bluuebunny/crossref_metadata_2025 huggingface dataset:
Vestibular Evoked Myogenic Potentials (VEMP) Can Detect Asymptomatic Saccular Hydrops
Authors: Lin Ming‐Yee , Timmer Ferdinand C. A. , Oriel Brad S. , Zhou Guangwei , Guinan John J. , Kujawa Sharon G. , Herrmann Barbara S. , Merchant Saumil N. , Rauch Steven D.
Published: June 2006

Objective: The objective of this study was to explore the useful of vestibular evoked myogenic potential (VEMP) testing for detecting endolymphatic hydrops, especially in the second ear of patients with unilateral Ménière disease (MD).

Methods: This study was performed at a tertiary care academic medical center. Part I consisted of postmortem temporal bone specimens from the temporal bone collection of the Massachusetts Eye & Ear Infirmary; part II consisted of consecutive consenting adult patients (n = 82) with unilateral MD by American Academy of Otolaryngology–Head and Neck Surgery criteria case histories. Outcome measures consisted of VEMP thresholds in patients and histologic saccular endolymphatic hydrops in postmortem temporal bones.

Results: Saccular hydrops was observed in the asymptomatic ear in six of 17 (35%) of temporal bones from donors with unilateral MD. Clinic patients with unilateral MD showed elevated mean VEMP thresholds and altered VEMP tuning in their symptomatic ears and, to a lesser degree, in their asymptomatic ears. Specific VEMP frequency and tuning criteria were used to define a “Ménière‐like” response. This “Ménière‐like” response was seen in 27% of asymptomatic ears of our patients with unilateral MD.

Conclusions: Bilateral involvement is seen in approximately one third of MD cases. Saccular hydrops appears to precede symptoms in bilateral MD. Changes in VEMP threshold and tuning appear to be sensitive to these structural changes in the saccule. If so, then VEMP may be useful as a detector of asymptomatic saccular hydrops and as a predictor of evolving bilateral MD.
Adenoid Cystic Carcinoma of the Sinonasal Tract: Treatment Results
Authors: Rhee Chae‐Seo , Won Tae‐Bin , Lee Chul Hee , Min Yang‐Gi , Sung Myung‐Whun , Kim Kwang‐Hyun , Shim Woo Sub , Kim Yong Min , Kim Jeong‐Whun
Published: June 2006

Objectives: Malignancies arising from the sinonasal tract, which includes the nose, paranasal sinuses, and nasopharynx, are uncommon. Although adenoid cystic carcinoma (ACC) is the second most common cancer occurring in the sinonasal tract, only few studies have been reported. This retrospective review was performed to identify the clinical features and treatment outcomes of sinonasal ACC.

Methods: Thirty‐five patients diagnosed and treated for ACC of the sinonasal tract were included in this study. Medical records, radiographs, and pathologic slides were retrospectively reviewed.

Results: In two thirds of the patients, the maxillary sinus was the site of origin and cribriform was the most common histologic subtype (61%). Seventy‐one percent of the patients had advanced disease (T3, T4) at the time of diagnosis. Five‐year overall survival rate was 86% and treatment failure occurred in 18 patients (51%). Five‐year local recurrence rate and distant metastasis rate were 30% and 25%, respectively. Adjunctive radiotherapy appeared to reduce local recurrence. Presence of distant metastasis correlated with decreased 5‐year survival (P = .001). Five‐year survival rate after development of distant metastasis or local recurrence were 17% and 58%, respectively.

Conclusions: Based on our findings, we suggest that sinonasal ACC be treated by a combined modality of radical surgery followed by postoperative radiation. The prognosis of sinonasal ACC seems to be determined by the presence of distant metastasis.
Monitoring of Cochlear Function During Cochlear Implantation
Authors: Adunka Oliver , Roush Patricia , Grose John , Macpherson Corinne , Buchman Craig A.
Published: June 2006

Objective: To report the feasibility of monitoring cochlear function during cochlear implantation.

Study Design: Case report.

Setting: Tertiary care referral center.

Methods: A child with audiologic features typical of bilateral auditory neuropathy underwent cochlear implantation. The scala tympani was entered inferior and slightly anterior to the round window membrane margin and smooth electrode insertion was achieved. Using single polarity click stimuli, the cochlear microphonic was measured at several steps during surgery.

Results: Cochlear microphonics were present at all stages during the implantation process and were clearly distinguished from neural responses by stimulus polarity inversion and constant latencies, despite changes in stimulus level. With the electrode in situ, amplitudes were smaller but persisted until the final measurement at 10 minutes after insertion. At follow‐up 2 weeks after surgery, behavioral audiometry results indicated profound hearing loss in the operated ear.

Conclusions: This paper demonstrates the feasibility of monitoring cochlear function during cochlear implantation. The routine surgical approach did not appear to adversely affect the functional measurements. Standard size, full electrode insertion did diminish the amplitude of the cochlear microphonics, possibly as a result of intracochlear mechanical impairment. Ultimately, profound hearing loss was documented, indicating that factors other than immediate changes induced by electrode insertion were likely responsible for the loss of cochlear function.
Primary Mucosal Melanoma of Head and Neck: Prognostic Value of Clear Margins
Authors: Penel Nicolas , Mallet Yann , Mirabel Xavier , Van Jean Ton , Lefebvre Jean‐Louis
Published: June 2006

Background: Primary mucosal melanomas of the head and neck (MMHN) are rare and carry a poor outcome. The impact of different treatments on survival is not yet clearly established.

