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Biomedical subjects

Stephen L Brown

Publications and source records attributed to Stephen L Brown.

At least 19 recordsLinked to original sources
PubMed2007

Five-year follow-up of trial of replication-competent adenovirus-mediated suicide gene therapy for treatment of prostate cancer.

Replication-competent adenovirus-mediated suicide gene therapy is an investigational cancer treatment that combines the oncolytic actions of human adenoviruses with the cytotoxic effects of chemo-radiosensitizing genes. Previously, we reported the short-term effects of this therapy in men with local recurrence of prostate cancer after definitive radiotherapy. With a median prostate-specific antigen (PSA) follow-up of 5 years, we report here the effect of the gene therapy on prostate-specific antigen doubling time (PSADT), a surrogate end point with significant prognostic power. When considering all evaluable subjects, the PSADT increased following the gene therapy from a mean of 17 to 31 months (median 16 to 22 months) (P=0.014). Assuming that salvage androgen suppression therapy androgen suppression therapy (AST) was uniformly initiated at a PSA of 15 ng/mL, the gene therapy would have delayed the projected onset of salvage therapy by an average of 2 years. The results indicate that replication-competent adenovirus-mediated suicide gene therapy may provide a potential long-term benefit to patients, as shown by a lengthening of the PSADT, and delay in when salvage therapy is indicated. Given the high morbidity associated with AST, we believe this approach could provide an attractive treatment option for selection of patients experiencing PSA relapse following definitive therapy.

Adenoviridae↗
PubMed2007

Early adolescents perceptions of health and health literacy.

BACKGROUND: Health illiteracy is a societal issue that, if addressed successfully, may help to reduce health disparities. It has been associated with increased rates of hospital admission, health care expenditures, and poor health outcomes. Because of this, much of the research in the United States has focused on adults in the health care system. This study investigated the effect of aspects of health literacy on the motivation to practice health-enhancing behaviors among early adolescents. METHODS: Measures were generally based on 3 National Health Education Standards for grades 5-8. Data were obtained from 1178 9- to 13-year-old students visiting 11 health education centers in 7 states. Students responded via individual electronic keypads. RESULTS: Multivariate logistic regression revealed that, in addition to age, difficulty understanding health information and belief that kids can do little to affect their future health, decreased the likelihood for interest in and desire to follow what they were taught about health. Further, low interest independently decreased motivation to follow what was taught. Girls were more likely to turn to school, parents, and medical personnel for health information. Older students were more likely to turn to school and to the Internet. CONCLUSIONS: Programs and curricula should be designed to increase student interest in health issues and their self-efficacy in controlling their own health destinies. Educators should also teach students to more effectively use nonconventional health information sources such as the Internet, parents, and medical professionals.

Adolescent↗
PubMed2006

Mitigation of radiation-induced optic neuropathy in rats by ACE inhibitor ramipril: importance of ramipril dose and treatment time.

PURPOSE: Radiation-induced optic nerve damage was reduced by ramipril, a prodrug angiotensin-converting enzyme inhibitor (ACEI). This study was to determine the optimum dose and administration time of ramipril for mitigating radiation-induced optic neuropathy. MATERIALS AND METHOD: Adult Fischer 344 male rats were treated with a single dose radiation 30 Gy by using radiosurgical technique. After irradiation, the animals were randomly assigned into groups of different ramipril doses and administration time; control (no treatment), radiation alone, radiation+ramipril in different doses and starting times of drug. Ramipril was given 0.5-1.5 mg/kg/day and AT1R blocker Losartan 20 mg/kg/day in drinking water for 180 days. Functional endpoint with visual evoked potential (VEP) and anatomical endpoint with gross and histological analysis with immunohistochemical (IHC) stain were used. RESULTS: Normal VEP measurements in un-irradiated rats were 46.2+/-7.9 ms. There was no change of VEP value until 4 months, but was lengthened to 188.1+/-58.7 ms at 6 months after radiation. By ramipril treatment with the dose of 1.5 mg starting at 2 weeks after radiation, VEP was significantly shortened to 105.7+/-88.5 ms at 6 months. Gross and microscopic structure of the irradiated optic nerve was well preserved in the ramipril-treated group. CONCLUSION: Ramipril can mitigate the radiation-induced optic nerve damage and preserve the functional integrity of the nerve. The results support early treatment with a high dose of ramipril after radiation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Application of arsenazo III in the preparation and characterization of an albumin-linked, gadolinium-based macromolecular magnetic resonance contrast agent.

