American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Jun 1998
Randomized Controlled Trial Comparative Study Clinical TrialRifapentine and isoniazid in the continuation phase of treating pulmonary tuberculosis. Initial report.
A randomized comparison has been made of three times weekly rifampin plus isoniazid (HR3) with rifapentine plus isoniazid given once weekly (HRp1) or on 2 of 3 wk (HRp1.2/3) in the continuation phase of 6-mo regimens (each starting with an initial 2 mo of 4-drug therapy) for the treatment of pulmonary tuberculosis in 672 Chinese patients in Hong Kong. Because of poor bioavailability of the rifapentine used (produced in China), its dose size was increased from 600 mg initially to about 750 mg in the last third of patients to obtain serum concentrations similar to those with rifapentine of Western origin; all doses were given after a meal promoting absorption. After initial exclusions, an intent to treat analysis, done on the remaining 592 patients, showed 45 adverse treatment events in 7 of 190 HR3 patients, in 17 of 199 HRp1 patients, and in 21 of 203 HRp1.2/3 patients; of these, 42 were bacteriological or radiographic relapses after the end of treatment (HR3 versus HRp1, p = 0.04; HR3 versus HRp1.2/3, p = 0.01). ⋯ The high relapse rate in the HRp1 regimen suggests that the rifapentine dose should be increased. Similarity of relapse rates, 8.9% and 10.4%, after the HRp1 and HRp1.2/3 regimens, respectively, indicates that irregularity in taking rifapentine/isoniazid could be tolerated. The few adverse side effects in the continuation phase in the rifapentine regimens were less frequent than in the HR3 regimen.
-
Am. J. Respir. Crit. Care Med. · Jun 1998
Randomized Controlled Trial Clinical TrialThe effect of sustained-release morphine on breathlessness and quality of life in severe chronic obstructive pulmonary disease.
Morphine has been proposed as a treatment for breathlessness in patients with severe chronic obstructive pulmonary disease (COPD), but there is uncertainty as to whether or not it is effective. Orally administered sustained-release morphine was compared with placebo in a randomized, double-blind, crossover trial with two 6-wk treatment periods separated by a 2-wk washout period. The primary end point was quality of life measured using the Chronic Respiratory Disease Questionnaire (CRQ). ⋯ There were no differences between treatments in breathlessness scored on daily diary cards or on the Dyspnea subscale of the CRQ. Almost all the subjects experienced adverse effects related to morphine. Sustained-release morphine was not a useful treatment for breathlessness in these patients with severe COPD.
-
Am. J. Respir. Crit. Care Med. · Jun 1998
Mismatches at the HLA-DR and HLA-B loci are risk factors for acute rejection after lung transplantation.
Early high-grade acute rejections (pathologic grade A2 or A3) in recipients of lung allografts are a major risk factor for the subsequent development of obliterative bronchiolitis (OB). We analyzed the risk factors for high-grade acute rejections in 152 recipients of single (100) or bilateral (52) lung allografts transplanted at our institution between 1990 and 1996. Using Kaplan-Meier product limit estimate analysis, there was a 50% probability of grade A2 or A3 rejection by 1 yr after transplant. ⋯ In addition, recipients with one or more HLA-B locus matches had a lower cumulative rate of grade A2 or A3 rejections in the first year than did recipients with no matches at the HLA-B locus (0.59 versus 1.30). These results indicate that mismatches between donors and recipients at the HLA-DR and HLA-B loci are important risk factors for early high-grade rejections after lung transplantation. Immunosuppressive protocols that are more effective in preventing recipient T-cell activation by donor alloantigens are likely to reduce the rate of high-grade acute rejections in recipients of lung transplants, and may directly impact on the time to onset of OB.
-
Am. J. Respir. Crit. Care Med. · Jun 1998
PentaLyte decreases lung injury after aortic occlusion-reperfusion.
Lung injury often occurs after hepatoenteric ischemia, with xanthine oxidase (XO, an oxidant-generating enzyme), released from reperfusing liver and intestines, mediating a significant component of this injury. Since pentastarch administration decreases intestinal reperfusion injury, we determined whether resuscitation with PentaLyte (a pentastarch-containing solution) would decrease hepatoenteric reperfusion injury, xanthine oxidase release, and concomitant lung injury after aortic occlusion- reperfusion. Aortic occlusion was established in rabbits for 40 min, and was followed by 3 h of reperfusion, during which either PentaLyte or lactated Ringer's solution-based resuscitation was administered. ⋯ The release of XO after aortic occlusion-reperfusion was 4-fold smaller after PentaLyte administration than after resuscitation with lactated Ringer's solution (p < 0.05). Pulmonary injury, as defined by an increase in bronchoalveolar lavage fluid (BALF) protein content and lactate dehydrogenase (LDH) activity, was 4-fold less after PentaLyte administration following aortic occlusion-reperfusion than after administration of lactated Ringer's solution (p < 0.05). We conclude that remote pulmonary injury is significantly decreased by concomitant PentaLyte-mediated reduction of hepatoenteric reperfusion injury and XO release.
-
Am. J. Respir. Crit. Care Med. · Jun 1998
ReviewChemistry and structure--activity relationships of leukotriene receptor antagonists.
Several strategies have been employed by medicinal chemists in the design of potent and selective leukotriene receptor antagonists-leukotriene structural analogs, FPL 55712 analogs, and random screening of corporate compound banks. Lead compounds were optimized, often through the exchange of ideas with groups working on other chemical series of leukotriene antagonists. ⋯ Zafirlukast is based on a lead compound that incorporated structural components from both FPL 55712 and the leukotrienes. Therefore, each medicinal chemistry strategy that was originally employed has successfully identified clinically effective leukotriene receptor antagonists.