Clinical parameters and outcomes of Pneumocystis jiroveci pneumonia in non-HIV/AIDS patients.
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Biomedical subjects
Publications and source records attributed to Yuan-jue Zhu.
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OBJECTIVE: To investigate the molecular mechanism of multiple-drug and pan-drug resistance among Acinetobacter species. METHODS: Non-repetitive 90 carbapenem-resistant strains of Acinetobacter species were collected in Beijing, Guangzhou, and Fuzhou 1999-2004. The homology of the isolates was determined by both pulsed field gel electrophoresis and randomly amplified polymorphic DNA typing. Seven representative clones were selected from the 90 strains of Acinetobacter isolated from different hospitals to be used for further study. Analytical isoelectric focusing was used to measure the isoelectric point of the beta-lactamase. Plasmid DNA was extracted and purified Genes of different beta-lactamase, including bla(TEM--), bla(SHV-), bla(PER-), blaI(MP-), bla(VIM-), and bla(OXA-) genes, in these clone strains were amplified and sequenced. PCR was used to analyze the integrons. RESULTS: The P clone strain isolated during an outbreak of pan-drug-resistant Acinetobacter species in Peking Union Medical College Hospital 2004 was not susceptible to most common antimicrobial agents tested. The 7 representative clones produced multiple beta-lactamases: TEM-1, high-level AmpC, SHV-type, OXA-23 carbapenemase and IMP-8 and metalloenzyme respectively. One clone produced PER-1 enzyme. These 7 clone strains were resistant to most beta-lactams (including carbapenems), erythromycin, chloramphenicol, and rifampin. Two clone strains were susceptible to cefoperazone/sulbactam and amikacin while 4 clone strains susceptible to levofloxacin. All of the 7 clones were susceptible to minocycline and colistin. Five different integrons were found, harboring the genes mediating the resistance to aminoglycosides, rifampin, chloramphenicol, and carbapenems (bla(IMP-8)). CONCLUSION: The molecular bases of multiple-drug or pan-drug resistance in Acinetobacter species include production of OXA-23 carbapenemase or IMP type metalloenzyme and integrons with different resistance gene cassettes. Pan-drug-resistant Acinetobacter species are susceptible to old antimicrobials agents, such as colistin and minocycline.
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OBJECTIVE: To analyze the characteristics of pathologically proved cases of cryptogenic organizing pneumonia (COP) including manifestation of CT scan, bronchoalveolar lavage (BAL) fluid cytology, pulmonary histopathological appearance. METHODS: Twenty-three consecutive patients from April 1994 to October 2005 in Peking Union Medical College Hospital with pathologic features of organizing pneumonia were enrolled in the study. RESULTS: Eighteen patients were diagnosed as COP. Percutaneous lung biopsy/transbronchial lung biopsy was performed in 10 patients, while open lung biopsy/video-assistant thorascopic biopsy was performed in 8 patients. There were 8 males and 10 females, aged (53.5 +/- 11.0) yr. Dyspnea, cough, inspiratory crackles were the most common symptoms and signs. Lung function tests showed a restrictive ventilatory defect (11/18), and impairment of carbon monoxide transfer factor (T(LCO), 18/18). Chest computed tomography scan in 18 cases mainly showed ground glass opacities (4/18), patchy areas of alveolar consolidation (13/18) with air bronchograms (3/18), and pleural effusion (4/18). BAL fluid cytological analysis showed the percentage of lymphocyte was 0.40 +/- 0.16, neutrophil 0.15 +/- 0.08, eosinophil 0.05 +/- 0.03; the CD(4)/CD(8) ratio was 0.43 +/- 0.21. All patients were treated with corticosteroids. Sixteen were alive and clinically improved or stabilized at the last follow up (8.7 +/- 6.2 months after diagnosis). Two patients died, one of respiratory failure, and another of pulmonary infection. CONCLUSIONS: The diagnosis of COP is usually suggested by clinical-radiological findings, but needs to be confirmed histopathologically. The combination of BAL fluid cytological findings and lung histological appearance obtained during a bronchoscopic procedure appears to be an effective method for diagnosing this disease.
