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Biomedical subjects

J S Brown

Publications and source records attributed to J S Brown.

At least 19 recordsLinked to original sources
PubMed2006

A comparison of outcomes for patients with oral squamous cell carcinoma at intermediate risk of recurrence treated by surgery alone or with post-operative radiotherapy.

Controversy remains about which patients at intermediate risk of recurrence of oral squamous cell carcinoma would benefit from radiotherapy. A retrospective review of computerised database and medical records for 462 consecutive patients at the Regional Maxillofacial Unit in Liverpool who were treated with primary surgery with or without post-operative radiotherapy was carried out. We classified 29% (134) of patients as being at 'low' risk of disease recurrence (pT1-2, N0 with clear margins), 29% (135) at 'high' risk (involved margins or lymph node extracapsular spread) and the remaining 42% (193) at 'intermediate' risk. Of those at intermediate risk, 41% (80/193) received adjuvant radiotherapy and their 5 year survival (SE) was 54% (6%) compared to 71% (5%) for those with primary surgery alone (P=0.002). A higher proportion of patients having radiotherapy had loco-regional recurrence (19/80 24%) compared to those treated by surgery alone (17/113 15%). The improved salvage rate for recurrent disease in the surgery alone group (8/17 53%), compared to those receiving radiotherapy (2/19 13%, P=0.05), indicates an advantage in withholding radiotherapy for patients at intermediate risk of recurrence. This study indicates a potential disadvantage associated with the use of postoperative radiotherapy for patients at intermediate risk of recurrence. A randomised trial comparing a watch and wait policy to postoperative radiotherapy in patients with an intermediate risk of recurrence is required to confirm the trend indicated in this retrospective data.

Aged↗
PubMed2006

An assessment of deprivation as a factor in the delays in presentation, diagnosis and treatment in patients with oral and oropharyngeal squamous cell carcinoma.

This study explores the relationship between deprivation and patient and professional delays in presentation and treatment of oral and oropharyngeal squamous cell carcinoma. The cohort comprised 559 consecutive previously untreated patients presenting to the Regional Maxillofacial Unit, Liverpool from 1 January 1992 to 31 December 2002. All had primary surgery. The head and neck database was searched together with a review of casenotes. Deprivation was scored using the Index of Multiple Deprivation 2000 (IMD 2000) from patient post codes. PATIENT DELAY: Similar numbers of patients presented to general dental and general medical practitioners. The predominant presenting symptom was either an ulcer or swelling and 38% had symptoms for 3 or more months. Patients with shorter duration of symptoms tended to be smokers, drinkers, with lower gum and floor of mouth tumours, and more advanced disease. Primary health professional, patient age, gender, marital status, and deprivation showed no obvious correlation with patient delay. PROFESSIONAL DELAY: For 78% of patients a referral letter from GPs and GDPs was sent to the MFU on the same day as the primary consultation. There was on average about 3 weeks from referral to definitive diagnosis and about another 3 weeks before having surgery. Professional delay was shorter in patients with more advanced tumours and for patients living in the most deprived of wards. Deprivation did not seem to significantly lengthen presentation or referral however it may be that it is associated with more rapidly growing tumours.

Adult↗
PubMed2006

Urinary incontinence and pelvic floor dysfunction in Asian-American women.

OBJECTIVE: The objective of the study was to describe the prevalence, risk factors, and impact of urinary incontinence and other pelvic floor disorders among Asian-American women. STUDY DESIGN: This was a population-based cohort study of older women randomly selected from age and race strata. RESULTS: Weekly urinary incontinence was reported by 65 of 345 Asian women (18%), with stress and urge incontinence being approximately equally common. In multivariate analysis, higher body mass index (greater than 25 kg/m2) was associated with both stress incontinence (odds ratio 4.90, 95% confidence interval 1.76 to 13.68) and urge incontinence (odds ratio 2.49, 95% confidence interval 1.01 to 6.16) in Asians. Hysterectomy was a significant risk factor for stress incontinence (odds ratio 2.79, 95% confidence interval 1.03 to 7.54). Only 34% of Asian women with weekly urinary incontinence reported ever having sought treatment. Pelvic floor exercises were the most common form of treatment, being used by 29% of Asian women with weekly incontinence. Asians were less likely then white women to report anal incontinence (21% versus 29%, P = .007), although this difference became nonsignificant after adjusting for differences in risk factors. CONCLUSION: Asian women share some risk factors for stress and urge urinary incontinence with white women. Urinary incontinence is associated with anal incontinence among Asian women.

