Formes sévères d'hypersensibilité médicamenteuse retardée [Severe delayed drug hypersensitivity reactions].

Although most delayed drug hypersensitivity reactions are mild and show rapid improvement after drug discontinuation, there are severe systemic and/or cutaneous drug reactions which may be life-threatening. These entities are discussed here, namely DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). Early detection of warning signs and symptoms may help to take appropriate measures precociously.

Immediate improvement in coronary flow reserve after alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: To examine whether percutaneous alcohol septal ablation affects coronary flow reserve (CFR) in patients with hypertrophic cardiomyopathy (HCM). METHODS: CFR was measured immediately before and after septal ablation in patients with symptomatic obstructive HCM. CFR was also obtained in normal subjects (NL) for comparison. RESULTS: Patients with HCM (n = 11), compared with NL (n = 22), had a lower mean (SD) baseline CFR (1.96 (0.5) vs 3.0 (0.7), p<0.001), a lower coronary resistance (1.04 (0.45) vs 3.0 (2.6), p = 0.002), a higher coronary diastolic/systolic velocity ratio (DSVR; 5.1 (3.0) vs 1.8 (0.5), p = 0.04) and a lower hyperaemic coronary flow per left ventricular (LV) mass (0.73 (0.4) vs 1.1 (0.6) ml/min/g, p = 0.007). Septal ablation in the HCM group (n = 7) reduced the outflow tract gradient but not the left atrial or LV diastolic pressures. Ablation resulted in immediate normalisation of CFR (to 3.1 (1), p = 0.01) and DSVR (to 1.9 (0.8), p = 0.09) and an increase in coronary resistance (to 1.91 (0.6), p = 0.02). This was probably related to an improvement in the systolic coronary flow. CONCLUSIONS: This study demonstrates that successful septal ablation in patients with symptomatic HCM results in immediate improvement in CFR, which is reduced in HCM partly because of the increased systolic contraction load.

Variation in thermal performance and reaction norms among populations of Drosophila melanogaster.

The major goal of evolutionary thermal biology is to understand how variation in temperature shapes phenotypic evolution. Comparing thermal reaction norms among populations from different thermal environments allows us to gain insights into the evolutionary mechanisms underlying thermal adaptation. Here, we have examined thermal adaptation in six wild populations of the fruit fly (Drosophila melanogaster) from markedly different natural environments by analyzing thermal reaction norms for fecundity, thorax length, wing area, and ovariole number under ecologically realistic fluctuating temperature regimes in the laboratory. Contrary to expectation, we found only minor differences in the thermal optima for fecundity among populations. Differentiation among populations was mainly due to differences in absolute (and partly also relative) thermal fecundity performance. Despite significant variation among populations in the absolute values of morphological traits, we observed only minor differentiation in their reaction norms. Overall, the thermal reaction norms for all traits examined were remarkably similar among different populations. Our results therefore suggest that thermal adaptation in D. melanogaster predominantly involves evolutionary changes in absolute trait values rather than in aspects of thermal reaction norms.

Unusual association of diseases/symptoms: Encephalitis with herpes simplex-2 in the cerebrospinal fluid and anti-RI (ANNA-2) antibodies: an infectious or a paraneoplastic syndrome?

We report on a 70-year-old woman with partial complex status epilepticus who was initially diagnosed with herpes simplex-2 (HSV-2) encephalitis, based on brain magnetic resonance imaging (MRI) findings, cerebrospinal fluid (CSF) lymphocytic pleocytosis and HSV-2 DNA detection by polymerase chain reaction (PCR) in the CSF, but without improvement on intravenous acyclovir. Anti-Ri antibodies were positive and computed tomography (CT) investigations revealed a small cell carcinoma at biopsy suggesting paraneoplastic encephalitis. The outcome was unfavourable and the autopsy showed typical features of paraneoplastic encephalitis but no evidence of viral inclusions. This case report is interesting because: (1) it is the first report of an autopsy proven paraneoplastic widespread encephalitis with anti-Ri antibodies; (2) despite a positive HSV-2 PCR in the CSF, there was no sign of herpetic infections of the nervous system; and (3) it illustrates the fact that if paraneoplastic antibodies are usually good markers of the underlying tumour, they are not always predictive of neurological deficits.

Improvement of cardiovascular risk prediction: time to review current knowledge, debates, and fundamentals on how to assess test characteristics.

