bluuebunny/crossref_metadata_2025_split huggingface dataset:
The diagnosis of polycystic ovary syndrome: the criteria are insufficiently robust for clinical research
Authors: Barth Julian H. , Yasmin Ephia , Balen Adam H. 
Published: September 2007

SummaryPolycystic ovary syndrome (PCOS) is a common disorder but has considerable phenotypic variability and this has led to controversy over its exact definition and diagnosis. The objective of this study was to review the recently proposed diagnostic criteria to determine whether they were sufficiently robust for clinical and research practise. We have reviewed the literature pertaining to clinical measurement and quality of laboratory analysis in relation to clinical and biochemical hyperandrogenism. The recently published statements regarding the diagnosis of PCOS assume that the clinical, laboratory and imaging studies are dichotomous variables, without considering the effect of observer subjectivity or measurement variability on the outcome. The data suggest that there is considerable uncertainty of all measurements and lack of clarity of the definition of the term ‘hyperandrogenaemia’ which can lead to misdiagnosis. The current diagnostic strategies for PCOS are defined too vaguely to ascertain that individuals fit the definition of the syndrome. A pragmatic approach may be taken in the management of an individual depending upon her particular symptoms and needs. However, research into the epidemiology, pathophysiology and treatment of PCOS will require the production of robust definitions of the diagnostic criteria. We propose specific criteria that would answer the criticisms that we have raised.
Unravelling the phenotypic map of polycystic ovary syndrome (PCOS): a prospective study of 634 women with PCOS
Authors: Diamanti‐Kandarakis Evanthia , Panidis Dimitrios 
Published: September 2007

SummaryBackground  The phenotypic spectrum of PCOS has been broadened but the prevalence and clinical significance of PCOS phenotypes continue to challenge the scientific community.Objective  Analysis of the phenotypic spectrum of PCOS and determination of the association between metabolic, hormonal and new ultrasonographic criteria.Design  Clinical prospective study.Patients  Six hundred and thirty‐four women with PCOS (18–35 years) and comparable body mass index (BMI), diagnosed by ESHRE/ASRM criteria, were categorized into two major groups of phenotypes: classic (NIH) and nonclassic (ESHRE/ASRM), and then subdivided into phenotypes with all possible combinations of diagnostic characteristics. One hundred and eight healthy women of reproductive age, matched for BMI, were recruited as the control group.Measurements  Ultrasonographic (ovarian follicle number and volume), hormonal and metabolic parameters.Results  Classic PCOS phenotype was more frequent (85·96%) than the nonclassic phenotype (14·04%). The patients were also classified according to the presence of biochemical (80·60%) or clinical hyperandrogenaemia (12·62%), and, in the newly introduced group, to absence of evidence of hyperandrogenaemia (6·78%). Subjects with classic PCOS with biochemical hyperandrogenaemia (74·76%) were more insulin resistant than controls. In women with PCOS, follicle number was positively related to both insulin resistance and biochemical hyperandrogenaemia. Additionally, women with PCOS had a 6·58‐fold increased relative risk (RR) of > 12 follicles on intravaginal ultrasound and a 2·94‐fold increased RR of ovarian volume > 10 cm3 compared to controls.Conclusion  The most frequent PCOS phenotype is the subgroup with biochemical hyperandrogenaemia only within the classic phenotype, which is more insulin resistant than the control group. The follicle number, a newly introduced ultrasonographic marker, is related to both metabolic and hormonal features of PCOS.
Concentrations of the acute phase reactants high‐sensitive C‐reactive protein and YKL‐40 and of interleukin‐6 before and after treatment in patients with acromegaly and growth hormone deficiency
Authors: Andreassen Mikkel , Vestergaard Henrik , Kristensen Lars Østergaard 
Published: September 2007

