bluuebunny/crossref_metadata_2025 huggingface dataset:
Micropapillary variant of urothelial carcinoma of the urinary bladder; a clinicopathological and immunohistochemical study
Authors: Samaratunga H , Khoo K
Published: December 2004

Aims:  To investigate whether prognosis in micropapillary urothelial carcinoma is related to the proportion of the micropapillary component (MPC), and to identify the immunohistochemical features of MPC.

Methods and results:  This study presents a clinicopathological analysis of 20 patients with micropapillary urothelial carcinoma of the bladder with cystectomy specimens for evaluation. Tumours were stratified on the extent of MPC: focal, <10%; moderate, 10–50%; extensive, >50%; and this was correlated with tumour stage and prognosis. Sixteen males and four females were aged 56–81 years (mean 69 years). All cases had high‐grade morphology in the micropapillary carcinoma and typical urothelial carcinoma. All cases with extensive MPC (n = 4) were of a high pathological stage (pT3 or pT4) and died of disease (DOD) or other causes. Eighty percent with moderate MPC (eight of 10 cases) were pT3 or pT4 and 50% DOD or are alive with disease. Eighty‐four percent with focal MPC (five of six cases) were pT1 or pTa. In high‐stage cases, the most invasive component was MPC. High‐stage cases had an 85% risk of being advanced at presentation with micropapillary carcinoma. All pT2 or lower stage cases had micropapillary carcinoma on prior transurethral resections of bladder tumour (TURB). High‐stage carcinomas had 30% and 54%, respectively, of surface MPC and urothelial carcinoma in situ, in comparison with 85% and 28% in lower stage carcinomas. Immunohistochemical staining was similarly positive in MPC and typical urothelial carcinoma with cytokeratin (CK)7, CK20, epithelial membrane antigen, carcinoembryonic antigen and cytokeratin 34βE12. CA125 staining was seen only in MPC in 43% of cases.

Conclusions:  Micropapillary urothelial carcinoma is a high‐grade carcinoma in which the prognosis is related to the proportion and location of the MPC. Cases with moderate or extensive MPC are at high risk of being advanced at presentation. Cases with <10% MPC and surface MPC have a high chance of detection at an early stage. The morphology and immunohistochemical profile of the MPC suggest that it is a form of glandular differentiation in urothelial carcinoma.
Variations in histological patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis
Authors: Tansey D , Wells A U , Colby T V , Ip S , Nikolakoupolou A , Du Bois R M , Hansell D M , Nicholson A G
Published: December 2004

Aims and methods:  Pulmonary parenchymal disease is common in patients with connective tissue disorders (CTDs). However, most reports precede recognition of non‐specific interstitial pneumonia (NSIP). We have therefore reviewed 54 lung biopsies from 37 patients with polymyositis/dermatomyositis (PM/DM) (n = 13), Sjögren's syndrome (n = 5), rheumatoid arthritis (n = 17) and systemic lupus erythematosus (SLE) (n = 2) to assess the overall and relative frequencies of patterns of interstitial pneumonia and their impact on prognosis.

Results and conclusions:  NSIP was the most common pattern with an overall biopsy prevalence of 39% and patient prevalence of 41%. There was variation in prevalence between individual CTDs, with PM/DM commonly showing organizing pneumonia (n = 5), rheumatoid arthritis showing follicular bronchiolitis (n = 6) and Sjögren's syndrome showing chronic bronchiolitis (n = 4). These patterns presented either separately or in association with NSIP, occasionally with different patterns in biopsies from separate lobes. Only four patients showed a pattern of usual interstitial pneumonia (UIP): two with rheumatoid arthritis and one each with PM/DM and SLE. Overall mortality was 24%, the most frequently associated pattern being fibrotic NSIP (n = 5). In nine cases, pulmonary presentation preceded the systemic manifestation of the CTDs. When patients with CTDs present with chronic interstitial lung disease, the most common pattern is NSIP, although there is variation in pattern prevalence between individual disorders and patterns of interstitial pneumonia frequently overlap. These data suggest a different biology for intestitial pneumonias in CTDs when compared with the idiopathic interstitial pneumonias where UIP is the most common pattern. Mortality is similar to that seen in idiopathic NSIP and, coupled with pulmonary presentation occurring prior to the systemic manifestation of disease, this may have a bearing on the origin of some cases of putative idiopathic NSIP.
Local invasiveness of ameloblastoma. Role played by matrix metalloproteinases and proliferative activity
Authors: Pinheiro J J V , Freitas V M , Moretti A I S , Jorge A G , Jaeger R G
Published: December 2004

Aims:  Ameloblastoma is an odontogenic neoplasm characterized by local invasiveness and recurrence. In this study we analysed the role played by matrix metalloproteinases (MMPs) in the local invasiveness of ameloblastoma. We also attempted to establish a relationship between the presence of MMPs and the proliferative activity of ameloblastoma cells.

Methods and results:  Immunohistochemistry was carried out to detect different MMPs in formalin‐fixed paraffin‐embedded samples of human ameloblastoma. Immunohistochemistry, however, does not establish whether a given MMP is latent or active. To address this point, we carried out biochemical methods, namely zymography and Western blotting. Our results showed expression of latent and active forms of MMPs 1, 2 and 9 in ameloblastoma. These enzymes may digest bone matrix and release mitogenic factors, which would increase tumour proliferation. This possibility prompted us to study the proliferation of ameloblastoma cells located in close proximity to bone. Silver‐stained nucleolar organizer region morphometry revealed that ameloblastoma cells in the vicinity of bone show increased proliferation, when compared with controls.

