bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro effects of gelatin solutions on platelet function: a comparison with hydroxyethyl starch solutions*
Authors: Thaler U. , Deusch E. , Kozek‐Langenecker S. A.
Published: May 2005

The aim of this study was to investigate the effects of various gelatin and hydroxyethyl starch solutions on platelet reactivity. Citrated whole blood was obtained from 20 healthy volunteers. Expression of glycoprotein (GP) IIb–IIIa and p‐selectin were determined using whole blood flow cytometry on both resting and agonist‐activated platelets before and after in vitro haemodilution (20% and 40%) using oxypolygelatin, modified gelatin, urea‐linked gelatin, hydroxyethyl starch (HES) 130 (mean molecular weight in kDa), HES 200, HES 450 and HES 550. High degrees of haemodilution using oxypolygelatin had no significant effect, similar to HES 130, whereas modified gelatin inhibited GP IIb–IIIa expression, similar to HES 200 and HES 450. Urea‐linked gelatin significantly increased the expression of GP IIb–IIIa, similar to HES 550. p‐Selectin expression remained unchanged in all samples. The present in vitro study indicates that chemical characteristics of colloidal solutions modulate their influence on platelet reactivity.
Survey of arrangements for anaesthesia for interventional neuroradiology for aneurysmal subarachnoid haemorrhage*
Authors: Webb S. T. , Farling P. A.
Published: May 2005

The management of patients with subarachnoid haemorrhage following rupture of an intracranial aneurysm is changing. The recent introduction of endovascular occlusion of the aneurysm using detachable coils offers an alternative to craniotomy and clipping of the aneurysm for the prevention of recurrent aneurysmal haemorrhage. The aim of this survey was to evaluate the current provision of peri‐operative care for patients with an aneurysmal subarachnoid haemorrhage in the United Kingdom and Republic of Ireland. A survey was conducted of the 34 neuroscience centres which provide an adult neurosurgery service in the United Kingdom and Republic of Ireland. Most centres reported an increasing role for coiling, and a decreasing role for clipping in the management of aneurysmal subarachnoid haemorrhage. The provision of peri‐operative care for patients undergoing interventional neuroradiology procedures varied greatly between centres. Neurovascular services in the UK are being reorganised and adequate staff and facilities should be available for the peri‐operative care of patients undergoing interventional neuroradiology procedures.
Association of thromboxane A2 receptor gene polymorphism with the phenotype of acetyl salicylic acid‐intolerant asthma
Authors: Kim S.‐H. , Choi J.‐H. , Park H.‐S. , Holloway J. W. , Lee S.‐K. , Park C.‐S. , Shin H.‐D.
Published: May 2005

Background and objective
The thromboxane A2 receptor (TBXA2R) is a receptor for a potent bronchoconstrictor, TBXA2 which is known to be related to bronchial asthma and myocardial infarction. TBXA2R antagonist and TBX synthase inhibitors have been found to be effective in the management of asthmatic patients. This study was aimed to evaluate whether genetic variants of TBXA2R may be related with development of acetyl salicylic acid (ASA)‐intolerant asthma (AIA).

Methods
TBXA2R gene polymorphisms (TBXA2R+795T>C, TBXA2R+924T>C) were determined using a single‐base extension method in 93 AIA patients compared with 172 patients with ASA‐tolerant asthma (ATA) and 118 normal controls (NCs) recruited from the Korean population. HLA DPB1*0301 genotype was performed using a direct sequencing method.

Results
The rare C allele frequency of TBXA2R+795T>C was significantly higher in AIA than in ATA (P=0.03) and the TBXA2R+795T>C polymorphism was also associated with extent of percent fall in forced expiratory volume in 1 s (FEV1) after the inhalation of lysine–acetyl salicylic acid in AIA patients (P=0.009); AIA patients homozygous for the +795 C allele had a greater percent fall of FEV1 compared with individuals with TBXA2R+795 CT or TT genotypes. The frequency of patients carrying both the TBXA2R+795T>C rare allele and HLA DPB1*0301 was significantly higher in AIA patients (29.4%) than in ATA patients (7.3%) (P=0.008, odds ratio=5.3).

Conclusion
These results suggest that the polymorphism of TBXA2R+795T>C may increase bronchoconstrictive response to ASA, which could contribute to the development of the AIA phenotype.
Identification of human T cell epitopes in Japanese cypress pollen allergen, Cha o 1, elucidates the intrinsic mechanism of cross‐allergenicity between Cha o 1 and Cry j 1, the major allergen of Japanese cedar pollen, at the T cell level
Authors: Sone T. , Dairiki K. , Morikubo K. , Shimizu K. , Tsunoo H. , Mori T. , Kino K.
Published: May 2005

Background
Pollens from species of Cupressaceae family are one of the most important causes of respiratory allergies worldwide. In Japan, many patients with pollinosis have specific IgE to both pollens of Japanese cypress (Chamaecyparis obtusa) and Japanese cedar (Cryptomeria japonica). The sequences between Cha o 1 and Cry j 1, the major allergens of Japanese cypress and Japanese cedar pollens, respectively, are 80% identical.

Objective
This study was undertaken to identify T cell epitopes in Cha o 1, and to elucidate the mechanism of cross‐allergenicity between Cha o 1 and Cry j 1, at the T cell level.

