antibioticsAt least 1.3 million people are admitted to the hospital with pneumonia each year in the United States, and approximately 10% of these patients will die within 30 days of admission.2 Many questions remain about the optimum empiric antibiotic treatment of patients with community-acquired pneumonia, as well as the treatment of patients in whom a causative organism is identified. A major area of debate is the role of agents that are active against “atypical” organisms. While several observational studies have demonstrated improved outcomes associated with atypical coverage, and pneumonia treatment guidelines recommend such treatment a recent metaanalysis and systematic review of randomized, controlled trials failed to demonstrate an advantage of this practice. Improved outcomes associated with atypical treatment in patients with pneumococcal bacteremia have also been report-ed, but there is poor understanding of the mechanism by which atypical coverage could improve outcomes when an alternative pathogen is identified. Possible mechanisms could include treatment of dual infection with an atypical pathogen such as Chlamydophila pneumoniae,14 the immunomodulatory effects of macrolide and fluoroquinolone antibiotics, or the achievement of broader coverage against unusual or resistant pathogens when these antibiotics are used in combination with (3-lactam antibiotics.

In order to better understand the effect of atypical antibiotic coverage in patients who are admitted to the hospital with pneumonia, we studied the relationship between the initial antibiotic regimen and several patient outcomes in a large cohort of Medicare beneficiaries who were hospitalized with bacteremic pneumonia. The large size of this cohort provided the unique opportunity to compare the effects of fluoroquinolones and macrolides. Because > 60% of the cases in this cohort were patients who were infected with an organism other than Streptococcus pneumoniae, this analysis also provided the opportunity to expand on the observations of prior studies that were limited to patients with pneumococcal bacteremia. Such kind of pneumonia may be treated if you order drugs via Canadian Neighbor Pharmacy. This online pharmacy is the best choice for you.

The data analyzed were part of the Medicare National Pneumonia Project, which is a component of the Medicare Quality Improvement Program. Therefore, neither informed consent nor institutional review board approval were required. Eligible patients were fee-for-service Medicare beneficiaries who had been discharged from the hospital between 1998 and 2001 with a principal diagnosis of pneumonia, and those with a principal diagnosis of septicemia or respiratory failure and a secondary diagnosis of pneumonia. Patients included in the study were admitted to the hospital from either home or a nursing facility. The details regarding the selection of the cohort used in this study, the data collection and validation methods have been previously described in detail.

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Endothelium-dependent FMDA total of 124 patients were enrolled (78 men; 63%; mean age, 67 ± 1 years); of these, 98 patients (79%) had positive EBCT results, ie, a CCS > 0. All patients were classified into three groups according to CCSs: group 1, no calcification (CCS 0) [n = 26]; group 2, small-to-moderate coronary calcification (CCS 1 to 199) [n = 50]; and group 3, moderate-to-severe calcification (CCS a 200) [n = 48]. The baseline characteristics of the three groups are shown in Table 1. In group 3, the patients were older than those in groups 1 and 2 (p < 0.05). No significant differences in baseline characteristics were found among the three groups, except there were more patients with hypertension and diabetes in group 3 than in groups 1 and 2 (p < 0.05) and higher body mass index in group 2. There were more patients receiving medications, including antiplatelet agents, P-blockers, and nitrates, in group 3 than in groups 1 and 2 (p < 0.05), as shown in Table 2.

Among the three groups, there was an inverse association between the extent of coronary artery calcification and endothelium-dependent FMD (6.9 ± 0.6% vs 5.3 ± 0.3% vs 3.7 ± 0.3%, respectively; p < 0.001), as shown in Table 3 and Figure 1, top, A. But no significant association existed between the CCS and endothelium-independent NMD (Fig 1, bottom, B). Both hsCRP and MCP-1 revealed no significant difference among the three groups (p = not significant), as shown in Table 3 and Figure 2. On the contrary, serum levels of hsCRP and MCP-1 were shown to be correlated significantly with endothelium-dependent FMD (r = — 0.211, p = 0.019; and r = — 0.188, p = 0.037, respectively) but not with endothelium-independent NMD (p = not significant), By multivariate analysis, enhanced coronary calcification was a strong independent predictor of endothelial dysfunction (p < 0.001).

