Combined use of QuantiFERON-TB Gold assay and chest computed tomography in a tuberculosis outbreak.

OBJECTIVE: To evaluate the value of the QuantiFERON-TB Gold (QFT-G) assay and chest computed tomography (CT), in addition to the conventional use of the tuberculin skin test (TST) and chest radiography (CXR), in a contact investigation of a tuberculosis (TB) outbreak. DESIGN: In a contact investigation of a TB outbreak in a high school, TST and CXR were performed on all 1044 employees and students. QFT-G was performed on TST-positive subjects, and CT on QFT-G-positive subjects and students with TST > or =20 mm. RESULTS: TST was positive in 388 subjects (37.2%), while QFT-G was positive in 7.6% (30/394). CXR showed abnormal findings suggestive of TB in 10 (1.0%) subjects, all of whom were TST-positive and six of whom were QFT-G-positive. Findings suggestive of active TB were noted in 17 (32.7%) of 52 subjects by CT. Collectively, among 21 (1.1%) TB patients, all were TST-positive, 12 (57.1%) were QFT-G-positive and active TB was diagnosed by CT, and not by CXR, in 11 subjects. CONCLUSION: Compared to the conventional approach, the additional use of QFT-G in TST-positive subjects and chest CT in subgroups with a high probability of infection was found to be more effective in the differentiation between active TB, latent TB and non-infected subjects in a contact investigation.

The gep oncogenes, Galpha(12) and Galpha(13), upregulate the transforming growth factor-beta1 gene.

Transforming growth factor-beta1 (TGFbeta1) plays a role in neoplastic transformation and transdifferentiation. Galpha(12) and Galpha(13), referred to as the gep oncogenes, stimulate mitogenic pathways. Nonetheless, no information is available regarding their roles in the regulation of the TGFbeta1 gene and the molecules linking them to gene transcription. Knockdown or knockout experiments using murine embryonic fibroblasts and hepatic stellate cells indicated that a Galpha(12) and Galpha(13) deficiency reduced constitutive, auto-stimulatory or thrombin-inducible TGFbeta1 gene expression. In contrast, transfection of activated mutants of Galpha(12) and Galpha(13) enabled the knockout cells to promote TGFbeta1 induction. A promoter deletion analysis suggested that activating protein 1 (AP-1) plays a role in TGFbeta1 gene transactivation, which was corroborated by the observation that a deficiency of the G-proteins decreased the AP-1 activity, whereas their activation enhanced it. Moreover, mutation of the AP-1-binding site abrogated the ability of Galpha(12) and Galpha(13) to induce the TGFbeta1 gene. Transfection of a dominant-negative mutant of Rho or Rac, but not Cdc42, prevented gene transactivation and decreased AP-1 activity downstream of Galpha(12) and Galpha(13). In summary, Galpha(12) and Galpha(13) regulate the expression of the TGFbeta1 gene through an increase in Rho/Rac-dependent AP-1 activity, implying that the G-protein-coupled receptor (GPCR)-Galpha(12) pathway is involved in the TGFbeta1-mediated transdifferentiation process.

Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia.

Most studies of idiopathic nonspecific interstitial pneumonia (NSIP) have primarily studied mortality. In order to clarify the detailed outcome and prognostic markers in idiopathic NSIP, the clinical course with initial radiological and clinical features was analysed. The clinical course of 83 patients who were classified with idiopathic NSIP (72 fibrotic, 11 cellular; 27 males and 56 females; mean+/-sd age 54.4+/-10.1 yrs) was retrospectively analysed. In fibrotic NSIP, 16 (22%) patients died of NSIP-related causes with a median (range) follow-up of 53 (0.3-181) months. Despite the favourable survival (5-yr 74%), patients with fibrotic NSIP were frequently hospitalised with recurrence rate of 36%. Reduced forced vital capacity at 12 months was a predictor of mortality. On follow-up, lung function was improved or stable in approximately 80% of the patients. The extent of consolidation and ground-glass opacity on initial high-resolution computed tomography correlated significantly with serial changes of lung function, and the presence of honeycombing was a predictor of poor prognosis. During follow-up, eight (10%) patients developed collagen vascular disease. In conclusion, the overall prognosis of fibrotic nonspecific interstitial pneumonia was good; however, there were significant recurrences despite initial improvement and a subset of the patients did not respond to therapy. Some patients developed collagen vascular diseases at a later date.