Methods
T cell epitopes in Cha o 1 were identified by the reactivity of T cell lines, generated from 19 patients, to stimulation with overlapping peptides. The subsets of T cell clones specific to rCha o 1 were determined according to their ability to produce IL‐4 and IFN‐γ. Peptide specificities of two T cell clones were determined by stimulation with the peptides from Cha o 1 and Cry j 1.

Results
Four dominant and six subdominant T cell epitopes were identified in Cha o 1. While four T cell epitopes, p11‐30, p211‐230, p251‐270 and p331‐350, were common to Cha o 1 and Cry j 1, 4 T cell epitopes, p61‐80, p71‐90, p311‐330 and p321‐340, were considered to be unique to Cha o 1. The subsets of T cell clones were predominantly of T helper2‐type. One T cell clone recognized p16‐30, which is common to Cha o 1 and Cry j 1, but another recognized p321‐330, which is unique to Cha o 1.

Conclusion
Presence of both T cells reactive to T cell epitopes common to Cha o 1 and Cry j 1 and T cells specific to T cell epitopes unique to Cha o 1 in patients with pollinosis contributes to prolonged symptoms after the cedar pollen season in March and the following cypress pollen season in April.
Bronchoalveolar lavage eosinophil cationic protein and interleukin‐8 levels in acute asthma and acute bronchiolitis
Authors: Kim Chang Keun , Kim Sang Woo , Kim Young‐Ki , Kang Hee , Yu Jinho , Yoo Young , Koh Young Yull
Published: May 2005

Objective
In this study, we measured the levels of eosinophil cationic protein (ECP) and interleukin (IL)‐8 in bronchoalveolar lavage (BAL) fluid from patients with acute asthma and acute bronchiolitis, to determine any similarities or dissimilarities in the profiles of these biochemical markers in the two diseases.

Methods
BAL fluids were obtained from children with acute asthma (n=16), infants with acute bronchiolitis caused by respiratory syncytial virus (n=18), and control subjects (n=14). Children with asthma were selected to be free of viral infection. BAL cell counts and differentials were determined, and ECP and IL‐8 levels were measured by radioimmunoassay and ELISA, respectively.

Results
ECP levels in BAL fluids were significantly higher in the asthma group than in the bronchiolitis (P<0.01) or control (P<0.0001) groups. However, IL‐8 levels were significantly higher in the bronchiolitis group than in the asthma (P<0.01) or control (P<0.001) groups. IL‐8 levels in the asthma group and ECP levels in the bronchiolitis group were similar to those of the control group.

Conclusion
This difference in profiles of ECP and IL‐8 in acute asthma and acute bronchiolitis, together with a different inflammatory cell pattern, suggests that the nature of the inflammatory process within the lower respiratory tract may be distinctive in these two diseases.
The effect of age on the relationship between birth order and immunoglobulin E sensitization
Authors: Turner S. W. , Palmer L. J. , Gibson N. A. , Rye P. J. , Goldblatt J. , Landau L. I. , Le Souëf P. N.
Published: May 2005

Background
An association between birth order and IgE sensitization or allergic diseases has been reported in many studies.

Objective
To assess the effect of age on the relationship between reduced IgE sensitization and increased birth order and to test the hypothesis that this would decline with increasing age.

Methods
As part of a birth cohort study, IgE sensitization to common allergens was determined by skin prick testing at ages 6 and 12 months, 6 and 11 years.

Results
The original cohort numbered 253 individuals of whom 96 (38%) were first born. Compared with individuals with older siblings, first‐born individuals had increased IgE sensitization at 6 (odds ratio (OR) 2.4 [95% confidence interval (CI) 1.0, 6.3], P=0.05, n=197) and 12 months of age (OR 6.7 [1.7, 25.0] P=0.002, n=172) and at 6 years of age (OR 2.3 [1.0, 5.6] P=0.05, n=113) but not at 11 years of age (OR 1.2, P>0.4, n=182). When age at onset of IgE sensitization was considered (n=61), 16 had infant onset IgE sensitization (nine were first born), 24 had early childhood onset IgE sensitization (nine first born) and 21 had late childhood onset IgE sensitization (two first born), P=0.0016. Further analysis revealed a similar pattern for children with older brothers (P=0.0097) but not older sisters (P=0.5).

Conclusions
These findings indicated that having an older brother delays the onset of IgE sensitization but may not prevent IgE sensitization per se. The apparent protective effect of older siblings on allergic diseases reported elsewhere might involve delaying the onset of IgE sensitization.
Childhood atopy and allergic disease and skin test responses to environmental mycobacteria in rural Crete: a cross‐sectional survey
Authors: Bibakis I. , Zekveld C. , Dimitroulis I. , Pedioti A. , Gerakianaki T. , Fanourgiaki S. , Kokiadi I. , Iliakou‐Bibakis V. , Newman Taylor A. J. , Stanford C. A. , Stanford J. L. , Cullinan P.
Published: May 2005

Background
Through its powerful immunoregulatory effects, infection with atypical mycobacteria may exert a protective effect on the development of childhood allergic disease.

Objective
To examine the relationship between childhood atopy or allergic disease and previous infection with four species of atypical mycobacteria.

