Biomedical subjects

D Roe

Publications and source records attributed to D Roe.

At least 19 recordsLinked to original sources

PubMed2003

Cost effectiveness of defibrillation by targeted responders in public settings.

BACKGROUND: Out-of-hospital cardiac arrest is frequent and has poor outcomes. Defibrillation by trained targeted nontraditional responders improves survival versus historical controls, but it is unclear whether such defibrillation is a good value for the money. Therefore, this study estimated the incremental cost effectiveness of defibrillation by targeted nontraditional responders in public settings by using decision analysis. METHODS AND RESULTS: A Markov model evaluated the potential cost effectiveness of standard emergency medical services (EMS) versus targeted nontraditional responders. Standard EMS included first-responder defibrillation followed by advanced life support. Targeted nontraditional responders included standard EMS supplemented by defibrillation by trained lay responders. The analysis adopted a US societal perspective. Input data were derived from published or publicly available data. Future costs and effects were discounted at 3%. Monte Carlo simulation and sensitivity analyses assessed the robustness of results. Standard EMS had a median of 0.47 (interquartile range [IQR]=0.32 to 0.69) quality-adjusted life years and a median of 14 100 dollars (IQR=8600 dollars to 21 900 dollars) costs per arrest. Targeted nontraditional responders in casinos had an incremental cost of a median 56 700 dollars (IQR=44 100 dollars to 77 200 dollars) per additional quality-adjusted life year. The results were sensitive to changes in time to defibrillation, incidence of arrest, and number of devices required to implement rapid defibrillation. CONCLUSIONS: Where cardiac arrest is frequent and response time intervals are short, rapid defibrillation by targeted nontraditional responders may be a good value for the money compared with standard EMS. The incidence of arrest should be considered when choosing locations to implement public access defibrillation.

Adult↗

PubMed2001

Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia.

PURPOSE: To determine the maximum-tolerated dose, pharmacokinetic interaction, and activity of PSC 833 compared with daunorubicin (DNR) and cytarabine in patients with poor-risk acute myeloid leukemia. PATIENTS AND METHODS: Patients received ara-C 3 g/m(2)/d on 5 consecutive days, followed by an IV loading dose of PSC 833 (1.5 mg/kg) and an 84-hour continuous infusion escalating from 6, 9, or 10 mg/kg/d. Daunorubicin was administered as a 72-hour continuous infusion at 34 or 45 mg/m2/d [corrected]. Responding patients received consolidation chemotherapy with DNR pharmacokinetics performed without PSC-833 on day 1, and with PSC-833 on day 4. Response was correlated with expression of P-glycoprotein and lung resistance protein (LRP), and in vitro sensitization of leukemia progenitors to DNR cytotoxicity by PSC 833. RESULTS: All 43 patients are assessable for toxicity and response. Grade 3 or greater hyperbilirubinemia (70%) was the only dose-dependent toxicity. Four patients (9%) succumbed to treatment-related complications. Twenty-one patients (49%) achieved a complete remission or restored chronic phase, including 10 of 20 patients treated at the maximum-tolerated dose of 10 mg/kg/d of PSC-833 and 45 mg/m(2) of DNR. The 95% confidence interval for complete response was 33.9% to 63.7%. Administration of PSC 833 did not alter the mean area under the curve for DNR, although clearance decreased approximately two-fold (P =.04). Daunorubicinol clearance decreased 3.3-fold (P =.016). Remission rates were not effected by mdr-1 expression, but LRP overexpression was associated with chemotherapy resistance. CONCLUSION: Combined treatment with infused PSC 833 and DNR is well tolerated and has activity in patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays elimination of daunorubicinol, but yields variable changes in DNR systemic exposure.

Acute Disease↗

PubMed2001

Comparing patients' and staff members' attitudes: does patients' competence to disagree mean they are not competent?