Aged↗
PubMed2006

Timing and presentation of recurrent oral and oropharyngeal squamous cell carcinoma and awareness in the outpatient clinic.

The aim of this study was to assess the timing of outpatient review appointments in relation to tumour recurrence. A retrospective review of 278 consecutive previously untreated patients with oral and oropharyngeal squamous cell carcinoma (SCC) between 1995 and 1999 was performed. Information on the time of recurrence, site, presentation, treatment and outcome was collected. There were 54 (19%) patients who developed recurrent disease. Recurrence occurred at a median time of 8 months after the initial operation and most (49/54) within 2 years. Thirty-five patients (65%) presented with a new lump (7 local, 22 regional and 5 locoregional). Our policy is to review patients once a month for the first year and every other month for the second year. Patients were seen less frequently than expected, and one in five patients attended half or less than half as frequently as intended in the first year. Although 20 patients were aware of new symptoms from their recurrent disease fewer than half (9) brought their appointment forward. This study has emphasised the need for close clinical follow-up of patients previously treated for oral/oropharyngeal SCC if recurrent tumours are to be discovered and treated at the earliest opportunity.

Aged↗
PubMed2006

The influence of allogenic blood transfusion in patients having free-flap primary surgery for oral and oropharyngeal squamous cell carcinoma.

The influence of perioperative blood transfusion in oral and oropharyngeal squamous cell carcinoma remains uncertain. It is believed that blood transfusion downregulates the immune system and may have an influence on cancer recurrence and survival. In all, 559 consecutive patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma between 1992 and 2002 were included in this study. Known prognostic variables along with transfusion details were obtained from head and neck cancer and blood transfusion service databases, respectively. Adjusting for relevant prognostic factors in Cox regression, the hazard ratio for patients having 3 or more transfused units relative to those not transfused was 1.52 (95% confidence interval (CI) 0.93-2.47) for disease-specific and 1.52 (95% CI 1.05-2.22) for overall mortality. Blood transfusion of 3 or more units might confer a worse prognosis in patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma. Therefore, every effort should be made to limit the amount of blood transfused to the minimum requirement.

Adult↗
PubMed2006

Promoter methylation of P16, RARbeta, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing.

Methylation profiling of cancer tissues has identified this mechanism as an important component of carcinogenesis. Epigenetic silencing of tumour suppressor genes through promoter methylation has been investigated by a variety of means, the most recent of which is pyrosequencing. We have investigated quantitative methylation status in oral squamous cell carcinoma patients. Fresh tumour tissue and normal control tissue from resection margin was obtained from 79 consecutive patients undergoing resection of oral squamous cell carcinoma. DNA was extracted and bisulphite treated. PCR primers were designed to amplify 75-200 bp regions of the CpG rich gene promoters of p16, RARbeta, E-cadherin, cytoglobin and cyclinA1. Methylation status of 4-5 CpG sites per gene was determined by pyrosequencing. Significant CpG methylation of gene promoters within tumour specimens was found in 28% for p16, 73% for RARbeta, 42% for E-cadherin, 65% for cytoglobin and 53% for cyclinA1. Promoter methylation was significantly elevated in tumours compared to normal tissue for p16 (P = 0.048), cytoglobin (P = 0.002) and cyclin A1 (P = 0.001) but not in RARbeta (P = 0.088) or E-cadherin (P = 0.347). Concordant methylation was demonstrated in this tumour series (P = 0.03). Significant differences in degree of methylation of individual CpG sites were noted for all genes except RARbeta and these differences were in a characteristic pattern that was reproduced between tumour samples. Cyclin A1 promoter methylation showed an inverse trend with histological grade. Promoter methylation analysis using pyrosequencing reveals valuable quantitative data from several CpG sites. In contrast to qualitative data generated from methylation specific PCR, our data demonstrated p16 promoter methylation in a highly tumour specific pattern. Significant tumour specific methylation of cyclin A1 promoter was also seen. Cytoglobin is a novel candidate tumour suppressor gene highly methylated in upper aero-digestive tract squamous cancer.

