Neutron-activation analysis: a novel method for the assay of iohexol

Accurate measurement of glomerular filtration rate (GFR) is of great importance in both research and clinical medicine. Available methods require radiation exposure or are technically difficult, thereby limiting their utility. Recent work has validated plasma clearance of nonradioactive contrast agents (iohexol and iothalamate) for the measurement of GFR. However, their clinical utility has been restricted by the difficulties associated with the detection of contrast agents in serum. In this investigation, we evaluate the sensitivity, accuracy and precision of neutron activation analysis (NAA) to measure serum iohexol at concentrations necessary for estimating GFR. We subjected aliquots of serum containing 0 to 6470 microg/mL iohexol to neutron activation by placing them in a neutron beam for 1 minute. The activation process resulted in the elevation of iohexol's naturally abundant iodine 127 to iodine 128. The spontaneous decay of (128)I to xenon 128 (proportional to the amount of total iodine in the sample) was calculated by means of spectrographic analysis. The correlation between the predetermined elemental mass of iodine in the sample and that measured on NAA was then determined. A similar analysis was performed to establish the intra- and interday accuracy and precision, with multiple measurements taken over a single day and over the course of a month. We noted excellent correlation between iodine measured on NAA and the known elemental mass (r(2) =.99). Measurements were highly accurate (mean accuracy 2.4% +/- 1.8%), with excellent intra- and interday reliability (mean coefficient of variation 4.1% +/- 1.6%). NAA is a feasible and reproducible method of detecting iohexol for the purpose of measuring GFR.     

Minimal flow sevoflurane and isoflurane anaesthesia and impact on renal function

BACKGROUND AND AIM: Compound A generation and accumulation in sevoflurane anaesthesia is dependent on fresh gas flow. We investigated the extent of generation of compound A. METHODS: After Institutional Review Board approval and informed consent, patients with normal renal function were randomized to receive either sevoflurane (n = 33) or isoflurane (n = 43) minimal flow anaesthesia (0.5 L min-1) for at least 2 h under standardized conditions. Compound A concentrations were quantified and blood and urine samples were taken to assess renal involvement. Both groups were comparable. RESULTS: No significant differences concerning blood chemistry and urine measurements were found. The maximum mean compound A concentration was observed 90 min after flow reduction being 40 +/- 9 p.p.m. at a corresponding mean sevoflurane concentration of 2.1 +/- 0.5 vol%. Mean inspiratory compound A exposure was 102 +/- 33 p.p.m h-1. CONCLUSION: Compound A concentrations using 0.5 L min-1 fresh gas flow and a heated absorber were higher than previously published values using an inflow of 1 L min-1. Compound A exposure was similar to other clinical studies which did not show changes in renal and hepatic function.     

2-(fluorine-18)fluoro-2-deoxy-D-glucose positron emission tomography in the detection and staging of malignant lymphoma. A bicenter trial

BACKGROUND: The authors undertook a prospective evaluation of the clinical value of 2-fluoro [18-]-2-deoxyglucose positron emission tomography (FDG-PET) in the detection and staging of malignant lymphoma compared with computed tomography (CT) and bone marrow biopsy (BMB). METHODS: Fifty-two consecutive patients with untreated malignant lymphoma were evaluated prospectively in a bicenter study. FDG-PET, CT, and BMB were performed for investigating lymph node/extranodal manifestations and bone marrow infiltration. Thirty-three percnt of the discrepant results were verified by biopsy, magnetic resonance imaging, or clinical follow-up (range, 4-24 month). RESULTS: Altogether, 1297 anatomic regions (lymph nodes, organs, and bone marrow) were evaluated. FDG-PET and CT scans were compared by receiver operating characteristic (ROC) curve analysis. The area under the ROC curve were as follows: lymph nodes, 0.996 (PET) and 0.916 (CT); extranodal, 0.999 (PET) and 0.916 (CT); supradiaphragmatic, 0.996 (PET) and 0.905 (CT); and infradiaphragmatic, 0.999 (PET) and 0.952 (CT). In these analyses, FDG-PET was significantly superior to CT (P < 0.05), except in infradiaphragmatic regions, in which the two methods produced equivalent results. In detecting bone marrow infiltration, FDG-PET was superior to CT and was equivalent to BMB. In 4 of 52 patients (8%), FDG-PET led to an upstaging and a change of therapy. CONCLUSIONS: Noninvasive FDG-PET is very accurate in the staging of malignant lymphoma. Compared with standard staging modalities (CT and BMB), PET was significantly superior and led to changes in the therapy regimen for 8% of patients.     

Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer

BACKGROUND: Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies. Several recent reports have documented over expression of VEGF in papillary thyroid cancer. We hypothesized that increased expression of VEGF would be associated with either an increased risk of recurrence or a decreased recurrence-free survival in papillary thyroid cancer. METHODS: Immunohistochemistry was used to detect VEGF expression in archival paraffin-embedded surgical thyroid specimens from 96 subjects with papillary thyroid cancer. RESULTS: VEGF expression was detected in 98% (94/96) of the samples, predominantly of slight-to-moderate intensity in the majority of malignant cells. However, the specific finding of a diffuse pattern of intense immunostaining for VEGF was detected significantly more often than less intense, patchy immunostaining patterns in subjects with distant metastasis at diagnosis (63% versus 15%, P =.005), local recurrence (58% versus 13%, P =.001), and distant recurrence (83% versus 14%, P =.001). Furthermore, this specific pattern of diffuse, intense VEGF expression was associated with a significantly shorter recurrence-free survival than other staining patterns (P =.007). CONCLUSIONS: These data demonstrate that the immunohistochemical pattern of VEGF staining in the initial surgical specimen is strongly associated with the incidence of local and distant metastasis in papillary thyroid cancer.     

The relevance of plasminogen activator inhibitor 1 (PAI-1) as a marker for the diagnosis of hepatic veno-occlusive disease in patients after bone marrow transplantation

Hepatic veno-occlusive disease (VOD) is the third most important fatal complication in allogeneic bone marrow transplantation (BMT), the second most significant one in the autologous setting and the most severe of all the regimen related toxicities. A growing number of VOD cases has to be expected due to the increasing number of high dose chemotherapies given with consecutive stem cell transplantation in patients with solid tumors. Confirmation of the diagnosis of VOD by biopsy is associated with a high risk of severe bleeding complications and, unfortunately, until now reliable laboratory markers have not as yet been established. Recently, plasminogen activator inhibitor 1 (PAI-1), the main inhibitor of the fibrinolytic system, has been found to be significantly elevated in VOD patients probably reflecting hypofibrinolysis in these patients. Furthermore, PAI-1 was able to distinguish between patients with VOD and those with hyperbilirubinemia after BMT caused by graft-versus-host-disease (GVHD) or toxic effects, in which cases the PAI-1 levels were mostly within the normal range. In this overview we summarize the data strongly indicating that PAI-1 is a useful marker for the diagnosis of VOD and helps in the differential diagnosis of hyperbilirubinemia after BMT.     

Catecholamines and cyclic AMP in allergic and exercise induced asthma of childhood

In order to provoke exercise induced asthma (EIA) a test which involved running for 7 min was performed with 21 asthmatic children. Eleven children not only developed a highly significant increase in airway resistance (R_t), but showed also a 4-fold increase in plasma noradrenaline (NA) levels. In 10 children who did not develop EIA only a 1.5-fold increase of NA could be observed. Following exercise cyclic AMP showed an identical increase in both groups studied, whereas adrenaline levels remained uninfluenced. Tests carried out after administration of phentolamine by inhalation showed a significant inhibition of post-exercise bronchoconstriction. It is concluded that EIA originates from a-receptor stimulation which is mediated by excessive noradrenaline release. However, since disodium cromoglycate—which does not act via adrenergic mechanisms—also protected against EIA, other factors should be involved. In 5 children with allergic asthma, asthmatic attacks were accompanied by a significant decrease in cAMP, whereas noradrenaline levels remained uninfluenced. Thus, evidence appears that both types of asthma result from different autonomic dysfunctions.Part of this work was supported by a grant from the Ministerium für Wissenschaft und Forschung, NRW     

A common variant of the angiotensinogen gene and the risk of coronary artery disease in a German population

The thymidine to cytosine transition at position 704 in exon 2 of the angiotensinogen gene leads to the amino acid substitution of threonine for methionine (T235 variant) and is responsible for elevated plasma levels of angiotensinogen. To examine the influence of T235 on the risk of coronary artery disease (CAD) we genotyped 184 CAD patients, 77 controls in whom CAD was excluded angiographically, and 155 healthy controls without signs of CAD by polymerase chain amplification and restriction enzyme digestion. Allele frequencies for A (wildtype) and a (mutant allele) in the total study population were 0.538 and 0.462, 0.536 and 0.464 in the healthy controls, and 0.481 and 0.519 in patients with excluded CAD, respectively. The allele frequencies and the genotype distribution in these groups did not show a significant difference. In conclusion, we did not observe an association between the T235 variant of the angiotensinogen gene and the risk of CAD.