The ability to process and compare the benefits and risks of a proposed treatment is considered an important component of being competent to make treatment decisions. Whether psychiatric patients' expressed treatment choice reflects their personal preferences or a deficit in their decision-making process is unclear. The aim of the study was to assess the extent to which patients and staff agree or not on various treatment-related issues. A literature search was conducted to identify published articles comparing the perceptions and attitudes of staff and patients toward various treatment issues. Twenty-eight published articles over the last 40 years were located and their main findings summarized. Analysis of the findings revealed disagreement between patients and staff in 26 of the 28 articles. The consistency of the disagreement over time and across studies suggests that the disagreement might have more to do with the fundamental difference between being a patient and a staff member rather than a patient's cognitive deficits or psychopathology. It is crucial that both patients and staff work toward building bridges when discord appears consistent and pervasive.

Attitude of Health Personnel↗

PubMed2001

Progressing from patienthood to personhood across the multidimensional outcomes in schizophrenia and related disorders.

The conceptualization of outcome in schizophrenia has been modified since Krapelin's dementia praecox and is now thought to be more heterogeneous and multidimensional. Qualitative research reveals a deeper and more complete understanding of the complex processes involved. This study investigates and describes the subjective experience of the multidimensional outcome of schizophrenia. The findings are based on bimonthly comprehensive assessments conducted over a 1-year period with 43 persons who were hospitalized for schizophrenia and related disorders. Results reveal ongoing person-environment interactions, which constitute the nonlinear progression from "patienthood" to 'personhood" across the multidimensional outcome domains of work, treatment, and social relationship. To facilitate this difficult process, it is essential to simultaneously help consumers develop their strengths and increase society's awareness and commitment to meet their unique needs.

Adolescent↗

PubMed2001

Differences in self-disclosure in psychotherapy between American and Israeli patients.

This study investigated differences in extent and patterns of disclosure in psychotherapy between American (n = 164) and Israeli (n = 45) patients. Participants completed the Disclosure to Therapist Inventory-R, an 80-item measure that uses a rating scale to assess the extent to which psychotherapy patients have discussed each of 80 moderately to highly intimate topics with their most recent therapist. Analysis yielded no significant difference between groups in overall disclosure and high overlap in the topics most and least discussed. Both groups frequently discussed aspects of their personalities they disliked, feelings of desperation or depression, and feelings of rage or anger towards parents. Findings suggest universal concerns may outweigh the cultural context in which therapy occurs.

Adolescent↗

PubMed2000

The effects of dietary selenomethionine on polyamines and azoxymethane-induced aberrant crypts.

We evaluated the effects of dietary selenomethionine supplementation on colonic polyamine levels and the ability of L-selenomethionine supplementation to modulate the carcinogenic activity of azoxymethane (AOM) in the rat colon. Four-week-old male F344 rats were treated with 15 mg/kg body weight of AOM once a week for 2 weeks. Dietary selenomethionine at a concentration of either 1 or 2 ppm was administered in AIN-76A rodent diet to AOM-treated animals for 16 weeks. Aberrant crypt foci (ACF), precursor lesions of colon cancer, were investigated after the 16 week treatment course. Selenomethionine given in the diet at 2 ppm markedly reduced the number of aberrant crypt foci. The multiplicity of ACFs (i.e. the number of aberrant crypts/focus) and the percentage of microadenomas were also affected by selenomethionine in a dose dependent manner. However, evaluation of the colonic tissue polyamine levels between control and treated groups showed no significant difference. These results demonstrate that selenomethionine can modulate the development of AOM-induced premalignant lesions through a polyamine-independent mechanism.

Alanine Transaminase↗

PubMed2000

Chromosome abnormalities in malignant melanoma: clinical significance of nonrandom chromosome abnormalities in 206 cases.

