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Diabetes mellitus (DM) is a known risk factor for pulmonary tuberculosis (PTB). This study aimed to determine if type 2 DM alters manifestations and treatment outcome of PTB. Records of 217 consecutive culture-proven PTB patients were analysed retrospectively. The manifestations and treatment outcomes of 74 patients with type 2 DM (PTB-DM group) were compared to 143 patients without DM (PTB group). PTB-DM patients showed higher frequencies of fever, haemoptysis, positive acid-fast bacilli sputum smears, and consolidation, cavity, and lower lung field lesions on chest radiographs, and higher mortality rate. Furthermore, type 2 DM, age 65 years, and extensive radiographic disease were factors independently associated with an unfavorable outcome. This study confirmed that clinical manifestations and chest radiographs of PTB patients associated with type 2 DM significantly depart from the typical presentation. Type 2 DM seems to have a negative effect on treatment outcome of PTB.

Background: The characteristics of pulmonary tuberculosis (TB) in the elderly are different from young patients. This leads to delay in diagnosis and higher mortality from TB in the aged population. The aim of this study was to investigate the impact of age on the demographic, clinical, radiographic characteristics, and treatment outcomes of pulmonary TB patients in Taiwan., Materials and Methods: We performed a retrospective analysis of the medical charts and chest radiographs of 83 elderly (> or =60 years old) and 74 young (< 60 years old) culture-proven pulmonary TB patients from 1 August 2003 to 31 July 2006., Results: Elderly patients showed lower frequencies of infectious TB contact history, alcoholism, cavity, and positive acid-fast bacilli sputum smears. In contrast, the elderly population had higher frequencies of chronic obstructive lung disease, heart failure, stroke, dyspnea, lower lung field involvement, pleural effusion and mortality. There were no differences between these two groups regarding sex, initial body weight, previous TB disease, hospital admission, diabetes mellitus, end-stage renal disease, neoplasm, liver cirrhosis, upper lung field involvement, cure, and treatment completion. Furthermore, age of 60 and older, lower initial body weight less than 50 kg, coexisting medical diseases, and extensive radiographic disease were factors independently associated with unfavorable outcomes., Conclusions: Elderly patients with pulmonary TB are more likely to present with negative sputum smears, cavity-negative lesions, lower lung field involvement and pleural effusion on chest radiographs. The prognosis is poor for the elderly pulmonary TB patients with lower body weight, coexisting medical diseases, and extensive radiographic disease.

beta-thalassemia major can be caused by homozygosity or compound heterozygosity for beta-globin gene mutations (HBB gene). Most cases are inherited from parents who both have diseased alleles of the HBB gene. We report a patient with late-onset beta-thalassemia major that evolved from beta-thalassemia minor in which only one of her parents had the diseased HBB gene. To study the cause of beta-thalassemia major in this patient, we performed the 100K single nucleotide polymorphism genotyping assay, fluorescence in situ hybridization, and DNA methylation analysis of the imprinting genes near the HBB gene. The results showed a loss of heterozygosity in the region of chromosome 11p14.3 to 11p15.5, which perfectly matched one allele of her father. Our study demonstrates that paternal uniparental isodisomy of chromosomal 11p15.5 is associated with the beta-thalassemia major in this patient. Key words: beta-thalassemia major, uniparental isodisomy, mosaicism.

Cytokine-induced inflammation is the predominant underlying mechanism in chronic obstructive pulmonary disease (COPD). Genetic factors may play a pivotal role in the development of this disease. This study looked at the relationship between COPD and genetic polymorphisms in the genes encoding some of these cytokines in a Taiwanese population. The genetic polymorphisms examined in this study were tumor necrosis factor (TNF)-alpha(-308), TNF-alpha(+489), interleukin(IL)-1beta(-31), interleukin-1 receptor antagonist (IL-1 RN), and IL-6(-174). In total, 30 patients with COPD, 64 subjects at risk of COPD and 115 controls were recruited to the study between 1999 and 2003. DNA was collected from these subjects and analyzed by polymerase chain reaction with sequence-specific primers and restriction enzyme fragment length polymorphism analysis. The frequencies of cytokine genotypes in COPD cases and controls, respectively, were as follows: for G/G in TNF-alpha(-308), 76.7% and 83.5%; for G/G in TNF-alpha(+489), 76.7% and 68.7%; for C/T in IL-1beta(-31), 60.0% and 55.7%; for 4R/4R in IL-1 RN, 80.0% and 86.1%; and for G/G in IL-6(-174), 100.1% and 98.3%. There was no difference in the distribution of the frequencies of these genotypes and alleles between COPD cases and controls. Moreover, no association was found between these genetic polymorphisms in cytokines and COPD (regardless of COPD subtypes) with respect to cigarette smoking or pulmonary function tests. Despite this, smoking is still an important risk factor for developing COPD.

Background/purpose: Clinicians need to decide whether to begin isolation and empiric therapy for patients suspected of having infectious tuberculosis (TB). This study aimed to identify the demographic, clinical and radiographic characteristics of acid-fast bacilli (AFB) smear-positive patients and to create a smear-positive TB prediction rule, which clinicians may use to predict risk., Methods: This was a retrospective study involving 105 patients with AFB smear-positive TB and 52 patients with AFB smear-negative TB at Kaohsiung Municipal Hsiao-Kang Hospital in southern Taiwan from August 1, 2003 to July 31, 2006. All of the patients had at least one sputum culture that was positive for Mycobacterium tuberculosis. Demographic, clinical and radiographic data of patients with AFB smear-positive TB were compared to those of patients with AFB smear-negative TB., Results: On univariate analysis, young age (p = 0.033), alcoholism (p = 0.036), weight loss (p = 0.003), fever (p = 0.018), consolidation (p = 0.001), infiltration (p = 0.012), cavitary pattern (p = 0.005), right upper lung field (p < 0.001) and left upper lung field (p = 0.001) lesions on chest radiographs were found to be predictive of smear-positive TB patients. In contrast, end-stage renal disease (p = 0.035) and normal chest radiograph (p = 0.006) were predictive of smear-negative TB patients. On multivariate analysis, age less than 65 years (p = 0.004), fever (p = 0.004), right upper lung field (p = 0.044), left upper lung field (p = 0.041), consolidation (p = 0.018) and cavitary (p = 0.049) lesions on chest radiograph were independently associated with an increased risk of an AFB positive smear finding. The smear-positive TB prediction model was created based on the results of the multivariate analysis that had an area of 0.788 under the receiver operating characteristic curve., Conclusion: The smear-positive TB prediction model may help clinicians decide if a patient with pending sputum smear results should first be placed in isolation and empiric anti-tuberculous therapy started.

This study aimed to identify the clinical characteristics of culture-positive pulmonary tuberculosis (TB) patients from a southern Taiwan hospital-based survey between August 1, 2003 and July 31, 2006. Demographics, symptoms, susceptibility patterns, sputum acid-fast bacilli (AFB) stain status and treatment outcomes were recorded. The medical records of 154 patients who presented to the Kaohsiung Municipal Hsiao-Kang Hospital were analyzed retrospectively. The mean age of patients was 59.5 years; 115 patients were male and 39 were female. Diabetes mellitus (48/154; 31.2%) was the most frequent risk factor for pulmonary TB infection. Nearly all patients (139/154; 90.3%) had a cough. Fever was only seen in 27.9% and hemoptysis in 14.9% of patients. The combined resistance rates of Mycobacterium tuberculosis to the tested first-line agents were as follows: isoniazid, 3.2%; rifampin, 7.8%; ethambutol, 5.8%; and streptomycin, 2.6%. The combined resistance rate to any one of four first-line drugs was 12.3%. The combined resistance rate to ofloxacin was 3.9%. The combined resistance rate of multidrug resistant-TB was 1.9%. Sputum AFB stains were positive in 68.2% of cases. Analysis of treatment outcomes showed overall treatment success at 76.6%. The proportions of patients who died, defaulted treatment or in whom treatment failed were 16.2%, 3.9% and 0.0%, respectively. In conclusion, our study showed: (1) a higher frequency of pulmonary TB in male subjects than in other areas of Taiwan; (2) a higher frequency of cough and lower frequency of fever and hemoptysis than previous studies; (3) that the combined resistance rates to isoniazid and streptomycin were lower than both average levels in Taiwan and the global combined drug resistance rate; and (4) a higher proportion of patients responding to treatment and lower proportions of patients suffering mortality, defaulting treatment or not responding to treatment compared with other areas of Taiwan. With regard to resistance rates, the combined resistance rate to ethambutol was similar to the average level in Taiwan and higher than the global combined drug resistance rate. However, the combined resistance rate to rifampin was higher than both the average level in Taiwan and the global combined drug resistance rate. The combined resistance rates to at least any one of four first-line drugs and multidrug resistant-TB were lower than the average levels in Taiwan and higher than the global combined drug resistance rate. Our results may help to identify local variations in the disease and improve the effectiveness of TB infection control programs.

