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Biomedical subjects

A Bostrom

Publications and source records attributed to A Bostrom.

At least 19 recordsLinked to original sources

Are initial demyelinating event recovery and time to second event under differential control?

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) begins with an initial demyelinating event (IDE) that can be monosymptomatic, polysymptomatic, or polyregional. Failure to recover from the IDE is a known predictor of later development of disability. Factors that predict IDE recovery (outside optic neuritis) and time to second event are relatively unknown. The authors speculate that IDE recovery and time to second event are under separate biologic or genetic control, and as such, their clinical predictors are different. METHODS: Data on all UCSF MS clinic patients are entered prospectively into an ACCESS database. The authors identified all patients seen at the UCSF clinic within 1 year of their IDE. Expanded Disability Status Scale scores, functional system scores, and visual acuity were used to define IDE severity and recovery. RESULTS: The cohort included 186 patients (127 women, 59 men) with an average onset age of 34 +/- 10 years with 150 whites (non-Hispanic), 15 African Americans, 11 Hispanics, eight Asians, and two unknown/unreported. Worse onset severity predicted worse IDE recovery (23.1% of the patients with severe onset vs 32.9% with moderate severity vs 56.4% with mild onset recovered completely, p < 0.001). Polyregional onset predicted poor recovery compared to monoregional onset (46.2% vs 14.4%, p < 0.001). Nonwhite patients were 2.48 times more likely than whites to experience a second episode within 1 year from onset (95% CI: 1.45 to 4.23, p < 0.001). Similarly, age younger than 30 years predicted higher risk of a second exacerbation (hazard ratio 1.92, 95% CI: 1.17 to 3.15, p = 0.010). CONCLUSION: Initial demyelinating event recovery and time to second event may have distinct predictors. These findings suggest that recovery and time to second event might be under separate biologic control.

Adult↗

Living donor kidney transplant recipients and clinical trials: participation profiles and impact on post-transplant care.

Many transplant physicians believe that transplant candidates who enroll in clinical trials may have better outcomes than those who do not enroll. We examined a 7-year cohort (1997-2003) of adult primary, non-HLA identical, living donor kidney transplant (LDKT) recipients to determine whether demographic characteristics predisposed to enrollment and whether participation affected posttransplant care intensity and/or allograft function. Overall, 146 of 512 (28.5%) LDKT recipients enrolled in clinical trials. LDKT recipients who were male and those who lived <100 miles from our transplant center were significantly more likely to participate. During the first post-transplant year, study patients (SPs) had more clinic visits (p < 0.0001) and more allograft biopsies (p = 0.024) compared to nonstudy patients (NSPs), but comparable numbers of hospital readmissions and allograft ultrasounds. SPs and NSPs did not differ in 1-year creatinine clearance, delta creatinine or rejection incidence. Overall graft and patient survival were comparable. We conclude that clinical trial participants were disproportionately male, had increased intensity of post-transplant care but comparable outcomes to nonparticipants.

Adolescent↗

Renal artery stenosis evaluated with 3D-Gd-magnetic resonance angiography using transstenotic pressure gradient as the standard of reference. A multireader study.

PURPOSE: To evaluate 3D-Gd-magnetic resonance angiography (MRA) in detecting hemodynamically significant renal artery stenosis (RAS). MATERIAL AND METHODS: Thirty patients evaluated for atherosclerotic RAS by MRA and digital subtraction angiography (DSA) were retrospectively included. Standard of reference for hemodynamically significant RAS was a transstenotic gradient of 15 mmHg. DSA visualized 60 main renal arteries and 9 accessory arteries. Pressure gradient measurement (PGM) was available from 61 arteries. Three radiologists evaluated all examinations independently in a blinded fashion. RESULTS: RAS was present in 26 arteries. On MRA, each reader identified 4 of 9 accessory renal arteries, a detection rate of 44%. The three readers correctly classified 22/25/22 of the 26 vessels with a significant gradient as > or =60% RAS and 31/25/32 of the 35 with no significant gradient as < 60% RAS on MRA. Interobserver agreement was substantial. MRA image quality was adequate for RAS evaluations in all patients. ROC curves indicated that MRA is an adequate method for evaluating RAS. When screening for RAS, a 50% diameter reduction cut-off is better than 60%. RAS with 40-80% diameter reductions accounted for 65% of discrepancies. CONCLUSION: MRA is an adequate method for evaluating RAS limited mainly by poor detection rate for accessory renal arteries.

Aged↗

Cyclosporin a affects signaling events differentially in human gingival fibroblasts.