Methods
Eight hundred and six children aged 8–18 years and living in rural Crete – most of whom had had previous BCG immunization – underwent skin prick testing with 10 aeroallergens; their parents completed a standardized questionnaire relating to allergic disease. No less than 8 weeks later each child underwent intradermal skin tests with 0.1 mL solutions of four selected mycobacterial reagents (Aviumin C, Gordonin, Chelonin and Ranin I).

Results
Twenty‐three percent of children were atopic on skin prick testing; far fewer had symptoms of asthma (5%) or hayfever in conjunction with a positive prick test to pollens (2%). Eighty percent of children had positive skin responses to one or more mycobacterial species. Among all children – and those with a BCG scar – there was no association between atopy or allergic symptoms and mycobacterial skin responses; among the few children without a BCG scar however those with positive mycobacterial responses were less likely to be atopic or to report allergic symptoms; these differences were not statistically significant.

Conclusions
Our findings, in a population of BCG‐immunized children, do not lend support to the suggestion that infection with atypical mycobacteria is protective against childhood allergic disease.
Rational design of hypoallergens applied to the major cat allergen Fel d 1
Authors: Saarne T. , Kaiser L. , Grönlund H. , Rasool O. , Gafvelin G. , Van Hage‐Hamsten M.
Published: May 2005

Background
Allergen‐specific immunotherapy is the only treatment for allergic disease providing long‐lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy.

Objective
The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen.

Methods
The three‐dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition‐ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay.

Results
Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400–900 times lower IgE‐binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1.

Conclusion
By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE‐binding capacities and retained T cell reactivities. This strategy may be applied to any well‐characterized allergen to improve immunotherapy for allergic patients.
Variability of total serum immunoglobulin E levels from birth to the age of 10 years. A prospective evaluation in a large birth cohort (German Multicenter Allergy Study)
Authors: Nickel R. , Illi S. , Lau S. , Sommerfeld C. , Bergmann R. , Kamin W. , Forster J. , Schuster A. , Niggemann B. , Wahn U. ,   the German Multicenter Allergy Study Group (MAS‐90)
Published: May 2005

Background
Many environmental factors influence the concentration of total serum IgE (tIgE); however, tIgE synthesis is believed to be under strong genetic influence. Multiple genetic studies on tIgE regulation have been performed. For these population‐based studies tIgE was commonly determined at one time‐point, assuming that tIgE phenotypes (adjusted for age and gender) are stable over time.

Objective
We assessed correlations of tIgE levels from birth to the age of 10 years in the birth cohort MAS (Multicenter Allergy Study; n=1314).

Materials and methods
We determined cord‐blood IgE levels, total and specific IgE at the age of 1, 2, 3, 5, 6, 7, and 10 years. Spearman correlation coefficients were calculated for tIgE at different time‐points. All analyses were performed in the entire cohort, adjusted for gender, as well as in non‐atopic children only.

Results
tIgE percentiles increased steadily from birth to the age of 10 years with higher values for boys than for girls at each time‐point. tIgE values from birth to 3 years of age correlated poorly with tIgE levels at 10 years (r<0.5). However, good correlations (r>0.8) were observed for tIgE concentrations at 6, 7 and 10 years. The same results were observed when the analyses were limited to non‐atopic children.

Conclusion
In childhood, tIgE levels underlie remarkable variation over time even in the absence of atopy. For cross‐sectional population‐based genetic and epidemiologic studies, tIgE values of children <5 years should be interpreted with caution since these values correlate poorly with tIgE levels later in life.
Intragastric administration of Mycobacterium vaccae inhibits severe pulmonary allergic inflammation in a mouse model
Authors: Hunt J. R. F. , Martinelli R. , Adams V. C. , Rook G. A. W. , Brunet L. Rosa
Published: May 2005

Background
Coexistence with harmless microorganisms such as lactobacilli, saprophytic mycobacteria and some helminths, throughout evolution, may have shaped the host immune system. Exposure to such organisms may have therapeutic benefits by triggering immunoregulatory mechanisms that control inappropriate immune responses to self, gut contents or allergens.

Objective
We determined whether treatment with Mycobacterium vaccae by gavage influences the host immune response both locally and systemically. We also investigated whether delivery by this route prevents severe symptoms of disease in a murine model of pulmonary allergic inflammation.

Results
A single intragastric administration of M. vaccae induced a transient increase in the production of IL‐10 and IFN‐γ by mesenteric lymph nodes cells and splenocytes. In addition, in a mouse model of pulmonary allergic inflammation, a single treatment with M. vaccae by gavage not only diminished the total cellular infiltrate and the eosinophilic component induced by subsequent intratracheal allergen challenge, but also biased local and systemic cytokine production towards IL‐10. Delivery of M. vaccae by gavage was as effective as subcutaneous treatment.

Conclusion
This is the first report to suggest that heat‐killed mycobacteria can down‐regulate symptoms of allergic inflammation by the intragastric route. These data suggest an alternative route of treatment with M. vaccae for patients with allergic conditions.
The safety of sublingual‐swallow immunotherapy: an analysis of published studies
Authors: Gidaro G. B. , Marcucci F. , Sensi L. , Incorvaia C. , Frati F. , Ciprandi G.
Published: May 2005

Background
As the main target of sublingual immunotherapy (SLIT) is to reduce at most the occurrence of adverse events (AE), safety represents a critical issue. This aspect deserves particular mention when a higher dose of allergen extract than traditional subcutaneous immunotherapy (SCIT) is required to be effective: that may be up to 500 times that employed for SCIT.

