tbuckley/cabot-search huggingface dataset:
Fluoromisonidazole. A metabolic marker of myocyte hypoxia.
Authors: G V Martin, M D Cerqueira, J H Caldwell, J S Rasey, L Embree, K A Krohn
Journal: Circulation Research (1990)

Fluoromisonidazole is metabolically trapped in viable hypoxic cells in vitro. This property is the basis for the hypothesis that [18F]fluoromisonidazole can be used to detect hypoxic tissues noninvasively using positron emission tomography. To assess the potential usefulness of this compound as a marker for hypoxic myocardium, we measured the accumulation of [3H]fluoromisonidazole in isolated adult rat myocytes under normoxic, hypoxic (5,000 ppm O2), and anoxic conditions. Both anoxia and hypoxia caused a marked increase in [3H]fluoromisonidazole accumulation. Relative to uptake during normoxia, uptake during anoxia was increased by 8.4-fold at 60 minutes and 26.5-fold at 180 minutes (p less than 0.001). During hypoxia, uptake was increased by 4.4-fold at 60 minutes and by 15.3-fold at 180 minutes (p less than 0.0001) and occurred in the absence of significant cell injury as measured by release of creatine kinase and changes in cell morphology. Additional studies demonstrated a slow oxygen-insensitive efflux of fluoromisonidazole or labeled metabolite(s) from myocytes reincubated in drug-free medium. We conclude that fluoromisonidazole is avidly retained in hypoxic myocytes and thus may be suitable for noninvasive detection of hypoxic myocardium using positron emission tomography.
Home-Based Primary Care and the Risk of Ambulatory Care–Sensitive Condition Hospitalization Among Older Veterans With Diabetes Mellitus
Authors: Samuel T. Edwards, Julia C. Prentice, Steven R. Simon, Steven D. Pizer
Journal: JAMA Internal Medicine (2014)

Primary care services based at home have the potential to reduce the likelihood of hospitalization among older adults with multiple chronic diseases.To characterize the association between enrollment in Home-Based Primary Care (HBPC), a national home care program operated by the US Department of Veterans Affairs (VA), and hospitalizations owing to an ambulatory care-sensitive condition among older veterans with diabetes mellitus.Retrospective cohort study. Patients admitted to VA and non-VA hospitals were followed up from January 1, 2006, through December 31, 2010.Veterans 67 years or older who were fee-for-service Medicare beneficiaries, were diagnosed as having diabetes mellitus and at least 1 other chronic disease, and had at least 1 admission to a VA or non-VA hospital in 2005 or 2006.Enrollment in HBPC, defined as a minimum of 2 HBPC encounters during the study period.Admission to VA and non-VA hospitals owing to an ambulatory care-sensitive condition, as measured by the Agency for Healthcare Research and Quality's Prevention Quality Indicators in VA medical records and Medicare claims. Outcomes were analyzed using distance from the veteran's residence to a VA facility that provides HBPC as an instrumental variable.Among 56 608 veterans, 1978 enrolled in HBPC. These patients were older (mean age, 79.1 vs 77.1 years) and had more chronic diseases (eg, 59.2% vs 53.5% had congestive heart failure). Multivariable predictors for HBPC enrollment included paralysis (odds ratio [OR], 2.11; 95% CI, 1.63-2.74), depression (OR, 1.99; 95% CI, 1.70-2.34), congestive heart failure (OR, 1.36; 95% CI, 1.17-1.58), and distance from the nearest HBPC-providing VA facility (OR, 0.59; 95% CI, 0.50-0.70 for >10-30 vs <5 miles). After controlling for selection using an instrumental variable analysis, HBPC was associated with a significant reduction in the probability of experiencing a hospitalization owing to an ambulatory care-sensitive condition (hazard ratio, 0.71; 95% CI, 0.57-0.89), with an absolute reduction in the probability of hospitalization of 5.8% in 1 year.Home-Based Primary Care is associated with a decreased probability of ambulatory care-sensitive condition hospitalization among elderly veterans with diabetes mellitus. In accountable care models, HBPC may have an important role in the management of older adults with multiple chronic diseases.
Future of Early Detection of Lung Cancer: The Role of Mouse Models
Authors: Alice T. Shaw, David G. Kirsch, Tyler Jacks
Journal: Clinical Cancer Research (2005)

