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The emerging SARS-CoV-2 variants have made great challenges to current vaccine and pandemic control strategies. B.1.1.529 (Omicron), which was classified as a variant of concern (VOC) by the World Health Organization on November 26th, 2021, has quickly become the dominant circulating variant and causing waves of infections. It is urgent to understand the current immune status of the general population given that pre-existing immunity has been established by national vaccination or exposure to past variants. Using sera from 85 individuals (including 21 convalescents of natural infection, 15 cases suffered a breakthrough infection after vaccination, and 49 vaccinated participants without infection history), we showed that the cross-neutralizing activity against VOCs such as Omicron can be detected in 53 (62.4%) cases, although less potent than against the Wuhan-1 strain (WT), with a 3.9-fold reduction in geometric mean neutralizing titer (GMT) (130.7, 95% CI 88.4-193.3 vs 506, 355.8-719.7, respectively). Subgroup analysis revealed significantly enhanced neutralizing activity against WT and VOCs in Delta convalescent sera. The neutralizing antibodies against Omicron were detectable in 75% of convalescents and 44.9% of healthy donors (p = 0.006), with a GMT of 289.5, 180.9-463.3 and 42.6, 31.3-59, respectively. However, the protective effect against VOCs was weaker in young convalescents (aged < 18y), with a detectable rate of 50% and a GMT of 46.4 against Omicron, similar to vaccinees. The pan-sarbecovirus neutralizing activities were not observed in vaccinated SARS-CoV-1 survivors. A booster dose significantly increased the breadth and magnitude of neutralization against WT and VOCs to different degrees than full vaccination. In addition, we showed that COVID-19 inactivated vaccines can elicit Omicron-specific T cell responses. The positive rates of ELISpot reactions were 26.7% (4/15) and 43.8% (7/16) in the full vaccination group and the booster vaccination group, respectively. The neutralizing antibody titers declined while T-cell responses remain robust over 6 months. These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants.
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To investigate the clinical significance of serum soluble programmed cell death ligand-1 (PD-L1) in adult patients with community-acquired pneumonia (CAP). A total of 44 CAP patients, 54 severe CAP patients and 30 healthy volunteers were recruited in this study. Serum soluble PD-L1 were detected. Univariate and multivariate regression analyses were used to assess the influence of multiple clinical variables on prognosis. Serum soluble PD-L1 level in severe CAP group was 98.20(57.94, 128.90) ng/L, which was significantly higher than that in the CAP group [59.32(33.55, 92.58) ng/L] and healthy controls [20.44(12.15, 36.20) ng/L] (all P<0.001). PD-L1 level was positively correlated with CRUB-65( r=0.481, P<0.001) and the pneumonia severity index (PSI) score ( r=0.442, P<0.001). Univariate regression analysis showed that CURB-65 ( HR=2.544, 95% CI 1.324-4.889, P=0.005), PSI score ( HR=1.036, 95% CI 1.012-1.061, P=0.004), soluble PD-L1( HR=1.013, 95% CI 1.001-1.026, P=0.041) were risk factors of mortality during hospitalization. Multivariate regression analysis suggested that PSI score ( HR=1.042, 95% CI 1.012-1.073, P=0.005), soluble PD-L1 ( HR=1.011, 95% CI 1.002-1.071, P=0.020) were independent predictors for mortality risk in CAP patients. CAP patients with soluble PD-L1≥98.20 ng/L had a significantly lower survival rate than those with soluble PD-L1<98.20 ng/L ( P=0.033). In conclusion, this study indicates that serum soluble PD-L1 level in CAP patients is correlated with the survival prognosis.
