After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial ...(N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P < .001) and nebivolol (both, P < .001), but not with valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further.
BACKGROUND
The implementation of new treatment protocols for locally advanced breast cancer is currently limited by inaccurate evaluation of response to neoadjuvant chemotherapy. A recently developed ...dedicated breast magnetic resonance imaging (MRI) method (RODEO MRI) was evaluated as a tool for determining tumor response and extent of residual disease after neoadjuvant chemotherapy.
METHODS
Thirty‐nine patients with Stage II, III, or IV breast carcinoma were prospectively evaluated prior to and following neoadjuvant chemotherapy by MRI, physical examination, and mammography. Assessment of response determined by the three methods was compared. In addition, detailed pathologic correlation of residual disease was determined by serial sectioning of 31 mastectomy specimens from 30 patients. Nine patients had breast conservation, and were included in the response evaluation only. Estimates of tumor response were made by both surgical and medical oncologists. Independent interpretations of MRI studies without knowledge of clinical response were made by three radiologists.
RESULTS
The surgical oncologists assessed complete response (CR), partial response (PR), and no response (NR) in 11, 22, and 7 cases, respectively. The medical oncologists assessed CR, PR, and NR in 12, 21, and 7 cases, respectively. The surgical and medical oncologists' clinical assessment of response agreed with the results of MRI in 52% and 55% of cases, respectively, and with each other in 30 of 40 cases (75%). Mammography correlated with MRI response in only 52% of cases. However, MRI accurately predicted the pathologic determination of residual disease in 30 of 31 cases (97%). There was no disagreement in the assessments of residual disease or response among the three radiologists.
CONCLUSIONS
RODEO breast MRI accurately estimates residual disease after induction chemotherapy. It assesses response to neoadjuvant chemotherapy better than traditional methods of physical examination or mammography. The information obtained from this MRI technique may be used as an objective tool during clinical trials, and to select patients better for breast conservation after neoadjuvant chemotherapy for locally advanced disease. Cancer 1996;78:91‐100.
OBJECTIVETo determine whether the administration of lisofylline (1-5R-hydroxyhexyl-3,7-dimethylxanthine) would decrease mortality in patients with acute lung injury (ALI) or acute respiratory ...distress syndrome (ARDS).
DESIGNA prospective, randomized, double-blind, placebo-controlled, multicenter study.
SETTINGIntensive care units at 21 hospitals at the ten centers constituting the ARDS Clinical Trials Network.
PATIENTSA total of 235 patients who met eligibility criteria were enrolled in the study (116 into the lisofylline group, 119 into the placebo group).
INTERVENTIONSPatients were randomized to receive either lisofylline or placebo. The dose of lisofylline was 3 mg/kg with a maximum dose of 300 mg intravenously every 6 hrs. The intravenous solution of study drug was administered over 10 mins every 6 hrs. Dosing was continued for 20 days or until the patient achieved 48 hrs of unassisted breathing.
MEASUREMENTS AND MAIN RESULTSThe trial was stopped by the Data Safety Monitoring Board for futility at the first scheduled interim analysis. The patient groups had similar characteristics at enrollment. No significant safety concerns were associated with lisofylline therapy. There was no significant difference between groups in the number of patients who had died at 28 days (31.9% lisofylline vs. 24.7% placebo, p = .215). There was no significant difference between the lisofylline and placebo groups in terms of resolution of organ failures, ventilator-free days, infection-related deaths, or development of serious infection during the 28-day study period. The median number of organ failure–free days for the five nonpulmonary organ failures examined (cardiovascular, central nervous system, coagulation, hepatic, and renal) was not different between the lisofylline and placebo groups. Although lisofylline has been reported to decrease circulating free fatty acid levels, we did not find any such treatment effect compared with placebo.
CONCLUSIONSIn this study, there was no evidence that lisofylline had beneficial effects in the treatment of established ALI/ARDS.
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