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ABSTRACT: Expression of survivin has been reported to be correlated with shorter survival in patients with non-small cell lung cancer (NSCLC), and overexpression of survivin may lead to radioresistance in various human cancers. In this study, we inhibited survivin expression by using an adenoviral vector (AdsiSurvivin)-mediated RNA interference to elucidate the combined effect of survivin-targeting gene therapy and radiotherapy on the NSCLC cells. Our data showed that AdsiSurvivin exerted survivin gene silencing, induced apoptosis, and significantly attenuated the growth potential in NSCLC cells within 72 h after infection. The combined treatment modalities with AdsiSurvivin infection and radiation were significantly more potent on cell-growth inhibition than monotherapy. In H1650, H460, A549, and H1975 human NSCLC cells, the survival ratios of AdsiSurvivin-treated groups at multiplicity of infection of 25 and 50 were significantly lower than those of control groups at varying radiation dose (0-8 Gy; three-way analysis of variance, P<0.05). The cytotoxicity of combined AdsiSurvivin infection and irradiation increased in a dose-dependent manner in both the virus and the irradiation treatment. Knockdown of the survivin gene expression seems to be a promising treatment strategy for NSCLC. Our data warrant the need for further effort to develop survivin-targeted radiosensitizer for lung cancer treatment.
Cancer gene therapy 09/2009; 17(2):120-30. · 3.13 Impact Factor
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ABSTRACT: Targeted gene expression through viral vectors has been a promising approach for gene therapy. However, the effects of viral gene products expressed from virus vectors on the expression of the host gene are not well known. In the present study, we examined the activities of cellular promoters, including the promoter for genes of human telomerase reverse transcriptase (hTERT), tyrosinase and probasin, in both tumor and normal cells after infection with herpes simplex virus type 1 (HSV-1) vectors. Our results showed that infection with replication-defective HSV-1 vectors significantly upregulated the activity of all three cellular promoters in a nonsequence specific fashion in all cell types tested. Furthermore, viral infection upregulated activities of the hTERT promoter and endogenous telomerase in nontumoral cells. Additional experiments suggested that the viral immediate-early gene product, infected cell protein 0, might be responsible for the deregulation of cellular promoter activity and activation of telomerase. Our study alerts to the potential risk of oncogenesis through deregulation of host gene expression, such as the telomerase by viral vectors in normal cells.
Gene Therapy 09/2003; 10(17):1494-502. · 3.71 Impact Factor
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ABSTRACT: The polymerase chain reaction (PCR) may be sensitive and specific for the diagnosis of tuberculosis, but most reports are of studies conducted in well-controlled laboratories. A study to evaluate the clinical value of bronchoalveolar lavage (BAL) combined with PCR was necessary.
One hundred and thirty one patients were recruited into the study from March 1994 to February 1997.
Patients with a positive acid-fast stain on sputum smear were recruited into group A as positive controls, patients with lung cancer and a negative acid-fast stain on sputum smear were put into group B as negative controls, and patients who had clinical symptoms of pulmonary TB without sputum or with negative smear results were the investigating group. PCR was performed on the sputum samples from group A and B patients and on the BAL fluid from those in group C.
The sensitivity of PCR was 96% in group A, and the specificity was 100% in group B. The sensitivity of PCR in the BAL fluid from the group C patients was 36% and the specificity was 96%; the positive predictive value was 94% and the negative predictive value was 45%.
BAL plus PCR is useful in the rapid diagnosis of pulmonary TB in non-productive or smear-negative patients.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 05/2002; 6(4):350-5. · 2.73 Impact Factor
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ABSTRACT: ONYX-015 has been reported to kill selectively tumor cells lacking functional p53. Genetic alterations of INK4a/ARF locus, which is a predominant event in malignant pleural mesothelioma, may result in loss of p14(ARF) and subsequent disruption of p53 pathway in cancer cells. In the present study, ONYX-015 was able to kill three mesothelioma cell lines (H28, H513, and 211H) with wild-type p53 but lacking p14(ARF). In contrast, MS-1 mesothelioma cells, which expressed both p53 and p14(ARF), were resistant to ONYX-015. Introducing p14(ARF) gene into the H28 cell, a mesothelioma cell without p14(ARF) expression, significantly increased the resistance of this cell line to the cytolytic effect of ONYX-015. Our results suggest that human mesotheliomas with wild-type p53 yet lacking p14(ARF) are potential candidates for ONYX-015 therapy.
