Pulmonary macrophage function during experimental cytomegalovirus interstitial pneumonia.

Since cytomegalovirus (CMV) infections may alter host defense against a variety of pathogens, phagocytosis, oxygen uptake, and H2O2 release by pulmonary macrophages obtained from guinea pigs with acute CMV interstitial pneumonia were evaluated. Experimental animals were inoculated subcutaneously on day zero with 10(7.5) 50% tissue culture infective doses of virulent guinea pig CMV. Control animals received an uninfected salivary gland suspension. The animals were sacrificed on day 7; the tissues were cocultivated for virus isolation, and the lungs were lavaged to obtain pulmonary macrophages. CMV was isolated from buffy coat cells (96%), bone marrow cells (71%), whole lungs (77%), pulmonary macrophages (60%), and pulmonary granulocytes (49%). There was no significant difference between groups at sacrifice in the total number of macrophages obtained by pulmonary lavage or in the phagocytic activity of the macrophages in vitro. However, in CMV-infected animals, the maximum rates of O2 consumption in response to the soluble stimulus, phorbol myristate acetate, and the particulate stimulus, Staphylococcus aureus, were 47 and 55%, respectively, of the rates in uninfected controls. Total macrophage O2 consumption in CMV-infected animals was 32 and 37%, respectively, of control values in response to the same stimuli. In CMV-infected animals, the maximum rates of H2O2 release were 22% of those in simultaneous controls for both stimuli, and total H2O2 release was 30 and 25%, respectively, of that in controls in response to these stimuli. Such alterations in macrophage oxidative function may contribute to superinfection during CMV pneumonia.     

Pulmonary interstitial fibrosis from paraquat in the hamster.

The effects of paraquat in hamsters were evaluated to find a rodent model of interstitial pulmonary disease free from spontaneous infection. Because the repeated doses necessary to produce chronic lung injury suggested hypersensitivity mechanisms, concurrently administered Freund adjuvant and adenocorticotrophic hormone (ACTH) were tested separately. Effects were measured by mortality, change in body weight, and morphometric estimate of lung injury. Findings were as follows: (1) only repeated doses in a very narrow range produced chronic interstitial injury; (2) ACTH clearly protected animals from the general systemic and pulmonary effects of paraquat; and (3) adjuvant specifically protected against the pulmonary injury alone. There was no evidence of immunologic contribution to paraquat injury.     

Pulmonary hypertension and interstitial fibrosis in von Recklinghausen neurofibromatosis

Neurofibromatosis von Recklinghausen (NFvR) has been reported to be associated with diffuse interstitial pulmonary fibrosis. We describe a patient with NFvR presenting in middle age with dyspnea and cyanosis. Chest radiographs showed right ventricular enlargement, dilated proximal pulmonary arteries, and bilaterally increased interstitial markings. Cardiac catheterization showed moderately severe pulmonary hypertension and no evidence of congenital heart defect. The interstitial fibrosis associated with NFvR can result in symptomatic pulmonary hypertension.     

Non-linear dependence of interstitial fluid pressure on joint cavity pressure and implications for interstitial resistance in rabbit knee

