Effects of tumor necrosis factor alpha on sin nombre virus infection in vitro.

Previous data indicate that immune mechanisms may be involved in developing capillary leakage during Sin Nombre virus (SNV) infection. Therefore, we investigated production of tumor necrosis factor alpha (TNF-alpha) by human alveolar macrophages and human umbilical vein endothelial cells (HUVEC) after infection with SNV. In addition, we examined the effect of TNF-alpha on HUVEC monolayer leakage. Our results reveal that although TNF-alpha decreases accumulation of viral nucleoproteins, TNF-alpha levels do not change in SNV-infected cells. In addition, supernatants from SNV-infected human alveolar macrophages did not cause a significant increase in endothelial monolayer permeability.

The penetration of ceftibuten into the respiratory tract.

STUDY OBJECTIVE: To determine the penetration of ceftibuten into various respiratory tissues and fluids. DESIGN: Single-dose, open-label, pharmacokinetic study. SETTING: Veterans Administration Medical Center. PATIENTS: Twelve hospitalized men aged 34 to 75 years with a variety of noninfectious pulmonary symptoms/diseases. INTERVENTIONS: Patients received a single oral dose of ceftibuten, 200 mg, prior to undergoing diagnostic fiberoptic bronchoscopy. Plasma samples for the determination of ceftibuten concentrations were collected pretreatment and up to 12 h postdosing. Nasal secretions, tracheal secretions, BAL fluid, and lung tissue from a biopsy were obtained at bronchoscopy from 2 to 7 h postdosing. MEASUREMENTS AND RESULTS: Mean pharmacokinetic parameters for ceftibuten in plasma were the following: maximum observed plasma concentration (Cmax), 8.77 microg/mL; time to reach Cmax, 2.2 h; area under the plasma concentration-time curve extraploated to infinity, 49.21 microg/h/mL; and terminal elimination half-life, 3.17 h. These parameters were similar to those obtained in studies using healthy volunteers. Mean penetration of ceftibuten into nasal, tracheal, and bronchial secretions was 47%, 50%, and 30%, respectively. Mean penetration into BAL fluid was 81%, whereas penetration into lung tissue was 39%. No patient experienced any adverse effects related to ceftibuten. CONCLUSIONS: Ceftibuten penetrates well into various tissues and fluids of the upper and lower respiratory tracts. The results support the activity of ceftibuten in the treatment of upper and lower respiratory tract infections.

Intravenous and oral mono- or combination-therapy in the treatment of severe infections: ciprofloxacin versus standard antibiotic therapy. Ciprofloxacin Study Group.

Five hundred and forty patients with severe infection were enrolled in a multicentre, prospective, randomized, non-blinded study to compare the efficacy and safety of i.v. ciprofloxacin with i.v. standard therapy. Five hundred and thirty-one patients received at least one dose of study drug for pneumonia (310), septicaemia (112) or skin and skin structure infection (109). Intravenous ciprofloxacin (400 mg, every 8 h) or i.v. ciprofloxacin (400 mg, every 8 h) plus a beta-lactam were compared with a standard monotherapy (beta-lactam) or combination (aminoglycoside plus a beta-lactam) therapy. Patients were treated parenterally for a minimum of 2 or 3 days, then at the discretion of the investigator could be switched to oral therapy (ciprofloxacin 750 mg, every 12 h or a standard oral therapy). Patients were randomized in the ratio of 2:1 for the ciprofloxacin and standard therapy treatment groups and stratified to monotherapy if the APACHE II score was < or = 20 or to combination therapy if the APACHE II score was 21-29. Three hundred and ninety-five (74%) patients were valid for the efficacy analysis: these comprised 242 pneumonia (167 ciprofloxacin and 75 standard therapy), 70 septicaemia (47 ciprofloxacin and 23 standard therapy), and 83 skin infections (56 ciprofloxacin and 27 standard). The primary efficacy variable was clinical response and the secondary efficacy assessment was bacteriological response at the end of therapy (2 or 3 days after treatment). The mean duration of therapy for patients receiving only i.v. monotherapy or combination therapy was shorter (9-10 days) than for patients receiving sequential i.v./p.o. therapy (14-17 days). At the end of therapy, overall clinical resolution/improvement (success) for monotherapy was 138/166 (83%) for the ciprofloxacin group, compared with 74/87 (85%) for standard-treated patients (95% CI = -11.5% to 7.6%), and for combination therapy the response was 43/51 (84%) for the ciprofloxacin group and 14/20 (70%) for standard-treated patients (95% CI = -6.3% to 34.9%). For pneumonia, the most frequent infection treated, clinical success rates following monotherapy were 85% for ciprofloxacin and 83% for standard-treated patients and 83% for ciprofloxacin compared with 69% for standard-treated patients in the combination therapy group. Bacteriological eradication/presumed eradication following monotherapy was 85/102 (83%) for ciprofloxacin and 31/46 (67%) for standard-treated patients (95% CI = 1.6% to 30.3%), and that for combination therapy was 29/36 (81%) for ciprofloxacin and 7/10 (70%) for standard-treated patients (95% CI = -18.3% to 39.5%). Drug-related adverse events, primarily diarrhoea and nausea, were reported in 22% of ciprofloxacin-treated patients and 20% of standard-treated patients. In summary, ciprofloxacin administered alone or in combination was found to be effective in treating a wide range of severe infections.