A macromolecular magnetic resonance contrast agent (MMCA) was prepared by linking bovine serum albumin (BSA) to gadolinium (Gd) via a chelating agent, diethylenetriaminepentaacetic acid (DTPA). Colorimetric testing with 2,7-bis(o-arsenophenylazo)-1,8-dihydroxynaphthalene-3,6-disulfonic acid (arsenazo III) was performed to check for the appearance of free gadolinium during preparation and to quantify the Gd content in the final product. The complex was purified by dialysis, concentrated by lyophilyzation and characterized by magnetic resonance (MR) proton relaxation times. The resultant product had a molecular weight of about 90 kDa, Gd:BSA ratio of 14:1, and T1 and T2 relaxation times of 128.3 and 48.9 ms, respectively, at a field strength of 7Tesla (T) and at 20% concentration. Contrast enhancement of Gadomer-17 (a dendritic MMCA) and Gd-linked to BSA (Gd-BSA) was sequentially evaluated in a rat brain gliosarcoma model (n = 5) by MR imaging (MRI). Following intravenous injection, the blood concentration of Gadomer-17 fell rapidly, whereas that of Gd-BSA was almost constant for the duration of imaging. The areas of enhancement of both MMCAs were comparable. The spatial distribution of Gd-BSA showed good agreement with Evans blue-tagged albumin. Treatment with dexamethasone decreased Gd-BSA enhancement in the tumor. These results suggest that the arsenazo III method is applicable in preparing Gd-BSA to image brain tumors and their response to treatment. This simple method may also be useful for preparing other gadolinium-linked MMCAs.

Animals↗
PubMed2006

Perceptions of tobacco use in early adolescents.

In an effort to strengthen tobacco use prevention programs, this study explores early (9- to 13-year-old) adolescent motivations for and perceptions of use. Data were collected, via electronic keypads, from students visiting 12 health education centers in the U.S. (N=1433). Multivariate logistic regression showed that perceptions of frequent peer tobacco use and popularity of adolescent smoking, in addition to absence of family discussion of tobacco use, were associated with greater likelihood for smoking and of reporting past smoking. Even though most participants thought adolescents who smoke are very unpopular, more than 60% said the primary reason for adolescent smoking was that smokers believe it will make them popular. Participants thought the best way to prevent use was to give kids "other fun things to do instead." Recommendations are given for customizing curricula or programs.

Adolescent↗
PubMed2006

Coping style and distress in newly incarcerated male adolescents.

PURPOSE: To research relations between coping style and well-being in adolescent prisoners; previous research suggests that the stress of incarceration may be moderated by coping style in adult prisoners. METHODS: This research examined links between coping style and distress in 133 male adolescent prisoners on two occasions over a six-week period shortly after the commencement of their imprisonment. RESULTS: Anxiety and depression both declined over this period, with T1-T2 depression reduction negatively associated with T1 emotion-based coping and positively associated with T1 detachment. Emotion coping declined over the six weeks, whereas detachment coping increased. These changes were associated with improved depression and anxiety scores. CONCLUSIONS: Detachment and low emotional expression may assist incarcerated adolescents to adapt more positively to the initial period of imprisonment, and prisoners may adopt these more effective coping styles over time. These findings are explained in terms of adaptation to stressors specific to the prison environment.

Adaptation, Psychological↗
PubMed2006

Model selection in magnetic resonance imaging measurements of vascular permeability: Gadomer in a 9L model of rat cerebral tumor.

