bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of endothelin to the coronary vasoconstriction in the isolated rat heart induced by nitric oxide synthase inhibition
Authors: Wang Q.‐D. , Gonon A. , Shimizu M. , Sjöquist P.‐O. , Pernow J.
Published: September 2003

The possible involvement of endothelin‐1 (ET‐1) and angiotensin II in the coronary vasoconstriction induced by nitric oxide synthase (NOS) inhibition was investigated in isolated Langendorff‐perfused rat hearts. Fifteen minutes of perfusion with the NOS inhibitor N G‐nitro‐L‐arginine (L‐NNA, 0.1 mM) reduced coronary flow by 31%. Pre‐treatment with the non‐selective ETA/ETB receptor antagonist bosentan (1 and 10 μM) attenuated this reduction in coronary flow to 16% (P < 0.05) and 8% (P < 0.01), respectively. The selective ETA receptor antagonist BQ‐123 (1 μM) induced a similar inhibitory action, whereas the selective ETB receptor antagonist BQ‐788 and the angiotensin II type 1 receptor antagonist candesartan did not affect the vasoconstrictor response to L‐NNA. In addition, bosentan administered after 15 min of L‐NNA perfusion reversed the L‐NNA‐induced reduction in coronary flow in a dose‐dependent manner. The high concentration of bosentan (10 μM) increased the basal coronary flow by 17%, while the lower concentration of bosentan, BQ‐123, BQ‐788 and candesartan did not affect basal coronary flow. Bosentan (10 μM) increased the level of ET‐like immunoreactivity (‐LI) in the coronary effluent twofold. L‐NNA did not affect ET‐LI level. These results indicate that ET‐1 contributes to the coronary vasoconstrictor effect of L‐NNA in the isolated rat heart, and that this action of ET‐1 is mediated through ETA receptor activation. Angiotensin II does not seem to contribute to L‐NNA‐induced vasoconstriction under the present condition.
Convergence of nociceptive and non‐nociceptive inputs onto spinal reflex pathways to the tibialis anterior muscle in humans
Authors: Ellrich J. , Treede R.‐D.
Published: September 2003

The interaction of low‐threshold mechanoreceptive and nociceptive inputs onto spinal neurones probably plays a major role in the pathophysiology of the clinical sign of allodynia. This phenomenon was investigated by modulation of the early component of the flexor reflex (FR) in the tibialis anterior (TA) muscle, elicited by electrical stimulation of the medial plantar nerve at the sole of the foot, by homotopically applied painful heat in humans. This early reflex with an electrical threshold of 2.7‐fold the detection threshold and a mean afferent conduction velocity of 49 m s−1 is a non‐nociceptive FR. When applying conditioning painful heat (46 °C) to the sole of the foot this reflex was significantly increased by a factor of 3.4 (non‐painful electrical stimuli; n = 5) and 2.0 (painful electrical stimuli; n = 11). The onset latencies were significantly shortened from 74.2 to 64.0 ms and 69.6 to 63.7 ms, respectively. A late nociceptive FR was also facilitated. While the Hoffmann reflex (HR) in the TA muscle was nearly abolished by painful heat, the HR in the soleus (SO) muscle remained unchanged. These data suggest a convergence of low‐threshold mechanoreceptive and nociceptive inputs onto spinal reflex pathways in humans, probably at an interneuronal level in humans.
Lack of effficacy of botulinum toxin in chronic anal fissure
Authors: Siproudhis L. , Sébille V. , Pigot F. , Hémery P. , Juguet F. , Bellissant E.
Published: September 2003

Background and aim:  Hypertonicity of internal anal sphincter plays a major role in the persistence of chronic anal fissure. Botulinum toxin could induce internal anal sphincter relaxation without the adverse effects of surgery (long‐term faecal incontinence) or topical nitrates (anal burning, headaches, hypotension).

Methods:  We conducted a placebo‐controlled, randomised, double‐blind study to assess the efficacy of a single injection of botulinum toxin in the internal anal sphincter of patients with chronic anal fissure in six ambulatory care clinics. Eligibility criteria included a mean value of post‐defecation anal pain ≥ 30 mm on a 100 mm visual analogue scale over the week preceding inclusion. Main endpoint was the proportion of patients with symptomatic improvement during the fourth week after inclusion (post‐defecation anal pain below 10 mm).

Results:  Forty‐four patients (22 in each group) were included. At inclusion, there was no significant difference between groups on age, sex ratio, pain duration, post‐defecation anal pain, analgesic consumption and stool frequency. Ten (45%) and 11 (50%) patients reported symptomatic improvement on the main endpoint (P=0.76) in placebo and botulinum toxin groups, respectively. Ten patients (five in each group) had healed fissure at week 4 and ten patients (five in each group) required surgical treatment between weeks 4 and 12. Similarly, there was no significant difference between groups on other variables between weeks 4 and 12.

Conclusions:  The efficacy of a single injection of botulinum toxin in the internal anal sphincter does not differ from that of a placebo in patients with chronic anal fissure.
Effects of asimadoline, a κ‐opioid agonist, on satiation and postprandial symptoms in health
Authors: Delgado‐Aros S. , Chial H. J. , Cremonini F. , Ferber I. , Mckinzie S. , Burton D. D. , Camilleri M.
Published: September 2003

Aim:  To evaluate the effect of single administrations of asimadoline, a κ‐opioid agonist, on satiation volume, postprandial symptoms and gastric volumes.

