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Biomedical subjects

E McGoogan

Publications and source records attributed to E McGoogan.

At least 19 recordsLinked to original sources
PubMed2001

Rapid real time PCR to distinguish between high risk human papillomavirus types 16 and 18.

AIMS: To assess the validity and practicality of real time polymerase chain reaction (PCR) for human papillomavirus (HPV) testing in combination with liquid based cytology samples for cervical screening. METHODS: Real time PCR using consensus (GPS+/6+) and type specific primers was developed to detect genital HPV types. This provides rapid, efficient amplification followed by denaturation of the product and computer analysis of the kinetics data that are generated. Liquid based cytology samples were obtained from patients attending routine cervical screening clinics. DNA was extracted from the residual cellular suspension after cytology using spin columns. RESULTS: Real time PCR successfully distinguished between HPV-16 and HPV-18 on the basis of amplification with consensus primers followed by DNA melting temperature (Tm) analysis. Sensitivities of one to 10 copies of HPV-16 (mean Tm = 79.4 degrees C; 2 SD, 0.8) and four to 40 copies of HPV-18 (mean Tm = 80.4 degrees C; 2 SD, 0.4) were obtained. In a mixed population of SiHa and HeLa cells containing known copy numbers of HPV-16 and HPV-18 genomes, HPV-16 and HPV-18 products were clearly separated by Tm analysis in mixtures varying from equivalence to 111000. Together with detailed melt analysis, type specific primers from the same region of the L1 gene confirmed the differential ability of this system. The method was applied to 100 liquid based cytology samples where HPV status using conventional GP5+/6+ PCR was already known. There was 95% agreement between the methods, with 55 positives detected by conventional PCR and 59 with real time PCR. The method was then tested on 200 routine liquid based cytology samples. Approximately 10% were positive by real time PCR, most of which were classified as HPV-16 by detailed melt analysis. Thirteen (6.8%) HPV positives were identified in 189 samples showing no evidence of cervical cytological abnormality. CONCLUSIONS: Real time PCR is a rapid, efficient method for the detection of HPV with the separation of HPV-16 and HPV-18 on the basis of differential Tm. Preliminary results suggest it could prove

Cell Line↗
PubMed2000

The borderline cervical smear: colposcopic and biopsy outcome.

AIMS: To review the outcome of women referred with smears showing borderline nuclear change (BNC), and to determine any differences in outcome if BNC was persistent, preceded by dyskaryosis, or followed treatment for cervical intraepithelial neoplasia (CIN). In addition, to determine criteria that might permit delineation of a BNC subtype, predictive of CIN. METHODS: The records of 178 women referred for colposcopy in 1993, with last smear showing BNC, were obtained from our laboratory database. The cytology, colposcopy, and biopsy follow up for a five year period were also obtained. The patients were divided into three categories according to their smear status before the last referral borderline smear: category 1, persistent BNC (n = 39); category 2, BNC preceded by dyskaryotic smears (n = 100); and category 3, BNC after treatment for CIN (n = 39). The referral borderline smears were reviewed on cases with negative outcome and those with a biopsy diagnosis of CIN2 and CIN3. RESULTS: In 50 women (28%) no biopsy was deemed necessary after colposcopic assessment. The biopsy results in the remaining 128 (72%) women were as follows: normal in 18 (10%), koilocytosis in 12 (7%), CIN1 in 45 (25%), CIN2 in 32 (18%), and CIN3 in 21 (12%) women. High grade lesions (CIN2, CIN3) were seen on biopsy in 14 of 39, 33 of 100, and six of 39 cases in category 1, category 2, and category 3, respectively. Blind review of the referral borderline smears from 53 women with a biopsy diagnosis of high grade lesions (32 CIN2, 21 CIN3) confirmed they were borderline in 23, upgraded them to mild dyskaryosis in 15, and found that 14 cases of isolated moderate or severe dyskaryotic cells had been missed originally. The borderline change was in mature squamous cells in five of 23 and in immature metaplastic epithelium in 18 of 23 cases. After smear review in 68 women with negative outcome, 36 smears were reclassified as negative in keeping with inflammation and atrophy, three were considered unsatisfactory, one was upgraded to CIN1, and 28 were confirmed as BNC. Of the latter, 25 of 28 were in mature squamous cells. The five year follow up on women with negative colposcopy (n = 50), negative loop excision of transformation zone (LETZ) (n = 18), and LETZ with koilocytosis (n = 12) showed subsequent high grade CIN on LETZ in 16, 0, and two patients, respectively. CONCLUSIONS: On referral of women for colposcopy with last smear showing BNC, the outcome was high grade CIN in over 30% of cases, irrespective of whether the borderline smear was preceded by another borderline smear or by a dyskaryotic smear. In contrast, in those referred because of BNC after treatment of CIN, high grade CIN was seen less frequently (15% of cases). Furthermore, in cases that necessitated loop excisions, high grade CIN was seen in 41%. This study also showed that BNC associated with inflammation or atrophy, or BNC in mature squamous cells, appears to have lower predictive value for CIN than those cases where BNC is associated with immature metaplastic epithelium. The use of terms such as "BNC favour reactive" for the former and "BNC favour dyskaryosis" for the latter is recommended, together with follow up by cytology and colposcopy, respectively.

