Evaluating different imaging strategies in children after first febrile urinary tract infection

We conducted a retrospective multicenter review to estimate the prevalence of urological abnormalities in Chinese children with first febrile urinary tract infection (UTI) and to evaluate the selective imaging strategy recommended by the NICE guideline for detecting underlying abnormalities. Atypical UTI was defined as in the NICE UTI guideline. Overall, 576 boys and 244 girls aged below 24 months were reviewed. All underwent ultrasound (US) and micturating cystourethrogram (MCUG) and 612 underwent DMSA scans. US was abnormal in 73 (8.9%) and vesicoureteral reflux was shown in 195 patients (23.8%). A total of 126 patients were considered to have remediable urological abnormalities requiring additional surgical or medical interventions. The NICE guideline yielded excellent negative predictive values (NPV) of 100–94.4% in girls but 91% in boys. If all boys underwent US and DMSA and only those with atypical UTI or abnormal US or DMSA proceeded to MCUG, then the NPV increased to 95.2% and 97.4% for boys aged below and above 6 months, respectively. These revised strategies would substantially save invasive studies—DMSA and MCUG in 27 and 74% of girls aged below and above 6 months, respectively, or MCUG in 23 and 59% of boys aged below and above 6 months, respectively.     

Chemotherapeutic drugs sensitize human renal cell carcinoma cells to ABT-737 by a mechanism involving the Noxa-dependent inactivation of Mcl-1 or A1

Background  

Human renal cell carcinoma (RCC) is very resistant to chemotherapy. ABT-737 is a novel inhibitor of anti-apoptotic proteins of the Bcl-2 family that has shown promise in various preclinical tumour models.     

A developmental framework for endodermal differentiation and polarity

The endodermis is a root cell layer common to higher plants and of fundamental importance for root function and nutrient uptake. The endodermis separates outer (peripheral) from inner (central) cell layers by virtue of its Casparian strips, precisely aligned bands of specialized wall material. Here we reveal that the membrane at the Casparian strip is a diffusional barrier between the central and peripheral regions of the plasma membrane and that it mediates attachment to the extracellular matrix. This membrane region thus functions like a tight junction in animal epithelia, although plants lack the molecular modules that establish tight junction in animals. We have also identified a pair of influx and efflux transporters that mark both central and peripheral domains of the plasma membrane. These transporters show opposite polar distributions already in meristems, but their localization becomes refined and restricted upon differentiation. This “central–peripheral” polarity coexists with the apical–basal polarity defined by PIN proteins within the same cells, but utilizes different polarity determinants. Central–peripheral polarity can be already observed in early embryogenesis, where it reveals a cellular polarity within the quiescent center precursor cell. A strict diffusion block between polar domains is common in animals, but had never been described in plants. Yet, its relevance to endodermal function is evident, as central and peripheral membranes of the endodermis face fundamentally different root compartments. Further analysis of endodermal transporter polarity and manipulation of its barrier function will greatly promote our understanding of plant nutrition and stress tolerance in roots.     

Impact of being underweight or overweight on factor VIII dosing in hemophilia A patients

Since 1981, the number of factor VIII units to infuse into patients with hemophilia A in order to achieve adequate circulating factor VIII levels has been calculated using the formula: [body weight(kg)×desired factor VIII increase(%)]/2, assuming a factor VIII recovery value of 2 for all patients. This study’s aim was to evaluate the impact of several morphometric parameters and various coagulation factor concentrates on factor VIII recovery. The analysis included 201 hemophilia A adults (>18 years of age) who were carefully selected from eight pharmacokinetic clinical trials using three recombinant factor VIII concentrates (Advate^®, Kogenate^® FS, or ReFacto AF^®/Xyntha^®). Regression tree analysis was used to identify factor VIII recovery predictors. The median factor VIII recovery was 2.16 for all patients. Using regression tree analysis, patients were separated into three groups on the basis of body mass index: below 20.3 kg/m², between 20.3 and 29.5 kg/m², and 29.6 kg/m² or more. Each group had a significantly different median factor VIII recovery (P<0.001): 1.60, 2.14, and 2.70, respectively. The type of coagulation factor concentrate had no influence on recovery in the regression tree. In conclusion, factor VIII dosing should be adapted to underweight and overweight patients, as a factor VIII recovery of 2 does not apply to these patients. Ideal body weight should be considered instead of actual body weight in the dose calculations.     