Adult↗
PubMed2006

Cost-effectiveness of migraine prevention: the case of topiramate in the UK.

The aim of this study was to assess the cost-effectiveness of topiramate vs. no preventive treatment in the UK. Model inputs included baseline migraine frequency, treatment discontinuation and response, preventive and acute medical cost per attack [2005 GBP ( pound)] and gain in health utility. Outcomes included monthly migraines averted, acute and preventive treatment costs and cost per quality-adjusted life year (QALY). Topiramate was associated with 1.8 fewer monthly migraines and a QALY gain of 0.0384. The incremental cost of topiramate vs. no preventive treatment was about 10 UK pounds per migraine averted and 5700 UK pounds per QALY. Results are sensitive to baseline monthly migraine frequency, triptan use rate and the gain in utility. Incorporating savings from reduced work loss (about 36 UK pounds per month) suggests that topiramate would be cost saving compared with no preventive treatment. This analysis suggests that topiramate is a cost-effective treatment for migraine prevention compared with no preventive treatment.

Adult↗
PubMed2005

A comparison of tongue and soft palate squamous cell carcinoma treated by primary surgery in terms of survival and quality of life outcomes.

In the surgical management of oral cancer the resection and reconstruction of the mobile tongue and soft palate are most important if function is to be maintained. The present trend towards primary laryngeal surgery for early disease has emphasized the importance of primary surgery if good functional outcomes can be achieved. This study compares the functional and health-related quality of life outcomes for primary surgery and reconstruction of the anterior tongue and soft palate. From a cohort of 566 patients treated from 1992 to 2002, 118 fitted the criteria for anterior tongue and 44 for soft palate resection. University of Washington Quality of Life scores were available in around three quarters of patients. In terms of speech and swallowing a 3/4 or total anterior glossectomy had a worse outcome than a 1/4 or 1/2. In patients having a 3/4 or total resection of the soft palate however, the results showed a similar outcome to those with 1/4 or 1/2 resection. The functional results of 3/4 and total soft palate reconstruction were superior to 3/4 and total anterior tongue resections and were similar to the whole cohort. This finding extends the role of functional surgery in the oropharynx for which primary radiotherapy is often preferred to preserve function.

Carcinoma, Squamous Cell↗
PubMed2005

Trends in head and neck microvascular reconstructive surgery in Liverpool (1992-2001).

Microvascular reconstructive techniques in head and neck surgery are well established, but we are now entering an era of modification exemplified by perforator and free style free flaps. We present a review of the database introduced into the unit in 1992 over a 10-year period, during which time 977 patients with malignant disease were operated on and 620 defects were reconstructed with free flaps. There were 358 radial forearm flaps, 78 composite radial forearm flaps, 84 iliac crest flaps, 43 fibular flaps, 24 from the scapula, 26 from the latissimus dorsi, 4 from the rectus abdominis, and 3 from the lateral arm. The main changes over this time have been the use of more bulky flaps for larger resections of the tongue and the preference for iliac crest flaps over those from the fibula and forearm for composite reconstructions. Improving reliability of tissue transfer remains an important aim, and further development of reliable objective methods of monitoring of flaps is required.

Anastomosis, Surgical↗
PubMed2005

Mind the gap: developing the PH workforce in the North East and Yorkshire and Humber regions: a scoping stakeholder study.

OBJECTIVES: The aim of this study was to identify key issues around public health workforce development in the North of England, considering the gap between need and current capacity and the training requirements to deliver the public health and health improvement agenda. METHODS: Interviews were carried out with over 50 professionals in a variety of stakeholder organizations, seeking their views on priorities for workforce development and perceived opportunities and threats to the development of a good public health workforce. RESULTS: There was general recognition of a gap between current public health resources and what is needed to meet the public health agenda. Priorities included both increasing capacity at the specialist end of public health and raising general public health awareness at all levels of public organizations. Major barriers identified to meeting these needs included organizational difficulties, professional barriers and shortages of appropriate training and resources. Opportunities were seen to be presented by the increased amount of joint working and by national and local raising of awareness of public health issues. CONCLUSIONS: Across the health sector, local authorities, training organizations and voluntary sectors, similar issues and expectations were mentioned at both specialist and practitioner levels. However, it has not been possible in North East England to translate this finding into practical programmes in the absence of nationally identified resources to address the issue.

