bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinocerebellar Ataxia Type 1 (SCA1) Presenting Similar to Oculopharyngeal Muscular Dystrophy
Authors: Hentschel Kenneth , Rubin Devon I
Published: July 2007

Spinocerebellar ataxia type 1 (SCA1) is a trinucleotide repeat disorder with a variable clinical phenotype consisting of ataxia, dysarthria, and peripheral neuropathy, but no primary muscle involvement. Another trinucleotide repeat disorder, oculopharyngeal muscular dystrophy (OPMD), is a progressive myopathic disorder characterized predominantly by dysarthria, dysphagia, ptosis, and proximal weakness. We describe the clinical and electrophysiologic, features of a patient with genetically confirmed SCA1 with an OPMD-like presentation. The findings of a peripheral neuropathy without myopathy on electrodiagnostic testing are useful to help in differentiation of the disorders and are supportive of SCA1. This case illustrates that the differential diagnosis of patients with dysphagia and dysarthria should be expanded to include SCA1.
Treatment Response to Steroid and Intravenous Immunoglobulin in a Patient with Chronic Sensory Demyelinating Neuropathy
Authors: Odaka Masaaki , Itoh Masafumi , Hirata Koichi , Yuki Nobuhiro
Published: July 2007

We report a patient with chronic sensory demyelinating neuropathy (CSDN) who did not initially have a beneficial response to intravenous immunoglobulin (IVIG) but who gradually improved with steroid therapy. An 18-year-old man had slowly progressive sensory ataxia with distal paresthesia and areflexia. Neither limb weakness nor cerebellar ataxia was present during the course of his illness. Electrophysiologic evaluations indicated demyelinating neuropathy in the motor and sensory nerves. Magnetic resonance imaging with gadolinium enhancement showed hypertrophic brachial and lumbosacral spinal roots. He received high intravenous doses of immunoglobulin but did not respond to them. Prednisolone was prescribed daily for 1 month in conjunction with IVIG; it was reduced by 5 mg on successive weeks. He slowly improved and for 1 year has remained in remission without any other treatment after steroid therapy was stopped. Our findings suggest that steroid therapy should be tried with patients with CSDN when there is no favorable response to IVIG. CSDN response to steroid but not to IVIG may distinguish it as a chronic inflammatory demyelinating polyneuropathy (CIDP) subgroup.
Lumbosacral Plexopathies: Etiology, Frequency, and Electrodiagnostic Localization
Authors: Karli Necdet , Zarifoglu Mehmet , Akgoz Semra , Chaudhry Vinay
Published: July 2007

Objective:

Lumbosacral plexopathies (LSP) may occur as a result of trauma, radiation, neoplastic invasion, or diabetes mellitus, or they may be idiopathic.

Methods:

We retrospectively analyzed relative frequencies of different LSP causes and their localizations and compared their electrophysiologic findings.

Results:

A retrospective review of 34 patients' charts showed the following: idiopathic (n = 12, 35.3%), trauma (n = 9, 26.4%), radiation (n = 9, 26.4%), and diabetes mellitus (n = 4, 11.8%).

Although all patients had significant weakness, sensory symptoms or deficits were present in only 44.1% of the patients. Twelve (35.2%) patients had bilateral lumbosacral plexus involvement. The majority of the patients (66.7%) in the radiotherapy group presented with bilateral involvement. Panplexopathy was the most frequent localization. The peroneal branch of the sciatic nerve was the most commonly involved nerve. Needle electromyography showed abnormal spontaneous denervation potentials in 31 (91.2%) patients. Myokymia was only present in the radiation therapy group.

Conclusions:

Idiopathic LSP is the most common type followed by radiation and diabetic plexopathy.
Asymmetric three-dimensional Stokes flows about two fused equal spheres
Authors: Zabarankin Michael
Published: July 2007

Exact solutions to three-dimensional Stokes flow problems for asymmetric translation and rotation of two fused rigid spheres of equal size have been obtained in toroidal coordinates. The problems have been reduced to three-contour equations for meromorphic functions from a certain class, and then the latter have been reduced to Fredholm integral equations of the second kind by the Mehler–Fock transform of order 1. For the specified class of functions, the equivalence of the corresponding three-contour and Fredholm equations has been established in the framework of Riemann boundary-value problems for analytic functions. As an illustration for the obtained solutions, the pressure has been calculated at the surface of the body for both problems, and resisting force and torque, experienced by the body in asymmetric translation and rotation, have been computed as functions of a geometrical parameter of the body.
Paradigm shifts in surface metrology. Part II. The current shift
Authors: Jiang X , Scott P.J , Whitehouse D.J , Blunt L
Published: July 2007

