tbuckley/cabot-search huggingface dataset:
Neighborhood Socioeconomic Disadvantage and 30-Day Rehospitalization
Authors: Amy J.H. Kind, Steve Jencks, Jane Brock, Menggang Yu, Christie Bartels, William Ehlenbach, Caprice Greenberg, Maureen Smith
Journal: Annals of Internal Medicine (2014)

Measures of socioeconomic disadvantage may enable improved targeting of programs to prevent rehospitalizations, but obtaining such information directly from patients can be difficult. Measures of U.S. neighborhood socioeconomic disadvantage are more readily available but are rarely used clinically.To evaluate the association between neighborhood socioeconomic disadvantage at the census block group level, as measured by the Singh validated area deprivation index (ADI), and 30-day rehospitalization.Retrospective cohort study.United States.Random 5% national sample of Medicare patients discharged with congestive heart failure, pneumonia, or myocardial infarction between 2004 and 2009 (n = 255,744).Medicare data were linked to 2000 census data to construct an ADI for each patient's census block group, which were then sorted into percentiles by increasing ADI. Relationships between neighborhood ADI grouping and 30-day rehospitalization were evaluated using multivariate logistic regression models, controlling for patient sociodemographic characteristics, comorbid conditions and severity, and index hospital characteristics.The 30-day rehospitalization rate did not vary significantly across the least disadvantaged 85% of neighborhoods, which had an average rehospitalization rate of 21%. However, within the most disadvantaged 15% of neighborhoods, rehospitalization rates increased from 22% to 27% with worsening ADI. This relationship persisted after full adjustment, with the most disadvantaged neighborhoods having a rehospitalization risk (adjusted risk ratio, 1.09 [95% CI, 1.05 to 1.12]) similar to that of chronic pulmonary disease (adjusted risk ratio, 1.06 [CI, 1.04 to 1.08]) and greater than that of uncomplicated diabetes (adjusted risk ratio, 0.95 [CI, 0.94 to 0.97]).No direct markers of care quality or access.Residence within a disadvantaged U.S. neighborhood is a rehospitalization predictor of magnitude similar to chronic pulmonary disease. Measures of neighborhood disadvantage, such as the ADI, could potentially be used to inform policy and care after hospital discharge.National Institute on Aging and University of Wisconsin School of Medicine and Public Health's Institute for Clinical and Translational Research and Health Innovation Program.
Radioimmunotherapy of Solid Tumors by Targeting Extra Domain B Fibronectin: Identification of the Best-Suited Radioimmunoconjugate
Authors: Dietmar Berndorff, Sandra Borkowski, Stephanie Sieger, Axel Rother, Matthias Friebe, Francesca Viti, Christoph S. Hilger, John E. Cyr, Ludger M. Dinkelborg
Journal: Clinical Cancer Research (2005)

The expression of extra domain B (ED-B) fibronectin is always associated with angiogenic processes and can be exclusively observed in tissues undergoing growth and/or extensive remodeling. Due to this selective expression, ED-B fibronectin is an interesting target for radioimmunotherapy of malignant diseases. The aim of this study was to identify the most appropriate ED-B-targeting radioimmunoconjugate for the therapy of solid tumors.Three ED-B fibronectin-binding human antibody formats of L19 were investigated: dimeric single-chain Fv (approximately 50 kDa), "small immunoprotein" (SIP, approximately 80 kDa), and immunoglobulin G1 (IgG1, approximately 150 kDa). These L19 derivatives were either labeled with I-125 or with In-111 (using MX-diethylenetriaminepentaacetic acid, MX-DTPA). Pharmacokinetics and tumor accumulation of the radiolabeled immunoconjugates were investigated in F9 (murine teratocarcinoma) tumor-bearing mice. Subsequently, dosimetry for the corresponding therapeutic isotopes I-13-1 and Y-90 was done. After testing the myelotoxicity of I-131-L19-SIP and I-131-L19-IgG1 in non-tumor-bearing mice, the therapeutic efficacy of these iodinated antibody formats was finally investigated in F9 tumor-bearing mice.The most favorable therapeutic index was found for I-131-L19-SIP followed by I-131-L19-IgG1. The therapeutic index of all In-111-labeled derivatives was significantly inferior. Considering the bone marrow as the dose-limiting organ, it was calculated that activities of 74 MBq I-131-L19-SIP and 25 MBq I-131-L19-IgG1 could be injected per mouse without causing severe myelotoxicity. The best therapeutic efficacy was observed using I-131-L19-SIP, resulting in significant tumor growth delay and prolonged survival after a single injection.Compared with other L19-based radioimmunoconjugates, I-131-L19-SIP is characterized by superior antitumor efficacy and toxicity profile in the F9 teratocarcinoma animal model. These results indicate that ED-B fibronectin-targeted radioimmunotherapy using I-131-L19-SIP has potential to be applied to treatment of solid cancers.
The Role of Vascular Endothelial Growth Factor Genetic Variability in Cancer
Authors: Bryan P. Schneider, Milan Radovich, Kathy D. Miller
Journal: Clinical Cancer Research (2009)

