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Lepidic growth is most often seen in adenocarcinoma in situ (Figure A, 40x magnification). Adenocarcinoma in situ is formerly known as bronchoalveolar cell carcinoma (BAC). A similar growth pattern in a morphologically very different tumor (mucinous adenocarcinoma) is shown for comparison (Figure B, 400x). Mucinous adenocarcinoma growing on alveolar septae nearly always is invasive, so the entity of mucinous adencioarcinoma in situ practically doesn't exist, further differentiating this entity from BAC.

Patients regularly request to take possession of their human tissues after they have become surgical pathology specimens. To date, few formal research studies have examined the prevalence of this practice or the reasoning patients' request that their specimens to be returned to them. This study interviews patients from 2015 to 2017 at one US academic medical center who requested their surgical pathology specimens. Of the 22 eligible patients, 8 patients agreed to be interviewed. Interviews lasted 10 to 30 minutes and included 5 questions. The questions were: (1) What motivated your decision to obtain your surgical pathology specimen, (2) What, if anything, did you do with your specimen, (3) What were positive aspects of your experience, (4) What were negative aspects of your experience, (5) What can the pathology department change to better support patients who request their surgical pathology specimens? Verbatim transcripts were generated and a mixed-methods analysis was performed. The type of specimens included products of conception, placenta and cord, costal cartilage and ribs, loop explant recorder, pacemaker, below knee amputation, and cervix, uterus, Fallopian tubes, and ovaries. The dominant themes included adversity, medical interest, souvenir, cultural beliefs, and curiosity. Subthemes included becoming whole in the afterlife, preservation, my body, restoration, honoring, and regret. In conclusion, pathologists can expand their role as patient advocates and advance patient-centered pathology by supporting patient's individual needs, motivations, and goals, when they request their surgical pathology specimens., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Tissue from 13 autopsy cases with invasive gastrointestinal candidiasis was studied for the binding of the pentraxins, C-reactive protein (CRP), pentraxin 3 (PTX3), and serum amyloid P component (SAP) to fungal surfaces. Invasive candidal infection was demonstrated using a hematoxylin and eosin stain and a Gomori methenamine silver stain (GMS). Immunohistochemistry was performed with CRP and PTX3 monoclonal antibodies and did not demonstrate CRP or PTX3 bound to fungi (0 of 13 cases), although CRP was extensively deposited on human tissue. A polyclonal antibody to SAP showed that SAP was bound to fungi in 12 of 13 cases. Although all three pentraxins have been reported to bind to fungi or bacteria, only SAP was bound to filamentous and yeast forms of Candida in human tissue, as detected by immunohistochemistry. SAP was abundantly present on fungi and may have affected the host innate immune response to the invading fungi.

It is a striking observation that tissue of patients invaded by the deep mycoses often lacks evidence of an inflammatory response. This lack of host response is often attributed to neutropenia secondary to chemotherapy. However, systematic studies do not support this simplistic explanation. However, invasive fungal lesions are characterized by abundant fungal functional amyloid, which in turn is bound by serum amyloid P component (SAP). We postulate that SAP is important in the local immune response in invasive fungal infections. The interaction between fungal functional amyloid, SAP, and the immune response in deep mycoses is discussed.

Background/objectives: We have demonstrated the presence of Candida cell surface amyloids that are important in aggregation of fungi and adherence to tissue. Fungal amyloid was present in invasive human candidal infections and host serum amyloid P component (SAP) bound to the fungal amyloid. SAP is a protease-resistant glycoprotein that binds avidly to amyloid and interferes with host defence, especially against bacterial pathogens for which neutrophils are important. In this study, we investigated whether biofilm of fungal amyloid and SAP was a feature of other disseminated fungal infections., Methods: Tissue specimens from 15 autopsies were systematically evaluated with multiple histochemical stains including thioflavin T and Congo red (dyes that stain amyloid), as well as antibody to SAP. We studied specimens with disseminated aspergillosis, mucormycosis and coccidioidomycosis. The structure of the lesions, host inflammatory cells and the presence of fungal amyloid and SAP were determined., Results: The structure of the lesions was characteristic in aspergillosis ('starburst') and mucormycosis (closely apposed bundles of hyphae). Host inflammatory cells were absent or few in number within these lesions. In Coccidioides lesions, host inflammation was sparse as well. Fungal amyloid was a prominent feature of all lesions along with abundant SAP bound to hyphae and spherules. Fungal amyloid and SAP perhaps contributed to persistence in caseous necrosis lesions. SAP also bound to Aspergillus and Mucorales amyloid in vitro ., Conclusions: A biofilm including amyloid and SAP is present in invasive fungal infections. This biofilm may dampen host defence leading to the characteristic sparse inflammatory reaction found in these infections.