This is the second part of the paper ‘Paradigm shifts in surface metrology’. In part I, the three historical paradigm shifts in surface metrology were brought together, and the subsequent evolution resulting from the shifts discussed. The historical philosophy highlighted the fact that the paradigm shifts must be robust and flexible, meaning that surface metrology must allow for full control of surface manufacture and provide an understanding of the surface functional performance. Part II presents the current paradigm shift as a ‘stepping stone’, building on the above historical context. Aspects of surface geometry will also have to cater for surfaces derived from disruptive application, i.e. structured and freeform surfaces are identified candidates. The current shift is presented in three aspects: from profile to areal characterization; from stochastic to structured surfaces; and from simple geometries to complex freeform geometries, all spanning the millimetre to sub-nanometre scales. In this paradigm shift, the scale of surface texture is beginning to approach some of the geometrical features in micro/nano electro-mechanical systems devices and is becoming one of the most important functionality indicators. Part II will contextualize the current shifts in the discipline of surface metrology, and cement surface metrology in place in the ultra precision and nanotechnology age.
Paradigm shifts in surface metrology. Part I. Historical philosophy
Authors: Jiang X , Scott P.J , Whitehouse D.J , Blunt L
Published: July 2007

Surface texture and its measurement are becoming the most critical factors and important functionality indicators in the performance of high precision and nanoscale devices and components. Surface metrology as a discipline is currently undergoing a huge paradigm shift: from profile to areal characterization, from stochastic to structured surfaces, and from simple geometries to complex free-form geometries, all spanning the millimetre to sub-nanometre scales.

This paper builds a complete philosophical framework for surface metrology through a review of the paradigm shifts that have occurred in the discipline of surface metrology, tracing the development of fundamental philosophies and techniques. The paper starts with a brief overview of the historical paradigm shifts and builds an up-to-date foundational philosophy, capable of rapid and effective development. The growth in interest in surface metrology stems mainly from the need to control the manufacture of armaments during the Second World War and the production of domestic goods and appliances since that time. The surfaces produced by manufacture seemed to offer the possibility of being useful for process control. Unfortunately, only a few tentative investigations had been carried out to establish usable relationships between the processes, the machine tools and the available surface parameters (with their limitations). Even fewer investigations had been carried out to relate surface geometry to the performance of manufactured products. The result was that the metrology was unprepared and, consequently, the progress was sporadic.

This overall review is given in two parts. Part I focuses on the historical philosophy of surface metrology and Part II discusses the progress within the current paradigm shift.
Heavy hydroelastic travelling waves
Authors: Toland J.F
Published: July 2007

This is a mathematical study of steady two-dimensional waves of prescribed period which propagate without change of form on the surface of an infinitely deep expanse of fluid that is moving under gravity and bounded above by heavy, frictionless, thin elastic sheet. The flow, which is supposed irrotational, is at rest at infinite depth and its velocity is stationary relative to a frame moving with the wave. In that frame, the elastic sheet coincides with the zero streamline and its material points move according to the equations of hyperelasticity.

From the mechanics of the surface material, the pressure on a point of the sheet in the moving frame is shown to be a function of its height, its slope and derivatives with respect to arc length of these quantities. Independently, according to classical fluid mechanics, the pressure in the fluid at the same point is determined by its height and the fluid velocity tangent to the zero streamline.

Therefore, this is a free-boundary problem: to find a non-self-intersecting curve in the plane which is the zero contour of a harmonic function (the stream function) and at which the normal derivative of the same harmonic function is a prescribed function of the shape of the curve.

With the wavelength fixed, the parameters are the density
ρ
of the undeformed sheet, the wave velocity
c
0
, the mean velocity
c
of the surface sheet relative to the wave and the gravitational acceleration
g
. The case of a weightless sheet, in which
ρ
=0 and
c
does not appear, is a special case. Under quite general hypotheses on the elastic response of the sheet, the existence of rapidly propagating or very slow (depending on parameter values) steady waves is established by finding a critical point of the Lagrangian. This is a saddle-point problem in the calculus of variations.
Expression evolution in yeast genes of single-input modules is mainly due to changes in trans-acting factors
Authors: Wang Daryi , Sung Huang-Mo , Wang Tzi-Yuan , Huang Chih-Jen , Yang Peggy , Chang Tiffany , Wang Yang-Chao , Tseng Da-Lun , Wu Jen-Pey , Lee Tso-Ching , Shih Ming-Che , Li Wen-Hsiung
Published: July 2007

Both cis- and trans-regulatory mutations contribute to gene expression divergence within and between species. To estimate their relative contributions, we examined two yeast strains, BY (a laboratory strain) and RM (a wild strain), for their gene-expression divergence by microarray. Using these data and published ChIP-chip data, we obtained a set of single-regulator-regulated genes that showed expression divergence between BY and RM. We randomly selected 50 of these genes for further study. We developed a step-by-step approach to assess the relative contributions of cis- and trans-variations to expression divergence by using pyrosequencing to quantify the mRNA levels of the BY and RM alleles in the same culture (co-culture) and in hybrid diploids. Forty genes showed expression divergence between the two strains in co-culture, and pyrosequencing of the BY/RM hybrid diploids showed that 45% (18/40) can be attributed to differences in trans-acting factors alone, 17.5% (7/40) mainly to trans-variations, 20% (8/40) to both cis- and trans-acting factors, 7.5% (3/40) mainly to cis-variations, and 10% (4/40) to cis-acting factors alone. In addition, we replaced the BY promoter by the RM promoter in each of 10 BY genes that were found from our microarray data to have expression divergence between BY and RM, and in each case our quantitative PCR analysis revealed a cis effect of the promoter replacement on gene expression. In summary, our study suggests that trans-acting factors play the major role in expression evolution between yeast strains, but the role of cis variation is also important.
Chemical Genetic Identification of Glutamine Phosphoribosylpyrophosphate Amidotransferase as the Target for a Novel Bleaching Herbicide in Arabidopsis
Authors: Walsh Terence A. , Bauer Teresa , Neal Roben , Merlo Ann Owens , Schmitzer Paul R. , Hicks Glenn R. , Honma Mary , Matsumura Wendy , Wolff Karen , Davies John P.
Published: July 2007

