Adjunctive Treatment with Rhodiola Crenulata in Patients with Chronic Obstructive Pulmonary Disease--A Randomized Placebo Controlled Double Blind Clinical Trial.

UNLABELLED: Chronic obstructive pulmonary disease (COPD) is a low grade systemic inflammatory disease characterized by dyspnea and exercise intolerance even under standard therapy. Rhodiola crenulata (RC) has been shown to exert anti-inflammatory effects and to enhance exercise endurance, thereby having the potential to treat COPD. In this 12-week, randomized, double-blind, placebo-controlled clinical trial, 57 patients with stable moderate-to-severe COPD aged 70±8.8 years were given RC (250 mg twice/day) (n=38) or a placebo (250 mg twice/day) (n=19) in addition to their standard regimen. There were no significant differences in anthropometrics, quality of life, lung function, six-minute walk and incremental exercise tests between the two groups at enrollment. Over the 12 weeks, RC was well tolerated, significantly reduced triceps skin thickness (Δ=-1 mm, p=.04), change of FEV1 (4.5%, p=.03), and improved workload (Δ=10%, p=.01); although there were no significant differences in these factors between the two groups. However, there were significant between-group differences in tidal volume and ventilation-CO2-output ratio at peak exercise (both p=.05), which were significantly related to peak work rate (both p<.0001). RC tended to protect against acute exacerbation of COPD (p=.1) but not other measurements. RC did not improve the six-minute walk test distance but significantly improved tidal breathing and ventilation efficiency, most likely through improvements in work rate. Further studies with a larger patient population are needed in order to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02242461.

Phase II study of epirubicin in combination with weekly docetaxel for patients with advanced NSCLC who have failed or relapsed after the frontline platinum-based chemotherapy.

BACKGROUND: We conducted a phase II study to evaluate the efficacy and toxicity of weekly docetaxel combined with epirubicin on D15 as second-line chemotherapy in Taiwanese patients with advanced non small cell lung cancer (NSCLC) who failed or relapsed after the frontline platinum-based chemotherapy. PATIENTS AND METHODS: Patients with histologically confirmed advanced NSCLC (Stage IIIB-IV) were entered into this Phase II trial. Eastern Cooperative Oncology Group performance status was 0 to 2 and adequate organ function was required. Docetaxel, 30 mg/m, was given intravenously on days 1, 8, and 15 for 30 minutes and epirubicin, 60 mg/m, was given intravenously on day 15, then following one week of rest. Treatment was repeated every 4 weeks for a maximal total of 6 cycles. RESULTS: Of the 43 eligible patients, 39 patients were evaluated for response, and all were evaluated for toxicity. The overall response rate was 11.6% [95% confidence interval (CI), 1.6-21.6%]. The median time to disease progression for all patients was 2.8 months (95% CI 1.3-4.3%). The median survival time for all patients was 7.7 months (95% CI 5.5-9.9%). The 1-year survival was 32.6% (95% CI 25.4%-39.7%). The major hematologic toxicities were neutropenia, 8/43 (19%) with grade 3-4 neutropenia, as well as anemia, 6/43 (14%) with grade 3-4 anemia. Nonhematological toxicities were modest. Fatigue was common, 77.8% in all, but only 3 (7%) patients with grade 3-4 toxicities. Diarrhea was also common but not severe, 7/43 (16%) with grade 1-2 episodes, and 1/43 (2%) with grade 3-4 episodes. Nail changes, peripheral edema, lacrimation, and alopecia were mild. Hepatic and renal impairment was also only mild. CONCLUSION: Combining weekly doses of docetaxel 30 mg/m with epirubicin 60 mg/m on D15 was not shown to improve both efficacy and tolerability for advanced NSCLC patients who have relapsed disease after frontline platinum-based chemotherapy.

Response to hypercapnic challenge is associated with successful weaning from prolonged mechanical ventilation due to brain stem lesions.

