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Biomedical subjects

Matthew S Mayo

Publications and source records attributed to Matthew S Mayo.

At least 19 recordsLinked to original sources

Reduction in proliferation with six months of letrozole in women on hormone replacement therapy.

The objective of this study was to determine if 6 months of the aromatase inhibitor letrozole, administered to postmenopausal women taking a stable dose of hormone replacement remedy, would be safe and would modulate biomarkers of breast cancer risk. The intent was to reduce the proliferation marker Ki-67 while maintaining adequate systemic levels of estradiol so as to avoid perimenopausal symptoms. Postmenopausal women at high risk for development of breast cancer and taking a stable dose of estrogen or estrogen plus progestin were screened by random periareolar fine needle aspiration (RPFNA). To be eligible, the acquired breast epithelial cells had to be characterized as cytologic atypia or borderline atypia with > or =1,000 epithelial cells on the cytomorphology slide; plus > or =500 epithelial cells on a slide processed for Ki-67 immunocytochemistry. Forty-two women were enrolled in the one arm study and received 2.5 mg letrozole per day for 6 months, followed by repeat assessment of biomarkers. Ki-67 was reduced by a median relative value of 66%. There was no significant change in breast cell cytomorphology; ER weighted index score; serum estradiol, testosterone, or IGF-1:IGFBP-3 ratio; mammographic breast density, or frequency or severity of perimenopausal symptoms. Given the dramatic reduction in proliferation, the effect of letrozole on risk and response biomarkers should be explored further in a randomized, placebo-controlled Phase IIB breast cancer chemoprevention trial.

Adult↗

Bayesian sample size calculations in phase II clinical trials using a mixture of informative priors.

A number of researchers have discussed phase II clinical trials from a Bayesian perspective. A recent article by Mayo and Gajewski focuses on sample size calculations, which they determine by specifying an informative prior distribution and then calculating a posterior probability that the true response will exceed a prespecified target. In this article, we extend these sample size calculations to include a mixture of informative prior distributions. The mixture comes from several sources of information. For example consider information from two (or more) clinicians. The first clinician is pessimistic about the drug and the second clinician is optimistic. We tabulate the results for sample size design using the fact that the simple mixture of Betas is a conjugate family for the Beta- Binomial model. We discuss the theoretical framework for these types of Bayesian designs and show that the Bayesian designs in this paper approximate this theoretical framework.

Algorithms↗

Pathways to health: a cluster randomized trial of nicotine gum and motivational interviewing for smoking cessation in low-income housing.

Despite high smoking rates among those living in poverty, few cessation studies are conducted in these populations. This cluster-randomized trial tested nicotine gum plus motivational interviewing (MI) for smoking cessation in 20 low-income housing developments (HDs). Intervention participants (10 HDs, n = 66) received educational materials, 8 weeks of 4 mg nicotine gum, and 5 MI sessions on quitting smoking. Comparison participants (10 HDs, n = 107) received 5 MI sessions and educational materials addressing fruit and vegetable consumption. Participants had a mean age of 46.3 years and were predominantly female (70%) and African American (83%). Biochemically-verified 7-day abstinence rates at 8 weeks were 6.1% and 5.6% in the intervention and comparison arms, respectively (p = ns); and at 26 weeks were 7.6% and 9.3%, respectively (p = ns). Results suggest that nicotine gum plus MI were not effective for smoking cessation in low-income housing. Programs are needed to enhance the effectiveness of pharmacotherapy and counseling in underserved populations.

Adult↗

Risk factors for lung cancer in Iowa women: implications for prevention.

