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Much of our long-term knowledge is organised in complex networks. Sleep is thought to be critical for abstracting knowledge and enhancing important item memory for long-term retention. Thus, sleep should aid the development of memory for networks and the abstraction of their structure for efficient storage. However, this remains unknown because past sleep studies have focused on discrete items. Here we explored the impact of sleep (night-sleep/day-wake within-subject paradigm with 25 male participants) on memory for graph-networks where some items were important due to dense local connections (degree centrality) or, independently, important due to greater global connections (closeness/betweenness centrality). A network of 27 planets (nodes) sparsely interconnected by 36 teleporters (edges) was learned via discrete associations without explicit indication of any network structure. Despite equivalent exposure to all connections in the network, we found that memory for the links between items with high local connectivity or high global connectivity were better retained after sleep. These results highlight that sleep has the capacity for strengthening both global and local structure from the world and abstracting over multiple experiences to efficiently form internal networks of knowledge.

It is difficult to separate an age-dependent fall in nitrogen use efficiency (NUE; N balance/N intake) in growing ruminants from a progressively decrease in animal protein requirements over time. This study examined the effect of dietary protein content on N partitioning, digestibility and N isotopic discrimination between the animal and its diet (Δ15Nanimal-diet) evaluated at two different fattening periods (early v. late). Twenty-four male Romane lambs (age: 19 ± 4.0 days; BW: 8.3 ± 1.39 kg) were equally allocated to three dietary CP treatments (15%, 17% and 20% CP on a DM basis). Lambs were reared with their mothers until weaning, thereafter housed in individual pens until slaughter (45 kg BW). During the post-weaning period, lambs were allocated twice (early fattening (30 days post-weaning) and late fattening (60 days post-weaning)) to metabolic cages for digestibility and N balance study. When diet CP content increased, the average daily gain of lambs increased (P < 0.05) while the age at slaughter decreased (P = 0.01), but no effect was observed on feed efficiency (P > 0.10). Diet CP content had limited effect on lamb carcass traits. Higher fibre digestibility was observed at the early v. late fattening period (P < 0.001). The N intake and the urinary N excretion increased when diet CP content increased (P < 0.001) and when shifting from early to late fattening period (P < 0.001). Faecal N excretion (P = 0.14) and N balance (P > 0.10) were not affected by diet CP content. Nitrogen digestibility increased (P < 0.001) as the diet CP content increased and on average it was greater at late v. early fattening period (P = 0.02). The NUE decreased (P = 0.001) as the diet CP content increased and as the lamb became older (P < 0.001). However, the age-dependent fall in NUE observed was lower at high v. low dietary CP content (CP × age interaction; P = 0.04). The Δ15Nanimal-diet was positively correlated (P < 0.05) with N intake (r = 0.59), excretion of faecal N (r = 0.41), urinary N (r = 0.69) and total manure N (r = 0.64), while negatively correlated with NUE (r = −0.57). Overall, the experiment showed NUE was lower in older lambs and when lambs were fed high diet CP content, and that Δ15Nanimal-diet was a useful indicator not only for NUE but also for urinary N excretion, which is a major environmental pollution factor on farm.

Background With a growing access to free ART, switching of ART to second line regimen has also become common following failure of first line ART regimens. Patients failing on first line ART regimens have been shown to stand a high risk of failing on subsequent second line ART regimens. The magnitude of those who are failing virologicaly on second line ART is not documented in our setting. This study was designed to assess the magnitude and correlates of second line ART treatment failure. Methods A retrospective analysis of patients on second line ART for at least 1 year was done at Bugando care and treatment center. Information on demographic, clinical and laboratory data were collected and analyzed using STATA 11. The proportion of patients with Virological failure was calculated and potential correlates of virological failure were determined by logistic regression model. Results In total 197 patients on second line ART were included in this study and 24 (12.18%) of them met criteria for virological failure. The odds of having virological failure on second line ART were independently associated with age of less than 30 years (AOR = 12.5, p = 0.001), being on first line for less than 3 years (AOR = 6.1, p = 0.002) and CD4 at switch to second line ART of less than 200cells/μl (AOR = 16.3, p

Hepatic lesions in nondomestic felids are poorly characterized. The purpose of this study was to evaluate hepatic lesions in 90 captive, nondomestic felids including tigers, cougars, and lions. Hepatic lesions were histologically characterized as vacuolar change (lipidosis or glycogenosis), biliary cysts, biliary hyperplasia, hepatitis, necrosis, neoplasia, fibrosis, veno-occlusive disease, cholestasis, hematoma, congestion, or hemorrhage. Stepwise logistic regression analyses were performed for vacuolar change, benign biliary lesions, hepatitis, lipogranulomas, extramedullary hematopoiesis, and hepatic stellate cell hypertrophy and hyperplasia, with species as the outcome variable. Ninety cats met the inclusion criteria. Seventy livers (78%) contained 1 or more lesions. Hepatocellular vacuolar change (41/90 [46%]) was the most common lesion overall. Extramedullary hematopoiesis, lipogranulomas, and hepatic stellate cell hyperplasia were also common. One snow leopard had veno-occlusive disease. Tigers were more likely than other felids to have no significant hepatic histologic lesions (odds ratio [OR], 12.687; P = .002), and lions were more likely to have biliary cysts (OR, 5.97; P = .021). Six animals (7%) died of hepatic disease: cholangiocellular carcinoma (n = 2) and 1 each of hepatic lipidosis, hepatocellular necrosis, pyogranulomatous hepatitis, and suppurative cholecystitis. Hepatocellular iron and copper accumulations were present in 72 of 90 (80%) and 10 of 90 (11%) sections, respectively. Sinusoidal fibrosis was common (74/90 [82%]) and primarily centrilobular (65/74 [88%]). Hepatocellular iron, copper, and fibrosis were not significantly associated with hepatic lesions. Primary hepatic disease was not a common cause of death in nondomestic felids in this study.

Despite a call for more training of clinical supervisors, little has emerged in the professional literature to offer pedagogical strategies for training. This article describes the use of supervision documentation to guide the development of supervisors-in-training (SITs). Specifically, supervision notes are used to assist and monitor SITs understanding and application of supervisor models.

Purpose The purpose of the study was to compare patients readmitted to the pediatric intensive care unit (PICU) unexpectedly within 48 hours (early), more than 48 hours from transfer (late), or not readmitted during the same hospitalization. Materials and Methods A retrospective study (2007-2009) was performed at a tertiary care pediatric academic hospital. Readmitted at-risk patients were grouped by timing of readmission, and a sample of nonreadmitted patients was randomly selected. Early readmissions were compared to late readmissions and to nonreadmissions. Results Of 3805 eligible patients, 3.9% had an unplanned PICU readmission with almost half occurring within 48 hours. Median times to readmission were 21.5 hours (early) and 7 days (late). Compared with late readmissions, early readmissions were more often admitted from and transferred to a surgical service, transferred on a weekend, and readmitted with the same primary diagnosis. Compared with nonreadmitted patients, independent risk factors for early readmission were admission source and respiratory support at PICU transfer. Readmitted patients had longer total PICU and hospital lengths of stay than nonreadmitted patients. Late readmissions had a higher mortality than early readmissions. Conclusions Patients requiring an unplanned PICU readmission had worse outcomes than those without a readmission. Future studies should focus on identifying modifiable risk factors for targeted interventions.