OBJECTIVE: We propose that higher airway occlusion pressure (P0.1) responses to hypercapnic challenge (HC) indicate less severe injury. The study aim was to determine whether P0.1 responses to HC were associated with successful weaning after prolonged mechanical ventilation (PMV) in patients with brainstem lesions and to determine a reference value for clinical use. DESIGN AND SETTING: Forty-two patients with brainstem lesions on PMV were recruited. Breathing parameters and P0.1 were measured before HC. Three-minute HC challenges with increasing CO(2) concentrations were initiated and P0.1, respiratory rate, minute ventilation (V (e)), tidal volume (V (t)) and end tidal CO(2) were measured. MEASUREMENTS AND RESULTS: Patients were classified into high (group I) and low (group II) response groups on the basis of P0.1 responses to HC. Increases in V (e) and V (t) after HC were significantly greater in group I patients (12.22 +/- 8.22 vs. 3.08 +/- 4.84 L/min, P < 0.001 and 399.11 +/- 278.18 vs. 110.54 +/- 18.275 ml, P < 0.001). P0.1 levels were significantly higher in group I compared to group II before HC (2.69 +/- 1.81 vs. 1.28 +/- 1.04 cmH(2)O, P = 0.003). The increase in P0.1 following HC was significantly greater in group I compared to group II patients (11.05 +/- 4.06 vs. 2.90 +/- 2.53 cmH(2)O, P < 0.001). Weaning success was significantly higher in group I compared to group II patients (72.2% vs. 33.3%, P = 0.02). A P0.1 increase of >6 cmH(2)O following HC was significantly associated with successful weaning. CONCLUSIONS: Assessing the P.01 response to serial increases in the level of HC may be a safe means to ascertain whether patients with brainstem lesions are ready for ventilator weaning.

Weekly short infusion of taxotere at a 4 week cycle in Chinese patients with advanced NSCLC who have failed or relapsed after the frontline platinum-based non-taxane chemotherapy--a Phase II trial.

BACKGROUND: This Phase II study was conducted to evaluate the efficacy and toxicity of weekly docetaxel at a 4 week cycle in second-line therapy for patients with advanced non-small cell lung cancer (NSCLC) who failed to respond or relapsed after the frontline platinum-based, non-taxane regimen. METHODS: Patients with histologically confirmed and progressive NSCLC after one platinum-based, non-taxane regimen were eligible for this study. Performance status of 0-2 and adequate organ function were required. Patients were treated with docetaxel 40 mg/m(2)/week for three consecutive weeks then following 1 week of rest. Cycles were repeated every 4 weeks for a maximum total of six cycles. Docetaxel was administered intravenously for 30 min with dexamethasone premedication. RESULTS: Fifty-three patients were eligible for this study. Hematologic toxicity was very mild and with the major toxicity of anemia. Non-hematologic toxicities were modest, Grades 3-4 mucositis, diarrhea and peripheral neuropathy occurred in 6-13% of patients and caused dose modifications. Fatigue (48%) was common but not severe with only 6% of Grades 3-4 toxicity. The overall response rate (ORR) was 13% [95% confidence interval (CI), 3.9-23%]. The median survival time (MST) for all patients was 25.0 weeks (95% CI, 12.7-37.3), and the 1 year survival was 31% (95% CI, 17-58%). For patients with PS 0-1, MST was 29.7 weeks and 1 year survival was 36%. CONCLUSIONS: Weekly docetaxel appeared to be well tolerated as second-line therapy for patients with NSCLC. The efficacy for this regimen was comparable with the standard 3 week schedule but hematologic toxicity was markedly reduced. A schedule of three consecutive weeks, with a 1 week break, may diminish the frequency of fatigue and diarrhea when compared with a schedule of six consecutive weeks.

Ventilation and exercise performance after phrenic nerve and multiple intercostal nerve transfers for avulsed brachial plexus injury.