Cardiovascular risk assessment might be improved with the addition of emerging, new tests derived from atherosclerosis imaging, laboratory tests or functional tests. This article reviews relative risk, odds ratios, receiver-operating curves, posttest risk calculations based on likelihood ratios, the net reclassification improvement and integrated discrimination. This serves to determine whether a new test has an added clinical value on top of conventional risk testing and how this can be verified statistically. Two clinically meaningful examples serve to illustrate novel approaches. This work serves as a review and basic work for the development of new guidelines on cardiovascular risk prediction, taking into account emerging tests, to be proposed by members of the 'Taskforce on Vascular Risk Prediction' under the auspices of the Working Group 'Swiss Atherosclerosis' of the Swiss Society of Cardiology in the future.

Improvement of Longitudinal Joints in Asphalt Pavement, HR-215, 1987

Research is reported which attempted to identify construction procedures that will provide an improved centerline joint on asphalt concrete pavements. Various construction procedures and their evaluation are described. Core densities were made and visual inspections were made 3 years after construction. Center cracking was measured at 4, 5, and 6 years. The only procedure to rank the same when comparing cracking and density (delete the 1:1 slope shoe on the edge) is described. This procedure had the highest average density and also the least cracking through 1985. This method provided the best performance for 4 years after construction and involved the removal of the 1:1 slope shoe from the paver when placing the surface course. This method had 9.0% cracked after 4 years and 100% cracked after 6 years of service.

Secondary prevention of osteoporotic fractures : room for improvement

Résumé : Introduction : l'ostéoporose est une maladie fréquente, invalidante, sous-diagnostiquée et sous-traitée, alors qu'il existe des évidences cliniques, densitométriques et biologiques de l'efficacité de la prévention secondaire. Matériel et méthode : dans cette étude, nous décrivons les habitudes de prescription de traitements en prévention secondaire dans les 6 mois qui suivent une fracture de fragilité et définissons les catégories de femmes recevant ou non un traitement, selon le type de fractures, les antécédents fracturaires et les données socio-démographiques. Il s'agit d'une étude suisse de cohorte, prospective de 7609 femmes de 70 ans et plus, suivies de 1998 à 2000. Deux groupes de patientes ont été analysés : celles avec un événement fracturaire durant le suivi (3 sous-groupes de fractures ont été considérés fractures vertébrales, fractures du radius distal et fractures de l'humérus proximal) et celles sans fractures durant le suivi (groupe contrôle). La détermination des événements fracturaires et l'instauration d'un traitement s'est faite par l'envoi aux patientes et à leurs médecins traitants d'un questionnaire structuré. Dans cette étude, le but primaire est de décrire les attitudes médicales de prévention secondaire, le but secondaire d'analyser les motifs dé décision thérapeutique (type de fracture, antécédents de fractures), alors que le but tertiaire cherche à caractériser les femmes non traitées. Résultats, discussion : 7354 femmes ont été incluses dans cette étude, 183 dans le groupe fracture et 7171 dans le groupe contrôle. Le suivi moyen a été de 21 mois. L'introduction d'un traitement est restée rare dans chaque catégorie de fracture et a été plus importante pour le sous-groupe avec fracture vertébrale (p<0.001). La seule donnée associée à l'adjonction d'un traitement a été la présence d'un antécédent anamnestique de fracture vertébrale. La description des attitudes thérapeutiques après une fracture de fragilité, a montré que. 44 % des femmes ne reçoivent aucun traitement en prévention secondaire. Seule la fracture vertébrale et les antécédents de fracture vertébrale entraînent une modification de l'attitude thérapeutique des médecins traitants mais de façon encore insuffisante puisque plus de 50 % des femmes avec une fracture de vertèbre n'ont aucun changement dans leur prise en charge. Les femmes non traitées ne différaient pas des autres sur un plan socio-démographique. Le nombre de patientes dans chaque sous-groupe est relativement faible ce qui limite !a puissance statistique de l'analyse. Les données consistent essentiellement en du « selfreporting » ce qui peut limiter la signification de celles-ci. Les résultats sont cependant suffisamment inquiétants pour que de nouvelles campagnes d'information soient lancées auprès des médecins de .premiers recours quant à la nécessité d'instaurer un traitement efficace lors de la survenue d'une fracture clinique ou radiologique chez une femme en post-ménopause.

Factors favoring a degradation or an improvement in activities of daily living (ADL) performance among nursing home (NH) residents: A survival analysis.