OBJECTIVE: To explore the etiology, diagnosis and differential diagnosis of lymphocytic interstitial pneumonia (LIP). METHOD: The clinical, radiographical and histological characteristics of three cases of LIP diagnosed in Peking Union Medical College Hospital were analyzed, and the literature was reviewed. RESULTS: The precise cause of LIP was unknown. However, LIP was strongly associated with autoimmune diseases and immunodeficiency. Clinically, patients presented with chronic cough and progressive dyspnea. Pulmonary function tests showed restrictive ventilatory pattern. HRCT of chest revealed ground-glass attenuation, centrilobular nodules, subpleural small nodules, thickening of bronchovascular bundles, interlobular septal thickening and cystic dilated air spaces. Bronchoalveolar lavage showed an increase in lymphocytes. The key finding in histopathology was dense interstitial lymphoid infiltrate with a polyclonal pattern. CONCLUSION: Idiopathic LIP is rare. Cases of LIP should be thoroughly investigated for any known causes and related disorders.
OBJECTIVE: To study the clinical, pathologic and radiologic features of amiodarone-induced lung injury. METHODS: The clinical, pathologic and radiologic features, including treatment and follow-up information of three cases diagnosed as amiodarone-induced lung injury from October 2004 to October 2005 in the Peking Union Medical College Hospital were reviewed. RESULTS: All the patients were males, with age ranging from 35 to 64 years. The duration of symptoms varied from 20 days to 3 years. All presented with cough. Worsening dyspnea and inspiratory crackles were noted in two patients. Computerized tomography showed bilateral patchy infiltration, ground-glass appearance and accentuation of bronchovascular markings. The most common pathologic manifestations included cellular interstitial pneumonia associated with intra-alveolar collections of macrophages and type II pneumocyte hyperplasia. Some of the macrophages contained finely vacuolated cytoplasm. An organizing pneumonia pattern was seen in one patient. CONCLUSIONS: Amiodarone-induced lung injury has characteristic pathologic features which may provide clues to diagnosis. Correlation with clinical and radiologic findings is also important.
OBJECTIVE: To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 (TGF-beta 1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and matrix metalloproteinase-13 (MMP-13) in lung tissue. METHODS: Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone (25-800 mg x kg(-1) x d(-1)), dexamethasone (3 mg/kg), or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg x kg(-1) x d(-1) at 7 days or 14 days after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in lung tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxyproline. Expression of proteins of TGF-beta 1, TIMP-1, and MMP-13 were detected by Western blotting. RESULTS: At doses of 25, 50, and 100 mg x kg(-1) x d(-1), pirfenidone had significant anti-fibrotic effects for bleomycin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg x kg(-1) x d(-1) (HE: P < 0.01, P < 0.01, and P = 0.064; sirius red: P < 0.05, P < 0.01, and P < 0.05; hydroxyproline: P = 0.595, P < 0.01, and P = 0.976). Pirfenidone at a dosage of 50 mg x kg(-1) x d(-1) inhibited protein expression of TGF-beta1 and TIMP-1 in lung tissue in the early phase (0.79 and 0.75 times of control group), but had no effect on expression of MMP-13. CONCLUSION: Low dose pirfenidone, especially at dosage of 50 mg x kg(-1) x d(-1), has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-beta 1 and TIMP-1 in lung tissue.