SummaryBackground  Acromegaly is accompanied by increased cardiovascular mortality and a cluster of proatherogenic risk factors. In the general population, ischaemic heart disease (IHD) is associated with elevated levels of inflammatory markers. The acute phase reactant (APR) C‐reactive protein (CRP) has been reported to be reduced in acromegaly and increase after treatment, suggesting that excess of GH/IGF‐I could have anti‐inflammatory effects. This is in accordance with results obtained in patients with growth hormone deficiency (GHD), where increased levels of CRP have been reported.Objective To investigate the hypothesis that the GH/IGF‐I system is a suppressive regulator of inflammatory processes.Subjects and methods  Twenty‐one acromegalic patients and 19 GH‐deficient patients were studied. The two APRs CRP and YKL‐40 and the proinflammatory cytokine interleukin‐6 (IL‐6) were measured before and after treatment and in healthy matched controls.Results  In acromegalic patients, serum concentrations of high‐sensitive CRP (hsCRP) and YKL‐40 were reduced compared to controls (P < 0·001) and increased (P < 0·001) after treatment, together with IL‐6 (P = 0·021), to levels comparable with controls. Pretreatment serum YKL‐40 and IL‐6 showed a significant inverse correlation with IGF‐I and GH. In GH‐deficient patients, hsCRP and YKL‐40 were elevated compared to controls (P = 0·001 and P = 0·048). During treatment, levels of both APRs showed a trend towards a decrease (P = 0·087 and P = 0·060), and after treatment, levels of YKL‐40 no longer differed from that of controls. Serum IL‐6 was not different from controls and did not change during GH treatment.Conclusion  The results point to the possibility of a relationship between GH disturbances and inflammatory processes.
Pregnancy outcomes following cabergoline treatment: extended results from a 12‐year observational study
Authors: Colao Annamaria , Abs Roger , Bárcena David González , Chanson Philippe , Paulus Wolfgang , Kleinberg David L. 
Published: September 2007

SummaryObjective  Cabergoline is a dopamine agonist used to treat hyperprolactinaemia. Because hyperprolactinaemia is a significant cause of infertility in women, cabergoline and other dopamine agonists are frequently prescribed to reduce prolactin levels and restore normal menses. They are usually discontinued shortly after the patient becomes pregnant. Although cabergoline has been used to treat hyperprolactinaemia since the mid‐1990s, safety data related to maternal and foetal exposure to this agent are still limited.Design  The current prospective, observational study reports on a total of 380 pregnancies. This extends by 154 pregnancies the results of a previously published interim report on the outcomes of 226 pregnancies in women treated with cabergoline up to 1994.Main outcome measures  Outcomes examined include the incidence of abortions and premature delivery and the number and types of foetal malformations or abnormalities.Results  Follow‐up data were available for 329 pregnancies, including 258 (78%) deliveries and 71 (22%) abortions. Of the 71 reported abortions, 31 (44%) were voluntary, 30 (42%) were spontaneous miscarriages, and nine (13%) were therapeutic. Of the 258 deliveries, 250 (97%) were live deliveries, four (2%) were stillbirths, and the status of delivery was unknown for the remaining four (2%). Of the 250 live deliveries, 193 (77%) were term deliveries (gestational period > 37 weeks), 45 (18%) were preterm deliveries (gestational period ≤ 37 weeks), and 62% of the infants had normal birthweights (i.e. 3–4 kg). Neonatal abnormalities were recorded for 23 (9%) of the infants with no apparent pattern in type or severity.Conclusion  The results of this study suggest that foetal exposure to cabergoline through early pregnancy does not induce any increase in the risk of miscarriage or foetal malformation.
Effect of the combination of the variants –75G/A APOA1 and Trp64Arg ADRB3 on the risk of type 2 diabetes (DM2)
Authors: Morcillo Sonsoles , Cardona Fernando , Rojo‐Martínez Gemma , Almaraz M Cruz , Esteva Isabel , Ruiz‐De‐Adana María Soledad , Olveira Gabriel , García‐Fuentes Eduardo , Gómez‐Zumaquero Juan Miguel , Soriguer Federico 
Published: September 2007

