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S L Vowler

Publications and source records attributed to S L Vowler.

13 recordsLinked to original sources
PubMed2006

Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia.

We previously developed an immunohistochemical method for estimating cell cycle state and phase in tissue samples, including biopsies that are too small for flow cytometry. We have used our technique to examine whether primary abnormalities of the cell cycle exist in laryngeal neoplasia. Antibodies against the markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67, and putative markers of cell cycle phase, cyclin D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis) were applied to paraffin-embedded sections of normal larynx (n = 8), laryngeal dysplasia (n = 10) and laryngeal squamous cell carcinoma (n = 10). Cells expressing each marker were determined as a percentage of total cells, termed the labelling index (LI), and as a percentage of Mcm-2-positive cells, termed the labelling fraction (LF). The frequency of coexpression of each putative phase marker was investigated by confocal microscopy. There was a correlation between Mcm-2 and Ki67 LIs (rho = 0.93) but Mcm-2 LIs were consistently higher. All cells expressing a phase marker coexpressed Mcm-2, whereas Ki67 was not expressed in a proportion of these cells. The putative phase markers showed little coexpression. Labelling index values increased on progression from normal larynx through laryngeal dysplasia to squamous cell carcinoma for Mcm-2 (P = 0.001), Ki67 (P = 0.0002), cyclin D1 (P = 0.015), cyclin A (P = 0.0001) and cyclin B1 (P = 0.0004). There was no evidence of an increase in the LF for any phase marker. Immunohistochemistry can be used to estimate cell cycle state and phase in laryngeal biopsies. Our data argues against primary cell cycle phase abnormalities in laryngeal neoplasia.

Biomarkers, Tumor↗
PubMed2006

A minimally invasive immunocytochemical approach to early detection of oral squamous cell carcinoma and dysplasia.

Squamous dysplasia of the oral cavity indicates increased risk of progression to squamous cell carcinoma (SCC). An important advance would be the development of a minimally invasive assay for identification of oral SCC and dysplasia. We have investigated the suitability in this context of immunostaining oral smears for minichromosome maintainance proteins (MCMs), sensitive and specific biomarkers of cell cycle entry. Immunohistochemical examination of 66 oral tissue samples showed a greater frequency of Mcm-2 expression in surface layers of moderate/severe dysplasia and SCC compared to benign keratosis/mild dysplasia. Immunocytochemistry for Mcm-2/Mcm-5 was performed on 101 oral smears. Conventional smears included 23 from normal mucosa, benign proliferative disease and mild dysplasia, all of which were MCM negative. Of 52 conventional smears of SCC tissue samples, 18 were inadequate. However, MCM-positive cells were present in 33/34 adequate samples. Of 26 liquid-based cytology smears, 19 out of 20 smears from SCC were adequate and all were MCM positive. Six smears from benign lesions were adequate and MCM negative. We conclude that MCMs are promising markers for early detection of oral SCC and dysplasia, particularly in a liquid-based cytology platform. Detection of MCMs would be amenable to automation and potentially applicable in the developing world. Further studies are now warranted.

Biomarkers, Tumor↗
PubMed2006

DC-SIGN association with the Th2 environment of lepromatous lesions: cause or effect?

The clinical spectrum of leprosy is related to patients' immune responses. Non-responsiveness towards Mycobacterium leprae (ML) seems to correlate with a Th2 cytokine profile. The reason for such a polarized immune response remains unclear. The C-type lectin, DC-SIGN, expressed by subsets of dendritic cells (DCs) and macrophages, has previously been associated with Th2 responses. Here we show abundant DC-SIGN expression in lepromatous but not borderline tuberculoid leprosy, in both HIV-positive and HIV-negative patients. Moreover, we demonstrate that DC-SIGN can act as an entry receptor for ML, as it does for M. tuberculosis, through the cell wall component lipoarabinomannan. DC-SIGN is expressed on virtually all ML-containing cells, providing further evidence for its role as a receptor. DC-SIGN may therefore be induced on macrophages in lepromatous leprosy and may then contribute to mycobacterial entry into these cells.

Adult↗
PubMed2006

The learning curve in stapes surgery and its implication to training.

OBJECTIVE: To identify the stapedotomy learning curve of two U.K. otolaryngologists. STUDY DESIGN: A retrospective review of the outcome of first 100 stapedotomy operations by each surgeon. Included in the study was a postal survey of the incidence of stapes surgery by U.K. otolaryngologists. SETTING: Two tertiary referral centers. PATIENTS: All ears in which primary stapedotomy was performed for otosclerosis. Nonotosclerotic cases and malleus stapedotomy cases were excluded. INTERVENTION: One surgeon used the technique of small fenestra stapedotomy with either a Teflon-wire or titanium piston but without vein graft interposition, whereas the second used the technique of stapedotomy with vein graft interposition and a Teflon piston. MAIN OUTCOME MEASURES: A moving average with a window of 15 dB was used to plot learning curves for the postoperative air-bone gaps. Using a postoperative air-bone gap of 20 dB or better as a definition of 'success,' the success rates with the increase in surgical experience of both surgeons were plotted on graphs, the learning curves. The end point of the learning curve was defined as the point where the curve reached its peak, and the results were sustainable. RESULTS: There was no clear-cut end point in both learning curves, although it appears that there is a landmark point at 60 to 80 cases for both surgeons. Both surgeons also had one "dead ear" in their first 15 cases. The postal survey showed that some trainers only performed small numbers of stapes surgery, whereas some otolaryngologists who performed stapedotomies regularly were not trainers. CONCLUSIONS: The study supports a learning curve in stapes surgery. To maximize the training opportunity of trainee surgeons, it may be advisable for learning centers to form network to provide target training for the trainee who has demonstrated the necessary dexterity and temperament of an otologist.