BACKGROUND: Amyloidosis is a collection of diseases in which different proteins are deposited. Amyloid deposits occur in systemic and organ-limited forms. In both systemic and localized forms of the disease, lung can be involved. The aim of this study was to explore the different respiratory manifestations of amyloidosis. METHODS: Chest radiology, clinical presentations, bronchoscopic/laryngoscopic findings and lung function data of 59 patients with amyloidosis involving respiratory tract collected during January 1986 to March 2005, were analysed. RESULTS: Of the 16 cases with localized respiratory tract amyloidosis, 8 had the lesions in the trachea and the bronchi, 2 in the larynx and the trachea, 5 in the larynx and/or the pharynx, and 1 in the lung parenchyma. Of 43 systemic amyloidosis with respiratory tract involvement, 3 had the lesions in bronchi, 13 in lung parenchyma, 33 in pleura, 8 in mediastina, 1 in nose and 1 in pharynx. Chest X-rays were normal in most cases of tracheobronchial amyloidosis. CT, unlike chest X-rays, showed irregular luminal narrowing, airway wall thickening with calcifications and soft tissue shadows in airway lumen. Localized lung parenchymal amyloidosis presented as multiple nodules. Multiple nodular opacities, patch shadows and reticular opacities were the main radiological findings in systemic amyloidosis with lung parenchymal involvement. In pleural amyloidosis, pleural effusions and pleural thickening were detected. Mediastinal and/or hilar adenopathy were also a form of lung involvement in systemic amyloidosis. The major bronchoscopic findings of tracheobronchial amyloidosis were narrowing of airway lumen, while nodular, 'tumour like' or 'bubble like' masses, with missing or vague cartilaginous rings, were detected in about half of the patients. CONCLUSIONS: Localized respiratory tract amyloidosis mostly affects the trachea and the bronchi. Chest X-rays are not sensitive to detect these lesions. Systemic amyloidosis often involves lung parenchyma and the pleura. Open lung biopsy or pleural biopsy should be performed for the diagnosis.
OBJECTIVE: To describe a form of interstitial lung disease pathologically characterized by small airway-centered interstitial fibrosis (ACIF). METHODS: We analyzed the clinical, pulmonary functional, radiographic, and histologic characteristics of one ACIF case in Peking Union Medical College Hospital and reviewed 12 cases in literatures. RESULTS: Clinically, patients presented with chronic cough and progressive dyspnea. Pulmonary function tests showed restrictive ventilatory pattern. Bronchoalveolar lavage showed a mild increase in lymphocytes in most cases. Chest radiography revealed diffuse reticulonodular infiltrates, with thickening of the bronchial walls and surrounding fibrosis. The key finding in histopathology was a distinctive pattern of ACIF centered on membranous and respiratory bronchioles. CONCLUSIONS: ACIF is a disease that do not fit into any known category of interstitial lung disease. Whether it is a unique disease remains to be determined.
OBJECTIVE: To investigate the clinical applications of portable spirometry in asthma. METHODS: Twenty patients with asthma were recruited from Peking Union Medical College Hospital. Flow-volume loop, simultaneous asthma symptoms, and mood were monitored three times a day for consecutive 14 days. RESULTS: In patients with a normal daytime spirometry, marked decline of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were observed at night and/or in the early morning. A within subject correlation analysis between FEV1, PEF, and asthma symptoms showed that the correlation between symptoms and airway obstruction was found only in seven out of twenty patients (35%). Four patients (20%) reported many symptoms with nearly normal portable spirometry. Accordingly, their symptoms were not correlated with FEV1 and PEF. This group of patients was defined as over-perceivers. On the contrary, another two patients (10%) did not report any symptoms while obvious airways obstruction was recorded by a portable spirometry. These patients were defined as under-perceivers. CONCLUSIONS: Dynamic monitoring of flow-volume loop with a portable spirometry is more accurate than routine lung function test in assessment of asthma severity. In addition, combined with simultaneous monitoring of symptoms, it would be of particularly helpful in identifying two specific types of asthma patients, e.g. over-perceivers and under-perceivers.
