Sodium MRI of the human kidney at 3 Tesla.

The sodium concentration gradient in the kidney (from the cortex to the medulla) serves to regulate fluid homeostasis and is tightly coupled to renal function. It was previously shown that renal function and pathophysiology can be characterized in rat kidneys by measuring the sodium gradient with (23)Na MRI. This study demonstrates for the first time the ability of (23)Na MRI to map the distribution of sodium in the human kidney and to quantify the corticomedullary sodium gradient. The study was performed on a 3T Signa LX scanner (GE) using an in-house-built quadrature surface coil. (23)Na images of volunteers were acquired using a 3D coronal gradient-echo sequence at a spatial resolution of 0.3 x 0.3 x 1.5 cm(3) in a 25-min scan time. The signal intensity (relative to the noise) increased linearly from the cortex to each of the medullae with a mean slope of 1.6 +/- 0.2 in relative arbitrary units per mm (Rel.u./mm, N = 6) and then decreased, as expected, toward the renal pelvis. Water deprivation (12 hr) induced a significant increase of 25% (P < 0.05) in this gradient. Based on these results, we suggest that sodium MRI can serve as a valuable noninvasive method for functional imaging of the human kidney.     

Improved diagnostic effectiveness with a sequential diagnostic paradigm in idiopathic pediatric sensorineural hearing loss.

OBJECTIVES: To determine whether a stepwise diagnostic paradigm is more diagnostically efficient and cost-effective than a simultaneous testing approach in the evaluation of idiopathic pediatric sensorineural hearing loss (SNHL). DESIGN: Prospective prevalence study. SETTING: Tertiary referral children's hospital. PATIENTS: Consecutive children (n = 150) presenting with idiopathic SNHL in the last 2 years. INTERVENTIONS: All children were evaluated with full diagnostic evaluations including GJB2 screens, temporal bone computed tomography scans, and laboratory investigations. MAIN OUTCOME MEASURES: 1) Diagnostic yields of GJB2 screens, imaging, and laboratory results per SNHL category; 2) Cost analysis comparing a sequential versus a simultaneous testing approach. RESULTS: Overall, 12.0% of patients had biallelic mutations in the GJB2 gene, whereas 30% of patients had an abnormality on temporal bone scan. Laboratory testing did not reveal the SNHL etiology in any patient. While maintaining diagnostic accuracy, significant cost savings were inferred by using a sequential diagnostic algorithm. Our data show children with severe to profound SNHL should first be tested with a GJB2 screen, as opposed to those with milder SNHL, who should undergo imaging as the initial testing step. In patients with initially positive GJB2 or imaging screens, logistic regression analysis significantly predicted negative results on further testing. CONCLUSIONS: A stepwise diagnostic paradigm tailored to the level of the hearing loss in children with bilateral SNHL is more diagnostically efficient and cost effective than the more commonly used full, simultaneous testing approach. Laboratory investigation should not be routine but based on clinical history.     

Time taken to produce dispensing labels in hospital pharmacies,and factors affecting it

The time taken in hospital pharmacies to produce labels for individual patients' medication was measured, and factors affecting the labelling process investigated. Labelling time was measured by direct observation using a stopclock at randomly chosen semi-stratified time periods. Four combinations of major London hospitals and computer systems were studied. The time to produce 2,167 labels was measured and 59 operators were observed. There were significant differences in average labelling time between the studied hospitals/systems (16.6 to 39.3 seconds per label). Operators' experience with their system and the occurrence of interruptions were found to affect labelling significantly (P<0.0001 in both cases). There was an overall trend for labelling time to decrease with increasing experience (P<0.0001), and interruptions added 11 to 12 seconds on average. Operator experience also affected the rate and duration of interruptions, which subsequently affected labelling time. Fewer interruptions occurred with more experienced staff (P=0.0015) and when interrupted, they took less time than inexperienced staff to complete the labelling process. A performance indicator of person-days per 100,000 labels varied from 62.3 to 147.6. Pharmacy managers should be aware that there are significant differences in performance using different labelling systems and that staff training and systems of work may have a marked effect on labelling time.     

