Biomedical subjects

A Flanagan

Publications and source records attributed to A Flanagan.

At least 19 recordsLinked to original sources

PubMed2006

A prospective, randomised study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: Periosteum covered versus type I/III collagen covered.

INTRODUCTION: The results for autologous chondrocyte implantation (ACI) in the treatment of full thickness chondral defects in the knee are encouraging. At present two techniques have been described to retain the chondrocyte suspension within the defect. The first involves using a periosteal cover (ACI-P) and the second involves using a type I/III collagen membrane (ACI-C). To the authors knowledge there are no comparative studies of these two techniques in the current literature. We have therefore undertaken such a study to establish if there is a difference between the 2 techniques based on a clinical and arthroscopic assessment. METHODS: A total of 68 patients with a mean age of 30.52 years with symptomatic articular cartilage defects were randomised to have either ACI-P (33 patients) or ACI-C (35 patients). The mean defect size was 4.54 cm2. All patients were followed up at 24 months. RESULTS: A clinical and functional assessment showed that 74% of patients had a good or excellent result following the ACI-C compared with 67% after the ACI-P at 2 years. Arthroscopy at 1 year also demonstrated similar results for both techniques. However, 36.4% of the ACI-P grafts required shaving for hypertrophy compared with none for the ACI-C grafts at 1 year. DISCUSSION: This study has shown no statistical difference between the clinical outcome of ACI-C versus ACI-P at 2 years. A significant number of patients who had the ACI-P required shaving of a hypertrophied graft. We conclude that there is no advantage in using periosteum as a cover for retaining chondrocytes within an osteochondral defect; as a result we advocate the use of an alternative cover such as a manufactured type I/III collagen membrane.

Adolescent↗

PubMed2006

COSMIC 2005.

The Catalogue Of Somatic Mutations In Cancer (COSMIC) database and web site was developed to preserve somatic mutation data and share it with the community. Over the past 25 years, approximately 350 cancer genes have been identified, of which 311 are somatically mutated. COSMIC has been expanded and now holds data previously reported in the scientific literature for 28 known cancer genes. In addition, there is data from the systematic sequencing of 518 protein kinase genes. The total gene count in COSMIC stands at 538; 25 have a mutation frequency above 5% in one or more tumour type, no mutations were found in 333 genes and 180 are rarely mutated with frequencies <5% in any tumour set. The COSMIC web site has been expanded to give more views and summaries of the data and provide faster query routes and downloads. In addition, there is a new section describing mutations found through a screen of known cancer genes in 728 cancer cell lines including the NCI-60 set of cancer cell lines.

Databases, Genetic↗

PubMed2006

Hibernoma: MRI features in eight consecutive cases.

AIM: To describe the preoperative magnetic resonance imaging findings of eight histologically-proven cases of hibernoma. MATERIALS AND METHODS: The site, size, and signal characteristics of eight consecutive hibernomas were retrospectively assessed on T1-weighted spin-echo and short T1 inversion recovery (STIR)/fat-saturated T2-weighted fast spin echo magnetic resonance images. Four patients also had gadolinium-enhanced fat-saturated T1-weighted spin echo imaging. Patient age and sex, and duration of symptoms were recorded. RESULTS: Three female and five male patients with an average age 36 years (range 16-53 years) were included. Seven lesions occurred in the thigh, four in the anterior compartment and three in the posterior compartment. One lesion occurred superficial to the scapula. All cases demonstrated common magnetic resonance imaging findings of a well-defined, heterogeneous mass, slightly or clearly hypo-intense to subcutaneous fat on T1-weighted spin-echo images, with prominent thin low signal bands throughout the tumour. The lesions failed to fully suppress on STIR or fat-saturated T2-weighted images. Only one of the four contrast-enhanced studies demonstrated increased vascularity in the tumour. CONCLUSION: The MRI findings of a lesion that is diffusely slightly hypointense to surrounding subcutaneous fat, should prompt the operator to consider hibernoma in the differential diagnosis.

Adipocytes, Brown↗

PubMed2005

Microbiological culture analysis of the tongue anaerobic microflora in subjects with and without halitosis.

