Treatment with corticosteroids.

Oral corticosteroids remain the cornerstone therapy for sarcoidosis. Critical clinical decisions include selecting the patient who should be treated, dose and duration of therapy, and accurate analysis of the anticipated benefits and potential side effects for the individual patient. The treatment of pulmonary and cardiac sarcoidosis is emphasized and the role of inhaled corticosteroids in the treatment of pulmonary sarcoidosis is reviewed.

The diagnosis of ventilator-associated pneumonia: a comparison of histologic, microbiologic, and clinical criteria.

STUDY OBJECTIVE: To evaluate histologic, microbiological, and clinical criteria in the recognition of ventilator-associated pneumonia (VAP) in patients who died while mechanically ventilated. METHODS: The study group consisted of 39 patients who died after a mean of 14 days of mechanical ventilation. Postmortem fiberoptic bronchoscopy (FOB) and open lung biopsy were performed with collection of specimens initiated <1 h after death. The microbiological specimens included suction catheter aspirate of tracheal secretions, FOB-guided protected specimen brush (PSB) of tracheal secretions, blindly placed PSB in a distal airway, FOB-guided PSB in a distal airway, and FOB-guided BAL fluid (BALF) in a distal airway. Qualitative bacteriologic study was performed on all specimens, and quantitative bacteriologic study was performed on all but the suction catheter aspirate of the trachea. A biopsy specimen of peripheral lung parenchyma from the same region sampled by FOB was sent for quantitative culture and histologic analysis. The BALF was analyzed for cell population and percent of neutrophils containing intracellular organisms. The clinical criteria selected for comparison with histologic and microbiological results included a temperature > or =38.5 degrees C during the 48 h prior to death, a WBC count > or =15,000/mm3 in the 48 h prior to death, presence of a bacterial or fungal pathogen on the last sputum culture, radiographic worsening in the week prior to death, and worsening gas exchange defined as a 15% decrease in the PaO2/fraction of inspired oxygen ratio in the 72 h prior to death. RESULTS: None of the quantitative cultures had a reliable positive predictive value for histologic pneumonia. None of the five clinical criteria tested showed agreement with the presence or absence of histologic pneumonia. There was a significant correlation between qualitative and quantitative microbiological results from the distal airway/FOB-guided PSB, distal airway/BALF, and quantitative culture of the lung parenchyma. Also, suction catheter aspirate of the trachea had a sensitivity of 87% in recognizing the bacterial species simultaneously present in lung parenchyma. None of the patients with histologic pneumonia had <50% neutrophils in the BALF. CONCLUSIONS: Neither the bacterial, density from the four airway quantitative cultures, nor the bacterial density from quantitative culture of lung parenchyma accurately separated the histologic pneumonia and nonpneumonia groups. No clinical criteria or combination of clinical criteria correlated with the presence or absence of histologic pneumonia. A BALF with <50% neutrophils had a 100% negative predictive value for histologic pneumonia. A BALF quantitative culture had a sensitivity of 63%, specificity of 96%, and positive predictive value of 91% in recognizing sterile lung parenchyma. Thus, BALF may have a role in excluding pneumonia/infection in the ventilated patient. Antibiotic choice for the empiric therapy of VAP can be accurately guided by the microbial population recognized through culture of a tracheal suction catheter aspirate.

Reproducibility of the histologic diagnosis of pneumonia among a panel of four pathologists: analysis of a gold standard.

