tbuckley/cabot-search huggingface dataset:
Effect of mixed micellar lipid on the absorption of cholesterol and vitamin D3 into lymph
Authors: Gilbert R. Thompson, Robert K. Ockner, Kurt J. Isselbacher
Journal: Journal of Clinical Investigation (1969)

The absorption of endogenous cholesterol, labeled with tracer doses of cholesterol (14)C or cholesterol-(3)H and of near physiological doses of vitamin D(3)-(3)H was studied in rats with cannulated intestinal lymphatics. The effects of administering mixed micellar solutions of fatty acid, monoglyceride, and bile salt on the absorption of these labeled sterols was determined. It was observed that the specific activity of free cholesterol and the amounts of vitamin D(3) appearing in lymph were significantly increased during the intraduodenal administration of mixed micellar solutions of either linoleic or palmitic acid, in contrast to control rats receiving a micellar solution of taurocholate. These increases were related linearly to the lymph triglyceride level. In addition it was observed that when the linoleic acid solution was administered there was a more marked increase in the ratio of the specific activities of free and esterified cholesterol in lymph than with either the palmitic acid or taurocholate solutions. Additional studies in rats with intact lymphatics showed that the uptake of labeled cholesterol and vitamin D(3) from the intestinal lumen into the wall was similar whether the sterols were administered in taurocholate or in mixed micellar solution. These findings suggest that mixed micellar lipid increased the rate of appearance of labeled free cholesterol and vitamin D(3) in lymph by enhancing their transport out of the intestinal mucosa, rather than by an effect on uptake.
Implementing Routine Screening for Distress, the Sixth Vital Sign, for Patients With Head and Neck and Neurologic Cancers
Authors: Barry D. Bultz, Amy Waller, Jodi Cullum, Paula Jones, Johan Halland, Shannon L. Groff, Catriona Leckie, Lisa Shirt, Scott Blanchard, Harold Lau, Jacob Easaw, Konrad Fassbender, Linda E. Carlson
Journal: Journal of the National Comprehensive Cancer Network (2013)

This study examined the benefits of incorporating screening for distress as a routine part of care for patients with head and neck and neurologic cancers in a tertiary cancer center. Using a comparative 2-cohort pre-post implementation sequential design, consecutive outpatients with head and neck and neurologic cancers were recruited into 2 separate cohorts. Cohort 1 included patients attending clinics during April 2010, before the implementation of the screening program. The program was then implemented and patients completed the Screening for Distress Minimum Dataset (the Edmonton Symptom Assessment System [ESAS] and the Canadian Problem Checklist [CPC]) at each clinic visit. Cohort 2 included patients attending clinics during March 2011. Consenting patients completed screening and outcome measures (ESAS, CPC, and either the Functional Assessment of Cancer Therapy-Brain or the Functional Assessment of Cancer Therapy-Head and Neck). A total of 146 patients (78 head and neck and 68 neurologic) provided data for Cohort 1, and 143 (81 head and neck and 62 neurologic) provided data for Cohort 2. Compared with Cohort 1, patients with neurologic cancers in Cohort 2 reported significantly higher scores on the Functional Assessment of Cancer Therapy: General total and emotional quality of life subscale; fewer high scores (≥4) on the ESAS breathlessness item; and fewer problems with fears/worries, frustration/anger, finding meaning in life, and worry about friends/family. Head and neck patients in Cohort 2 reported significantly higher emotional quality of life and fewer problems with eating and weight than those in Cohort 1. Although no definitive causal attributions can be made, patients exposed to routine screening for distress reported better well-being and fewer emotional, physical, and practical problems than historical controls.
Computer-Assisted Analysis of Biopsy Specimen Microvessels Predicts the Outcome of Esophageal Cancers Treated with Chemoradiotherapy
Authors: Shi-chuan Zhang, Shuichi Hironaka, Atsushi Ohtsu, Shigeaki Yoshida, Takahiro Hasebe, Masashi Fukayama, Atsushi Ochiai
Journal: Clinical Cancer Research (2006)