A novel phenyltriazole acetic acid compound (DAS734) produced bleaching of new growth on a variety of dicotyledonous weeds and was a potent inhibitor of Arabidopsis (Arabidopsis thaliana) seedling growth. The phytotoxic effects of DAS734 on Arabidopsis were completely alleviated by addition of adenine to the growth media. A screen of ethylmethanesulfonate-mutagenized Arabidopsis seedlings recovered seven lines with resistance levels to DAS734 ranging from 5- to 125-fold. Genetic tests determined that all the resistance mutations were dominant and allelic. One mutation was mapped to an interval on chromosome 4 containing At4g34740, which encodes an isoform of glutamine phosphoribosylamidotransferase (AtGPRAT2), the first enzyme of the purine biosynthetic pathway. Sequencing of At4g34740 from the resistant lines showed that all seven contained mutations producing changes in the encoded polypeptide sequence. Two lines with the highest level of resistance (125-fold) contained the mutation R264K. The wild-type and mutant AtGPRAT2 enzymes were cloned and functionally overexpressed in Escherichia coli. Assays of the recombinant enzyme showed that DAS734 was a potent, slow-binding inhibitor of the wild-type enzyme (I50 approximately 0.2 μ  m), whereas the mutant enzyme R264K was not significantly inhibited by 200 μ  m DAS734. Another GPRAT isoform in Arabidopsis, AtGPRAT3, was also inhibited by DAS734. This combination of chemical, genetic, and biochemical evidence indicates that the phytotoxicity of DAS734 arises from direct inhibition of GPRAT and establishes its utility as a new and specific chemical genetic probe of plant purine biosynthesis. The effects of this novel GPRAT inhibitor are compared to the phenotypes of known AtGPRAT genetic mutants.
Development of silver carp (Hypophthalmichthys molitrix) and bighead carp (Aristichthys nobilis) genetic maps using microsatellite and AFLP markers and a pseudo‐testcross strategy
Authors: Liao M. , Zhang L. , Yang G. , Zhu M. , Wang D. , Wei Q. , Zou G. , Chen D.
Published: July 2007

Silver carp (Hypophthalmichthys molitrix) and bighead carp (Aristichthys nobilis) are two of the four most important pond‐cultured fish species inhabiting the major river basins of China. In the present study, genetic maps of silver carp and bighead carp were constructed using microsatellite and AFLP markers and a two‐way pseudo‐testcross strategy. To create the maps, 60 individuals were obtained from a cross of a single bighead carp (female) and a single silver carp (male). The silver carp map consisted of 271 markers (48 microsatellites and 223 AFLPs) that were assembled into 27 linkage groups, of which 22 contained at least four markers. The total length of the silver carp map was 952.2 cM, covering 82.8% of the estimated genome size. The bighead carp map consisted of 153 markers (27 microsatellites and 126 AFLPs) which were organized into 30 linkage groups, of which 19 contained at least four markers. The total length of the bighead carp map was 852.0 cM, covering 70.5% of the estimated genome size. Eighteen microsatellite markers were common to both maps. These maps will contribute to discovery of genes and genetic regions controlling traits in the two species of carp.
Genetic relationships among Chinese pigs and other pig populations from Hunan Province, China
Authors: Tao J. , Qin Z.‐Q. , Tao Y. , Wen L. , Shu X.‐S. , Wang Z.‐C. , Liu X.‐W. , Li W.‐J. , Hu W.‐X.
Published: July 2007

In this study, protein‐level polymorphisms of transferrin, pre‐albumin, hemopexin, ceruloplasmin and amylase were investigated in Hunan native pigs and Large Yorkshire pigs collected from Hunan (a province of China), allowing calculations of allele frequencies, average heterozygosities, inbreeding coefficients and genetic distances. The genetic relationship between Southeast Asian native pigs and American pigs was more distant than those among Southeast Asian native pig breeds. The genetic relationship between Southeast Asian native pig breeds and Hampshire pigs was the most distant.
Psychometric analysis of the Functional Independence Score in Haemophilia (FISH)
Authors: POONNOOSE P. M. , THOMAS R. , KESHAVA S. N. , CHERIAN R. S. , PADANKATTI S. , PAZANI D. , KAVITHA M. L. , DEVADARASINI M. , BHATTACHARJI S. , VISWABANDYA A. , JOHN J. A. , MACADEN A. S. , MATHEWS V. , SRIVASTAVA A.
Published: July 2007