England↗
PubMed2005

Predictors of speech and swallowing function following primary surgery for oral and oropharyngeal cancer.

OBJECTIVES: To examine the association between the speech and swallowing aspect of health-related quality of life (HRQOL) and selected clinical parameters, and particularly to determine those that are predictive of good outcomes at 1 year after surgery. DESIGN: Prospective questionnaire and clinical study. SETTING: Regional Maxillofacial Unit. PARTICIPANTS: A total of 278 consecutive patients undergoing primary surgery for squamous cell carcinoma between 1995 and 1999. HRQOL was assessed using the University of Washington Quality of Life questionnaire (UW-QOL) pre-surgery, and post-surgery at 6 months, 1 year and later (median 39 months). MAIN OUTCOME MEASURES: Presentation of results was mainly descriptive, involving percentages and mean scores. Association of clinico-demographic factors with tumour site, and with UW-QOL swallowing and speech after 12 months, was tested with Fisher's exact or chi-squared tests as appropriate and modelled using logistic regression methods. RESULTS: Univariate relationships were seen between speech and swallowing scores and with tumour size, T staging, radiotherapy, type of surgery (primary closure or free tissue transfer), tumour site, extent of resection of posterior tongue and soft palate, and UW-QOL taste and saliva scores. Multiple logistic regression showed that no radiotherapy (P<0.001) and primary surgical closure/laser surgery (P=0.003) were the main predictors of good swallowing, and primary surgical closure/laser surgery was the main predictor of good speech (P<0.001) at 1 year. CONCLUSIONS: A number of clinical parameters can influence the speech and swallowing aspect of quality of life in these patients and when feasible, primary closure results in a better outcome than free flap reconstruction.

Aged↗
PubMed2004

Urinary incontinence in elderly women: findings from the Health, Aging, and Body Composition Study.

OBJECTIVE: To estimate the prevalence of and risk factors for stress and urge incontinence in a biracial sample of well-functioning older women. METHODS: We performed a cross-sectional analysis of 1,584 white and black women, aged 70-79 years, enrolled in a longitudinal cohort study. Participants were asked about incontinence, medical problems, and demographic and reproductive characteristics and underwent physical measurements. Using multivariable logistic regression, we compared women reporting at least weekly incontinence with those without incontinence. RESULTS: Overall, 21% reported incontinence at least weekly. Of these, 42% reported predominantly urge incontinence, and 40% reported stress. Nearly twice as many white women as black women reported weekly incontinence (27% versus 14%, P <.001). Factors associated with urge incontinence included white race (odds ratio [OR] 3.1, 95% confidence interval [CI] 2.0-4.8), diabetes treated with insulin (OR 3.5, 95% CI 1.6-7.9), depressive symptoms (OR 2.7, 95% CI 1.4-5.3), current oral estrogen use (OR 1.7, 95% CI 1.1-2.6), arthritis (OR 1.7, 95% CI 1.1-2.6), and decreased physical performance (OR 1.6 per point on 0-4 scale, 95% CI 1.1-2.3). Factors associated with stress incontinence were chronic obstructive pulmonary disease (OR 5.6, 95% CI 1.3-23.2), white race (OR 4.1, 95% CI 2.5-6.7), current oral estrogen use (OR 2.0, 95% CI 1.3-3.1), arthritis (OR 1.6, 95% CI 1.0-2.4), and high body mass index (OR 1.3 per 5 kg/m2, 95% CI 1.1-1.6). CONCLUSION: Urinary incontinence is highly prevalent, even in well-functioning older women, whites in particular. Many risk factors differ for stress and urge incontinence, suggesting differing etiologies and prevention strategies.

Age Factors↗
PubMed2003

Resistance gene homologues in Theobroma cacao as useful genetic markers.

