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.     

Influence of pain and urinary symptoms on quality of life in young men with chronic prostatitis-like symptoms

BACKGROUND: Our aims in the present study were to estimate the influences of pain and urinary symptoms on quality of life, and to determine which of these two variables has the most predictive power with respect to quality of life in young men with chronic prostatitis-like symptoms. METHODS: Chronic prostatitis-like symptoms were measured by the National Institutes of Health-Chronic Prostatitis Symptom Index. Of the 28,841 men aged 20 years who lived in the study community, 18,495 men (a response rate 64.1%) agreed to participate in the study. A total of 1057 men who complained of symptoms indicative of chronic prostatitis were included in the study. The influences of pain and urinary symptoms on quality of life were determined using logistic regression analysis. The receiver operating characteristic (ROC) curve was used to estimate the predictive ability of each of these variables with respect to quality of life. RESULTS: Results from multivariate analysis showed that both pain and urinary symptoms were associated with an increased likelihood of impaired quality of life, although pain contributed more to a reduced quality of life than urinary symptoms. Relative to men who experienced mild pain, men who experienced moderate pain had a 3.9-fold risk of poor quality of life (odds ratio [OR], 3.87; 95% confidence interval [CI], 2.86-5.23; P < 0.001) and those who experienced severe pain had a 15.7-fold risk of reduced quality of life (OR, 15.68; 95% CI, 6.59-37.35; P < 0.001). Moderate urinary symptoms were associated with a 1.4-fold risk of bother (OR, 1.41; 95% CI, 1.01-1.99; P < 0.001) and severe urinary symptoms were associated with 2.4-fold risk (OR, 2.39; 95% CI, 1.37-4.12; P < 0.001), relative to mild urinary symptoms. Comparison of the effects of pain and urinary symptoms showed that pain severity had the most predictive power for bother, quality of life, and quality-of-life impact. The areas under the ROC curves for bother, quality of life, and quality-of-life impact were 71.3%, 69.3% and 72.5%, respectively. CONCLUSION: Urinary symptoms and pain might be associated with an increased likelihood of impaired quality of life in young men with chronic prostatitis-like symptoms. In addition, our findings suggest that pain severity is the most influential variable for determining quality of life in this population.     

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.