Depression following traumatic spinal cord injury

OBJECTIVES: To describe the epidemiology of depression following traumatic spinal cord injury (SCI) and identify risk factors associated with depression. METHODS: This population-based cohort study followed individuals from date of SCI to 6 years after injury. Administrative data from a Canadian province with a universal publicly funded health care system and centralized databases were used. A Cox proportional hazards model was developed to identify risk factors. RESULTS: Of 201 patients with SCI, 58 (28.9%) were treated for depression. Individuals at highest risk were those with a pre-injury history of depression [hazard rate ratio (HRR) 1.6; 95% CI: 1.1-2.3], a history of substance abuse (HRR 1.6; 95% CI: 1.2-2.3) or permanent neurological deficit (HRR 1.6; 95% CI: 1.2-2.1). CONCLUSION: Depression occurs commonly and early in persons who sustain an SCI. Both patient and injury factors are associated with the development of depression. These should be used to target patients for mental health assessment and services during initial hospitalization and following discharge into the community.     

Subcortical ischemic vascular dementia: assessment with quantitative MR imaging and 1H MR spectroscopy

BACKGROUND AND PURPOSE: Subcortical ischemic vascular dementia is associated with cortical hypometabolism and hypoperfusion, and this reduced cortical metabolism or blood flow can be detected with functional imaging such as positron emission tomography. The aim of this study was to characterize, by means of MR imaging and 1H MR spectroscopy, the structural and metabolic brain changes that occur among patients with subcortical ischemic vascular dementia compared with those of elderly control volunteers and patients with Alzheimer's disease. METHODS: Patients with dementia and lacunes (n = 11), cognitive impairment and lacunes (n = 14), and dementia without lacunes (n = 18) and healthy age-matched control volunteers (n = 20) underwent MR imaging and 1H MR spectroscopy. 1H MR spectroscopy data were coanalyzed with coregistered segmented MR images to account for atrophy and tissue composition. RESULTS: Compared with healthy control volunteers, patients with dementia and lacunes had 11.74% lower N-acetylaspartate/creatine ratios (NAA/Cr) (P = .007) and 10.25% lower N-acetylaspartate measurements (NAA) in the cerebral cortex (P = .03). In white matter, patients with dementia and lacunes showed a 10.56% NAA/Cr reduction (P = .01) and a 12.64% NAA reduction (P = .04) compared with control subjects. NAA in the frontal cortex was negatively correlated with the volume of white matter signal hyperintensity among patients with cognitive impairment and lacunes (P = .002). Patients with dementia, but not patients with dementia and lacunes, showed a 10.33% NAA/Cr decrease (P = .02) in the hippocampus compared with healthy control volunteers. CONCLUSION: Patients with dementia and lacunes have reduced NAA and NAA/Cr in both cortical and white matter regions. Cortical changes may result from cortical ischemia/infarction, retrograde or trans-synaptic injury (or both) secondary to subcortical neuronal loss, or concurrent Alzheimer's pathologic abnormalities. Cortical derangement may contribute to dementia among patients with subcortical infarction.     

Intensity-modulated radiotherapy for carcinoma of the head and neck

Intensity-modulated radiotherapy (IMRT) is the next evolutionary step of three-dimensional conformal radiotherapy (3-DCRT). IMRT plans are generated with computeroptimized nonuniform radiation beam intensities incident on a target or patient. The dose distributions in IMRT show significantly higher conformality compared with other methods of external-beam radiation delivery, including conventional 3-DCRT. This significant conformality is advantageous in malignancies of the head and neck, where differential dosage is needed to deliver higher doses to the primary tumor and lower doses to areas of subclinical disease. Topics discussed in this review include target delineation, salivary gland sparing, and treatment of specific primary sites. Available data from the literature are presented, including patterns of failure after IMRT. To illustrate the potential role of IMRT in dose escalation and sparing of normal tissues, fractionation strategies in the definitive treatment of head and neck malignancies are presented. In addition, the role of IMRT in treatment of recurrent malignancies of the head and neck is explored. Finally, general concepts of helical tomotherapy are discussed.     

Quantitative determination of coronary vascular calcinosis (coronary calcium score) with double-helical CT

Coronary heart disease is a common disease, with the typical characteristic of coronary sclerosis, an abnormal calcification of the heart's blood vessels. The amount of coronary calcification is in direct correlation to the extent of coronary heart disease. With the double-detector-helical-CT it is possible to detect and quantify these calcifications. The correlation of the "Calcium-Scoring" with the results of coronary-angiography, myocardial scintigraphy and clinical findings shows the value of this method of coronary heart diagnostic. False negative results, based on low calcified fatty stenotic plaques and false positive results, based on high calcificated plaques without significant stenosis should be taken into account.