Adult↗
PubMed1998

Anal cytological abnormalities in HIV-infected homosexual men.

This study aimed to examine the prevalence of anal cytological abnormalities in groups of HIV-infected and non-infected homosexual men, and to monitor changes with time. Dyskaryosis suggestive of anal intraepithelial neoplasia (AIN) was noted in 24 (30%) of the 80 satisfactory anal smears from 66 HIV-seropositive homosexual men; such changes were found in only 7 (4.7%) of the 149 satisfactory smears from 181 HIV-seronegative homosexual men (P < 0.005), and in none of 34 satisfactory preparations from 51 HIV-seronegative heterosexual men. In the follow-up of 20 HIV-seropositive men, the severity of the cytological abnormalities found in 2 men increased, with the most recent smear showing changes suggestive of AIN III; one of these men subsequently developed anal cancer. Smears from 4 men showed apparent regression in the degree of dyskaryosis. Although the numbers of patients studied were small, there appeared to be a trend towards a more severe degree of dyskaryosis in those men with increasing immunodeficiency. There was no significant difference in the detection of human papillomavirus types 6b, 11, 16 and 18 between HIV-infected and non-infected men.

Adolescent↗
PubMed1996

Expression of p21waf1/Cip1, MDM2 and p53 in vivo: analysis of cytological preparations.

The aim of this study was to test the hypothesis that expression of p21waf1/Cip1 and MDM2 could be used as indicators of the activity of wild-type p53 which can transcriptionally activate the p21waf1/Cip1 and mdm2 genes. In cytological preparations of serous fluids, the expression of p53, p21waf1/Cip1 and MDM2 protein was assessed by immunohistochemistry. A series of 50 cases was assessed for both p53 and p21waf1/Cip1 expression and a subset of 37 cases had sufficient material for analysis of MDM2. In samples in which there were reactive mesothelial cells (n = 48) there was general concordance between p53 and p21waf1/Cip1 expression, but in nine cases p21waf1/Cip1 was expressed in the absence of detectable p53. Similarly, MDM2 expression was not correlated with p53 in 15 of 31 cases. p21waf1/Cip1 was correlated with MDM2 in 24 of 31 cases, while in the remaining seven, MDM2 was expressed without detectable p21waf1/Cip1 immunoreactivity. In samples with neoplastic cells (n = 18) the presence of p21waf1/Cip1 and MDM2 expression was always associated with p53 expression. Polymorphonuclear leucocytes frequently showed p21waf1/Cip1 immunoreactivity, and this was confirmed by immunoblotting of peripheral blood polymorphonuclear leucocytes. These data indicate that in general p21waf1/Cip1 expression correlates with p53 expression in reactive mesothelial cells, consistent with a known mechanism of regulation. However, in reactive mesothelial cells, MDM2 expression is perhaps dissociated from p53 expression, contrary to current models of MDM2 regulation. Finally, in addition to many normal tissues, it is likely that in reactive mesothelial cells and some tumours p21waf1/Cip1 expression is not dependent on the presence of wild-type p53 protein. In conclusion, p53 status cannot be reliably predicted based only on p21waf1/Cip1 or MDM2 expression.

