Histopathological effects of different therapy strategies in experimental sinus thrombosis

The optimal treatment for cerebral venous thrombosis is still under debate. The histological consequences of different treatments have not been systematically studied and may be of value in this debate. Thrombosis of the superior sagittal sinus was induced in rats by topical application of ferric chloride. Animals were treated 6 h after operation with subcutaneous injection of 450 IU/kg enoxaparin twice daily (n = 10), with 10 mg recombinant tissue plasminogen activator (rt-PA)/kg (n = 12), and with 6 mg abciximab/kg (n = 10). Eleven animals were treated with saline (controls), and four animals were sham-operated without thrombosis induction. Animals were killed on day 7. Coronal brain slices were stained with hematoxylin–eosin (HE) and against glial fibrillary acidic protein (GFAP), and factor VIII. Histology was quantified in parasagittal and temporal regions of interest. Compared with controls, counts of pyknotic neurons on HE stain were significantly lower in the enoxaparin group. Counts for GFAP-expressing astrocytes were highest in the enoxaparin (p < 0.001) and rt-PA (p < 0.05)-treated groups. Angiogenesis defined as factor VIII-expressing vessels was significantly (p < 0.01) higher in the enoxaparin and significantly lower (p < 0.01) in the rt-PA group compared with controls. In this animal model, we found histological differences related to the different treatments, which cannot be explained by recanalization and its speed alone.     

Dissatisfied patients after total knee arthroplasty: A registry study involving 114 patients with 8–13 years of follow-up

Background and purpose

In 2003, an enquiry by the Swedish Knee Arthroplasty Register (SKAR) 2–7 years after total knee arthroplasty (TKA) revealed patients who were dissatisfied with the outcome of their surgery but who had not been revised. 6 years later, we examined the dissatisfied patients in one Swedish county and a matched group of very satisfied patients.

Patients and methods

118 TKAs in 114 patients, all of whom had had their surgery between 1996 and 2001, were examined in 2009–2010. 55 patients (with 58 TKAs) had stated in 2003 that they were dissatisfied with their knees and 59 (with 60 TKAs) had stated that they were very satisfied with their knees. The patients were examined clinically and radiographically, and performed functional tests consisting of the 6-minute walk and chair-stand test. All the patients filled out a visual analog scale (VAS, 0–100 mm) regarding knee pain and also the Hospital and Anxiety and Depression scale (HAD).

Results

Mean VAS score for knee pain differed by 30 mm in favor of the very satisfied group (p < 0.001). 23 of the 55 patients in the dissatisfied group and 6 of 59 patients in the very satisfied group suffered from anxiety and/or depression (p = 0.001). Mean range of motion was 11 degrees better in the very satisfied group (p < 0.001). The groups were similar with regard to clinical examination, physical performance testing, and radiography.

Interpretation

The patients who reported poor response after TKA continued to be unhappy after 8–13 years, as demonstrated by VAS pain and HAD, despite the absence of a discernible objective reason for revision.The results of TKA are regarded as being favorable (Robertsson et al. 2000, Kane et al. 2005, Nilsdotter et al. 2009, Carr et al. 2012) with few surgical complications and a revision rate of less than 5% after 10 years (Vessely et al. 2006, Robertsson et al. 2010). Poor outcome after primary TKA, apart from the revision, is between 6% and 14% (Anderson et al. 1996, Hawker et al. 1998, Heck et al. 1998, Robertsson et al. 2000, Robertsson and Dunbar 2001, Brander et al. 2003, Noble et al. 2006, Fisher et al. 2007, Wylde et al. 2008, Kim et al. 2009, Bourne et al. 2010, Scott et al. 2010). The reason for poor outcome after TKA may be related to problems with the knee surgery itself, although it has been suggested that extra-articular causes such as hip disease, spine disorder, vascular disease, or reflex sympathetic dystrophy may contribute. Some studies have suggested that factors not primarily related to structural tissue changes, but of psychological nature instead, may be involved (Wylde et al. 2007, Rolfson et al. 2009).The Swedish Knee Arthroplasty Register (SKAR) registers primary arthroplasties performed in Sweden as well as revisions, and has been estimated to capture 97% of the surgeries performed (SKAR 2012). The SKAR sends questionnaires regarding satisfaction to patients who were operated on during certain time periods (Robertsson et al. 2000, and Dunbar 2001). We used the SKAR to identify patients who had not undergone revision surgery and who were dissatisfied with their outcome 2–7 years after TKA surgery. As a reference we chose an age-, sex-, date-of-surgery-, and hospital-matched control group of highly satisfied patients who were operated during the same period. Our aim was to assess the differences between these 2 patient groups.     