BACKGROUND: Multiple risk factors possibly associated with lung cancer were examined as part of a large-scale residential radon case-control study conducted in Iowa between 1994 and 1997. We were particularly interested in stratifying risk factors by smoking status. Relatively little risk factor information is available for Midwestern rural women. METHODS: Four hundred thirteen female lung cancer cases and 614 controls aged 40-84, who were residents of their current home for at least 20 years, were included. Risk factors examined included cigarette smoking, passive smoking, occupation, chemical exposure, previous lung disease, family history of cancer, and urban residence. Multiple logistic regression analysis was conducted after adjusting for age, education, and cumulative radon exposure. RESULTS: As expected, active cigarette smoking was the major risk factor for lung cancer. While cessation of smoking was significantly associated with a reduced risk for lung cancer, the risk remained significantly elevated for 25 years. Among all cases, asbestos exposure was a significant risk. Among ex-smokers, pack-year history predominated as the major risk. Among never smokers, a family history of kidney or bladder cancer were significant risk factors (OR=7.34, 95% CI=1.91-28.18; and OR=5.02, 95% CI=1.64-15.39, respectively), as was a history of previous lung disease (OR=2.28, 95% CI=1.24-4.18) and asbestos exposure. No statistically significant increase in lung cancer risk was found for occupation or urban residence. CONCLUSIONS: Smoking prevention activities are urgently needed in rural areas of the United States. Relatives of individuals with smoking-related cancers are potentially at increased risk. Genetic risk factors should be more fully investigated in never smokers.

Adult↗

Treatment of pediatric suppurative mastoiditis: is peripherally inserted central catheter (PICC) antibiotic therapy necessary?

OBJECTIVE: A review of the treatment of pediatric acute mastoiditis requiring surgical intervention managed with and without PICC therapy postoperatively. STUDY DESIGN AND SETTING: Retrospective study of 42 cases from 1989 to 2004 treated at a regional children's hospital. RESULTS: Sixteen patients received postoperative PICC therapy and 26 received a course of oral antibiotics. The PICC group received on average 12.12 days of intravenous antibiotics compared to only 3.53 days for the non-PICC group (P < 0.001). No differences were observed between the two groups in treatment outcomes. One patient from each group required rehospitalization. One minor complication was experienced in a patient in the PICC group. There were no surgical complications. The total cost for outpatient PICC therapy increased treatment costs by approximately $1500 to $2500. CONCLUSIONS: Oral antibiotic therapy is sufficient after surgical intervention for acute pediatric suppurative mastoiditis without intracranial complications and does not result in adverse treatment outcome. SIGNIFICANCE: Use of PICC therapy after surgical intervention for mastoiditis should be limited. EBM RATING: B-3b.

Acute Disease↗

Prevalence of the metabolic syndrome in elementary school children.

AIM: To determine the prevalence of the metabolic syndrome (MS) and its related components in elementary-aged school children. METHODS: Three hundred and seventy-five 7-9-y-old boys (n=182) and girls (n=193) in the eastern Kansas area served as participants. Criteria for the MS were the presence of three or more of the following components: 1) central obesity (waist circumference>or=90th percentile in males and females); 2) elevated triglyceride concentrations (>or=1.13 mmol/l); 3) low HDL-C concentrations ( or=90th percentile, age and gender specific); or 5) elevated fasting glucose levels (>or=6.10 mmol/l). RESULTS: The prevalence of the MS in this sample was 5%, and was similar across gender and race. Fifty percent of the children had no components and 15% had at least two components, with elevated blood pressure the most common component (37%). CONCLUSION: The MS is prevalent even in young children at rates similarly reported in adolescents.

Black or African American↗

The effects of nicotine gum and counseling among African American light smokers: a 2 x 2 factorial design.