Skeletal coccidioidomycosis is a rare complication of pulmonary coccidioidomycosis that remains incompletely characterized, and its histopathologic features have not been systematically evaluated. All skeletal coccidioidal infections (2000 to 2012) were retrieved from the University of Arizona and Mayo Clinic in Arizona pathology archives. Clinical history and histologic features were reviewed. Among 25 patients (median age 40 y; 17 men), infections involved bones (2 cases), joints (6), or both (17), usually in the distal extremities (68%), especially the wrist (32%). History included previously documented coccidioidomycosis (13), autoimmune disease (8), diabetes (6), malignancy (4), and iatrogenic immunosuppression (10). Common symptoms (median 3 mo) included pain/arthralgia (21) and swelling (10). Cultures and serology were positive in 15 of 17 (88%) and 19 of 22 patients (86%), respectively. Treatment included surgical debridement(s) and chronic antifungal medication(s). Histologic review showed granulomas in all cases, ranging from poorly to well formed, with or without necrosis. Spherule density varied widely (mean 4.8/HPF; range <0.1 to 13.5/HPF). Composition of inflammatory infiltrates, degree of necrosis, and extent of fibrosis did not significantly differ between immunocompetent and immunocompromised patients. Eosinophils were only seen in one third of cases; when present, eosinophils were almost always rare. 10 patients experienced recurrent infection, 8 of whom were immunocompromised; the remaining patients recovered. In conclusion, distal extremities are the most common sites of skeletal coccidioidomycosis encountered by surgical pathologists. This condition is strongly associated with autoimmune disorders and immunosuppression. Spherules are sometimes rare, and multiple modalities including serology, culture, and histology may be required for diagnosis.

Most pulmonary coccidioidal infections are intraparenchymal; the pleurae are rarely involved. Pleuritis is a recognized complication of ruptured cavitary infections and occasionally occurs in other settings but has not been fully characterized. To define the clinical and histopathologic characteristics of pleural coccidioidomycosis as encountered by surgical pathologists, we reviewed the clinical history, imaging, and histology of 36 biopsy-, resection-, or autopsy-confirmed cases (with coccidioidal spherules present in pleural tissue; median age, 39 years; 22 men). These represented 7% of all pulmonary coccidioidal infections and showed 2 modes of presentation, including ruptured cavitary infection (26) and pleural-predominant disease with milder parenchymal involvement (10). Risk factors included immunodeficiency, smoking, and occupational exposure to soil. Common symptoms (median, 5 weeks) included cough (47%), chest pain (44%), and dyspnea (39%). Imaging often showed pleural adhesions (64%) and effusions (61%). Treatment included lobectomy or decortication, with antifungal medications. All cases showed granulomatous pleuritis. Both modes of presentation showed similar histologic features, including the composition of inflammatory infiltrates, degree of fibrosis, and extent of necrosis. Spherules were usually few (mean density, <1/10 high-power field). Three deaths occurred (all with ruptured cavities); the remaining patients recovered. Differential diagnosis of pleural effusions should include coccidioidomycosis, particularly in endemic areas, even without significant intrapulmonary disease. Most cases of coccidioidomycotic pleuritis are encountered by pathologists after resection of ruptured cavities with decortication, but pleural-predominant infections may be biopsied for diagnostic purposes. Spherules are usually rare in pleural tissue, and liberal sampling, cultures, or serologic studies may be required to confirm the diagnosis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Many fungal cell adhesion proteins form functional amyloid patches on the surface of adhering cells. The Candida albicans Agglutinin-like sequence (Als) adhesins are exemplars for this phenomenon, and have amyloid forming sequences that are conserved between family members. The Als5p amyloid sequence mediates amyloid fibril formation and is critical for cell adhesion and biofilm formation, and is also present in the related adhesins Als1p and Als3p. We have developed a fluorescent peptide probe containing the conserved Als amyloid-forming sequence. This peptide bound specifically to yeast expressing Als5p, but not to cells lacking the adhesin. The probe bound to both yeast and hyphal forms of C. albicans. Δals1/Δals3 single and double deletion strains exhibited reduced fluorescence, indicating that probe binding required expression of these proteins. Additionally, the Als peptide specifically stained fungal cells in abscesses in autopsy sections. Counterstaining with calcofluor white showed colocalization with the amyloid peptide. In addition, fungi in autopsy sections derived from the gastrointestinal tract showed colocalization of the amyloid-specific dye thioflavin T and the fluorescent peptide. Collectively, our data demonstrate that we can exploit amyloid sequence specificity for detection of functional amyloids in situ.

