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Biomedical subjects

M Sexton

Publications and source records attributed to M Sexton.

At least 19 recordsLinked to original sources
PubMed2005

Importance of radiation time and dose factors on outcome for childhood medulloblastoma.

The purpose of this study was to investigate the relationship of posterior fossa radiation therapy duration (PFRTD) and relapse-free survival (RFS) following adjuvant craniospinal RT for childhood medulloblastoma. A retrospective audit was performed assessing all children aged <18 years managed with adjuvant craniospinal RT for medulloblastoma in Australia and New Zealand in 1980-1993. Children receiving prolonged (>180 days) pre-RT chemotherapy were excluded. Data were obtained for potential prognostic factors in domains of patient, tumour and treatment factors. Radiation therapy time factors assessed were PFRTD and time interval from surgery to commencement of RT (SRTD). The end-point assessed was RFS and analysis was performed using Cox regression and Kaplan-Meier survival. One hundred and eighty-nine children were identified from 10 oncology units, with data available from 182 children for analysis. Median follow up was 5.3 years. Seventy-three per cent of children presented with disease confined to the cerebellum; 13% had initial neuraxis disease. Macroscopic resection was described in 54%; 42% received adjuvant chemotherapy. Median RT dose and RT duration to PF was 55 Gy and 45 days, respectively. Seventy-eight relapses occurred with a 10-year actuarial RFS of 58.2% (standard error +/- 4%). On univariate analysis, increasing PF dose (P = 0.002), age >5 years (P = 0.006), and more thorough extent of surgical resection (P = 0.043) were associated with improved RFS; PFRTD (P = 0.20) and SRTD (P = 0.51) were not associated with RFS. On multivariate analysis, although both PF dose (P = 0.004) and extent of surgery (P = 0.045) remained strongly significant, RT duration was now associated with RFS (P = 0.049). Other factors assessed that did not reach significance were patient age, local tumour extent, presence of internal shunt and use of chemotherapy. The importance of local treatment factors was confirmed in this audit with established prognostic factors such as primary tumour macroscopic resection and adequate PF RT dose being associated with RFS. A treatment time effect is weakly suggested, although less significant than RT dose delivered.

Adolescent↗
PubMed2001

Laryngo-pharyngeal carcinoma in childhood.

Laryngo-pharyngeal carcinoma is rare in children. We present two cases of squamous cell carcinoma of the laryngopharynx in children less than 15 years of age. Both patients presented with a prolonged history of symptoms and extensive disease at diagnosis. Early visualisation the vocal cords with flexible larygnoscopy is important in children presenting with symptoms suggestive of laryngeal pathology. Long-term complications of definitive local therapy for laryngopharyngeal carcinoma are important in young children. Evidence from studies in adult patients suggests that adjuvant chemotherapy may play a role in laryngeal preservation in a select group of patients.

Carcinoma, Squamous Cell↗
PubMed2001

Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer.

PURPOSE: To determine the maximum-tolerated dose of tirapazamine when combined with cisplatin and radiation in patients with T3/4 and/or N2/3 squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The starting schedule was conventionally fractionated radiotherapy (70 Gy in 7 weeks) with concomitant cisplatin 75 mg/m2 and tirapazamine 290 mg/m2 (before cisplatin) in weeks 1, 4, and 7 and tirapazamine alone 160 mg/m2 three times a week in weeks 2, 3, 5, and 6. Positron emission tomography scans for tumor hypoxia (18F misonidazole) were performed before and during radiotherapy. RESULTS: We treated 16 patients with predominantly oropharyngeal primary tumors, including 10 patients with T4 or N3 disease. Febrile neutropenia occurred toward the end of radiotherapy in three out of six patients treated on the initial dose level. Two of these patients also developed grade 4 acute radiation reactions. Another 10 patients were treated with the same doses, but the week 5 and week 6 tirapazamine doses were omitted. This resulted in less neutropenia and only one dose-limiting toxicity (DLT) (febrile neutropenia), and eight out of 10 patients completed treatment without any dose omissions. In these 10 patients, the acute radiation toxicities were not obviously enhanced compared with chemoradiotherapy regimens using concurrent platinum and fluorouracil. 18F misonidazole scans detected hypoxia in 14 of 15 patients at baseline, with only one patient having detectable hypoxia at the end of treatment. With a median follow-up of 2.7 years, the 3-year failure-free survival rate was 69% (SE, 12%), the 3-year local progression-free rate was 88% (SE, 8%), and the 3-year overall survival rate was 69% (SE, 12%). CONCLUSION: DLT was due unexpectedly to febrile neutropenia, which could be overcome by omitting tirapazamine in weeks 5 and 6. The combination of tirapazamine, cisplatin, and radiotherapy resulted in remarkably good and durable clinical responses in patients with very advanced head and neck cancers. It warrants further investigation.