Biomarkers↗
PubMed1994

Fine needle aspiration cytology of breast in invasive carcinoma of tubular type and in radial scar/complex sclerosing lesions.

Fine needle aspirates (FNA) from 31 invasive carcinomas of tubular type and 22 radial scar/complex sclerosing lesions (RS/CSL), diagnosed in Edinburgh between 1986 and 1991, were reviewed. The lesions in this study varied in size and palpability at presentation, but are of increasing interest in the differential diagnosis of non-palpable areas of increased mammographic density. In agreement with previously published information, it was found that the tubular cancers were usually selected for biopsy following aspiration, but less often definitively diagnosed as malignant. Nearly 50% of the RS/CSL group were correctly reported benign on cytology, but in 40%, biopsy was recommended to exclude malignancy. In addition, cytological features helpful in suggesting malignancy in aspirates from tubular cancers, also raised suspicion in aspirates from the RS/CSL group, with a risk of overdiagnosis of cancer.

Adenocarcinoma↗
PubMed1994

A population-based, controlled study of the relation between HIV infection and cervical neoplasia.

OBJECTIVE: To study a geographically defined population of women exposed to a drug-related risk for human immunodeficiency virus (HIV), together with carefully matched neighbourhood controls, in order to examine (1) the proportion of different groups having cervical cytopathology screening; (2) the association between HIV infection and cervical intraepithelial neoplasia; (3) the independent effect of CD4+ lymphocyte count and duration of HIV infection; and (4) the correspondence between cervical cytopathology and colposcopically directed biopsy. DESIGN: A population-based study. SUBJECTS: All women domiciled in Lothians with the following characteristics: between 1983 and 1987 they had a history of injection drug use or a seropositive partner with a history of injection drug use; they had a pregnancy after that exposure where their serostatus was known. In addition, neighbourhood controls were identified by computer matching for the following criteria--post-code sector, housing deprivation score, age, parity, pregnancy outcome, ethnic group, year of pregnancy, smoking. MAIN OUTCOME MEASURES: Search was carried out for the cervical smear nearest in time to the index pregnancy end date, providing serostatus was known at that time. All identified smears were assessed by a cytopathologist without knowledge of clinical information, study group or serostatus. RESULTS: Of 376 women, appropriate cervical smears were identified for 336. The proportions screened in the different groups were similar. There were more abnormal smears in the seropositive group than in the drug-related seronegative (P < 0.01) or the neighbourhood control groups (P < 0.001). HIV-infected women with abnormal smears had lower CD4+ lymphocyte counts (P < 0.0005). There was a reasonable correspondence between cytopathological classification and histological grading, and this was of similar strength in cases and controls (weighted kappa 0.72, 0.74). CONCLUSIONS: There is a definite relation between HIV infection and cervical intraepithelial neoplasia. This is related to immune depletion but whether this is the sole mechanism for the association is unclear.

Adult↗
PubMed1994

A collaborative trial of a semi-automatic system for slide preparation and screening in cervical cytopathology.