AIMS: Synovium retains lubricating fluid in the joint cavity. Synovial outflow resistance estimated as dPj/dQs (Pj, joint fluid pressure and Qs trans-synovial flow) is greater, however, than expected from interstitial glycosaminoglycan concentration. This study investigates whether subsynovial fluid pressure increases with intra-articular pressure, as this would reduce the estimated resistance estimate. METHODS: Interstitial fluid pressure (Pif) was measured as a function of distance from the joint cavity in knees of anaesthetized rabbits, using servo-null pressure-measuring micropipettes and using an external 'window'. Joint fluid pressure Pj was either endogenous (-2.4 +/- 0.4 cmH2O, mean +/- SEM) or held at approximately 4, 8 or 15.0 cmH2O by a continuous intra-articular saline infusion that matched the trans-synovial interstitial drainage rate. RESULTS: At endogenous Pj the peri-articular Pif was subatmospheric (-1.9 +/- 0.3 cmH2O, n = 19). At raised Pj the Pif values became positive. Gradient dPif /dx was approximately 20 times steeper across synovium than subsynovium. Pif close to the synovium-subsynovium border (Pif*) increased as a non-linear function of Pj to 1.4 +/- 0.2 cmH2O (n = 23) at Pj = 4.3 +/- 0.1 cmH2O : 2.3 +/- 0.2 cmH2O (n = 17) at Pj = 7.6 +/- 0.2 cmH2O: and 3.0 +/- 0.4 cmH2O (n = 26) at Pj = 15 +/- 0.2 cmH2O (P = 0.03, anova). CONCLUSIONS: Synovial resistivity is approximately 20x subsynovial resistivity. The increase in Pif*with Pj means that true synovial resistance d(Pj-Pif*)/dQs is overestimated 1.5x by dPj/dQs. This narrows but does not eliminate the gap between analysed glycosaminoglycan concentration, 4 mg ml(-1), and the net interstitial biopolymer concentration of 11.5 mg ml(-1) needed to generate the resistance.     

Pulmonary interstitial edema and hyaline membranes in adult burn patients. Electron microscopic observations

Pulmonary insufficiency has become a major problem in the care of patients with extensive cutaneous burns and other forms of trauma. Although a variety of pathological changes have been described in the lungs of such patients, probably the most common underlying lesion is interstitial edema with the development of hyaline membranes. Previous light microscopic investigations have shown that interstitial edema with hyaline membrane development is a nonspecific pulmonary reaction that occurs in many conditions and in response to a variety of stimuli. In this study, postmortem electron microscopic observations on the lungs of six burn patients with the lesion are described. Interstitial edema of the alveolar wall was marked and involved primarily the thick portion of the air-blood membrane. The thin portion of the membrane, where epithelial and endothelial basement membranes are normally in close proximity, did not demonstrate accumulation of edema fluid. There was widespread necrosis of the alveolar epithelium. Cellular debris from necrotic alveolar epithelium and fibrin-like material formed a layer that corresponded to the hyaline membranes observed by light microscopy. Hyaline membranes occurred both with and without edema of the underlying interstitium, seemingly indicating that interstitial edema per se was not solely responsible for the epithelial necrosis and resulting hyaline membranes. Evidence of alveolar epithelial regeneration was also found. The regenerated cells had the appearance of type II alveolar cells (granular pneumocytes), which are thought to be the reserve cells of the alveolus. Changes in the alveolar capillaries were minimal. This was a surprising finding, since changes in the interstitium suggested an altered capillary permeability. However, the possibility that endothelial injury had occurred early in our patients and was repaired by the time of their demise could not be ruled out. Futher ultrastructural studies are needed to describe the sequential development of the lesion and to compare the trauma-related lesion with the interstitial edema-hyaline membrane pattern in other clinical and experimental settings.     

Pulmonary interstitial macrophages: isolation and flow cytometric comparisons with alveolar macrophages and blood monocytes