Cavitary pulmonary coccidioidomycosis is a difficult diagnosis to establish due to the poor sensitivity of serological tests and rarity of culture from sputum. A pathologic and clinical analysis was performed of 21 consecutive patients with surgically resected cavities that proved to be coccidioidomycosis. Ten patients (48%) had serological evidence of Coccidioides infection, and 1 patient cultured Coccidioides spp. from sputum. The definitive diagnosis of coccidioidomycosis was made in the remaining 10 patients (48%) upon microscopic examination of tissue. The pleura showed fibrous pleuritis in 7 patients (33%) and eosinophilic pleuritis in 4 cases (19%); granulomas without microorganisms were demonstrated in 4 cases (19%). The cavity wall showed chronic inflammation and occasional giant cells but no granulomas and no microorganisms. The cavity contents included a mycetoma in 6 cases (28%); the cavity lining showed neutrophils and caseous necrosis; Coccidioides hyphae were present in 13 (62%) and spherules in 16 (76%) cases but often were rare. Adjacent lung showed lymphoid hyperplasia with chronic bronchiolitis in all cases; satellite granulomas with diagnostic spherules were variably present. The histopathology of cavitary coccidioidomycosis is strikingly variable depending on what area is sampled by biopsy, and microorganisms may be rare. This may explain the high rate of failure of diagnosis by fine needle aspiration and bronchoalveolar lavage. Pathologists in nonendemic areas must be aware of these findings, as this disease is now diagnosed worldwide., (© 2013.)

Objective: Left ventricular assist device (LVAD) experience and follow-up data in children are limited. We report the deployment and successful weaning from LVAD in young children with severe heart failure (HF)., Design: From 2004--2009, 13 children suffering from HF were placed on LVAD. All presented with a dilated left ventricle (LV) with severely reduced contractility, secondary to myocarditis, atrial arrhythmia or idiopathic HF. This study reports their outcomes and longitudinal follow-up., Results: Of 13 young children with HF (ages 1 month--6 years; mean 19.2 months) placed on LVAD: eight weaned to recovery and successful hospital discharge, one was transplanted and four died. Echo follow-up in the weaned patients (mean age 22.1 months) revealed significant improvements from pre-LVAD measurements: LV end-diastolic dimension (LVED) mean z-score decreased from +4.8 to +0.95 (P < .001); fractional shortening (FS %) improved from a mean of 9.3% to 33% (P < .001); and the degree of mitral regurgitation (MR) significantly improved (P < .05). Time to LVAD deployment from HF diagnosis was more likely to be less than 30 days in the successfully weaned patients (100%) than patients who died or were transplanted (20%); P = .007., Conclusions: LVAD support can be utilized as a bridge to recovery in young children with HF. Following LVAD weaning, children sustain improvements in LV size, function and degree of MR. LVAD deployment less than 30 days from HF diagnosis improves the likelihood of successful weaning and illustrates that children with acute etiologies of HF are more likely to achieve recovery., (© 2011 Copyright the Authors. Congenital Heart Disease © 2011 Wiley Periodicals, Inc.)

Aim: The significance of finding Candida species in heart blood cultures obtained at postmortem examination has never been studied. This article describes the findings of autopsy patients with postmortem candidaemia and it compares them with findings in autopsy patients with antemortem candidaemia., Method: 23 patients with Candida species isolated from heart blood at autopsy were identified over a 10-year period. These patients were compared with 10 autopsy patients found during the same time period with antemortem blood cultures isolating Candida species, but not positive postmortem heart blood cultures. Antemortem and postmortem records were reviewed., Results: All 23 patients with Candida species isolated from postmortem blood culture had one or more antemortem risk factors for disseminated candidiasis, such as positive antemortem blood cultures, isolation of Candida from sterile internal sites, neutropenia, recent abdominal surgery, broad-spectrum antibiotic administration or the use of central venous catheters or other invasive devices. Eight patients showed histological proof of invasive candidiasis in addition to the positive heart blood cultures. This group did not differ with respect to risk factors from 10 autopsy patients with disseminated candidiasis and antemortem blood cultures with Candida species. However, all the patients with antemortem candidaemia had histological evidence of disseminated candidiasis at autopsy., Conclusion: Candidaemia, when documented by heart blood culture performed at autopsy or by antemortem blood culture, is an insensitive, but highly specific, indicator of disseminated candidiasis.