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A 26-year female was admitted to hospital with fever and cough. Blood routine test showed leukopenia and thrombocytopenia. CT scan indicated pneumonia-like disease. Antibiotics therapy was ineffective, and primary pulmonary extranodal NK/T-cell lymphoma (ENKTL), nasal type was confirmed by percutaneous lung biopsy. Twenty cases of ENKTL were collected from 14 reports through literature retrieval. Patients aged 19-80 years with a male to female ratio of 3∶1. Main clinical symptoms included fever (85%), cough (65%), and shortness of breath (55%). CT findings of primary pulmonary ENKTL varied widely and might occur in all lobes of both lungs; the lesions were nodular or mass-like (60%) and pneumonia-like (20%). Few cases showed pleural effusion (25%) and/or mediastinal lymphadenopathy (25%). ENKTL presented NK/T cell phenotype, cytotoxic granule protein, and evidence of EB virus infection. The pulmonary ENKTL progressed rapidly, the hemophagocytic syndrome presenting with high fevers, hepatosplenomegaly or cytopenias usually indicated a late stage of the disease. The survival time ranged from 8 days to 12 months. The primary pulmonary ENKTL is a rare disease. The clinical course tends to be rapidly progressive, with life-threatening complications occurring less than a year after the disorder becomes apparent. When a non-responding pneumonia is associated with hemophagocytic syndrome (fever, leukopenia, splenomegaly), lung biopsy should be considered for the diagnosis of ENKTL.
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This study assessed the in vitro antibacterial activity of minocycline-aminoglycoside combination against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Seventy non-duplicate clinical isolates of KPC-producing K. pneumoniae were collected from patients with bloodstream infections. The synergistic activity of minocycline-aminoglycoside combination was studied by the checkerboard method and time-kill assays in strains with different susceptibilities, and the mutant prevention concentration (MPC) and mutant selection window (MSW) of drugs alone and in combination were determined. The checkerboard method found this combination displayed synergistic and partial synergistic activity against aminoglycoside-susceptible isolates, but indifferent activity against aminoglycoside-resistant isolates. Time-kill assays further demonstrated strong synergistic and bactericidal effect of this combination existed against isolates which were susceptible to both drugs. But for resistant isolates, the time-kill assays showed no synergy. The MPCs of minocycline or aminoglycosides were 8- to 32-fold higher than the MICs, suggesting the MSWs of these drugs were quite wide. For the antibiotic combinations, the addition of 1×MIC concentration of amikacin or gentamicin could reduce the MPCs of minocycline by 4- to 16-fold. Generally, no mutants recovered in the plates containing 1×MIC concentration of minocycline and 2×MIC concentration of amikacin or gentamicin. In summary, these results suggest that minocycline-aminoglycoside combination can be an alternative for infections caused by KPC-producing K. pneumoniae because this combination displays strong synergistic and bactericidal activity in susceptible isolates, and can effectively prevent the emergence of resistant mutants. Further in vitro pharmacokinetic/pharmacodynamic studies and clinical trials should be performed to fully evaluate the efficacy of this drug combination.
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Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Minociclina/farmacologia , beta-Lactamases/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Sinergismo Farmacológico , Humanos , Infecções por Klebsiella/microbiologia , Testes de Sensibilidade MicrobianaRESUMO
Objective@#Human rhinovirus A21 (HRVA21) with mutations in antigenic gene has been reported causing severe human infections. This study aimed to investigate intensively the pathogenesis of HRVA21 by identifying the characteristics of neutralizing antibodies (NAbs) distribution.@*Methods@#Virus stock was isolated from HRVA21-positive respiratory specimens. The tissue culture infective dose 50 (TCID50) was applied. Sera from healthy volunteers in different age groups were used to analyze the NAbs by using the diluted serum and fixed viral TCID50.@*Results@#We obtained the HRVA21 virus stock and its whole genome sequences shared 100% similarity to the used clinical sample. In the 379 collected serum samples, the positive rates of NAbs were 21.7%, 14.1%, 28.2%, 25.4%, 27.9% and 20.7% in age groups of 0-5 y, 5-14 y, 15-25 y, 26-45 y, 46-60 y and > 60 y, respectively. In age groups of >5-14 y and 15-25 y, the positive rate of NAbs showed significantly different (χ2=4.68454, P=0.03044). Higher geometric mean titers were found in 15-25 y group compared to 5-14 y age groups (P=0.0313).@*Conclusions@#The low level of HRVA21 NAbs in different age groups indicated a low epidemic of HRV21 infection and high susceptability to infections by the virus.
