Cancer screening: protecting the public's health.
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Female↗
Biomedical subjects
H Mitchell
Publications and source records attributed to H Mitchell.
Cervical cytology reported as negative and risk of adenocarcinoma of the cervix: no strong evidence of benefit.
The relationship between negative cervical cytology reports and risk of adenocarcinoma of the cervix was evaluated in a case-control study of 113 cases and 452 controls. All cases and controls had received at least two negative cytology reports. There was no significant difference between the cases and controls in the number of negative cytology reports or in history of cervical abnormality; while a test for trend in the time since last negative cytology report was significant (P < 0.001), the estimated benefit was very modest. Although the estimates of relative protection were higher in women aged less than 35 years than in women aged 35-69 years, this difference was not statistically significant. These results suggest that cervical screening as practised in the 1970s and 1980s was much less effective in preventing adenocarcinoma than squamous carcinoma of the cervix.
Adenocarcinoma↗
Differences between Papanicolaou smears with correct and incorrect diagnoses.
A case control study of women with carcinoma in situ (CINIII) was undertaken comparing Papanicolaou smears for which false negative reports had been issued with slides for which true positive reports had been made. The number of abnormal cells was the strongest differentiating factor. Where there were less than 50 abnormal cells on the slide, the odds of a false negative report being issued was 23.7 times greater (95% confidence interval 3.7-150) than when there were 200 or more abnormal cells. In false negative slides, the abnormal cells were likely to be not represented throughout the slide, present only as single cells rather than as groups, small in size and with finely granular normochromatic nuclei. We conclude that there are intrinsic differences between true positive and false negative slides. Given these characteristics, rapid rescreening of slides that are considered negative may not be an effective method of reducing the false negative rate.
Adolescent↗
The endocervical component of Pap smears.
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Adult↗
Structure of the human gene encoding the associated microfibrillar protein (MFAP1) and localization to chromosome 15q15-q21.
Microfibrils with a diameter of 10-12 nm, found either in association with elastin or independently, are an important component of the extracellular matrix of many tissues. To extend our understanding of the proteins composing these microfibrils, the cDNA and gene encoding the human associated microfibril protein (MFAP1) have been cloned and characterized. The coding portion is contained in 9 exons, and the sequence is very homologous to the previously described chick cDNA, but does not appear to share homology or domain motifs with any other known protein. Interestingly, the gene has been localized to chromosome 15q15-q21 by somatic hybrid cell and chromosome in situ analyses. This is the same chromosomal region to which the fibrillin gene, FBN1, known to be defective in the Marfan syndrome, has been mapped. MFAP1 is a candidate gene for heritable diseases affecting microfibrils.
Amino Acid Sequence↗
An evaluation of cervical screening in general practice.
OBJECTIVES: To identify the technical practices of general practitioners (GPs) in relation to Papanicolaou (Pap) smear screening, and the differences in screening practices between male and female practitioners; to determine the cellular content of smears taken; and to correlate screening practices and demographic variables with smear results. DESIGN: During February-May 1992, a sample of Melbourne GPs filled in a questionnaire concerning their screening practices, and the results were correlated retrospectively with results of Pap smears taken in March and October 1991. SETTING: Melbourne metropolitan general practice. PARTICIPANTS: One hundred and seventy-nine GPs (72% participation rate among eligible practitioners) from a sample obtained from the register of the Medical Board of Victoria. RESULTS: Female doctors took significantly more smears than male doctors. An opportunistic approach to cervical screening was most commonly practised, with the patient being asked to ring for her results and the practice staff only contacted her if the result was abnormal. Only 43% of doctors indicated the use of a specific reminder system when rescreening was due. Endocervical cells were present in 79% of smears. The presence of endocervical cells was found to be related to the year of a doctor's graduation (with both very recent and older graduates [pre-1960s] having lower endocervical cell rates), and to be positively correlated with more postgraduate training. CONCLUSIONS: Our study suggests that further education and training in cervical screening is needed for some GPs, in particular, male doctors, graduates of less than four or greater than 20 years, and those without postgraduate training.