Pulmonary interstitial macrophages (IM) were isolated from rat lungs by an Fc gamma receptor-based affinity technique coupled with multiparameter flow cytometry. Single cell suspensions obtained by collagenase digestion of extensively perfused and lavaged lungs were applied to carpets of opsonized sheep red blood cells (SRBC-IgG) bound to plastic tissue culture flasks. At 0-4 degrees C, optimal binding of lung cells occurred within 60 min at plating densities of 1-2 X 10(6) lung cells/cm2 when the SRBC substrate was opsonized with 10 micrograms/ml anti-SRBC IgG. Nonadherent cells were removed by gently rinsing the plates and adherent cells were recovered by lysing the SRBC-IgG substrata. By light microscopy, the mixture of adherent cells was comprised of mononuclear cells (approximately 54%), many of which appeared to be macrophages, lymphocytes (approximately 20%), polymorphonuclear leukocytes (approximately 15%), plasma cells (approximately 8%), eosinophils (approximately 2%), and mast cells (approximately 0.5%). The cells which adhered to the SRBC-IgG monolayers were further resolved into subpopulations by multiparameter flow cytometry and sorted according to their electro-optical characteristics. One subpopulation appeared morphologically to be macrophages, and greater than 90% of these cells readily phagocytized SRBC-IgG in vitro. Peroxidase staining of this population was minimal, indicating that these cells were not blood monocytes (BM). Using a method by which alveolar macrophages (AM) were prelabeled with SRBC-IgG in situ, we demonstrated that alveolar macrophages constituted only approximately 5% of the total adherent cell population. We concluded from these observations that the macrophage population harvested in this manner were neither BM nor AM, but, rather, were harvested from the lung's interstitial compartment. Flow cytometric analyses indicated that the IM exhibited electro-optical characteristics intermediate between those of BM and AM, which is consistent with the concept of the lung's interstitium as a maturation compartment for the BM prior to migration into the alveolar compartment. However, the IM more closely resembled the BM than the AM, indicating that if the IM is in fact a precursor to the AM population, substantial maturation or differentiation must occur subsequent to its migration into the alveolar compartment. This isolation technique will be useful for harvesting highly purified IM for in vitro investigations.     

Non‐linear dependence of interstitial fluid pressure on joint cavity pressure and implications for interstitial resistance in rabbit knee

Aims: Synovium retains lubricating fluid in the joint cavity. Synovial outflow resistance estimated as dP_j/d (P_j, joint fluid pressure and trans‐synovial flow) is greater, however, than expected from interstitial glycosaminoglycan concentration. This study investigates whether subsynovial fluid pressure increases with intra‐articular pressure, as this would reduce the estimated resistance estimate. Methods: Interstitial fluid pressure (P_if) was measured as a function of distance from the joint cavity in knees of anaesthetized rabbits, using servo‐null pressure‐measuring micropipettes and using an external ‘window’. Joint fluid pressure P_j was either endogenous (?2.4 ± 0.4 cmH₂O, mean ± SEM) or held at ～4, 8 or 15.0 cmH₂O by a continuous intra‐articular saline infusion that matched the trans‐synovial interstitial drainage rate. Results: At endogenous P_j the peri‐articular P_if was subatmospheric (?1.9 ± 0.3 cmH₂O, n = 19). At raised P_j the P_if values became positive. Gradient dP_if /dx was ～20 times steeper across synovium than subsynovium. P_if close to the synovium–subsynovium border () increased as a non‐linear function of P_j to 1.4 ± 0.2 cmH₂O (n = 23) at P_j = 4.3 ± 0.1 cmH₂O : 2.3 ± 0.2 cmH₂O (n = 17) at P_j = 7.6 ± 0.2 cmH₂O: and 3.0 ± 0.4 cmH₂O (n = 26) at P_j = 15 ± 0.2 cmH₂O (P = 0.03, anova ). Conclusions: Synovial resistivity is ～20× subsynovial resistivity. The increase in with P_j means that true synovial resistance d()/d is overestimated 1.5× by dP_j/d. This narrows but does not eliminate the gap between analysed glycosaminoglycan concentration, 4 mg ml^?1, and the net interstitial biopolymer concentration of 11.5 mg ml^?1 needed to generate the resistance.     

