Lipoid pneumonia in lung cancer: radiographic and pathological features

BACKGROUND: Obstructive pneumonia, a synonym for endogenous lipoid pneumonia, is often seen in patients with lung cancer, but details of this condition are still uncertain. METHODS: To elucidate the features of obstructive pneumonia, we radiopathologically studied 147 patients with lung cancer that had been resected. RESULTS: Gross inspection of the resected materials revealed evidence of endogenous lipoid pneumonia in 33 of the 147 patients with radiography that corresponded to obstructive pneumonia. We classified the 33 cases into three types as follows: (1) type I lipoid pneumonia, localized to the lung parenchyma distal to an airway obstructed by a tumor (23 cases); (2) type II lipoid pneumonia, features of type I lipoid pneumonia and consecutively spreading to the adjacent segment whose airway was not affected (five cases); (3) type III lipoid pneumonia, features of type II lipoid pneumonia and spreading to the isolated segments (five cases). Lipoid pneumonia was found in 16 of 89 (18%) adenocarcinoma cases and in 17 of 55 (31%) squamous cell carcinoma cases. In type I lipoid pneumonia, squamous cell carcinoma cases were predominant over adenocarcinoma cases (14 vs nine cases), but in type III lipoid pneumonia, adenocarcinoma cases predominated (four vs one case). Further, in cases of type III lipoid pneumonia, radiographs frequently revealed that lung cancers were cavitated. CONCLUSION: Lipoid pneumonia in lung cancer may be associated with factors that play a larger role than the cancer alone. It can be speculated that transbronchial dissemination of breakdown products of adenocarcinoma cells, including mucin, may contribute to the spread of the non-obstructive component of lipoid pneumonia, because the local physical effect of obstructed bronchus does not affect the non-obstructive component.     

Kinetics and quantitation of eosinophil and neutrophil recruitment to allergic lung inflammation in a brown Norway rat model

We quantitated neutrophil and eosinophil migration into lung parenchyma using specific peroxidase enzyme assays, and into the bronchoalveolar compartment by bronchoalveolar lavage (BALF), in sensitized brown Norway (BN), Fischer, and Lewis rats and also assessed the lungs by histopathology. Fourteen days after sensitization with ovalbumin (OA in alum [given subcutaneously] and OA with Bordetella pertussis [given intraperitoneally]), rats were challenged with an OA aerosol for 1 h. In BN rats, there was marked perivascular and peribronchial edema, focal hemorrhages, and increase in lung wet weight and BALF protein content, accompanied by neutrophilic infiltration at 3-14 h postchallenge. Few eosinophils were seen at 14 h in lung tissue or in BALF. Neutrophils peaked at 24 h in parenchyma ([94 +/- 7] x 10[6]) and in BALF ([2.7 +/- 0.4] x 10[6]) and declined rapidly thereafter. Marked eosinophil infiltration into parenchyma was apparent by 24 h. Eosinophil accumulation peaked at 48 h in parenchyma ([127 +/- 18] x 10[6]) and at 72 h in BALF ([10 +/- 2.4] x 10[6]), comprising up to 85% of lavage cells at this time. Lung eosinophilia persisted for at least 6 d with only a slow decline or clearance, not approximating baseline until day 13 after challenge. Histopathology showed peribronchial and interstitial eosinophilic pneumonia, most severe on day 3. In contrast to the BN rats, essentially no pulmonary inflammation was observed in Lewis and Fischer rats. This model in the BN rat, and the specific peroxidase assays for quantitating tissue eosinophils and neutrophils, should be useful for investigating the regulation of allergen-induced eosinophil and neutrophil migration into and clearance from the lung.     

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.     

