Biomedical subjects

R E Stanford

Publications and source records attributed to R E Stanford.

At least 19 recordsLinked to original sources

PubMed1987

Mild emphysema is associated with reduced elastic recoil and increased lung size but not with air-flow limitation.

Thirty-nine excised human lungs were examined to identify early changes in the small airways, their size distribution, and their elastic recoil in relation to mild degrees of emphysema. Elastic recoil measurement, single-breath nitrogen (SBN2) tests, and FEV1 were obtained from 18 lungs with no emphysema and 21 emphysematous lungs with no greater than Grade 5 emphysema score. The mean number of alveolar attachments per brochiole was determined from all the bronchioles cut in cross section. When the 2 groups of lungs were compared, the percentage of predicted elastic recoil of the nonemphysematous lungs was significantly greater at 50, 70, 80, and 90% of TLC than in the mildly emphysematous lungs. The TLC of the emphysematous lungs (% of predicted) was also significantly greater than in the nonemphysematous lungs. Pigment of the small airways was the only pathologic feature that was significantly greater in the emphysematous lungs than in the nonemphysematous lungs. Size distribution in the small airways was similar except for the airways zero to 0.2 mm, which were more frequent in the emphysematous lungs. When data from both groups were combined, elastic recoil was shown to be related to both the number of alveolar attachments (p less than 0.03) and the mean diameter of the small airways (p less than 0.01). We conclude that structural and functional changes in lungs with mild emphysema include reduced elastic recoil, increased lung size, and some size distribution changes in the small airways. Mild emphysema is not associated with air-flow limitation.

Airway Resistance↗

PubMed1987

Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy.

Analysis of bronchoalveolar lavage cellular constituents has been recommended as a valuable method for the characterization of the inflammatory cellular population and for studying cellular interactions in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF). However, the clinical relevance of the enumeration of cells in bronchoalveolar lavage fluid (BALF) from patients with IPF remains controversial. We therefore examined the correlations between BALF cellular constituents and both the histopathologic abnormalities and the subsequent clinical response to corticosteroid therapy in 26 newly diagnosed, untreated patients with IPF. The BALF lymphocytosis was associated with moderate-to-severe alveolar septal inflammation (p less than 0.0005) and with a relative lack of histologic honeycombing (p less than 0.05). On the other hand, BALF neutrophil and eosinophil contents did not significantly correlate with any of eleven particular histopathologic abnormalities, and BALF neutrophil and lymphocyte contents did not correlate with the degree of clinical impairment (quantitated by a composite score based on dyspnea, radiographic abnormalities, and physiologic impairment) upon presentation. However, BALF eosinophil content correlated significantly with the severity of clinical impairment, higher eosinophil counts being associated with more severe initial clinical impairment (p less than 0.01). Neither pretreatment BALF neutrophil nor eosinophil content was related to the frequency or magnitude of subsequent clinical change in 20 patients evaluated before and after 1 yr of corticosteroid therapy. In contrast, pretreatment BALF lymphocytosis was associated with significant subsequent clinical improvement (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗

PubMed1986

Bronchoalveolar lavage fluid neutrophils increase after corticosteroid therapy in smokers with idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) are often cigarette smokers and are often being treated with corticosteroids at the time of bronchoalveolar lavage. We addressed the question of whether or not the bronchoalveolar lavage fluid (BALF) neutrophil content of patients with IPF undergoes changes in smokers different from those in nonsmokers after institution of corticosteroids. Eighteen patients were studied (10 smokers and 8 nonsmokers). Fourteen patients (6 smokers and 8 nonsmokers) were treated orally with prednisone. The histologic assessment of alveolar inflammation and inflammatory small airways disease was no different in smokers than in nonsmokers. None of the smokers treated with prednisone had pathologic evidence of emphysema in addition to IPF. Five of 6 smokers showed an increase in BALF neutrophils after 3 months of prednisone (p less than 0.05), whereas the nonsmokers' BALF neutrophils decreased or remained unchanged. This increase in BALF neutrophils in smokers was not associated with concomitant or subsequent clinical deterioration but, in fact, with clinical improvement after 3 months of therapy. These data indicate that the combination of cigarette smoking and corticosteroid therapy influences the BALF neutrophil content in patients with IPF and suggest that interval changes in BALF neutrophil content may not reflect the status of the inflammatory process or structural derangements in the lungs of some patients with IPF.