Abstract Purpose: A computer-assisted microvessel analysis system was developed to evaluate correlations between the architecture of biopsy specimen microvessels and the outcome for patients with esophageal cancer treated with chemoradiotherapy. Experimental Design: Biopsy specimens from 51 patients with esophageal cancer (T2-3, any N, M0) treated with chemoradiotherapy were immunostained with an anti-CD31 antibody and quantified using computerized image analysis. We evaluated the association of several microvessel factors with overall survival, including the ratio of total microvessel perimeter to total tumor area (TP/TA), the tumor hypoxic ratio, and the ratio of total microvessel number to total tumor area (TN/TA). Results from traditional manual microvessel density (MVD) hotspot count and computerized hotspot count were compared and the relation between hotspot MVD count and survival rate was evaluated. Results: The median follow-up time was 32 months. Both univariate and multivariate analyses revealed that computer-counted hotspot MVD and TN/TA and TP/TA ratios correlated significantly with the outcome of chemoradiotherapy. Kaplan-Meier survival curves showed that patients with high computer-counted hotspot MVDs and high TN/TA and TP/TA ratios had better overall survival rate than patients with low MVDs or ratios (P = 0.025, 0.008, and 0.031, respectively). Combining computer-counted MVD or TN/TA ratio with TP/TA ratio proved more predictive than any single factor. Two researcher-counted hotspot MVDs had no significant relation with outcome. Conclusion: Computer-assisted tumor microvessel analysis is a powerful tool in predicting the outcome for patients with esophageal cancer treated with chemoradiotherapy because intraobserver and interobserver variability is minimized.
EARLY EVENTS IN OLFACTORY PROCESSING
Authors: Rachel I. Wilson, Zachary F. Mainen
Journal: Annual Review of Neuroscience (2006)

Olfactory space has a higher dimensionality than does any other class of sensory stimuli, and the olfactory system receives input from an unusually large number of unique information channels. This suggests that aspects of olfactory processing may differ fundamentally from processing in other sensory modalities. This review summarizes current understanding of early events in olfactory processing. We focus on how odors are encoded by the activity of primary olfactory receptor neurons, how odor codes may be transformed in the olfactory bulb, and what relevance these codes may have for downstream neurons in higher brain centers. Recent findings in synaptic physiology, neural coding, and psychophysics are discussed, with reference to both vertebrate and insect model systems.
Genetic risk of knee osteoarthritis: a sibling study
Authors: R L Neame
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To determine whether there is a genetic contribution to knee osteoarthritis (OA) as defined by structural change on plain radiographs. <b>Design:</b> Sibling study. Comparison of knee OA prevalence in the community with knee OA prevalence among siblings of index cases with knee OA. <b>Subjects:</b> 490 knee OA index cases listed for total knee replacement and 737 of their siblings aged &gt;40 years, 1729 community subjects aged &gt;40 years. <b>Main outcome measure:</b> Odds ratio for radiographic knee OA in siblings <i>v</i> community participants. <b>Results:</b> The age, sex, and knee pain adjusted odds ratios in siblings were 2.9 (95% confidence interval 2.3 to 3.7) for tibiofemoral OA and 1.7 (1.4 to 2.2) for patellofemoral OA. This difference remained after adjustment for important environmental risk factors. The heritability estimate for knee OA was 0.62. <b>Conclusions:</b> Siblings are at increased risk of knee OA in comparison with the general population. This is likely to be due to genetic factors.
Sexual health—what are users’ views?
Authors: Toni Belfield
Journal: Journal of the Royal Society of Medicine (2007)

This article is the fifth in a series of articles on sexuality and sexual health. People's understanding of and needs in sexual health are complex. In recognition of this, fpa—with funding from the Department of Health—published The Handbook of Sexual Health in Primary Care in 2006. a This multi-authored book is written by practising professionals working in sexual health providing evidence-guided and accessible information to support practice. This article is adapted from Chapter 10 and published with permission from fpa.
Interferon-α in Patients with Asymptomatic Human Immunodeficiency Virus (HIV) Infection
Authors: H. Clifford Lane
Journal: Annals of Internal Medicine (1990)