Vasculature in and around the cerebral tumor exhibits a wide range of permeabilities, from normal capillaries with essentially no blood-brain barrier (BBB) leakage to a tumor vasculature that freely passes even such large molecules as albumin. In measuring BBB permeability by magnetic resonance imaging (MRI), various contrast agents, sampling intervals, and contrast distribution models can be selected, each with its effect on the measurement's outcome. Using Gadomer, a large paramagnetic contrast agent, and MRI measures of T(1) over a 25-min period, BBB permeability was estimated in 15 Fischer rats with day-16 9L cerebral gliomas. Three vascular models were developed: (1) impermeable (normal BBB); (2) moderate influx (leakage without efflux); and (3) fast leakage with bidirectional exchange. For data analysis, these form nested models. Model 1 estimates only vascular plasma volume, v(D), Model 2 (the Patlak graphical approach) v(D) and the influx transfer constant K(i). Model 3 estimates v(D), K(i), and the reverse transfer constant, k(b), through which the extravascular distribution space, v(e), is calculated. For this contrast agent and experimental duration, Model 3 proved the best model, yielding the following central tumor means (+/-s.d.; n = 15): v(D) = 0.07 +/- 0.03 for K(i) = 0.0105 +/- 0.005 min(-1) and v(e) = 0.10 +/- 0.04. Model 2 K(i) estimates were approximately 30% of Model 3, but highly correlated (r = 0.80, P < 0.0003). Sizable inhomogeneity in v(D), K(i), and k(b) appeared within each tumor. We conclude that employing nested models enables accurate assessment of transfer constants among areas where BBB permeability, contrast agent distribution volumes, and signal-to-noise vary.

Animals↗
PubMed2006

Physical activity and negative emotional response after percutaneous coronary intervention.

BACKGROUND: The aims of this study were to investigate the association between negative emotional response (NER) and physical activity levels in percutaneous coronary intervention (PCI) patients, and to examine the extent to which physical activity levels were influenced by factors such as the patients' age, sex, and attendance at a cardiac rehabilitation (CR) programme. METHODS: A consecutive series of 200 PCI patients [mean age 59.0 (+/-10.1) years] completed telephone interviews 2 weeks and 6 months after their procedure. NER was assessed using 12 items addressing patients' perceptions and concerns regarding symptoms, diagnosis and prognosis. Physical activity was assessed by asking four questions relating to the frequency and duration of walking and of moderate activity. CR attendance, medical history and sociodemographic data were also collected. Hierarchical linear regression was used to assess the association between NER and physical activity over time. RESULTS: After controlling for baseline levels of moderate activity and other covariates, NER significantly predicted change in moderate activity over 6 months. Only baseline walking levels predicted the duration and frequency of walking at 6 months. CONCLUSION: NER can be considered an inhibitive factor towards increased moderate activity uptake after PCI. Walking after PCI does not appear to be affected by NER. These findings highlight the need to focus on improving the emotional aspects of patients' recovery.

Aged↗
PubMed2006

Gender, age, and behavior differences in early adolescent worry.

Early adolescents in the United States are increasingly exposed to a culture of worrisome messages. A degree of adolescent worry is normal, but the likelihood of a young person being anxious or depressed increases with the perceived number of worries. This study examined the effect of age, gender, and worry behavior on frequency of 8 adolescent worries. Data were obtained from 1,004 9- to 13-year-old students visiting 10 health education centers in 7 states. Students responded via individual, electronic keypads. Multivariate logistic regression revealed that boys worry more about the future, whereas girls worry more about being liked or being overweight. The oldest adolescents worry most about their appearance, being overweight, their friends, and problems at home. Adolescents who prefer talking to parents when worried are less likely to worry about being liked, while those who keep worries to themselves have more worries about grades. Those who turn to parents for information are less likely to worry about being liked, failure, their future, and their friends than those who turn to other sources (teachers, Internet, and friends). Recommendations are given to assist health educators and other school staff to recognize frequent worriers and plan school-based approaches to address their needs.