Gingival overgrowth is a common side-effect of the administration of cyclosporin A (CSA), phenytoin, and calcium blockers. To identify the signaling mechanisms possibly involved in the overgrowth, we examined how CSA affects the activities of MAP kinases and transcription factors in human gingival fibroblasts (HGF). The HGF were treated with CSA and TNF-alpha or PDGF. DNA-binding activity of NFAT, NFkappaB, and AP-1 transcription factors was determined by gel shift assay, and JNK, p38, and ERK1 and ERK2 activation was assessed by Western blot analysis of immunoprecipitates. The CSA inhibited NFAT, NFkappaB, and p38 and JNK activities; however, ERK1 and ERK2 were not affected significantly. AP-1 activity increased approximately 4.5-fold. Our results indicate that CSA affects signaling molecules in HGF differently from other cell types, and that a CSA-induced increase in AP-1 activity may affect the expression of fibrogenic molecules in gingiva and promote gingival overgrowth.

Cells, Cultured↗

IFNbeta lowers MMP-9/TIMP-1 ratio, which predicts new enhancing lesions in patients with SPMS.

OBJECTIVE: To 1)determine serum levels of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in patients with secondary progressive (SP) MS; 2)determine the relationship between these serum levels and MRI activity; and 3) evaluate the effect of interferon (IFN) therapy on these measures. BACKGROUND: High serum levels of MMP-9 and low levels of TIMP-1 predict the appearance of new gadolinium-enhancing (Gd+) lesions in relapsing-remitting (RR) MS. METHODS: Monthly Gd+ brain MRI and measures of serum MMP-2, MMP-9, TIMP-1, and TIMP-2 at 3-month intervals were performed for up to 3 years in 33 patients with SPMS participating in a phase III study of IFNbeta-1b. RESULTS: Patients who developed new Gd+ lesions had higher levels of MMP-9 than patients who did not develop Gd+ lesions (median 351 vs 226 ng/mL, p = 0.049). The ratio of MMP-9/TIMP-1 predicted new Gd+ lesion on the concurrent scan (OR = 2.23, 95% CI 0.99 to 4.99, p = 0.052) and on the following scan (OR = 2.16, 95% CI 1.01 to 4.63, p = 0.048), whereas levels of MMP-2/TIMP-2 did not. Median levels of TIMP-1 were higher and MMP-9 trended lower for IFNbeta compared to placebo recipients (TIMP-1: 1,450 vs 1,185 ng/mL, p = 0.024; MMP-9: 225 vs 339 ng/mL, p = 0.081). IFNbeta did not influence levels of MMP-2 and TIMP-2. CONCLUSION: The ratio of MMP-9/TIMP-1 may predict MRI activity in SPMS. The effect of IFNbeta-1b in MS, as measured by reduction in new Gd+ lesions, may be partly explained by altering MMP-9/TIMP-1 ratio.

Disease Progression↗

Induction of p53 expression in skin by radiotherapy and UV radiation: a randomized study.

BACKGROUND: p53 protein plays an important role in the response to DNA damage, and radiotherapy can cause radiation dermatitis. p53 and p21 levels increase in vitro when DNA is damaged by UVA, UVB, or gamma-radiation. To determine whether this response occurs in human skin and predicts the level of radiation dermatitis, we investigated levels of p53 and p21 in skin exposed to different types of radiation as part of a randomized study of women with breast cancer to evaluate topical steroid or emollient cream treatments for radiation dermatitis of their irradiated breast. METHODS: After surgery but before receiving tangential 5-mV photo-beam radiotherapy (2 Gy and 54 Gy) to the affected breast parenchyma, multiple areas on the backs of 50 women were irradiated with UVA and other areas were irradiated with UVB. Skin biopsy samples were taken from areas of normal unirradiated skin and all irradiated areas, and p53 and p21 were detected immunohistochemically. All statistical tests are two-sided. RESULTS: In skin irradiated with UVA or UVB, medians of 4.4% (range = 0%-40.5%) or 45.5% (range = 5.3%-74.6%) p53-positive keratinocytes, respectively, were observed. Radiotherapy produced medians of 31.0% (range = 0%-79.3%) p53-immunoreactive cells after 2 Gy of radiation and 83.2% (range = 37.6%-95.2%) after 54 Gy of radiation. Despite large interindividual differences in p53 response, comparable increases in epidermal p53 response were independent of the type of radiation. A correlation between p53 and p21 was also evident (r(s) =.78). In breast skin, there was no association between the p53 response and the degree of erythema (a measure of radiation dermatitis) and no statistically significant difference between treatment arms and p21/p53 responses. CONCLUSIONS: Individual responses to radiation-induced DNA damage varied widely and may be independent of the type of radiation. The epidermal p53 response does not predict the degree of radiation dermatitis.

