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.

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.

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.

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.

An optimal dose of perfluorocarbon for respiratory mechanics in partial liquid ventilation for dependent lung-dominant acute lung injury.

BACKGROUND: Despite increasing knowledge about partial liquid ventilation (PLV), the optimal dose of perfluorocarbon (PFC) is not yet established. Because there exist normal regions in the lung with ARDS and because PLV in the normal lung results in worsened gas exchange, we postulated that the optimal dose of PFC for PLV may be less than the functional residual capacity (FRC) dose in the lung with limited disease. DESIGN AND SETTING: Animal study at the Asan Institute for Life Sciences, Seoul, Korea. SUBJECTS: Twelve rabbits in which dependent lung-dominant lung injury was created by a modified saline solution lavage. INTERVENTIONS: PLV performed at six different doses of perfluorodecalin in sequence (3, 6, 9, 12, 15, and 18 mL/kg every 15 min). MEASUREMENTS AND RESULTS: Our modified saline solution lavage induced atelectasis and hemorrhage confined to the dependent lung with severe hypoxia (PaO(2)/fraction of inspired oxygen = 37 +/- 6 mm Hg). Peak airway pressure (Ppeak) and inspiratory pause pressure (Ppause) with PLV were lower at doses of 3 to 15 mL/kg (all p < 0.05), but not different at a dose of 18 mL/kg, when compared with gas ventilation. Ppeak increased at doses of 12, 15, and 18 mL/kg, when each was compared with the preceding PFC dose. At increasing PFC doses, the change in the elastic component of airway pressure (Ppause after minus Ppause before) was negative until the dose of 9 mL/kg, but was positive at doses of 12 mL/kg and above. The change in the resistive component ([Ppeak minus Ppause] after minus [Ppeak minus Ppause] before) was negative until the dose of 6 mL/kg, but was positive at the dose > or = 9 mL/kg. CONCLUSION: Respiratory mechanics during PLV for dependent lung-dominant lung injury were optimal at a PFC dose less than the FRC.

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 effect of varying inspiratory to expiratory ratio on gas exchange in partial liquid ventilation.

BACKGROUND: In partial liquid ventilation (PLV), the nondependent lung was observed to be inflated first and the dependent lung later. The inflational time difference between the lung regions can lead to maldistribution of tidal gas and inefficient gas bubbling in the slow-inflating region during PLV. In this situation, increasing the inspiratory to expiratory (I:E) ratio of the mechanical ventilator would lessen the heterogeneity of regional ventilation and improve gas exchange possibly to a greater degree than in gas ventilation (GV). DESIGN AND SETTING: Animal study at the Asan Institute for Life Sciences, Seoul, Korea Subjects: Eighteen rabbits (2.6 +/- 0.5 kg) with acute lung injury by saline solution lavage. INTERVENTIONS: Three I:E ratios were tried in GV and then in PLV. I:E ratios were changed by adjusting pause (1:2, 1:1, and 2:1; group 1) or by adjusting inspiratory flow rate (1:3, 1:1, and 2:1; group 2). MEASUREMENTS AND RESULTS: With increasing I:E ratio in all animals, PaO(2)/FIO(2) increased (80 +/- 24, 143 +/- 74, and 147 +/- 88 mm Hg; p = 0.001), and PaCO(2) decreased (74 +/- 15, 66 +/- 16, and 66 +/- 15 mm Hg; p = 0.006). The increases of PaO(2)/FIO(2) from 1:2/1:3 to 1:1 (p = 0.006) and from 1:1 to 2:1 (p = 0.036) were both greater in group 1 than in group 2. PaCO(2) decreased with increasing I:E ratio in group 1, but not in group 2. The change of PaO(2)/FIO(2) by varying the I:E ratio was 49 +/- 65% in PLV and 14 +/- 14% in GV (p = 0.003). CONCLUSIONS: Extending the I:E ratio, especially by adding pause, improved gas exchange in PLV. Oxygenation in PLV was affected by the I:E ratio to a greater degree than in GV.

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.

Value of ICAM-1 expression and soluble ICAM-1 level as a marker of activity in sarcoidosis.