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Three cases of Good's syndrome with pulmonary lesions in our hospital from June 1,2010 to June 1,2013 were retrospective analyzed and relevant literatures were reviewed.Clinical manifestation,characteristics of pulmonary lesions,diagnosis and treatment were summarized.Abnormality of lymphocyte subpopulation to varying degrees in peripheral blood was detected in all 3 cases.However none showed hypogammaglobulinemia.If thymoma patients developed recurrent respiratory infections,Good's syndrome should be considered.Pulmonary manifestations of Good's syndrome have lesions similar to those of diffuse panbronchiolitis or interstitial lung disease.Early screening of immune competency and treatment for immunodeficiency may improve prognosis.
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<p><b>BACKGROUND</b>Novel influenza A viruses of avian-origin may be the precursors of pandemic strains. This descriptive study aims to introduce a novel avian-origin influenza A (H10N8) virus which can infect humans and cause severe diseases.</p><p><b>METHODS</b>Collecting clinical data of three cases of human infection with a novel reassortment avian influenza A (H10N8) virus in Nanchang, Jiangxi Province, China.</p><p><b>RESULTS</b>Three cases of human infection with a new reassortment avian influenza A(H10N8) virus were described, of which two were fatal cases, and one was severe case. These cases presented with severe pneumonia that progressed to acute respiratory distress syndrome (ARDS) and intractable respiratory failure.</p><p><b>CONCLUSION</b>This novel reassortment avian influenza A (H10N8) virus in China resulted in fatal human infections, and should be added to concerns in clinical practice.</p>
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antivirais , Usos Terapêuticos , Fluoroquinolonas , Usos Terapêuticos , Imipenem , Usos Terapêuticos , Vírus da Influenza A Subtipo H10N8 , Virulência , Influenza Humana , Diagnóstico , Tratamento Farmacológico , Oseltamivir , Usos TerapêuticosRESUMO
<p><b>BACKGROUND</b>The extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae has increasingly become a major contributor to nosocomial infections and can exhibit multiple antibiotic resistance. Previous studies have focused on the resistance genes in ESBL-producing strains, and the resistance-associated genetic environment of non-ESBL-producing strains has been ignored until now. Here, we investigated the occurrence and characteristics of non-ESBL-producing K. pneumoniae, which potentially carries unexpressed resistance genes.</p><p><b>METHODS</b>K. pneumoniae strains were collected from five medical institutions in China from February 2010 to August 2013. The VITEK-2 ESBL detection system was used as a primary screen to identify the ESBL-producing phenotype, and the three primary types of ESBL-associated genes (CTX, SHV, and TEM) were detected by polymerase chain reaction (PCR) to confirm the strains presenting with a non-ESBL-producing phenotype. mRNA expression in the non-ESBL-producing strains was further screened by reverse-transcription PCR (RT-PCR) to validate their transcriptional efficiency.</p><p><b>RESULTS</b>Out of 224 clinically isolated antibiotic-sensitive K. pneumoniae strains with a non-ESBL-producing phenotype, 5 (2.2%) were identified to carry inactivated ESBL blaSHV genes with intact upstream promoter regions and resistance gene sequences. Interestingly, three of the five antibiotic-sensitive K. pneumoniae strains containing ESBL blaSHV genes still exhibited mRNA transcription of blaSHV, while the other two exhibited no mRNA transcription.</p><p><b>CONCLUSION</b>These findings suggest that inactivated ESBL genes exist in non-ESBL-producing antibiotic-sensitive K. pneumoniae strains, which have the potential to transform the strain into an ESBL phenotype if an inappropriate application or overdose of antibiotics is implemented during clinical management.</p>
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Humanos , Antibacterianos , Farmacologia , China , Farmacorresistência Bacteriana Múltipla , Genética , Klebsiella pneumoniae , Genética , Testes de Sensibilidade Microbiana , beta-Lactamases , GenéticaRESUMO