We report a test of an experimental system for machine-aided screening in cervical cytology, comprising the 'CYTOPRESS' semi-automatic slide preparation system (Nijmegen) and the 'CERVIFIP' interactive scanner (Edinburgh). Material from women attending clinics in Edinburgh and Nijmegen was stratified according to the severity of the conventional laboratory diagnosis and selected randomly within strata for inclusion in the test. Monolayered slides were prepared by CYTOPRESS from cervical scrape material remaining after preparation of conventional smears and scanned by CERVIFIP to determine the positions of the most 'suspicious' objects. The test was based on a set of 701 monolayers, divided equally between 'negatives' and 'abnormals' of various grades, of which 585 (83.4%) were passed automatically as adequate for machine-aided analysis. Approximately 15% of adequate slides were passed as 'negative' without operator interaction. In the remaining 85%, the suspicious objects were inspected by a human operator and a decision was then made either to refer each monolayer for conventional microscopic analysis, or to pass it as 'negative'. Where discrepancies occurred between the conventional laboratory and the system results, a consensus diagnosis was reached by taking into account all relevant information including clinical data. Of those with a consensus diagnosis of CIN 3 or worse an estimated 9.3 +/- 4.1% were passed by the system as 'negative'. Closer investigation of these false-negatives revealed that most, and perhaps all, were preventable by system improvements either planned or in progress. Corresponding false-negative rates for those graded 'CIN 1 or 2' and 'negative-early recall' were estimated, respectively as 18.9 +/- 5.3% and 22.9 +/- 3.1%. Of those with a 'negative-routine recall' consensus, 19.4 +/- 2.5% were referred for conventional microscopic analysis, a level well within acceptable limits for cost-effectiveness. Women whose initial laboratory smears were negative, but whose consensus diagnosis was 'negative-early recall' or CIN, are being investigated further to determine whether cervical abnormalities were in fact present. Over two-thirds of this group were referred by the machine-aided system for conventional microscopic analysis.

Diagnosis, Computer-Assisted↗
PubMed1992

The British Society for Clinical Cytology Certificate of Competence in Cytology Screening: a report of the first 3 years' experience.

In 1988 the Department of Health (DOH) recognized the cytology screener grade of laboratory staff. Cytology screeners have a 2 year training period after which they must sit a 'competence examination'. The British Society for Clinical Cytology offers an examination to meet the DOH specification. It consists of a written paper, a practical screening test, a spot test and a short viva voce. The screening test is paramount and candidates who miss a dyskaryotic smear cannot be successful. In the first 3 years there have been 22 examinations, 294 candidates and a pass rate of 76%. The majority of candidates were Cytology Screeners of 2-3 years experience but significant numbers of Medical Laboratory Scientific Officers (MLSOs) and senior MLSOs also chose to sit the examination.

Cell Biology↗
PubMed1992

The cytological detection of persistent cervical intraepithelial neoplasia after local ablative treatment: a comparison of sampling devices.

OBJECTIVE: To determine whether the cytological detection of persistent cervical intraepithelial neoplasia (CIN) after local ablative treatment is improved by the use of sampling devices other than the Ayre's spatula. DESIGN: A randomized controlled study. SETTING: Lothian Area Colposcopy Clinic. SUBJECTS: 856 patients who had received local therapy (CO2 laser or cold coagulation) for CIN II or III between 9 and 30 months earlier. INTERVENTION: Each patient had three consecutive cervical smears taken, one with the Ayre's spatula, one with either the Aylesbury, the Rocket or the Multispatula device, and finally one with the Cytobrush. The allocation of which spatula and the order of the first two was randomized. Each patient had a colposcopic examination immediately after the smears were taken. MAIN OUTCOME MEASURES: A comparison of the detection of histologically proven persistent CIN by the Ayre's spatula with the detection of persistent disease by alternative sampling devices. RESULTS: Of the 856 patients 130 had histologically proven persistent CIN. Another 98 had suspicious findings on colposcopy but punch biopsies reported as histologically normal. Of the remaining patients with normal colposcopy 130 were randomly selected to form a control group. The cervical smears from these 358 women were reported. Significantly fewer Ayre's samples contained endocervical cells than Aylesbury samples (47% vs 59%, difference 12%; 95% CI 3%-21%; P less than 0.001), Rocket samples (47% vs 67%; difference 20%, 95% CI; 12%-32%; P less than 0.001) or Multispatula samples (47% vs 76%; difference 29%, 95% CI 19-38%; P less than 0.001). When punch biopsies contained CIN, dyskaryotic cells were seen in 10% of Ayre's samples, 4.3% of Aylesbury samples, 8.3% of Rocket samples, and in no smear taken with the Multispatula. Obtaining a third smear with the Cytobrush did not substantially improve the detection rate of dyskaryosis. Neither the order of use of the spatulas, the form of initial treatment nor the size of the transformation zone had any apparent effect on the cytological detection of persistent CIN. CONCLUSIONS: We recommend that surveillance of patients who have received local ablative therapy for CIN should be by both cytology and colposcopy, and that cytological samples should be obtained using the Ayre's spatula.