Chemotherapy plus G-CSF (C+G) and G-CSF alone are two of the most common methods used to mobilize CD34(+) cells for autologous hematopoietic SCT (AHSCT). In order to compare and determine the real-world outcomes and costs of these strategies, we performed a retrospective study of 226 consecutive patients at 11 medical centers (64 lymphoma, 162 multiple myeloma), of whom 55% of lymphoma patients and 66% of myeloma patients received C+G. Patients with C+G yielded more CD34(+) cells/day than those with G-CSF alone (lymphoma: average 5.51 × 10(6) cells/kg on day 1 vs 2.92 × 10(6) cells/kg, P=0.0231; myeloma: 4.16 × 10(6) vs 3.69 × 10(6) cells/kg, P0.00001) and required fewer days of apheresis (lymphoma: average 2.11 vs 2.96 days, P=0.012; myeloma: 2.02 vs 2.83 days, P=0.0015), although nearly all patients ultimately reached the goal of 2 × 10(6) cells/kg. With the exception of higher rates of febrile neutropenia in myeloma patients with C+G (17% vs 2%, P0.05), toxicities and other outcomes were similar. Mobilization with C+G cost significantly more (lymphoma: median $10,300 vs $7300, P0.0001; myeloma: $8800 vs $5600, P0.0001), although re-mobilization adds $6700 for drugs alone. Our results suggest that although both C+G and G-CSF alone are effective mobilization strategies, C+G may be more cost-effective for patients at high risk of insufficient mobilization.

There is limited information regarding the cost-effectiveness of sevelamer for the treatment of hyperphosphatemia in chronic kidney disease (CKD) patients on dialysis in the UK. Using a UK National Health Service (NHS) perspective and final results of the Dialysis Clinical Outcomes Revisited (DCOR) study, an evaluation was performed to determine the cost-effectiveness of sevelamer compared to calcium-based phosphate binders for the first-line treatment of hyperphosphatemia in CKD patients on dialysis.A Markov model was developed to estimate life years, quality-adjusted life years (QALYs), costs, incremental cost per life year (LY) gained, and QALY gained. Treatment-specific overall survival up to 44 months, hospitalizations, and resource utilization were derived from the DCOR study. Survival was extrapolated to a lifetime horizon using Weibull regression analysis. Unit costs and utility estimates specific to the UK were obtained from the published literature. Sub-group analyses were conducted based on data reported from the DCOR study for increasing age cut-points. Outcomes and costs were modeled for a lifetime horizon.In the base case analysis, the use of sevelamer resulted in a gain of ∼0.73 LYs and 0.44 QALYs per patient (discounted at 3.5% per year). Total per-patient costs were higher for sevelamer, resulting in an incremental cost of £22,157 per QALY gained and £13,427 per LY gained (in £2009). Increasingly favorable cost per QALY ratios were observed with increasing age cut-points, ranging from £15,864 for patients ≥45 to £13,296 for patients ≥65 years of age. Results were most sensitive to assumptions regarding overall survival and the inclusion of dialysis costs. Key limitations of the analysis included the use of non-UK trial data for survival and hospitalizations, and the exclusion of quality-of-life impacts associated with hospitalization.In CKD patients receiving dialysis, treatment of hyperphosphatemia with sevelamer offers good value for money compared with calcium-based binders.

Objective To propose a method of diagnosis of mild papilloedema (PO) using peripapillary total retinal (PTR) thickness measurement by spectral domain optical coherence tomography (OCT). Methods 24 eyes in 24 patients with PO caused by increased intracranial pressure and 22 eyes in 22 normal subjects were studied. OCT high-quality fundus images were analysed and graded by three masked observers using the Modified Frisen Scale. Eyes with PO were divided into two subgroups: those with mild PO (n=18) and those with moderate-severe PO (n=6). Two methods of measurements were evaluated and compared: retinal nerve fibre layer (RNFL) thickness measurements using standard optic disc cube 200×200 acquisition protocol and PTR thickness measurements using the ‘macular’ cube 512×128 acquisition protocol centred on the optic disc. Thickness values were calculated globally and for each quadrant (temporal, superior, nasal, inferior) and compared among the three groups (control, mild PO, moderate-severe PO). The main outcome measures were RNFL and PTR thickness. Results Average RNFL and PTR thickness in the moderate-severe PO, mild PO and control groups were 299.3±10.9, 112.4±6.3, 96±5.7 and 804.5±17, 463.1±9.8 and 332.4±8.9 μm, respectively. Moderate-severe PO differed from mild PO and control groups using both RNLF thicknesses and PTR thicknesses measurements. Mild PO did not differ from controls using RNLF thickness measurement (p=0.17), but was statistically different using PTR thickness measurement (p Conclusion PTR thickness measurement increases the sensitivity of detection of mild PO compared with conventional RNFL measurement. This new way of using OCT may be useful for clinicians to detect mild PO.

Objective.To assess whether use of oral vancomycin for treatment during an outbreak of Clostridium difficile infection (CDI) was associated with increased rates of colonization with vancomycin-resistant enterococci (VRE)..Design.A retrospective analysis of hospital databases.Setting.The Jewish General Hospital in Montreal, Quebec, Canada.Methods.We collected data regarding VRE colonization and CDI from November 1, 2000, through September 30, 2007, during which policies of preferential oral metronidazole or vancomycin treatment were implemented to control an outbreak of CDI. Four periods were considered: period 1, the preoutbreak period when metronidazole was used; period 2, the CDI outbreak period when metronidazole was used; period 3, the postoutbreak period when vancomycin was used; and period 4, the postoutbreak period when metronidazole was used.Results.A total of 2,412 cases of CDI and 425 cases of VRE colonization were identified. The rate of CDI increased significantly during period 2 and decreased to preoutbreak levels during period 3. The rate of VRE also increased during period 2 and decreased during the first 18 months of period 3. A clonal outbreak of cases of VRE (VanA) colonization was observed toward the end of period 3 and into period 4. Excluding the period of the clonal outbreak, there was a strong correlation between the number of cases of CDI and VRE colonization (r = 0.736; P = .001) and a negative association between VRE colonization and vancomycin use (r = —0.765; P = .04).Conclusions.Increased vancomycin use was not associated with an increase in VRE colonization over a 2-year period. Restriction of vancomycin use during CDI outbreaks because of the fear of increasing VRE colonization may not be warranted.

This study assessed secondborn adolescents' perceptions of changes in the allocation of family resources following their firstborn siblings' departure from home after high school, and whether perceived changes were related to changes over 1 year in secondborns' academic functioning. Participants were secondborn siblings (mean age = 16.58, SD = 0.91) from 115 families in which the older sibling had left the family home in the previous year. Allocation of resources was measured via coded qualitative interviews. Most (77%) secondborns reported increases in at least one type of family resource (i.e., parental companionship, attention, material goods), and many reported an increase in multiple types of resources in the year following their older sibling's departure. Consistent with resource dilution theory, perceptions of increases in fathers' companionship, fathers' attention, and mothers' companionship were related to improvements over time in secondborns' academic functioning.

We assessed the benefit of predeposite autologous blood donation (PAD) before bone marrow (BM) donation on transfusion requirements, haemoglobin concentrations (Hb) and the occurrence of adverse events (AE). We collected data retrospectively from 50 donors of BM with PAD from 2010 to 2014. An autologous transfusion (AT) was given to 50% of the donors (group 1). In the group 2, the products from PAD were not used. The total volume median of marrow harvested was 17.7 mL/k (range 12.3-21.4) in the group 1 and 13.3 mL/k (8.6-22.6) in the group 2. The female ratio was higher in the group 1 (60%) than in the group 2 (16%). Bone marrow harvest led to a decline in Hb (from PAD to first day after BM donation) by 2.9 g/dL (1.5-5.5) in the group 1 and by 3.5 g/dL (1.2-5) in the group 2. The post-harvest Hb (D+1) median was identical in the two groups: 10.9 g/dL (7.6-13.5) in the group 1 versus 11.5 g/dL (9.3-13.4) in the group 2. Six AE were reported in each group. In the group with AE, the median weight was lower: 58 k (50-71) versus 75 k (52-110); and the median total volume of marrow harvested was higher: 20.1 mL/k (9.9-21.4) versus 14.3 mL/k (8.6-22.6). All post-harvest Hb were ≥ 7.6g/dL. This study shows the high loss of Hb after BM donation but not enough to prove a blood transfusion in BM donors with median age of 36 years (16-62) and without comorbidity. The occurrence of AE (25% of BM donors) justifies a careful surveillance after the BM donation. The PAD should not be routinely offered to bone marrow donors.