<p><b>BACKGROUND</b>Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) is one of the most popular pathogens that cause refractory respiratory tract infection. The genetic environment, including insertion sequences and the types of promoter, plays a key role in exploration of the mechanism of prevalence and dismission of the ESBL-producing K. pneumoniae isolates. The aim of the investigation was to target analysis the genetic environment and promoter sequences of blaCTX-M, blaSHV and blaTEM, the most popular β-lactamase genes harbored by ESBL-producing K. pneumoniae isolates.</p><p><b>METHODS</b>From February 2010 to July 2011, 158 of 416 K. pneumoniae isolates producing ESBL from patients with lower respiratory tract infection were collected from seven tertiary hospitals from Beijing, Anhui, Fujian, Liaoning, Hebei and Inner Mongolia Autonomous Region in China. The genetic environment including promoters of 10 types of blaCTX-M, 18 types of blaSHV and 2 types of blaTEM were analyzed by amplification and direct sequencing with various sets of PCR primers.</p><p><b>RESULTS</b>ISEcp1 was located upstream of the 5' end of the blaCTX-M gene in 130 (97.0%) out of 134 K. pneumoniae isolates harboring blaCTX-M and provided a conserved promoter to blaCTX-M. A non-coding sequence preceded by kdpC and recF was identified in all of the blaSHV genes except blaSHV-12 and blaSHV-2a. IS26 was also found upstream of 1 blaCTX-M-15, 10 blaSHV-1 strains, 4 blaTEM-1 and all of the blaSHV-2, blaSHV-2a, blaSHV-5 and blaSHV-12. Eighty-seven of 91 strains harboring blaTEM-1 carried a copy of Tn2 and IS26-blaTEM-1 fragments were also detected in 4 strains. With respect to K. pneumoniae, the genetic environment of blaCTX-M-38, blaSHV-142 and blaTEM-135 were firstly elaborated, and four kinds of novel genetic environment of blaCTX-M-3, blaCTX-M-15 and blaTEM-1 have been detected as well.</p><p><b>CONCLUSIONS</b>Perfective implementation of the genetic environment information of bgr;-lactamase gene needs to be further explored and supplemented. ISEcp1 and IS26 elements are widespread upstream of the blaCTX-M, blaSHV and blaTEM genes and contribute to horizontal transmission and genetic expression.</p>
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Humanos , Antibacterianos , Farmacologia , Proteínas de Bactérias , Genética , Metabolismo , China , Farmacorresistência Bacteriana Múltipla , Genética , Klebsiella pneumoniae , Genética , Testes de Sensibilidade Microbiana , Regiões Promotoras Genéticas , Genética , beta-Lactamases , Genética , MetabolismoRESUMO
Timely and accurate diagnosis of pathogens plays important role in the controlling of infectious respiratory diseases.Serum detection of specific antibodies against pathogens could indirectly determine the infection and immune status.Serodiagnosis includes enzyme-linked immunosorbent assay,indirect immunofluorescence assay,hemagglutination inhibition test,neutralization test and others.Studies showed that indirect immunofluorescence assay had its technique advantages and diagnostic value.Combining with other methods,immunofluorescence assay would offer objective and comprehensive etiological results for clinical practice.
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Objective To evaluate the clinical significance of the level of [gG4 in the bronchoalveolar lavage fluid (BALF) of patients with rheumatic disease related interstitial lung disease (RD-ILD).Methods Eighteen patients with RD-ILD,14 patients with pulmonary infection and 12 patients without ILD or pulmonary infection,were recruited consecutively from the in-patient ward of Peking University People's Hospital.Clinical features and laboratory data were extracted from the medical record database of Peking University People's Hospital.The level of IgG4 was determined by ELISA.The statistical analysis of data using t test,and the correlation between the two variables were analyzed using linear regression analysis.Results The level of IgG4 was significantly higher in BALF of patients with RD-ILD than patients' without ILD or pulmonary infection,whereas there was no difference compared to patients with pulmonary infection.The level of IgG4 in BALF of patients with RD-ILD was positively correlated with the percentage of lymphocytes (r=0.53,P=0.03),and significantly negatively correlated with the percentage of macrophages (r=-0.65,P=0.005).Conclusion The level of IgG4 is significantly elevated in BALF of patients with RD-ILD,which is probably secreted from the lymphocyte of the lung.
