Non-contrast-enhanced MR angiography using time-spin labelling inversion pulse technique for detecting crossing renal vessels in children with symptomatic ureteropelvic junction obstruction: comparison with surgical findings.

OBJECTIVES: Investigate the feasibility and evaluate the accuracy of non-contrast-enhanced MR angiography (NC-MRA) using time-spin labelling inversion pulse (time-SLIP)to identify crossing renal vessels (CRVs) in children requiring surgical treatment of ureteropelvic junction (UPJ) obstructionand compare to laparoscopic findings. MATERIALS AND METHODS: Nineteen children ranging from 6 to 16 years of age underwent NC-MRA using the time-SLIP technique before surgery. Two independent readers analysed the MRA images. Number of renal arteries and presence or absence of CRVs were identified and compared with surgicalfindings. Image quality was assessed, as well as the presence of CRVs and measurement of renal pelvis diameter. Intra and inter-reader agreement was calculated using Cohen's kappa coefficient and Bland-Altman plots. RESULTS: The overall image quality was fair or good in 88% of cases. NC-MRA demonstrated CRVs at the level of the obstruction in 10 children and no CRV in 9 children. All were confirmed intra-operatively except in one of the nine children. Sensitivity, specificity, NPV, PPV for predicting CRVs were 92%, 100%, 100% and 87.5%, respectively, for both readers. CONCLUSION: NC-MRA is a good alternative to contrast-enhanced MRA and CT scanning for identifying CRVs in children with symptomatic UPJ. KEY POINTS: • Time-SLIP technique offers acceptable imaging quality for identifying crossing renal vessel. • Time-SLIP technique is easy to apply to the renal MRA examination. • Time-SLIP technique is an alternative to contrast-enhanced MRA and CT scanning.

A rare cause of anaemia associated with hypertension in a 14-year-old girl.

We report a rare example of anaemia and hypertension due to an incomplete Carney triad in a 14-year-old girl with no previous medical history. This rare non-familial syndrome generally involves two disparate tumours: gastrointestinal stromal tumour, paraganglioma and/or pulmonary chondroma. The complete triad is a syndrome that involves at least five loci: stomach, oeophagus, lung, the paraganglionic system, adrenal (cortex or medulla). The pathogenesis is unclear as these tumours have different embryological origins. Surgical treatment is necessary, and long-term follow-up is advisable as patients with Carney triad may re-present with tumour(s), even several years after the first presentation.

Anatomic variations of the renal vessels: focus on the precaval right renal artery.

The aim of this study was to determine the prevalence of precaval right renal artery and to investigate the distribution of renal arteries and veins. We discuss a theory of development of renal vascular variants. We retrospectively reviewed 120 arterial phase contrast material-enhanced spiral computerized tomography scans of the abdomen (1- to 2-mm section thickness) performed during a two-month period. Forty percent of the study group (48 patients) had one artery and one vein on each side, with typical course. There was a 9.17% prevalence of precaval right renal artery: 10 patients had a lower pole accessory artery in precaval position and one patient had the main and the accessory arteries that pass anterior to the inferior vena cava. In these cases, associated variations of renal vessels were higher than in the patients without precaval artery variant. There were multiple arteries in 28.3% of the right kidneys and in 26.7% of the left ones. Variants of the right renal vein consisted in multiple veins in 20% (24 cases). We detected no case of multiple left renal veins, but we described variations of its course (circum- or retroaortic vein) in 9.17% (11 cases). Twenty-six patients (21.7%) had associated variations of the renal pedicle. The current technical support allows for a minimally invasive study of vessels anatomy. In our study the prevalence of a precaval right renal artery appears to be higher than previously reported (9.17%). Knowledge on anatomical variations of right renal artery and associated renal vessels variations has major clinical implications.

Deep brain stimulation changes basal ganglia output nuclei firing pattern in the dystonic hamster.