Aged↗

PubMed1986

Radial traction and small airways disease in excised human lungs.

We studied 47 excised human lungs in order to examine the relationship between the number of alveolar attachments surrounding bronchioles 2 mm or less in diameter and the presence of small airways disease and overall lung function. Expiratory pressure-volume curves, the FEV1, and the single-breath nitrogen washout were obtained from 11 lungs without emphysema and 36 lungs with various degrees of emphysema. The lungs were subsequently inflation-fixed at 20 cm H2O. Gough sections were used to measure emphysema. Six to 10 blocks of tissue were cut at random from a midsagittal slice of lung tissue for the small airways and alveolar attachment study. We measured the inside diameters of all nonrespiratory bronchioles (2 mm or less in diameter) and made corrections for shrinkage during processing. The number of alveolar attachments on the outside wall of the bronchioles cut in cross section were obtained from all the sections observed. The mean number of alveolar attachments per bronchiole was determined for each lung. The histopathologic features of the bronchioles were evaluated by the method of Cosio and coworkers (2). We found a positive correlation between the number of alveolar attachments and the percentage of predicted FEV1 (r = 0.328, p less than 0.03) and the percentage of predicted closing capacity (r = 0.553, p less than 0.01). There was a negative correlation of the mean number of alveolar attachments and the small airways fibrosis score (r = -0.344, p less than 0.02). A correlation also existed between the number of alveolar attachments and the mean internal bronchiolar diameter (r = 0.561, p less than 0.001). We conclude that the alveolar attachments and elastic recoil are related to the size and function of the small airways.

Bronchi↗

PubMed1986

A clinical, radiographic, and physiologic scoring system for the longitudinal assessment of patients with idiopathic pulmonary fibrosis.

In order to develop a reproducible, quantifiable means of assessment of the clinical status of patients with idiopathic pulmonary fibrosis (IPF), a composite clinical-radiographic-physiologic (CRP) scoring system was devised, using 7 variables: dyspnea, chest radiograph, spirometry, lung volume, diffusion capacity, resting alveolar-arterial PO2, and exercise O2 saturation. To assess this scoring system, we examined the relationships between CRP scores and histopathologic findings, including a cellular pathology score composed of abnormalities deemed to be potentially reversible, a fibrotic pathology score based on abnormalities felt to be essentially irreversible, and an index of overall pathologic derangement (total pathology score), derived from the sum of the cellular and fibrotic scores. The initial CRP determination at the time of open lung biopsy correlated significantly with the total pathology score (r = 0.61, p less than 0.001). The CRP score determined after 6 months of corticosteroid therapy showed a significant correlation with the fibrotic pathology score present on open lung biopsy (r = 0.76, p less than 0.001). The change in CRP after 6 months of corticosteroid therapy tended to reflect the cellular histopathologic component of the open lung biopsy (r = -0.43, p less than 0.10). Moreover, in none of these relationships did any individual component of the CRP score correlate better with the respective histopathologic index than did the CRP score itself. These data suggest that this CRP score is useful for the estimation of the severity of underlying pathologic derangement and for the longitudinal quantitative assessment of clinical impairment in patients with IPF.

Adult↗

PubMed1979

The elastic properties of lobes of excised human lungs.

Static pressure-volume curves were obtained from the upper and lower lobes of 5 excised human lungs. Comparison of the upper and lower lobe pressure-volume curves showed a small but significant difference. The upper lobes contained a greater percentage of total lobar capacity above approximately 80 per cent of the lung volume. It would thus appear that the difference in lobar elastic properties could influence ventilation distribution in normal humans.