BACKGROUND: The natural course of sarcoidosis is variable, but no single parameter has been generally accepted as a good marker for disease activity. Adhesion molecules are required for the migration of inflammatory cells; thus, they may be markers of activity in sarcoidosis. METHODS: In 16 patients with active sarcoidosis and 11 with inactive disease (10 were male, 17 were female; mean age [-/+ SD], 39.6+/-11.0 years; mean follow-up, 21+/-16 months), the expression of adhesion molecules on cells obtained with BAL (measured by flow cytometry) and the level of soluble intercellular adhesion molecule 1 (sICAM-1) in the serum and BAL fluid (BALF) were measured at the time of diagnosis and during the follow-up. The changes in serum sICAM-1 level and ICAM-1 expression on cells obtained with BAL were compared with the clinical course of the disease. RESULTS: In patients with active disease, the ICAM-1 on alveolar macrophage (AM) (relative linear median fluorescence intensity [RMFI], 3.21+/-1.55) and sICAM-1 levels in serum (575+/-221 ng/mL) and BALF (47.3+/-19.3 ng/mL) were higher than those for patients with inactive disease (RMFI, 1.67+/-0.66; p = 0.0034; serum, 263+/-98.5 ng/mL; p = 0.0001; BALF, 27.5+/-19.0 ng/mL; p = 0.0209). In the patients with active disease, ICAMN-1 on AM and serum sICAM-1 decreased (RMFI, 1.51+/-0.84; 284+/-118 ng/mL, respectively) after steroid therapy, but no significant change was noted in patients with inactive disease. We also found that the initial ICAM-1 on AM and serum sICAM-1 had a significant correlation with the degree of improvement in pulmonary function tests after the therapy. The disease relapsed in four patients after the discontinuation of steroids, and the serum sICAM-1 level was elevated again at the time of relapse. CONCLUSION: Our data suggest that the serum sICAM-1 level and the ICAM-1 expression on AM may be good markers of disease activity and also a predictor of outcome in sarcoidosis.

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.

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.

The value of interleukin-12 as an activity marker of pulmonary sarcoidosis.

BACKGROUND: Sarcoidosis is characterized by hyperactivity of T-helper lymphocytes and recent studies showed that they were mainly Th1 cells. IL-12 is a major cytokine inducing Th1 differentiation of naive T cells. This study was performed to test whether IL-12 can be a marker for disease activity and possibly a prognosis in sarcoidosis. METHODS: IL-12 levels of BALF (BALF-IL-12) and conditioned medium of alveolar macrophages (AM) were measured by ELISA in 36 patients with pulmonary sarcoidosis (14 males and 22 females, mean age: 39.6 +/- 11.0 years) and eleven normal controls. Clinically, 16 patients had active sarcoidosis and 20 had an inactive disease. RESULTS: BALF-IL-12 of sarcoidosis patients (41.3 +/- 43.9 pg/ml) was significantly higher than that of normal controls (2.5 +/- 0.4 pg/ml) (p < 0.001). The patients with active disease (71.3 +/- 54.3 pg/ml) had a higher BAL-IL-12 level than those with inactive disease (17.3 +/- 13.8 pg/ml) (p = 0.0001). It had a significant correlation with the number of T4 cells (p = 0.0001), total cell number, number and percentage of lymphocytes (p = 0.0001) and AM (p = 0.001) in BALF. It was also significantly correlated with soluble ICAM-1 levels in serum (p = 0.0001) and BALF (p = 0.002), and ICAM-1 expression of AM (p = 0.001). Furthermore the patients whose condition worsened without therapy had a significantly higher initial BALF-IL-12 level than the patients whose condition improved spontaneously. The AM of sarcoidosis secreted significantly more IL-12 (133 +/- 177 pg/ml) than AM of controls (68.3 +/- 43.7 pg/ml) (p = 0.038). CONCLUSION: Our data suggest that the BALF-IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis and possibly prognosis.

Risk factors for the development of hemodynamically significant cardiac arrhythmias in patients with mechanical ventilation.