Periodontal repair in intrabony defects treated with a calcium carbonate implant and guided tissue regeneration

OBJECTIVE: To determine mortality and factors that might predict outcome in severe community-acquired pneumococcal pneumonia treated by a standard protocol. DESIGN: Prospective, non-concurrent study. SETTING: Respiratory intensive care unit (ICU) in a teaching hospital. PATIENTS: 63 patients who were diagnosed by positive blood culture or Gram stain and culture of sputum or tracheal aspirate were included. MEASUREMENTS AND RESULTS: Clinical features, severity scores including Acute Physiology and Chronic Health Evaluation (APACHE) II, organ failure and lung injury scores, and the clinical course in the ICU were documented; 79% of patients required mechanical ventilation. Bacteraemia was present in 34 patients (54%); there were no distinguishing clinical features between bacteraemic and non-bacteraemic cases. The overall mortality was 21%, with only 5 deaths (15% mortality) in the bacteraemic group. Shock and a very low serum albumin (< 26 g/l) were the only clinical features that differentiated survivors from non-survivors; lung injury, APACHE II and multiple organ failure scores were all predictive of outcome. The positive predictive value and specificity in predicting death in individuals for the modified British Thoracic Society rule 1 were 26 and 64%; APACHE II > 2057 and 88%; > 2 organ failure 64 and 92%; and lung injury > 233 and 73%, respectively. CONCLUSIONS: These results suggest that even in bacteraemic cases mortality should be below 25% with intensive care management and that conventional scoring systems, while predictive of group mortality, are unreliable in individuals.     

Morphometric approaches for evaluating pulmonary toxicity in mammals: implications for risk assessment

Recent advances in quantitative morphology provide all the tools necessary to obtain structural information in the lung that can be quantified and interpreted in the three-dimensional world of toxicology. Structural hierarchies of conducting airways and parenchyma of the lung provide: (1) numbers of cells per airway, lobe, or lung; (2) surface areas of cells, airways, and alveoli; (3) length of airways and vessels; and (4) volumes of cells, alveoli, airways, vessels, and individual lobes or the entire lung. Unbiased sampling of these subcompartments of the lung requires fractionation of lobes or individual airways. Individual airways of proximal and distal generations are obtained by airway microdissection along one axial pathway and comparisons made between airway generations. Vertical sections of selected airways are used to sample epithelium and interstitium. Using this unbiased approach of quantitative morphology, we have shown that inhalation of low ambient concentrations of ozone ([O3]0.15 ppm) near or at the United States National Ambient Air Quality Standard (NAAQS) (0.12 ppm O3) induces significant alterations in bronchiolar epithelium and interstitium in nonhuman primates but not rats. The alterations do not appear to be concentration- or time-dependent, thereby bringing into question the current NAAQS that may be at or above the threshold for distal airway injury in primates. Unbiased morphometric methods are critical in a quantitative evaluation of toxicological injury of mammalian tracheobronchial airways.     

Humoral (antibody-mediated) rejection in lung transplantation

To confirm the existence and characterize the pathologic features of humoral (antibody-mediated) lung rejection, we prospectively studied 55 lung transplant recipients (24 male [44%] and 31 female [56%], age range 14 to 69 years [mean 45]). The time between transplantation and biopsy ranged from 2 to 1546 days (mean 274). We performed direct immunofluorescence with C3, immunoglobulin M, and immunoglobulin G antibodies on frozen sections of 106 transbronchial biopsies and one wedge biopsy and compared the results with 13 explanted lungs, one donor lung, and two controls. The histologic diagnoses of these 107 biopsies included acute cellular rejection (62, 58% [minimal 23, mild 33, moderate 5, and severe 1]), chronic rejection (eight, 7%), chronic vascular rejection (two, 2%), acute vasculitis (five, 5%), cytomegalovirus pneumonitis (two, 2%), acute pneumonia (two, 2%), acute organizing pneumonia (two, 2%), diffuse alveolar damage (one, 1%), no evidence of rejection or infection (30, 28%), lipoid pneumonia (one, 1%), and inadequate for histologic diagnosis (one, 1%). Eighty-nine of 106 (84%) transbronchial biopsies, the wedge biopsy, and control lungs were satisfactory for direct immunofluorescence, because each contained alveolate lung parenchyma and arterioles or venules. There was no demonstrable immunofluorescence in the wall of the blood vessels or in the lung parenchyma in any case. We conclude that (1) transbronchial biopsies and wedge biopsies provide adequate material to evaluate humoral rejection, and (2) in spite of the large population studied, the satisfactory material obtained, and the wide range of histologic diagnoses, we could not demonstrate the occurrence of humoral rejection in the lung.     