SummaryObjective  Numerous genes have been associated with the risk for type 2 diabetes mellitus (DM2). In an attempt to understand how specific variants of different genes interact and intervene in the molecular and physiological mechanisms of disorders such as diabetes or insulin resistance, the search for gene–gene interactions is constantly growing. We searched for a possible interaction between two polymorphisms (Trp64Arg of ADRB3 gene and –75G/A of APOA1gene) and the risk for DM2 in a population from southern Spain.Design and methods  A cross‐sectional study in southern Spain of 1020 people, aged 18–65 years. All persons underwent a clinical, anthropometrical and biochemical evaluation, including an oral glucose tolerance test (OGTT). Insulin resistance was measured by homeostasis model of assessment (HOMA). The polymorphisms –75G/A of APOA1 and Trp64Arg of ADRB3 were detected by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and real‐time PCR, respectively.Results  The genotype frequencies of the –75G/A polymorphism of the APOA1 gene were 62·7% GG, 25·7% GA and 11·6% AA, whereas for the Trp64Arg polymorphism of the ADRB3 gene, they were 87·5% Trp/Trp, 11·7% Trp/Arg and 0·8% Arg/Arg. Subjects with both gene variants had a greater odds ratio (OR) of having DM2 [OR = 5·5; 95% confidence interval (CI) = 1·2–23·5] than persons with one or none of the variants, after adjusting for age, sex, body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA‐IR).Conclusions  Joint association of allele –75A (APOA1) and allele Arg64 (ADRB3) increase the risk of DM2 in a population from southern Spain.
Transbronchial needle aspiration in the diagnosis of malignant and benign pulmonary disease
Authors: Linnane S. J. 
Published: September 2007

Transbronchial needle aspiration (TBNA) is a useful adjunct to bronchoscopic airway sampling. A 21 or 19 gauge needle is past down the bronchoscope and through the airway wall into the target regions. Material is aspirated into the needle core for cytological analysis.Exophytic endobronchial tumours, submucosal disease or extra luminal peribronchial tissue such as mediastinal lymphnodes can be sampled. The technique is useful for the diagnosis in particular malignant but also benign pulmonary disease. It also has a useful role in the staging of malignant disease.Health economic analysis have demonstrated the relative cheap cost of implementing this service with significant savings in bed days by patients who can avoid mediastinoscopy or other invasive tissue sampling.Repeated surveys in Europe and North America have consistently demonstrated that this technique is under utilized. The exact reasons for this are unclear but probably include the fact that the procedure must be done blindly and that initial yields are often disappointing.With adequate training and preparation a diagnostic yield of 40%–80% is reported in the literature. A number of factors affect performance; these include operative skill, pre‐text probability of malignancy, size of the target lesion and availability of rapid onsite cytological evaluation (ROSE).The most significant recent development has been the introduction of real time endobronchial ultrasound. This allows the placement of a cytological analysis needle within the target lesion under direct vision. While this innovation is associated with increased cost it is significantly increased sensitivity and is likely to see the more widespread application of TBNA as a diagnostic tool.The optimum integration of TBNA services with PET evaluation of malignant mediastinal lesions remains to be evaluated.
CPA assessment – the regional assessors’ experience
Authors: Guthrie G. 
Published: September 2007

With the introduction in January 2006 of the new posts of Regional Assessors, the process and focus of CPA assessment changed to reflect the inclusion in the current standards of Quality Management systems and processes.Regional Assessors, trained in Quality Management Systems and their assessment against international standards, now form a vital part of the CPA assessment teams, looking specifically at this aspect of laboratory service provision. Their role in the new assessment process will be explained.The presentation will cover differences and similarities in the nature and number of non‐compliances experienced since April 2006 when the new format of assessment was introduced. It will also look at a new format of timetable for assessment visits and explain the benefits of good two‐way communication between all parties involved in the process ‐ the laboratory, the assessors, particularly the Regional Assessor assigned to that site, and CPA Office staff.Understanding what is required by the standards, particularly in terms of evidential material, their interpretation and their classification of status – Critical, Non‐Critical or Observation ‐ is an aspect of assessment which is often not well understood. The presentation will seek to clarify these issues.The successful and timely clearance by laboratories of any non‐compliances raised during the visits is vital to the achievement of accredited status and the presentation will give guidance as to how this is best achieved.The current standards, based on the international ISO 15189 standards, are considerably more challenging than the old ones. There is now a significant emphasis on Quality Management and its understanding, ethos and implementation within the laboratory, a key element which underpins all aspects of a laboratory's service. The achievement of accredited status assures our users of␣the type of client and patient focused service expected of a modern laboratory.
Cervical screening policies 2008 and beyond
Authors: Winder R. 
Published: September 2007