STUDY OBJECTIVE: To establish a histologic diagnosis of pneumonia by consensus of a panel of pathologists, to test the interobserver and intraobserver variation in the histologic diagnosis of pneumonia, to compare the diagnostic accuracy of diagnosing pneumonia with and without preselected histologic criteria, and to establish more specific histologic criteria for the diagnosis of pneumonia. METHODS: The study group consisted of 39 patients who died after a mean of 14 days of mechanical ventilation. A postmortem open lung biopsy was performed on all patients. The tissue was reviewed independently by four pathologists who categorized the slides from each patient as showing or not showing pneumonia. Interobserver variation was calculated using the kappa statistic. Six months following the initial evaluation, the same slides were resubmitted to one of the pathologists for reevaluation to look for intraobserver error. Finally, the slides were reviewed and categorized by the criteria of Johanson et al into no pneumonia, mild, moderate, or severe bronchopneumonia. A comparison was made of the patients selected as demonstrating histologic pneumonia by each of the examinations. RESULTS: The reliability coefficient (kappa) measuring agreement among the four pathologists was good at 0.916. However, the prevalence of pneumonia as determined by each of the four pathologists varied; pathologist A, 15 of 39 (38%); pathologist B, 12 of 39 (31%); pathologist C, 9 of 39 (23%); and pathologist D, 7 of 39 (18%). Resubmitting the same slides to the same pathologist 6 months later resulted in reclassification of 2 of 39 patients. Using the histologic criteria of Johanson and colleagues, 14 patients were selected as having pneumonia compared with only nine patients selected by consensus of three of four pathologists. CONCLUSIONS: Recognition of histologic pneumonia varies among pathologists. The preselected criteria of Johanson and colleagues detected histologic pneumonia in eight of nine patients picked by consensus of pathologists, but six additional patients classified as "no histologic pneumonia" by the consensus of pathologists were judged to have histologic pneumonia by these criteria. The results established the necessity for standardization of histologic criteria for studies using biopsy as the gold standard for bacterial pneumonia. An atlas showing the criteria used in our selection was developed.

Collagen vascular diseases.

Systemic lupus erythematosus, polymyositis/dermatomyositis, connective tissue disease, and polyarteritis nodosa are the collagen vascular diseases (CVDs) most likely to mimic pneumonia. All can be associated with an acute illness characterized by fever, cough, dyspnea, pleural symptoms, and an abnormal chest roentgenogram. Recognition of the CVD-associated pulmonary process requires sophisticated serological testing and chemical pleural fluid analysis coupled with the exclusion of pulmonary infection and pulmonary embolization. This review emphasizes the clinical characteristics of these CVDs, the diagnostic tests most helpful in recognizing them, and the differential diagnosis of pleuroparenchymal disorders that occur in these patients.

Infectious diseases that result in slowly resolving and chronic pneumonia.

Familiarity with the natural history of common pneumonias is obligatory for the clinician to determine whether a specific case of pneumonia is resolving at the expected rate. To many clinicians, the term slowly resolving pneumonia conjures an association with underlying neoplasm and/or less common pathogens. In reality, host factors or common pathogens such as Streptococcus pneumoniae and Legionella pneumophila are more likely responsible for delayed resolution. Familiarity with the pattern of resolution of pneumonias caused by these organisms should allow the clinician to follow such patients and avoid premature invasive evaluation. In contrast, Mycoplasma pneumoniae and Chlamydia species rarely result in slowly resolving pneumonia. Chronic bacterial pneumonia is an infectious syndrome that may present in the absence of systemic symptoms. The presentation is varied and may mimic neoplasm, interstitial lung disease, or chronic fungal or mycobacterial infection. Bacteria most commonly associated with chronic pneumonia include Haemophilus influenzae, Staphylococcus aureus, alpha-hemolytic streptococci (not S pneumoniae), and Pseudomonas aeruginosa.

Thiol-group modification of Torpedo californica acetylcholine receptor: subunit localization and effects on function.

The effects of thiol-group modifications on acetylcholine receptor (ACHR) function were measured with purified ACHR reconstituted into asolectin vesicles. N-Phenylmaleimide (NPM) was used to modify sulfhydryl groups on ACHR in the absence of any prior reduction of dithiothreitol, so that only the functional relevance of free sulfhydryls was examined. Modification by NPM led to the inhibition of ion-channel activity without a detectable effect on ligand binding. The ion flux inhibition by NPM primarily affected channel activation, since the initial rates of activation were decreased over a wide range of carbamylcholine concentrations. The [3H]NPM subunit labeling pattern of ACHR (a multisubunit membrane protein with alpha 2 beta gamma delta stoichiometry) revealed that there was preferential labeling of the gamma subunit. At high NPM concentrations, the number of sulfhydryl groups on the gamma subunit that could be modified with NPM was approximately two. Detergent was required during labeling for functionally relevant thiol-group modifications, and most of the label was protected from protease digestion in the reconstituted membranes. These results are consistent with the presence of the NPM modification in a bilayer and/or cytoplasmic domain.