Conclusions:  Our results suggest an interdependent mechanism involving MMPs and proliferation of ameloblastoma cells, which may contribute to the local invasiveness of this tumour.
Testing for HER2 in breast cancer
Authors: Lewis F , Jackson P , Lane S , Coast G , Hanby A M
Published: December 2004

HER2 is a paradigm of a molecular target whose appropriate assessment is pivotal in the targeting of novel therapies for breast cancer, notably including Herceptin/TrastuzumabTM. Determining the correct levels requires immunohistochemical and molecular biological skills that are reproducible and measurable, coupled with a knowledge of the appropriate morphological and pathobiological context. Attaining these goals is not easy and laboratories testing for HER2 should maintain a high level of throughput of tests and engage in a recognized external quality assurance scheme. Fluorescence in‐situ hybridization testing remains a particular challenge and there is a range of testing strategies. This testing forms the model for the identification of other novel molecular targets. In the future rapid throughput techniques such as real‐time quantitative polymerase chain reaction (rqPCR), tissue microarrays or both should bring significant economies of cost and scale.
The frequency of intratubular embryonal carcinoma: implications for the pathogenesis of germ cell tumours
Authors: Berney D M , Lee A , Randle S J , Jordan S , Shamash J , Oliver R T D
Published: December 2004

Aims:  To define the frequency and distribution of intratubular embryonal carcinoma (IEC) in an attempt to shed light on the pathogenesis of non‐seminomatous germ cell tumours (NSGCTs). Intratubular germ cell neoplasia of unclassified type (IGCNU) is common in NSGCT; however, IEC is rarely described.

Methods and results:  Sixty‐two germ cell tumours were reviewed. Immunochemistry for CD30, placental alkaline phosphatase (PLAP) and c‐kit was performed. The distribution, immunohistochemistry and morphology of the intratubular neoplasia were noted. All cases showed widespread IGCNU with PLAP and c‐kit staining. CD30 showed strong focal intratubular positivity in 20/31 NSGCTs, 1/29 seminomas and 1/4 mixed seminomas/NSGCTs. In 17 of these cases, the CD30+ tubules were not easily identified as IEC on routine stains. These tubules were scanty in number and c‐kit was negative, though some showed patchy PLAP staining. The cells within these tubules differed morphologically from IGCNU.

Conclusions:  IEC defined by CD30 positivity is not always easily identified on haematoxylin and eosin staining. We suggest that IEC is a common intermediate step between IGCNU and NSGCTs. The patchy and focal distribution of IEC suggests it may evolve quickly to invasive disease.
Malignant transformation within benign adnexal skin tumours
Authors: Liegl B , Leibl S , Okcu M , Beham‐Schmid C , Regauer S
Published: December 2004

Aims:  To report five malignant trichogenic tumours arising in longstanding, previously benign adnexal neoplasms through malignant transformation. Malignant trichogenic adnexal tumours are extremely rare neoplasms.

Methods and results:  The patients were between 55 years and 79 years of age. Three of the tumours were located on the arms, two on the face. Three of our patients had a history of chronic lymphocytic leukaemia, one patient had a history of colonic adenocarcinoma. The duration of the tumour nodules was reported as between 20 and 40 years before sudden changes occurred. These changes included rapid growth, pain, itching, ulceration and bleeding. Histologically, all tumours were well circumscribed and encapsulated. There was a residual benign tumour component and morphological signs such as bone formation, dystrophic calcification and sclerosis suggesting long duration of the lesions. All patients except for one, who refused further clinical investigation due to her advanced age of 79 years, had an underlying systemic malignancy.

Conclusions:  The growth stimulus in these benign adnexal neoplasms resulting in malignant transformation may be attributed to the acquisition of additional genetic events or to immunosuppression due to an underlying neoplastic disease. Therefore, patients with systemic diseases or malignancy should be carefully examined and followed for sudden changes in pre‐existing benign cutaneous tumours.
Pleomorphic adenoma and carcinoma ex pleomorphic adenoma: immunohistochemical demonstration of the association between tenascin expression and malignancy
Authors: Félix A , Rosa J C , Fonseca I , Cidadão A , Soares J
Published: December 2004

Aims:  To investigate tenascin expression in salivary gland tumours. Tenascin is a matricellular protein that has been studied in several tumour types. Its expression has been correlated with tumour morphogenesis as well as with local invasiveness and tumour metastatic behaviour.

Methods and results:  The distribution pattern of tenascin in a series of 63 pleomorphic adenomas (PA) and 20 carcinomas ex‐ pleomorphic adenoma (Ca ex PA) was studied immunohistochemically. Ten normal adult salivary glands were used as controls. Tenascin surrounded the excretory ducts of normal adult salivary gland tissue. It was absent in the basement membrane compartment of both benign and malignant mixed tumours. In the interstitial compartment of the extracellular matrix, the fibro‐hyaline type expressed tenascin in a statistically significantly (P < 0.001) lower number of PA cases (25%) in comparison with both malignant and benign areas of Ca ex PA (75% and 90%, respectively). In the Ca ex PA group, a statistically significantly difference (P < 0.001) was found in the frequency of tenascin deposits around aggregates of neoplastic cells between metastasizing (73%) and non‐metastasizing neoplasms (0%).

