattractants, extracellular matrix proteins, and cytochrome b558. The cytoskeleton of the neutrophil is a complex system of microfilaments and microtubules and is responsible for the orderly movement of this highly motile cell. Chemotactic factors generated by the interaction of plasma proteins with antigens, pathogens, chemokines released by activated T cells attract neutrophils from the blood to sites of infection. Diffusion of these factors creates a chemical gradient that directs the migration of neutrophils toward the source of the chemotactic factor. Plasma, in addition to elaborating chemoattractants, provides antibodies and complement that coat microorganisms in a process called opsonization, which is derived from the Greek word for "providing victuals. The cytoplasmic granules of the neutrophil fuse with the phagosome and discharge their contents through the membrane, a process called degranulation. The neutrophil reduces molecular oxygen enzymatically to generate "activated" metabolites such as superoxide (O2 -) and hydrogen peroxide (H2 O2), which join with material discharged into the phagosome from the granules to destroy the ingested microbes. Granule contents and oxygen metabolites under certain circumstances may leak from the activated neutrophil into extracellular fluid, where they can injure surrounding tissue and engender tissue inflammation. Because neutrophils move by crawling, they must adhere to surfaces to migrate through the tissues to an inflammatory site. A likely sequence of events leading to neutrophil activation during the acute inflammatory response in vivo is becoming better understood. Specific oligosaccharide molecules expressed on the neutrophil membrane glycolipids and glycoproteins serve as counterreceptors for E-selectin and P-selectin (sialyl-Lewis X and Lewis X, respectively). In conjunction with neutrophil membrane L-selectin, which recognizes oligosaccharide molecules expressed by endothelial cells, the selectins promote low-affinity neutrophil-endothelial binding under flow conditions termed neutrophil "rolling. Subsequent to neutrophil rolling, high-affinity interactions are induced by a separate class of adhesion molecules. Once the neutrophils adhere through their beta2 -integrin receptors to the endothelium, subsequent transendothelial migration by neutrophils occurs in response to local gradients of chemotactic factors. The neutrophil finds its target through a chemical sensor that detects substances known as chemotactic factors. These factors are continuously released at sites where microorganisms have invaded tissue, thereby establishing a concentration gradient. Circulating neutrophils recognize this gradient and travel toward its source by migrating between endothelial cells and penetrating the subendothelial basement membrane. Once outside the capillaries, they continue their directed migration, eventually reaching the microorganism-invaded site in which the chemotactic factors originated.
The blood chemistries are usually normal asthma treatment stepwise buy singulair toronto, with the exception of the serum amylase value asthma symptoms or anxiety 5 mg singulair amex, which may be slightly increased asthma symptoms older adults purchase singulair 4mg. The suspected diagnosis can be confirmed by the identification of free intraperitoneal air, which is demonstrable in about 80% of cases and is best seen on erect chest radiograph or a left decubitus film of the abdomen rather than a plain abdominal film. When the diagnosis is suspected and the radiographs are negative, it is worthwhile to repeat the radiographic evaluation after several hours. The diagnosis may be confirmed by an upper gastrointestinal series using Gastrografin, especially if it is combined with computed tomography to enhance the ability to identify the perforation and exclude other pathology. Initial management is to prepare the patient for presumed surgery (see Chapter 129). The steps include resuscitation by correction of fluid and electrolyte abnormalities, treatment of complications, continuous nasogastric suction, parenteral administration of broad-spectrum antibiotics (ampicillin-sulbactam and gentamicin) and, if a tension pneumoperitoneum is present, needle aspiration of the peritoneal cavity. Nasogastric suction is one of the mainstays of therapy, and it is important to confirm that the aspirating ports of the nasogastric tube are positioned in the most dependent portion of the stomach. A randomized trial comparing non-operative treatment to emergency surgery showed that an initial period of non-operative observation yielded similar outcome, and the decision not to operate immediately could be based on the age and clinical condition of the patient. If there is evidence of increasing peritoneal irritation after 6 hours of treatment, it is best to declare non-operative therapy a failure and to proceed to surgery. Alternatively, surgery may be chosen immediately in any patient in whom there is not good evidence that the perforation has sealed. Simple closure of the perforation and proximal selective gastric vagotomy is the preferred operation. Obstruction Approximately 2% of ulcer patients develop gastric outlet obstruction; 90% are caused by previous or coexistent duodenal or channel ulcers. Inflammatory swelling surrounding the ulcer, muscular spasm associated with nearby ulcer, or cicatricial narrowing with fibrosis are the factors responsible for the obstruction. The mainstay of initial resuscitation and therapy is conservative medical management with decompression of the obstructed stomach; correction of fluid, electrolyte, and acid-base abnormalities; plus intravenous H2 -receptor antagonist therapy. Resuscitation and antisecretory therapy usually provide rapid relief for most patients in whom the obstruction is functionally related to edema. For those with stricture, endoscopic balloon dilatation of the pylorus combined with anti-secretory therapy. For patients in whom the stricture rapidly recurs, missed gastric cancer becomes a likely diagnosis, and endoscopic biopsy is required and is often followed by surgery. A scoring system has been devised to separate those with essentially no risk from those with a high risk of dying. Those with all three risk factors have a very high risk of dying; it " denotes such a critical state that it is problematic whether any form of early operative intervention will be tolerated, much less beneficial. A randomized trial of non-operative treatment versus emergency surgery showed that an initial period of non-operative treatment with careful observation yielded similar outcome. However, the rate of emergent surgery for complications of peptic ulcer (bleeding and perforation) has not changed. Perhaps as a result, the average age of patients with perforation has increased from 40 to 50 years two decades ago to 60 to 70 years now. Indications for emergent or urgent operative intervention are more common and include perforation, bleeding, and gastric outlet obstruction. A patient clearly needs surgery if there is acute peritonitis due to a perforated peptic ulcer. In the patient with equivocal signs of peritonitis, some have advocated examination of the upper gastrointestinal tract with water-soluble contrast medium followed by conservative management if the studies show that the perforation is sealed. When patients present more than 48 hours after a perforation, non-operative management is indicated provided that the perforation is sealed and the patient is not septic. In older patients or patients with more life-threatening bleeding, a surgical consultation should be obtained promptly. Truncal vagotomy and pyloroplasty should be reserved for elderly or high-risk patients in whom expediency is desirable.
