Aortic intramural hematoma (IMH) is related to but is pathologically distinct from aortic dissection. In this potentially lethal entity, there is hemorrhage into the aortic media in the absence of an intimal tear. Although intimal disruption is not present, the prognosis is similar to that of classic aortic dissection; therefore, early diagnosis is critical. In this review, symptoms and prognosis of aortic IMH are discussed, as well as current diagnostic techniques and therapy.

The purpose of the meta-analysis was to understand the antitussive effect of treatment with dextromethorphan hydrobromide, 30 mg, vs placebo over a 3-h treatment period in patients with cough due to uncomplicated upper respiratory tract infection (URTI), and to show that the computerized system for acquisition and analysis of cough sound was consistent and reproducible across the individual studies.

Theoretically, cystic fibrosis transmembrane conductance regulator (CFTR) gene replacement during the neonatal period can decrease morbidity and mortality from cystic fibrosis (CF). In vivo gene transfers have been accomplished in CF patients. Choice of vector, mode of delivery to airways, translocation of genetic information, and sufficient expression level of the normalized CFTR gene are issues that currently are being addressed in the field. The advantages and limitations of viral vectors are a function of the parent virus. Viral vectors used in this setting include adenovirus (Ad) and adeno-associated virus (AAV). Initial studies with Ad vectors resulted in a vector that was efficient for gene transfer with dose-limiting inflammatory effects due to the large amount of viral protein delivered. The next generation of Ad vectors, with more viral coding sequence deletions, has a longer duration of activity and elicits a lesser degree of cell-mediated immunity in mice. A more recent generation of Ad vectors has no viral genes remaining. Despite these changes, the problem of humoral immunity remains with Ad vectors. A variety of strategies such as vector systems requiring single, or widely spaced, administrations, pharmacologic immunosuppression at administration, creation of a stealth vector, modification of immunogenic epitopes, or tolerance induction are being considered to circumvent humoral immunity. AAV vectors have been studied in animal and human models. They do not appear to induce inflammatory changes over a wide range of doses. The level of CFTR messenger RNA expression is difficult to ascertain with AAV vectors since the small size of the vector relative to the CFTR gene leaves no space for vector-specific sequences on which to base assays to distinguish endogenous from vector-expressed messenger RNA. In general, AAV vectors appear to be safe and have superior duration profiles. Cationic liposomes are lipid-DNA complexes. These vectors generally have been less efficient than viral vectors but do not stimulate inflammatory and immunologic responses. Another challenge to the development of clinically feasible gene therapy is delivery mode. Early pulmonary delivery systems relied on the direct instillation of aerosolized vectors, which can result in the induction of adverse reactions because vector is delivered into the lung parenchyma. More recent studies have examined the potential for using spray technologies to target aerosolized AAV vectors to the larger central airways, thereby avoiding alveolar exposure and adverse effects. Comparisons of lung deposition with nebulized delivery of aerosol and spray delivery indicate that spraying results in a more localized deposition pattern (predominantly in the proximal airways) and significantly higher deposition fractions than nebulization. These findings could lead to more efficient and targeted lung delivery of aerosolized gene vectors in the future.

Because of the pain, inconvenience, and disruption of lifestyle associated with the injection of insulin, many patients with diabetes are noncompliant in terms of treatment regimens that require daily multiple injections. To eliminate the pain and to improve treatment outcome, there has been increasing interest in the development of aerosolized insulin to replace subcutaneously (SC) delivered formulations. Recent studies in human volunteers have shown that when aerosolized insulin is effectively delivered to the alveolar region of the lung, absorption rates and decreases in glucose levels are similar to those achieved with SC-delivered insulin during the fasting state. Other human trials have shown that inhaled insulin also effectively controls postprandial glucose levels. Aerosolized insulin is well-tolerated, and there is no evidence of irritation, hypoglycemia, or changes in pulmonary function when administered over short periods. At present, limitations in the delivery device result in less efficient administration of insulin aerosol compared to SC dosing. However, new devices and different formulations of insulin, which are currently under development, should improve the efficiency. It is likely that the treatment of diabetes with aerosolized insulin will provide an effective alternative means for controlling plasma glucose levels in diabetic individuals. Aerosolized insulin also will serve as a developmental model for this route of administration for a number of other therapeutic peptides that are currently administered by injection only.