Conclusions:  These findings strongly support the hypothesis that tenascin deposition is involved in the mechanisms of malignant transformation of pleomorphic adenomas into carcinomas as well as being associated with clinical disease progression.
Clinical utility of bone marrow flow cytometry in B‐cell non‐Hodgkin lymphomas (B‐NHL)
Authors: Perea G , Altés A , Bellido M , Aventín A , Bordes R , Ayats R , Remacha A F , Espinosa I , Briones J , Sierra J , Nomdedéu J F
Published: December 2004

Aim : To determine the efficacy of flow cytometry (FC) in the assessment of bone marrow (BM) in B‐cell non‐Hodgkin lymphoma (B‐NHL). FC is a common practice, but is far from being validated.

Methods and results : Morphological analysis and FC immunophenotyping were perfomed on 421 samples. T‐cell lymphomas, Hodgkin's disease, chronic lymphocytic leukaemia and hairy cell leukaemia were not included in the study. Clonality was assessed by the standard κ/λ/CD19 test. Aberrant immunophenotypes present in the B‐cell subpopulation were also investigated. A double‐step procedure was employed in all cases to increase the sensitivity of the FC procedure. Of 380 evaluable samples, 188 corresponded to follicular lymphoma (FL), 58 to diffuse large B‐cell lymphoma (DLBCL), 57 to mantle cell lymphoma (MCL), seven to Burkitt's lymphoma and the remaining 70 samples to other low‐grade lymphomas. Morphological marrow infiltration was found in 148 cases, and flow immunophenotyping identified 138 cases with BM involvement. A concordance between the two methods was detected in 298 cases (79%). There was a discordance in 82 cases (21%): morphology positive/FC negative in 46 cases and morphology negative/FC positive in 36 (61% of all cases with discordance were from FL). There was no difference in outcome when patients with discordances were compared with patients without discordances.

Conclusions : Most samples showed concordance between morphological and FC results. FC identified BM involvement in the absence of morphological infiltration. Morphology/FC discordance seems to have no influence on the outcome of FL patients.
The role of nuclear morphometry in prediction of prognosis for rhabdomyosarcoma in children
Authors: Kazanowska B , Jelen M , Reich A , Tarnawski W , Chybicka A
Published: December 2004

Aims : To determine whether nuclear morphometry can be used in pretreatment diagnostic procedures to guide the therapy of childhood rhabdomyosarcoma (RMS).

Materials and methods : Biopsy specimens obtained from 108 patients with rhabdomyosarcoma aged between 1 and 217 months treated in 12 paediatric oncology departments in Poland were evaluated. There were 65 (60.2%) specimens of embryonal rhabdomyosarcoma (RME), 32 (29.6%) of alveolar RMS (RMA) and 11 (10.2%) cases of undifferentiated RMS (RMU). The clinical data from all analysed patients were evaluated. Nuclear morphometry was performed semiautomatically on haematoxylin–eosin‐stained sections using the MultiScan v.8.08 Computer Scanning System and an Olympus BX 50 microscope with a × 40 magnification lens.

Results : In the RMA subtype cells with spindle‐shape nuclei were less common (P = 0.013) and cell nuclei were generally more round in comparison with RME (P = 0.033). The clinical outcome was better if the nuclei seen in biopsies of RMS were more spindle‐shaped (event‐free survival 0.51 and 0.23, respectively; P = 0.04) or more cells with spindle‐shaped nuclei were observed (event‐free survival 0.5 and 0.28, P =0.035). RME patients with small nuclei had a better outcome then patients with large nuclei (P = 0.014). In the RMA/RMU group, patients with small tumour cell nuclei had a worse prognosis than patients with larg tumour cell nuclei (P = 0.046).

Conclusions : Nuclear morphometry is a useful tool in the assessment of children with RMS. Additionally, certain morphometric parameters could be easily applied in a selection of patients with good prognosis.
Neutrophilic phlebitis is characteristic of intestinal Behçet's disease and simple ulcer syndrome
Authors: Hayasaki N , Ito M , Suzuki T , Ina K , Ando T , Kusugami K , Goto H
Published: December 2004

Aim : To characterize the histological features of intestinal Behçet's disease and simple ulcer syndrome and to clarify the possible mechanisms involved in their development by analysing the type of inflammatory infiltrates in the diseased intestine and the expression of adhesion molecules on endothelial cells.

Methods and results : Tissue samples from 10 patients diagnosed as having intestinal Behçet's disease or simple ulcer syndrome were studied. Immunohistochemical studies were performed on paraffin‐embedded tissue using a labelled streptavidin–biotin method. In all cases, phlebitis was remarkably seen in submucosal inflammatory lesions, but the adjacent arteries were not affected. Inflammatory infiltrates around the affected vessels consisted of neutrophils and mononuclear cells, and neutrophils predominated over CD68+ macrophages and lymphocytes. The majority of mononuclear cells were CD3+ T cells, and CD4+ cells were more frequent than CD8+ T cells. As for adhesion molecule expression, intercellular adhesion molecule‐1, but not vascular cell adhesion molecule‐1, was expressed in most endothelial cells of the vessels with phlebitis, some of which were also positive for HLA‐DR.