Cancer Research 09/2001; 61(16):5959-63. · 7.86 Impact Factor
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ABSTRACT: BACKGROUND: The p14(ARF) protein encoded by the INK4a/ARF locus promotes degradation of the MDM2 protein and thus prevents the MDM2-mediated inhibition of p53. Homozygous deletion of the INK4a/ARF locus is common in human mesothelioma and may result in the loss of p14(ARF) and the inactivation of p53. We designed this study to evaluate the biologic and potential therapeutic roles of p14(ARF) expression in mesothelioma cells. Methods and Results: We constructed Adp14, an adenoviral vector carrying human p14(ARF) complementary DNA, and used it to transfect human mesothelioma cell lines H28, H513, H2052, and MSTO-211H. Overexpression of p14(ARF) led to increased amounts of p53 and the p21(WAF) proteins and dephosphorylation of the retinoblastoma protein. The growth rate of mesothelioma cells was inhibited markedly by infection with Adp14 compared with mock infection or infection with a control adenovirus vector, AdCtrl. Overexpression of p14(ARF) induced G(1)-phase cell cycle arrest and apoptotic cell death. Cytotoxicity assays showed that Adp14 had a statistically significantly (P =.002) greater effect on colon cancer (HCT116) cell lines containing two copies of the wild-type p53 gene than on p53-null cells, suggesting that functional p53 is a critical determinant of p14(ARF)-mediated cytotoxicity. CONCLUSIONS: The transfection of p14(ARF) into mesothelioma cells led to the overexpression of p14(ARF), which resulted in G(1)-phase arrest and apoptotic cell death. These results suggest that this gene therapy-based approach may be of use in the treatment of mesothelioma.
JNCI Journal of the National Cancer Institute 05/2000; 92(8):636-41. · 13.76 Impact Factor
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ABSTRACT: p53 mutations and loss of heterozygosity (LOH) have been detected in >50% of lung cancers. Wild-type p53 can prevent replication of damaged DNA and promote apoptosis of cells with abnormal DNA. A human adenovirus, ONYX-015, which has a deletion in the E1B region, has shown tumor-specific cytolytic effect in tumor cells with nonfunctional p53 and antitumor efficacy that can be augmented by chemotherapeutic agents. A recent report from an independent group, however, indicates that wild-type p53 is necessary for the infection of this replicating virus, and it is in direct contradiction to previous observations of the ONYX group. In this study, we carried out cytopathic effect (CPE) assays using ONYX-015 on five human lung cancer cell lines with known p53 status. Two of these cell lines, NCI-H522 and NCI-H1703, have mutations and LOH in their p53 gene. Both lines were lysed in a dose-dependent manner and showed 100% cytolysis at a multiplicity of infection of 0.1. Two additional cell lines, NCI-H2347 and NCI-H838, both of which have wild-type p53 gene, showed near complete lysis at a multiplicity of infection of 1. We demonstrate here that the lung cancer cells with nonfunctional p53 are at least 10 times more sensitive to ONYX-015 cytolysis than the lung cancer cells with wild-type p53. In addition, standard chemotherapeutic agents (paclitaxol and cisplatin) showed a synergistic effect when combined with ONYX-015, and this effect was p53 mutant dependent. Furthermore, we tested the cytolytic effect of ONYX-015 on a panel (n = 7) of primary first-passage cultures made from freshly resected lung cancers. ONYX-015 lysed primary lung cancer cells in six of seven (86 %) primary cultures. Two of four primary cultures treated with chemotherapeutic agents had a synergistic effect with ONYX-015. Our data indicate that wild-type p53 is not required for the infection of this replicating virus, and also we demonstrate that ONYX-015 is effective alone and works synergistically with chemotherapeutic agents in lung cancer cell lines and primary cultures. This study suggests that ONYX-015 may be effective, especially in combination with conventional chemotherapy, in the treatment of patients with lung cancer.