Objective: To investigate the association between family history of cardiovascular disease (CVD) and cholesteryl ester transfer protein (CETP) TaqIB polymorphism in Taiwanese subjects., Subjects and Methods: In this cross-sectional study, 240 subjects (115 men and 125 women) were divided into two groups based on whether or not they had a parental history of CVD. Polymerase chain reaction/restriction fragment length polymorphism was used to analyze the genotype of the subjects for the TaqIB polymorphism of CETP in intron 1., Results: The frequency of the B1B1 genotype was significantly higher in Taiwanese subjects with a family history of CVD than in those without it (31.2 vs. 18.8%, odds ratio = 1.97, 95% confidence interval = 1.084-3.579, p = 0.035). Siblings with the B1B1 genotype had lower levels of serum high-density lipoprotein cholesterol (HDL-C) than siblings with either B1B2 (46.7 +/- 11.0 vs. 52.5 +/- 11.1 mg/dl, p = 0.034) or B2B2 genotypes (46.7 +/- 11.0 vs. 55.2 +/- 9.6 mg/dl, p = 0.01)., Conclusion: CETP TaqIB polymorphism is associated with plasma HDL-C levels. The CETP B1B1 genotype may influence the susceptibility to CVD in Taiwan., ((c) 2008 S. Karger AG, Basel.)

The present study systematically explores the biological pathways and altered expression of genes speculatively participating in lung carcinogenesis by using oligonucleotide microarray-bioinformatic analysis methods. The results revealed that 1,396 genes were up-regulated and 1,965 were down-regulated in lung adenocarcinoma carcinogenesis. Gene ontology and relevant bioinformatics tools indicated that the functional category to which the most frequently differentially expressed genes were classified, was to the cytokine-cytokine receptor interaction pathway, focal adhesion pathway and the mitogen-activated protein kinase signaling pathway. Furthermore, we constructed a membrane array, consisting of 51 up-regulated genes in lung adenocarcinoma, in order to verify the biological pathways involved in the carcinogenesis of lung cancer. The analysis of 45 lung adenocarcinoma tissue specimens demonstrated that the genes involved in these three biological pathways had high rates of overexpression. Out of the 51 genes, 17 genes were demonstrated to be overexpressed in all 45 lung adenocarcinoma tissues compared to the paired normal lung tissues. These findings could have implications in understanding the process of lung adenocarcinoma carcinogenesis. Moreover, our developed membrane arrays could be a potentially feasible and promising tool in clinical practice for analyzing the molecular mechanisms of lung adenocarcinoma carcinogenesis.

Studies have shown that weekend or night admissions to intensive care units (ICUs) are associated with increased mortality in critically ill patients. Our study aimed to evaluate the effects of admission time and day on patient outcomes in a medical ICU equipped with patient management guide-lines, and staffed by intensivists on call for 24 hours, who led the morning rounds on all days of the week but did not stay in-house overnight. The study enrolled 611 consecutive patients admitted to a 26-bed medical ICU in a university hospital during a 7-month period. We divided them into two groups, which we labeled as "office hours" (08:00-18:00 on weekdays) and "non-office hours" (18:00-08:00 on weekdays, and all times on weekends) according to their ICU admission times. The clinical outcomes were compared between the groups. The effects of admission on weekends, at night, and various days of the week on hospital mortality were also evaluated. Our results showed that there were no significant differences in ICU and hospital mortalities between patients admitted during office hours and those admitted during non-office hours (27.2% vs. 27.4%, p = 1.000; 38.9% vs. 37.6%, p = 0.798). The ICU length of stay, ICU-free time within 21 days, and length of stay in the hospital were also comparable in both groups. Among the 392 patients requiring mechanical ventilation, the ventilator outcomes were not significantly different between those in the office-hour group and the non-office-hour group. Multivariate logistic regression analyses showed that the adjusted odds of hospital mortality were not significantly higher for patients admitted to our ICU on weekends, at night, or on any days of the week. In conclusion, our results showed that non-office-hour admissions to our medical ICU were not associated with poorer ICU, hospital, and ventilator outcomes, compared with office-hour admissions. Neither were time of day and day of the week admissions to our ICU associated with significant differences in hospital mortality.

The ability to detect K-ras oncogene may provide additional information for the management of patients with non-small cell lung cancer (NSCLC). In the present study, we detected the K-ras oncogene in 76 patients with NSCLC by two methods: direct sequencing of K-ras in tumor tissues and membrane array detection of the gene overexpression specific for activated K-ras in peripheral blood. The results showed that 28 (36.8%) of the 76 Taiwanese NSCLC patients had K-ras mutations, with a frequency of 36.4% (20/55) in adenocarcinomas and 38.1% (8/21) in squamous cell carcinomas. The K-ras mutations were more frequently found in smokers than in non-smokers (51.4 vs. 24.4%, P=0.015). The incidences of K-ras mutation in the subgroups of non-smokers and squamous cell carcinomas are relatively higher in Taiwan than in other countries. On the other hand, the membrane array method could positively detect circulating activated K-ras in all of the 27 NSCLC patients with K-ras mutations at codons 12, 13 and 61, and in 4 of the 48 patients with wild-type K-ras. Our results suggest that the K-ras oncogene membrane array serves as a sensitive and convenient tool for the detection of K-ras oncogene, and therefore, has a great potential for clinical applications.

Background and Objective: The value of routine culture for mycobacterium from bronchoscopic washings and the cost-effectiveness is still uncertain in countries where tuberculosis is endemic. This study examined the epidemiology of positive cultures for M. tuberculosis obtained by bronchoscopy to determine the health benefit and cost of a policy of routine culture and smear., Methods: All positive cultures for Mycobacterium tuberculosis in bronchial washings and the corresponding CXR features were analysed., Results: The incidence of tuberculosis in routine bronchoscopy was 3.71%, and in patients who presented with typical tuberculosis features on CXR was 6.5%. Up to 10.6% of culture-proven pulmonary tuberculosis relied on bronchoscopy for diagnosis. The total cost of routine mycobacterium culture and acid-fast bacillus smear during the 2-year period was approximately US $24,800., Conclusion: Routine mycobacterium culture and acid-fast staining from bronchoscopic specimens appears to be valuable in countries where tuberculosis is prevalent.

The expression of the melanoma-associated antigen (MAGE) genes consists of variables in all tumor types, such as lung cancer, which are relevant to be silent in all normal tissues except germ cells. They are considered as tumor-specific antigens, and are ideal targets for cancer immunotherapy. A complete MAGE genes differential expression profile analysis of lung cancer can provide this study not only various target genes for immunotherapy, but also valuable markers for further diagnosis and prognosis. This research has constructed a membrane array, which was consisted 32 MAGE genes, to detect whether the differential expression profile occurred in 52 pairs of non-small-cell lung cancer (NSCLC) samples. Nearly 32 MAGE genes have been differential expressed in NSCLC except MAGE-B1 and -E2. MAGE-B, -C, -D, and subgroup -B6, -D4 have showed prominences in lung adenocarcinoma. High-frequent expression of MAGE-D, and subgroup -A2, -D2 has also been discovered in non-metastasis group (p<0.05). However, there is no significant difference of MAGE genes differential expression shown among different primary tumor (T), nodal involvement (N) and overall stages. Several MAGE subgroup genes, such as MAGE-A5, -A7, -A8, -A9, -A11, -B3, -B4, -B10, -D2, -D3, -F1, -G1, -H1, and -L2, have been first discovered to show differential expression in NSCLC. Although the small size of the sample may limit the diagnostic and prognostic value of MAGE genes, the function of the membrane array can provide this study a high-throughput method to detect the whole MAGE genes differential expression profile.