Methods: Twenty patients treated from 1991 to 2004 at a single referral center were retrospectively reviewed.

Results: Primary sites were oral mucosa in 14 cases, paranasal sinuses in three cases, and nasal cavities in three cases. The sex ratio was equal to 1, and the median age at diagnosis was 63 years (range, 17–77 y). At presentation, one patient had lymph node metastases, one patient had distant metastases, and one patient had both. Surgery was performed with curative intent in 19 cases (and achieved clear margins in 14 cases). Postoperative radiation therapy was delivered in four cases. The actuarial 2‐year and 5‐year survival rates were 13/19 and 7/16. The risk factors for death were male gender (RR = 9.3 [1.2–72], P = .024) and positive margins (RR = 21 [1.9–47], P = .013). In addition, we observed three metachromous cancers (one breast cancer, one kidney cancer and one lymphoma) during the follow‐up period.

Conclusion: The present study suggests that obtaining clear margins must be the goal in the treatment of MMNH.
Age‐Related Changes on the Morphology of the Otoconia
Authors: Jang Yoon Seok , Hwang Chan Ho , Shin Ji Young , Bae Woo Yang , Kim Lee Suk
Published: June 2006

Objectives/Hypothesis: Although there are numerous reports on otoconial morphology using field‐emission scanning electron microscopy (FESEM), there are few reports regarding the changes of otoconial morphology with aging. The aim of the current study was to investigate changes in otoconial morphology in rats according to age, using FESEM.

Study Design: Laboratory study using experimental animals.

Methods: We investigated age‐related changes in otoconial morphology using FESEM in three groups of rats: young (1 wk old), middle‐aged (6 mo old), and aged (23 mo old).

Results: There was great size variation in utricular otoconia in the young and aged rats, but we found no clear regional separation of saccular otoconia in all groups based on size. In the oldest rats, the bodies of many otoconia in both maculae were pitted, fissured, penetrated, and eventually broken into several fragments. However, the terminal facets were smooth and the lines of intersection of facets were sharp, despite the degenerated bodies of the otoconia in this group. Giant otoconia were discovered frequently on the outer margin of the utricular maculae in aged rats. We directly observed weakened or broken linking filaments and otoconial fragments in the aged group.

Conclusion: The oldest rats showed the most degeneration of otoconia and linking filaments with otoconial fragments. This study of age‐related morphologic changes in otoconia might help us understand the origin of idiopathic benign paroxysmal positional vertigo.
A Comparison of the Long‐Term Outcome and Effects of Surgery or Continuous Positive Airway Pressure on Patients with Obstructive Sleep Apnea Syndrome
Authors: Lin Shih‐Wei , Chen Ning‐Hung , Li Hsueh‐Yu , Fang Tuan‐Jen , Huang Chong‐Chi , Tsai Yiang‐Huang , Lee Cheng‐Huei
Published: June 2006

Objectives: To compare the long‐term (3‐year) outcome and effects of continuous positive airway pressure (CPAP) and extended uvulopalatoplasty (EUPF) treatment on patients with obstructive sleep apnea syndrome.

Methods: Eighty‐four patients who received CPAP titration and bought a CPAP machine to use from March 2000 to October 2001 were included as the CPAP group. Another 55 patients who underwent EUPF surgery were included as the EUPF group. Overnight polysomnography was performed 6 months and 3 years after CPAP titration or EUPF. The disease‐specific questionnaire‐Snore Outcome Survey (SOS), Epworth Sleepiness Scale (ESS), and the generic health questionnaire‐MOSF‐36 were administered at the 6‐month and 3‐year follow‐up examinations.

Results: The age, body mass index, respiratory disturbance index, and ESS before treatment were higher in the CPAP group. The snore index was higher in the surgery group. Fifty‐four patients (64.3%) in CPAP group continued treatment for 6 months; the success rate for EUPF at 6 months was 82%. The polysomnographic variables improved significantly in both groups. Improvements in the SOS and ESS scores were better in surgery group than the CPAP group. The subscales of SF‐36 in surgery group were more than those in CPAP group.

Conclusions: EUPF had a better effect on snoring than CPAP 6 months after treatment in patients with obstructive sleep apnea syndrome (OSAS). This effect had gradually declined at the 3‐year follow‐up examination. Improvement in the quality of life of OSAS patients receiving EUPF is equal to those receiving CPAP treatment.
Salivary Gland Choristoma of the Middle Ear
Authors: Enoz Murat , Suoglu Yusufhan
Published: June 2006

Choristoma is a mass of tissue histologically normal for an organ or part of the body other than the site at which it is located. A rare case of ectopic salivary gland choristoma in the middle ear is described in a 14‐year‐old girl whose only symptom was a 55 dB conductive hearing loss. The left middle ear mass appeared whitish and was located behind the intact tympanic membrane. We first suspected it to be congenital middle ear cholesteatoma. Exploratory tympanotomy, however, revealed a salivary gland choristoma that adhered tightly to the facial nerve. Differential diagnosis and treatment of this rare condition are discussed.
Demographics of Pediatric Head and Neck Infections in a Tertiary Care Hospital
Authors: Schweinfurth John M.
Published: June 2006

Educational Objective: Discuss potential patterns in the epidemiology of infectious disease of the head and neck.

Study Objectives: To investigate patterns in the epidemiology of severe head and neck infections that may reflect the impact of host factors.

Study Design: Population‐based, historic cohort study.