Adult↗

PubMed1979

Abnormalities in lung elastic properties and surfactant function in adult respiratory distress syndrome.

We have examined the lungs from five patients who died with the adult respiratory distress syndrome (ARDS). Pressure volume curves were obtained and bronchoalveolar lavage fluid was studied on a surface balance. The pressure volume curves revealed reduced compliance compared to normal or near normal lungs. A significant loss of volume was also found. The data obtained from the surface balance studies show a normal range of minimum surface tension when compared to "normals," but the ARDS lung lavage fluid revealed an increase in surface film compressibility relative to "normal." The increased compressibility may be an important factor contributing to the stiff lungs of patients with the adult respiratory distress syndrome.

Adult↗

PubMed1978

Circulating immune complexes in the idiopathic interstitial pneumonias.

We determined circulating immune complex levels and their correlation with pulmonary histopathology, immunofluorescence and steroid responsiveness in 24 patients with idiopathic interstitial pneumonias. Levels were elevated in all but three of 16 patients with cellular disease, but in none of eight with diffuse fibrosis (P less than 0.001). Granular deposition of IgG, usually with elevated levels, but in only 11 per cent of those with normal levels (P less than 0.001). The radiographic and physiologic response to corticosteroid therapy was better in patients with initially elevated levels than in those with normal levels (P less than 0.03). Circulating immune complexex are present in patients with cellular idiopathic interstitial pneumonias, have a pathogentic role in this disease and may identify a patient population that is potentially steroid responsive.

Adrenal Cortex Hormones↗

PubMed1978

Acute nephritis and pulmonary alveolitis following pneumococcal pneumonia.

Acute glomerulonephritis developed in a man with pneumococcal pneumonia. Serum complement studies revealed decreased levels of C4, properdin, and C3. Renal immunofluorescence studies demonstrated pneumococcal antigen, C1q, C4, C3 proactivator, properdin, C3, IgG, and IgM. Circulating cryoglobulin contained pneumococcal antigen and antibody, C3, and immunoglobulins. Serial pneumococcal antigen and antibody levels did not display patterns that were characteristic of classical immune elimination, but the patterns may have been influenced by the reentry of antigen. A diffuse, pulmonary alveolitis also developed in the patient. Lung immunofluorescence studies revealed pneumococcal antigen, IgG, and C3 in alveolar walls and capillary basement membranes. The glomerulonephritis and alveolitis resolved after a prolonged course. These findings provide presumptive evidence for pneumococcal, immune complex glomerulonephritis with complement activation via both classical and alternative pathways and suggest an immunologic pathogenesis for the pulmonary alveolitis.

Adult↗

PubMed1978

Immunofluorescent patterns in the idiopathic interstitial pneumonias.

Immunologic mechanisms have been implicated in the pathogenesis of the IIP's. Thirty five patients with IIP were divided into three groups: group I, seven subjects with DIP; group II, thirteen with UIP; and group III, fifteen with mural fibrosis. Lung biopsies were exposed to fluorescein-conjugated antisera to IgG, IgA, IgE, IgM, C3, fibrinogen, and albumin. In group I, all patients demonstrated IgG and C3 in a granular pattern lining alveolar walls. Similarly, in group II, all had IgG and 10 had C3 within alveolar walls. In contrast, only two group III subjects demonstrated IgG and none C3. Only one of 19 control subjects hav alveolar wall immunoglobulin and C3 deposition. The incidence of positive rheumatoid and antinuclear factors was similar in all three study groups. These data suggest that immune complex deposition may play a role in the pathogenesis of the cellular interstitial pneumonias and that once mural fibrosis supervenes, these complexes are no longer present.

Adult↗

PubMed1977

Effect of increased static lung recoil on ventilation distribution in excised human lungs.