Prognostic factors and etiology in patients with severe community-acquired pneumonia admitted at the ICU. Spanish multicenter study. Study Group on Severe Community-Acquired Pneumonia in Spain

OBJECTIVE: To determine the techniques used for the etiological diagnosis of community-acquired pneumonia in patients admitted to the intensive care unit (ICU) and to describe the predominant causative organisms as well as prognostic factors of ICU mortality. PATIENTS AND METHODS: A total of 262 patients with community-acquired pneumonia admitted to 26 ICUs between 1 November of 1991 and 31 October of 1992 were included in a prospective, open, multicenter study. RESULTS: The diagnostic techniques most frequently used were blood culture (243 cases) and simple tracheal aspirate (166 cases). Simple tracheal aspirate (58.4%), bronchoalveolar lavage (47.7%), and protected-specimen brush (44.2%) were the techniques that showed the highest diagnostic reliability. In 220 cases, techniques considered of high diagnostic probability were employed. With the use of these procedures, the most frequent causative pathogens were Streptococcus pneumoniae (13.6%) and Legionella pneumophila (9.5%). In 100 cases (45.5%), no pathogen was isolated. A total of 88 patients (33.6%) died during the ICU stay. Predictive variables of poor outcome selected by means of a multivariate analysis were as follows: multisystemic failure (OR = 28.6; 95% CI: 12.8-65.1; p = 0.0001), APACHE II at the time of ICU admission (OR = 5.3; 95% CI: 2.5-11.3; p = 0.0001), progression and/or spread of lung infection (OR = 4.5; 95% CI: 2.4-8.4; p = 0.0001), and shock on admission (OR = 8.48; 95% CI: 4.5-15.9; p = 0.0001). CONCLUSIONS: In 45.5% of patients with community-acquired pneumonia admitted to ICU, no causative pathogen was identified. The prognosis of these patients was influenced by the severity of disease assessed by APACHE II score and presence of multisystemic failure and shock at the time of ICU admission.     

Optic chiasm astrocytomas of childhood. 1. Long-term follow-up

There are many in vivo animal models for studying airway mucus secretion and hypersecretion, each with advantages and disadvantages. Use of a particular test system will depend upon the aspect of secretion to be modelled. Airway hypersecretory diseases exhibit chronic mucus hypersecretion, of which the clinical impact is predominantly in the distal airways. The majority of documented test preparations study acute secretion, invariably using tracheal preparations, but have been invaluable in elucidating the normal physiology of airway mucus secretion. Chronic models of the hypersecretory state in the distal airways have been developed, but are predominantly histologic in nature (for example quantification of increased goblet cell number). There are few investigations of mucus hypersecretion. Examination of the 'antisecretory' potential of pharmaceutical compounds has been investigated predominantly in chronic histologic models with the drug being given 'prophylactically' rather than 'therapeutically'. Refinement of chronic hypersecretory models should lead to elucidation of the connection between airway irritation, inflammation, MUC gene expression, mucous cell hyperplasia/metaplasia, airway hypersecretion and bronchial hypersecretory disease.     

Lung transplantation for Williams-Campbell syndrome

Williams-Campbell syndrome is a rare disorder characterized by a deficiency of cartilage in subsegmental bronchi leading to distal airway collapse and bronchiectasis. We report the first case of lung transplantation in a patient with end-stage lung disease secondary to Williams-Campbell syndrome. Although the patient did not have proximal airway collapse prior to transplantation, his posttransplant course was complicated by the development of bronchomalacia of the right and left mainstem bronchi. The patient experienced recurrent pulmonary infections and died of bacterial pneumonia 1 year after transplantation. Autopsy revealed cartilage deficiency in both right and left mainstem bronchi. A hypothesis may be made that a combination of proximal cartilage deficiency and posttransplant airway ischemia led to the development of bronchomalacia after lung transplantation. Thus, in contrast to previous reports, the cartilage deficiency in Williams-Campbell syndrome can involve both proximal and distal airways. Consequently, bilateral sequential lung transplantation may not be an effective therapeutic option in patients with this syndrome.     

Early diagnosis of ventilator-associated pneumonia. Is it possible to define a cutoff value of infected cells in BAL fluid?