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respiratory systemAll 14 patients underwent routine pulmonary function testing and measurements of total respiratory system compliance. Lung compliance was then measured in four of the muscular dystrophic and in five of the quadriplegic subjects who agreed to placement of an esophageal balloon. After the above measurements, each subject received 20 minutes of IPPB using a Bennett PR-2 device delivering 20 to 30 cm HaO pressure. Tidal volumes during IPPB were at least triple the resting tidal volume (Table 3). Total respiratory system compliance was measured immediately, 30 and 90 minutes after IPPB in all subjects. Only four subjects (all quadriplegic) agreed to keep the esophageal balloon in place after IPPB; therefore, lung compliance measurements were limited to these volunteers after IPPB.

Six normal subjects recruited from laboratory personnel also had measurements of CRS and CL before and after IPPB.

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coronary heart diseaseDefects on myocardial scans that improve on serial imaging are considered an expression of regional reductions in coronary blood flow. Resting 201Tl scans obtained in patients with known coronary heart disease at a time when they are angina-free can show reversible abnormalities of myocardial uptake, but only in the area of distribution of severely stenotic coronary arteries. Our findings indicate that similar abnormalities can frequently be identified in patients without known previous heart disease during the administration of vasopressin at low doses. Even individuals with insignificant or nonexistent coronary artery disease can show abnormal xaH scintigraphy in this setting. This phenomenon most likely reflects the capacity of vasopressin to increase coronary vascular resistance even at blood levels that are within the physiologic range.

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DiabetesAs more and more Americans combine an increase in food consumption with a decrease in physical activity, it is not surprising that there is a growing trend toward overweight and obesity in the United States. The prevalence of obesity has increased from 14.5 to 22.5% in the past 10 to 15 years. In 1998, 97 million American adults, representing 55% of the population, were designated as being overweight or obese. With the obese population in the United States continuing to rise, it becomes evident that obesity and obesity-related disorders will be encountered more frequently in the health-care industry.

On the basis of guidelines released by the National Institutes of Health, a person with a body mass index (BMI) of 25 to 29.9 is defined as overweight, whereas obesity is defined as having a BMI of >30Л In addition to psychological and social difficulties faced by people who are categorized as obese, they are more susceptible to physiologic complications and having decreased length of life.

Many studies concur that as BMI increases, so does the risk of mortality. The overall mortality is approximately twice as high in the severely obese and may be 2 to 25 times higher than normal in disease-specific mortality. In addition, obesity increases the risk of cardiovascular disease, noninsulin-dependent diabetes mellitus, hypertension, respiratory dysfunction, and certain types of cancer. Obese patients undergo more frequent hospitalizations because obesity exacerbates the onset and progression of illnesses. Although many hospitalized patients pass through the ICU at some time during their stay, it is expected that the number of obese patients requiring intensive care will also increase substantially. There are several studies that do not concur that BMI correlates with mortality; however, this is normally a result of smaller populations. In larger populations, the significant association is shown. This study examines the effect of BMI on the outcome of patients in a medical ICU (MICU).

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pulmonary hypertensive disorderRecent Experience with Vasodilator Drugs

Because of these unfavorable results with hydralazine, recent investigators have turned to the use of calcium channel blocking drugs for the treatment of patients with primary pulmonary hypertension. Because calcium may play an important role in the pathogenesis of pulmonary hypertensive disorders and because calcium channel antagonists produce favorable effects in experimentally induced pulmonary hypertension, it was logical to apply nifedipine, verapamil, and diltiazem to the treatment of primary pulmonary hypertension in man. The primary hope with the use of these agents was that selective pulmonary vasodilation could be achieved without marked systemic vasodilator effects. Early clinical experience confirmed that nifedipine lowered pulmonary vascular resistance and pulmonary artery pressures at rest and during exercise, during short- and long-term treatment, and these effects were accompanied by symptomatic improvement.