Poisoning due to organophosphate pesticides is an important cause of morbidity and mortality worldwide. Although standard treatments involving the administration of atropine and oximes have been used, there remain many controversial areas concerning organophosphate poisoning (OPP). Herein, we present our 10 years of experience in assessing the severity of OPP in southern Taiwan. A retrospective study was performed on patients admitted with OPP. A total of 75 patients (50 males and 25 females) were studied between January 1996 and December 2005. Diagnosis was based on a clinical assessment and serum acetylcholinesterase (AChE) level at the time of hospital admission. The severity of OPP was assessed using the grading system of Bardin et al. The duration and dosage of atropine and palidroxime were recorded. All the biochemical data were analyzed. Sixty-one of the patients had attempted suicide and 14 patients had accidental exposure. The overall mortality rate was 8%. Muscarinic effects were observed in 66 (88%) of the OPP patients and the most frequent symptom was bronchial hypersecretion (52%). Among these three different severity groups, prolonged length of stay, higher infection rates, and higher mortality were found in the life-threatened group. The initial serum C-reactive protein (CRP) level was strongly correlated to the severity grading of the OPP. Nearly half of the patients were admitted to the intensive care unit (ICU) and, of this, 21 patients developed respiratory failure within 72 hours. Low serum AChE levels support the diagnosis of OPP, but no significant association was found between the severity of OPP and serum AChE levels. The grading system of Bardin et al is very helpful for physicians to facilitate the recognition of seriously poisoned subjects, and to permit their early admission to an ICU. Initial serum CRP, an acute phase reactant, had significant value in assessing the severity of the OPP. Although the management of acute OPP is supportive and the recovery rate is high, anti-cholinergic therapy should be used as soon as possible to counteract muscarinic effects. Physicians must be aware of the potential dangers of respiratory failure, which could occur within 72 hours of OPP.

Objective: The potential difficulty in doing initial dilation in the percutaneous dilational tracheostomy (PDT) with the Ciaglia Blue Rhino (CBR) technique has been reported by others and encountered in our clinical practice. To resolve this problem, we developed a modified CBR technique by using a guidewire dilating forceps (GWDF) to facilitate initial dilation. The present before-and-after comparison study aimed to evaluate the clinical benefits of this modified CBR technique., Methods: Consecutive 120 patients undergoing CBR technique in the pre-conversion year and 114 patients undergoing GWDF-CBR technique in the post-conversion year were enrolled for analysis. The procedure time and procedure-related complications were compared between these two groups., Results: The mean procedure time with GWDF-CBR technique was 4.5+/-1.6min, significantly shorter than 5.7+/-3.0min with CBR technique (p<0.001). Only two patients in the GWDF-CBR group required prolonged procedure time (>8min), compared with 14 patients in the CBR group. Thirty three (27.5%) of 120 patients undergoing CBR technique and 15 (13.1%) of 114 patients undergoing GWDF-CBR technique had PDT-related complications (p=0.006). Most of the complications were minor and transient. Only 13 patients in the CBR group and 3 patients in the GWDF-CBR group encountered major complications (10.8% vs 2.6%, p=0.012). Regarding the high-risk patients, 21 (36.2%) of 58 patients in the CBR group and 9 (15.8%) of 57 patients in the GWDF-CBR group had PDT-related complications (p=0.011)., Conclusions: Pre-dilation with a GWDF in the CBR technique helped to prevent prolonged procedure time and procedure-related complications. We suggest that the bronchoscopy-guided GWDF-CBR serves an easy-to-operate and relatively safe PDT technique for critically ill patients.

Mutations of K-ras gene have been demonstrated in 40-50% of colorectal cancer and large adenoma (>1 cm). This study was intended to clarify the correlation between the existence of K-ras oncogene and the pathological features of colorectal adenomas using our recently developed membrane arrays. Moreover, the downstream genes regulated by K-ras oncogene were explored to serve as potential biomarkers in the early diagnosis and risk assessment of patients with colorectal adenoma. Specimens were collected from 70 patients with colorectal adenoma. The alterations of K-ras oncogene were analyzed by direct sequencing and our constructed membrane arrays, respectively. The results of direct sequencing showed that 21 of 70 samples (30%) had K-ras gene mutations. The most frequently mutated sites included codons 12, 13, 15 and 18. Furthermore, activated K-ras oncogene was identified in 18 of 70 (25.7%) adenoma by membrane arrays. Statistical analyses showed that the membrane array had the accuracy of 90.0%, sensitivity of 88.9%, and specificity of 90.4%. The frequency of the mutational sites of K-ras gene was located as follows: codon 12, 100% (4/4); codon 13, 100% (4/4); codon 15, 75% (6/8); and codon 18, 100% (2/2). The analysis of the correlation between the experimental data and pathological characteristics of adenoma showed that activated K-ras oncogenes were significantly associated with the size, number and histology of adenomas (all P<0.001). Finally, we found the downstream genes activated by K-ras oncogene, including B-cell CLL/lymphoma 2 (BCL2), Homo sapiens H2A histone family, member Z (H2AFZ), Homo sapiens RAP1B, member of RAS oncogene family (RAP1B), Homo sapiens T-box 19 (TBX19), Homo sapiens E2F transcription factor 4, p107/p130-binding (E2F4) and matrix metallopeptidase 1 (MMP1), of which were overexpressed in most of all examined adenomas. These genes were then suggested to have functions involved in cell growth. The preliminary results indicated that the accuracy of membrane arrays was comparable to conventional DNA sequencing in the detection of activated K-ras oncogenes. Therefore, we propose that activated K-ras oncogene in colorectal adenomas may play an important role in the subsequent colorectal carcinogenesis through a group of K-ras-related molecular targets.

Symptomatic gastro-intestinal (GI) metastasis in lung carcinomas is extremely rare and only a few case reports have been published. Here we review all of the cases of lung cancer from January 2003 to April 2005 in a tertiary teaching hospital in Taiwan. A total of six patients (1.77%, 6/339) with primary lung cancer demonstrated symptomatic gastro-intestinal metastasis. Three patients had squamous cell carcinoma, one had adenocarcinoma, and two had small cell carcinoma. Three patients with gastric metastasis were diagnosed via gastro-endoscopy while one with cecal involvement was diagnosed via colon fiberscopy. Two patients with small bowel perforation and intussusception were diagnosed via laparotomy. We presented these rare cases and made a review of the literature.

Research on molecular mechanisms underlying the carcinogenesis of non-small cell lung cancer (NSCLC) may provide gene targets in critical pathways valuable for improving the efficacy of therapy and survival of patients with NSCLC. However, the molecular markers highly sensitive for the prognosis and treatment evaluation of NSCLC are not yet available. To explore candidates, we conducted an oligonucleotide microarray study with three pairs of NSCLC and normal lung tissue, and determined 8 differentially expressed genes including the Human MutT homologue (hMTH1), Surfactant protein D (SPD), Human hyaluronan binding protein 2 (HABP2), Crystalline-mu (CRYM), Ceruloplasmin (CP), Integrin alpha-11 subunit (ITGA11), Collagen type XI alpha I (COL11A1), and Lung-specific X protein (Lun X). Four lung cancer-related markers MUC-1, hTERT, hnRNP B1, and CK-19 were also incorporated for further analysis. The expression profiles of the twelve genes in seventy pairs of NSCLC tumor and normal lung tissue were then detected quantitatively by using membrane array and quantitative real-time PCR (qRT-PCR). The data of the membrane array and qRT-PCR were compared for consistency and the potential of these mRNA markers in clinical application. The results showed that membrane array and qRT-PCR obtained consistent data for the tested genes in both sensitivity and specificity (correlation coefficient 0.921, p<0.0001). For patients' clinicopathological characteristics, the overexpression of hMTH1, SPD, HABP 2, ITGA11, COL11A1, and CK-19 was significantly correlated with the pathological stage (p<0.05). In addition, the overexpression of hMTH1, SPD, ITGA11, and COL11A1 was correlated with lymph node metastasis and poor prognosis. This is the first report relating SPD to a prognosis marker for NSCLC. Moreover, the combined detection of these four mRNA markers by membrane array had a sensitivity of 89% and a specificity of 84% for NSCLC, significantly higher than these markers had achieved separately. In conclusion, we identified mRNA markers for NSCLC prognosis and therapy evaluation from differentially expressed genes determined by using micro-array. Further studies are needed to collect the data of the mRNA markers used in clinical practice.

Since its introduction in 1985 by Ciaglia et al, percutaneous dilational tracheostomy (PDT) has gradually become the procedure of choice in establishing a long-term airway in many intensive care units (ICU). However, the safety of performing PDT in patients with barotrauma is still unknown and has never been reported. We present the case of a 35-year-old man with AIDS, who was admitted to our medical ICU for pneumonia and acute respiratory distress syndrome. He developed subcutaneous emphysema and pneumomediastinum as complications of mechanical ventilation. After stabilization of the barotrauma, he underwent PDT with the standard Ciaglia Blue Rhino technique. However, rapid and extensive progression of preexisting barotraumas occurred shortly after PDT. This severe complication was nearly fatal. The prolonged procedure during which the susceptible lung was exposed to longer duration of high airway pressure was thought to be the mechanism of rapid deterioration of the preexisting barotrauma. With aggressive supportive care, the patient survived. To prevent further deterioration of preexisting barotraumas during and after PDT in future cases, we propose some principles that should be strictly followed. Under administration of these principles, we safely performed PDT in another case with preexisting barotrauma 1 month later.