Dystonia is a heterogeneous syndrome of movement disorders characterized by involuntary muscle contractions leading to abnormal movements and postures. While medical treatment is often ineffective, deep brain stimulation (DBS) of the internal pallidum improves dystonia. Here, we studied the impact of DBS in the entopeduncular nucleus (EP), the rodent equivalent of the human globus pallidus internus, on basal ganglia output in the dt(sz)-hamster, a well-characterized model of dystonia by extracellular recordings. Previous work has shown that EP-DBS improves dystonic symptoms in dt(sz)-hamsters. We report that EP-DBS changes firing pattern in the EP, most neurons switching to a less regular firing pattern during DBS. In contrast, EP-DBS did not change the average firing rate of EP neurons. EP neurons display multiphasic responses to each stimulation impulse, likely underlying the disruption of their firing rhythm. Finally, neurons in the substantia nigra pars reticulata display similar responses to EP-DBS, supporting the idea that EP-DBS affects basal ganglia output activity through the activation of common afferent fibers.

A comparative risk assessment for Listeria monocytogenes in prepackaged versus retail-sliced deli meat.

Deli meat was ranked as the highest-risk ready-to-eat food vehicle of Listeria monocytogenes within the 2003 U.S. Food and Drug Administration and U.S. Department of Agriculture, Food Safety and Inspection Service risk assessment. The comparative risk of L. monocytogenes in retail-sliced versus prepackaged deli meats was evaluated with a modified version of this model. Other research has found that retail-sliced deli meats have both higher prevalence and levels of L. monocytogenes than have product sliced and packaged at the manufacturer level. The updated risk assessment model considered slicing location as well as the use of growth inhibitors. The per annum comparative risk ratio for the number of deaths from retail-sliced versus prepackaged deli meats was found to be 4.89, and the per-serving comparative risk ratio was 4.27. There was a significant interaction between the use of growth inhibitors and slicing location. Almost 70% of the estimated deaths occurred from retail-sliced product that did not possess a growth inhibitor. A sensitivity analysis, assessing the effect of the model's consumer storage time and shelf life assumptions, found that even if retail-sliced deli meats were stored for a quarter of the time prepackaged deli meats were stored, retail-sliced product is 1.7 times more likely to result in death from listeriosis. Sensitivity analysis also showed that the shelf life assumption had little effect on the comparative risk ratio.

Application of quantitative microbial risk assessments for estimation of risk management metrics: Clostridium perfringens in ready-to-eat and partially cooked meat and poultry products as an example.

The U.S. Department of Agriculture, Food Safety and Inspection Service is exploring quantitative risk assessment methodologies to incorporate the use of the Codex Alimentarius' newly adopted risk management metrics (e.g., food safety objectives and performance objectives). It is suggested that use of these metrics would more closely tie the results of quantitative microbial risk assessments (QMRAs) to public health outcomes. By estimating the food safety objective (the maximum frequency and/or concentration of a hazard in a food at the time of consumption) and the performance objective (the maximum frequency and/or concentration of a hazard in a food at a specified step in the food chain before the time of consumption), risk managers will have a better understanding of the appropriate level of protection (ALOP) from microbial hazards for public health protection. We here demonstrate a general methodology that allows identification of an ALOP and evaluation of corresponding metrics at appropriate points in the food chain. It requires a two-dimensional probabilistic risk assessment, the example used being the Monte Carlo QMRA for Clostridium perfringens in ready-to eat and partially cooked meat and poultry products, with minor modifications to evaluate and abstract required measures. For demonstration purposes, the QMRA model was applied specifically to hot dogs produced and consumed in the United States. Evaluation of the cumulative uncertainty distribution for illness rate allows a specification of an ALOP that, with defined confidence, corresponds to current industry practices.

Dietary estimates of dioxins consumed in U.S. Department of Agriculture-regulated meat and poultry products.

The U.S. Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS) examined whether levels of dioxin-like compounds (DLCs) measured in FSIS-regulated meat and poultry products indicate possible concern for U.S. public health based on usual and recommended consumption patterns of meat and poultry for the U.S. population. The FSIS estimated daily dietary exposures and compared them with the reference dose (RfD) established by the U.S. Environmental Protection Agency (EPA) for potential noncancer risks from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), assuming that all measured DLCs were represented by the RfD (i.e., not just TCDD alone). The estimates indicate that a typical U.S. adult daily exposure of DLCs from FSIS-regulated products is below the EPA-established RfD. Only children consuming chronic average daily servings of meat or poultry products containing the highest measured levels of DLCs may exceed the RfD. If one follows the recommendations from the 2010 Dietary Guidelines for Americans, all expected exposures to DLCs from FSIS-regulated products are estimated to be well below the RfD.