Angiogenesis is a hallmark of tumor pathogenesis. Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis and its inhibition has become a successful approach to antitumor therapy across tumor types. The VEGF gene is highly polymorphic with multiple common single nucleotide polymorphisms (SNPs) in the promoter, 5' untranslated region and 3' untranslated region. There is evidence that these SNPs in the regulatory regions can affect VEGF expression. In vitro and in vivo data show that genetic variability affects the activity and expression of VEGF. Case-control and cohort studies suggest that genetic variability may affect risk and outcome of a variety of disease states that are tightly regulated by angiogenesis. Recently, genetic variability in VEGF has been studied as a potential predictive biomarker for bevacizumab. The VEGF-1154 AA and -2578 AA genotypes predicted an improved median overall survival, whereas the VEGF-634 CC and -1498 TT genotypes predicted protection from grade 3-4 hypertension in the pivotal trial, E2100. If validated, these finding could help direct which subgroup of patients should receive bevacizumab.
Psychiatric Inpatient, Outpatient, and Medication Utilization and Costs Among Privately Insured Youths, 1997–2000
Authors: Andrés Martin, Douglas Leslie
Journal: American Journal of Psychiatry (2003)

The study examined trends in use of inpatient and outpatient mental health services, including pharmacotherapy, among privately insured children and adolescents from 1997 to 2000.Data from a national database of more than 1.7 million privately insured individuals were used in an analysis of inpatient, outpatient, and pharmacy claims of users of mental health care age 17 years and younger (approximately 20,000 patients per year). Annual utilization rates and adjusted costs for services and dispensed psychotropic medications were calculated. Results from 1997 and 2000 were compared across diagnostic and age categories.The proportion of youths with an inpatient psychiatric admission decreased by 23.7% from 1997 to 2000, and annual inpatient and outpatient costs decreased by 1,216 US dollars (18.4%) and 157 US dollars (14.4%), respectively. Decreases were driven by a reduction in inpatient days (20.0%) and by a combination of a reduction in outpatient visits (11.3%) and declining payments per outpatient visit (6.1%). Payment trends across diagnoses varied considerably, with the largest reductions seen in treatment of depression, hyperactivity, adjustment disorders, and anxiety disorders. Over the same period, the proportion of youths receiving medication increased by 4.9%, and mean annual medication-related costs per outpatient increased by 41 US dollars (12.1%).Reductions in inpatient and outpatient mental health service intensity and reimbursements documented in previous research continued through the late 1990s. Declines were accompanied by concurrent increases in the use of and costs associated with psychotropic medications, particularly for youths with mood and anxiety disorders. These results document a shift toward medication-based outpatient treatment modalities.
Glucocorticoids decrease c-fos expression in human nasal polyps in vivo
Authors: J. N Baraniuk, G. Wong, M. Ali, M. Sabol, T. Troost
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Activated<i>c-fos</i> binds to<i>jun</i> proteins to form the activation protein 1 (<i>AP-1</i>) transcription factor that regulates cytokine and other proinflammatory genes.<i>c-Fos</i> may play a key role in nasal polyp formation. Glucocorticoids may exert their anti-inflammatory effects through an interaction of glucocorticoid receptors with<i>AP-1</i> that leads to mutual inactivation of both factors, and a “default” termination of<i>AP-1</i> mediated gene activation. This may explain the beneficial effects of glucocorticoids in the treatment of nasal polyps. <h3>METHODS</h3> To test this hypothesis in humans in vivo the immunohistochemical expression of<i>c-fos</i>-immunoreactive material (<i>c-fos</i>-irm) was assessed in nasal polyps from eight steroid naive subjects, polyps from eight subjects treated with topical beclomethasone dipropionate (BDP), and normal inferior turbinate nasal mucosa (n = 6). <h3>RESULTS</h3> mRNA for<i>c-fos</i> was detected in all nasal polyps and normal mucosa. In contrast, <i>c-fos</i>-irm was present in all steroid naive subjects but in only two of the eight subjects treated with BDP (p = 0.007, two-tailed Fisher’s exact test).<i>c-Fos</i>-irm was expressed solely in epithelial cells and glandular structures; it was expressed in normal epithelium and glands, but the staining intensity was low. <h3>CONCLUSION</h3> Glucocorticoids appear to modulate expression of <i>c-fos</i>-irm and possibly <i>AP-1</i> in human airway epithelial cells in vivo.
Effects of Doubling the Highest Indicated Dose of Budesonide/Formoterol (BUD/FM) on Lung Function and Symptoms in Moderate-to-Severe Asthma with Fixed Airflow Obstruction (FAO)
Authors: Michael DePietro, Donald P. Tashkin, Bradley E. Chipps, Frank Trudo
Journal: Journal of Allergy and Clinical Immunology (2015)
Pfiesteria-related educational products and information resources available to the public, health officials, and researchers.
Authors: J L Kleindinst, D M Anderson
Journal: Environmental Health Perspectives (2001)