The contour of a modified Fowler single-breath nitrogen washout was determined in 15 postmortem human lungs before and after static lung recoil had been increased by ventilation. Before ventilation, expiratory nitrogen versus volume curves exhibited the 4 phases similar to those seen in intact human lungs. The tests were repeated after ventilation with humidified air at room temperature for 3 hours at pleural pressures between -20 and +10 cm H2O at 15 breaths per min. After ventilation, the slope of the alveolar plateau (Phase III) decreased (P less than 0.01); the volume of Phase IV increased (P less than 0.01); and the closing capacity (Phase IV plus minimal volume) decreased (P less than 0.01). The data suggest that in the human lung the onset of Phase IV is not solely dependent on a pleural pressure gradient and that after ventilation, when static lung recoil is increased, the distribution of inspired gas in the excised human lung is more uniform, and at least some lung units empty more completely before zero transpulmonary pressure is reached.

Adult↗

PubMed1976

Interstitial lung disease in polymyositis and dermatomyositis: analysis of six cases and review of the literature.

Interstitial pneumonitis may be the presenting manifestation of polymyositis-dermatomyositis, or may occur later in the evolution of the disease. The clinical picture is characterized by non-productive cough, dyspnea and hypoxemia. The chest radiograph demonstrates interstitial infiltrates with predilection for the lung bases, often with an alveolar pattern in addition. The histopathologic features are those of organizing and interstitial pneumonitis and pleuritis, with variable fibrosis. In the present series, the patients with mixed alveolar and interstitial infiltrates on chest radiograph and organizing pneumonia and bronchiolitis obliterans in addition to interstitial pneumonitis. In one patient evolution from pulmonary inflammation to interstitial fibrosis was demonstrated. The etiology of primary lung disease in PM-DM is not known, but cell-mediated autoimmunity to an unidentified component of lung tissue is suggested. Including the present series, 50 percent of patients have responded favorably to corticosteroids with decreased dyspnea, clearing of the chest radiograph and improved pulmonary function tests.

Adult↗

PubMed1976

Prognosis after recovery from adult respiratory distress syndrome.

Ten patients who survived an acute episode of the adult respiratory distress syndrome were studied on recovery. Serial pulmonary function tests performed in 3 subjects revealed a tendency toward normalization of values at 4 to 6 months after the episode, with a subsequent serial decrease in maximal mid-expiratory flow rates, and a partial reversal by bronchodilators. Of the 10 patients, 6 had dyspnea on exertion and all but one of the 6 were smokers. The ventilatory tests revealed a predominantly restrictive pattern in 2 patients and an obstructive pattern in 4. The 4 asymptomatic patients had essentially normal pulmonary function. Pathologic features of the lung, available in 3 cases, are discussed.

Adolescent↗

PubMed1976

The morphologic features of the bronchi, bronchioles, and alveoli in chronic airway obstruction: a clinicopathologic study.

A 6-year semiquantitative clinicopathologic study revealed that among 196 men and 46 women 40 or more years of age at death, the severity of destructive emphysema was overwhelmingly the most important morphologic correlate of the clinical state of chronic airway obstruction. The pathogenic mechanisms whereby emphysema may lead to airway obstruction are probably multifactorial, but our data are consistent with a growing consensus that loss of small airway support by surrounding lung tissue in emphysema may cause kinking, tortuosity, and collapse of the airways, with subsequent increased airflow resistance and clinical obstruction. Pathologic changes (inflammation, fibrosis, increased goblet cells, and mucous gland enlargement) in large or small airways in the absence of much emphysema were very seldom associated with significant chronic airway obstruction, and correlated rather poorly with chronic airway obstruction, regardless of severity of emphysema. A subjective method of evaluating mucous gland enlargement in the large airways was consistently better than the Reid Index in correlations with clinical and anatomic abnormalities, presumably because it took all glands into consideration. The clinical features of subjects with severe centrilobular versus severe panlobular emphysema were essentially the same. "Blue bloater" and "pink puffer" clinical types of chronic airway obstruction continued to reveal differences in airway pathologic features, but no longer revealed a major difference in the severity of emphysema at the time of death. Presumably this was due, at least partially, to improved treatment, longer survival, and fusion into a similar end-stage. The total exposure to cigarette smoke was quantitatively related to clinical chronic airway obstruction and to both alveolar and airway pathologic features.