International audience; Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within the range of asymmetry coefficients measured on corresponding real data. The features of the proposed approach are compared with those of other methods previously described to obtain datasets appropriate for the assessment of fusion methods.

Adverse Drug Reactions (ADRs) leading to hospital admission was estimated to 3.6 to 21.7%. Despite its importance in terms of patients care, readmission to hospital due to ADRs remains poorly documented. The aim of our study was to investigate the rate and main characteristics of readmission for ADRs.We undertook a retrospective study during two years (2011-2012) in the post-emergency unit of Toulouse university hospital (south western, France). We selected all unplanned hospitalization for acute disease and included all cases of patients admitted twice fold or more for ADRs. Characteristics of drug-induced ADRs were assessed according to appropriate use or not.Out of the 197 readmitted patients, 71 was related to ADRs (3.6%) corresponding to 17.8‰ patients-year. Mean age was 82.3 years and 67% were women. The most frequent ADRs found were vascular (n=41, 18.4%), gastro-intestinal (n=28, 12.6%), cardiac (n=28, 12.6%), neurologic (n=26, 11.7%), metabolic (n=26, 10.3%) and psychiatric (n=24, 9.9%). The drugs mainly involved were psychoactive, cardiovascular, digestive or antithrombotic agents. The context of occurrence of ADRs was related to inappropriate drug prescription in 56% of cases. A total of 24 patients were admitted twice for the same ADR and 2 others three times. For 22 patients (30.9%), the same drugs were involved.Our data show hospital readmission was due to ADRs in 3.6% of cases. In 1.1% of cases, the same couple "drug-ADR" was involved. Furthermore, in 56% of cases, repeated admissions are related to an inappropriate drug prescription.

In patients with significant mitral regurgitation (MR) at high risk of mortality and morbidity from mitral valve surgery, transcatheter mitral valve repair with the MitraClip System is associated with a reduction in MR and improved quality-of-life and functional status compared with baseline. The objective was to evaluate the cost-effectiveness of MitraClip therapy compared with standard of care in patients with significant MR at high risk for mitral valve surgery from a Canadian payer perspective.A decision analytic model was developed to estimate the lifetime costs, life years, quality-adjusted life years (QALYs), and incremental cost per life year and QALY gained for patients receiving MitraClip therapy compared with standard of care. Treatment-specific overall survival, risk of clinical events, quality-of-life, and resource utilization were obtained from the Endovascular Valve Edge-to-Edge REpair High Risk Study (EVEREST II HRS). Health utility and unit costs (CAD $2013) were taken from the published literature. Sensitivity analyses were conducted to explore the impact of alternative assumptions and parameter uncertainty on results.The base case incremental cost per QALY gained was $23,433. RESULTS were most sensitive to alternative assumptions regarding overall survival, time horizon, and risk of hospitalization for congestive heart failure (CHF). Probabilistic sensitivity analysis showed MitraClip therapy to have a 92% chance of being cost-effective compared with standard of care at a willingness-to-pay threshold of $50,000 per QALY gained.Key limitations include the small number of patients included in the EVEREST II HRS which informed the analysis, the limited data available to inform clinical events and disease progression in the concurrent comparator group, and the lack of a comparator group from a randomized control trial.MitraClip therapy is likely a cost-effective option for the treatment of patients at high risk for mitral valve surgery with significant MR.

Since most nosocomial systemic yeast infections arise from the endogenous flora of the patient, we prospectively evaluated the species stratification and antifungal susceptibility profile of Candida spp. associated with heavy colonization and systemic infection in patients at Memorial Sloan-Kettering Cancer Center in New York. A total of 349 Candida isolates were obtained from 223 patients during the later half of 1998. Cancer was the most common underlying disease, occurring in 91% of the patients, including 61.8% with organ and 23.7% with hematological malignancies; 4.4% of the patients had AIDS. Candida albicans was the predominant species (67.3%); among 114 non- albicans Candida spp., C. glabrata (45.6%) was the most frequent, followed by C. tropicalis (18.4%), C. parapsilosis (16.6%), and C. krusei (9.6%). The overall resistance to triazole-based agents among all yeast isolates was 9.4 and 10.8% for fluconazole and itraconazole, respectively. A total of 5% of C. albicans strains were resistant to triazole antifungals, whereas 30.8 and 46.2% of C. glabrata strains were resistant to fluconazole (MIC ≥ 64 μg/ml) and itraconazole (MIC ≥ 1 μg/ml), respectively. A significant association was observed between prior treatment with triazole and isolation of fluconazole-resistant C. albicans ( P = 0.005, OR 36), although this relationship was not seen in C. glabrata isolates ( P = 0.4). This study reinforces the importance of periodic, prospective surveillance of clinical fungal isolates to determine appropriate prophylactic, empiric, and preemptive antifungal therapy for the highly susceptible patient population.

The authors present a case report documenting the evaluation of monostotic fibrous dysplasia by magnetic resonance imaging. This type of evaluation demonstrates specificity for this disease process when combined with other imaging studies, laboratory findings, and clinical presentation. This technique is extremely useful in the identification of a no-touch lesion, allowing avoidance of an unnecessary bone biopsy. (J Am Podiatr Med Assoc 91(6): 306-310, 2001)

Exposure to waterborne and foodborne pathogens can occur via drinking water (associated with fecal contamination), seafood (due to natural microbial hazards, toxins, or wastewater disposal) or fresh produce (irrigated or processed with contaminated water). Weather influences the transport and dissemination of these microbial agents via rainfall and runoff and the survival and/or growth through such factors as temperature. Federal and state laws and regulatory programs protect much of the U.S. population from waterborne disease; however, if climate variability increases, current and future deficiencies in areas such as watershed protection, infrastructure, and storm drainage systems will probably increase the risk of contamination events. Knowledge about transport processes and the fate of microbial pollutants associated with rainfall and snowmelt is key to predicting risks from a change in weather variability. Although recent studies identified links between climate variability and occurrence of microbial agents in water, the relationships need further quantification in the context of other stresses. In the marine environment as well, there are few studies that adequately address the potential health effects of climate variability in combination with other stresses such as overfishing, introduced species, and rise in sea level. Advances in monitoring are necessary to enhance early-warning and prevention capabilities. Application of existing technologies, such as molecular fingerprinting to track contaminant sources or satellite remote sensing to detect coastal algal blooms, could be expanded. This assessment recommends incorporating a range of future scenarios of improvement plans for current deficiencies in the public health infrastructure to achieve more realistic risk assessments.

Jumping translocation (JT) is a very rare cytogenetic event, occurring especially in cancer. We describe a case of secondary acute monocytic leukemia (AML5b) with a JT involving the 3q13-3qter segment and leading to a partial trisomy 3. Each clone with JT was associated with trisomy 8 or tetrasomy 8. The literature of JT in AML cases is reviewed: only 13 cases of AML associated with JT have been previously described, seven of which are AML4/5 FAB subtype. Jumping translocation involvement in leukemogenesis is discussed. Leukemia (2000) 14, 119-122.