Summary.  Joint morbidity in haemophilia has traditionally been measured using clinical and radiological scores. There have been no reliable, validated tools for the assessment of functional independence in persons with haemophilia till recently. The Functional Independence Score in Haemophilia (FISH) has been developed as a performance based assessment tool to address this need. The FISH is designed to measure the patient’s independence in performing activities of daily living (grooming and eating, bathing and dressing), transfers (chair and floor), and mobility (walking, step climbing and running). On assessment of its psychometric properties in 63 patients with haemophilia (mean age 14 years), FISH was found to have good internal consistency (Cronbach’s alpha of 0.85). It had moderate correlation with the World Federation of Hemophilia clinical score (r = −0.61), and a correlation with the Pettersson score of −0.38. It had good correlation with other self‐rated functional scores, such as the Stanford Health Assessment Questionnaire (r = −0.75); the Western Ontario and McMaster Universities Osteoarthritis Index (r = −0.66) and the Haemophilia Activities List (HAL) (r = −0.66). It had good reliability with a pooled intra class correlation of 0.98. On assessing responsiveness following treatment of flexion deformities of the knee in 12 patients, the FISH showed significant changes in the score with a standardized responsiveness mean of −1.93. In conclusion, the FISH was found to be a reliable and valid tool with good internal consistency and responsiveness to therapy, for the assessment of functional independence in persons with haemophilia.
Combining δ13C and δ18O analyses to unravel competition, CO2 and O3 effects on the physiological performance of different‐aged trees
Authors: GRAMS THORSTEN E. E. , KOZOVITS ALESSANDRA R. , HÄBERLE KARL‐HEINZ , MATYSSEK RAINER , DAWSON TODD E.
Published: July 2007

Combined δ13C and δ18O analyses of leaf material were used to infer changes in photosynthetic capacity (Amax) and stomatal conductance (gl) in Fagus sylvatica and Picea abies trees growing under natural and controlled conditions. Correlation between gl and δ18O in leaf cellulose (δ18Ocel) allowed us to apply a semi‐quantitative model to infer gl from δ18Ocel and also interpret variation in δ13C as reflecting variation in Amax. Extraction of leaf cellulose was necessary, because δ18O from leaf organic matter (δ18OLOM) and δ18Ocel was not reliably correlated.

In juvenile trees, the model predicted elevated carbon dioxide (CO2) to reduce Amax in both species, whereas ozone (O3) only affected beech by reducing CO2 uptake via lowered gl. In adult trees, Amax declined with decreasing light level as gl was unchanged. O3 did not significantly affect isotopic signatures in leaves of adult trees, reflecting the higher O3 susceptibility of juvenile trees under controlled conditions. The isotopic analysis compared favourably to the performance of leaf gas exchange, underlining that the semi‐quantitative model approach provides a robust way to gather time‐integrated information on photosynthetic performance of trees under multi‐faced ecological scenarios, in particular when information needed for quantitative modelling is only scarcely available.
Volatile fluxes from volcanoes
Authors: Cloarec Marie‐Françoise Le , Marty Bernard
Published: July 2007

Volatile fluxes from Mid Ocean Ridge (MOR) and subaerial volcanism have been estimated or re‐evaluated using several natural tracers‐3He, 210Po, SO2‐and chemical ratios of volatile species in lavas and volcanic gases.

These estimates confirm the net predominance of anthropogenic fluxes over volcanic fluxes for CO2, SO2 and trace metals.

They also suggest that, while most of the volatiles transferred during MOR volcanism come from the mantle, volatiles stored at the surface of the Earth supply an appreciable fraction of subaerial fluxes and can be the dominant source for some of them.

The surface inventory of volatile species cannot result from steady‐state degassing with constant rate and needs much greater fluxes in the past or other volatile supply processes. This inventory is the result of several of the following processes: capture of the solar nebula and its subsequent partial escape, impact degassing of accreting bodies, and, from Archean to present mantle, degasssing through volcanism and associated phenomena, with recycling into the mantle through subduction.
TERRA BOOKS PALAEOBIOLOGY A SYNTHESIS
Authors: Briggs Derek.E.G. , Crowther Peter R.
Published: July 2007

1990, £89.50 (hbk), 583 pp. Blackwell Scientific Publications, Oxford ISBN 0–632–02525–5
DRIFTlNG CONTINENTS AND COLLIDING PARADIGMS: PERSPECTIVES ON THE GEOSCIENCE REVOLUTION
Authors: Stewart John A.
Published: July 2007

1990, $35.00, xiii+286 pp, Indiana University Press, Bloomington. ISBN 0–253–35405–6.
Carbo‐Permian pteridophyll leaf fragments from an amphibolite facies basement, Tauern Window, Austria
Authors: Franz G. , Mosbruggr V. , Menge R.
Published: July 2007

Graphitic schists from the Pennine Basement, Tauern Window, Austria, contain fragments of pteridophyll leaves. They are preserved, despite the overall strong deformation and metamorphism at amphibolite facies conditions (˜ 525°C, 750°100 MPa), due to a particular strain path with volume loss by pressure solution. They were determined as cf. Callipteridium sp. indicating a Permo‐Carboniferous age. This depositional age is similar to radiometric age data obtained for the intrusion of nearby metagranitoids, indicating either tectonic contacts between the metagranitoids and the graphite schists, or a very active and rapidly changing tectonic regime during the Hercynian event.
Stepwise mass extinctions: the case for the Late Cenomanian event
Authors: Hart Malcolm B. , Leary Paul N.
Published: July 2007