AIM: Approximately 50% of African American smokers are light smokers (smoke < or = 10 cigarettes a day). The prevalence of light smoking in the United States is increasing, yet there has not been a single smoking cessation clinical trial targeting light smokers. The purpose of this 2 x 2 factorial, randomized clinical trial was to evaluate the efficacy of nicotine gum (2 mg versus placebo) and counseling (motivational interviewing versus health education) for African American light smokers. DESIGN: Participants were assigned randomly to one of four study arms: 2 mg nicotine gum plus health education (HE); 2 mg nicotine gum plus motivational interviewing (MI); placebo gum plus HE; and placebo gum plus MI. PARTICIPANTS AND SETTING: A total of 755 African American light smokers (66% female, mean age = 45) were enrolled at a community health center over a 16-month period. INTERVENTION AND MEASUREMENTS: Participants received an 8-week supply of nicotine gum and six counseling sessions during the course of the 26-week study. Biochemical measures included expired carbon monoxide (CO) and serum and salivary cotinine. FINDINGS: Seven-day quit rates for nicotine gum were no better than for the placebo group (14.2% versus 11.1%, P = 0.232) at 6 months. However, a counseling effect emerged, with HE performing significantly better than MI (16.7% versus 8.5%, P < 0.001). These results were consistent across outcome time-points (weeks 1, 8, and 26). CONCLUSIONS: Results highlight the potential positive impact of directive information and advice-oriented counseling on smoking cessation. Studies are needed to assess other interventions that may further improve quit rates among African American light smokers who are motivated to quit.

Adult↗

Predictors of quitting among African American light smokers enrolled in a randomized, placebo-controlled trial.

OBJECTIVE: To examine the predictors of quitting among African American (AA) light smokers (<10 cigarettes per day) enrolled in a smoking cessation trial. METHODS: Baseline variables were analyzed as potential predictors from a 2 x 2 cessation trial in which participants were randomly assigned to 1 of 4 treatment groups: nicotine gum plus health education (HE) counseling, nicotine gum plus motivational interviewing (MI) counseling, placebo gum plus HE counseling, or placebo gum plus MI counseling. Chi-square tests, 2 sample t-tests, and multiple logistic regression analyses were used to identify predictors of cotinine (COT) verified abstinence at month 6. RESULTS: In the final regression model, HE rather than MI counseling (odds ratio [OR]=2.26%, 95% confidence interval [CI]=1.36 to 3.74), older age (OR=1.03%, 95% CI=1.01 to 1.06), and higher body mass index (OR=1.04%, 95% CI=1.01 to 1.07) significantly increased the likelihood of quitting, while female gender (OR=0.46%, 95% CI=0.28 to 0.76),</=$1,800/month income (OR=0.60%, 95% CI=0.37 to 0.97), higher baseline COT (OR=0.948%, 95% CI=0.946 to 0.950), and not completing all counseling sessions (OR=0.48%, 95% CI=0.27 to 0.84) reduced the odds of quitting. CONCLUSIONS: Individual characteristics may decrease the likelihood of quitting; however, the provision of directive, advice-oriented counseling focused on the addictive nature of nicotine, health consequences of smoking, benefits of quitting, and development of a concrete quit plan may be an important and effective facilitator of quitting among AA light smokers.

Black People↗

Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane.

We have completed a phase I trial in women of the proposed chemopreventive natural product indole-3-carbinol (I3C). Women received oral doses of 400, 600, 800, 1,000, and 1,200 mg I3C. Serial plasma samples were analyzed by high-performance liquid chromatography-mass spectrometry for I3C and several of its condensation products. I3C itself was not detectable in plasma. The only detectable I3C-derived product was 3,3'-diindolylmethane (DIM). Mean Cmax for DIM increased from 61 ng/mL at the 400-mg I3C dose to 607 ng/mL following a 1,000-mg dose. No further increase was observed following a 1,200-mg dose. A similar result was obtained for the area under the curve, which increased from 329 h ng/mL at the 400-mg dose to 3,376 h ng/mL after a 1,000-mg dose of I3C. Significant interindividual quantitative variation was seen in plasma DIM values within each dosing group, but the overall profiles were qualitatively similar, with no quantifiable DIM before dosing, tmax at approximately 2 h, and DIM levels near or below 15 ng/mL (the limit of quantitation), by 24 h. Different results were obtained for 14 subjects who received a 400-mg dose of I3C after 8 weeks of twice-daily I3C dosing. Although the predose sampling occurred at least 12 h after the last known ingestion of I3C, 6 of 14 subjects exhibited Cmax for DIM in their predose plasma. Despite this high initial value, plasma DIM for all subjects decreased to near or below the limit of quantitation within the 12-h sampling period. Possible reasons for this disparity between apparent t1/2 of DIM and the high predose values are discussed.