Adolescent↗
PubMed2005

9L gliosarcoma cell proliferation and tumor growth in rats are suppressed by N-hydroxy-N'-(4-butyl-2-methylphenol) formamidine (HET0016), a selective inhibitor of CYP4A.

The present study examined the effects of N-hydroxy-N'-(4-butyl-2 methylphenyl) formamidine (HET0016), a selective inhibitor of the formation of 20-hydroxyeicosatrienoic acid (20-HETE) on the growth of 9L rat gliosarcoma cells in vitro and in vivo. After 48 h of incubation, HET0016 reduced the proliferation of 9L in vitro by 55%, and this was associated with a fall in p42/p44 mitogen-activated protein kinase and stress-activated protein kinase/c-Jun NH(2)-terminal kinase phosphorylation and increased apoptosis. HET0016 inhibited epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-induced proliferation and diminished phosphorylation of PDGF receptors. A stable 20-HETE analog increased 9L cell proliferation. In vivo, chronic administration of HET0016 (10 mg/kg/day i.p.) for 2 weeks reduced the volume of 9L tumors by 80%. This was accompanied by a 4-fold reduction in the mitotic index, a 3- to 4-fold increase in the apoptotic index, and a approximately 50% decrease in vascularization in the tumor. HET0016 treatment increased mean survival time of the animals from 17 to 22 days. Liquid chromatography/mass spectrometry experiments indicated that neither 9L cells grown in vitro nor 9L tumors removed produce 20-HETE when incubated with arachidonic acid. The normal surrounding brain tissue, however, avidly makes 20-HETE, and this activity is selectively inhibited by HET0016. These results suggest that HET0016 may be the prototype of a class of antigrowth compounds that may be efficacious for treating malignant brain tumors. In vivo, it may act in part by inhibiting the formation of 20-HETE by the surrounding tissue. However, the antiproliferative effects of HET0016 on 9L cells in vitro seem unrelated to its ability to inhibit the formation of 20-HETE.

Amidines↗
PubMed2005

Second-generation replication-competent oncolytic adenovirus armed with improved suicide genes and ADP gene demonstrates greater efficacy without increased toxicity.

Replication-competent adenovirus-mediated suicide gene therapy has proven to be safe in humans when delivered intraprostatically. Although signs of efficacy are emerging, it is likely that further improvements will be needed before this technology will have widespread applicability in the clinic. Toward this end, we have developed a second-generation, replication-competent adenovirus (Ad5-yCD/mutTK(SR39)rep-ADP) containing an improved yeast cytosine deaminase (yCD)/mutant(SR39) herpes simplex virus thymidine kinase fusion (yCD/mutTK(SR39)) gene and the adenovirus death protein (ADP) gene. Relative to the first-generation Ad5-CD/TKrep adenovirus, Ad5-yCD/mutTK(SR39)rep-ADP demonstrated greater tumor cell kill in vitro and significantly greater tumor control in preclinical models of human cancer. Quantification of transgene volume following direct injection of fadenovirus into human tumor xenografts and the naïve canine prostate demonstrated that ADP enhanced adenoviral spread in vivo. Toxicology studies were performed to determine whether the improved yCD/mutTK(SR39) fusion and ADP genes increased toxicity. Intraprostatic injection of Ad5-yCD/mutTK(SR39)rep-ADP did not result in significantly increased toxicity relative to the parental Ad5-CD/TKrep adenovirus, the latter of which has proven to be safe in two Phase I prostate cancer clinical trials. Together, these results provide the scientific basis for evaluating the safety and efficacy of the second-generation Ad5-yCD/mutTK(SR39)rep-ADP adenovirus in humans.

Adenovirus E3 Proteins↗
PubMed2005

The posterolateral corner of the knee: repair versus reconstruction.