The various extinctions of marine taxa in the Late Cenomanian can be shown as conforming to the ‘step‐wise extinction’ model. The order of such extinctions is, however, compatible with the presence of an expanded oxygen minimum zone in the world ocean. The occurrence of iridium anomalies at this level in the succession may, however, indicate a volcanogenic control on the global environment. Detailed time‐analysis of the Late Cenomanian event has been used to produce a correlation of some key successions.
The Rukwa earthquake of 13 December 1910 in East Africa
Authors: Ambraseys N.N.
Published: July 2007

We reappraised the Rukwa earthquake of 1910 in the East African Rift System. With a magnitude of 7.4, no earthquake in East Africa is known to be larger and it is rivalled only by the recent earthquake in southern Sudan on 20 May 1990. More than 80 per cent of the moment release in the Rift during the last 110 years is due to the Rukwa earthquake and its aftershocks that occurred between the Tanganyka and Nyasa systems. In spite of its large magnitude, the Rukwa earthquake caused very little damage to local types of dwellings and no loss of life. With increasing development of urban areas with modern types of houses, there is now increasing risk in East Africa from major earthquakes.
Patient involvement in patient safety: what factors influence patient participation and engagement?
Authors: Davis Rachel E. , Jacklin Rosamond , Sevdalis Nick , Vincent Charles A.
Published: July 2007

Background Patients can play an important role in improving patient safety by becoming actively involved in their health care. However, there is a paucity of empirical data on the extent to which patients take on such a role. In order to encourage patient participation in patient safety we first need to assess the full range of factors that may be implicated in such involvement.

Objective To delineate factors that could affect the participation of the patient in quality and safety issues in their health care.

Method Literature review of patient involvement in health care, drawing from direct evidence (specifically from the safety context) and indirect evidence (extrapolated from treatment decision‐making research and the wider patient involvement in health care literature); synthesis and conceptual framework developed, illustrating the known and putative factors that could affect the participation of the patient in safety issues in their health care.

Main results Five categories of factors emerged that could affect patient involvement in safety: patient‐related (e.g. patients’ demographic characteristics), illness‐related (e.g. illness severity), health‐care professional‐related (e.g. health care professionals’ knowledge and beliefs), health care setting‐related (e.g. primary or secondary care), and task‐related (e.g. whether the required patient safety behaviour challenges clinicians’ clinical abilities).

Conclusion The potential for engaging patients in patient safety is considerable but further research is needed to examine the influences on patient involvement, the limits and the possible dangers. Patients can act as ‘safety buffers’ during their care but the responsibility for their safety must remain with the health care professionals.
The role and value of written information for patients about individual medicines: a systematic review
Authors: Grime Janet , Blenkinsopp Alison , Raynor David K. , Pollock Kristian , Knapp Peter
Published: July 2007

Objective  To review research on the role and value of written medicines information for patients from the perspective of patients and health professionals.

Context  Providing written information to patients about their medicines is acknowledged as a priority but there is poor understanding of how best to meet patients’ needs.

Method  A sensitive search strategy was developed to maximize the identification of relevant studies. We used a data extraction form designed to appraise qualitative research. Findings were synthesized into a narrative account.

Main results  There were three broad categories of study: those which related to policy initiatives; those where the aim was to increase compliance; and those concerned with using information to support decision‐making (‘informed patient’ studies). While the policy initiative and compliance studies reported that, mostly, patients were positive about written information, the ‘informed patient’ studies showed a more complex picture. Patients valued medicines information tailored to their condition. They did not want it to be a substitute for spoken information from their doctor. Not everyone wanted written information but those who did wanted sufficient detail to meet their need. Need varied over time and between patients. The small number of studies relating to health professionals showed widespread ambivalence towards using written information. Some thought it should be brief and simple, only partially disclose side‐effects and saw its main role as being to increase compliance.

Conclusion  The different perspectives of patients and health professionals, and the diverse and changing information needs of patients pose a challenge to providers of written medicines information.
Nonallergic angioedema: role of bradykinin
Authors: Bas M. , Adams V. , Suvorava T. , Niehues T. , Hoffmann T. K. , Kojda G.
Published: July 2007

Angioedema is an underestimated clinical problem. Many cases are nonallergic reactions, e.g. bradykinin‐induced angioedema caused by genetic defects and angiotensin‐converting enzyme (ACE) inhibitors. This difference is crucial for successful therapy, in particular when complete emergency care is not available. Five important forms of nonallergic angioedema can be distinguished: hereditary (HAE), acquired (AAE), renin‐angiotensin‐aldosterone system (RAAS)‐blocker‐induced (RAE), pseudoallergic angioedema (PAE) and idiopathic angioedema (IAE). Some angioedema are present in the larynx and may cause death. A vast majority of nonallergic angioedema are RAE, particularly those caused by ACE inhibitors. It appears important to emphasize that in patients with complete intolerance to RAAS‐blockers, cessation of RAAS‐blockers is likely to be associated with increased cardiovascular risk. Currently, there is no published algorithm for diagnosis and treatment. Angioedema is usually treated by a conservative clinical approach using artificial ventilation, glucocorticoids and antihistamines. Today, a plasma pool C1‐esterase inhibitor (C1‐INH) concentrate is the therapy of choice in HAE. The current pharmacotherapy of nonallergic angioedema is not satisfactory, thus requiring the identification of effective agents in clinical trials. Recently, several new drugs were developed: a recombinant C1‐INH, a kallikrein inhibitor (ecallantide) and a specific bradykinin‐B2‐receptor antagonist (icatibant). According to currently available reports, these drugs may improve the treatment of kinin‐induced angioedema.
Placebo reactions in double‐blind, placebo‐controlled food challenges in children
Authors: Vlieg‐Boerstra B. J. , Van Der Heide S. , Bijleveld C. M. A. , Kukler J. , Duiverman E. J. , Dubois A. E. J.
Published: July 2007

Background:  A cardinal feature of the double‐blind, placebo‐controlled food challenge (DBPCFC) is that placebo administration is included as a control. To date, the occurrence and diagnostic significance of placebo events have not extensively been documented.