Methods: Information on 1,010, incident head and neck infections occurring over a 5‐year period was reviewed for demographics, location, and time of year. A nonparametric Kruskal‐Wallis test was used to identify significant differences in the age distributions among the diagnosis groups. A Bonferroni, pair‐wise comparison procedure was used for comparison of the average age of first onset of severe head and neck infections. Chi‐square test was used to identify any significant association between season of the year and disease.

Results: Significant differences were identified in the age distributions among the diagnosis groups (P < .001). The average age of first onset of cellulitis of the neck and retropharyngeal abscess is earlier than peritonsillar abscess, at 2 to 3 years and 13 years, respectively. Parapharyngeal and periapical abscesses and cellulitis of the face occur at approximately age 6. The incidence of parapharyngeal abscess and diseases of the pharynx is decreased during Spring, whereas peritonsillar abscesses and acute periodontitis occurs more often in Spring and Summer. Age does not appear to be related to season of first occurrence.

Conclusions: Head and neck infections are not random occurrences based on exposure alone; host factors are clearly important. Given the lack of correlation with school age, the results cannot be explained on the basis of exposure alone. Developmental patterns of the host immune response may be related to the age differential identified in the current study and are cause for further investigation.
Carcinoma Arising in a Pharyngeal Pouch Previously Treated by Endoscopic Stapling
Authors: Acharya Aanand , Jennings Stephen , Douglas Susan , Mirza Showkat , Beasley Nigel
Published: June 2006

Objectives: A case is described in which squamous cell carcinoma was found during surgery for a recurrent pharyngeal pouch previously treated by endoscopic stapling. A search of the English language literature suggests this is the first reported case of a carcinoma developing in a pharyngeal pouch previously treated by endoscopic stapling.

Study Design: Case report and literature review.

Materials and Methods: The records of a patient who presented with a recurrent pharyngeal pouch after a previous endoscopic stapling procedure were reviewed. The presentation, imaging, and histopathologic findings are presented and the implications of these discussed.

Results: Imaging confirmed a recurrent pharyngeal diverticulum. An endoscopic assessment revealed the presence of tumor in the recurrent pouch that histopathologic evaluation confirmed to be squamous cell carcinoma. The patient underwent an external excision of this diverticulum followed by a course of external beam radiotherapy.

Conclusions: This is the first reported case of a carcinoma developing in a recurrent pharyngeal diverticulum previously treated by endoscopic stapling and brings to light a rare risk of endoscopic stapling procedures for the treatment of pharyngeal diverticula.
Phase-field theory of edges in an anisotropic crystal
Authors: Wheeler A.A
Published: June 2006

In the presence of sufficiently strong surface energy anisotropy, the equilibrium shape of an isothermal crystal may include corners or edges. Models of edges have, to date, involved the regularization of the corresponding free-boundary problem resulting in equilibrium shapes with smoothed out edges. In this paper, we take a new approach and consider how a phase-field model, which provides a diffuse description of an interface, can be extended to the consideration of edges by an appropriate regularization of the underlying mathematical model. Using the method of matched asymptotic expansions, we develop an approximate solution which corresponds to a smoothed out edge from which we are able to determine the associated edge energy.
Determining the contribution of Antarctica to sea-level rise using data assimilation methods
Authors: Arthern Robert J , Hindmarsh Richard C.A
Published: June 2006

The problem of forecasting the future behaviour of the Antarctic ice sheet is considered. We describe a method for optimizing this forecast by combining a model of ice sheet flow with observations. Under certain assumptions, a linearized model of glacial flow can be combined with observations of the thickness change, snow accumulation, and ice-flow, to forecast the Antarctic contribution to sea-level rise. Numerical simulations show that this approach can potentially be used to test whether changes observed in Antarctica are consistent with the natural forcing of a stable ice sheet by snowfall fluctuations. To make predictions under less restrictive assumptions, improvements in models of ice flow are needed. Some of the challenges that this prediction problem poses are highlighted, and potentially useful approaches drawn from numerical weather prediction are discussed.
Physical map-assisted whole-genome shotgun sequence assemblies
Authors: Warren René L. , Varabei Dmitry , Platt Darren , Huang Xiaoqiu , Messina David , Yang Shiaw-Pyng , Kronstad James W. , Krzywinski Martin , Warren Wesley C. , Wallis John W. , Hillier LaDeana W. , Chinwalla Asif T. , Schein Jacqueline E. , Siddiqui Asim S. , Marra Marco A. , Wilson Richard K. , Jones Steven J.M.
Published: June 2006

We describe a targeted approach to improve the contiguity of whole-genome shotgun sequence (WGS) assemblies at run-time, using information from Bacterial Artificial Chromosome (BAC)-based physical maps. Clone sizes and overlaps derived from clone fingerprints are used for the calculation of length constraints between any two BAC neighbors sharing 40% of their size. These constraints are used to promote the linkage and guide the arrangement of sequence contigs within a sequence scaffold at the layout phase of WGS assemblies. This process is facilitated by FASSI, a stand-alone application that calculates BAC end and BAC overlap length constraints from clone fingerprint map contigs created by the FPC package. FASSI is designed to work with the assembly tool PCAP, but its output can be formatted to work with other WGS assembly algorithms able to use length constraints for individual clones. The FASSI method is simple to implement, potentially cost-effective, and has resulted in the increase of scaffold contiguity for both the Drosophila melanogaster and Cryptococcus gattii genomes when compared to a control assembly without map-derived constraints. A 6.5-fold coverage draft DNA sequence of the Pan troglodytes (chimpanzee) genome was assembled using map-derived constraints and resulted in a 26.1% increase in scaffold contiguity.
Stimulation of hippocampal adenylyl cyclase activity dissociates memory consolidation processes for response and place learning
Authors: Martel Guillaume , Millard Annabelle , Jaffard Robert , Guillou Jean-Louis
Published: June 2006

