Does the measurement of the difference of resistive indexes in spleen and kidney allow a selective assessment of chronic kidney injury?

Purpose: To determine whether the difference of resistive indexes (RIs) in spleen and kidney (DI-RISK) is a more specific ultrasonographic (US) marker of intrarenal parenchymal damage than intrarenal RI alone. Materials and Methods: The study was approved by the local ethics committee. All study participants provided informed consent. The authors defined standard values for renal RI, splenic RI, and DI-RISK in 152 healthy subjects; carotid intima media thickness (IMT) was assessed as a marker of systemic vascular disease. Next, the authors measured these US parameters and collected echocardiographic data in 290 patients with chronic kidney disease (stage 2-4) recruited between September 2008 and February 2011 to evaluate the DI-RISK across the spectrum of stages of kidney function. Correlation coefficients were calculated with the Spearman test, and multivariate linear regression was used to analyze independent predictors of renal RI, splenic RI, and DI-RISK. Results: Healthy subjects had a mean age of 34.3 years ± 8.7, and patients with chronic kidney disease had a mean age of 65.0 years ± 12.3 (P < .001). In healthy subjects, both renal and splenic RIs were associated with IMT (renal RI: r = 0.19, P = .022; splenic RI: r = 0.23, P = .005); there was no correlation between DI-RISK and IMT (r = -0.10, P = .215). Similarly, in patients with chronic kidney disease, renal and splenic RIs correlated with IMT (renal RI: r = 0.33, P < .001; splenic RI: r = 0.30, P = .001). DI-RISK was associated with the estimated glomerular filtration rate (eGFR; r = -0.19, P = .001) but not with IMT (r = 0.08, P = .174). At multivariate regression analysis, DI-RISK was independently associated with eGFR but not with extrarenal factors. Conclusion: In patients with chronic kidney disease, renal RIs do not selectively indicate organ damage, but also mirror systemic vascular disease. The authors introduced DI-RISK as a potential US marker that may more specifically reflect kidney damage. ? RSNA, 2012.     

Investigating a lingual thyroid.

During a 15-year-period, in a thyroid investigation centre in Sri Lanka comprising 16,593 cases, 8 lingual thyroids were seen. All patients were female. Radioisotope studies and scintiscanning performed during the investigations of these cases are presented. All subjects were euthyroid at presentation and the clinical courses of 5 cases during follow-up are discussed.     

Effect of Stabilization on the Healing Process of Femur Fractures in Aged Mice

Background: The influence of mechanical stability on fracture healing has previously been studied in adult mice, but is poorly understood in aged animals. Therefore, we herein studied the effect of stabilization on the healing process of femur fractures in aged mice. Methods: Twenty-four 18-month-old CD-1 mice were stabilized after midshaft fracture of the femur with an intramedullary screw. In another 24 18-month-old mice, the femur fractures were left unstabilized. Bone healing was studied by radiological, biomechanical, histomorphometric, and protein expression analyses. Results: After 2 and 5 weeks of healing, the callus of nonstabilized fractures compared to stabilized fractures was significantly larger, containing a significantly smaller amount of osseous tissue and a higher amount of cartilaginous tissue. This was associated with a significantly lower biomechanical stiffness during the early phase of healing. However, during the late phase of fracture healing both nonstabilized and stabilized fractures showed a biomechanical stiffness of ～40%. Of interest, Western blot analyses of callus tissue demonstrated that the expression of proteins related to angiogenesis, bone formation and remodeling, i.e. VEGF, CYR61, BMP-2, BMP-4, Col-2, Col-10, RANKL, OPG, did not differ between nonstabilized and stabilized fractures. Conclusion: Nonstabilized fractures in aged mice show delayed healing and remodeling. This is not caused by an altered protein expression in the callus but rather by the excessive interfragmentary movements.     