Objective
All published controlled studies concerning SLIT‐swallow were analysed to evaluate AE rates.

Methods
Studies were subdivided in two groups: (i) studies using low allergen dose (LAD), i.e. ranging from 1 to 50 times the dose commonly administered with SCIT, and (ii) studies with high allergen dose (HAD), i.e. ranging from 50 to 500 times the dose administered with SCIT.

Results
Twenty‐five studies were altogether analysed: 13 studies belonged to the low‐dose group, 12 belonged to the high‐dose group. We considered all patients with at least one AE. Local reactions were significantly more frequent in the LAD group than in the HAD group (P<0.0001), while there was no difference in the rate of systemic reactions. Severe systemic reactions were never reported.

Conclusion
This study represents the first analysis of the safety of SLIT concerning the allergen dose employed in the treatment. There is evidence that AE occurrence is substantially not dose‐dependent. This fact highlights two main clinical aspects: the elevated tolerability of SLIT in general and the safety of HAD regimen.
The pro‐fibrogenic effect of nerve growth factor on conjunctival fibroblasts is mediated by transforming growth factor‐β
Authors: Micera A. , Puxeddu I. , Lambiase A. , Antonelli A. , Bonini S. , Bonini S. , Aloe L. , Pe'er J. , Levi‐Schaffer F.
Published: May 2005

Background
Nerve growth factor (NGF) and nerve growth factor receptor (NGFR) expressions have been found to be increased in sub‐conjunctival scarring.

Objective
The aim of this study was to investigate the in vitro effects of NGF on some pro‐fibrogenic properties of human conjunctival fibroblasts.

Methods
Expression of NGF, trkANGFR and p75NTR on human fibroblasts grown from conjunctival biopsies and incubated for 2 or 6 days with NGF were evaluated by immunofluorescence, RT‐PCR, flow cytometry and ELISA. The fibrogenic effect of NGF on conjunctival fibroblasts was investigated by evaluating their migration (wound model), proliferation ([3H]‐thymidine incorporation), collagen production (3H]‐proline incorporation), expression of alpha‐smooth muscle actin (α‐SMA) (cell surface ELISA) and contraction of 3D collagen gels.

Results
NGF induced the expression of p75NTR in the fibroblasts that constitutively expressed only trkANGF and increased the migration of wounded fibroblasts, but not their proliferation and collagen production. NGF induced the conversion of fibroblasts into myofibroblasts expressing α‐SMA, and enhanced their contraction of a collagen matrix. Interestingly, chronic NGF treatment induced transforming growth factor‐β1 (TGF‐β1) production by fibroblasts, and following specific TGF‐β neutralization, all the NGF‐induced effects were completely abrogated.

Conclusion
Our findings indicate that NGF, via TGF‐β induction, is likely to be involved in the healing or fibrotic processes occurring in conjunctiva during some pathological conditions.
Persistence of rhinovirus RNA after asthma exacerbation in children
Authors: Kling S. , Donninger H. , Williams Z. , Vermeulen J. , Weinberg E. , Latiff K. , Ghildyal R. , Bardin P.
Published: May 2005

Background
Rhinoviruses (RVs) are believed to cause most asthma exacerbations but their role in the severity of acute asthma and subsequent recovery of airway function is not defined. The importance of atopy in virus‐host interactions is also not clear.

Objective
We postulated that RV infection and atopic skin prick responses influence the severity of asthma exacerbations as measured by peak expiratory flow (PEF).

Methods
Patients aged 4–12 years admitted with acute severe asthma to a hospital emergency room (ER) were recruited. PEF measurements were obtained and nasal aspirates (NA) were taken. Atopy was diagnosed by skin prick responses to allergen and the presence of RV RNA and respiratory syncytial virus (RSV) RNA in NAs was detected using validated PCR assays. Patients were restudied after 6 weeks and after 6 months.

Results
Fifty children with acute asthma (mean age±SD, 7.4±2.7) were enrolled; atopy was present in 37 (74%). RV RNA was detected in 41 (82%) and RSV RNA in six (12%) subjects. After 6 weeks 41 patients were restudied and RV RNA was again detected in 18 (44%). RV RNA was detected after 6 months in four of 16 patients restudied (25%; P=0.008 vs. ER) and in two of nine children from a control group with stable asthma (22%; P=0.009 vs. ER). Overall PEF measurements were reduced in asthmatics admitted to ER (% predicted, 63.4±16.4%) but did not differ between patients with RV RNA, RSV RNA or neither virus present. In subjects with RV RNA detectable in ER and after 6 weeks, measurements of PEF in ER were significantly lower than in patients in whom RV RNA was present in ER but absent after 6 weeks (P=0.009). Regression analysis linked persistence of RV RNA, but not skin prick responses to allergen, to severity of PEF reductions in ER.