Amoxicillin/Clavulanate related extreme thrombocytosis during the treatment of pneumonia has never been reported. We present a 54-year-old patient who was admitted due to pneumonia, and was treated with amoxicillin/clavulanate IV and 3-day course of 500 mg azithromycin. Despite clinical and radiological evidence showing that pneumonia improved, thrombocytes increased rapidly. After stopping the antibiotic, the thrombocytes returned gradually to normal. Considering the clinical course, we propose that this extreme thrombocytosis was caused by the administration of amoxicillin/clavulanate. We describe this rare and unique patient and review the literature.

Combination of multiple mRNA markers has been largely investigated for detection of circulating cancer cells. However, current PCR-based methods are relatively expensive and time consuming. The aim of this study was to develop a membrane array-based multimarker assay for detection of circulating cancer cells in nonsmall cell lung cancer (NSCLC) patients. At first, we selected 22 candidate genes by means of suppression subtractive hybridization and Northern blot analysis. The diagnostic value of each candidate gene was then preliminarily evaluated in 50 pairs of blood samples by membrane array method. Accordingly, 17 genes with area under the ROC curve (AUC) > or = 0.8 were selected as target genes to reconstruct the diagnostic membrane array, which was then used to test peripheral blood samples from 100 NSCLC patients and 147 control subjects. ROC curve analysis demonstrated that the optimal threshold number of overexpressed markers on membrane array for discrimination between NSCLC patients and control subjects was 12. As a result, the diagnostic membrane array could detect circulating cancer cells in 90 (90%) of 100 NSCLC patients and in 14 (9.5%) of 147 control subjects (including 6 of 100 normal persons, 3 of 20 breast cancer patients, 3 of 15 colorectal cancer patients and 2 of 12 gastric cancer patients). Moreover, the detection rate was significantly correlated with NSCLC patients' metastatic status and overall stage (p = 0.028 and 0.014, respectively). These results suggested that our blood-based membrane array assay for molecular detection of circulating lung cancer cells has great potential for clinical applications.

Nicotine is potentially associated with the onset of chronic obstructive pulmonary disease (COPD) and lung cancer. To gain insights into the molecular mechanism underlying such nicotine-induced conditions, microarray- bioinformatics analysis was carried out in the present study to explore the gene expression profiles in human bronchial epithelial cells (HBECs) treated with 5 microM nicotine for 4, 8, and 10 h. Of 1,800 assessed genes overall, 260 (14.4%) were upregulated and 17 (0.9%) down regulated significantly. Gene ontology analysis demonstrated that most of the differentially expressed genes belonged to the category of molecular function, especially to the subcategories of enzyme activity. The integration of obtained information with bioinformatics tools in DAVID and KEGG databases indicated that the greatest number of overexpressed genes was involved in mitogen-activated protein kinase (MAPK) pathway. Membrane array analysis subsequently suggested that both extracellular signal-regulated kinase (ERK) 1/2 and c-Jun-NH(2)-terminal kinase (JNK) signalings but not p38 MAPK signaling were activated in response to nicotine. Pretreatment of HBECs with specific inhibitors against ERK 1/2 and JNK but not p38 could significantly inhibit nicotine-induced interleukin- 8 production. These results suggest that MAPK pathway may mediate the effect of nicotine through ERK 1/2 and JNK but not p38 in HBECs treated with nicotine.

Infective endocarditis has been the major cause of morbidity and mortality among intravenous drug users (IDUs) with infections, mostly involving the tricuspid valve and presenting multiple septic pulmonary embolisms. Numerous pulmonary complications of septic pulmonary embolism have been described, but only a few have reported spontaneous pneumothorax. Our patient, a 23-year-old heroin addict, was hospitalized for tricuspid endocarditis and septic pulmonary embolism. Acute onset of respiratory distress occurred on his seventh hospital day and rapidly resulted in hypoxemia. Immediate bedside chest radiograph demonstrated left pneumothorax. It was thought to be a spontaneous pneumothorax, because he had not undergone any invasive procedure before the occurrence of pneumothorax. His clinical condition improved after the insertion of an intercostal chest tube. He later underwent surgery to replace the tricuspid valve as a result of the large size of the vegetation and poor control of infection. He ultimately survived. Pneumothorax is a possible lethal complication of septic pulmonary embolism in IDUs with right-sided endocarditis and should be considered in such patients when respiratory distress occurs acutely during their hospitalization.

The objective of this study was mainly to evaluate the simultaneous detection of expression levels of a multiple mRNA marker panel in the peripheral blood of colorectal cancer (CRC) patients for use in complementary CRC diagnosis. Twenty-seven tumor tissue specimens and 80 peripheral blood specimens were collected from CRC patients. Firstly, the levels of multiple molecular markers in the tumor tissue and blood specimens were evaluated by using real-time quantitative PCR (RT-QPCR) and membrane array. The result of linear regression showed a high degree of correlation (r=0.954, P<0.0001) between the data of these two methods. CK-19 was the marker with the highest detection rate (87.5%) in the peripheral blood, followed by CEA (82.6%), REG4 (80.8%), and then uPA (80.0%) and TLAM1 (80.0%). The levels of the six markers in the peripheral blood were extensively explored. In the 80 patients, the frequency of CK-19, CK-20, CEA, REG4, uPA, and TIAM1 mRNA overexpression was 82.5% (66/80), 78.8% (63/80), 82.5% (66/80), 80.0% (64/80), 78.8% (63/80), and 80.0% (64/80), respectively. Then, a panel combining these 6 mRNA markers was evaluated for its utility in the clinical diagnosis of CRC. The sensitivity, specificity, and accuracy of membrane array-based diagnostic method were 88.8%, 87.8%, and 88.2%, respectively; much higher than those of examinations with single markers. Finally, lymph node metastasis (P=0.024) and TNM stage (P=0.009) were found to be significantly correlated with overexpression of the multiple mRNA marker panel. The detection rates of stage-I and -II CRC by using the multi-marker membrane array were 54.5% (6/11) and 92.0% (23/25), respectively. In conclusion, the results of the present study have shown that this innovative membrane array technique with a multiple mRNA marker panel can significantly improve the diagnosis rate of early colorectal cancer.

Objective: Detection of tumor-related mRNA in blood has become a potential cancer diagnostic approach. However, the sensitivity of single-marker assays is not high enough for clinical applications. The present study was aimed to evaluate the efficacy of a multimarker panel for molecular diagnosis of non-small cell lung cancer (NSCLC)., Methods: Carcinoembryonic antigen (CEA), cytokeratin 19 (CK-19), c-met and heterogeneous nuclear ribonucleoprotein (hnRNP) B1 mRNAs were quantified by quantitative real-time reverse transcriptase polymerase chain reaction in 34 tumor tissues and 69 peripheral blood samples of NSCLC patients., Results: All four markers displayed high overexpression rates (range 82.3-97.1%) in NSCLC tumors. When used as single markers in blood for NSCLC diagnosis, CEA, CK-19, c-met and hnRNP B1 could only reach sensitivities of 52.2, 50.7, 42 and 17.4%, respectively. However, the sensitivity was enhanced up to 85.5% when CEA, CK-19 and c-met were combined in a 3-marker panel. Moreover, the expression of c-met and hnRNP B1 in blood was significantly correlated with patients' pathological stages., Conclusions: The combined detection of CEA, CK-19 and c-met mRNAs in blood provided a valuable tool for molecular diagnosis of NSCLC. In addition, our results also suggested that hnRNP B1 was not a valuable diagnostic marker but a potential prognostic marker for NSCLC., (Copyright 2006 S. Karger AG, Basel.)

Objective: Early detection is a prerequisite to the effective reduction of morbidity and mortality from breast cancer. The present study intended to employ a high-throughput membrane array to detect a panel of mRNA markers expressed by circulating tumor cells (CTCs) in the peripheral blood of female patients with breast cancer., Methods: Peripheral blood was sampled from 92 breast cancer patients and 100 normal persons. CTCs were detected by using a membrane array technique. The markers used included the pituitary tumor transforming gene 1, survivin, UbcH10 and thymidine kinase 1., Results: The results showed that the membrane array could positively detect 5 cancer cells per 1 ml of peripheral blood in breast cancer cell dilution experiments. For the panel of 4 mRNA markers, sensitivity and specificity were elevated up to 86 and 88%, respectively. Furthermore, it was found that the patients' clinicopathological characteristics tumor size (p = 0.006), histologic grade (p = 0.012), lymph node metastasis (p = 0.001) and TNM stage (p = 0.006) significantly correlated with the positive detection rate of the multimarker panel., Conclusions: These findings demonstrated that our multimarker membrane array method could detect CTCs in the circulation of breast cancer patients with considerably high sensitivity and specificity., (Copyright (c) 2006 S. Karger AG, Basel.)

