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We aimed to test the hypothesis that patients with cervical intraepithelial neoplasia (CIN) III treated by large loop excision of the cervical transformation zone (LLETZ) are more likely to suffer recurrence of cervical abnormalities if the CIN reaches the margins of the index specimen. Three hundred and forty-five women treated by LLETZ in 1991, and 1992, and in whom the histological diagnosis was CIN III, were studied. The reports were reviewed and the cases were categorised as completely excised, incompletely excised, or undetermined. Cytological follow-up, or in some cases histological follow-up in the same year and in each of the 5 following years was tabulated. Follow-up data were recorded from the same and also surrounding institutions. The chi-squared test was used to compare the differences in recurrence rates between the three groups at the various points in time. A small advantage was demonstrated for those cases where excision was complete. This was statistically significant in the third following year (P=0.022). The resection margin status of LLETZ specimens for CIN III has only a minor effect on the likelihood of recurrence. Nevertheless, recording the status may be important in case of unexpected invasion. The relative reassurance the information will provide when the lesion has been excised may also be seen as worthwhile.

This paper describes the use of a questionnaire designed to enable students to comment on aspects of the teaching they received from their tutor during the preclinical course in Conservative Dentistry. The information was subsequently used by the teachers themselves, to modify their performance.

To assess the effect of echogenic foci in the fetal heart on the risk for Down's syndrome.Prospective evaluation of fetal echocardiograms at a fetal cardiology referral center and systematic postnatal follow-up. A relative risk was calculated from the prevalence of echogenic foci in fetuses subsequently demonstrated to have trisomy 21 divided by that in normal fetuses. For a subgroup of 548 fetuses with echogenic foci but otherwise normal detailed anomaly scans, the expected number of trisomy 21 fetuses calculated from maternal age risks was compared with the observed number to derive a relative risk for isolated echogenic foci.Echogenic foci occurred in 905 of 6904 fetuses scanned, but after excluding those referred specifically because of an echogenic focus and those with heart defects, the incidence was 9.5%. Overall, echogenic foci were more frequent in fetuses with trisomy 21 than those without by a factor of 2.93. For the 548 fetuses with echogenic foci but otherwise normal detailed anomaly scans, the actual number of trisomy 21 fetuses exceeded that expected on the basis of maternal age risks by a factor of 5.54. Combination with data from several previous studies suggests a consensus relative risk of about 3.0.Echogenic foci are associated with increased risk of trisomy 21 even when present as an isolated finding. Their significance in an individual should be interpreted in the light of prior risk assessment based on maternal age and results of any first-trimester screening tests. We suggest that the prior risk is increased by a factor of 3.0.

The authors estimated the prevalence of heart malformation during the first year of life, using five data sets with varying degrees of completeness from two English regional health authorities. These areas covered a total population of 6,872,000. Analysis was carried out using capture-recapture methods, including log-linear modeling, on data collected between June 1993 and August 1994. A large number of cases in the community were unrecorded by any of the current sources of information. In South East Thames, where an antenatal training screening program for detecting heart malformations had been implemented in the late 1980s, the estimated prevalence rate varied from 5.5 per 1,000 births (95% confidence interval (Cl): 3.5, 10.8) to 9.0 per 1,000 births (95% Cl: 6.4, 14.2), depending on the assumptions in the model and the number of sources used in the analysis. In the Wessex region, which did not have a formal training program, prevalence was lower and varied little, from 4.3 per 1,000 (95% Cl: 3.4, 6.0) to 5.1 per 1,000 (95% Cl: 4.0, 7.2), according to assumptions. These two estimates were reasonable rates in comparison with reports in the literature. This analysis was helpful in demonstrating that the training program designed to identify severe heart malformations during the antenatal period in one of these regions had no lasting impact on prevalence. Am J Epidemiol 1999;150:778-85. capture-recapture; heart defects, congenital; models, statistical; prevalence

The aim of the study was to assess levels of anxiety and depression in three groups: pregnant mothers referred to foetal cardiology, subdivided into those with a confirmed diagnosis and those for which no abnormality was detected, and mothers who had a child with a heart malformation. Psychological status was measured between 6 and 10 months after diagnosis using the Hospital Anxiety and Depression scale in 108 females. Levels of anxiety were higher in the two groups with a confirmed diagnosis in the antenatal period or after birth (62%) than in those who were screened positively but in whom no abnormality was found (30%) (p = 0.0055). Anxiety was the highest in young females who had a foetus with a heart malformation. Depression scores were higher in those who had a child with heart malformation (18%) than in the other two groups (5%). Mothers who terminated a pregnancy after diagnosis remained depressed long after the event. Younger mothers may be especially vulnerable to mood problems associated with a traumatic obstetric experience.

Previous histochemical studies have shown that changes occur in the composition of mucins both in preneoplastic and neoplastic lesions of the gastric mucosa. Since monoclonal antibodies are now available which recognize the protein product of distinct mucin genes, they are likely to provide useful tools for evaluating these changes. Thus, a monoclonal antibody 996/1 raised against a peptide epitope of the colonic mucin MUC2 was examined for its potential as a prognostic indicator in gastric cancer. 996/1 works well on formalin-fixed paraffin sections and shows good staining of the colonic goblet cells in the region of the golgi, while there is no staining of normal control gastric mucosa. The epitope was detected in all cases of intestinal metaplasia (44 samples) and some but not all cases of dysplasia (26 samples) and gastric carcinoma (74 samples). There was no significant difference between the positivity of the tumours according to their classification, stage and lymph node status. These results unfortunately gave little indication that this antibody would be a useful prognostic tool in gastric cancer. However, the pattern of 996/1 staining provides useful information about the molecular changes in mucin expression that occur in gastric carcinogenesis.