Pulmonary tuberculosis with acute respiratory failure.

The aim of the present study was to evaluate the clinical characteristics, prognoses and predictors of mortality of patients with pulmonary tuberculosis (TB) with acute respiratory failure (ARF), and to investigate the adjunctive use of corticosteroids in such cases. TB patients with ARF requiring mechanical ventilation (n = 90) were enrolled retrospectively during 1989-2006. The patients were divided into two groups: tuberculous pneumonia (TBP; n = 66), and miliary TB (MTB; n = 24). The TBP patients were older than the MTB patients (mean age 68.0 versus 54.5 yrs), and the mean+/-SD interval from hospital admission to start of anti-TB treatment was longer for the TBP than for the MTB group (5.0+/-7.0 versus 2.8+/-2.5 days). However, there was no difference in in-hospital mortality rate between the two groups (68.2 versus 58.3%). In the TBP patients, multivariate analysis showed that advanced age and shock unrelated to sepsis were associated with poor outcomes. Even though corticosteroid use was a predictor of survival in TBP patients, it was difficult to conclusively determine the efficacy of corticosteroids in TBP with ARF because of the retrospective study design. The present study reveals the need for randomised controlled trials to clarify the role of corticosteroids as adjunctive therapy in the management of tuberculous pneumonia with acute respiratory failure.

Incidence of tuberculosis among health care workers at a private university hospital in South Korea.

SETTING: A private university hospital in South Korea. OBJECTIVE: To investigate the incidence of tuberculosis (TB) among health care workers (HCWs) employed at a university hospital in South Korea. DESIGN: The occurrence of TB cases among HCWs over a 6-year period (2001-2006) was reviewed. The prevalence of TB was compared with that of the general population using a prevalence ratio (PR) adjusted by age and sex. RESULTS: The study involved 8433 people. TB developed in 61 HCWs (0.72%). The prevalence ratio among all HCWs was 1.05 (95%CI 0.80-1.35). In occupational subgroups, the PRs for doctors, nurses and employees in other departments were respectively 0.58 (95%CI 0.30-1.01), 1.81 (95%CI 1.21-2.59) and 0.95 (95% CI 0.58-1.46). For nurses working in TB-related departments, the relative risk of developing TB was 3.4 times higher (95%CI 1.52-8.25) than for employees in other departments (P=0.005). The PR for nurses working in TB-related department was 5.1 (95%CI 3.23-8.42). CONCLUSION: Among HCWs, nurses working in TB-related departments were at increased risk of developing TB. This suggests that some TB develops via in-hospital infection.

In vitro evaluation of poly(caporlactone) grafted dextran (PGD) nanoparticles with cancer cell.

This study dealt with the preparation and characterization of coumarin-6 loaded poly(caprolactone) grafted dextran (PGD) nanoparticles (NPs) and evaluation of cellular uptake by using human gastric cancer cell line (SNU-638), in vitro. The potential application of these PGD NPs for sustained drug delivery was evaluated by the quantification and localization of the cellular uptake of fluorescent PGD NPs. Coumarin-6 loaded PGD NPs were prepared by a modified oil/water emulsion technique and characterized by various physico-chemical methods such as, laser light scattering for particle size and size distribution, atomic force microscopy (AFM), zeta-potential and spectrofluorometry to identify the release of fluorescent molecules from the NPs. SNU-638 was used to measure the cellular uptake of fluorescent PGD NPs. Confocal laser scanning microscopic images clearly showed the internalization of NPs by the SNU-638 cells. Cell viability was assessed by treating the SNU-638 cells with PGD NPs for 48 h. The results reveal, that these biodegradable polymeric NPs holds promise in biomedical field as a carrier.

Impact of short-term exposure to fluoroquinolones on ofloxacin resistance in HIV-negative patients with tuberculosis.