STUDY OBJECTIVE: To assess the usefulness of quantification of infected cells (ICs) in BAL fluid for the diagnosis of ventilator-associated pneumonia (VAP). DESIGN: A prospective study. SETTING: A medico-surgical ICU in a tertiary health-care institution. PATIENTS: One hundred thirty-two patients (mean age, 52 +/- 19 years). The suspicion of nosocomial pneumonia was strong in these patients: all had fever (> or = 38.5 degrees C), purulent tracheal aspirates, leukocytosis (> or = 10,000 cells per cubic millimeter), and new or persistent radiographic lung infiltrates. INTERVENTIONS: One hundred sixty-three samples (BAL and protected specimen brushes [PSB]) were obtained. RESULTS: VAP was present in 56 cases. The diagnosis was excluded in the remaining 107 cases. The IC count was performed on 100 cells in BAL fluid. The percentage of IC was significantly higher (12.6 +/- 12.4 vs 1.14 +/- 3.39; p < 0.0001) in patients with pneumonia: the area under the receiver operating characteristic (ROC) curve was 0.888 and a threshold of 2% of IC corresponded to a sensitivity of 84%, a specificity of 80%, a positive predictive value of 69%, and a negative predictive value of 90%. CONCLUSIONS: It is possible to define a threshold of IC in BAL fluid with a good reliability by using an ROC curve. This technique is useful for the early diagnosis (< 2 h) of nosocomial bacterial pneumonia in mechanically ventilated patients and allows a rapid and appropriate treatment of most of the patients with suspected VAP.     

The role of neutrophils in the pathogenesis of idiopathic pulmonary fibrosis

STUDY OBJECTIVES: The prognostic value of the neutrophil count in BAL fluid (BALF) has been controversial. The role of neutrophils in this inflammatory lung disease, therefore, was evaluated in this study by additional measures. MATERIALS AND METHODS: We performed BAL in 22 patients with idiopathic pulmonary fibrosis (IPF) diagnosed by open lung biopsy specimen. Percent polymorphonuclear leukocyte (PMN) in BALF and absolute neutrophil counts were compared with those of normal nonsmokers. Elastase complexed to alpha-1-proteinase inhibitor (alpha1-PI) in plasma and BALF was measured as a marker of elastase burden, and neutrophil distribution in 22 lung tissues was observed by immunohistochemistry using antineutrophil elastase antibody. RESULTS: Percent PMN and absolute neutrophil counts in BALF did not increase in patients with IPF as compared with normal nonsmokers (n=15); the plasma elastase-alpha1-PI complex value (mean+/-SE) of patients with IPF (668.5+/-112.4 ng/mL) was significantly high as compared with that of normal nonsmokers (130.3+/-21.3, p<0.001). In addition, the BALF elastase-alpha1-PI complex value (mean+/-SE) of patients with IPF was also significantly high (333.1+/-87.0 ng/mg albumin) as compared with that of normal nonsmokers (83.1+/-29.3 ng/mg albumin, p<0.05). Immunohistochemistry demonstrated considerable numbers of neutrophils infiltrating the lung parenchyma in biopsy specimens obtained by open lung biopsy. CONCLUSIONS: These results suggested that although the neutrophil count in BALF could not represent the distribution of neutrophil in the lung, high levels of neutrophil elastase were demonstrated in lung parenchyma and also in both BALF and sera. Therefore, neutrophils might indeed play an important role in the pathogenesis of IPF.     

Time-course effects of human recombinant luteinizing hormone on porcine Leydig cell specific differentiated functions