Resistance gene homologue (RGH) sequences have been developed into useful genetic markers for marker-assisted selection (MAS) of disease resistant Theobroma cacao. A plasmid library of amplified fragments was created from seven different cultivars of cacao. Over 600 cloned recombinant amplicons were evaluated. From these, 74 unique RGHs were identified that could be placed into 11 categories based on sequence analysis. Primers specific to each category were designed. The primers specific for a single RGH category amplified fragments of equal length from the seven different cultivars used to create the library. However, these fragments exhibited single-strand conformational polymorphism (SSCP), which allowed us to map six of the RGH categories in an F(2) population of T. cacao. RGHs 1, 4 and 5 were in the same linkage group, with RGH 4 and 5 separated by less than 4 cM. As SSCP can be efficiently performed on our automated sequencer, we have developed a convenient and rapid high throughput assay for RGH alleles.

Amino Acid Sequence↗
PubMed2003

Factors that influence the outcome of salvage in free tissue transfer.

INTRODUCTION: The success of salvage techniques for free tissue transfer is well documented. The aim of this study was to identify factors that influenced the results of salvage operations in a group of patients who required early exploration. METHODS: From a database survey of 408 patients who had a total of 427 free tissue transfer reconstructions, 65 (16%) returned to the operating theatre within 7 days. A retrospective analysis of their progress was made from the case records. RESULTS: The flap chart was found to be highly accurate for the 65 patients who had returned to the operating theatre, reporting two false positives and one false negative. Forty patients had compromised flaps and 25 had haematomas that required evacuation. The commonest problem with flaps was venous congestion (33/40, 83%), and 29 flaps were successfully salvaged (73%). Most successful salvage attempts were made within 24 hours of the end of the initial operation. The salvage rate was higher for the radial fasciocutaneous flaps (25/30, 83%), than for composite flaps (2/7, 29%). A total of 24/427 flaps failed (6%). CONCLUSIONS: We now recommend hourly observations of the flap for 24 hours followed by 4-hourly monitoring for 48 hours. Improved monitoring techniques for composite grafts may result in more being salvaged and a better overall survival.

Anastomosis, Surgical↗
PubMed2003

Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread.

The prognostic significance of extracapsular spread of cervical metastases in oral cancer is still controversial. To investigate the importance of extent of extracapsular spread; the relationship between extracapsular spread and both traditional measures of metastatic disease and clinical/histological features of the primary tumour, and to determine their relative prognostic significance. The survival of 173 patients undergoing radical surgery and simultaneous neck dissection for oral/oropharyngeal squamous cell carcinoma with histologically confirmed nodal metastasis and followed for 2.2-12.3 years is reported and related to pathological features. The most predictive clinical/histopathological features were determined by Cox regression modelling. The 3-year survival probability was similar for patients with macroscopic and only microscopic extracapsular spread (33 and 36%, respectively, compared with 72% for patients with intranodal metastasis). The Cox model showed the most predictive factor was extracapsular spread followed by status of resection margins. Extracapsular spread should be incorporated into pathological staging systems. Even microscopic extracapsular spread is of critical importance and must be sought especially in small-volume metastatic disease.

Adult↗
PubMed2003

The prognostic implications of the surgical margin in oral squamous cell carcinoma.

The prime objective of tumour ablation in oral squamous cell carcinoma (OSCC) is the removal, with a 'margin' of normal tissue, of the whole tumour. Definition of what constitutes margin involvement varies. This study aims to examine the factors associated with close and involved surgical margins in the management of OSCC. A cohort of 200 consecutive patients with previously untreated OSCC provided the material for the study. Various clinical, operative and pathological parameters were related to the status of the surgical margin, as well as time to recurrence, and survival. Cox regression analysis of the survival was also undertaken. Of the 200 patients 107 (53.5%) had clear margins, 84 (42%) close and 9 (4.5%) involved. Poor correlation was found between the status of the surgical margin and clinical factors, but in contrast high correlation between histological indicators of aggressive disease and close or involved surgical margins. These results imply that close surgical margins in OSCC could be regarded as an indictor of aggressive disease.

Aged↗