Aim
The aim of this work was to perform a long‐term evaluation of a randomized trial focusing on functional aspects after excisional haemorrhoidectomy with a minimum follow‐up of 9 years.
Method
A ...questionnaire‐based study including patients operated on for haemorrhoids in Sweden between 1999 and 2003. A total of 225 patients were randomized to Milligan’s or Ferguson’s operation. Twenty‐six patients had died and 151 (76%) participated after a median follow‐up of 10.7 years (range 9.2–12.6 years).
Results
Seventy‐seven patients were in the Milligan group and 74 in the Ferguson group. Forty‐eight (32%) reported recurrence. Anal bleeding was reported in 80% at baseline but in 28% at long‐term follow‐up (P < 0.0001). At baseline, 49% had spontaneous anal pain and 25% pain at defaecation. At follow‐up, these figures were 17% and 11%. At follow‐up, 19% described a sense of anal stenosis. At baseline, soiling was reported in 51% but in 20% at long‐term follow‐up (P < 0.001). Nineteen per cent used pads preoperatively and 6% at follow‐up (P < 0.0001). Straining at defaecation was reported by 35% at baseline. At follow‐up, this figure was 25% (P = 0.055).
Conclusion
Symptoms associated with haemorrhoids were reduced at long‐term follow‐up. The most common problems were perceived recurrence and a sense of anal stenosis.
Background: Revision of the guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy, published in 2005, has become appropriate owing to publication of more relevant articles. ...Most of the new studies focused on small fiber neuropathy (SFN), a subtype of neuropathy for which the diagnosis was first developed through skin biopsy examination. This revision focuses on the use of this technique to diagnose SFN.
Methods: Task force members searched the Medline database from 2005, the year of the publication of the first EFNS guideline, to June 30th, 2009. All pertinent articles were rated according to the EFNS and PNS guidance. After a consensus meeting, the task force members created a manuscript that was subsequently revised by two experts (JML and JVS) in the field of peripheral neuropathy and clinical neurophysiology, who were not previously involved in the use of skin biopsy.
Results and Conclusions: Distal leg skin biopsy with quantification of the linear density of intraepidermal nerve fibers (IENF), using generally agreed upon counting rules, is a reliable and efficient technique to assess the diagnosis of SFN (Recommendation Level A). Normative reference values are available for bright‐field immunohistochemistry (Recommendation Level A) but not yet for confocal immunofluorescence or the blister technique. The morphometric analysis of IENF density, either performed with bright‐field or immunofluorescence microscopy, should always refer to normative values matched for age (Recommendation Level A). Newly established laboratories should undergo adequate training in a well‐established skin biopsy laboratory and provide their own stratified for age and gender normative values, intra‐ and interobserver reliability, and interlaboratory agreement. Quality control of the procedure at all levels is mandatory (Good Practice Point). Procedures to quantify subepidermal nerve fibers and autonomic innervated structures, including erector pili muscles, and skin vessels, are under development but need to be confirmed by further studies. Sweat gland innervation can be examined using an unbiased stereologic technique recently proposed (Recommendation Level B).A reduced IENF density is associated with the risk of developing neuropathic pain (Recommendation Level B), but it does not correlate with its intensity. Serial skin biopsies might be useful for detecting early changes of IENF density, which predict the progression of neuropathy, and to assess degeneration and regeneration of IENF (Recommendation Level C). However, further studies are warranted to confirm its potential usefulness as an outcome measure in clinical practice and research. Skin biopsy has not so far been useful for identifying the etiology of SFN. Finally, we emphasize that 3‐mm skin biopsy at the ankle is a safe procedure based on the experience of 10 laboratories reporting absence of serious side effects in approximately 35 000 biopsies and a mere 0.19% incidence of non‐serious side effects in about 15 years of practice (Good Practice Point).
Time-resolved photoelectron spectroscopy can give insights into carrier dynamics and offers the possibility of element and site-specific information through the measurements of core levels. In this ...paper, we demonstrate that this method can access electrons dynamics in PbS quantum dots over a wide time window spanning from pico- to microseconds in a single experiment carried out at the synchrotron facility BESSY II. The method is sensitive to small changes in core level positions. Fast measurements at low pump fluences are enabled by the use of a pump laser at a lower repetition frequency than the repetition frequency of the X-ray pulses used to probe the core level electrons: Through the use of a time-resolved spectrometer, time-dependent analysis of data from all synchrotron pulses is possible. Furthermore, by picosecond control of the pump laser arrival at the sample relative to the X-ray pulses, a time-resolution limited only by the length of the X-ray pulses is achieved. Using this method, we studied the charge dynamics in thin film samples of PbS quantum dots on n-type MgZnO substrates through time-resolved measurements of the Pb 5d core level. We found a time-resolved core level shift, which we could assign to electron injection and charge accumulation at the MgZnO/PbS quantum dots interface. This assignment was confirmed through the measurement of PbS films with different thicknesses. Our results therefore give insight into the magnitude of the photovoltage generated specifically at the MgZnO/PbS interface and into the timescale of charge transport and electron injection, as well as into the timescale of charge recombination at this interface. It is a unique feature of our method that the timescale of both these processes can be accessed in a single experiment and investigated for a specific interface.
To cite this article: Glaumann S, Nopp A, Johansson SGO, Rudengren M, Borres MP, Nilsson C. Basophil allergen threshold sensitivity, CD‐sens, IgE‐sensitization and DBPCFC in peanut‐sensitized ...children. Allergy 2012; 67: 242–247.