Adult↗
Capsaicin-sensitive stretch responses in ferret trachealis muscle.
1. Stretch-induced electrical and mechanical responses in segments of ferret trachealis muscle were studied. Stretches and post-stretch length changes were quantified by measuring distances between two marker spheres placed on the muscle surface. Electrical responses were determined by measuring membrane potential in the muscle cell syncytium. 2. Smooth muscle mechanical and electrical responses to the stretch manoeuvre were characterized by an initial shortening and depolarization phase and a reversal-repolarization phase. Both phases were resistant to atropine and tetrodotoxin. During the initial phase, the membrane depolarized to potentials as low as -20 mV. For stretches to 1.0 Lmax, from a holding length of 0.75 Lmax, 50% repolarization occurred at 6.8 +/- 0.4 min post-stretch; 50% reversal of shortening of the stretched segment occurred at 6.9 +/- 0.8 min post-stretch. 3. Depolarizing currents generated within muscle cells in the stretched segment spread into cells in non-stretched muscle. Space constants in the transverse and longitudinal directions averaged 480 +/- 46 and 146 +/- 50 microns, respectively. 4. During infusion of capsaicin (10 microM), muscle cells depolarized by 5.5 +/- 2.3 mV. Maximal depolarization was achieved after 15-20 min. After inhibition of neutral enkephalinase, capsaicin-evoked depolarization occurred more rapidly. Muscles depolarized by 11.2 +/- 2.1 mV after about 10 min of capsaicin and then slowly repolarized during continued treatment. When muscle segments were stretched during administration of capsaicin, the initial phase was similar to that observed before capsaicin, but the reversal-repolarization phase was prolonged. Following wash exposure to capsaicin, maximal stretch-induced depolarization was unchanged, but the time for 50% repolarization (t50-repolarization) decreased from the pre-capsaicin value of 8.4 +/- 1.3 to 4.1 +/- 0.5 min. The t50-reversal of stretch-evoked muscle shortening decreased to 54% of control values. 5. Short exposures (< 2 min) to substance P (SP, 1-7.5 microM) depolarized smooth muscle cells. Maximal depolarization was delayed, and occurred after [SP] had decreased to < 10 nM. Repolarization was delayed as long as 6 min following wash-out of SP. Stretches performed when SP-induced depolarization had nearly reversed showed no changes in the initial mechanical or electrical responses, but t50-repolarization increased to 162% of control values. 6. Immunochemical studies showed networks of neurones which react with SP antibodies. 7. These findings suggest that stretch induces SP release from capsaicin-sensitive C fibres, and that released SP affects smooth muscle ionic mechanisms which control and delay the reversal of stretch-induced membrane depolarization and shortening.
Animals↗
Recent negative cytology prior to histologically confirmed carcinoma in situ of the cervix.
Women with histologically confirmed carcinoma in situ of the cervix were studied within the records of the Victorian Cervical Cytology Registry. The prevalence of histologically confirmed carcinoma in situ during 1992 was 2.67 per 1,000 women screened. Thirty per cent (401 of 1,327) of the women with carcinoma in situ had negative cervical cytology reported during the 2 years prior to the diagnosis of carcinoma in situ and at least 49% (648 of 1,327) had negative cytology during the preceding 5 years. Adenocarcinoma in situ comprised 3.4% of all cases; these women were significantly older and more likely to have had a recent negative smear report than women with squamous carcinoma in situ. Fifty-five per cent of the women with squamous carcinoma in situ had HPV reported on the biopsy compared with only 27% of the women with adenocarcinoma in situ. Ten per cent of the women with carcinoma in situ had a past history of cytological or histological abnormality; this proportion did not vary by type of carcinoma in situ. This relatively high proportion of negative cytology in close proximity to a diagnosis of carcinoma in situ is to be expected if there is active treatment of lesser lesions and frequent screening of members of the community.