SETTING: Seoul, Korea, a country with an intermediate tuberculosis (TB) burden and low prevalence of human immunodeficiency virus (HIV) infection. OBJECTIVES: To determine the frequency of ofloxacin (OFX) resistance in Mycobacterium tuberculosis, and to assess whether short-term use of fluoroquinolones (FQNs) induces ofloxacin-resistant M. tuberculosis. DESIGN: The subject cohort consisted of 2788 patients with culture-confirmed TB with drug susceptibility testing data; only four were HIV-positive. The patients were divided into two groups: those who were or were not recently exposed to FQNs. RESULTS: Of the 2788 isolates, the rates of OFX resistance were 1.1% and 8.5% in initially treated and retreated patients, respectively (P < 0.05). Of the 94 OFX-resistant isolates, 83 (88.3%) were multidrug-resistant (MDR). There was no difference in rates of OFX resistance throughout the study period, or between the FQN-exposed (1/39, 2.6%) and control groups (93/2749, 3.4%). The median duration of FQN treatment was 7 days (range 1-47 days). One OFX-resistant isolate in the FQN-exposed group was MDR. CONCLUSION: The rate of OFX-resistant M. tuberculosis was low and stationary throughout the study period in Korea. Most OFX resistance was accompanied by MDR, and the frequency of OFX-resistant M. tuberculosis was low in subjects taking short-term FQNs.

Comparison of two commercial interferon-gamma assays for diagnosing Mycobacterium tuberculosis infection.

The clinical usefulness of ex vivo interferon-gamma assays may largely depend on the assay format and epidemiological status of tuberculosis (TB) in the region studied. From July 2004 to June 2005 a prospective comparison study was undertaken at a tertiary referral hospital in South Korea. The results of tuberculin skin tests (TST) and the commercially available QuantiFERON-TB Gold (QFT-G) and T SPOT-TB (SPOT) assays were compared in an intermediate TB-burden country. Of the 224 participants studied, results from all three tests (TST, QFT-G, and SPOT) were available in 218; 87 with active TB and 131 at a low risk for TB. Using 10 mm as a cut-off for TST, SPOT sensitivity (96.6%) was significantly higher than that seen for TST (66.7%) and QFT-G (70.1%). QFT-G showed superior specificity over TST (91.6 versus 78.6%). Although the specificity of QFT-G was higher than that of SPOT (91.6 versus 84.7%), the difference was not statistically significant. Whilst some differences were found in the performance of the two commercialised interferon-gamma assays, they seemed to be superior in their detection of Mycobacterium tuberculosis infection compared with tuberculin skin tests. The most appropriate choice of interferon-gamma assay to use may depend on the clinical setting.

Hypothermia attenuates vascular manifestations of ventilator-induced lung injury in rats.

Alveolar hemorrhage and pulmonary edema induced by mechanical ventilation are partly dependent on cardiac output. Because cardiac output is low during hypothermia, we hypothesized that hypothermia may protect against these vascular manifestations of ventilator-induced lung injury. Twenty-seven Sprague-Dawley rats were assigned to either normothermia (37 +/- 1 degrees C)-injurious ventilation (NT; n = 10), hypothermia (27 +/- 1 degrees C)- injurious ventilation (HT; n = 10), or nonventilated control ( n = 7). The two ventilated groups were subjected to injurious ventilation of peak airway pressure 30 cm H(2)O with zero end-expiratory pressure for 20 min. Compared with the NT group, the hemorrhage/congestion score of the lung (11.2 +/- 1.5 vs. 4.7 +/- 1.6; p < 0.001) and the ratio of wet/dry lung weight (6.1 +/- 0.8 vs. 5.0 +/- 0.1; p = 0.046) of the HT group were lower. Compared with the NT group, protein concentration (3,471 +/- 1,985 micro g/ml vs. 1,374 +/- 726 micro g/ml; p = 0.003) and lactate dehydrogenase level (0.43 +/- 0.22 U/ml vs. 0.18 +/- 0.1 U/ml; p = 0.046) in bronchoalveolar lavage fluid of the HT group were lower. Whereas pressure-volume curve was shifted to the right in the NT group after injurious ventilation, it was not shifted in the HT group. In conclusion, hypothermia in rats attenuated the degrees of vascular manifestations and alveolar epithelial injuries induced by injurious ventilation, and preserved the mechanical properties of the lung.