Abstract Early detection represents one of the most promising approaches to improving lung cancer survival. To date, no screening strategies have been shown to decrease mortality from the disease. Furthermore, no reliable circulating biomarkers of lung cancer have been identified that allow early diagnosis. With the advent of gene targeting technology, new genetically engineered mouse models of lung cancer closely recapitulate the pathobiology of human disease. These mouse models have enabled novel approaches to early detection, including the identification of cancer-associated serum markers using proteomic technologies and the development of new molecular imaging tools. The application of innovative technologies to accurate mouse models promises to accelerate the discovery of new molecular targets and imaging biomarkers for the early detection of lung cancer.
Exhaled Nitric Oxide Is Higher Both at Day and Night in Subjects with Nocturnal Asthma
Authors: NICK H. T. ten HACKEN, HESTER van der VAART, THOMAS W. van der MARK, GERARD H. KOËTER, DIRKJE S. POSTMA
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Nitric oxide in exhaled air is thought to reflect airway inflammation. No data have been reported so far on circadian changes in NO in subjects with nocturnal asthma. To determine whether exhaled NO shows a circadian rhythm inverse to the circadian rhythm in airway obstruction in subjects with nocturnal asthma, we conducted a study involving six healthy controls, eight individuals without nocturnal asthma (4-h to 16-h variation in peak expiratory flow [PEF] ⩽ 15%), and six individuals with nocturnal asthma (4-h to 16-h PEF variation > 15%). Smoking, use of corticosteroids, and recent respiratory infections were excluded. NO concentrations were measured at 12, 16, 20, and 24 h, and at 4, 8, and 12 h of the next day, using the single-breath method. At the same times, FEV1 and PEF were also measured. Mean NO concentrations were significantly higher in subjects with nocturnal asthma than in subjects without nocturnal asthma, and higher in both groups than in healthy controls at all time points. Mean exhaled NO levels over 24 h correlated with the 4-h to 16-h variation in PEF (r = 0.61, p < 0.01). Exhaled NO did not show a significant circadian variation in any of the three groups as assessed with cosinor analysis, in contrast to the FEV1 in both asthma groups (p < 0.05). At 4 h, mean ± SD NO levels were higher than at 16 h in subjects with nocturnal asthma; at 50 ± 20 ppb versus 42 ± 15 ppb (p < 0.05); other measurements at all time points were similar. Differences in NO and FEV1 from 4 h to 16 h did not correlate with one another. We conclude that subjects with nocturnal asthma exhale NO at higher levels both at night and during the day, which may reflect more severe diurnal airway-wall inflammation. A circadian rhythm in exhaled NO was not observed. NO levels did not correspond to the circadian rhythm in airway obstruction. The small increase in NO at 4 h may indicate an aspect of inflammation, but it is not associated with increased nocturnal airway obstruction.
The impact of weekends on outcome for acute exacerbations of COPD
Authors: R. Barba, A. Zapatero, J.E. Losa, J. Marco, S. Plaza, C. Rosado, J. Canora
Journal: European Respiratory Journal (2011)

Differences in hospital staffing may influence outcomes for patients with acute conditions, including acute exacerbations of chronic obstructive pulmonary disease (COPD), depending on which day of the week the patients are admitted. This study was conducted to determine whether weekend admission increases the risk of dying in hospital. We analysed the clinical data of 289,077 adults with acute exacerbations of COPD admitted to the hospital at any public centre in Spain, during 2006 and 2007. We analysed the following factors for their association with death rate: day of admission, demographics, medical history and comorbidity. During the study period, there were 35,544 (12.4%) deaths during admission in COPD patients. Weekend admissions were associated with a significantly higher in-hospital mortality (12.9%) than weekday admissions (12.1%) among COPD patients (OR 1.07 (95% CI 1.04–1.10)). The differences in mortality persisted after adjustment for age, sex and coexisting disorders (OR 1.05 (95% CI 1.02–1.08)). Analyses of deaths within 2 days after admission showed larger relative differences in mortality between the weekend and weekday admissions (OR 1.17 (95% CI 1.11–1.23)). We conclude that patients with acute exacerbations of COPD are more likely to die in the hospital if they are admitted on a weekend compared with a weekday.
Risk Factors for Financial Hardship in Patients Receiving Adjuvant Chemotherapy for Colon Cancer: A Population-Based Exploratory Analysis
Authors: Veena Shankaran, Sanjay Jolly, David Blough, Scott D. Ramsey
Journal: Journal of Clinical Oncology (2012)