Pseudomonas aeruginosa (PA), which colonizes the airways of approximately 90% of patients with cystic fibrosis (CF) at some point during their lives, is an important contributor to the vicious cycle of infection and inflammation leading to bronchiectasis and eventual respiratory failure. Oral antibiotic therapy is often ineffective in treating PA infections. Instead, in-hospital IV aminoglycoside therapy administered in combination with other IV antibiotics, such as beta-lactams or quinolones, is the mainstay of treatment. The specific chemical and physical properties of CF sputum require high serum antibiotic levels for effective antimicrobial treatment; however, IV aminoglycoside therapy is associated with an increased risk of ototoxicity and nephrotoxicity. In an attempt to avoid systemic toxicity and effectively treat PA infections, clinicians have combined IV antibiotics with sterile solutions of saline or water to aerosolize the mixture for inhalation. Experience with such "home brews" has clearly demonstrated that IV preparations are neither intended nor medically indicated for inhalation. Patients may experience coughing, mucosal irritation, or bronchospasm in response to the preservatives, stabilizing agents, and other additives commonly found in IV preparations. While the rationale for aerosolized drug delivery remains compelling, concerns about uniform dose delivery, ineffective nebulization, and therapeutic adherence arise. Since the 1940s, when these efforts began, ongoing research and clinical trials have identified several additional factors affecting inhaled drug delivery and deposition in the airways. This article chronicles some of the challenges faced by researchers and elucidates factors critical to the reformulation of a safe and effective antibiotic solution for aerosolized delivery.

Vasopressin is emerging as a rational therapy for the hemodynamic support of septic shock and vasodilatory shock due to systemic inflammatory response syndrome. The goal of this review is to understand the physiology of vasopressin relevant to septic shock in order to maximize its safety and efficacy in clinical trials and in subsequent therapeutic use. Vasopressin is both a vasopressor and an antidiuretic hormone. It also has hemostatic, GI, and thermoregulatory effects, and is an adrenocorticotropic hormone secretagogue. Vasopressin is released from the axonal terminals of magnocellular neurons in the hypothalamus. Vasopressin mediates vasoconstriction via V1-receptor activation on vascular smooth muscle and mediates its antidiuretic effect via V2-receptor activation in the renal collecting duct system. In addition, vasopressin, at low plasma concentrations, mediates vasodilation in coronary, cerebral, and pulmonary arterial circulations. Septic shock causes first a transient early increase in blood vasopressin concentrations that decrease later in septic shock to very low levels compared to other causes of hypotension. Vasopressin infusion of 0.01 to 0.04 U/min in patients with septic shock increases plasma vasopressin levels to those observed in patients with hypotension from other causes, such as cardiogenic shock. Increased vasopressin levels are associated with a lesser need for other vasopressors. Urinary output may increase, and pulmonary vascular resistance may decrease. Infusions of > 0.04 U/min may lead to adverse, likely vasoconstriction-mediated events. Because clinical studies have been relatively small, focused on physiologic end points, and because of potential adverse effects of vasopressin, clinical use of vasopressin should await a randomized controlled trial of its effects on clinical outcomes such as organ failure and mortality.

Dyslipidemia is a major risk factor for coronary heart disease (CHD). While some uncertainty exists about the clinical significance of improving high-density lipoprotein cholesterol and triglyceride levels, large primary- and secondary-prevention studies aimed at lowering low-density lipoprotein cholesterol levels with statins have convincingly reduced CHD events and total mortality. Despite the strong clinical evidence and widely publicized treatment guidelines, many hyperlipidemic patients receive inadequate lipid-lowering treatment. This failure to achieve clinical treatment goals may be due to poor physician adherence to treatment guidelines, patient noncompliance, and the presence of concomitant medical conditions that modify typical hyperlipidemia management. This review considers the challenges and available strategies to optimize lipid management in patients at risk for CHD.

To systematically review the evidence examining the use of incentive spirometry (IS) for the prevention of postoperative pulmonary complications (PPCs).

Ventilator-associated pneumonia (VAP) is an important health problem that still generates great controversy. A consensus conference attended by 12 researchers from Europe and Latin America was held to discuss strategies for the diagnosis and treatment of VAP. Commonly asked questions concerning VAP management were selected for discussion by the participating researchers. Possible answers to the questions were presented to the researchers, who then recorded their preferences anonymously. This was followed by open discussion when the results were known. In general, peers thought that early microbiological examinations are warranted and contribute to improving the use of antibiotherapy. Nevertheless, no consensus was reached regarding choices of antimicrobial agents or the optimal duration of therapy. Piperacillin/tazobactam was the preferred choice for empiric therapy, followed by a cephalosporin with antipseudomonal activity and a carbapenem. All the peers agreed that the pathogens causing VAP and multiresistance patterns in their ICUs were substantially different from those reported in studies in the United States. Pathogens and multiresistance patterns also varied from researcher to researcher inside the group. Consensus was reached on the importance of local epidemiology surveillance programs and on the need for customized empiric antimicrobial choices to respond to local patterns of pathogens and susceptibilities.