OBJECTIVE: To identify areas that should be targeted for improvement in care, we examined internal medicine resident practice patterns and beliefs regarding diabetes in a large urban hospital outpatient clinic. RESEARCH DESIGN AND METHODS: Internal medicine residents were surveyed to assess the frequency at which they performed key diabetes quality of care indicators. Responses were compared with recorded performance derived from chart and laboratory database reviews. Resident attitudes about diabetes were determined using the Diabetes Attitude Survey for Practitioners. Finally, an eight-item scale was used to assess barriers to diabetes care. RESULTS: Both self-described and recorded performance of recommended diabetes services short of national recommendations. For yearly eye examinations and lipid screening, recorded performance levels were similar to trainees' reports. However, documented inquiries about patient self-monitoring of blood glucose, performance of foot examinations, and urine protein screening were lower than trainees' reports. Some 49% of the residents selected a target HbA1c of 6.6-7.5% as an attainable goal, yet half of the patients using oral agents or insulin had HbA1c values > 8.0%. No differences in self-described or recorded performance were found by year of training. Most residents did not perceive themselves to need additional training related to diabetes care, and residents were generally neutral about patient autonomy. Patient nonadherence and time constraints within the clinic were most often cited as barriers to care. CONCLUSIONS: The study identifies several areas that require improvement in resident care of diabetes in the ambulatory setting. Because experience during training contributes to future practice patterns, developing a program that teaches trainees how to implement diabetes practice guidelines and methods to achieve optimal glycemic control may be key to future improvements in the quality of diabetes care.

Summary: Purpose: Single photon emission computed tomography (SPECT) is used as an adjunctive method in preoperative localization of epileptic foci. In temporal lobe epilepsy (TLE), interictal hypoperfusion is observed in 60–70% of cases. Correlation with ictal EEG changes is observed in ∼50–60% of cases. Relationships with interictal EEG have been studied less. We compared interictal SPECT data obtained in 20 patients with their interictal intracerebral electrical activity recorded by depth electrodes to evaluate a potential relationship. Methods: We studied 20 sequential patients whose clinical, surface, and depth EEG data indicated seizure originating in the temporal lobe and who had interictal [99mTc]hexamethyl-propylene amine oxime (HMPAO)-SPECT stereo-EEG (SEEG). Intracerebral electrodes were placed according to the patient's profile. The interictal extent of epileptiform activity allowed delineation of the irritative zone. Interictal spike frequency was also analyzed semiquantitatively. Visual and numerical SPECT analysis was performed blind to SEEG data. Results: Interictal hypoperfusion was observed in 16 patients, involving the epileptogenic temporal lobe in 14. Except for 1 patient who manifested lateral temporal hypoperfusion corresponding to a mass lesion, two distinctive patterns of hypoperfusion were noted: (a) mesial hypoperfusion (5 patients), and (b) global temporal hypoperfusion (8 patients). In 8 patients, hypoperfusion had also extended into the adjacent cortex. Temporal mesial hypoperfusion was associated with spiking limited to the mesial structures, whereas global temporal hypoperfusion or hypoperfusion extending beyond the temporal lobe was associated with a similar topographic pattern of spikes. Conclusions: Comparison between SPECT and SEEG data collected in the interictal phase indicated that the extent of the hypoperfused area correlated topographically with that of the underlying irritative zone.

Insertion and maintenance of an interscalene catheter is technically challenging using lateral or anterior approaches. We report a technique to provide continuous brachial plexus blockade through a 48-h infusion of ropivacaine 0.1% (5 mL/h with a 5 mL bolus dose, 20-min lockout interval) using a catheter inserted with cannula-over-needle technique on the posterior side of the neck in 120 patients undergoing shoulder surgery. All catheters were successfully placed. There were no technical complications (impossibility to thread catheter, accidental vascular, epidural or subarachnoid location), catheter dislodgment, or analgesic solution leakage. Dysphonia, Horner's syndrome, and difficulty breathing were observed in 12 patients, four patients, and one patient, respectively. One patient complained of minor paresthesia that spontaneously resolved. Three patients complained of cervical pain. Pain scores as well as ropivacaine requirement via a patient-controlled analgesia device were low. Evaluation of acute and nonacute complications in a large-size study is needed to compare efficacy and safety of this approach with existing techniques.

Tannins may bind to alkaloids in endophyte-infected (E+) tall fescue and attenuate fescue toxicosis. To test this hypothesis, thirty-two 4-mo-old lambs were randomly assigned to 4 treatments (8 lambs/treatment) in a 2 by 2 factorial design that included a basal diet of tall fescue hay [E+ or endophyte-free (E-)] supplemented with (TS) or without (CS) bioactive Quebracho tannins. The concentration of ergovaline in E+ fed in 2 successive phases was 65 ± 21 µg/kg (Phase 1) and 128 ± 4 µg/kg (Phase 2). After exposure to hays and supplements, all lambs were offered choices between TS and CS and between E+ and E- hays. During Phase 1, lambs offered E+ consumed more hay than lambs offered E- (P = 0.03). Lambs on E+/TS displayed the greatest intake of hay and the least intake of TS (P0.05). During Phase 2, when the concentration of ergovaline increased, lambs offered E+ consumed less hay than lambs fed E- (P0.0001). Lambs on E+/CS consumed less hay than lambs on E-/CS (P = 0.02), but hay intake by lambs on E-/TS and E+/TS did not differ (P = 0.96). Lambs preferred CS to TS during preference tests (P0.0001) and lambs on E+/TS ingested the least amounts of supplement TS and the greatest amounts of supplement CS (P = 0.001). Lambs offered E+ displayed greater body temperatures than lambs offered E- in both phases (P0.05). When offered a choice among the 3 hays, lambs previously exposed to E+ preferred E+ (low content of ergovaline)E-E+ (greater content of ergovaline; P0.001). Thus, decreased concentrations of ergovaline increased rectal temperatures, and affected intake of and preference for tannins and fescue hay. Quebracho tannins did not attenuate the effects of E+ on body temperature and feed intake. Ingestion of E+ reduced intake of quebracho tannins, suggesting that alkaloids in E+ antagonized ingestion of condensed tannins.

To determine the cost effectiveness of sevelamer vs calcium carbonate in patients with chronic kidney disease and not on dialysis (CKD-ND) from the perspective of the National Health Service (NHS) in the UK.A Markov decision analytic model was developed to estimate (1) total life years (LYs), quality-adjusted life years (QALYs), and costs for patients treated with sevelamer or calcium carbonate; and (2) incremental costs per LY gained (LYG) and per QALY gained for sevelamer vs calcium carbonate. Data informing probability transitions to all-cause death and dialysis inception in CKD-ND patients were taken directly from the INDEPENDENT-CKD study and were extrapolated beyond the 3-year clinical trial using Weibull regression analysis. Estimates of health utility and costs (in £2011) were derived from the published literature.Over a lifetime horizon, sevelamer treatment resulted in a gain of 2.05 LYs and 1.56 QALYs per patient, an increase of £37,282 in total costs per patient vs calcium carbonate (3.5% discount), and a per-patient cost of £18,193/LYG and £23,878/QALY gained. Results were robust to alternative assumptions in key parameters; results were most sensitive to alternative assumptions regarding the mean daily dose of sevelamer, impact of sevelamer on dialysis initiation, cost of dialysis, and health utility estimates. The probabilistic sensitivity analysis showed that sevelamer was cost-effective vs calcium carbonate in 93% of simulations at a willingness-to-pay threshold of £30,000/QALY gained.While the model simulated a real-world clinical setting, this analysis was subject to limitations common to all decision analytic models, in that it used a mix of data sources and relied on several assumptions. Not all variables that impact real-world outcomes and costs were included in this model.Sevelamer is a cost-effective option compared to calcium carbonate for the first-line treatment of hyperphosphatemia in CKD-ND patients in the UK.