Conclusion : Neutrophilic phlebitis may be involved in the pathogenesis of intestinal Behçet's disease and simple ulcer syndrome.
The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases
Authors: Pan C‐C , Chen P C‐H , Ho D M‐T
Published: December 2004

Aims:  To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell carcinoma marker (RCC Ma) and CD10 in the classification of RCC and renal oncocytoma, based upon a comprehensive immunohistochemical analysis.

Methods and results:  Immunohistochemistry was performed on 328 samples consisting of 256 clear cell/conventional, 27 papillary, 28 chromophobe, five collecting duct, five unclassified RCCs and seven renal oncocytomas using antibodies MOC31, BerEP4 and antibodies against cytokeratins (KL‐1, CAM5.2, 34βE12, cytokeratin 7), RCC Ma, epithelial membrane antigen, E‐cadherin, CD10, CD15 and vimentin. Multivariate analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory value. MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma and CD10 labelled the proximal tubules. Twenty‐three chromophobe RCCs (82%) were reactive for MOC31, while only four clear cell RCCs and three papillary RCCs were positive for this marker. Clear cell RCCs were characterized by a high positive rate for CD10 (82%) and a low positive rate for BerEP4 (27%). Papillary RCCs frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were negative for MOC31 and CD10.

Conclusions:  MOC31 has diagnostic merit in discerning chromophobe RCC. The CD10+/BerEP4– profile and RCC Ma+/BerEP4+ profile achieve moderate sensitivity and good specificity for clear cell RCC and papillary RCC, respectively. The non‐reactivity for both MOC31 and CD10 is helpful in distinguishing renal oncocytoma from RCC. When properly selected, antibodies have immunohistochemical diagnostic utility for the classification of renal cortical epithelial tumours.
Prevalence of CD99 protein expression in pancreatic endocrine tumours (PETs)
Authors: Goto A , Niki T , Terado Y , Fukushima J , Fukayama M
Published: December 2004

Aims : To determine the prevalence of CD99 expression in pancreatic endocrine tumours (PETs). We evaluated CD99 expression and analysed Ki67 labelling by immunohistochemistry in PETs.

Methods and results : Thirty‐eight PETs from 33 patients were analysed. CD99 immunoreactivity was consistently observed in normal islets of the pancreas, regardless of the cell type. Tumours comprising more than 30% CD99+ cells were defined as positively immunoreactive for CD99. CD99 expression was observed in 20 of the 38 PETs examined, but not in any of the pancreatic tumours of other histological subtypes (10 ductal adenocarcinomas, five intraductal papillary‐mucinous tumours, and two acinar cell tumours). Loss of CD99 expression was related to markers of worse prognosis for PET, including gross local invasion, metastasis to the lymph nodes or other organs, lymphatic or blood vessel invasion, and neuroendocrine carcinoma (NEC). Thus, CD99 expression may have an efficiency comparable to that of high Ki67 labelling index (5% or more) for prognostication.

Conslusions : CD99 expression was observed frequently and exclusively in PETs, and loss of CD99 expression in PETs was found to be associated with ominous prognostic indicators.
CD10 is a diagnostic and prognostic marker in renal malignancies
Authors: Langner C , Ratschek M , Rehak P , Schips L , Zigeuner R
Published: December 2004

Aims:  To determine the diagnostic and prognostic value of CD10 immunoreactivity in renal cell carcinomas (RCCs) and transitional cell carcinomas (TCCs).

Methods and results:  CD10 expression was investigated in primary (n = 180) and metastatic (n = 58) RCCs and upper urinary tract TCCs (n = 53) using a tissue microarray technique. One hundred and fifty‐four of 172 (90%) evaluable primary and 48/56 (86%) evaluable metastatic RCCs expressed CD10. Extensive immunoreactivity (positivity of >50% cancer cells) decreased with rising tumour grade in conventional RCCs [G1/G2 72/81 (89%), G3/G4 33/48 (69%); P = 0.009]. Chromophobe RCCs showed a significantly lower overall and extensive immunoreactivity compared with conventional tumours (P < 0.001). In papillary RCCs immunoreactivity of more than 10% of cancer cells for CD10 was seen more often in type 2 (7/8, 88%) compared with type 1 (5/12, 42%; P =0.054) tumours. In conventional RCCs, pure apical membranous staining was associated with low tumour stage (P = 0.003), low grade (P = 0.004) and improved prognosis on univariate analysis (P = 0.031). TCCs were less frequently stained (51%). Extensive staining, however, was associated with high‐stage tumours (P = 0.024), high‐grade (P = 0.073) tumours, and was associated with shorter disease‐free survival in univariate analysis (P = 0.003).

Conclusions:  CD10 proved to be an additional marker for renal malignancies with predominantly diagnostic potential.
Gastric medullary carcinoma, a distinct entity associated with microsatellite instability‐H, prominent intraepithelial lymphocytes and improved prognosis
Authors: Lü B‐J , Lai M , Cheng L , Xu J‐Y , Huang Q
Published: December 2004

Aims:  To determine the clinicopathological and molecular features of gastric medullary cancer.

