tbuckley/cabot-search huggingface dataset:
Relationship of Metabolic Syndrome and Fibrinolytic Dysfunction to Cardiovascular Disease
Authors: Sonia S. Anand, Qilong Yi, Hertzel Gerstein, Eva Lonn, Ruby Jacobs, Vlad Vuksan, Koon Teo, Bonnie Davis, Patty Montague, Salim Yusuf
Journal: Circulation (2003)

The clustering of impaired glucose metabolism, elevated triglycerides, low HDL cholesterol, and abdominal obesity is known as the metabolic syndrome. Individuals with this syndrome suffer an excess of cardiovascular disease (CVD) for reasons that are unclear.We randomly sampled 1276 adults of South Asian, Chinese, European, and Native Indian ancestry from 4 communities in Canada. Participants provided fasting blood samples for glucose, lipids, and fibrinolytic measurements; had an oral glucose tolerance test; and underwent a B-mode carotid ultrasound examination. CVD was determined by history and ECG. The prevalence of the metabolic syndrome was 25.8% (95% CI, 23.5 to 28.2) and varied substantially by ethnic group: 41.6% among Native Indians, 25.9% among South Asians, and 22.0% among Europeans, compared with 11.0% among the Chinese (overall, P=0.0001). People with the metabolic syndrome had more atherosclerosis (maximum intimal medial thickness, 0.78+/-0.18 versus 0.74+/-0.18 mm; P=0.0005), CVD (17.2% versus 7.0%; P=0.0001), and elevated plasminogen activator inhibitor-1 (24.2 versus 14.6 U/mL; P=0.001) compared with levels among people without the metabolic syndrome. For the same amount of atherosclerosis, people with the metabolic syndrome had a greater prevalence of CVD, even among nondiabetic individuals. This difference in CVD prevalence among the groups was attenuated after adjustment for plasminogen activator inhibitor-1 levels, suggesting that fibrinolytic dysfunction mediates the increased risk of CVD in individuals with the metabolic syndrome.CVD among people with the metabolic syndrome is explained by their excess of atherosclerosis and impaired fibrinolysis. Interventions to prevent atherosclerosis progression and improve fibrinolytic function require evaluation in this high-risk group.
Association Between Asthma and Risk of Developing Obstructive Sleep Apnea
Authors: Mihaela Teodorescu, Jodi H. Barnet, Erika W. Hagen, Mari Palta, Terry B. Young, Paul E. Peppard
Journal: JAMA (2015)

<h3>Importance</h3> Obstructive sleep apnea (OSA) is more common among patients with asthma; whether asthma is associated with the development of OSA is unknown. <h3>Objective</h3> To examine the prospective relationship of asthma with incident OSA. <h3>Design, Setting, and Participants</h3> Population-based prospective epidemiologic study (the Wisconsin Sleep Cohort Study) beginning in 1988. Adult participants were recruited from a random sample of Wisconsin state employees to attend overnight polysomnography studies at 4-year intervals. Asthma and covariate information were assessed during polysomnography studies through March 2013. Eligible participants were identified as free of OSA (apnea-hypopnea index [AHI] of &lt;5 events/h and not treated) by 2 baseline polysomnography studies. There were 1105 4-year follow-up intervals provided by 547 participants (52% women; mean [SD] baseline age, 50 [8] years). <h3>Exposures</h3> Questionnaire-assessed presence and duration of self-reported physician-diagnosed asthma. <h3>Main Outcomes and Measures</h3> The associations of presence and duration of asthma with 4-year incidences of both OSA (AHI of ≥5 or positive airway pressure treatment) and OSA concomitant with habitual daytime sleepiness were estimated using repeated-measures Poisson regression, adjusting for confounders. <h3>Results</h3> Twenty-two of 81 participants (27% [95% CI, 17%-37%]) with asthma experienced incident OSA over their first observed 4-year follow-up interval compared with 75 of 466 participants (16% [95% CI, 13%-19%]) without asthma. Using all 4-year intervals, participants with asthma experienced 45 cases of incident OSA during 167 4-year intervals (27% [95% CI, 20%-34%]) and participants without asthma experienced 160 cases of incident OSA during 938 4-year intervals (17% [95% CI, 15%-19%]); the corresponding adjusted relative risk (RR) was 1.39 (95% CI, 1.06-1.82), controlling for sex, age, baseline and change in body mass index, and other factors. Asthma was also associated with new-onset OSA with habitual sleepiness (RR, 2.72 [95% CI, 1.26-5.89],<i>P</i> = .045). Asthma duration was related to both incident OSA (RR, 1.07 per 5-year increment in asthma duration [95% CI, 1.02-1.13],<i>P</i> = .01) and incident OSA with habitual sleepiness (RR, 1.18 [95% CI, 1.07-1.31],<i>P</i> = .02). <h3>Conclusions and Relevance</h3> Asthma was associated with an increased risk of new-onset OSA. Studies investigating the mechanisms underlying this association and the value of periodic OSA evaluation in patients with asthma are warranted.
Mesenchymal stem cells: Figure 1
Authors: Sara Rankin
Journal: Thorax (2012)