We report the cytogenetic abnormalities from a series of 206 primary malignant melanoma specimens referred to a single institution. A total of 169 out of 206 unique cases had chromosome breakpoints. A previously described statistical method was used to detect nonrandom distribution of chromosome breakpoints at the level of chromosome regions. Nonrandom occurrence of chromosome breakpoints (indicating that the observed number of breaks significantly exceeded the expected number of breaks) was detected in 28 regions, suggesting a hierarchy of genetic abnormalities in melanoma. Clinical variables and tumor characteristics were analyzed for associations with the presence of any nonrandom chromosome breakpoints; with individual, nonrandomly involved chromosome regions; and with paired, nonrandomly involved chromosome regions. No nonrandomly involved chromosome regions or pairs of regions appeared to significantly affect survival. These results identify recurring, nonrandom chromosome abnormalities in malignant melanoma. These results suggest that recurring, nonrandom chromosome alterations play a key role in the etiology and/or progression of malignant melanoma and identify targets within the genome for molecular genetic studies.

Chromosome Aberrations↗

PubMed2000

SPECT imaging with the D(4) receptor antagonist L-750,667 in nonhuman primate brain.

The suitability of an (123)I-labeled form of the putative D(4) receptor ligand L750,667 as a radiotracer for single photon emission computed tomography imaging was assessed in nonhuman primates. [(123)I]L750,667, labeled by iododestannylation, was administered to baboons in bolus and bolus plus constant infusion paradigms and imaged for 6 h. Total [(123)I]L750,667 brain uptake peaked (2.3% injected dose) at 15 min postinjection. [(123)I]L750,667 uptake was observed in all brain regions measured including diencephalon, brainstem, basal ganglia, cingulate cortex, and cerebellum, and slightly lower levels were noted in the frontal, parietal, temporoinsular, and occipital cortices. Administration of the D(4) receptor antagonist NGD 94-1 (2 mg/kg) did not displace radioactivity from any of the brain regions examined. Thus, while L750,667 is selective for the D(4) receptor in vitro, because brain [(123)I]L750,667 uptake was not displaced by NGD 94-1 at receptor saturating doses, [(123)I]L750,667 does not appear to be a suitable radiotracer for in vivo imaging of the D(4) receptor.

Animals↗

PubMed2000

The NAD+ precursors, nicotinic acid and nicotinamide protect cells against apoptosis induced by a multiple stress inducer, deoxycholate.

The bile salt, sodium deoxycholate (NaDOC), is a natural detergent that promotes digestion of fats. At high physiologic levels, NaDOC activates many stress-response pathways and induces apoptosis in various cell types. NaDOC induces DNA damage and activates poly(ADP-ribose) polymerase (PARP), an enzyme that utilizes NAD+ as a substrate to repair DNA. NaDOC also induces oxidative stress, endoplasmic reticulum (ER) stress and contributes to protein malfolding. The NAD+ precursors, nicotinic acid (NA) and nicotinamide (NAM) were found to protect cells against NaDOC-induced apoptosis. NA and NAM also decreased constitutive levels of both activated NF-kappaB and GRP78, two proteins that respond to oxidative stress. However, the mechanism by which NA and NAM protects cells against apoptosis does not involve a reduction in constitutive levels of oxidative stress. NA or NAM treatment increased the protein levels of glyceraldehyde-3-phosphate dehydrogense (GAPDH), a multi-functional enzyme, in the nucleus and cytoplasm, respectively. NAM did not activate the promoter/response elements of 13 stress response genes nor reduce intracellular non-protein thiols, suggesting that it is non-toxic to cells. NAM thus has promise as a dietary supplement to help prevent disorders involving excessive apoptosis.

Apoptosis↗

PubMed2000

Effects of piroxicam on prostaglandin E2 levels in rectal mucosa of adenomatous polyp patients: a randomized phase IIb trial.

