Methylmalonic aciduria in pregnancy: a case report

Methylmalonic aciduria is a rare metabolic disorder of amino acid metabolism that is characterized by accumulation of large amounts of methylmalonic acid in the blood and urine. To our knowledge this is the first case report of a patient with methylmalonic aciduria who carried a pregnancy to term; the outcome was favorable despite high levels of methylmalonic acid in the serum and urine.     

The effects of age and gender on the single dose pharmacokinetics of avitriptan administered to healthy volunteers

The effects of age and gender on the single dose pharmacokinetics of avitriptan and its three metabolites were assessed in 15 young men, 15 young women, 15 elderly men and 15 elderly women. Avitriptan was administered as a 150-mg capsule after a 10-hour fast and serial plasma and urine samples were collected up to 36 hours after the dose. Plasma samples were analyzed for avitriptan and its metabolites, N-desmethyl avitriptan (ND048), O-desmethyl avitriptan (OD048), and methoxypyrimidinyl piperazine (MPP). Urine samples were analyzed for only avitriptan and MPP. Avitriptan was well tolerated in all four groups. The drug was rapidly absorbed with a median time to maximum plasma concentration (tmax) between 0.5 and 1.5 hours. No significant gender-related differences were found in the maximum plasma concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUC0-infinity) of avitriptan. Renal clearance of avitriptan was significantly smaller in young women compared with young men, but this is clinically not relevant because only 2% to 3% of the total dose is excreted unchanged. Compared with the young volunteers, mean Cmax was approximately 50% higher in the elderly but there was no difference in the AUC0-infinity between the 2 age groups. Plasma concentrations of ND048, OD048, and MPP were each 50 to 100 fold lower than those of avitriptan. Hence some age- and gender-related differences found in the pharmacokinetics of avitriptan metabolites are probably not relevant in the assessment of overall safety and efficacy of avitriptan. Based on the pharmacokinetics and tolerability, no age or gender-related dose adjustment is necessary for avitriptan.     

Enhanced detection of proximal right coronary artery stenosis with the additional analysis of right ventricular thallium-201 uptake in stress scintigrams

The value of right ventricular thallium-201 analysis in detecting proximal right coronary artery stenosis in exercise myocardial scintigraphy was analyzed in 52 patients, 27 with and 25 without proximal right coronary artery stenosis. For the detection of proximal right coronary artery stenosis, the sensitivity and specificity of thallium scintigraphic analysis were 59 and 88% for a right ventricular abnormality, 67 and 68% for a left ventricular inferior wall abnormality, and 93 and 56% for an abnormality of either. When both right and left ventricular thallium images were abnormal, all 9 patients had proximal right coronary artery stenoses, and when both were normal, 26 of 28 patients had a normal proximal right coronary artery. The sensitivity and specificity of blood pool scintigraphic variables during exercise (right ventricular ejection fraction and left ventricular inferior wall motion) were not significantly different for detection of proximal right coronary artery stenosis. Thus, the additional analysis of the right ventricle on thallium-201 stress scintigrams can improve the detection of proximal right coronary artery stenosis. When both right ventricular and left ventricular thallium scintigrams are abnormal (or normal), the ability to predict the presence (or absence) of proximal right coronary artery stenosis is very high.     

The decerebrate human: associative learning

Phasic changes in cardiac reactivity to innocuous stimuli, presented in a sensory disparity paradigm, were used to evaluate habituation and learning processes in five decerebrate subjects. Three subjects showed systematic changes over trials in the pattern of cardiac response to simple auditory or visual stimuli, indicative of habituation. In addition, tests for associative learning were given after repeated presentations of two paired stimuli. The appearance of a marked cardiac orienting response, to the unpredictable omission of the second stimulus, documented the development of a conditioned association in these same three subjects. One additional subject failed to show a consistent pattern of response to the stimuli, and another demonstrated a consistent response which was not subject to habituation. Overall, these findings support the view that learning processes are not solely the product of the cerebral hemispheres, but reflect general integrative features of the human neuraxis.