Procedural and declarative memory systems are postulated to interact in either a synergistic or a competitive manner, and memory consolidation appears to be a highly critical stage for this process. However, the precise cellular mechanisms subserving these interactions remain unknown. To investigate this issue, 24-h retention performances were examined in mice given post-training intrahippocampal injections of forskolin (FK) aiming at stimulating hippocampal adenylyl cyclases (ACs). The injection was given at different time points over a period of 9 h following acquisition in either an appetitive bar-pressing task or water-maze tasks challenging respectively “response memory” and “place memory.” Retention testing (24 h) showed that FK injection altered memory formation only when given within a 3- to 6-h time window after acquisition but yielded opposite memory effects as a function of task demands. Retention of the spatial task was impaired, whereas retention of both the cued-response in the water maze and the rewarded bar-press response were improved. Intrahippocampal injections of FK produced an increase in pCREB immunoreactivity, which was strictly limited to the hippocampus and lasted less than 2 h, suggesting that early effects (0–2 h) of FK-induced cAMP/CREB activation can be distinguished from late effects (3–6 h). These results delineate a consolidation period during which specific cAMP levels in the hippocampus play a crucial role in enhancing memory processes mediated by other brain regions (e.g., dorsal or ventral striatum) while eliminating interference by the formation of hippocampus-dependent memory.
Post-retrieval effects of icv infusions of hemicholinium in mice are dependent on the age of the original memory
Authors: Boccia Mariano M. , Blake Mariano G. , Acosta Gabriela B. , Baratti Carlos M.
Published: June 2006

CF-1 male mice were trained in an inhibitory avoidance task using a high footshock (1,2 mA, 50 Hz, 1 sec) in order to reduce the influence of extinction on retention performance. At 2, 7, 14, or 30 d after training, the first retention test was performed and hemicholinium (HC-3, 1.0 μg/mice), a specific inhibitor of high-affinity choline uptake in brain cholinergic neurons, was given intracerebroventricularly immediately after. Twenty four hours after treatment, mice were tested in an inhibitory avoidance task during five consecutive days, each 24 h apart. Retention performance was impaired by HC-3 when the first re-exposure took place at 2, 7, or 14 d, but the effect was no longer seen when re-exposure occurred 30 d after training. We did not find spontaneous recovery 21 d after training, when memory was retrieved 2 d after training and HC-3 was given immediately after. Although we cannot definitively discard a retrieval deficit, this lack of spontaneous recovery is in accordance with the storage-deficit interpretation. These results confirm and extend previous ones, suggesting that central cholinergic mechanisms are involved in the hypothetical reconsolidation memory processes of an inhibitory avoidance task in mice and also suggest that this participation depends on the “age” of the original memory trace. This implies that the vulnerability of a reactivated memory to a specific treatment, as the one used in this study, inversely correlates with the age of the original memory, and it is likely to determine memory reconsolidation processes.
Protein synthesis-dependent long-term memory induced by one single associative training trial in the parasitic waspLariophagus distinguendus
Authors: Collatz Jana , Müller Caroline , Steidle Johannes L.M.
Published: June 2006

Protein synthesis-dependent long-term memory inApis melliferaandDrosophila melanogasteris formed after multiple trainings that are spaced in time. The parasitic waspLariophagus distinguendusremarkably differs from these species. It significantly responds to the artificial odor furfurylheptanoate (FFH) in olfactometer experiments, when this odor was presented during one single training trial, consisting of one sequence of host recognition behavior on a wheat grain infested by its hosts. Feeding wasps with actinomycin D erases the learned response 24 h after the training, demonstrating that protein synthesis-dependent long-term memory has been formed inL. distinguendusalready after one single training.
Hippocampal train stimulation modulates recallof fear extinction independently of prefrontalcortex synaptic plasticity and lesions
Authors: Farinelli Mélissa , Deschaux Olivier , Hugues Sandrine , Thevenet Aurélie , Garcia René
Published: June 2006

It has been shown that long-term potentiation (LTP) develops in the connection between the mediodorsal thalamus (MD) and the medial prefrontal cortex (mPFC) and between the hippocampus (HPC) and the mPFC following fear extinction, and correlates with extinction retention. However, recent lesion studies have shown that combined lesions of the MD and mPFC do not interfere with extinction learning and retention, while inactivation of the dorsal HPC disrupts fear extinction memory. Here we found in rats that immediate post-training HPC low-frequency stimulation (LFS) suppressed extinction-related LTP in the HPC–mPFC pathway and induced difficulties in extinction recall. HPC tetanus, applied several hours later, failed to re-establish mPFC LTP but facilitated recall of extinction. Delayed post-training HPC LFS also provoked mPFC depotentiation and difficulties with extinction recall. HPC tetanus abolished these two effects. We also found that damage to the mPFC induced fear return only in rats that received HPC LFS following extinction training. HPC tetanus also reversed this behavioral effect of HPC LFS in lesioned rats. These data suggest that the HPC interacts with the mPFC during fear extinction, but can modulate fear extinction independently of this interaction.
Impaired memory retrieval correlates with individual differences in cortisol response but not autonomic response
Authors: Buchanan Tony W. , Tranel Daniel , Adolphs Ralph
Published: June 2006