A 79-year-old male presented with symptoms suggesting giant cell arteritis (GCA) and elevation of acute-phase reactants. Bilateral superficial temporal artery (STA) biopsies were negative for GCA. However, the right-sided biopsy showed a STA dissection. Spontaneous isolated STA dissection has never been reported previously. The pertinent available literature is also discussed.

Patients with cardiac sarcoidosis may present with clinical and morphological features similar to arrhythmogenic right ventricular dysplasia (ARVD) or cardiomyopathy (ARVC). Three cases of cardiac sarcoidosis are presented that clinically mimicked ARVD or ARVC until a pathology diagnosis of sarcoidosis was made at biopsy or autopsy. A diagnostic distinction, while often difficult to make, is important since treatment with corticosteroids may benefit those with sarcoidosis but is not expected to be useful in cases with ARVD or ARVC.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia is characterized by the progressive replacement of myocardium by fatty or fibrofatty tissue. Presenting symptoms are generally related to ventricular arrhythmias, including sudden cardiac death. Heart failure due to right ventricular and sometimes left ventricular dysfunction is uncommon in the early stages of the disease, but is known to occur in advanced cases. This case report describes identical adolescent twins with presenting symptoms related predominantly to right heart failure.

We have determined that fractal analysis of the alveolar perimeter (Df) changes with aging in human lung tissue in twenty-nine patients, age range of 25 hours to 76 years, who died of non-respiratory related causes. There was a very significant difference (p = 0.0004) in Df between the young (less than 16 years old, N = 9, mean Df of 1.047 [0.01]) and adult (greater than 16 years old, N = 20, mean Df of 1.093 [0.013]) groups. Furthermore, there was a significant difference in Df between the Adult group and the group of patients who died of chronic obstructive pulmonary disease (COPD, N = 10) (p = 0.012). Additionally, the Df values for the COPD and cystic fibrosis (CF, N = 5) groups were virtually identical; 1.061 and 1.070, respectively. Regression analysis showed a significant (p = 0.0041) exponential relationship with a correlation coefficient of 0.59 between aging and Df. We have demonstrated that the correlation between Df and aging in humans is an exponential function and that the end-stage pulmonary diseases of COPD and CF decrease Df.

Acute viral respiratory infections are commonly associated with alterations in lung growth. Recently, fractal techniques have been demonstrated to show changes in alveolar perimeter after canine adenovirus type 2 (CAV2) infection in a beagle puppy model. In the present study, we investigated whether the fractal dimension (Df) of the alveolar perimeter was changed in the acute phase (2-3 weeks after inoculation, 131d CAV2 group) or during the recovery phase (approximately 22 weeks after inoculation, 235d CAV2 group) after a single bout of CAV2. There were sham CAV2 groups, 130d and 238d controls, corresponding to the CAV2 groups. The Df of alveolar perimeter length was significantly increased in the 235d CAV2 puppies compared to all of the other beagle puppy groups. On the other hand, the fractal dimensions for alveolar perimeter length for the other beagle puppy groups were very similar. In a related human study of patients (age range of 25 h to 19 y, N = 11), who died of non-respiratory causes, showed no consistent change in Df of alveolar perimeter length with normal lung growth and development. We conclude that fractal analysis of alveolar perimeter length can be used as an index of permanent lung injury after insult to the growing lungs.

This gathering of new observations about chronic obstructive pulmonary disease, collected under the loosely defined heading of "pathology," creates a certain air of excitement. Vascular engorgement in concert with muscle contraction produces small airways narrowing in asthma, but not in chronic obstructive pulmonary disease. Stenotic small airways can be visualized in three dimensions. Fibrosis may be an integral part of emphysema, stretching its definition somewhat. Microvascular injury seems to produce emphysema. The protease-antiprotease theory of emphysema has competition from the inflammation-repair-fibrosis sequence seen in other organs. The mystery of why some smoker's lungs remain unaffected by tobacco smoke is further documented but unsolved; neuroendocrine cells and their neuropeptides may be important.