Methods:  Healthy subjects received oral placebo, or 0.5 or 1.5 mg asimadoline in a randomized, double‐blind fashion 1 h prior to testing. We assessed effects on the volume of Ensure to achieve full satiation and postprandial symptoms 30 min after meal, and on gastric volume (fasting and postprandial) measured by 99mTc‐single photon emission tomography (SPECT) imaging.

Results:  Thirteen healthy subjects were studied in each treatment arm. Compared to placebo, asimadoline 0.5 mg decreased postprandial fullness (P = 0.027) without affecting the volume ingested at full satiation (P = 0.6). Asimadoline 1.5 mg decreased satiation during meal, allowing increased satiation volumes (P = 0.008) and tended to decrease postprandial fullness (P = 0.067), despite higher volumes ingested. There was a significant treatment–gender interaction in the effect of asimadoline on gastric volumes (P < 0.05). Asimadoline 0.5 mg (not 1.5 mg) increased fasting (P = 0.047) and postprandial (P = 0.009) gastric volumes in females but decreased fasting volumes in males (P = 0.008). The effect of asimadoline on gastric volume did not explain the effect observed on satiation volume (P = 0.371) or postprandial fullness (P = 0.399).

Conclusion:  A single oral administration of asimadoline decreases satiation and postprandial fullness in humans independently of its effects on gastric volume.
Azathioprine and prednisone combination therapy in refractory coeliac disease
Authors: Goerres M. S. , Meijer J. W. R. , Wahab P. J. , Kerckhaert J. A. M. , Groenen P. J. T. A. , Van Krieken J. H. J. M. , Mulder C. J. J.
Published: September 2003

Introduction:  Refractory coeliac disease (RCD) is a rare syndrome with a poor prognosis, defined by malabsorption due to gluten‐related enteropathy after initial or subsequent failure of a strict gluten‐free diet and after exclusion of any disorder mimicking coeliac disease.

Patients and methods : Nineteen patients were included and treated. Based on intraepithelial T‐lymphocyte(IEL) phenotyping, patients were recorded as having RCD type I with normal IELs, or RCD type II with phenotypically immature IELs defined by a lack of characteristic T‐cell markers. Treatment consisted of azathioprine combined with prednisone for 1 year, which was tapered and, if possible, stopped.

Results : Clinical improvement was seen in nearly all patients in both groups. Eight of 10 RCD type I patients responded histologically, and complete normalization of villi was seen in four patients. In RCD type II, 6/8 patients developed enteropathy‐associated T‐cell lymphoma (EATL) and 7/8 patients died.

Conclusions : For the first time we report a promising therapeutic treatment option for RCD type I. In RCD type II, azathioprine and prednisone therapy (APT) is not effective, therefore we suggest that other (chemo)therapeutic agents are considered. Not all RCD type II patients presented with a monoclonal TCRγ‐gene rearrangement and immunohistological changes as is currently reported in the literature. Therefore, immunophenotyping seems mandatory in the work‐up of RCD.
Systematic review: hepatotoxic events associated with herbal medicinal products
Authors: Pittler M. H. , Ernst E.
Published: September 2003

Background : Large proportions of patients use herbal medicinal products, and encouraging data in terms of effectiveness exist for some of these. One aspect, however, which is still largely under‐investigated is the question of potential harm.

Aim : To review the recent evidence on hepatotoxic events associated with the use of herbal medicinal products.

Methods : Systematic literature searches were performed on Medline, Embase, The Cochrane Library, Amed and Ciscom. To identify additional data, searches were conducted by hand in relevant medical journals and in our own files. The screening and selection of articles and the extraction of data were performed independently by the two authors. There were no restrictions regarding the language of publication. In order to be included articles were required to report data on hepatotoxic events associated with the therapeutic use of herbal medicinal products.

Results : Single medicinal herbs and combination preparations are associated with hepatotoxic events. Clinically, the spectrum ranges from transient elevations of liver enzyme levels to fulminant liver failure and death. In most instances hepatotoxic herbal constituents are believed to be the cause, while others may be due to herb–drug interactions, contamination and/or adulteration.

Conclusions : A number of herbal medicinal products are associated with serious hepatotoxic events. Incidence figures are largely unknown, and in most cases a causal attribution is not established. The challenge for the future is to systematically research this area, educate all parties involved, and minimize patient risk.
Gastroduodenal tolerability of lumiracoxib vs. placebo and naproxen: a pilot endoscopic study in healthy male subjects
Authors: Rordorf C. , Kellett N. , Mair S. , Ford M. , Milosavljev S. , Branson J. , Scott G.
Published: September 2003

Background : Lumiracoxib (Prexige®) is a cyclooxygenase‐2 (COX‐2) selective inhibitor.

Aim : To compare the gastroduodenal tolerability of lumiracoxib with placebo and naproxen in a randomized, parallel‐group, double‐blind study.

Methods : Sixty‐five healthy male subjects were randomized to receive 8 days' dosing with lumiracoxib 200 mg twice daily (b.d.) (n = 21), placebo (n = 22) or naproxen 500 mg b.d. (n = 22). Endoscopic evaluations of gastric and duodenal mucosae were conducted at baseline and after 8 days' dosing. Serum was assayed for ex‐vivo concentrations of thromboxane B2 (TxB2) to determine cyclooxygenase‐1 (COX‐1) inhibitory activity.