Cancer Research 02/2000; 60(4):1009-13. · 7.86 Impact Factor
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ABSTRACT: This study was performed to assess the changes in pulmonary mechanics before and after tracheostomy in patients with prolonged mechanical ventilation and to detect pre-tracheostomy physiologic factors that predict the outcome of weaning from mechanical ventilation. Pulmonary mechanics were recorded before and after tracheostomy in 20 patients. Work of breathing, mean airway resistance and pressure/time product showed no significant differences after tracheostomy. Peak inspiratory pressure was significantly reduced (pre 33.4 +/- 11.8 vs post 28.6 +/- 9.2 mmHg). There was no difference in age or duration of mechanical ventilation between two different groups according to the outcome (weaned and not-weaned). Pre-tracheostomy intrinsic positive end expiratory pressure (PEEPi) was significantly lower in the weaned group (1.1 +/- 1.6 vs 2.7 +/- 1.4 mmHg). A significant difference was also found in pre-tracheostomy compliance (Cstatic) (47.3 +/- 36.9 vs 28.8 +/- 16.5 ml/cmH2O). We concluded that tracheostomy changed pulmonary mechanics very little except for a fall in peak inspiratory pressure. Patients who had better underlying lung mechanics (higher Cstatic and lower PEEPi) had better chances of weaning from mechanical ventilation after tracheostomy.
Anaesthesia and intensive care 01/2000; 27(6):581-5. · 1.28 Impact Factor
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ABSTRACT: Many different cisplatin-based regimens have been used on advanced non-small cell lung cancer (NSCLC) in previous studies but there have been few such references in Taiwan. In this study, we evaluated the efficacy and toxicity of two different regimens including 5-Fluorouracil, Leucovorin, Etoposide and cisPlatin (FLEP) and cisPlatin, Etoposide and Mitomycin (PEM) in the treatment of patients with advanced NSCLC.
We retrospectively analyzed the records of 44 patients with NSCLC who met the selection criteria from February 1995 through April 1998. All of them were confirmed, using histologic tests, that they were in advanced stages, i.e. stage IIIB or IV. Twenty-two patients received FLEP and 22 patients received PEM.
Three patients with FLEP therapy and 3 patients with PEM therapy had partial response. No patient had complete response. The response rate was 13.6% in both groups, respectively. The median survival was 160 +/- 30 (median + SD) days for patients with FLEP therapy and 263 +/- 104 days for patients with PEM therapy. The factors that were associated with longer survival in all patients included response (Stable Disease vs Disease Progression p = 0.004, Partial Response vs Disease Progression p = 0.047) and regimen of chemotherapy (PEM vs FLEP p = 0.008). The major clinically significant toxicity was myelosupression.
The responses to regimens, FLEP and PEM, were low in our study groups that might be due to the low dose of cisplatin and etoposide in our regimens. The patients with response to chemotherapy and PEM therapy had longer median survival than those who underwent FLEP therapy.
Changgeng yi xue za zhi / Changgeng ji nian yi yuan = Chang Gung medical journal / Chang Gung Memorial Hospital. 07/1999; 22(2):220-6.