Methods and results:  Clinicopathological review and microsatellite instability (MSI) analysis were carried out on 17 gastric medullary and 64 non‐medullary cancers. In addition to characteristic histopathology, gastric medullary cancers had certain prominent features: (i) the average survival time was longer in medullary and low‐grade non‐medullary cancers than in high‐grade (P = 0.004); (ii) serosal involvement was less common in medullary cancers (29.4%, 5/17) than in non‐medullary cancers (9.4%, 6/64) (P < 0.05) while pushing borders were more common in medullary cancers (70.6%, 12/17 versus 17.2%, 11/64, P = 0); (iii) the presence of intraepithelial lymphocytes (IELs) in medullary and non‐medullary cancers was 2380/10 high‐power field (HPF) and 147/10 HPF (P = 0), respectively. Both peritumoural infiltrating lymphocytes (pTIL) and a Crohn's‐like reaction were more common in medullary cancers than in non‐medullary (pTIL 35.3%, 6/17 versus 3.1%, 2/64; a Crohn's‐like reaction 70.6%, 12/17 versus 32.8%, 21/64; P < 0.05); (iv) medullary and high‐grade non‐medullary cancers were more associated with reduced ECD expression in comparison with low‐grade cancers (P < 0.05); (v) higher MSI‐H (Bat26+) rate was observed in medullary cancers (41.2%, 7/17) than in non‐medullary (1.6%, 1/64) (P = 0).

Conclusions:  Gastric medullary cancer has distinct clinicopathological features and genetic alterations. Two subtypes of gastric medullary cancers, Bat26+ and Bat26–, might have prognostic implications, thus analysis of Bat26 may be of clinical value.
Use of a molar clamp to isolate two adjacent single‐rooted teeth: a clinical aid
Authors: Chen K. L. , Wu Y. H. , Chen Y.‐H. M.
Published: December 2004

Aim  To emphasize the importance of rubber dam isolation in root canal treatment and to present a technique to simultaneously isolate two single‐rooted teeth using a molar clamp.

Summary  Isolation of two adjacent teeth with inadequate tooth structure is a challenge. The split‐dam technique or using two clamps have drawbacks. This report presents a technique to simultaneously isolate two adjacent single‐rooted teeth that are difficult to isolate by conventional methods. Its advantages are efficiency, reduction of radiation exposure, better access, good visibility and isolation.

Key learning points  • The basis of this technique is to isolate two teeth as two roots of a molar tooth.

• The indications for this technique are two adjacent prepared crowns and crownless roots.

• The appropriate molar clamp can be selected on the basis of the mesial–distal clamp jaw distance being equal to the mesial–distal spacing of the two roots. The buccal–lingual jaw distance of the clamp should be smaller than the dimension of the roots to provide adequate retention.
Efficacy, cleaning ability and safety of different rotary NiTi instruments in root canal retreatment
Authors: Hülsmann M. , Bluhm V.
Published: December 2004

Aim  To evaluate the efficacy, cleaning ability and safety of three different rotary nickel‐titanium instruments with and without a solvent (eucalyptol) versus hand files in the removal of gutta‐percha root fillings.

Methodology  Eighty extracted single‐rooted anterior teeth were enlarged to size 35 and obturated with laterally condensed gutta‐percha using AHPlus as the sealer. Removal of gutta‐percha was performed with the following devices and techniques: FlexMaster, GT Rotary, ProTaper and Hedström files. All techniques were used with and without the solvent eucalyptol. The following data were recorded: time taken to reach the calculated working length and time required for the removal of gutta‐percha. The teeth were split longitudinally and photographed. Cleanliness of the root canal walls was scored using the projected slides with a total magnification of approximately 70×. Statistical analysis was performed using the two‐way anova (P < 0.001) for the analysis of working time.

Results  The technique that reached the working length most rapidly was that using ProTaper instruments and eucalyptol (+E), followed by FlexMaster + E, ProTaper, FlexMaster, Hedström files + E, GT Rotary + E, Hedström files, and GT Rotary. No significant differences were found for retreatment with or without a solvent in all groups. ProTaper and FlexMaster worked significantly more rapidly than Hedström files and GT Rotary (anova, P < 0.001). Time for complete removal of gutta‐percha was again shortest with ProTaper + E, followed by FlexMaster + E, ProTaper, FlexMaster, GT Rotary + E, Hedström files + E, Hedström files, and GT Rotary. ProTaper and FlexMaster again worked significantly faster than the other techniques (anova, P < 0.001). There was no visible filling material extruded apically. Root canal cleanliness proved best following the use of FlexMaster + E, and Hedström files + E, followed by ProTaper + E, and GT Rotary + E.

Conclusion  Under the experimental conditions, FlexMaster and ProTaper NiTi instruments proved to be efficient and time‐saving devices for the removal of gutta‐percha. The use of eucalyptol as a solvent shortened the time to reach the working length and to remove the gutta‐percha, but this was not significant.
Investigation of the root canal configurations of mandibular permanent teeth in the Turkish population
Authors: Sert S. , Aslanalp V. , Tanalp J.
Published: December 2004

Aim  To investigate the root and canal morphology of mandibular permanent teeth collected from an indigenous Turkish population.