An evaluation of the effectiveness of the patellar tendon bar in the trans-tibial patellar-tendon-bearing prosthesis socket.

The aim of this study is to determine the relationship between varying depths of the patellar tendon bar in trans-tibial prosthesis sockets and the pressures exerted by other regions within the socket, such as the tibial crest, medial and lateral tibial condyles, lateral femoral condyle and the distal tibial end. Five (5) patients selected from a population of trans-tibial amputees in Singapore. Patellar-tendon-bearing (PTB) sockets were made for them. Polypropylene spacers 2 mm thick were used to simulate the increasing depths of the patellar tendon bar. P-Scan pressure transducers were inserted into the sockets to measure the pressures exerted by the socket and the data collected were analysed statistically to see if there was a relationship between varying PTB depths and pressures exerted from selected parts of the socket.

Cerebral metabolic abnormalities in COPD patients detected by localized proton magnetic resonance spectroscopy.

STUDY OBJECTIVES: To investigate changes in the cerebral metabolism of patients with COPD, using localized in vivo proton magnetic resonance spectroscopy ((1)H MRS), and to evaluate the clinical significance of cerebral metabolic abnormalities in COPD patients. PATIENTS AND METHODS: Seventeen symptomatic COPD patients and 21 age-matched healthy volunteers participated in this study. All subjects underwent (1)H MRS, and neuropsychological tests (Wechsler memory scale-revised [WMS-R], color trail test, and grooved pegboard test) were performed by COPD patients. Magnetic resonance spectra were obtained from localized regions of parietal white matter (PWM) and occipital gray matter (OGM). Absolute levels of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI) were calculated. RESULTS: In COPD patients, the mean (+/- SD) FEV(1) was 38 +/- 10% predicted, the PaCO(2) was 39 +/- 7 mm Hg, and the PaO(2) was 89 +/- 18 mm Hg, and these values did not exhibit statistical correlation with the levels of cerebral metabolites. NAA, Cr, and Cho levels in PWM were all significantly lower in COPD patients than in control subjects (p < 0.0125 [Bonferroni adjusted]). Neuropsychological parameters were lower in COPD patients compared with standardized values. However, they were not correlated with the levels of cerebral metabolites except for a positive correlation between the Cho level in PWM and the general memory quotient of WMS-R (r = 0.52; p < 0.05). CONCLUSIONS: Our results demonstrate that the cerebral metabolism is significantly altered in symptomatic COPD patients. The relationship between decreased Cho levels and memory dysfunction, and the clinical significance of other cerebral metabolic changes in COPD patients need to be further investigated.

The prognosis of respiratory failure in patients with tuberculous destroyed lung.

SETTING: The medical intensive care unit of a tertiary referral hospital. OBJECTIVE: To determine the prognosis of patients whose lungs are damaged by previous and/or present tuberculosis infection and who have subsequently been presented with acute respiratory failure requiring mechanical ventilation. DESIGN: A consecutive series of 38 patient cases with retrospective data analysis. RESULTS: Pulmonary function test results for tests performed within the previous year were made available in 21 of the 38 cases (55%). These showed a mean (+/- SD) forced vital capacity (FVC) of 1.52 +/- 0.46 L (41.0 +/- 14.5% predicted), a forced expiratory volume/second (FEV1) of 0.77 +/- 0.18 L (29.3 +/- 13.6% predicted), and an FEV1/FVC ratio of 55.1 +/- 16.2%. The acid-fast bacilli (AFB) positive group had a significantly higher mortality and more severe lung destruction when compared with the AFB-negative group. Patients with positive AFB were significantly more hypocapnic than those with negative AFB (6.4 +/- 2.7 vs. 9.3 +/- 3.9 kPa, P = 0.020). In multivariate analysis, the level of PaCO2 on admission was identified as the only significant prognostic index (OR 0.76, 95%CI 0.60-0.96). CONCLUSION: Patients with positive AFB smears or cultures may have higher mortality rates than those with negative AFB in the tuberculosis destroyed lung patients with acute respiratory failure. A higher PaCO2 measurement could indicate a better survival rate in this group of patients.