Objective:  To analyse the occurrence and features of placebo events in DBPCFCs and to assess their contribution to the diagnostic accuracy of the DBPCFC in children.

Methods:  The study population consisted of 132 challenges in 105 sensitized children (age range 0.7–16.6 years, median 5.3 years), who underwent DBPCFCs with cow’s milk, egg, peanut, hazelnut and soy. Placebo and active food challenges were performed on different days.

Results:  A total number of 17 (12.9%) positive placebo events occurred, which could be classified as immediate (9/17), late‐onset (8/17), objective (11/17) or subjective (6/17). Four of 74 (5.4%) positive active food challenges were revealed to be false positive by administration of a placebo challenge. This is 3% (4/132) of all challenges. When computed by a statistical model, the false positive rate was 0.129 (12.9% of all challenges).

Conclusion:  Placebo events with diverse clinical characteristics occur in DBPCFCs in a significant number of children. The diagnostic significance of the administration of a placebo challenge is first, to identify false positive diagnoses in DBPCFCs by refuting false positive tests in individual patients. Secondly, to allow for blinding of the active food challenge. Thirdly, applying a statistical model demonstrates that some positive challenges may be false positive and that the test may need to be repeated in selected cases.
Comparison of international guidelines for the emergency medical management of anaphylaxis
Authors: Alrasbi M. , Sheikh A.
Published: July 2007

Background:  Guideline‐based treatment approaches for managing anaphylaxis are widely believed to result in good outcomes, but the strength of evidence underpinning the recommendations made therein is unclear.

Objective:  To identify and compare national guidelines for the emergency medical management of anaphylaxis and to describe the extent to which the evidence base in support of key recommendations is made clear.

Methods:  We systematically searched key medical databases and contacted the World Allergy Organization and anaphylaxis charities in several countries to identify national guidelines. Full text copies of relevant papers were obtained and, where necessary, translated. Data were abstracted onto a customized data extraction sheet; this process was independently checked by a second reviewer.

Results:  Guidelines originating from Australia, Canada, Russia, UK, Ukraine and the USA were identified. While these were in agreement on the broad principles of management, there were important variations in relation to the treatments to be used and the dose and route of administration of these preparations. Most guidelines failed to make clear the strength of evidence underpinning the recommendations being made.

Conclusions:  There are important international differences in the recommended emergency management of anaphylaxis. It is important that an agreed core evidence‐based guideline for the management of anaphylaxis is now developed, which can then be adapted for national/local use. Clinicians need to be aware of the limitations of existing guidelines.
Specific immunotherapy has long‐term preventive effect of seasonal and perennial asthma: 10‐year follow‐up on the PAT study
Authors: Jacobsen L. , Niggemann B. , Dreborg S. , Ferdousi H. A. , Halken S. , Høst A. , Koivikko A. , Norberg L. A. , Valovirta E. , Wahn U. , Möller C. ,   (The PAT investigator group)
Published: July 2007

Background:  3‐year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5‐year follow‐up) indicating long‐term preventive effect of SIT.

Objective:  We evaluated the long‐term clinical effect and the preventive effect of developing asthma 7‐years after termination of SIT.

Methods:  One hundred and forty‐seven subjects, aged 16–25 years with grass and/or birch pollen allergy was investigated 10 years after initiation of a 3‐year course of SIT with standardized allergen extracts of grass and/or birch or no SIT respectively. Conjunctival provocations were performed outside the season and methacholine bronchial provocations were performed during the season and winter. Asthma was assessed by clinical evaluation.

Results:  The significant improvements in rhinoconjunctivitis and conjunctival sensitivity persisted at the 10‐year follow‐up. Significantly less actively treated subjects had developed asthma at 10‐year follow‐up as evaluated by clinical symptoms [odds ratio 2.5 (1.1–5.9)]. Patients who developed asthma among controls were 24/53 and in the SIT group 16/64. The longitudinal treatment effect when adjusted for bronchial hyper‐responsiveness and asthma status at baseline including all observations at 3, 5 and 10 years follow‐up (children with or without asthma at baseline, n = 189; 511 observations) was statistically significant (P = 0.0075). The odds ratio for no‐asthma was 4.6 95% CI (1.5–13.7) in favor of SIT.

Conclusion:  A 3‐year course of SIT with standardized allergen extracts has shown long‐term clinical effects and the potential of preventing development of asthma in children with allergic rhinoconjunctivitis up to 7 years after treatment.