OBJECTIVE: Determination of the microflora present on the tongue dorsum of subjects with and without halitosis using conventional microbiological culture methods. METHODS: Twenty-one halitosis and 20 control patients were recruited using a strict clinical protocol. Samples were collected from the posterior dorsum of the tongue using a sterile brush. Each sample was vortex mixed for 30 s and serial 10-fold dilutions to 10(-7) were carried out. Samples were plated onto fastidious anaerobe agar (FAA) and FAA enriched with vancomycin. These were incubated under anaerobic conditions for 10 days at 37 degrees C. Strict anaerobes were identified by metronidazole sensitivity and bacteria were identified to genus level by a combination of colony morphology, Gram staining and biochemical and enzymatic tests (rapid ID 32 A). RESULTS: The predominant species in test and control groups were Veillonella sp. and Prevotella sp. Greater species diversity was found in the halitosis samples compared with controls. The halitosis samples contained an increased incidence of unidentifiable Gram-negative rods, Gram-positive rods and Gram-negative coccobacilli. CONCLUSIONS: There was no obvious association between halitosis and any specific bacterial genus. The increased species diversity found in halitosis samples suggests that halitosis may be the result of complex interactions between several bacterial species. The role of uncultivable bacteria may also be important in contributing to this process.

Bacteria, Anaerobic↗

PubMed2004

The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website.

The discovery of mutations in cancer genes has advanced our understanding of cancer. These results are dispersed across the scientific literature and with the availability of the human genome sequence will continue to accrue. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website have been developed to store somatic mutation data in a single location and display the data and other information related to human cancer. To populate this resource, data has currently been extracted from reports in the scientific literature for somatic mutations in four genes, BRAF, HRAS, KRAS2 and NRAS. At present, the database holds information on 66 634 samples and reports a total of 10 647 mutations. Through the web pages, these data can be queried, displayed as figures or tables and exported in a number of formats. COSMIC is an ongoing project that will continue to curate somatic mutation data and release it through the website.

Databases, Factual↗

PubMed2003

Modelling oral malodour in a longitudinal study.

The aim of this study was to develop an in vitro model of the tongue microflora in order to assess anti-malodour compounds before clinical evaluation. Biofilms, derived from the tongue microflora, were grown in a constant depth film fermentor (CDFF) with nutrients supplied in the form of mucin- and serum-containing artificial saliva. Differential agars and a halimeter were used to determine the bacterial microflora and production of volatile sulphur compounds (VSCs), respectively. The resulting biofilms had a bacterial population which contained, on average, 29% streptococci, 48% Gram-negative anaerobes and 2.5% with an H2S-producing phenotype. When the biofilms were pulsed with either chlorhexidine or zinc acetate there was a reduction in the number of H2S-producing bacteria, however these counts subsequently recovered as pulsing continued. The generation of VSCs was correlated to the viable counts of the H2S-producing bacteria. By pulsing with anti-malodour compounds over time we observed a reduction in the quantity of VSCs produced and a change in the composition of the plaque to one which contained fewer H2S-producing bacteria.

Anti-Infective Agents, Local↗

PubMed2003

The RAD30 cancer susceptibility gene.

The human skin cancer-prone disease xeroderma pigmentosum variant (XPV) results from a mutation in RAD30, which encodes the novel lesion bypass DNA polymerase eta. XPV cells are characterized by delayed completion of DNA replication and increased mutagenesis following UV irradiation. In cell-free extracts of XPV lymphoblasts, functional DNA polymerase eta is required for the complete replication of a double-stranded plasmid containing either a single (6-4) photoproduct or a cyclobutane pyrimidine dime(CPD), the major mutagenic UV-induced lesion. In cultured XPV cells, replication arrest activates downstream signalling pathways, leading to hyperphosphorylation of the 34-kDa subunit of the trimeric single-stranded DNA-binding protein, RPA (replication protein A). Many of the RAD30 mutations identified in XPV cells result in truncation and inactivation of DNA polymerase eta. To examine whether polymorphisms in the RAD30 gene that result in altered polymerase eta function, rather than enzyme inactivation, might contribute to individual susceptibility to skin cancer, methods to screen for sequence changes in the RAD30 gene in human genomic DNAhave been developed.

Animals↗

PubMed2001

Mucosal immunity, respiratory illness, and competitive performance in elite swimmers.