Adenocarcinoma↗
Healing hands.
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Complementary Therapies↗
Improving consistency in cervical cytology reporting.
BACKGROUND: During the 1970s, the Papanicolaou method of classifying cervical cytology specimens and reporting diagnoses was replaced by more descriptive reporting systems. The plethora of reporting terms caused much confusion and a lack of standardization. To improve this situation, "The Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses" was approved at a National Cancer Institute Workshop in 1988. In Australia, the Victorian Cervical Cytology Registry (VCCR) was established in 1989. Because of the absence of a standard format for reporting cervical cytology in that country, a coding schedule was developed by local cytopathologists. While the pattern of reporting smear diagnoses was found to be reasonably consistent within individual laboratories, substantial variation in reporting abnormal cervical smear diagnoses by 29 laboratories in Victoria, Australia, was observed. In 1992, a working party of the National Health and Medical Research Council of Australia proposed that a modified Bethesda System be adopted by Australian laboratories. PURPOSE: The aim of this study was to promote more uniform reporting of cervical/vaginal cytologic diagnoses by cytopathology laboratories in Victoria, Australia. METHODS: From the computer database, VCCR staff identified 80 slides that had been registered during the first half of 1991 and that covered the range of low-grade reports and negative reports. Each slide was identified by research number only. Two sets of 40 slides were compiled. Of the 29 laboratories that had worked with the VCCR during 1991, 22 agreed to participate in this study in 1992. One slide set was sent to each laboratory. An evaluation of the intralaboratory and interlaboratory consistency in reporting a set of 40 slides was undertaken. Analysis of the results compared the degree of consistency using current descriptive terminology that operates locally in Victoria with that which would pertain if the proposed Australian modification to the Bethesda System were adopted. RESULTS: Intralaboratory agreement with previously reported slides was low on the squamous descriptor (49% agreement with original report) but higher on the human papillomavirus descriptor (76% agreement with original report) when the results were analyzed using the current terminology. Wide variation in reporting was apparent between laboratories; only 5% of the slides had agreement by all laboratories. Both intralaboratory and interlaboratory agreement improved substantially when results were grouped into the categories of the proposed Australian modification of the Bethesda Reporting System. CONCLUSION AND IMPLICATION: Substantial improvement in the consistency of reporting cervical cytology specimens would be likely if terminology incorporating the broad categories of the Bethesda System were adopted.
Australia↗
Hyponatraemic convulsion associated with desmopressin and imipramine treatment.
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Child↗
Inappropriate publication of trial results and potential for allegations of illegal share dealing.
There is increasing evidence of fraud in clinical research, and one aspect concerns trading in pharmaceutical company shares by people who may have confidential information about the results of clinical trials. Plainly this has implications for honest investigators, who may find themselves exposed to such allegations. In this paper Dr D S Freestone and Mr H Mitchell, QC, identify three interlinked issues which they think underlie the potential for these allegations. They are pressure for premature or inappropriate communication of research results; trading in pharmaceutical company shares by academic clinical investigators; and the possibility that clinical investigators might succumb to temptation. Dr Freestone and Mr Mitchell suggest that whenever possible results of clinical studies should be published in appropriate medical journals without prior public disclosure. This conflicts with Stock Exchange rules, which require that price sensitive information should be published at the earliest opportunity and preclude priority of publication in medical journals. Freestone and Mitchell believe that rarely rapid public disclosure is acceptable if it is to protect patients' interests but that it must not prejudice publication in the medical or scientific press. When rapid public disclosure is needed, they say, every attempt should be made to inform prescribers before patients. Dr Freestone and Mr Mitchell warn that academic clinical investigators who have access to unpublished price sensitive information about pharmaceutical companies whose shares they trade in will almost certainly be in breach of the Company Securities (Insider Dealing) Act 1985. Furthermore, disclosing such information to third parties, they say, exposes those people also to potential criminal liability. Freestone and Mitchell advise that when potential for allegations of conflict of interest exists clinical investigators should consider declaring their position to ethics committees and any sponsoring organisations.