Aged↗

Does centralized intake improve drug abuse treatment outcomes?

This study was designed to assess whether centralized intake and assessment in a drug abuse treatment system would lead to improved outcomes. Clients entering treatment through a centralized intake unit (CIU) or through individual programs (non-CIU) were interviewed at admission, and at 1 month and 1 year postadmission. Interviews included measures of treatment access and satisfaction, psychiatric symptoms, social support, and Addiction Severity Index composite scores. At treatment entry, CIU participants had more employment and psychological problems and lower social support, were more often required to be in treatment, and were more often placed on a waiting list. In analyses controlling for baseline differences between groups, there were main effects of time, but no CIU status effects or CIU status by time interactions. The CIU may have improved access to treatment for a more disabled population; however, clients entering treatment through the CIU did not have better outcomes than those entering treatment directly.

Adult↗

Appraisals of controllability and coping in caregivers and HIV+ men: testing the goodness-of-fit hypothesis.

The authors examined goodness of fit between controllability appraisals and coping in 82 HIV+ and 162 HIV-gay men experiencing the chronic stress of caregiving and 61 HIV+ gay men who were not caregiving. Multiple assessments of each individual over a 2-year period allowed replication of prior cross-sectional research examining goodness of fit, as well as the creation of intraindividual goodness-of-fit scores that were then used to examine within-person fluctuations in goodness of fit over time and goodness of fit as an individual difference variable related to adjustment. Results indicate that the importance of goodness of fit varies for different kinds of coping: The concept was supported for problem-focused coping and, to a lesser extent, for emotion-focused coping but not for meaning-focused coping. Within-subject variation in goodness of fit was related to within-subject variation in depressed mood, but between-subjects variation (individual differences) in fit was not associated with depressed mood, suggesting that goodness of fit is better understood as a transactional variable than as a personality or "coping style" variable.

Adaptation, Psychological↗

Crewmember and ground personnel interactions over time during Shuttle/Mir space missions.

BACKGROUND: Anecdotal reports from space and results from simulation studies on Earth have suggested that space crewmembers may experience decrements in their mood and interpersonal environment during the 2nd half of the mission and that negative emotions may be displaced to outside monitoring personnel. METHODS: To evaluate these issues, we studied 5 American astronauts, 8 Russian cosmonauts, and 42 American and 16 Russian mission control personnel who participated in the Shuttle/Mir space program. Subjects completed questions from the Profile of Mood States, the Group Environment Scale (GES), and the Work Environment Scale (WES) on a weekly basis during the missions. Subscale scores from these measures were analyzed using a piecewise linear regression approach that analyzed normally distributed subscales using a mixed model and non-normally distributed subscales by dichotomizing the variables and using a generalized estimating equation. RESULTS: After protecting against possible Type I errors due to multiple significance tests, only weak support was found for the biphasic model: the only significant findings in favor of the hypothesized 2nd half decrements in the interpersonal environment were in crewmember GES Leader Support and astronaut WES Work Pressure. Strongly consistent confirmation was found on all six tested measures for the hypothesized displacement of tension and dysphoria from crewmembers to mission control personnel. The hypothesized displacement of tension and dysphoria from mission control personnel to management was found on five of the six tested measures. CONCLUSIONS: The absence of moderate to strong support for the biphasic model suggests that crewmember interpersonal functioning does not depend appreciably on 1st half/2nd half time effects. The consistent support found for the displacement of tension and dysphoria suggests that countermeasures need to be developed to deal with this phenomenon in both crewmembers and mission control personnel.

Astronauts↗

Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis.

This study compared the efficacy of 3 16-week treatments for depression in 63 patients with multiple sclerosis (MS) and major depressive disorder (MDD): individual cognitive-behavioral therapy (CBT), supportive-expressive group therapy (SEG). and the antidepressant sertraline. Significant reductions were seen from pre- to posttreatment in all measures of depression. Intent-to-treat and completers analyses using the Beck Depression Inventory (BDI; A. T. Beck, C. H. Ward. M. Medelson. J. Mock, & J. Erbaugh, 1961) and MDD diagnosis found that CBT and sertraline were more effective than SEG at reducing depression. These results were largely supported by the BDI-18, which eliminates BDI items confounded with MS. However, the Hamilton Rating Scale for Depression (M. Hamilton, 1960) did not show consistent differences between treatments. Reasons for this inconsistency are discussed. These findings suggest that CBT or sertraline is more likely to be effective in treating MDD in MS compared with supportive group treatments.