BACKGROUND: Injuries to the posterolateral corner of the knee are disabling. Despite improved understanding of this group of tendons and ligaments, the best surgical treatment of an unstable corner is not clear. HYPOTHESIS: Surgical repair of acute tears of the posterolateral corner has outcomes that are as good as those from reconstruction combined with an early motion rehabilitation protocol. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Sixty-three patients with 64 posterolateral corner tears were included in this study, with 39 posterolateral corner repairs and 25 reconstructions using the modified 2-tailed technique. Patients were evaluated with clinical and KT-2000 arthrometer examinations, as well as with Lysholm, International Knee Documentation Committee, and Short Form-36 scores. RESULTS: Fifty-six patients with 57 corner tears had minimum clinical follow-up of 24 months (range, 24-59 months). Acute primary repairs were performed on 35 patients, with 22 successful outcomes and 13 (37%) failures. Primary reconstructions were performed on 22 patients, with 20 successful outcomes and 2 (9%) failures. The difference in stability on clinical examination between repairs and reconstructions was significant (P < .05). Fourteen of 15 patients with failures of the primary posterolateral corner repair or reconstruction underwent successful revision reconstruction. The final patient with failure of the primary repair elected not to have a revision reconstruction. The final mean Lysholm knee score for both repair and reconstruction patients was 88.7 (range, 53-100). Final International Knee Documentation Committee objective scores yielded 14 (26%) normal, 28 (52%) near-normal, 9 (17%) abnormal, and 3 (6%) severely abnormal knees; the mean score was 60 at the most recent clinical evaluation. CONCLUSION: Results with repair followed by early motion rehabilitation have been significantly inferior when compared with results from reconstruction using the modified 2-tailed technique. The authors now use reconstruction rather than repair in the majority of patients who sustain posterolateral corner tears after high-energy injuries.

Adolescent↗
PubMed2005

Reconstruction of the posterolateral corner of the knee.

PURPOSE: To describe a technique for reconstruction of the posterolateral corner (PLC) of the knee and report the results of a prospective series of patients. TYPE OF STUDY: Case series. METHODS: Twenty-two patients with PLC injuries underwent reconstruction; 15 patients had multiligamentous knee injuries and 7 had isolated PLC injuries. We used the modified 2-tailed technique that reconstructs the popliteofibular ligament and fibulocollateral ligament. The technique includes use of an allograft tendon placed through transtibial and transfibular bone tunnels and around a screw on the lateral femoral condyle. All patients have been followed-up prospectively with clinical examinations, Lysholm knee scores, KT-2000 ligament arthrometer examinations, and evaluation of work and recreational functional status. RESULTS: There were 15 male and 7 female patients (mean age, 32 years; range, 17 to 55 years). Follow-up was a minimum of 24 months (mean, 29.5 months; range, 24 to 38 months). Mean range of motion is extension of 0.2 degrees (range, 0 degrees to 5 degrees) and flexion of 133.4 degrees (80 degrees to 144 degrees). The range of motion for the multiligamentous knees was 0.3 degrees to 129 degrees compared with 0 degrees to 143 degrees for knees with isolated corner injuries. Mean Lysholm knee scores were 90 for the entire group with a score of 92 for the multiligamentous knees and 88 for the isolated corners. Stability was clinically graded on a scale of 0 to 3 for both varus stress and external rotation, with a score of 2 or 3 indicating a failed PLC reconstruction. The mean score for varus stress was 0.2 for the whole group, with 0.3 in the multiligamentous knee and 0.1 for the isolated injuries. Similarly, the mean score for external rotation was 0.4, with a 0.5 for multiligamentous knee and 0.3 for isolated PLC injuries. There were 2 failures in the multiligamentous knee injury group (13%), compared with no failures in the isolated PLC group. The failure rate for the whole study was 9%. CONCLUSIONS: Reconstruction of the PLC using an allograft reconstruction of the popliteus, popliteofibular, and fibulocollateral ligaments yielded a stable reconstruction with excellent functional results. Predictably, range of motion and incidence of failure were both better for patients with isolated PLC injuries than for those with multiligamentous knees. Both groups, however, showed excellent overall functional results. LEVEL OF EVIDENCE: Level IV, case series.