BACKGROUND: Diaphragmatic excursion, lung function, exercise performance, and clinical symptoms have not been previously described in patients after phrenic nerve transfer (PNT) and/or multiple intercostal nerve transfer (MIT) for the repair of avulsed brachial plexus injury (ABPI) to prevent functional musculoskeletal impairment in the shoulder. SETTING: A university-based hospital. METHODS: Dyspnea scores, chest ultrasonography to assess diaphragmatic excursion, and pulmonary function testing were performed to assess ventilation in patients sustaining trauma to their brachial plexus. In addition, cardiopulmonary exercise testing was also performed. These studies were obtained prior to surgical intervention, and were repeated postoperatively at 6, 12, 18, 24, and 36 months. The results obtained preoperatively were compared to those obtained throughout the postoperative monitoring period. RESULTS: This study demonstrates that the PNT-MIT procedure results in permanent ipsilateral diaphragmatic paralysis accompanied by an approximately 8% decrease in inspiratory capacity, FVC, and total lung capacity. There was also an 11% increase in diffusing capacity noted during the period between 6 months and 3 years after PNT-MIT procedure. Despite these measurable changes in lung function, the patients reported amelioration of their dyspnea complaint within 6 months of undergoing this procedure, which was due mainly to an improvement in their cardiovascular exercise performance related to increased daily activity. CONCLUSIONS: This study demonstrates that the PNT-MIT procedure is a safe method for the restoration of drop shoulder incurred by ABPI. This surgery has an impact on measurable diaphragmatic and lung function but with minimal impact in terms of postoperative clinical symptoms and exercise performance.

Dose-finding and phase 2 study of weekly paclitaxel (taxol) and cisplatin combination in treating Chinese patients with advanced nonsmall cell lung cancer.

OBJECTIVES: The aim of the present study is to evaluate the efficacy and toxicity of weekly paclitaxel combined with cisplatin as first-line chemotherapy in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) and to identify the optimal dose of weekly paclitaxel to be administered safely and effectively. METHODS: Chemonaive patients with NSCLC, stage 3B with malignant pleural effusion, or stage 4 were enrolled in this study. In the dose-finding study, patients took paclitaxel once weekly at an initial dose of 50 mg/m2 and 3 weeks followed by cisplatin on day 15 at a fixed dose of 80 mg/m2. The escalating dose for paclitaxel was 10mg/m2 for each level. In the phase 2 study, patients received paclitaxel at maximum tolerated dose (MTD). RESULTS: The MTD for paclitaxel was 60 mg/m2. Of the 47 eligible patients, 7 patients had a complete response and 15 achieved a partial response. The overall response was 46.8% (95% CI, 32.0% to 61.6%). The median survival was 16 months (95% CI, 13.4 to 18.6 months). Twenty-four patients (51.1%) completed 6 cycles of treatment. With regard to hematological toxicity, although grade 3/4 neutropenia was observed in 5 patients (10.6%), there was no febrile neutropenia. The major nonhematological toxicity was asthenia, which was observed in all patients (17 patients grade 1/2 and 30 patients with grade 3/4). CONCLUSIONS: Weekly paclitaxel combined with cisplatin on day 15 is a safe and effective regimen as a first-line chemotherapy in NSCLC. The MTD for this regimen was 60 mg/m.

Shifts of T4/T8 T lymphocytes from BAL fluid and peripheral blood by clinical grade in patients with pulmonary tuberculosis.

OBJECTIVES: We investigated the shifts of T4/T8 lymphocytes from BAL fluid (BALF) and peripheral blood by the clinical grade of pulmonary tuberculosis (TB), which is determined by factors such as extent of pulmonary involvement, fever, and loss of body weight. MATERIALS AND METHODS: In order to explore these questions, BALF was collected from 45 patients presenting with active pulmonary TB and 14 healthy control subjects. The percentages for T-lymphocyte subpopulations, including CD4(+), CD8(+), and CD3(+) T cells, were measured using two-color flow cytometry. RESULTS: A higher percentage of CD3(+)CD4(+) T lymphocytes, with a relatively lower percentage of CD3(+)CD8(+) T lymphocytes, was revealed for the patients with a higher grade of pulmonary TB, compared to patients with a lower grade of pulmonary TB, resulting in an increased BALF C4(+)/CD8(+) ratio. By contrast, a higher percentage of CD3(+)CD8(+) T lymphocytes with a relatively low percentage of CD3(+)CD4(+) T lymphocytes was demonstrated for these patients with a higher grade of pulmonary TB, resulting in a decreased peripheral blood CD4(+)/CD8(+) ratio. CONCLUSIONS: Our findings suggest that compartmentalization of the CD4(+) T lymphocytes in the infected lungs may occur for patients with higher grades of pulmonary TB.