Polymerase chain reaction (PCR)-based assays were developed to detect virulent Rhodococcus equi in transtracheal aspirate samples from sick foals showing respiratory signs. An oligonucleotide primer pair from the sequence of the virulence-associated 15- to 17-kDa antigen gene of the virulence plasmid in virulent R. equi was used to amplify a 564 bp region by PCR, and the result was confirmed by Southern blot hybridization. No positive reaction was seen in DNA from 13 different microorganisms typically found in the respiratory tract. In tracheal aspirates seeded with virulent R. equi, a visible band could detect 10 to 10(2) bacteria per PCR assay (10(3) to 10(4)/ml of the aspirate). Virulent R. equi was demonstrated in 31 of 42 transtracheal aspirates by culture and colony blot analysis, whereas a positive PCR result was observed in only 12 of the 31 culture positive samples. To prevent false-negative results, two methods were developed: a nested PCR and a PCR in combination with enrichment cultures of aspirates in the selective medium to increase the number of bacteria to 10(4)/ml or more. All of the PCR-negative and culture-positive samples were positive by the two methods. These results indicated that PCR-based assays provide a specific and sensitive means to detect virulent R. equi in tracheal aspirates of foals, and they are more rapid than the routine culture procedures for the diagnosis of R. equi pneumonia in foals.     

Guiding occlusal development with functional appliances

In 24 patients with bacterial pneumonia, reliability of the samples routinely taken for etiologic diagnosis (sputum, throat swab, bronchial brushing, bronchoalveolar lavage fluid--BALF, blood, pleural fluid) was determined. Organisms detected in blood, pleural fluid, transbronchial biopsy (TBB) or percutaneous transthoracic needle aspiration biopsy (PTNAB) samples were considered as truly causative, whereas those isolated in at least two various samples from a single patient were considered as presumably causative. Most sensitive diagnostic samples were BALF, TBB and PTNAB (100% each). However, the specificity of BALF was very low (17%). Bronchial aspirate was highly sensitive (95%) but not specific (14%). Bronchial brushing was sensitive (86%) but its specificity low (14%). Sputum was hardly sensitive (40%) and had no specificity. Throat swab had virtually no diagnostic value because of its low sensitivity (10.5%) and specificity (50%).     

A new bronchoscopic technique for the diagnosis of bacterial pneumonia in HIV-positive patients

The aim of the present study was to evaluate in HIV-positive patients with bacterial pneumonia, the diagnostic value of a new endoscopic technique that uses a single catheter to perform a telescopic plugged catheter (TPC) followed by a modified protected bronchoalveolar lavage (mpBAL). Fifty-eight HIV-positive patients with respiratory infection were included in the study. Samples from TPC and mpBAL were cultured quantitatively. Standard bronchoalveolar lavage was performed to rule out opportunistic infections. According to the clinical and microbiological results, patients were classified in the study group (27 with bacterial pneumonia) or the control group (31 without bacterial pneumonia). Sensitivity of TPC was 56% [95% confidence intervals (CI) 37-75%] and its specificity was 100%; these figures were 56% (CI, 37-75%) and 94% (CI, 86-100%) for mpBAL. When both techniques were assessed together, sensitivity increased to 70% (CI, 53-87%). The use of a single catheter reduced the cost of the originally described pBAL procedure by approximately 50%. The use of a single catheter to perform a TPC followed by a mpBAL can improve the diagnostic yield in HIV-positive patients with bacterial pneumonia, and reduces its cost.     

Characterization of redox activity in resting and activated mast cells by reduction and reoxidation of lipophilic nitroxides

OBJECTIVES: Our goal was to examine the relationship between viral pneumonia and outcome in pediatric patients undergoing lung or heart-lung transplantation. METHODS: Prospective surveillance for common respiratory viruses of childhood was performed in all patients undergoing lung or heart-lung transplantation. Specimens were examined for the presence of replicating virus (by culture), viral genome (by polymerase chain reaction), and viral antigen (by immunofluorescence and immunohistochemical staining). The relationship between viral infection and outcome was examined. RESULTS: Sixteen patients underwent 19 transplants during the study period, with follow-up of 1 to 26 months. Virus was identified in the transplanted lung in 29 instances; adenovirus was identified most commonly (8/16 patients) and had the greatest impact on outcome. In 2 patients with early, fulminant infection, adenovirus was also identified in the donor. Adenovirus was significantly associated with respiratory failure leading to death or graft loss and with the histologic diagnosis of obliterative bronchiolitis (P < or = .002 in each case). CONCLUSIONS: Adenovirus infection in the transplanted lung is significantly associated with graft failure, histologic obliterative bronchiolitis, and death. Health care personnel and families must be vigilant in preventing exposure of transplant recipients to this virus. Availability of a rapid and reliable test for adenovirus in donors and recipients would have an impact on management and could improve outcome for pediatric lung recipients.     