Results : Sixty subjects (20 per group) completed the study. No gastroduodenal erosions were observed in subjects receiving lumiracoxib. Thirteen subjects receiving naproxen developed duodenal erosions. At the gastric site, one subject in each of the naproxen and placebo groups had erosions; one subject receiving naproxen also developed a small asymptomatic gastric ulcer. Gastrointestinal adverse events accounted for 42.3% of all adverse events, occurring in 3/21, 4/22 and 6/22 of the lumiracoxib, placebo and naproxen groups, respectively. TxB2 levels were similar for patients receiving placebo or lumiracoxib, but were reduced by > 95% in patients receiving naproxen, compared with placebo.

Conclusions : Multiple doses of lumiracoxib resulted in gastroduodenal tolerability similar to placebo and superior to naproxen.
Review article: a medicine based on cell transplantation – is there a future for treating liver diseases?
Authors: Di Campli C. , Gasbarrini G. , Gasbarrini A.
Published: September 2003

Cell‐based therapies, comprising isolated hepatocyte transplantation, ex vivo gene therapy and bioartificial liver devices, may actually design a new scenario in the treatment of patients with liver failure. Recent advances in the liver repopulation field and the considerable excitement surrounding the use of haematopoietic stem cells for a ’regenerative medicine’, allow us to see under a new light the alternative cell sources actually under investigation. In particular, the major drawbacks and the most important advantages of xenogenic primary cells, tumour‐derived cell lines, immortalised hepatocytes and stem cells in the wide range of experimental and clinical applications are presented. Even if up to now none of them represent a ’gold standard’ in the clinical practice, the intersecting advances in the development of mechanical components of artificial devices and in the liver biology and bioengineering will open tantalising possibilities to treat patients with liver failure, by tailoring the therapeutic choice on the basis of the aetiology and the stage of liver disease.
Evaluation of Helicobacter species in inflammatory bowel disease
Authors: Bell S. J. , Chisholm S. A. , Owen R. J. , Borriello S. P. , Kamm M. A.
Published: September 2003

Background : Bacteria have been implicated in the pathogenesis of inflammatory bowel disease. Helicobacter species have been shown to cause colitis in animal models and have been identified in human diarrhoeal illness and Crohn's disease.

Aim: : To determine whether Helicobacter species are present in human inflammatory bowel disease tissue.

Methods: : Thirty patients undergoing colonoscopy for clinical reasons were studied. Nine had Crohn's disease, 11 had ulcerative colitis and 10 had histologically normal colons. Tissue was snap‐frozen at −70 °C. DNA was extracted and examined by five different polymerase chain reaction (PCR) assays that were either genus or species specific for Helicobacter.

Results : Analyses of colonic biopsies by two Helicobacter genus‐specific PCR assays, two H. pylori‐specific assays and a PCR assay designed to amplify fragments of ‘H. heilmannii’‐like organisms demonstrated that product was not generated by any test. Internal control PCR demonstrated that PCR results for the five assays were not negative due to the presence of residual substances inhibitory to PCR.

Conclusions : Helicobacter species were not identified in this study, using multiple PCRs to eliminate the problems of non‐specific cross‐reaction. This suggests that Helicobacter species do not play a role in the pathogenesis of inflammatory bowel disease.
The effect of Lactobacillus plantarum 299v on the bacterial composition and metabolic activity in faeces of healthy volunteers: a placebo‐controlled study on the onset and duration of effects
Authors: Goossens D. , Jonkers D. , Russel M. , Stobberingh E. , Van Den Bogaard A. , StockbrÜgger R.
Published: September 2003

Aim : To study the onset and duration of a possible effect of a fermented oatmeal drink containing Lactobacillus plantarum 299v on the composition of the faecal flora of healthy volunteers in a placebo‐controlled, double‐blind study.

Methods : Twenty‐two participants consumed a fermented oatmeal drink with or without L. plantarum 299v for 4 weeks. Faecal samples were collected weekly: two samples before, four during and four after the consumption of the drink. Several bacterial species were counted and enzyme activities, short‐chain fatty acid concentrations, endotoxin concentration and pH were determined. L. plantarum 299v was identified using randomly amplified polymorphic DNA.

Results : In contrast with the placebo group, median lactobacilli counts increased significantly from 4.2 (3.4–6.3) to 8.2 (7.3–8.5) log colony‐forming units/gram faeces (P = 0.005) after 1 week of consumption of L. plantarum 299v, thereafter remaining stable during the treatment period. One week after cessation, a significant decrease in lactobacilli [to 4.4 (2.2–6.5) log colony‐forming units/gram faeces] was observed (P = 0.003). These lactobacilli were identified as L. plantarum 299v. All other bacterial counts, enzyme activities, short‐chain fatty acid concentrations, endotoxin concentration and pH remained unchanged.

Conclusions : L. plantarum 299v significantly increased the number of lactobacilli in the faecal flora within 1 week, and this effect disappeared within 1 week after cessation of intake. No other changes in bacterial counts and metabolic products were observed.
Dilated intercellular spaces as a marker of oesophageal damage: comparative results in gastro‐oesophageal reflux disease with or without bile reflux
Authors: Calabrese C. , Fabbri A. , Bortolotti M. , Cenacchi G. , Areni A. , Scialpi C. , Miglioli M. , Di Febo G.
Published: September 2003

Background : The dilation of oesophageal intercellular spaces, clearly apparent in transmission electron microscopy images, is a marker of cellular damage induced by acid.

