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Introduction: Breast Cancer Index (BCI) is a genomic assay that evaluates the benefit of extending endocrine therapy (ET) from 5 to 10 years and predicts recurrence risk (RR). We evaluated the association between BCI and Oncotype DX (ODX)., Patients: Women with hormone receptor (HR)-positive early-stage breast cancer (EBC) who had BCI and ODX performed were included., Methods: We performed a retrospective review of women with HR-positive EBC. BCI was categorized as predictive of extended ET versus not and ODX recurrence score (RS) as low (0-10), intermediate (11-25), and high (26-100). Univariate and multivariable logistic and linear regression models assessed the relationship between BCI and ODX, factors associated with each, and discordance between scores., Results: We identified 153 women, 22% were premenopausal and 18% were lymph node positive. The univariate logistic and linear models revealed an association between BCI predictive score and ODX RS (OR 7.84, CI, 2.63-23.36, P < .001) and log of BCI RR (Beta 0.04, CI, 0.02-0.06, P < .001). Seventy-four percent of BCI predictive scores were concordant with ODX RS and 83% of BCI RR was concordant with ODX RR. In a univariate logistic regression model, BCI predictive of ET benefit was associated with discordance (OR 28.00, CI, 10.58-74.02, P < .001). Higher ODX RR was associated with discordance (OR 1.92, CI, 1.42-2.59, P < .001)., Conclusion: We found a significant association between ODX and BCI predictive and prognostic scores. BCI predictive of extended ET benefit was associated with discordance with ODX RS. Higher predicted RR on ODX was associated with discordance with BCI predicted RR., Competing Interests: Disclosure Nicole Casasanta, Rima Patel, Melanie Kier, Sophie Sohval, Malin Hovstadius, Catherine Wu, Brittney Zimmerman, and Krystal Cascetta have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Ovarian cancer (OC) survivors commonly experience chronic symptoms including anxiety, depression, sleep disturbances, fatigue, physical symptoms, poor health-related quality of life (HRQOL), and a generally poor prognosis. Additionally, factors such as social isolation, stress, and depression are associated with key biological processes promoting tumor progression and poorer survival. Accessible psychosocial interventions to improve HRQOL and clinical outcomes are needed. This need is particularly true in rural settings where survivors may have less access to clinic-based support systems., Methods: The Living Well Study, a cluster-randomized Phase II multi-site clinical trial, is designed to evaluate the efficacy of a group-based, web-delivered psychosocial intervention (Mindful Living) verses a Health Promotion active control (Healthy Lifestyles) in increasing HRQOL and decreasing perceived stress (primary outcomes), depressive mood, anxiety, and fatigue (secondary outcomes) for 256 OC survivors who are <5 years post-primary therapy. Mindful Living targets key concerns of OC survivors and teaches stress reduction skills and coping strategies utilizing cognitive behavioral, mindfulness, and acceptance and commitment therapies. Healthy Lifestyles provides lifestyle information including exercise, nutrition, sleep, and other survivorship topics. Interventions consist of 11 consecutive weekly group sessions lasting 1.5-2 h led by trained facilitators and two booster sessions. Participants complete psychosocial questionnaires at baseline, post-intervention, at 6-months, and at 12-months. A subset completes bloodspots for analysis of inflammatory biology., Conclusion: Easily accessible psychosocial interventions addressing key concerns of OC survivors are an unmet need. The Mindful Living intervention has the potential to substantially enhance HRQOL and decrease distress in OC survivors. Trial registrationclinicaltrials.gov Identifier: NCT04533763., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct., Patients and Methods: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations., Results: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded., Conclusions: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial., Competing Interests: Disclosure The authors report the following conflicts of interest: ZB non-financial support, Bristol Myers Squibb (BMS); research support, Genentech/imCore. Honoraria from UpToDate. CL research support, Genentech/imCore. AS educational travel support, Pfizer and Astellas. MMA research support, BMS Lilly, AstraZeneca, and Genentech; consulting/advisory role, BMS, Lilly, AstraZeneca, Genentech, Merck, Achilles, and Abbvie. RH consulting/advisory role, BMS, Merck, Pfizer, Genetech, AstraZeneca, and GSK; research grant/funding, Merck, BMS, Pfizer, Genentech, GSK, and AstraZeneca. ST institutional research funding from AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Exelixis, BMS, Eisai, Nanostring, Cyclacel, Odonate, and Seattle Genetics; has served as an advisor/consultant to AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, BMS, Eisai, Nanostring, Puma, Sanofi, Celldex, Paxman, Puma, Silverback Therapeutics, G1 Therapeutics, AbbVie, Athenex, OncoPep, Outcomes4Me, Kyowa Kirin Pharmaceuticals, Daiichi-Sankyo, and Samsung Bioepsis Inc. MDG reports: Stock, Rappta Therapeutics; consulting/advisory role, BioMotiv, Janssen, Dendreon, Merck, GlaxoSmithKline, Lilly, Astellas, Genentech, BMS, Novartis, Pfizer, EMD Serono, AstraZeneca, Seattle Genetics, Incyte, Alleron Therapeutics, Dracen, Inovio Pharmaceuticals, Numab, Dragonfly Therapeutics; institutional research funding, Janssen, Dendreon, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, Genentech/Roche. TKC research support, AstraZeneca, Alexion, Bayer, BMS/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Lilly, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Sanofi/Aventis, Takeda; honoraria, AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, NCCN, Michael J. Hennessy (MJH) Associates, Inc. (Healthcare Communications Company with several brands such as OnClive, PeerView and PER), Research to Practice, L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Medical Oncology, NEJM, Lancet Oncology, Heron Therapeutics, Lilly Oncology; consulting or advisory role, AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Heron Therapeutics, Lilly, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, Pionyr, Tempest, Lilly Ventures; Stocks: Pionyr, Osel, and Tempest; leadership role, Director of Genitourinary Oncology Division at Dana-Farber and past President of Medical Staff at Dana-Farber, member of NCCN Kidney panel and the GU Steering Committee, past chairman of the Kidney Cancer Association Medical and Scientific Steering Committee, KidneyCan Advisory board, Kidney cancer Research Summit co-chair (2019-); patents, royalties or other intellectual properties related to checkpoint inhibitors biomarkers and ctDNA (no royalties made as to date); travel, accommodations, expenses, in relation to consulting, advisory roles, or honoraria; medical writing and editorial assistance support may have been funded by Communications companies funded by pharmaceutical companies (ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis, and others). TKC’s institution (Dana-Farber Cancer Institute) may have received additional independent funding of drug companies or/and royalties potentially involved in research around the subject matter. TKC has mentored several non-US citizens on research projects with potential funding (in part) from non-US sources/Foreign Components. DD Consulting/Advisory role, Mirati, Ipsen, Boehringer Ingelheim, Atheneum Partners, Boston Healthcare Associates, Dedham Group, Guidepoint Global Advisors; travel expenses, Ipsen. All other authors have declared no conflicts of interest., (Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Decline in fluid abilities in normal aging is associated with increased white matter lesions, measured on T1-weighted images as white matter signal abnormalities (WMSAs). WMSAs are particularly evident in hypertensive older adults, suggesting vascular involvement. However, because hypertension is assessed systemically, the specific role of cerebral arterial stiffening in WMSAs has yet to be demonstrated. In 93 cognitively normal adults (aged 18-87 years), we used a novel method to measure cerebral arterial elasticity (pulse relaxation function [PReFx]) with diffuse optical tomography (pulse-DOT) and investigated its association with WMSAs, age, and cognition. PReFx was associated with WMSAs, with older adults with low PReFx showing the greatest WMSA burden. PReFx in brain regions perfused by the middle cerebral artery showed the largest associations with WMSAs and partially mediated the relationship between age and WMSAs. Finally, WMSAs partially mediated the relationship between PReFx and fluid but not crystallized abilities scores. Taken together, these findings suggest that loss of cerebral arterial elasticity is associated with cerebral white matter lesions and age-related cognitive decline., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Despite important recent work, US public attitudes toward specific biobank consent models are not well understood. Public opinion data can help shape efforts to develop ethically sound and publicly trusted mechanisms for informing and consenting prospective biobank donors. The purpose of this study was to explore public perspectives toward a range of consent models currently being used or considered for use among comprehensive US biobanks., Methods: The study used an exploratory mixed-methods design, using focus groups and telephone surveys. Eligible participants were English-speaking residents in the catchment area of a comprehensive biobank being developed at the University of Iowa., Results: Forty-eight participants in seven focus groups and 751 survey participants were recruited. Biobanks were unfamiliar to almost all study participants but were seen as valuable resources. Most focus group (63%) and survey (67%) participants preferred a prospective opt-in over an opt-out consent approach. Broad, research-unspecific consent was preferred over categorical and study-specific consent models for purposes of approving future research use., Conclusion: Many individuals may want to make an active and informed choice at the point of being approached for biobank participation but are prepared to consent broadly to future research use and to forego additional choices as a result.