Adult↗
PubMed2000

Surveillance for uterine abnormalities in tamoxifen-treated breast carcinoma survivors: a community based study.

BACKGROUND: Tamoxifen-treated breast carcinoma survivors are at elevated risk of endometrial carcinoma. Whether to recommend annual surveillance for uterine abnormalities in this population is currently under debate. METHODS: This study was a cross-sectional, community-based investigation of tamoxifen use and the frequency of surveillance for endometrial carcinomas in 541 women with breast carcinoma. Study participants whose breast carcinoma was diagnosed in 1994 were interviewed in 1998. Data were collected from a telephone interview and from a cancer registry record. Tests for uterine abnormalities, based on participant reports of endometrial biopsy and transvaginal ultrasound, were categorized according to frequency. Testing for uterine abnormalities was defined as irregular if women reported tests once every 3 years, on average, and as regular, if they reported annual tests. RESULTS: Forty-nine percent of respondents were current tamoxifen users, 12% were former tamoxifen users, and 39% reported never taking tamoxifen. Of respondents with a uterus (n = 385), 19% reported irregular and 30% regular testing for uterine abnormalities after their breast carcinoma diagnosis. Respondents more frequently reported transvaginal ultrasound (37%) than endometrial biopsy (29%). Women 65 years of age and older were significantly less likely to report regular surveillance for uterine abnormalities (16%) than those younger than 65 years (35%). Current tamoxifen users more frequently reported regular surveillance (43%) than either former (35%) or never tamoxifen users (15%). Multivariable analyses showed tamoxifen users were more likely to have regular (odds ratio [OR], 9.8; 95% confidence interval [CI], 4.4-21.8) or to have irregular testing for uterine abnormalities (OR, 3.9; 95% CI, 1.9-8.1) compared with women who never used tamoxifen, after adjustment for age, number of recent gynecologic visits, and gynecologic symptoms. CONCLUSIONS: The results of the current study indicate that half of the breast carcinoma survivors in this population were tested for uterine abnormalities. Although at increased risk, 38% of tamoxifen users never had a test. Clear guidelines need to be established for the type and frequency of testing for uterine abnormalities among tamoxifen-treated breast carcinoma patients.

Adult↗
PubMed1999

Cigarette smoking, alcohol consumption, and screening mammography among women ages 50 and older.

BACKGROUND: The associations among cigarette smoking and alcohol consumption with recent screening mammograms were evaluated among women ages 50 years and older. METHODS: The sample included 946 white and African-American women ages 50 years and older from the 1995 Maryland Behavioral Risk Factor Survey. Bivariate and logistic regression analyses were performed to evaluate the associations between current cigarette smoking and alcohol consumption in the past month (none, 1-7 drinks, >7 drinks) with obtaining a screening mammogram in the past 2 years (recent mammogram), controlling for sociodemographic and health variables. RESULTS: Seventy-eight percent of respondents had recent mammograms, 15% smoked cigarettes, 18% reported 1-7 drinks, and 12% reported >7 drinks in the past month. Smokers had lower mammography rates than nonsmokers (odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.30-0.75). Women who drank alcoholic beverages had higher mammography rates than nondrinkers (OR = 1.37, 95% CI = 1.03-1.83). Smokers had the lowest mammography rates, regardless of their consumption of alcohol. An interaction was observed among white but not African-American women: nonsmokers who consumed moderate amounts of alcohol (1-7 drinks) had the highest mammography rates in this subgroup. CONCLUSIONS: To reduce breast cancer mortality, it is important to increase screening mammography among all women over age 50 and especially among smokers and the oldest women.

Black or African American↗
PubMed1999

Adherence to asthma guidelines in general practices.