The first clinical isolate of Legionella parisiensis, from a liver transplant patient with pneumonia

A bluish white autofluorescent strain of Legionella was isolated from the tracheal aspirate of a female liver transplant patient who developed hospital-acquired pneumonia. This strain had biochemical characteristics compatible with those of L. cherrii, L. anisa, and L. parisiensis and could not be differentiated from L. bozemanii and L. parisiensis by the direct fluorescent-antibody assay. Phylogenetic analysis of partial 16S rRNA gene sequences of this strain (ATCC 700174) revealed the closest homology to the species L. parisiensis (99.5%). An L. parisiensis species-specific profile was also identified by a random amplified polymorphic DNA technique. This is the first report of L. parisiensis isolation from humans.     

Purified soluble guanylyl cyclase expressed in a baculovirus/Sf9 system: stimulation by YC-1, nitric oxide, and carbon monoxide

Neonatal respiratory function depends on the development of a well-formed pulmonary capillary bed. Vascular endothelial growth factor (VEGF) is a potent inducer of endothelial cell growth and angiogenesis. High levels of VEGF protein and messenger RNA (mRNA) have been detected in the developing lung, suggesting that VEGF plays a role in the development of the pulmonary capillary bed. To begin to understand the role of VEGF in human lung development, we explored the regulation of VEGF gene expression and the localization of VEGF protein and mRNA in a model of the developing human lung. VEGF protein and mRNA were detected in midtrimester human fetal lung tissue, and their levels increased with time in explant culture. VEGF protein and mRNA were increased by the maintenance of human fetal lung explants in 2% O2 environments compared with 20% O2 environments. VEGF mRNA levels were found to be increased by cyclic adenosine monophosphate (cAMP) in explants that were incubated in 20% O2, but not in those incubated in 2% O2. Immunostaining for VEGF protein demonstrated localization primarily in airway epithelial cells in midtrimester human fetal lung tissue. Immunostaining for VEGF increased with incubation of human fetal lung explants in 2% and 20% O2. Interestingly, VEGF protein was localized primarily in the basement membrane subjacent to airway epithelial cells after 4 d of incubation in 20% O2. Incubation of tissues in the presence of dibutyryl cAMP resulted in an increase in immunostaining for VEGF, primarily in the basement membranes of prealveolar ducts in 20% O2-treated tissues. In situ hybridization studies indicated that VEGF mRNA was present in both mesenchymal cells and airway epithelial cells. These data suggest that VEGF gene expression is regulated by both oxygen and cAMP in the developing human lung. The detection of VEGF mRNA and protein in distal airway epithelial cells and the detection of VEGF protein in the basement membrane subjacent to the airway epithelial cells suggest that translocation of VEGF protein occurs after its synthesis in the epithelium. Localization of VEGF to the basement membrane of airway epithelial cells may be important for directing capillary development in the human lung.     

Clavicular osteomyelitis as a complication of head and neck surgery

To investigate the development of airway hyperresponsiveness in infantile guinea pigs, animals (10 days old) were immunized twice and challenged by inhalation of 1% ovalbumin for 10 min with 7 days intervals. Similar to adult guinea pigs, infantile ones developed an increased airway responsiveness to acetylcholine 24 hr after antigen challenge. There was a marked increase in the number of total leukocytes, eosinophils and lymphocytes in bronchoalveolar lavage fluid (BALF). Suplatast tosilate (suplatast) and pemirolast potassium (pemirolast) given orally throughout the experiments suppressed the development of airway hyperresponsiveness in infantile animals. They showed similar potency in the suppression of eosinophil accumulation in BALF and lung tissue, while suplatast inhibited lymphocyte accumulation stronger than pemirolast. Collectively, the present model of airway hyperresponsiveness in infantile guinea pigs may be useful in predicting the efficacy of antiallergic agents in the treatment of asthmatic children.     