本院近两年肺结核患者抗结核药物的耐药性调查

目的探讨肺结核的耐药性特点。方法对我院2004年9月～2006年9月期间就诊的肺结核患者51例的药物敏感性结果进行回顾性分析。结果肺结核患者初始耐药性为20.0%,继发耐药率为90.5%,总耐药率为49.0%;初始祖耐多药率为3.3%,复治组为19.0%,总耐多药率为9.8%。结论近年来肺结核患者耐药率较高,应重视对抗结核药物的耐药性监测,以便了解耐药趋势;并应加强肺结核患者的管理,合理用药以减少耐药的发生。     

循经低流阻通道组织液压的初步观察

目的 测量循经低流阻通道与周围的组织液压,观察其差异及变化情况。方法 在麻醉的小型猪上,使用连续流阻测量仪测出低流阻点和非低流阻点,然后采取针中芯方法测量组织液压。结果 统计结果表明,小型猪胃经、肾经和任脉的低流阻通道平均压力均显著低于旁开的高流阻区域,其压力差分别为1.06、0.70、3.69 mmHg（1 mmHg=0．133 kPa）,总压力差为1.44 mmHg,压力梯度为1.44~2.88 mmHg/cm。在一些低流阻点上发现了与呼吸频率一致的压力波。结论 外周皮下组织中存在着指向经脉低流阻通道的压力差,可能构成组织液向经脉流动的动力。     

Pulmonary metastasis of epidermoid carcinoma of the larynx: a case with an interstitial pattern of growth

We describe a pulmonary metastasis from a laryngeal epidermoid carcinoma, characterized by an interstitial pattern of growth. The patient, a 71-year-old man, smoker, presented with a large laryngeal neoplasm and with two pulmonary masses, one located in the apex and the other in the lower lobe of the right lung. The patient underwent a total laryngectomy and a right pneumonectomy and he died from neoplastic progression 2 years after surgery. Microscopically, the laryngeal tumour was an epidermoid carcinoma and the apical pulmonary mass was an adenocarcinoma. The pulmonary neoplasm of the lower lobe, 5.5 cm across, was an epidermoid carcinoma that we interpreted to be a metastasis from the larynx. The case is peculiar because tumour cells proliferated exclusively in the interstitium. When extensive as in our case, this pattern of growth is rare and it may pose some diagnostic problems.     

Pulmonary alveolar proteinosis developing from desquamative interstitial pneumonia in long term toxicity studies of iprindole in the rat

Summary The material obtained from 11 cases of gliosis and 4 cases of tumours associated with Rosenthal fibres was studied under optical and electron microscope.Ultrastructurally the Rosenthal fibres appear in the form of osmiophil amorphous masses deposited in the cellular cytoplasm among the glial filaments, the latter showing no degenerative phenomena.The development of Rosenthal fibre-forming gliosis is closely linked to dysplastic processes, resulting in discontinuity of the ependymal epithelium, concomitantly affecting the normal embryonic development of the subependymal glial system.The spongioblast, a Rosenthal fibre-forming element, represents the type of dysplastic, subependymal glial cell with fibrillofoming and proliferative potentiallites (Bielschowsky, Hallervorden, Schlote). The presence of osmiophil bodies next to Rosenthal fibres forms the specific ultrastructural properties of the spongioblastic cell in contrast to the situation in normally differentiated astrocyte.     

Pulmonary vascular resistance rises with lung volume on exercise in obstructed airflow disease

There has been experimental evidence that lung distension produces an increase in pulmonary vascular resistance (PVR). To study this effect in patients, we measured functional residual capacity (FRC) by helium dilution at rest and during low-load supine exercise in 30 patients with chronic obstructive pulmonary disease. Pulmonary haemodynamics were studied in these patients under the same conditions. FRC increased from rest (4.32 +/- 0.21 l) to exercise (4.71 +/- 0.20, P less than 0.001) but the change was smaller in the patients with the highest FRC at rest: there was a significant negative correlation between FRC change and FRC at rest (r = -0.38, P less than 0.01). There were seven patients with a small FRC change (less than 0.2 l) with exercise and 10 patients with a marked increase (greater than 0.5 l). Exercise was of the same load on average. FRC at rest was 5.1 l in the first group and 4 l in the second (P less than 0.05). Blood gases were almost identical at rest, and almost unchanged during exercise. PVR decreased from rest to exercise by 33 dyn.s.cm-5 in the first group and increased by 24 in the second (P less than 0.01). There was a significant correlation (P less than 0.05) between PVR and FRC changes from rest to exercise. These results suggest that lung distension may play a role in the PVR increase seen in some COPD patients with exercise.     