Adherence to asthma practice guidelines is low. Improved compliance could potentially improve care of patients with asthma. The purpose of this study was to determine if patients managed in a general practice with an associated asthma clinic are more likely to use asthma medications according to clinical practice guidelines than patients managed in the general surgery of the practice. A cross-sectional study of adult asthmatics, aged 18-55 years, was conducted in six British general practices. Prescription data on all asthma medication was collected for a 6-month period. Information on asthma clinic attendance, age, sex, employment status, other medical illness, and how patients used their inhaled beta2-agonist was collected through questionnaire. The prescription data for asthma medication and patient use of inhaled beta2-agonist were compared to the British Thoracic Society's (BTS) Guidelines for Management of Asthma in Adults to determine if the patient's asthma medication regimen was appropriate. There was no significant association found between appropriate asthma medication and asthma clinic attendance or other patient characteristics. Adherence to the BTS guidelines was low. Fifty-eight percent of the asthma patients used asthma medication regimens that were not consistent with the BTS guidelines published 1 year earlier. Adherence to the BTS guidelines was low regardless of patient characteristics, including asthma clinic attendance, age, sex, employment status, other medical illness, or individual practice. These findings underscore the need to document the utility of clinical practice guidelines which may improve physician compliance.

Adrenergic beta-Agonists↗
PubMed1999

Cigarette smoking and asthma symptom severity among adult asthmatics.

Contrary to what would be expected, smoking habits of asthmatics do not differ from those of the general population: approximately 30% of asthmatic patients smoke cigarettes. Although the relationship between smoking and the incidence of asthma has been well explored, little attention has been paid to documenting the relationship between smoking and asthma symptoms among adults with asthma. The objective of this study was to assess the association of cigarette smoking with asthma symptom severity. The present report is of a cross-sectional study of 225 asthmatics, aged 20-54 years, from six general practice clinics in East Anglia, U.K. The outcome measures are overall asthma symptom score (range 6.3-28) and three asthma symptom domains: respiratory (range 1.3-8), daily activity interference (range 2-8), and physical activity interference (range 3-12), generated from the sum of ordinal responses to questions on asthma symptom severity. Of the sample, 27.0% were current and 22.1% were former smokers. Current smokers more frequently had bothersome asthma symptoms than nonsmokers in both unadjusted analyses and analyses controlling for age, gender, recent visits to the general practitioner for asthma, and asthma medication use (p = 0.06). Respiratory symptoms (p = 0.03) and symptoms that affect daily activities (p = 0.03) were more strongly associated with smoking than symptoms that affect physical activities (p = 0.62). Our data suggest that smoking hastens asthma progression or affects disease control. Increased frequency of symptoms may be an indicator for potential morbidity among asthmatics, especially those who smoke cigarettes. The hazards associated with smoking among asthmatics need to be more clearly emphasized by physicians and public health officials in order to convince people with asthma who smoke to stop.

Adult↗
PubMed1998

Sex differences in the use of asthma drugs: cross sectional study.

OBJECTIVES: To assess the use of asthma drugs by men and women with asthma and to identify sex specific predictors for the use of oral steroids. DESIGN: Cross sectional study. SETTING: Six general practices in East Anglia. SUBJECTS: 103 men and 134 women aged 20-54 with asthma. MAIN OUTCOME MEASURES: Self reported use of agonists, inhaled steroids, and oral steroids. RESULTS: No sex difference was found in use of agonists or inhaled steroids. However a strong association existed between sex and oral steroid use. 40 (30%) women reported using oral steroids compared with nine (9%) men. Women were more than five times (odds ratio=5.5, 95% confidence interval 2.2 to 13.7) more likely to report use of oral steroids than men after asthma symptoms, age, visits to the general practitioner in previous six months, and time since diagnosis of asthma were controlled for. Women who had visited the general practitioner for asthma one or more times in the previous six months were four times (3.9, 1.6 to 9.5) as likely to report use of oral steroids. In addition, more frequent visits to the general practitioner for asthma were related in a dose-response manner to a greater likelihood of using oral steroids among women after asthma symptoms, age, and time since diagnosis were controlled for. This relation was not observed among men. CONCLUSION: Women used oral steroids more than men. The more frequent consultations with a doctor by women may result in more requests for oral steroids or doctors may preferentially prescribe oral steroids to women.

Adrenergic beta-Antagonists↗
PubMed1997

The association of nocturnal asthma with asthma severity.