The mechanical properties of dentin and enamel affect the reliability and wear properties of a tooth. This study investigated the influence of clinical dental treatments and procedures, such as whitening treatments or etching prior to restorative procedures. Both autoclaved and non-autoclaved teeth were studied in order to allow for both comparison with published values and improved clinical relevance. Nanoindentation analysis with the Oliver-Pharr model provided elastic modulus and hardness across the dentin-enamel junction (DEJ). Large increases were observed in the elastic modulus of enamel in teeth that had been autoclaved (52.0 GPa versus 113.4 GPa), while smaller increases were observed in the dentin (17.9 GPa versus 27.9 GPa). Likewise, there was an increase in the hardness of enamel (2.0 GPa versus 4.3 GPa) and dentin (0.5 GPa versus 0.7 GPa) with autoclaving. These changes suggested that the range of elastic modulus and hardness values previously reported in the literature may be partially due to the sterilization procedures. Treatment of the exterior of non-autoclaved teeth with Crest Whitestrips, Opalescence or UltraEtch caused changes in the mechanical properties of both the enamel and dentin. Those treated with Crest Whitestrips showed a reduction in the elastic modulus of enamel (55.3 GPa to 32.7 GPa) and increase in the elastic modulus of dentin (17.2 GPa to 24.3 GPa). Opalescence treatments did not significantly affect the enamel properties, but did result in a decrease in the modulus of dentin (18.5 GPa to 15.1 GPa). Additionally, as expected, UltraEtch treatment decreased the modulus and hardness of enamel (48.7 GPa to 38.0 GPa and 1.9 GPa to 1.5 GPa, respectively) and dentin (21.4 GPa to 15.0 GPa and 1.9 GPa to 1.5 GPa, respectively). Changes in the mechanical properties were linked to altered protein concentration within the tooth, as evidenced by fluorescence microscopy and Fourier transform infrared spectroscopy., (Published by Elsevier Ltd.)

Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia and several lymphocyte-mediated inflammatory diseases. Persistent HTLV-1 infection is determined by a balance between host immune responses and virus spread. Immunomodulatory therapy involving HTLV-1-infected patients occurs in a variety of clinical settings. Knowledge of how these treatments influence host-virus relationships is not understood. In this study, we examined the effects of cyclosporine A (CsA)-induced immune suppression during early infection of HTLV-1. Twenty-four New Zealand white rabbits were split into 4 groups. Three groups were treated with either 10 or 20 mg/kg CsA or saline before infection. The fourth group was treated with 20 mg/kg CsA 1 week after infection. Immune suppression, plasma CsA concentration, ex vivo lymphocyte HTLV-1 p19 production, anti-HTLV-1 serologic responses, and proviral load levels were measured during infection. Our data indicated that CsA treatment before HTLV-1 infection enhanced early viral expression compared with untreated HTLV-1-infected rabbits, and altered long-term viral expression parameters. However, CsA treatment 1 week after infection diminished HTLV-1 expression throughout the 10-week study course. Collectively, these data indicate immunologic control is a key determinant of early HTLV-1 spread and have important implications for therapeutic intervention during HTLV-1-associated diseases.

Human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ) is dispensable for HTLV-1-mediated cellular transformation in cell culture, but is required for efficient viral infectivity and persistence in rabbits. In most adult T-cell leukemia (ATL) cells, Tax oncoprotein expression is typically low or undetectable, whereas Hbz gene expression is maintained, suggesting that Hbz expression may support infected cell survival and, ultimately, leukemogenesis. Emerging data indicate that HBZ protein can interact with cAMP response element binding protein (CREB) and Jun family members, altering transcription factor binding and transactivation of both viral and cellular promoters. Herein, lentiviral vectors that express Hbz-specific short hairpin (sh)-RNA effectively decreased both Hbz mRNA and HBZ protein expression in transduced HTLV-1-transformed SLB-1 T cells. Hbz knockdown correlated with a significant decrease in T-cell proliferation in culture. Both SLB-1 and SLB-1-Hbz knockdown cells engrafted into inoculated NOD/SCID(gammachain-/-) mice to form solid tumors that also infiltrated multiple tissues. However, tumor formation and organ infiltration were significantly decreased in animals challenged with SLB-1-Hbz knockdown cells. Our data indicate that Hbz expression enhances the proliferative capacity of HTLV-1-infected T cells, playing a critical role in cell survival and ultimately HTLV-1 tumorigenesis in the infected host.

The adaptive immune response of ovarian cancer patients has been linked to survival, and is known to be impaired in the tumor microenvironment. Little is known about relationships between biobehavioral factors such as depressed mood and anxiety and the adaptive immune response in ovarian cancer. Thirty-seven patients with epithelial ovarian cancer and 14 patients with benign ovarian neoplasms completed psychosocial questionnaires pre-surgery. Lymphocytes from peripheral blood, tumor, and ascites (fluid around the tumor), were obtained on the day of surgery. Expression of the Type-1 cytokine interferon-gamma (IFN gamma), and the Type-2 cytokine interleukin-4 (IL-4) by T-helper (CD4(+)) and T-cytotoxic (CD8(+)) cells was measured under autologous tumor-stimulated, polyclonally-stimulated, or unstimulated conditions. Links with mood were examined. Among cancer patients, marked elevations in unstimulated and tumor-stimulated Type-2 responses were seen, particularly in ascites and tumor-infiltrating lymphocytes (P values<0.01). With polyclonal stimulation, lymphocytes from all compartments expressed elevated Type-1 cytokines (P values<0.014). Depressed and anxious mood were both associated with significantly lower ratios of polyclonally-stimulated CD4(+) cells producing IFN gamma (TH(1) cells) vs. IL-4 (TH(2) cells) in all compartments (depressed mood: P=0.012; anxiety: P=0.038) and depressed mood was also related to lower ratios of polyclonally-stimulated CD8(+) cells producing IFN gamma (TC(1)) vs. IL-4 (TC(2)) (P=0.035). Although effects of polyclonal stimulation should be generalized with caution to the in vivo immune response, findings suggest that depressed and anxious mood are associated with greater impairment of adaptive immunity in peripheral blood and in the tumor microenvironment among ovarian cancer patients.