The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study

CONTEXT: Aspiration of oropharyngeal material, with its high concentration of anaerobic bacteria, has been implicated in the pathogenesis of both ventilator-associated pneumonia (VAP) and aspiration pneumonitis (AP). Consequently, patients with these disorders are usually treated with antimicrobial agents with anaerobic activity. OBJECTIVE: To determine the incidence of anaerobic bacteria in patients with VAP and AP. DESIGN: Prospective, nonrandomized, interventional study. SETTING: University-affiliated community teaching hospital. PATIENTS AND INTERVENTIONS: We performed sequential blind protected specimen brush (PSB) sampling and mini-BAL in 143 patients with 185 episodes of suspected VAP and 25 patients with AP who required mechanical ventilation. Quantitative aerobic and anaerobic cultures were performed on all specimens. Pneumonia was considered to be present when either > 500 cfu/mL cultured from blind PSB sampling or > 5,000 cfu/mL cultured from mini-BAL were present. RESULTS: Using the predefined criteria, bacterial pneumonia was diagnosed in 63 of 185 suspected VAP episodes (34%) and 12 of 25 patients with AP (48%). At least one dose of an antibiotic was given in the 24 h prior to bacteriologic sampling in 106 suspected VAP episodes (57%) and in 12 patients with AP (48%). More than one pathogen was isolated from 11 VAP and four AP patients. Pseudomonas aeruginosa, Staphylococcus aureus, and enteric Gram-negative organisms were isolated most frequently from patients with VAP. In the patients with AP, enteric Gram-negative organisms were isolated in patients with GI disorders and Streptococcus pneumoniae and Haemophilus influenzae predominated in patients with "community-acquired" aspiration. Only one anaerobic organism was isolated from the entire group of patients; Veillonella paravula was isolated from a blind PSB specimen in a patient with suspected aspiration pneumonia. CONCLUSION: Despite painstaking effort, we were able to isolate only one anaerobic organism (nonpathogenic) from this group of patients. The spectrum of aerobes in patients with VAP was similar to that reported in the literature. The organisms found in patients with AP was a reflection of the organisms likely to colonize the oropharynx. The use of antibiotics with anaerobic coverage may not be necessary in patients with suspected VAP and AP. Furthermore, penicillin G and clindamycin may not be the antibiotics of choice in patients with AP.     

Relationship of inhaled ozone concentration to acute tracheobronchial epithelial injury, site-specific ozone dose, and glutathione depletion in rhesus monkeys

Acute pulmonary epithelial injury produced by short-term exposure to ozone varies by site within the tracheobronchial tree. To test whether this variability is related to the local dose of ozone at the tissue site or to local concentrations of glutathione, we exposed adult male rhesus monkeys for 2 h to filtered air or to 0.4 or 1.0 ppm ozone generated from 18O2. Following exposure, lungs were split into lobes and specimens were selected by microdissection so that measurements could be made on airway tissue of similar branching history, including trachea, proximal (generation one or two) and distal (generation six or seven) intrapulmonary bronchi, and proximal respiratory bronchioles. One half of the lung was lavaged for analysis of extracellular components. In monkeys exposed to filtered air, the concentration of reduced glutathione (GSH) varied throughout the airway tree, with the proximal intrapulmonary bronchus having the lowest concentration and the parenchyma having the highest concentration. Exposure to 1.0 ppm ozone significantly reduced GSH only in the respiratory bronchiole, whereas exposure to 0.4 ppm increased GSH only in the proximal intrapulmonary bronchus. Local ozone dose (measured as excess 18O) varied by as much as a factor of three in different airways of monkeys exposed to 1.0 ppm, with respiratory bronchioles having the highest concentration and the parenchyma the lowest concentration. In monkeys exposed to 0.4 ppm, the ozone dose was 60% to 70% less than in the same site in monkeys exposed to 1.0 ppm. Epithelial disruption was present to some degree in all airway sites, but not in the parenchyma, in animals exposed to 1.0 ppm ozone. The mass of mucous and ciliated cells decreased in all airways, and necrotic and inflammatory cells increased. At 0.4 ppm, epithelial injury was minimal, except in the respiratory bronchiole, where cell loss and necrosis occurred, and was 50% that found in monkeys exposed to 1.0 ppm ozone. We conclude that there is a close association between site-specific O3 dose, the degree of epithelial injury, and glutathione depletion at local sites in the tracheobronchial tree.