Aim : To analyse the presence of dilated intercellular spaces and to quantify the scores in controls and in patients with gastro‐oesophageal reflux disease or duodenal gastro‐oesophageal reflux accompanied by erosive or non‐erosive reflux disease.

Methods : Thirty‐eight symptomatic patients with gastro‐oesophageal reflux disease or duodenal gastro‐oesophageal reflux and 12 asymptomatic controls, classified on the basis of pH‐metry and bilimetry, underwent endoscopy. Six tissue biopsies were taken from the normal mucosa for light microscopy and transmission electron microscopy evaluation. Dilated intercellular spaces were measured on photomicrographs of the specimens (at least 100 transects were measured for each patient).

Results : Twenty‐two patients with gastro‐oesophageal reflux disease had normal macroscopic mucosa but, at histology, five patients with erosive gastro‐oesophageal reflux disease had mild oesophagitis and one had moderate oesophagitis. Seven patients with duodenal gastro‐oesophageal reflux had normal mucosa, whilst three with erosive duodenal gastro‐oesophageal reflux had mild oesophagitis at histology. At transmission electron microscopy, all controls had dilated intercellular spaces of less than 1.69 µm. Each symptomatic patient had a mean dilated intercellular space value and a mean value of the maximum dilated intercellular space at least three or more times greater than that in controls (P < 0.001). No statistical differences were observed between erosive and non‐erosive oesophagitis.

Conclusions : The dilated intercellular space is an extremely sensitive marker of damage in gastro‐oesophageal reflux disease, duodenal gastro‐oesophageal reflux and non‐erosive reflux disease, and serves as the most appropriate marker of damage evaluation in non‐erosive reflux disease reported to date. A mean dilated intercellular space of 0.74 µm provides a cut‐off score for damage. No quantitative or qualitative differences in dilated intercellular space scores were found between pure and mixed acid reflux.
Guest Lecture  8.45–9.30 Monday 15 September 2003  Endocervical Adenocarcinoma and its Precursors
Authors: McCluggage W. G.
Published: September 2003

The incidence of malignant and pre‐malignant endocervical glandular lesions is increasing. Part of this is an apparent increase due to a reduction in the number of invasive cervical squamous carcinomas but there is evidence that there is a real increase in malignant and pre‐malignant endocervical glandular lesions. Different terminologies are in use in the UK where the term cervical glandular intraepithelial neoplasia (CGIN) is commonly used and the rest of the world where pre‐malignant lesions are classified as glandular dysplasia and adenocarcinoma in situ (AIS) (WHO classification). It is well established that high‐grade CGIN (AIS in WHO terminology) is a precursor lesion of cervical adenocarcinoma but it is controversial whether a recognizable precursor to high grade CGIN (namely low‐grade CGIN) exists and criteria for diagnosing this are poorly established and poorly reproducible. Most cases of CGIN are of usual or endocervical type but other morphological subtypes described include endometrioid, intestinal, tubal and stratified mucinous intraepithelial lesion (SMILE). The presence of skip lesions and lesions high up the endocervical canal has been overemphasised in CGIN with most cases occurring close to the transformation zone. Treatment is on an individualized basis but local excision with negative margins and close cytological follow‐up may be employed. There is evidence in the literature that early invasive adenocarcinomas behave in a similar fashion to early invasive squamous carcinomas and that, on selected occasions, conservative therapy can be safely undertaken. However, further studies are needed to ascertain the behaviour and natural history of early invasive cervical adenocarcinoma. In 10%–15% of cases it may be impossible to ascertain whether a malignant endocervical glandular lesion is invasive or in situ. There are many benign mimics of CGIN and adenocarcinoma, including tuboendometrial metaplasia (TEM), endometriosis and microglandular hyperplasia (MGH). Although careful morphological examination usually allows confident distinction of these lesions, a panel of immunohistochemical stains including MIB1, bcl2 and p16 may assist.
Proffered Papers  10.30–11.15 Monday 15 September 2003 5 Colposcopic excisional biopsies with normal histology. Is this a cytology problem?
Authors: Giles J. , Knowles S. , Cox S.
Published: September 2003

Introduction  Colposcopy Quality Standards state that more than 85% of excisional biopsies should show CIN 1 or worse. Data from the National KC65 reports show a large difference between units (50% to 100%). This study investigates the reasons for failure to meet the standard.

Methods  A review of 1158 consecutive new and 1043 follow‐up colposcopy examinations from a colposcopy database in East Somerset. Patients were treated at the time of initial examination if there was a clinically significant lesion, or at follow‐up depending on the results of investigations.

Results  Only 59% of excisional biopsies showed CIN 1 or worse. The possible reasons for failure to meet the standard were explored. Possible explanations explored are erroneous colposcopy, false negative histology, and false positive cytology. The cytology–histology correlation was compared between excisional and directed biopsies, and between the two local cytology screening departments.