Little epidemiologic data are available on the occurrence of interstitial lung diseases (ILDs) in the general population. To describe the prevalence and incidence of ILDs a population-based registry of patients with ILDs was established in Bernalillo County, New Mexico in October 1988. All patients 18 yr of age and older who had a clinical diagnosis of an ILD were identified during the period 10/1/88 through 9/30/90 from physician referrals, hospital discharge diagnoses, histopathology reports, and death certificates. In addition, the prevalence of preclinical or undiagnosed cases was identified by screening lung specimens from 510 autopsy cases. A total of 2,936 referrals were screened; 8.8% were prevalent cases and 6.9% were incident cases. Overall, the prevalence of ILDs was 20% higher in males (80.9 per 100,000) than in females (67.2 per 100,000). Similarly the overall incidence of ILDs was slightly more common in males (31.5 per 100,000/year) than females (26.1 per 100,000/year). The estimated prevalence of preclinical or undiagnosed ILDs among all deaths was 1.8%. The most common incident diagnosed among both sexes were pulmonary fibrosis and idiopathic pulmonary fibrosis, together accounting for 46.2% of all ILD diagnoses in males and 44.2% in females. We conclude that the occurrence of ILDs in the general population may be more common than previous estimates based on selected populations, and these disorders may frequently be unrecognized.

The results of all fiberoptic bronchoscopic examinations that detected Coccidioides immitis at two medical centers in an area endemic for coccidioidomycosis were retrospectively reviewed. Coccidioides immitis was detected by cytologic examination of fluid from either bronchial wash or bronchoalveolar lavage (BAL) fluid in eight (42%) of 19 HIV-infected patients and in 11 (31%) of 35 patients without HIV infection (P = 0.627). In all cases, the fluid samples grew C. immitis. The median time to positive identification of the fungus was 25 days. Preliminary identification of C. immitis, however, took a median of 3.5 days (range, 2-9 days) in 10 patients on whom these data were available. Transbronchial biopsy was performed simultaneously in eight cases, and C. immitis was identified by morphologic examination in all eight. These results indicate that cytologic examination of bronchial wash or BAL fluid from patients with and without HIV infection is diagnostic in less than half of cases of pulmonary coccidioidomycosis. Culture of the same fluid appears to be more sensitive than cytologic examination in establishing this diagnosis.

We are reporting a case of manic depressive illness in a patient with a falxial chondroma in the right parietal region. Neurological symptoms were absent except for right hemicranial headache and examination was normal, prior to the presentation with mania. The mania responded to psychotropics. Subsequent evaluation with a head CT scan using contrast enhancement showed a 2.5 x 2 cm high density mass which on craniotomy and biopsy was noted to be a chondroma. For two years following removal, the patient remained euthymic without medication. To our knowledge, this is the fourth reported case of a chondroma in the parietal region and the first case of secondary mania associated with such a tumor.

Possible antioxidant effects of pretreatment with vitamin A on bleomycin-induced rat lung injury were studied. Intratracheal bleomycin was administered to rats pretreated with vitamin A (50,000 IU/day) or vehicle control. Analysis of bronchoalveolar lavage fluid (BAL) total and differential cell counts, lung weight, lung pathology, and alveolar macrophage superoxide anion production were performed before and at various time points after the instillation of bleomycin. Bleomycin with vehicle raised total BAL cell count and the per cent of BAL neutrophils at day 7 post injury. The percent of lung involved with pneumonitis, the lung wet weight/body weight ratio and the alveolar macrophage superoxide anion production were also increased after bleomycin alone compared to the group pretreated with vitamin A. Rats pretreated with vitamin A demonstrated a statistically significant reduction in total BAL cell count and in alveolar macrophage superoxide anion production 7 days after bleomycin compared with vehicle control. Lung wet weight/body weight ratio 7 days after bleomycin was reduced in the vitamin A treated rats. There was a trend to less pneumonitis in the vitamin A pretreated group. These data suggest that vitamin A attenuates bleomycin induced pulmonary damage by a mechanism which involves inhibition of bleomycin-induced alveolar macrophage superoxide anion production.

Acute viral respiratory infections are commonly associated with alteration in lung growth and with chronic obstructive disease. However, it is difficult to quantify these changes in lung function. We determined that the recently described techniques of fractal analysis gave additional information about the changes in lung function after viral illness compared to standard morphometric techniques. Fractal and morphometric parameters change with lung growth after acute infection with canine adenovirus type 2 (CAV2, n = 5) or no infection (controls, n = 6) in beagle puppies. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation but no emphysema in the CAV2-infected puppies. Morphometric studies at approximately 236 days of age demonstrated accelerated lung growth in the CAV2-infected dogs as evidenced by significant increases in lung volume (VL) and internal surface area (ISA). Fractal analysis showed an increased fractal dimension (Df) of the alveolar perimeter length in the CAV2 group associated with increased growth that was similar to the percentage change in VL and ISA. These data suggest that a single infection with CAV2 in beagle puppies accelerates lung growth and increases the complexity (Df) of the alveolar structure.