Adult↗
PubMed2005

Relative humidity of the external auditory canal in normal and abnormal ears, and its pathogenic effect.

OBJECTIVE: To find the relative humidity of the normal external ear canal and to demonstrate that the relative humidity of the external auditory canal was higher in abnormal ears, i.e. ears commonly associated with chronic discharge. SETTING: Secondary health care within the ENT departments of Addenbrooke's and Hinchingbrooke hospitals. DESIGN: A clinical observational study. PARTICIPANTS: Volunteers seen in ENT outpatients. Inclusion criteria for the normal ear group, was a normal ear with no history of infection or previous ear disease. Inclusion criteria for abnormal ear group commonly associated with chronic discharge. Exclusion criteria were the presence of pus or infection within the ear canal. METHOD: The relative humidity of the external ear canal was measured in normal and abnormal ears. Abnormal ears were grouped as those commonly associated with chronic discharge, mastoid cavities, tympanic perforations, recurrent otitis externa and hearing-aided ears. RESULTS: The range of relative humidity of normal ears is 40-70%. The humidity in abnormal ears was found to be significantly higher than the humidity in normal ears (P < 0.0001). CONCLUSION: The raised relative humidity in the external canal may explain the predisposition of certain abnormal ears to chronic discharge and infection. If the humidity of the canal could be brought down to a normal level, this could offer a new therapeutic treatment.

Animals↗
PubMed2004

Thyroid carcinoma after Chernobyl latent period, morphology and aggressiveness.

The large numbers of papillary thyroid carcinomas that have occurred in those exposed to high levels of short-lived isotopes in fallout after Chernobyl provide a unique opportunity to correlate latency and tumour biology. We show that short latency is associated with tumours with a phenotype that is significantly less structurally differentiated, shows significantly less peritumour fibrosis, and significantly more invasive spread when compared to tumours with a longer latent period. In contrast, the type of differentiation (papillary or follicular architecture) is associated with age at exposure. These findings suggest that the initial mutation at the time of exposure played a major role in tumour latency and aggressiveness. We and others have shown that RET-PTC3 rearrangements are associated with the solid morphology seen in these short latency tumours, while classical papillary carcinomas more often show RET-PTC1 rearrangements. Studies in transgenic mice show similar findings, and in vitro studies show that RET-PTC3 induces more rapid growth than RET-PTC1. We therefore suggest that the solid morphology, high frequency of RET-PTC3 rearrangements and aggressive behaviour noted in early investigations of post-Chernobyl tumours were characteristic of short latency rather than the nature of the mutagen, and that successive overlapping waves of papillary carcinoma with differing latency, differing patterns of mutations and differing clinical behaviour are occurring in those exposed to Chernobyl fallout.

Adolescent↗
PubMed2004

A novel immunohistochemical method for estimating cell cycle phase distribution in ovarian serous neoplasms: implications for the histopathological assessment of paraffin-embedded specimens.

We have investigated whether immunohistochemical markers can identify differences in cell cycle phase distribution in ovarian serous neoplasms, including borderline tumours of different grades. Sections of normal ovary (n=18), serous cystadenoma (n=21), borderline serous tumours (n=21) and serous cystadenocarcinoma (n=15) were analysed by immunohistochemistry using markers of cell cycle entry (Mcm-2) and cell cycle phase, including cyclin D1 (mid-to-late G1), cyclin A (S phase), cyclin B1 (G2 phase) and phosphohistone H3 (mitosis). Double-labelling confocal microscopy confirmed marker phase specificity and phase estimations were corroborated by flow cytometry. On progression from normal ovary through serous cystadenoma and borderline tumours to cystadenocarcinomas, expression of Mcm-2 (P<0.0001), cyclin D1 (P=0.002), cyclin A (P<0.0001), cyclin B1 (P<0.0001) and phosphohistone H3 (P<0.0001) increased, paralleled by an increase in the S-phase fraction (cyclin A : Mcm-2 ratio; P=0.002). Borderline tumours of increasing grade also showed increased Mcm-2 and cyclin A expression, together with an increase in the S-phase fraction. Immunohistochemistry can be used to estimate cell cycle phase distribution in ovarian serous neoplasms, giving results similar to flow cytometric analysis and enabling direct assessment of tumour heterogeneity. Immunohistochemical estimates of the S-phase fraction may identify serous borderline tumours likely to exhibit malignant progression and/or select serous cystadenocarcinomas likely to respond to adjuvant therapy.