Conclusion
RV RNA was detectable in >40% of asthmatic children 6 weeks after an acute exacerbation. Asthma exacerbations were more severe in patients with persistence of RV RNA suggesting that the severity of acute asthma may be linked to prolonged and possibly more severe RV infections.
Immunotherapy with depigmented glutaraldehyde‐polymerized extracts: changes in quality of life
Authors: Alvarez‐Cuesta E. , Aragoneses‐Gilsanz E. , Martín‐Garcia C. , Berges‐Gimeno P. , Gonzalez‐Mancebo E. , Cuesta‐Herranz J.
Published: May 2005

Background
Immunotherapy (IT) with modified allergens reduces allergic rhinitis (AR) symptoms and medications requirements. Improvement of quality of life (QOL) is a key point in the treatment of AR. The aim of this study was to provide evidence of changes related to the patient's QOL (well‐being) induced by a modified (depigmented glutaraldehyde‐polymerized) therapeutic vaccine and of its safety.

Material and Methods
Fifty‐three patients with a well‐documented clinical history of seasonal AR sensitized to Dactylis glomerata and Olea europaea pollens were included in a randomized clinical trial. Twenty‐five patients (Group‐A) received a mixture of D. glomerata and O. europaea pollen extracts and 28 patients received placebo (group‐C). Any adverse event was recorded and graded in accordance with EAACI guidelines. RQLQ was recorded before the treatment (pollen season 2000) and after 1 year of treatment (pollen season 2001). Dose–response skin prick test with each allergen extract was conducted at baseline and at the end of the study.

Results
Each patient received 17 injections during this period. All patients completed the trial and no systemic adverse reactions were recorded. Symptom scores (P<0.001) and medication requirements (P<0.001) were significantly reduced in the IT group during the pollen season. This patient group also experienced greater and statistically significant improvement in overall RQLQ score and in five of the seven domains, all of them surpassing the threshold of ‘minimal important difference’ of 0.5 points.

Conclusions
Results of this study provided evidence that IT with depigmented, glutaraldehyde‐modified allergen extracts was well‐tolerated and added beneficial effects to AR treatment in pollen allergic patients eliciting an improvement in QOL enough to justify a change in the patient's treatment.
The Ossicle Bank of the University Medical Centre (UMCU), the Netherlands
Authors: Meeuwsen F. , Veldman J.E. , Hordijk G.J.
Published: May 2005

Keypoints

• Long term results show high extrusion rates of porous and ceramic ossicle prosthesis.

• For this reason, allogenic ossicular bone remains the first choice for many Otolaryngologists.

• The combination of adequate tissue preservation and definite donor selection criteria guarantees the safe use of allogenic ossicles for ossiculoplasty.
Extended high‐frequency audiometry in patients with acoustic trauma
Authors: Balatsouras D.G. , Homsioglou E. , Danielidis V.
Published: May 2005

Objectives:  The aim of this study was to examine extended high‐frequency (EHF) hearing in patients with acoustic trauma.

Design:  A prospective, case–control study in a group of soldiers with acoustic trauma caused by shooting practice during basic training.

Setting:  Tertiary referral centre.

Participants:  A total of 39 young soldiers hospitalized for hearing loss and tinnitus following exposure to weapon impulse noise were studied. Conventional audiometry in the frequency range 0.25–8 kHz and EHF audiometry in the frequency range 9–20 kHz were performed, both on admittance and before discharge. Thirty healthy recruits of similar age and sex were used as controls.

Main outcome measures:  Pure‐tone threshold changes documented by conventional and EHF audiometry.

Results:  The most significant differences in pure‐tone thresholds on initial testing were found in the frequency range 0.25–11.2 kHz, and especially in the 4–8 kHz region. Reduction in thresholds across most frequencies was observed after treatment, although recovery was partial in most cases.

Conclusions:  The EHF audiometry adds no significant additional information to conventional pure‐tone audiometry in assessing and monitoring noise‐induced hearing loss.
How we do it: Head and neck cancer waiting times
Authors: Tandon S. , Machin D. , Jones T.M. , Lancaster J. , Roland N.J.
Published: May 2005

Keypoints

After instigation of rapid access referrals from GPs and the Calman‐Hine 2‐week rule, the times taken from initial presentation to the GP, until the start of definitive treatment for patients with head and neck cancer managed was audited and compared with national guidelines.

• An improvement in time from GP referral to first outpatient clinic (2.1 weeks), time to fine needle aspiration cytology (FNAC; 2.9 days), time to endoscopic examination (2.3 weeks) and to staging scans (3.3 weeks) was seen, these fell just outside the standards set. Time to histological report was within the standards set (0.4 weeks).

• As a result of the improvement in preoperative work up of cancer patients, there has been an increased delay to primary surgery (7.7 weeks) and a continued delay to primary radiotherapy (10.2 weeks).

• Delays because of poor patient education about head and neck cancer are still very apparent and need to be addressed, as well as further improvement in GP education about early referral to ENT services.

• The shortfalls seen need to be addressed by an increase in infrastructure as well as medical and paramedical staffing to ensure patients are managed within given time standards. Although patient throughput can be enhanced by improvements in system efficiency, it is unlikely that targets will be met consistently without an increase in resources to fund greater capacity and more personnel.
Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (≤20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours)
Authors: Makimoto Y , Nabeshima K , Iwasaki H , Miyoshi T , Enatsu S , Shiraishi T , Iwasaki A , Shirakusa T , Kikuchi M
Published: May 2005

Aims:  A micropapillary pattern (MPP) in lung adenocarcinoma, characterized by papillary structures with epithelial tufts lacking a central fibrovascular core, has been reported to be a new pathological marker of poor prognosis. However, its clinicopathological and prognostic significance in small lung adenocarcinomas (≤20 mm) remains undetermined. A new histological classification of small lung adenocarcinoma proposed by Noguchi et al. has been found to be useful since it has defined surgically curable bronchioloalveolar carcinoma (BAC)‐type tumours (Noguchi's type A and B) based on the absence of active fibroblastic proliferation. However, BAC‐type tumours with active fibroblastic proliferation (Noguchi's type C), which is adenocarcinoma with mixed subtypes including BAC and invasive carcinoma in the new World Health Organization (WHO) classification, account for most of the small adenocarcinomas and represent a heterogeneous group ranging from minimal to overtly invasive cancer with variable prognoses. Therefore, in this study the aim was to investigate whether MPP can be an additional histological marker(s) to subclassify this heterogeneous group in small lung adenocarcinoma.