The objective of this study is to assess nocturnal asthma as a marker for poor control of asthma. Cross-sectional study of asthmatic patients was conducted in six general practices in East Anglia, England. Subjects were 240 asthma patients, between the ages of 20 and 54 years, from the above general practices. A continuous asthma severity score (range 6-26), consisting of the summation of ordinal responses to questions regarding asthma symptoms during the last 6 months, was used for analysis. The crude association between nocturnal asthma and severity score was statistically highly significant. Regression analysis suggests that, after controlling for possible confounding variables, there remains a strong association between nocturnal asthma (NA) and severity, which is modified by self-report of current consultation for "nervous/emotional trouble" (current NT). In the absence of current NT, NA raises the severity score by 5.3 (95% CI 4.5, 6.2), whereas in the presence of current NT, NA raises the severity score by 8.2 (95% CI 4.8, 11.6). NA appears promising as a marker for poorly controlled asthma. Confirmation of the association found in this study by objective measures of severity would strengthen the utility of NA as a marker.

Adult↗
PubMed1996

Relationship between blood lead and dietary iron intake in preschool children. A cross-sectional study.

The relationship between dietary iron intake and blood lead levels in urban preschool children was investigated in a cross-sectional study of 299 children from 9 months to 5 years old. Mothers of children attending the University of Maryland Pediatric Ambulatory Clinic volunteered for the children and themselves to join the study. The data collected included nutritional status, socioeconomic status, medical history, and potential sources of lead exposure. Blood samples from all participants were evaluated for levels of blood lead, serum iron (ferritin), free erythrocyte protoporphyrin, calcium, and hematocrit. The average blood lead level (standard deviation) in the studied population was 11.4 (7.3) micrograms/dL. With multiple linear and logistic regression analyses to adjust for covariates, a negative association (P = 0.03) between blood lead and dietary iron intake was found. This finding is consistent with similar results from experimental studies. It is concluded that there is evidence that higher dietary iron intake is associated with lower blood lead among urban preschool children in the studied population.

Anemia, Iron-Deficiency↗
PubMed1996

Relationship between blood lead and nutritional factors in preschool children: a cross-sectional study.

OBJECTIVE: The purpose of this study was to assess the relationships between selected nutritional factors and blood lead levels of preschool children. METHODOLOGY: Data on 296 children, aged 9 to 72 months, who were cared for at the University of Maryland at Baltimore Pediatric Ambulatory Center were examined in this cross-sectional study. Nutritional status, socioeconomic aspects, medical history, and potential sources of lead exposure were assessed. Blood samples were evaluated for levels of blood lead, serum iron (ferritin), free erythrocyte photoporphyrin, calcium, and hematocrit. RESULTS: The average blood lead level was 11.4 micrograms/dL. Multicollinearity of nutritional factors was addressed using regression techniques. After adjusting for confounders, significant positive associations with blood lead were found for total caloric intake (P = .01) and dietary fat (P = .05). CONCLUSIONS: The findings of this study suggest that even when behavioral and environmental exposures to lead were statistically controlled, total caloric intake and dietary fat each had an independent and significant association with the level of blood lead.

Child, Preschool↗
PubMed1995

The evolving role of radiation therapy in paediatric oncology, Philadelphia, USA, 19-21 January 1995.

A summary of a conference reviewing recent developments and changes in the use of radiation therapy in paediatric oncology is reported. Although the use of radiation therapy has resulted in improved cure rates, the long-term complications of radiation in a paediatric population are recognised. More intensive systemic therapy and the increasing availability of prognostic data, including biological markers to tailor therapy to the individual patient, has resulted in a more selective use of radiation therapy. Changes in the management of specific tumour types are discussed.

Child↗
PubMed1995

Integrating smoking cessation into routine public prenatal care: the Smoking Cessation in Pregnancy project.

OBJECTIVES: In 1986, the state health departments of Colorado, Maryland, and Missouri conducted a federally-funded demonstration project to increase smoking cessation among pregnant women receiving prenatal care and services from the Women, Infants, and Children (WIC) program in public clinics. METHODS: Low-intensity interventions were designed to be integrated into routine prenatal care. Clinics were randomly assigned to intervention or control status; pregnant smokers filled out questionnaires and gave urine specimens at enrollment, in the eighth month of pregnancy, and postpartum. Urine cotinine concentrations were determined at CDC by enzyme-linked immunosorbent assay and were used to verify self-reported smoking status. RESULTS: At the eighth month of pregnancy, self-reported quitting was higher for intervention clinics than control clinics in all three states. However, the cotinine-verified quit rates were not significantly different. CONCLUSIONS: Biochemical verification of self-reported quitting is essential to the evaluation of smoking cessation interventions. Achieving changes in smoking behavior in pregnant women with low-intensity interventions is difficult.