Cognitive Behavioral Therapy↗

Psychosocial issues in space: results from Shuttle/Mir.

Important psychosocial issues involving tension, cohesion, leader support, and displacement of negative emotions were evaluated in a 4 1/2-year study involving five U.S. and four Russian Shuttle/Mir space missions. Weekly mood and group climate questionnaires were completed by five U.S. astronauts, eight Russian cosmonauts, and 42 U.S. and 16 Russian mission control subjects. There were few findings that supported our hypothesized changes in tension, cohesion, and leader support in crew and ground subjects using various time models, although crewmembers reported decreasing leader support in the 2nd half of the missions, and astronauts showed some evidence of a novelty effect in the first few weeks. There was no evidence suggesting a 3rd quarter effect among crewmembers on any of the 21 subscales evaluated. In contrast, there was strong evidence to support the hypothesized displacement of tension and negative emotions from crewmembers to mission control personnel and from mission control personnel to management. There were several significant differences in response between Americans vs. Russians, crewmembers vs. mission control personnel, and subjects in this study vs. people in comparable groups on Earth. Subject responses before, during, and after the missions were similar, and we did not find evidence for asthenia in space. Critical incidents that were reported generally dealt with events on-board the Mir and interpersonal conflicts, although most of the responses were from a relatively small number of subjects. Our findings have implications for future training and lead to a number of countermeasures.

Adaptation, Psychological↗

Changes in HIV-related risk behaviors following drug abuse treatment.

OBJECTIVES: To measure changes in HIV-related injection drug and sexual risk behaviors following drug treatment in a therapeutic community program. METHODS: We conducted a prospective cohort study of 261 drug users, randomly assigned to day or residential treatment. Participants were interviewed 2 weeks after entering treatment and 6, 12 and 18 months later (follow-up rate: 83%). RESULTS: Greater reductions in injection risk behaviors were associated with more time in treatment and the later waves of measurement. Wave was also associated with a reduction of sexual risk behavior. CONCLUSIONS: Drug abuse treatment was associated with a decrease in HIV-related risk behavior.

Adult↗

A randomized trial comparing day and residential drug abuse treatment: 18-month outcomes.

Extending an earlier report of 6-month outcomes, this study reports 12- and 18-month follow-up data for clients (N = 188) entering a therapeutic community drug treatment program who were randomly assigned to day or residential treatment conditions. Outcomes included Addiction Severity Index composite scores and measures of depression, psychiatric symptoms, and social support. Both groups showed significant change over time. The pattern of change indicated decreased problem severity in the 1st 6 months and then maintenance of lowered problem severity. Comparisons between groups indicated greater improvement for residential treatment clients on social problems and psychiatric symptoms but no differences on the remaining outcomes. Although residential treatment may offer some specific advantages, the conclusion here is that improvement among day treatment clients was not significantly different from that of residential treatment clients.

Adult↗

Caregiver supports: outcomes from the Medicare Alzheimer's disease demonstration.

A randomized 3-year study assessed the effect of expanded community-based services and case management on 5,254 caregivers of dementia clients. A tested policy concern was whether the financing of formal care would result in a reduction of informal assistance. Unmet needs task assistance for the demonstration's treatment group caregivers decreased by 30 percent within 6 months and by about 20 percent over 36 months relative to controls. While treatment group members used slightly more formal care over time, there were no differences between treatment and control groups in primary caregiver hours after 36 months, or in the number of tasks in which primary or secondary caregivers provided assistance.

Activities of Daily Living↗

Designing risk communications: completing and correcting mental models of hazardous processes, Part I.

Many risk communications are intended to help the lay public make complex decisions about risk. To guide risk communicators with this objective, a mental models approach to the design and characterization of risk communications is proposed. Building on text comprehension and mental models research, this approach offers an integrated set of methods to help the risk communication designer choose and analyze risk communication content, structure, and organization. An applied example shows that two radon brochures designed with this approach present roughly the same expert facts as a radon brochure widely distributed by the U.S. EPA but meet higher standards on other content, structure, and organization criteria.

Communication↗

Evaluating risk communications: completing and correcting mental models of hazardous processes, Part II.

We propose a decision-analytic framework, called the mental models approach, for evaluating the impact of risk communications. It employs multiple evaluation methods, including think-aloud protocol analysis, problem solving, and a true-false test that allows respondents to express uncertainty about their answers. The approach is illustrated in empirical comparisons of three brochures about indoor radon.

Air Pollution, Indoor↗