Stress can enhance or impair memory performance. Both cortisol release and sympathetic nervous system responses have been implicated in these differential effects. Here we investigated how memory retrieval might be affected by stress-induced cortisol release, independently of sympathetic nervous system stress responses. Thirty-two healthy participants (16 women) learned emotionally arousing and neutral words. One hour later, half of the participants underwent a stressor (cold pressor test) and the other half, a control warm water exposure, both followed by a delayed free recall task. The stressed participants were split into those who did (responders, N = 8) and those who did not (nonresponders, N = 6) show a cortisol response. Both responders and nonresponders showed comparable sympathetic nervous system activity (skin conductance level) during the cold pressor. The cortisol responders recalled significantly fewer words compared to nonresponders, and compared to control participants; this effect was most pronounced for moderately arousing words (compared to highly arousing and neutral words). These results suggest that individual differences in cortisol reactivity affect memory retrieval performance, and help to explain the differential effects of stress on memory.
Novel elicitin‐like proteins isolated from the cell wall of the biocontrol agent Pythium oligandrum induce defence‐related genes in sugar beet
Authors: TAKENAKA SHIGEHITO , NAKAMURA YUMI , KONO TAMAKI , SEKIGUCHI HIROYUKI , MASUNAKA AKIRA , TAKAHASHI HIDEKI
Published: June 2006

We previously reported that cell wall protein fractions (CWPs) of the biocontrol agent Pythium oligandrum have elicitor properties in sugar beet and wheat. Here we have examined the effect of treatment with the D‐type of CWP, a fraction that contains two major forms (POD‐1 and POD‐2), on the induction of defence‐related genes in sugar beet. Using PCR‐based cDNA library subtraction, we identified five genes that were highly expressed in response to CWP treatment. The five genes are probably of oxalate oxidase‐like germin (OxOLG), glutathione S‐transferase (GST), 5‐enol‐pyruvylshikimate‐phosphate synthase (EPSPS), phenylalanine ammonia‐lyase (PAL) and aspartate aminotransferase (AAT). In addition, we purified and characterized POD‐1 and POD‐2 and found that POD‐1 induced all five genes, whereas POD‐2 induced three of the genes, but not OxOLG or GST. A sugar beet bioassay indicated that CWP, POD‐1 and POD‐2 are each sufficient to induce resistance to sugar beet seedling disease caused by Aphanomyces cochlioides. Although carbohydrate analyses indicated that POD proteins were glycoproteins with similar carbohydrate compositions, containing approximately 15.0% carbohydrate by weight, their peptide portions have elicitor activity. Furthermore, cDNAs of POD‐1 and POD‐2 proteins were cloned, and the deduced amino acid sequences were found to be 82.9% identical. Characterization of their molecular structures indicated that they have an elicitin domain followed by a C‐terminal domain with a high frequency of Ser, Thr, Ala and Pro, which is structurally similar to class III elicitins. However, phylogenetic analysis with 22 representative elicitin and elicitin‐like proteins showed that POD‐1 and POD‐2 are distinct from previously defined elicitin and elicitin‐like proteins. Therefore, POD‐1 and POD‐2 are novel oomycete cell wall elicitin‐like glycoproteins.
Genetic polymorphisms of interleukin‐1‐beta in association with sustained response to anti‐viral treatment in chronic hepatitis B in Chinese
Authors: CHAN H. L.‐Y. , TSE A. M.‐L. , ZHANG M.‐D. , WONG V. W.‐S. , CHIM A. M.‐L. , HUI A. Y. , SUNG J. J.‐Y.
Published: June 2006

Background

Interleukin‐1β is a pro‐inflammatory cytokine that may influence host defence against viral infection.

Aim

To investigate the impact of interleukin‐1β gene polymorphism on the response to anti‐viral treatment.

Method

Hepatitis B e antigen‐positive chronic hepatitis B patients who have completed a randomized study of peginterferon alpha‐2b and lamivudine combination vs. lamivudine monotherapy were included. Sustained responders were patients who had persistent hepatitis B e antigen loss and less than two occasions with hepatitis B virus DNA >100 000 copies/mL at any time up to week 76 post‐treatment. Polymorphisms at interleukin‐1β‐511, ‐31 and ‐3954 and interleukin‐1 receptor antagonist (RN) were studied.

Results

Eighty‐eight patients were studied and 18 (20%) patients developed sustained response. Near complete linkage disequilibrium was observed between interleukin‐1β‐511 and ‐31 loci. After adjustment for the potential confounding effects of treatment allocation, hepatitis B virus genotype, pre‐treatment alanine aminotransferase and hepatitis B virus DNA levels, genotype C/T at interleukin‐1β‐511 was found to be associated with higher sustained response than genotype C/C (adjusted odds ratio 10.4, 95% CI 1.1, 96.9, P = 0.040). The proportion of sustained responders tend to be higher among patients with allele T at interleukin‐1β‐511 (83%) than those without (70%) (P = 0.058).

Conclusion

High interleukin‐1β production genotype at position ‐511 has a favourable response to anti‐viral treatments.
Prescribing of acid suppressive therapy: interactions between hospital and primary care
Authors: KRAG A. , TEGLBJERG L. S. , MALCHOW‐MØLLER A. , HALLAS J. , BYTZER P.
Published: June 2006

Background

Overuse of acid suppressive therapy in the hospital setting and in primary care is well documented.

Aim

To describe interactions between prescriptions of acid suppressive therapy in hospital and in primary care.

Methods

All patients admitted to hospital over a 24‐month period were identified. Details about prescription of acid suppressive therapy were retrieved. All prescriptions of acid suppressive therapy redeemed by these patients 12 months before and after discharge were retrieved from a prescription database.