OBJECTIVE: To investigate the clinical features and diagnostic procedures for diffuse panbronchiolitis in Chinese patients. METHODS: With literature review, the clinical features and diagnostic procedures of diffusely panbronchiolitis in a series of 9 patients with histopathological confirmation were retrospectively described and discussed. RESULTS: Of the 9 cases, 8 had persistent cough, sputum production and exertion dyspnea, 7 had chronic sinusitis, 9 had centrilobular micronodules on chest CT, 7 had coarse crackles, 4 had FEV(1)/FVC < 70%, 5 had PaO(2) < 80 mm Hg and 1 had titer of cold hemagglutinin > or = 1:64. According to the Japanese revised clinical diagnostic criteria for diffuse panbronchiolitis, definite diagnosis could be made in 4 cases, probable in 3 and excluded in 2 cases, respectively, but it was clinically diagnosed or suspected only in 2 cases before clinicopathological confirmation, the remaining 7 cases were missed or mistaken for other diseases. Of the 9 cases, 8 had received transbronchial biopsy and all showed non-specific inflammation, which was in agreement with but nondiagnostic for diffuse panbronchiolitis. CONCLUSIONS: Most cases of diffuse panbronchiolitis can be clinically diagnosed or suggested according to the clinical diagnostic criteria, proposed solely by Japanese experts which should be further validated in non-Japanese populations. If difficulty in diagnosis arises, the diagnosis of diffuse panbronchiolitis should be based on its clinicopathological features and exclusion of other mimicking diseases. Of note, few cases can be confirmed by transbronchial biopsy, and in this case, surgical lung biopsy should be considered.
BACKGROUND: Medically unexplained dyspnea occurs commonly in medical settings and remains poorly understood. This study was conducted to investigate the psychophysiological characteristics of medically unexplained dyspnea and the efficacy of breathing retraining for these patients. METHODS: A group of patients with medically unexplained dyspnea were compared to patients with a variety of organic lung diseases and healthy subjects. In another group of patients, the influence of breathing therapy on complaints, anxiety, and breath-holding was evaluated for an average of 1.5 years. RESULTS: Patients with medically unexplained dyspnea reported more intense dyspnea than patients with a variety of organic lung diseases. Additionally, they were anxious and presented a broad range of symptoms in daily life and under challenge, for instance voluntary hyperventilation. More than one third of them qualified for panic disorder. They had shorter breath-holding time at rest, less increase in breath-holding time and higher chances of showing a "paradoxical" decrease of breath-holding time after hyperventilation. A combination of PaO2, forced expiratory volume in one second (FEV1), and anxiety measures distinguished them from organic dyspnea. Breathing retraining profoundly improved their symptoms and decreased the level of state and trait anxiety. Moreover, they better tolerated the voluntary hyperventilation and the symptoms induced were also markedly decreased after therapy. Breath-holding time was prolonged and PetCO2 in a representative group of patients increased. CONCLUSIONS: Patients with medically unexplained dyspnea appear to have the feature of a "psychosomatic" patient: an anxious patient with a wide variety of symptoms of different organ systems that do not have an organic basis. They can be distinguished from organic dyspnea using a small set of physiological and psychological measures. Breathing retraining turns out to be an effective therapy for those "difficult to treat patients".
OBJECTIVE: To investigate the risk factors for multi-drug resistant Pseudomonas aeruginosa (MDRP) infections, and the factors related with poor prognosis of P. aeruginosa infections. METHODS: The data of 44 cases of MDRP nosocomial infections were analyzed from Jan, 1999. to Dec, 2002 in Peking Union Medical Hospital; 68 cases of antibiotic-sensitive P. aeuroginosa infection were randomized as control. T test, chi-square test and Logistic regression analysis were used for statistics. RESULTS: According to univariate analysis, the factors associated with the development of MDRP nosocomial infection were age, APACHE II, co-infection with other pathogens, hospital acquired pneumonia (HAP), mechanical ventilation, COPD, fluoroquinolone and imipenem/meropenem use 15 days before isolation of MDRP. Multivariate logistic regression analysis identified two independent factors: mechanical ventilation and previous imipenem/meropenem use. Of 44 cases of MDRP infections, 24 died, and 20 survived. Univariate analysis revealed that three factors (APACHE II, mechanical ventilation, resistance switch) were associated with clinical prognosis. But a ccording to multivariate logistic regression analysis, only resistance switch was a predictive factor. CONCLUSIONS: Mechanical ventilation and previous imipenem/meropenem use were independent risk factors for MDRP infection. Resistance switch was a predictive factor for the prognosis of MDRP infection.