Prostaglandin E2 (PGE2) has served as a surrogate end point biomarker in colorectal tumor progression. Colonic mucosa PGE2 levels of patients with colorectal adenomas or carcinomas have been shown to be higher than in control subjects. Our dose-finding study on piroxicam, a nonsteroidal anti-inflammatory drug with chemopreventive effects in preclinical colon carcinoma models, suggested that 7.5 mg/day was well tolerated and associated with significant depression of rectal mucosa PGE2 concentrations in comparison with baseline values. We therefore conducted a randomized Phase IIb cancer prevention clinical trial to investigate the chemopreventive properties of piroxicam in patients with a history of resected colorectal adenomatous polyps. After a 2-month run-in period, 47 participants were randomized to piroxicam at a dose of 7.5 mg/day, and 49 were randomized to a placebo. Rectal biopsy specimens were taken at the initial visit, at 2 months later during the run-in period, and at 6, 12, and 24 months after the start of the interventions. Mean PGE2 concentrations in the rectal mucosa of the piroxicam-treated patients differed significantly between visits (P < 0.001), and the values at the 6-month visit (P < 0.001) and 12-month visit (P = 0.005) differed significantly from the average baseline value. Unfortunately, we observed an incidence of adverse gastrointestinal side effects in patients treated with 7.5 mg/day of piroxicam similar to that seen for arthritis patients treated with 20 mg/day. Consequently, the gastrointestinal toxicities appear to override the potential benefit that piroxicam may offer as a long-term colon cancer chemopreventive agent.

Adenomatous Polyps↗

PubMed1999

Physical activity, body mass index, and prostaglandin E2 levels in rectal mucosa.

BACKGROUND: Evidence suggests a relationship between prostaglandin levels in colonic mucosa and risk of colon cancer. Physical inactivity and a higher body mass index (BMI; weight in kilograms divided by [height in meters]2) have been consistently shown to increase risk of this cancer. We investigated whether higher levels of leisure-time physical activity or a lower BMI was associated with lower concentrations of prostaglandin E2 (PGE2) in rectal mucosa. METHODS: This study was conducted in 41 men and 22 women, 42-78 years of age, with a history of polyps, who participated in a randomized clinical trial testing the effects of piroxicam on rectal mucosal PGE2 levels. An [125I]PGE2 radioimmunoassay kit was used to determine PGE2 levels in samples of extracted rectal mucosa collected before randomization. Leisure-time physical activity was assessed through a self-administered questionnaire collected at baseline. The reported time spent at each activity per week was multiplied by its typical energy expenditure, expressed in metabolic equivalents (METs), to yield a MET-hours per week score. A repeated measures model was used to assess the effect of BMI and physical activity as predictors of PGE2 concentration. All statistical tests were two-sided. RESULTS: After adjustment for age, a higher BMI was associated with higher PGE2 levels (P = .001). A higher level of leisure-time physical activity was inversely associated with PGE2 concentration (P<.03). An increase in BMI from 24.2 to 28.8 kg/m2 was associated with a 27% increase in PGE2. An increase in activity level from 5.2 to 27.7 MET-hours per week was associated with a 28% decrease in PGE2. CONCLUSIONS: Physical activity and obesity may alter the risk of colon cancer through their effects on PGE2 synthesis.

Adult↗

PubMed1999

Does Gustave Dax deserve to be forgotten? The temporal lobe theory and other contributions of an overlooked figure in the history of language and cerebral dominance.

Gustave Dax played an important role in the early history of cerebral dominance for language. He not only sent the 1836 memoir of Marc Dax, his deceased father, to Paris in 1863, but saw to it that this important document was published before Paul Broca's own article on cerebral dominance appeared later in 1865. In addition, he supported his father's contention that the left hemisphere is special for speech with 140 additional clinical cases. Gustave Dax's own unique contribution, however, has been almost completely overlooked. Although his theory lacked specificity, he preceded Meynert, Schmidt, and Wernicke in suggesting that the left temporal lobe may be especially important for speech.

Dominance, Cerebral↗

PubMed1999

Influence of health care, cost, and culture on breast cancer screening: issues facing urban American Indian women.