PURPOSE: Exercise and training are known to elicit changes in mucosal humoral immunity, but whether these alterations have any impact on competitive performance remains unclear. This investigation examined relationships between salivary immunoglobulin (Ig) concentration, the incidence of respiratory tract illness (RTI), and competitive performance in elite swimmers. METHODS: Forty-one members of the Australian Swimming Team (21 males and 20 females) aged 15-27 yr were monitored during preparations for the 1998 Commonwealth Games. Twenty-five coaches and staff (19 males and 6 females) aged 32-65 yr, serving as "environmental controls," were also monitored. Salivary IgA, IgM, and IgG and albumin concentration (mg.L-1) were measured in both groups in May 1998 and again in August 1998, 17 d before competition. Subjects were categorized as "ill" (at least one RTI) or "healthy". RESULTS: There were no significant changes in salivary IgA, IgM, or IgG concentration in the swimmers between May and August, nor were there any differences between healthy (N = 23) and ill (N = 18) swimmers. There was a significant positive relationship between IgM and performance in the male swimmers (r = 0.85, P < 0.001) but not for any other parameter. There was no significant difference in performance between ill and healthy swimmers (P = 0.11). Gold medal winners (N = 9) had higher IgM levels than other swimmers (N = 32) in May (P = 0.02) and higher IgG in August (P = 0.02). CONCLUSION: These data indicate that a season of training by elite swimmers did not alter salivary immunoglobulin concentrations, and the presence of RTI had no significant impact on competitive performance.

Adolescent↗

PubMed2001

Is conservative treatment for adenocarcinoma in situ of the cervix safe?

OBJECTIVE: To determine the long term results of treatment of adenocarcinoma in situ by conisation of the cervix using survival analysis. DESIGN: A retrospective study in six teaching hospitals in North West Thames. POPULATION: Eighty-five women with a histological diagnosis of adenocarcinoma in situ of the cervix in punch or cone biopsy were identified from pathology and clinical databases. RESULTS: In one patient a small focus of adenocarcinoma in situ was found in a cervical polyp. Subsequent cytology was normal and no further treatment was undertaken. The 84 remaining women underwent diathermy loop, cold knife cone biopsy, laser cone biopsy, or needle excision of the transformation zone. A hysterectomy or second conisation was performed in 31/84 women (36.9%) as part of the initial treatment. In all, nine (10.6%) had early invasive lesions of which four were squamous. Fifty-nine patients were treated conservatively following one or two conisations (median follow up 78 weeks, range 0-543 weeks). One had a subsequent hysterectomy for menorrhagia. Five women have undergone treatment for suspected recurrence, a 21.5% cumulative rate of further treatment by four years. The cumulative rate of histologically proven recurrence after conservative management was 4.3% at one year and 15% at four years. CONCLUSIONS: In those cases with clear margins in the cone biopsy, there is a place for conservative management of a selected group of patients who wish to preserve fertility. However, 16.7% of these will require further treatment after four years because of recurrent cytological abnormalities. Women who opt for conservative management should undergo regular, long term surveillance in a colposcopy clinic. Among those women with involved margins in the initial cone biopsy, there is a high incidence of residual disease. A second cone biopsy may be appropriate 'definitive treatment' for young women who wish to preserve their fertility if the margins of the second biopsy are clear and there is no evidence of invasion. Even among those for whom a hysterectomy is the proposed 'definitive treatment', a second cone biopsy may be required before hysterectomy to avoid inappropriate treatment of an occult invasive lesion.

Adenocarcinoma↗

PubMed1998

Safety study of nonoxynol-9 as a vaginal microbicide: evidence of adverse effects.

Nonoxynol-9 (N-9) is virucidal in vitro, and is therefore a candidate microbicide for preventing sexual transmission of HIV. However, the activity of N-9 is nonspecific, suggesting that virucidal levels may produce adverse effects including epithelial disruption, inflammation of the genital mucosa, or both. A randomized placebo controlled trial of daily use of 100 mg of N-9 took place for 1 week in 40 female volunteers. Outcome measures included symptoms, colposcopic and histologic changes in the genital tract, and impact on vaginal flora. Genital irritation was reported by 10 of the N-9 and 5 of the placebo group. Colposcopy showed erythema in 9 of the N-9 group and 2 of the placebo group. Histologic inflammation was found in 7 of the N-9 group and 2 of the placebo group. Inflammatory changes were characterized by patchy infiltration of the lamina propria predominantly with CD8+ lymphocytes and macrophages, in the absence of epithelial disruption. A transient reduction in numbers of lactobacilli was observed in 9 of the 15 women using N-9, and 6 of 18 women using placebo. N-9 used for 7 days in a standard spermicidal dose was associated with increased irritation, colposcopic and histologic evidence of inflammation and was more frequently associated with reduction in numbers of lactobacilli during gel use. The clinical significance of the recruitment of cells susceptible to HIV infection to the genital mucosa is unknown but raises concerns about the suitability of N-9 as a microbicide when given in this dose.