Conclusions  The collection of meaningful national data has more to do with careful definition than clinical practice or data collection.
Proffered Papers  16.00–16.30 Monday 15 September 2003 6 Development of a multiplex PCR protocol for rapid screening of ThinPrep® cervical samples for HPV and Chlamydia trachomatis
Authors: Helen Keegan , Helen Lambkin , Alison Malkin , Mairead Griffin , Fergus Ryan
Published: September 2003

Human papillomaviruses and Chlamydia trachomatis are two of the most commonly found sexually transmitted infections in cervical Pap smears. They are often asymptomatic and if left untreated can progress to cause serious complications such as pre‐cancerous lesions and tubal factor infertility, respectively. The aim of this study was to develop a rapid multiplex PCR for the simultaneous detection of HPV and C. trachomatis in ThinPrep® liquid cytology samples. Two multiplexes were optimized. (A) For the detection of C. trachomatis using primers for the cryptic plasmid and for a chromosomal gene (Hsp60); (B) for the simultaneous detection of HPV and C. trachomatis using consensus primers for HPV and plasmid primers for C. trachomatis. Both multiplexes included a set of primers for a human housekeeping gene‐β‐globin. DNA from 34 ThinPrep® cervical samples was extracted using the QiAmp DNA Mini Kit (Qiagen Ltd, UK). All 34 samples were previously confirmed positive for C. trachomatis using another nucleic‐acid based test. Using multiplex A.for the detection of C. trachomatis, 33 of 34 samples were positive for C. trachomatis by either the plasmid or chromosomal gene primer set. All samples were positive for β‐globin. Ten of the 34 C. trachomatis positive samples were known positives for HPV. Using the combined HPV and C. trachomatis multiplex 10 of 10 were positive for both HPV and C. trachomatis. These simple multiplexes are cost‐effective, rapid and have potential for rapid screening of cervical ThinPrep samples simultaneously for both HPV and C. trachomatis.
Proffered Papers  16.00–16.30 Monday 15 September 2003 7 Papillomavirus testing using Hybrid capture II in a community‐based primary screening setting: preliminary results and potential clinical applications
Authors: Chana P. , Ktori E. , Nowicki M. , Best J. , Herbert A. , Kubba A. A.
Published: September 2003

Introduction  The aims of this study were (i) to assess the use of Hybrid‐capture II (HCII) alongside conventional cytology for triage of mildly abnormal smears and (ii) to establish the local prevalence of high‐risk human papillomavirus (HRHPV).

Study design  In an on‐going study, 669 women aged 20–50 were recruited into (i) a study group, with current abnormal cytology or a history of previous abnormal cytology and (ii) an anonymous control group with current negative cytology and no history of abnormal smears. HCII positive was used as a surrogate for mild dyskaryosis in women with negative smears in the study group.

Results  There was strong correlation between positive HCII tests with degree of cytological abnormality. HCII was positive in 13 of 13 (100%) of women with at least moderate dyskaryosis, 27 of 34 (79%) with mild dyskaryosis, 18 of 36 (50%) with borderline abnormalities, 36 of 250 (14%) of negative smears. In the control group, 50 of 308 (16%) of negative smears were positive. HCII was positive in four of 28 (14%) women with inadequate smears in both groups. HCII was positive at low levels (<10 RLU) in 3% of samples from both groups. No indication of clinical outcome is yet available and also further work is in progress to assess the significance of low‐level positive results. Overall, 148 of 669 (22%) of women were HCII positive.

Conclusion  HCII can be carried out alongside conventional cytology for the triage of women with mildly abnormal smears. The results suggest a role for HPV testing in re‐assuring women with a past history of abnormal cytology.
Proffered papers  14.00–15.00 Tuesday 16 September 2003 8 Ampullary, pancreatic and biliary duct exfoliative brush cytology prepared by the thinprep method: performance and morphology
Authors: Duggan Máire A. , Brasher Penny , Medlicott Shaun
Published: September 2003

Background  ERCP‐directed brush cytology is used to sample lesions of the pancreatic and biliary ducts and the ampulla of Vater. With conventional preparations, the sensitivity and specificity range from 44% to 63% and 80% to 98%, respectively, and increased N : C ratio, nuclear molding and loss of honeycombing are reliable features of malignancy. The performance and morphology of specimens prepared by ThinPrep, a liquid‐based cytology technique is mostly unknown.

Methods  The laboratory information system was searched for all cases prepared by ThinPrep. Patient disease classification of benign or malignant was determined by linkage with the provincial cancer registry and was the gold standard against which sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. True positives and negatives were reviewed to identify predictive cytomorphologic features.

Results  Between 1996 and 2001, there were 149 ThinPrep specimens; 55 (37%) were reported as positive for malignancy and 94 (63%) as negative. Disease was classified as malignant in 86 (58%) patients and benign in 63 (42%). There were 42 false negative, 11 false positive, 52 true negative, and 44 true positive cytology results. Sensitivity was 51.2% (CI; 40.2 : 62.0), specificity 82.5% (CI; 70.5 : 90.6), and PPV and NPV 80.0% (CI; 66.6 : 89) and 55.3% (CI; 44.7 : 65.5), respectively. Cell groups with crowded, enlarged, irregular nuclei and nuclear features of vesicular chromatin and large, multiple irregular nucleoli correlated with malignant disease, while monolayered sheets of uniform columnar cells, regular nuclei and a finely granular chromatin correlated with benign disease.

Conclusions  The performance of ThinPrep brushings from this anatomic site equals conventional preparations. Cytomorphologic features of malignancy are more frequent and pronounced with ThinPrep.
Proffered papers  14.00–15.00 Tuesday 16 September 2003 10 Multilingual image gallery and web‐based training for cytopathology
Authors: Schenck Ulrich , Seidl Stefan , Weirich Gregor , Schenck Ulrike
Published: September 2003

Aims  A multilingual image gallery on the web (http://zytologie.schenck.de) with user administration (free registration) has been offered since several years and reaches more than 2500 registrants. The aim of this study was to implement web‐based training (WBT) into the technical context of the image gallery with the purpose to offer structured information and monitor student activities and success.