Public and political concerns about Pfiesteria from 1997 to the present vastly exceed the attention given to other harmful algal bloom (HAB) issues in the United States. To some extent, the intense focus on Pfiesteria has served to increase attention on HABs in general. Given the strong and continuing public, political, and research interests in Pfiesteria piscicida Steidinger &amp; Burkholder and related organisms, there is a clear need for information and resources of many different types. This article provides information on Pfiesteria-related educational products and information resources available to the general public, health officials, and researchers. These resources are compiled into five categories: reports; website resources; state outreach and communication programs; fact sheets; and training manuals and documentaries. Over the last few years there has been rapid expansion in the amount of Pfiesteria-related information available, particularly on the Internet, and it is scattered among many different sources.
CELLULAR LOCALIZATION OF ROUS SARCOMA VIRUS AS STUDIED WITH FLUORESCENT ANTIBODY
Authors: Robert C. Mellors, J. Spencer Munroe
Journal: The Journal of Experimental Medicine (1960)

A study has been made of the immunospecific, apple-green staining patterns imparted by fluorescent antibody to Rous virus in frozen sections of wing tumors produced in young chickens by various initiating doses of virus. Variations in the cellular site (cytoplasm, cell membrane, and nucleus), the distribution (particulate or homogeneous), and the quantity (little or much) of Rous viral antigens were seen. The per cent of sarcoma cells containing viral antigens was related to the tumor initiating dose of virus and to the infectivity titer of virus extracted from the wing tumor. With certain assumptions it was estimated that a quantity of virus approaching one tumor-producing dose (1 TD50) per tissue section was detectable with fluorescent antibody. Sarcoma cells containing viral antigens were identified as early as 4 days after inoculation of Rous virus. At this time viral antigens were also localized in the skeletal muscle of the inoculated wing in a characteristic focal pattern of deposition near or on the sarcolemma. This association between viral antigens and skeletal muscle fibers was observed also at 3 days after virus inoculation, when sarcoma cells were not yet demonstrable in the tissue sections. Viral antigens were detected in sarcoma cells in lung tumors of young chickens and in tumors of the chorioallantoic membrane of chick embryos.
Nonselective Versus Selective β-Adrenergic Receptor Blockade in Congestive Heart Failure
Authors: Eduardo R. Azevedo, Toshihiko Kubo, Susanna Mak, Abdul Al-Hesayen, Anne Schofield, Rebecca Allan, Susan Kelly, Gary E. Newton, John S. Floras, John D. Parker
Journal: Circulation (2001)