Mesenchymal Stem cells (MSCs) are stromal cells that can be readily harvested from adult bone marrow and adipose tissue, but also umbilical cords. With respect to respiratory disease, the therapeutic potential of these cells lies in their paracrine effects which underlie their ability to enhance tissue regeneration and modulate immune responses. MSCs have been shown to be effective in a range of murine models of respiratory disease, and there are currently five clinical trials involving the administration of MSCs for respiratory diseases, including COPD and emphysema. This paper summarises the features of MSCs.
Cardiac Dilatation Without Hypertrophy from Reduced Ambient Pressure in Rats
Authors: J. CLIFFORD STICKNEY, DAVID W. NORTHRUP, EDWARD J. VAN LIERE
Journal: Circulation Research (1956)

Short exposures of rats to greatly reduced ambient pressure after explosive decompression was found to result in cardiac dilatation. The dilatation, determined roentgenographically, was seen to persist for two or three days. Some rats were submitted to one long exposure, while others were repeatedly subjected to short exposures. Sacrifice of the rats sufficiently long after exposure to permit cardiac hypertrophy to develop revealed no evidence of it as determined from heart weightbody weight ratios.
Transcutaneous vaccination via laser microporation
Authors: Richard Weiss, Michael Hessenberger, Sophie Kitzmüller, Doris Bach, Esther E. Weinberger, Wolf D. Krautgartner, Cornelia Hauser-Kronberger, Bernard Malissen, Christof Boehler, Yogeshvar N. Kalia, Josef Thalhamer, Sandra Scheiblhofer
Journal: Journal of Controlled Release (2012)

Driven by constantly increasing knowledge about skin immunology, vaccine delivery via the cutaneous route has recently gained renewed interest. Considering its richness in immunocompetent cells, targeting antigens to the skin is considered to be more effective than intramuscular or subcutaneous injections. However, circumvention of the superficial layer of the skin, the stratum corneum, represents the major challenge for cutaneous immunization. An optimal delivery method has to be effective and reliable, but also highly adaptable to specific demands, should avoid the use of hypodermic needles and the requirement of specially trained healthcare workers. The P.L.E.A.S.E.® (Precise Laser Epidermal System) device employed in this study for creation of aqueous micropores in the skin fulfills these prerequisites by combining the precision of its laser scanning technology with the flexibility to vary the number, density and the depth of the micropores in a user-friendly manner. We investigated the potential of transcutaneous immunization via laser-generated micropores for induction of specific immune responses and compared the outcomes to conventional subcutaneous injection. By targeting different layers of the skin we were able to bias polarization of T cells, which could be modulated by addition of adjuvants. The P.L.E.A.S.E.® device represents a highly effective and versatile platform for transcutaneous vaccination.
Ethanolamine Injection for Sclerotherapy of Angiodysplasia of the Colon
Authors: G A Bemvenuti, M M Jülich
Journal: Endoscopy (1998)

Background and Study Aims: Endoscopic sclerotherapy has been a very useful method for the management of bleeding vascular lesions of the gastrointestinal tract. In this report, the injection of a sclerosant agent was evaluated for the treatment of angiodysplasias of the colon.
Treatment of HCV Infection by Targeting MicroRNA
Authors: Harry L.A. Janssen, Hendrik W. Reesink, Eric J. Lawitz, Stefan Zeuzem, Maribel Rodriguez-Torres, Keyur Patel, Adriaan J. van der Meer, Amy K. Patick, Alice Chen, Yi Zhou, Robert Persson, Barney D. King, Sakari Kauppinen, Arthur A. Levin, Michael R. Hodges
Journal: New England Journal of Medicine (2013)