Primary mediastinal germ-cell tumors (GCTs) without gonadal involvement are rare and can be divided into benign mature teratoma and malignant seminoma or nonseminoma. We describe our experience of malignant mediastinal GCTs and compare the presentations and outcome with those of benign teratomas. Four malignant GCTs (1 seminoma, 1 choriocarcinoma, and 2 yolk-sac tumors) have been treated in our hospital. All patients were men with obvious symptoms before diagnosis. The patient with seminoma was treated with surgery and radiation, while those with nonseminoma tumors were treated with chemotherapy and/or surgery. Two patients died, one with extended pulmonary metastasis and the other with relapsed disease and high levels of tumor markers. Compared with the nine cases of benign teratomas, the four malignant GCTs showed overwhelming male dominance, advanced symptoms at presentation, and poor outcome. These cases highlight the important role of disease staging and tumor-marker levels in malignant GCTs, and suggest that new treatment strategies for malignant GCTs await further investigation.

Background: The c-met receptor and its ligand hepatocyte growth factor have been shown to be involved in tumor invasiveness and metastasis. Overexpression of c-met has been demonstrated in lung cancer tissues and cell lines, but the expression of c-met in peripheral blood (circulating c-met) has not been addressed. The molecular monitoring of circulating c-met could be helpful for selecting patients for adjuvant therapy., Objectives: To investigate the expression of circulating c-met in non-small cell lung cancer (NSCLC) patients and to assess its prognostic implications., Methods: We quantified the levels of c-met messenger RNA (mRNA) in paired tumor and normal lung tissues and their peripheral bloods in 45 patients with NSCLC by real-time polymerase chain reaction (PCR). The expression status of c-met protein in tumor tissues was further evaluated by immunohistochemistry., Results: c-Met mRNA was significantly higher by 1.5 to 11 times in 34 of 45 tumor tissues (75.5%) than it was in their normal counterparts by real-time PCR. A comparison of this assay to immunohistochemistry suggested that real-time PCR was more sensitive than immunohistochemistry (27 of 45 tumor tissues, 60.0%) for the detection of c-met (p = 0.016). Of these patients with overexpression of c-met in tumors, 67.6% (23 of 34 patients) expressed higher amounts of circulating c-met by 1.4 to 8 times that of the normal control subjects. In addition, overexpression of circulating c-met was significantly correlated with nodal (N) stage (p = 0.011), but weakly correlated with tumor (T) stage (p = 0.056) and overall stages (p = 0.054) in patients with NSCLC. However, no correlations were found among circulating c-met and other factors such as age, gender, and pathologic types. Moreover, by univariate analysis, circulating c-met overexpression and pathologic stages (including T and N stages) were the most important factors correlated with early recurrence (p < 0.05). Only the circulating c-met remained as an independent predictor of early recurrence (hazard ratio, 3.94; 95% confidence interval, 1.17 to 13.33; p = 0.027) after Cox regression multivariate analysis., Conclusions: Overexpression of circulating c-met is significantly correlated with the N stage and early recurrence. Moreover, early recurrence is frequently noted in patients with overexpression of circulating c-met, indicating that circulating c-met is an independent negative prognostic indicator in NSCLC.

Extensive researches have found that the mutation of p53 tumor suppressor gene is the most frequent event in many human cancers and associated with a poor clinical outcome in lung cancer patients. Because the p53 molecular mutation involved in tumorigenesis of patients with lung cancer in Taiwan remains poorly defined, the aim of this study was to assess the p53 mutation spectrum and possible etiological factors of Taiwan's patients with Non-Small Cell Lung Cancer (NSCLC). Cancer specimens were obtained surgically from 61 patients with pathologically proven NSCLC. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were used to study p53 mutations in exon 4-8. We also performed immunohistochemistry (IHC) to detect p53 protein expression. Our results provided that 34 mutations of p53 gene were found in 27 cases with a mutation rate of 44% (27/61). There were six cases having more than two p53 mutations. Among the 34 mutations, 19 were point mutations (56%, 19/34) consisted of a majority of missense mutations including transversion (13/19, 68%) and transitions (6/19, 32%) with four cases (4/6, 67%) occurring in the CpG sequence. One of the most important finding in our study was the high frequency of frameshift (44%, 15/34) which included 11 insertions and 4 deletions of p53 in NSCLC in Taiwan. Surprisingly, our results disclosed distinct novel mutations at codon 181, 185, 208 (Exon 5-6) of p53. Especially, 4 cases with mutation at codon181 and codon 185 seemed to have more advanced clinical outcome with survival time less than 6 months. In addition, there were two recurring mutations at codon 168 and three at condon193. The different mutation spectrum in our series, including a high frequency of frameshift mutations and distinctly novel hot spots suggested the heterogenous entity of exogenous mutagens in NSCLC in Taiwan.

The aims of this study were to present the clinical status of pulmonary tuberculosis in Southern Taiwan and to analyze the reasons for failure of antituberculosis treatment in order to achieve a higher rate of success after treatment. Two hundred and senventeen adult patients, aged 15 to 90 years old who presented to the Chest Division, Kaohsiung Medical University Hospital from 1999 to 2002 with a diagnosis of Pulmonary Tuberculosis, were retrospectively studied. We compared the rate of recurrence of pulmonary tuberculosis by dividing the cases into 2 groups: those who completed treatment and those who did not. We also determined the age distributions for when initial diagnosis of pulmonary tuberculosis was made among these 217 cases. In 90 culture proven cases, antituberculosis drug susceptibility was tested to determine the rate of drug resistance. We also assessed the reasons for failure of treatment. Age distribution analysis showed that initial infection began at a young age, was widely spread, and occurred regardless of age. There were 116 cases that completed antituberculosis treatment and 101 cases that did not. Of the 116 cases, only 16 relapsed, whereas 79 of the 101 cases relapsed. In cases where completely treated patients relapsed, the period before recurrence was indefinite. Most of the cases of incompletely treated patients relapsed earlier. In the 90 culture proven cases in which antituberculosis drug susceptibility was tested, 39 patients showed resistance to at least one drug, 9 patients were resistant to only one drug, 9 patients were resistant to two drugs and 21 patients were resistant to more than 3 drugs. The common reasons for failure of treatments were: 1) poor patient compliance to medication: 50 cases, 2) multiple drug resistance: 30 cases, 3) delayed treatment: 19 cases. Some cases included a combination of the above.

Cigarette smoking causes inflammation mainly confined to the airway and lung. Nicotine is one of the primary constituents in cigarette smoke. Alveolar macrophages apparently play a pivotal role in mediating pulmonary inflammation via the production of chemokines. Macrophage inflammatory protein-1 alpha (MIP-1 alpha), a member of CC chemokines, has been shown to contribute to monocyte/macrophage and neutrophil chemotaxis and activation. Our previous work demonstrated that MIP-1 alpha mRNA expression in macrophages is induced by a variety of stimuli. In the present study, we further investigate whether nicotine can regulate the gene expression of MIP-1 alpha in macrophages and determine the mechanism leading to increased expression. A rat alveolar macrophage (RAM) cell line, NR8383, was treated with nicotine at a dose of 3.1, 31, 310 microM, or 3.1 mM. Northern blot analysis showed that the induction of MIP-1 alpha mRNA expression was dose-dependent. To define the time course of the inflammatory response, RAM cells were exposed to 31 microM nicotine, MIP-1 alpha mRNA was induced as early as 1 h after treatment, was maximally expressed at 4 and 6 hours, and reduced by 8 hours. Western blot analysis demonstrated a single band with an estimated molecular weight of 10 kD for MIP-1 alpha which was induced after nicotine treatment, suggesting that expression of MIP-1 alpha mRNA could reflect in protein synthesis. In addition. the increase in MIP-1 alpha mRNA expression induced by nicotine was attenuated by co-treatment with the antioxidant N-acetylcysteine (NAC), at doses of 10 and 20 mM, suggesting that the induction of MIP-1 alpha mRNA is mediated via the generation of reactive oxygen species (ROS). To further investigate transcriptional regulation of the MIP-1 alpha gene expression, RAM cells were exposed to nicotine. MIP-1 alpha mRNA levels were significantly increased in nuclear RNA preparations, indicating that transcriptional activation is involved in increased expression of MIP-1 alpha mRNA. Moreover, we performed RNA decay assay by measuring the half-life of MIP-1 alpha mRNA. Treatment of RAM cells with the transcriptional inhibitor actinomycin D following exposure to nicotine revealed that the half-life of MIP-1 alpha mRNA was markedly increased by nicotine treatment, supporting a role of post-transcriptional stabilization in MIP-1 alpha gene expression. These observations indicate that nicotine can induce MIP-1 alpha mRNA expression and protein synthesis in RAM cells, mediating, at least in part, via the generation of ROS. In addition, the increase in MIP-1 alpha mRNA level involves, both transcriptional activation and post-transcriptional stabilization.