Results

A total of 549 of 4477 patients (12.3%) were treated with acid suppressive therapy while in hospital, but acid suppressive therapy was prescribed de novo in only 192 (35%) of these cases. Information about indication for acid suppressive therapy and planned duration of therapy were given in the discharge letter in only 25% and 17% of the cases, respectively. Among patients treated with acid suppressive therapy during admission, prescriptions on acid suppressive therapy were redeemed by 67% in the year before admission and by 74% in the year after discharge. Among patients who had the acid suppressive therapy discontinued during admission (n = 67), 48% resumed acid suppressive therapy within the following 12 months. Of all subjects treated with acid suppressive therapy in the hospital catchment area, 7.8% were seen in our department.

Conclusions

Decisions about acid suppressive therapy prescribing in hospital has little influence on prescribing in primary care.
Gastro‐oesophageal reflux symptoms and health‐related quality of life in the adult general population – the Kalixanda study
Authors: RONKAINEN J. , ARO P. , STORSKRUBB T. , LIND T. , BOLLING‐STERNEVALD E. , JUNGHARD O. , TALLEY N. J. , AGREUS L.
Published: June 2006

Background

The impact of gastro‐oesophageal reflux symptoms on health‐related quality of life in the general population is poorly characterized.

Aim

To identify the frequency of troublesome reflux symptoms associated with impaired health‐related quality of life in the general population.

Methods

A representative random sample of 3000 adult inhabitants of northern Sweden was surveyed using the validated Abdominal Symptom Questionnaire (response rate 74%). In total, 1001 random responders were endoscoped and assessed using the Short Form‐36 Health Survey.

Results

Complete data were obtained for 999 subjects: 6% reported reflux symptoms (heartburn and/or regurgitation) daily, 14% weekly and 20% less than weekly during the previous 3 months. Compared with no reflux symptoms, a clinically relevant impairment of health‐related quality of life (≥5 points and P < 0.05) was seen in all eight Short Form‐36 dimensions for daily symptoms, in five dimensions for weekly symptoms and in one dimension for less than weekly symptoms. There were no meaningful differences in Short Form‐36 scores between subjects with and without oesophagitis.

Conclusions

Most aspects of health‐related quality of life were impaired in individuals with daily or weekly reflux symptoms. Troublesome reflux symptoms at least weekly may identify gastro‐oesophageal reflux disease.
Alternating bowel pattern: what do people mean?
Authors: CHOUNG R. S. , LOCKE G. R. , ZINSMEISTER A. R. , MELTON L. J. , TALLEY N. J.
Published: June 2006

Background

With the introduction of new therapies, the subgrouping of patients based on bowel pattern has become important. However, the appropriate definition of an alternating bowel pattern remains unclear.

Aim

To determine if specific symptoms are reported by people with an alternating bowel pattern.

Methods

Using the Rochester Epidemiology Project, a series of population‐based surveys were undertaken in which valid self‐report gastrointestinal symptom questionnaires were mailed to 4029 randomly selected members of the community. One question asked was ‘How would you describe your usual bowel pattern in the last year'?

Results

3022 subjects (74%) provided questionnaire data and 2718 were eligible for this analysis, the mean age was 57 years, with a range of 20–98 years (median = 61). Of these, 9.2%, 2.5% and 7.6% reported their usual bowel pattern as being constipated, diarrhoea, or alternating respectively. At least 50% of those reporting alternating bowel pattern reported incomplete evacuation (63%), urgency (57%), straining (55%) and loose stool (50%). The proportion of alternators reporting each individual symptom was between that of diarrhoea and constipation except for mucus and incomplete evacuation; however, no symptom was unique to alternators.

Conclusion

People who self‐report an alternating bowel pattern appear to represent a blend of constipation and diarrhoea symptoms, rather than a distinct subgroup.
Polymorphisms in innate immunity genes and risk of non‐Hodgkin lymphoma
Authors: Forrest Matthew S. , Skibola Christine F. , Lightfoot Tracy J. , Bracci Paige M. , Willett Eleanor V. , Smith Martyn T. , Holly Elizabeth A. , Roman Eve
Published: June 2006

Genetic variation in innate immunity may alter host‐pathogen defence mechanisms and promote aberrant immune responses and non‐Hodgkin lymphoma (NHL). To test this hypothesis, we investigated polymorphisms in innate immune genes in a pooled analysis of two population‐based case‐control studies of NHL from the San Francisco Bay Area (308 cases, 684 controls) and UK (596 cases, 758 controls). The caspase recruitment domain‐containing protein 1007fs homozygote variant was positively associated with NHL risk (odds ratios (OR) = 3·1, 95% confidence intervals (CI) 1·1–8·8), whereas the toll‐like receptor 4 1063A>G variant allele was inversely associated with diffuse large cell lymphoma (OR = 0·67, 95% CI 0·45–0·99). These results suggest that variation in innate immune genes may alter NHL susceptibility.
The identification of a recurrent phosphoglycerate kinase mutation associated with chronic haemolytic anaemia and neurological dysfunction in a family from USA
Authors: Flanagan Jonathan M. , Rhodes Melissa , Wilson Meredith , Beutler Ernest
Published: June 2006