Methodology  A total of 1400 extracted mandibular permanent teeth were evaluated. The teeth were divided into seven groups as central incisors, lateral incisors, canines, first premolars, second premolars, first molars and second molars in order to evaluate their root canal configurations. Access cavities were prepared and pulp tissue removed using 5.25% sodium hypochlorite solution. The teeth were stored in 5% nitric acid solution for 5 days, then rinsed under running water for 4 h and placed in increasing concentrations of ethyl alcohol. The teeth were rendered transparent by immersion in xylene solution for 3 days until complete transparency was achieved. Following this procedure, India ink was injected in the root canal systems and their configurations were examined and compared with the classification of Vertucci. The following observations were made: (i) root canal classification of mandibular teeth; (ii) morphology of the mandibular permanent teeth. The classification of Vertucci was taken as a reference during the evaluation; however additional canal morphological types were evaluated as separate groups.

Results  The presence of a second canal was detected in 68% of mandibular central incisors and 63% of lateral incisors. Lateral canals were found in 6.5% of mandibular central incisors and in 13% of lateral incisors. Overall, 62% of mandibular first premolar teeth had a single canal whereas 71% of second premolars had a single canal. The mandibular first and second molar teeth exhibited similar root canal configurations except for a group of second molar teeth that had a single root and canal.

Conclusions  The morphological characteristics of teeth in this Turkish population were consistent with those of other studies performed on different populations using similar methodology.
Idiopathic pneumonia syndrome after bone marrow transplantation: the role of pre‐transplant radiation conditioning and local cytokine dysregulation in promoting lung inflammation and fibrosis
Authors: Shankar Gopi , Cohen Donald A.
Published: December 2004

Pulmonary complications and graft‐vs.‐host disease (GVHD) remain severe threats to survival after bone marrow transplantation (BMT). Idiopathic pneumonia syndrome (IPS) accounts for nearly 50% of all the cases of interstitial pneumonitis after BMT. IPS is characterized by an early inflammatory phase followed by chronic inflammation and fibrosis of lung tissue; however, the immunopathogenesis of this disease is not yet clearly understood. This biphasic syndrome has been reported to be associated with pre‐transplant radiation conditioning in some studies while others have suggested that GVHD or autoimmune phenomena may be responsible for its development. The early post‐BMT phase is characterized by the presence of inflammatory cytokines whose net effect is to promote lymphocyte influx into lungs with minimal fibrosis, that leads to an acute form of graft‐vs.‐host reaction‐mediated pulmonary tissue damage. Gradual changes over time in leucocyte influx and activation lead to dysregulated wound repair mechanisms resulting from the shift in the balance of cytokines that promote fibrosis. Using data from new animal models of IPS and information from studies of human IPS, we hypothesize that cytokine‐modulated immunological mechanisms which occur during the acute and chronic phases after bone marrow transplantation lead to the development of the progressive, inflammatory, and fibrotic lung disease typical of idiopathic pneumonia syndrome.
Epstein‐Barr virus infection and human malignancies
Authors: Niedobitek Gerald , Meru Nadine , Delecluse Henri‐Jacques
Published: December 2004

The Epstein‐Barr virus (EBV) is a herpes virus which establishes a life‐long persistent infection in over 90% of the human adult population world‐wide. Based on its association with a variety of lymphoid and epithelial malignancies, EBV has been classified as a group 1 carcinogen by the International Agency for Research on Cancer. In this article we discuss the evidence supporting an aetiological role for EBV in the pathogenesis of human tumours. The biology of EBV infection will be described with special emphasis on viral transforming gene products. A brief survey of EBV‐associated tumours is followed by a discussion of specific problems. Evidence is presented which suggests that failures of the EBV‐specific immunity may play a role in the pathogenesis of EBV‐associated tumours also in patients without clinically manifest immunodeficiencies. Finally, the timing of EBV infection in the pathogenesis of virus‐associated malignancies is discussed. There is good evidence that EBV infection precedes expansion of the malignant cell populations in some virus‐associated tumours. However, this is clearly not always the case and for some of these tumours there are indications that clonal genetic alterations may occur prior to EBV infection. Thus, whilst there is good evidence to suggest that EBV is a human carcinogen, its precise role(s) in the development of virus‐associated human tumours requires clarification.<
Viruses and apoptosis
Authors: Thomson Brian J.
Published: December 2004

Apoptosis, or programmed cell death, is essential in development and homeostasis in multi‐cellular organisms. It is also an important component of the cellular response to injury. Many cells undergo apoptosis in response to viral infection, with a consequent reduction in the release of progeny virus. Viruses have therefore evolved multiple distinct mechanisms for modulating host cell apoptosis. Viruses may interfere with either the highly conserved ‘effector’ mechanisms of programmed cell death or regulatory mechanisms specific to mammalian cells. In addition to conferring a selective advantage to the virus, the capacity to prevent apoptosis has an essential role in the transformation of the host cell by oncogenic viruses. This article provides a focussed review of apoptosis and illustrates how the study of viruses has informed our understanding of this process. Selected mechanisms by which viral gene products interfere with cell death are discussed in detail and used to illustrate the general principles of the interactions between viruses and apoptosis.
Effects of hyaluronan on the invasive properties of human breast cancer cells in vitro
Authors: Herrera‐Gayol Andrea , Jothy Serge
Published: December 2004