Different factors influence ADL performance among nursing home (NH) residents in long term care. The aim was to investigate which factors were associated with a significant change of ADL performance in NH residents, and whether or not these factors were gender-specific. The design was a survival analysis. The 10,199 participants resided in ninety Swiss NHs. Their ADL performance had been assessed by the Resident Assessment Instrument Minimum Data Set (RAI-MDS) in the period from 1997 to 2007. Relevant change in ADL performance was defined as 2 levels of change on the ADL scale between two successive assessments. The occurrence of either an improvement or a degradation of the ADL status) was analyzed using the Cox proportional hazard model. The analysis included a total of 10,199 NH residents. Each resident received between 2 and 23 assessments. Poor balance, incontinence, impaired cognition, a low BMI, impaired vision, no daily contact with proxies, impaired hearing and the presence of depression were, by hierarchical order, significant risk factors for NH residents to experience a degradation of ADL performance. Residents, who were incontinent, cognitively impaired or had a high BMI were significantly less likely to improve their ADL abilities. Male residents with cancer were prone to see their ADL improve. The year of NH entry was significantly associated with either degradation or improvement of ADL performance. Measures aiming at improving balance and continence, promoting physical activity, providing appropriate nourishment and cognitive enhancement are important for ADL performance in NH residents.

Rapid Improvement in Health-Related Quality of Life (HRQoL) in Gouty Arthritis Patients Treated with Canakinumab (ACZ885) Compared to Triamcinolone Acetonide

Background: Gouty arthritis is a painful inflammatory disease with a significant impact on patients' HRQoL. In gouty arthritis, the inflammatory response is initiated by interleukin-1b (IL-1b) release, due to activation of the NALP3 inflammasome by MSU crystals. Canakinumab, a fully human anti-IL-1b antibody has a long half-life and has been shown to control inflammation in gouty arthritis. This study evaluated changes in HRQoL in gouty arthritis patients following treatment with canakinumab or triamcinolone acetonide (TA).Methods: This was an 8-week, dose-ranging, multi-center, active controlled, single-blind study. Patients (>=18 to <=80 years) experiencing an acute gouty arthritis flare, refractory to or contraindicated to NSAlDs and/or colchicine, were randomized to canakinumab 10, 25, 50, 90, 150 mg sc or TA 40 mg im. HRQoL was assessed as an exploratory endpoint at baseline and different pre-specified time-points using patient reported outcomes evaluating general mental and physical component summary scores and subscale scores of SF-36® (acute version 2) and functional disability (HAQ-DI©). We report HRQoL results for canakinumab 150 mg, the dose that was selected for the Phase III studies.Results: Baseline assessments showed a major impact on the HRQoL during acute gouty arthritis. Compared to TA, canakinumab 150 mg showed greater improvements in SF-36® physical and mental component summary and subscale scores at 7 days post-dose.In the canakinumab 150 mg group, the most severe impairment at baseline was reported for physical functioning and bodily pain; levels of 41.5 and 36.0, respectively, which improved within 7 days to 80.0 and 72.2 (mean increases of 39.0 and 35.6) approaching levels of the general US population (84.2 and 75.2). 8 weeks post-dose patients reached levels of 86.1 and 86.6 (mean increases of 44.6 and 50.6 for physical functioning and bodily pain, respectively) and these were higher than levels seen in the general US population. This was in contrast to patients treated with TA, who showed less improvement within 7 days (mean increases of 23.3 and 21.3 for physical function and bodily pain, respectively). None of the scores reached levels of the general US population 8 weeks post-dose. Functional disability scores, as measured by the HAQ-DI© decreased in both treatment groupsConclusions: All canakinumab doses showed a rapid improvement in physical and mental well-being of gouty arthritis patients based on SF-36® scores, in particular the 150 mg dose. In contrast to the TA group, patients treated with canakinumab showed improvement within 7 days in physical function and bodily pain approaching levels of the general population. The 150 mg dose of canakinumab was selected for further development in Phase III studies.

Quantifying Accuracy Improvement in Sets of Pooled Judgments: Does Dialectical Bootstrapping Work?

Galton (1907) first demonstrated the "wisdom of crowds" phenomenon by averaging independent estimates of unknown quantities given by many individuals. Herzog and Hertwig (2009; hereafter H&H in Psychological Science) showed that individuals' own estimates can be improved by asking them to make two estimates at separate times and averaging them. H&H claimed to observe far greater improvement in accuracy when participants received "dialectical" instructions to consider why their first estimate might be wrong before making their second estimates than when they received standard instructions. We reanalyzed H&H's data using measures of accuracy that are unrelated to the frequency of identical first and second responses and found that participants in both conditions improved their accuracy to an equal degree.