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ABSTRACT: We examined the relationships between exposure to different indoor allergens and demographic factors in 515 adult Taiwanese patients with allergic diseases such as asthma and rhinitis. Patients who had positive screening results on an immunoglobulin E (IgE) test were recruited from the outpatient clinics of Chang Gung Memorial Hospital. Patients were divided into the following three groups: asthma (n = 332), combined asthma and allergic rhinitis (n = 165), and allergic rhinitis (n = 18). Serum samples were analyzed for IgE by enzyme-linked immunosorbent assay. Significantly elevated titer of dust mite-specific IgE were found in all three groups, with markedly higher levels in the combined asthma and allergic rhinitis group (p < 0.05). Allergen scores were significantly related to the demographic variables of older age (> or = 65 years), female gender, and spring season, with significantly lower scores (p < 0.05). No significant difference in allergen scores was found among cigarette smoking subjects and subjects from residential areas. Multiple linear regression analysis revealed significant allergic contributors to be, in order of importance, age, gender, and atopic disease category. We conclude that mite allergen exposure is the most significant factor associated with asthma and/or allergic rhinitis in Taiwan. Younger subjects and males had a higher rate of asthma and/or allergic rhinitis.
Journal of the Formosan Medical Association 07/1999; 98(7):486-91. · 1.13 Impact Factor
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ABSTRACT: The proportions and absolute cell count of gamma/delta T-lymphocytes in the peripheral blood of patients with pulmonary tuberculosis (PTB) remains controversial. Since PTB is an infections airway disease, bronchoalveolar T-lymphocytes should be a better indicator of local immune T-cell reaction after TB infection than peripheral blood T-lymphocytes.
To quantitate the absolute cell count and proportions of gamma/delta T-lymphocytes in the bronchoalveolar lavage fluid (BALF) of patients with active PTB.
Bronchoalveolar lavage (BAL) and analysis of lymphocytes in the BALF was performed in 25 patients with active PTB and 16 normal controls. All of the patients were negative for HIV infection and none was immunocompromised. BALF and blood were prepared for cell differential count and flow cytometry analysis using monoclonal antibodies CD3, CD4, CD8, CD25, HLA-DR and gamma/delta as well as alpha/beta T-lymphocyte receptors.
The number of cells per volume of recovered BALF was significantly higher in the patients with active PTB than in normal controls. BALF from active PTB patients also showed increased percentage of lymphocytes and neutrophils. The absolute number of total lymphocytes, CD3+ lymphocytes and CD3+ gamma/delta T-lymphocytes were significantly higher in the BALF, but not in the blood, of patients with TB, however, the proportions of CD3+ gamma/delta T-lymphocytes in BALF of patients with TB was comparable to that of normal controls. gamma/delta T-lymphocytes in the BALF rarely expressed CD4, CD25, and HLA-DR in both groups.
These results suggest that gamma/delta T-lymphocytes are not the major subpopulation of CD3+ lymphocytes in the BALF that react to mycobacterial infection in the patients with clinically established active TB.
Tubercle and Lung Disease 02/1999; 79(4):215-20.
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ABSTRACT: This study was undertaken to observe whether dialysis-induced alveolar hypoventilation and arterial hypoxaemia occur during bicarbonate haemodialysis in patients receiving partial mechanical support with pressure support ventilation. Nineteen patients admitted to the medical intensive care unit requiring mechanical ventilation and haemodialysis were enrolled. Arterial blood gas, white blood cell (WBC) count, minute ventilation, respiratory rate, breathing pattern and blood pressure were measured according to the following time schedule: pre-dialysis (time 0), and at 15, 30, 60, 120, 180, 240 min thereafter. Results showed that, with the use of cuprammonium dialyser, the WBC count dropped immediately and reached the nadir 15 min after haemodialysis. Thereafter, it recovered and overshot the pre-dialysis values until the end of dialysis. The bicarbonate dialysate indeed resulted in rapid and significant metabolic alkalosis. However, no decrease of PaO2 occurred throughout haemodialysis. The tidal volume, minute ventilation and breathing pattern remained stable during haemodialysis. We conclude that neither dialysis-induced alveolar hypoventilation nor arterial hypoxaemia developed during bicarbonate dialysis in patients mechanically ventilated with the pressure support ventilation.