Administration, Oral↗

Some statistical issues in microarray gene expression data.

In this paper we discuss some of the statistical issues that should be considered when conducting experiments involving microarray gene expression data. We discuss statistical issues related to preprocessing the data as well as the analysis of the data. Analysis of the data is discussed in three contexts: class comparison, class prediction and class discovery. We also review the methods used in two studies that are using microarray gene expression to assess the effect of exposure to radiofrequency (RF) fields on gene expression. Our intent is to provide a guide for radiation researchers when conducting studies involving microarray gene expression data.

Artifacts↗

Papanicolaou testing among Native American and Hispanic populations.

OBJECTIVE: The purpose of this study was to explore the perceptions and knowledge of, and access to, Papanicolaou (Pap) testing among Hispanic and Native-American women. DESIGN: A cross-sectional descriptive study was conducted by surveying Hispanic and Native-American women. The survey was developed with the constructs of the Preventive Health Model and was designed to assess background characteristics, representation factors, social influence factors, and program factors among Hispanic and Native-American females. PARTICIPANTS: Hispanic (n=48) and Native-American (n=68) women aged 18 to 89 years. SETTING: The surveys were distributed in several community health event sites throughout the Kansas City Metropolitan Area. MAIN OUTCOME MEASURES: The primary response (dependant) variables include knowledge, cervical screening intentions, and perceptions regarding the use of the Pap test. RESULTS: Most of the women surveyed (97%) had heard about Pap testing and reported having had a Pap test. Abnormal Pap test results were reported by 36% of the respondents. Acculturation and less income were significant factors in whether respondents could afford a Pap test, had health insurance, had a regular healthcare provider, and worried that a Pap test would uncover cervical cancer. Income was additionally related to having a doctor recommend Pap testing, the ability to get to the doctors' office during office hours, and fear of a cervical cancer diagnosis. CONCLUSION: Acculturation (or language) and income were determinants of Pap screening behavior among Native-American and Hispanic women.

Acculturation↗

Selective Runx2-II deficiency leads to low-turnover osteopenia in adult mice.

Runx2 transcribes Runx2-II and Runx2-I isoforms with distinct N-termini. Deletion of both isoforms results in complete arrest of bone development, whereas selective loss of Runx2-II is sufficient to form a grossly intact skeleton with impaired endochondral bone development. To elucidate the role of Runx2-II in osteoblast function in adult mice, we examined heterozygous Runx2-II (Runx2-II(+/-)) and homozygous Runx2-II (Runx2-II(-/-))-deficient mice, which, respectively, lack one or both copies of Runx2-II but intact Runx2-I expression. Compared to wild-type mice, 6-week-old Runx2-II(+/-) had reduced trabecular bone volume (BV/TV%), cortical thickness (Ct.Th), and bone mineral density (BMD), decreased osteoblastic and osteoclastic markers, lower bone formation rates, impaired osteoblast maturation of BMSCs in vitro, and significant reductions in mechanical properties. Homozygous Runx2-II(-/-) mice had a more severe reduction in BMD, BV/TV%, and Ct.Th, and greater suppression of osteoblastic and osteoclastic markers than Runx2-II(+/-) mice. Non-selective Runx2(+/-) mice, which have an equivalent reduction in Runx2 expression due to the lack one copy of Runx2-I and II, however, had an intermediate reduction in BMD. Thus, selective Runx2-II mutation causes diminished osteoblastic function in an adult mouse leading to low-turnover osteopenia and suggest that Runx2-I and II have distinct functions imparted by their different N-termini.

Animals↗

Stress and quitting among African American smokers.