Phosphoglycerate kinase (PGK) deficiency is a rare X‐linked disease that is characterised by mild to severe haemolytic anaemia, rhabdomyolysis, and variable defects in the central nervous system. In a white American family, two sons presented with haemolytic anaemia, seizures, and developmental delay. The diagnosis of PGK deficiency was made based on the remarkably low (<5% of normal) erythrocyte PGK enzyme activity level and the identification of a missense (c. 491A → T) PGK1 gene mutation. This mutation results in an Asp164Val amino acid substitution, which has previously been designated PGK‐Amiens and PGK‐New York. The two new patients have the full clinical syndrome of PGK deficiency including haemolytic anaemia, developmental delay and seizures, and in the proband, hemiplegic migraines, retinal dystrophy and muscle fatigue. The PGK‐Amiens/New York mutation had previously been found in a French patient and also in a large Chinese‐Australian kindred, indicating that either the c. 91A → T mutation is a recurrent mutation or that there is shared ancestry between the patients that have been identified so far with the mutation. Haplotype analysis of the c. 91A → T mutation indicated that this was a recurrent mutation.
Ultra‐rush venom immunotherapy induces differential T cell activation and regulatory patterns according to the severity of allergy
Authors: Mamessier E. , Birnbaum J. , Dupuy P. , Vervloet D. , Magnan A.
Published: June 2006

Background
Venom immunotherapy (VIT) induces immune tolerance to hymenoptera venom antigens in allergic patients and is therefore a helpful model for studying modulation of allergic immune response. The objectives were to assess the early effects of ultra‐rush VIT on T lymphocyte activation and regulatory profile induction, in all subjects combined and according to the four severity grades of the Mueller classification.

Materials and Methods
Blood samples from 30 vespid‐allergic patients were taken before and after the first day of treatment, and before day 15 and day 45 booster injections. IFN‐γ and IL‐4 levels were assayed by ELISA, in whole‐blood supernatants. IFN‐γ and IL‐13‐producing T cells, but also natural CD4+CD25+high regulatory T cells and acquired regulatory T cell proportions were assessed by flow cytometry. Results were analysed in the whole population and compared between patients with I–II or III–IV allergic reactions.

Results
During VIT, IFN‐γ increased in whole blood when IL‐4 decreased. Among T cells, the percentage of CD3+IFN‐γ+ cells increased while IL‐13‐producing T cells decreased. Proportions of CD4+CD25+high cells and IL‐10‐producing T cells increased with VIT. In I–II subjects, IFN‐γ increased gradually, whereas it remained at low levels in III–IV patients. By contrast, IL‐4 decrease was more pronounced in III–IV patients. Increase in CD4+CD25+high T cells occurred early in I–II patients but was delayed in III–IV patients. IL‐10‐producing T cells increased gradually in both groups but were in a lower proportion in III–IV patients.

Conclusion
A T helper type 2 (Th2)‐to‐Th1 switch occurs during ultra‐rush VIT, in parallel with natural and acquired regulatory T cell increase. These events occur earlier and at a higher level in less severe subjects, suggesting that VIT tolerance induction is easier to achieve in these patients.
Quantification of Ara h 1 in peanuts: why roasting makes a difference
Authors: Pomés A. , Butts C. L. , Chapman M. D.
Published: June 2006

Background
Increased allergenicity of roasted vs. raw peanut has been reported by showing higher IgE binding to roasted peanut extracts.

Objective
To study the effect of roasting on Ara h 1 quantification in peanut using a specific monoclonal antibody‐based ELISA, and to compare the Ara h 1 content from different kernel size peanuts from four runner cultivars.

Methods
Raw or oven‐roasted (177°C for 5–30 min) runner peanuts were crushed and extracted at 60°C. Inhibition ELISA was used to study binding of Ara h 1 purified from raw or roasted peanut. Runner peanuts of four different cultivars were collected, shelled, sized and roasted for 15 min at 177°C. Ara h 1 in the extracts was compared by ELISA.

Results
Ara h 1 levels were up to 22‐fold higher in roasted than in raw peanuts (820 vs. 37 μg/mL, in a representative experiment) with an Ara h 1 peak at 10–15 min of roasting. Inhibition ELISA indicated that this increase was not due to conformational changes in the Ara h 1 monoclonal antibody epitopes. Ara h 1 was found at lower levels in number 1 than in jumbo‐ and medium‐sized peanuts, and no differences were found among cultivars.

Conclusion
These results suggest that roasting increases the efficiency of Ara h 1 extraction, and/or that the monoclonal antibody binding epitopes were more accessible in roasted peanut. Expression of Ara h 1 is associated with peanut maturity.
Evidence of in vivo basophil activation in chronic idiopathic urticaria
Authors: Vasagar K. , Vonakis B. M. , Gober L. M. , Viksman A. , Gibbons S. P. , Saini S. S.
Published: June 2006

Background
Approximately 40% of chronic idiopathic urticaria (CIU) subjects have autoantibodies to either FcɛRIα or IgE. The effect of such autoantibodies on circulating basophil activation status is unknown.

Objective
The expression of cell surface activation markers on basophils from CIU, non‐allergic, and allergic subjects were compared. Further, the relationship between marker expression and serum factors reported in CIU, such as histamine‐releasing activity (HRA) and immunoreactivity to FcɛRIα were examined.

Methods
Peripheral blood was obtained from CIU, allergic, and non‐allergic donors and fractionated by density gradients. Enriched basophils (1–12%) were analysed by flow cytometry for expression of activation markers including CD63, CD69, and CD203c. Dilutions of serum (5–50%) were analysed for HRA on basophils from a normal donor. Serum was tested for immunoreactivity by western blotting to a standard cell lysate prepared from an RBL‐SX38 cell line transfected with human FcɛRIα.