The pneumocandins are semisynthetic analogs of echinocandin-like compounds that have shown efficacy in animal models of systemic candidiasis, disseminated aspergillosis, and pneumocystis pneumonia. However, the most common form of Aspergillus infection in susceptible patients is pulmonary aspergillosis, which was not directly tested in the mouse models used in the past. We have evaluated three pneumocandins, L-693,989, L-731,373, and L-733,560, in a rat model of pulmonary aspergillosis. Male Sprague-Dawley rats were treated for 2 weeks with cortisone and tetracycline and fed a low-protein diet before being inoculated via the trachea with 10(6) conidia of Aspergillus fumigatus H11-20. In the absence of drug treatment, the animals developed a progressive, rapidly fatal bronchopneumonia. All three pneumocandins at doses of 5 mg/kg (intraperitoneally [i.p.] every 12 h [q12h]) were effective in delaying mortality in this model. Survival at day 7 postinfection was 20% among controls (n = 10 for all groups), while it was 60, 80, and 90% in groups that were treated with L-693,989, L-731,373, and L-733,560, respectively. In another trial, survival at day 7 postinfection was 25% among controls (n = 8 for all groups); it was 87.5% in a group treated with amphotericin B (0.5 mg/kg i.p. q12h) and was 100% in a group treated with L-733,560 (0.625 mg/kg i.p. q12h). In a separate trial, aerosol L-693,989 administered 2 h before infection (5 mg/kg) delayed mortality. Eight of the 10 animals treated with aerosol L-693,989 survived for 7 days, whereas only 2 of 10 control animals survived. We conclude that the pneumocandins we tested were highly effective in an animal model of pulmonary aspergillosis.

This study evaluates the possible interaction between chronic oat bran intake and the postmeal metabolic response. Six normolipidemic men consumed three different diets for 14 d, at the end of which they consumed a test meal. The diets were C (control), basal low-fiber diet (15.6 g fiber/d) and a low-fiber (2.8 g fiber) test meal; OB (oat bran), basal low-fiber diet and a 40-g oat bran-enriched test meal (12.8 g fiber); and OB-A (oat bran-adaptation), 14-d oat bran (40 g/d) supplemented diet (23.8 g fiber/d) and an oat bran test meal (12.8 g fiber). The diets were fed in a random order. Fasting and postmeal blood samples were obtained for 7 h and lipoproteins were isolated. Adding oat bran to the test meals markedly reduced the postmeal insulin rise (P < 0.05). Compared with the low-fiber control diet, the effects elicited postprandially by adding oat bran to a single meal were enhanced after 14 d of oat bran feeding, ie, increased plasma triglycerides, phospholipids, and free cholesterol; decreased plasma esterified cholesterol; increased chylomicron and small-sized triglyceride-rich lipoprotein triglycerides; increased LDL and HDL free cholesterol; and decreased HDL esterified cholesterol. Thus, chronic oat bran feeding alters the postmeal response in human subjects.

The avoidance of hospitalizations and the maintenance of in-center dialysis sessions in patients receiving dialysis for end-stage renal disease (ESRD) have obvious benefits to patients, dialysis providers and payers. Benefits include better continuity of care, better patient outcomes, improved quality of life, and reduced healthcare expenditures. The objective of this study was to quantify, from the perspective of a dialysis provider in the US, the potential impact of sevelamer versus calcium-based binders (CBBs) on hospitalization days and maintenance of in-center dialysis sessions among hyperphosphatemic dialysis patients.A Microsoft Excel-based model was developed to simulate the number of missed dialysis sessions among three hypothetical cohorts of hyperphosphatemic patients treated with either sevelamer or CBBs. The cohorts were characterized by their size to represent a small, mid-size, or large dialysis organization (75, 30,000, and 120,000 patients, respectively). In any given month, a patient in the model could receive dialysis treatments within the center, experience a hospitalization, or die. Treatment-specific monthly survival rates, hospitalization rates, length of stay, and binder dosages were derived from the Dialysis Clinical Outcomes Revisited (DCOR) study. A dialysis schedule of three treatments per week was assumed. Analyses were conducted for a 1-year time horizon.For a small dialysis center, CBBs were associated with an increased number of missed in-center dialysis treatments (447) compared to sevelamer (395). Thus, sevelamer use avoided 52 missed in-center dialysis sessions during 1 year of treatment compared to CBBs. The magnitude of sevelamer's impact on maintaining in-center dialysis treatments increased with the size of the dialysis organization; for a mid-size dialysis organization sevelamer use avoided 20,571 missed in-center dialysis sessions and for a large dialysis organization sevelamer use avoided 82,286 missed in-center dialysis sessions.Treatment of hyperphosphatemic dialysis patients with sevelamer relative to CBBs was associated with a reduction in the number of missed in-center dialysis treatments across small, mid-size, and large dialysis organizations. This reduction could contribute to improved patient outcomes via undisrupted delivery of care within the dialysis clinic. The use of sevelamer versus CBBs could also result in an increased number of reimbursement payments to dialysis clinics and providers by avoiding missed in-center dialysis sessions due to hospitalization.

Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no-cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects.

Mycobacterium haemophilum is an emerging opportunistic pathogen, and since 1989, infections caused by this organism have been identified more frequently in the New York City area than in any other region of the United States. A DNA fingerprinting method, based on restriction fragment length polymorphisms (RFLPs) was developed. A genomic library of M. haemophilum isolate 1A was constructed; screening the library yielded a recombinant strain that incorporated a genetic element present in multiple copies in the M. haemophilum genome. This clone was used to produce a probe for RFLP analyses of PvuII digests of genomic DNA. We used this probe to determine the RFLP patterns of 43 clinical isolates of M. haemophilum from 28 patients. A total of six distinct patterns were observed. Two patterns, designated types 1 and 2, accounted for 91% of the infections in patients from the New York City area. Two isolates from Arizona had identical patterns but were distinct from those of New York isolates, and an isolate from Israel, the type strain, had another distinct pattern (type 6). The type 6 pattern was also seen in a recent isolate from Norway. All of the type 1 isolates and 60% of the type 2 isolates were recovered from patients with AIDS in the New York City area. This molecular subtyping method should provide a useful tool for epidemiological studies and may help identify the associated risk factors, vehicles, and possible reservoirs of this newly emerging pathogen.

Muscle relaxation times can now be measured accurately with magnetic resonance imaging (MRI), distinguishing working muscles from non-working muscles. A correlation between T2 increase and work intensity has been shown in healthy volunteers. The small amount of data on T1 relaxation times is contradictory. In addition, all the published studies have concerned short-duration exercise in subjects of unknown training level. The goals of this study were (i) to determine T1 and T2 variations in thigh muscles after long dynamic exercise, (ii) to analyse the effects of training and (iii) to determine the relationship between power output and relaxation times after exercise. Sedentary men, soccer players and tri-athletes performed submaximal dynamic exercise at a constant heart rate for 15 min. MRI was performed before and 5 min after the end of exercise. The results showed (i) that T1 increased in parallel to T2 in anterior thigh muscles and (ii) that multiple correspondence analysis and hierarchical ascending classification can discriminate three subjects classes according to power output, training level and relaxation times, which fitted well with our three groups of subjects.