Purpose: To compare the measurements of posterior elevation above the best-fit sphere and of pachymetry in established keratoconus patients using 2 different technologies--Scheimpflug imaging with the Pentacam and scanning slit combined with Placido imaging with Orbscan IIz., Design: Retrospective comparative case series., Participants: Patients with confirmed keratoconus by biomicroscopy and Placido topography who had corneal topography scans by the Pentacam and Orbscan IIz on their visit from April 2004 to April 2005. These scans were obtained routinely for patient diagnosis, treatment, and progression., Methods: The mean difference, standard deviation (SD), and 95% limits of agreement (LOA) were calculated, and Bland-Altman plots were constructed for best-fit sphere radius of curvature, posterior elevation above the best-fit sphere, and pachymetry of the thinnest point., Results: Thirty-six eyes of 29 patients were analyzed. The average radius for posterior best-fit sphere was 5.97 microm (range, 4.69-6.79) for the Pentacam and 6.00 microm (range, 4.97-6.55) for Orbscan IIz. The mean difference (Pentacam - Orbscan IIz) for the radius generated for the best-fit sphere was -0.03+/-0.22 SD with a 95% confidence interval (CI) of -0.11 to 0.04 and a 95% LOA of -0.46 to 0.40 (P = 0.362). The mean posterior elevation by best-fit sphere fixed to the apex was 34.86 microm (range, 3-120) for the Pentacam and 48.50 microm (range, 11-118) for Orbscan IIz. The mean difference was -13.64+/-26.08 SD (95% CI, -22.46 to -4.81; 95% LOA, -64.75 to 37.48; P = 0.003). The average thinnest point for the Pentacam was 443.6 microm (range, 164-587), and that for Orbscan IIz was 445.9 microm (range, 204-597). The mean difference in the thinnest point for the Pentacam and Orbscan IIz was -2.28+/-35.55 (95% CI, -14.31 to 9.75; 95% LOA, -71.95 to 67.39; P = 0.703)., Conclusion: Both the Pentacam and Orbscan IIz determine similar thinnest points but have a measurable difference in posterior elevations above the best-fit sphere, despite similar radii of curvature. This difference may be important in the screening of patients for refractive surgery to avoid surgery on patients with early keratoconus. This study cannot determine if the Pentacam is underestimating the posterior vault or if Orbscan is overestimating this height, and further studies with a standardized test object are needed.

Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD)., Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the first year and every 3 months thereafter., Results: At baseline, subjects were approximately the expected height for their age and somewhat heavier than expected. Subjects gained height steadily throughout the study and were on average 0.23 cm less than expected at month 21. Weight did not increase and BMI decreased slightly in the first 4 months. Thereafter, weight Z score and BMI Z score remained relatively constant and children were on average 1.23 kg less than expected at month 21. Previous stimulant therapy tended to be associated with a smaller decrease in Z score during the study compared with no previous stimulant therapy. Drug holidays did not significantly affect growth., Conclusions: The effects of prolonged OROS MPH therapy on growth were clinically insignificant and limited to slight decreases in weight during the first months of therapy. Drug holidays did not reduce any impact on growth and are thus of questionable utility for limiting potential effects of treatment on growth.

The study objective was to determine the feasibility of implementation of personal health records (PHRs) by case managers (CMs) in a Veterans Affairs Medical Center (VAMC) Continuity of Care (COC) Clinic, to ascertain the impact of PHRs on patient access to vital health information, and to assess the effect on provider-patient communication. One hundred and fifty patients and 8 nurse CMs in the general medicine COC Clinic at the Iowa City VAMC participated in a prospective cohort study in which an intervention, implementation of PHRs, was performed in one half of the patients, selected at random by their CMs. All participants responded to questions about their personal possession of documentation of vital health information. Initially, the majority of subjects possessed poor documentation of basic health information. At follow-up, significant differences occurred between the cohort with PHRs and the cohort without in their documentation of immunizations, allergies, medications, and operations.

Reducing red meat intake to lower serum cholesterol may also lower iron and zinc intake. Eighty-six seventh and eighth graders who enrolled in a study comparing serum ferritin, zinc, and cholesterol levels were randomized to a low-fat eating pattern emphasizing either lean beef or lean poultry and fish. Serum data and three 24-hour recalls were collected at baseline and 3 months. The lean beef group ate significantly more beef [26 (4, 37) g/d; P<.01] and both groups reduced total and saturated fat intake. Although serum ferritin level change between baseline and intervention was significantly different between the lean beef and lean poultry and fish groups (median [interquartile range] 0.7 [-6, 8] and -6.8 [-12, 2] microg/dL, respectively), the drop in the lean poultry and fish group was not clinically significant. No differences were observed in iron and zinc intake or in serum zinc and cholesterol levels. Teenagers eating diets low in saturated fat may benefit from adequate amounts of lean red meat.

Objective: The purpose of this study was to investigate the effect of the rapid fetal fibronectin on the length of hospital stay and the use of preterm labor interventions in a tertiary care center., Study Design: Women who were seen in the Labor and Delivery Unit with symptoms of preterm labor were assigned randomly to receive fetal fibronectin (n=46 women) or to preterm labor management without fetal fibronectin (n=51 women). Physicians were not blinded to the result; groups were compared., Results: There was no difference between groups in demographic or obstetric characteristics, the hours spent in labor and delivery, the number of women who were admitted to the antepartum service, the length of stay, or medical interventions. When the results for women with a negative fetal fibronectin test were compared to women with a positive fetal fibronectin test, a significant difference was found in admissions to the antepartum service (P=.032) and the length of stay (P=.008)., Conclusions: A negative fetal fibronectin test was associated with fewer admissions to the antepartum ward and a shorter length of stay.