Pathogenic role of endothelin 1 in hemodynamic dysfunction in experimental acute pulmonary thromboembolism.

The plasma endothelin-1 (ET-1) level is elevated in patients with acute pulmonary thromboembolism (APE). Whether ET-1 is a pathogenic mediator or a simple marker of APE is not known. We investigated the role of ET-1 in hemodynamic dysfunction in APE through evaluating the effects of ET(A) receptor antagonist in an experimental APE model. We also examined ET-1 expression in embolized lungs. In a canine autologous blood clot pulmonary embolism model, ET(A) receptor antagonist ZD2574 (10 mg/kg, intravenous; ZD2574 group; n = 6) or vehicle (control group; n = 5) was administered. Hemodynamic and gas exchange parameters and plasma levels of ET-1 were serially measured. Prepro-ET-1 mRNA expression and the distribution of ET-1 peptide in lung tissues were also examined. With ZD2574 pulmonary arterial pressure and pulmonary vascular resistance significantly decreased, and were lower compared with the control group. The decrease in cardiac output was also less in the ZD2574 group. Plasma ET-1 levels increased after embolization. Prepro-ET-1 mRNA expression increased in embolized lungs and ET-1 peptide expression also increased in embolized lungs, particularly in the muscular pulmonary arteries, compared with normal lungs. These findings suggest that ET-1 partially contributes to hemodynamic derangements of APE, and that ET(A) receptor antagonists might constitute a useful therapeutic tool for APE.

Lung cancer in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) was reported to be associated with increased risk of lung cancer as a result of the occurrence of atypical or dysplastic epithelial changes in fibrosis which progressed to invasive malignancy. In that situation, the cancer will develop in the area of major fibrosis. To investigate the direct relationship between fibrosis and cancer development, the real concordance rate of the two lesions in the chest computed tomography (CT) was analysed and compared to the histological types of lung cancer. The subjects included 63 patients with combined lung cancer and IPF (IPF-CA), 218 patients with lone IPF, and 2,660 patients with primary lung cancer. All patients were diagnosed at Asan Medical Center during the same period. The age, percentage of smokers, and the male sex were significantly higher in IPF-CA compared with lone IPF. The odds ratio of smoking was 2.71 compared to nonsmoking IPF controls. In IPF-CA, 56% of the cancer was located in the periphery of the lung and 52% in the upper lobe. The majority of the cancers (64%) were found in the nonfibrotic area at chest CT. The most frequent cell type was squamous cell carcinoma (35%), and there was no significant difference in the cancer cell type between IPF-CA and total lung cancer population. These findings suggest that in combined lung cancer and idiopathic pulmonary fibrosis patients, the features of the lung cancer are similar to the total lung cancer population.

Cigarette smoke extract induces endothelin-1 via protein kinase C in pulmonary artery endothelial cells.

We examined the mechanism of endothelin (ET)-1 regulation by cigarette smoke extract (CSE) and the effect of platelets on CSE-induced stimulation of ET-1 gene expression in human and bovine pulmonary artery endothelial cells (PAECs). Our data show that CSE (1%) induces ET-1 gene expression (after 1 h) and ET-1 peptide synthesis (after 4 h) in bovine PAECs. The induction of preproET-1 mRNA level was due to de novo transcription, and new protein synthesis was not required for this induction. The protein kinase C inhibitors staurosporine (10(-8) mol/l) and calphostin C (10(-7) mol/l) abolished the induction of ET-1 gene expression by CSE in bovine and human PAECs. Although a lower concentration of platelets (10(6) cells/ml in bovine PAECs; 10(7) cells/ml in human PAECs) did not significantly alter ET-1 gene expression in PAECs, incubation of platelets with CSE (1%) and PAECs produced a significant increase in preproET-1 mRNA and ET-1 peptide compared with the values in the presence of CSE (1%) alone. CSE (1%) induced platelet aggregation and increased the expression of platelet membrane glycoproteins ex vivo. Thus our data suggest that CSE stimulates ET-1 gene expression via PKC in PAECs. CSE and platelets showed a synergistic effect on ET-1 gene expression, possibly through the activation of platelets by CSE.