Respiratory Medicine 04/1998; 92(3):534-40. · 2.47 Impact Factor
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ABSTRACT: To determine the diagnostic value of pleural fluid telomerase activity in distinguishing a malignant from a nonmalignant pleurol effusion in a cohort of patients undergoing thoracentesis.
Using a polymerase chain reaction (PCR)-based assay, telomerase activity was examined in the pleural fluid cells obtained from 144 consecutive, unselected patients. According to the final diagnosis achieved, these patients were classified into three groups: group I consisted of 70 malignant pleural effusions diagnosed by either fluid cytology or pleural biopsy, group II consisted of 52 nonmalignant pleural effusions, and another 22 samples were categorized to be suspicious malignant pleural effusions (group III) due to inconclusive results in effusion cytology and percutaneous pleural biopsy, but were strongly suspicious in clinical settings.
The presence of telomerase activity was observed in 64 of 70 samples in group I (91.4%), three of 52 samples in group II (5.8%), and 20 of 22 samples in group III. All three nonmalignant, telomerase-positive pleural effusion samples in group II were obtained from patients with tuberculosis. As a diagnostic criterion for malignant pleural effusion in group I and group II patients, positive telomerase activity had a sensitivity of 91.4%, a specificity of 94.2%, and a positive and negative predictive value of 0.96 and 0.89, respectively.
Our results indicate that the detection of telomerase activity may be a useful adjunct to cytopathologic methods in the diagnosis of malignant pleural effusions.
Journal of Clinical Oncology 03/1998; 16(2):567-73. · 18.37 Impact Factor
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ABSTRACT: The improvements of respiratory drive and pulmonary mechanics which follow haemodialysis with ultrafiltration in mechanically ventilated renal failure patients seem predictable but have not been studied before. In this study, 14 renal failure patients with stable haemodynamics mechanically ventilated with pressure support ventilation (PSV) were enrolled. Respiratory drive (represented as P0.1), pulmonary mechanics, breathing pattern, arterial blood gas and haemodynamics were measured according to the time schedule: pre-dialysis (Time 0), and at 60, 120, 180, 240 minutes thereafter. Following the removal of excess lung water during haemodialysis, auto-PEEP and patient's work of breathing (WOBp) decreased gradually. P0.1 lessened progressively along with the improvement in pulmonary mechanics. The changes in auto-PEEP and WOBp correlated closely to the pre- and post-dialysis decline of P0.1 (delta P0.1). There was a negative, moderately significant correlation between the amount of fluid ultrafiltrated during dialysis (delta UF) and the delta P0.1 (R = -0.54). The breathing pattern remained stable during dialysis. No hypoventilation or hypoxaemia occurred despite the development of metabolic alkalosis induced by bicarbonate dialysate. We have shown that respiratory drive decreases gradually during bicarbonate haemodialysis. The improvements of pulmonary mechanics, rather than the rapid alkalization of body fluids, responds to the decrease of P0.1 in renal failure patients ventilated with PSV.
Anaesthesia and intensive care 11/1997; 25(5):464-70. · 1.28 Impact Factor
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ABSTRACT: The prognosis of Stage III unresectable non-small cell lung cancer may be improved by concurrent chemoradiotherapy. In this study, we attempted to evaluate the feasibility, tolerance, efficacy and toxicities of the combination of thoracic radiation and chemotherapy with a novel regimen that included 5-fluorouracil, leucovorin, etoposide and cisplatin (the FLEP regimen) in the treatment of this group of patients.
From July 1995 to September 1996, 20 untreated patients with locally advanced non-small cell lung cancer were enrolled in the study. Radiation at a dose of 44 Gy was initially delivered in daily fractions of 2 Gy 5 days a week to the tumor and mediastinum, followed by a boost to the tumor (20 to 26 Gy according to patients tolerance). Concurrently with thoracic irradiation, patients were treated with chemotherapy consisting of cisplatin at the dose of 60 mg/m2/d for 1 day, etoposide at the dose of 60 mg/m2/d for 2 days, and 5-FU 500 mg/m2/d plus leucovorin 50 mg/d infusion for 48 hours. Cycles of chemotherapy were repeated every 3 weeks for a maximum of 3 cycles.