Methods  The WBT platform was programmed externally in php‐script language in a linux software surrounding and is running on remote web servers. It has been implemented in a way that user administration of image gallery and WBT are closely linked. User, trainer and administrative access is via web browsers and optimized for use with Microsoft Internet Explorer 5.5+.

Results  Users, trainers and administrators have access (http://zytotraining.schenck.de) by their username and password which is identical with that for the image gallery. A symbol oriented navigation surface allows training in different languages according to the availability of teachers. Documents are integrated in various formats including html, ppt, pdf, word, jpg, excel. Links and tests with a variety of question types are implemented into training programs. Documents and tests may be shared by different courses. Administration takes care of user access and regulates trainer's rights. Trainers can rearrange the presentation or implement new information for free or supervised training. Model applications were the implementation of the proceedings of the 16. Munich postgraduate course of clinical cytology, medical student training at the Technical University of Munich and a course of lung cytology for the School of Cytotechnology in Munich.

Conclusions  The software has the essential components to offer continuing education. More trainings related to different fields of cytopathology will be integrated.
Proffered papers  14.00–15.00 Tuesday 16 September 2003 11 Galectin‐3 in thyroid nodules: a cytohistological correlation
Authors: Davies R. , Dina R.
Published: September 2003

Aim  To assess sensitivity and specificity of galectin‐3 to identify malignant lesions of thyroid in cytological specimens.

Methods  Fifteen FNA biopsies with a histological correlation out of 392 have been considered suitable for immunostaining with galectin‐3. Galectin‐3 (mouse monoclonal antibody supplied by Novocastra Laboratories Ltd, Newcastle‐upon‐Tyne) primary antibody solution was used at a concentration of 1 : 400. Immunostaining was assessed using a score from 0 to 3 considering 0–1, negative and 2–3, positive.

Results  Four cases were cytologically reported as malignant (27%), five as suspicious (33%), six as benign (40%). Histologically, six were follicular adenomas, two hyperplastic nodules, three papillary carcinomas, two follicular carcinomas and one was a medullary carcinoma.

Only in one case galectin‐3 immunostaining was positive in cytology, which resulted in histology to be a benign hyperplastic nodule. In histology, the galectin‐3 immunostaining was positive both in benign (three of nine) and malignant (three of six) nodules and negative in half of the carcinomas (three of six). Only in one case, galectin‐3 immunostaining was consistently positive both in cytology and histology (hyperplastic colloid nodule).

Conclusion  In our experience, galectin‐3 staining is poorly reproducible in cytological and histological samples and is of little help in the differential between malignant and benign lesions of the thyroid.

Galectin score on cytology
Cytological diagnosis
Galectin score on histology
Histological diagnosis

0
Follicular lesion
2
Benign hyperplasia nodule

0
Follicular neoplasm
1
Follicular adenoma

1
Papillary carcinoma
2
Papillary carcinoma

0
Follicular lesion
0
Follicular adenoma

0
Follicular lesion
0
Hyperplastic colloid nodule

0
Follicular lesion
2
Follicular adenoma

3
Atypical cells
2
Nodular hyperplasia

0
Follicular lesion
1
Follicular adenoma

0
No malignant cells
0
Follicular adenoma

3
Suspicious for malignancy
1
Follicular carcinoma

0
Follicular lesion
1
Follicular adenoma with papillary hyperplasia

0
Malignant cells? Papill. or med. carc.
0
Medullary carcinoma

0
Follicular lesion
3
Low grade minimal invasive follicular carcinoma

1
Papillary carcinoma
3
Papillary carcinoma

0
Suspicious for malignancy
0
Papillary carcinoma with Hurtle change
Posters. P1 A 2‐year audit of thyroid fine needle aspiration cytology
Authors: Cameron I. , Venkatraman L. , Anderson N.
Published: September 2003

Introduction  Fine needle aspiration (FNA) cytology of the thyroid is a well‐established test in the clinical work‐up of patients with solitary nodules of the thyroid. Thyroid FNA does however have limitations and audit of diagnostic performance is important.

Methods  The histopathology archives of the Royal Victoria Hospital were searched for all thyroid resections and the histopathological diagnosis was correlated with the pre‐operative cytological diagnosis, where available. Special emphasis was placed on the accuracy of tumour diagnosis.

Results  A total of 173 cases were identified during the 2‐year period, of these 93 had available pre‐operative FNA. A total of 57 tumours were identified. A small number (six of 57) of significant discrepancies were identified. These included a malignant lymphoma diagnosed as Hashimoto's thyroiditis, a metastasis which the FNA had suggested was a medullary carcinoma and an insular carcinoma diagnosed as medullary carcinoma on FNA. False positives included a colloid cyst diagnosed as suspicious of malignancy and a cytological diagnosis of papillary carcinoma not confirmed on histology.

Discussion  At present, the majority of thyroid FNAs in our clinics are performed by surgeons and material is not routinely available for immunocytochemistry. In spite of these limitations, there were few major discrepancies. These might be reduced if pathologist aspirators were able to perform FNAs and collect material for further studies, where necessary. This would allow identification of medullary carcinomas and malignant lymphomas.