Characteristics that predispose patients to financial hardship during cancer treatment are poorly understood. We therefore conducted a population-based exploratory analysis of potential factors associated with financial hardship and treatment nonadherence during and following adjuvant chemotherapy for colon cancer.Patients diagnosed with stage III colon cancer between 2008 and 2010 were identified from a population-based cancer registry representing 13 counties in Washington state. Patients were asked to complete a comprehensive survey on treatment-related costs. Patients were considered to have experienced financial hardship if they accrued debt, sold or refinanced their home, borrowed money from friends or family, or experienced a 20% or greater decline in their annual income as a result of treatment-related expenses. Logistic regression analysis was used to investigate factors associated with financial hardship and treatment nonadherence.A total of 284 responses were obtained from 555 eligible patients (response rate, 51.2%). Nearly all patients in the final sample were insured during treatment. In this sample, 38% of patients reported one or more financial hardships as a result of treatment. The factors most closely associated with treatment-related financial hardship were younger age and lower annual household income. Younger age, lower income, and unemployment or disability (which occurred in most instances following diagnosis) were most closely associated with treatment nonadherence.A significant proportion of patients undergoing adjuvant chemotherapy for stage III colon cancer may experience financial hardship, despite having health insurance coverage. Interventions to help at-risk patients early on during therapy may prevent long-term financial adverse effects.
CCAAT/Enhancer-Binding Protein δ: A Molecular Target of 1,25-Dihydroxyvitamin D3 in Androgen-Responsive Prostate Cancer LNCaP Cells
Authors: Takayuki Ikezoe, Sigal Gery, Dong Yin, James O'Kelly, Lise Binderup, Nathan Lemp, Hirokuni Taguchi, H. Phillip Koeffler
Journal: Cancer Research (2005)

Abstract 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D3, inhibits the proliferation of prostate cancer cells. However, the molecular mechanisms by which 1,25(OH)2D3 inhibits the proliferation of these cells remain to be fully elucidated. In this study, we used microarray technology to identify target genes of 1,25(OH)2D3 in androgen-responsive prostate cancer LNCaP cells. 1,25(OH)2D3 up-regulated CCAAT/enhancer-binding protein δ (C/EBPδ) by ∼5-fold in these cells. Knockdown of C/EBPδ expression by RNA interference showed that C/EBPδ is essential for the significant growth inhibition of LNCaP cells in response to 1,25(OH)2D3 treatment. Moreover, we found that 1,25(OH)2D3 induced C/EBPδ in other cancer cells, including the estrogen receptor (ER)–expressing MCF-7 and T47D breast cancer cells that are sensitive to the growth inhibitory effects of 1,25(OH)2D3. On the other hand, 1,25(OH)2D3 was not able to induce C/EBPδ in either androgen receptor–negative PC-3 and DU145 or ER-negative breast cancer MDA-MB-231 cells that were relatively resistant to growth inhibition by 1,25(OH)2D3. Furthermore, forced expression of C/EBPδ in prostate cancer LNCaP as well as breast cancer MCF-7 and T47D cells dramatically reduced their clonal growth. Taken together, forced expression of C/EBPδ in cancer cells may be a promising therapeutic strategy.
Significance of sodium, sympathetic innervation, and central adrenergic structures on renal vascular responsiveness in DOCA-treated rats.
Authors: K H Berecek, R D Murray, F Gross
Journal: Circulation Research (1980)