Seventeen of 20 patients were assessable. The overall response rate was 70.6% (95% confidence interval = 49-92%). No complete response was achieved. The median response duration for all responding patients is not yet estimable, with a range of 3.5 to 15.5+ months. Eleven patients remain progression-free for 4 to 15 months. The median survival for the entire group is not estimable. The major toxicity was esophagitis. Other grade 3 or 4 toxicities were not frequently observed.
Combined-modality therapy with FLEP regimen and radiation is a promising treatment with a high response rate and acceptable toxicity for locally advanced non-small cell lung cancer.
Changgeng yi xue za zhi / Changgeng ji nian yi yuan = Chang Gung medical journal / Chang Gung Memorial Hospital. 10/1997; 20(3):187-94.
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ABSTRACT: In patients who have malignant pleural effusion, it is difficult to diagnose trapped lung before thoracoscopy, thoracostomy, and drainage of the effusion. Predicting the outcome of pleurodesis in patients who have malignant pleural effusion without trapped lung is also difficult.
To investigate the factors that may be useful in diagnosing trapped lung and predicting the outcome of pleurodesis.
Prospective cohort study.
University medical center.
65 patients with symptomatic malignant pleural effusion.
A chest tube was inserted for drainage of the effusion, and pleurodesis was done using bleomycin as the sclerosant.
The pH and glucose levels of the effusion and the elastance of the pleural space (defined as the decline in pleural fluid pressure in cm H2O after removal of 500 mL of effusion) were measured. The outcome of pleurodesis was evaluated 1 month after the chest tube was removed.
Patients with an elastance of 19 cm H2O or more had a higher incidence of trapped lung (11 of 14 patients) than did those with an elastance less than 19 cm H2O (3 of 51 patients) (P < 0.001). None of the 14 patients with an elastance of 19 cm H2O or more and none of the 14 patients with a trapped lung had successful pleurodesis. Forty-two of 43 patients with an elastance less than 19 cm H2O who did not have a trapped lung had successful pleurodesis. Elastance seemed to be the best predictor for trapped lung and outcome of pleurodesis, although outcome was also correlated with pH and glucose levels of the effusion. Low-dose bleomycin (30 mg) is as effective as the usual dose of bleomycin (60 mg) for pleurodesis.
In patients with symptomatic malignant pleural effusion, measurement of the elastance of the pleural space is a simple and effective method for the diagnosis of trapped lung and prediction of the outcome of chemical pleurodesis with bleomycin.
Annals of internal medicine 06/1997; 126(10):768-74. · 16.73 Impact Factor
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ABSTRACT: The purposes of this research project were to establish an integrated home care model and understand the influence of an integrated home care model on demented elders and their families. The changes in cognitive function and self-care ability of demented elders were also explored longitudinally. The disciplines involved in the integrated home care model included doctors, home care nurses and social workers. The integrated home care model was developed according to the functions and roles of different disciplines in their actual working process. Services provided included home nursing care, telephone consultation and a support group. Home care nurses played the role of case manager in this model. Twenty-five families participated in this study. Among them, 22 received home care service, and 20 of them participated in a caregiver support group. The cognitive function of the demented elders did not significantly decrease over the 6-month period. Among their self-care ability, grooming and eating dependency were found significantly increased during this period. Overall, 81% families reported that home nursing care services could help them to develop care skills, care knowledge and provided emotional support. However, the caregiver burden did not significantly decrease after the home nursing care services. Seventy percent of caregivers reported that telephone consultation could support them emotionally and provided them with information concerning care. Over half of the caregivers reported that in getting related information and receiving emotional support was helpful. This integrated model developed from this research project can be adapted and used in networking home care agencies, the community and health care resources. The small and convenient sample was one of the limitations of this study. The insignificance of some of the findings might be due to the short time period (6 months) and some effects of the model might appear later than 6 months. For further research, larger and random samples and a longer period of follow-up with more health disciplines involved were suggested.