To report five new cases of Pneumocystis carinii pneumonia (PCP) and to review and analyze the existing reports on the subject.

The clinical spectrum of mitochondrial diseases has expanded dramatically in the last decade. Abnormalities of mitochondrial function are now thought to participate in a number of common adult diseases, ranging from exercise intolerance to aging. This review outlines the common presentations of mitochondrial disease in ICUs and in the outpatient setting and discusses current diagnostic and therapeutic options as they pertain to the pulmonary and critical-care physician.

Pulse oximetry is a well-established tool routinely used in many settings of modern medicine to determine a patient's arterial oxygen saturation and heart rate. The decreasing size of pulse oximeters over recent years has broadened their spectrum of use. For diagnosis and treatment of sleep-disordered breathing, overnight pulse oximetry helps determine the severity of disease and is used as an economical means to detect sleep apnea. In this article, we outline the clinical utility and economical benefit of overnight pulse oximetry in sleep and breathing disorders in adults and highlight the controversies regarding its limitations as presented in published studies.

The cytotoxic agent bleomycin is feared for its induction of sometimes fatal pulmonary toxicity, also known as bleomycin-induced pneumonitis (BIP). The central event in the development of BIP is endothelial damage of the lung vasculature due to bleomycin-induced cytokines and free radicals. Ultimately, BIP can progress in lung fibrosis. The diagnosis is established by a combination of clinical symptoms, radiographic alterations, and pulmonary function test results, while other disorders resembling BIP have to be excluded. Pulmonary function assessments most suitable for detecting BIP are those reflecting lung volumes. The widely used transfer capacity of the lungs for carbon monoxide appeared recently not to be specific when bleomycin is used in a polychemotherapeutic regimen. There are no proven effective treatments for BIP in humans, although corticosteroids are widely applied. When patients survive BIP, they almost always recover completely with normalization of radiographic and pulmonary function abnormalities. This review focuses on BIP, especially on the pathogenesis, risk factors, and its detection.

Spontaneous rupture of the pulmonary alveoli after a sudden increase in intra-alveolar pressure is a common cause of pneumomediastinum, which is usually seen in healthy young men. Other common causes are traumatic and iatrogenic rupture of the airway and esophagus; however, pneumomediastinum following cervicofacial emphysema is much rarer and is occasionally found after dental surgical procedures, head and neck surgery, or accidental trauma. We present four cases of subcutaneous emphysema and pneumomediastinum with two secondary pneumothoraces after self-induced punctures in the oral cavity. They constitute an uncommon clinical entity that, to our knowledge, has not been reported in the literature. Its radiologic appearance, clinical presentation, and diagnosis are described.

beta(2)-Adrenergic agonists are commonly used as bronchodilators to treat patients with COPD. In addition to prolonged bronchodilation, long-acting beta(2)-agonists (LABAs) exert other effects that may be of clinical relevance. These include inhibition of airway smooth-muscle cell proliferation and inflammatory mediator release, as well as nonsmooth-muscle effects, such as stimulation of mucociliary transport, cytoprotection of the respiratory mucosa, and attenuation of neutrophil recruitment and activation. This review details the possible alternative mechanisms of action of the LABAs, salmeterol and formoterol, in COPD.

About 10% of American children have asthma, and its prevalence, morbidity, and mortality have been increasing. Asthma is an inflammatory disease with edema, bronchial constriction, and mucous plugging. Status asthmaticus in children requires aggressive treatment with beta-agonists, anticholinergics, and corticosteroids. Intubation and mechanical ventilation should be avoided if at all possible, as the underlying dynamic hyperinflation will worsen with positive-pressure ventilation. If mechanical ventilation becomes necessary, controlled hypoventilation with low tidal volume and long expiratory time may lessen the risk of barotrauma and hypotension. Unusual and nonestablished therapies for severe asthma are discussed.

To determine the characteristic features and outcome of pulmonary carcinoid tumors in Israel.

Lactic acidosis is a frequent laboratory finding in patients with severe exacerbations of asthma. The pathogenesis of lactic acidosis in asthma is not well understood, but it has been presumed, by some, to be generated by fatiguing respiratory muscles. We herein report the cases of three patients with status asthmaticus and lactic acidosis despite pharmacologic muscle relaxation. No common etiologies were found for lactic acidosis that abated after bronchospasm improved and the intensity of pharmacologic therapies was reduced. We review the literature describing lactic acidosis with asthma and discuss mechanisms by which lactic acidosis may occur in patients with status asthmaticus.