Measurement of xenon diffusing capacity in the rat lung by hyperpolarized 129Xe MRI and dynamic spectroscopy in a single breath-hold.

We used the dual capability of hyperpolarized 129Xe for spectroscopy and imaging to develop new measures of xenon diffusing capacity in the rat lung that (analogously to the diffusing capacity of carbon monoxide or DLCO) are calculated as a product of total lung volume and gas transfer rate constants divided by the pressure gradient. Under conditions of known constant pressure breath-hold, the volume is measured by hyperpolarized 129Xe MRI, and the transfer rate is measured by dynamic spectroscopy. The new quantities (xenon diffusing capacity in lung parenchyma (DLXeLP)), xenon diffusing capacity in RBCs (DLXeRBC), and total lung xenon diffusing capacity (DLXe)) were measured in six normal rats and six rats with lung inflammation induced by instillation of fungal spores of Stachybotrys chartarum. DLXeLP, DLXeRBC, and DLXe were 56 +/- 10 ml/min/mmHg, 64 +/- 35 ml/min/mmHg, and 29 +/- 9 ml/min/mmHg, respectively, for normal rats, and 27 +/- 9 ml/min/mmHg, 42 +/- 27 ml/min/mmHg, and 16 +/- 7 ml/min/mmHg, respectively, for diseased rats. Lung volumes and gas transfer times for LP (TtrLP) were 16 +/- 2 ml and 22 +/- 3 ms, respectively, for normal rats and 12 +/- 2 ml and 35 +/- 8 ms, respectively, for diseased rats. Xenon diffusing capacities may be useful for measuring changes in gas exchange associated with inflammation and other lung diseases.     

Pharmacokinetics of intravenous immunoglobulin (Gammagard) in bone marrow transplant patients.

The pharmacokinetics of an intravenous immunoglobulin (IVIG), Gammagard (Baxter Healthcare Corp., Glendale, CA), were measured in 31 cytomegalovirus (CMV) antibody negative bone marrow transplant (BMT) patients as part of a multicenter efficacy trial of 2 weekly dose regimens. Since all patients lacked antibody to CMV and received only screened CMV negative blood products, the half-life of the exogenous CMV antibody could be measured with an ELISA assay. The CMV antibody titer was related to the immunoglobulin concentration using a standard curve. Compared with the 22-day half-life in normal subjects, the half-life in BMT patients was approximately 6 days for either the 250 mg/kg or 500 mg/kg dose regimen. The half-life did not change over the subsequent 3 weekly doses. Peak concentrations were 3.5 +/- 1.4 and 2.6 +/- 0.7 mg/mL of IVIG in week 1 as well as 5.5 +/- 2.6 and 3.4 +/- 1.2 mg/mL in week 3 after the 250 mg/kg and 500 mg/kg, respectively. Total body clearance of IVIG was 0.61 and 0.46 mL/kg/hr for the 500 mg/kg and 250 mg/kg, respectively.     

Tyramine-Induced cardiac arrhythmias

Five out of 12 physically healthy patients with depression undergoing a tyramine pressor test developed cardiac arrhythmias. These arrhythmias occurred in drug-free patients in three out of 12 infusions following as little as 0.03 mg/kg of tyramine and after moclobemide, a reversible inhibitor of monoamine oxidase-A, in four out of 14 tyramine infusions with as little as 0.04 mg/kg of tyramine. The arrhythmias seen were independent of patient's age and occurred both before and after 30 mmHg elevations in systolic blood pressure. Electrocardiographic abnormalities and arrhythmias seen were a loss of p waves, sinus tachycardia, frequent atrial ectopic beats, atrial premature beats, Wenckebach phenomenon, junctional rhythm, ventricular ectopics, varying QRS configurations, and ventricular bigeminy. Tyramine, both oral and intravenous, caused similar reproducible changes in dogs, though not in rats, mice or guinea pigs. Practical implications are that tyramine pressor testing in humans should be performed cautiously and only with adequate cardiac monitoring and resuscitation facilities at hand. These findings suggest that a normal dietary component can induce serious cardiac arrhythmias, and that a low-tyramine diet may be of value for patients who are susceptible to cardiac arrhythmias.     

A highly variable STR at the D12S391 locus

A total of 103 fragments in the STR D12S391 locus were sequenced. 24 different alleles were found which can be grouped into 12 allelic classes based on the total number of repeats. The structure of this compund STR consists of blocks of (AGAT) and (AGAC) repeats with a consensus structure (AGAT)_8–l7 (AGAC)_6–10 (AGAT)_0–1. Whereas shorter alleles only have (AGAT) repeats, > 225 bp alleles are more complex, having two motifs (AGAT) and (AGAC). Population data showed that this to be a highly polymorphic STR with a heterozygosity of 0.9. This fact together with its simple structure make this STR very suitable for forensic and genetic purposes.     

Automated CTA quantification of internal carotid artery stenosis: a pilot trial.

PURPOSE: To evaluate the feasibility and accuracy of automated analysis software for use with multidetector computed tomographic angiography (CTA) in the exact grading of internal carotid artery stenosis. METHODS: A retrospective pilot trial was performed using CTA datasets from 87 stenotic carotid arteries in 46 consecutive patients (34 men; median age 73.5 years) with known cerebrovascular disease. Internal carotid artery (ICA) stenosis was graded according to NASCET criteria by 2 experienced vascular radiologists in consensus using axial source images as well as curved planar reformations and digital subtraction angiography (DSA). These results were then compared to those obtained from the automated CTA analysis software and the results of manually adapted automated CTA analysis. RESULTS: Measurements from automated CTA analysis as well as manually adapted automated CTA analysis correlated significantly to those of axial/reformatted CTA and DSA (r=0.53 and r=0.82, r=0.58 and 0.70, respectively, all p<0.05). Compared to axial/reformatted CTA measurements, automated CTA analysis had a median difference of -16%, while manually adapted automated CTA had a difference of -10%. Corresponding differences in a comparison with DSA were +4% and -2%, respectively. Circumferential calcification or kinking of the ICA origin did not significantly interfere with these differences (all p>0.05). Sensitivities for the detection of ICA stenosis >70% by manually adapted automated CTA analysis and automated measurement were 44.2% and 34.9%, respectively, versus axial/reformatted CTA. Compared with DSA as the gold standard, the sensitivities were 54.2% and 62.5%, respectively. Specificities for both methods and gold standards all exceeded 90%. CONCLUSION: Commercially available automated CTA analysis is a feasible tool, but sensitivities are still not sufficient for clinical application.     

Alcohol and Platelet Function

Epidemiological studies have shown that moderate consumption of alcoholic beverages is inversely related to the incidence of the complications of coronary artery disease. The protective effect of ethanol may be partially attributable to an inhibitory effect of ethanol on platelets. This article summarizes the experimental observations that ethanol inhibits platelet responses to specific physiological agonists. In alcoholics, various platelet defects have been observed, but these may be influenced by metabolic factors rather than the presence of ethanol alone. The acute effects of ethanol on platelet functions both in vivo and ex vivo will be reviewed. Evidence will be presented demonstrating that ethanol added acutely in vitro inhibits phospholipase A₂ in stimulated platelets. The interaction of ethanol with other signal transduction pathways will also be discussed.