Background: The rapid increase in mobile telephone use has generated concern about possible health risks of radiofrequency electromagnetic fields from these devices. Methods: A case-control study of 1105 patients with newly diagnosed acoustic neuroma (vestibular schwannoma) and 2145 controls was conducted in 13 countries using a common protocol. Past mobile phone use was assessed by personal interview. In the primary analysis, exposure time was censored at one year before the reference date (date of diagnosis for cases and date of diagnosis of the matched case for controls); analyses censoring exposure at five years before the reference date were also done to allow for a possible longer latent period. Results: The odds ratio (OR) of acoustic neuroma with ever having been a regular mobile phone user was 0.85 (95% confidence interval 0.69-1.04). The OR for >= 10 years after first regular mobile phone use was 0.76 (0.52-1.11). There was no trend of increasing ORs with increasing cumulative call time or cumulative number of calls, with the lowest OR (0.48 (0.30-0.78)) observed in the 9th decile of cumulative call time. In the 10th decile (>= 1640 h) of cumulative call time, the OR was 1.32 (0.88-1.97); there were, however, implausible values of reported use in those with >= 1640 h of accumulated mobile phone use. With censoring at 5 years before the reference date the OR for >= 10 years after first regular mobile phone use was 0.83 (0.58-1.19) and for >= 1640 h of cumulative call time it was 2.79(1.51-5.16). but again with no trend in the lower nine deciles and with the lowest OR in the 9th decile. In general, ORs were not greater in subjects who reported usual phone use on the same side of the head as their tumour than in those who reported it on the opposite side, but it was greater in those in the 10th decile of cumulative hours of use. Conclusions: There was no increase in risk of acoustic neuroma with ever regular use of a mobile phone or for users who began regular use 10 years or more before the reference date. Elevated odds ratios observed at the highest level of cumulative call time could be due to chance, reporting bias or a causal effect. As acoustic neuroma is usually a slowly growing tumour, the interval between introduction of mobile phones and occurrence of the tumour might have been too short to observe an effect, if there is one. (C) 2011 Elsevier Ltd. All rights reserved.

Background: DNA-based vaccines have been safe but weakly immunogenic in humans to date. Methods and Findings: We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines. Conclusions: This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate. Trial Registration: ClinicalTrials.gov NCT00545987

Azithromycin, rifabutin, and rifapentine were used to treat or prevent disseminated Mycobacterium avium complex (MAC) infections produced in rats immunosuppressed with cyclosporine. Animals with bacteremic infections were treated 1 week after intravenous inoculation with 10(7) CFU of MAC with azithromycin, 100 mg/kg of body weight administered subcutaneously for 5 days and then 75 mg/kg on Monday, Wednesday, and Friday, or with rifabutin or rifapentine, 20 mg/kg administered intraperitoneally on Monday through Friday. All three drugs showed efficacy after 1 and 2 months. Rifabutin cleared the organisms from tissues more rapidly than azithromycin or rifapentine. To approximate prophylaxis, treatment was started 2 weeks before intravenous inoculation with 10(4) organisms. MAC infections were undetectable in treated animals after 4 months, while control animals had disseminated infections. These findings support the rationale for clinical trials of treatment and prophylaxis with these agents. The cyclosporine-treated rat appears to be a useful model in which to evaluate compounds for the treatment and prophylaxis of disseminated MAC infections.

The most advanced and fastest growing form of bariatric surgery is laparoscopic gastric bypass. Very little is known about population-based 180-day laparoscopic bypass costs, complication rates, readmission rates, and post-operative care.To examine the 6-month costs and outcomes of laparoscopic vs. open bariatric bypass surgery using a national population-based sample.We use the 1998-2003 Nationwide Inpatient Sample to examine national trends in the rate of laparoscopic bypass. To examine postoperative outcomes, we examine insurance claims for 2,384 bariatric bypass surgeries, at 308 hospitals, among a population of 5.6 million non-elderly people covered by large employers across 49 states in 2001 and 2002. Multivariate logit regression analysis is performed to risk-adjust outcomes.180-day outcomes: 12 complications specific to bariatric surgery and 44 general post-operative conditions, readmission rates, ER rates, and expenditures following bariatric surgery.Between 1998 and 2003, the national percentage of bariatric bypass surgeries that were laparoscopic grew from 1.5 to 17.1%. There was no significant difference in in-hospital mortality between laparoscopy and open surgery. With the 2001-2002 claims data, we find that of the patients having bypass surgery, men had 48% lower odds of having laparoscopy and that high bariatric volume hospitals were close to four times more likely to use laparoscopy. Laparoscopic bypass, compared with open bypass, had 34% lower odds of a complication during the initial surgical stay, 27% lower odds of a 30-day complication, but no statistically significant difference in 180-day complications. Laparoscopy had 49% higher odds of having the general 44 post-operative conditions, with 45% higher odds of a readmission and 54% higher odds of an ER visit. However, overall, laparoscopy resulted in a 23% lower number of hospital days and 9% lower 180-day expenditures.The laparoscopic cost-savings during the less invasive initial surgery stay outweigh the increase in post-discharge utilization. Further cost-savings will only emerge from laparoscopy only if its late post-operative complications are reduced. More cost-savings will also emerge as more physicians switch to the use of laparoscopy for bypass surgery.

Maintenance of nitric oxide (NO) homeostasis is an important concept for myocardial protection. Here, we have investigated the NO pathway by analysing total nitrate concentration (NOx) and NO synthase (NOS) isoforms expression as well as the myocardial integrity by lactate dehydrogenase and creatine kinase contents in the rat heart graft arrested by CRMBM solution, submitted to 3 hr cold ischemia in the same solution and 24 hr blood reperfusion following heterotopic abdominal heart transplantation. NOx level was similar to baseline value after ischemia and significantly increased after 24 hr reperfusion. NOS isoforms expression was highly modulated after cold ischemia followed by blood reperfusion. Endothelial NOS expression was decreased after ischemia but restored after 24 hr reperfusion. Neuronal NOS expression was drastically decreased after ischemia and 24 hr reperfusion. Inducible NOS protein was present only after 24 hr reperfusion. Cold ischemia induced a severe loss of creatine kinase without any modification after blood reperfusion. In conclusion, we show here that CRMBM solution did not increase NO production during ischemia but induced an enhanced synthesis of NO during reperfusion which may be related to restoration of endothelial NOS expression and/or induction of inducible NOS expression.

Clonidine, an alpha 2 adrenoreceptor agonist, has nonopiate antinociceptive properties, which might be an alternative for postoperative analgesia free of opioid-induced side effects. To document the analgesic properties of intravenous clonidine during the postoperative period, 50 ASA physical status 1 patients, immediately after spinal fusion, were randomly assigned to two groups, blindly administered either clonidine (5 micrograms/kg infused the 1st h and then 0.3 microgram-1.kg-1.h-1 during 11 h) or a placebo. A visual analog scale graded from 0 (no pain) to 100 mm was used to assess pain before clonidine or placebo administration (T0), at the end of the loading dose (T1) and then every 2 h (T3, T5, T7, T9, and T11). Morphine (0.1 mg/kg) was administered intramuscularly after each pain measurement if the score was greater than 50 mm. No morphine was given at T0. Hemodynamics, blood gases and plasma clonidine concentrations were measured each time the pain score was measured. The pain score decreased from 42 +/- 5 to 26 +/- 3 mm (mean +/- standard error) in the clonidine group whereas it was unchanged in the placebo group despite a greater morphine requirement (dose for each patient: 3.8 +/- 1 vs. 10.8 +/- 1.2 mg). Clonidine delayed the onset of pain and the first request for morphine injection. Mean arterial pressure decreased to 74 +/- 2 mmHg in the clonidine group (-26 +/- 2 vs. -15 +/- 2% in the placebo group at T11) despite a significant increase in the cumulative fluid volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystic fibrosis (CF), is the most common life-shortening autosomal recessive disorder in Caucasians. It is caused by mutations in a single gene on the long arm of chromosome 7 that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CF is characterized by abnormal Na+ and Cl- ion transport in several tissues, including the lungs, pancreas, gastrointestinal tract, liver, sweat glands, and male reproductive system. Progressive pulmonary disease is the dominant clinical feature of CF and accounts for morbidity and mortality. The inflammation characterized by an overabundance of activated neutrophils and macrophages on the respiratory epithelial surface is associated to a high production of reactive oxygen species (ROS) which contribute to the pathogenesis of cystic fibrosis. ROS could have different origins but the role of the NADPH oxidase system is essential. The "NADPH oxidases" (NOX/DUOX) family is an enzymatic complex formed by cytosolic and membrane subunits. Until now several homologues of the phagocytic NADPH oxidase have been identified in different tissues and it has been shown that the lungs preferentially expressed DUOX1-2. Thus, DUOX1-2 could be implicated in the anti-infectious defense system. The role of DUOX enzymes as a source of ROS in cystic fibrosis is examined as they could contribute to a better understanding of molecular mechanisms in CF. Moreover they could be a potential target for a new therapeutic approach.