Viscous airflow through a rigid tube with a compliant lining: a simple model for the air-mucus interaction in pulmonary airways.

The respiratory tract of mammals is lined with a layer of mucus, described as viscoelastic semi-solid, above a layer of watery serous fluid. The interaction of these compliant layers with pulmonary airflow plays a major role in lung clearance by two-phase gas-liquid flow and in increased flow resistance in patients with obstructive airway diseases such as cystic fibrosis, chronic bronchitis and asthma. Experiments have shown that such coupled systems of flow-compliant-layers are quite susceptible to sudden shear instabilities, leading to formation of relatively large amplitude waves at the interface. Although these waves enhance the lung clearance by mobilizing the secretions, they increase the flow resistance in airways. The objective of this paper is to understand the basic interaction mechanism between the two media better by studying airflow through a rigid pipe that is lined by a compliant layer. The mathematical model that has been developed for this purpose is capable of explaining some of the published experimental observations. Wave instability theory is applied to the coupled air-mucus system to explore the stability of the interface. The results show that the onset flow speed for the initiation of unstable surface waves, and the resulting wavelength, are both very sensitive to mucus thickness. The model predicts that the instabilities initiate in the form of propagating waves for the elastic mucus where the wave speed is about 40 percent of the flow speed. The wavelength and phase speed to air velocity ratio are shown to increase with increasing mucus thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Ceftibuten versus cefaclor for the treatment of bronchitis.

Ceftibuten is an oral third generation cephalosporin with potent antimicrobial activity against Enterobacteriaceae, beta-lactamase positive Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, Neisseria gonorrheae, penicillin-susceptible pneumococci, and beta-hemolytic streptococci. To study the efficacy and safety of ceftibuten for treatment of bronchitis, 58 patients were randomized to therapy with either ceftibuten 400 mg once a day or cefaclor 250 mg every 8 h at a ratio of two to one. Of 45 clinically evaluable patients, 28 (87.5%) of the 32 ceftibuten patients and 12 (92.3%) of the 13 cefaclor patients were clinically improved or cured. Of 33 microbiologically evaluable patients, 21 (87.5%) of the 24 ceftibuten patients and eight (80%) of the ten cefaclor patients were cured. Of 56 patients evaluable for adverse effects, three (7.9%) of the 38 ceftibuten patients and one (5.6%) of the 18 cefaclor patients had adverse reactions. In this small study, once-daily ceftibuten appeared as safe and as effective as cefaclor for the treatment of bronchitis.

Diagnosis of obstructive sleep apnea.

The diagnosis of obstructive sleep apnea is frequently made by taking a meticulous history coupled with a high index of suspicion. Snoring and hypersomnolence are clinical features common to individuals with sleep apnea. Since snoring is said to be a "disease of listeners," it is not uncommon that bed partners reported an increased incidence of depression and marital displeasure. It is for this reason that the spouse or bed partner should be interviewed, since the patient may not be aware of any sleeping problems. Physicians should also be alert to complaints of excessive daytime somnolence, because studies have shown that patients with obstructive sleep apnea are at increased risk for automobile crashes. It has been estimated that approx 58,000 motor vehicle accidents involving people with sleep apnea will occur in the US each yr. By proper diagnosis and treatment, the physician is in a unique position to prevent at least some of the automobile accidents that result from falling asleep while driving. Polysomnography is the only definitive way to obtain a diagnosis of sleep apnea. This allows the physician not only to diagnosis the disorder, but also helps in the evaluation of the severity of the syndrome and selection of therapy. An ENT evaluation is also important in ruling out anatomic disorders that can cause upper airway obstruction. Certain factors, such as alcohol and sedative ingestion, may aggravate the condition in a person predisposed to sleep apnea, and subtle changes, such as unexplained hypertension, polycythemia, and cor pulmonale, should lead one to investigate the possibility of sleep apnea as the etiology.