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ObjectiveTo investigate the value of serum procalcitonin (PCT) in diagnosing lower respiratory tract infection (LRTI) in adult.MethodsIn a retrospective study,97 patients were enrolled,who admitted into Peking University People's Hospital with suspected LRTI from July to December 2008.During analysis,the subjects are categorized into groups of LRTI with sepsis,hospital-acquired pneumonia(HAP),community-acquired pneumonia(CAP),acute exacerbation of chronic obstructive lung disease (AECOPD),other LRTI and non-infectious diseases.In these cases,the following parameters were assessed regularly,such as white blood cell count,erythrocyte sedimentation rate( ESR),C-reactive protein (CRP),PCT,bacterial culture of both sputum and blood,and Acute Physiology and Chronic Health Evaluation (APACHE)Ⅱ score.PCT levels were determined using antibody-coated tubes as a complete diagnostic-kit (LUMI test Pro-Calcitonin) in a Luminometer.ResultsMean PCT levels in groups of LRTI with sepsis, hospital-acquired pneumonia ( HAP ), community-acquired pneumonia ( CAP ), acute exacerbation of chronic obstructive lung disease( AECOPD),other LRTI,non-infectious diseases were 10.1 (0.7 -37.0),0.3(0.1 -0.8),0.2(0.1 -0.9),0.2(0.1 -0.4),0.3(0.1 -0.5),0.1 (0.1 -0.2) mg/L,respectively.There were statistical differences between these groups (H =19.898,P < 0.01 ).And the PCT levels in groups of LRTI with sepsis,HAP,CAP,AECOPD,other LRTI were higher than group of non-infectious diseases ( U values were 0,18.000,81.000,20.000,all P < 0.01 ).Patients with sepsis exhibited strongly higher PCT levels than patients with other lung diseases ( U values were 11.000,45.000,3.000,4.500,all P < 0.01 ).Pearson correlation analysis of PCT levels with positive bacterial cultures and APACHE Ⅱ score was performed ( r =0.449).ROC analysis revealed that optimal discrimination between LRTI and non-infectious diseases could be performed at the cut-off point of 0.5 mg/L with a sensitivity of 32.6% and specificity of 100%,while at a suggested cut-off point of 0.235 mg/L with a sensitivity of 53.9% and specificity of 100%.Conclusions PCT is a more useful parameter for diagnosing lower respiratory tract infections( especially for those with sepsis) than other infectious markers such as CRP,ESR and white blood cell count.The sensitivity of PCT could be elevated with a reduction of the cut-off level.
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Objective To explore the correlation between the levels of nitrite/nitrate(NO2/NO3) in exhaled breath condensate (EBC) and pulmonary infection in mechanically ventilated patients.Methods The clinical data from ventilated patients in critical care units of Peking University People' s Hospital from November 2006 to August 2007 were collected and analyzed.The patients' clinical pulmonary index score (CPIS) were calculated.EBC of those patients were collected via endotracheal tube or tracheostomy cannula, and the concentrations of NO2/NO3 were assayed.The level of NO2/NO3 in different CPIS patients in 24 hours' ventilation,weaning proportion in 3 days and mortality in different NO2/NO3 level patients were compared.The correlation of the CPIS and level of NO2/NO3 were explored between survival and non-survival patients.Results A total of 76 patients were enroled.The NO2/NO3 levels in patients of CPIS≤3 ,CPIS 3-6 and CPIS >6 in 24 hours of ventilation were (23.31±5.79), (28.72±9.10) and (35.42±12.10) μmoL/L respectively, with significantly differences between each other (P < 0.01).The lower the patients' concentration of NO2/NO3 was, the earlier the weaning and the lower the mortality were.The NO2/NO3 levels on 4th and 7th day were detected in 24 survival patients and 23 non-survival patients.The difference of NO2/ NO3 levels between the survival patients and non-survival patients became significant on 7th day [(29.32±9.52) μmol/L vs.(37.22±12.03) μmol/L, P < 0.01].Linear correlation analysis showed that the NO2/ NO3 level was positively correlated with CPIS (r = 0.76, P < 0.01).Condusions The NO2/NO3 level of EBC in ventilated patients is positively correlated to the severity of pulmonary infection, thus may be used as a new predictor for weaning and prognosis.