BACKGROUND: Breast cancer is the second leading cause of cancer death among American Indian women. Southwestern American Indian women are more likely to have distant spread of the disease, and 5-year survival from breast cancer is poor in comparison to U.S. whites. Mortality from breast cancer could be reduced by more than 30% in American Indian women if current recommendations for screening were followed. METHODS: A random household cross-sectional survey was conducted among 519 adult American Indian women in Phoenix, Arizona. Logistic regression was used to identify predictors of recent clinical breast examination and mammogram among those women aged 40 years and older. RESULTS: Just more than half (53.0%) of the women surveyed reported they had received a clinical breast examination in the last year, and 35.7% indicated they had received a mammogram in the last 2 years. Access to care, knowledge of the examinations, and health beliefs were positively associated with breast cancer screening in the multivariate analyses. CONCLUSIONS: The cancer screening rates observed in urban American Indian women are far below current national estimates and Healthy People 2000 Objectives. This study confirms the limited access of urban Indians to preventive health services, and supports a role for cancer education in improving screening participation in this special population.

Adult↗

PubMed1999

Enhancement of chemotherapy by manipulation of tumour pH.

The extracellular (interstitial) pH (pHe) of solid tumours is significantly more acidic compared to normal tissues. In-vitro, low pH reduces the uptake of weakly basic chemotherapeutic drugs and, hence, reduces their cytotoxicity. This phenomenon has been postulated to contribute to a 'physiological' resistance to weakly basic drugs in vivo. Doxorubicin is a weak base chemotherapeutic agent that is commonly used in combination chemotherapy to clinically treat breast cancers. This report demonstrates that MCF-7 human breast cancer cells in vitro are more susceptible to doxorubicin toxicity at pH 7.4, compared to pH 6.8. Furthermore 31P-magnetic resonance spectroscopy (MRS) has shown that the pHe of MCF-7 human breast cancer xenografts can be effectively and significantly raised with sodium bicarbonate in drinking water. The bicarbonate-induced extracellular alkalinization leads to significant improvements in the therapeutic effectiveness of doxorubicin against MCF-7 xenografts in vivo. Although physiological resistance to weakly basic chemotherapeutics is well-documented in vitro and in theory, these data represent the first in vivo demonstration of this important phenomenon.

Animals↗

PubMed1999

Exploring the relationship between the person and the disorder among individuals hospitalized for psychosis.

Recent research has suggested that people suffering from severe mental illness develop strategies to cope with their disorder. This study describes one specific strategy of coping with psychosis--through the use of narrative or a story. The report is based on bimonthly, semistructured research interviews conducted with 43 persons who were hospitalized for severe mental illness with psychotic features over a 1-year period. Qualitative analysis revealed five distinct categories, which seem to reflect different interactions between the participants' sense of self in relation to their illness. Narrative theory helped to identify subtleties in these interactions described by participants and conceptualize the categories. Conceptual and clinical implications of this process and future research opportunities are discussed.

Adaptation, Psychological↗

PubMed1999

Erythromycin-resistant Neisseria gonorrhoeae and oral commensal Neisseria spp. carry known rRNA methylase genes.

Two Neisseria gonorrhoeae isolates from Seattle and two isolates from Uruguay were resistant to erythromycin (MIC, 4 to 16 microg/ml) and had reduced susceptibility to azithromycin (MIC, 1 to 4 microg/ml) due to the presence of the self-mobile rRNA methylase gene(s) ermF or ermB and ermF. The two Seattle isolates and one isolate from Uruguay were multiresistant, carrying either the 25.2-MDa tetM-containing plasmid (Seattle) or a beta-lactamase plasmid (Uruguay). Sixteen commensal Neisseria isolates (10 Neisseria perflava-N. sicca, 2 N. flava, and 4 N. mucosa) for which erythromycin MICs were 4 to 16 microg/ml were shown to carry one or more known rRNA methylase genes, including ermB, ermC, and/or ermF. Many of these isolates also were multiresistant and carried the tetM gene. This is the first time that a complete transposon or a complete conjugative transposon carrying an antibiotic resistance gene has been described for the genus Neisseria.