Study Objective: To evaluate the toxicity and clinical efficacy of interferon-α2b (IFN-α) in patients with asymptomatic human immunodeficiency virus (HIV) infection. Design: Randomized, placebo-controlled, and double-blind study. Setting: Outpatient clinic of a government referral-based research hospital. Patients: Volunteer sample of 34 patients with asymptomatic HIV infection who had CD4 counts of 400 cells/mm3 or more, positive peripheral blood mononuclear cell cultures for HIV, or p24 antigenemia. Interventions: Patients were randomly assigned to receive either IFN-α or placebo, 35 x 106 units per day subcutaneously. Doses of IFN-α or placebo were modified according to predefined laboratory and clinical criteria. Therapy lasted at least 12 weeks. Measurements and Main Results: Seventeen patients were randomly assigned to each group. The two groups had similar mean CD4 counts at study entry. Thirty-five percent of patients assigned to receive IFN-α withdrew from the study because of toxicity. The average daily dose of IFN-α was 17.5 x 106 units. All patients receiving IFN-α reported flu-like symptoms; other toxicities included granulocytopenia (55%) and elevated liver enzyme levels (45%). While receiving IFN-α, 7 patients (41%) became HIV culture negative (three or more consecutive negative peripheral blood mononuclear cell cultures taken at least 2 weeks apart). In contrast, 2 patients in the placebo group (13%) became culture negative while on study (P = 0.05). During the treatment period, CD4 lymphocyte percentages were sustained at or above the baseline level in patients receiving IFN-α and declined slightly in patients receiving placebo. Of the 32 study patients followed after study (range, 5 to 33 months), no patients in the IFN-α group developed an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection, compared with 5 patients in the placebo group (P = 0.02). Conclusions: Treatment of early-stage HIV infection with IFN-α can result in a decrease in frequency of viral isolation. Although its use may be accompanied by dose-dependent toxicities, IFN-α may have a role in slowing progression of HIV disease.
Physical activity in patients with COPD
Authors: H. Watz, B. Waschki, T. Meyer, H. Magnussen
Journal: European Respiratory Journal (2008)

The present study aimed to measure physical activity in patients with chronic obstructive pulmonary disease (COPD) to: 1) identify the disease stage at which physical activity becomes limited; 2) investigate the relationship of clinical characteristics with physical activity; 3) evaluate the predictive power of clinical characteristics identifying very inactive patients; and 4) analyse the reliability of physical activity measurements. In total, 163 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I–IV; BODE (body mass index, airway obstruction, dyspnoea, exercise capacity) index score 0–10) and 29 patients with chronic bronchitis (normal spirometry; former GOLD stage 0) wore activity monitors that recorded steps per day, minutes of at least moderate activity, and physical activity levels for 5 days (3 weekdays plus Saturday and Sunday). Compared with patients with chronic bronchitis, steps per day, minutes of at least moderate activity and physical activity levels were reduced from GOLD stage II/BODE score 1, GOLD stage III/BODE score 3/4 and from GOLD stage III/BODE score 1, respectively. Reliability of physical activity measurements improved with the number of measured days and with higher GOLD stages. Moderate relationships were observed between clinical characteristics and physical activity. GOLD stages III and IV best predicted very inactive patients. Physical activity is reduced in patients with chronic obstructive pulmonary disease from Global Initiative for Chronic Obstructive Lung Disease stage II/ body mass index, airway obstruction, dyspnoea, exercise capacity score 1. Clinical characteristics of patients with chronic obstructive pulmonary disease only incompletely reflect their physical activity.
Inhibitory effect of cyclosporin A on eosinophil infiltration in the guinea-pig lung induced by antigen, platelet-activating factor and leukotriene B4
Authors: V Lagente, C Carre, F Kyriacopoulos, E Boichot, JM Mencia-Huerta, P Braquet
Journal: European Respiratory Journal (1994)