Purpose: To report the incidence and extent of visual deterioration in patients with giant cell arteritis (GCA) on high doses of systemic corticosteroids during the early stages of treatment; the various factors that may influence the outcome; and whether intravenous megadose corticosteroid therapy is more effective than oral therapy., Design: Noncomparative interventional case series., Participants: One hundred forty-four patients with GCA (271 eyes) seen initially with visual loss (91 patients) and without visual loss (53 patients). All patients had biopsy-confirmed GCA and were followed while on high doses of systemic corticosteroid therapy for at least 2 weeks., Methods: Every patient at the initial visit had an ophthalmic evaluation, including visual acuity, visual fields, intraocular pressure, slit-lamp and ophthalmoscopic evaluation, erythrocyte sedimentation rate (ESR; Westergren) and C-reactive protein (CRP) estimation, and temporal artery biopsy as soon as possible. If GCA was either strongly suspected or confirmed by biopsy, they were immediately started in our clinic on high doses of oral (80-120 mg) prednisone daily or intravenous megadose systemic corticosteroids (usually 150 mg dexamethasone sodium phosphate every 8 hours for 1-3 days) followed by oral prednisone. At each visit they underwent all the initial ophthalmic evaluations and had an ESR and CRP evaluation done. Tapering of steroid therapy was not started until both ESR and CRP had reached their lowest stable levels. These showed marked interindividual variation and usually took approximately 2 weeks to stabilize. Then the steroid therapy was gradually tapered, guided primarily by the levels of ESR and CRP. No generalization is possible regarding the period required to achieve the maintenance dosage, because this also varied markedly from patient to patient., Main Outcome Measures: Visual acuity deterioration., Results: While on high doses of steroid therapy during the initial stages of the treatment, only 9 (11 eyes) of the 91 patients seen initially with visual loss developed further visual acuity deterioration in one or both eyes within 5 days after the start of therapy (one of the eyes had normal vision initially), but none of the 53 patients initially seen without visual loss developed any visual deterioration. Six of the 48 patients (13%) who were on intravenous steroid therapy had visual deterioration compared with 3 of 97 patients (3%) who were only on oral steroid therapy (P = 0.060)., Conclusions: Our study shows that although a few eyes can develop visual deterioration while on high doses of steroid therapy, early, adequate steroid therapy is effective in preventing further visual loss in most. When further visual deterioration occurred despite high doses of systemic corticosteroids, it almost invariably started within 5 days after the start of the high-dose steroid therapy. There was no evidence that intravenous megadose steroid therapy was more effective than oral therapy in preventing visual deterioration.

Objective: To evaluate the effectiveness of incorporating two self-regulation strategies (goal setting and self-monitoring) into a nutrition education class to enhance dietary fiber self-efficacy and foster a positive change in dietary fiber consumption., Design: College students in an introductory nutrition class (n = 113) were randomly assigned to one of four treatment conditions: goal setting, self-monitoring, goal setting and self-monitoring, and no goal setting and no self-monitoring. Twenty-six college students from an introductory health class served as the control group., Statistical Analyses: The main and interaction effects of goal setting and self-monitoring on postintervention variables were analyzed using analysis of covariance with baseline intake levels as the covariate. Analysis of variance was used to examine differences in the mean changes between the groups. Path analysis was conducted to analyze the causal linkage among the pretest and intervening variables to predict postintervention knowledge, self-efficacy, and fiber consumption., Results: Goal setting had a significant main effect on dietary fiber self-efficacy and on dietary fiber consumption Subjects who set goals scored 15% higher on the dietary fiber self-efficacy scale and consumed 91% more fiber than subjects who did not set goals. Self-monitoring had no significant main effect on either dietary fiber self-efficacy or dietary fiber consumption. There was no significant interaction between goal setting and self-monitoring. Changes in dietary fiber scores differed between the groups. Increases in dietary fiber for the goal setting and self-monitoring group were significantly higher than the goal-setting, self-monitoring, no goal setting and no self-monitoring, and control groups. In addition, the goal setting only group had significantly greater increases in fiber intake than the self-monitoring, no goal setting and no self-monitoring, and control groups. Changes in self-efficacy scores were significantly different between the groups. The goal setting and goal setting and self-monitoring groups had significantly higher self-efficacy scores than the control group. Path analysis revealed that both goal setting and self-monitoring affected dietary fiber consumption through knowledge and dietary fiber self-efficacy, goal setting had a strong direct effect on fiber consumption, and postintervention knowledge affected fiber consumption only through self-efficacy., Applications/conclusions: Our findings suggest that dietary change requires active self-regulation of food intake. Combining goal setting and self-monitoring significantly enhances dietary behavior change. This strategy can easily be incorporated into nutrition education or counseling programs to enhance dietary behavior change.