Mechanistic scheme and effect of "extended sigh" as a recruitment maneuver in patients with acute respiratory distress syndrome: a preliminary study.

OBJECTIVE: To devise a new form of sigh ("extended sigh") capable of providing a sufficient recruiting pressure x time, and to test it as a recruitment maneuver in patients with acute respiratory distress syndrome. DESIGN: Prospective uncontrolled clinical trial. SETTING: Medical intensive care unit of a university-affiliated hospital. PATIENTS: Twenty consecutive patients diagnosed with acute respiratory distress syndrome (18 men, 2 women, age 59 +/- 10 yrs). INTERVENTIONS: From baseline settings of tidal volume (Vt) 8 mL/kg and positive end-expiratory pressure (PEEP) 10 cm H2O on volume control mode with the high pressure limit at 40 cm H2O, the Vt-PEEP values were changed to 6-15, 4-20, and 2-25, each step being 30 secs (inflation phase). After Vt-PEEP 2-25, the mode was switched to continuous positive airway pressure of 30 cm H2O for a duration of 30 secs (pause), after which the baseline setting was resumed following the reverse sequence of inflation (deflation phase). This extended sigh was performed twice with 1 min of baseline ventilation between. MEASUREMENTS AND RESULTS: Airway pressures and hemodynamic parameters were traced at each step during the extended sigh. Arterial blood gases and physiologic parameters were determined before the extended sigh (pre-extended sigh), at 5 mins after two extended sighs (post-extended sigh), and then every 15 mins for 1 hr. In our average patient, the recruiting pressure x time of the inflation phase was estimated to be 32.8-35.4 cm H2O x 90 secs. Compared with the inflation phase, inspiratory pause pressure of the deflation phase was lower at Vt-PEEP 6-15 (28.9 +/- 2.7 cm H2O vs. 27.3 +/- 2.8 cm H2O) and 4-20 (31.8 +/- 2.9 cm H2O vs. 31.1 +/- 2.9 cm H2O; both p <.05). Compared with pre-extended sigh, Pao2 (81.5 +/- 15.3 mm Hg vs. 104.8 +/- 25.0 mm Hg; p <.001) and static respiratory compliance both increased post-extended sigh (27.9 +/- 7.9 mL/cm H2O vs. 30.2 +/- 9.7 mL/cm H2O; p =.009). Improvement in these parameters was sustained above pre-extended sigh for the duration of the study. Major hemodynamic or respiratory complications were not noted during the study. CONCLUSION: We present a new form of sigh (i.e., extended sigh) capable of achieving an augmented recruiting pressure x time through a prolonged inflation on a gradually increased end-expiratory pressure. In view of the sustained effect and absence of major complications in our patients, extended sigh could be a useful recruitment maneuver in acute respiratory distress syndrome.

Effects of heat pretreatment on histopathology, cytokine production, and surfactant in endotoxin-induced acute lung injury.

To determine the effect of heat stress on histopathology of acute lung injury (ALI) caused by administration of lipopolysaccharide (LPS), and to determine the roles of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, interferon (IFN)-gamma, IL-10 and surfactants in heat-induced tolerance to ALI, we administered either saline or LPS (3 mg/kg of body weight) intravenously to male Sprague-Dawley rats without and with heat pretreatment. Five hours after LPS or saline treatment (23 h after heat-pretreatment), samples were obtained. We found that the histopathologic features of LPS-induced ALI were attenuated by heat-pretreatment. Heat-pretreatment did not decrease the elevated plasma or BAL fluid levels of TNF-alpha, IL-1beta, and IFN-gamma by LPS. The plasma level of IL-10 in LPS-treated rats with heat-pretreatment, however, was increased compared to that of LPS-treated rats without heat-pretreatment (P = 0.001). There were no differences in the BAL fluid concentrations of light or heavy density pulmonary surfactant phospholipids depending on heat-pretreatment in LPS-treated rats. These observations suggest that IL-10 might play a role in decreasing LPS-induced acute lung injury after heat-pretreatment.