The Kaohsiung journal of medical sciences 07/1996; 12(6):359-69. · 0.61 Impact Factor
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ABSTRACT: Our study was to assess whether there were differential effects of nasal continuous positive airway pressure (nCPAP) on different kinds of obstruction in either upper or lower airways in patients with chronic obstructive pulmonary disease (COPD). nCPAP (6 cmH2O for ten minutes) was applied to 7 patients with reversible extrathoracic upper airway obstruction (RUAO) and 3 patients with fixed extrathoracic upper airway obstruction (FUAO). Eighteen stable asthmatics, receiving methacholine challenge to induce a more than 20% reduction in FEV1, were randomly investigated for the effect of nCPAP or sham pressure on reversible lower airway obstruction. Nine stable COPD patients were enrolled to study the effect on irreversible lower airway obstruction. Maximal expiratory and inspiratory flow volume curves and dyspnoea scores were obtained before and after immediate withdrawal of nCPAP. In the RUAO group, nCPAP significantly improved stridor and dyspnoea scores, decreased the ratio of FEF50/FIF50 from 2.05 +/- 0.25 to 1.42 +/- 0.16, and increased peak inspiratory flow (PIF) as well as forced inspiratory vital capacity by 26 +/- 8% and 9 +/- 4%, respectively. In expiratory phase, there was no significant change in pulmonary functions. In asthmatics, nCPAP significantly reversed methacholine-induced bronchoconstriction increasing forced vital capacity by 10 +/- 3%, FEV1 by 15 +/- 4% and PIF by 32 +/- 11%. nCPAP significantly increased the response to bronchodilators. The improvement in airflow rate persisted for at least 5 min after nCPAP withdrawal and was highly correlated with the response to bronchodilators. There was no significant effect of nCPAP on airflow rate in COPD patients. Subjective dyspnoea score changes paralleled the pulmonary function improvement. We conclude that there are differential effects of nCPAP on airflow rates in patients with different nature of airway obstruction. Patients with airway obstruction caused by structural changes may not benefit from the use of nCPAP in improving airflow rates.
European Respiratory Journal 06/1996; 9(5):952-9. · 5.89 Impact Factor
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ABSTRACT: The effect of beta 2-adrenoceptor agonist-induced hypokalaemia on cardiac arrhythmias might be exacerbated during exercise, especially in patients with more compromised airway function.
To evaluate the effect of beta 2-adrenoceptor agonists on plasma potassium and cardiopulmonary function during exercise, two identical submaximal treadmill exercise tests were performed, at least 48 h apart, by 13 patients with moderate to severe COPD (11 men and 2 women, mean age 66 y, mean FEV1/FVC ratio 48.9 (2.8)% 30 min after they had received nebulised fenoterol or salbutamol (2 mg). The experiment was done as a randomised, double-blind, crossover trial after an initial baseline study with vehicle (0.45% saline). Plasma potassium concentration, spirometry and the degree of breathlessness (Borg scale) were measured before treatment and immediately after exercise; oxygen saturation, QTc interval and cardiac rhythm were monitored continuously before, during and for 30 min after exercise.
After the saline control, exercise caused an increase in Borg rating (of 4.9), a premature ventricular contractions (VPC) (2.8 beats/min), and a fall in oxygen saturation (-6.7%), but no significant change in plasma potassium (+0.04 mEq.dl-1), FEV1 or QTc interval. Inhalation of fenoterol and salbutamol did not affect QTc interval, Borg scale or VPC frequency at rest, but significantly increased the duration of exercise undertaken to reach the submaximal levels (786 s, versus 783 s) compared to the vehicle control. Following exercise, plasma potassium fell after fenoterol by 0.2 mEq.dl-1 and it increased after salbutamol by 0.1 mEq.dl-1 compared to baseline levels. Plasma potassium after exercise was significantly lower after fenoterol (3.2 mEq.dl-1) compared to the saline control (3.7 mEq.dl-1) and salbutamol (3.6 mEq.dl-1). Neither fenoterol nor salbutamol had any significant effect on the change in FEV1, oxygen saturation, Borg scale, frequency of VPCs or QTc interval during or after exercise compared to the saline control.