Diagnosis of gastrobronchial fistula by measurement of bronchial secretion pH. Case report and literature review.

A patient with prior GBF and new-onset hemoptysis was diagnosed as having recurrent GBF by measurement of bronchial secretion pH. This is a previously unreported means of diagnosing this process. Bronchoscopic findings were substantiated by upper GI contrast study and surgical findings.

Approach to the patient with diffuse lung disease.

When evaluating diffuse lung infiltrates, the clinician should place special emphasis on the acuity of symptoms, nonpulmonary complaints and findings, environmental exposures, and risk factors for immunosuppressive diseases. Certain radiographic features, such as the distribution of opacities, hilar adenopathy, Kerley-B lines or pneumothorax, or pulmonary function tests demonstrating air flow limitation also narrow the differential diagnosis. One can direct the subsequent workup based on the narrowed differential diagnosis, the pace of disease, the activity of the ongoing inflammatory-immune process, and the age, overall medical condition, and wishes of the patient. Unless a specific diagnosis (for example, hypersensitivity pneumonitis, the treatment of which is withdrawal of the offending agent) can be made, therapy of noninfectious diffuse lung disease is quite unsatisfactory. Immunosuppressive therapy is indicated to arrest the active inflammatory process with the hope that objective signs of improvement will occur after a 3- to 12-month course. Important areas of basic research in pulmonary fibrosis include cell-cell and cell-matrix interactions in the lung interstitium and delineation of fibroblast biology and cytokine-mediated lung connective tissue pathology. More successful therapies will probably evolve from better understanding of the molecular and cellular biology of the lung fibrogenic process.

Speech restoration post-pharyngolaryngoesophagectomy using tracheogastric fistula.

Restoration of voice and speech in patients with gastric pull-up presents a formidable challenge, and many of these patients are left at best with a poorly functional electrolaryngeal speech. To improve this condition, a tracheogastric puncture stented with a biflanged self-retaining Groningen voice button was accomplished, resulting in gastric mucosa vibrations during exhalatory phase. The biomechanical characteristics of gastric vibrations and tracheogastric puncture candidate selection criteria are discussed.

Epidermal Langerhans cell density in patients with pulmonary malignancies and chronic obstructive pulmonary disease.

To evaluate the relationship between ELC density and pulmonary malignancies, as reported in previous investigations, we examined the nonsun-exposed epidermis of 18 patients with pulmonary cancer (CA) not receiving immunosuppressive therapy, 20 patients with chronic obstructive pulmonary disease (COPD-S), and 10 patients with COPD receiving glucocorticosteroid (GCS) therapy (COPD + S). The ELC density was not significantly different between lung tumor patients (1024 +/- 167) and COPD-S (1072 +/- 200, p less than 0.4) control patients, and we found no significant correlation between ELC density and tumor cell type, presence or absence of metastases, tumor stage, or present smoking status. Although we did detect that systemic GCS therapy significantly reduced the ELC density in COPD + S patients (910 +/- 211, p less than 0.05); use of inhaled or chronic low dose (less than or equal to 20 mg daily) GCS did not appear to significantly alter ELC density. In addition, anergy to epicutaneous dinitrochlorobenzene in CA and COPD + S patients positively correlated with a reduction in ELC density, suggesting a possible functional deficit arising from the numerical change. Further investigation is needed to elucidate whether factor(s) other than a reduction in ELC density are involved in the anergic state.

The aging respiratory system.

In this review article, the effects of old age on lung structure and function are discussed. Changes in lung morphology and biochemistry are correlated with changes in lung mechanics and gas exchange, as well as with the respiratory system's adaptability to the stresses of exercise and sleep. The effects of aging on the lungs' defense mechanisms are related to pulmonary diseases of the elderly.