The effect of the immunosuppressive compound, cyclosporin A, and the corticosteroid, betamethasone, was investigated on eosinophil accumulation in guinea-pig lung tissue induced by antigen, platelet-activating factor (PAF) and leukotriene B4 (LTB4). The accumulation of eosinophils in the peribronchial area was evaluated on histological preparations. The lung sections were stained with Luna's reagent specific for eosinophil granule content. Oral treatment of the guinea-pigs with cyclosporin, 10 mg.kg-1 three times a day for two days, and 10 mg.kg-1 1 h before antigen challenge, significantly reduced the accumulation of eosinophils observed at 4 and 24 h, in the peribronchial area of sensitized guinea-pig lung. Betamethasone (3 mg.kg-1), administered orally 24 h and 1 h before antigen challenge elicited a moderate but significant reduction of antigen-induced eosinophil accumulation. Pretreatment of the guinea-pigs with cyclosporin or betamethasone elicited a marked inhibition of the accumulation of eosinophils in the peribronchial area induced by aerosolized PAF (100 micrograms.ml-1) or LTB4 (5 micrograms.ml-1). Since cyclosporin and betamethasone significantly inhibit the antigen-induced eosinophil accumulation, these results suggest that antigen-induced lung eosinophilia is dependent of T-lymphocytes. However, cyclosporin and betamethasone may also reduce the chemotactic activity of PAF and LTB4 on guinea-pig eosinophils.
Desmoglein-2 interaction is crucial for cardiomyocyte cohesion and function
Authors: Angela Schlipp, Camilla Schinner, Volker Spindler, Franziska Vielmuth, Katja Gehmlich, Petros Syrris, William J. Mckenna, Andreas Dendorfer, Eva Hartlieb, Jens Waschke
Journal: Cardiovascular Research (2014)

We determined the contribution of the desmosomal cadherin desmoglein-2 to cell-cell cohesion in cardiomyocytes. In the intercalated disc, providing mechanical strength and electrical communication between adjacent cardiomyocytes, desmoglein-2 is closely associated with N-cadherin and gap junctions.We studied intercalated discs of HL-1 cardiomyocytes by immunostaining of desmoglein-2 and N-cadherin. Cohesion was measured using a liberase-based dissociation-assay and compared with cell-free single-molecule atomic force microscopy measurements. L-tryptophan caused irregular desmoglein-2 condensation, weakened cell-cell cohesion and impaired both homophilic desmoglein-2 and N-cadherin trans-interaction, whereas l-phenylalanine had no effect. L-tryptophan did not affect N-cadherin localization and its inhibitory effect on cell-cohesion and desmoglein-2 binding, but not on N-cadherin interaction, was blocked by a desmoglein-specific tandem peptide. Moreover, Ca(2+)-depletion, desmoglein-2 knockdown, a desmoglein-specific single peptide and certain desmoglein-2 mutations associated with arrhythmogenic cardiomyopathy reduced cell-cell cohesion, whereas cell adhesion was strengthened by desmoglein-2 overexpression. Since single peptide did not interfere with N-cadherin trans-interaction, these data indicate that (i) desmoglein-2 binding is crucial for cardiomyocyte cohesion and (ii) L-tryptophan reduced both desmoglein-2 and N-cadherin binding, whereas single and tandem peptide can be used to specifically target desmoglein-2-mediated adhesion. L-tryptophan and single peptide also induced ultrastructural alterations of areae compositae. Functional analyses at the organ level revealed reduced cardiomyocyte function and inefficient response to adrenergic stimulation in both L-tryptophan- and single peptide-challenged murine Langendorff hearts paralleled by redistribution of connexin 43 in L-tryptophan-treated heart slices.Our data demonstrate that desmoglein-2 plays a critical role in cardiomyocyte cohesion and function.
Predictors of Prostate Cancer Tissue Acquisition by an Undirected Core Bone Marrow Biopsy in Metastatic Castration-Resistant Prostate Cancer—A Cancer and Leukemia Group B Study
Authors: Robert W. Ross, Susan Halabi, San-San Ou, Barur R. Rajeshkumar, Bruce A. Woda, Nicholas J. Vogelzang, Eric J. Small, Mary-Ellen Taplin, Philip W. Kantoff
Journal: Clinical Cancer Research (2005)