Methods and results:  One hundred and twenty‐two cases of small lung adenocarcinomas (≤20 mm in maximum dimension) classified according to the new WHO classification and Noguchi's proposal were analysed with reference to the presence of MPP. Of the 122 cases, 67 (55%) were MPP‐positive and 55 (45%) were MPP‐negative. Lymph node metastasis and pleural invasion were significantly more frequent in the MPP‐positive group: 74% and 66% in the positive group versus 26% and 34% in the negative group, respectively. The 5‐year survival of the MPP‐positive group was 54%, whereas that of the MPP‐negative group was 81% (P = 0.024). The 5‐year survival rates of BAC (Noguchi's type A and B) (n =14), mixed BAC and invasive adenocarcinoma (Noguchi's type C) (n = 85) and invasive adenocarcinoma (Noguchi's type D and F) (n = 23) were 100%, 68% and 36%, respectively. In patients with mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours), the 5‐year survival of the MPP‐positive group (n = 51) was 54%, significantly lower than that of the MPP‐negative group (n = 23) of 100% (P = 0.02).

Conclusions:  MPP is a simple and distinct pathological marker to subclassify tumours with a significantly poor prognosis within small (≤20 mm) mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours).
Ki67 and p53 immunohistochemistry reduces interobserver variation in assessment of Barrett's oesophagus
Authors: Lörinc E , Jakobsson B , Landberg G , Veress B
Published: May 2005

Aims:  To devise clinically applicable methods for assessing p53 and Ki67 immunohistochemical (IHC) reactivity in Barrett's oesophagus (BE) and to compare the interobserver agreement between these methods and routine haematoxylin and eosin (H&E) evaluation.

Methods and results:  One hundred and fifteen biopsies diagnosed as BE, selected from the files of the University Hospital MAS, Malmö, were re‐evaluated for dysplasia by three pathologists. For IHC analysis areas with the most prominent positivity were evaluated. The mean of p53+ epithelial nuclei/high‐power field (HPF) was obtained by counting between 1 and 5 HPFs/biopsy. A proliferation quotient (PQ) was obtained by dividing the number of Ki67+ epithelial nuclei in the upper half by the lower half of the mucosa, using two HPFs. Mean κ values were 0.24, 0.71 and 0.52 for H&E, p53 and Ki67 evaluations, respectively. There was a correlation between increasing severity of dysplasia, IHC measurable overexpression of p53 and shift of the mucosal proliferation zone towards the surface, measured as PQ.

Conclusions:  The described methods for p53 and Ki67 evaluation are more reproducible than routine H&E evaluation of BE. Furthermore, the IHC methods correlate with the severity of dysplasia and are useful supplementary prognostic markers.
Evaluation of sentinel lymph nodes in breast cancer
Authors: Cserni G
Published: May 2005

Sentinel lymph node biopsy is an accurate method for the detection of axillary metastases in cases of breast carcinoma and is of value as a replacement for axillary dissection. There is variation, however, in the methods and protocols used for the histopathological evaluation of sentinel lymph nodes, standardisation of which will be required if results of sentinel lymph node analysis are to be used to stratify patients into prognostic groups. The significance of micrometastases, isolated tumour cells (ITCs) and the value of immunohistochemistry are also matters for further definition. In this Expert Opinion we present reviews from two authors, providing American and European perspectives on the approach to sentinel lymph node evaluation.
Effectiveness in cleaning oval‐shaped root canals using Anatomic Endodontic Technology, ProFile and manual instrumentation: a scanning electron microscopic study
Authors: Zmener O. , Pameijer C. H. , Banegas G.
Published: May 2005

Aim  To compare in vitro the cleanliness of root canal walls in oval‐shaped root canals following automated or manual instrumentation.

Methodology  Forty‐five oval‐shaped single‐rooted maxillary and mandibular premolars with straight canals were divided into three groups of 15. Automated canal preparation was performed using Anatomic Endodontic Technology (AET, group 1) and the ProFile system (group 2). Manual instrumentation (group 3) was performed with K‐Flexofiles. Irrigation was performed using alternately 5.25% NaOCl and 17% EDTA, followed by rinsing with saline. The roots were split longitudinally into halves and the canals examined at ×200 and ×400 in a scanning electron microscope. The presence of debris and smear layer was recorded at distances of 1, 5 and 10 mm from the working length using a three‐step scoring scale and a 300 μm square grid. Mean scores for debris and smear layer were calculated and statistically analysed for significance (P < 0.05) between and within groups, using the Kruskal–Wallis nonparametric anova and Dunn's tests.