气道中心性肺间质纤维化

患者男,53岁。因咳嗽、咳痰,进行性气促3年于2004年3月入院。既往体健,无职业接触史,吸烟指数400支/年。2001年初无明显诱因出现咳嗽,少量白色黏痰,同时伴有活动后气喘。经抗生素治疗后,病性时轻时重,呈进行性发展。2004年2月起咳黄痰,气喘进行性加重,外院诊断“继发性肺结核”,     

Azathioprine-associated interstitial pneumonitis

Seven renal allograft recipients taking azathioprine (Imuran) for immunosuppression developed bilateral pulmonary infiltrates and a falling pO2 that did not respond to antibiotic therapy. Open lung biopsies revealed changes ranging from diffuse alveolar damage (DAD) to usual interstitial pneumonia (UIP) culminating in pulmonary fibrosis. There was no evidence of immune deposits, eosinophilia, vasculitis, granulomas, or microorganisms by cultures and appropriate stains. Following discontinuance of Imuran, the two cases with DAD revealed a significant clearing of the lung infiltrates, whereas four of five patients with UIP died while suffering from respirator-dependent ARDS. Biopsies showing hyaline membranes, intraalveolar edema and cuboidalization of alveolar epithelium were associated with total doses from 2,850 to 4,355 mg, whereas atypical epithelial hyperplasia, reorganization of distal air spaces, and fibrosis were noted in cases receiving from 5,600 to 28,625 mg of azathioprine. Ultrastructural changes were indistinguishable from those induced by other drugs causing pulmonary toxicity. In three cases atypical epithelial cells were detected cytologically in brushing specimens and appeared identical to those noted in the lung biopsies. Our findings are consistent with the view that azathioprine should be added to the list of agents capable of causing direct, dose-dependent pulmonary toxicity. Accordingly, drug-associated diffuse interstitial pulmonary disease should enter the differential diagnosis of a lung infiltrate that develops in renal transplant patients receiving Imuran.     

Pulmonary involvement in type 1 Gaucher disease: functional and exercise findings in patients with and without clinical interstitial lung disease

Pulmonary disease is a well-known complication of Type 1 Gaucher disease (GD), although its incidence is not well established and its severity varies. The purpose of this study was to determine the frequency and extent of pulmonary involvement in patients with GD. Pulmonary involvement was assessed by history, physical examination and chest radiograph in 150 consecutive patients with Type 1 GD presenting at a specialized center for genetic diseases. Five patients were noted to have clinical evidence of pulmonary involvement. Full pulmonary function tests were performed in these five patients and in an additional 13 patients randomly selected from the remaining 145. Many of the 18 patients also underwent radionuclide body imaging with 67 Gallium citrate and 111Indium-tagged leucocyte scans, as well as incremental cardiorespiratory exercise tests. Lung biopsies were available in two patients with lung disease, and a second examination of lung tissue was performed in one of these two patients post-mortem. Clinical lung disease was detected in five patients. All five had dyspnea, diffuse infiltrates, restrictive impairment and low single breath CO diffusing capacity (DLCOSB). Two of these patients underwent exercise testing and showed abnormalities consistent with lung disease (ventilatory limitation, excessive ventilation and increased dead space) as well as decreased VO2 max. and anaerobic threshold (AT). In contrast, in the other 13 patients, physical examination, chest radiographs and pulmonary function were normal (except for a low DLCOSB in one patient). Responses on exercise testing (performed in six of the 13 patients) were consistent with a circulatory impairment (decreased VO2 max. and AT). Our study found that <5% of patients with Type 1 GD have clinical interstitial lung disease. In addition, we found that some patients, without evident lung involvement, may experience limitations in physical exertion and are easily fatigued; this is attributable to impaired circulation.