Analyzing metastatic prostate cancer tissue is of considerable importance in evaluating new targeted agents, yet acquiring such tissue presents a challenge due to the predominance of bone metastases. We assessed factors predicting a successful tumor harvest from bone marrow biopsies (BMBx) in castration-resistant metastatic prostate cancer patients.Data from Cancer and Leukemia Group B study 9663 were reviewed. Bone marrow biopsies were obtained from 184 patients who underwent an office-based, unguided bone marrow biopsy of the posterior iliac crest.Forty-seven of the 184 patients (25.5%) had a positive bone marrow biopsy. When considered in a multivariate logistic regression analysis, lower hemoglobin levels, higher alkaline phosphatase, and higher lactate dehydrogenase levels were associated with a higher likelihood of a positive BMBx. The median survival time was 11 months (95% confidence interval, 8.0-14) among patients with a positive BMBx compared with 23 months (95% confidence interval, 19-27) with a negative BMBx. The median time to progression and time to prostate-specific antigen progression-free survival were also significantly decreased among positive BMBx patients. No patients with a positive BMBx survived beyond 3 years, whereas 11 of the 137 patients with a negative BMBx survived beyond 5 years.Using common laboratory values, a specific patient cohort can be defined from whom the yield of a nonguided BMBx would be high enough to justify this approach. For studies that require broader entry criteria, a more directed approach with image guidance is recommended.
Systemic amyloid associated with carcinoma of the bronchus.
Authors: I Richmond, P S Hasleton, S Samadian
Journal: Thorax (1990)

An association of systemic amyloid with a squamous cell carcinoma of the bronchus is described. Amyloid may be associated with myeloma and neuroendocrine tumours but has not been described in squamous cell carcinoma of the bronchus.
Human Rhinovirus Species and Season of Infection Determine Illness Severity
Authors: Wai-Ming Lee, Robert F. Lemanske, Michael D. Evans, Fue Vang, Tressa Pappas, Ronald Gangnon, Daniel J. Jackson, James E. Gern
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Human rhinoviruses (HRVs) consist of approximately 160 types that cause a wide range of clinical outcomes, including asymptomatic infections, common colds, and severe lower respiratory illnesses.Objectives: To identify factors that influence the severity of HRV illnesses.Methods: HRV species and types were determined in 1,445 nasal lavages that were prospectively collected from 209 infants participating in a birth cohort who had at least one HRV infection. Questionnaires were used during each illness to identify moderate to severe illnesses (MSI).Measurements and Main Results: Altogether, 670 HRV infections were identified, and 519 of them were solitary infections (only one HRV type). These 519 viruses belonged to 93 different types of three species: 49 A, 9 B, and 35 C types. HRV-A (odds ratio, 8.2) and HRV-C (odds ratio, 7.6) were more likely to cause MSI compared with HRV-B. In addition, HRV infections were 5- to 10-fold more likely to cause MSI in the winter months (P < 0.0001) compared with summer, in contrast to peak seasonal prevalence in spring and fall. When significant differences in host susceptibility to MSI (P = 0.004) were considered, strain-specific rates of HRV MSI ranged from less than 1% to more than 20%.Conclusions: Factors related to HRV species and type, season, and host susceptibility determine the risk of more severe HRV illness in infancy. These findings suggest that anti-HRV strategies should focus on HRV-A and -C species and identify the need for additional studies to determine mechanisms for seasonal increases of HRV severity, independent of viral prevalence, in cold weather months.
Cost comparison of predictive genetic testing versus conventional clinical screening for familial adenomatous polyposis
Authors: B Bapat, H Noorani, Z Cohen, T Berk, A Mitri, B Gallie, K Pritzker, S Gallinger, A S Detsky
Journal: Gut (1999)

Mutations of the APC gene cause familial adenomatous polyposis (FAP), a hereditary colorectal cancer predisposition syndrome.To conduct a cost comparison analysis of predictive genetic testing versus conventional clinical screening for individuals at risk of inheriting FAP, using the perspective of a third party payer.All direct health care costs for both screening strategies were measured according to time and motion, and the expected costs evaluated using a decision analysis model.The baseline analysis predicted that screening a prototype FAP family would cost $4975/ pound3109 by molecular testing and $8031/ pound5019 by clinical screening strategy, when family members were monitored with the same frequency of clinical surveillance (every two to three years). Sensitivity analyses revealed that the genetic testing approach is cost saving for key variables including the kindred size, the age of screening onset, and the cost of mutation identification in a proband. However, if the APC mutation carriers were monitored at an increased (annual) frequency, the cost of the genetic screening strategy increased to $7483/ pound4677 and was especially sensitive to variability in age of onset of screening, family size, and cost of genetic testing of at risk relatives.In FAP kindreds, a predictive genetic testing strategy costs less than conventional clinical screening, provided that the frequency of surveillance is identical using either strategy. An additional significant benefit is the elimination of unnecessary colonic examinations for those family members found to be non-carriers.