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Objective: To investigate the protective factors and risk factors of nosocomial infection of severe acute respiratory syndrome (SARS) among health care workers (HCWs) , and thus provide the scientific basis for prevention and control of nosocomial infection. Methods: With the case-control study,a standardized questionnaire was used for data collection in three general hospitals where nosocomial infection had occurred. Univariate analysis was done at first. All concerned factors about SARS infection were scanned by using Chi-square test and Fisher' s exact test one by one, and determined as to whether they were risk factors or protective factors according to odd ratio (OR) score. Then, multivariate unconditional logistic regression analysis was used to re-analyze the picked-out factors for finding out which factors played independent roles. Results: Twenty-two factors (nineteen protective factors and three risk factors), among the total fifty-six factors, were significantly associated with SARS infection. Multivariate unconditional logistic regression revealed that factors such as double exposure suits ( OR = 0.053 ), education ( OR =0.072), gloves ( OR =0.102), hands sterilized by iodine ( OR =0.231 ), room air ventilation (OR = 0.32), were significantly protective; conversely, tracheal intubation ( OR = 30.793 ) was a significant risk factor. Conclusion: Strict defense and antisepsis measures were pivotal in preventing SARS infection among high-risk medical personnel. Education about associated knowledge and effective air ventilation were also important factors.
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65yrs, diabetes mellitus, chronic renal failure, etc; of which 7 were independent risk factors associated with death (P
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Objective To improve the understanding and diagnosis of pulmonary lymphangioleiomyomatosis (PLAM) by the comprehensive review of domestic literatures in the past ten years.Methods Three new cases with PLAM were reported and integraed with other 45 cases reported domestically in the past ten years for analysis of their clinical features.Results The newly reported three cases of PLAM were all women at child-bearing age, with initial symptom of dyspnea after activity. Two of them complicated with extra-pulmonary PLAM. All the three cases were free of chylous effusion. Forty-seven of 48 cases with PLAM were pathologically diagnozed, with ages of onset of 5~69 (mean?s of 34?10) years. Their clinical manifestations were mainly respiratory, including dyspnoea (95.8%), haemoptysis (52.1%), pneumothorax (45.8%), chylous effusion (33.3%),cough (31.3%) and chest pain (12.5%). Abnormal manifestations in abdomen, including renal mass, retroperitoneal mass and retroperitoneal lymphadenopathy, were detected in 16 cases. Thirty-nine cases had their high-resolution CT (HRCT) examined and appearance of multiple cysts distributed throughout the bilateral lung fields could be discerned in 38 of them. Obstructive ventilation disturbance could be observed in 23 of 30 cases with the data or conclusions on pulmonary function tests, and mixed ventilation disturbance in seven cases. Respiratory failure was complicated in 17 of 28 cases with the data of arterial blood gas analyses.Conclusions HRCT had confirmative value for diagnosis of PLAM. In practice, HRCT, as well as other routine abdominal and pelvic imaging examinations, should be performed in time for child-bearing-age women with progressive dyspnoea, haemoptysis, or spontaneous pneumothorax, to detect if they complicate with PLAM.
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<p><b>OBJECTIVE</b>To explore the clinical and radiological features of severe acute respiratory syndrome (SARS).</p><p><b>METHODS</b>Analysis of the clinical presentation, chest radiographs, course of disease and features of severe pneumonia in 45 SARS patients diagnosed at our hospital in Beijing between April 5 - 20, 2003. Also included is a summation of the clinical features of SARS.</p><p><b>RESULTS</b>(1) SARS appears to have high infectivity; (2) the most common symptom is fever; (3) the count of leukocyte is normal or decreased; (4) most patients (35/45, 77.8%) had experienced a 24-hour fever prior to the abnormal chest X-ray changes which showed progression of pulmonary infiltrates within 48 hours in 71.1% (32/45) of the patients and, (5) the percentage of patients who developed severe pneumonia (24.4%) is higher than those who developed typical pneumonia.</p><p><b>CONCLUSION</b>SARS is a disease with high infectivity and has its own clinical and radiological features. Early recognition, prompt isolation, and appropriate therapy are the key to combat this infection.</p>
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Síndrome Respiratória Aguda Grave , Diagnóstico , Mortalidade , TerapêuticaRESUMO