Conclusion  FNA of thyroid lesions is a useful investigation in our clinical setting, however, some areas of potential for improvement have been identified.
Posters. P2 Randomized controlled trial of the adequacy of cytological sampling with the cervex brush and aylesbury spatula: results of long‐term follow‐up
Authors: Dey P. , Stocks S. J. , Collins S. , Desai M. , Wright Y. , Woodman C.
Published: September 2003

Introduction  A randomized controlled trial comparing the adequacy of cytological sampling using the Cervex brush and the Aylesbury spatula, published in 1996, revealed that the Cervex brush did not reduce the inadequate smear rate but smears were more likely to contain cytological abnormalities (odds ratio 1.19; P = 0.05). We report the long‐term follow‐up of women who had a normal smear during the trial.

Methods  The trial has been described elsewhere.1 Matching of trial and laboratory databases identified follow‐up smears taken before 31/12/2000 from women with a normal smear during the trial. The analysis was restricted to 66 centres using the laboratory during the follow‐up period when all were supplied with the Aylesbury spatula. The Kaplan–Meier method was used to estimate the cumulative risk of cytological abnormality following a normal smear. The difference between study arms was estimated using the hazards ratio (HR) derived from a Cox proportional hazards model adjusted for the cluster‐randomized design and controlling for centre type.

Results  A total of 7129 women had at least one follow‐up smear: 3716 were first sampled with the Cervex brush and 3413 with the Aylesbury spatula. There was no difference between study groups in the incidence of any cytological abnormality (HR 1.11; 95% CI 0.92–1.34) or of moderate dyskaryosis or worse (HR 1.02; 95% CI 0.70–1.49).

Conclusion  The excess of abnormal smears observed during the trial in women sampled with the Cervex brush is unlikely to be due to earlier detection, because the incidence of cytological abnormality following a normal smear was similar in the two study arms.
Posters. P3 North west non‐gynaecological cytology EQA pilot CD ROM scheme 2002–2003
Authors: Hales S. A. , Hamid B. N.
Published: September 2003

The 8th circulation of this scheme was preceded by a CD ROM circulation of selected digital images and presented as individual JPEG file images in a single folder on the CD ROM. The number of images per case ranged from three to eight. The delegates will have an opportunity to assess these themselves prior to uncovering the consensus diagnosis provided by the participants. Of the 76, 29 participants of the scheme provided a completed answer sheet for the image‐based circulation. To date, 19 have now also supplied answers on the actual slide circulation. The same diagnosis on image and slide circulation varied from 5/19 to 19/19 with a mode of 14/19. The case that provided the poorest correlation was because of a generalized undercall of suspicious in a case which achieved almost complete consensus on the slide circulation. It had been the most difficult to photograph. The case that provided the next poorest correlation 11/19 was the case that had the poorest consensus diagnosis on the slide circulation. The two cases that provided the best correlation 18/19 and 19/19 were two cases that provided 100% consensus diagnosis on the slide‐based circulation. Comments were received from 20 participants about the image circulation ranging from ‘great’ to ‘awful’ with the majority of 12 participants not happy for their diagnostic capability to be assessed on such images alone. Two stated that the CD was easier to use on their home computer than their NHS one. In conclusion an image circulation overcomes many of the inherent problems with a slide circulation for EQA purposes and can provide an overall 70% correlation with a slide circulation but a significant number of pathologists do not find this an acceptable method for EQA.
Posters. P4 Retrospective audit of smear and biopsy correlation
Authors: Akhtar Khalida , Curran G , Sheaff M , Baithun S
Published: September 2003

The computer files at Barts and the London NHS trust were examined for the calendar year 2002 and correlation was made between cytology reports and histological outcomes and the positive predictive values for both low‐ and high‐grade lesions were calculated. There were 1421 patients with abnormal cytology confirmed by histology. Of those, 717 were called high grade and 704 low grade on cytology alone. Comparison of the histology and cytology showed concordance in 581/717 (81%) in high grade and 566/704 (80%) for low grade. Therefore, the positive predicative value is above 80% for both groups. Further analysis of the mismatches for the 136 high‐grade cytology group found 24/136 normal, HPV 26/136 and CIN1 86/136. Further analysis of the 138 low‐grade cytology group shows that 50/138 high grade, 85/138 no CIN and 3/138 cervical carcinoma. We also examined the ethnic origin of the patients with abnormal biopsies and found the prevalence of disease to be lower in the Asian and Moslem population compared with the non‐Asian community. This study shows the value of cytology in predicting both low‐ and high‐grade cytology. Our positive predictive value for both the high‐ and low‐grade lesions is above 80%, which is well above the expected average set by the NHSCSP. Further work is ongoing to review both cytology and histology for the non‐matching cases and also to establish whether specialization in histological and cytological reporting demonstrates increase specificity in reporting.
Posters. P5 Comparison of cervical smears including HPV status in systemic lupus erythematosus patients compared with controls
Authors: McHenry M. , Cubie H. A. , Clarke R. , Bell A. L. , Anderson N.
Published: September 2003