The aim of this study was to evaluate the usefulness of systematic screening of asymptomatic neurofibromatosis type 1 (NF1) children with magnetic resonance imaging (MRI).We retrospectively reviewed the MRIs of children diagnosed with NF1 disease according to the National Institutes of Health criteria, who had been followed for at least 1 year by the department of pediatric neurology (Lyon, France). Brain MRI was systematically performed in asymptomatic patients under 6 years of age.One hundred patients with a median follow-up of 3.7 years (range, 1-8.6 years) were reviewed. Brain MRI was performed in a total of 94 children. Nine optic pathway gliomas were detected in symptomatic patients. Six children had symptoms caused by the tumor. Gliomas remained stable in 10 patients; 1 symptomatic glioma in an 8-year-old girl required treatment. Spontaneous regression was seen in 1 patient.Our results suggest that MRI screening of asymptomatic children to detect optic pathway gliomas does not improve the therapeutic decision and should not be performed systematically. We suggest further investigation in collaboration with the French NF Network.

In a model of bronchopulmonary aspergillosis terbinafine did not improve survival of experimental animals in doses up to 80 mg/kg/day despite adequate lung concentrations. Pretreatment and aerosolization of the compound were also ineffective. Terbinafine was markedly less active in vitro when serum was used instead of Yeast-Nitrogen-Glucose-broth. It is concluded that a lack of bioavailability in the presence of serum may explain the lack of activity of terbinafine in experimental aspergillosis.

The National Cholesterol Education Program (NCEP) for high blood cholesterol case-finding and treatment recommended discrete treatments according to the results of sequential mea surements of continuous variables (total and low-density lipoprotein cholesterol [LDL-C]). These measurements are subject to intra- and interindividual variability. The authors describe a computer simulation of the NCEP that acknowledges these complexities. The simulation reduces the NCEP into steps, which are represented in a decision tree. The calculation of probabilities at chance nodes takes into account the conditional nature of sequential mea surements of blood cholesterol. The simulation tracks medical resource use and estimates LDL-C reductions within 20 strata, each defining 5% of population distribution for LDL-C. This approach enables a detailed representation of the case-finding process—the sequence of blood cholesterol tests and associated cut-off values that identify individuals needing more intensive evaluation and treatment. Key words: mathematical modeling; screening programs; hypercholesterolemia. (Med Decis Making 1990;10:135-146)

Gliomas represent 50% of primary brain tumors, and their prognosis remains poor despite the advances in diagnosis and therapeutic strategies. Low grade gliomas (LGG) are infiltrative tumors and they constantly undergo malignant transformation. Metabolic exploration of human gliomas in vivo, in animals and by using cell culture models showed important differences between tumor tissues and normal brain tissues, which can provide new markers for diagnosis, prognosis and therapeutic targets. In this study, energetic and oxidant metabolisms were explored in biopsy extracts of LGG obtained from the centre and the periphery of tumors. Metabolic pattern of these tumors was explored and the differences between the centre and the periphery pointed. Our study showed a metabolic heterogeneity between tumors, with hypermetabolic and hypometabolic profiles. Lactate to pyruvate ratio was1, suggesting that the energy metabolism in LGG is glycolytic in nature, particularly in the centre of the tumors. Peripheral samples of tumors showed increased glucose consumption and cytochrome c oxidase activity. Lipid peroxidation and catalase activity were also increased in the periphery compared to the centre of tumors. A relationship between the main antioxidant and energy metabolism enzymes activities was observed, suggesting that periphery of tumors is more active metabolically and more resistant to free radical injury.

Meningioma is an unfrequent optic nerve tumor. Clinical symptoms are not specific, and pathology exam not easily accessible. The diagnosis is usually based on imaging findings. We report our experience, based on twenty patients. Most of them were middle-aged women (mean age=47 years old). The optic nerve meningioma (ONM) was often revealed by visual dysfunction. Ophthalmological evaluation was altered in most patients (visual acuity, visual fields, fundi). The gold-standard exam was MRI of the optic nerve, with and without gadolinium, and with fat-sat sequences. Thirty percent of the lesions remain stable without treatment. Functional prognosis has been improved only by conformal fractionated radiotherapy, but indications and modalities remain to be specified.

Mortality related to complications of cirrhosis is increasing in patients with insulin-resistance factors. Hyperlipidaemic patients have multiple risk factors of insulin resistance. It is impossible to perform liver biopsy in such a large number of hyperlipidaemic patients to identify patients with advanced liver fibrosis or with steatohepatitis (non-alcoholic steatohepatitis, NASH).To use the non-invasive biomarkers, FibroTest (FT), SteatoTest and NashTest, and to assess the prevalence of advanced liver disease in a large population of hyperlipidaemic patients.A consecutive cohort of hyperlipidaemic patients was followed prospectively in a lipid centre and the sera were analysed retrospectively.A total of 2834 subjects were included: 1909 hyperlipidaemic patients and 925 blood donors (BD). Advanced fibrosis was identified by FT in 53/1909 (2.8%) hyperlipidaemic patients vs. 0/925 BD (0%) (P0.0001); advanced steatosis in 569/1893 hyperlipidaemic patients (30.1%) vs. 8/164 (4.9%) BD (P0.0001) and NASH in 132/1893 (7%) vs. 0/164 (0%), respectively (P0.0001). There was a highly significant and linear association between the number of metabolic syndrome factors and liver disease prevalence - the highest being for type 2 diabetics: advanced steatosis 66%, NASH 24% and advanced fibrosis 6%. CONCLUSIONS The prevalence of fibrosis, steatosis and NASH in hyperlipidaemic patients appears to be high (3%, 30% and 7%, respectively). Biomarkers could be useful for screening of advanced fibrosis and NASH in patients with several metabolic syndrome factors, to prevent liver mortality.