Background: Immunoglobulin E (IgE)‐sensitization to peanut is common and can indicate an allergy. A positive test needs to be confirmed by a double‐blind, placebo‐controlled food challenge (DBPCFC), which is regarded as ‘the gold standard’. The aim of the study was to evaluate the basophil allergen threshold sensitivity (CD‐sens) and antibodies to peanut allergen components in relation to DBPCFC in the diagnoses of peanut allergy in children.
Methods: Thirty‐eight children with suspected peanut allergy underwent a DBPCFC. CD‐sens to peanut and Ara h 2 were analysed as well as IgE‐antibody to peanut and some of its allergen components (Ara h 1, 2, 3, 8 and 9).
Results: Twenty‐five children had a positive DBPCFC, and 92% of these were positive in CD‐sens to peanut and Ara h 2. Two children with a positive DBPCFC were classified as ‘low‐responders’ and were not further evaluated. Children positive in DBPCFC had higher CD‐sens values to peanut (median 1.3; range 0.4–29, n = 21) compared with children negative in DBPCFC (median 0; range 0–0.5, n = 13) (P < 0.0001). A positive DBPCFC correspond with increased levels of IgE‐antibody to Ara h 1, 2 and 3 compared with those with a negative challenge (P < 0.0001 for all). All children with a negative CD‐sens were negative in DBPCFC.
Conclusion: In this study, a negative CD‐sens to peanut excluded peanut allergy. Both tests, CD‐sens to peanut and immunoassay for IgE‐antibody to the peanut components, appear to be safe, time saving and cost‐effective complements to DBPCFC.
The
ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). ApoE protein aggregation plays a central role in AD pathology, including the accumulation of β-amyloid ...(Aβ). Lipid-poor ApoE4 protein is prone to aggregate and lipidating ApoE4 protects it from aggregation. The mechanisms regulating ApoE4 aggregation
are surprisingly not known. ApoE lipidation is controlled by the activity of the ATP binding cassette A1 (ABCA1). ABCA1 recycling and degradation is regulated by ADP-ribosylation factor 6 (ARF6). We found that ApoE4 promoted greater expression of ARF6 compared with ApoE3, trapping ABCA1 in late-endosomes and impairing its recycling to the cell membrane. This was associated with lower ABCA1-mediated cholesterol efflux activity, a greater percentage of lipid-free ApoE particles, and lower Aβ degradation capacity. Human CSF from
ε4/ε4 carriers showed a lower ability to induce ABCA1-mediated cholesterol efflux activity and greater percentage of aggregated ApoE protein compared with CSF from
ε3/ε3 carriers. Enhancing ABCA1 activity rescued impaired Aβ degradation in ApoE4-treated cells and reduced both ApoE and ABCA1 aggregation in the hippocampus of male ApoE4-targeted replacement mice. Together, our data demonstrate that aggregated and lipid-poor ApoE4 increases ABCA1 aggregation and decreases ABCA1 cell membrane recycling. Enhancing ABCA1 activity to reduce ApoE and ABCA1 aggregation is a potential therapeutic strategy for the prevention of ApoE4 aggregation-driven pathology.
ApoE protein plays a key role in the formation of amyloid plaques, a hallmark of Alzheimer's disease (AD). ApoE4 is more aggregated and hypolipidated compared with ApoE3, but whether enhancing ApoE lipidation
can reverse ApoE aggregation is not known. ApoE lipidation is controlled by the activity of the ATP binding cassette A1 (ABCA1). In this study, we demonstrated that the greater propensity of lipid-poor ApoE4 to aggregate decreased ABCA1 membrane recycling and its ability to lipidate ApoE. Importantly, enhancing ABCA1 activity to lipidate ApoE reduced ApoE and ABCA1 aggregation. This work provides critical insights into the interactions among ABCA1, ApoE lipidation and aggregation, and underscores the promise of stabilizing ABCA1 activity to prevent ApoE-driven aggregation pathology.
•The overall accident risk for e-bikes is somewhat higher than that of conventional bicycles, but only for female cyclists.•Males have a higher accident risk on bicycles than females.•Being ...unfamiliar with your bicycle increases accident risk.•E-bike accident victims are more likely to be unfamiliar with their bicycle, and females are more often novel e-bike users.•E-bikes are more often involved in balance-related accidents, but these are rare.
E-bikes are becoming increasingly popular, and are given an important role in the green mobility of the future. However, some have raised concerns that the increased speed and the increased weight of the e-bike can lead to more accidents among cyclists riding an e-bike, as compared to conventional bicycles. Furthermore, it has been suggested that e-bikes may appeal to new groups of cyclists with little cycling experience, which may further impede cyclist safety. Previous research has not provided a clear picture. We investigate these questions with data from three surveys carried out in Norway (N = 7752). A logistic regression analysis comparing conventional and electric bicycles, controlling for age gender and exposure, shows an overall risk increase (all accidents) for e-bike users. The results suggest that this increased risk derives from females having a higher accident risk on e-bikes. For men there is no risk difference between e-bikes and conventional bikes. Some, but not all, of this elevated risk can be attributed to being unfamiliar with the bicycle. E-bikes are not more likely to cause serious accidents than conventional bicycles. In-depth analysis of accident causation showed that there was no difference in the factors leading to accidents, except that there was a somewhat higher prevalence of accidents resulting from balance problems with e-bikes.
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