Administration, Intravaginal↗

PubMed1996

Histological verification of computerised carotid plaque characterisation.

The correlation between the computerised measurement of carotid plaque echogenicity on high resolution ultrasound imaging and plaque histology was studied in 52 patients undergoing carotid endarterectomy. Thirteen plaques were from asymptomatic patients, 15 were associated with amaurosis fugax, 10 with transient ischaemic attacks and 14 with stroke. Longitudinal images of the anterior and posterior component of each plaque were obtained by ATL Ultramark-4 Duplex scanner and were transferred to a computer. Using an image analysis program the median of the overall grey scale content of each plaque component was evaluated and used as a measure of echogenicity. Following carotid endarterectomy each plaque specimen was divided into anterior and posterior component and then fixed, oriented, sectioned and stained in the longitudinal plane corresponding to the ultrasound image. Plaque histology sections were then examined by computer morphometric analysis and the percentage surface areas of fibrous tissue, lipid deposits and haemorrhage were calculated. This was then correlated with the grey scale median for each plaque component. Plaques with a high lipid and haemorrhage content as established histologically had a low grey scale median (Spearman correlation r=-0.351, p<0.05) and those with a high fibrous content had a high grey scale median (r=0.411, p<0.001). This study has shown that computerised measurement of carotid plaque echogenicity correlates well with histology and could be used to predict plaque composition, thus identifying high risk plaques with high lipid and haemorrhage content.

Carotid Arteries↗

PubMed1994

Chronic pelvic pain caused by residual ovaries and ovarian remnants.

OBJECTIVE: To determine the diagnostic effectiveness and treatment of women with chronic lower abdominal pain due to residual ovaries or ovarian remnants. DESIGN: A prospective observational study. SETTING: Tertiary referral pelvic pain clinic. SUBJECTS: Seventeen women complaining of chronic pelvic pain of up to 25 years' duration, of whom seven had residual ovaries and 10 ovarian remnant(s). MAIN OUTCOME MEASURES: Persistent lower abdominal pain, pelvic tenderness and quality of life one year post-operatively. RESULTS: Six of the seven women with residual ovaries, and nine of the 10 women with presumed ovarian remnants experienced relief of the original pain, loss of pelvic tenderness and an improved quality of life. CONCLUSIONS: Residual ovaries after hysterectomy and ovarian remnants are established causes of chronic pelvic pain. Diagnosis and surgical removal is frequently difficult. Management strategies are proposed for both conditions.

Adult↗

PubMed1988

Pigmented dermatofibrosarcoma protuberans (Bednar tumour): melanocytic colonization or neuroectodermal differentiation? A clinicopathological and immunohistochemical study.

Approximately 5% of cases of dermatofibrosarcoma protuberans contain dendritic melanocytes; such lesions are often known as Bednar tumours. These neoplasms have received little attention in the literature but seem to show no great clinicopathological differences from conventional dermatofibrosarcoma protuberans except for the presence of melanocytes. The existence of such tumours, combined with ultrastructural evidence, has led some leading authors to regard them all as being of neuroectodermal origin. Seven examples of the pigmented variant are presented herein, of which six have been studied immunohistochemically and one has been examined ultrastructurally. Except for the presence of melanocytes in each tumour, no evidence of neuroectodermal (in particular perineural fibroblastic) differentiation has been demonstrated. The histogenesis of dermatofibrosarcoma protuberans and its pigmented variant is discussed. The possibility that the pigmentation may simply reflect secondary melanocyte colonization from the epidermis should be considered.

Adolescent↗

PubMed1987

Intrascrotal adenomatoid tumours.

The adenomatoid tumour occurs in the genital tract of both sexes and is probably of mesothelial origin. We describe its occurrence in five men, two of whom had an intratesticular tumour, and discuss the clinical features of this lesion and the lessons to be learned regarding the management of testicular and paratesticular swellings.

Adenoma↗

PubMed1986