Amino Acid Sequence↗

PubMed1999

Chromosome abnormalities in ovarian adenocarcinoma: II. Prognostic impact of nonrandom chromosome abnormalities in 244 cases.

In a large series of ovarian carcinomas from 244 patients, 134 cases had chromosome rearrangements. We showed before that the pattern of chromosome breakpoints involved 21 separate chromosome regions nonrandomly and, in 90% of cases with breaks, the breakpoints occurred within 13 commonly involved regions. Log-rank and proportional hazards regression analyses showed that the aggregate presence of a chromosome breakpoint in any of 21 nonrandomly involved regions and breaks in 9 distinct regions (1p1, 1q2, 1p3, 3p1, 6p2, 11p1, 11q1, 12q2, and 13p1) were associated with reduced patient survival. Breakpoints in other areas of the genome, including other nonrandomly involved regions, were not associated with decreased survival. Because many cases had breakpoints in more than one nonrandomly involved region, proportional hazards regression was also used to analyze for effects of each nonrandomly involved region, controlling for effects of other regions. With this approach, only breakpoints within 1p1 and 3p1 retained independent, deleterious effects on survival. Similarly, when nonrandomly involved regions were entered into a proportional hazards model containing clinical variables associated with altered patient survival (tumor grade, tumor stage, and residual disease > 1 cm after resection), only 1p1 (P = 0.007) and 3p1 (P = 0.04) were associated with independent, negative effects on survival. These studies demonstrate that chromosome breakpoints within specific, nonrandomly involved chromosome regions are associated with impaired survival in ovarian cancers. Regions 1p1 and 3p1 are identified as areas of particular significance and are appropriate targets for analytical techniques such as SAGE and microarray analysis.

Adenocarcinoma↗

PubMed1999

Chromosome abnormalities in ovarian adenocarcinoma: I. Nonrandom chromosome abnormalities from 244 cases.

Cytogenetics provides important insights into the molecular pathogenesis of human cancers. Although extensive data exist on recurring cytogenetic abnormalities in hematologic cancers, data on individual solid tumor types remain limited. Previous studies of ovarian carcinoma indicated the presence of multiple, complex clonal chromosome abnormalities. Cytogenetics remains one of a few techniques capable of detecting these multiple, simultaneously occurring genetic abnormalities. We describe cytogenetic abnormalities from a series of 244 primary ovarian cancer specimens referred to a single institution. A total of 201/244 cases had fully characterized clonal chromosome abnormalities, of which 134 showed clonal chromosome breakpoints. We used a novel statistical technique to detect nonrandom chromosome breakpoints at the level of chromosome regions. Nonrandom occurrence of chromosome breakpoints was detected at regions 1p1*, 1q1*, 1p2*, 1q2*, 1p3*, 1q3, 3p1*, 1q4*, 6q1*, 6p2, 6q2, 7p1*, 7q1, 7p2*, 11p1*, 11q1, 11q2*, 12p1, 12q2*, 13p1, and 19q1. Simultaneous occurrence of multiple abnormalities was common. However, 120/134 cases had breakpoints at one or more of 13 commonly involved regions (*), suggesting a hierarchy of genetic abnormalities. Among clinical and tumor variables that predict patient survival, tumor grade was significantly associated with the presence of chromosome breakpoints. In additional studies, we show that nonrandom chromosome abnormalities are associated with impaired survival in ovarian cancer and that specific, nonrandomly involved chromosome regions retain significant effects on survival when analyses are controlled for important clinical variables. Additional specific chromosome abnormalities in this series are described, including chromosome gains and losses in near-diploid cases and homogeneously staining regions. These results suggest that recurring, nonrandom chromosome abnormalities are important in the pathogenesis and/or progression of ovarian cancers, and target areas of the genome for molecular genetic studies.

Adenocarcinoma↗