Effect of induced field inhomogeneity on transverse proton NMR relaxation in tissue water and model systems

The effect of induced field inhomogeneity (IFI) on transverse NMR relaxation of water protons in tissue has been investigated by examining the field dependence of the effective transverse relaxation rates (1/T2 eff) for in vitro canine brain tissue samples. At fields of 0.47, 2.35, 7.05 T (corresponding to 20, 100, and 300 MHz, respectively) the transverse relaxation rates for both white and gray matter samples follow a field dependence of the form 1/T2 eff = C0 + C1 B0, where B0 is the applied field. The linearly dependent term, C1 B0, which reflects the IFI contribution, does not contribute much (i.e., less than 20%) at fields less than 2.0 T. However, at greater field strengths the contribution is appreciable, e.g., greater than 60% at 7.0 T. Results from model systems of glass beads are also reported to illustrate IFI effects. For both the model systems and canine brain tissue samples, the effects of restricted diffusion are qualitatively evident in Hahn spin-echo experiments.     

Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis.

Expression of platelet-derived growth factor (PDGF) and its receptor (R) subunits was evaluated in normal human liver and in cirrhotic liver tissue by in situ hybridization and immunohistochemistry. In normal liver, PDGF and PDGF-R subunit expression was limited to a few mesenchymal cells of the portal tract stroma and vessels. In cirrhotic liver, PDGF-A and -B chain mRNA expression was markedly increased and was co-distributed with immunoreactivity for PDGF-AA and -BB in infiltrating inflammatory cells and along vascular structures within fibrous septa. These aspects were paralleled by a marked overexpression of PDGF-R alpha- and beta-subunit mRNAs and of the relative immunoreactivities in a wide range of mesenchymal cells in fibrous septa and in perisinusoidal alpha-smooth-muscle-actin-positive cells. In general expression and distribution of PDGF-R subunits appeared to be related to the activation of different mesenchymal cell types involved in the fibroproliferative process. Therefore, we evaluated the expression of PDGF-R subunits in liver tissue specimens with increasing degrees of necroinflammatory activity. The results of this additional study confirmed that expression of PDGF-R subunits is highly correlated with the severity of histological lesions and collagen deposition. Our results, providing evidence for a functional involvement of PDGF/PDGF-R in liver fibrogenesis, greatly support the results of previous in vitro studies and direct attention toward pharmacological strategies able to affect the series of signaling events arising from the autophosphorylation of PDGF-R subunits.     

Interaction of folate and homocysteine pathway genotypes evaluated in susceptibility to neural tube defects (NTD) in a German population

Neural tube defects (NTD) are likely to result from an interaction of several genes and environmental factors. Because periconceptional folate intake reduces the NTD risk in the fetus, and because mothers of children with NTD showed elevated plasma homocysteine levels, gene polymorphisms of the folate and homocysteine pathway, such as 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T, MTHFR 1298A→C and cystathionine β-synthase (CBS) 844ins68, have been implicated in the etiology of NTD. Several studies have demonstrated that these polymorphisms may indeed be associated with NTD in some populations. In order to evaluate the role of these polymorphisms and their interaction in NTD, we genotyped 417 individuals for case-control studies and 129 families for transmission disequilibrium tests. We are the first to present detailed data on MTHFR haploid genotypes in combination with CBS 844ins68. The MTHFR risk genotype 677CT/1298AC, known to be associated with decreased enzyme activity and increased homocysteine, was found significantly more often in patients than in controls (P = 0.02). A CBS insertion allele in addition to MTHFR 677CT/1298AC heterozygosity or MTHFR 677TT/1298AA homozygosity did not result in an increased risk for NTD. This is in agreement with the recently reported homocysteine-lowering effect of the CBS 844ins68 allele in carriers of MTHFR variants. Received: August 28, 2000 / Accepted: December 4, 2000