OBJECTIVE: To analyze the clinical characteristics and treatment of hematogenous disseminated tuberculosis. METHODS: Twenty-seven cases of hematogenous disseminated tuberculosis diagnosed by autopsy from 1961 to 2000 were retrospectively analyzed. RESULTS: Among these patients the disease was acute in 22 cases (including 3 non-reactive) and chronic in 5. Twenty cases (74%) were misdiagnosed before death, most of which were due to concomitant with or misdiagnosed as connective tissue disease, hematological disease or tumor. 63% of the cases had long-term use of corticosteroids or repeated chemotherapy. Most cases showed atypical clinical manifestations and chest X-ray lesions. The positive rate of tuberculin skin test and sputum for smear were low. Autopsy showed that all cases had active lung tuberculosis and the major extra-pulmonary organs involved were liver, spleen and lymph nodes. CONCLUSION: Unaware of the risk for tuberculosis among immune compromised patients was the main reason for misdiagnosis and corticosteroid abuse was common. Physician should be alert to the occurrence of hematogenous disseminated tuberculosis, especially in immune compromised patients with long-term fever and systemic injury. Direct smear and cultural examination as well as newer diagnostic approaches with sputum and tissue may be useful for a rapid and correct diagnosis.
Medically unexplained dyspnea refers to a group of patients presenting marked dyspnea without structural alterations of organs/systems after thorough examinations. This clinically neglected group of patients accounts for about 14% of patients with dyspnea in secondary health care. They appear very difficult to manage clinically. In this paper an organized approach used to diagnose medically unexplained dyspnea is presented. Breathing re-training is recommended as a therapy for those "difficult to treat patients".
OBJECTIVE: Medically unexplained dyspnea is common in adult and accounts for 14% patients complaining of dyspnea. Its occurrence in children is seldom recognized. In the present paper, 34 children with medically unexplained dyspnea (age 10 to 18 years) seen in Peking Union Medical College Hospital from 1996 to 2002 are reported. METHODS: The diagnosis of medically unexplained dyspnea was clinical: it was based on the presence of dyspnea and other complaints which cannot be explained by an organic disease. The patients answered Nijmegen questionnaire and state and trait anxiety (STAI), and performed hyperventilation provocation test. Twenty sessions of breathing therapy were applied and 13 out of 34 children were followed up after the therapy. RESULTS: Among the children, 75% started to have symptoms at the age of 13 to 16 years, though the age of first episode could be as early as 8 years. In most of the cases, the course was chronic clinically. In addition to marked dyspnea, their clinical profile included symptoms of hyperventilation i.e. blurred vision, dizziness, tingling, stiff fingers or arm. The symptoms of anxiety were less frequent in children and accordingly the level of anxiety evaluated by means of STAI was lower in children compared to adult patients. The precipitating psychological factors appeared to be related to middle school competition. Pressure from exams, reprimand from stern and unsympathetic teachers coupled with high parental expectation could be emotionally damaging to psychologically susceptible children. Thirteen patients were followed up after 2-3 months of breathing therapy with emphasis on abdominal breathing and slowing down of expiration. After therapy, the sum score of the Nijmegen Questionnaire was markedly decreased. Dyspnea and symptoms of hyperventilation were improved. The level of anxiety was minimally modified. CONCLUSION: The cases illustrated the need for careful diagnostic evaluation and treatment because of the high rate of chronicity of the disorder.