Results  At 1, 5 and 10‐mm levels the root canals prepared with AET had significantly less surface debris and smear layer on the canal walls compared with canals prepared with ProFile or manual instrumentation. For all three groups significantly lower mean smear layer scores (P < 0.05) were recorded at 5 and 10‐mm levels compared with the 1 mm level. Significantly lower mean debris scores (P < 0.05) were also recorded at 5 and 10‐mm levels for the AET group whereas no significant differences were found between the three levels for the ProFile and manual instrumentation groups.

Conclusions  Although better instrumentation scores were obtained in canals prepared with AET, complete cleanliness was not achieved by any of the techniques and instruments investigated.
The environmental control of plant species density on a Himalayan elevation gradient
Authors: Carpenter Chris
Published: May 2005

Aim In eastern Nepal, forests occupy an elevation gradient of 4000 m with bioclimatic zones from near tropical to alpine. Understorey plants and trees were censused to measure species density and identify patterns of ecological change. By sampling in a manner robust against spurious mid‐domain effects, I aim to identify biologically valid controls on species density.

Location The study area consists of land below 4250 m elevation between 27.1 and 27.8° N latitude, 86.5 and 88.0° E longitude on the southern slopes of the Himalaya Range in eastern Nepal. Sampling sites are limited to intact, natural forest with relatively little human impact.

Methods Team members counted species of understorey plants and trees ≥ 10 cm d.b.h. in 0.04 ha plots throughout the study area. In addition, basal area, leafing phenology and species composition were determined for the trees in each plot. Estimates of regional species density were compiled for successive 250 m elevation bands from 250 to 4250 m elevation. Species density trends were identified and compared with the expectations of O'Brien's [Journal of Biogeography25(1998) 379–398] climate‐based water–energy dynamics model.

Results Stand basal area, tree leafing phenology and taxonomic composition (angiosperm vs. gymnosperm) show non‐random change with elevation. Understorey plant and tree species density both have a humped, unimodal trend with more species near the bottom of the gradient and fewest at the top. These trends are consistent with expected effects of the climatically active water and energy variables. After curve‐fitting, significant spatial structure in the residuals suggests that tree communities within the 1750–2250 m elevation range do not realize their climatic potential species richness.

Main conclusions Neither mid‐domain effects nor biologically valid boundary effects like dispersal limitation explain the plant species density trends observed. Trends do fit a model in which species density is controlled by the same ‘active’ climatic variables that predict species richness on continental scales. Patterns of leafing phenology on the elevation gradient provide further support for the hypothesis of environmental control of species density. The productivity–diversity linkage that exists on continental scales may also apply on the smaller scale of a Himalayan elevation gradient. Human activity and possible competitive exclusion byCastanopsis tribuloidesare the two best explanations for the observed decline in tree species density at 1750–2250 m elevation. Burning, lopping for fodder and livestock grazing might account for the decline, but this study does not assess the relative importance of these activities. The elevation richest for understorey plant and tree species (500–1500 m) also has the most severe reduction in forest cover. Local farmers deserve credit for sustaining plant biodiversity in forest enclaves, but further loss of forest at these elevations should be discouraged.
Masticatory function in patients with an extremely resorbed mandible restored with mandibular implant‐retained overdentures: comparison of three types of treatment protocols
Authors: STELLINGSMA K. , SLAGTER A. P. , STEGENGA B. , RAGHOEBAR G. M. , MEIJER H. J. A.
Published: May 2005

summary  The objective of the present study was to analyse the effects of implant supported overdentures on masticatory function in patients with an extremely resorbed mandible, and to compare the masticatory function in these patients using three differing types of implant treatment protocols. The mandibular overdentures were retained by a transmandibular implant, by four endosseous implants following augmentation of the mandible, and by four short endosseous implants, respectively. Sixty patients (50 women, 10 men, mean age 59·4 years) were randomly allocated to one of the three treatment groups. Masticatory function was assessed before and after treatment using a questionnaire, a masticatory performance test, and a structured interview. The patient‐based masticatory function improved significantly. Concerning these parameters there were no significant differences between the three groups before and after treatment. A significant difference existed between the three groups for the laboratory‐assessed masticatory function before treatment, but after treatment this difference was no longer significant. From this study it can be concluded that patients with an extremely resorbed mandible and functional complaints of their lower denture report significant improvement in masticatory function after implant‐overdenture treatment. Differences in masticatory function between the three studied modalities were not significant after treatment.
In vitro evaluation of the bonding of auto‐polymerizing soft denture liner to cobalt–chromium alloy
Authors: MINAMI H. , SUZUKI S. , OHASHI H. , MINESAKI Y. , TANAKA T.
Published: May 2005