Beagle puppies infected with both canine parainfluenza virus type 2 (CPI2) and Bordetella bronchiseptica (Bb) develop more severe acute bronchiolitis and airways hyperresponsiveness than do those infected with CPI2 or Bb alone. The aim of our study was to characterize the inflammatory response associated with airway hyperresponsiveness, and to determine whether the inflammatory cell response of bronchoalveolar lavage fluid (BALF) reflected changes in the bronchioles in this model. We investigated 25 beagle puppies (ages 76 +/- 5 days, mean +/- SEM) in four groups: controls (n = 6), or puppies inoculated with both CPI2 and Bb (CPI2-Bb) (n = 11), with only CPI2 (n = 4), or only Bb (n = 4). The puppies were killed 3-4 days after inoculation, the lungs excised, the intermediate lobe lavaged, and BALF and the bronchiolar wall tissue examined for neutrophils and other inflammatory cells. Control puppies had no evidence of inflammation. However, the CPI2-Bb puppies had developed cough and rhinitis, positive cultures for CPI2 and Bb, and a neutrophilic cellular response in both the bronchioles and the BALF. Puppies inoculated with only CPI2 or Bb had milder illnesses and no significant bronchiolar and BALF neutrophilic response. For all groups, the severity of bronchiolar wall inflammation correlated with the total number of BALF inflammatory cells, and bronchiolar wall neutrophil counts correlated with the percentage of neutrophils in the BALF. The illness and the airway hyperresponsiveness observed in the CPI2-Bb group were associated with airway neutrophilia. Our studies support the hypothesis that neutrophils are associated with airway dysfunction in this model, and the use of BALF to study the process.

The cause of bleeding in a patient with recurrent massive hemoptysis was not apparent after bronchoscopy and gross examination of the lobectomy specimen. Histologic submission of all major bronchi uncovered dilated, tortuous bronchial arteries just below the bronchial mucosa with sites of both current and healing arterial rupture. This bronchial arterial abnormality is common to several chronic pulmonary diseases, but is rarely diagnosed as a cause of massive hemoptysis. Careful pathologic examination of major bronchi in the setting of hemoptysis of unknown causation is recommended.

We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection.

Beagle puppies develop bronchiolar inflammation and histamine hyperresponsiveness with canine adenovirus type 2 (CAV2) infections. We determined the distribution of bronchiolar lesions and correlated inflammation with virions and bronchoalveolar lavage fluid (BALF) cytology. Nineteen beagle puppies were inoculated with tissue culture fluid (control puppies, n = 8), or CAV2 (CAV2, n = 11). The puppies had clinical assessments and measurements of lung resistance (RL), and dynamic compliance (Cdyn) immediately before inoculation (Day zero) and 3 days later (Day 3). The puppies were killed on Day 3, the lungs were removed, and the right intermediate lobe was lavaged. The BALF was assessed for total and differential cell counts. Bronchiolar inflammation was quantitated by bronchiolar inflammation scores (BIS). CAV2 was localized by immunofluorescent antibody staining and electron microscopy. The control puppies remained healthy. The CAV2 puppies had positive cultures for CAV2, respiratory symptoms, and generalized necrotizing bronchiolitis. Alveolar inflammation was quantitatively less prominent than bronchiolar inflammation, and RL and Cdyn were unchanged. The BALF neutrophilia correlated with the BIS. CAV2 was present within bronchiolar epithelium, alveolar epithelial type 2 cells, neutrophils, and macrophages. CAV2 was not found in airways smooth muscles or nerves, nor in any noninflamed tissues of CAV2 puppies or in control animals. Our data suggest that acute CAV2 in beagle puppies produces an inflammation of most bronchioles. Intracellular CAV2 was found in bronchiolar epithelium, macrophages, neutrophils, and alveolar epithelial type 2 cells. Bronchiolar inflammation was reflected in BALF cytology. We conclude that bronchiolar inflammation as indicated by BIS and BALF cytology is related temporarily to histamine hyperresponsiveness in our beagle puppies.