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bronchial mucosaAnti-inflammatory Effects

Inflammation contributes to the pathophysiology of many pulmonary diseases, including asthma and other hypersensitivity reactions, acute and chronic infections, and injuries induced by inhalation of noxious chemicals. The inflammatory process amplifies the deleterious effects of the initial injury and increases the interference with pulmonary function. In asthma, for example, the obstruction to air flow is not limited to the constriction of airway smooth muscle, but also includes mucous plugs and an exudate containing inflammatory cells and desquamated epithelium in the airway lumen, and edema and cellular infiltration of the bronchial mucosa and submucosa. IgE-mediated late-phase reactions to allergens are associated with inflammation. Studies of bronchial secretions and bronchial lavage fluids also demonstrate that an inflammatory response accompanies various non-IgE-medi-ated forms of bronchitis. In addition, as discussed later, there is increasing evidence that inflammation contributes to the airway hyperreactivity that is associated with a number of pulmonary diseases.

The development of an inflammatory reaction requires several essential components. First, there is absolute dependence on the presence of leukocytes. Neutrophils are required for acute inflammation; monocyte-macrophages and various recruited cells are needed for chronic inflammation and delayed hypersensitivity reactions. Chemoattractants aid in the recruitment of leukocytes and promote their migration into tissue. In addition, a vasoactive factor is needed to increase the permeability of the microvasculature and allow extravasation of fluid and cells. Mechanisms that enhance local blood flow increase the accumulation of fluids and leukocytes into inflammatory foci. If you cannot allow to buy the drugs you are prescribed you may order them at a considerable low price. It means to order drugs via the Internet for example see here.

Glucocorticoids suppress acute and chronic inflammation, irrespective of cause, by inhibiting each of the essential components of the inflammatory reaction. They inhibit recruitment of leukocytes for acute and chronic inflammation through their effects on leukocyte migration and distribution. The effects on neutrophils are illustrative. Within hours after administration of a single dose of glucocorticoids, neutrophils that are normally marginated on the capillary endothelium of storage sites in the lung and other tissues reenter the circulating pool. This is associated with depletion of tissue stores of neutrophils and diminished accumulation into inflammatory foci and inflammatory exudates. Glucocorticoids also suppress a number of leukocyte functions that contribute to glucocorticoidsimmunologic and inflammatory processes. These include suppression of the binding of complement components and antibody IgE and IgG to receptors on leukocytes and suppression of the synthesis of or the response to various lympholdnes. In addition, glucocorticoids suppress the leakage of fluids and cells into areas of inflammation by causing constriction of the microvasculature.

Influence on Mediators of Pulmonary Disease

Many of the anti-inflammatory actions of glucocorticoids stem from their influence on the formation of or the responses to various chemotactant and vasoactive substances that participate in the inflammatory response. In the past decade a number of these bioactive mediators have been characterized chemically and their biologic roles defined. It has become apparent that some of the mediators of inflammation are also responsible for other pathophysiologic processes in the lung, Tables 1 and 2 provide a partial listing of mediators that contribute to pulmonary disease and the effects of glucocorticoids in modifying their effects.

Arachidonate Metabolites: One group of compounds of particular interest in pulmonary disease are the products derived from arachidonic acid (AA), a polyunsaturated fatty acid that is a normal component of phospholipids in cell membranes. Stimulation of cells by a variety of mechanisms allows entry of Ca+ +and activates calcium-dependent phospholipases that cleave AA from phospholipids. The AA then serves as precursor for the formation of a large family of biologically active products, which include prostaglandins, thromboxane, and prostacyclin synthesized by the cyclooxygenase pathway and the leukotrienes synthesized by the lipoxygenase pathway. The latter products are proinflammatory and also have a large role in the pathogenesis of other disturbances of pulmonary function, including airway constriction with preferential action on peripheral airways, constriction of the pulmonary vasculature, and mucous secretion. In addition, during the metabolism of AA, toxic derivatives of oxygen are generated and contribute to tissue injury.