<p><b>OBJECTIVE</b>To investigate adenoviral vector mediated exogenous gene expression in mouse lungs and the effect of mIFN-gamma transgene expression on allergen-induced pulmonary eosinophil infiltration in a murine asthmatic model.</p><p><b>METHODS</b>LacZ marker gene was transduced into CD-1 mouse airway epithelial cells by installation of a replication-deficient adenovirus with LacZ gene (AdCMVLacZ) 5 x 10(9) plaque forming unit (pfu) in the intratrachea or nostril. C57 mice were sensitized intraperitoneally and challenged by aerosol with ovalbumin (OVA) to produce an asthmatic model. AdCMVmIFNgamma 5 x 10(9) pfu was administered via nostril in asthmatic mice 48 h before OVA challenge. Sera, bronchial alveolar lavage (BAL) and lungs were recovered 48 h after OVA challenge.</p><p><b>RESULTS</b>After administration with AdCMVLacZ by intratracheal installation or nose-drop, the lungs revealed a high level of widespread LacZ transduction with X-gal staining, mainly along airways. IFN-gamma via adenoviral vector transduction could be overexpressed both in vitro and in vivo (1624.7 +/- 1321.5 pg/ml in BAL 96 h after AdCMVIFNgamma infection). In AdCMVIFNgamma treated asthmatic models, histological evaluation revealed marked suppression of eosinophil peribronchial and perivascular infiltration; the recoverable percentage of eosinophils in BAL was an average of 9.00% +/- 4.58%, which was a statistically significant decrease versus that of the positive control group (75.13% +/- 6.85%) (P < 0.001). The total cell number in BAL ((145 +/- 55.6) x 10(3) cells/ml) in AdCMVmIFNgamma treated mice also was tremendously reduced compared to the positive control group ((216.6 +/- 71.1) x 10(3) cells/ml).</p><p><b>CONCLUSIONS</b>Adenoviral vector was able to overexpress exogenous gene in murine lungs. IFN-gamma overexpression via adenoviral vector in pulmonary epithelia in vivo can abrogate allergen-induced eosinophilic infiltration in lungs in an asthmatic model, which may suggest a new preventively therapeutic method for cytokine immunogenetic transfer in allergic asthma.</p>
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Animais , Masculino , Camundongos , Adenoviridae , Genética , Asma , Terapêutica , Modelos Animais de Doenças , Eosinofilia , Terapia Genética , Interferon gama , Genética , Pulmão , Patologia , Camundongos Endogâmicos C57BL , Ovalbumina , Alergia e Imunologia , TransgenesRESUMO
Cytomegalovirus is the most common pathogen resulting in pulmonary pneumonia in the immunocompromised host.The clinical manifestation of cytomegaloviral pneumonia shows acute onset of illness and rapid progress.It will develop to acute lung injury or acute respiratory distress syndrome in several days if delaying the diagnosis and proper intervention.It also shows high mortality and poor prognosis.It plays a very important role for the laboratory pathogen assay to make the confirmed diagnosis.Regarding to the therapeutic strategies,early administration of gancyclovir with intravenous immunoglobin is a recommended cocktail intervention,which could improve the prognosis and decrease the mortality.Combination of antibiotics is usually not recommended except with confirmed bacterial infection or invasive mechanical ventilation in order to refrain from making a further complicated situation.
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Objective To explore the current therapeutic strategy for community acquired pneumonia(CAP) in the tertiary hospitals in Beijing district,and provide the evidence-based medicine for recommending application of Chinese community acquired pneumonia(CAP) guideline in our country widely.Methods The data of 225 hospitalized CAP patients from July 1st,2002 to June 30,2004 was documented retrospectively. The patient's situation was scored by either Chinese CAP guideline or Fine's risk classification.The data was analyzed with SPSS 10.0 to identify the correlation between the results evaluated by the two guidelines,and the differences of the combining use of antibiotics and antibiotic selection between group 1 and group 2 classified by Chinese CAP guideline.Results There was a significantly statistical correlation between the two guidelines(P=0.0000).There was a significantly statistical difference both in alternative administration of single or combining antibiotics(P=0.0290) and alternative application of penicillin or the third generation of cephalosporins(P=0.0001,P=0.005,respectively) between hospitalized criteria mismatched and matched groups classified by Chinese CAP guideline.The ratio of using fluroquinolone in above two groups was significantly high compared with other reagents,and there was no significant difference between them(P=0.182).Conclusion There is significant correlation between Chinese CAP guideline and Fine's risk classification.Chinese CAP guideline can be used to distinguish CAP from different risk levels.It is necessary to enforce and standardize the CAP diagnosis and treatment guideline widely.