Comparison of the response to the prone position between pulmonary and extrapulmonary acute respiratory distress syndrome.

OBJECTIVES: To determine whether the response to the prone position differs between acute respiratory distress syndrome (ARDS) resulting from a pulmonary cause (ARDSp) and that from an extrapulmonary cause (ARD-Sexp). DESIGN AND SETTING: Prospective observational study in a medical ICU of a university-affiliated hospital. SUBJECTS: A consecutive series of 31 patients with ARDSp and 16 with ARDSexp within 3 days of onset of ARDS. INTERVENTION: Prone position for at least 2 h. MEASUREMENTS AND RESULTS: In ARDSp, compared with the supine position (121 +/- 49 mmHg), PaO2/FIO2 was not increased after 0.5 h but was increased after 2 h in the prone position (158 +/- 60 mmHg). In ARDSexp, compared with the supine position (106 +/- 53 mmHg), PaO2/FIO2 was increased after 0.5 h (155 +/- 91 mmHg), but was not further changed after 2 h. Marked oxygenation response (increase in PaO2/FIO2 > 40% from baseline) after 0.5 h was 23% in ARDSp and 63% in ARDSexp, and that after 2 h was 29% and 63%, respectively. Static respiratory compliance decreased in the prone position in ARDSexp (30 +/- 11 ml/cmH2O at baseline, 27 +/- 11 after 0.5 h and 25 +/- 9 after 2 h) but not in ARDSp. Consolidation score as determined on the first chest radiography taken in the prone position decreased to a greater degree in ARDSexp (-2.4 +/- 4.1) than in ARDSp (0.3 +/- 4.1). CONCLUSION: Pulmonary ARDS and extrapulmonary ARDS in their early stages respond differently to the prone position with regard to the time course of oxygenation, respiratory mechanical behaviour, and radiographic change. These findings suggest that the early pathophysiology of ARDS differs according to the type of primary insult to the lung.

Nitric oxide and molsidomine in the management of pulmonary hypertension in Takayasu's arteritis.

We present three patients with pulmonary hypertension in Takayasu's arteritis who showed long-term favorable response, clinically and hemodynamically, to nitric oxide donor molsidomine. In these patients, nitric oxide inhalation was effective in reducing pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). Molsidomine (single dose of 4 mg p.o.) was also effective in reducing PAP and PVR, but nifedipine was not. With molsidomine, 4 mg tid, dyspnea, exercise capacity, and hemodynamic parameters were improved. These favorable responses have lasted during the 3-month follow-up period in all patients.

Transforming growth factor-beta1 induces endothelin-1 in a bovine pulmonary artery endothelial cell line and rat lungs via cAMP.

We investigated the mechanism of Endothelin-1 regulation by transforming growth factor-beta1 (TGF-beta1) in bovine pulmonary artery endothelial cells (BPAECs) and in isolated perfused rat lungs. Our data show that TGF-beta1 induces ET-1 gene expression and ET-1 peptide synthesis in BPAECs. The induction of preproET-1 mRNA level was due to de novo transcription, as well as mRNA stabilization, and new protein synthesis was not required for this induction. To investigate the role of cAMP-protein kinase A pathway in TGF-beta1-stimulated-ET-1 induction, we exposed BPAECs to various compounds which modulate this pathway. Dibutyryl-cAMP led to an increase in preproET-1 mRNA and Rp-cAMP abolished the induction of preproET-1 mRNA and ET-1 peptide by TGF-beta1. TGF-beta1 increased cAMP in BPAECs. Dexamethasone up-regulated preproET-1 mRNA expression and ET-1 peptide synthesis under basal and TGF-beta1-stimulated conditions. In isolated perfused rat lungs, TGF-beta1 increased preproET-1 mRNA abundance whereas Rp-cAMP inhibited the TGF-beta1-induced ET-1 gene activation. Thus our data suggest that TGF-beta1 stimulates ET-1 gene expression in BPAECs and in rat lungs via a cAMP dependent mechanism.