It is often brief in duration and uncomplicated asthma symptoms from cats proven singulair 5 mg, although vigilance for progression to asthmatic bronchitis icd 9 cm code discount 10mg singulair free shipping tamponade is always prudent asthma breathing test generic 4mg singulair with amex. Chest pain of acute infectious (viral) pericarditis typically develops in younger adults 1 to 2 weeks after a "viral illness. Pain may be preceded by low-grade fever (in contrast to myocardial infarction, in which the pain precedes the fever). Although radiation to the arms in a manner similar to myocardial ischemia may also occur, it is less common. The physical examination in patients with acute pericarditis is most notable for a pericardial friction rub. Although classically described as triphasic, with systolic and both early (passive ventricular filling) and late (atrial systole) diastolic components, more commonly a biphasic (systole and diastole) or a monophasic rub may be heard. Also common are a resting tachycardia (rarely atrial fibrillation) and, if the etiology is infectious, a low-grade fever. In the setting of a large pericardial effusion, loss of R wave voltage (absolute R wave magnitude of 5 mm or less in limb leads and 10 mm or less in precordial leads) and electrical alternans. If the pericardial effusion is not significant, the chest radiograph is often unrevealing, although a small left pleural effusion may be seen. An elevated erythrocyte sedimentation rate and mild elevation of the white blood cell count are also common. Non-steroidal anti-inflammatory agents such as indomethacin (25 to 50 mg three times daily) are generally quite effective, although aspirin (325 to 650 mg three times daily) may also be used. Glucocorticoids (prednisone, 20 to 60 mg/day) may be useful for resistant situations. Anti-inflammatory agents should be continued at a constant dose until the patient is afebrile and asymptomatic for 1 week, followed by a gradual taper over the next several weeks. The use of warfarin and/or heparin should be avoided if possible to minimize the risk of hemopericardium, but anticoagulation may be required in the setting of atrial fibrillation. Avoidance of vigorous physical activity is also recommended during the acute and early convalescent period. However, Figure 65-2 Twelve-lead electrocardiogram from a patient with acute pericarditis. Note the resting sinus tachycardia with relatively low voltage and electrical alternans. For this group, prolonged treatment with colchicine, 1 mg/day, or pericardiectomy should be considered. Patients with recurrent pericarditis are at increased risk for progression to constrictive pericarditis (see below). Most commonly, the fluid is exudative and reflects pericardial injury/inflammation. Serosanguineous effusions are typical of tuberculous and neoplastic disease but may also be seen in uremic and viral/idiopathic disease or in response to mediastinal irradiation. Hemopericardium is most commonly seen with trauma, myocardial rupture following myocardial infarction, catheter-induced myocardial or epicardial coronary artery rupture, aortic dissection with rupture into the pericardial space, or primary hemorrhage in patients receiving anticoagulant therapy (often after cardiac valve surgery). Chylopericardium is quite rare and results from leakage or injury to the thoracic duct. Although the presence of pericardial effusion is indicative of underlying pericardial disease, the clinical relevance of pericardial effusion is most closely associated with the rate of collection, intrapericardial pressure, and subsequent development of tamponade physiology. A rapidly accumulating effusion, as in hemopericardium caused by trauma, may result in tamponade physiology with collection of only 100 to 200 mL. By comparison, a more slowly developing effusion may allow for gradual stretching of the pericardium, with effusions exceeding 1500 mL in the absence of hemodynamic embarrassment. Pericardial effusion is often suspected clinically when the patient has symptoms and signs of tamponade physiology (see below), but it may also be first suggested by unsuspected cardiomegaly on the chest radiograph, especially if loss of the customary cardiac borders and a "water bottle" configuration are noted. Fluoroscopy, which may display minimal or absent motion of cardiac borders, is commonly performed when myocardial or epicardial coronary artery perforation is suspected during a diagnostic or interventional percutaneous procedure. In most situations, two-dimensional transthoracic echocardiography is the diagnostic imaging procedure of choice for the evaluation and semiquantitative assessment of suspected pericardial effusion. In emergency situations, it can be performed at the bedside, with the subcostal four-chamber view being the most informative imaging plane. This imaging plane is particularly relevant because it allows the size and location of the effusion to be assessed from an orientation that determines whether the effusion can be drained percutaneously. Stranding, which may be appreciated in the setting of organized or chronic effusions, suggests an inability to drain the effusion fully by percutaneous approaches.
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