Heat,Heat Waves,and Hospital Admissions among the Elderly in the United States, 1992–2006

Background: Heat-wave frequency, intensity, and duration are increasing with global climate change. The association between heat and mortality in the elderly is well documented, but less is known regarding associations with hospital admissions.Objectives: Our goal was to determine associations between moderate and extreme heat, heat waves, and hospital admissions for nonaccidental causes among Medicare beneficiaries ≥ 65 years of age in 114 cities across five U.S. climate zones.Methods: We used Medicare inpatient billing records and city-specific data on temperature, humidity, and ozone from 1992 through 2006 in a time-stratified case-crossover design to estimate the association between hospitalization and moderate [90th percentile of apparent temperature (AT)] and extreme (99th percentile of AT) heat and heat waves (AT above the 95th percentile over 2–8 days). In sensitivity analyses, we additionally considered confounding by ozone and holidays, different temperature metrics, and alternate models of the exposure–response relationship.Results: Associations between moderate heat and hospital admissions were minimal, but extreme heat was associated with a 3% (95% CI: 2%, 4%) increase in all-cause hospital admissions over the subsequent 8 days. In cause-specific analyses, extreme heat was associated with increased hospitalizations for renal (15%; 95% CI: 9%, 21%) and respiratory (4%; 95% CI: 2%, 7%) diseases, but not for cardiovascular diseases. An added heat-wave effect was observed for renal and respiratory admissions.Conclusion: Extreme heat is associated with increased hospital admissions, particularly for renal causes, among the elderly in the United States.Citation: Gronlund CJ, Zanobetti A, Schwartz JD, Wellenius GA, O’Neill MS. 2014. Heat, heat waves, and hospital admissions among the elderly in the United States, 1992–2006. Environ Health Perspect 122:1187–1192; http://dx.doi.org/10.1289/ehp.1206132     

Neural correlates of anticipation and processing of performance feedback in social anxiety

Fear of negative evaluation, such as negative social performance feedback, is the core symptom of social anxiety. The present study investigated the neural correlates of anticipation and perception of social performance feedback in social anxiety. High (HSA) and low (LSA) socially anxious individuals were asked to give a speech on a personally relevant topic and received standardized but appropriate expert performance feedback in a succeeding experimental session in which neural activity was measured during anticipation and presentation of negative and positive performance feedback concerning the speech performance, or a neutral feedback‐unrelated control condition. HSA compared to LSA subjects reported greater anxiety during anticipation of negative feedback. Functional magnetic resonance imaging results showed deactivation of medial prefrontal brain areas during anticipation of negative feedback relative to the control and the positive condition, and medial prefrontal and insular hyperactivation during presentation of negative as well as positive feedback in HSA compared to LSA subjects. The results indicate distinct processes underlying feedback processing during anticipation and presentation of feedback in HSA as compared to LSA individuals. In line with the role of the medial prefrontal cortex in self‐referential information processing and the insula in interoception, social anxiety seems to be associated with lower self‐monitoring during feedback anticipation, and an increased self‐focus and interoception during feedback presentation, regardless of feedback valence. Hum Brain Mapp 35:6023–6031, 2014. © 2014 Wiley Periodicals, Inc.     

Vitamin D in the General Population of Young Adults with Autism in the Faroe Islands

Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D₃ (25(OH)D₃) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15–24 years) had significantly lower 25(OH)D₃ than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D₃ than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D₃ in the ASD group suggests some underlying pathogenic mechanism.     

Lefetamine‐derived designer drugs N‐ethyl‐1,2‐diphenylethylamine (NEDPA) and N‐iso‐propyl‐1,2‐diphenylethylamine (NPDPA): Metabolism and detectability in rat urine using GC‐MS,LC‐MSn and LC‐HR‐MS/MS

N‐Ethyl‐1,2‐diphenylethylamine (NEDPA) and N‐iso‐propyl‐1,2‐diphenylethylamine (NPDPA) are two designer drugs, which were confiscated in Germany in 2008. Lefetamine (N,N‐dimethyl‐1,2‐diphenylethylamine, also named L‐SPA), the pharmaceutical lead of these designer drugs, is a controlled substance in many countries. The aim of the present work was to study the phase I and phase II metabolism of these drugs in rats and to check for their detectability in urine using the authors’ standard urine screening approaches (SUSA). For the elucidation of the metabolism, rat urine samples were worked up with and without enzymatic cleavage, separated and analyzed by gas chromatography‐mass spectrometry (GC‐MS) and liquid chromatography‐high resolution‐tandem mass spectrometry (LC‐HR‐MS/MS). According to the identified metabolites, the following metabolic pathways for NEDPA and NPDPA could be proposed: N‐dealkylation, mono‐ and bis‐hydroxylation of the benzyl ring followed by methylation of one of the two hydroxy groups, combinations of these steps, hydroxylation of the phenyl ring after N‐dealkylation, glucuronidation and sulfation of all hydroxylated metabolites. Application of a 0.3 mg/kg BW dose of NEDPA or NPDPA, corresponding to a common lefetamine single dose, could be monitored in rat urine using the authors’ GC‐MS and LC‐MSⁿ SUSA. However, only the metabolites could be detected, namely N‐deethyl‐NEDPA, N‐deethyl‐hydroxy‐NEDPA, hydroxy‐NEDPA, and hydroxy‐methoxy‐NEDPA or N‐de‐iso‐propyl‐NPDPA, N‐de‐iso‐propyl‐hydroxy‐NPDPA, and hydroxy‐NPDPA. Assuming similar kinetics, an intake of these drugs should also be detectable in human urine. Copyright © 2014 John Wiley & Sons, Ltd.     