summary  This study evaluated the effects of surface pre‐treatments on the bonding of auto‐polymerizing silicone soft denture liner to a Co–Cr alloy denture base after cyclic thermal stressing. The bonding surfaces of Co–Cr alloy cylinders (8 mm diameter and 4 mm high) were polished with a 600‐grit silicon carbide paper. The bonding surfaces received one of three pre‐treatments, which included either the application of a metal primer, a metal primer after air abrasion, or a resin primer after adhesive resin coating. Tensile specimens were fabricated by polymerizing a 2‐mm thickness of soft denture liner between a pair of pre‐treated denture base cylinders. Failure loads were measured by tensile testing after subjecting the specimen to 0, 5, 10, 20, and 30 thousand thermal cycles. Seven specimens were fabricated for 15 groups, including three pre‐treatments and five thermal cycle groups. Failure loads of resin‐bonded specimens, which were formerly reported, were used as references. All data were statistically analysed by two‐way anova and Bonferroni test at the 95% confidence level. Adhesive resin coating of the metal surface was effective in enhancing the failure loads up to 5000 thermal cycles. However, failure loads of all metal‐bonded groups were significantly lower than those of resin‐bonded groups at all thermal cycling intervals. The results of this in vitro study implied that polymerizing adhesive resin on the Co–Cr alloy might be a promising method, when the clinicians need to acquire improved bonding of an auto‐polymerizing soft denture liner to Co–Cr alloy denture bases.
Effect of luting agents and reconstruction techniques on the fracture resistance of pre‐fabricated post systems
Authors: TOKSAVUL S. , TOMAN M. , UYULGAN B. , SCHMAGE P. , NERGİZ İ.
Published: May 2005

summary  Fracture resistance and fracture modes of endodontically treated maxillary central incisors restored with different post‐and‐core systems covered with all‐ceramic copings were evaluated. Ten samples were prepared for each group. Groups 1, 2 and 3 consisted of tooth‐coloured post‐and‐core, zirconia post (Cosmopost) with a composite core (Tetric Ceram), zirconia post (Cosmopost) with a custom made ceramic core (Cosmo Ingot), glass fibre‐reinforced post (FRC Postec) with a composite core (Tetric Ceram), respectively. Group 4 consisted of a titanium post (ERpost) with a composite core (Tetric Ceram). The control group (group 5) consisted of root‐filled incisors without posts. Tooth‐coloured posts were cemented in the roots using Variolink‐2, while titanium posts were cemented in the roots using Harvard cement. The all‐ceramic copings were cemented using Variolink‐2. Static load was applied to 2 mm below the incisal edge on the palatinal surface of each sample until they were fractured. Fracture data were obtained and statistically analysed with One‐way anova and a Tukey's test. The results of the means and standard deviations of the fracture resistance during static loading were: 497·5 ± 61·94 (1), 474·61 ± 96·84 (2), 494·61 ± 104·67 (3), 581·34 ± 105·36 (4), 420·42 ± 127·48 (5). There were statistically significant differences between groups 4 and 5. Glass fibre‐reinforced posts and composite cores (group 3) showed the most catastrophic failure. Consequently, zirconia ceramic posts can be used in clinical practice.
An experimental analysis of stresses in simulated flared root canals subjected to various post–core applications
Authors: YOLDAS O. , AKOVA T. , UYSAL H.
Published: May 2005

summary  Cervical root fracture is a major clinical problem in flared root canals treated with different post and core applications. This in vitro study evaluated the stress transfer of different post and core systems to the cervical part of the artificially created flared root canals, by using strain gauges. The post–core systems investigated were: (a) cast post–core system without resin reinforcement, (b) cast post–core system with resin reinforcement, (c) pre‐fabricated post and resin core with resin reinforcement. The post–core systems which were cemented on simulated roots were subjected to a load applied at an angle of 45° to the long axis of the simulated roots. The strain gauges which were cemented to the cervical part of simulated roots were connected to the data acquisition module to measure and record the changes in strain data. Specimens restored with resin reinforcement either with cast post–core or pre‐fabricated post and resin core transferred the stress to the cervical part of the artificial roots at a rate lower than conventional cast post–core system (P = 0·001; anova and Tukey's post hoc test). It was concluded that the resin reinforcement of root canals before post–core applications reduces the stresses at the cervical part of the root surfaces.
Surface EMG of jaw elevator muscles: effect of electrode location and inter‐electrode distance
Authors: CASTROFLORIO T. , FARINA D. , BOTTIN A. , PIANCINO M. G. , BRACCO P. , MERLETTI R.
Published: May 2005

summary  This study addresses methodological issues on surface electromyographic (EMG) signal recording from jaw elevator muscles. The aims were (i) to investigate the sensitivity to electrode displacements of amplitude and spectral surface EMG variables, (ii) to analyse if this sensitivity is affected by the inter‐electrode distance of the bipolar recording, and (iii) to investigate the effect of inter‐electrode distance on the estimated amplitude and spectral EMG variables. The superficial masseter and anterior temporalis muscles of 13 subjects were investigated by means of a linear electrode array. The percentage difference in EMG variable estimates from signals detected at different locations over the muscle was larger than 100% of the estimated value. Increasing the inter‐electrode distance resulted in a significant reduction of the estimation variability because of electrode displacement. A criterion for electrode placement selection is suggested, with which the sensitivity of EMG variables to small electrode displacements was of the order of 2% for spectral and 6% for amplitude variables. Finally, spectral and, in particular, amplitude EMG variables were very sensitive to inter‐electrode distance, which thus should be fixed when subjects or muscles are compared in the same or different experimental conditions.
Occlusion – time to reflect? A personal view
Authors: BARTLETT D.
Published: May 2005

summary  The topic of occlusion presents a conundrum to many practitioners. To some the topic is very complex and yet to others, although important, it illustrates how adaptive the dentition is to change. This commentary presents some arguments as to how the importance of occlusion and its understanding have evolved since the Journal of Oral Rehabilitation was first published.