Primary pulmonary choriocarcinoma is an extremely rare tumor in men, with 13 cases reported in the literature. Due to its rarity, primary choriocarcinoma of the lung in men is often incorrectly diagnosed as more common diseases, such as primary or metastatic lung cancer, and therefore potentially curative chemotherapy or surgery may be withheld from the patient. In this report, we present the case of a 23-year-old man with hemoptysis and progressive dyspnea. Airspace consolidation with multiple nodules of varying sizes was found on a chest radiograph. The results of a urine pregnancy test were positive, and the beta-human chorionic gonadotropin level was markedly elevated both in the serum and the urine. Subsequently, testing of a bronchoscopic biopsy specimen proved these tumors to be choriocarcinoma. We conclude that the urine pregnancy test, a simple and convenient method, would be very useful in the rapid diagnosis of primary pulmonary choriocarcinoma in men.

Environmental and occupational exposure to vanadium dusts results in toxic effects mainly confined to the respiratory system. Using a rat model of acute lung inflammation induced by intratracheal instillation of sodium metavanadate (NaVO3) at the dose of 200 microg V/kg, we investigated the relationship between the cytologic characterization of pulmonary inflammation and the expression of chemokine mRNA. Significant polymorphonuclear leukocyte (PMN) influx (P < 0.01) into the lung was noted 4 h after NaVO3 instillation, whereas alveolar macrophages (AMs) in bronchoalveolar lavage (BAL) cells appeared to decrease significantly. In contrast, neither PMNs nor AMs changed substantially 1 h after NaVO3 instillation. By Northern analysis, macrophage inflammatory protein (MIP)-2 mRNA in BAL cells increased markedly 1 h after NaVO3 instillation and reduced a little bit at 4 h, whereas MIP-1alpha mRNA in BAL cells was expressed relatively high 1 h after NaVO3 instillation, although a basal expression was detected in control group, and returned rapidly nearly to control level at 4 h. Since MIP-2 is a potent PMN chemoattractant and MIP-1alpha is a potent macrophage/monocyte chemoattractant has been well known. The facts that PMN influx was preceded by increased MIP-2 mRNA expression, suggesting that MIP-2 is involved in the development of NaVO3-induced pulmonary inflammation, whereas increased MIP-1alpha mRNA expression was followed by decreased AMs in BAL cells, suggesting AMs might be activated by MIP-1alpha, adherent to the lining surface of the airways and then resistant to be washed out. To delineate the mechanisms of transcriptional activation, we recently cloned the 5'-flanking region of the MIP-2 gene. The promotor region contains consensus binding sites for transcription factor nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1). Using electrophoretic mobility shift assay, increased nuclear NF-kappaB, not AP-1, binding activity was detected 1 h after NaVO3 instillation, which correlated with the induction of MIP-2 mRNA. p65 (Rel A) and p50 protein appears to be involved in MIP-2 NF-kappaB binding. Taken together, our studies suggest that MIP-2 is an important mediator of NaVO3-induced pulmonary inflammation in the rat model. In addition, elevated MIP-2 mRNA levels are accompanied by increased NF-kappaB binding activity in BAL cells, suggesting possible MIP-2 transcriptional regulation through NF-kappaB.

Environmental and occupational exposure to vanadium (V) dusts results in inflammation mainly confined to the respiratory tract. Macrophages apparently play an important role in mediating the inflammation via the production of many chemokines. In the current study, we investigated whether vanadium can regulate the gene expression of a CXC chemokine macrophage inflammatory protein-2 (MIP-2), and to determine the molecular mechanisms controlling MIP-2 gene expression. A mouse macrophage cell line RAW 264.7 was treated with sodium metavanadate (NaVO3) at the dose of 0.5, 5, or 10 microg/mi V. Northern blot analysis showed that induction of MIP-2 mRNA expression was in a dose-dependent manner. To define the time course of the inflammatory response, RAW 264.7 cells were exposed to 5 microg/ml V, MIP-2 mRNA in macrophages increased markedly as early as 1 h after treatment, maximally induced at 4 h and reduced to 2-fold above control levels by 6 and 8 h. The protein levels of MIP-2 in conditioned media, measured by enzyme-linked immunosorbent assay (ELISA), was well correlated with the levels of MIP-2 mRNA following all of the treatments in the study. In addition, the increase in MIP-2 mRNA expression by vanadium was attenuated by co-treatment with the antioxidant N-acetylcysteine (NAC), at the doses of 10 and 20 mM, suggesting that the induction of MIP-2 mRNA is mediated via the generation of reactive oxygen species (ROS). To further investigate transcriptional regulation of the MIP-2 gene expression by vanadium, we performed RNA decay assay by measuring the half-life of MIP-2 mRNA. Co-treatment of macrophages with the transcriptional inhibitor actinomycin D at 5 microg/ml following exposure to 5 microg/ml V for 4 h revealed complete stabilization of vanadium-induced MIP-2 mRNA and no sign of mRNA degradation, at least, for 6 h, in comparison to the half-life of MIP-2 mRNA was approximately 2.5 h by bacterial lipopolysaccharide (LPS) treatment, supporting post-transcriptional stabilization as the predominant role of MIP-2 gene expression. In conclusion, these observations demonstrate that in vitro vanadium can induce MIP-2 mRNA expression, mediating, at least in part, via the production of ROS. In addition, the increase in MIP-2 mRNA level involves, most likely, post-transcriptional control via increased mRNA stability.

HGF is a pulmotrophic factor in the regeneration of an injured lung. However, the physiological role of HGF in vivo remains largely unknown. We studied HGF in patients with inflammatory lung diseases to investigate the clinical significance of HGF and compared with C-reactive protein (CRP) in inflammatory lung diseases. Forty-seven patients with inflammatory lung diseases (16 tuberculosis, 18 pneumonia, and 13 chronic obstructive pulmonary disease (COPD)) were studied. Fifty normal, healthy individuals were analyzed as normal control subjects. Serum HGF levels were measured by enzyme-linked immunosorbent assays (ELISA). Serum CRP levels were also performed. The mean +/- SE numbers of serum HGF levels in the patients with inflammatory lung diseases (4.33 +/- 0.41 ng/ml) were significantly elevated when compared with those in normal control subjects (0.36 +/- 0.02 ng/ml) (p < 0.0001). Serum HGF levels in patients with COPD was significantly lower than those were with tuberculosis or pneumonia (p < 0.05). There was a significant correlation between serum HGF levels and CRP in inflammatory pulmonary diseases (r = 0.48, p = 0.00087). The significantly decreased serum HGF levels in patients with improved inflammatory lung diseases were also observed subsequently. Our results suggest that secreted HGF may play an important role in bronchial epithelium reconstruction during respiratory inflammation.

Chemokines are important inflammatory mediators that function by activating and recruiting leukocytes to an inflamed tissue. We have recently cDNA cloned the rat chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) (1). In the present study, we characterize the biological function of recombinant MIP-1 alpha protein and describe expression of its mRNA both in vitro and in a rat model of lung inflammation. In vitro rat rMIP-1 alpha protein was chemotactic for both polymorphonuclear leukocytes (PMNs) and macrophages with maximal activity at 50 nM for both cell types. In in vivo studies, we found that intratracheal instillation of 1 and 5 micrograms of rMIP-1 alpha resulted in a significant (P < 0.05) influx of cells, primarily monocytes/macrophages, into the airspace of the lungs after 6 h. Mean numbers of lavagable PMNs were not elevated significantly (P < 0.05) for either dose of MIP-1 alpha. As a model of inflammation, rats were intratracheally instilled with 0.1 mg/kg bacterial lipopolysaccharide (LPS). Bronchoalveolar lavage (BAL) was performed 3 h later. Instillation of LPS resulted in an acute neutrophilia, but no significant change in lavagable macrophages. BAL cells from control animals (saline instilled) displayed no basal mRNA expression of either MIP-1 alpha or MIP-2 (positive control). In contrast, both MIP-1 alpha and MIP-2 mRNA levels increased markedly in BAL cells from rats instilled with LPS. The rat alveolar macrophage cell line (NR8383) also showed increased MIP-1 alpha mRNA levels in response to LPS (10 micrograms/ml) with a maximal increase after 6-8 h. The induction of MIP-1 alpha mRNA expression by LPS in NR8383 cells was attenuated by cotreatment with the antioxidants N-acetylcysteine and dimethylsulfoxide, suggesting that the induction of MIP-1 alpha mRNA by LPS is mediated via the generation of reactive oxygen species. We conclude that MIP-1 alpha is a potent chemoattractant for macrophages in vivo, and its mRNA expression in macrophages and BAL cells in response to inflammatory stimuli suggests a fundamental role in acute pulmonary inflammation.