Diagnosis and management of Non-IgE gastrointestinal allergies in breastfed infants—An EAACI Position Paper

It is well-established that food proteins, such as egg, soya, cow's milk and wheat, are detectable in breastmilk for many hours or days after ingestion. Exposure to these proteins is important to the process of developing tolerance but can also sometimes elicit IgE-mediated and non–IgE-mediated allergic symptoms in breastfed infants. Non–IgE-mediated allergy, outside of food protein-induced allergic proctocolitis and eosinophilic oesophagitis, is not well understood, leading to variations in the diagnosis and management thereof. A primary objective of the European Academy for Allergy and Clinical Immunology is to support breastfeeding in all infants, including those with food allergies. A Task Force was established, to explore the clinical spectrum of non–IgE-mediated allergies, and part of its objectives was to establish diagnosis and management of non–IgE-mediated allergies in breastfed infants. Eight questions were formulated using the Patient, Intervention, Comparison, Outcome (PICO) system and Scottish Intercollegiate Guideline Network (SIGN) criteria for data inclusion, and consensus was achieved on practice points through the Delphi method. This publication aims to provide a comprehensive overview on this topic with practice points for healthcare professionals.     

EAACI position paper on diet diversity in pregnancy,infancy and childhood: Novel concepts and implications for studies in allergy and asthma

To fully understand the role of diet diversity on allergy outcomes and to set standards for conducting research in this field, the European Academy of Allergy and Clinical Immunology Task Force on Diet and Immunomodulation has systematically explored the association between diet diversity and allergy outcomes. In addition, a detailed narrative review of information on diet quality and diet patterns as they pertain to allergic outcomes is presented. Overall, we recommend that infants of any risk category for allergic disease should have a diverse diet, given no evidence of harm and some potential association of benefit in the prevention of particular allergic outcomes. In order to harmonize methods for future data collection and reporting, the task force members propose relevant definitions and important factors for consideration, when measuring diet diversity in the context of allergy. Consensus was achieved on practice points through the Delphi method. It is hoped that the definitions and considerations described herein will also enable better comparison of future studies and improve mechanistic studies and pathway analysis to understand how diet diversity modulates allergic outcomes.     

Systemic immunogenicity of para-Phenylenediamine and Diphenylcyclopropenone: two potent contact allergy-inducing haptens

p-Phenylenediamine (PPD) and Diphenylcyclopropenone (DPCP) are two potent haptens. Both haptens are known to cause delayed-type hypersensitivity, involving a cytokine response and local infiltration of T-cell subpopulations, resulting in contact dermatitis. We investigated the systemic immune effects of PPD and DPCP, two relatively unexplored skin allergens. The dorsal sides of the ears of BALB/c mice were exposed to PPD or DPCP (0.1 % w/v or 0.01 % w/v), or vehicle alone. Mice were treated once daily for 3 days (induction period) and subsequently twice per week for 8 weeks. Local and systemic immune responses in the auricular and pancreatic lymph nodes, spleen, liver, serum, and ears were analyzed with cytokine profiling MSD, flow cytometry, and qPCR. Ear swelling increased significantly in mice treated with 1 % PPD, 0.01 % DPCP or 0.1 % DPCP, compared with vehicle treatment, indicating that the mice were sensitized and that there was a local inflammation. Auricular lymph nodes, pancreatic lymph nodes, spleen, and liver showed changes in regulatory T-cell, B-cell, and NKT-cell frequencies, and increased activation of CD8⁺ T cells and B cells. Intracellular cytokine profiling revealed an increase in the IFN-γ- and IL-4-positive NKT cells present in the liver following treatment with both haptens. Moreover, we saw a tendency toward a systemic increase in IL-17A. We observed systemic immunological effects of PPD and DPCP. Furthermore, concentrations too low to increase ear thickness and cause clinical symptoms may still prime the immune system. These systemic immunological effects may potentially predispose individuals to certain diseases.