Control of Concrete Deterioration Due to Trace Compounds in Deicers, Phase II, HR-299, 1989

This report presents results of research on ways to reduce the detrimental effects of sulfate-tainted rock salt deicers on portland cement concrete used for highway pavements. Repetitious experiments on the influence of fly ash on the mortar phase of concrete showed significant improvement in resistance to deicing brines is possible. Fifteen to twenty percent by weight of fly ash replacement for portland cement was found to provide optimum improvement. Fly ashes from five sources were evaluated and all were found to be equally beneficial. Preliminary results indicate the type of coarse aggregate also plays an important role in terms of concrete resistance to freeze-thaw in deicing brines. This was particularly true for a porous ferroan dolomite thought to be capable of reaction with the brine. In this case fly ash improved the concrete, but not enough for satisfactory performance. An intermediate response was with a porous limestone where undesirable results were observed without fly ash and adequate performance was realized when 15% fly ash was added. The best combination for making deicer-resistant concrete was found to be with a non-porous limestone. Performance in brines was found to be adequate without fly ash, but better when fly ash was included. Consideration was given to treating existing hardened concrete made with poor aggregate and no fly ash to extend pavement life in the presence of deicers, particularly at joints. Sodium silicate was found to improve freeze-thaw resistance of mortar and is a good candidate for field usage because of its low cost and ease of handling.

Audit report on the Mid-Iowa School Improvement Consortium, Carlisle, Iowa for the year ended June 30, 2013

Audit report on the Mid-Iowa School Improvement Consortium, Carlisle, Iowa for the year ended June 30, 2013

Time-Temperature Strength-Reaction Product Relationships in Lime-Bentonite-Water Mixtures, HR-111, 1965

The interrelation of curing time, curing temperature, strength, and reactions in lime-bentonite-water mixtures was examined. Samples were molded at constant density and moisture content and then cured for periods of from 1 to 56 days at constant temperatures that ranged from 5C to 60C. After the appropriate curing time the samples were tested for unconfined compressive strength. The broken samples were then analyzed by x-ray diffractometer and spectrophotometer to determine the identity of the reaction products present after each curing period. It was found that the strength gain of lime-clay mixtures cured at different temperatures is due to different phases of the complex reaction, lime & clay to CSH(gel) to CSH(II) to CSH(I) to tobermorite. The farther the reaction proceeds, the higher the strength. There was also evidence of lattice substitutions in the structure of the calcium silicate hydrates at curing temperatures of 50C and higher. No consistent relationship between time, temperature, strength, and the S/A ration of reaction products existed, but in order to achieve high strengths the apparent C/S ration had to be less than two. The curing temperature had an effect on the strength developed by a given amount of reacted silica in the cured lime-clay mixture, but at a given curing temperature the cured sample that had the largest amount of reacted silica gave the highest strength. Evidence was found to indicate that during the clay reaction some calcium is indeed adsorbed onto the clay structure rather than entering into a pozzolanic reaction. Finally, it was determined that it is possible to determine the amount of silica and alumina in lime-clay reaction products by spectrophotometric analysis with sufficient accuracy for comparison purposes. The spectrophotometric analysis techniques used during the investigation were simple and were not time consuming.

Improvement of Granular Base Course Materials with Portland Cement, Special Report, HR-99

A highway base course may be defined as a layer of granular material which lies immediately below the wearing surface of a pavement and must possess high resistance to deformation in order to withstand pressures imposed by traffic. A material commonly used for base course construction is crushed limestone. Sources of limestone, acceptable for highway bases in the state of Iowa, occur almost entirely in the Pennsylvanian, Mississippian and Devonian strata. Performance records of the latter two have been quite good, while material from the Pennsylvanian stratum has failed on numerous occasions. The study reported herein is one segment of an extensive research program on compacted crushed limestone used for flexible highway base courses. The primary goals of the total study are: 1. Determination of a suitable and realistic laboratory method of compaction. 2. Effect of gradation, and mineralogy of the fines, on shearing strength. 3. Possible improvement of the shear strength with organic and inorganic chemical stabilization additives. Although the study reported herein deals primarily with the third goal, information gathered from work on the first two was required for this investigation. The primary goal of this study was the evaluation of various factors of stability of three crushed limestones when treated with small amounts of type I Portland cement. Investigation of the untreated materials has indicated that shear strength alone is not the controlling factor for stability of crushed stone bases. Thus the following observations were made in addition to shear strength parameters, to more adequately ascertain the stability of the cement treated materials: 1. Volume change during consolidation and shear testing. 2. Pore pressure during shear. The consolidated-undrained triaxial shear test was used for determination of the above factors.