Purpose: This study aimed to determine the relationship between visual function impairment in 776 patients who had extracapsular cataract extraction with posterior chamber intraocular lens implantation and gender, age, preoperative visual acuity (VA) of both the operative and the contralateral eye, and presence of other ocular disease in the operative eye., Design: Retrospective cross-sectional study., Participants: 1139 patients whose medical records were abstracted and who had cataract surgery performed at 1 of 10 participating academic medical centers in 1990., Main Outcome Measure: In the 776 patients who had explicit statements about impairment of visual function documented in their medical records, univariate and multivariable logistic analyses were used to assess the above relationship., Results: The most severe visual functional deficit that justified the cataract operation varied in relation to gender, age, and VA. On bivariate analysis, men were more likely to have impairment with employment, driving, and glare, whereas women were more likely to have impairment with activities of daily living and recreational activities. Significant findings between visual impairment and the independent variables from the logistic regression models included: (1) employment limitation and male gender (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.08-3.40); (2) employment limitation and younger age (OR, 0.12; 95% CI, 0.050-0.28 for ages 70-79); (3) recreational impairment and older age (OR, 2.77; 95% CI, 1.64-4.70 for ages 80+); (4) impairment in performing activities of daily living and female gender (OR, 0.72; 95% CI, 0.53-0.98 for male gender); (5) impairment in performing activities of daily living and worse VA in the operative eye (OR, 5.13; 95% CI, 2.93-9.00 for VA < 20/100); (6) glare-associated impairment and younger age (OR, 0.40; 95% CI, 0.24-0.69 for age 80+); and (7) glare-associated impairment and better VA (OR, 0.16; 95% CI, 0.067-0.38 for VA < 20/100)., Conclusion: When deciding whether to perform cataract surgery, functional impairment must be considered in relation to the age and the gender of the patient, for the type of functional impairment varies in association with age and gender.

Sulfonylureas have been available for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) since the 1950s. With the introduction of new oral agents, there is a tendency to discount the value of sulfonylurea therapy. Sulfonylureas have the advantage of multiple formulations, low costs, minimal side effects, and demonstrated efficacy in controlling hyperglycemia. The major disadvantage of sulfonylureas is secondary failure, which may occur with all oral agents as part of the progression of NIDDM. Sulfonylureas should continue to play an important role in the treatment of NIDDM.

Purpose: To develop criteria for the appropriateness of cataract surgery (extracapsular cataract extraction or phacoemulsification with planned implantation of a posterior chamber intraocular lens) and to apply these criteria to patients from ten academic medical centers., Methods: The study is a retrospective case series from ten academic medical centers. One thousand one hundred thirty-nine patients who had had cataract surgery in 1990 at the medical centers were selected randomly. Patients, identified by specific ICD-9-CM or CPT-4 codes, had no other ocular surgery performed at the same time as cataract surgery. Rates of inappropriate, uncertain, appropriate, and appropriate and crucial surgeries were determined by application of the criteria established by a multidisciplinary expert panel., Results: Approximately 2% of the procedures were classified as inappropriate, after adjusting for missing or nonspecific visual function by use of discriminant analysis. Ninety-one percent of the procedures were classified as appropriate (52%) or appropriate and crucial (39%). Seven percent were designated as uncertain, either due to a median rating in the uncertain range or to disagreement in ratings among the panelists. Significant variation occurred in the results among the different institutions: inappropriate surgeries ranged from 0% to 4%, uncertain from 1% to 14%, appropriate from 35% to 66%, and appropriate and crucial from 21% to 62% (P=0.02)., Conclusion: A small percentage of cataract surgeries was performed at these ten academic medical centers for inappropriate indications using the study criteria. Given the large number of cataract surgeries performed annually, the small percentage of uncertain and inappropriate surgeries may translate into a large number of surgeries performed for less than appropriate or appropriate and crucial indications. Significant variation existed among the institutions in the distribution of appropriate and crucial and appropriate compared with uncertain and inappropriate surgeries.

Reperfusion of ischemic organs can result in tissue injury that is manifested as microvascular and parenchymal cell dysfunction. Reactive oxygen metabolites and polymorphonuclear leukocytes (PMN) have been implicated in the pathobiology of reperfusion injury. Reactive oxygen metabolites mediate the lipid peroxidation detected in postischemic tissues and promote the formation of inflammatory agents that recruit and activate PMN. These PMN appear to inflict reperfusion-induced tissue injury. Drugs that scavenge or inhibit the formation of reactive oxygen metabolites and/or prevent the recruitment of PMN may be useful in the treatment of reperfusion injury.

Objective: To describe a model for providing breastfeeding support in the neonatal intensive-care unit (NICU)., Design: Naturalistic, participant observation., Setting: Suburban Level III NICU., Patients: One hundred thirty-two mother-infant pairs over 1 year. Infants were hospitalized in the NICU, and mothers had initiated lactation efforts., Interventions: Investigators provided breastfeeding interventions for the mother-infant pairs, based on identified problems, the research literature, or both., Main Outcome Measures: Percentage of mothers who were breastfeeding at the time of discharge from the NICU., Result: Interventions were classified into five categories: expression and collection of mothers' milk, gavage feeding of expressed mothers' milk, in-hospital breastfeeding sessions, postdischarge breastfeeding management, and additional consultation., Conclusions: This model was effective in preventing breastfeeding failure for this population. The model can provide the basis for NICU breastfeeding standards of care, protocols, and chart records, or for reimbursement purposes. The model also provides a framework for studying a specific category or breastfeeding intervention.