The stability and propagation of hepatitis C virus (HCV) is dependent on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122). Miravirsen is a locked nucleic acid-modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122 in a highly stable heteroduplex, thereby inhibiting its function.In this phase 2a study at seven international sites, we evaluated the safety and efficacy of miravirsen in 36 patients with chronic HCV genotype 1 infection. The patients were randomly assigned to receive five weekly subcutaneous injections of miravirsen at doses of 3 mg, 5 mg, or 7 mg per kilogram of body weight or placebo over a 29-day period. They were followed until 18 weeks after randomization.Miravirsen resulted in a dose-dependent reduction in HCV RNA levels that endured beyond the end of active therapy. In the miravirsen groups, the mean maximum reduction in HCV RNA level (log10 IU per milliliter) from baseline was 1.2 (P=0.01) for patients receiving 3 mg per kilogram, 2.9 (P=0.003) for those receiving 5 mg per kilogram, and 3.0 (P=0.002) for those receiving 7 mg per kilogram, as compared with a reduction of 0.4 in the placebo group. During 14 weeks of follow-up after treatment, HCV RNA was not detected in one patient in the 5-mg group and in four patients in the 7-mg group. We observed no dose-limiting adverse events and no escape mutations in the miR-122 binding sites of the HCV genome.The use of miravirsen in patients with chronic HCV genotype 1 infection showed prolonged dose-dependent reductions in HCV RNA levels without evidence of viral resistance. (Funded by Santaris Pharma; ClinicalTrials.gov number, NCT01200420.).
Relationship Between Posttrauma GABA Plasma Levels and PTSD at 1-Year Follow-Up
Authors: Guillaume Vaiva, Virginie Boss, François Ducrocq, Monique Fontaine, Patrick Devos, Alain Brunet, Philippe Laffargue, Michel Goudemand, Pierre Thomas
Journal: American Journal of Psychiatry (2006)

Objective: Gamma-aminobutyric acid (GABA) exerts a prominent effect on central adrenergic stress responses in times of high stress and has been associated with acute posttraumatic stress disorder (PTSD). The authors examined the association between low posttrauma plasma GABA levels and long-term PTSD. Method: Plasma GABA levels were measured in 78 victims of road traffic accidents who met criteria for trauma exposure on arrival at a trauma department and were admitted for at least 3 days. Patients were assessed for PTSD and major depressive disorder at 6-week and 1-year follow-ups. Results: At 6 weeks and at 1 year, mean posttrauma GABA levels were significantly lower among subjects who met all or nearly all criteria for PTSD than among those who did not. Among patients who met all or nearly all criteria for PTSD at 6 weeks, 75% of those with posttrauma GABA levels above 0.20 mmol/ml no longer met criteria at 1 year. By contrast, among patients whose GABA levels were below 0.20 mmol/ml, 80% met all or nearly all criteria for PTSD at 1 year. Two-thirds of patients who met all or nearly all criteria for PTSD at 1 year also met criteria for major depressive disorder. Conclusions: A plasma GABA level above 0.20 mmol/ml may protect against chronic PTSD and may represent a marker of recovery from trauma.
Peak coronary vasodilation occurs after peak flow with both endothelium-dependent and independent agents: A study using simultaneous intravascular ultrasound and doppler wire
Authors: Paul Tamburro, Maryl R. Johnson, Lloyd W. Klein, Tony L. Hursey, Diana Spokas, Maria Rosa Costanzo, Joseph E. Partilo, Steven M. Hollenberg
Journal: Journal of the American College of Cardiology (1996)
Management of Chronic Heart Failure in Adults: Synopsis of the National Institute for Health and Clinical Excellence Guideline
Authors: Jonathan Mant, Abdallah Al-Mohammad, Sharon Swain, Philippe Laramée
Journal: Annals of Internal Medicine (2011)

Description: The National Institute for Health and Clinical Excellence released its first clinical guideline on heart failure in 2003. This synopsis describes the update of that guideline, which was released in August 2010 and discusses the diagnosis, treatment, and monitoring of heart failure. Methods: Guideline developers considered clinical evidence, health economic analyses, clinical expert opinion, and patient views. Systematic literature searches were performed, and an original decision model assessed the cost-effectiveness of serial measurement of serum natriuretic peptide to monitor patients with chronic heart failure. Recommendations: First, this guideline update describes the role of serum natriuretic peptide measurement, echocardiography, and specialist assessment in the diagnosis of heart failure. Second, it presents a pathway for pharmacologic treatment, rehabilitation, and pacing therapy (including implantable cardioverter-defibrillator and cardiac resynchronization therapy) for patients with heart failure and left ventricular systolic dysfunction and patients with heart failure and preserved ejection fraction. Finally, it explains the recommendation to monitor patients with heart failure by using serial measurement of serum natriuretic peptide.
Sialic Acids Sweeten a Tumor's Life
Authors: Christian Büll, Marieke A. Stoel, Martijn H. den Brok, Gosse J. Adema
Journal: Cancer Research (2014)