Effect of programmed number of intervals to detect ventricular fibrillation on implantable cardioverter-defibrillator aborted and unnecessary shocks

INTRODUCTION: Detection of self-terminating arrhythmias by implantable cardioverter-defibrillators (ICDs) causes unnecessary battery depletion and unnecessary shocks. Our goal was to estimate the effect of the programmed number of intervals to detect (NID) ventricular fibrillation (VF) on ICD temporal episode rate, unnecessary shocks, and delay in detection of VF. METHODS AND RESULTS: We analyzed 773 ICD-detected VF episodes in 875 patients. The number of intervals to detect VF was programmed to 12 of 16 (NID 12) in 305 patients and 18 of 24 (NID 18) in 570 patients. For patients with NID 12, we estimated the increase of mean cumulative episode rate at 6 months since implant and decrease in detection time for VF compared with a hypothetical NID 18. For patients with NID 18, we estimated the decrease of mean cumulative episode rate and unnecessary shocks compared with a hypothetical NID 12. Patients with NID 12 had a 17% increased episode rate resulting in unnecessary capacitor charging for self-terminating arrhythmias. Patients with NID 18 had a 22% decreased episode rate. In patients with NID 12, hypothetical NID 18 would have delayed detection of 273 VF episodes in 1.8 seconds. In patients with NID 18, hypothetical NID 12 would have resulted in inappropriate delivery of 14 aborted shocks in 10% of patients with episodes. CONCLUSION: In patients with self-terminating device-detected VF, increasing the number of intervals to detect VF from 12/16 to 18/24 results in a clinically significant decrease in ICD detections and fewer unnecessary shocks with minimal incremental delay in VF detection.     

Development of a New Method for Assessing Global Risk of Alzheimer’s Disease for Use in Population Health Approaches to Prevention

Alzheimer’s disease (AD) affects approximately 35 million people worldwide. Increasing evidence suggests that many risk factors for AD are modifiable. AD pathology develops over decades. Hence risk reduction interventions require very long follow-ups to show effects on AD incidence. Focussing on AD risk, instead of diagnosis, provides a more realistic target for prevention strategies. We developed a novel methodology that yields a global approach to risk assessment for AD for use in population-based settings and interventions. The methodology was used to develop a risk assessment tool that can be updated as more evidence becomes available. First, a systematic search strategy identified risk and protective factors for AD. Eleven risk factors and four protective factors for AD were identified for which odds ratios were published or could be calculated (age, sex, education, body mass index, diabetes, depression, serum cholesterol, traumatic brain injury, smoking, alcohol intake, social engagement, physical activity, cognitive activity, fish intake, and pesticide exposure). An algorithm was developed to combine the odds ratios into an AD risk score. The approach allows for interactions among risk factors which provides for their varying impact over the life-course as current evidence suggests midlife is a critical period for some risk factors. Finally, a questionnaire was developed to assess the risk and protective factors by self-report. Compared with developing risk indices on single cohort studies, this approach allows for more risk factors to be included, greater generalizeability of results, and incorporation of interactions based on findings from different stages of the lifecourse.     

Platensimycin and platencin congeners from Streptomyces platensis

Platensimycin (1a) and platencin (2) are inhibitors of FabF and FabF/H bacterial fatty acid synthase. The discovery of natural congeners is an approach that can render a better understanding of the structure-function relationships of complex natural products. The isolation and structure elucidation of nine new congeners (11-20) of platensimycin and platencin are described from a fermentation broth of Streptomyces platensis. These hydroxylated congeners are likely derived by cytochrome P450 oxidation of the terpenoid units post-cyclization. Polar groups in the terpenoid portion of the molecule produce negative interactions with the hydrophobic pocket of FabF, resulting in poor activities. However, the discovery of these compounds serves an important purpose, not only to understand structure-function relationships, which cannot be easily accessed by chemical modification, but also to provide access to compounds that could be used for structural identification/confirmation of the oxidative trace metabolites produced in vivo during animal experiments.