This study examined the relationship between stress and the likelihood of quitting among 300 urban African American smokers enrolled in the placebo arm of a controlled randomized trial assessing the efficacy of bupropion for smoking cessation. Participants were predominantly female, middle-aged, and of lower income. Participants received 7 weeks of placebo treatment and counseling as well as a self-help guide. Quit status and stress, measured with the Perceived Stress Scale and an adapted Hassles Index, were assessed at baseline, end of treatment, and 6 month follow-up. Results indicated that although baseline stress did not predict quitting at later visits, higher concurrent stress levels were associated with not being abstinent. Furthermore, changes (reductions) in perceived stress from baseline also predicted abstinence at the end of treatment. Results suggest that methods to help African Americans cope with stress as they attempt to quit smoking may prevent relapse to smoking.

Adult↗

The frequency of Barrett's esophagus in high-risk patients with chronic GERD.

BACKGROUND: The reported frequency of Barrett's esophagus (BE) in patients with reflux symptoms varies from 5% to 15%. The exact frequency of long-segment BE (LSBE) (>3 cm) and short-segment BE (SSBE) (<3 cm) in patients with chronic symptoms of GERD is uncertain. The aim of this study was to determine the frequency of LSBE and SSBE in consecutive patients presenting for a first endoscopic evaluation with GERD as the indication. METHODS: Consecutive patients presenting to the endoscopy unit of a Veterans Affairs Medical Center for a first upper endoscopy with the indication of GERD were prospectively evaluated. Demographic information (gender, race, age), data on tobacco use and family history of esophageal disease, and body mass index (BMI) were recorded for all patients. Before endoscopy, all patients completed a validated GERD questionnaire. The diagnosis of BE was based on the presence of columnar-appearing mucosa in the distal esophagus, with confirmation by demonstration of intestinal metaplasia in biopsy specimens. All patients with erosive esophagitis on the initial endoscopy underwent a second endoscopy to document healing and to rule-out underlying BE. Patients with a history of BE, alarm symptoms (dysphagia, weight loss, anemia, evidence of GI bleeding), or prior endoscopy were excluded. RESULTS: A total of 378 consecutive patients with GERD (94% men, 86% white; median age 56 years, range 27-93 years) were evaluated. A diagnosis of BE was made in 50 patients (13.2%). The median length of Barrett's esophagus (BE) was 1.0 cm (range 0.5-15.0 cm). Of the patients with BE, 64% had short-segment BE (SSBE) (overall SSBE frequency 8.5%). The overall frequency of long-segment BE (LSBE) was 4.8%. A hiatal hernia was detected in 62% of the patients with BE. Of the 50 patients with BE (median age 62 years, range 29-81 years), 47 (94%) were men and 98% were white. Eighteen patients (36%) were using tobacco at the time of endoscopy; 23 (46%) were former users. The median body mass index (BMI) of patients with BE was 27.3 (overweight). There were no significant differences between patients with LSBE and SSBE with respect to age, gender, ethnicity, BMI, and GERD symptom duration. CONCLUSIONS: The frequency of BE in a high-risk patient group (chronic GERD, majority white men, age > 50 years) who sought medical attention is 13.2%, with the majority (64%) having SSBE. These data suggest that the frequency of BE in patients with GERD has not changed. The true prevalence of BE in the general population, including those who do not seek care, is undoubtedly lower, currently and historically. The majority of patients with BE are overweight and have a hiatal hernia. Demographic data for patients with LSBE and SSBE are similar, indicating that these are a continuum of the same process.

Adult↗

The influence of depressive symptoms on smoking cessation among African Americans in a randomized trial of bupropion.

The influence of depressive symptoms on smoking cessation was examined among 600 African American smokers who participated in a randomized, placebo-controlled trial of sustained-release bupropion hydrochloride. Depressive symptoms were assessed at baseline, at week 6 (end of treatment), and at 6-month follow-up. The study examined three separate questions: (a) Whether depressive symptom levels were related to smoking cessation, (b) whether bupropion was more effective for smokers who had higher depressive symptoms at baseline (i.e., a moderator model), and (c) whether changes in depressive symptoms would account for the efficacy of bupropion for smoking cessation (i.e., a mediator model). Depressive symptoms at baseline were not predictive of cessation; however, increases in depressive symptoms from baseline predicted reduced cessation at the end of treatment, and higher depressive symptoms at week 6 and month 6 were associated with a reduced likelihood of smoking cessation at those time points. The moderator model was not supported, but the mediation analyses indicated that alleviation of depressive symptoms partly accounted for bupropion-assisted smoking cessation at end of treatment. Results extend prior findings to African American smokers and suggest that clinicians consider increases in depressive symptoms after quitting rather than baseline depressive symptoms in predicting risk of treatment failure. Results also suggest that even though bupropion may facilitate cessation in part by reducing depressive symptoms, it appears to be no more effective for more depressed smokers, and that mechanisms other than depressive symptom alleviation account for most of its efficacy.