PURPOSE: The purpose of this article was to identify the risk factors related to development of hemodynamically significant cardiac arrhythmias in patients with mechanical ventilation. MATERIALS AND METHODS: Holter recording and echocardiogram were performed within 24 hours of ventilator initiation in patients on mechanical ventilation (MV) owing to respiratory failure (RF) from various reasons. RESULTS: From 68 patients, hemodynamically significant cardiac arrhythmias were detected in 18 patients (26.5%). Initial mean arterial pressure, maximal heart rate, and initial pH were identified as risk factors for hemodynamically significant cardiac arrhythmias. Additionally, the patients with pressure-controlled ventilation as an initial ventilatory mode developed hemodynamically significant cardiac arrhythmias less frequently than the patients with other modes (15.8% vs. 40%, P = .03). In multivariate analysis, initial mean arterial pressure (< 70 mm Hg, odds ratio [OR]: 5.5; 95% confidence interval [CI]: 1.2 to 24.2, P = .026), maximal heart rate (> 120/min, OR: 19.7; 95% CI: 2.0 to 190.9, P = .01), and pressure-controlled ventilation (OR: 0.13; 95% CI: 0.03 to 0.55, P = .006) were associated with the development of hemodynamically significant cardiac arrhythmias. CONCLUSIONS: These findings suggest that during the early stages of mechanical ventilation with acute respiratory failure, hemodynamically significant cardiac arrhythmias are directly associated with tachycardia (> or = 120/min), initial MAP (<70 mm Hg), and, inversely, the initial use of pressure-controlled ventilation.

Effect of an additional 1-hour T-piece trial on weaning outcome at minimal pressure support.

PURPOSE: The purpose of this article was to investigate the effect of an additional 1-hour T-piece trial at the level of minimum pressure support (PSmin) on weaning outcome. MATERIALS AND METHODS: Open, randomized, prospective study of 44 patients who had received mechanical ventilation for more than 3 days.Thirty-six patients satisfied the protocol. There were 42 weaning trials. The patients were randomized into an intervention group (additional 1-hour period of T-piece trial) and a control group (extubation directly) at PSmin. Blood gas analysis and estimation of respiratory and hemodynamic variables were performed at the 15 cm H2O level of pressure support. Measurements were repeated at PSmin and during weaning process (in intervention group). RESULTS: Mean PSmin level was 7.6 (+/- 1.9) cm H2O. There were no differences in total ventilation time (TVT), acute physiology and chronic health evaluation (APACHE) II score, nutritional indices, and respiratory mechanics on PSmin between the two groups. The weaning success rate and the reintubation rate were similar for the intervention group (55% and 18%, respectively) and control group (70% and 20%, respectively). Work of breathing, pressure time product, and tidal volume significantly worsened after a 1-hour T-piece trial when compared with those values measured at PSmin in the intervention group (P < .05). For the combined patient sample, TVT and tidal volume at PSmin were significantly different between the patients with weaning success (246 +/- 195 hours, 0.43 +/- 0.11 L) and those with weaning failure (407 +/- 248 hours, 0.35 +/- 0.10 L) (P < .05 in each). CONCLUSION: There were no advantages in weaning outcome by the addition of a 1-hour T-piece trial compared with prompt extubation at PSmin.

Phase II trial of a novel platinum analog, SKI 2053R, in patients with previously untreated extensive-stage small-cell lung cancer.

A phase II trial of a novel platinum analog, SKI 2053R, was performed in patients with previously untreated extensive-stage disease (ED) small-cell lung cancer (SCLC). SKI 2053R was administered at the dose of 400 mg/m2 every 3 to 4 weeks as a 1-h infusion. After the first cycle, the dose was escalated to 440 mg/m2 based on toxicity. Thirty-eight patients (31 male) were enrolled between June 1995 and August 1997. The median age was 61 years (range, 36-70 years). Six of 37 evaluable patients achieved a partial response (16.2%; 95% confidence interval [CI], 4.4-28.0%). The durations of response were 1.1, 1.5, 1.7, 1.9, 3.4, and 4.6 months. The estimated median survival time was 7.4 months (95% CI, 5.1-9.7 months). Grade 3 or 4 toxicities were not observed. Grade 1 to 2 leukopenia, anemia, and thrombocytopenia were seen in 5 of 68 cycles, 16 of 68, and 2 of 68, respectively. Nonhematologic toxicities included grade 1 to 2 nausea or vomiting (30 of 68 cycles), nephrotoxicity (27 of 68), and hepatotoxicity (13 of 68). SKI 2053R showed a modest antitumor activity with limited toxicities in patients with ED SCLC. Further clinical trials are warranted in SCLC with a higher dose of SKI 2053R.

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.

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.

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.

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.