Over four decades ago, specific tumor characteristics were ascribed to the increased expression of sialic acid sugars on the surface of cancer cells, and this led to the definition of sialic acids as potential therapeutic targets. Recent advances in glycobiology and cancer research have defined the key processes underlying aberrant expression of sialic acids in cancer, and its consequences, more precisely. These consequences include effects on tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. Collectively, these novel insights provide further rationale for the design and development of therapeutic approaches that interfere with excessively high expression of sialic acids in cancer cells. Strategies to target aberrant sialylation in cancer, however, have evolved comparatively slowly. Here, we review recent findings that emphasize the detrimental effects of hypersialylation on multiple aspects of tumor growth and behavior. We also discuss novel therapeutic strategies.
Iron deficiency is neglected in women's health
Authors: D H. Rushton
Journal: BMJ (2002)

EDITOR—The data by Waalen et al show that 38% of menstruating women living in San Diego are iron deficient using the accepted cut-off point of <20% for transferrin saturation as an indicator of deficiency. These data support our hypothesis that haematological distributions contain a large proportion of iron deficient women.1

By focusing on the mean haemoglobin distribution, Waalen et al lose sight of a fundamental part of our work: why should women have lower reference …
Restoration of Tamoxifen Sensitivity in Estrogen Receptor–Negative Breast Cancer Cells: Tamoxifen-Bound Reactivated ER Recruits Distinctive Corepressor Complexes
Authors: Dipali Sharma, Neeraj K. Saxena, Nancy E. Davidson, Paula M. Vertino
Journal: Cancer Research (2006)

Abstract Breast tumors expressing estrogen receptor-α (ER) respond well to therapeutic strategies using selective ER modulators, such as tamoxifen. However, ∼30% of invasive breast cancers are hormone independent because they lack ER expression due to hypermethylation of ER promoter. Treatment of ER-negative breast cancer cells with demethylating agents [5-aza-2′-deoxycytidine (5-aza-dC)] and histone deacetylase (HDAC) inhibitors (trichostatin A) leads to expression of ER mRNA and functional protein. Here, we examined whether epigenetically reactivated ER is a target for tamoxifen therapy. Following treatment with trichostatin A and 5-aza-dC, the formerly unresponsive ER-negative MDA-MB-231 breast cancer cells became responsive to tamoxifen. Tamoxifen-mediated inhibition of cell growth in these cells is mediated at least in part by the tamoxifen-bound ER. Tamoxifen-bound reactivated ER induces transcriptional repression at estrogen-responsive genes by ordered recruitment of multiple distinct chromatin-modifying complexes. Using chromatin immunoprecipitation, we show recruitment of two different corepressor complexes to ER-responsive promoters in a mutually exclusive and sequential manner: the nuclear receptor corepressor-HDAC3 complex followed by nucleosome remodeling and histone deacetylation complex. The mechanistic insight provided by this study might help in designing therapeutic strategies directed toward epigenetic mechanisms in the prevention or treatment of breast cancer. (Cancer Res 2006; 66(12): 6370-8)
Mechanisms of vasodilation induced by NKH477, a water-soluble forskolin derivative, in smooth muscle of the porcine coronary artery.
Authors: J Shafiq, S Suzuki, T Itoh, H Kuriyama
Journal: Circulation Research (1992)

