The clinical value of ferric ammonium citrate: a positive oral contrast agent for T1-weighted MR imaging of the upper abdomen.

This study was undertaken to determine whether ferric ammonium citrate (FAC), a positive magnetic resonance (MR) contrast agent, is of clinical value in demonstrating or excluding pathology of the upper gastrointestinal tract. A retrospective review was performed of pre- and post-FAC studies of MR examinations in 203 patients from phase II and III clinical trials in whom final diagnoses had been established based on the results of biopsy, surgery, or independent imaging procedures. Two independent reviewers made randomized and blinded assessments of the stomach, duodenum, and pancreas. FAC significantly increased the certainty of diagnosis for normal studies of the stomach and duodenum for both readers (P < 0.001) and for abnormal studies of the stomach for one reader (P = 0.004). FAC also significantly increased the certainty of diagnosis for normal pancreas for one reader (P < 0.001). FAC significantly (P < 0.001) increased accuracy and specificity for diagnoses involving the stomach and duodenum for both readers and for one reader for the pancreas. There was significant improvement in sensitivity for gastric diagnoses (P = 0.013) for one reader but not for the duodenum or pancreas. We conclude that FAC is helpful in demonstrating and excluding upper gastrointestinal pathology on MR.

A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group.

We report the results of the Ticlopidine Aspirin Stroke Study, a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride (500 mg daily) with those of aspirin (1300 mg daily) on the risk of stroke or death. The medications were randomly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia. Follow-up lasted for two to six years. The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin--a 12 percent risk reduction (95 percent confidence interval, -2 to 26 percent) with ticlopidine (P = 0.048 for cumulative Kaplan-Meier estimates). The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin--a 21 percent risk reduction (95 percent confidence interval, 4 to 38 percent) with ticlopidine (P = 0.024 for cumulative Kaplan-Meier estimates). Ticlopidine was more effective than aspirin in both sexes. The adverse effects of aspirin included diarrhea (10 percent), rash (5.5 percent), peptic ulceration (3 percent), gastritis (2 percent), and gastrointestinal bleeding (1 percent). With ticlopidine, diarrhea (20 percent), skin rash (14 percent), and severe but reversible neutropenia (less than 1 percent) were noted. The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin (P less than 0.01). The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups. We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population, although the risks of side effects were greater.

Intravenous infusion of prostacyclin sodium in man: clinical effects and influence on platelet adenosine diphosphate sensitivity and adenosine 3':5'-cyclic monophosphate levels.

Clinical tolerance, inhibition of platelet aggregation and intracellular platelet adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were evaluated in normal volunteers given i.v. infusions of prostacyclin sodium at rates up to 15 ng/kg/min. Short-term infusions (30 and 60 minutes) were tolerated at rates up to 10.0 ng/kg/min; higher rates produced headaches, anxiety, nausea and vomiting. Six-hour and 24-hour infusions were tolerated at rates up to only 4.0 ng/kg/min. Twenty-four hour infusions at 4 ng/kg/min produced a consistent 4-7 microM shift to the right in the platelet ADP dose-response curve; this platelet inhibitory activity did not diminish during the infusion. Prostacyclin sodium infusion elevated intracellular cyclic AMP levels, the increases corresponding to the onset of measurable inhibition of ADP-induced aggregation, although the magnitude of the increase did not necessarily reflect the degree of inhibition. Increased template bleeding times were seen with a greater than 10-microM shift in the ADP dose-response curve. We conclude that although prostacyclin sodium has a narrow safety margin, the drug does produce platelet inhibition at infusion rates generally tolerated by healthy volunteers.