Characterizing uncertainty when evaluating risk management metrics: risk assessment modeling of Listeria monocytogenes contamination in ready-to-eat deli meats.

This report illustrates how the uncertainty about food safety metrics may influence the selection of a performance objective (PO). To accomplish this goal, we developed a model concerning Listeria monocytogenes in ready-to-eat (RTE) deli meats. This application used a second order Monte Carlo model that simulates L. monocytogenes concentrations through a series of steps: the food-processing establishment, transport, retail, the consumer's home and consumption. The model accounted for growth inhibitor use, retail cross contamination, and applied an FAO/WHO dose response model for evaluating the probability of illness. An appropriate level of protection (ALOP) risk metric was selected as the average risk of illness per serving across all consumed servings-per-annum and the model was used to solve for the corresponding performance objective (PO) risk metric as the maximum allowable L. monocytogenes concentration (cfu/g) at the processing establishment where regulatory monitoring would occur. Given uncertainty about model inputs, an uncertainty distribution of the PO was estimated. Additionally, we considered how RTE deli meats contaminated at levels above the PO would be handled by the industry using three alternative approaches. Points on the PO distribution represent the probability that - if the industry complies with a particular PO - the resulting risk-per-serving is less than or equal to the target ALOP. For example, assuming (1) a target ALOP of -6.41 log10 risk of illness per serving, (2) industry concentrations above the PO that are re-distributed throughout the remaining concentration distribution and (3) no dose response uncertainty, establishment PO's of -4.98 and -4.39 log10 cfu/g would be required for 90% and 75% confidence that the target ALOP is met, respectively. The PO concentrations from this example scenario are more stringent than the current typical monitoring level of an absence in 25 g (i.e., -1.40 log10 cfu/g) or a stricter criteria of absence in 125 g (i.e., -2.1 log10 cfu/g). This example, and others, demonstrates that a PO for L. monocytogenes would be far below any current monitoring capabilities. Furthermore, this work highlights the demands placed on risk managers and risk assessors when applying uncertain risk models to the current risk metric framework.

Quickly finding a needle in a haystack: a new automated cardiac arrhythmia detection software for preclinical studies.

INTRODUCTION: The occurrence of drug-induced arrhythmias in safety pharmacology or toxicology studies is a primary safety concern. The risk assessment requires an accurate knowledge of background arrhythmia incidence and frequency in the test system/species, as well as a rigorous evaluation of the effects of the potential new medical entities on the electrocardiogram (ECG). However, the direct assessment of arrhythmia in ECG recordings is a time-consuming effort and is rarely achieved due to lack of suitable automated tools. A new software application named ARR30a was developed for fast automated detection in preclinical studies, for the five major arrhythmia types, namely sinus pauses, atrial beats, junctional beats, ventricular beats and type 2 atrio-ventricular blocks (AV-blocks II). The purpose of this study was to characterize the performance of ARR30a in large and small animal species. METHODS: Detection sensitivity and predictivity were evaluated on a database of 84 ECG recordings representative of each animal species and experimental protocols typically used in efficacy, safety pharmacology and toxicology studies. Automated arrhythmia detection was compared with manual analysis. RESULTS: In large animals such as dogs, non-human primates and pigs, ARR30a sensitivity reached 90.6%, 82.2% and 78.0% for ventricular beats, AV-blocks II and junctional beats with predictivity of 83.4%, 94.4% and 93.5%, respectively. Significantly lower sensitivity was observed in rats for junctional beats due to challenging problems of detection for low amplitude P-waves. Robustness to noise was assessed by adding increasing noise levels to ECG signals and showed no significant impact on arrhythmia detection at moderate noise levels. Processing time for a 24 hour recording was approximately 4 min for dogs and 6 min for rats on a 3 GHz processor. DISCUSSION: This newly validated ECG arrhythmia detector ARR30a allows evaluating all major ECG signal abnormalities and enhances the quantification of arrhythmia incidence in all major laboratory animal species. The mark editor RME10a enables manual validation of the automated analysis and refinement of the arrhythmia classification.

Systemic sarcoidosis revealed by ventricular tachycardia: electrocardiography and MRI correspondence.

We describe a case presenting with ventricular tachycardia as the manifestation leading to the diagnosis of sarcoidosis. The ventricular tachyacardia's origin is correlated with granuloma localization on magnetic resonance imaging.