We studied the effects of acute smoke exposure on lung permeability, eicosanoids, and inflammatory cell activity. Thirty-five New Zealand white rabbits were anesthetized, paralyzed, and exposed to 60 tidal volume breaths of diesel fuel-polycarbonate plastic smoke or sham smoke within 10 min. At 1 h postexposure the rabbits were killed and their lungs were removed for bronchoalveolar lavage (BAL) or pathologic procedures. Smoke exposure caused decreases in technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, mol. wt. 492 Da) biological half-life (t1/2), BAL plasminogen activator, and BAL leukotriene B4 (LTB4). In addition, alveolar macrophage acid phosphatase enzyme activity increased in smoke-exposed rabbits. The leukotriene synthesis inhibitor, piriprost (U-60,257), given before smoke exposure, caused attenuation of the changes in 99mTcDTPA uptake and plasminogen activator, swelling of type I alveolar cell epithelium, a large increase in lung inflammatory cells, and decreases in BAL LTB4, prostaglandin E2 (PGE2), and TxB2 (stable metabolite of thromboxane, TxA2). We conclude that changes in alveolar-capillary barrier permeability and plasminogen activator activity occur within 1 h after exposure to smoke and may play an early role in the inflammatory process associated with smoke inhalation injury. Furthermore, piriprost attenuates the smoke-induced increase in alveolar-capillary barrier permeability and decrease in plasminogen activator activity and causes a swelling of type I alveolar epithelium. However, our data suggest that neither lung eicosanoids or the alveolar macrophage lysis process plays a major role in the smoke-induced increase in alveolar-capillary barrier permeability.

Bronchoalveolar lavage (BAL) was performed in 51 adult immunocompromised patients (30 acquired immunodeficiency syndrome [AIDS] and 21 non-AIDS) as part of an extensive diagnostic evaluation for diffuse pulmonary infiltrates. Because multiple episodes occurred in several patients, a total of 60 BALs were performed. A diagnosis of fungal pneumonia was eventually made in 12 patients (24 percent). The organism was identified in BALs from seven of the 12, including five of seven cases of cocciodoidomycosis, one of two cases of aspergillosis, and one of three cases of cryptococcosis. Among the AIDS patients, only one case of coccidioidomycosis was diagnosed, whereas six such diagnoses were made from the 25 BALs performed on the 21 non-AIDS patients. This suggests that coccidioidomycosis is not as frequent an infection in AIDS patients in this endemic area as has been suggested previously. Candida-like organisms were identified in 23 BALs, but in no case were they clinically pathogenic. Their presence correlated with oral candidiasis (p = 0.01). Twenty-seven of 29 episodes related to Pneumocystis carinii were identified by Papanicolaou-stained cytocentrifuged BAL preparations, all but two of which were in AIDS patients. In addition, BALs detected six episodes of bacterial pneumonia and three of five cases of radiation pneumonitis. Overall, the diagnostic sensitivity of BAL was 52 of 60 or 87 percent. While examination of induced sputum for the presence of Pneumocystis may eliminate the need for bronchoscopy in some AIDS patients, BAL remains an excellent diagnostic procedure in the immunocompromised patient without AIDS.

Acute infection with canine adenovirus was studied in 23 specific pathogen-free outbred beagle puppies (median age = 78 days, range = 67 to 86 days) to determine its effects on pulmonary function and airway responsiveness to aerosolized histamine. The following groups were studied: uninoculated (n = 6, Control); inoculated with canine adenovirus type 2 (CAV2) (n = 11, Infected); and subclinical spontaneous infection with CAV2 (n = 6, Subclinical). While anesthetized with chloralose and mechanically ventilated, lung function and responsiveness to aerosolized histamine were measured 3 days before inoculation (Day -3), the day of inoculation (Day 0), and 3 to 4 (Day 3-4), 6 (Day 6), 8 to 10 (Day 8-10), and 12 to 14 (Day 12-14) days after inoculation. Histamine responsiveness was assessed by calculating the provocation concentration of histamine diphosphate to increase lung resistance (RL) to 150% (PC 150% RL), or decrease dynamic lung compliance (Cdyn) to 75% (PC 75% Cdyn) of the response to saline [RL(sal) and Cdyn(sal), respectively]. Arterial blood gases, functional residual capacity (FRC), specific static lung compliance (spCst), RL, Cdyn, and histamine responsiveness were not significantly different on Day 0 among the groups (p greater than 0.05). Control and Subclinical puppies remained healthy, had a mean weight gain of 0.7 kg, and did not change their histamine responsiveness during the study period. Infected puppies developed moderate to severe clinical illnesses, had poor weight gain, and were histamine hyperresponsive on Days 3-4 and 6. One infected puppy died on Day 3-4, and two died on Day 6 of their illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Histamine hyperresponsiveness with viral bronchiolitis may depend on previous exposures to viruses or to other pathogens. We studied 32 outbred beagle puppies 80 to 155 days of age who were raised in isolation and who were specific pathogen-free. Puppies were inoculated with canine parainfluenza type 2 (CPI2, n = 8), Bordetella bronchiseptica (Bb, n = 7), or both CPI2 and Bb (CPI2-Bb, n = 9). Control puppies (C, n = 8) were not inoculated. The puppies were anesthetized with sodium thiopental (5 mg/kg) and chloralose (80 mg/kg) and were ventilated mechanically. Lung resistance (RL), dynamic lung compliance (Cdyn), functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured 3 days prior to inoculation (Day -3), on the day of inoculation (Day 0), and on Days 3-4, 6, 8-10, and 12-14 after inoculation. Histamine responsiveness was measured as: (1) the concentration of histamine base that increased RL to 150% (PC 150% RL) or decreased Cdyn to 75% (PC 75% Cdyn) of the response to saline (RL sal and Cdyn sal, respectively), and (2) the change in RL or Cdyn after inhalation of 11 mg/ml of histamine when compared with RL sal and Cdyn sal. On Day 0 there were no significant (p greater than 0.05) differences among groups with regard to age-corrected weights, FRC, RL, Cdyn, or histamine responsiveness. Control puppies remained healthy, and their pulmonary function and histamine responsiveness did not change. CPI2-Bb puppies increased RL and decreased FRC on Day 3-4, and were moderately ill and histamine-hyperresponsive on Day 3-4 and on Day 6.(ABSTRACT TRUNCATED AT 250 WORDS)