Phase II study of paclitaxel (Genaxol) and cisplatin combination in treating Chinese patients with advanced non-small cell lung cancer (NSCLC).

PURPOSE: To assess the efficacy of 3-h paclitaxel infusion (Genaxol) combined with cisplatin as the first line chemotherapy for patients with advanced/metastatic non-small cell lung cancer (NSCLC). The aim of the present study is to evaluate the efficacy, safety, and quality of life of the combination of paclitaxel (Genaxol) and cisplatin on Chinese patients. METHODS: Forty-five patients with histology confirmed NSCLC, who met the selection criteria were enrolled in this study between June 1999 and May 2000. They were all at an advanced stage, i.e. stage IIIB with pleural effusion, or stage IV. Paclitaxel (Genaxol) at a dose of 175 mg/m(2) and cisplatin at a dose of 75 mg/m(2) were administered every 3 weeks. RESULTS: Of the 45 eligible patients, one had a CR and 19 achieved a PR. The overall response was 44.4% (95% CI: 29.3-59.5%). Eleven (24.4%) patients were in stable disease. The median time to disease progression for all patients was 5.5 months (95% CI: 4.0-7.0 months). The median survival was 11.1 months (95% CI: 6.6-15.6 months), the 1-year survival probability was 46.5%. Major non-hematology toxicities were asthenia, paresthesias, nausea, and vomiting. Hematological toxicity results showed 18 (40%) patients experienced grade 3/4 neutropenia but there was no febrile neutropenia, three (6.6%) patients experienced Grade 3 anemia, and one (2.2%) patient experienced Grade 3 thrombocytopenia. CONCLUSIONS: The combined paclitaxel and cisplatin regimen is safe and effective in the treatment of NSCLC but the quality of life is disappointed.

Acute ingestion poisoning with insecticide formulations containing the pyrethroid permethrin, xylene, and surfactant: a review of 48 cases.

BACKGROUND: Forty-eight patients poisoned with insecticide formulations containing permethrin (a Type I pyrethroid insecticide), xylene, and surfactants are reported here. These patients were diagnosed and treated in the Chang Gung Memorial Hospital in Taiwan from January 1987 to June 1999. Ten patients ingested permethrin in error and 38 patients attempted suicide. Gastrointestinal tract signs and symptoms were most common (35/48; 73%), and included sore throat, mouth ulcerations, dysphagia, epigastric pain, and vomiting. Pulmonary abnormalities were documented in 29% (14/48) of patients. Aspiration pneumonitis occurred in eight patients, including onefatal case. Pulmonary edema was observed in two patients. Sixteen patients (33%) had central nervous system involvement including confusion (6/48; 13%), coma (10/48; 21%), and seizures (4/48; 8%). Cardiovascular symptoms in 3/48 (7%) patients were limited to arrhythmias and shock. Mild renal and hepatic dysfunction was found in 5/48 (10%) and 3/48 (6%) of patients, respectively. Leukocytosis occurred in 16 patients (33%) but was not associated with infection. Only one death occurred during this 12.5-year period. CONCLUSION: Poisoning caused by ingesting insecticides containing permethrin, xylene, and surfactant manifests primarily gastrointestinal tract symptoms and signs. The involvement of the central nervous system and lungs were less common, but clinically more significant. The relative contributions of the 20% permethrin, 70% xylene, and 10% surfactant to these toxic manifestations, however, is uncharacterized.