Adolescent↗
PubMed2005

Bullying perspectives: experiences, attitudes, and recommendations of 9- to 13-year-olds attending health education centers in the United States.

Because 1 in 5 elementary school and 1 in 10 middle school students in the United States report being bullied, understanding student perspectives is crucial to prevention. This study solicited opinions of 9- to 13-year-olds regarding the magnitude of, causes of, and remedies for bullying. Data were obtained from 1229 students visiting 11 health education centers in seven states. Students responded via anonymous, electronic keypads. Half the respondents said they have been bullied at least once in a while. When bullied, almost half said they fight back, about a fourth tell an adult, and 20% do nothing; only 8% try to talk to the bully. Nearly two thirds claimed they tell or try to stop bullying when they see it, but 16% do nothing, and 20% join in. Almost three fourths believed bullying is "uncool," yet 42% said they bully at least occasionally. Bullies and victims were more likely to be middle school age. Frequent bullies were more likely to think it is cool, to fight back when bullied, and to join in when others are bullied. Two classes of victims were apparent. Victims who also bully often said that bullying occurs because others are not friendly to bullies or because bullies want to get their way; many also admitted that they do not know how it can be stopped. Victims who do not bully were most likely to do nothing when bullied but to try to stop the bullying of others. Recommendations are given for using these findings to customize curricula or programs.

Adolescent↗
PubMed2005

Relationships between risk-taking behaviour and subsequent risk perceptions.

Research has suggested that engagement in patterns of risk-taking behaviour might have a negative influence on the processing of risk information. However, risk-takers display higher risk perceptions than non-risk takers. This paradox might be resolved by removing the confounding effect of risk takers' increased exposure to risk. A longitudinal survey was administered to 255 motorists to examine the extent to which Time 1 (T1) self-reported speeding behaviour predicted exposure-free measures of Time 2 (T2) risk perceptions. Hierarchical regression analyses, controlling for demographics and T1 risk perceptions, showed that T1 speeding, and T1 to T2 speeding changes, both inversely predicted T2 risk perceptions. This suggests that successive increments in risk-taking behaviour will lead to progressively lower increases in personal risk perception. Possible foundations and implications of this effect are discussed.

Adult↗
PubMed2005

Optimism, coping style and emotional well-being in cardiac patients.

OBJECTIVE: Optimism is associated with superior emotional well-being in people with chronic and acute health problems, possibly because optimists are more likely to implement problem-focused coping. Another interpretation posits that optimism can be a defensive response designed to diminish affective reactions to health problems. The study objective is to investigate this possibility. DESIGN: A cross-sectional examination of relationships between dispositional and relative optimism, threat avoidance and emotional well-being in 85 cardiac patients. RESULTS: Blunting, a measure of threat avoidance, was found to be associated with both optimism and emotional well-being, and the common variance was predictive of positive affect. As expected, this link was stronger in people with low self-efficacy for problem-focused coping. CONCLUSION: These findings support a defensive interpretation of optimism amongst patients with recently-experienced cardiac disease, particularly as the effect was more pronounced in the low self-efficacy subsample. We discuss possible explanations for these findings and implications for the study of coping with serious illness.

Adaptation, Psychological↗
PubMed2004

Differences between problem and nonproblem gamblers in subjective arousal and affective valence amongst electronic gaming machine players.

Arousal-based theories of gambling suggest that excitement gained from gambling reinforces further gambling behavior. However, recent theories of emotion conceptualize mood as comprising both arousal and valence dimensions. Thus, excitement comprises arousal with positive valence. We examined self-reported changes in arousal and affective valence in 27 problem and 40 nonproblem gamblers playing electronic gaming machines (EGMs). Problem gamblers reported greater arousal increases after gambling and increases in negative valence if they lost. This accords poorly with an excitement-based explanation of problem gambling.

Adolescent↗