Double-blind, randomized trial of an anti-CD18 antibody in conjunction with recombinant tissue plasminogen activator for acute myocardial infarction: limitation of myocardial infarction following thrombolysis in acute myocardial infarction (LIMIT AMI) study.

BACKGROUND: Inhibition of leukocyte adhesion can reduce myocardial infarct size in animals. This study was designed to define the safety and efficacy of a recombinant, humanized, monoclonal antibody to the CD18 subunit of the beta2 integrin adhesion receptors (rhuMAb CD18), in reducing infarct size in patients treated with a thrombolytic agent. METHODS AND RESULTS: The Limitation of Myocardial Infarction following Thrombolysis in Acute Myocardial Infarction Study (LIMIT AMI) was a randomized, double-blind, placebo-controlled, multicenter study conducted in 60 centers in the United States and Canada. A total of 394 subjects who presented within 12 hours of symptom onset with ECG findings (ST-segment elevation) consistent with AMI were treated with recombinant tissue plasminogen activator and were also given an intravenous bolus of 0.5 or 2.0 mg/kg rhuMAb CD18 or placebo. Coronary angiography was performed at 90 minutes, 12-lead ECGs were obtained at baseline, 90, and 180 minutes, and resting sestamibi scans were performed at >/=120 hours. Adjunctive angioplasty and use of glycoprotein IIb/IIIa antiplatelet agents at the time of angiography were discretionary. There were no treatment effects on coronary blood flow, infarct size, or the rate of ECG ST-segment elevation resolution, despite the expected induction of peripheral leukocytosis. A slight trend toward an increase in bacterial infections was observed with rhuMAb CD18 (P=0.33). CONCLUSIONS: RhuMAb CD18 was well tolerated but not effective in modifying cardiac end points.

Preexercise meal composition alters plasma large neutral amino acid responses during exercise and recovery.

This study was designed to determine the effect of ingesting three preexercise meals on energy metabolism during exercise and recovery and to relate metabolic perturbations to subjective and objective measurements associated with central fatigue. Twelve subjects consumed isoenergetic meals consisting of oat, wheat, or corn cereals 90 min before cycling. A fasting trial served as the control. Blood samples and cognitive function, perceived hunger, and sleepiness measurements were obtained before and after feeding and during recovery when self-selected food intake was also measured. After meal ingestion, plasma insulin was lower for oat than for wheat or corn whereas the ratio of tryptophan to large neutral amino acids (LNAAs) for corn was less than for all others. During exercise, the tryptophan-LNAA ratio increased from preexercise values for the fasting and wheat trials, but exercise performance was unaffected. During recovery, tryptophan:LNAA increased from postexercise values in fasting trials. Also, hunger and fatigue ratings were greater in fasted subjects, but self-selected food intake measured at the end of the recovery period was not different among groups. We conclude that preexercise meal consumption affected tryptophan:LNAA before, during, and after exercise, but these changes were not sufficient to alter physical and cognitive performance.

Oat, wheat or corn cereal ingestion before exercise alters metabolism in humans.

This study was designed to determine metabolic and physical performance responses to ingestion of pre-exercise meals with different macronutrient and fiber profiles. Twelve physically active subjects (6 males and 6 females) were used to investigate the metabolic and physical performance consequences of consuming pre-exercise meals consisting of oat, corn, or wheat cereals. A fasting trial served as the control, and all subjects received each treatment in a Latin-square design. Blood samples were drawn before and 85 min after meal ingestion, during 90 min of cycling exercise (60% VO2peak), after a 6.4 km performance ride, and during 60 min of recovery. Expired air samples were collected to determine nutrient utilization. Resting carbohydrate oxidation rates and plasma insulin concentrations after oat ingestion were less than after wheat, and corn and wheat ingestion, respectively (P < 0.05). During exercise, the change in plasma glucose from pre-exercise was greater after consuming wheat and corn compared with oat (P < 0.05), and it was inversely related to pre-exercise plasma insulin concentration (r = -0.55, P = 0.0001). Plasma free fatty acid concentrations were inversely related to plasma lactate concentrations (r = -0.58, P = 0.0001). Free fatty acid concentrations and fat oxidation were greater in fasting trials than all others, but performance ride times did not differ among treatments. Plasma branched-chain amino acid concentrations resembled their respective meal profiles throughout exercise, the performance ride, and recovery. These results indicate that pre-exercise meal composition can influence glucose homeostasis during early exercise and plasma branched-chain amino acid concentrations over a substantial range of metabolic demands.

Duplication of the cervical esophagus. An unrecognized cause of respiratory distress in infants.

Infants with respiratory distress demand prompt action and thorough evaluation for possible causes. An urgent but infrequent source of upper airway obstruction is a duplication cyst of the cervical esophagus. Standard references omit this diagnosis in the consideration of both respiratory distress and neck masses in infants. Two patients were admitted with respiratory distress and delayed recognition of a neck mass. Contrast and sonographic studies revealed a cystic mass displacing the trachea in each case. Careful excision promptly relieved symptoms, and histopathologic evaluation confirmed the diagnosis. Duplication of the esophagus can compromise the normal airway, thereby presenting with respiratory difficulty prior to recognition of a neck mass. X-ray studies demonstrating displacement of the trachea or esophagus due to a soft-tissue mass and documentation of a cyst by ultrasound will aid in establishing the diagnosis. Surgical principles include aspiration and excision of the mucosal lining, with preservation of the muscular coat and mucosal septum. Duplication of the cervical esophagus should be considered in the differential diagnosis of both respiratory distress and an enlarging neck mass in infants.

Nitrate reductase activity and protein concentration of two populas clones.

Nitrate reductase activity and protein percentage of various tree parts of two Populus clones were determined in relation to nitrate ion activity. Nitrogen was supplied as NH(4)NO(3) in a nutriculture system. Wisconsin-5 had significantly greater nitrate reductase activity than Tristis No. 1. Protein percentages of leaf plastochron index 10 leaves (tenth leaf below first leaf lamina exceeding 20 mm in length), bottom leaves, and roots in relation to nitrate ion activity were not appreciably different between clones. The nitrate reductase activity and protein percentage of Tristis No. 1 apex started to level off at the same nitrate ion activity, about 0.09 mm. In Wisconsin-5 apex protein percentage continued to increase at nitrate ion activities where nitrate reductase activity decreases sharply, suggesting that protein nitrogen was being supplied by ammonium ion. The difference in nitrate reductase activity between clones was probably due to genetically determined ability to synthesize nitrate reductase in response to nitrate ion. The expression of nitrate reductase activity was not an index of nitrogen assimilation ability but may be a useful index of growth potential when nitrate ion does not limit nitrate reductase synthesis.