Clinical implication:  Specific immunotherapy has long‐term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination.
Clinical presentation and time course in hypersensitivity reactions to β‐lactams
Authors: Bousquet P. J. , Kvedariene V. , Co‐Minh H.‐B. , Martins P. , Rongier M. , Arnoux B. , Demoly P.
Published: July 2007

Background:  β‐lactam hypersensitivity reactions are classified as immediate or nonimmediate. Diagnosis is usually based upon skin tests and provocation challenges.

Objective:  The time course of the reactions in proven β‐lactam hypersensitivities was studied and then correlated with the symptoms to determine the relationship between the clinical presentations and the time course.

Method:  All of the patients who consulted between 1996 and 2004 for a suspected β‐lactam hypersensitivity reaction were studied. Two hundred and ten patients with a proven hypersensitivity reaction diagnosed according to the European Network on Drug Allergy were included in the present study.

Results:  Of the patients, 36.7% had urticaria as a single symptom, 19.1% anaphylaxis without shock, 17.6% anaphylactic shock and 19.1% maculopapular exanthema. Anaphylactic shock and anaphylaxis mostly occurred within 1 h after drug administration. Exanthema mainly occurred after 24 h. Urticaria as a single symptom occurred at any time. A firm diagnosis was determined using immediate‐reading skin prick (10.0%) and intradermal tests (38.1%), late‐reading skin tests (19.1%) or provocation tests (32.9%).

Conclusion and clinical implication:  Depending on the time course of the reaction, three clinical groups were identified: anaphylaxis and anaphylactic shock (immediate reaction); maculopapular exanthema (late reaction) as well as urticaria (immediate and late reaction).
Clinical score of 62 Italian patients with Cornelia de Lange syndrome and correlations with the presence and type of NIPBL mutation
Authors: Selicorni A , Russo S , Gervasini C , Castronovo P , Milani D , Cavalleri F , Bentivegna A , Masciadri M , Domi A , Divizia MT , Sforzini C , Tarantino E , Memo L , Scarano G , Larizza L
Published: July 2007

Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder characterized by facial dysmorphisms, upper limb abnormalities, growth and cognitive retardation. About half of all patients with CdLS carry mutations in the NIPBL gene. The first Italian CdLS cohort involving 62 patients (including 4 related members) was screened for NIPBL mutations after a clinical evaluation using a quantitative score that integrates auxological, malformation and neurodevelopmental parameters. The patients were classified as having an overall ‘severe’, ‘moderate’ or ‘mild’ phenotype. NIPBL screening showed 26 mutations so classified: truncating (13), splice‐site (8), missense (3), in‐frame deletion (1) and regulatory (1). The truncating mutations were most frequently found in the patients with a high clinical score, whereas most of the splice‐site and all missense mutations clustered in the low‐medium score groups. The NIPBL‐negative group included patients covering the entire clinical spectrum. The prevalence of a severe phenotype in the mutated group and a mild phenotype in the non‐mutated group was statistically significant. In terms of the isolated clinical signs, the statistically significant differences between the mutation‐positive and mutation‐negative individuals were pre‐ and post‐natal growth deficits, limb reduction, and delayed speech development. The proposed score seems to be a valuable means of prioritizing the patients with CdLS to undergo an NIPBL mutation test.
Optical rhinometry: Application on children and adolescents for nasal provocation tests
Authors: Mittenzwey Holger , Wüstenberg Eike Gunther , Leupold Wolfgang
Published: July 2007

Optical rhinometry is a new method that allows the direct, real time measurement of changes in swelling of the nasal mucosa by external measurement. The measurement is carried out with monochromatic near‐infrared light. The change of intensity of the swelling is displayed and recorded. Different preceding studies on adults already showed the reliability and absence of side effects of the measuring method. With the help of a prototype of an optical rhinometer specially developed for children, 65 measurements were performed on a total of 13 children and adolescents having one‐sided nasal provocation tests with histamine and allergens, negative provocation tests with control solution and decongestion with xylometazoline. The nasal provocation tests were implemented by optical rhinometry while simultaneously using the established method of active anterior rhinomanometry. We found significant differences between positive and negative provocation tests in both methods (p < 0.01). Decongestion was different from all other groups in both methods (p < 0.01). No clear connection could be made between the percentage increase of rhinometric extinction and the percentage increase of obstruction measured by anterior rhinomanometry. The evaluation of the nasal provocation test via continuous direct measurement of swelling of the nasal mucosa membrane seems feasible in children. Data which so far could not be measured, such as the beginning of swelling and the time of the maximum state of swelling, might increase the diagnostic validity of provocation tests.
Cross‐sectional study of allergic disorders associated with breastfeeding in Japan: The Ryukyus Child Health Study
Authors: Miyake Yoshihiro , Arakawa Masashi , Tanaka Keiko , Sasaki Satoshi , Ohya Yukihiro
Published: July 2007