A surfactant-depletion lung-injury model was produced in 37 New Zealand white rabbits by saline lavage. During the next 2 to 3 h, rabbits were ventilated with conventional mechanical ventilation (CMV, group 1), high-frequency jet ventilation (HFJV, group 2), or CMV for 1 h followed by HFJV for 2 h (CMV/HFJV, group 3). Survival until planned termination of the protocol was 56%, 77%, and 63% in groups 1, 2 and 3, respectively. Causes of early demise were usually pneumothorax or metabolic acidosis. There were no statistically significant differences among the groups with respect to survival, incidence of pneumothorax or metabolic acidosis. Arterial oxygenation was more efficient with HFJV (group 2) (P[A-a]O2 = 372 +/- 51 torr [mean +/- SE] at 2 h) than with CMV (group 1) (P[A-a]O2 = 512 +/- 18 torr at 2 h, p less than .01). Furthermore, oxygen gas exchange in 3 of 5 group 3 rabbits improved after institution of HFJV. In contrast to previous findings with high-frequency oscillation (HFO), there were no qualitative histologic differences between lungs ventilated with HFJV vs. CMV. Thus, although HFJV produced more efficient gas exchange in this model, it did not improve pulmonary pathology. HFO may be preferable to HFJV in infant respiratory distress syndrome.

New Zealand white rabbits were evaluated for recovery from paraquat induced pneumonitis six weeks after the last exposure. The animals were exposed to a respirable aerosol of 100 ml distilled water or 250 mg paraquat in 100 ml distilled water. Blood gases, breathing frequency, and body weights were recorded before and at regular intervals after exposure. Groups included control and two paraquat exposures (separated by a five day interval). Morphometric and pathological measurements were made at death either three days or 42 days after the second exposure. The animals killed three days after the second exposure showed hypoxia, decreased breathing frequency, decreased body weight, increased A-aO2 gradient, decreased per cent macrophages in bronchoalveolar lavage fluid, increased per cent neutrophils in bronchoalveolar lavage fluid, increased lung weight, and reduced lung volume compared with animals allowed to recover. None of these measures differed between control animals and animals allowed to recover, except that animals exposed to paraquat had significantly increased lung volume and lung weights. Pathological changes noted three days after two exposures were no longer found six weeks after exposure. It is concluded that rabbits exposed to paraquat aerosol develop a severe pneumonitis that resolves if exposure is stopped and recovery time is allowed; physiological abnormalities remain, however.

A 24 year old man had a nonproductive cough and chest pain. Chest roentgenogram showed a diffuse infiltrate, and pulmonary function studies showed restrictive lung disease. Extremity weakness, deteriorating mental status and neuropathy progressed as pulmonary findings diminished on corticosteroid therapy. Lung biopsy showed lymphomatoid granulomatosis. The neurologic status deteriorated despite treatment with Cytoxan, intrathecal methotrexate and brain irradiation. Autopsy showed mass lesions of lymphomatoid granulomatosis in the brain and healed lesions in the lungs. A review of the neurologic and pulmonary findings in reported cases show that diminution of pulmonary disease with progression of neurologic disease manifest by mass lesion is unusual. Since the etiology, prognosis and prevalence of this disease remains undefined, all patients with this disease should be reported on.