Adult↗
PubMed1993

Radical radiation therapy for carcinoma of the vagina--impact of treatment modalities on outcome: Peter MacCallum Cancer Institute experience 1970-1990.

To determine the outcome of radical radiation therapy for carcinoma of the vagina, a retrospective analysis has been made of 103 patients referred with this diagnosis to the Peter MacCallum Cancer Institute from 1970 to 1989. Eighty-four patients were treated for cure, seventy-four patients with definitive radical radiotherapy and 10 patients with adjuvant post-operative radiotherapy. Results were analyzed from two eras--before and after 1985--reflecting changes in referral pattern, treatment policy, and outcome. Forty-eight patients were treated before 1985 (Stage I--24, Stage II--6, Stage III--15, Stage IV--3) and 36 patients after 1985 (Stage I--20, Stage II--3, Stage III--6, Stage IV--7). After 1985 more patients were treated with combined beam radiation and brachytherapy (23/36 vs. 16/48 prior to 1985). More extensive tumors were systematically implanted (Ir 192). (No implants before 1985; 15 implants and 8 intracavitary applications post 1985). Fewer were treated with external beam alone after 1985; 11/36 (31%) vs. 27/48 (55%) before 1985. A small number (7/84-8%) were treated with brachytherapy alone. Survival results were markedly improved after 1985 (22/36-61% vs 16/48-33%) due partly to the shorter period of follow-up, but due also to marked improvement in local control particularly in early stage disease. (1/23 vs. 12/30 recurrences in Stage I, II disease). Results indicate optimal results with radical radiation therapy occur only with adequate dose delivery best achieved with a judicious combination of external beam radiotherapy and brachytherapy. Interstitial implantation plays a crucial role.

Adenocarcinoma↗
PubMed1993

Microcystic adnexal carcinoma of the skin. A reappraisal of the differentiation and differential diagnosis of an underrecognized neoplasm.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a locally aggressive adnexal neoplasm whose histogenesis is disputed. Many cases referred to us had been misdiagnosed. OBJECTIVE: Our purpose was to clarify the differential diagnosis and differentiation of MAC. METHODS: We sought follow-up data and examined routinely stained sections from 17 cases. We performed immunoperoxidase stains for carcinoembryonic antigen, pilar keratin (AE13), proliferating cell nuclear antigen (PCNA), type IV collagen, p53, and CD34 on selected cases. RESULTS: Nine biopsy specimens had initially been misinterpreted. Cysts containing compact keratin or shadow cells were present in 11 cases, which we interpret as evidence of follicular differentiation. Sebaceous gland and duct as well as inner root sheath structures were seen in one case each. CD34 did not mark the clear cells as it does those of the outer root sheath. Staining for PCNA, type IV collagen, and p53 did not distinguish MAC from benign adnexal neoplasms. CONCLUSION: MAC can be distinguished from its simulants in adequate biopsy specimens. Incompletely excised lesions usually recur. Both follicular and sudoriforous differentiation is present. Type IV collagen, PCNA, and p53 antisera were not useful in differential diagnosis.

Adult↗
PubMed1992

Characterization of antibody-mediated inhibition of Pseudomonas aeruginosa adhesion to epithelial cells.

An enzyme-linked immunosorbent assay system was developed and used to study adhesion of Pseudomonas aeruginosa to human epithelial cells and the abilities of specific antibodies to inhibit this process. Human buccal epithelial cells coated onto microtiter plates were incubated with P. aeruginosa suspensions, and adherent bacteria were detected by using anti-P. aeruginosa serum and a horseradish peroxidase-conjugated secondary antiserum. Adhesion, quantitated as an increase in A405, varied linearly with increasing numbers of bacterial CFU added per well in the range of 10(5) to 10(8) CFU per well. Adhesion of P. aeruginosa increased following trypsinization of buccal epithelial cells. Preincubation of bacteria with monoclonal antibodies directed against P. aeruginosa outer membrane protein H2 inhibited adhesion with all eight of the isolates tested. Preincubation of P. aeruginosa with sera from infected cystic fibrosis patients also resulted in inhibition of adhesion in the enzyme-linked immunosorbent assay system. This inhibitory activity was shown to be due to two factors: P. aeruginosa-specific immunoglobulin G and a non-immunoglobulin G serum component. These data support the hypothesis that bacterial components other than pili are involved in adhesion and suggest that anti-P. aeruginosa antibodies may be of use in preventing adhesion and subsequent colonization with P. aeruginosa.

Animals↗