The effects of sodium, sympathetic innervation, and central adrenergic structures on the development of changes in renal vascular reactivity were studied in unilaterally nephrectomized rats treated with a single implant of deoxycorticosterone acetate (DOCA; 100 mg/kg). Vascular reactivity to norepinephrine (NE) and vasopressin (ADH) was assessed in isolated kidneys perfused with a synthetic medium. Influence of sodium was determined by placing DOCA-treated rats on high, normal, and low sodium intakes. Neural influence was studied by means of local denervation of the renal artery and by intravenous (iv) and intraventricular (ivt) administration of 6-hydroxydopamine (6-OHDA). Marked changes in renal vascular reactivity in DOCA-treated rats were already apparent prior to the rise in blood pressure. Dose-response curves for NE and ADH showed parallel leftward shifts and decreased threshold doses. Normal sodium intake, local denervation, and peripheral sympathectomy had no effect on the development of these vascular changes in DOCA-treated rats. However, sodium deficiency and ivt administration of 6-OHDA totally prevented development of enhanced vascular reactivity. These results imply that increased vascular reactivity is a major factor in the development of DOCA-hypertension.
Adverse Effects of Methylmercury: Environmental Health Research Implications
Authors: Philippe Grandjean, Hiroshi Satoh, Katsuyuki Murata, Komyo Eto
Journal: Environmental Health Perspectives (2010)

The scientific discoveries of health risks resulting from methylmercury exposure began in 1865 describing ataxia, dysarthria, constriction of visual fields, impaired hearing, and sensory disturbance as symptoms of fatal methylmercury poisoning.Our aim was to examine how knowledge and consensus on methylmercury toxicity have developed in order to identify problems of wider concern in research.We tracked key publications that reflected new insights into human methylmercury toxicity. From this evidence, we identified possible caveats of potential significance for environmental health research in general.At first, methylmercury research was impaired by inappropriate attention to narrow case definitions and uncertain chemical speciation. It also ignored the link between ecotoxicity and human toxicity. As a result, serious delays affected the recognition of methylmercury as a cause of serious human poisonings in Minamata, Japan. Developmental neurotoxicity was first reported in 1952, but despite accumulating evidence, the vulnerability of the developing nervous system was not taken into account in risk assessment internationally until approximately 50 years later. Imprecision in exposure assessment and other forms of uncertainty tended to cause an underestimation of methylmercury toxicity and repeatedly led to calls for more research rather than prevention.Coupled with legal and political rigidity that demanded convincing documentation before considering prevention and compensation, types of uncertainty that are common in environmental research delayed the scientific consensus and were used as an excuse for deferring corrective action. Symptoms of methylmercury toxicity, such as tunnel vision, forgetfulness, and lack of coordination, also seemed to affect environmental health research and its interpretation.
Lung volume reduction surgery versus conservative treatment in severe emphysema
Authors: H. Wilkens, S. Demertzis, J Konig, C.k Leitnaker, H.j Schafers, G.w Sybrecht
Journal: European Respiratory Journal (2000)

Lung volume reduction surgery (LVRS) has been proposed for patients with severe emphysema to improve dyspnoea and pulmonary function. It is unknown, however, whether prognosis and pulmonary function in these patients can be improved compared to conservative treatment. The effect of LVRS and conservative therapy were compared prospectively in 57 patients with emphysema, who fulfilled the standard criteria for LVRS. The patients were divided into two groups according to their own decision. Patients in group 1 (n=29, eight females, mean+/-SEM 58.8+/-1.7 yrs, forced expiratory volume in one second (FEV1) 27.6+/-1.3% of the predicted value) underwent LVRS. Patients in group 2 (n=28, five females, 58.5+/-1.8 yrs, FEV1 30.8+/-1.4% pred) preferred to postpone LVRS. There were no significant differences in lung function between the two groups at baseline; however, there was a tendency towards better functional status in the control group. The control group had a better modified Medical Research Council (MMRC) dyspnea score (3.1+/-0.15 versus 3.5+/-0.1, p<0.04). Model-based comparisons were used to estimate the differences between the two groups over 18 months. Significant improvements were observed in the LVRS group compared to the control group in FEV1, total lung capacity (TLC), Residual volume (RV), MMRC dyspnea score and 6-min walking distance on all follow up visits. The estimated difference in FEV1 was 33% (95% confidence interval 13-58%; p>0.0001), in TLC 12.9% (7.9-18.8%; p>0.0001), in RV 60.9% 32.6-89.2%; p>0.0001), in 6-min walking distance 230 m (138-322 m; p<0.002) and in MMRC dyspnoea score 1.17 (0.79-1.55; p<0.0001). In conclusion, lung volume reduction surgery is more effective than conservative treatment for the improvement of dyspnoea, lung function and exercise capacity in selected patients with severe emphysema.
Pharmacological Inhibition of PI3K Reduces Adiposity and Metabolic Syndrome in Obese Mice and Rhesus Monkeys
Authors: Ana Ortega-Molina, Elena Lopez-Guadamillas, Julie A. Mattison, Sarah J. Mitchell, Maribel Muñoz-Martin, Gema Iglesias, Vincent M. Gutierrez, Kelli L. Vaughan, Mark D. Szarowicz, Ismael González-García, Miguel López, David Cebrián, Sonia Martinez, Joaquin Pastor, Rafael de Cabo, Manuel Serrano
Journal: Cell Metabolism (2015)
Localisation of fibronectin mRNA in the rheumatoid synovium by in situ hybridisation.
Authors: H A Waller, M G Butler, J G McClean, G S Dowd, D L Scott
Journal: Annals of the Rheumatic Diseases (1992)