Adult↗

Pathophysiological manifestations in mice exposed to anthrax lethal toxin.

Pathophysiological changes associated with anthrax lethal toxin included loss of plasma proteins, decreased platelet count, slower clotting times, fibrin deposits in tissue sections, and gross and histopathological evidence of hemorrhage. These findings suggest that blood vessel leakage and hemorrhage lead to disseminating intravascular coagulation and/or circulatory shock as an underlying pathophysiological mechanism.

Animals↗

A phase I study of indole-3-carbinol in women: tolerability and effects.

We completed a phase I trial of indole-3-carbinol (I3C) in 17 women (1 postmenopausal and 16 premenopausal) from a high-risk breast cancer cohort. After a 4-week placebo run-in period, subjects ingested 400 mg I3C daily for 4 weeks followed by a 4-week period of 800 mg I3C daily. These chronic doses were tolerated well by all subjects. Hormonal variables were measured near the end of the placebo and dosing periods, including determination of the urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio. Measurements were made during the follicular phase for premenopausal women. Serum estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin showed no significant changes in response to I3C. Caffeine was used to probe for cytochrome P450 1A2 (CYP1A2), N-acetyltransferase-2 (NAT-2), and xanthine oxidase. Comparing the results from the placebo and the 800 mg daily dose period, CYP1A2 was elevated by I3C in 94% of the subjects, with a mean increase of 4.1-fold. In subjects with high NAT-2 activities, these were decreased to 11% by I3C administration but not altered if NAT-2 activity was initially low. Xanthine oxidase was not affected. Lymphocyte glutathione S-transferase activity was increased by 69% in response to I3C. The apparent induction of CYP1A2 was mirrored by a 66% increase in the urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio in response to I3C. The maximal increase was observed with the 400 mg daily dose of I3C, with no further increase found at 800 mg daily. If the ratio of hydroxylated estrone metabolites is a biomarker for chemoprevention, as suggested, then 400 mg I3C daily will elicit a maximal protective effect.

Adult↗

Comparison of a visual to a computer-assisted technique for detecting apoptosis.

In many studies, fluorescent dyes (ethidium bromide [EB] and acridine orange [AO]) are used to stain DNA to determine if nuclei are apoptotic. However, there are numerous visual methods for counting these stained DNA that may lead to inaccuracies Measuring apoptosis by the visual counting method may be imprecise because of the variability of individuals' perception of color. Therefore, the authors compared a visual method of counting chromatin for apoptosis with a method relying on a computer program. They began counting chromatin using the visual method, in which individuals identify the stained DNA using their own visual perception. For comparison, they used a software-based counting method (analySIS software) to determine the color (hue) of the stained DNA. Using the numeric hue values from the software eliminates the variations in human color perception. Intra and interrater reliability of the visual and computer-assisted counting methods were evaluated with Spearman's. The authors found statistical significance in the intrarater reliability (r = 1.0, P = 0.0001 for all chromatin categories) and interrater reliability (r = 0.975, P = 0.005 for both readings) when using the software program. No statistical significance was found for the visual counting method, indicating inaccuracy between and within raters. Thus, the computer-assisted counting method of identifying the damaged DNA is more accurate and precise than the individual's visual perception of color. Based on these data, apoptosis measurements using color staining with EB and AO should be determined using hue values generated by a computer program and not by a researcher's visual assessment.

Acridine Orange↗