Systemic lupus erythematosus (SLE) is an autoimmune multi‐system disease with a variable course and prognosis. Significant immunosuppressive therapy is occasionally required to control active disease. It remains uncertain from existing studies whether patients with SLE have an increased incidence of abnormality on cervical smears. Previous studies of abnormalities on cervical smears in SLE are flawed, mostly because of small size of the lupus cohort examined. In Nortern Ireland, we are particularly fortunate to have a stable population and a good regional pathology database, which records the cervical screening history for all women in the province. Due to other reports of genitourinary cancers developing in SLE patients with or without cytotoxic medication, we are currently reviewing our experience to date, to confirm if patients with SLE have an increased incidence of abnormality on cervical smears, and if so, if this is related to disease activity, pre‐disposition to infection or treatment, and to perform a real‐time cervical smear analysis of our SLE patients as well as HPV status. HPV infection is known to be a risk factor for cervical cancer. However any role with regard to SLE and cervical abnormality is yet to be defined. Lupus patients may be either immunosuppressed or suffer immune deficits as a result of disease and may be more prone to develop HPV infection. This research will be able to identify if the SLE population in NI have a different pattern of abnormality on cervical smears and if they have a different or more frequent prevalence of HPV. These changes if present can then be related directly to the disease, it's activity or treatment. Though this research is currently underway, sufficient results are currently not available for statistical analysis to be documented in this abstract, but will be by September for the BSCC.
Posters. P6 Infiltrating micropapillary carcinoma of the breast‐cytological and histological correlation in two cases with review of the literature
Authors: Ghataura S. S. , Chan S. Y.
Published: September 2003

Introduction  Invasive micropapillary carcinoma of the breast has been described as a specific entity over a decade ago. Histologically, it is characterized by a morular growth pattern with surrounding artefactual spaces and reverse polarity in the cellular architecture. It is a distinct entity in histology, but not in the cytology literature and only a handful of case reports describe the cytological features. However, it is an important diagnosis to make as these tumours behave aggressively with a high rate of lymphotropism and axillary lymph node metastases, as well as local chest wall recurrence.

Method  We describe two cases of invasive micropapillary carcinoma of the breast, one diagnosed initially on FNA with follow‐up histological confirmation, the other from a local chest wall recurrence, which was confirmed retrospectively after review of the initial histology.

Conclusion  The cytological features of invasive micropapillary carcinoma of the breast are unique and differ from other invasive and in situ carcinomas and should be recognized because of its aggressive behaviour.
Posters. P8 Repeat ThinPrep® filtrations for teaching and testing – a cautionary note for cytology trainers
Authors: Evered Andrew
Published: September 2003

The aim of this study was to challenge the assumption that reprocessing residual material from ThinPrep® vials to produce replicate sets of slides is a valid and reproducible means of producing cervical cytology slides for testing purposes. Twenty cervical ThinPrep® samples known to contain dyskaryotic cells were reprocessed six times on a ThinPrep 3000 processor. Cell counts were performed on each of the repeats. In 14 of the 20 cases examined, the number of abnormal cells retrieved varied by a factor of up to three in the repeat slides. Such variation may be unacceptable if the repeat slides are to be used to produce replicate test sets, particularly if the results of such tests are used to calculate screener sensitivity.
Posters. P9 A case of carcinosarcoma presenting in a cervical ThinPrep® sample
Authors: Evered Andrew
Published: September 2003

A case of carcinosarcoma of the female genital tract detected in a cervical ThinPrep® sample is presented. Cytology showed numerous pleomorphic cells with nuclear hyperchromasia and coarsened nuclear chromatin. Nucleoli were absent or inconspicuous. The cells presented as a dispersed population with only a few small groups. The background was relatively free of blood and necrotic debris, as would be expected in a ThinPrep® sample. A report of severe dyskaryosis ?invasive was given. The cervical biopsy showed the morphological appearances and immunohistochemical profile of a carcinosarcoma. Additional ThinPrep® slides were produced from the original vial and immunocytochemistry performed. The sarcomatous element of the tumour was clearly demonstrated with the appropriate markers. This case demonstrates that carcinosarcoma should be included in the differential diagnosis when malignant cells are identified in cervical samples. Immunocytochemical staining of residual ThinPrep® material is feasible and can be beneficial in the further characterization of tumour cells. To the author's knowledge, this is the first report of carcinosarcoma of the female genital tract detected in a ThinPrep® liquid‐based cervical sample.
Posters. P11 Positive predictive values for high and low‐grade cytological abnormalities as surrogates for specificity and sensitivity
Authors: Neda S. , Herbert A. , Blanks R. G. , Moss S. M.
Published: September 2003

Introduction  Positive predictive value (PPV), measuring the percentage of moderate dyskaryosis or worse confirmed as CIN2 or worse, is used as a measure of accuracy in cervical screening. However, it relates more to specificity than sensitivity because the denominator includes false positives rather than false negatives. Low values reflect over‐reporting of high‐grade dyskaryosis but high values may reflect under‐reporting. Sensitivity is impossible to measure from correlation of cytology with outcome because women with negative cytology are rarely referred for colposcopy. Rates of CIN3 resulting from referrals for low‐grade cytology may be used as a surrogate for sensitivity, as high values may reflect under‐reporting (ref).

Study design  Outcome of colposcopy referrals was monitored during a period of 4 years, using a fail‐safe database.

Results  PPV at Guy's & St Thomas rose from 54% in 1998/1999 to 69% in 2001/2002. The former was below the NHSCSP recommended range. During the same period of time CIN1 rates for moderate dyskaryosis fell from 37% to 24%, reflecting the main source of discrepancy. While specificity increased (as reflected by increasing PPV) sensitivity remained constant in that CIN3 rates for mild dyskaryosis and borderline remained below 6%: average rates in England have fallen over the last 3 years and were 7.4% in 2000/2001 (ref). CIN2 rates for mild dyskaryosis also remained constant at 11% to 12%.

Conclusion  Correlation of biopsy results with high‐ and low‐grade cytological abnormalities is a useful method of monitoring accuracy of cytology reporting, and can be used to measure over‐ and under‐reporting as surrogates for specificity and sensitivity.