Activation of the sympathetic nervous system has important prognostic implications in chronic heart failure. Nonselective versus selective beta-adrenergic receptor antagonists may have differential effects on norepinephrine release from nerve terminals mediated by prejunctional beta(2)-adrenergic receptors.Thirty-six patients with chronic heart failure were randomized to the nonselective beta-blocker carvedilol or the selective beta-blocker metoprolol (double-blind). Measurements of hemodynamics and cardiac and systemic norepinephrine spillover as well as microneurographic recordings of muscle sympathetic nerve traffic were made before and after 4 months of therapy. In the carvedilol group (n=17), there were significant reductions in both total body (-1.7+/-0.5 nmol/min, P<0.01) and cardiac norepinephrine spillover (-87+/-29 pmol/min, P<0.01). By contrast, in the metoprolol group (n=14), there were no significant changes in total body or cardiac norepinephrine spillover. Responses in the carvedilol group were significantly different from those observed in the metoprolol group (P<0.05). Both agents caused a reduction in heart rate and increases in pulse pressure, although mean arterial pressure did not change. Importantly, microneurographic measures of sympathetic nerve traffic to skeletal muscle did not change in either group.Therapy with carvedilol caused significant decreases in systemic and cardiac norepinephrine spillover, an indirect measure of norepinephrine release. Such changes were not observed in patients treated with metoprolol. There was no effect of either agent on sympathetic efferent neuronal discharge to skeletal muscle. These findings suggest that carvedilol, a nonselective beta-blocker, caused its sympathoinhibitory effect by blocking peripheral, prejunctional beta-adrenergic receptors.
Shifted T-cell polarisation after agricultural dust exposure in mice and men
Authors: P Robbe, EAJ Spierenburg, C Draijer, CA Brandsma, E Telenga, AJM van Oosterhout, M van den Berge, M Luinge, BN Melgert, D Heederik, W Timens, IM Wouters, MN Hylkema
Journal: Thorax (2014)

<h3>Rationale</h3> A low prevalence of asthma and atopy has been shown in farmers and agricultural workers. However, in these workers, a higher prevalence of respiratory symptoms has been reported, in which T helper 1 (Th1) and/or Th17 responses may play a role. <h3>Aim</h3> We investigated the effect of exposure to dust extracts (DEs) from different farms on airway inflammation and T-cell polarisation in a mouse model and assessed T-cell polarisation in agricultural workers from the same farms. <h3>Methods</h3> DEs were prepared from settled dust collected at cattle and pig farms and bulb and onion industries. Mice were exposed to phosphate-buffered saline (PBS), DEs, house dust mite (HDM) or HDM+DE via nasal instillation, four times per week during 5 weeks. Hyperresponsiveness, airway inflammation, IgE levels and T-cell polarisation were assessed. Th-cell and T cytotoxic (Tc)-cell subsets were investigated in peripheral blood samples from 33 agricultural workers and 9 non-exposed controls. <h3>Results</h3> DEs induced interleukin(IL)-17, IL-1β and IL-6 in mouse lung homogenates. DE-exposed mice had more mixed inflammatory infiltrates in the lungs, and more neutrophils compared with PBS-exposed mice. DEs protected against the HDM-induced Th2 response and methacholine hyperresponsiveness. Interestingly, occupationally exposed humans had higher frequencies of Th cells spontaneously expressing IL-17 and interferon γ compared with controls. <h3>Conclusion</h3> Chronic exposure to different types of farm dust induces a Th/Tc-17 inflammatory response in mice and agricultural workers. This may contribute to the low prevalence of Th2-related diseases but may constitute a risk for other chronic respiratory diseases.
The impact of passive smoking on the frequency of respiratory infections in preschool children
Authors: Neven Pavlov, Franjo Bozic
Journal: European Respiratory Journal (2014)

Aim: To determine whether passive smoking increases the frequnecy of respiratory infections in children.