There are many developments in cytology and in the NHS that will impact on the NHS Cervical Screening Programme over the next few years. In the short term HPV is a major issue, whether triage, primary screening or vaccination with further evidence coming forward from NHS early implementers and from research trials. Cytology automation is also already being trialled for the UK.So far as NHS developments go, we already have the two Carter reports, one on pathology modernisation and one on commissioning are both likely to impact on our service, as is the forthcoming Cancer Reform Strategy which should be out in a few months time. This will set out a blue print for cancer services in 2012, by which time the cervical screening programme could have a very different shape.
HPV trials update
Authors: Arbyn M. 
Published: September 2007

Background: More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods.Methods: A summary is given from recently published meta‐analyses on three possible clinical applications of HPV DNA testing: triage of women with equivocal or low‐grade cytological abnormalities; prediction of the therapeutic outcome after treatment of CIN lesions, and last not but not least, primary screening for cervical cancer and pre‐cancer.Results: Consistent evidence is available indicating thatHPV‐triage with the Hybrid Capture‐2 assay (HC2) is more accurate (significantly higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. When triaging women with LSIL, a reflex HC2 test shows a not significantly higher sensitivity, but a substantially and significantly lower specificity compared to a repeat Pap smear. After conservative treatment of cervical lesions, HPV testing picks up more quickly, with higher sensitivity and not lower specificity residual or recurrent CIN than follow‐up cytology. Primary screening with HC2 generally detects 23% (95% CI: 13%–23%) more CIN2+ compared to cytology at the lowest cutoff ASCUS or LSIL, but is 6% (95% CI: 4%–8%) less specific. By combined HPV and cytology screening a further 4% (95% CI: 3%–5%) more CIN3 lesions can be identified but at the expense of a 7% (95% CI: 5%–9%) loss in specificity, in comparison with isolated HC2 screening.Conclusions: Sufficient evidence exists to recommend HPV testing in triage of women with atypical cytology and in surveillance after treatment of CIN lesions. In the United States, recently reviewed knowledge has resulted in the approval of combined cytology and HC2 primary screening in women older than 30 years. However, in Europe, cytology‐based screening still remains the standard screening method. The European screening policy will be reviewed based on the results of randomized population trials which are currently underway.
Erica Wachtel Lecture of Mice & Women
Authors: Williams D. 
Published: September 2007

Diagnostic cytology of the female genital tract was introduced almost simultaneously by Aurel Babes in Bucharest, and George Papanicolaou in New York, in 1928. However, neither of these seminal observations made any immediate major clinical impact, and it was not until Papanicolaou and Traut's later published works on uterine cancer detection in the 1940’s, that any momentum was really gained.George Papanicolaou was neither a pathologist nor a gynaecologist. He was an anatomist, and the original Pap smear was designed to assess the hormonal status of mice. However, womankind eventually somehow replaced the mice, and modern exfoliative cytology was born, and the face of cervical cancer management was changed forever.My talk will be scroll through the history of cervical cancer prevention in Britain from 1960 until now, and will be based for the most part on my personal experiences and observations of 36 years before the mast in the Department of Gynaecology and Obstetrics at Birmingham University, and my brushes with some of the past and present Pioneers of the cytology screening programme in the UK, especially in those early years.
O‐2 Preliminary results of the ARTISTIC study: a randomised trial in screening to improve cytology
Authors: Almonte M. , Kitchener H. , Desai M. , Sargent A. , Bailey A. , Turner A. , Thomson C. , Julian P. 
Published: September 2007