Biomedical Research↗
Cytological reporting of cervical abnormalities according to endocervical status.
An analysis of cytology reporting within Victorian Cytology Service demonstrates that the proportion of Papanicolaou smears which were reported as including an endocervical component increased from approximately one half during 1987-89 to more than three quarters during 1990-91. The improvement coincided with the routine provision of special sampling instruments to all practitioners supplemented by an education program. Despite the increase in endocervical sampling, no increase in the rate of reporting of high-grade intraepithelial lesions of the cervix has occurred. An increase between the two time periods in the cytological reporting of adenocarcinoma, adenocarcinoma in situ and endocervical dyskaryosis has occurred, but does not reach statistical significance.
Adenocarcinoma↗
Accuracy and survival benefit of cytological prediction of endometrial carcinoma on routine cervical smears.
Among 359 women who received a cytology report of endometrial malignancy from the Victorian Cytology Service during 1982-87, the positive predictive value for a later histological diagnosis of endometrial malignancy was 64%. The positive predictive value was significantly higher for the group of women in whom the cytopathologists made definite predictions of endometrial malignancy as compared to the group where the cytologic features were only suggestive of endometrial malignancy (75% vs. 50%, chi 2 = 23.4; p < 0.001). The sensitivity of cervical cytology performed within two years of the diagnosis of endometrial malignancy was 28%. The odds ratio of death from endometrial cancer among women where the cytology may have allowed for an early diagnosis in comparison to women where cytology did not hasten the diagnosis was 0.78 (95% confidence interval = 0.25-2.47; p > 0.05). We conclude that while cervical cytology can predict the presence of malignancy for a small proportion of women with endometrial cancer, there remains no evidence that a cervical cancer screening program will make a major impact on reducing the morbidity and mortality from endometrial cancer.
Endometrial Neoplasms↗
Cellular differences between true negative and false negative Papanicolaou smears.
A matched case-control study of 123 false negative Papanicolaou smears and 488 true negative Papanicolaou smears was undertaken to determine the association between the types of cells present on the smear and the correctness of the cytology report. The false negative slides were significantly more likely to include endocervical columnar cells than the true negative slides (odds ratio 1.90, 95% confidence interval (CI) 1.21-3.01). No statistically significant difference in metaplastic cell status was evident (odds ratio 1.48, 95% CI 0.95-2.30). When considered together, metaplastic and/or columnar cells were significantly more likely to be present in false negative smears than in true negative smears (odds ratio 1.87, 95% CI 1.13-3.08). The implications of these findings for improving the accuracy of cervical cytology for the detection of precancerous lesions are discussed.
Case-Control Studies↗
Decline in cervical cancer screening.
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Australia↗
An eighteenth-century medical view of the diseases of the Jews in northeastern France: medical anthropology and the politics of Jewish emancipation.
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Anthropology, Cultural↗
Pap smears collected by nurse practitioners: a comparison with smears collected by medical practitioners.
This paper evaluates the results of a pilot study in which nurse practitioners (NPs) collected Pap smears to screen for cervical cancer in women in Victoria, Australia. A comparison is made between women screened by NPs and women screened by three other types of medical practitioners. Women screened by NPs were more likely to be older, of non-English-speaking background, and to have had fewer smears collected previously. The quality of the smears collected by the NPs and the other medical practitioners did not differ, but a higher proportion of smears collected by the NPs were from women who had undergone a hysterectomy. The abnormality rate was lower in the smears collected by the NPs. This difference was statistically significant, even after the data were age standardized. As a result of this short-term evaluation, it has been concluded that NPs are able to effectively screen a hard-to-reach group of women, collect technically adequate specimens, and arrange for appropriate follow-up care for women with screen-detected abnormalities.
Adult↗