Methods: A retrospective cohort study was conducted from 2011 to 2013 at the pediatric clinics of primary healthcare phsysician Dr. Mira Pavlov in the Sucidar area of Split. The study included 203 preschool children who were brought to the pediatric clinic by their parents for a medical examination. The children were divided into two groups: 114 children whose household members smoked, and 89 children whose household members didn't smoke. All the necessary data were obtained by a questionnaire filled out by the parents and access to the electronic medical records.

Results: The difference in the frequencies of bronchitis between the two groups of children bordered on statistical significance ( P = 0.052). The number of bronchitis was significantly higher in the group of children whose household members smoked inside the home compared to the group of children whose household members didn't smoke ( P = 0.008). The number of cigarettes smoked per day inside the home statistically correlated with the number of bronchitis in children ( P = 0.003). Maternal smoking statistically increased the number of pneumonia cases in children compared to paternal smoking ( P = 0.001). Children with allergic diseases whose household members smoked didn't have significantly higher number of respiratory infections compared to children with allergic diseases whose household members didn't smoke.

Conclusion: Passive smoking increases the frequency of respiratory infections in children but only if household members smoke inside the home.
Lulling septic shock to sleep
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

A sleep-inducing neuropeptide can also inhibit lethal septic shock, according to Gonzalez-Rey and colleagues on page 563. This natural neuropeptide—called cortistatin—curbed the production of cytokines and inflammatory mediators that trigger organ failure and vascular collapse in mice exposed to lethal doses of bacteria.






Figure 1

Cortistatin protects mice against lethal endotoxic shock.




Many neuropeptides that regulate activity in the central nervous system (CNS) double as regulators of inflammation. The stress hormone neuropeptide Y, for example, controls both metabolism and heart rate via the CNS and cytokine production by macrophages in the periphery. Cortistatin is no exception—it was originally described as a sleep-promoting hormone produced in response to circadian rhythms, but was recently shown to be produced by activated immune cells.

But the consequences of cortistatin production by immune cells had not been investigated. Gonzalez-Rey and colleagues now show that cortistatin treatment shuts down the synthesis of cytokines and inflammatory mediators by macrophages and protects mice against septic shock. Immune cells produce cortistatin during infection—probably as a means of keeping inflammation in check—but levels of endogenous cortistatin may be too low to shut down cytokine production in the face of a massive bacterial infection.

Cortistatin's close relative somatostatin (which is used to treat certain neuroendocrine cancers) also inhibits cytokine production by macrophages. But somatostatin is not produced by immune cells and, in this model, did not protect against sepsis. If cortistatin, like somatostatin, proves safe in humans, it may be an effective way to treat patients who have septic shock.
The German etanercept registry for treatment of juvenile idiopathic arthritis
Authors: G Horneff
Journal: Annals of the Rheumatic Diseases (2004)

To describe a registry set up to monitor children treated with etanercept in Germany and Austria.Giannini's criteria, duration of morning stiffness, number of swollen, tender and contracted joints, adverse events, and reasons for discontinuation were assessed.322 patients with juvenile idiopathic arthritis (JIA) and 12 additional patients with non-JIA rheumatic diagnoses were included. Therapeutic efficacy was observed from one month after treatment was started. The number of patients with significant improvement and the degree of improvement increased during the first year. The mean (SD) number of tender and swollen joints decreased from 9 (9) and 8.4 (9) to 3.0 (6.5) and 4.5 (7) after one month, and to 2.2 (5.5) and 3.3 (5.5) after three months; morning stiffness decreased from 45 (65) minutes to 12 (30) and 7 (19) after one and three months (p<0.001 for all). Using Gianinni's criteria of 30%, 50%, and 70% improvement, a therapeutic response in JIA patients was achieved in, respectively, 66%, 54%, and 30% after one month, 78%, 61%, and 38% after three months, and 83%, 72%, and 52% after six months. Therapeutic efficacy was lower in patients with systemic onset arthritis. Overall tolerability was good: in 592 patient treatment-years there were 69 reports of adverse events in 56 patients, including one CNS demyelination. There were no opportunistic infections or lupus-like reactions. Treatment was discontinued in 53 JIA patients, in 25 because of lack of efficacy.Etanercept treatment was safe and led to a significant improvement in most JIA patients resistant to conventional treatment.