The alexithymia construct is mainly characterized by a difficulty in identifying and expressing feelings that is thought to reflect a deficit in cognitive processing and regulation of emotional states. During the last decade, alexithymia has been associated with a large variety of medical and psychiatric disorders in the adult population. Although adolescence is probably an opportune time to explore processes of emotion regulation, alexithymia has been rarely examined during this period. The 20-item Toronto alexithymia scale (TAS-20) is the most widely used self-report measure of alexithymia. For this scale, a three-factor structure was proposed: difficulty identifying feelings (DIF), difficulty describing feelings (DDF) and externally oriented thinking (EOT). Research has yielded considerable evidence that the TAS-20 is a reliable and valid measure of alexithymia in normal and clinical adult samples. To date, no psychometric data concerning the use of the TAS-20 with adolescent samples are available.The aim of the study is to provide psychometric data concerning the TAS-20 when administered to healthy adolescents. Furthermore, in a developmental perspective, this study explores the evolution of alexithymia across age groups in adolescence.The TAS-20 was administered to a sample of 264 adolescents aged from 14 to 19 years. In order to compare alexithymia across age groups, the sample was divided into three groups: group 1 (16 years old), group 2 (16-17 years old) and group 3 (17 years old).Results of a confirmatory factor analysis (CFA) confirmed that the data fitted well to the three-factor model of the TAS-20 (chi(2)/df=2.22, GFI=0.88, AGFI=0.84 and RMSEA=0.068). The internal reliability coefficients and mean interitem correlations are acceptable for DIF (alpha0.60; mean interitem correlation=0.22) and good for DDF (alpha0.70, mean interitem correlation=0.33). As often reported in most translations of the TAS-20, the internal reliability of EOT is poor. Results of a one-way Anova showed a significant linear trend indicating that, with age, the level of alexithymia (TAS-20 total score), the difficulty in identifying feelings and the externally oriented thinking decreased.This study demonstrated that the TAS-20 has sufficient construct validity in a non-clinical sample of adolescents. Our results support the idea that adolescence period is associated with the development of the ability to regulate emotions.

Use of cell phones has increased dramatically since 1992 when they were first introduced in France. Certain electromagnetic fields (at extremely low frequency) have been recognized as possibly carcinogenic by the International Agency for Research on Cancer. Given the use of radiofrequency technology in cell phones, the rapid increase in the number of cell phones has generated concerns about the existence of a potential health hazard. To evaluate the relationship between the use of cell phones and the development of tumors of the head, a multicentric international study (INTERPHONE), coordinated by the International Agency for Research on Cancer, was carried out in 13 countries. This publication reports the results of the French part of the INTERPHONE study.INTERPHONE is a case-control study focused on tumors of the brain and central nervous system: gliomas, meningiomas and neuromas of cranial nerves. Eligible cases were men and women, residents of Paris or Lyon, aged 30-59, newly diagnosed with a first primary tumor between February 2001 and August 2003. The diagnoses were all either histologically confirmed or based upon unequivocal radiological images. Controls were matched for gender, age (+/-5 years) and place of residence. They were randomly drawn from electoral rolls. Detailed information was collected for all subjects during a computer-assisted face-to-face interview. Conditional logistic regression was used to estimate the odds ratio (OR) for an association between the use of cell phones and risk of each type of cancer.Regular cell phone use was not associated with an increased risk of neuroma (OR=0,92; 95% confidence interval=[0.53-1.59]), meningioma (OR=0,74; 95% confidence interval=[0.43-1.28]) or glioma (OR=1.15; 95% confidence interval=[0.65-2.05]). Although these results are not statistically significant, a general tendency was observed for an increased risk of glioma among the heaviest users: long-term users, heavy users, users with the largest numbers of telephones.No significant increased risk for glioma, meningioma or neuroma was observed among cell phone users participating in Interphone. The statistical power of the study is limited, however. Our results, suggesting the possibility of an increased risk among the heaviest users, therefore need to be verified in the international INTERPHONE analyses.

We report the case of a 57-year-old man who presented bilateral subacute and painless optic neuropathy after meningopolyradiculitis revealing a primary human immunodeficiency virus infection. Both antiretroviral and steroid treatments were ineffective. Clinical symptoms and evolutive pattern were consistent with a mechanism of microvascular ischaemia of the optic nerve head. Optic neuropathies related to HIV infection are rare compared to those resulting from opportunistic infections. There are several pathophysiological mechanisms involved.

Background: The purpose of this study was to characterize current patterns of treatment of glaucoma and ocular hypertension and to examine the effect of those patterns on intraocular pressure (IOP) control and persistence on therapy. Methods: A retrospective chart review was conducted at 3 ophthalmology practices in Alberta. Data were collected for patients who had begun therapy for newly diagnosed primary open-angle glaucoma or ocular hypertension between May 1, 1998, and Sept. 30, 1999 (phase 1), and for patients who had begun second-line therapy after initial therapy with a β-blocker had failed (phase 2). Data were collected for a minimum of 24 months for phase 1 and a minimum of 18 months for phase 2. Results: We included 115 patient charts in phase 1 and 93 in phase 2. In each phase, the patients for whom latanoprost had been prescribed in unfixed combination with a β-blocker had the greatest mean percentage reduction in IOP at month 24, and the patients for whom latanoprost had been prescribed alone or in combination with a β-blocker were more likely to still be on initial therapy at month 24;the difference in persistence on therapy was statistically significant only in phase 1 ( p = 0.001). The mean number of switches in therapy was smaller in phase 1 than in phase 2 in all therapy groups. Interpretation: Compared with other first- and second-line forms of therapy, treatment with latanoprost, alone or in combination with a β-blocker, was associated with greater reductions in IOP, better therapeutic persistence, fewer therapy switches and fewer ophthalmologist visits over a 2-year period.

In this study we describe the results of adoption of local guidelines for conscious sedation (CS) during endoscopic-retrograde-cholangiopancreatography (ERCP) in Belluno Hospital. Local guidelines were created referring to SIED-SIAARTI-ANOTE guidelines for CS in gastrointestinal endoscopy.Between January 2002 and February 2004, 300 ERCPs to be performed under CS have been scheduled. According to local guidelines CS was performed by the gastroenterologist assisted by an anesthesia nurse. An anesthesiologist was always on call in the intensive care unit (ICU) for emergencies and could be on the site in less than 5 min.In 278 patients the procedure was performed safely and effectively by the gastroenterologist without any anesthesiological assistance. At follow-up controls patients had either positive or no recollection of the procedure. An anesthesiologist was called in 13 cases to perform deep sedation and in 9 cases to deal with undesired effects (arterial hypertension in 5 patients, 1 episode of bradycardia, 1 of ventricular tachycardia, 1 of atrial fibrillation and 1 of hypoxia).In our experience, CS during ERCP can be safely performed autonomously by a gastroenterologist in the majority of cases. Drug prescription protocol and the presence of an anesthesia nurse create ideal conditions for the operator, patient comfort and good results with a low incidence of undesired events and few calls for the anesthesiologist. To allow safe and effective performance of CS, the Department of Anesthesia should promote the in-service training and up dating of gastroenterologists and anesthesia nurses.

Long duration ischemia in hypothermic conditions followed by reperfusion alters membrane transport function and in particular Na,K-ATPase. We compared the protective effect of two well-described cardioplegic solutions on cardiac Na,K-ATPase activity during reperfusion after hypothermic ischemia. Isolated perfused rat hearts (n = 10) were arrested with CRMBM or UW cardioplegic solutions and submitted to 12 hr of ischemia at 4 degrees C in the same solution followed by 60 min of reperfusion. Functional recovery and Na,K-ATPase activity were measured at the end of reperfusion and compared with control hearts and hearts submitted to severe ischemia (30 min at 37 degrees C) followed by reflow. Na,K-ATPase activity was not altered after 12 hr of ischemia and 1 hr reflow when the CRMBM solution was used for preservation (55 +/- 2 micromolPi/mg prot/hr) compared to control (53 +/- 2 micromol Pi/mg prot/hr) while it was significantly altered with UW solution (44 +/- 2 micromol Pi/mg prot/hr, p0.05 vs control and CRMBM). Better preservation of Na,K-ATPase activity with the CRMBM solution was associated with higher functional recovery compared to UW as represented by the recovery of RPP, 52 +/- 12% vs 8 +/- 5%, p0.05 and coronary flow (70 +/- 2% vs 50 +/- 8%, p0.05). The enhanced protection provided by CRMBM compared to UW may be related to its lower K+ content.