Observer variation in the grading of dysplasia in 100 colorectal adenomas has been analysed by kappa statistics. Intraobserver agreement was only 70% and 67% for the two principal observers, and, as would be expected, interobserver agreement was even lower at 59% and 66%. Although the kappa values were significantly different from chance at the 0.1% level, there were substantial disagreements. When the study was extended to four observers, agreement between observer pairings was considerably worse (as low as 34%), and in four pairings the kappa values did not differ significantly from those expected by chance alone even at the 5% level. In an endeavour to improve agreement we adopted a percentage estimation grading method; but this failed to achieve any improvement when comparing overall grades. The percentage estimates of the two observers, however, showed a highly significant correlation. To identify the cytological features given most weight by the principal observers in assessing dysplasia we undertook morphometry on 30 adenomas using an image analysis computer. The nuclear to cytoplasmic ratio, variation in nuclear area, and variation in nuclear height above the basement membrane showed significant differences between mild, moderate, and severely dysplastic epithelia. While evaluation of these parameters therefore appears to be most important in the subjective interpretation of dysplasia, this study has shown that such evaluation is poorly standardised between observers and poorly reproduced within observers. Our findings of poor agreement in the grading of dysplasia in colorectal adenomas has serious implications for the assessment of dysplasia in inflammatory bowel disease, where the added problem of reactive cellular atypia brings greater complexity to these subjective judgments.

The variation between two observers in grading 100 biopsies and the corresponding main specimens of rectal carcinomas has been examined. Using kappa statistics, which take account of chance agreement, we found a highly significant level of agreement. As expected, higher levels were obtained for intraobserver agreement. However, disagreements between observers were in many instances "haphazard" and there were differences in bias between them. Fifty paired biopsies and main tumours were graded by five observers and the results analysed for bias and by kappa statistics for overall and conditional agreement. These methods revealed significant overall agreement but the levels for some observer pairs did not differ significantly from chance. Examination for observer bias indicated differing standards of grading, and haphazard disagreements reached high levels for some observer pairs. The intraobserver agreement between the grade of the biopsy and the corresponding main tumour varied from 56-69% but only 52% of the poorly differentiated tumours were diagnosed as such in the preoperative biopsy by the "specialist" observer. The poor predictive value was not improved by taking multiple biopsies. We conclude that the grade of a rectal carcinoma cannot be accurately assessed on a preoperative biopsy and that this has serious implications for the management of low rectal cancers. Furthermore the wide discrepancies in diagnostic standards between some pathologists mean that studies on the treatment and prognosis of rectal cancer which utilise histological grade for comparison purposes must be viewed with considerable skepticism.

Six histopathologists allocated 100 sections from patients with long-standing ulcerative colitis into four diagnostic categories, regular hyperplasia, reactive atypia, low-grade and high-grade dysplasia. Their allocations were analysed using kappa statistics, including Fleiss's multiple kappa for groups of observers, and agreement on specific diagnoses was explored by constructing a conditional probability matrix. The nature of their disagreements was investigated using coefficients for systematic and haphazard errors. Over the four diagnostic categories there was a wide range of pairwise agreement from a low of 49% up to 72% and kappa values were only ‘fair’ or ‘moderate’. As expected, agreement over the two categories ‘dysplasia’vs‘no dysplasia’ was better, ranging from 68% to 84%, and for ‘atypia present’ (reactive atypia, low- and high-grade dysplasia) vs‘no atypia’ two pairings achieved over 90% and 11 pairings over 80% agreement. In view of its clinical importance, conditional agreement on high-grade dysplasia was examined. Given that a first observer allocates a case as high-grade dysplasia, pairwise agreement on this diagnosis ranged from 100% down to as low as 33%. However, most of these disagreements fell into the low-grade dysplasia category so that closer follow-up and further biopsies would still have been indicated. It is a truism that the basis for safe management is careful co-operation between clinicians and pathologists who have all the relevant facts and who know and trust one another's judgement. Thus, several aspects of the ideal diagnostic process cannot be evaluated in inter-observer studies and the element of artificiality should be borne in mind when applying the findings to diagnostic practice. Nevertheless, the low level of agreement on the diagnosis of high-grade dysplasia achieved by certain pairings of specialist pathologists is a disturbing outcome of this study. Inaccuracies should be minimized by a concensus approach and we therefore recommend referral of putative cases of dysplasia to interested pathologists for further opinions. We would also advocate that pathologists faced with appearances which are indefinite between reactive atypia and dysplasia, would do better to describe them in terms of ‘atypia, significance uncertain’, so that closer surveillance is undertaken, rather than force them into more precise diagnostic categories which may be incorrect.

The Second National Morbidity Survey, conducted in England and Wales between 1970 and 1976, contains a unique body of information on episodes of mental illness experienced by individuals registered in a representative sample of general practices around the country. This information is used to construct the episode distribution among the individuals surveyed. The Poisson and negative binomial distributions are then used to model the episodes. The Poisson model gives a very poor fit but the negative binomial model is found to fit the data very well. Deviations of the observed data from this model are discussed. The possibility of applying this model at the local practice level is then considered.