Platelet Activating Factor (PAF): PAF is another phospholipid derivative that is synthesized in part through the action of the enzyme phospholipase A. PAF is generated by basophils, alveolar macrophages, and platelets in response to IgE-mediated as well as non-immunologic stimuli. Its potent pro-inflammatory effects include vasodilation, increased vascular permeability, aggregation of platelets, recruitment and activation of leukocytes, and induction of the release of various bioactive products from activated leukocytes and platelets; the latter products include enzymes and cationic proteins that contribute to tissue injury and to the sustained inflammatory reaction induced by PAF. In addition, PAF causes bronchoconstriction, prolonged decrease in dynamic compliance, pulmonary hypertension and edema, systemic hypotension, constriction of coronary arteries and myocardial depression. Many of the effects of PAF mimic the changes induced by antigens in patients with allergy, including the wheal and flare responses to intradermal injection, biphasic early and late bronchoconstrictor responses to inhalation, and prolonged airway inflammation. Some effects of PAF, such as bron-choconstriction, are platelet-dependent; other effects are independent of platelet activation and stem from PAF interaction with other target tissues, such as macrophages and vascular epithelium.

pulmonary hypertensionHistamine: Histamine is a mediator of bronchocon-striction and inflammation that is released from basophils and mast cells by IgE-mediated mechanisms and is found in human plasma after allergen inhalation. Histamine can also be released by non-IgE-mediated mechanisms, including exposure to toxins, that induce entry of Ca++ and degranulation of the cells. Glucocorticoids suppress IgE-mediated release in basophils by influencing a step that precedes and prevents entry of Ca*+ into the cell.

Inhibition of Mediator Release

Role of Lipomodulin: Glucocorticoids suppress synthesis of all products derived from both pathways of AA metabolism by inhibiting the action of phospholipase enzymes that cleave precursor AA from membrane phospholipids. Glucocorticoids also suppress the initial stage in synthesis of phospholipid-derived PAF. These effects stem from the induction by glucocorticoids of an inhibitory protein (or group of proteins), termed lipomodulin or macrocortin, that block the actions of phospholipase enzymes. Lipomodulin is synthesized normally by neutrophils, macrophages and by cells in lung. Glucocorticoids have two effects: first, they induce the release of preformed lipomodulin; then they enhance synthesis of additional protein. Lipomodulin functions as an extracellular mediator that suppresses release and metabolism of AA in other cells; it also regulates the activity of phospholipases intracellularly. When injected into animals, the protein exhibits anti-inflammatory activity in experimental models of inflammation.

It is possible that glucocorticoid-induced proteins other than lipomodulin also contribute to the inhibition of mediator release. Additionally, as noted before, glucocorticoids modulate mediator release through their effects on Ca++ transport.

Although glucocorticoids have considerable influence on synthesis and release of the mediators, they are not fully suppressive in all instances. Thus, although IgE-mediated histamine release can be inhibited in human basophils and rodent mast cells by incubation with glucocorticoids in vitro for 16 hours, a recent report indicated that similar exposure to glucocorticoid did not suppress IgE-mediated release of histamine or the mast cell cyclooxygenase products (PGD2 and thromboxane) in isolated human lung mast cells or fragments of human lung; cyclooxygenase products synthesized by other lung cells were inhibited. Variations in cellular sensitivity to glucocorticoid action may account for these differences. The effects of short- and long-term administration of glucocorticoid may be due to their influence on the more sensitive cell populations.

Influence on Mediator Actions

Many of the mediators, including catecholamines, histamine, leukotrienes and probably PAF, produce their effects through interaction with specific cellular receptors. Glucocorticoids modify the tissue responses to such mediators by influencing the availability and binding affinity of the various receptors and the coupling of the receptors to intracellular enzymes. The influence of glucocorticoids on the beta adrenergic receptor system has been studied in detail (see below). Similar mechanisms modulate tissue responses to other mediators.

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