Transforming growth factor-alpha (TGF-alpha), a member of the epidermal growth factor (EGF) family that binds to the EGF receptor (EGFR), is thought to function in an autocrine manner in non-small cell lung cancers (NSCLC). Heparin-binding EGF-like growth factor (HB-EGF), a novel member of the EGF family, also binds to EGFR. To compare the expression of HB-EGF, TGF-alpha and EGFR genes in NSCLC and normal lung tissue, we measured the levels of messenger RNA (mRNA) for these genes in human NSCLC and normal lung tissues by Northern hybridization, reverse transcription-polymerase chain reaction (RT-PCR), and in situ hybridization. A total of eight specimens (paired tumor tissue and normal lung tissue) were harvested from four patients who underwent resection of primary resectable NSCLC. HB-EGF was not expressed in either tumor tissue or normal lung tissue, while EGFR and TGF-alpha were expressed in all samples. TGF-alpha was overexpressed in all tumor tissue samples by several hundred-fold, while the expression of EGFR was not significantly different in tumor tissue and normal lung tissue. There was no correlation between the expression of TGF-alpha and EGFR. In situ hybridization showed that TGF-alpha mRNA was localized mainly in the cancer cells of tumor tissues and in the macrophages of alveoli in normal lung tissue. Our results showed that HB-EGF plays no role in the growth of NSCLC, and that there was no significant overexpression of EGFR in tumor tissue. TGF-alpha may play a major role in the growth of NSCLC. This supports a new direction in rational NSCLC treatment.

To elevate the diagnostic value of the serum cytokeratin 19 fragment (CYFRA 21-1) and compare it with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) in bronchogenic carcinoma, the sera of 161 patients (58 with benign pulmonary disease and 103 with bronchogenic carcinoma) was investigated using immunoradiometric assay. Sensitivities for CYFRA 21-1, CEA and TPA (using 3.5 ng ml-1, 5.0 ng ml-1, 110 U l-1, respectively, cut-off values corresponding to a 95% specificity for benign pulmonary disease) in bronchogenic carcinoma were 64, 47 and 61%, respectively. Positive CYFRA 21-1 levels were identified in 75% of patients with squamous cell carcinoma (n = 36), in 67% with adenocarcinoma (n = 45), in 17% with large cell carcinoma (n = 6), and in 50% with small cell lung cancer (SCLC) (n = 16). However, CYFRA 21-1 levels were not significantly different between squamous cell carcinoma and the other histological types. The sensitivity of the combined measurement of CYFRA 21-1 with any other tumour marker was significantly higher than that of CYFRA 21-1 measurement alone. Elevated CYFRA 21-1 levels were observed in 44% of Stages I and II (n = 18) and 72% of Stage III and IV (n = 69) patients with non-small cell lung cancer (P < 0.05). A significant inter-marker correlation was observed between CYFRA 21-1 and TPA (n = 103, r = 0.448, P < 0.0001). Twenty-one patients were monitored by CYFRA 21-1, and significantly different changes in progressive patients (P = 0.0058) and regressive patients (P = 0.016) were obtained. These results indicate that CYFRA 21-1 may be not only a sensitive tumour marker in the diagnosis of bronchogenic carcinoma, but also a useful marker for the monitoring of bronchogenic carcinoma.

To establish the spirometric values for normal, healthy Chinese women in Taiwan, the spirometry of 506 life-long non-smoking, healthy Chinese women was examined, including 140 subjects over the age of 60 years. Significant correlations among age, height and forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC%, peak expiratory flow (PEF), Vmax75, Vmax50, Vmax25 were found. However, there were no significant correlations between age and FEV1/FVC%, nor age and Vmax25 in the elderly group. FEV1 (FEV1*) and FVC (FVC*) were standardized to the overall mean height for elderly women using Cole's formula. The decline in FEV1* and FVC* with age were observed. The predicted value for the average 70-year-old woman with a height of 1.5 m derived from the present study is compared with those from other surveys of the elderly. The values from the present study are somewhat higher than the values from the Hong Kong study. The authors believe the fact that all of the present subjects were life-long non-smokers might explain the differences.

To evaluate the diagnostic value of the serum cytokeratin 19 fragment (CYFRA 21-1) in bronchogenic carcinoma, we investigated the sera of 138 patients (58 with benign pulmonary disease and 80 with non-small cell lung cancer (NSCLC)) using immunoradiometric assay. The mean (SD) value of serum CYFRA 21-1 in NSCLC (13.26 (16.54)) was significantly higher than in benign lung diseases (1.74 (1.55)) (p < 0.0001). Sensitivity for CYFRA 21-1 (using 3.5 ng/ml, a cut-off value corresponding to a 95% specificity for benign pulmonary disease) in NSCL was 62%. Positive CYFRA 21-1 levels were significantly higher in 75% of patients with squamous cell carcinoma (n = 36) than in 53% with other NSCLC (n = 44) (p < 0.05). CYFRA 21-1 levels were significantly different between squamous cell carcinoma (17.28 (19.94)) and the other NSCLC (9.96 (12.44)) (P < 0.05). Elevated CYFRA 21-1 levels in patients with stage III and IV disease (n = 64, 18.19 (26.51)) were significantly higher than in stage I and II (n = 16, 4.41 (5.76)) (p < 0.02). The positive rate of CYFRA 21-1 in tumor stage I and II was only 37%. Our results indicate that CYFRA 21-1 may be a useful tumor marker in NSCLC, especially in squamous cell carcinoma. However, CYFRA 21-1 cannot be used for the diagnosis of early stage disease of NSCLC. CYFRA 21-1 may also contribute to the monitoring of NSCLC.

Aspergillus-associated pulmonary diseases are aspergilloma, invasive aspergillosis, and allergic bronchopulmonary aspergillosis. Allergic bronchopulmonary aspergillosis is caused by a complex of immunologic reactions to the presence of the Aspergillus species colonizing the bronchial trees. The disease is not common in Taiwan. The major diagnostic criteria for allergic bronchopulmonary aspergillosis are 1) bronchial asthma, 2) pulmonary infiltration, 3) peripheral eosinophilia, 4) positive skin test to Aspergillus fumigatus, 5) serum precipitin to Aspergillus fumigatus, 6) elevated serum Ig E, and 7) central bronchiectasis. We report a case who has had a chronic asthmatic-like cough for 5 years. He worked in a silo for two years before he was troubled by the disease. He was admitted to hospitals four times in the past, and received five bronchoscopic examinations and one open lung biopsy without definite diagnosis. Sputum eosinophilia directed our attention to the differentiation of eosinophilic lung diseases. A bronchogram which revealed central brochiectasis helped us to make the diagnosis of allergic bronchopulmonary aspergillosis, despite negative sputum culture for Aspergillus fumigatus and negative serum precipitin to Aspergillus fumigatus.

Agyrophilic staining of nucleolar organizer regions (NOR) has been used to differentiate between cells of small cell carcinoma and lymphocytes in tissue specimens. We used cytologic smears which were previously Papanicolaou-destained to study the one-step agyrophilic staining technique for nucleolar organizer regions (AgNOR) in cell of small cell carcinoma and lymphocyte. The purposes of this study were to assess the feasibility and usefulness of AgNOR staining in diagnostic cytology and to try to set up a procedure that could be used on prestained smears for retrospective study. While the NOR of each lymphocyte appeared to be one round dot after AgNOR staining, the NOR of cell of small cell carcinoma showed dots, slightly variable in size and shape. The mean number of NOR was significantly higher (p < 0.01) in cells of small cell carcinoma (4.7 +/- 0.7) than in lymphocytes (1.4 +/- 0.4). In conclusion, AgNOR staining was demonstrated to be a useful method to differentiate between cells of small cell carcinoma and lymphocyte in Papanicolaou-destained smears.