Evaluation of bronchial air leaks by auscultation and phonopneumography.

Bronchial fistulae in communication with atmospheric pressure can be identified by the presence of a squeaking sound heard over the chest wall during a Valsalva maneuver. Furthermore, these leak sounds can help identify the size, location, and communications of the bronchial fistulae. The size of the leak can be inferred by the pitch of the leak sound. Large leaks produce low pitched sounds, smaller leaks (or partially obstructed leaks) produce high pitched squeaks , and multiple leaking sites produce polyphonic leak squeaks . The bronchus responsible for the leak can be identified by cessation of the leak sound during balloon occlusion of the correct bronchial stump. A communication of a bronchial fistula with the chest wall facial plane produces massive subcutaneous emphysema and an early inspiratory click. This click suggests a check valve mechanism of air exiting the leaking bronchus.

Reverse ventilation--perfusion mismatch.

Patients having lobar airway obstruction or consolidation usually have decreases of both ventilation and perfusion on lung scans. We report three patients in whom hypoxic vasoconstriction was apparently incomplete, resulting in a "reversed" ventilation-perfusion mismatch. Perfusion of the hypoxic lobe on the radionuclide scan was associated with metabolic alkalosis, pulmonary venous and pulmonary arterial hypertension in these patients.

Alcohol and the respiratory tract.

Possible mechanisms by which alcohol may adversely affect the respiratory system are considered. Alcohol ingestion impairs glottic reflexes, and alcoholics are predisposed to pneumonias and lung abscesses from aspiration of oropharyngeal bacteria. Alcohol intoxication also increases the frequency of sleep apnea and may result in respiratory failure from oversedation.

The detection and quantification of sleep apnea by tracheal sound recordings.

Tracheal sound recordings and O2 saturation were compared with conventional recordings of respiratory events (thermistors, strain gauges, and O2 saturation) in 14 patients referred for assessment of sleep apnea syndrome. There was no significant difference in the number of respiratory events associated with desaturation recorded during the sleep by the two methods. Tracheal sound recordings were more useful in analyzing the cause of the respiratory event. Hypopnea without desaturation was seen more often with tracheal sound recordings than with the conventional methods. The durations of apneic and hypopneic events were significantly longer when recorded by thermistors and strain gauges than by breath sounds.

Computerized rapid analysis of pulmonary function test: use of a least mean squares correlation for interpretation of data.

Although systems for automated calculation and interpretation of screening pulmonary function tests (PFT) have been discussed by previous investigators, these systems are often unavailable to other users, require large or hybrid computers, or are difficult to modify. The use of a branching decision tree for PFT interpretation may also limit the number of correlations possible and make revision of the program difficult because changes in the proximal branches of the tree require a rewriting of the entire distal program. We have developed a system based on a minicomputer which uses a least mean squares analysis for rapidly analyzing the patient's PFT data. This program considers the following types of PFT data singly and in combination: percentage predicted total lung capacity and/or alveolar volume, forced expiratory volume in one second to forced vital capacity ratio (before and after bronchodilator or 80% helium challenge), and percentage predicted single breath diffusing capacity for carbon monoxide. The interpretation program (IP) then selects the 'best interpretation' for the patient by computing the variance between the patient's data and data from a menu of over 120 interpretation statements. During the past two years we have used this system for screening over 3000 patients. In about 90% of patients the computer selected interpretation statements which were acceptable to a sub-specialty pulmonary physician. The use of this IP for screening purposes has facilitated the efficient use of laboratory personnel and equipment.

The bronchial leak squeak: a new sign for the physical diagnosis of bronchopleurocutaneous fistula.

We describe a unique physical diagnostic sign that we have observed in seven patients with bronchopleurocutaneous fistulas. Such patients have a highpitched squeak over the affected chest area during sustained Valsalva maneuver. We postulate that turbulence across the bronchial fistula due to high transbronchial pressure gradient during the Valsalva maneuver produces the squeaking sound. The pitch of the leak squeak sign is higher in smaller fistulas than in larger fistulas; decreases in intensity and increases in pitch occurred in two patients in whom the bronchial fistula slowly closed. The absence of the leak squeak sound in patients with spontaneous pneumothorax suggests that this sign can be used to differentiate central airways from alveolar air leaks.