The objectives of this study were twofold: 1) to determine whether a microdissected rabbit intrarenal arterial network (IAN), consisting mainly of interlobar, arcuate, and interlobular arteries exhibits endothelium-dependent vasodilatation, and 2) to establish a means of selectively abolishing this response. The IAN was perfused at a constant flow with heated-oxygenated Krebs-bicarbonate buffer through the main renal artery, and evoked responses were limited to vessels distal to the renal artery. A decrease in perfusion pressure reflected a vasodilator response, after vascular tone had been induced by intraarterial infusion of phenylephrine. Bolus injections of acetylcholine produced graded endothelium-dependent vasodilator responses, whereas glyceryl trinitrate caused endothelium-independent responses. Manual de-endothelialization was accomplished by gently stroking the IAN and at the same time removing any remaining glomeruli. This procedure blocked the response to acetylcholine, but not to glyceryl trinitrate (n = 6). A 10-min infusion of NG nitro-L-arginine (NArg) (4 x 10(-5)-3 x 10(-4) M) into the IAN also selectively attenuated the response to acetylcholine (n = 7). The third procedure, consisting of a 10-min infusion of 22-44 mM hydrogen peroxide into the IAN also attenuated the response to acetylcholine, but not to glyceryl trinitrate in nine of 12 experiments. This investigation demonstrates that intrarenal arteries are capable of undergoing endothelium-dependent vasodilatation, and the potential use of the IAN for further study of renal endothelium-derived vasoactive factors.

Background: Currently, there are no animal models of primary uveal melanoma in an eye large enough to allow documentation of the clinical evolution of the lesion by either funduscopy or fundus photography., Methods: The authors induced primary uveal melanocytic lesions in the eyes of Dutch (pigmented) rabbits using a two-stage carcinogenesis protocol involving initiation with 4 weekly topical applications of 10 microliters of a 1% solution of 7,12-dimethyl-benz[a]anthracene (DMBA) in acetone (21 eyes) followed by 12 weekly topical applications of a 10 microliters solution of either 0.25% or 0.5% croton oil in acetone. They also investigated the effect of initiation with DMBA without promotion and the effects of chronic topical exposure to acetone and proparacaine., Results: Exposure to DMBA followed by promotion with croton oil in either concentration was the most effective means of inducing clinically detectable fundus lesions. Histologically, a spectrum of melanocytic proliferations developed including benign nevi, nevi with varying grades of cytologic atypia, and clusters of confluent atypical melanocytes that may represent early melanomas. Although clinical regression of fundus lesions was noted in eight eyes after promotion had been stopped, five of these eyes showed unequivocal histologic evidence of a residual uveal melanocytic lesion. Chronic ocular irritation is capable of inducing cytologically benign subclinical uveal melanocytic proliferations., Conclusions: The conventional classification of human uveal melanocytic lesions includes only nevi and melanomas, but a comparison of the results of this study with descriptions of human uveal melanocytic nevi suggests the existence of a spectrum of intermediate atypical precursor lesions in humans.

An analysis of hospital discharge data showed that Brampton children 4 years and under had higher rates of hospital admissions for asthma, bronchitis and upper respiratory infections than children in the same age group living in Mississauga and other Ontario municipalities. The present study was done to compare the prevalence and treatment of wheezing and coughing between Brampton and Mississauga children 4 and 5 years of age. The study showed that increased use of pediatricians on the part of Mississauga children in comparison to Brampton children resulted in a higher proportion being placed on anti-asthmatic medications even though the underlying prevalence rate of wheezing and coughing was the same in the two samples. Further study is required to determine whether differences in primary care between the two samples can explain a two-fold increase in hospital admission rates for lower respiratory illness among Brampton preschool children in comparison to their counterparts in Mississauga.

Fecal neutral and acidic sterols and cholesterol absorption were measured in 12 normal control subjects, 40 diabetic subjects with and without hyperlipidemia, and 27 subjects with hyperlipidemia but without diabetes mellitus. All subjects were on a low-cholesterol diet (less than 300 mg cholesterol/day). Fecal excretion of neutral and acidic sterols was increased in patients with hypertriglyceridemia and was more marked in diabetic patients with hypertriglyceridemia. Cholesterol absorption was decreased in diabetic patients with hypertriglyceridemia. Otherwise, there were no significant differences in sterol excretion or cholesterol absorption in diabetic and nondiabetic subjects compared with control groups with similar lipid levels. The best predictors of fecal neutral- and acidic-sterol excretion and of estimated cholesterol synthesis were very low [corrected]-density lipoprotein triglycerides and high-density lipoprotein cholesterol. Correction of hyperlipidemia may be beneficial in decreasing cholesterol synthesis and, thereby, in decreasing the risk of atherogenesis.