OBJECTIVE: To investigate the effects of dexamethasone on human lung fibroblast cell proliferation, cell cycles, and cell mitogen-activated protein kinases (MAPKs) passway. METHODS: Dexamethasone was used at various concentration in culture medium. Cell number was counted using a hemacytometer. Whole cell propidium iodide staining and flow cytometric analysis were performed to determine cellular DNA content. MAPK proteins and activation were tested by Western blot analysis with antibodies to c-Jun N-terminal kinase (JNK), phospho-JNK, extracellular signal-regulated kinase (ERK), phospho-ERK, p38 and phospho-p38. RESULTS: 1x10(-7) mol/L and 1x10(-6) mol/L dexamethasone suppressed the proliferation of lung fibroblast cells by 34% and 72%, respectively, than that of control. This suppression was dose-dependant. Dexamethasone suppressed cell cycle with accumulation of cells in G1/G0 stage. It increased from 81.9% to 90.1% compared with that of control. We did not find any apoptosis induced by dexamethasone for lung fibroblast cells. Using Western blot analysis, we found that dexamethasone resulted in decreased activity of ERK, but had no effects on JNK and p38. CONCLUSIONS: Dexamethasone may suppresses the proliferation of lung fibroblast cells, which is partly resulted from the facts that it can inhibit ERK activation in MAPK-signaling pathway but has little effect on JNK and p38 pathway. Dexamethasone may not induce lung fibroblast cell apoptosis directly.
OBJECTIVE: To investigate the changes of interferon-gamma (IFNgamma), interleukin (IL)-4, matrix metalloproteinase (MMP)-9, MMP-12 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in smoke-induced chronic obstructive pulmonary disease (COPD) rat models and the therapeutic effect of N-acetylcysteine (NAC). METHODS: Male Wistar rats were exposed to cigarette smoke for 3.5 months. NAC was given in the last month. Lung function was measured at the end of the study. The levels of IL-4 and IFNgamma in broncho-alveolar lavage fluid (BALF) and lung tissues were determined by ELISA. The expression of MMP-9, MMP-12 and TIMP-1 mRNA in lung tissues were determined by RT-PCR. RESULTS: (1) In comparison with the control group, smoke exposed group presented a significant decrease in forced expiratory volume in 0.3 second (FEV(0.3))/forced vital capacity (FVC), dynamic lung compliance (Cdyn), mean alveolar numbers (MAN) and a significant increase in expiratory resistance (Re), pulmonary mean linear intercept (Lm) (P < 0.05). After treatment with NAC, FEV(0.3)/FVC, Re and Cdyn were improved significantly (P < 0.05). No significant changes were found in Lm and MAN (P > 0.05). (2) In the lung tissues of smoke exposed group, IL-4 level was 10.00 pg/ml, IFNgamma level was 19.37 pg/ml, and the IL-4/IFNgamma ratio was 0.49. In the lung tissues of the control group, they were 4.38 pg/ml, 54.94 pg/ml and 0.10, respectively. There were significant differences in these indexes between the smoke exposed group and the control group (P < 0.05). IL-4 level in the NAC group was 7.99 pg/ml which was similar to that in the smoke exposed group (P > 0.05). IFNgamma and IL-4/IFNgamma ratio were 43.40 pg/ml and 0.15, the former being significantly higher and the latter being significantly lower than those in the smoke exposed group (P < 0.05). (3) The expression of MMP-12 mRNA and MMP-12/TIMP-1 ratio in the smoke exposed group (0.36, 1.21) were significantly higher than those in the control group (0.24, 0.88) (P < 0.05). There was no difference in TIMP-1 (P > 0.05). The expression of MMP-12, TIMP-1 mRNA and the MMP-12/TIMP-1 ratio in NAC group were similar to those in the smoke exposed group (P > 0.05). CONCLUSIONS: (1) Cigarette smoke exposure increased IL-4 and decreased IFNgamma. This may contribute to smoke-induced changes in lung function. NAC had no effect on IL-4, but increased IFNgamma, and the IL-4/IFNgamma ratio returned to normal. This might be one of the mechanisms of NAC in improving lung function. (2) Cigarette smoke promoted MMP-12 gene expression and increased the MMP-12/TIMP-1 ratio. This may play a role in smoke-induced emphysema. NAC did not alter MMP-12/TIMP-1 ratio when given in the late phase of smoke exposure. This result could explain the emphysematous changes in the NAC group.