When compared to salbutamol 2 mg, fenoterol 2 mg caused more marked hypokalaemia but no significant difference in cardiopulmonary response in patients with COPD during exercise.
European Journal of Clinical Pharmacology 02/1996; 49(5):341-5. · 2.85 Impact Factor
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ABSTRACT: Bronchial hyper-responsiveness is a cardinal feature of asthma. To determine whether nasal continuous positive airway pressure (NCPAP) influences airway smooth muscle in response to exogenous stimuli, we examined the effect of NCPAP on aerosolized methacholine-induced bronchoconstriction in 16 stable asthmatic patients. The dose-response curve for each subject was measured by a log transformation and linear regression analysis as well as a formula fitted to the data points to obtain values for a (slope) and b (position). The PD20FEV1 significantly increased in patients receiving 8 cmH2O of NCPAP by one doubling dose compared with that in patients using sham pressure. NCPAP shifted the dose-response curves to be flatter, deviated upwards and to the right. The coefficient a, indicating bronchial reactivity, was significantly lower in patients receiving NCPAP. The coefficient b, indicating the bronchial sensitive threshold, was higher after applying NCPAP. In contrast, coefficients a and b did not change in subjects with sham pressure. NCPAP also significantly enhanced the bronchodilator effect of inhaled salbutamol in response to methacholine-induced bronchoconstriction. In summary, we have shown that NCPAP therapy improves bronchial smooth reactivity with an increase in PD20FEV1 and a reduction in the bronchial reactivity and bronchial sensitivity. Therefore, NCPAP may provide an adjuvant therapy in patients with acute bronchial asthma.
Respiratory Medicine 03/1995; 89(2):121-8. · 2.47 Impact Factor
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ABSTRACT: A hybrid technique of multiplexing holography as shown in figure below was developed to characterise microfluidic behaviors for the needs from microfluidics. Following the spirit of holographic PIV (HPIV), a high sensitive photopolymer (CROP), a ferroelectric liquid crystal (FLC) shutter and a rotational stage were introduced to constitute an novel system for 3D3C microflow measurements. CROP photopolymer in the system serves as an intermediate recording media, while FLC shuttle associates with rotational stage serves as a hybrid mechanism of holographic multiplexing. A high-sensitivity CCD on a traverse stage was used to retrieve the holographic images for post processing to derive a 3D instant flow field based on a concise cross-correlation algorithm (CCC). To evaluate the practicability, a microchannel was measured of its inner free flow with a preset exposure time of 6 ms for each image. The flow in a 550 µm × 26 µm microchannel was calculated of its average velocity to be 9.18 µm/s and central velocity to be 12.2 µm/s. The profile accorded with the simulated laminar flow situation. The results thus proved the practicability of the innovative design. Some encountered difficulties in the experiments will also be expatiated for future improvement. In addition, a visualisation technique based on the effect that light of different wavelength results in different refractive index was employed to rapidly view through the whole 3D flow field. Object Ref 1 Ref 2 ∆t ∆t Τ Time Series Image 1:1 Image 1:2 Image 2:1 Image 2:2 Depiction of the hybrid multiplexed manipulations for recording stereo-images: Two image pairs are shown above, The first multiplexing is operated by using a FLC shutter to divert the path of reference beam. The rapid non-mechanical switching is proper to control the time interval between image 1:1 and image 1:2 (∆t). The second multiplexing is a mechanically angular rotating which require a longer time (T), and is thus used to prepare memory for the next image pair (image 2:1 and image 2:2). Repeat the two multiplexing operations, serial image pairs can be stored in the photopolymer simultaneously.