Six OKT4+ human T-cell lines that require continuing PHA stimulation and TCGF for continuous growth were established. The cells from all six of these T-cell lines became smaller in size and lost the cell surface Ia antigen when they were grown in phytohemagglutinin (PHA)-depleted growth factor. These cells were unable to survive in the absence of PHA even if exogenous factor was present in great abundance. One of the cell lines (FL) was capable of providing helper functions. In the presence of PHA and phorbol myristate acetate, FL cells produced a growth factor, tentatively identified as Interleukin 2 (IL-2) by its ability to promote the proliferation of an IL-2-dependent murine T-cell line. Moreover, when FL cells were cocultured with B cells, pokeweed mitogen-induced immunoglobulin production was enhanced.

Murine embryonal carcinoma cells (EC) can be induced to differentiate by a variety of chemical agents, including retinoid acid (RA) and dimethyl acetamide (DMA). However, it is not known how these agents exert their effects. In this study we demonstrate that murine EC cells can also be induced to differentiate by ouabain at concentrations which inhibit Na+, K+-ATPase activity as measured by inhibition of 86Rb+ uptake. Since the pharmacologic action of ouabain is thought to be specific, we investigated the role of Na+, K+-ATPase inhibition and specific metabolic consequences of this inhibition in the induction of EC differentiation, and explored whether this might be a common mode of action for a variety of structurally diverse inducers. Although the Na+, K+-ATPase maintains ion gradients in cells, our studies failed to demonstrate a consistent role for alterations of ion flux or ion concentration on the differentiation process. Ouabain inhibited cell growth, but a direct correlation between the degree of growth inhibition and the extent of differentiation could not be demonstrated. There was also no evidence that RA or DMA induces differentiation by inhibiting the Na+, K+-ATPase. The mechanism of ouabain induction may be mediated by some alternative consequence of Na+, K+-ATPase inhibition, but it appears to be specific for that inducer and cannot be generalized to that of other inducers of EC differentiation.

Fractionation of lactoperoxidase iodinated cell surface material on miniature DEAE-cellulose columns provided a rapid method for separating labeled lipid from cell surface antigens. The procedure also removed poorly solubilized aggregates yielding a labeled preparation which demonstrated stable, reproducible immunoprecipitation results. Using these fractionated antigens components tentatively designated as human 'T' cell specific antigens have been identified.

The purpose of this study is to examine the clinical durability and caries inhibition potential of a fluoride-exchanging resin (FER) when used as an orthodontic bracket-bonding adhesive. In the clinical durability investigation, orthodontic brackets were bonded to alternate teeth with the FER in 10 patients scheduled for routine orthodontic procedures. The remaining teeth were bonded with Concise orthodontic resin. Number of bonding failures and the site and mode (adhesive or cohesive) of failure were recorded. Also included in the study were 10 patients scheduled for orthodontic care with prescribed extraction of four first premolars. Bracketed teeth were extracted after 60 days and were sectioned and examined with polarized light microscopy using H2O and quinoline as imbibition media. Failure rates for the FER and Concise were 10.8% and 7.3%, respectively. Occurrence of adhesive rather than cohesive, failure indicates that structural integrity was maintained for both adhesives. Microscopic examination of specimens with H2O showed lesion formation to be 2.78% for the FER and 1.73% for Concise. These lesions were large and not seen in positions near the brackets indicating presence before bonding. With quinoline, dark zone formation was 2.3% for the FER and 33.5% for Concise, indicating a 93% reduction in the first stages of enamel alteration. Results demonstrate that the fluoride-exchanging resin holds promise as a practical caries-preventive adhesive.

We studied the reproducibility of four tests of peripheral occlusive arterial disease in 54 subjects, 32 of whom had this disease. We found that the reproducibility of systolic blood pressures obtained at rest from the thighs, calves, and ankles approximated that of arm systolic and diastolic blood pressures, as did the ankle-to-arm systolic blood pressure ratios. The average of the tenth and ninetieth percentile ranges of the resting systolic blood pressure ankle-to-arm ratios was +/- 0.10. Systolic blood pressures from the fingers were somewhat less reproducible, and those from the toes were even more variable. Systolic blood pressure ankle-to-arm ratios measured after the patient had exercised were less reproducible than resting ratios. The average of the tenth and ninetieth percentile ranges of the 1-, 3-, 5-, and 10-minute ratios after exercise was -0.13 to +0.16. Skin temperatures from the fingers and toes were approximately as reproducible as systolic blood pressures from the arms and legs and as the resting ankle-to-arm blood pressure ratios. Pulse-volume recordings from the thighs, calves, ankles, feet, toes, and fingers were very poorly reproducible. We conclude that information on the reproducibility of these measurements is essential in the evaluation of noninvasive arterial tests that are used to determine the course of peripheral occlusive arterial disease.

A patient with idiopathic hypercalciuria and some features suggestive of Bartter syndrome is reported. Excessive urinary prostaglandin E (PGE) excretion and renal calcium leak were documented in this child. Treatment with aspirin and indomethacin reduced urinary PGE excretion and was associated with a decrease in daily calcium excretion. At the lowest levels of urinary PGE, the renal calcium leak was no longer evident although mild hypercalciuria persisted. These results suggest that PGE may play a role in some cases of idiopathic hypercalciuria.