To study the mechanism of vasodilation induced by 6-(3-dimethylaminopropionyl) forskolin (NKH477), a water-soluble forskolin derivative, its effects on the acetylcholine (ACh)-induced contraction of muscle strips of porcine coronary artery were examined. [Ca2+]i, isometric force, and cellular concentrations of cAMP and inositol 1,4,5-trisphosphate were measured. NKH477 (0.1-1.0 microM), isoproterenol (0.01-0.1 microM), or forskolin (0.1-1.0 microM) increased cAMP and attenuated the contraction induced by 128 mM K+ or 10 microM ACh in a concentration-dependent manner. These agents, at concentrations up to 0.3 microM, did not change the amount of cGMP. NKH477 (0.1 microM) attenuated the contraction induced by 128 mM K+ without corresponding changes in the evoked [Ca2+]i responses. ACh (10 microM) produced a large phasic increase followed by a small tonic increase in [Ca2+]i and produced a sustained contraction. The ACh-induced phasic increase in [Ca2+]i, but not the tonic increase, disappeared after application of 0.1 microM ionomycin. NKH477 (0.1 microM) attenuated both the increase in [Ca2+]i and the force induced by 10 microM ACh in muscle strips that were not treated with ionomycin and inhibited the ACh-induced contraction without corresponding changes in [Ca2+]i in ionomycin-treated muscle strips. These results suggest that NKH477 inhibits ACh-induced Ca2+ mobilization through its action on ionomycin-sensitive storage sites. In ionomycin-treated and 128 mM K(+)-treated muscle strips, 0.1 microM NKH477 shifted the [Ca2+]i-force relation to the right in the presence or absence of 10 microM ACh. In beta-escin-skinned smooth muscle strips, 0.1 microM NKH477 shifted the pCa-force relation to the right but had no effects on Ca(2+)-independent contraction. We conclude that in smooth muscle of porcine coronary artery, NKH477 inhibits ACh-induced contraction by both attenuating ACh-induced Ca2+ mobilization and reducing the sensitivity of the contractile machinery to Ca2+, possibly by activating cAMP-dependent mechanisms.
Modulation of N-Nitrosomethylurea-Induced Mammary Tumor Promotion by Dietary Fiber and Fat
Authors: L. A. Cohen, M. E. Kendall, E. Zang, C. Meschter, D. P. Rose
Journal: JNCI Journal of the National Cancer Institute (1991)

A test of the anticancer effects of dietary fiber was conducted using the N-nitrosomethylurea (NMU)-induced rat mammary tumor model. Starting 3 days after NMU treatment, four different groups of F344 rats (30 rats in each group) were fed as follows: Group 1 received a high-fat diet; group 2, a high-fat plus fiber diet (soft white wheat bran, 10% wt/wt); group 3, a low-fat diet; and group 4, a low-fat plus fiber diet. The rats remained on these diets for 15 weeks. Tumor incidence in group 1 was 90% compared with 66% in group 2 (P<.001). Tumor incidence in group 3 was 63% compared with 47% in group 4 (P>.4). These results show that supplemental dietary fiber exerts an inhibitory effect on the promotional phase of NMU-induced mammary carcinogenesis in rats when fed a high-fat but not a low-fat diet. To test whether fiber may exert its antipromoting effect by reducing circulating estrogens, serum 17β-estradiol was assayed. No changes were observed in serum 17β-estradiol levels among the four groups, suggesting that the protective effect of fiber in this animal model is not mediated by a fiber-induced reduction of circulating 17β-estradiol. [J Natl Cancer Inst 83: 496–501, 1991]
Late sequelae of pulmonary tuberculosis treated by thoracoplasty.
Authors: M S Phillips, W J Kinnear, J M Shneerson
Journal: Thorax (1987)

With the help of information provided by the Office of Population, Censuses and Surveys the survival up to 1 July 1985 of the 171 patients treated for pulmonary tuberculosis by thoracoplasty at Papworth from 1951 to 1953 was determined. Thirteen (8%) could not be traced, 65 (38%) had died, and 93 (54%) were alive. For those who were traced the survival at 10, 20, and 30 years from the date of operation was 93%, 79%, and 65%. This represents a significantly greater mortality rate than that predicted from the Registrar General9s review of deaths in England and Wales (1841-1984). Nineteen patients died from cardiorespiratory failure. Eight of the survivors are known to have developed respiratory failure, five having enjoyed apparently good health before this was precipitated by intercurrent illness or drugs. A stepwise logistic regression analysis using information from the 124 patients for whom full details were available showed significant associations between the development of cardiorespiratory or respiratory failure and a preoperative contralateral artificial pneumothorax, older age at operation, the presence of cavities before operation, and male sex. In a questionnaire 50 of the survivors (57% of those who replied) reported cough, 45 (51%) breathlessness, 41 (47%) wheeze, and 24 (27%) ankle swelling. Nineteen (22%) smoke and the same number now attend a chest clinic. Many patients treated for tuberculosis by thoracoplasty have respiratory symptoms and some are at risk of respiratory failure. There are grounds for considering that they should be reviewed periodically by a chest physician.