Uncertainties remain as to whether breastfeeding is protective against childhood allergic disorders. Positive relationships of breastfeeding with asthma and atopic eczema were observed in two previous Japanese studies. This cross‐sectional study investigated the association between the feeding pattern after birth and the prevalence of allergic disorders during the past 12 months in Japanese schoolchildren. Study subjects were 24,077 children aged 6–15 yr in Okinawa. The outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Allowance was made for age, sex, number of siblings, smoking in the household, paternal and maternal history of asthma, atopic eczema, and allergic rhinitis, and paternal and maternal educational level. Breastfeeding, regardless of exclusivity, for 13 months or longer and exclusive breastfeeding for 4–11 months were independently associated with a higher prevalence of atopic eczema, particularly among children without a parental allergic history. A clear positive dose–response relationship was observed between prolonged duration of breastfeeding, regardless of exclusivity, but not exclusive breastfeeding, and the prevalence of atopic eczema. We found a significant positive trend for atopic eczema across the three categories (formula milk, partial and exclusive breastfeeding) in the first 4 months of life although the odds ratio for exclusive breastfeeding was not statistically significant. No material association was found between the feeding pattern after birth and the prevalence of wheeze or allergic rhinoconjunctivitis. Prolonged breastfeeding may be associated with a higher prevalence of atopic eczema in Japanese children.
SENSORY NEURAL TARGETS FOR THE TREATMENT OF COUGH
Authors: Mazzone Stuart B , McGovern Alice E
Published: July 2007

Cough is a primary defensive reflex that protects the airways from potentially harmful stimuli.

During many respiratory diseases, the cough reflex threshold is lowered and coughing becomes excessive.

Currently available therapeutics are mostly ineffective at suppressing excessive coughing.

In the present review, we describe the sensory neural pathways involved in cough, how these pathways may become dysfunctional in airway disease and the most recent advances that have been made in identifying future targets for cough suppression.
WHAT MAKES A CGRP2RECEPTOR?
Authors: Hay DL
Published: July 2007

Heterogeneity in the receptors for the neuropeptide calcitonin gene‐related peptide (CGRP) has been apparent for nearly 20 years. This is most clearly manifested in the observation of CGRP8–37‐sensitive and ‐insensitive populations of CGRP‐activated receptors. The pA2values for CGRP8–37in excess of 7 are widely considered to be the result of antagonism of CGRP1receptors, whereas those below 7 are believed to be the consequence of antagonism of a second population of receptors, namely CGRP2receptors.

However, a multitude of pA2values exist for CGRP8–37, spanning several log units, and as such no obvious clusters of values are apparent. Understanding the molecular nature of the receptors that underlie this phenomenon is likely to aid the development of selective pharmacological tools to progress our understanding of the physiology of CGRP and related peptides. Because there is active development of CGRP agonists and antagonists as therapeutics, such information would also further this pursuit.

The CGRP1receptor is pharmacologically and molecularly well defined as a heterodimer of the calcitonin receptor‐like receptor (CL) and receptor activity modifying protein (RAMP) 1. The CL/RAMP1 complex is highly sensitive to CGRP8–37. Conversely, the constituents of the CGRP2receptor have not been identified. In fact, there is little evidence for a distinct molecular entity that represents the CGRP2receptor.

Recent pharmacological characterization of receptors related to CGRP1has revealed that some of these receptors may explain CGRP2receptor pharmacology. Specifically, AMY1(a)(calcitonin receptor/RAMP1) and AM2(CL/RAMP3) receptors can be activated by CGRP but are relatively insensitive to CGRP8–37.

This, along with other supporting data, suggests that the ‘CGRP2receptor’ that has been extensively reported in the literature may, in fact, be an amalgamation of contributions from a variety of CGRP‐activated receptors. The use of appropriate combinations of agonists and antagonists, along with receptor expression studies, could allow such receptors to be separated.
DESENSITIZATION OF GUINEA‐PIG TAENIA CAECI SMOOTH MUSCLE INDUCED BY A LOW CONCENTRATION OF CARBACHOL
Authors: Hishinuma Shigeru , Sato Ryo , Saito Masaki
Published: July 2007

In guinea‐pig taenia caeci smooth muscle we have found that 10−4 mol/L carbachol‐induced desensitization to muscarinic agonists develops within 15–30 s, followed by transient resensitization at 1 min, whereas the desensitization to depolarizing high K+develops with maximal desensitization at 1 min followed by sustained resensitization up to 30 min. In both cases, Ca2+‐dependent processes play a crucial role in determining the development of desensitization.

To elucidate whether these peculiar processes of desensitization/resensitization may be induced by a lower concentration of carbachol, we examined the development of desensitization induced by 10−6 mol/L carbachol, because at this concentration carbachol is known to induce biphasic changes in intracellular Ca2+concentrations, with a smaller transient increase followed by a larger sustained increase than seen with 10−4 mol/L carbachol.

Contractile responses to muscarinic agonists (carbachol or AHR‐602) and high K+were desensitized by pretreatment with 10−6 mol/L carbachol for 30 min in a manner dependent on the presence of extracellular Ca2+.

The development of 10−6 mol/L carbachol‐induced desensitization to these muscarinic agonists in the presence of extracellular Ca2+showed three successive phases: fast desensitization within 30 s, followed by transient resensitization at 1 min and the subsequent development of desensitization up to 30 min. In contrast, desensitization to high K+did not develop up to 10 min and significant desensitization occurred at 30 min, with no apparent resensitization phase.

These results suggest that the characteristics of the Ca2+‐dependent development of desensitization to muscarinic agonists, but not to high K+, are well maintained in desensitization induced by a lower concentration of carbachol.