The distribution of fibronectin, an extracellular matrix glycoprotein which plays a part in fibrosis and tissue repair, has previously been described using immunohistochemical methods. These do not differentiate between locally synthesised and plasma derived fibronectin. In this work the distribution of cells actively synthesising fibronectin was assessed by in situ hybridisation using a radiolabelled antisense RNA probe in synovial biopsy samples from patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and control subjects without inflammatory disease. Large amounts of fibronectin mRNA were found specifically in synovial lining cells, providing evidence for the local production of fibronectin in the synovium. Levels of fibronectin mRNA were variable between patients. These differences were not related to the diagnosis or to the subintimal inflammatory cell infiltrate; where there was synovial lining cell hyperplasia there was a concomitant increase in the number of cells containing fibronectin mRNA, which was consistent with increased levels of immunoreactive fibronectin at this site. Increased levels of fibronectin in synovial fluid in patients with rheumatoid arthritis may be due to an increased number of lining cells secreting the protein, rather than upregulation of the gene by these cells.
Late Creation of Vascular Access for Hemodialysis and Increased Risk of Sepsis
Authors: Matthew J. Oliver, Deanna M. Rothwell, Kinwah Fung, Janet E. Hux, Charmaine E. Lok
Journal: Journal of the American Society of Nephrology (2004)

The creation of fistulas or grafts before starting dialysis is recommended, but whether it reduces major adverse events is largely unknown. The objective of this study was to determine if early access creation was associated with a reduced risk of hospitalization from sepsis and mortality. Fistulas or grafts created at least 4 mo before starting hemodialysis were defined as Early creations (n = 1240), and accesses created between 4 mo and 1 mo before starting hemodialysis were defined as Just Prior creations (n = 997). Accesses created within 1 mo of starting dialysis or after were defined as Late creations (reference group, n = 3687). Hemodialysis catheter use was defined as insertion, removal, or manipulation of a catheter before the occurrence of sepsis. Eighty percent of accesses were fistulas. Early access creation was associated with a relative risk (RR) of sepsis of 0.57 (95% CI, 0.41 to 0.79) compared with Late access creation. Catheter use increased the risk of sepsis by 1.41 (95% CI, 1.14 to 1.81). The risk of sepsis with Early creation decreased to 0.48 (95% CI, 0.35 to 0.65) if catheter use was not adjusted. Early access creation was associated with lower mortality (RR 0.76; 95% CI 0.58 to 1.00), but this association became nonsignificant if catheter use and sepsis were adjusted. Catheter use and sepsis independently increased mortality. This study demonstrates that fistula creation at least 4 mo before starting chronic hemodialysis is associated the lowest risk of sepsis and death, primarily by reducing the use of hemodialysis catheters.
Intravenous volume replacement
Authors: A da Silva
Journal: BMJ (1988)

with peripheral vascular disease before and after the recent introduction of percutaneous trans- luminal angioplasty and identified a new group of patients who could be treated.'Referral for angio- graphy was increased by 66%, but the rate of surgery performed remained static at about 22%.A further 24% were treated by percutaneous trans- luminal angioplasty.Lamberton documents an impressive 87% early clinical success rate with 80% patency at one year.2Mortality (1-2%) was associated with using the procedure in a group including patients with critically ischaemic limbs and poor general health.We now have more to offer patients with mild to moderate claudication than the simple sound advice to stop smoking and keep walking.Thrombolysis is not a treatment for stable claudication.If sudden severe claudication or rest pain develops, however, the limb may have been