Biomarkers, Tumor↗
PubMed2004

Increased expression of minichromosome maintenance protein 2 in active inflammatory bowel disease.

OBJECTIVE: Minichromosome maintenance protein 2 (Mcm2) is an accurate indicator of cell cycle entry in tissue samples, but its expression in inflammatory bowel disease (IBD) has not previously been investigated. We have used immunohistochemistry to assess the expression of Mcm2, in comparison to the existing proliferation marker Ki-67, in active IBD and IBD without inflammatory activity. MATERIALS AND METHODS: For this experimental study, sections from colonic biopsy and resection specimens of 48 patients with IBD (5 inactive/quiescent Crohn's disease (CD), 13 active CD, 19 inactive/quiescent ulcerative colitis (UC) and 11 active UC) and 15 normal controls were immunostained with antibodies to Mcm2 and Ki-67. The percentage of immunopositive epithelial nuclei was determined by calculating a labelling index (LI) for entire glands and for gland thirds (superficial, middle and basal). RESULTS: The Mcm2 LI was significantly increased in the superficial third of glands in active vs. inactive/quiescent UC (P < 0.0001) and active vs. inactive/quiescent CD (P = 0.001). The Mcm2 LI was significantly greater than the Ki-67 LI in active IBD, both in entire glands (P < 0.0001) and in the superficial third of glands (UC, P = 0.001; CD, P = 0.0002). Mcm2 LIs for entire glands were significantly higher in UC (all cases) compared to CD (all cases) (P = 0.032). CONCLUSIONS: There is increased cell cycle entry, as indicated by expression of Mcm2 and to a lesser extent Ki-67, in the superficial third of colonic glands in active IBD compared to inactive/quiescent IBD. Detection of Mcm2 may contribute to improved histological assessment of small tissue biopsies and may enable the development of a direct stool-based test for detection of active IBD and potentially for assessment of disease activity.

Cell Cycle Proteins↗
PubMed2004

Training improves medical student performance in image interpretation.

The aim of this study was to objectively quantify the effects of radiological teaching on student performance in interpreting radiological images, and to establish whether training location affects performance. 114 clinical students were asked to anonymously interpret radiological cases before and after 26 weeks clinical training. Improvements were assessed by comparing performance on the median question in each assessment using the Kruskal-Wallis analysis. Variations according to different placements were assessed by the Mann-Whitney U-test. There was a highly significant (p<0.001) improvement in the performance of the group with training. The proportion of correct answers to the median question improved from 8% to 43%. Differences between training placements were non-significant. Our study suggests that radiology teaching significantly improves student performance. Future work should look to define the contribution of "clinical exposure" towards this improvement, as well as the various teaching methods employed.

Clinical Competence↗
PubMed2003

Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions.

Histological classification of laryngeal epithelial lesions is highly subjective, and methods of cytological detection are not well developed. Improved determination of aberrant cell cycle entry may allow increased objectivity in histological assessment and enable the development of less invasive diagnostic cytology tests. Sections of normal larynx (n=10), laryngeal dysplasia (n=20) and laryngeal squamous cell carcinoma (SCC) (n=10) were classified according to the Ljubljana classification and stained for markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67. Expression patterns were compared using double labelling confocal microscopy. There was a correlation between Mcm-2 and Ki67 labelling indices (rho=0.93; 95% CI [0.84, 0.97]) and both markers showed increased expression from normal epithelium to SCC (Mcm-2, P=0.001; Ki67, P=0.0002). Importantly, there was minimal expression of Mcm-2 or Ki67 in the most superficial layers of normal larynx and abnormal or atypical hyperplasia, in contrast to carcinoma in situ and SCC. Clusters of Mcm-2/5-positive cells were present in cytological preparations from SCC, but not from those showing atypical hyperplasia or inflammation in non-neoplastic tissue. Minichromosome maintenance protein-2 staining may increase the objectivity and reliability of histological grading of laryngeal epithelial lesions. Laryngeal brushings, combined with immuno-enhanced liquid-based cytology, could be useful, as a less invasive approach, to the detection of laryngeal malignant and premalignant lesions.

Antigens, Neoplasm↗
PubMed2003

Is physical function a more appropriate measure than volume excess in the assessment of breast cancer-related lymphoedema (BCRL)?

The aim of this study was to objectively measure impairment of arm function in women with breast cancer-related lymphoedema (BCRL), and investigate possible associations between this, arm volume excess, and psychological morbidity as measured by the Medical Outcomes Study 36-item short form (SF-36) questionnaire. A total of 48 patients were recruited. Manual dexterity was significantly impaired in the affected arm, independent of dominant or non-dominant arm involvement, but was not associated with arm volume excess. Psychological morbidity was significantly impaired in the domains of 'physical function' and 'bodily pain' when compared with population controls. Degree of impairment in the 'physical function' domain correlated with the absolute level of objectively tested manual dexterity. Impairment of manual dexterity appears to have a greater impact than arm volume excess on the overall psychological morbidity associated with BCRL, suggesting that greater emphasis should be placed upon arm function in the assessment, treatment targeting, and monitoring of patients with this condition.

Adult↗