The validation of a bioanalytical method for the determination of clopidogrel in human plasma.

A fast, sensitive and specific LC-MS/MS bioanalytical method for the determination of unchanged clopidogrel in human plasma has been developed and validated over the range of 10-12,000 pg mL(-1) (r2 0.9993) by the Contract Research group at HFL. Samples (0.3 mL) were buffered (pH 6.8), extracted using diethyl ether and 10 microL of the sample extract was injected onto the LC-MS/MS system. Analysis was performed using a C8 column (temperature controlled to 50 degrees C) by gradient elution at a flow rate of 0.9 mL min(-1) over a 3 min run time. Retention times of 1.61 and 1.59 min were observed for clopidogrel and 2H3-clopidogrel (I.S.), respectively. Detection was achieved using a Sciex API 4000, triple quadrupole mass spectrometer, in positive TurboIonspray (electrospray) ionisation mode. Ion transitions were monitored using MRM (multiple reaction monitoring) for clopidogrel (m/z 322-212) and for 2H3-clopidogrel (m/z 327-217). This validated method was used to support a pharmacokinetic study in healthy volunteers.

Emergency percutaneous transluminal coronary angioplasty in acute myocardial infarction: a 3 year experience.

In 151 patients experiencing acute myocardial infarction, emergency coronary angioplasty was performed as primary therapy. Overall, angioplasty was successful in 132 patients (87%); it was successful in 91 (85%) of 107 patients with a totally occluded infarct-related artery and in 41 (93%) of 44 patients with a subtotally occluded infarct-related artery. After successful angioplasty, mean residual stenosis was 29% (range 0 to 70). Eighteen patients were in cardiogenic shock (12%) including four patients receiving cardiopulmonary resuscitation during the angioplasty procedure. Hospital mortality was 9%, with 7 of 13 deaths occurring in patients presenting with cardiogenic shock or intractable ventricular arrhythmia. Hospital mortality was 5% in patients with successful angioplasty versus 37% in those with unsuccessful angioplasty (p less than 0.001). In the immediate period after angioplasty, left ventricular ejection fraction was significantly lower for patients with lesions of the left anterior descending artery (34 +/- 10%) than for patients with lesions of the left circumflex or right coronary artery (43 +/- 11%). In patients with successful angioplasty, significant improvement in left ventricular ejection fraction averaged 13 +/- 12% (p less than 0.001) for those with lesions of the left anterior descending artery and 10 +/- 12% (p less than 0.001) for those with lesions of the left circumflex or right coronary artery. Repeat coronary angiography was performed in 85 (70%) of 121 patients who had successful angioplasty and survived hospitalization without requiring bypass surgery; restenosis was found in 26 (31%), and angioplasty was repeated in 22 patients, successfully in each.(ABSTRACT TRUNCATED AT 250 WORDS)

Are corresponding points fixed?

Several investigators have claimed that the retinal coordinates of corresponding points shift with vergence eye movements. Two kinds of shifts have been reported. First, global shifts that increase with retinal eccentricity; such shifts would cause a flattening of the horopter at all viewing distances and would facilitate fusion of flat surfaces. Second, local shifts that are centered on the fovea; such shifts would cause a dimple in the horopter near fixation and would facilitate fusion of points fixated at extreme viewing distances. Nearly all of the empirical evidence supporting shifts of corresponding points comes from horopter measurements and from comparisons of subjective and objective fixation disparity. In both cases, the experimenter must infer the retinal coordinates of corresponding points from external measurements. We describe four factors that could affect this inference: (1) changes in the projection from object to image points that accompany eye rotation and accommodation, (2) fixation errors during the experimental measurements, (3) non-uniform retinal stretching, and (4) changes in the perceived direction of a monocular point when presented adjacent to a binocular point. We conducted two experiments that eliminated or compensated for these potential errors. In the first experiment, observers aligned dichoptic test lines using an apparatus and procedure that eliminated all but the third error. In the second experiment, observers judged the alignment of dichoptic afterimages, and this technique eliminates all the errors. The results from both experiments show that the retinal coordinates of corresponding points do not change with vergence eye movements. We conclude that corresponding points are in fixed retinal positions for observers with normal retinal correspondence.