Carcinoma in Situ↗
PubMed1989

Stereotaxic localisation and aspiration cytology of impalpable breast lesions.

As part of a programme of assessment of the 'Sterotix' localisation device, aspiration cytology was carried out on 50 patients with 52 impalpable, mammographically detected breast lesions using the stereotaxic guidance device. This was followed by an open localisation biopsy of the area for confirmation. In 12 patients (23%) the aspirations failed to yield sufficient material for diagnosis. This was frequently due to the poorly cellular nature or very small size of the lesions. Of the remaining 40 patients, 15 were regarded as having both mammographically and cytologically benign changes which were confirmed histologically; they could thus have been spared diagnostic surgery. Ten patients had a diagnosis of malignancy with both investigations, and could have had planned investigation and subsequent definitive surgery. Of the remainder, 14 lesions had a report of malignancy or suspicion of it with either technique and these patients would have come to conventional localisation biopsy. Only one patient was found to have a malignancy, who had cytologically benign and mammographically 'probably benign' disease: this was an invasive lobular carcinoma with a dominant in-situ component and may well have been an incidental finding on biopsy.

Adult↗
PubMed1981

A prospective study of 1152 hospital autopsies: I. Inaccuracies in death certification.

Comparison of certified clinical diagnoses with autopsy findings showed that, while the major cause of death was confirmed in 61 per cent. of cases, many diagnoses--both major and contributory--were wrong; many clinical diagnoses were either disproved or relegated to a less important role, and many autopsy findings had not apparently been anticipated. Accuracy was particularly poor in some clinical categories: notably cerebrovascular disease and infections. In these, the diagnosis was more often wrong than right. Thus, death certificates are unreliable as a source of diagnostic data. The clinician's confidence in his major diagnosis bore a fairly close relationship to the frequency of its confirmation. Nevertheless, even when certified as "fairly certain", the major diagnosis was wrong in about one-quarter of these cases. An attempt was made to assess the significance of incorrect diagnoses; one half of these might be clinically significant. Diagnostic accuracy did not improve with the time spent in hospital, and it bore an inverse relationship to the patient's age.

Adolescent↗
PubMed1981

A prospective study of 1152 hospital autopsies: II. Analysis of inaccuracies in clinical diagnoses and their significance.

A further analysis of 1152 hospital autopsies provides data on inaccuracies of specific diagnoses; there are many examples of overdiagnosis and underdiagnosis. All were encountered in a routine hospital autopsy service and their frequency confirms the importance of the hospital autopsy in medical audit. A knowledge of the misdiagnoses which recur frequently could provide guidance in the selection of cases for autopsy.

Abdomen, Acute↗
PubMed1980

Necropsy: a yardstick for clinical diagnoses.

An attempt to obtain necropsies on all deaths from a selected group of clinical units resulted in a necropsy rate of 65% (compared with a normal of 30% in these units). The effect of increasing the necropsy rate was to produce a higher rate of confirmation of clinical diagnoses; nevertheless, 15% of main diagnoses and 42% of causes of death were not confirmed. A large proportion of these were deemed by clinicians in consultations with pathologists to be clinically significant. Of main diagnoses considered certain, 10% were not confirmed. The proportion of diagnostic discrepancies was virtually identical in two groups--those in which the clinicial believed he would normally have requested necropsy, and those in which he would not. Thus clinical confidence in the diagnosis is not an adequate assurance of its accuracy. Although in this survey necropsy was requested on almost all cases, permission was refused in many which may be attributed either to resistance by relatives or to an inadequate approach by the medical staff. The proportion of permissions secured by individual units varied from 50% to 92%. This indicates that the nature of the approach to relatives is the more important factor. As present practices do not adequately allow for the detection of a wide range of misdiagnoses and missed diagnoses it is proposed that a "partial audit" would provide a valuable yardstick; clinicians would be asked to obtain permission for necropsy on an agreed proportion (say, 20%) of deaths over and above those cases in which they are particularly interested and would normally request a necropsy.

Age Factors↗