Results
CIU subjects (n=9) and allergic subjects (n=8) exhibited enhanced expression of CD63 and CD69, as compared with non‐allergic subjects (n=7); however, no difference was seen among groups for CD203c expression. Five CIU and two non‐allergic subjects had evidence of significant serum HRA (>20%), whereas two CIU, two allergic, and three non‐allergic subjects had evidence of serum immunoreactivity to FcɛRIα. Serum HRA and serum immunoreactivity to FcɛRIα were not associated with enhanced surface marker expression.

Conclusion
Basophil activation marker expression is increased in CIU subjects and is not associated with serum factors. In addition, serum HRA and FcɛRIα immunoreactivity are not unique to CIU, or related to enhanced circulating basophil marker expression.
Phl p 3: Structural and immunological characterization of a major allergen of timothy grass pollen
Authors: Petersen Arnd , Suck Roland , Lindner Buko , Georgieva Dessi , Ernst Martin , Notbohm Holger , Wicklein Daniel , Cromwell Oliver , Becker Wolf‐Meinhard
Published: June 2006

Background
The relevant importance of individual allergens for allergic sensitization is only partially understood. More detailed information on allergen structure and how it influences immunological responses can lead to better diagnosis of disease and improved preparations for allergen‐specific immunotherapy. Grass pollen contains several different allergens, and although the group 3 allergens have been classified long ago, their structure and allergenicity have been poorly investigated.

Objective
To characterize Phl p 3 from timothy grass pollen and compare it with Phl p 2 with respect to biochemical structure and allergenicity.

Methods
Natural Phl p 2 and Phl p 3 were separated from a pollen extract by chromatography and characterized by 2D electrophoresis and protein sequencing. The complete sequences were determined by DNA cloning and detected in natural pollen extracts by mass spectrometry. Further comparisons of the allergens were made for IgE‐binding and cross‐reactivity, allergenicity was determined by basophil CD203c activation and skin prick test and 3D structures were compared by molecular modelling.

Results
Phl p 3 reveals molecular masses of 10.958 and 10.973 kDa and pIs of 8.9 and 9.3, respectively, Phl p 2 a molecular mass of 10.816 kDa and a pI of 4.6. The sequence identity is 58%. In spite of these differences in the primary structures, both allergens reveal similar conformational structures, resulting in similar immunological and allergological moieties.

Conclusions
The group 3 and group 2 allergens are major allergens with similar 3D structures. Although they differ considerably in their protein sequences and their pIs, they show only a slightly higher immunological reactivity for Phl p 3 on the B‐cell level (conformational epitopes). But distinct differences between the sequences may influence reactivity at the T cell level.
Association between alcohol consumption and aeroallergen sensitization in Danish adults
Authors: Linneberg A. , Hertzum I. , Husemoen L. L. N. , Johansen N. , Jørgensen T.
Published: June 2006

Background
It has been proposed that alcohol consumption may be one of the lifestyle factors associated with a westernized, urban, and affluent lifestyle contributing to the rise in atopic disease.

Objective
The aim was to investigate the association between alcohol consumption and atopy (aeroallergen sensitization).

Methods
In 1982, a population‐based cross‐sectional study of 3608 Danes (79% of the invited), aged 30, 40, 50, and 60 years, was carried out. Information on alcohol consumption was obtained by a questionnaire. Aeroallergen sensitization was defined as a positive test for the detection of specific IgE against a panel of 19 common inhalant allergens in stored serum samples. A total of 3317 subjects with complete information on all variables were included in the analyses.

Results
We found a statistically significant association between alcohol consumption and aeroallergen sensitization (independent of the type of alcoholic drink consumed). This association appeared to relate only to those who consumed more than 8 drinks/week. After adjustment for confounders this association was only statistically significant for those who consumed 15–21 drinks/week (adjusted odds ratio 1.8, 95% confidence interval 1.2–2.8).

Conclusion
In this adult general population, self‐reported alcohol consumption was positively associated with aeroallergen sensitization.
The cysteinyl‐leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma
Authors: Hao L. , Sayers I. , Cakebread J. A. , Barton S. J. , Beghé B. , Holgate S. T. , Sampson A. P. , Holloway J. W.
Published: June 2006

Background
The cysteinyl‐leukotriene receptor type 1 (CysLT1) mediates the bronchoconstrictor and pro‐inflammatory actions of cysteinyl‐leukotrienes (LTC4, LTD4, LTE4) in asthma and is the molecular target of the lukast class of oral anti‐leukotriene drugs. We screened the CYSLTR1 gene on chromosome Xq13‐21 for coding region polymorphisms, and investigated their associations with allergy and asthma.

Methods
Solid‐phase chemical cleavage was used to screen polymorphisms in the coding region of CYSLTR1. A TaqMan allelic discrimination assay was used to genotype a 927T/C SNP and oligonucleotide ligation assays were used to genotype the previously reported 617T/C and 898G/A SNPs of CYSLTR1 in 341 asthmatic families from the UK. Associations with asthma diagnosis, atopic status, serum‐specific IgE and severity of allergy and asthma were examined.

Results
Family‐based association tests showed that the 927 T allele was associated with atopy severity, especially in female subjects, but not with asthma diagnosis or severity, atopic status, bronchial hyper‐responsiveness to methacholine or forced expiratory volume in 1 s.

Conclusion
Mutation screening identified only one polymorphism, 927T/C, in the coding region of the CysLT1 receptor. This polymorphsim is predictive of atopy severity, but not associated with asthma.