Determination of 1,4-benzodiazepines and their metabolites by capillary electrophoresis and high-performance liquid chromatography using ultraviolet and electrospray ionisation mass spectrometry.

A study is presented for the separation and determination of fifteen 1,4-benzodiazepine drugs and metabolites by capillary electrophoresis (CE) compared with high-performance liquid chromatography (HPLC). A comparison is made between the CE determination of the compounds by conventional UV detection and LC determination with electrospray ionisation (ESI) ion-trap mass spectrometry. CE is shown to provide superior separation to HPLC but the MS-MS capability of the ion-trap allows for the specific detection and determination of four of the compounds, diazepam, N'-desmethyldiazepam, oxazepam and temazepam in the hair of a patient under clinical treatment with diazepam and temazepam. Selected mixtures of drugs and metabolites are determined by CE and LC and the determination of diazepam and its metabolites by CE-UV-ESI-MS-MS is also presented.

The effect of the physical characteristics of cues and targets on facilitation and inhibition.

The present experiment was conducted in order to examine the role of cue-target discriminability on early occurring attentional cuing effects and late occurring inhibition of return (IOR). The experiment used a single target stimulus in conjunction with three different cue stimuli. The cues were the same as the target, different in color, shape, and luminance to the target, or did not spatially overlap with the target. At shorter stimulus onset asynchronies (SOAs; 100 and 200 msec), attentional cuing effects were only found with the nonoverlapping cues. However, at longer SOAs (400 and 800 msec), approximately equal IOR effects were found with all three types of cues. The results indicated that the physical characteristics of the cues and targets affected the pattern of reaction times at the shorter SOAs but not at the longer SOAs. The conclusion is that the biphasic pattern of early facilitation and late inhibition following a peripheral cue should not be considered the definitive signature of the peripheral cuing paradigm.

Medical radiologic technologist review: effects on a population-based breast cancer screening program.

PURPOSE: To evaluate the effects of medical radiologic technologist review of mammograms in a population-based breast cancer screening program. MATERIALS AND METHODS: A technologist review pilot project was incorporated into the Regina, Saskatchewan, Canada, reading center. Technologists received special training in mammographic interpretation. They reviewed all 27,863 mammograms obtained at the center from July 1995 to September 1996 that were reviewed by a radiologist and selected cases for second blind reading by another radiologist. When the two radiologists' readings were in agreement, the report was sent. When the readings differed, a third opinion was obtained from the program's consulting radiologist. Changes in the number of mammograms interpreted as abnormal and the number of cancers detected were assessed. RESULTS: The technologist review was responsible for the detection of nine cancers missed at the first radiologist's interpretation. Technologists were very discriminating; only 391 cases (1.4%) were sent for double reading. The positive predictive value of screening did not change significantly (7.5% without review, 8.1% with review; P > .20). CONCLUSION: A substantial number of cancers were found with the technologist review. The number of mammograms interpreted as abnormal was reduced slightly. The technologist review proved to be a cost-effective alternative to double reading by two radiologists.

Combining sensory information: mandatory fusion within, but not between, senses.

Humans use multiple sources of sensory information to estimate environmental properties. For example, the eyes and hands both provide relevant information about an object's shape. The eyes estimate shape using binocular disparity, perspective projection, etc. The hands supply haptic shape information by means of tactile and proprioceptive cues. Combining information across cues can improve estimation of object properties but may come at a cost: loss of single-cue information. We report that single-cue information is indeed lost when cues from within the same sensory modality (disparity and texture gradients in vision) are combined, but not when different modalities (vision and haptics) are combined.