Agyrophil staining was applied to nucleolar organizer regions (NOR) to differentiate cells of adenocarcinoma and histiomesotheliosis in pleural effusion. The smears were either nuclearly unstained, but cytoplasmically counterstained by Papanicolaou method or Papanicolaou-destained before agyrophil staining of nucleolar organizer regions (AgNOR). The purposes of this study were to assess the feasibility and usefulness of AgNOR staining in diagnostic cytology and to try to set up a procedure that could be used on prestained smears for retrospective study. All smears showed good background and cellular outline. The distribution of NOR was either intranuclearly or in the nucleoplasm diffusely. In previously nuclearly unstained smears, NOR showed granular to powder-like appearance. The mean number of NOR in adenocarcinoma (38.4 +/- 12.5) was significantly higher than that in histiomesotheliosis (15.6 +/- 2.9). In Papanicolaou-destained smears, the NOR showed confluent dots. The mean number of NOR was much lower as compared to that of previously nuclearly unstained smears. Furthermore, the mean number of NOR in adenocarcinoma (3.6 +/- 1.4) showed no significant difference with that of histiomesotheliosis (2.7 +/- 0.8). In conclusion, AgNOR staining is one of the methods to differentiate benign from malignant cells, but not in Papanicolaou-destained smears.

From 1982 to 1991, we experienced 76 patients with Mycoplasma pneumoniae pneumonia which were confirmed by serologic tests. There were 32 (42%) male and 44 (58%) female patients. One patient had underlying disease of diabetes mellitus while the other patients were in good health. The age ranged from 9 months old to 72 years old. All the patients complained of fever and coughing; 63% had dry cough and 37% had sputum production. Upper respiratory tract complaints such as rhinorrhea, sore throat, or earache were noted in 57% of the patients. Fifty-five percent of the patients had GI symptoms of anorexia, nausea, vomiting, or diarrhea. Other complaints included myalgia/arthralgia (29%), headache (30%), and general malaise (32%). Dyspnea (17%) and chest pain (20%) were occasional complaints. Seventy-one percent of the patients had WBC counts < 10000/cu mm and 29% > 10000/cu mm. The mean value of C-reactive protein (CRP) was 53.1 micrograms/ml, while 16% of the patients had a CRP value above 100 micrograms/ml. Thirty-one percent of the patients were noted to have a transient elevation of serum transaminase. Four different patterns of infiltration were seen in chest radiographic manifestation: 1) peribronchial and perivascular interstitial infiltrates (18.4%), 2) nonhomogeneous patchy consolidations (22.4%), 3) homogeneous acinar consolidations (27.6%), and 4) mixed interstitial and alveolar infiltrates (27.6%). Interstitial infiltration was more commonly seen in pediatric than adult patients (46% vs 20%). Other features of the radiologic manifestation were as follows: unilateral lesions in 80% of patients, single lobe lesions in 77%, lower lobe predominant in 69%, pleural effusion in 7%, and radiographic deterioration in 10%. Mycoplasmal pneumonia should be considered in the differential diagnosis of community-acquired pneumonias.

A total of 71 cases of pleural effusion in patients with and without cancer were analyzed by conventional cytology and flow cytometry (FCM) in order to detect cells with an abnormal DNA content (aneuploidy). For cytologic examination, the samples were prepared using standard techniques. Sample for FCM analysis were centrifuged and exposed to hypotonic solution containing detergent and propidium iodide. Thirty-eight patients had pleural effusion due to benign disease, whilst 33 patients had primary lung cancer. All 38 patients with benign pleural effusions showed FCM diploidy. There were 17 aneuploidy (52%) and 16 diploidy (48%) in the 33 patients with lung cancer by FCM analysis. Four of these 33 effusions were cytologically negative, however, FCM showed aneuploidy in 2 of these 4 patients. Based on these results, FCM analysis combined with conventional cytopathology yielded 100% specificity, 94% sensitivity and 100% predictive value of positive result. There were no false-positive results but 2 false-negative results. These findings suggest that FCM is a rapid and useful technique in the analysis of pleural effusion and can be a very useful adjunct to conventional cytopathology.

Sonographic characteristics of various chest diseases in 154 cases were analysed according to margin of the lesion, internal echogenecity, posterior echo enhancement, air bronchogram etc. We intended to present the basic sonographic patterns of common chest diseases. The study included 10 normal cases, 10 cases with lung abscesses, 31 cases of pneumonia, 24 cases of tumors, 11 cases of obstructive atelectasis, 8 cases of pleuropericarcadial effusions, 10 cases of minimal effusions, 6 cases with pleural thickening, 32 cases of massive pleural effusion with simple compression atelectasis and 12 cases of pneumonia with parapneumonic effusion. Sonographically, normal lung showed hyperechoic zone beneath the chest wall. Identification of arc or ring-shaped wall favored lung abscess. Air bronchogram could only be found in pneumonia. Mass showed various internal echogenecity. The internal echogenecity in obstructive atelectasis was very homogeneous which could not be found in tumor. Pleural thickening showed linear hyperechogenecity beneath the chest wall. In minimal effusion, the line of the diaphragm could be easily identified. Pleuropericardial effusion could be easily diagnosed by chest sonography. The line of the pericarcadium could be clearly identified. The internal echogenecity of massive effusion were various. The internal echogenecity of simple compression atelectasis showed very homogeneous hyperdense internal echogenecity. The internal echogenecity of lung parenchyma in pneumonia with parapneumonic effusion was similar to that of pneumonia. Obstructive atelectasis, mass, consolidation and encapsulated effusion could be differentiated by chest sonography without much difficulty. Sonography could aid chest radiography by giving more morphologic information and was cheaper than computed tomography.

An argyrophil technique for the staining nucleolar organizer regions (AgNOR) was applied to cytological preparations obtained from bronchoscopic brushing materials. The number of AgNOR has been thought to be related to cellular activation. To differentiate malignant cells from non-malignant atypical cells, this study was carried out in 20 cases of adenocarcinoma of the lung (mean AgNOR: 18.34), 12 cases of pulmonary inflammatory diseases (mean AgNOR: 6.54) and 10 normal bronchial epithelial specimens for control (mean AgNOR: 2.07). On the basis of AgNOR number, we could differentiate between the three groups. The differences observed were statistically highly significant (p less than 0.0001). Moreover, the nucleolar organizer regions (NOR) in cancer cells were found the more irregularly distributed and more variable in sized than those in atypical and normal bronchial columnar cells. We suggest that the AgNOR technique will find increasing application as a complementary test in diagnostic cytopathology.

Pulmonary tuberculosis remains a significant clinical and public health problem in the elderly population. To describe age-related differences in disease manifestations, a comparison of the clinical features, predisposing factors, diagnostic approaches and radiographic findings in cases of pulmonary tuberculosis among 52 young and 62 elderly patients was performed. The elderly patients had a higher number of underlying disease than younger patients (p less than 0.05). Prior to admission, symptoms occurring with equal frequency in both younger and elderly patients included coughing, malaise, and weight loss. Elderly patients had significantly higher incidences of negative reactions to the PPD test (p less than 0.05). Radiographic findings revealed that upper lung field infiltrates were still common in both groups, but the elderly had more severe lung field involvement (two or more lobes affected), and more frequent pleural reactions than younger patients (p less than 0.05). Since there were non-specific clinical features, false negative skin test and complex radiographic manifestations, tuberculosis was frequently not suspected in the differential diagnosis, especially among elderly patients with multiple medical problems. We suggest that physicians need to have a high level of suspicion and awareness of varied manifestations for tuberculosis, especially elderly patients.

A total of 207 cases were selected to evaluate the diagnostic value of C-reactive protein (CRP) in pulmonary infections. The mean +/- SD of CRP values in various pulmonary infections were as follows: 18.62 +/- 11.34 micrograms/ml for 32 cases of exudative-fibrotic tuberculosis; 15.98 +/- 16.66 micrograms/ml for 15 cases of tuberculous pneumonia; 25.61 +/- 18.96 micrograms/ml for 29 cases of tuberculous effusion; 16.66 +/- 10.18 micrograms/ml for 11 cases of tuberculous cavity; 81.1 +/- 24.9 micrograms/ml for 10 cases of miliary tuberculosis; 36.4 +/- 22.1 micrograms/ml for 19 cases of mycoplasmal pneumonia; 241 +/- 72 micrograms/ml for 38 cases of bacterial pneumonia; 225 +/- 65 micrograms/ml for 30 cases of bacterial pneumonia with effusion; 169 +/- 50 micrograms/ml for 16 cases of lung abscess. The CRP values of other pulmonary infections were as follows: 20.6, 20.8 micrograms/ml for two cases of Strongyloides stercoralis pneumonia; 7.4, 1.6 micrograms/ml for two cases of aspergilloma; 11.2, 12.4, 7.6 micrograms/ml for three cases of Pneumocystis carinii pneumonia. Serial changes in CRP values in 13 cases of well-treated bacterial pneumonia showed that values of CRP decreased to below half of the initial value on the 3rd to 4th day, and returned to about normal value on the 10th to 13th day. The study suggested that: a) various types of infections had different levels of CRP values, b) level of CRP values was determined both by the pathogen and the severity of inflammation, c) serial CRP values in bacterial infection could be used as a guide in treatment.