Aged↗

PubMed1976

The right ventricle in chronic airway obstruction: a clinicopathologic study.

In men 40 or more years of age at death, the upper limits of normal (means plus 2 SD) cardiac ventricular weights were 69 g for the right ventricle and 203 g for the left ventricle plus septum. Right ventricular thickness, as usually determined at autopsy, was a relatively poor index of hypertrophy. When one ventricle hypertrophies as a result of stress, the other tends to enlarge simultaneously, even if no stress on it has been evident. Right ventricular weight correlated positively, although not strongly, with severity of emphysema and with the severity of clinical chronic airway obstruction. Correlations between right ventricular weight and pathologic changes in the airways were weak or absent, except that subjects with abnormal large airways, but normal small airways, showed improved correlation between severity of emphysema and right ventricular hypertrophy, compared with the entire series. There was no correlation between left ventricular weight and severity of emphysema. The electrocardiogram was very reliable in the diagnosis of right ventricular hypertrophy (corpulmonale) due to chronic airway obstruction; the chest roentgenogram was somewhat less sensitive in this regard.

Cardiomegaly↗

PubMed1976

Unsuspected pulmonary alveolar proteinosis complicating acute myelogenous leukemia.

A patient with acute myelogenous leukemia developed pulmonary alveolar proteinosis in the terminal phase of the leukemia. The diagnosis of pulmonary alveolar proteinosis was unsuspected during life and was established only at autopsy. Other reported cases of the same association are reviewed. This report serves to stress the importance of considering the diagnosis of pulmonary alveolar proteinosis in malignant hematologic diseases and the need for hematologic evaluations in pulmonary alveolar proteinosis.

Autopsy↗

PubMed1976

Interstitial pneumonia in angio-immunoblastic lymphadenopathy with dysproteinemia. A case report with special histopathologic studies.

A patient presented with characteristic historical, physical, and laboratory findings of angio-immunoblastic lymphadenopathy with dysproteinemia. This newly described entity apparently represents a nonneoplastic proliferation of the B-lymphocyte system with immunoblastic transformation of many lymphocytes and excessive production of immunoglobulins. It is associated with fever, sweats, weight loss, skin rash, lymphadenopathy, splenomegaly, hepatomegaly, and characteristic histologic features of the involved lymph nodes. Noteworthy in the patient reported here are the extent and course of radiographically and clinically evident pulmonary involvement and the biopsy documentation of an interstitial pneumonia marked by histopathologic changes closely resembling those found in the lymph nodes, with immunohistologic demonstration of immunoglobulins in the alveolar walls.

Aged↗

PubMed1976

Leukocytoclastic vasculitis.

Patients with leukocytoclastic vasculitis have purpuric, palpable lesions, most commonly on the lower part of the legs. Systemic involvement, particularly of the kidneys, is found frequently. Characteristic pathological features include necrosis of small vessels within the dermis, infiltration by polymorphonuclear leukocytes within and around the vessel walls, hemorrhage, and occasionally thrombosis. Immunofluorescence study frequently shows granular deposits of immunoglobulins and complement in vessel walls. Etiologic agents that have been implicated include infection, foreign proteins, chemicals, drugs, and a variety of diseases. The mechanism causing tissue damage is thought to be mediated by immune complexes, although specific antigens have only occasionally been unequivocally identified. Treatment includes bedrest, corticosteroids, and sometimes, cytotoxic agents.

Animals↗