Hyaluronan (HA) is a high molecular weight glycosaminoglycan present mostly in the extracellular matrix (ECM). HA binds to specific receptors such as CD44. Its production is increased at the tumour–stroma interface, including those in breast cancer tumours. It has been suggested that it facilitates invasion of tumour cells into the ECM by a hydrodynamic effect, or by altering tumour cell behaviour. Using in vitro tests we studied the effect of immobilized (iHA) and soluble (sHA) HA on the invasive properties of four human breast cancer cell lines with different levels of CD44 expression. Our results show that iHA acts as an adhesive, haptotactic, and motility stimulating factor for the CD44 positive Hs578T cells and induces the expression of membrane CD44. sHA also changes the motility properties of the Hs578T and MDA‐231 cells and increases their CD44 expression. sHA or iHA have no measurable effect on the adhesion, motility or CD44 expression of the ZR‐75–1 and MCF‐7 breast cancer cells. Our results establish that in high CD44 expressing breast cancer cells HA modulates tumour cell adhesion and motility and also increases the expression of its own receptor, CD44.
Helper T cells, dendritic cells and CTL Immunity
Authors: Behrens Georg , Li Ming , Smith Christopher M , Belz Gabrielle T , Mintern Justine , Carbone Francis R , Heath William R
Published: December 2004

In this review, we examine the emerging view that all CTL responses depend on CD4 T‐cell help for the generation of efficient memory. We further review the evidence that CD4 and CD8 T cells must recognize antigen on the same dendritic cell, and examine why this corecognition is required. Earlier studies have suggested that CD4 T cells must activate the dendritic cell via CD40 to license it for the capacity to prime CTL immunity. More recently, however, CD40 signalling of the CTL has been reported. Here, we argue that the main reason for corecognition of antigen on the dendritic cell may be related to the time taken to activate and release CD4 and CD8 T cells from their priming dendritic cell. CD4 T cells may only be capable of activating one dendritic cell during the period that CD8 T cells are primed. In this case, corecognition of this same dendritic cell would be essential.
Interleukin‐17: the missing link between T‐cell accumulation and effector cell actions in rheumatoid arthritis?
Authors: Stamp Lisa K , James Michael J , Cleland Leslie G
Published: December 2004

The prominence of T cells and monocyte/macrophages in rheumatoid synovium suggests T cells may localize and amplify the effector functions of monocyte/macrophages in rheumatoid disease. However, while T cells are abundant in rheumatoid joints, classic T‐cell derived cytokines are scarce, especially when compared to the levels of monokines IL‐1β and TNF‐α. For this reason, it has been speculated that monocyte/macrophages may act independently of T cells in rheumatoid disease and that the role of T cells may be more or less irrelevant to core disease mechanisms. The question of T‐cell influence requires re‐evaluation in light of the characterization of IL‐17, a T‐cell derived cytokine that is abundant in rheumatoid synovium and synovial fluid. IL‐17 has a number of pro‐inflammatory effects, both directly and through amplification of the effects of IL‐1β and TNF‐α. IL‐17 is able to induce expression of pro‐inflammatory cytokines and stimulate release of eicosanoids by monocytes and synoviocytes. Furthermore, IL‐17 has been implicated in the pathogenesis of inflammatory bone and joint damage through induction of matrix metalloproteinases and osteoclasts, as well as inhibition of proteoglycan synthesis. In animal models of arthritis, intra‐articular injection of IL‐17 results in joint inflammation and damage. The recognition of IL‐17 as a pro‐inflammatory T cell derived cytokine, and its abundance within rheumatoid joints, provides the strongest candidate mechanism to date through which T cells can capture and localize macrophage effector functions in rheumatoid arthritis. As such, IL‐17 warrants consideration for its potential as a therapeutic target in rheumatoid arthritis.
Alternative routes of mucosal immunization in large animals
Authors: Sedgmen Bradley J , Meeusen Els N T , Lofthouse Shari A
Published: December 2004

Mucosal immunization regimes that employ the oral route of delivery are often compromised by antigen degradation in the stomach. Moreover, tolerance or immunological unresponsiveness to orally delivered vaccine antigens is also a major problem associated with this route of immunization. Immunization by alternative routes including intrarectal (i.r.) and intranasal (i.n.) is becoming increasingly recognized in large animals for generating protective antibody responses at mucosal surfaces. These approaches are particularly useful in ruminant species which have four stomachs that can potentially interfere with antigen presentation to mucosal inductive sites of the gut. Modifications to enhance existing mucosal immunization regimes have also been explored through the use of alternative antigen delivery systems and mucosal adjuvants. The combination of alternative immunization routes and the use of appropriate antigen delivery systems appear to be a rational approach for providing protective immunity at mucosal surfaces. There has been a considerable amount of research conducted on evaluating the efficacy of emerging antigen delivery systems and novel adjuvants for improved immunity to mucosal immunization but very little of this work has been specific to the mucosal compartment of large animals. The aim of this review is therefore to assess the feasibility and practicality of using large animals (particularly sheep, cattle and pigs) for inducing and detecting specific immune responses to alternative mucosal routes of immunization.
Family life in grocery stores – a study of interaction between adults and children
Authors: Pettersson Anette , Olsson Ulf , Fjellström Christina
Published: December 2004