Introduction:  The ARTISTIC trial was set up within the NHS Cervical Screening Programme in Greater Manchester to evaluate the effectiveness of human papillomavirus (HPV) testing in primary cervical screening. Here we present preliminary final results.Methods:  24 510 women aged 25–64 were enrolled in the study after consenting to be tested for high‐risk human papillomavirus infection (HR–HPV) in addition to liquid‐based cytology. Participants were randomised to HPV revealed or HPV concealed results arms in a 3:1 ratio. HPV testing was carried out using the Hybrid Capture‐II test (HC‐II) and all HC‐II positive samples were genotyped using the Roche line blot assay (LBA). Those in the revealed arm who had negative cytology and were HPV positive at entry were recalled every other 12 months for repeated HPV tests.Results:  1675 women showed no abnormality on cytology and tested positive for HPV at entry. At the time of analysis, 1200 (72%) of them had returned for a second HC‐II test. The overall HR‐HPV persistence rate by HC‐II was 43% in women who were retested less than 6 months after a positive entry sample, 40% between 16–24 months and 29% after more than 24 months. The prevalence of infections with HPV16 and HPV18 were 15%, and 7% at entry, and 38% and 32% of these infections were persistent at second screening. Among women with negative cytology and HPV positive test at entry, there were 1 and 12 cases of CIN3+ at the second visit and six and nine at exit in the concealed and revealed arm respectively.Discussion:  These preliminary data suggests that the combination of liquid‐based cytology with additional HPV testing over two screening rounds is not more sensitive than cytology alone.
O‐3 Assessment of the tripath focal point™ slide profiler as a quality assurance tool within the cervical screening programme in wales
Authors: Rose B. , Nuttall D. , Beer H. , Seager V. , Savage A. 
Published: September 2007

The use of computer assisted screening (CAS) in cervical screening is established in the USA and Europe and is currently undergoing trials in the UK (HTA). Following the introduction of SurePath™ LBC technology to Wales, Cervical Screening Wales (CSW) has implemented a study into applications of CAS within the CSP in Wales, agreed during LBC procurement negotiations. Technological support was provided by TriPath Europe and Medical Solutions UK Ltd. Evaluation centred on the use of CAS in Quality Assurance procedures, comparing it with rapid screening (review and preview), as HTA studies are already established to assess the primary screening role.Assessment included• Evaluation of CAS across a laboratory network – assessing sample identification, tracking processes and transportation• Assessment of Quintile Ranking verses abnormality distribution• Assessment of the NFR (no further review) category as a reliable indicator of sample negativity• Monitoring screener performance using CAS: Focal Point/LGS has the capability to monitor operator/observer functionsThree laboratories in North Wales participated in the study. Slides were scanned centrally using Focal Point LGS and returned to laboratories for assessment.Slide assessment followed a twin track protocol.• The ‘manual’ arm assessed slides according to standard laboratory procedures• The ‘CAS’ arm assessed slides using location guidance and screeningData were collected and analysed by CSW. Approximately 12 000 samples were scanned; results were compared for both arms.Results show that the technology has a number of benefits, in supporting and enhancing performance within the screening programme.• CAS compares favourably with rapid screening• Quintile ranking data reflects the distribution of abnormalities• The technology is well suited to shared use through laboratory networks• Variations in screener aptitude were noted.
O‐6 Preliminary results from the CPA funded virtual microscope pilot of the north west non gynaecological cytology EQA scheme
Authors: Hales S. A. 
Published: September 2007

Circulation E of the North West non gynaecological cytology EQA scheme was split into two with one half receiving conventional glass slides and the other half receiving digital images supplied by the SlidePath company over the web. More of the participants eligible participated in the slide half (43/65) than the digital half (17/41).Similar results were obtained for seven out of ten of the scoring cases and for both the educational cases. However for one case eight of the digital participants could not obtain the images over the web. In the remaining three scoring cases the digital participants were less good at obtaining the correct answer compared to the slide based participants. The use of this virtual microscopy has shortened the circulation length considerably. The digital participants complained about the speed the digital slides appeared on their computers and whilst most agreed that this is the way forward they are still uncomfortable with their performance being marked on their digital submissions. Delegates will have the opportunity of viewing still images taken for each case from this circulation.