Today the family is seen as a unit for food choice and consumption. The influence of family members on food choice comprises several stages that can be carried out both in the private home and in the public sphere, such as the grocery store. This makes the grocery store a context in which ordinary family life can be observed. The aim was to study families and the interaction between children and adults in the grocery store, focusing on young people's involvement in food shopping. Hidden observation and family interview methods were used. A total of 338 people were observed in seven different grocery stores in Stockholm during the summer and autumn of 2003. Seven family interviews, involving a total of 29 persons, were conducted in Uppsala in the spring of 2003. In the interviews, parents reported avoiding shopping for food together with children as they experienced it as stressful and exhausting. The observations showed that family life in the grocery store comprises not only the food purchase, but also bringing up children and consumer education. Young people's involvement in the food purchase varied depending on their age and the specific product. The different behaviour observed may be interpreted as reflecting the variation in ways of bringing up children at home. Another conclusion is that a public place such the grocery store facilitates pedagogical situations and can work as a tool for informal education.
The dietary and health behaviour of young people aged 18–25 years living independently or in the family home in Liverpool, UK
Authors: Beasley Lucy J. , Hackett Allan F. , Maxwell Sheila M.
Published: December 2004

An individual's dietary habits are largely developed during childhood and adolescence, and are likely to be determined by both nature (the development of sensory perceptions) and nurture (parental influence, and later on the influence of peers). However, diet is likely to evolve throughout the life cycle as circumstances change and new influences are introduced to an individual's lifestyle. An example of this is the changes in diet that occur as a result of the transition young people make away from the family home into independent living. Leaving behind the meals provided and cooked by parents/guardians and learning how to shop on a budget and prepare and cook for themselves may result in the adoption of poor eating habits, which is likely to have a detrimental effect on health. Leaving behind the restrictions of parental control may also result in the adoption of unhealthy lifestyle practices such as smoking and excessive alcohol consumption. This study therefore seeks to investigate the effect of leaving home on a young person's diet and lifestyle. Health behaviour and food intake was assessed by questionnaire. Findings suggest that a young person's diet may change after leaving home, but these changes are not necessarily negative. More negative health behaviour was observed in young people living independently.
Adolescent consumers: reaching them, border crossings and pedagogical challenges
Authors: Ahava Anna‐Maija , Palojoki Päivi
Published: December 2004

Consumerism is part of living in the contemporary post‐modern world. It is claimed that schools and consumer education have a rather marginal impact on the consumer behaviour of young people. This qualitative study explores adolescents’ ways of consuming in three different worlds: home, school and peer groups. The aim is to understand how the adolescents experience border crossings between these worlds. What do they think about consumerism and consumer education? Finally, the pedagogical challenges of consumer education are discussed. The qualitative data was collected through mind maps, written questionnaires and semi‐structured group interviews. Qualitative content analysis was used to analyse the data. The data was collected from 59 teens (between 14 and 15 years of age) from Vantaa, Finland. According to the results, the adolescents’ way of consuming in each world differs from each other. However, border crossings occur with natural strategies and smooth transitions. The adolescents feel that ‘real’ consumerism does not begin until adulthood. Then, it is time to act like responsible consumers. Their motivation to study consumer issues at school is poor, because they feel the substance of consumer education not corresponding to their lives. Because of this, consumer education needs pedagogical renovation based on the needs of the adolescents and the special features of their consumerism.
Finnish young people's narrative construction of consumer identity
Authors: Autio Minna
Published: December 2004

This article examines how young Finns represent their consumer identity through narratives. Young consumers are easily seen as careless spenders and selfish hedonists in the contemporary consumer society. However, an empirical approach is required in order to find out whether this generation of young Finnish consumers is one of ‘raving hedonists’ or ‘ultimate materialists’, as their peers are often presented in public discussion in many western societies. The empirical data was collected in five upper secondary schools between the end of November 2001 and the beginning of January 2002. These schools are located in five different districts in Finland, varying from metropolitan to rural areas. The study focused on students aged 16–19 years and used essay writing as the method for collecting qualitative data. The data thus consists of 159 life stories as a consumer written by young Finnish people. Qualitative research methods, such as narrative analysis, were used in this study. It is argued that Finnish young people are representing their identities as consumers through a combination of various levels of consumer discourses besides hedonism and squandering: rationality and economizing are an essential part of their consumer identities. Some youngsters also present themselves as responsible consumers including ecological and ethical choices as part of their narrative. The way these youngsters combine discourses gives evidence of the various features of the present‐day young consumer. It is also suggested that their consumer identity develops and changes with age. Young people describe their identity changing through a hedonist/squanderer discourse to a rational and economical one or vice versa. They also combine hedonist, rational, economical and responsible discourses simultaneously.
METRO—the creation of a taxonomy for medical education
Authors: Haig Alex , Ellaway Rachel , Dozier Marshall , Liu Don , McKendree Jean
Published: December 2004

Aims:  There is a proven and immediate need for a shared vocabulary for medical education in the United Kingdom, both to support the practice of medical education and the research of medical education practice. It would be inefficient to create a complete and independent vocabulary from scratch, the proposed alternative being to create differential terms between the MeSH and BET vocabularies.

Methods:  Existing schemas were reviewed against the needs of stakeholders. Seed terms were submitted to the METRO work environment, discussed, scoped and voted upon.

Results:  A set of procedures, initial terms and recommendations for further development are the principal deliverables from METRO's first phase, while the ongoing second phase will see the creation and testing of an essential branch of descriptors for assessment.

Conclusions:  Further work in a number of areas will be required and long‐term issues of resourcing and sustainability have yet to be substantially addressed to allow for full adoption by the user community.